Usefulness of PCR Screening in the Initial Triage of Trauma Patients During COVID-19 Pandemic.
Hospitals worldwide have postponed all nonessential surgery during the COVID-19 pandemic, but non-COVID-19 patients are still in urgent need of care. Uncertainty about a patient's COVID-19 status risks infecting health care workers and non-COVID-19 inpatients. We evaluated the use of quantitative reverse transcription polymerase chain reaction (RT-qPCR) screening for COVID-19 on admission for all patients with fractures. We conducted a retrospective cohort study of patients older than 18 years admitted with low-energy fractures who were tested by RT-qPCR for SARS-CoV-2 at any time during hospitalization. Two periods based on the applied testing protocol were defined. During the first period, patients were only tested because of epidemiological criteria or clinical suspicion based on fever, respiratory symptoms, or radiological findings. In the second period, all patients admitted for fracture treatment were screened by RT-qPCR. We identified 15 patients in the first period and 42 in the second. In total, 9 (15.8%) patients without clinical or radiological findings tested positive at any moment. Five (33.3%) patients tested positive postoperatively in the first period and 3 (7.1%) in the second period (P = 0.02). For clinically unsuspected patients, postoperative positive detection went from 3 of 15 (20%) during the first period to 2 of 42 (4.8%) in the second (P = 0.11). Clinical symptoms demonstrated high specificity (92.1%) but poor sensitivity (52.6%) for infection detection. Symptom-based screening for COVID-19 has shown to be specific but not sensitive. Negative clinical symptoms do not rule out infection. Protocols and separated areas are necessary to treat infected patients. RT-qPCR testing on admission helps minimize the risk of nosocomial and occupational infection. Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Prevalence of parents' perceptions of sensory processing disorders among kindergarten children.
This study is the first to systematically examine estimated rates of sensory processing disorders using survey data. Parents of incoming kindergartners from one suburban U.S. public school district were surveyed using the Short Sensory Profile, a parent-report screening tool that evaluates parents' perceptions of functional correlates of sensory processing disorders (McIntosh, Miller, Shyu, & Dunn, 1999a). A total of 703 completed surveys were returned, which represents 39% of the kindergarten enrollment (n = 1,796) in the district for the 1999-2000 school year. Of the 703 children represented by the surveys, 96 children (13.7% of 703) met criteria for sensory processing disorders based upon parental perceptions. A more conservative prevalence estimate of children having sensory processing disorders based on parental perceptions was calculated by assuming that all non-respondents failed to meet screening criteria. This cautious estimate suggests that based on parents' perceptions, 5.3% (96 of 1796) of the kindergarten enrollment met screening criteria for sensory processing disorders. These percentages are consistent with hypothesized estimates published in the literature. Findings suggest a need for rigorous epidemiological studies of sensory processing disorders.


A Method to Study Adaptation to Left-Right Reversed Audition.
An unusual sensory space is one of the effective tools to uncover the mechanism of adaptability of humans to a novel environment. Although most of the previous studies have used special spectacles with prisms to achieve unusual spaces in the visual domain, a methodology for studying the adaptation to unusual auditory spaces has yet to be fully established. This study proposes a new protocol to set-up, validate, and use a left-right reversed stereophonic system using only wearable devices, and to study the adaptation to left-right reversed audition with the help of neuroimaging. Although individual acoustic characteristics are not yet implemented, and slight spillover of unreversed sounds is relatively uncontrollable, the constructed apparatus shows high performance in a 360° sound source localization coupled with hearing characteristics with little delay. Moreover, it looks like a mobile music player and enables a participant to focus on daily life without arousing curiosity or drawing attention of other individuals. Since the effects of adaptation were successfully detected at the perceptual, behavioral, and neural levels, it is concluded that this protocol provides a promising methodology for studying adaptation to left-right reversed audition, and is an effective tool for uncovering the adaptability of humans to a novel environments in the auditory domain.


Body image and weight change in middle age: a qualitative study.
To explore men's and women's experiences of weight change in adulthood, body image preferences and beliefs about the health consequences of overweight and to inform the development of a primary care intervention to prevent obesity. Seventy-two men and women aged 35-55, with a range of BMIs from 22 to 29.9, were identified from two UK general practice registers and invited to participate in an interview about experiences of weight change in adulthood. Audio tape recorded, semi-structured interviews were conducted in respondents' homes by trained researchers. Open-ended questions were used to collect experiences of weight change since early adulthood and views about weight change in middle age. Illustrations of a range of men's and women's body shapes were used to prompt discussion of respondents' preferences for male and female body shapes and their perspectives of the health, social and practical problems associated with underweight and overweight. The data were analysed using both quantitative and qualitative methods. Some 87% (33/38) of the women and 59% (20/34) of the men said that they had ever tried to lose weight. At least one instance of successful weight loss was reported by 58% of the women and 47% of the men, although many of these attempts were relatively short-lived and often motivated by specific goals such as a holiday or a wedding. Respondents were sceptical of the possibility of controlling weight without considerable personal sacrifice. Explanations for middle-age weight gain included a sedentary lifestyle, as well as several gender-specific reasons, including hormonal changes and comfort eating for women and beer drinking for men. Nearly all (97%) respondents associated heart disease with overweight, while diabetes was mentioned by only 22% and none mentioned cancer. People who have gained weight in middle age may be deterred from trying to prevent further gain by pessimism about the effort required. The efficacy of interventions to encourage relatively small substitutions and changes to diet and physical activity need to be tested. Interventions to help prevent weight gain in middle age could include information about the less widely known health risks such as diabetes and cancer.


Changes in leptin and peptide YY do not explain the greater-than-predicted decreases in resting energy expenditure after weight loss.
It is unknown whether leptin and peptide YY (PYY) influence changes in resting energy expenditure (REE), independently of fat mass (FM) and fat-free mass (FFM) in addition to changes in other energy expenditure (EE) components during weight loss. The objective of the study was to examine the relationships between leptin, PYY, and body composition with different EE components before and after weight loss and whether changes in leptin and PYY were associated with differences in predicted vs measured REE after the intervention. This was a randomized controlled design. The study was conducted in a laboratory. Participants were ninety-three overweight/obese postmenopausal women (aged 58.1 ± 4.8 y; body mass index 32.1 ± 4.3 kg/m(2)). Interventions included a 6-month caloric restriction diet alone or caloric restriction diet+resistance training. Body composition (dual energy x-ray absorptiometry), REE (indirect calorimetry), total EE (TEE; doubly labeled water), and fasting leptin and total PYY before and after weight loss were measured. Both interventions yielded significant decreases in weight, FFM, REE, and leptin, whereas a significant time × group interaction was noted for FM (greater decrease in FM in the diet+resistance training group) (P < .05 for all outcomes). No significant differences in TEE, physical activity EE, and PYY were noted between baseline and after the intervention. Age, FFM, leptin, and PYY were the best predictors of baseline REE (R(2) = 0.77; P = .0001), whereas age, FFM, and FM were associated with REE after the intervention (R(2) = 0.88; P = .0001). The same predictors, except for leptin, were significantly related to TEE at baseline (R(2) = 0.70; P = .0001) and after the intervention (R(2) = 0.29; P = .0001), whereas only PYY was a significant predictor of physical activity EE at baseline and after the intervention. Changes in FM and leptin accounted for 27% of the variance in ΔREE (P = .0001). Greater predicted vs measured REE was noted after the intervention (P = .02). However, Δ leptin and ΔPYY were not significant predictors of the differences between postintervention measurement and predicted REE. Δ Leptin and ΔFM were strong contributors to changes in REE. However, Δ leptin and ΔPYY were not significant predictors of the differences between predicted and measured REE after the intervention.


Screening and prevention of hereditary gynecologic cancers.
Endometrial and ovarian cancer are the fourth and fifth most common malignancies in women, with approximately 40,000 new endometrial and 25,000 new ovarian cancers expected to be diagnosed in the Unites States this year. While the majority of these cancers will occur in the absence of a family history, approximately 5% of endometrial cancers and 10% of ovarian cancers will be the result of inherited defects in high-penetrance cancer susceptibility genes. With the identification and subsequent availability of clinical genetic testing for mutations in the genes associated with hereditary breast-ovarian cancer and the Lynch/hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, targeted risk-reduction using intensive screening, chemoprevention, and prophylactic surgery has become possible for women at inherited risk of gynecologic malignancies. We review the options for gynecologic cancer risk reduction in women with an inherited mutation in BRCA1, BRCA2, or one of the mismatch repair (MMR) genes associated with Lynch/HNPCC syndrome. Additionally, we outline ongoing questions and areas for future research.


COVID-19 vaccine hesitancy in Zambia: a glimpse at the possible challenges ahead for COVID-19 vaccination rollout in sub-Saharan Africa.
With unprecedented speed, multiple vaccines against SARS-CoV-2 are available 1 year after the COVID-19 pandemic was first identified. As we push to achieve global control through these new vaccines, old challenges present themselves, including cold-chain storage, the logistics of mass vaccination, and vaccine hesitancy. Understanding how much hesitancy toward COVID-19 vaccines might occur and what factors may be driving these concerns can improve the ability of public health workers and communicators to maximize vaccine uptake. We nested a survey within a measles-rubella mass vaccination campaign in Zambia in November 2020 and asked about sentiments and beliefs toward COVID-19 and COVID-19 vaccines. Among parents bringing their children to receive a measles-rubella vaccine, we found high acceptability of COVID-19 vaccination of their children, but substantial uncertainty and hesitancy about receiving the vaccine themselves. COVID-19 vaccination hesitancy was correlated with beliefs around COVID-19 severity and risk, as well as vaccine safety and effectiveness.


Prevention of gynecologic contact bleeding and genital sandy patches by childhood anti-schistosomal treatment.
Schistosoma haematobium infection may cause genital mucosal pathology in women with and without urinary schistosomiasis. This report seeks to explore the long-term effect of anti-schistosomal treatment on the clinical manifestations of S. haematobium infection in the lower genital tract. Prior treatment was reported by 248 (47%) of 527 women. Treatment received before the age of 20 years was significantly associated with the absence of sandy patches and contact bleeding, and this association was independent of current waterbody contact. Treatment in the past five years did not influence the prevalence of gynecologic schistosoma-induced lesions. The study indicates that early treatment may be more efficient for gynecologic morbidity control. Findings warrant an exploration into several chemotherapeutic agents administered at an early age, as well as in adults.


A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial.
Attention-deficit hyperactivity disorder (ADHD) is a common paediatric neurodevelopmental disorder with substantial effect on families and society. Alternatives to traditional care, including novel digital therapeutics, have shown promise to remediate cognitive deficits associated with this disorder and may address barriers to standard therapies, such as pharmacological interventions and behavioural therapy. AKL-T01 is an investigational digital therapeutic designed to target attention and cognitive control delivered through a video game-like interface via at-home play for 25 min per day, 5 days per week for 4 weeks. This study aimed to assess whether AKL-T01 improved attentional performance in paediatric patients with ADHD. The Software Treatment for Actively Reducing Severity of ADHD (STARS-ADHD) was a randomised, double-blind, parallel-group, controlled trial of paediatric patients (aged 8-12 years, without disorder-related medications) with confirmed ADHD and Test of Variables of Attention (TOVA) Attention Performance Index (API) scores of -1·8 and below done by 20 research institutions in the USA. Patients were randomly assigned 1:1 to AKL-T01 or a digital control intervention. The primary outcome was mean change in TOVA API from pre-intervention to post-intervention. Safety, tolerability, and compliance were also assessed. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02674633 and is completed. Between July 15, 2016, and Nov 30, 2017, 857 patients were evaluated and 348 were randomly assigned to receive AKL-T01 or control. Among patients who received AKL-T01 (n=180 [52%]; mean [SD] age, 9·7 [1·3] years) or control (n=168 [48%]; mean [SD] age, 9·6 [1·3] years), the non-parametric estimate of the population median change from baseline TOVA API was 0·88 (95% CI 0·24-1·49; p=0·0060). The mean (SD) change from baseline on the TOVA API was 0·93 (3·15) in the AKL-T01 group and 0·03 (3·16) in the control group. There were no serious adverse events or discontinuations. Treatment-related adverse events were mild and included frustration (5 [3%] of 180) and headache (3 [2%] of 180). Patient compliance was a mean of 83 (83%) of 100 expected sessions played (SD, 29·2 sessions). Although future research is needed for this digital intervention, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events. Sponsored by Akili Interactive Labs.


Atmospheric methane removal: a research agenda.
Atmospheric methane removal (e.g. in situ methane oxidation to carbon dioxide) may be needed to offset continued methane release and limit the global warming contribution of this potent greenhouse gas. Because mitigating most anthropogenic emissions of methane is uncertain this century, and sudden methane releases from the Arctic or elsewhere cannot be excluded, technologies for methane removal or oxidation may be required. Carbon dioxide removal has an increasingly well-established research agenda and technological foundation. No similar framework exists for methane removal. We believe that a research agenda for negative methane emissions-'removal' or atmospheric methane oxidation-is needed. We outline some considerations for such an agenda here, including a proposed Methane Removal Model Intercomparison Project (MR-MIP). This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.


Nine Novel Phages from a Plateau Lake in Southwest China: Insights into Aeromonas Phage Diversity.
Aeromonas species are common pathogens of fish and some of them can opportunistically cause infectious diseases in humans. The overuse of antibiotics has led to the emergence of bacterial drug-resistance. To date, only 51 complete genome sequences of Aeromonas phages are available in GenBank. Here, we report the isolation of nine Aeromonas phages from a plateau lake in China. The protein cluster, dot plot and ANI analyses were performed on all 60 currently sequenced Aeromonas phage genomes and classified into nine clusters and thirteen singletons. Among the nine isolated phages, the DNA-packaging strategy of cluster 2L372D (including 2L372D, 2L372X, 4L372D, 4L372XY) is unknown, while the other five phages use the headful (P22/Sf6) DNA-packaging strategy. Notably, the isolated phages with larger genomes conservatively encode auxiliary metabolism genes, DNA replication and metabolism genes, while in smaller phage genomes, recombination-related genes were conserved. Finally, we propose a new classification scheme for Aeromonas phages.


Heterogeneous catalytic ozonation of cationic dyes using volcanic sand.
This work aims to present experimental results on the treatment of methylene blue contaminated waters using heterogeneous catalytic ozonation promoted by volcanic sand. The effect of pH (2-8), and the presence of radical scavengers (acetate ions) in homogeneous and heterogeneous systems are evaluated at laboratory scale. Heterogeneous catalytic ozonation using volcanic sand increases methylene blue removal rate. In the presence of free radical scavengers, only a 37% reduction on methylene blue removal rate is observed in the heterogeneous system, as compared with 70% when homogeneous ozonation is used. The results obtained here indicate the importance of chemical surface properties on methylene blue oxidation reactions, suggesting that acid surface sites of volcanic sand play a key role on the reaction mechanism.


Incidence and determinants of stillbirth among women who gave birth in Jimma University specialized hospital, Ethiopia.
Worldwide approximately 2.7 million are stillborn, more than 98% of these occur in developing countries. To address the problem, incidence and determinants of stillbirth must be understood. Therefore the aim of this study was to assess incidence and determinants of stillbirth among women who gave birth in Jimma University specialized hospital. A cross-sectional study design among 413 mothers who gave birth in Jimma specialized hospital was employed. Study subjects were selected by systematic sampling technique from the list of women who gave birth in hospital in one month study period. Data were collected by using pretested and structured questionnaire. Data were edited, cleaned, coded, entered and analyzed using SPSS-20 statistical software. Univarate and bivariate (logistic regressions) analysis was employed. The incidence rate of stillbirth in the Hospital during a month period was 8% or 80 per 1000 total births. The predictors that showed an independent close association with stillbirth were absence of complication (OR = 0.1, 95% CI (0.04-0.2)), referral from other health facility (OR = 0.3, 95% CI (0.1-0.7)), having antenatal care (OR = 0.3, 95% CI (0.1-0.7)) and normal vaginal delivery (OR = 0.2, 95% CI ( 0.1-0.8)). The incidence rate of stillbirths in our setting is high and the identified determinants were related to both ante-partum and intra-partum-period. Therefore, effort should be made to improve antenatal, obstetric services and delivery services in terms awareness, access, timing and referral system to emergency care and specialized service to reduce the number of stillbirths.


Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex.
The feasibility of producing a visual prosthesis for the blind using intracortical microstimulation (ICMS) of the visual cortex was studied in a 42-year-old woman who had been totally blind for 22 years secondary to glaucoma. Thirty-eight microelectrodes were implanted in the right visual cortex, near the occipital pole, for a period of 4 months. Percepts reported as small spots of light, called phosphenes, were produced with 34 of the 38 implanted microelectrodes. Threshold currents for phosphene generation with trains of biphasic pulses were as low as 1.9 microA, and most of the microelectrodes had thresholds below 25 microA. Phosphene brightness could be modified with stimulus amplitude, frequency and pulse duration. Repeated stimulation over a period of minutes produced a gradual decrease in phosphene brightness. Phosphenes did not flicker. The apparent size of phosphenes ranged from a "pin-point' to a "nickel' (20 mm diameter coin) held at arm's length. Phosphene size usually decreased as stimulation current was increased but increased slightly as the train length (TL) was increased. At levels of stimulation near threshold, the phosphenes were often reported to have colours. As the stimulation level was increased, the phosphenes generally became white, greyish or yellowish. Individual phosphenes appeared at different distances from the subject. When two phosphenes were simultaneously generated, the apparent distances of the individual phosphenes sometimes changed to make them appear to be at about the same distance. When three or more phosphenes were simultaneously generated, they became coplanar. Except for rare occasions, phosphenes extinguished rapidly at the termination of the stimulation train. When stimulation TLs were increased beyond 1 s, phosphenes usually disappeared before the end of the train. The duration of phosphene perception could be increased by interrupting a long stimulation train with brief pauses in stimulation. Intracortical microelectrodes spaced 500 microns apart generated separate phosphenes, but microelectrodes spaced 250 microns typically did not. This two-point resolution was about five times closer than has typically been achieved with surface stimulation. With some individual microelectrodes, a second closely spaced phosphene was sometimes produced by increasing the stimulation current. Phosphenes moved with eye movements. When up to six phosphenes were simultaneously elicited, they all moved with the same relative orientation during eye movements. All phosphenes were located in the left hemi-field with the majority above the horizontal meridian. There was a clustering of most of the phosphenes within a relatively small area of visual space. The potentially greater microelectrode density and lower power requirements of ICMS compared with surface stimulation appears encouraging for a visual prosthesis. However, further studies with blind subjects are required to optimize stimulation parameters and test complex image recognition before the feasibility of a visual prosthesis based on ICMS can be established.


Ethical issues arising from a research, technology and development project to support frail older people and their family carers at home.
The present paper provides an overview of the application of the key ethical issues which arose in an EU-funded research, technology and development project, Assisting Carers using Telematics Interventions to meet Older Persons' Needs (ACTION). The primary aim of the ACTION project was to support frail older people and their family carers in their own homes across England, Northern Ireland, the Republic of Ireland, Sweden and Portugal via the use of user-friendly information and communication technology. Ethical guidelines were developed in the project and used as a tool to enable the multidisciplinary project team to increase their awareness of ethical issues in their everyday work, and to act as a useful ethical framework for regular team discussions at international and local meetings across the partner countries. A range of ethical issues arose during the field-study phases of the project when the ACTION services were introduced into a number of families' own homes. It can be argued that these ethical issues reflect factors relating both to the application of research into practice, as well as those relating more directly to the use of new technology by families and care professionals. Key issues centre upon the ethical concepts of autonomy, independence, quality of life, beneficence, non-maleficence and justice, and more specifically, on ethical issues of security, privacy and confidentiality, increased expectations, and withdrawal of the service. This paper is intended to facilitate dialogue and debate in the area of enabling (assistive) technology in home care for older people and their families.


The prevalence and etiology of elevated aminotransferase levels in the United States.
Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates. The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05). Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.


Home parenteral nutrition provision modalities for chronic intestinal failure in adult patients: An international survey.
The safety and effectiveness of a home parenteral nutrition (HPN) program depends both on the expertise and the management approach of the HPN center. We aimed to evaluate both the approaches of different international HPN-centers in their provision of HPN and the types of intravenous supplementation (IVS)-admixtures prescribed to patients with chronic intestinal failure (CIF). In March 2015, 65 centers from 22 countries enrolled 3239 patients (benign disease 90.1%, malignant disease 9.9%), recording the patient, CIF and HPN characteristics in a structured database. The HPN-provider was categorized as health care system local pharmacy (LP) or independent home care company (HCC). The IVS-admixture was categorized as fluids and electrolytes alone (FE) or parenteral nutrition, either commercially premixed (PA) or customized to the individual patient (CA), alone or plus extra FE (PAFE or CAFE). Doctors of HPN centers were responsible for the IVS prescriptions. HCC (66%) was the most common HPN provider, with no difference noted between benign-CIF and malignant-CIF. LP was the main modality in 11 countries; HCC prevailed in 4 European countries: Israel, USA, South America and Oceania (p < 0.001). IVS-admixture comprised: FE 10%, PA 17%, PAFE 17%, CA 38%, CAFE 18%. PA and PAFE prevailed in malignant-CIF while CA and CAFE use was greater in benign-CIF (p < 0.001). PA + PAFE prevailed in those countries where LP was the main HPN-provider and CA + CAFE prevailed where the main HPN-provider was HCC (p < 0.001). This is the first study to demonstrate that HPN provision and the IVS-admixture differ greatly among countries, among HPN centers and between benign-CIF and cancer-CIF. As both HPN provider and IVS-admixture types may play a role in the safety and effectiveness of HPN therapy, criteria to homogenize HPN programs are needed so that patients can have equal access to optimal CIF care.


Transcriptomic and proteomic profiling of KEAP1 disrupted and sulforaphane-treated human breast epithelial cells reveals common expression profiles.
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a potent inhibitor of experimental mammary carcinogenesis and may be an effective, safe chemopreventive agent for use in humans. SFN acts in part on the Keap1/Nrf2 pathway to regulate a battery of cytoprotective genes. In this study, transcriptomic and proteomic changes in the estrogen receptor negative, non-tumorigenic human breast epithelial MCF10A cell line were analyzed following SFN treatment or KEAP1 knockdown with siRNA using microarray and stable isotopic labeling with amino acids in culture (SILAC), respectively. Changes in selected transcripts and proteins were confirmed by PCR and Western blot in MCF10A and MCF12A cells. There was strong correlation between the transcriptomic and proteomic responses in both the SFN treatment (R = 0.679, P < 0.05) and KEAP1 knockdown (R = 0.853, P < 0.05) experiments. Common pathways for SFN treatment and KEAP1 knockdown were xenobiotic metabolism and antioxidants, glutathione metabolism, carbohydrate metabolism, and NADH/NADPH regeneration. Moreover, these pathways were most prominent in both the transcriptomic and the proteomic analyses. The aldo-keto reductase family members, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, as well as NQO1 and ALDH3A1, were highly upregulated at both the transcriptomic and the proteomic levels. Collectively, these studies served to identify potential biomarkers that can be used in clinical trials to investigate the initial pharmacodynamic action of SFN in the breast.


Relationship between the severity of retinopathy and progression to photocoagulation in patients with Type 2 diabetes mellitus in the UKPDS (UKPDS 52).
to establish the degree to which the severity of retinopathy determines the risk for the need for subsequent photocoagulation in those with newly diagnosed Type 2 diabetes mellitus. Of 5102 patients entered into the UK Prospective Diabetes Study (UKPDS), 3709 had good quality retinal photographs that could be graded at entry. They were followed until the end of the study or until lost to follow-up, or until they received photocoagulation. Retinopathy severity was categorized as no retinopathy, microaneurysms (MA) only in one eye, MA in both eyes or more severe retinopathy features. The risk of photocoagulation was assessed in relation to severity of retinopathy at baseline, 3 and 6 years. Of the 3709 patients assessed at entry to the UKPDS, 2316 had no retinopathy. Of these 0.2% needed photocoagulation at 3 years, 1.1% at 6 years and 2.6% at 9 years. Those with MA in one eye only (n = 708) were similar, with 0%, 1.9% and 4.7% needing photocoagulation by 3, 6 and 9 years, respectively. Amongst those who had more retinopathy features at entry (n = 509), 15.3% required photocoagulation by 3 years, and 31.9% by 9 years. When those without retinopathy at 6 years (n = 1579) were examined 3 and 6 years later (9 and 12 years after diagnosis), 0.1% and 1.8% required photocoagulation. Those with more severe retinopathy (n = 775) needed earlier treatment, 6.6% after 3 years and 13.3% after 9 years. The commonest indication for laser therapy was maculopathy, but those with more severe retinopathy were more likely to be treated for proliferative retinopathy and to need both eyes treated. Few type 2 diabetic patients without retinopathy progress to photocoagulation in the following 3-6 years, while patients with more severe retinopathy lesions need to be monitored closely.


Nucleases in higher plants and their possible involvement in DNA degradation during leaf senescence.
During leaf senescence, macromolecules such as proteins and lipids are known to be degraded for redistribution into upper tissues. Similarly, nucleic acids appear to undergo fragmentation or degradation during senescence, but the physiological role of nucleic acid degradation, particularly of genomic DNA degradation, remains unclear. To date, more than a dozen of plant deoxyribonucleases have been reported, whereas it remains to be verified whether any of them degrade DNA during leaf senescence. This review summarizes current knowledge related to the plant nucleases that are induced developmentally or in a tissue-specific manner and are known to degrade DNA biochemically. Of these, several endonucleases (BFN1, CAN1, and CAN2) and an exonuclease (DPD1) in Arabidopsis seem to act in leaf senescence because they were shown to be inducible at the transcript level. This review specifically examines DPD1, which is dual-targeted to chloroplasts and mitochondria. Results show that, among the exonuclease family to which DPD1 belongs, DPD1 expression is extraordinary when estimated using a microarray database. DPD1 is the only example among the nucleases in which DNA degradation has been confirmed in vivo in pollen by mutant analysis. These data imply a significant role of organelle DNA degradation during leaf senescence and implicate DPD1 as a potential target for deciphering nucleotide salvage in plants.


The application of cost-effective lasers in coherent UDWDM-OFDM-PON aided by effective phase noise suppression methods.
Digital coherent passive optical network (PON), especially the coherent orthogonal frequency division multiplexing PON (OFDM-PON), is a strong candidate for the 2nd-stage-next-generation PON (NG-PON2). As is known, OFDM is very sensitive to the laser phase noise which severely limits the application of the cost-effective distributed feedback (DFB) lasers and more energy-efficient vertical cavity surface emitting lasers (VCSEL) in the coherent OFDM-PON. The current long-reach coherent OFDM-PON experiments always choose the expensive external cavity laser (ECL) as the optical source for its narrow linewidth (usually<100 KHz). To solve this problem, we introduce the orthogonal basis expansion based (OBE) phase noise suppression method to the coherent OFDM-PON and study the possibility of the application of the DFB lasers and VCSEL in coherent OFDM-PON. A typical long-reach coherent ultra dense wavelength division multiplexing (UDWDM) OFDM-PON has been set up. The numerical results prove that the OBE method can stand severe phase noise of the lasers in this architecture and the DFB lasers as well as VCSEL can be used in coherent OFDM-PON. In this paper, we have also analyzed the performance of the RF-pilot-aided (RFP) phase noise suppression method in coherent OFDM-PON.


A new perspective on the perceptual selectivity of attention under load.
The human attention system helps us cope with a complex environment by supporting the selective processing of information relevant to our current goals. Understanding the perceptual, cognitive, and neural mechanisms that mediate selective attention is a core issue in cognitive neuroscience. One prominent model of selective attention, known as load theory, offers an account of how task demands determine when information is selected and an account of the efficiency of the selection process. However, load theory has several critical weaknesses that suggest that it is time for a new perspective. Here we review the strengths and weaknesses of load theory and offer an alternative biologically plausible computational account that is based on the neural theory of visual attention. We argue that this new perspective provides a detailed computational account of how bottom-up and top-down information is integrated to provide efficient attentional selection and allocation of perceptual processing resources.


Feasibility assessment of yttrium-90 liver radioembolization imaging using amplitude-based gated PET/CT.
The usage of PET/computed tomography (CT) to monitor hepatocellular carcinoma patients following yttrium-90 (Y) radioembolization has increased. Respiratory motion causes liver movement, which can be corrected using gating techniques at the expense of added noise. This work examines the use of amplitude-based gating on Y-PET/CT and its potential impact on diagnostic integrity. Patients were imaged using PET/CT following Y radioembolization. A respiratory band was used to collect respiratory cycle data. Patient data were processed as both standard and motion-corrected images. Regions of interest were drawn and compared using three methods. Activity concentrations were calculated and converted into dose estimates using previously determined and published scaling factors. Diagnostic assessments were performed using a binary scale created from published Y-PET/CT image interpretation guidelines. Estimates of radiation dose were increased (P<0.05) when using amplitude-gating methods with Y PET/CT imaging. Motion-corrected images show increased noise, but the diagnostic determination of success, using the Kao criteria, did not change between static and motion-corrected data. Amplitude-gated PET/CT following Y radioembolization is feasible and may improve Y dose estimates while maintaining diagnostic assessment integrity.


Representation of Maximally Regular Textures in Human Visual Cortex.
Naturalistic textures with an intermediate degree of statistical regularity can capture key structural features of natural images (Freeman and Simoncelli, 2011). V2 and later visual areas are sensitive to these features, while primary visual cortex is not (Freeman et al., 2013). Here we expand on this work by investigating a class of textures that have maximal formal regularity, the 17 crystallographic wallpaper groups (Fedorov, 1891). We used texture stimuli from four of the groups that differ in the maximum order of rotation symmetry they contain, and measured neural responses in human participants using functional MRI and high-density EEG. We found that cortical area V3 has a parametric representation of the rotation symmetries in the textures that is not present in either V1 or V2, the first discovery of a stimulus property that differentiates processing in V3 from that of lower-level areas. Parametric responses were also seen in higher-order ventral stream areas V4, VO1, and lateral occipital complex (LOC), but not in dorsal stream areas. The parametric response pattern was replicated in the EEG data, and source localization indicated that responses in V3 and V4 lead responses in LOC, which is consistent with a feedforward mechanism. Finally, we presented our stimuli to four well developed feedforward models and found that none of them were able to account for our results. Our results highlight structural regularity as an important stimulus dimension for distinguishing the early stages of visual processing, and suggest a previously unrecognized role for V3 in the visual form-processing hierarchy. Significance statement: Hierarchical processing is a fundamental organizing principle in visual neuroscience, with each successive processing stage being sensitive to increasingly complex stimulus properties. Here, we probe the encoding hierarchy in human visual cortex using a class of visual textures--wallpaper patterns--that are maximally regular. Through a combination of fMRI and EEG source imaging, we find specific responses to texture regularity that depend parametrically on the maximum order of rotation symmetry in the textures. These parametric responses are seen in several areas of the ventral visual processing stream, as well as in area V3, but not in V1 or V2. This is the first demonstration of a stimulus property that differentiates processing in V3 from that of lower-level visual areas.


A multimethod research investigation of consumer involvement in Australian health service accreditation programmes: the ACCREDIT-SCI study protocol.
Health service accreditation programmes are a regulatory mechanism adopted to drive improvements inpatient safety and quality. Research investigating the benefits or limitations, of consumer involvement in accreditation programmes is negligible. To develop our knowledge in this area the ACCREDIT collaboration (Accreditation Collaborative for the Conduct of Research, Evaluation and Designated Investigations through Teamwork) has developed a research plan, known as the ACCREDIT-SCI (Standards of Consumer Involvement) study protocol. Two complementary studies have been designed: one, to examine the effectiveness of a standard for consumer participation and two, to explore how patient experiences vary across a range of settings with differing accreditation results. The research setting is the Australian healthcare system, and the two studies focus on three accreditation programmes in the primary, acute and aged care domains. The studies will use multimethods: document analysis; interviews and surveys. Participants will be stakeholders across the three domains including: policy officers; frontline healthcare professionals; accreditation agency personnel, including surveyors and healthcare consumers. Drawing on previous experience, the research team has developed purpose-designed tools. Data will be analysed using thematic, narrative and statistical (descriptive and inferential) procedures. The University of New South Wales Human Research Ethics Committee has approved the two studies (HREC 10274). Findings will be disseminated through seminars, conference presentations, academic publications and research partner websites. The findings will be formulated to facilitate uptake by policy and accreditation agency professionals, researchers and academics, and consumers, nationally and internationally.


Intentional weight loss and dose reductions of antihypertensive medications: a retrospective cohort study.
Though it is well known that weight loss tends to decrease blood pressure, the quantitative association between the magnitude of weight loss and the effect on the need for antihypertensive medications is not well studied. We analyzed this association among overweight and obese attendees at two outpatient weight management centers. Case records of patients with a body mass index >25 at baseline were analyzed. The weight loss intervention consisted of a calorie-restricted diet (~1,000 kcal/day deficit), a behavior modification plan, and a plan for increasing physical activity. The study cohort consisted of 100 participants, and the mean follow-up period was 15 ± 3.5 months. Significant weight loss (12.2 ± 3.4 kg) and systolic/diastolic blood pressure reductions (9.1/6.3 mm Hg) were observed by study exit. For 5, 10, and 15% weight loss, respectively, 3, 39, and 39% of the patients achieved at least 1 discontinuation of any antihypertensive medication, and 8, 42, and 21 dose reductions were achieved. Dose reductions or discontinuations occurred in all classes of antihypertensive medications with similar magnitudes of weight loss. Intentional weight loss can potentially result in dose reductions/discontinuations of antihypertensive medications. Our results should be validated with data from larger randomized controlled studies and may help to inform the conduct of a systematic review of prior randomized controlled trials that contain data on medication changes accompanying weight loss.


Using stars for remote sensing of the Earth's stratosphere.
A new UV-visible spectrometer system that measures the absorption of light from stars and planets by constituents in the Earth's atmosphere is described. Because it can be used to make measurements at night, the system has a significant advantage for measuring polar constituents in winter, when conditions that might give rise to ozone loss are initiated. Other advantages arise from the use of a cooled two-dimensional CCD array as the detector: an array detector avoids spectral noise resulting from scintillation of stars or from clouds passing overhead and allows for the possibility of measuring several constituents simultaneously; its second dimension permits auroral light from the atmosphere adjacent to the star to be measured simultaneously and subtracted from the stellar light, and a modern low-noise CCD allows us to use a telescope of modest diameter. The few previous measurements of constituents made by the use of stellar absorption did not have these advantages. The instrument was configured for simplicity and ease of use in field measurements and was deployed outside in winter in Northern Sweden in 1991. Examples of ozone measurements are shown.


Reconstructing the Backbone of the Saccharomycotina Yeast Phylogeny Using Genome-Scale Data.
Understanding the phylogenetic relationships among the yeasts of the subphylum Saccharomycotina is a prerequisite for understanding the evolution of their metabolisms and ecological lifestyles. In the last two decades, the use of rDNA and multilocus data sets has greatly advanced our understanding of the yeast phylogeny, but many deep relationships remain unsupported. In contrast, phylogenomic analyses have involved relatively few taxa and lineages that were often selected with limited considerations for covering the breadth of yeast biodiversity. Here we used genome sequence data from 86 publicly available yeast genomes representing nine of the 11 known major lineages and 10 nonyeast fungal outgroups to generate a 1233-gene, 96-taxon data matrix. Species phylogenies reconstructed using two different methods (concatenation and coalescence) and two data matrices (amino acids or the first two codon positions) yielded identical and highly supported relationships between the nine major lineages. Aside from the lineage comprised by the family Pichiaceae, all other lineages were monophyletic. Most interrelationships among yeast species were robust across the two methods and data matrices. However, eight of the 93 internodes conflicted between analyses or data sets, including the placements of: the clade defined by species that have reassigned the CUG codon to encode serine, instead of leucine; the clade defined by a whole genome duplication; and the species Ascoidea rubescens These phylogenomic analyses provide a robust roadmap for future comparative work across the yeast subphylum in the disciplines of taxonomy, molecular genetics, evolutionary biology, ecology, and biotechnology. To further this end, we have also provided a BLAST server to query the 86 Saccharomycotina genomes, which can be found at http://y1000plus.org/blast.


[Standards, options and recommendations for tumor markers in colorectal cancer].
The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the French National Federation of Comprehensive Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public University or General Hospitals, and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome of cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in colorectal cancer and their potential role in the management of patients with this malignancy. Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 117 independent reviewers, and to the medical committees of the 20 French Cancer Centers. The main recommendations for the tumor markers in colorectal cancer are: 1) The carcinoembryonic antigen (CEA) is the reference serum marker (standard). 2) All the analyses for a given patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 3) CEA or CA 19-9 should not be used for screening or diagnosis (standard, level of evidence B2). 4) High initial serum concentration of CEA is of bad predictive value (standard, level of evidence C). CEA is an independent prognostic factor of survival in colorectal cancers with lymph node metastases (standard, level of evidence B2). 5) CEA is the most sensitive biological parameter for the screening of hepatic metastases (standard, level of evidence B2). 6) CEA serum concentration before palliative chemotherapy is an independent prognostic factor of survival (standard, level of evidence B2). The combination of CEA assay with imagery techniques and clinical examination can help monitor the response to palliative chemotherapy (standard), in particular in non measurable disease (standard, expert agreement). 7) In 65% of the cases, CEA is the first indicator of relapse (standard, level of evidence B2). CEA is the choice marker for monitoring patients with colorectal cancer (standard, level of evidence B2). 8) A sustained biological follow-up including CEA assay can be used to predict the operability of recurring tumors (standard, level of evidence B2). Nevertheless, no survival advantage has been shown (standard).


Patterns and quality of treatment for patients with schizophrenia in routine psychiatric practice.
This study provided generalizable national data on the treatment of adult patients with schizophrenia in the United States and assessed conformance with the practice guideline treatment recommendations of the Schizophrenia Patient Outcomes Research Team and the American Psychiatric Association. National data from the American Psychiatric Institute for Research and Education's 1999 Practice Research Network study of psychiatric patients and treatments were used to examine treatment patterns for 151 adult patients with schizophrenia. Analyses were performed and adjusted for the weights and sample design to generate nationally representative estimates. Findings indicated that patients with schizophrenia who were treated by psychiatrists had complex clinical problems and were markedly disabled. Forty-one percent of patients had a comorbid axis I disorder, and 75 percent were currently unemployed. Thirty-five percent were currently experiencing medication side effects, and 37 percent were currently experiencing problems with treatment adherence. Although most patients received guideline-consistent psychopharmacologic treatment, treatment was characterized by significant polypharmacy. Rates of conformance with the guideline recommendations were significantly lower for psychosocial recommendations than for psychopharmacologic recommendations. Although 69 percent of patients received at least some psychosocial treatment, none of the unemployed patients received vocational rehabilitation services in the past 30 days. These data suggest unmet need for psychosocial treatment services among individuals with schizophrenia. These findings raise questions about whether currently available antipsychotic medications are being used optimally or whether they offer limited effectiveness for patients with complex clinical problems who are treated in routine psychiatric practice.


Infant temperament and feeding history predict infants' responses to novel foods.
The purpose of the present study was to investigate whether infant temperament and previous feeding history were associated with infants' acceptance and rejection of a novel food at 12 months of age. Mother-infant dyads (n = 89) were video-recorded during a novel food (hummus, cottage cheese) feeding task. Infants' reactions (acceptance and rejection behaviors) and maternal responsiveness and affect during the interaction were coded from the recordings by teams of coders. Mothers reported on their infants' temperamental approach via the Infant Behavior Questionnaire-Revised (IBQ-R) and their infants' feeding history (previous exposure to solid foods and exclusive breastfeeding). Regression analyses revealed that infants rated lower on approach showed less acceptance of the first offer of novel food than infants rated higher on approach. Additionally, low approach infants who were previously exposed to a greater number of solid foods showed fewer rejection behaviors in response to the later offers of food. Exclusive breastfeeding for 4 months did not appear to have an effect on acceptance or rejection. Finally, greater maternal responsiveness was related to the infants' acceptance of the new food whereas lower maternal responsiveness was associated with rejection of the novel food. These results suggest that the acceptance and rejection of new foods by infants is dependent upon their temperament and previous exposure to solid foods, as well as the manner in which mothers present the novel food.


Characterizing T-cell receptor gamma-variable gene in Aotus nancymaae owl monkey peripheral blood.
Gammadelta T lymphocytes have a heterodimeric complex formed by the association of gamma and delta chains as receptor. Proliferation of this lymphocyte population has been observed, when infection by several pathogens such as Mycobacterium tuberculosis and Plasmodium spp. occurs. The New World Monkey Aotus nancymaae has become a very good experimental model for the immunological and physiopathological study of these infectious agents. The A. nancymaae gamma-variable region was characterized from peripheral blood samples by using cDNA and genomic DNA polymerase chain reaction amplification, DNA sequencing, and dot-blot hybridization techniques. Seventeen different T-cell receptor gamma-variable (TCRGV) sequences were obtained. These sequences were distributed among TCRGV subsets 1, 2, or 3, according to human subset classification. Although no subset 4 amplification was obtained, this subset was detected by dot-blot hybridization. The presence of these 4 subsets resembles the behavior displayed by 'gammadelta-low species' (humans and mice), where high diversity among these lymphocytes can be observed. Homologies greater than 70% were found with respect to humans. Sequence convergence between human and A. nancymaae subsets 1 and 3 highlights Aotus as a promising model for studying these lymphocyte functions.


Streptomyces silvae sp. nov., isolated from forest soil.
A bacterial strain, named For3T, was isolated from forest soil sampled in Champenoux, France. Based on its 16S rRNA gene sequence, the strain was affiliated to the family Streptomycetaceae and, more specifically, to the genus Streptomyces. The strain had 99.93% 16S rRNA gene sequence similarity to its closest relative strains Streptomyces pratensis ATCC 33331T, Streptomyces anulatus ATCC 27416T, Streptomyces setonii NRRL ISP-5322T and Kitasatospora papulosa NRRL B-16504T. The phylogenomic tree using the genome blast distance phylogeny method showed that the closest relative strain was Streptomyces atroolivaceus NRRL ISP-5137T and that For3T represents a new branch among the Streptomyces. Genome relatedness indexes revealed that the average nucleotide identity and digital DNA-DNA hybridization values between For3T and its closest phylogenomic relative (S. atroolivaceus NRRL ISP-5137T) were 88.39 and 39.2 %, respectively. The G+C content of the genome was 71.4 mol% and its size was 7.96 Mb with 7492 protein-coding genes. Strain For3T harboured complete metabolic pathways absent in the closest relative strains such as cellulose biosynthesis, glycogen degradation I, glucosylglycerate biosynthesis I. Anteiso-C15:0, iso-C15:0, anteiso-C17:0 and MK-9(H4)/MK-9(H6) were the predominant cellular fatty acids and respiratory quinones, respectively. Phenotypic and genomic data supported the assignment of strain For3T to a novel species Streptomyces silvae sp. nov., within the genus Streptomyces, for which the type strain is For3T (=CIP 111908T=LMG 32186T).


Effects of fermentable starch and straw-enriched housing on energy partitioning of growing pigs.
Both dietary fermentable carbohydrates and the availability of straw bedding potentially affect activity patterns and energy utilisation in pigs. The present study aimed to investigate the combined effects of straw bedding and fermentable carbohydrates (native potato starch) on energy partitioning in growing pigs. In a 2 × 2 factorial arrangement, 16 groups of 12 pigs (approximately 25 kg) were assigned to either barren housing or housing on straw bedding, and to native or pregelatinised potato starch included in the diet. Pigs were fed at approximately 2.5 times maintenance. Nitrogen and energy balances were measured per group during a 7-day experimental period, which was preceded by a 30-day adaptation period. Heat production and physical activity were measured during 9-min intervals. The availability of straw bedding increased both metabolisable energy (ME) intake and total heat production (P < 0.001). Housing conditions did not affect total energy retention, but pigs on straw bedding retained more energy as protein (P < 0.01) and less as fat (P < 0.05) than barren-housed pigs. Average daily gain (P < 0.001), ME intake (P < 0.001) and energy retention (P < 0.01) were lower in pigs on the native potato starch diet compared to those on the pregelatinised potato starch diet. Pigs on the pregelatinised potato starch diet showed larger fluctuations in heat production and respiration quotient over the 24-h cycle than pigs on the native potato starch diet, and a higher activity-related energy expenditure. The effect of dietary starch type on activity-related heat production depended, however, on housing type (P < 0.05). In barren housing, activity-related heat production was less affected by starch type (16.1% and 13.7% of total heat production on the pregelatinised and native potato starch diet, respectively) than in straw-enriched housing (21.1% and 15.0% of the total heat production on the pregelatinised and native potato starch diet, respectively). In conclusion, the present study shows that the availability both of straw bedding and of dietary starch type, fermentable or digestible, affects energy utilisation and physical activity of pigs. The effects of housing condition on protein and fat deposition suggest that environmental enrichment with long straw may result in leaner pigs. The lower energy expenditure on the physical activity of pigs on the native potato starch diet, which was the most obvious in straw-housed pigs, likely reflects a decrease in foraging behaviour related to a more gradual supply of energy from fermentation processes.


Broadband THz lasing from a photon-phonon quantum cascade structure.
Laser emission over a broad range of frequencies from 2.8 to 4.1 THz is reported for a two-quantum well, photon-phonon cascade structure. Maximum operating temperatures of 125 K are reported, with optical peak powers in eccess of 30 mW from a double-metal ridge waveguide. The broadband nature of the gain curve is identified as due to coherent coupling of the injector and upper lasing states. Internal quantum efficiencies reaching 43 % are evaluated at 10 K.The laser operates in both polarities, showing laser action in reverse bias up to a temperature of 90 K. Simulations based on a full treatment of the structure with density matrix formalism are also presented and discussed.


Chain length of dietary alkylresorcinols affects their in vivo elimination kinetics in rats.
Two phenolic acids, 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)- propanoic acid (DHPPA), are the major metabolites of cereal alkylresorcinols (ARs). Like their precursors, AR metabolites have been suggested as biomarkers for intake of whole-grain wheat and rye and as such could aid the understanding of diet-disease associations. This study estimated and compared pharmacokinetic parameters of ARs and their metabolites in rats and investigated differences in metabolite formation after ingestion of different AR homologs. Rats were i.v. infused for 30 min with 2, 12, or 23 μmol/kg DHBA or DHPPA or orally given the same amounts of the AR homologs, C17:0 and C25:0. Repeated plasma samples, obtained from rats for 6 h (i.v.) or 36 h (oral), were simultaneously analyzed for ARs and their metabolites by GC-mass spectrometry. Pharmacokinetic parameters were estimated by population-based compartmental modeling and noncompartmental calculation. A 1-compartment model best described C25:0 pharmacokinetics, whereas C17:0 and AR metabolites best fitted 2-compartment models. Combined models for simultaneous prediction of AR and metabolite concentration were more complex, with less reliable estimates of pharmacokinetic parameters. Although the AUC of C17:0 was lower than that of C25:0 (P < 0.05), the total amount and composition of AR metabolites did not differ between rats given C17:0 or C25:0. The elimination half-life of ARs and their metabolites increased with length of the side chain (P-trend < 0.001) and ranged from 1.2 h (DHBA) to 8.8 h (C25:0). The formation of AR metabolites was slower than their elimination, indicating that the rate of AR metabolism and not excretion of DHBA and DHPPA determines their plasma concentrations in rats.


An unexpected case of primary peritoneal carcinoma.
Primary peritoneal carcinoma (PPC) is a rare tumor that is histologically and immunohistochemically indistinguishable from epithelial ovarian carcinoma. The diagnosis is usually made after excluding gross ovarian involvement or the ovarian involvement is only confined to the surface. A 68-year-old lady presented with right iliac fossa pain and increasing CA125. The CT scan showed bilateral pelvic adnexal masses with peritoneal deposits within the right side of abdomen. She was initially diagnosed as carcinomatosis peritonei from the omental cake removed after exploratory surgery. She was managed as advanced ovarian tumor with peritoneal metastasis and was then administered six cycles of chemotherapy. Surgical intervention included debulking surgery consisting of total abdominal hysterectomy, bilateral salpingooophorectomy and omentectomy and also with right hemicolectomy. The histopathological findings were of primary peritoneal serous carcinoma with only minimal involvement of the serosal surface of the right ovarian capsule. No microscopic invasion into underlying ovarian cortex and stroma was observed. Multiple tumor deposits were also seen over the right paratubal and paraovarian tissue, both parametrium as well as serosal surface of the terminal ileum and periappendicular tissue. Immunohistochemically, the malignant cells were positive to CA125, focally positive to CK7 and negative to CD20 and Calretinin. PPC is one of important differential diagnosis which needs to be considered in cases of advanced ovarian tumor, although the former can only be ascertained after excluding the ovarian involvement microscopically.


The athletic profile of fast bowling in cricket: a review.
Cricket is a global sport played in over 100 countries with elite performers attracting multimillion dollar contracts. Therefore, performers maintaining optimum physical fitness and remaining injury free is important. Fast bowlers have a vital position in a cricket team, and there is an increasing body of scientific literature that has reviewed this role over the past decade. Previous research on fast bowlers has tended to focus on biomechanical analysis and injury prevention in performers. However, this review aims to critically analyze the emerging contribution of physiological-based literature linked to fast bowling in cricket, highlight the current evidence related to simulated and competitive in-match performance, and relate this practically to the conditioning coach. Furthermore, the review considers limitations with past research and possible avenues for future investigation. It is clear with the advent of new applied mobile monitoring technology that there is scope for more ecologically valid and longitudinal exploration capturing in-match data, providing quantification of physiological workloads, and analysis of the physical demands across the differing formats of the game. Currently, strength and conditioning specialists do not have a critical academic resource with which to shape professional practice, and this review aims to provide a starting point for evidence in the specific area.


Development and Validation of the Computerized Family Relations Test for Children.
The aim of the present study was to develop and investigate the psychometric properties of the Computerized Family Relations Test (CFRT) for children. This test assesses the quality of family relationships with the mother and father from a child's perspective. The CFRT consists of six scales relating to control (Restrictiveness and Justice), and support (Affection, Vulnerability, Acknowledgment, and Trust) within the family relationships. CFRT is an innovative approach to the Dutch Nijmegen Family Relations Test (NFRT) developed by Oud and Welzen (1989). The administration of the test has been computerized and graphical representations of female and male silhouettes were included to facilitate the child's parental identification. In total, 404 primary school children, aged 8 to 13 years (M = 11.0; SD = 1.17), took part in this study. The CFRT's reliability was assessed by McDonald's omega coefficients, and ranged from 0.71 to 0.86, except for Vulnerability which achieved the lowest reliability 0.57 for mothers' ratings and 0.56 for fathers' ratings. The test-retest procedure revealed higher stability for the ratings on father-child relationships of 0.71 compared to mother-child relationships of 0.67. Confirmatory factor analysis indicated that a six-factor model provided an adequate fit. Measurement invariance across the children's assessments of the quality of family relationships was achieved. The construct validity of CFRT was assessed by examining differences in the child's ratings of the relationships with the mother and father, the child's gender, and associations of CFRT scales with other variables such as depression, anxiety symptoms, and prosocial behavior.


Efficient production of Rift Valley fever virus-like particles: The antiviral protein MxA can inhibit primary transcription of bunyaviruses.
Rift Valley fever virus (RVFV) is a highly pathogenic member of the family Bunyaviridae that needs to be handled under biosafety level (BSL) 3 conditions. Here, we describe reverse genetics systems to measure RVFV polymerase activity in mammalian cells and to generate virus-like particles (VLPs). Recombinant polymerase (L) and nucleocapsid protein (N), expressed together with a minireplicon RNA, formed transcriptionally active nucleocapsids. These could be packaged into VLPs by additional expression of viral glycoproteins. The VLPs resembled authentic virus particles and were able to infect new cells. After infection, VLP-associated nucleocapsids autonomously performed primary transcription, and co-expression of L and N in VLP-infected cells allowed subsequent replication and secondary transcription. Bunyaviruses are potently inhibited by a human interferon-induced protein, MxA. However, the affected step in the infection cycle is not entirely characterized. Using the VLP system, we demonstrate that MxA inhibits both primary and secondary transcriptions of RVFV. A set of infection assays distinguishing between virus attachment, entry, and subsequent RNA synthesis confirmed that MxA is able to target immediate early RNA synthesis of incoming RVFV particles. Thus, our reverse genetics systems are useful for dissecting individual steps of RVFV infection under non-BSL3 conditions.


Oral Health Knowledge and Attitudes of Community Health Workers in East Azerbaijan, Iran.
Prevention is the key factor in acquiring dental and oral health. Community health workers, as a part of health care networks in Iran, play an important role in delivering primary care and their knowledge and attitude directly affect the population whom they interact with in their service scope. The aim of this research was to evaluate the knowledge and attitude level of community health workers regarding oral health. This descriptive analytical study was carried out on 1170 community health workers who were employed in health offices in East Azerbaijan to evaluate their knowledge and attitude level about oral health. Data were acquired through filled out questionnaires and were analyzed by SPSS software. There was no significant statistical relationship between knowledge and gender (p= 0.063), level of education (p= 0.08) and the period spent from the last continuing education course (p= 0.148).However, by increasing age (p= 0.016), work experience (p=0.083) and number of attended continuing education courses (p= 0.023), the knowledge scores were reduced. No statistically significant relationships were found between attitude and any of research variables. The level of knowledge and attitude of community health workers in East Azerbaijan regarding oral health was good. There was a reverse relationship between age, work experience, and frequency of participation in continuing education courses and knowledge scores which emphasizes the necessity of continuous training and revising the method of training in education of community health workers and other staffs of health care system.


Alteration of water structure by peptide clusters revealed by neutron scattering in the small-angle region (below 1 Å(-1)).
Solution scattering of neutrons and x-rays can provide direct information on local interactions of importance for biomolecular folding and structure. Here, neutron scattering experiments are combined with molecular-dynamics simulation to interpret the scattering signal of a series of dipeptides with varying degrees of hydrophobicity (GlyAla, GlyPro, and AlaPro) in concentrated aqueous solution (1:20 solute/water ratio) in which the peptides form large segregates (up to 50-60 amino acids). Two main results are found: 1), the shift to lower Q of the so-called water-ring peak (Q ≈ 2 Å(-1)) arises mainly from an overlap of water-peptide and peptide-peptide correlations in the region of 1.3 <Q< 2 Å(-1), rather than from a shift of the water signal induced by the presence of the clusters; and 2), in the low-Q region (Q ≈ 0.6 Å(-1)) a positive peak is observed originating from both the solute-solute correlations and changes in the water structure induced by the formation of the clusters. In particular, the water molecules are found to be more connected than in the bulk with hydrogen-bonding directions tangential to the exposed hydrophobic surfaces, and this effect increases with increasing peptide hydrophobicity. This work demonstrates that important information on the (hydrophobic) hydration of biomolecules can be obtained in the very-small-angle region.


Parvovirus B19 infection and severe anaemia in Kenyan children: a retrospective case control study.
During acute Human parvovirus B19 (B19) infection a transient reduction in blood haemoglobin concentration is induced, due to a 5-7 day cessation of red cell production. This can precipitate severe anaemia in subjects with a range of pre-existing conditions. Of the disease markers that occur during B19 infection, high IgM levels occur closest in time to the maximum reduction in haemoglobin concentration. Previous studies of the contribution of B19 to severe anaemia among young children in Africa have yielded varied results. This retrospective case/control study seeks to ascertain the proportion of severe anaemia cases precipitated by B19 among young children admitted to a Kenyan district hospital. Archival blood samples from 264 children under 6 years with severe anaemia admitted to a Kenyan District Hospital, between 1999 and 2004, and 264 matched controls, were tested for B19 IgM by Enzyme Immunosorbent Assay and 198 of these pairs were tested for B19 DNA by PCR. 536 samples were also tested for the presence of B19 IgG. 7 (2.7%) cases and 0 (0%) controls had high B19 IgM levels (Optical Density > 5 x cut-off value) (McNemar's exact test p = 0.01563), indicating a significant association with severe anaemia. The majority of strongly IgM positive cases occurred in 2003.10/264 (3.7%) cases compared to 5/264 (1.9%) controls tested positive for B19 IgM. This difference was not statistically significant, odds ratio (OR) = 2.00 (CI95 [0.62, 6.06], McNemar's exact test p = 0.3018. There was no significant difference between cases and controls in the B19 IgG (35 (14.8%) vs 32 (13.6%)), OR = 1.103 (CI95 [0.66, 1.89], McNemar's exact test, p = 0.7982), or the detection of the B19 DNA (6 (3.0%) vs 5 (2.5%)), OR = 1.2 (CI95 [0.33, 4.01], McNemar's exact test p = 1). High B19 IgM levels were significantly associated with severe anaemia, being found only among the cases. This suggests that 7/264 (2.7%) of cases of severe anaemia in the population of children admitted to KDH were precipitated by B19. While this is a relatively small proportion, this has to be evaluated in the light of the IgG data that shows that less than 15% of children in the study were exposed to B19, a figure much lower than reported in other tropical areas.


Activity of enzymes of adenyline compounds metabolism during crush and decompression of muscle tissue. Part II. Adenosine deaminase activity at experimental crush syndrome.
Publications on investigation of crush syndrome pathogenesis, particularly of enzymatic systems upon traumatic toxicosis are rather limited. Such investigations are necessary for opportune diagnosis and definition of a treatment tactic. To replenish this deficiency, the adenosine deaminase level was studied in 12 rat tissues at experimental crush syndrome in vivo. The experimental model of crush syndrome on white rats was induced by crush and decompression of femoral muscle tissue. The crush syndrome influence on activity of adenosine deaminase isoenzymes was investigated in hemisphere, cerebellum, hypothalamus, pituitary body, heart, lung, liver, spleen, kidney, adrenal, as well as in crushed and native muscles. In 2 and 5 hours after compression, the enzyme activity decreased in muscles, lung and heart; increased in hypothalamus; remains near the control value in kidney and spleen. In cerebellum the parameter practically does not vary during 2 hours compression, while increased in 5 hours. In adrenal, liver, pituitary body and hemisphere the data after 5 hours compression approximated the level of control value in account of compensating mechanism. In 48 hours decompression after 2 hours crush, the adenosine deaminase activity becomes higher than control value in hemisphere, hypothalamus, cerebellum, liver, heart, adrenal, intact muscle, lung and kidney; in the crushed muscle and spleen the activity is reduced down to 60% of control value. In 48 hours decompression after 5 hours compression, the enzyme activity is higher than control value in hypothalamus, pituitary body, hemisphere, cerebellum, kidney, adrenal, heart and lung. The activity is reduced in muscles, spleen and liver. The level of adenosine deaminase in most of studied tissues differs from the control value depending on compression and decompression time. It is worthy of note that namely during decompression, the enzyme level deviates from the control in the majority of tissues.


Comparison of some physical parameters of whole and scored lisinopril and lisinopril/hydrochlorthiazide tablets.
Tablets are one of the most popular and preferred solid dosage forms because they can be accurately dosed, easily manufactured and packaged on a large scale, have good physical and chemical stability, and can contribute to good patient compliance given their ease of administration. The ability to match doses to patients depends on the availability of multiple dose sizes and adequate dose-response information. These are not always provided, so splitting of the tablets is sometimes necessary. Tablet splitting is an accepted practice in dispensing medication. It has been used when a dosage form of the required strength is not available commercially. The aim of our study was to compare some physical parameters of whole and scored lisinopril and lisinopril/hydrochlorthiazide tablets and to accept or exclude their influence on the obtaining of required dosage. According to the results obtained, we may conclude that tablets from batch "I", "II", "III" and "IV" satisfied pharmacopeial requirements concerning crushing strength, friability, disintegration time and mass uniformity. The hardness testing showed acceptable reproducibility and indicate that the data variation was primarily from the irreversible changes in the structure of tablet samples. The act of compacting powders stores energy within the tablets, by shifting or compressing the intermolecular bonds within the particles. The tablets have a natural tendency to relax once pressure is removed, and this tendency works against the interparticle bonding formed during compression. Hardness testing procedure causes irreversible changes in this structure.


Expression and targeting to the plasma membrane of xClC-K, a chloride channel specifically expressed in distinct tubule segments of Xenopus laevis kidney.
ClC-K channels are Cl- channels specifically expressed in vertebrate kidneys. Although their heterologous functional expression is still controversial, indirect evidence points to them as major factors involved in Cl- reabsorption in the nephron. We cloned xClC-K, an amphibian (Xenopus) homologue of mammalian ClC-K. The cDNA encodes a 77 kDa protein presenting 62% similarity with human ClC-Kb. The protein is monoglycosylated and is expressed primarily in the Xenopus kidney. It is localized in the basolateral membranes of proximal convoluted tubules of the nephron and in the apical region of the diluting segments. Heterologous expression of xClC-K in HEK-293 cells showed that the full-length protein is glycosylated and targeted to the cell membrane, but no associated Cl- current could be observed with the patch-clamp recording technique. N-glycosylation of both the native kidney channel and the recombinant protein expressed in HEK-293 conferred on them anomalous behaviour in denaturing PAGE, which is indicative of strong interactions at the extracellular side of the plasma membrane. The expression of ClC-K channels in both mesonephric and metanephric kidneys will permit further comparative physiological studies of Cl- permeabilities at the molecular level.


Cultural transmission of tool use combined with habitat specializations leads to fine-scale genetic structure in bottlenose dolphins.
Socially learned behaviours leading to genetic population structure have rarely been described outside humans. Here, we provide evidence of fine-scale genetic structure that has probably arisen based on socially transmitted behaviours in bottlenose dolphins (Tursiops sp.) in western Shark Bay, Western Australia. We argue that vertical social transmission in different habitats has led to significant geographical genetic structure of mitochondrial DNA (mtDNA) haplotypes. Dolphins with mtDNA haplotypes E or F are found predominantly in deep (more than 10 m) channel habitat, while dolphins with a third haplotype (H) are found predominantly in shallow habitat (less than 10 m), indicating a strong haplotype-habitat correlation. Some dolphins in the deep habitat engage in a foraging strategy using tools. These 'sponging' dolphins are members of one matriline, carrying haplotype E. This pattern is consistent with what had been demonstrated previously at another research site in Shark Bay, where vertical social transmission of sponging had been shown using multiple lines of evidence. Using an individual-based model, we found support that in western Shark Bay, socially transmitted specializations may have led to the observed genetic structure. The reported genetic structure appears to present an example of cultural hitchhiking of mtDNA haplotypes on socially transmitted foraging strategies, suggesting that, as in humans, genetic structure can be shaped through cultural transmission.


Retinal pigment epithelial cells of the posterior pole have fewer Na/K adenosine triphosphatase pumps than peripheral cells.
The density of Na/K adenosine triphosphatase (ATPase) pumps in retinal pigment epithelial (RPE) cells in different retinal regions was quantified by measuring the binding of 3H-ouabain to RPE in cow and human eyecups. In bovine eyes, pump density was estimated in RPE samples isolated from three retinal regions outlined with a 7-mm trephine: one from the posterior pole in the area centralis and two from the superior, equatorial retina representing unpigmented (in the tapetum) and pigmented zones. In human eyes, RPE samples were isolated from a posterior region centered around the macula and one superior region. Ouabain binding to RPE of the posterior pole of both species was approximately 40-60% lower than binding to RPE of more peripheral regions in the same eyes. For bovine eyes, ouabain binding did not differ between pigmented and unpigmented cells of the superior retina, suggesting that reduced binding in the relatively amelanotic posterior cells was not related to levels of pigmentation. For human RPE, binding to posterior cells was lower in eyes from donors of all ages (range, 17-90 yr). The data suggest that Na/K ATPase pump site density is lower in posterior RPE cells of both bovine and human eyes, perhaps due to a regional difference in requirements for ionic regulation.


PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development.
Upon fertilisation by sperm, mammalian eggs are activated by a series of intracellular Ca(2+) oscillations that are essential for embryo development. The mechanism by which sperm induces this complex signalling phenomenon is unknown. One proposal is that the sperm introduces an exclusive cytosolic factor into the egg that elicits serial Ca(2+) release. The 'sperm factor' hypothesis has not been ratified because a sperm-specific protein that generates repetitive Ca(2+) transients and egg activation has not been found. We identify a novel, sperm-specific phospholipase C, PLC zeta, that triggers Ca(2+) oscillations in mouse eggs indistinguishable from those at fertilisation. PLC zeta removal from sperm extracts abolishes Ca(2+) release in eggs. Moreover, the PLC zeta content of a single sperm was sufficient to produce Ca(2+) oscillations as well as normal embryo development to blastocyst. Our results are consistent with sperm PLC zeta as the molecular trigger for development of a fertilised egg into an embryo.


Using a gender lens to understand eating behaviours of adolescent females living in low-income households in Bangladesh.
Adolescence is a critical period characterized by rapid physical, psychological, and social development and growth. In Bangladesh, high rates of undernutrition persist among adolescent females living in low-income households. Prevalence of adolescent marriage and pregnancy is extremely high, with almost half of Bangladeshi women giving birth by 18 years of age. Qualitative research was carried out from April to June 2017 to examine individual, social, and environmental factors influencing eating behaviours of female adolescents between 15 and 19 years of age living in low-income families in urban and rural settings in Bangladesh. Methods included freelisting exercises (33), key informant interviews (11), in-depth interviews (24), direct observations (16), and focus group discussions (12). Findings show that household food insecurity necessitates adjustments in meal food quality and frequency. Gender norms prescribe that females receive small meal portions and make sacrifices in food consumption so that male family members can eat more. Work and school schedules cause long breaks between meal consumption, restricting food intake of adolescent females for extended periods. Gender discrimination and its manifestations likely amplify susceptibility to psychological stresses in adolescent females. An inferior social position makes adolescent females living in food insecure households vulnerable to undernutrition, with factors affecting food deprivation increasing as they approach childbearing. Policies to increase age of marriage and reduce adolescent pregnancy must continue. Programmes must ensure that school-going adolescents eat adequately during the school day. Prolonging school education and strengthening the economic viability of women should alter cultural expectations regarding marriage age and normative female roles.


Diminished 11β-hydroxysteroid dehydrogenase type 2 activity is associated with decreased weight and weight gain across the first year of life.
Low birth weight is associated with adverse metabolic outcome in adulthood. Exposure to glucocorticoid (GC) excess in utero is associated with decreased birth weight, but the prospective longitudinal relationship between GC metabolism and growth has not been examined. We have hypothesized that changes in GC metabolism leading to increased availability may impair growth. This was a prospective, longitudinal study with clinical measurements and 24-hour urinary steroid metabolite analysis at 1, 4, 12, 26, and 52 weeks after delivery in mothers and their babies. The study was conducted with observations and samples collected in the volunteers' own homes. Healthy mothers and newborn babies/infants participated in the study. There were no interventions. Urinary steroid metabolite excretion quantified by gas chromatography/mass spectroscopy across the first year of life in relation to change in weight was measured. The total production of the GC metabolites quantified increased across the first year of life. Markers of 11β-hydroxysteroid dehydrogenase type 1 activity increased from the age of 3 months as did those of 5α-reductase activity. After correcting for confounding variables, low markers of 11β-hydroxysteroid dehydrogenase type 2 activity was associated with reduced absolute weight and decreased weight gain over the first year of life. In the mothers, 5α-reductase activity was low at birth and progressively increased to normal over the first 6 months postpartum. Increased GC exposure as a consequence of reduced 11β-hydroxysteroid dehydrogenase type 2 activity is likely to be a critical determinant of growth in early life. This not only highlights the central role of GCs and their metabolism, but also emphasizes the need for detailed longitudinal analyses.


Method for measuring veiling glare in high-performance display devices.
An experimental method for measuring the veiling glare characteristics of display devices is presented. The measured veiling glare ratio (G) is taken to be the luminance in the surrounding bright field divided by the luminance in a dark circle. The method is based on a collimated conic probe that minimizes signal contamination from bright surroundings allowing for measurements of low luminance in a circular dark spot of a test pattern. A correction factor computed with test patterns having opaque spots is introduced. The factor is expressed as a bivariate function of the dark-spot radius and the distance between the probe and the emissive surface. We studied the uncertainty introduced by the method by measuring veiling glare test patterns printed on radiographic film for which the transmission of the dark spots was determined experimentally. Performance characterization measurements show that signal contamination is less than 10(-4) of the bright field surrounding a dark circle. Our results show that G of a few hundred can be measured with an uncertainty of a few percent, and ratios of approximately 10(3) can be reported within 10%. Finally, we demonstrate the method by measuring G for a high-performance monochrome cathode-ray tube display.


Distinctive electrophoretic patterns of Esterases from Levinea malonatica, Levinea amalonatica and Citrobacter.
Esterases of 42 strains of Levinea malonatica, Levinea amalonatica and Citrobacter were analysed by horizontal slab electrophoresis in polyacrylamide-agarosegel using several synthetic substrates. On the basis of esterase zymograms a distinctive pattern was established for each of the three species. Levinea malonatica was characterized by two major bands: one hydrolysing acetate esters but not butyrate esters; and the other hydrolysing alpha-naphthyl acetate and reacting weakly with alpha-naphthyl butyrate and beta-naphthyl acetate. Levinea amalonatica showed one prominent band that hydrolysed alpha-naphthyl esters and reacter weakly with beta-naphthyl esters. Citrobacter strains showed one major band that hydrolysed alpha-naphthyl esters and appeared slightly more towards beta-naphthyl esters than that of L. amalonatica. Considerable variations in electrophoretic mobility were observed among Citrobacter strains. Levinea amalonatica was less variable. In addition, one minor anodal band reacting with beta-naphthyl acetate was observed in both L. malonatica and Citrobacter. The relative molecular sizes of the major esterase bands were determined by disc electrophoresis with gels of different acrylamide concentrations. The molecular size of the major band of Citrobacter appeared to be smaller than that of the corresponding esterase band of L. amalonatica.


Integral-based parameter identification for long-term dynamic verification of a glucose-insulin system model.
Hyperglycaemia in critically ill patients increases the risk of further complications and mortality. This paper introduces a model capable of capturing the essential glucose and insulin kinetics in patients from retrospective data gathered in an intensive care unit (ICU). The model uses two time-varying patient specific parameters for glucose effectiveness and insulin sensitivity. The model is mathematically reformulated in terms of integrals to enable a novel method for identification of patient specific parameters. The method was tested on long-term blood glucose recordings from 17 ICU patients, producing 4% average error, which is within the sensor error. One-hour forward predictions of blood glucose data proved acceptable with an error of 2-11%. All identified parameter values were within reported physiological ranges. The parameter identification method is more accurate and significantly faster computationally than commonly used non-linear, non-convex methods. These results verify the model's ability to capture long-term observed glucose-insulin dynamics in hyperglycemic ICU patients, as well as the fitting method developed. Applications of the model and parameter identification method for automated control of blood glucose and medical decision support are discussed.


Outcome of intravenous thrombolysis in stroke patients weighing over 100 kg.
Intravenous thrombolysis with alteplase for ischemic stroke is fixed at a maximal dose of 90 mg for safety reasons. Little is known about the clinical outcomes of stroke patients weighing >100 kg, who may benefit less from thrombolysis due to this dose limitation. Prospective data on 1,479 consecutive stroke patients treated with intravenous alteplase in six Swiss stroke units were analyzed. Presenting characteristics and the frequency of favorable outcomes, defined as a modified Rankin scale (mRS) score of 0 or 1, a good outcome (mRS score 0-2), mortality and symptomatic intracranial hemorrhage (SICH) were compared between patients weighing >100 kg and those weighing ≤100 kg. Compared to their counterparts (n = 1,384, mean body weight 73 kg), patients weighing >100 kg (n = 95, mean body weight 108 kg) were younger (61 vs. 67 years, p < 0.001), were more frequently males (83 vs. 60%, p < 0.001) and more frequently suffered from diabetes mellitus (30 vs. 13%, p < 0.001). As compared with patients weighing ≤100 kg, patients weighing >100 kg had similar rates of favorable outcomes (45 vs. 48%, p = 0.656), good outcomes (58 vs. 64%, p = 0.270) and mortality (17 vs. 12%, p = 0.196), and SICH risk (1 vs. 5%, p = 0.182). After multivariable adjustment, body weight >100 kg was strongly associated with mortality (p = 0.007) and poor outcome (p = 0.007). Our data do not suggest a reduced likehood of favorable outcomes in patients weighing >100 kg treated with the current dose regimen. The association of body weight >100 kg with mortality and poor outcome, however, demands further large-scale studies to replicate our findings and to explore the underlying mechanisms.


Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser.
Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II (PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth's oxygenic atmosphere. In this process, the oxygen-evolving complex (OEC) of PSII cycles through five states, S0 to S4, in which four electrons are sequentially extracted from the OEC in four light-driven charge-separation events. Here we describe time resolved experiments on PSII nano/microcrystals from Thermosynechococcus elongatus performed with the recently developed technique of serial femtosecond crystallography. Structures have been determined from PSII in the dark S1 state and after double laser excitation (putative S3 state) at 5 and 5.5 Å resolution, respectively. The results provide evidence that PSII undergoes significant conformational changes at the electron acceptor side and at the Mn4CaO5 core of the OEC. These include an elongation of the metal cluster, accompanied by changes in the protein environment, which could allow for binding of the second substrate water molecule between the more distant protruding Mn (referred to as the 'dangler' Mn) and the Mn3CaOx cubane in the S2 to S3 transition, as predicted by spectroscopic and computational studies. This work shows the great potential for time-resolved serial femtosecond crystallography for investigation of catalytic processes in biomolecules.


Yeast pol4 promotes tel1-regulated chromosomal translocations.
DNA double-strand breaks (DSBs) are one of the most dangerous DNA lesions, since their erroneous repair by nonhomologous end-joining (NHEJ) can generate harmful chromosomal rearrangements. PolX DNA polymerases are well suited to extend DSB ends that cannot be directly ligated due to their particular ability to bind to and insert nucleotides at the imperfect template-primer structures formed during NHEJ. Herein, we have devised genetic assays in yeast to induce simultaneous DSBs in different chromosomes in vivo. The repair of these breaks in trans could result in reciprocal chromosomal translocations that were dependent on classical Ku-dependent NHEJ. End-joining events leading to translocations were mainly based on the formation of short base pairing between 3'-overhanging DNA ends coupled to gap-filling DNA synthesis. A major proportion of these events were specifically dependent on yeast DNA polymerase Pol4 activity. In addition, we have discovered that Pol4-Thr(540) amino acid residue can be phosphorylated by Tel1/ATM kinase, which could modulate Pol4 activity during NHEJ. Our data suggest that the role of Tel1 in preventing break-induced chromosomal translocations can, to some extent, be due to its stimulating effect on gap-filling activity of Pol4 to repair DSBs in cis. Overall, this work provides further insight to the molecular mechanisms of DSB repair by NHEJ and presents a new perspective to the understanding of how chromosomal translocations are formed in eukaryotic cells.


Prevalence of overweight and abdominal obesity in Greek children 6-12 years old: Results from the National Epidemiological Survey.
To provide estimates of overweight (OW), obesity (OB) and abdominal obesity (AO) in a sample of children throughout the whole of Greece. This epidemiological, cross-sectional survey examined 3,140 children aged 6-12 y (1,589 boys and 1,551 girls) who were selected by stratified sampling through household family members of Greek adolescents attending school. Participants reported data on height, weight and waist circumference (WC). BMI and Waist-to-Height ratio (WHtR) were calculated. AO was estimated using WC and WHtR. Overall prevalence of OW including OB was 31.2% in boys and 26.5% in girls, while OB prevalence was 9.4% and 6.4% respectively. The prevalence of AO based on WC (AO-WC), was similar in girls (14.2%) and boys (12.5%) while the prevalence of AO, based on WHtR (AO-WHtR), was higher in boys than in girls (25.6% vs 20.0%, p<0.0001). With increasing age, the prevalence of OW and OB decreases in both genders, and AO-WHtR only in girls. Rates of OW were significantly more prevalent in Greeks than in immigrants. Overweight and obesity in Greek children is very prevalent, particularly in boys, comparable with that reported for Mediterranean European countries. Abdominal obesity also appears high. Preventive and treatment strategies are urgently needed to combat this national epidemic.