Assessment of preferential T-helper 1 or T-helper 2 induction by low molecular weight compounds using the local lymph node assay in conjunction with RT-PCR and ELISA for interferon-gamma and interleukin-4.
The local lymph node assay (LLNA) is a new and promising test in mice used to identify contact allergens by means of dermal exposure. Experimentally this assay, which comprises a sensitizing phase only, is also used to identify respiratory allergens. Another, experimentally used test in mice to identify allergens is also based on dermal exposure, but comprises both a sensitizing and effector phase. In this latter test, it has been shown that contact allergens preferentially induce a T-helper 1 (TH1) response, whereas respiratory allergens preferentially induce a T-helper 2 (TH2) response. These responses can be discriminated on the basis of cytokine production, such as IFN-gamma, which is produced by TH1 cells, and IL-4, which is produced by TH2 cells. The aim of the study was to establish whether the LLNA was sufficient to not only identify allergens but also mark them as either a contact or a respiratory allergen. To this end, LLNA responses to the contact allergen dinitrochlorobenzene (DNCB) and the respiratory allergen trimellitic anhydride (TMA) were determined using IFN-gamma and IL-4 mRNA expression and production as parameters. Topical application of TMA resulted in a threefold higher lymphocyte proliferation compared to DNCB 3 and 5 days after the first application, while a similar proliferation was found from Day 7 and onward. RT-PCR showed a similar induction of IFN-gamma and IL-4 mRNA expression. While both DNCB and TMA induced IFN-gamma production, TMA but not DNCB induced IL-4 production. Thus, only IL-4 production seemed a suitable parameter to discriminate between the two compounds. In a second study, the respiratory allergens toluene-2,4-diisocyanate (TDI) and phthalic anhydride (PA) were also assayed 7 days after the first application. Topical application of DNCB and PA resulted in a similar lymphocyte proliferation, while application of TMA and TDI resulted in a 1.8-fold higher proliferation. IFN-gamma production was similar for DNCB, TMA, and TDI, and fourfold lower for PA, while IL-4 production was similar for TMA, TDI, and PA, and 24-fold lower for DNCB. In summary, both studies showed induction of IL-4 production by respiratory allergens, with little or no induction by the contact allergen, holding promise for the possibility of identifying respiratory allergens within the LLNA by measuring IL-4 production 7 days after the first application.


Socio-demographic, anthropometric, and psychosocial predictors of attrition across behavioral weight-loss trials.
Preventing attrition is a major concern in behavioral weight loss intervention studies. The purpose of this analysis was to identify baseline and six-month predictors associated with participant attrition across three independent clinical trials of behavioral weight loss interventions (PREFER, SELF, and SMART) that were conducted over 10 years. Baseline measures included body mass index, Barriers to Healthy Eating, Beck Depression Inventory-II (BDI), Hunger Satiety Scale (HSS), Binge Eating Scale (BES), Medical Outcome Study Short Form (MOS SF-36 v2) and Weight Efficacy Lifestyle Questionnaire (WEL). We also examined early weight loss and attendance at group sessions during the first 6 months. Attrition was recorded at the end of the trials. Participants included 504 overweight and obese adults seeking weight loss treatment. The sample was 84.92% female and 73.61% white, with a mean (± SD) age of 47.35 ± 9.75 years. After controlling for the specific trial, for every one unit increase in BMI, the odds of attrition increased by 11%. For every year increase in education, the odds of attrition decreased by 10%. Additional predictors of attrition included previous attempts to lose 50-79 lbs, age, not possessing health insurance, and BES, BDI, and HSS scores. At 6 months, the odds of attrition increased by 10% with reduced group session attendance. There was also an interaction between percent weight change and trial (p<.001). Multivariate analysis of the three trials showed education, age, BMI, and BES scores were independently associated with attrition (ps ≤ .01). These findings may inform the development of more robust strategies for reducing attrition.


Understanding the loss-of-function in a triple missense mutant of DNA polymerase β found in prostate cancer.
Human DNA polymerase (pol) β is essential for base excision repair. We previously reported a triple somatic mutant of pol β (p.P261L/T292A/I298T) found in an early onset prostate tumor. This mutation abolishes polymerase activity, and the wild-type allele was not present in the tumor, indicating a complete deficiency in pol β function. The effect on polymerase activity is unexpected because the point mutations that comprise the triple mutant are not part of the active site. Herein, we demonstrate the mechanism of this loss-of-function. In order to understand the effect of the individual point mutations we biochemically analyzed all single and double mutants that comprise the triple mutant. We found that the p.I298T mutation is responsible for a marked instability of the triple mutant protein at 37˚C. At room temperature the triple mutant's low efficiency is also due to a decrease in the apparent binding affinity for the dNTP substrate, which is due to the p.T292A mutation. Furthermore, the triple mutant displays lower fidelity for transversions in vitro, due to the p.T292A mutation. We conclude that distinct mutations of the triple pol β mutant are responsible for the loss of activity, lower fidelity, and instability observed in vitro.


A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice.
Synthetic biology has advanced the design of genetic devices that can be used to reprogram metabolic activities in mammalian cells. By functionally linking the signal transduction of melanopsin to the control circuit of the nuclear factor of activated T cells, we have designed a synthetic signaling cascade enabling light-inducible transgene expression in different cell lines grown in culture or bioreactors or implanted into mice. In animals harboring intraperitoneal hollow-fiber or subcutaneous implants containing light-inducible transgenic cells, the serum levels of the human glycoprotein secreted alkaline phosphatase could be remote-controlled with fiber optics or transdermally regulated through direct illumination. Light-controlled expression of the glucagon-like peptide 1 was able to attenuate glycemic excursions in type II diabetic mice. Synthetic light-pulse-transcription converters may have applications in therapeutics and protein expression technology.


Metabolic characteristics of dominant microbes and key rare species from an acidic hot spring in Taiwan revealed by metagenomics.
Microbial diversity and community structures in acidic hot springs have been characterized by 16S rRNA gene-based diversity surveys. However, our understanding regarding the interactions among microbes, or between microbes and environmental factors, remains limited. In the present study, a metagenomic approach, followed by bioinformatics analyses, were used to predict interactions within the microbial ecosystem in Shi-Huang-Ping (SHP), an acidic hot spring in northern Taiwan. Characterizing environmental parameters and potential metabolic pathways highlighted the importance of carbon assimilatory pathways. Four distinct carbon assimilatory pathways were identified in five dominant genera of bacteria. Of those dominant carbon fixers, Hydrogenobaculum bacteria outcompeted other carbon assimilators and dominated the SHP, presumably due to their ability to metabolize hydrogen and to withstand an anaerobic environment with fluctuating temperatures. Furthermore, most dominant microbes were capable of metabolizing inorganic sulfur-related compounds (abundant in SHP). However, Acidithiobacillus ferrooxidans was the only species among key rare microbes with the capability to fix nitrogen, suggesting a key role in nitrogen cycling. In addition to potential metabolic interactions, based on the 16S rRNAs gene sequence of Nanoarchaeum-related and its potential host Ignicoccus-related archaea, as well as sequences of viruses and CRISPR arrays, we inferred that there were complex microbe-microbe interactions. Our study provided evidence that there were numerous microbe-microbe and microbe-environment interactions within the microbial community in an acidic hot spring. We proposed that Hydrogenobaculum bacteria were the dominant microbial genus, as they were able to metabolize hydrogen, assimilate carbon and live in an anaerobic environment with fluctuating temperatures.


A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit.
Mixed lineage leukemia (MLL) and its metazoan Trithorax orthologs have been linked with the epigenetic maintenance of transcriptional activity. To identify mechanisms by which MLL perpetuates active transcription in dividing cells, we investigated its role during M phase of the cell cycle. Unlike other chromatin-modifying enzymes examined, we found that MLL associates with gene promoters packaged within condensed mitotic chromosomes. Genome-wide location analysis identified a globally rearranged pattern of MLL occupancy during mitosis in a manner favoring genes that were highly transcribed during interphase. Knockdown experiments revealed that MLL retention at gene promoters during mitosis accelerates transcription reactivation following mitotic exit. MLL tethers Menin, RbBP5, and ASH2L to its occupied sites during mitosis, but is dispensable for preserving histone H3K4 methylation. These findings implicate mitotic bookmarking as a component of Trithorax-based gene regulation, which may facilitate inheritance of active gene expression states during cell division.


Quality control in oocytes by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level.
Mammalian oocytes are arrested in the dictyate stage of meiotic prophase I for long periods of time, during which the high concentration of the p53 family member TAp63α sensitizes them to DNA damage-induced apoptosis. TAp63α is kept in an inactive and exclusively dimeric state but undergoes rapid phosphorylation-induced tetramerization and concomitant activation upon detection of DNA damage. Here we show that the TAp63α dimer is a kinetically trapped state. Activation follows a spring-loaded mechanism not requiring further translation of other cellular factors in oocytes and is associated with unfolding of the inhibitory structure that blocks the tetramerization interface. Using a combination of biophysical methods as well as cell and ovary culture experiments we explain how TAp63α is kept inactive in the absence of DNA damage but causes rapid oocyte elimination in response to a few DNA double strand breaks thereby acting as the key quality control factor in maternal reproduction.


Experimental results of ground-layer and tomographic wavefront reconstruction from multiple laser guide stars.
We describe results from the first multi-laser wavefront sensing system designed to support tomographic modes of adaptive optics (AO). The system, now operating at the 6.5 m MMT telescope in Arizona, creates five beacons by Rayleigh scattering of laser beams at 532 nm integrated over a range from 20 to 29 km by dynamic refocus of the telescope optics. The return light is analyzed by a Shack-Hartmann sensor that places all five beacons on a single detector, with electronic shuttering to implement the beacon range gate. A separate high-order Shack-Hartmann sensor records simultaneous measurements of wavefronts from a natural star. From open-loop measurements, we find the average beacon wavefront gives a good estimate of ground layer aberration. We present results of full tomographic wavefront analysis, enabled by supplementing the laser data with simultaneous fast image motion measurements from three stars in the field. We describe plans for an early demonstration at the MMT of closed-loop ground layer AO, and later tomographic AO.


Cost-effectiveness analysis of quadrivalent seasonal influenza vaccines in England.
As part of the national seasonal influenza vaccination programme in England and Wales, children receive a quadrivalent vaccine offering protection against two influenza A strains and two influenza B strains. Healthy children receive a quadrivalent live attenuated influenza vaccine (QLAIV), whilst children with contraindications receive the quadrivalent inactivated influenza vaccine (QIIV). Individuals aged younger than 65 years in the clinical risk populations and elderly individuals aged 65+ years receive either a trivalent inactivated influenza vaccine (TIIV) offering protection from two A strains and one B strain or the QIIV at the choice of their general practitioner. The cost-effectiveness of quadrivalent vaccine programmes is an open question. The original analysis that supported the paediatric programme only considered a trivalent live attenuated vaccine (LAIV). The cost-effectiveness of the QIIV to other patients has not been established. We sought to estimate the cost-effectiveness of these programmes, establishing a maximum incremental total cost per dose of quadrivalent vaccines over trivalent vaccines. We used the same mathematical model as the analysis that recommended the introduction of the paediatric influenza vaccination programme. The incremental cost of the quadrivalent vaccine is the additional cost over that of the existing trivalent vaccine currently in use. Introducing quadrivalent vaccines can be cost-effective for all targeted groups. However, the cost-effectiveness of the programme is dependent on the choice of target cohort and the cost of the vaccines: the paediatric programme is cost-effective with an increased cost of £6.36 per dose, though an extension to clinical risk individuals younger than 65 years old and further to all elderly individuals means the maximum incremental cost is £1.84 and £0.20 per dose respectively. Quadrivalent influenza vaccines will bring substantial health benefits, as they are cost-effective in particular target groups.


Assessing the accuracy of observer-reported ancestry in a biorepository linked to electronic medical records.
The Vanderbilt DNA Databank (BioVU) is a biorepository that currently contains >80,000 DNA samples linked to electronic medical records. Although BioVU is a valuable source of samples and phenotypes for genetic association studies, it is unclear whether the administratively assigned race/ethnicity in BioVU can accurately describe and be used as a proxy for genetic ancestry. We genotyped 360 single nucleotide polymorphisms on the Illumina DNA Test Panel containing ancestry informative markers in 1910 BioVU samples with observer-reported ancestry and 384 samples from the Multiple Sclerosis Genetics Group with self-reported ancestry. Genetic ancestry was inferred for all individuals using Structure 2.2. More than 98% of observer-reported European Americans were genetically inferred to have at least 60% European ancestry. Ninety-three percent of observer-reported African Americans were genetically inferred to be predominantly of African ancestry. We determined that the concordance of observer-reported race/ethnicity and inferred genetic ancestry was not significantly different from that of self-reported race/ethnicity in either population (P = 0.09 and 0.94 in European Americans and African Americans, respectively). Observer-reported race/ethnicity for European Americans and African Americans approximates genetic ancestry as well as self-reported race/ethnicity, making biorepositories linked to electronic medical records such as BioVU a viable source of DNA samples for future large-scale genetic association studies.


Description of a new genus of ponyfishes (Teleostei: Leiognathidae), with a review of the current generic-level composition of the family.
In order to recognize a monophyletic taxonomy for Leiognathidae based on unique features of the bacterially mediated light-organ system, we describe a new sexually-dimorphic genus of elongate, shallow-bodied ponyfishes within the tribe Equulitini, which itself is recovered within the subfamily Gazzinae. Photolateralis, new genus, is unique among ponyfishes in possessing a translucent mid-lateral flank stripe, which depending on the species, may be either a composite "stripe" comprised of numerous independent translucent windows (P. stercorarius and P. moretoniensis), or a continuous translucent lateral stripe (P. antongil). This translucent lateral stripe is either lacking entirely in females, or is considerably less well developed. In contrast, males in its sister taxon, Equulites, are characterized by the presence of an expansive, triangular, translucent lateral flank patch that also exhibits species-specific morphology. Internally, in Photolateralis the light organ system is characterized by a moderately enlarged, donut-shaped, and conspicuously spotted light organ in males that extends only slightly posteriorly into the gas bladder. In contrast, in members of Equulites the dorsolateral lobes of the light organ in males are greatly enlarged, heavily pigmented, and extend posteriorly well into the gas bladder. In addition, internally male members of Photolateralis exhibit lateral clearing of the silvery gas bladder lining posteriorly, corresponding in extent to the external translucent lateral stripe or windows on the flank. Including the new genus described herein, we now recognize 10 monophyletic genera of extant ponyfishes.


Platelet-rich plasma supplementation in arthroscopic repair of full-thickness rotator cuff tears: a randomized clinical trial.
Results on the effectiveness of PRP supplementation in arthroscopic rotator cuff repair are conflicting, making it difficult to draw definitive conclusions. This was a prospective, randomized, and double-blind study with two groups of 20 patients each (PRP group and control group). Degenerative supraspinatus full-thickness tears grade C2-C3 were subjected to arthroscopic repair; PRP supplementation was given to patients in the PRP group. The outcomes were assessed by DASH, Constant scales, and ultrasound before and 6 months after surgery. Pain measured by VAS was evaluated preoperatively and 7 and 30 days after surgery. The two groups did not differ significantly by age, sex, and dominance of the affected side. In all surgical procedures, a long head of the biceps tenotomy and single-row repair were performed. The preoperative VAS was 5.6 ± 2.4 in PRP group and 6.4 ± 1.5 in the control group (p > 0.05). The group supplemented with PRP reported a VAS significantly better in the first week (2.5 ± 1.9 vs 5.3 ± 2.1, p < 0.05) and during the first month after surgery (1.5 ± 1.0 vs 3.2 ± 1.7, p < 0.05) compared to the control group. The preoperative Constant and DASH scores were 39.95 ± 12 and 51 ± 15.2, respectively, in the PRP group and 41 ± 11 (p > 0.05) and 45 ± 12.6 (p > 0.05) in the control group. The average Constant score improved significantly after 6 months to 81 ± 11.2 (p < 0.05) in the PRP group and 78.5 ± 9 (p < 0.05) in the control group. No differences were noted between the two groups (p > 0.05). The DASH score after 6 months was 17.4 ± 8 (p < 0.05) for the treatment group (the PRP group) and 21 ± 8.4 (p < 0.05) for the control group. No statistically significant differences were found as regards the DASH score in the two groups after 6 months (p > 0.05). The two groups showed no differences in the ultrasound evaluation after 6 months either. No re-ruptures occurred in either group. PRP leads to a reduction in pain during a short-term follow-up. Pain reduction allows for a more rapid recovery of mobilization and improvement in functionality. Randomized controlled trial, Level of evidence, 1.


Treatment of individuals with chronic bicipital tendinopathy using dry needling, eccentric-concentric exercise and stretching; a case series.
Objectives: To describe the outcomes of 10 patients with chronic biceps tendinopathy treated by physical therapy with the novel approach of dry needling (DN), eccentric-concentric exercise (ECE), and stretching of the long head of the biceps tendon (LHBT). Methods: Ten individuals reporting chronic anterior shoulder symptoms (> 3 months), pain with palpation of the LHBT, and positive results on a combination of tests including active shoulder flexion, Speed's, Hawkins Kennedy, Neer, and Yergason's tests participated in this case series. Validated self-reported outcome measures including the mean numeric pain rating scale (NPRS) and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) were taken at baseline. Participants were treated with two to eight sessions of DN to the LHBT and an ECE program and stretching of the biceps muscle. At discharge, patients completed the global rating of change (GROC), QuickDASH and NPRS. Results: Patients had an improved mean NPRS of 3.9 (SD, 1.3; p < 0.001), QuickDASH of 19.01% (SD, 10.8; p < 0.02) and GROC +5.4 (SD, 1.3). Conclusion: Findings from this case series suggest that DN and ECE may be beneficial for the management of patients with chronic LHBT tendinopathy. Further research on the efficacy of this novel treatment approach is warranted.


Survey of natural enemies of spider mites (Acari: Tetranychidae) in citrus orchards in eastern Spain.
Field surveys were conducted from 2004 to 2007 to determine the species composition and relative abundance of natural enemies associated with colonies of either the citrus red mite, Panonychus citri, or the two spotted spider mite, Tetranychus urticae, in Valencian citrus orchards (eastern Spain). Fourteen species were recorded, six phytoseiid mites and eight insect predators. Two of them are reported for the first time on citrus in Spain and two more are first reports as predators associated with T. urticae. The community of predators associated with T. urticae and P. citri was almost identical, and the Morisita-Horn index of similarity between both natural enemy complexes was close to one, suggesting that predators forage on both pest species. Quantifying the presence of many known spider mites predators in Valencian citrus orchards is an important first step towards spider mite control. A challenge for future studies will be to establish conservation and/or augmentation management strategies for these predators, especially to improve T. urticae biological control.


The genome sequence of Barbarea vulgaris facilitates the study of ecological biochemistry.
The genus Barbarea has emerged as a model for evolution and ecology of plant defense compounds, due to its unusual glucosinolate profile and production of saponins, unique to the Brassicaceae. One species, B. vulgaris, includes two 'types', G-type and P-type that differ in trichome density, and their glucosinolate and saponin profiles. A key difference is the stereochemistry of hydroxylation of their common phenethylglucosinolate backbone, leading to epimeric glucobarbarins. Here we report a draft genome sequence of the G-type, and re-sequencing of the P-type for comparison. This enables us to identify candidate genes underlying glucosinolate diversity, trichome density, and study the genetics of biochemical variation for glucosinolate and saponins. B. vulgaris is resistant to the diamondback moth, and may be exploited for "dead-end" trap cropping where glucosinolates stimulate oviposition and saponins deter larvae to the extent that they die. The B. vulgaris genome will promote the study of mechanisms in ecological biochemistry to benefit crop resistance breeding.


Validation of alternate modes of administration of the lung function questionnaire (LFQ) in subjects with smoking history.
The lung Function Questionnaire (LFQ) was developed and validated as a case-finding tool to identify patients at risk of airflow obstruction (AO) that should be evaluated further using spirometry. Our objective was to assess the usability and validity of additional questionnaire-administration modes, including Web-based, interactive voice response system (IVRS)-based, and interviewer-based modes. This multicenter, prospective, noninterventional data-collection study enrolled 149 individuals aged ≥40 years with current or former smoking history. A two-visit crossover design was employed; patients completed the paper-based LFQ and were randomly assigned to complete one of three alternate modes. Statistical evaluation included item-level, scale-level, and AO risk-classification comparisons; a satisfaction survey assessed patient preference. this study showed a great degree of concordance between alternate forms of the LFQ and the paper version. Results indicated an absence of floor and ceiling effects and the average LFQ item-level means were consistent across modes. LFQ scores were stable between assessments, (administered approximately one week apart) showed exceptionally good agreement, and AO risk classification using the LFQ cut point was consistent across modes. The LFQ is an important case-finding tool to aid primary care physicians in further evaluating symptomatic patients at risk of AO. The alternate modes will further facilitate the implementation and widespread uptake of this tool.


Evaluating social and behavioural impacts of English smoke-free legislation in different ethnic and age groups: implications for reducing smoking-related health inequalities.
To explore social and behavioural impacts of English smoke-free legislation (SFL) in different ethnic groups. A longitudinal, qualitative panel study of smokers using in-depth interviews conducted before and after introduction of SFL. A purposive sample of 32 smokers selected from three ethnic groups in deprived London neighbourhoods with approximately equal numbers of younger and older, male and female respondents. SFL has had positive impacts with half smoking less and three quitting. Although there were no apparent differences in smoking and quitting behaviours between groups, there were notable differences in the social impacts of SFL. The greatest negative impacts were in smokers over 60 years, potentially increasing their social isolation, and on young Somali women whose smoking was driven more underground. In contrast, most other young adult smokers felt relatively unaffected by SFL, describing unexpected social benefits. Although there was high compliance, reports of illegal smoking were more frequent among young, ethnic minority smokers, with descriptions of venues involved suggesting they are ethnically distinct and well hidden. Half of respondents reported stopping smoking in their own homes after SFL, but almost all were Somali or Turkish. White respondents tended to report increases in home smoking. Although our study suggests that SFL can lead to reductions in tobacco consumption, it also shows that impacts vary by ethnicity, age and sex. This study highlights the importance of understanding the meaning of smoking in different social contexts so future tobacco control interventions can be developed to reduce health and social inequalities.


Fractured narratives of psy disciplines and the LGBTQIA+ rights movement in India: A critical examination.
In 2018, a day before the Supreme Court of India commenced hearing the curative petition on Section 377 of the Indian Penal Code (which criminalised carnal intercourse against the order of nature), the Indian Psychiatric Society (IPS) issued an official statement that homosexuality is not a mental pathology. In 2014, a year after the top court recriminalised homosexuality, the then IPS president had termed it as a pathology requiring treatment. By examining articles on LGBTQIA+ rights published in two flagship Indian journals in psychiatry and clinical psychology, position statements by professional bodies, and international and national developments in human rights mechanisms, we argue that psychiatry's voice for human rights protection of the marginalised has been akin to whispering sweet nothings in tune with the juridico-penal system. In turn, clinical psychology appears to huddle with biomedical psychiatry without raising its voice against coercive and traumatising practices within mainstream technocratic psychiatry. We seek to explore the troubled relationship between mainstream psy disciplines and LGBTQIA+ persons characterised by psychological evasion: failure of mainstream psy disciplines to take up sensitive, socio-political issues like same sex love in a broader human rights framework leading to individualisation- pathologisation complex which further side-lines persons living on the margins of society.


Adequate vitamin D3 skin synthesis versus erythema risk in the Northern Hemisphere midlatitudes.
Health-optimum-exposure index (HOEI) is proposed to assess if the prescribed amount of vitamin D3 (target value) could be synthesized in the human skin without erythema appearance. It is defined as the ratio between the vitamin D3 quantity received during the maximum allowed outdoor exposure without erythema risk and the target value. Sunbathing is safe for HOEI>1 and 1/HOEI represents a part of minimal erythema dose (MED) necessary to obtain the target value. We examine the following targets: a vitamin D3 quantity equivalent to 1000 IU vitamin D3 taken orally, and an optimal vitamin D3 quantity defined by Krzyścin et al. (2016). The biologically weighted (previtamin D3 and erythemal) doses from the Northern Hemisphere midlatitudinal stations are analyzed to find HOEI dependence on personal and meteorological factors. HOEI depends mostly on the exposed skin area, person's age, and sun elevation at noon but not on the Fitzpatrick skin phototype. We found that only young adults (<21 yr) could safely obtain vitamin D3 quantity, which is equivalent to 1000 IU taken orally, almost throughout the whole year. Duration of such exposures appears <1 h only in the warm subperiods of the year (April-September) for a person with minimal erythema dose of 330 J m-2. Exposing larger part of the body (~30%) enables the oldest persons (>59 yr) to reach 1000 IU target during warm days in spring and summer. The optimal daily vitamin D3 quantity could only be synthesized only by young adults for about 40-60% of days in the May-August period if they expose at least 1/3 part of their body surface area. Vitamin D3 supplementation seems to be necessary over the whole year for the oldest persons with daily dosage of ~2000 IU but reduced to ~1000 IU in summer for sunseekers exposing significant part of the body.


Managing Stigma Effectively: What Social Psychology and Social Neuroscience Can Teach Us.
Psychiatric education is confronted with three barriers to managing stigma associated with mental health treatment. First, there are limited evidence-based practices for stigma reduction, and interventions to deal with stigma against mental health care providers are especially lacking. Second, there is a scarcity of training models for mental health professionals on how to reduce stigma in clinical services. Third, there is a lack of conceptual models for neuroscience approaches to stigma reduction, which are a requirement for high-tier competency in the ACGME Milestones for Psychiatry. The George Washington University (GWU) psychiatry residency program has developed an eight-week course on managing stigma that is based on social psychology and social neuroscience research. The course draws upon social neuroscience research demonstrating that stigma is a normal function of normal brains resulting from evolutionary processes in human group behavior. Based on these processes, stigma can be categorized according to different threats that include peril stigma, disruption stigma, empathy fatigue, moral stigma, and courtesy stigma. Grounded in social neuroscience mechanisms, residents are taught to develop interventions to manage stigma. Case examples illustrate application to common clinical challenges: (1) helping patients anticipate and manage stigma encountered in the family, community, or workplace; (2) ameliorating internalized stigma among patients; (3) conducting effective treatment from a stigmatized position due to prejudice from medical colleagues or patients' family members; and (4) facilitating patient treatment plans when stigma precludes engagement with mental health professionals. This curriculum addresses the need for educating trainees to manage stigma in clinical settings. Future studies are needed to evaluate changes in clinical practices and patient outcomes as a result of social neuroscience-based training on managing stigma.


Anthropometric changes in non-medicated ADHD boys.
The aim of the study is to compare complex anthropometric characteristics in non medicated boys with ADHD and normal population. Complex anthropometric examination of non-medicated ADHD boys (n=46, average age 11.03 years), statistical and clinical comparison to the actual population growth norm. In contrast to the most of the previous studies, which analyzed mostly only BMI or basic signs of growth as height and weight, the presented study operates with a complex anthropometrical measurement and comparison with actual population norm. The results of the study show significant differences in the signs of nutrition (percentage of fat) and growth indicators (lower values of height) between ADHD and non ADHD children. Further anthropometrical parameters show other possible but in the studied sample statistically non-significant differences. Many studies analyzed growth relation to medication of ADHD children, but did not consider that the changes could appear also in non-medicated children and thus they might not be only a side effect of the treatment but a manifestation of the disorder itself. Growth changes in non-medicated children are not described well enough, so the presented study was performed to compare anthropometrics characteristics in ADHD boys with norm of nonclinical population and specify the differences. The results points to hypothesis that the growth changes are primarily caused by the disorder itself.


The Impact of Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE) Flags on Hospital Operations.
OBJECTIVE To determine the impact of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus (MRSA/VRE) designations, or flags, on selected hospital operational outcomes. DESIGN Retrospective cohort study of inpatients admitted to the Massachusetts General Hospital during 2010-2011. METHODS Operational outcomes were time to bed arrival, acuity-unrelated within-hospital transfers, and length of stay. Covariates considered included demographic and clinical characteristics: age, gender, severity of illness on admission, admit day of week, residence prior to admission, hospitalization within the prior 30 days, clinical service, and discharge destination. RESULTS Overall, 81,288 admissions were included. After adjusting for covariates, patients with a MRSA/VRE flag at the time of admission experienced a mean delay in time to bed arrival of 1.03 hours (9.63 hours [95% CI, 9.39-9.88] vs 8.60 hours [95% CI, 8.47-8.73]). These patients had 1.19 times the odds of experiencing an acuity-unrelated within-hospital transfer [95% CI, 1.13-1.26] and a mean length of stay 1.76 days longer (7.03 days [95% CI, 6.82-7.24] vs 5.27 days [95% CI, 5.15-5.38]) than patients with no MRSA/VRE flag. CONCLUSIONS MRSA/VRE designation was associated with delays in time to bed arrival, increased likelihood of acuity-unrelated within-hospital transfers and extended length of stay. Efforts to identify patients who have cleared MRSA/VRE colonization are critically important to mitigate inefficient use of resources and to improve inpatient flow. Infect Control Hosp Epidemiol 2016;37:782-790.


Maternal postpartum depressive symptoms and infant externalizing and internalizing behaviors.
Maternal postpartum depression has been shown to be one of the main predictors of externalizing and internalizing behaviors in toddlers and adolescents. Research suggests that presence of such behaviors can be observed as early as infancy. The current study uses longitudinal data from 247 mothers to examine the relationship between postpartum depressive symptoms at 8 weeks and the infant's externalizing and internalizing behaviors at 12 months. In unadjusted linear regression models, there were associations between postpartum depressive symptoms and infant externalizing behaviors (β=0.082, SE=0.032, p=0.012) and internalizing behaviors (β=0.111, SE=0.037, p=0.003). After controlling for potential confounding factors, including maternal age, race, education, home ownership, smoking status in the postpartum period, marital status, parenting stress, and happiness from becoming a parent, the associations between postpartum depressive symptoms and infant externalizing (β=0.051, SE=0.034, p=0.138) and internalizing behaviors (β=0.077, SE=0.040, p=0.057) were reduced and became non-significant. Furthermore, in these models the total amount of variance explained was 17.2% (p<0.0001) for externalizing behaviors and 10.5% (p<0.01) for internalizing behaviors; the only significant predictor of externalizing behaviors was maternal age (β=-0.074, SE=0.030, p=0.014), and of internalizing behaviors was white non-Hispanic ethnicity (β=-1.33, SE=0.378, p=0.0005). A combined effect of the confounding factors seems to explain the finding of no significant independent association between postpartum depressive symptoms and infant externalizing and internalizing behaviors.


Prognostic value of plasma HIV RNA in the natural history of Pneumocystis carinii pneumonia, cytomegalovirus and Mycobacterium avium complex. Multicenter AIDS Cohort Study.
To use follow-up on untreated HIV-positive men to assess the prognostic information provided by baseline data on plasma HIV RNA, CD4 cell count, age, and HIV-related symptom status, separately for three specific AIDS-defining illnesses: Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV), and Mycobacterium avium complex (MAC). The study population were 734 HIV-positive homosexual men enrolled in the Multicenter AIDS Cohort Study, with follow-up (1984-1985 through mid-1988) restricted to the antiretroviral treatment-free and prophylaxis-free era. Baseline marker values were categorized and assessed as predictor variables in separate time-to-event analyses for each of the three specific outcomes. A total of 138 cases of PCP, 25 cases of CMV, and 25 cases of MAC were observed. For PCP and CMV, higher categories of HIV RNA and lower categories of CD4 cell count were associated with increased risk relative to the respective reference groups. For MAC, oral candidiasis or fever and elevated HIV RNA at baseline were the primary risk factors. Further analysis highlighted the importance of monitoring HIV RNA levels in addition to CD4 cell counts when evaluating patients' risk of developing PCP. In the absence of treatment, plasma HIV RNA levels provide prognostic information about the risk of these three specific AIDS-defining illnesses, independently of the CD4 cell count. These data provide a useful reference as researchers investigate changing patterns in the incidence and predictors of opportunistic infections in the era of increasingly active antiretroviral therapies.


Muscle injuries of the dominant or non-dominant leg in male football players at elite level.
The aim was to study possible differences of muscle injuries regarding type, localization and the extent of injury between the dominant and non-dominant leg in elite male football players. Another aim was to study the injury incidence of muscle injuries of the lower extremity during match and training. Data were consecutively collected between 2007 and 2013 in a prospective cohort study based on 54 football players from one team of the Swedish first league. The injury incidence was calculated for both match and training, injuries to the hip adductors, quadriceps, hamstrings and triceps surae were diagnosed and evaluated with ultrasonography, and their length, depth and width were measured to determine the extent of structural muscle injuries. Fifty-four players suffered totally 105 of the studied muscle injuries. Out of these 105 injuries, the dominant leg was affected in 53 % (n = 56) of the cases. A significantly greater extent of the injury was found in the dominant leg when compared with the non-dominant leg with regard to structural injuries of the hamstrings. No other significant differences were found. Structural hamstring muscle injuries were found to be of greater extent in the dominant leg when compared with the non-dominant leg. This new finding should be taken into consideration when allowing the football player to return to play after leg muscle injuries. IV.


Local immune response to injection of Plasmodium sporozoites into the skin.
Malarial infection is initiated when the sporozoite form of the Plasmodium parasite is inoculated into the skin by a mosquito. Sporozoites invade hepatocytes in the liver and develop into the erythrocyte-infecting form of the parasite, the cause of clinical blood infection. Protection against parasite development in the liver can be induced by injection of live attenuated parasites that do not develop in the liver and thus do not cause blood infection. Radiation-attenuated sporozoites (RAS) and genetically attenuated parasites are now considered as lead candidates for vaccination of humans against malaria. Although the skin appears as the preferable administration route, most studies in rodents, which have served as model systems, have been performed after i.v. injection of attenuated sporozoites. In this study, we analyzed the early response to Plasmodium berghei RAS or wild-type sporozoites (WTS) injected intradermally into C57BL/6 mice. We show that RAS have a similar in vivo distribution to WTS and that both induce a similar inflammatory response consisting of a biphasic recruitment of polymorphonuclear neutrophils and inflammatory monocytes in the skin injection site and proximal draining lymph node (dLN). Both WTS and RAS associate with neutrophils and resident myeloid cells in the skin and the dLN, transform inside CD11b(+) cells, and induce a Th1 cytokine profile in the dLN. WTS and RAS are also similarly capable of priming parasite-specific CD8(+) T cells. These studies delineate the early and local response to sporozoite injection into the skin, and suggest that WTS and RAS prime the host immune system in a similar fashion.


Homozygous variants in KIAA1549, encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa.
Retinitis pigmentosa (RP) shows substantial genetic heterogeneity. It has been estimated that in approximately 60%-80% of RP cases, the genetic diagnosis can be found using whole exome sequencing (WES). In this study, the purpose was to identify causative variants in individuals with genetically unexplained retinal disease, which included one consanguineous family with two affected siblings and one case with RP. To identify the genetic defect, WES was performed in both probands, and clinical analysis was performed. To obtain insight into the function of KIAA1549 in photoreceptors, mRNA expression, knockdown and protein localisation studies were performed. Through analysis of WES data, based on population allele frequencies, and in silico prediction tools, we identified a homozygous missense variant and a homozygous frameshift variant in KIAA1549 that segregate in two unrelated families. Kiaa1549 was found to localise at the connecting cilium of the photoreceptor cells and the synapses of the mouse retina. Both variants affect the long transcript of KIAA1549, which encodes a 1950 amino acid protein and shows prominent brain expression. The shorter transcript encodes a 734 amino acid protein with a high retinal expression and is affected by the identified missense variant. Strikingly, knockdown of the long transcript also leads to decreased expression of the short transcript likely explaining the non-syndromic retinal phenotype caused by the two variants targeting different transcripts. In conclusion, our results underscore the causality of segregating variants in KIAA1549 for autosomal recessive RP. Moreover, our data indicate that KIAA1549 plays a role in photoreceptor function.


Microbially Induced Precipitation of Strontianite Nanoparticles.
The objectives of this study were to investigate the microbially mediated precipitation of strontium by microorganisms, and to examine the mineralogical characteristics of the precipitates. Wu Do-1 (Proteus mirabilis) enriched from rhodoliths was used to precipitate strontium at room temperature under aerobic environment. The growth of Wu Do-1 gradually increased over 16 days (OD600 = 2.6) and then decreased until 22 days (OD600 = 2.0) during microbial incubation for strontium precipitation. Also, the pH decreased from 6.5 to 5.3 over 4 days of incubation due to microbial oxidation of organic acids, and then the pH increased up to 8.6 at 25 days of incubation due to NH3+ generation. The Sr2+ concentration in the biotic group sharply decreased from 2,953 mg/L to 5.7 mg/L over 29 days of incubation. XRD, SEM-/TEM-EDS analyses revealed that the precipitates formed by Wu Do-1 (Proteus mirabilis) were identified as 20-70 nm sized strontianite (SrCO3). Therefore, these results suggested that formation of sparingly soluble Sr precipitates mediated by Wu Do-1 (Proteus mirabilis) sequesters strontium and carbon dioxide into a more stable and less toxic form such as strontianite (SrCO3). These results also suggest that bioremediation of metal-contaminated water and biominealization of carbonate minerals may be feasible in the marine environment.


Dietary fibre for the prevention of recurrent colorectal adenomas and carcinomas.
This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental evidence has supported the hypothesis that dietary fibre may protect against the development of CRC, although epidemiologic data have been inconclusive. To assess the effect of dietary fibre on the recurrence of colorectal adenomatous polyps in people with a known history of adenomatous polyps and on the incidence of CRC compared to placebo. Further, to identify the reported incidence of adverse effects, such as abdominal pain or diarrhoea, that resulted from the fibre intervention. We identified randomised controlled trials (RCTs) from Cochrane Colorectal Cancer's Specialised Register, CENTRAL, MEDLINE and Embase (search date, 4 April 2016). We also searched ClinicalTrials.gov and WHO International Trials Registry Platform on October 2016. We included RCTs or quasi-RCTs. The population were those having a history of adenomatous polyps, but no previous history of CRC, and repeated visualisation of the colon/rectum after at least two-years' follow-up. Dietary fibre was the intervention. The primary outcomes were the number of participants with: 1. at least one adenoma, 2. more than one adenoma, 3. at least one adenoma greater than or equal to 1 cm, or 4. a new diagnosis of CRC. The secondary outcome was the number of adverse events. Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. We used risk ratios (RR) and risk difference (RD) with 95% confidence intervals (CI) to measure the effect. If statistical significance was reached, we reported the number needed to treat for an additional beneficial outcome (NNTB) or harmful outcome (NNTH). We combined the study data using the fixed-effect model if it was clinically, methodologically, and statistically reasonable. We included seven studies, of which five studies with 4798 participants provided data for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions that we would draw. Therefore, the reliability of the findings may have been compromised by these missing data (attrition bias) and should be interpreted with caution. There is a lack of evidence from existing RCTs to suggest that increased dietary fibre intake will reduce the recurrence of adenomatous polyps in those with a history of adenomatous polyps within a two to eight year period. However, these results may be unreliable and should be interpreted cautiously, not only because of the high rate of loss to follow-up, but also because adenomatous polyp is a surrogate outcome for the unobserved true endpoint CRC. Longer-term trials with higher dietary fibre levels are needed to enable confident conclusion.


In Vitro Antibacterial and Antioxidant Activities of Roasted and Green Coffee Beans Originating from Different Regions of Ethiopia.
Coffee is among the most traded commodities and consumed beverages worldwide primarily for its stimulating effects. Moreover, coffee is known to contain various bioactive compounds with significant health benefits including antibacterial and antioxidant activities. However, Ethiopia as the origin of coffee and producer and exporter of varieties of Coffea arabica has made little study on the health aspects of this beverage. The aim of this study was to examine the antibacterial and antioxidant activities and content of coffee samples from different localities of Yorgacheffe and Jimma; and roasted, ground, and packed samples purchased from a coffee shop in Addis Ababa. Medium-roasted-boiled and lyophilized coffee extracts were tested on eight gram-negative and gram-positive bacterial strains. The agar-well diffusion method was used to test the extracts determining the minimum inhibitory and bactericidal concentrations. For coffee antioxidant activity and content, light-roasted (both field and shop samples) and green coffee bean extracts were tested using the free radical 2.2-diphenyl-l-pict1hydrazyl (DPPH) IC50 percent inhibition protocol. The samples showed strong antibacterial and antioxidant activity and substantial antioxidant content. Significant variation was noted in the antibacterial activities of the different coffee samples. Moreover, the growth-inhibitory strength of each coffee sample was variable for different test bacteria. A coffee sample with the best antibacterial activity had also the highest antioxidant activity/content. The shop coffee had the lowest bioactivity. The observed variations in the antibacterial and antioxidant activities among the samples probably indicate the diversity of the Ethiopian coffee related, among other factors, to the coffee plant genetics and agroecology.


Harvesting light at the nanoscale by GaAs-gold nanowire arrays.
A nanoscale metal-semiconductor-metal photodetector with a 40 nm-thick GaAs absorbing layer has been studied numerically and experimentally. A gold nanowire array is the top mirror of a Fabry-Perot cavity and forms interdigitated Schottky contacts. Nearly perfect absorption is achieved in TE polarization. It is shown numerically that the gold nanowire array induces light absorption in GaAs nanowires with tiny sections (100 nm × 40 nm). High external quantum efficiency (η > 40 %) is demonstrated.


Early statin initiation and outcomes in patients with acute coronary syndromes.
The secondary prevention benefit of therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been clearly demonstrated; however, the role of early initiation of statins after acute coronary syndromes (ACSs) is unknown. To evaluate the association of early statin initiation (< or = 7 days) after ACS with 90-day and 1-year outcomes. Observational cohort from databases of 2 randomized clinical trials, SYMPHONY and 2nd SYMPHONY. Nine hundred thirty-one clinical centers in 37 countries. A total of 12,365 ACS patients randomized from August 1997 to August 1999 who were not taking statins prior to the index ACS and who either started statin therapy early (median, 2.0 [interquartile range, 1.0-3.1] days after ACS; n = 3952) or survived more than 5 days after ACS and never received statin therapy (n = 8413). Ninety-day incidence of death; death or myocardial infarction (MI); and death, MI, or severe recurrent ischemia; as well as 1-year incidence of death. Ninety-day and 1-year unadjusted mortality comparison suggested early statin benefit (1.2% for early statins vs 2.1% for no statins; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.42-0.81 for 90-day comparisons and 2.3% for early statins vs 4.4% for no statins; HR, 0.52; 95% CI, 0.40-0.68 for 1-year comparison). However, no benefit was evident for 90-day death or MI (6.5% vs 6.9%; HR, 0.95; 95% CI, 0.82-1.11) or death, MI, or severe recurrent ischemia (9.2% vs 8.9%; HR, 1.04; 95% CI, 0.92-1.18). After propensity and covariate adjustment, there were no 90-day or 1-year differences between the early-statin group and the no-statin group. The 90-day adjusted HR for death was 1.08 (95% CI, 0.75-1.56); for death or MI, 1.08 (95% CI, 0.91-1.29); and for death, MI, or severe recurrent ischemia, 1.15 (95% CI, 0.99-1.34). One-year mortality-adjusted HR was 0.99 (95% CI, 0.73-1.33). Among 2711 patients with core laboratory lipid analysis, early statin was associated with higher adjusted risk for death or death or MI at cholesterol levels below treatment guidelines but was more favorable at higher levels. In this study, there was no relationship between early initiation of statin therapy and improved outcomes although our subset analysis suggests that outcomes after early statin initiation may vary with cholesterol levels. Confirmation of early treatment effects of statins on outcomes awaits the results of adequately powered randomized clinical trials.


Activation of extracellular signal-regulated protein kinase is associated with colorectal distension-induced spinal and supraspinal neuronal response and neonatal maternal separation-induced visceral hyperalgesia in rats.
The activation of extracellular signal-regulated protein kinase (ERK) is essential for pain sensation and development of hyperalgesia in chronic pathological pain. Neonatal maternal separation (NMS) could trigger behavioral hyperalgesia and upregulate central neuronal activity in rats. The present study aims to investigate whether ERK associates with the colorectal distension (CRD)-evoked neuronal response and the upregulated central sensitivity to CRD in NMS rats. Male Sprague-Dawley rat pups were either subjected to NMS or not handled (NH) from postnatal day 2 to day 14. The protein expression of phospho-ERK (p-ERK) and c-fos at the spinal and supraspinal levels of adult rats were quantified and their correlation was analyzed. Western blot analysis revealed significant NMS effect on p-ERK expression in the lumbosacral dorsal horn and thalamus. Immunohistochemistry analysis demonstrated that CRD elevated p-ERK and c-fos expression in the dorsal root ganglia (DRG), laminae I-II of the lumbosacral dorsal horn, thalamic nucleus central medial (CM), paraventricular thalamic nucleus (PV), and anterior cingulate cortex (ACC). Significant NMS effect on p-ERK and c-fos expression was observed in the DRG, and laminae I-II, III-IV, and X of the lumbosacral dorsal horn. Furthermore, a significant interactive effect of NMS and CRD on p-ERK expression was observed in laminae III-IV of the lumbosacral dorsal horn. Correlation analysis revealed the positive association between c-fos- and p-ERK-immunoreactive nuclei numbers in the DRG, lumbosacral dorsal horn, and ACC. These results demonstrate that ERK is actively involved in CRD-evoked neuronal activation in both NH and NMS rats. Moreover, ERK is associated with the upregulated central neuronal sensitivity to noxious CRD in NMS rats, which may be responsible for the behavioral hyperalgesia in NMS rat.


Contributions to the millipede genus Nepalella Shear, 1979 from China, with four new species and first results on phylogeny based on DNA-barcoding (Diplopoda, Chordeumatida, Megalotylidae).
Four new species of the chordeumatidan millipede genus Nepalella Shear, 1979, family Megalotylidae, are described from caves in southern China: N. troglodytes sp. nov., N. lobata sp. nov., N. jinfoshan sp. nov., and N. wangi sp. nov. Three of them (except N. lobata sp. nov.) are presumed troglobites. Additional locality records of two cave congeners, N. caeca Shear, 1999 and N. grandoides Golovatch, Geoffroy & Mauriès, 2006, are also provided. DNA-barcoding based on the COI mitochondrial gene is documented in this genus and for species of the order Chordeumatida outside Europe for the first time. Interspecific p-distances between Nepalella species amount to 8.5-15.9%, while intraspecific p-distances are 0-6.8%. The species of Nepalella are found to show a surprisingly low genetic distance from the European genus Atractosoma Fanzago, 1876, family Craspedosomatidae Gray in Jones, 1843, potentially based on the very limited number of barcoding sequences of the order Chordeumatida being available.


Two nonallelic tRNAiMet genes are located in the p23 leads to q12 region of human chromosome 6.
Two nonallelic human tRNAiMet genes were assigned to chromosome 6 by filter hybridization of DNA from human-rodent somatic cell hybrids by using probes containing unique sequences from the regions flanking each tRNAiMet gene. These unique sequence probes thus allowed each tRNAiMet gene to be analyzed individually in cell hybrids. Both tRNAiMet genes segregated in the hybrid cells with the chromosome 6 enzyme markers, soluble malic enzyme and the mitochondrial form of superoxide dismutase, and also with a karyotypically normal chromosome 6. By using hybrid clones containing translocations that divide chromosome 6 into five segments, both tRNAiMet genes were assigned to the p23 leads to q12 region. These results raise the possibility that other tRNAiMet genes may be syntenic with the two described in this study and illustrate the utility of using unique flanking sequences to identify members of a multigene family.


Global estimates of diabetes prevalence for 2013 and projections for 2035.
Diabetes is a serious and increasing global health burden and estimates of prevalence are essential for appropriate allocation of resources and monitoring of trends. We conducted a literature search of studies reporting the age-specific prevalence for diabetes and used the Analytic Hierarchy Process to systematically select studies to generate estimates for 219 countries and territories. Estimates for countries without available source data were modelled from pooled estimates of countries that were similar in regard to geography, ethnicity, and economic development. Logistic regression was applied to generate smoothed age-specific prevalence estimates for adults 20-79 years which were then applied to population estimates for 2013 and 2035. A total of 744 data sources were considered and 174 included, representing 130 countries. In 2013, 382 million people had diabetes; this number is expected to rise to 592 million by 2035. Most people with diabetes live in low- and middle-income countries and these will experience the greatest increase in cases of diabetes over the next 22 years. The new estimates of diabetes in adults confirm the large burden of diabetes, especially in developing countries. Estimates will be updated annually including the most recent, high-quality data available.


A smectic dodecagonal quasicrystal.
We report a solid smectic phase that exhibits dodecagonal global order. It is composed of axially stacked hexagonally ordered particle layers, and its 12-fold rotational symmetry induced by the 30° rotation of adjacent layers with respect to each other. A quasicrystal was produced in a molecular-dynamics simulation of a single-component system of particles interacting via a spherically-symmetric potential. It was formed as a result of a first-order phase transition from an isotropic liquid state that occurred under constant-density cooling. This finding implies that a similarly structured quasicrystal can possibly be produced by the same class of systems as those forming smectic-B crystals. This quasicrystal can also be expected to arise in a system of spherically-shaped colloidal particles with appropriately tuned potential.


Rational design of dinitroxide biradicals for efficient cross-effect dynamic nuclear polarization.
A series of 37 dinitroxide biradicals have been prepared and their performance studied as polarizing agents in cross-effect DNP NMR experiments at 9.4 T and 100 K in 1,1,2,2-tetrachloroethane (TCE). We observe that in this regime the DNP performance is strongly correlated with the substituents on the polarizing agents, and electron and nuclear spin relaxation times, with longer relaxation times leading to better enhancements. We also observe that deuteration of the radicals generally leads to better DNP enhancement but with longer build-up time. One of the new radicals introduced here provides the best performance obtained so far under these conditions.


Effects of cobalt-60 exposure on health of Taiwan residents suggest new approach needed in radiation protection.
The conventional approach for radiation protection is based on the ICRP's linear, no threshold (LNT) model of radiation carcinogenesis, which implies that ionizing radiation is always harmful, no matter how small the dose. But a different approach can be derived from the observed health effects of the serendipitous contamination of 1700 apartments in Taiwan with cobalt-60 (T(1/2) = 5.3 y). This experience indicates that chronic exposure of the whole body to low-dose-rate radiation, even accumulated to a high annual dose, may be beneficial to human health. Approximately 10,000 people occupied these buildings and received an average radiation dose of 0.4 Sv, unknowingly, during a 9-20 year period. They did not suffer a higher incidence of cancer mortality, as the LNT theory would predict. On the contrary, the incidence of cancer deaths in this population was greatly reduced-to about 3 per cent of the incidence of spontaneous cancer death in the general Taiwan public. In addition, the incidence of congenital malformations was also reduced--to about 7 per cent of the incidence in the general public. These observations appear to be compatible with the radiation hormesis model. Information about this Taiwan experience should be communicated to the public worldwide to help allay its fear of radiation and create a positive impression about important radiation applications. Expenditures of many billions of dollars in nuclear reactor operation could be saved and expansion of nuclear electricity generation could be facilitated. In addition, this knowledge would encourage further investigation and implementation of very important applications of total-body, low-dose irradiation to treat and cure many illnesses, including cancer. The findings of this study are such a departure from expectations, based on ICRP criteria, that we believe that they ought to be carefully reviewed by other, independent organizations and that population data not available to the authors be provided, so that a fully qualified epidemiologically-valid analysis can be made. Many of the confounding factors that limit other studies used to date, such as the A-bomb survivors, the Mayak workers and the Chernobyl evacuees, are not present in this population exposure. It should be one of the most important events on which to base radiation protection standards.


Transgenic expression of CD40 ligand produces an in vivo antitumor immune response against both CD40(+) and CD40(-) plasmacytoma cells.
Because tumor-specific antigens have been identified in multiple myeloma (MM), immunotherapy might provide an additional treatment modality for the disease. Expression of CD40 ligand (CD40L) proximate to the MM cells might serve this purpose, either by increasing their capacity to present self-antigens by activation through their CD40 receptor or by the recruitment of professional antigen-presenting cells (APCs) able to take up and present tumor-associated antigens. To distinguish between these possibilities and predict whether human CD40(-) myeloma might respond to this approach, we examined 3 murine plasmacytoma cell lines, 2 (MPC-11 and S107) expressing the CD40 molecule and 1 (X-24) lacking such expression. Syngeneic BALB/CBYJ mice were inoculated subcutaneously with tumor cells mixed with CL7.1 fibroblasts, retrovirally transduced to express either the mCD40L or the neo gene. For all 3 plasmacytoma cell lines, coinjection with CL7.1/mCD40L significantly reduced local tumor growth compared with controls. This effect was mediated by a systemic antitumor immune response, since mice immunized with tumor and CL7.1/mCD40L were resistant to subsequent challenge with tumor, and tumor growth inhibition was abolished when CD8(+) or CD4(+) lymphocytes were depleted. Because expression of CD40L gave equivalent protection from CD40(+) and CD40(-) tumors and transgenic-CD40L failed to up-regulate costimulatory molecules in either tumor, the protective effects of CD40L probably resulted from recruitment/activation of professional APCs rather than from CD40 activation of plasmacytoma cells. As further support of this concept, we found that mice were also well protected if CL7.1 and CD40L were injected together with apoptotic plasmacytoma cells from these tumors. Hence, transgenic CD40L expression may produce an antimyeloma immune response against either CD40(+) or CD40(-) tumors and may be of therapeutic value for both types of myeloma in humans.


An integrated computational/experimental model of lymphoma growth.
Non-Hodgkin's lymphoma is a disseminated, highly malignant cancer, with resistance to drug treatment based on molecular- and tissue-scale characteristics that are intricately linked. A critical element of molecular resistance has been traced to the loss of functionality in proteins such as the tumor suppressor p53. We investigate the tissue-scale physiologic effects of this loss by integrating in vivo and immunohistological data with computational modeling to study the spatiotemporal physical dynamics of lymphoma growth. We compare between drug-sensitive Eμ-myc Arf-/- and drug-resistant Eμ-myc p53-/- lymphoma cell tumors grown in live mice. Initial values for the model parameters are obtained in part by extracting values from the cellular-scale from whole-tumor histological staining of the tumor-infiltrated inguinal lymph node in vivo. We compare model-predicted tumor growth with that observed from intravital microscopy and macroscopic imaging in vivo, finding that the model is able to accurately predict lymphoma growth. A critical physical mechanism underlying drug-resistant phenotypes may be that the Eμ-myc p53-/- cells seem to pack more closely within the tumor than the Eμ-myc Arf-/- cells, thus possibly exacerbating diffusion gradients of oxygen, leading to cell quiescence and hence resistance to cell-cycle specific drugs. Tighter cell packing could also maintain steeper gradients of drug and lead to insufficient toxicity. The transport phenomena within the lymphoma may thus contribute in nontrivial, complex ways to the difference in drug sensitivity between Eμ-myc Arf-/- and Eμ-myc p53-/- tumors, beyond what might be solely expected from loss of functionality at the molecular scale. We conclude that computational modeling tightly integrated with experimental data gives insight into the dynamics of Non-Hodgkin's lymphoma and provides a platform to generate confirmable predictions of tumor growth.


New Risk-Adjustment Policies Reduce But Do Not Eliminate Special Enrollment Period Underpayment.
Millions of uninsured Americans do not sign up for available coverage despite job loss or other factors that would make them eligible for special enrollment periods (SEPs). Such periods let people enroll in nongroup insurance outside the usual open enrollment period for Marketplace coverage. Concerned that risk adjustment results in underpayment for the health risks associated with SEP enrollees, carriers rarely market their products to consumers eligible for SEPs, and many do not pay agents and brokers to enroll such consumers. To address the apparent underpayments, federal officials added enrollment duration factors that, starting in 2017, increased risk scores for SEP enrollees and other part-year members. Using individual-market claims data for 2015 from two large carriers, we found that risk adjustment did, in fact, undercompensate plans for part-year members. However, underpayment was much larger for SEP enrollees than for part-year members who joined during open enrollment periods. Short-term, urgent health problems appeared to drive enrollment more for SEP enrollees than for part-year members who signed up during open enrollment. We also found that the federal government's enrollment duration factors will remedy underpayment for part-year members whose coverage begins during open enrollment but leave carriers significantly underpaid for SEP enrollees. For carriers to recruit rather than avoid SEP enrollees, further increases to risk adjustment for such enrollees are likely needed.


Endodontic treatment outcomes in a large patient population in the USA: an epidemiological study.
Outcome assessment of endodontic treatment is critical for appropriate case selection and treatment planning. However, reports on outcomes of nonsurgical endodontic treatment vary considerably. Epidemiological studies done in a large patient population and over a long follow-up period can provide the clinician with useful tools for clinical decision-making and assessment of tooth prognosis. In this study, outcomes of initial endodontic treatment done in 1,462,936 teeth of 1,126,288 patients from 50 states across the USA was assessed over a period of 8 yr. Treatment was done by private general practitioners and endodontists participating in the Delta Dental Insurance plan that insures approximately 14 million individuals in the USA. Overall, 97% of teeth were retained in the oral cavity 8 yr after initial nonsurgical endodontic treatment. The combined incidence of untoward events such as retreatments, apical surgeries, and extractions was 3% and occurred mostly within 3 yr from completion of treatment. Analysis of the extracted teeth revealed that 85% had no full coronal coverage. A significant difference was found between covered and noncovered teeth for all tooth groups tested (p < 0.001). In conclusion, it appears that initial nonsurgical endodontic treatment is a predictable procedure with high incidence of tooth retention after 8 yr.


Genetic variability and robustness of host odor preference in Drosophila melanogaster.
Chemosensory stimuli play a crucial role for host selection in insects, including the fruit fly Drosophila melanogaster. Drosophila has been instrumental in unraveling the neurological basis of olfactory processing in insects. Basic knowledge regarding chemical ecology and thorough studies of olfactory preferences are still lacking to a great extent in D. melanogaster, however. We have characterized repeatable variation in olfactory preference between five classical D. melanogaster wild-type strains toward a large array of natural host odors and synthetic compounds. By recording the rate of attraction over up to 24 hr, we could compare stimuli varying in attractiveness and characterize phenotypic parameters on the basis of individual stimuli and the whole stimulus array. Behavioral differences between strains were predominantly due to variation in a single phenotypic parameter: their overall responsiveness toward optimal and suboptimal olfactory stimuli. These differences were not explained by variation in olfactory sensitivity, locomotory activity, or general vigor monitored by survival. Comparisons with three recently established wild-type strains indicated that a high behavioral threshold against accepting suboptimal olfactory stimuli is the characteristic phenotype of wild D. melanogaster.


Quality of life: a critical review of current concepts, measures and their clinical implications.
Quality of life (Q/L) measurements are used to justify or refute different forms of medical treatment; to identify the sequelae of disease or treatment which are resolved by other interventions including nursing and to provide a basis for allocating resources to those treatments judged to be most cost-effective. This paper reviews some of the difficulties in defining and measuring Q/L and the ethical issues raised in relation to their use in allocation of treatment resources. It is suggested that Q/L tests should include a range of dimensions known to contribute to Q/L and that they are applied at different times during the progression of illness and incorporate information obtained from patients. It is essential that weightings by individuals of dimensions investigated in the test are included. Further research is necessary to determine the effects of coping strategies and personality variables on Q/L.


Renovascular hypertension with low-to-normal plasma renin: clinical and angiographic features.
1. Low-to-normal renin renovascular hypertension (RVH) and the accuracy of renal vein renin ratios were investigated in 129 consecutive patients referred for suspected RVH. Forty-nine had essential hypertension, 24 unilateral renoparenchymal hypertension and 56 renal artery obstruction. Of the latter, 86% were diagnosed retrospectively as RVH, based on fall in blood pressure with correction of renal ischaemia. We measured baseline, captopril-stimulated and renal vein plasma renin activity (PRA) levels, as well as several other parameters. 2. PRA was low-to-normal in 37% of the RVH patients [low-to-normal renin (LNR-) RVH group] and elevated in the remaining 63% [high-renin (HR-) RVH group]. In the LNR-RVH group, low-to-normal renin levels, by immunoreactive active renin and plasma renin concentration measurements, and a blunted response of PRA to captopril, were seen. As compared with HR-RVH, LNR-RVH patients had a longer duration of hypertension (P < 0.05), higher serum K+ (P = 0.04) and lower diastolic blood pressure (P = 0.02). However, they did not differ for the other variables, including the fall in blood pressure after correction of renal ischaemia. Although the number of bilateral stenoses was similar in the two groups, no patient in the LNR-RVH group had total renal artery occlusion compared with 53% in the HR-RVH group (P = 0.00015). The accuracy of renal vein renin indices were high enough to justify their use only in the patients with total occlusion of a renal artery. 3. Thus LNR-RVH is common in patients with longstanding hypertension without a totally occluded renal artery. Since the sensitivity of renin measurements is low, cure of hypertension would be precluded for more than one third of RVH patients, if these tests were a prerequisite for identifying RVH.


Allicin purified from fresh garlic cloves induces apoptosis in colon cancer cells via Nrf2.
Allicin (diallyl thiosulfinate) is the best-known biologically active component in freshly crushed garlic extract. We developed a novel, simple method to isolate active allicin, which yielded a stable compound in aqueous solution amenable for use in in vitro and in vivo studies. We focused on the in vitro effects of allicin on cell proliferation of colon cancer cell lines HCT-116, LS174T, HT-29, and Caco-2 and assessed the underlying mechanisms. This allicin preparation exerted a time- and dose-dependent cytostatic effect on these cells at concentrations ranging from 6.2 to 310 μM. Treatment with allicin resulted in HCT-116 apoptotic cell death as demonstrated by enhanced hypodiploid DNA content, decreased levels of B-cell non-Hodgkin lymphoma-2 (Bcl-2), increased levels of bax and increased capability of releasing cytochrome c from mitochondria to the cytosol. Allicin also induced translocation of NF-E2-related factor-2 (Nrf2) to the nuclei of HCT-116 cells. Luciferase reporter gene assay showed that allicin induces Nrf2-mediated luciferase transactivation activity. SiRNA knock down of Nrf2 significantly affected the capacity of allicin to inhibit HCT-116 proliferation. These results suggest that Nrf2 mediates the allicin-induced apoptotic death of colon cancer cells.


Motion of the human mandibular condyle during mastication.
It has been reported that loading to the mandible during closing movement makes the condylar path move more in the superior direction than that during the free closing movement. In this study, the hypothesis was tested that the displacement of the condyle on the chewing side is greater in the direction of the mandibular fossa than that on the non-chewing side. Using a six-degrees-of-freedom jaw movement recording system, we recorded condylar motion in 12 healthy adults without TMD, during the chewing of a large hard gummy jelly. The maximum displacements at the condyle on the chewing side from the maximum intercuspation (CO) position were significantly larger in the superior and medial directions at the initial stage and in the posterior direction at all stages (0.5 mm, 0.5 mm, and 0.6 mm, respectively) than those on the non-chewing side (0.0 mm, 0.1 mm, and 0.1 mm, respectively). This suggests that, in healthy adults, the condyles at CO are located in a position such that excessive load is not applied to the temporomandibular joint when there are the aforementioned displacements.


Stepped wedge randomised controlled trials: systematic review of studies published between 2010 and 2014.
In a stepped wedge, cluster randomised trial, clusters receive the intervention at different time points, and the order in which they received it is randomised. Previous systematic reviews of stepped wedge trials have documented a steady rise in their use between 1987 and 2010, which was attributed to the design's perceived logistical and analytical advantages. However, the interventions included in these systematic reviews were often poorly reported and did not adequately describe the analysis and/or methodology used. Since 2010, a number of additional stepped wedge trials have been published. This article aims to update previous systematic reviews, and consider what interventions were tested and the rationale given for using a stepped wedge design. We searched PubMed, PsychINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science, the Cochrane Library and the Current Controlled Trials Register for articles published between January 2010 and May 2014. We considered stepped wedge randomised controlled trials in all fields of research. We independently extracted data from retrieved articles and reviewed them. Interventions were then coded using the functions specified by the Behaviour Change Wheel, and for behaviour change techniques using a validated taxonomy. Our review identified 37 stepped wedge trials, reported in 10 articles presenting trial results, one conference abstract, 21 protocol or study design articles and five trial registrations. These were mostly conducted in developed countries (n = 30), and within healthcare organisations (n = 28). A total of 33 of the interventions were educationally based, with the most commonly used behaviour change techniques being 'instruction on how to perform a behaviour' (n = 32) and 'persuasive source' (n = 25). Authors gave a wide range of reasons for the use of the stepped wedge trial design, including ethical considerations, logistical, financial and methodological. The adequacy of reporting varied across studies: many did not provide sufficient detail regarding the methodology or calculation of the required sample size. The popularity of stepped wedge trials has increased since 2010, predominantly in high-income countries. However, there is a need for further guidance on their reporting and analysis.


TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling.
Bone marrow (BM) produces all blood and immune cells deriving from hematopoietic stem cells (HSCs). The decrease of immune cell production during aging is one of the features of immunosenescence. The impact of redox dysregulation in BM aging is still poorly understood. Here we use TP53INP1-deficient (KO) mice endowed with chronic oxidative stress to assess the influence of aging-associated redox alterations in BM homeostasis. We show that TP53INP1 deletion has no impact on aging-related accumulation of HSCs. In contrast, the aging-related contraction of the lymphoid compartment is mitigated in TP53INP1 KO mice. B cells that accumulate in old KO BM are differentiating cells that can mature into functional B cells. Importantly, this phenotype results from B cell-intrinsic events associated with defective redox control. Finally, we show that oxidative stress in aged TP53INP1-deficient mice maintains STAT5 expression and activation in early B cells, driving high Pax5 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.


Personal experiences of women with diabetes who do not attend pre-pregnancy care.
To explore the views of women who did not attend pre-pregnancy care (PPC), in particular their accounts of contraception, previous pregnancies and the influence of healthcare advice. We conducted semi-structured interviews with 29 pregnant women (21 with Type 1 diabetes, eight with Type 2 diabetes) at three UK specialist diabetes antenatal clinics. Interviews explored women's journeys to becoming pregnant, including use of contraception, their views regarding diabetes and pregnancy and the factors which encouraged and discouraged them from attending PPC. All women had some understanding of the issues concerning diabetes during pregnancy, predominantly regarding the benefits of PPC (90%) and optimal glycaemic control (80%) and risks of malformation (48%) and macrosomia (35%). Most were not regularly using contraception (70%), having stopped deliberately (45%), become unintentionally less rigorous (28%) or experienced side effects/contraindications (14%). Knowledge concerning the risks of pregnancy (90%) and past pre-conception counselling (38%) did not encourage women to attend PPC, and neither did personal experience of miscarriage, malformation or stillbirth in women with previous poor pregnancy outcome (41%). Barriers included conceiving faster than anticipated (45%), fertility concerns (31%), negative experiences with health professionals (21%), desire for a 'normal' pregnancy (17%) and the logistics of attending (10%). More integrated diabetes and reproductive health/contraceptive advice, increased awareness of the potentially short time between stopping contraception and conception and more intensive support between pregnancies are required, particularly for women with previously poor outcomes. Research is also needed into how communication between health professionals and women with diabetes can be improved.


Eliciting preferences for social health insurance in Ethiopia: a discrete choice experiment.
As low-income countries are initiating health insurance schemes, Ethiopia is also planning to move away from out-of-pocket private payments to health insurance. The success of such a policy depends on understanding and predicting preferences of potential enrolees. This is because a scarce health care budget forces providers and consumers to make trade-offs between potential benefits within a health insurance. An assessment of preferences of potential enrolees can therefore add important information to optimal resource allocation in the design of health insurance. We used a discrete choice experiment to elicit preferences for social health insurance (SHI) among formal sector employees in Ethiopia. Respondents were presented with 18 binary hypothetical choices of SHI. Each insurance package was described by eight policy relevant attributes: premium, enrolment, exclusions, providers and coverage of inpatient services, outpatient services, drugs and tests. A mixed logit model was estimated to determine respondents' willingness to pay (WTP) for the different health insurance attributes. We also predicted probabilities of uptake for alternative SHI scenarios. Health insurance packages with 'no exclusions', 'public and private' providers, low rate of premium and full coverage of tests and drugs were highly valued and had greatest impact on the choices . Other things being equal, respondents were willing to contribute 1.52% (95% confidence interval (CI): 0.71, 2.32) of their salary to a SHI package with no service exclusions having public and private service providers. This is substantially lower than the proposed 3% premium in the draft SHI strategy. For the typical SHI package proposed by the SHI strategy at the time, the uptake probability was predicted to be 29% (95% CI: 0.25, 0.33). The low uptake probability and WTP for the proposed SHI package suggests considering preferences of the potential enrolees' in revisions of the draft SHI strategy for introduction of optimal SHI scheme would enhance acceptance.


Farmer health and adaptive capacity in the face of climate change and variability. Part 2: Contexts, personal attributes and behaviors.
This study extends the emerging body of research on farmer adaptation to climate change, by segmenting farmers on the basis of specific attributes (health, values, belief about climate change, sense of responsibility for climate change, desire to change, social, human and financial capitals and farmer demographics) and considering such attributes as critical social aspects of the contextualized capacity to adapt. The segmental analysis was based on a nationally representative sample of 3,993 farmers concerned with farmer adaptation of climate risks. The resulting data were subjected to two-step cluster analysis to identify homogenous groups of farmers based on factors related to climate change adaptation. A three-cluster solution was identified wherein farmers were distinguishable on the basis of belief in climate change, desire for financial assistance and advice, social connectedness, information seeking, and adverse farm conditions. The largest group (Cluster 1: 55%) was characterized by farmers who recognized being affected by drought and drying and who were actively engaged in adaptive practices, despite the fact that they had little income and poor farm resources. One third of these farmers reported that their health was a barrier to sustained activity in farming. Cluster 2 (26%) was characterized by farmers not readily affected by drying, who enjoyed good incomes, good health and better farming conditions. They expressed little desire to adapt. The smallest cluster (Cluster 3: 19%) was also characterized by farmers who recognized that they were affected by drying. However, despite a desire to adapt, they had very little means to do so. They reported the poorest natural resources and the poorest health, despite being younger. The findings suggest that it is the intent to adapt, starting from where people are at, which is a more important indicator of the capacity to work towards sustainable practices than assets tests alone.


Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces cerevisiae.
Uncovering genetic control of variation in ethanol tolerance in natural populations of yeast Saccharomyces cerevisiae is essential for understanding the evolution of fermentation, the dominant lifestyle of the species, and for improving efficiency of selection for strains with high ethanol tolerance, a character of great economic value for the brewing and biofuel industries. To date, as many as 251 genes have been predicted to be involved in influencing this character. Candidacy of these genes was determined from a tested phenotypic effect following gene knockout, from an induced change in gene function under an ethanol stress condition, or by mutagenesis. This article represents the first genomics approach for dissecting genetic variation in ethanol tolerance between two yeast strains with a highly divergent trait phenotype. We developed a simple but reliable experimental protocol for scoring the phenotype and a set of STR/SNP markers evenly covering the whole genome. We created a mapping population comprising 319 segregants from crossing the parental strains. On the basis of the data sets, we find that the tolerance trait has a high heritability and that additive genetic variance dominates genetic variation of the trait. Segregation at five QTL detected has explained approximately 50% of phenotypic variation; in particular, the major QTL mapped on yeast chromosome 9 has accounted for a quarter of the phenotypic variation. We integrated the QTL analysis with the predicted candidacy of ethanol resistance genes and found that only a few of these candidates fall in the QTL regions.


Identification of acquired antimicrobial resistance genes.
Identification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic laboratories and is anticipated to substitute traditional methods for resistance gene identification. Thus, the current challenge is to extract the relevant information from the large amount of generated data. We developed a web-based method, ResFinder that uses BLAST for identification of acquired antimicrobial resistance genes in whole-genome data. As input, the method can use both pre-assembled, complete or partial genomes, and short sequence reads from four different sequencing platforms. The method was evaluated on 1862 GenBank files containing 1411 different resistance genes, as well as on 23 de-novo-sequenced isolates. When testing the 1862 GenBank files, the method identified the resistance genes with an ID = 100% (100% identity) to the genes in ResFinder. Agreement between in silico predictions and phenotypic testing was found when the method was further tested on 23 isolates of five different bacterial species, with available phenotypes. Furthermore, ResFinder was evaluated on WGS chromosomes and plasmids of 30 isolates. Seven of these isolates were annotated to have antimicrobial resistance, and in all cases, annotations were compatible with the ResFinder results. A web server providing a convenient way of identifying acquired antimicrobial resistance genes in completely sequenced isolates was created. ResFinder can be accessed at www.genomicepidemiology.org. ResFinder will continuously be updated as new resistance genes are identified.


Environmental mercury contamination in China: sources and impacts.
This review article focused on the current status of mercury (Hg) contamination in different ecological compartments in China, and their possible environmental and health impacts, focusing on some major cities. Mercury emission from non-ferrous metals smelting (especially zinc smelting), coal combustion and miscellaneous activities (of which battery and fluorescent lamp production and cement production are the largest), contributed about 45%, 38% and 17%, respectively, to the total Hg emission based on the data of 1999. Mercury contamination is widespread in different ecological compartments such as atmosphere, soil and water. There is evidence showing bioaccumulation and biomagnification of Hg in aquatic food chains, with higher concentrations detected in carnivorous fish. In terms of human exposure to Hg, fish consumption is the major exposure pathway for residents living in coastal cities such as Hong Kong, but inhalation may be another major source, affecting human health in areas with severe atmospheric Hg, such as Guiyang City (Guizhou Province). The first case study indicated that after closure of the acetic acid plant 20 years at Songyuan City (Jilin Province), 16.7% of residents' hair still contained Hg concentration in excess of 1 mg/kg (the reference dosage value, RfD set by USEPA). The second case study indicated that the male residents of Hong Kong who consumed more than four or more meals of fish per week tended to contain higher Hg in their hair, which was linked to their subfertility. There is also increasing evidence showing that skin disorders and autism in Hong Kong children are related to their high Hg body loadings (hair, blood and urine), through prenatal methyl Hg exposure. There seems to be an urgent need to identify the sources of Hg, speciation and concentrations in different ecological compartments, which may lead to high body loadings in human beings. Adverse health effects of residents living in places with a higher background level of Hg, due to long-term exposure to chronic levels of Hg through oral intake should not be overlooked.


The Hebb repetition effect in simple and complex memory span.
The Hebb repetition effect refers to the finding that immediate serial recall is improved over trials for memory lists that are surreptitiously repeated across trials, relative to new lists. We show in four experiments that the Hebb repetition effect is also observed with a complex-span task, in which encoding or retrieval of list items alternates with an unrelated processing task. The interruption of encoding or retrieval by the processing task did not reduce the size of the Hebb effect, demonstrating that incidental long-term learning forms integrated representations of lists, excluding the interleaved processing events. Contrary to the assumption that complex-span performance relies more on long-term memory than standard immediate serial recall (simple span), the Hebb effect was not larger in complex-span than in simple-span performance. The Hebb effect in complex span was also not modulated by the opportunity for refreshing list items, questioning a role of refreshing for the acquisition of the long-term memory representations underlying the effect.


Complex regional pain syndrome type I in children: What is new?
Complex regional pain syndrome type I (CRPS-I), although first described by the French surgeon Ambroise Paré as far back as the 16th century, nevertheless remains shrouded in mystery. The most common symptoms are pain in an entire hand or foot, allodynia, functional impairment induced by the pain, local oedema and skin color changes and transient sweating abnormalities. Most cases occur after a minor injury (i.e., a sprain or fracture), although there may be no identifiable triggering event, particularly in children. Primarily cold CRPS-I is by far the most common variant in children. Development of the Budapest criteria has benefited the diagnosis. These criteria are clinical and no specific diagnostic investigation is available. In vitro and in vivo studies have established that several pathogenic mechanisms can be involved concomitantly. However, there is no satisfactory explanation to the full clinical spectrum. Blood tests and imaging studies are useful for ruling out other diagnoses then monitoring the course of the condition, which may involve the development of demineralisation or osteopenia. High-resolution peripheral quantitative computed tomography may be helpful, as it provides quantitative assessments of the cortical and trabecular bone. CRPS-I has several specific characteristics in children compared to adults and whether the condition is the same entity in these two age groups is a legitimate question. The optimal management involves an early diagnosis followed by a multidisciplinary management programme of functional rehabilitation therapy and cognitive behavioral therapy. Analgesics are useful only during the phase of acute pain and to facilitate physical therapy. Studies in adults showed that bisphosphonates were effective within the first 12 months after symptom onset and calcitonin in longer-lasting cases. No high-quality clinical research studies into the aetiopathogenesis and treatment of CRPS-I in children and adolescents are available to date.