Health issues for adults with developmental disability.
The aim of this paper is to review recent literature on health issues for adults with developmental disability and reflect on how this research informs service provision, future research work, and social and health policy. Studies based on mortality data are most likely to aim at identifying individuals most at risk of premature death, and some researchers argue that health-oriented service systems appear ill-equipped to address the needs of the at risk groups. Morbidity studies highlight specific health concerns found in this population and commonly report high rates of untreated, yet treatable, conditions. The emerging literature on the behavioral determinants of health suggests risk of preventable morbidity and mortality because of the lack of health-promoting behaviors, particularly in relation to diet and physical activity. Of particular interest in this literature is the affect of living arrangements on health promoting activities. This paper concludes that future directions in health research for adults with developmental disability will be concerned with the complexity of the interactions between biology, pathology, and behavioral and environmental determinants. More use of self-reported health studies is suggested, as well as further exploration of effective strategies of health promotion and health promoting decision-making and self-determination among this population.


Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats.
Dopamine D2-like partial agonists such as aripiprazole have received some attention as potential pharmacotherapies for the treatment of psychostimulant addiction. However, the preclinical evaluations so far have focused on acute effects of aripiprazole. We tested the hypothesis that aripiprazole, both as acute and as chronic treatment, would preferentially decrease cocaine self-administration while sparing behavior maintained by a natural reinforcer, resulting in a shift in the allocation of behavior from cocaine-taking towards the alternative reinforcer. Rats were trained to self-administer intravenous cocaine in a concurrent choice procedure, with a palatable food as the competing reinforcer, under a fixed ratio (FR) 1 FR 5 chain schedule. Aripiprazole was then administered as continuous infusion by osmotic minipumps for 5 days, during which performance in the choice procedure was assessed daily. An intermediate dose of aripiprazole decreased cocaine self-administration and shifted the cocaine choice curve to the right as an acute treatment. However, as a chronic treatment, aripiprazole failed to decrease cocaine self-administration or cocaine choice, despite a dose-dependent decrease in overall response rates and food-maintained behavior. Our results confirm and extend earlier findings and indicate that acute administration of aripiprazole can decrease cocaine self-administration. However, based on the present data, chronic treatment with aripiprazole does not show much promise as a potential pharmacotherapy for cocaine addiction. Both acute and chronic treatment data are in agreement with published clinical findings, suggesting that the concurrent choice procedure in rats has predictive validity of efficacy in humans.


Evidence on the cost-effectiveness of lifelong antiretroviral therapy for prevention of mother-to-child transmission of HIV: implications for resource-limited countries in sub-Saharan Africa.
The 2016 World Health Organization (WHO) consolidated guideline recommends lifelong antiretroviral therapy (ART) for all HIV-infected pregnant and breastfeeding women for preventing mother-to-child HIV transmission (PMTCT). Ambiguity remains about the cost-effectiveness of this strategy in resource-limited developing countries. Areas covered: We reviewed model-based studies on the cost-effectiveness of lifelong ART (formerly Option B+) relative to previous WHO guidelines for PMTCT. Our search using PubMed, Medline and Google Scholar for articles on Option B+ resulted in the final inclusion of seven studies published between 2012 and 2016. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to assess the quality of reporting. Outcomes of interest, which included infant infections averted, maternal quality and length of life, and the Incremental Cost Effectiveness Ratio (ICER), were used in comparing cost-effectiveness. Expert commentary: Despite most model-based studies favouring lifelong ART (Option B+) in terms of its cost-effectiveness in comparison to Options A and B, inclusiveness of the evidence remains weak for generalization. This is largely because setting specificity for providing lifelong ART to all pregnant and breastfeeding women may differ significantly in each setting. Consequently, future cost-effectiveness studies should be robust, setting-specific, and endeavor to assess the willingness and ability to pay of each setting.


Atmospheric particulate matter pollution during the 2008 Beijing Olympics.
Size fractionated particulate matter (PM) samples (including PM2.5 and PM10) were collected at Peking University in Northwestern Beijing, China for a 2 week period prior to the Olympics, during the 2 week period of the Olympics, and for a 4 week period following the 2008 Olympics, during both source control and nonsource control periods. PM10 concentrations in this study were high correlated with, but a factor of 1.3 times higher than, the Beijing Environmental Protection Bureau's PM10 concentrations at near-by sites because of differences in the measurement methods used. The mean PM2.5 and PM10 concentrations were statistically different, and lower by 31 and 35%, during the Olympic period compared to the non-Olympic period. However, the PM concentrations were not statistically different between the source control and nonsource control periods. While meteorological parameters (air masses from the south and precipitation) accounted for 40% of the total variation in PM10 concentration, source control accounted for 16%, suggesting that meteorology accounted for more of the variation in PM concentration than source control measures. The PM10 concentrations in Beijing during the Olympic period were 2.9, 3.5, and 1.9 times higher than those in Atlanta, Sydney, and Athens. In addition, the PM2.5 and PM10 concentrations during the Olympic period exceeded the WHO 24-h guideline 100% and 81% of the time, respectively. Finally, the PM10 concentrations in October, November, and December 2008 were reduced by 9-27% compared to the same months in 2007, suggesting that the Olympic source control efforts (and possibly a down turn in the economy) have resulted in lower PM10 concentrations in Beijing.


Ecologic observations on anopheline vectors of malaria in the Brazilian Amazon.
Human intervention in the Brazilian Amazon region promotes contacts between humans and vectors that may favor the propagation of anopheline mosquitoes and the spread of malaria in the absence of planning and infrastructure to control this disease. Vector ecology studies were carried out to determine the risk areas. These data should help in designing appropriate malaria control measures. Data from 14 different regions are reported. Vectors are able to adapt to different environments, which made it necessary to study each area. The parameters studied were Anopheles breeding sites, species distribution, incidence, feeding preferences, hours of maximum activity of adult mosquitoes, seasonality, resting places, and the presence of Plasmodium. Species complexes were also studied. Anopheles darlingi may be responsible for maintaining malaria in human populations in this region. A reduction in the population density of A. darlingi in a particular geographic area can sometimes cause the disappearance of malaria. This species feeds at night but has a peak of activity at the beginning of the evening and another at dawn. Other species are mainly crepuscular and all anophelines demonstrated pronounced exophilia. The timing of feeding activities was found to vary in areas altered by human intervention and also depended on the time of the year and climatic conditions. The larvae were more abundant in the rivers with a less acidic pH and rural areas showed the highest larval index.


The role of alternative anastomosis sites in occipital artery-posterior inferior cerebellar artery bypass in the absence of the caudal loop using the far-lateral approach.
OBJECTIVE Occipital artery-posterior inferior cerebellar artery (OA-PICA) bypass is a technically challenging procedure for posterior fossa revascularization. The caudal loop of the PICA is considered the optimal site for OA-PICA anastomosis, however its absence can increase the technical difficulty associated with this procedure. The use of the far-lateral approach for accessing alternative anastomosis sites in OA-PICA bypass in patients with absent or unavailable caudal loops of PICA is evaluated. METHODS A morphometric analysis of OA-PICA bypass with anastomosis on each segment of the PICA was performed on 5 cadaveric specimens through the conventional midline foramen magnum and far-lateral approaches. The difficulty level associated with anastomoses at each segment was qualitatively assessed in each approach for exposure and maneuverability by multiple surgeons. A series of 8 patients who underwent OA-PICA bypass for hemodynamic ischemia or ruptured dissecting posterior fossa aneurysms are additionally reviewed and described, and the clinical significance of the caudal loop of PICA is discussed. RESULTS Anastomosis on the caudal loop could be performed more superficially than on any other segment (p < 0.001). A far-lateral approach up to the medial border of the posterior condylar canal provided a 13.5 ± 2.2-mm wider corridor than the conventional midline foramen magnum approach, facilitating access to alternative anastomosis sites. The far-lateral approach was successfully used for OA-PICA bypass in 3 clinical cases whose caudal loops were absent, whereas the midline foramen magnum approach provided sufficient exposure for caudal loop bypass in the remaining 5 cases. CONCLUSIONS The absence of the caudal loop of the PICA is a major contributing factor to the technical difficulty of OA-PICA bypass. The far-lateral approach is a useful surgical option for OA-PICA bypass when the caudal loop of the PICA is unavailable.


Incidence, Management and Short-Term Outcome of Stroke in a General Population of 1.4 Million Japanese - Shiga Stroke Registry.
This study determined the current status of the incidence, management, and prognosis of stroke in Japan using a population-based stroke registry.Methods and Results:Shiga Stroke Registry is an ongoing population-based registry that covers approximately 1.4 million residents of Shiga Prefecture. Cases of acute stroke were identified using standard definitions through surveillance of both all acute-care hospitals with neurology/neurosurgery facilities and death certificates in 2011. A total of 2,956 stroke cases and 2,176 first-ever stroke cases were identified. The age- and sex-adjusted incidence rate for first-ever stroke using the 2013 European Standard Population as standard was per 100,000 person-years: 91.3 for ischemic stroke, 36.4 for intracerebral hemorrhage, and 13.7 for subarachnoid hemorrhage. It was estimated that approximately 220,000 new strokes occurred in 2011 in Japan. Among the 2,956 cases, most stroke patients underwent neuroimaging, 268 received surgical or endovascular treatment, and 2,158 had rehabilitation therapy; 78 patients received intravenous thrombolysis. A total of 1,846 stroke patients had died or were dependent at hospital discharge, and 390 died within 28 days of onset. Incidence rates of stroke by subtypes were clarified and the total number of new strokes in Japan was estimated. More than half of stroke patients die or become dependent after a stroke. This study re-emphasized the importance of public health measures in reducing the burden of stroke in Japan.


Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development.
What is the origin and composition of cell-free DNA in human embryo spent culture media? Cell-free DNA from human embryo spent culture media represents a mix of maternal and embryonic DNA, and the mixture can be more complex for mosaic embryos. In 2016, ~300 000 human embryos were chromosomally and/or genetically analyzed using preimplantation genetic testing for aneuploidies (PGT-A) or monogenic disorders (PGT-M) before transfer into the uterus. While progress in genetic techniques has enabled analysis of the full karyotype in a single cell with high sensitivity and specificity, these approaches still require an embryo biopsy. Thus, non-invasive techniques are sought as an alternative. This study was based on a total of 113 human embryos undergoing trophectoderm biopsy as part of PGT-A analysis. For each embryo, the spent culture media used between Day 3 and Day 5 of development were collected for cell-free DNA analysis. In addition to the 113 spent culture media samples, 28 media drops without embryo contact were cultured in parallel under the same conditions to use as controls. In total, 141 media samples were collected and divided into two groups: one for direct DNA quantification (53 spent culture media and 17 controls), the other for whole-genome amplification (60 spent culture media and 11 controls) and subsequent quantification. Some samples with amplified DNA (N = 56) were used for aneuploidy testing by next-generation sequencing; of those, 35 samples underwent single-nucleotide polymorphism (SNP) sequencing to detect maternal contamination. Finally, from the 35 spent culture media analyzed by SNP sequencing, 12 whole blastocysts were analyzed by fluorescence in situ hybridization (FISH) to determine the level of mosaicism in each embryo, as a possible origin for discordance between sample types. Trophectoderm biopsies and culture media samples (20 μl) underwent whole-genome amplification, then libraries were generated and sequenced for an aneuploidy study. For SNP sequencing, triads including trophectoderm DNA, cell-free DNA, and follicular fluid DNA were analyzed. In total, 124 SNPs were included with 90 SNPs distributed among all autosomes and 34 SNPs located on chromosome Y. Finally, 12 whole blastocysts were fixed and individual cells were analyzed by FISH using telomeric/centromeric probes for the affected chromosomes. We found a higher quantity of cell-free DNA in spent culture media co-cultured with embryos versus control media samples (P ≤ 0.001). The presence of cell-free DNA in the spent culture media enabled a chromosomal diagnosis, although results differed from those of trophectoderm biopsy analysis in most cases (67%). Discordant results were mainly attributable to a high percentage of maternal DNA in the spent culture media, with a median percentage of embryonic DNA estimated at 8%. Finally, from the discordant cases, 91.7% of whole blastocysts analyzed by FISH were mosaic and 75% of the analyzed chromosomes were concordant with the trophectoderm DNA diagnosis instead of the cell-free DNA result. This study was limited by the sample size and the number of cells analyzed by FISH. This is the first study to combine chromosomal analysis of cell-free DNA, SNP sequencing to identify maternal contamination, and whole-blastocyst analysis for detecting mosaicism. Our results provide a better understanding of the origin of cell-free DNA in spent culture media, offering an important step toward developing future non-invasive karyotyping that must rely on the specific identification of DNA released from human embryos. This work was funded by Igenomix S.L. There are no competing interests.


Sea-level projections representing the deeply uncertain contribution of the West Antarctic ice sheet.
There is a growing awareness that uncertainties surrounding future sea-level projections may be much larger than typically perceived. Recently published projections appear widely divergent and highly sensitive to non-trivial model choices. Moreover, the West Antarctic ice sheet (WAIS) may be much less stable than previous believed, enabling a rapid disintegration. Here, we present a set of probabilistic sea-level projections that approximates the deeply uncertain WAIS contributions. The projections aim to inform robust decisions by clarifying the sensitivity to non-trivial or controversial assumptions. We show that the deeply uncertain WAIS contribution can dominate other uncertainties within decades. These deep uncertainties call for the development of robust adaptive strategies. These decision-making needs, in turn, require mission-oriented basic science, for example about potential signposts and the maximum rate of WAIS-induced sea-level changes.


An optimally evolved connective ratio of neural networks that maximizes the occurrence of synchronized bursting behavior.
Synchronized bursting activity (SBA) is a remarkable dynamical behavior in both ex vivo and in vivo neural networks. Investigations of the underlying structural characteristics associated with SBA are crucial to understanding the system-level regulatory mechanism of neural network behaviors. In this study, artificial pulsed neural networks were established using spike response models to capture fundamental dynamics of large scale ex vivo cortical networks. Network simulations with synaptic parameter perturbations showed the following two findings. (i) In a network with an excitatory ratio (ER) of 80-90%, its connective ratio (CR) was within a range of 10-30% when the occurrence of SBA reached the highest expectation. This result was consistent with the experimental observation in ex vivo neuronal networks, which were reported to possess a matured inhibitory synaptic ratio of 10-20% and a CR of 10-30%. (ii) No SBA occurred when a network does not contain any all-positive-interaction feedback loop (APFL) motif. In a neural network containing APFLs, the number of APFLs presented an optimal range corresponding to the maximal occurrence of SBA, which was very similar to the optimal CR. In a neural network, the evolutionarily selected CR (10-30%) optimizes the occurrence of SBA, and APFL serves a pivotal network motif required to maximize the occurrence of SBA.


Gauging the Purported Costs of Public Data Archiving for Long-Term Population Studies.
It was recently proposed that long-term population studies be exempted from the expectation that authors publicly archive the primary data underlying published articles. Such studies are valuable to many areas of ecological and evolutionary biological research, and multiple risks to their viability were anticipated as a result of public data archiving (PDA), ultimately all stemming from independent reuse of archived data. However, empirical assessment was missing, making it difficult to determine whether such fears are realistic. I addressed this by surveying data packages from long-term population studies archived in the Dryad Digital Repository. I found no evidence that PDA results in reuse of data by independent parties, suggesting the purported costs of PDA for long-term population studies have been overstated.


Carbohydrate-dense snacks are a key feature of the nutrition transition among Ghanaian adults - findings from the RODAM study.
African populations in sub-Saharan Africa and African migrants in Europe are facing a rapid upsurge in obesity. This trend has been related to urbanization, migration and associated shifts in lifestyle, including dietary habits. Whether changes in eating patterns contribute to the rising burden of obesity among African populations is currently unknown. Our aims in conducting this study were to characterize eating patterns among Ghanaian adults living in their country of origin and in Europe and to explore associations of meal patterns with body mass index (BMI). Within the cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study, data of single 24-h dietary recalls from Ghanaian adults in rural Ghana (n = 20), urban Ghana (n = 42), and Europe (n = 172) were recorded. Eating frequencies, energy intake, and macronutrient composition of eating occasions (EOs, i.e. meals or snacks) were compared between study sites based on descriptive statistics and χ 2-/Kruskal-Wallis tests. A rising gradient of EO frequencies from rural Ghana through urban Ghana to Europe was observed, mainly reflecting the differences in snacking frequencies (≥1 snack per day: 20 vs. 48 vs. 52%, P = 0.008). Meal frequencies were similar across study sites (≥3 meals per day: 30 vs. 33 vs. 38%, P = 0.80). Meals were rich in carbohydrates (median 54.5, interquartile range (IQR): 43.2-64.0 energy%) and total fats (median: 27.0, IQR: 19.9-34.4 energy %); their protein content was lowest in rural Ghana, followed by urban Ghana and Europe (P = 0.0005). Snacks mainly contained carbohydrates (median: 75.7, IQR: 61.0-89.2 energy%). In linear regression analyses, there was a non-significant trend for an inverse association between snacking frequencies and BMI. The observed integration of carbohydrate-dense snacks into the diet supports the growing evidence for a nutrition transition among African populations undergoing socioeconomic development. This analysis constitutes a starting point to further investigate the nutritional implications of increased snacking frequencies on obesity and metabolic health in these African populations.


Sodium and salt content of Portuguese rolls produced in a city of southern Brazil: a comparison of laboratory analysis, food labelling and nutrition standards.
To analyse the Na content of bread by comparing the amount of salt and Na among the label, laboratory analysis and international guidelines. Ten selected bakeries provided 3239 randomly selected samples of bread, which were weighed on-site. Triplicate samples were retrieved from each bakery (thirty samples) for analysis. Bread production was observed, and ingredient labels were queried to determine salt weights, which were used for comparison with the laboratory analysis. Flame photometry and the method for chlorides were utilised for analysing Na. Laboratory findings were compared to nine different international nutritional guidelines for Na consumption. Florianopolis, south of Brazil. Ninety independent bakeries locally producing Portuguese rolls were queried; rolls from ten conveniently selected bakeries were retrieved for further analysis. The average weight of the rolls was 50·2 ± 5·3 g. The average amount of salt (g) per roll, by laboratory and label analyses, was 0·69 ± 0·0 and 0·62 ± 0·1 g, respectively. The mean level of Na (mg) reported on nutrient labels (478·2 ± 93·4/100 g) was significantly lower than by laboratory analysis (618·2 ± 73·8/100 g), P < 0·001. There was a difference for Na in rolls produced in the bakeries considering the unit weight of rolls (P ≤ 0·001) per 100 g (P = 0·026) and the mode of production. The consumption of two averaged units of rolls was equivalent to 51·7 % of the Brazilian guideline daily amount for Na for children and 31 % for adults. The nutrient labels underreported Na values. This study strengthens the importance of monitoring Na of breads in Brazil.


Comparison of the effects of micro-osteoperforation and corticision on the rate of orthodontic tooth movement in rats.
To investigate the effects of flapless micro-osteoperforation and corticision on the rate of orthodontic tooth movement in rats. Forty-five 8-week-old male Sprague-Dawley rats were divided into the following groups: micro-osteoperforation and orthodontic force (MOP + F), corticision and orthodontic force (C + F), and orthodontic force only (F, control). The left maxillary first molars were pulled forward with a force of 50 g. Flapless surgical interventions were conducted in the MOP + F and C + F groups. The total duration of the experiment was 6 weeks. Alveolar bone density and the number of osteoclasts were evaluated using microcomputed tomography and histologic examination, respectively. The tooth movement distance was significantly higher in both experimental groups than in the control group. Bone density and bone mineral density decreased in the MOP + F and C + F groups. The number of osteoclasts in the MOP + F and C + F groups was significantly higher than in the control group F. The two minimally invasive flapless surgical interventions increased bone remodeling and osteoclast activity and induced faster orthodontic tooth movement for at least 2 weeks in rats. No differences were observed between the outcome of flapless micro-osteoperforation and corticision in the rats.


[Quality criteria in Qualitative Research in Health: notes for a necessary debate].
The importance of gaining further knowledge as to the health-related needs and expectations of individuals, as well as of the factors involved in the effectiveness of health care activities, particularly of the professionals proper, make it possible to anticipate a boom in Qualitative Research in fields such as Public Health and Health Service Research. Such an increase should go hand in hand with a progressive improvement in the quality of the outcomes of research, to which end tools for assessing said quality are required. However, the epistemological implications of the qualitative focus contribute to the setting of the bounds of these tolls having been a source of controversy at both the conceptual level as well as with regard to the methods and techniques to be employed, although without hardly any involvement on the part of the health sciences in our country. This article provides a brief review of the main points of reference of said debate and, after stressing the importance of the theoretical development and of precision in practice, as well as the function of the guides with regard thereto, the epistemological adaptation, relevance, validity and reflexivity as possible basic criteria for the assessment of the quality of Qualitative Research are proposed.


Effects of awareness that food intake is being measured by a universal eating monitor on the consumption of a pasta lunch and a cookie snack in healthy female volunteers.
To date, there have been no studies that have explicitly examined the effect of awareness on the consumption of food from a Universal Eating Monitor (UEM - hidden balance interfaced to a computer which covertly records eating behaviour). We tested whether awareness of a UEM affected consumption of a pasta lunch and a cookie snack. 39 female participants were randomly assigned to either an aware or unaware condition. After being informed of the presence of the UEM (aware) or not being told about its presence (unaware), participants consumed ad-libitum a pasta lunch from the UEM followed by a cookie snack. Awareness of the UEM did not significantly affect the amount of pasta or cookies eaten. However, awareness significantly reduced the rate of cookie consumption. These results suggest that awareness of being monitored by the UEM has no effect on the consumption of a pasta meal, but does influence the consumption of a cookie snack in the absence of hunger. Hence, energy dense snack foods consumed after a meal may be more susceptible to awareness of monitoring than staple food items.


Infective pentastomid larvae from Pygocentrus nattereri Kner (Pisces, Characidae) from the Miranda River, Pantanal, Mato Grosso do Sul State, Brazil, with notes on their taxonomy and epidemiology.
During parasitological surveys of freshwater fish from the Miranda River, Brazil, 199 Pygocentrus nattereri Kner (Characidae) were caught. Two pentastomid families, Subtriquetridae Fain, 1961, represented by its single genus Subtriquetra Sambon, 1922, and Sebekidae Sambon, 1922, represented by three genera, were present. Free-living larvae of Subtriquetra subtriquetra (Diesing, 1835) were collected from the swim bladder. Encysted larvae of Alofia Giglioli, 1922 were found in the abdominal cavity, chambers of the heart, musculature, on the surface of the gonads and swim bladder. Some Alofia larvae were moving freely in the swim bladder. Larvae of Sebekia Sambon, 1922 were encysted in the musculature. Some larvae of Leiperia Sambon, 1922 were found encysted in the musculature and on the surface of the pyloric caeca, whereas others occurred free in the abdominal cavity. In some of the latter, the head was buried deep in the wall of the intestine, stomach or ovaries, whereas the rest of their body remained free. Infective pentastomid larvae were present throughout the year with an overall prevalence of 77%. Both prevalence and intensity were higher in members of the Sebekidae than in Su. subtriquetra, possibly due to the latter's mode of transmission and its high pathogenicity. No sex-related, statistically significant differences (p > 0.05) in prevalence or abundance were found. Fish weight and length had significant but weak positive correlations (r < or = 0.27) with the abundance of pentastomid larvae, possibly reflecting an increased likelihood of prior exposure in older fish. Parasite abundance had no significant effect on host body condition (p > or = 0.69). A higher prevalence and monthly mean abundance of pentastomids were seen in the dry season and might be due to increased host densities as habitats dry up. Pygocentrus nattereri represents a new intermediate host record for the genera Alofia, Leiperia and Subtriquetra.


Regulation of mitosis-meiosis transition by the ubiquitin ligase β-TrCP in male germ cells.
The mitosis-meiosis transition is essential for spermatogenesis. Specific and timely downregulation of the transcription factor DMRT1, and consequent induction of Stra8 expression, is required for this process in mammals, but the molecular mechanism has remained unclear. Here, we show that β-TrCP, the substrate recognition component of an E3 ubiquitin ligase complex, targets DMRT1 for degradation and thereby controls the mitosis-meiosis transition in mouse male germ cells. Conditional inactivation of β-TrCP2 in male germ cells of β-TrCP1 knockout mice resulted in sterility due to a lack of mature sperm. The β-TrCP-deficient male germ cells did not enter meiosis, but instead underwent apoptosis. The induction of Stra8 expression was also attenuated in association with the accumulation of DMRT1 at the Stra8 promoter in β-TrCP-deficient testes. DMRT1 contains a consensus β-TrCP degron sequence that was found to bind β-TrCP. Overexpression of β-TrCP induced the ubiquitylation and degradation of DMRT1. Heterozygous deletion of Dmrt1 in β-TrCP-deficient spermatogonia increased meiotic cells with a concomitant reduction of apoptosis. Collectively, our data indicate that β-TrCP regulates the transition from mitosis to meiosis in male germ cells by targeting DMRT1 for degradation.


Effects of serum protein opsonization on cytokine release by titanium-alloy particles.
This study tested whether macrophages respond differently to retrieved titanium-alloy particles than they do to machined titanium-alloy particles and assessed whether pretreatment of machined titanium-alloy particles with human serum would influence macrophage activation and cytokine release in vitro. Human monocyte/macrophages were isolated from normal healthy donors and exposed to increasing concentrations of machined and retrieved titanium-alloy particles. The profile of cytokine release was determined by commercially available ELISA kits. Machined titanium-alloy particles were opsonized with human serum and added to macrophage cultures. Serum protein binding was confirmed by SDS-PAGE analysis. The results showed that machined titanium-alloy particles and retrieved titanium-alloy particles stimulate a similar level of cytokine release when tested at comparable concentrations. Opsonization of the machined particles with human serum increased the macrophage release of cytokines in the first 12 h after exposure compared to nonopsonized particles. At 24 h, the opsonized particles stimulated significantly higher levels of cytokine release, but only at the greatest particle concentrations. This study demonstrates that machined titanium alloy induces a metabolic response in macrophages similar to that of titanium-alloy particles retrieved from failed total hip arthroplasty. In addition, these data show that serum protein binding to orthopedic biomaterial debris alters the macrophage reaction to the particles.


Comparing acute fatty liver of pregnancy from hemolysis, elevated liver enzymes, and low platelets syndrome.
Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are both associated with significant maternal and perinatal morbidity and mortality. Because of the overlap of several clinical and laboratory findings differentiation can sometimes be difficult. Both disorders have been of interest for more than 100 years, however they were not completely characterized until the early 1980s. It was not until the 1980s that AFLP and HELLP syndrome, and more specifically their clinical, laboratory, and pathologic findings, were further differentiated in the literature. More recently, the pathophysiologic mechanisms have been elucidated. In this review, we outline the similarities and differences in the clinical presentation, laboratory findings, maternal and perinatal outcomes, and clinical recovery for women diagnosed with these two syndromes. From our observations, we suggest that levels of fibrinogen, creatinine, cholesterol, and total bilirubin be used to assist with differentiating AFLP from HELLP syndrome upon admission in women presenting with either suspected disease. The rationale for identifying the specific conditions is that clinical consequences for recovery vary considerably. Specifically, AFLP is associated with significantly more hepatic and renal dysfunction as well as coagulopathy. Fortunately, both conditions can be managed with supportive measures with overall improved perinatal outcomes including morbidity and mortality.


A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma.
Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC.


Clinical evaluation of anti-mutated citrullinated vimentin by ELISA in rheumatoid arthritis.
Anti-cyclic citrullinated peptide (CCP) antibodies have emerged as sensitive and specific serological markers of rheumatoid arthritis (RA). However, antibodies to several other citrulline-containing proteins, including citrullinated fibrin and vimentin, have been detected in patients with RA, suggesting that citrulline is an essential constituent of autoantigens for RA-specific autoantibodies. We examined the diagnostic performance of the newly developed anti-mutated citrullinated vimentin (MCV) antibody assay. Concentrations of anti-MCV, anti-CCP2, and rheumatoid factors (RF) were determined in the sera of 237 individuals: 119 patients with RA and 118 controls, including patients with other rheumatic diseases and healthy subjects. Diagnostic properties were compared by receiver-operating characteristic curve analysis. Using manufacturer's recommended cutoff values, sensitivity and specificity of anti-MCV antibodies were 75.6% and 91.5% in RA, compared to 66.4% and 98.3% for anti-CCP2. Introducing cutoff values to obtain the same 95% specificity resulted in decreased sensitivity of the anti-MCV test (69.7%) and increased sensitivity of the anti-CCP2 test (74.8%). At optimal cutoff levels, 29.4% of IgM RF-negative cases as well as 13.3% of anti-CCP2-negative cases in the RA group were anti-MCV-positive. Double-positivity for anti-MCV and anti-CCP2 provided 98.3% specificity with 97.5% positive predictive value in RA. Overall, the performance of the novel anti-MCV ELISA for the diagnosis of RA is similar to that of the anti-CCP2 test [area under the curve 0.853 (95% CI 0.801-0.905) vs 0.910 (95% CI 0.873-0.946); p not significant]. As the diagnostic spectrum of the anti-MCV assay is somewhat different from that of anti-CCP2, the combined application of the 2 assays can improve the laboratory diagnostics of RA.


Cell-heritable stages of tumor progression in transgenic mice harboring the bovine papillomavirus type 1 genome.
Tumorigenesis of dermal fibroblasts in a line of transgenic mice carrying the BPV-1 genome was found to involve distinct proliferative stages. Cell cultures derived from normal skin, from benign proliferative fibromatoses, and from malignant fibrosarcomas each evidenced distinguishable, cell-heritable characteristics. The latent viral genome was transcriptionally inactive in normal-appearing skin and was activated in the dermal fibromatoses. Fibrosarcoma cells grew continuously in culture, formed domelike foci, and had a more rounded, anaplastic appearance. Independent cultures derived from the fibromatoses varied in their proliferative characteristics, which correlated well with the levels of viral gene expression. In contrast, progression to malignancy was not accompanied by a further increase in transgene activity, which strongly implicated cellular genetic changes in the later stages of tumorigenesis.


Local-scale topoclimate effects on treeline elevations: a country-wide investigation of New Zealand's southern beech treelines.
Although treeline elevations are limited globally by growing season temperature, at regional scales treelines frequently deviate below their climatic limit. The cause of these deviations relate to a host of climatic, disturbance, and geomorphic factors that operate at multiple scales. The ability to disentangle the relative effects of these factors is currently hampered by the lack of reliable topoclimatic data, which describe how regional climatic characteristics are modified by topographic effects in mountain areas. In this study we present an analysis of the combined effects of local- and regional-scale factors on southern beech treeline elevation variability at 28 study areas across New Zealand. We apply a mesoscale atmospheric model to generate local-scale (200 m) meteorological data at these treelines and, from these data, we derive a set of topoclimatic indices that reflect possible detrimental and ameliorative influences on tree physiological functioning. Principal components analysis of meteorological data revealed geographic structure in how study areas were situated in multivariate space along gradients of topoclimate. Random forest and conditional inference tree modelling enabled us to tease apart the relative effects of 17 explanatory factors on local-scale treeline elevation variability. Overall, modelling explained about 50% of the variation in treeline elevation variability across the 28 study areas, with local landform and topoclimatic effects generally outweighing those from regional-scale factors across the 28 study areas. Further, the nature of the relationships between treeline elevation variability and the explanatory variables were complex, frequently non-linear, and consistent with the treeline literature. To our knowledge, this is the first study where model-generated meteorological data, and derived topoclimatic indices, have been developed and applied to explain treeline variation. Our results demonstrate the potential of such an approach for ecological research in mountainous environments.


STUDIES IN THE DYNAMICS OF HISTOGENESIS : II. TENSION OF DIFFERENTIAL GROWTH AS A STIMULUS TO MYOGENESIS IN THE ESOPHAGUS.
Esophageal Development. 1. The region of most active mitosis per mm. of cross-section in the esophagus is the entodermal epithelial tube. The mitotic figures follow a spiral path in the manner of a left-handed helix from the cephalic to the caudal direction. 2. The region of least active growth per mm. of cross-section in the esophagus is the mesenchyme surrounding the epithelial tube. 3. The helicoidal activity of the epithelial tube causes a vortical reaction in the surrounding mesenchyme. The mesenchymal whirlpool represents a reaction to the spirally grooving epithelial tube. 4. In embryos 9.5 to 14 mm. in length the esophageal epithelial tube grows relatively more rapidly in width than in length. During this period the myoblasts which form the inner, close spiral, muscle coat of the esophagus are becoming rapidly differentiated in the outer condensed margin of the mesenchymal maelstrom. 5. The nuclei, first spherical then oval, and finally rod shaped with rounded ends, are drawn out in the direction of the circumference of the mesenchymal rim which is directed tangentially. 6. The cytoplasm is also drawn out in the direction of the mesenchymal rim of the vortex. The elongated rows of isolated granules appear which subsequently, by confluence, form the myofibrillae. These cytoplasmic derivatives are elongated in the direction of the circumference of the vortex. 7. Between the epithelial tube and the myoblastic rim at the periphery of the mesenchymal whorl is found the embryonic connective tissue. From this direct observation the conclusion is made that an optimum tensional stress stimulus is necessary to elicit the formation of muscular tissue at the circumference of the mesenchymal vortex. Consequently, the formation of a specific derivative from a pluripotent mesenchymal cell is due to the fortuitous circumstance of position. 8. In embryos from 14 to 24 mm. in length, the esophagus grows relatively more rapidly in length than in width. This elongation is due to two factors; first, the descent of the stomach, and, second, the resistance to diametrical growth presented by the inner close spiral musculature. The epithelial tube, still the dominant zone of mitotic activity, pursues the lines of least resistance, and consequently growth in length takes place. This is due to the shifting of the planes of cell division on account of the compression of the inner, close spiral, muscle coat. 9. The undifferentiated mesenchyme peripherad to the inner, close spiral musculature is elongated and the histogenetic changes in muscular formation are gradually taking place between 14 and 24 mm. A very attenuated, outer, elongated, spiral, or longitudinal muscle coat is detected in the esophagus of a 24 mm. pig embryo. 10. The characteristic intestino-colic flexure is a torsional reaction of the mesenchyme. The mesenchymal cells are thrown into a left-handed helicoidal series, corresponding to the activity in the epithelial tube. The right-handed helicoidal reaction of the mesenchyme, therefore, is due to the left-handed helicoidal growth of the epithelial tube. 11. The normal asymmetry of the abdominal viscera as well as the position of the gut is dependent upon the clockwise reaction of the stretched mesenchymal cell. These cells are stretched by the left-handed helicoidal growth of the epithelial tube. One factor producing situs inversus viscerum could be the reversal of the spiral growth of the epithelial tube resulting in a reaction of the mesenchyme in a direction opposite, namely counterclockwise, to that which occurs normally.


No neural evidence for dynamic auditory tuning of the A1 receptor in the ear of the noctuid moth, Noctua pronuba.
By examining the mechanical properties of the tympanum of the noctuid moth, Noctua pronuba, Windmill et al. (2006) suggested that this insect increases (up-tunes) the frequencies of its best hearing when exposed to high intensity sounds (HIS) resembling the echolocation calls of attacking bats. We tested whether this biophysical phenomenon was encoded in the neural responses of this moth's most sensitive auditory receptor (A1 cell) before and after exposure to HIS. We measured: (1) the number of A1 action potentials (spikes) per stimulus pulse; (2) the proportion of A1 spike periods below that determined to elicit evasive flight maneuvers and, (3) the change in A1 cell firing (spike number, interspike interval, stimulus/spike latency) over a duration of time similar to that in which up-tuning lasts. We observed no significant spiking response changes in the predicted direction to any of the frequencies tested following exposure to HIS and we observed only two of the 24 predicted time-dependent changes to A1 firing. These results indicate that tympanal up-tuning does not result in a change to this moth's auditory frequency sensitivity and we suggest either sensillar resonances or increases in thoracic muscle tension following exposure to HIS as alternative explanations.


Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage.
The cytokine interleukin (IL)-7 exerts essential roles in lymph node (LN) organogenesis and lymphocyte development and homeostasis. Recent studies have identified lymphatic endothelial cells (LECs) as a major source of IL-7 in LNs. Here, we report that LECs not only produce IL-7, but also express the IL-7 receptor chains IL-7Rα and CD132. Stimulation with recombinant IL-7 enhanced LEC in vitro activity and induced lymphangiogenesis in the cornea of wild-type (WT) mice. Whereas in IL-7Rα(-/-) mice, dermal lymphatic vessels (LVs) were abnormally organized and lymphatic drainage was compromised, transgenic overexpression of IL-7 in mice resulted in an expanded dermal LV network with increased drainage function. Moreover, systemic treatment with recombinant IL-7 enhanced lymphatic drainage in the skin of WT mice and of mice devoid of lymphocytes. Experiments in IL-7Rα(-/-) bone marrow chimeras demonstrated that the drainage-enhancing activity of IL-7 was exclusively dependent on IL-7Rα expression in stromal but not in hematopoietic cells. Finally, near-infrared in vivo imaging performed in IL-7Rα(-/-) mice revealed that the pumping activity of collecting vessels was normal but fluid uptake into lymphatic capillaries was defective. Overall, our data point toward an unexpected new role for IL-7 as a potential autocrine mediator of lymphatic drainage.


Post-event processing and autobiographical memory in social anxiety: the influence of negative feedback and rumination.
Two experiments investigated the extent to which the content of feedback and the style of post-event processing are associated with a bias in the retrieval of autobiographical memories by individuals high in social anxiety. In each experiment high and low socially anxious individuals responded to questions about autobiographical experiences, participated in a task involving real or imagined social encounters, and then recalled autobiographical memories. In Experiment 1 (n=50) participants focused on positive or negative feedback following the social task, while in Experiment 2 (n=59) participants engaged in either a ruminative or reflective response style following the social task. Experiment 1 showed that negative feedback led to the recall of memories with a significantly greater average anxiety rating only in the high social anxiety group. Experiment 2 demonstrated that the high social anxiety group who engaged in a ruminative response style recalled memories with the highest average anxiety rating. Implications of these findings for understanding the role of post-event processing as a maintaining factor in social anxiety are discussed.


Predicting free-space occupancy on novel artificial structures by an invasive intertidal barnacle using a removal experiment.
Artificial structures can create novel habitat in the marine environment that has been associated with the spread of invasive species. They are often located in areas of high disturbance and can vary significantly in the area of free space provided for settlement of marine organisms. Whilst correlation between the amount of free space available and recruitment success has been shown in populations of several marine benthic organisms, there has been relatively little focus on invasive species, a group with the potential to reproduce in vast numbers and colonise habitats rapidly. Invasion success following different scales of disturbance was examined in the invasive acorn barnacle, Austrominiusmodestus, on a unique art installation located in Liverpool Bay. Population growth and recruitment success were examined by comparing recruitment rates within disturbance clearings of 4 different sizes and by contrasting population development with early recruitment rates over a 10 week period. Disturbed areas were rapidly recolonised and monocultures of A. modestus formed within 6 weeks. The size of patch created during disturbance had no effect on the rate of recruitment, while a linear relationship between recruit density and patch size was observed. Density-dependent processes mediated initial high recruitment resulting in population stability after 8-10 weeks, but densities continued to greatly exceed those reported in natural habitats. Given that artificial structures are likely to continue to proliferate in light of climate change projections, free-space is likely to become more available more frequently in the future supporting the expansion of fast-colonising species.


In vitro binding of the Salmonella dublin virulence plasmid regulatory protein SpvR to the promoter regions of spvA and spvR.
The spv regulon of Salmonella dublin is essential for virulence in mice. SpvR, a LysR-type regulator, induces the expression of the spvABCD operon and its own expression in the stationary phase of bacterial growth and in macrophages. We constructed fusion proteins to the maltose-binding protein (MBP) and a His tag peptide (His) to overcome the insolubility and to facilitate purification of SpvR. We demonstrated that both fusion proteins, MBP-SpvR and His-SpvR, were able to induce spvA expression in vivo. MBP-SpvR was produced as soluble protein, whereas His-SpvR was only marginally present in the soluble cell fraction. Affinity chromatography resulted in at least 95% pure MBP-SpvR protein and in an enrichment of His-SpvR. Gel mobility shift assay revealed that the SpvR fusion proteins were able to bind to 125-and 147-bp DNA fragments of the spvA and spvR promoter regions, respectively. DNase I footprint experiments showed that the fusion proteins protected DNA regions of 54 and 50 bp within the spvA and spvR promoter regions, respectively.


Neodymium-doped NaHoF4 nanoparticles as near-infrared luminescent/T2-weighted MR dual-modal imaging agents in vivo.
The achievement of efficient near-infrared (NIR) luminescence of lanthanide ions in a paramagnetic nanoparticle (NP) host is highly desirable to optimize the performance of multimodal bioprobes. Herein, we present a facile coprecipitation method to prepare highly uniform NaHoF4:Nd3+ nanoplates. Upon NIR excitation at 785 nm, efficient NIR luminescence of Nd3+ can be obtained from the paramagnetic NaHoF4 hosts. More interestingly, due to energy transfer from the excited state of Nd3+ to the adjacent Ho3+, NIR emission at around 1200 nm from Ho3+ ions is also observed. The r2 value of NaHoF4:Nd3+ NPs reaches 143.7 s-1 mM-1 at a high magnetic field of 11.7 T. By modifying with hydrophilic alpha-cyclodextrin, the NaHoF4:Nd3+ NPs were further successfully applied for the NIR luminescent/T2-weighted MR dual-modal in vivo imaging of nude mice, high contrast NIR imaging of the liver and T2-weighted MR imaging of stem cells in the mouse brain using the NaHoF4:Nd3+ NPs as multimodal bioprobes.


Increasing the applicability of density functional theory. V. X-ray absorption spectra with ionization potential corrected exchange and correlation potentials.
Core excitation energies are computed with time-dependent density functional theory (TD-DFT) using the ionization energy corrected exchange and correlation potential QTP(0,0). QTP(0,0) provides C, N, and O K-edge spectra to about an electron volt. A mean absolute error (MAE) of 0.77 and a maximum error of 2.6 eV is observed for QTP(0,0) for many small molecules. TD-DFT based on QTP (0,0) is then used to describe the core-excitation spectra of the 22 amino acids. TD-DFT with conventional functionals greatly underestimates core excitation energies, largely due to the significant error in the Kohn-Sham occupied eigenvalues. To the contrary, the ionization energy corrected potential, QTP(0,0), provides excellent approximations (MAE of 0.53 eV) for core ionization energies as eigenvalues of the Kohn-Sham equations. As a consequence, core excitation energies are accurately described with QTP(0,0), as are the core ionization energies important in X-ray photoionization spectra or electron spectroscopy for chemical analysis.


Relationship of plasma neuropeptide Y with angiographic, electrocardiographic and coronary physiology indices of reperfusion during ST elevation myocardial infarction.
The co-transmitter neuropeptide Y (NPY) is released during high levels of sympathetic stimulation and is a potent vasoconstrictor. We defined the release profile of plasma NPY during acute ST elevation myocardial infarction, and tested the hypothesis that levels correlate with reperfusion measures after treatment with primary percutaneous coronary intervention (PPCI). Prospective observational study. University hospital heart centre. 64 patients (62.6±11.7 years-old, 73% male) presenting throughout the 24-h cycle of clinical activity with ST elevation myocardial infarction. PPCI. NPY was measured (ELISA) in peripheral blood taken before and immediately after PPCI and at 6, 24 and 48 h post-PPCI. Reperfusion was assessed by angiographic criteria, ST segment resolution, invasive measurement of coronary flow reserve and the index of microcirculatory resistance. Plasma NPY levels were highest before PPCI (17.4 (8.8-42.2) pg/ml, median (IQR)) and dropped significantly post-PPCI (12.4 (6.5-26.7) pg/ml, p<0.0001) and after 6 h (9.0 (2.6-21.5) pg/ml, p=0.008). Patients with admission NPY levels above the median were significantly more hypertensive and tachycardic and were more likely to have diabetes mellitus. Patients with angiographic no-reflow (less than thrombolysis in myocardial infarction 3 flow and myocardial blush grade >2, n=16) or no electrocardiographic ST resolution (<70%, n=30) following PPCI had significantly higher plasma NPY levels. Patients with a coronary flow reserve <1.5 or index of microcirculatory resistance >33 also had significantly higher plasma NPY levels pre-PPCI and post-PPCI. Plasma NPY levels correlate with indices of reperfusion and coronary microvascular resistance.


Overexpression of Apaf-1 promotes apoptosis of untreated and paclitaxel- or etoposide-treated HL-60 cells.
Recent studies have demonstrated that Apaf-1 is the adaptor molecule which in the presence of cytosolic cytochrome c (cyt c) and dATP interacts with procaspase-9, resulting in the sequential cleavage and activity of caspase-9 and caspase-3, followed by apoptosis. In the present studies, we determined the effect of enforced overexpression of Apaf-1 on the apoptotic threshold in the human myeloid leukemia HL-60 cells. Our findings demonstrate that both transient and stable transfections resulted in a 2.5-fold higher expression of Apaf-1, which was associated with approximately a 5-fold increase in the percentage of apoptosis in the transfectants (HL-60/Apaf-1) as compared with the control HL-60/neo cells. In cells overexpressing either Bcl-2 or Bcl-xL, transient overexpression of Apaf-1 did not induce apoptosis. Stably overexpressing Apaf-1 levels significantly sensitized HL-60/Apaf-1 cells to apoptosis induced by clinically achievable concentrations of paclitaxel or etoposide (P < 0.01). This increase in paclitaxel- or etoposide-induced apoptosis of HL-60/Apaf-1 cells was not associated with any significant alterations in Bcl-2, Bcl-xL, Bax, Fas, or Fas ligand expression. It was, however, clearly associated with caspase-9 cleavage, as well as the poly(ADP-ribose) polymerase and DFF45 cleavage activity of caspase-3. Coexpression of the catalytically inactive, dominant-negative, mutant caspase-9, XIAP, or treatment with the caspase inhibitor, zVAD, significantly inhibited the increase in apoptosis of HL-60/Apaf-1 cells (P < 0.01). These data indicate that the intracellular levels of Apaf-1 is an important molecular determinant of the threshold for apoptosis induced by paclitaxel and etoposide.


Carbapenem-resistant and carbapenem-susceptible isogenic isolates of Klebsiella pneumoniae ST101 causing infection in a tertiary hospital.
In this study we describe the clinical and molecular characteristics of an outbreak due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) producing CTX-M-15 and OXA-48 carbapenemase. Isogenic strains, carbapenem-susceptible K. pneumoniae (CS-KP) producing CTX-M-15, were also involved in the outbreak. From October 2010 to December 2012 a total of 62 CR-KP and 23 CS-KP were isolated from clinical samples of 42 patients (22 had resistant isolates, 14 had susceptible isolates, and 6 had both CR and CS isolates). All patients had underlying diseases and 17 of them (14 patients with CR-KP and 3 with CS-KP) had received carbapenems previously. The range of carbapenem MICs for total isolates were: imipenem: 2 to >32 μg/ml vs. <2 μg/ml; meropenem: 4 to >32 μg/ml vs. <2 μg/ml; and ertapenem: 8 to >32 μg/ml vs. <2 μg/ml. All the isolates were also resistant to gentamicin, ciprofloxacin, and cotrimoxazole. Both types of isolates shared a common PFGE pattern associated with the multilocus sequence type 101 (ST101). The bla CTX-M-15 gene was detected in all the isolates, whereas the bla OXA-48 gene was only detected in CR-KP isolates on a 70 kb plasmid. The clonal spread of K. pneumoniae ST101 expressing the OXA-48 and CTX-M-15 beta-lactamases was the cause of an outbreak of CR-KP infections. CTX-M-15-producing isolates lacking the bla OXA-48 gene coexisted during the outbreak.


Theoretical evidence for the direct 3MLCT-HS deactivation in the light-induced spin crossover of Fe(ii)-polypyridyl complexes.
Spin-orbit couplings have been calculated in twenty snapshots of a molecular dynamics trajectory of [Fe(bpy)3]2+ to address the importance of geometrical distortions and second-order spin-orbit coupling on the intersystem crossing rate constants in the light-induced spin crossover process. It was found that the effective spin-orbit coupling between the 3MLCT and 5T2 state is much larger than the direct coupling in the symmetric structure, which opens the possibility of a direct 3MLCT-5T2 deactivation without the intervention of triplet metal-centered states. Based on the calculated deactivation times, we conclude that both the direct pathway and the one involving intermediate triplet states are active in the ultrafast population of the metastable HS state, bringing in agreement two experimental observations that advocate for either deactivation mechanism. This resolves a long-standing dispute about the deactivation mechanism of Fe(ii)-polypyridyl complexes in particular, and about light-induced magnetism in transition metal complexes in general.


A smart curtailment approach for reducing bat fatalities and curtailment time at wind energy facilities.
The development and expansion of wind energy is considered a key global threat to bat populations. Bat carcasses are being found underneath wind turbines across North and South America, Eurasia, Africa, and the Austro-Pacific. However, relatively little is known about the comparative impacts of techniques designed to modify turbine operations in ways that reduce bat fatalities associated with wind energy facilities. This study tests a novel approach for reducing bat fatalities and curtailment time at a wind energy facility in the United States, then compares these results to operational mitigation techniques used at other study sites in North America and Europe. The study was conducted in Wisconsin during 2015 using a new system of tools for analyzing bat activity and wind speed data to make near real-time curtailment decisions when bats are detected in the area at control turbines (N = 10) vs. treatment turbines (N = 10). The results show that this smart curtailment approach (referred to as Turbine Integrated Mortality Reduction, TIMR) significantly reduced fatality estimates for treatment turbines relative to control turbines for pooled species data, and for each of five species observed at the study site: pooled data (-84.5%); eastern red bat (Lasiurus borealis, -82.5%); hoary bat (Lasiurus cinereus, -81.4%); silver-haired bat (Lasionycteris noctivagans, -90.9%); big brown bat (Eptesicus fuscus, -74.2%); and little brown bat (Myotis lucifugus, -91.4%). The approach reduced power generation and estimated annual revenue at the wind energy facility by ≤ 3.2% for treatment turbines relative to control turbines, and we estimate that the approach would have reduced curtailment time by 48% relative to turbines operated under a standard curtailment rule used in North America. This approach significantly reduced fatalities associated with all species evaluated, each of which has broad distributions in North America and different ecological affinities, several of which represent species most affected by wind development in North America. While we recognize that this approach needs to be validated in other areas experiencing rapid wind energy development, we anticipate that this approach has the potential to significantly reduce bat fatalities in other ecoregions and with other bat species assemblages in North America and beyond.


Understanding single enzyme activity via the nano-impact technique.
To evaluate the possible detection of single enzyme activity via electrochemical methods, a combined finite difference and random walk simulation is used to model individual enzyme-electrode collisions where such events are monitored amperometrically via the measurement of products formed by the enzyme in solution. It is found that the observed signal is highly sensitive to both the enzyme turnover number, the size of the electrode and the bandwidth of the electronics. Taking single catalase impacts as an example, simulation results are compared with experimental data. Our work shows the requirement for the detection of electrochemically active product formed by individual enzymes and gives guidance for the design of experiments.


An optical fiber bundle sensor for tip clearance and tip timing measurements in a turbine rig.
When it comes to measuring blade-tip clearance or blade-tip timing in turbines, reflective intensity-modulated optical fiber sensors overcome several traditional limitations of capacitive, inductive or discharging probe sensors. This paper presents the signals and results corresponding to the third stage of a multistage turbine rig, obtained from a transonic wind-tunnel test. The probe is based on a trifurcated bundle of optical fibers that is mounted on the turbine casing. To eliminate the influence of light source intensity variations and blade surface reflectivity, the sensing principle is based on the quotient of the voltages obtained from the two receiving bundle legs. A discrepancy lower than 3% with respect to a commercial sensor was observed in tip clearance measurements. Regarding tip timing measurements, the travel wave spectrum was obtained, which provides the average vibration amplitude for all blades at a particular nodal diameter. With this approach, both blade-tip timing and tip clearance measurements can be carried out simultaneously. The results obtained on the test turbine rig demonstrate the suitability and reliability of the type of sensor used, and suggest the possibility of performing these measurements in real turbines under real working conditions.


Complications of plate fixation in fresh displaced midclavicular fractures.
The role of plate fixation in the management of fresh displaced midclavicular fractures is unsettled. The objective of this study was to evaluate the drawbacks and pitfalls of this treatment method. We analyzed the complications encountered in 103 consecutive adult patients with severely displaced fresh fractures of the middle third of the clavicle who were treated by open reduction and internal fixation using AO/ASIF plates. These 103 patients accounted for 9.5% of the 1,081 patients with fresh midclavicular fractures seen between 1989 and 1995. The mean age of the 103 patients was 33.4 years (range, 19-62 years). Seventy-nine patients had an uneventful recovery, whereas 24 (23%) suffered one or several complications. The major complications included deep infection, plate breakage, nonunion, and refracture after plate removal. The most common of the minor complications was plate loosening resulting in malunion. The infection rate was 7.8%. A total of 14 reoperations were performed because of the complications. Permanent nonunion ensued in two patients. A severely comminuted fracture (relative risk of failure, 5.15) as well as a state of alcohol intoxication on admission (relative risk of failure, 3.12) were identified as markers of increased complication risk. Patient noncompliance with the postoperative regimen could be suspected to have been a major cause of the failures. The high complication rate supports a reserved attitude toward plate fixation of fresh midclavicular fractures. The method should be reserved for patients who have trustworthy personal motives for quick pain relief and functional recovery.


The Molecular Basis of Freshwater Adaptation in Prawns: Insights from Comparative Transcriptomics of Three Macrobrachium Species.
Elucidating the molecular basis of adaptation to different environmental conditions is important because adaptive ability of a species can shape its distribution, influence speciation, and also drive a variety of evolutionary processes. For crustaceans, colonization of freshwater habitats has significantly impacted diversity, but the molecular basis of this process is poorly understood. In the current study, we examined three prawn species from the genus Macrobrachium (M. australiense, M. tolmerum, and M. novaehollandiae) to better understand the molecular basis of freshwater adaptation using a comparative transcriptomics approach. Each of these species naturally inhabit environments with different salinity levels; here, we exposed them to the same experimental salinity conditions (0‰ and 15‰), to compare expression patterns of candidate genes that previously have been shown to influence phenotypic traits associated with freshwater adaptation (e.g., genes associated with osmoregulation). Differential gene expression analysis revealed 876, 861, and 925 differentially expressed transcripts under the two salinities for M. australiense, M. tolmerum, and M. novaehollandiae, respectively. Of these, 16 were found to be unannotated novel transcripts and may be taxonomically restricted or orphan genes. Functional enrichment and molecular pathway mapping revealed 13 functionally enriched categories and 11 enriched molecular pathways that were common to the three Macrobrachium species. Pattern of selection analysis revealed 26 genes with signatures of positive selection among pairwise species comparisons. Overall, our results indicate that the same key genes and similar molecular pathways are likely to be involved with freshwater adaptation widely across this decapod group; with nonoverlapping sets of genes showing differential expression (mainly osmoregulatory genes) and signatures of positive selection (genes involved with different life history traits).


A parasacral approach to rectal prolapse.
A posterior parasacral approach is introduced for management of third-degree rectal prolapse. Anterior approximation of the levator musculature and posterior fixation of the rectum are accomplished readily through the York Mason approach.


Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults.
This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I-II, lateral lobules IV-IX, and vermis IV-VI) in all participants, suggesting multiple sites of associative learning-related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during EBC.


Investigation of Borrelia burgdorferi genotypes in Australia obtained from erythema migrans tissue.
Lyme disease (LD) is an emerging infectious disease in Australia. There has been controversy regarding endemic lyme disease in the country for over 20 years. Borrelia burgdorferi sensu stricto (Bbss) and sensu lato (Bbsl) are closely related spirochetal species that are the causative agents of LD in humans. Clinical transmission of this tick-borne disease is marked by a characteristic rash known as erythema migrans (EM). This study employed molecular techniques to demonstrate the spirochetal agent of Lyme disease isolated from EM biopsies of patients in Australia and then investigate their genetic diversity. Four patients who presented to the author's practice over a one-year period from mid 2010 to mid 2011 returned positive results on central tissue biopsy of EM lesions using polymerase chain reaction (PCR) analysis. The findings were confirmed by DNA sequencing, and basic local alignment search tool (BLAST) analysis was then used to genetically characterize the causative organisms. Three isolates were identified as Bbss that lay genotypically between strains B31 and ZS7 and were then characterized as strain 64b. One of the three isolates though may have similarity to B. bissettii a Bbsl. The fourth isolate was more appropriately placed in the sensu lato group and appeared to be similar, but not identical to, a B. valaisiana-type isolate. In this study, a central biopsy taken within 6 days of infection was used instead of conventional sampling at the leading edge, and the merits of this are discussed. These patients acquired infection in Australia, further proving endemic LD on the continent. Central biopsy site of EM is a useful tool for PCR evaluation. BLAST searches suggest a genetic diversity of B. burgdorferi, which has implications concerning the diagnosis, clinical severity, and testing of LD in Australia.


Healthcare workplace conversations on race and the perspectives of physicians of African descent.
Although experts recommend that healthcare organizations create forums for honest dialogue about race, there is little insight into the physician perspectives that may influence these conversations across the healthcare workforce. To identify the range of perspectives that might contribute to workplace silence on race and affect participation in race-related conversations within healthcare settings. In-person, in-depth, racially concordant qualitative interviews. Twenty-five physicians of African descent practicing in the 6 New England states. Line-by-line independent coding and group negotiated consensus to develop codes structure using constant comparative method. Five themes characterize perspectives of participating physicians of African descent that potentially influence race-related conversations at work: 1) Perceived race-related healthcare experiences shape how participating physicians view healthcare organizations and their professional identities prior to any formal medical training; 2) Protecting racial/ethnic minority patients from healthcare discrimination is a top priority for participating physicians; 3) Participating physicians often rely on external support systems for race-related issues, rather than support systems inside the organization; 4) Participating physicians perceive differences between their interpretations of potentially offensive race-related work experiences and their non-minority colleagues' interpretations of the same experiences; and 5) Participating physicians are uncomfortable voicing race-related concerns at work. Creating a healthcare work environment that successfully supports diversity is as important as recruiting diversity across the workforce. Developing constructive ways to discuss race and race relations among colleagues in the workplace is a key step towards creating a supportive environment for employees and patients from all backgrounds.


Hydrological conditions control in situ DOM retention and release along a Mediterranean river.
Uncertainties exist regarding the magnitude of in situ dissolved organic matter (DOM) processing in lotic systems. In addition, little is known about the effects of extreme hydrological events on in-stream DOM retention or release during downriver transport. This study quantified the net in-stream retention/release efficiencies (η) of dissolved organic carbon (DOC) and its humic and protein-like fluorescent fractions along a Mediterranean river during drought, baseflow and flood conditions. High performance size exclusion chromatography was used to describe the apparent size distributions of the humic and protein-like DOM moieties. A snapshot mass balance allowed estimating the η values of DOC and humic and protein-like fractions. Significant DOM net retention (η < 0) was detected during the drought condition and the protein-like fraction was more retained than the humic-like fraction and bulk DOC. In addition, small substances were more efficiently retained than larger substances. DOC retention decreased under baseflow conditions, but it remained significant. The humic and protein-like net efficiencies exhibited high variability, but the net retention were not significant. From a longitudinal perspective, the entire fluvial corridor contributed net retention of DOC and humic and protein-like moieties net retention during drought condition. In contrast, net retention/release efficiencies exhibited spatial variability during baseflow condition. The flood preferentially mobilized large size DOM molecules and the fluvial corridor behaved as a homogeneous passive DOM (η = 0) conduit. This research highlights the relevance of hydrological extreme events on the magnitude of DOM retention/release mass balance and emphasizes the need to perform measurements during these conditions to quantify the impact of fluvial corridors on DOM fate and transport.


Current evidence and clinical implications of aspirin resistance.
Atherothrombosis, characterized by atherosclerotic plaque rupture and subsequent occlusive or subocclusive thrombus formation is the primary cause of acute ischemic syndromes involving all vascular beds and accounts for more than one-third of all deaths in the developed world. Platelet activation and aggregation constitute the most critical component in the pathophysiology of atherothrombotic disease. Aspirin is currently the most commonly used antiplatelet agent and one of the most frequently prescribed drugs, with as many as 30 million Americans on chronic aspirin regimens. Multiple well-designed prospective randomized clinical trials have demonstrated aspirin's efficacy in both primary and secondary prevention of a wide variety of entities that the atherothrombotic disease spectrum encompasses, such as cerebrovascular, coronary artery, and peripheral vascular disease. Despite its proven benefit, however, a growing body of evidence suggests that up to 70% of aspirin-takers may still be at risk for atherothrombotic complications due to resistance. Patients with laboratory-confirmed aspirin resistance seem to have an almost fourfold increase in their risk for acute thrombotic episodes, which underlines the magnitude of the problem for the vascular specialist. In this article, we review the physiology of platelet activation and the role of aspirin as an antiplatelet agent; the various laboratory assays used in assessing aspirin effectiveness; and current data on aspirin resistance and its clinical implications in patients with cardiovascular disease. We also review the studies that explore this phenomenon in patients with peripheral arterial disease and discuss the optimal management options in aspirin-resistant individuals. Suggestions are advanced for the direction of future trials evaluating aspirin resistance in patients with vascular disease.


The contributions of prevention and treatment to the decline in cardiovascular mortality: lessons from a forty-year debate.
Mortality from coronary heart disease in the United States has fallen 60 percent from its peak in the mid-1960s. Cardiologists and epidemiologists have debated whether this decline reflects better control of risk factors, including lifestyle interventions to reduce smoking or intake of dietary fats, or the power of medical interventions, including defibrillators and therapeutics such as statins. Attempts to resolve this debate and guide health policy have generated sophisticated data sets and techniques for modeling cardiovascular mortality. Neither effort has provided specific guidance for health policy. Historical analysis of the debate over the causes of the decline, concomitant with development of cardiovascular modeling, offers valuable policy lessons about tensions among medical and public health strategies, the changing meanings of disease prevention, and the ability of evidence-based research and models to guide health policy. Policy makers must learn to open up the "black box" of epidemiological models-and of their own decision-making processes-to produce the best evidence-informed policy.


Comparing optical coherence tomography radial and cube scan patterns for measuring Bruch's membrane opening minimum rim width (BMO-MRW) in glaucoma and healthy eyes: cross-sectional and longitudinal analysis.
To compare the cube and radial scan patterns of the spectral domain optical coherence tomography (SD-OCT) for quantifying the Bruch's membrane opening minimum rim width (BMO-MRW). Sixty healthy eyes and 189 glaucomatous eyes were included. The optic nerve head cube and radial pattern scans were acquired using Spectralis SD-OCT. BMO-MRWs were automatically delineated using the San Diego Automated Layer Segmentation Algorithm. The BMO-MRW diagnostic accuracy for glaucoma detection and rates of change derived from the two scan patterns were compared. There was a significant difference between the baseline global BMO-MRW measurements of cube and radial scans for healthy (301.9±57.8 µm and 334.7±61.8 µm, respectively, p<0.003) and glaucoma eyes (181.2±63.0 µm and 210.2±67.2 µm, respectively, p<0.001). The area under the receiver operating characteristic curve for differentiating between healthy and glaucoma eyes was 0.90 for both the radial scan-based and cube scan-based BMO-MRW. No significant difference in the rate of BMO-MRW change (mean follow-up years) by scan pattern was found among both healthy (cube: -1.47 µm/year, radial: -1.53 µm/year; p=0.48) (1.6 years) and glaucoma eyes (cube: -2.37 µm/year, radial: -2.28 µm/year; p=0.45) (2.6 years). Although the cube scan-based BMO-MRW was significantly smaller than the radial scan-based BMO-MRW, we found no significant difference between the two scan patterns for detecting glaucoma, identifying BMO location and measuring the rate of BMO-MRW change. These results suggest that although BMO-MRW estimates are not interchangeable, both scan patterns can be used for monitoring BMO-MRW changes over time.


Toward Game-Based Digital Mental Health Interventions: Player Habits and Preferences.
Designers of digital interventions for mental health often leverage interactions from games because the intrinsic motivation that results from game-based interventions may increase participation and translate into improved treatment efficacy. However, there are outstanding questions about the suitability (eg, are desktop or mobile interventions more appropriate?) and intervention potential (eg, do people with depression activate enough to play?) of games for mental health. In this paper, we aimed to describe the presently unknown relationship between gaming activity and indicators of well-being so that designers make informed choices when designing game-based interventions for mental health. We gathered validated scales of well-being (Beck's Depression Inventory [BDI-II], Patient Health Questionnaire [PHQ-9], trait anxiety [TA], and basic psychological needs satisfaction [BPNS]), play importance (control over game behavior: control; gamer identity: identity), and play behavior (play frequency, platform preferences, and genre preferences) in a Web-based survey (N=491). The majority of our participants played games a few times a week (45.3%, 222/490) or daily (34.3%, 168/490). In terms of depression, play frequency was associated with PHQ-9 (P=.003); PHQ-9 scores were higher for those who played daily than for those who played a few times a week or less. Similarly, for BDI-II (P=.01), scores were higher for those who played daily than for those who played once a week or less. Genre preferences were not associated with PHQ-9 (P=.32) or BDI-II (P=.68); however, platform preference (ie, mobile, desktop, or console) was associated with PHQ-9 (P=.04); desktop-only players had higher PHQ-9 scores than those who used all platforms. Platform preference was not associated with BDI-II (P=.18). In terms of anxiety, TA was not associated with frequency (P=.23), platform preference (P=.07), or genre preference (P=.99). In terms of needs satisfaction, BPNS was not associated with frequency (P=.25) or genre preference (P=.53), but it was associated with platform preference (P=.01); desktop-only players had lower needs satisfaction than those who used all platforms. As expected, play frequency was associated with identity (P<.001) and control (P<.001); those who played more had identified more as a gamer and had less control over their gameplay. Genre preference was associated with identity (P<.001) and control (P<.001); those who played most common genres had higher control over their play and identified most as gamers. Platform preference was not associated with control (P=.80), but was with identity (P=.001); those who played on all devices identified more as a gamer than those who played on mobiles or consoles only. Our results suggest that games are a suitable approach for mental health interventions as they are played broadly by people across a range of indicators of mental health. We further unpack the platform preferences and genre preferences of players with varying levels of well-being.


Oxidative stress and antioxidant defense in Egyptian favism patients.
Favism occurs as the result of intolerance to the ingesting of fava beans or to the inhalation of pollen from the Vicia faba plant. Patients with favism are always Glucose-6-phosphate dehydrogenase (G6PD)-deficient, but not all G6PD-deficient individuals develop hemolysis as a result of fava beans consumption. Blood samples were collected from children with favism (n = 55) between age (2-12 years) on EDTA tubes divided into 3 groups: group 1 control group (n = 15), group 2 before blood transfusion (during hemolytic action) (n = 20) and group 3 after blood transfusion (treated) (n = 20). It was found that in group 2 GSH level was significantly low; (1.11 ± 0.39, p < 0.001) compared to controls (26.31 ± 5.26, p < 0.001). In group 3 after blood transfusion Level of GSH rose but remained lower than normal level (5.88 ± 2.33, p < 0.001) compared to controls. As for oxidative stress parameters, both levels of H2O2 and MDA were highly significant in group 2; (213.49 ± 57.56, p < 0.001), (98.05 ± 22.34, p < 0.001) compared to controls (3.75 ± 1.164, p < 0.001), (7.38 ± 2.07, p < 0.001), respectively. Moreover, in group 3 after blood transfusion, levels of H2O2 and MDA were decreased but remained high compared to controls (66.55 ± 22.49, p < 0.001), (47.18 ± 9.62, p < 0.001) sequentially. Also, there was a negative correlation between GSH that acts as antioxidant defense enzyme and each one of oxidative stress parameters MDA & H2O2. However, there was a positive correlation between H2O2 and MDA. From this study, it could be concluded that the favic patients have high oxidative stress (H2O2 and MDA) more than normal individuals and less antioxidant defense (GSH). With the passage of time these individuals, cells would be more vulnerable for H2O2-induced senescence.


Interoceptive signals impact visual processing: Cardiac modulation of visual body perception.
Multisensory perception research has largely focused on exteroceptive signals, but recent evidence has revealed the integration of interoceptive signals with exteroceptive information. Such research revealed that heartbeat signals affect sensory (e.g., visual) processing: however, it is unknown how they impact the perception of body images. Here we linked our participants' heartbeat to visual stimuli and investigated the spatio-temporal brain dynamics of cardio-visual stimulation on the processing of human body images. We recorded visual evoked potentials with 64-channel electroencephalography while showing a body or a scrambled-body (control) that appeared at the frequency of the on-line recorded participants' heartbeat or not (not-synchronous, control). Extending earlier studies, we found a body-independent effect, with cardiac signals enhancing visual processing during two time periods (77-130 ms and 145-246 ms). Within the second (later) time-window we detected a second effect characterised by enhanced activity in parietal, temporo-occipital, inferior frontal, and right basal ganglia-insula regions, but only when non-scrambled body images were flashed synchronously with the heartbeat (208-224 ms). In conclusion, our results highlight the role of interoceptive information for the visual processing of human body pictures within a network integrating cardio-visual signals of relevance for perceptual and cognitive aspects of visual body processing.


Management of burn wounds.
Small and moderate scalds in toddlers are still the most frequent thermal injuries the pediatric surgeons have to face today. Over the last years, surgical treatment of these patients has changed in many aspects. Due to new dressing materials and new surgical treatment strategies that are particularly suitable for children, today, far better functional and aesthetic long-term results are possible. While small and moderate thermal injuries can be treated in most European pediatric surgical departments, the severely burned child must be transferred to a specialized, ideally pediatric, burn center, where a well-trained multidisciplinary team under the leadership of a (ideally pediatric) burn surgeon cares for these highly demanding patients. In future, tissue engineered full thickness skin analogues will most likely play an important role, in pediatric burn as well as postburn reconstructive surgery.


Familial correlation and segregation analysis of forced expiratory volume in one second (FEV1), with and without smoking adjustments, in a Tucson population.
Previous researchers have found significant familial aggregation but no evidence of Mendelian inheritance of forced expiratory volume in one second (FEV1) in general population studies. However, the influence of cigarette smoking on familial aggregation of FEV1 has been difficult to assess in these studies. The main objective of our study was to attempt to discern the effects of smoking on familial correlation and segregation models of FEV1. In a randomly selected sample of white, non-Mexican American families in Tucson, Arizona, we performed two separate familial correlation and segregation analyses of FEV1, one adjusted for cigarette smoking and one unadjusted for smoking. In both, initial survey measures of FEV1 for 1329 females and 1291 males in 746 families were standardized for gender, age, height and height-squared using piecewise linear regression models. In the smoking-adjusted model, total number of pack-years smoked, current and ex-smoking status, and the interaction between total pack-years and current smoking status were also included. FEV1 was significantly correlated among sibling pairs and parent-offspring pairs (both p < 0.001), regardless of smoking adjustment, but sibling correlation was significantly higher than parent-offspring correlation (p < 0.05), suggesting additional effects beyond common parentage. Spousal correlations were not significant even when both spouses smoked. We found no evidence of major gene segregation of FEV1, with or without smoking adjustment, and all of the segregation models were significantly different from the unrestricted model. The best-fitting model was an environmental model with three distinct distributions of FEV1 and significant residual familial effects. A significant familial component suggests the presence of polygenic factors and/or effects due to a shared environment (multifactorial). That familial correlations of smoking-adjusted and smoking-unadjusted residuals were not appreciably different suggests that current smoking status and number of pack-years smoked do not account for the observed familial aggregation of FEV1.


Crossbred steer temperament as yearlings and whole genome association of steer temperament as yearlings and calf temperament post-weaning.
cattle often have the reputation for a poor or dangerous temperament. Identification of genomic regions that associate with temperament of such cattle may be useful for genetic improvement strategies. The objectives of this study were to evaluate subjective temperament scores (1 to 9; higher scores indicated more unfavorable temperament) for aggressiveness, nervousness, flightiness, gregariousness, and overall temperament of one-half steers in feedlot conditions at 1 yr of age and compare those scores of those steers when evaluated approximately 1 mo postweaning, and conduct whole genome association analyses using SNP markers and the temperament traits of those steers at 1 yr of age and for temperament traits of all calves at weaning. Contemporary groups ( < 0.001) were steers born in the same year and season, and fed in the same feedlot pen. Aggressiveness of steers at 1 yr of age was not associated with aggressiveness at weaning (linear regression coefficient did not differ from 0; = 0.96), but regressions of all other yearling scores of steers on the scores at weaning were positive (coefficients ranged from 0.26 ± 0.04 to 0.32 ± 0.04; < 0.001). Estimates of Pearson correlation coefficients (using unadjusted values and residual values) of the different traits measured at 1 yr of age were large ( > 0.63; < 0.008) except for aggressiveness with nervousness, flightiness, or gregariousness, which did not differ from 0 ( > 0.1). Five SNP on BTA 1, 24, and 29 had suggestive associations (0.17 < [adjusted for FDR] < 0.24) with aggressiveness, nervousness, or flightiness at evaluation postweaning and 13 SNP on 11 chromosomes had suggestive associations (0.07 < [adjusted for FDR] < 0.24) with aggressiveness, nervousness, flightiness, or overall temperament score of steers at 1 yr of age. Genes close to these loci with roles in neural systems of various organisms included synaptotagmin 4 (BTA 24), FAT atypical cadhedrin 3 (BTA 29), tubulin tyrosine ligase-like 1 (BTA 5), spermatogenesis associated 17 (BTA 16), stanniocalcin 2 (BTA 20), and GABA receptor γ 3 (BTA 21).


3D printed silk-gelatin hydrogel scaffold with different porous structure and cell seeding strategy for cartilage regeneration.
Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics. However, most hydrogels offer limited cell growth and tissue formation ability due to their submicron- or nano-sized gel networks, which restrict the supply of oxygen, nutrients and inhibit the proliferation and differentiation of encapsulated cells. In recent years, 3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds. In this study, we fabricated a macroporous hydrogel scaffold through horseradish peroxidase (HRP)-mediated crosslinking of silk fibroin (SF) and tyramine-substituted gelatin (GT) by extrusion-based low-temperature 3D printing. Through physicochemical characterization, we found that this hydrogel has excellent structural stability, suitable mechanical properties, and an adjustable degradation rate, thus satisfying the requirements for cartilage reconstruction. Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel. Moreover, the chondrogenic differentiation of stem cells was explored. Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used. Finally, the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model. After implantation for 12 and 16 weeks, histological evaluation of the sections was performed. We found that the enzymatic cross-linked and methanol treatment SF5GT15 hydrogel combined with cell aggregates promoted articular cartilage regeneration. In summary, this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.


Atypical updating of face representations with experience in children with autism.
Face identity aftereffects are significantly diminished in children with autism relative to typical children, which may reflect reduced perceptual updating with experience. Here, we investigated whether this atypicality also extends to non-face stimulus categories, which might signal a pervasive visual processing difference in individuals with autism. We used a figural aftereffect task to measure directly perceptual updating following exposure to distorted upright faces, inverted faces and cars, in typical children and children with autism. A size-change between study and test stimuli limited the likelihood that any processing atypicalities reflected group differences in adaptation to low-level features of the stimuli. Results indicated that, relative to typical children, figural aftereffects for upright faces, but not inverted faces or cars, were significantly attenuated in children with autism. Moreover, the group difference was amplified when we isolated the 'face-selective' component of the aftereffect, by partialling out the mid-level shape adaptation common to upright and inverted face stimuli. Notably, the aftereffects of typical children were disproportionately larger for upright faces than for inverted faces and cars, but the magnitude of aftereffects of autistic children was not similarly modulated according to stimulus category. These findings are inconsistent with a pervasive adaptive coding atypicality relative to typical children, and suggest that reduced perceptual updating may constitute a high-level, and possibly face-selective, visual processing difference in children with autism.


Phylogenetic relationships within the family potyviridae: wheat streak mosaic virus and brome streak mosaic virus are not members of the genus rymovirus.
ABSTRACT The complete nucleotide sequence of wheat streak mosaic virus (WSMV) has been determined based on complementary DNA clones derived from the 9,384-nucleotide (nt) RNA of the virus. The genome of WSMV has a 130-nt 5' leader and 149-nt 3'-untranslated region and is polyadenylated at the 3' end. WSMV RNA encodes a single polyprotein of 3,035 amino acid residues and has a deduced genome organization typical for a member of the family Potyviridae (5'-P1/HC-Pro/P3/6K1/CI/6K2/VPg-NIa/NIb/CP-3'). Because WSMV shares with ryegrass mosaic virus (RGMV) the biological property of transmission by eriophyid mites, WSMV has been assigned to the genus Rymovirus, of which RGMV is the type species. Phylogenetic analyses were conducted with complete polyprotein or NIb protein sequences of 11 members of the family Potyviridae, including viruses of monocots or dicots and viruses transmitted by aphids, whiteflies, and mites. WSMV and the monocot-infecting, mite-transmitted brome streak mosaic virus (BrSMV) are sister taxa and share a most recent common ancestor with the whitefly-transmitted sweet potato mild mottle virus, the type species of the proposed genus "Ipomovirus." In contrast, RGMV shares a most recent common ancestor with aphid-transmitted species of the genus Potyvirus. These results indicate that WSMV and BrSMV should be classified within a new genus of the family Potyviridae and should not be considered species of the genus Rymovirus.