PAPP-A2 expression by osteoblasts is required for normal postnatal growth in mice.
Pregnancy associated plasma protein-A2 (PAPP-A2) is a protease that cleaves insulin-like growth factor binding protein-5 (IGFBP-5), the most abundant IGFBP in bone. Deletion of Pappa2 reduces postnatal growth and bone length in mice. The aim of this study was to determine whether locally produced PAPP-A2 is required for normal bone growth. We deleted Pappa2 primarily in osteoblasts by crossing conditional Pappa2 deletion mice with mice expressing Cre recombinase under the control of the Sp7 (Osterix) promoter. Effects of disrupting Pappa2 in Sp7-expressing cells were examined by measuring body mass and tail length at 3, 6, 10 and 12 weeks of age and bone dimensions at 12 weeks. Body mass, tail length, and linear bone dimensions were significantly reduced at all ages by osteoblast-specific Pappa2 deletion. Mice homozygous for the conditional Pappa2 deletion allele and carrying the Cre transgene were smaller than controls carrying the Cre transgene, whereas mice homozygous for the conditional Pappa2 deletion allele were not smaller than controls when comparing mice not carrying the transgene. This result unambiguously demonstrates that PAPP-A2 produced by Sp7 expressing cells is required for normal growth. However, constitutive Pappa2 deletion had greater effects than osteoblast-specific Pappa2 deletion for many traits, indicating that post-natal growth is also affected by other sources of PAPP-A2. Immunohistochemistry revealed that PAPP-A2 localized in the epiphysis and metaphysis as well as osteoblasts, consistent with a role in bone growth. Locally-produced PAPP-A2 is required for normal bone growth.


Psychometric evaluation of the Spanish version of CONNECT: a measure of continuity of care in mental health services.
This article provides the results of the psychometric testing of the Spanish version of CONNECT(-S), a measure of continuity of care in mental health services. CONNECT-S is a multidimensional measure designed for use with seriously mentally ill respondents. Consisting of 12 scales and one single-item indicator, it addresses qualities of interaction in current relationships between mental health service providers and consumers in five conceptual domains: (1) practitioner knowledge of their clients, (2) creating flexibility, (3) practitioner availability, (4) practitioner co-ordination, and (5) smoothing transitions. One-hundred-and-fifty participants took part in the study. Participants were recruited from mental health outpatient clinics in both the Puerto Rican (n = 109) and the San Antonio (n = 41) samples. Internal consistency for scales in a combined site estimate ranged from 0.68 to 0.96. Test-retest reliability ranged from fair to substantial in all but one scale. Concurrent validity hypotheses based on a priori predictions were mostly supported. The Spanish translation and adaptation of CONNECT-S provided sound psychometric results across both sites. CONNECT-S addresses the gap in measurement of continuity of care for the two largest US Latino subgroups, Mexican Americans and Puerto Ricans; and provides an encouraging starting point for a measure that is both relevant and culturally sensitive.


DNA recognition by Escherichia coli CbpA protein requires a conserved arginine-minor-groove interaction.
Curved DNA binding protein A (CbpA) is a co-chaperone and nucleoid associated DNA binding protein conserved in most γ-proteobacteria. Best studied in Escherichia coli, CbpA accumulates to >2500 copies per cell during periods of starvation and forms aggregates with DNA. However, the molecular basis for DNA binding is unknown; CbpA lacks motifs found in other bacterial DNA binding proteins. Here, we have used a combination of genetics and biochemistry to elucidate the mechanism of DNA recognition by CbpA. We show that CbpA interacts with the DNA minor groove. This interaction requires a highly conserved arginine side chain. Substitution of this residue, R116, with alanine, specifically disrupts DNA binding by CbpA, and its homologues from other bacteria, whilst not affecting other CbpA activities. The intracellular distribution of CbpA alters dramatically when DNA binding is negated. Hence, we provide a direct link between DNA binding and the behaviour of CbpA in cells.


Transcriptome Analysis Reveals Nonfoamy Rather Than Foamy Plaque Macrophages Are Proinflammatory in Atherosclerotic Murine Models.
Monocyte infiltration into the subintimal space and its intracellular lipid accumulation are the most prominent features of atherosclerosis. To understand the pathophysiology of atherosclerotic disease, we need to understand the characteristics of lipid-laden foamy macrophages in the subintimal space during atherosclerosis. We sought to examine the transcriptomic profiles of foamy and nonfoamy macrophages isolated from atherosclerotic intima. Single-cell RNA sequencing analysis of CD45+ leukocytes from murine atherosclerotic aorta revealed that there are macrophage subpopulations with distinct differentially expressed genes involved in various functional pathways. To specifically characterize the intimal foamy macrophages of plaque, we developed a lipid staining-based flow cytometric method for analyzing the lipid-laden foam cells of atherosclerotic aortas. We used the fluorescent lipid probe BODIPY493/503 and assessed side-scattered light as an indication of cellular granularity. BODIPYhiSSChi foamy macrophages were found residing in intima and expressing CD11c. Foamy macrophage accumulation determined by flow cytometry was positively correlated with the severity of atherosclerosis. Bulk RNA sequencing analysis showed that compared with nonfoamy macrophages, foamy macrophages expressed few inflammatory genes but many lipid-processing genes. Intimal nonfoamy macrophages formed the major population expressing IL (interleukin)-1β and many other inflammatory transcripts in atherosclerotic aorta. RNA sequencing analysis of intimal macrophages from atherosclerotic aorta revealed that lipid-loaded plaque macrophages are not likely the plaque macrophages that drive lesional inflammation.


The business cycle and health behaviors.
While it is well documented that economic expansions provide widespread and immediate financial benefits, the evidence on how an economic downturn affects individual's health behaviors is surprisingly mixed. In this paper, we take a structural approach to investigate the effects of wages and working hours on health behaviors of low-educated persons using variations in wages and hours caused by changes in local economic activity. In the empirical analysis, we adopt a two-sample instrumental variables approach to combine the data on individual health behaviors from the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS) with the data on individual employment from the Current Population Survey (CPS). The total sample size of the combined CPS-BRFSS data for the time period of 1984-2005 is 967,594, while that of the combined CPS-NHIS data for the time period of 1976-2001 is 364,078. We find that increases in wages caused by economic expansions are associated with greater consumption of cigarettes in the United States. We also find that increases in hours of work caused by economic expansions are associated with more cigarette consumption, but less physical activity and physician visits. More importantly, the evidence suggests that most of such effects associated with changes in hours of work can be attributed to the changes at the extensive margin of employment, meaning the changes in employment status, rather than the changes at the intensive margin, meaning changes in hours of work conditional on being employed. These findings imply that changes in employment may have heterogeneous impacts on time-intensive and less time-intensive health behaviors and also provide additional evidence on the importance of time in health production, particularly for time-intensive activities.


Single-cell analyses of nitrergic neurons in simple nervous systems.
Understanding the role of the gaseous messenger nitric oxide (NO) in the nervous system is complicated by the heterogeneity of its nerve cells; analyses carried out at the single cell level are therefore important, if not critical. Some invertebrate preparations, most especially those from the gastropod molluscs, provide large, hardy and identified neurons that are useful both for the development of analytical methodologies and for cellular analyses of NO metabolism and its actions. Recent modifications of capillary electrophoresis (CE) allow the use of a small fraction of an individual neuron to perform direct, quantitative and simultaneous assays of the major metabolites of the NO-citrulline cycle and associated biochemical pathways. These chemical species include the products of NO oxidation (NO2-/NO3-), l-arginine, l-citrulline, l-ornithine, l-argininosuccinate, as well as selected NO synthase inhibitors and cofactors such as NADPH, biopterin, FMN and FAD. Diverse cotransmitters can also be identified in the same nitrergic neuron. The sensitivity of CE methods is in the femtomole to attomole range, depending on the species analysed and on the specific detector used. CE analysis can be combined with prior in vivo electrophysiological and pharmacological manipulations and measurements to yield multiple physiological and biochemical values from single cells. The methodologies and instrumentation developed and tested using the convenient molluscan cell model can be adapted to the smaller and more delicate neurons of other invertebrates and chordates.


Thymol and carvacrol induce autolysis, stress, growth inhibition and reduce the biofilm formation by Streptococcus mutans.
Organic compounds from plants are an attractive alternative to conventional antimicrobial agents. Therefore, two compounds namely M-1 and M-2 were purified from Origanum vulgare L. and were identified as carvacrol and thymol, respectively. Antimicrobial and antibiofilm activities of these compounds along with chlorhexidine digluconate using various assays was determined against dental caries causing bacteria Streptococcus mutans. The IC50 values of carvacrol (M-1) and thymol (M-2) against S. mutans were 65 and 54 µg/ml, respectively. Live and dead staining and the MTT assays reveal that a concentration of 100 µg/ml of these compounds reduced the viability and the metabolic activity of S. mutans by more than 50%. Biofilm formation on the surface of polystyrene plates was significantly reduced by M-1 and M-2 at 100 µg/ml as observed under scanning electron microscope and by colorimetric assay. These results were in agreement with RT-PCR studies. Wherein exposure to 25 µg/ml of M-1 and M-2 showed a 2.2 and 2.4-fold increase in Autolysin gene (AtlE) expression level, respectively. While an increase of 1.3 and 1.4 fold was observed in the super oxide dismutase gene (sodA) activity with the same concentrations of M-1 and M-2, respectively. An increase in the ymcA gene and a decrease in the gtfB gene expression levels was observed following the treatment with M-1 and M-2. These results strongly suggest that carvacrol and thymol isolated from O. vulgare L. exhibit good bactericidal and antibiofilm activity against S. mutans and can be used as a green alternative to control dental caries.


Summer drought decreases soil fungal diversity and associated phenol oxidase activity in upland Calluna heathland soil.
Natural moisture limitation during summer drought can constitute a stress for microbial communities in soil. Given globally predicted increases in drought frequency, there is an urgent need for a greater understanding of the effects of drought events on soil microbial processes. Using a long-term field-scale drought manipulation experiment at Clocaenog, Wales, UK, we analysed fungal community dynamics, using internal transcribed spacer-denaturing gradient gel electrophoresis (DGGE), over a 1-year period in the 6th year of drought manipulation. Ambient seasonality was found to be the dominant factor driving variation in fungal community dynamics. The summer drought manipulation resulted in a significant decline in the abundance of dominant fungal species, both independently of, and in interaction with, this seasonal variation. Furthermore, soil moisture was significantly correlated with the changes in fungal diversity over the drought manipulation period. While the relationship between species diversity and functional diversity remains equivocal, phenol oxidase activity was decreased by the summer drought conditions and there was a significant correlation with the decline of DGGE band richness among the most dominant fungal species during the drought season. Climatically driven events such as droughts may have significant implications for fungal community diversity and therefore, have the potential to interfere with crucial ecosystem processes, such as organic matter decomposition.


Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity.
Developmental pathways such as Notch play a pivotal role in tissue-specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch(+)) or reduced activity (Notch(-)) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays, we investigated the role of the Notch pathway in breast CSC regulation. Breast cancer cells with increased Notch activity displayed increased sphere formation as well as expression of breast CSC markers. Interestingly Notch(+) cells displayed higher Notch4 expression in both basal and luminal breast cancer cell lines. Moreover, Notch(+) cells demonstrated tumor initiation capacity at serial dilutions in mouse xenografts, whereas Notch(-) cells failed to generate tumors. γ-Secretase inhibitor (GSI), a Notch blocker but not a chemotherapeutic agent, effectively targets these Notch(+) cells in vitro and in mouse xenografts. Furthermore, elevated Notch4 and Hey1 expression in primary patient samples correlated with poor patient survival. Our study revealed a molecular mechanism for the role of Notch-mediated regulation of breast CSCs and provided a compelling rationale for CSC-targeted therapeutics.


Lipoplexes formulation and optimisation: in vitro transfection studies reveal no correlation with in vivo vaccination studies.
The aim of these studies was to compare the effect of liposome composition on physico-chemical characteristics and transfection efficacy of cationic liposomes both in vitro and in vivo. Comparison between 4 popularly used cationic lipids, showed 3b-N-(dimethylaminoethyl)carbamate (DC-Chol) to promote the highest transfect levels in cells in vitro with levels being at least 6 times higher than those of 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA). 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and dimethyldioctadecylammonium (DDA) and approximately twice as efficient as dipalmitoyl-trimethylammonium-propane (DPTAP). To establish the role of the helper lipid, DC-Chol liposomes were formulated in combination with either 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) or cholesterol (Chol) (1:1 molar ratio) with and without the addition of phosphatidyl choline. The choice of helper lipid incorporated within the bilayer was found to influence the formation of complexes, their resultant structure and their transfection efficiency in vitro, with SUV-DNA complexes containing optimum levels of DOPE giving higher transfection than those containing cholesterol. The inclusion of PC within the formulation also reduced transfection efficiency in vitro. However, when administered in vivo, SUV-DNA complexes composed of PC:Chol:DC-Chol at a molar ratio of 16:8:4 micromole/ml were the most effective at inducing splenocyte proliferation upon exposure to antigen in comparison to control spleens. These results demonstrate that there is no in vitro/in vivo correlation between the transfection efficacy of these liposome formulations and in vitro transfection in the above cell model cannot be taken as a reliable indicator for in vivo efficacy of DNA vaccines.


Refined Generalization Bounds of Gradient Learning over Reproducing Kernel Hilbert Spaces.
Gradient learning (GL), initially proposed by Mukherjee and Zhou (2006) has been proved to be a powerful tool for conducting variable selection and dimensional reduction simultaneously. This approach presents a nonparametric version of a gradient estimator with positive definite kernels without estimating the true function itself, so that the proposed version has wide applicability and allows for complex effects between predictors. In terms of theory, however, existing generalization bounds for GL depend on capacity-independent techniques, and the capacity of kernel classes cannot be characterized completely. Thus, this letter considers GL estimators that minimize the empirical convex risk. We prove generalization bounds for such estimators with rates that are faster than previous results. Moreover, we provide a novel upper bound for Rademacher chaos complexity of order two, which also plays an important role in general pairwise-type estimations, including ranking and score problems.


The double tragedy of agriculture vulnerability to climate variability in Africa: How vulnerable is smallholder agriculture to rainfall variability in Ghana?
This article analysed vulnerability of smallholder agriculture to climate variability, particularly the alternating incidences of drought and heavy precipitation events in Ghana. Although there is an unmet need for understanding the linkages between climate change and livelihoods, the urgent need for climate change adaptation planning (CCAP) in response to climate change makes vulnerability assessment even more compelling in development research. The data for analysis were collected from two complementary studies. These included a regional survey in the Upper West Region and an in-depth study in three selected communities in the Sissala East District. The results showed that smallholder agriculture is significantly vulnerable to climate variability in the region and that three layers of vulnerability can be identified in a ladder of vulnerability. Firstly, farmers are confronted with the double tragedy of droughts and heavy precipitation events, which adversely affect both crops and livestock. Secondly, farmers have to decide on crops for adaptation, but each option - whether indigenous crops, new early-maturing crops or genetically modified crops - predisposes farmers to a different set of risks. Finally, the overall impact is a higher-level vulnerability, namely the risk of total livelihood failure and food insecurity. The article recommended CCAP and an endogenous development (ED) approach to addressing agriculture vulnerability to climate variability within the framework of decentralisation and local governance in Ghana.


After Posterior Fusions for Adult Spinal Deformity, Operative Time is More Predictive of Perioperative Morbidity, Rather Than Surgical Invasiveness: A Need for Speed?
A retrospective cohort study. The aim of this study was to determine the independent effects of operative time and surgical invasiveness on perioperative outcomes after posterior spinal fusions for adult spinal deformity. Morbidity is high after posterior fusions for adult spinal deformity. Although previous reports have demonstrated an association between perioperative outcomes and the extent of correction and fusion (number of posterior levels fused, pelvic fixation, combined anterior-posterior fusion), no study has looked at the independent effects of the surgical invasiveness after controlling for operative time. All adult patients, undergoing posterior spinal fusion for spinal deformity, were identified in the 2010 to 2014 National Surgical Quality Improvement Program (NSQIP) database. Multivariate analysis was used to determine the independent effects of longer operative timing and the surgical invasiveness (number of levels fused, anterior or transforaminal interbody fusions, osteotomies, and pelvic fixation) on 30-day complications. A total of 1540 patients undergoing posterior spinal fusion for adult spinal deformity were identified. The overall rate of complications was 15.3%. In multivariate analysis, greater operative timing was associated with increased inpatient complications [odds ratio (95% confidence interval, 95% CI) from 2.23 (1.25-3.98) for 7-8 hours to 4.46 (2.61-7.64) for 9+ hours; P < 0.001]. Although the number of levels fused, anterior/interbody fusions, osteotomies, and pelvic fixation were associated with complications on bivariate analysis, these factors were not associated with increased complications in multivariate analysis when controlling for other factors such as operative time. For adult deformity surgery, longer operative time appears to be a better predictor of the overall rate perioperative complications than surgical invasiveness in multivariate analysis. Rather than avoidance of a more extensive and invasive surgical procedure, which may be indicated to improve alignment and stability, these data suggest the importance of safely and efficiently minimizing overall operative time. 4.


Evaluation and management of laryngopharyngeal reflux.
Laryngopharyngeal reflux (LPR) is a major cause of laryngeal inflammation and presents with a constellation of symptoms different from classic gastroesophageal reflux disease. To provide a practical approach to evaluating and managing cases of LPR. The PubMed database and the Ovid Database of Systematic Reviews were systematically searched for laryngopharyngeal reflux, laryngopharyngeal reflux fundoplication, laryngopharyngeal reflux PPI treatment, and gastroesophageal reflux AND laryngitis. Pertinent subject matter journals and reference lists of key research articles were also hand-searched for articles relevant to the analysis. Reflux of gastric contents is a major cause of laryngeal pathology. The pathophysiology and symptom complex of LPR differs from gastroesophageal reflux disease. Laryngeal pathology results from small amounts of refluxate--typically occurring while upright during the daytime--causing damage to laryngeal tissues and producing localized symptoms. Unlike classic gastroesophageal reflux, LPR is not usually associated with esophagitis, heartburn, or complaints of regurgitation. There is no pathognomonic symptom or finding, but characteristic symptoms and laryngoscopic findings provide the basis for validated assessment instruments (the Reflux Symptom Index and Reflux Finding Score) useful in initial diagnosis. There are 3 approaches to confirming the diagnosis of LPR: (1) response of symptoms to behavioral and empirical medical treatment, (2) endoscopic observation of mucosal injury, and (3) demonstration of reflux events by impedance and pH-monitoring studies and barium swallow esophagram. While pH monitoring remains the standard for confirming the diagnosis of gastroesophageal reflux, the addition of multichannel intraluminal impedance technology improves diagnostic accuracy for describing LPR events. Ambulatory multichannel intraluminal impedance assessment allows for identification of gaseous as well as liquid refluxate and detection of nonacid reflux events that are likely significant in confirming LPR. Although some patients respond to conservative behavioral and medical management, as is the case with gastroesophageal reflux, most require more aggressive and prolonged treatment to achieve regression of symptoms and laryngeal tissue changes. Surgical intervention such as laparoscopic fundoplication is useful in selected recalcitrant cases with laxity of the gastroesophageal sphincter. Laryngopharyngeal reflux should be suspected when the history and laryngoscopy findings are suggestive of the diagnosis. Failure to respond to a 3-month trial of behavioral change and gastric acid suppression by adequate doses of proton pump inhibitor medication dictates need for confirmatory studies. Multichannel intraluminal impedance and pH-monitoring studies are most useful in confirming LPR and assessing the magnitude of the problem.


Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension.
Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care. The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.


GORAB Missense Mutations Disrupt RAB6 and ARF5 Binding and Golgi Targeting.
Gerodermia osteodysplastica is a hereditary segmental progeroid disorder affecting skin, connective tissues, and bone that is caused by loss-of-function mutations in GORAB. The golgin, RAB6-interacting (GORAB) protein localizes to the Golgi apparatus and interacts with the small GTPase RAB6. In this study, we used different approaches to shed more light on the recruitment of GORAB to this compartment. We show that GORAB best colocalizes with trans-Golgi markers and is rapidly displaced upon Brefeldin A exposition, indicating a loose association with Golgi membranes. A yeast two-hybrid screening revealed a specific interaction with the small GTPase ADP-ribosylation factor (ARF5) in its active, GTP-bound form. ARF5 and RAB6 bind to GORAB via the same internal Golgi-targeting RAB6 and ARF5 binding (IGRAB) domain. Two GORAB missense mutations identified in gerodermia osteodysplastica patients fall within this IGRAB domain. GORAB carrying the mutation p.Ala220Pro had a cytoplasmic distribution and failed to interact with both RAB6 and ARF5. In contrast, the p.Ser175Phe mutation displaced GORAB from the Golgi compartment to vesicular structures and selectively impaired ARF5 binding. Our findings indicate that the IGRAB domain is crucial for the Golgi localization of GORAB and that loss of this localization impairs its physiological function.


The Evolving Role of Pharmacists in Transgender Health Care.
Pharmacists are increasingly part of a multifaceted team providing health care to members of the often marginalized transgender (TG) community. Some pharmacists, however, may feel unprepared to care for and interact with TG individuals. By providing comprehensive, respectful, and gender-affirming support, improving physical pharmacy environments with policies and procedures, pharmacists can be trustworthy providers for TG patients. This review focuses primarily on the health issues of TG persons and the pharmacist's role in promoting health, identifying barriers to health care, and providing health care resources for TG persons. The evolution of psychiatric diagnostic criteria, access to health care, and inclusion of TG, lesbian, gay, and bisexual topics in the educational curriculum are presented. Cultural competency and diversity training that addresses gender identity and sexual orientation issues should be important interdisciplinary and interprofessional activities for all health care professional education programs. Pharmacists play a key role in the health care needs of TG persons that include appropriate laboratory monitoring, complex pharmacotherapeutic challenges, and providing unbiased gender-affirming interactions. The pharmacy's physical environment, staff training, and policies and procedures can offer unique services to TG persons.


Primer terminus recognition and highly processive replication by Epstein-Barr virus DNA polymerase.
The Epstein-Barr virus (EBV) DNA polymerase is essential for viral DNA replication in the lytic phase of the EBV life cycle. It efficiently extends RNA primers on the template DNA, suggesting the possible involvement of the EBV DNA polymerase in synthesizing Okazaki fragments from RNA primers on the lagging strand template. Competition experiments revealed that the EBV DNA polymerase had significantly higher affinity for primer termini hybridized to the template DNA than for the single-stranded DNA template or the single-stranded primer itself. ATP was not required either for primer terminus recognition or for sustainment of polymerization. The stimulation of the enzyme by (NH4)2SO4 was dependent on the template/primers utilized. These observations suggest that the primary and secondary structure of the template/primers are important factors for primer terminus recognition by the EBV DNA polymerase. The enzyme elongated synthetic RNA primer annealed to circular single-stranded M13 DNA coated with Escherichia coli single-stranded DNA-binding protein without dissociation. The processivity of the EBV DNA polymerase was strikingly high (greater than 7200 nucleotides) and the rate of polymerization was 12 nucleotides/s per polymerase molecule. The high processing capacity is a desirable feature in the synthesis of multiple copies of the EBV genome in rolling-circle DNA replication.


Direct T helper-B cell interactions induce an early B cell activation antigen.
We have explored the consequences for the B cell of cognate interaction with T cells. Early expression of the B cell-restricted cell surface activation antigen, BLAST-2, has been used as an assay system to measure direct T-B cell collaboration. BLAST-2 is preferentially expressed by allogenic B cells cultured with MHC class II antigen-restricted Th clone cells matched to the DR specificity of the target B cells. B cells cultured with DR-mismatched allospecific Th cells express minimal BLAST-2. Th cell-induced BLAST-2 expression appears to be accessory cell independent and occurs as early as 8 h after initiation of culture, with peak expression at 18 h. Direct T-B cell contact, rather than Th-derived lymphokines, provides the most efficient stimulus for BLAST-2 expression. Crosslinking of sIg on B cells is a poor stimulus for BLAST-2 expression. The BLAST-2 assay permits the evaluation of early events associated with B cell activation through cognate interactions, and may facilitate subsequent studies of the mechanism of B cell differentiation.


Oxandrolone protects against the development of multiorgan failure, modulates the systemic inflammatory response and promotes wound healing during burn injury.
Oxandrolone is a synthetic oral non-aromatizable testosterone derivative. This drug has been used successfully for several decades to safely treat growth delays in various diseases including Turner's syndrome. Currently the use of oxandrolone is under clinical testing in children with burn injury; the available data indicate that the anabolic steroid increases net muscle protein balance, maintains lean body mass, and reduces intensive care unit stay. Although oxandrolone is already in clinical trials in burn patients, preclinical burn-related studies with oxandrolone - especially those that go beyond muscle-related parameters and focus on burn-associated organ dysfunction, inflammatory response and wound healing - remain to be conducted. In the current project, using a well-characterized murine model of third-degree burn, we have tested the effect of oxandrolone on indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. In oxandrolone-treated mice (1mg/kg/day for up to 21 days) there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart and lung (but not the liver and kidney) and significantly lower degree of malon dialdehyde accumulation in the liver (but not the heart, lung and kidney). Oxandrolone-treated mice showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and amylase levels, while blood urea nitrogen and creatinine levels remained unaffected, indicative of protective effects of the anabolic hormone against burn-induced hepatic and pancreatic (but not renal) functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12, IP-10, G-CSF, GM-CSF and interferon-γ) were significantly lower in the plasma of oxandrolone-treated animals after burn injury than in the plasma of controls subjected to burns. Finally, oxandrolone significantly accelerated burn wound healing. We conclude that oxandrolone improves organ function, modulates the systemic inflammatory response and accelerates wound healing in a murine model of burn injury.


Determination of P-glycoprotein surface expression and functional ability after in vitro treatment with darunavir or raltegravir in lymphocytes of healthy donors.
It has been shown that P-glycoprotein (P-gp) can greatly affect the cell uptake of antiretroviral drugs, thus hampering their access to HIV-1 replication sites. Lymphocytes are important sites of replication of HIV and target of other drugs, modification on these cells of P-gp could have an effect on pharmacokinetic of antiretrovirals and drug substrates. Blood samples from 16 healthy volunteers were used to determine the expression of P-gp on total, T and T helper lymphocytes after exposure to darunavir, a second generation protease inhibitor, and raltegravir, the first approved integrase inhibitor. Moreover, the effect of the drugs on P-gp functional activity was also studied by the rhodamine-123 efflux test. Darunavir, but not raltegravir, exposure caused a moderate, dose-dependent increment in P-gp expression in total, T and T helper lymphocytes, as demonstrated by the relative frequency of P-gp+ cells and by the amount of P-gp molecules present on cell surface. Functionally, incubation with darunavir led to a marked inhibition of P-gp activity measured by the efflux of rhodamine-123 similar to that observed by verapamil, a specific P-gp inhibitor. Raltegravir was not able to modify the efflux of rhodamine-123 level. Data show that darunavir, unlike raltegravir, may modify the expression and functionality of P-gp on human lymphocytes, thus leading to potential changes in intracellular concentrations of darunavir in patients treated with other drugs substrate of P-gp and vice versa. Our study highlights the need for studies on drug interactions via the P-gp modulation mechanism, especially with the current multi-drug regimens.


Recipient Outcomes Following Transplantation of Allografts From Live Kidney Donors Who Subsequently Developed End-Stage Renal Disease.
Live kidney donors have an increased risk of end-stage renal disease (ESRD) compared with nondonors; however, it is unknown whether undetected, subclinical kidney disease exists at donation that subsequently contributes to this risk. To indirectly test this hypothesis, the authors followed the donated kidneys, by comparing the outcomes of 257 recipients whose donors subsequently developed ESRD with a matched cohort whose donors remained ESRD free. The compared recipients were matched on donor (age, sex, race/ethnicity, donor-recipient relationship), transplant (HLA mismatch, peak panel-reactive antibody, previous transplantation, year of transplantation), and recipient (age, sex, race/ethnicity, body mass index, cause of ESRD, and time on dialysis) risk factors. Median recipient follow-up was 12.5 years (interquartile range 7.4-17.9, maximum 20 years). Recipients of allografts from donors who developed ESRD had increased death-censored graft loss (74% versus 56% at 20 years; adjusted hazard ratio [aHR] 1.7; 95% confidence interval [CI] 1.5-2.0; p < 0.001) and mortality (61% versus 46% at 20 years; aHR 1.5; 95% CI 1.2-1.8; p < 0.001) compared with matched recipients of allografts from donors who did not develop ESRD. This association was similar among related, spousal, and unrelated nonspousal donors. These findings support a novel view of the mechanisms underlying donor ESRD: that of pre-donation kidney disease. However, biopsy data may be required to confirm this hypothesis.


Detection of Chlamydia trachomatis in male and female urine specimens by using the amplified Chlamydia trachomatis test.
The amplified Chlamydia trachomatis test (AMP-CT; Gen-Probe), a new diagnostic test for the detection of Chlamydia trachomatis, was evaluated with urine specimens from 1,000 patients visiting the outpatient department for sexually transmitted diseases at the University Hospital Rotterdam, Rotterdam, The Netherlands, by comparing the results to those of cell culture. From February 1996 to July 1996, urine samples for the AMP-CT test and urethral swabs for cell culture were collected from 544 men, while cervical swabs from 456 women were also taken for cell culture. Positive test results were obtained for 130 (13%) of the patients. AMP-CT test and cell culture results were discordant for 70 (7%) specimens. Analysis of the samples with discordant results was performed by an in-house PCR. After resolution of the discordant results, the sensitivity, specificity, and positive and negative predictive values of the AMP-CT test were 84.3, 98.8, 89.6, and 98%, respectively, for samples from females and 100, 99.2, 93.1, and 100%, respectively, for samples from males, while for cell culture these values were 72.5, 99.2, 92.5, and 98%, respectively, for samples from females and 57.4, 99.0, 86.1, and 95.4%, respectively, for samples from males. We conclude that the AMP-CT test is a fast and reliable test for the detection of C. trachomatis in urine specimens from females and, in particular, males.


Upper and lower arch changes after Mixed Palatal Expansion protocol.
The aim of this study was to evaluate upper and lower dental changes after Mixed Palatal Expansion (MPE) treatment in growing patients with posterior single or bilateral crossbite and mild-to-moderate crowding, as compared to untreated growing subjects by dental cast analysis. A group of 24 patients (18 girls, 6 boys) was treated with Hyrax-type device and compared with an untreated matched control group at T0 (8.6 yrs. ± 2) and at T1 (10 yrs. ± 2) using dental casts. The dental cast analysis was performed on four dental bilateral landmarks, on upper and lower casts; also upper and lower arch depths were measured. The groups were compared using independent sample t-test to estimate dental changes in upper and lower arches. The MPE group showed significant upper and lower arch changes when compared with the control group. Upper intermolar, interpremolar-2nd, interpremolar-1st (P<0.001) and intercanine widths (P<0.05) showed considerable changes in the treated group, while mandibular intermolar (P<0.001), interpremolar-1st (P<0.05) and intercanine widths (P<0.01) were slightly greater in the MPE group when compared with the control group. The changes in transverse upper and lower arch dimensions were significant, when compared with those seen in the control group.


Fast trains, slow boats, and the ancestry of the Polynesian islanders.
The question of the origins of the Polynesians has, for over 200 years, been the subject of adventure science. Since Captain Cook's first speculations on these isolated Pacific islanders, their language affiliations have been seen as an essential clue to the solution. The geographic and numeric centre of gravity of the Austronesian language family is in island Southeast Asia, which was therefore originally seen as their dispersal homeland. However, another view has held sway for 15 years, the 'out of Taiwan' model, popularly known as the 'express train to Polynesia'. This model, based on the combined evidence of archaeology and linguistics, proposes a common origin for all Austronesian-speaking populations, in an expansion of rice agriculturalists from south China/Taiwan beginning around 6,000 years ago. However, it is becoming clear that there is, in fact, little supporting evidence in favour of this view. Alternative models suggest that the ancestors of the Polynesians achieved their maritime skills and horticultural Neolithic somewhere between island Southeast Asia and Melanesia, at an earlier date. Recent advances in human genetics now allow for an independent test of these models, lending support to the latter view rather than the former. Although local gene flow occurring between the bio-geographic regions may have been the means for the dramatic cultural spread out to the Pacific, the immediate genetic substrate for the Polynesian expansion came not from Taiwan, but from east of the Wallace line, probably in Wallacea itself.


Linguistic processing in high-functioning adults with autism or Asperger's syndrome. Is global coherence impaired?
Linguistic processing was explored in normally intelligent adults with either autism or Asperger's syndrome, to test if global coherence was impaired. Global coherence is the ability to establish causal connections and interrelate local chunks into higher-order chunks so that most linguistic elements are linked together thematically. Since individuals with autism are hypothesized to have weak central coherence then one would predict that the clinical groups would have difficulty integrating information globally so as to derive full meaning. Two experiments were designed to test global coherence. Experiment 1 investigated whether individuals on the autism spectrum condition could arrange sentences coherently. Experiment 2 investigated whether they were less able to use context to make a global inference. The clinical groups were less able to arrange sentences coherently and use context to make a global inference. The results suggest that individuals on the autism spectrum have impaired global coherence. Arranging sentences and making global inferences correlated highly, suggesting that central coherence may be a unitary force in these different tasks. Of the two clinical groups, the autism group had the greater deficit. The effect that such a deficit would have on one's daily life is discussed, along with possible explanations for the clinical groups' greater difficulty, and suggestions for future research.


Review of Journal of Cardiovascular Magnetic Resonance 2013.
There were 109 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR) in 2013, which is a 21% increase on the 90 articles published in 2012. The quality of the submissions continues to increase. The editors are delighted to report that the 2012 JCMR Impact Factor (which is published in June 2013) has risen to 5.11, up from 4.44 for 2011 (as published in June 2012), a 15% increase and taking us through the 5 threshold for the first time. The 2012 impact factor means that the JCMR papers that were published in 2010 and 2011 were cited on average 5.11 times in 2012. The impact factor undergoes natural variation according to citation rates of papers in the 2 years following publication, and is significantly influenced by highly cited papers such as official reports. However, the progress of the journal's impact over the last 5 years has been impressive. Our acceptance rate is <25% and has been falling because the number of articles being submitted has been increasing. In accordance with Open-Access publishing, the JCMR articles go on-line as they are accepted with no collating of the articles into sections or special thematic issues. For this reason, the Editors have felt that it is useful once per calendar year to summarize the papers for the readership into broad areas of interest or theme, so that areas of interest can be reviewed in a single article in relation to each other and other recent JCMR articles. The papers are presented in broad themes and set in context with related literature and previously published JCMR papers to guide continuity of thought in the journal. We hope that you find the open-access system increases wider reading and citation of your papers, and that you will continue to send your quality manuscripts to JCMR for publication.


Bilingual lexical selection as a dynamic process: Evidence from Arabic-French bilinguals.
The nature of the lexical selection process in bilingual spoken word production is one of the pending questions of research on bilingualism. According to one view this competitive process is language-specific, while another holds that it is language-nonspecific (i.e., lexical competition is cross-linguistic). In recent years, research on bilingual language production has seen the rise of a third view that postulates that lexical selection is in fact dynamic and may function as language-specific or nonspecific depending on a number of factors. The aim of the present study was to investigate the lexical selection process among moderately proficient bilinguals whose two languages are typologically distant: Tunisian Arabic and French. The picture-word interference task was used in two experiments where moderately proficient Tunisian Arabic (L1)-French (L2) bilinguals were asked to name pictures in their L2 while ignoring auditory distractors (semantic, phono-translation, phonological, or unrelated) in their L2 (Experiment 1) or their L1 (Experiment 2). Thus, the language context was entirely monolingual in Experiment 1 and bilingual in Experiment 2. In Experiment 1, only a phonological facilitation effect was observed. In Experiment 2, interference was found in the phono-translation, semantic, and phonological conditions. Taken together, these results indicate that cross-language competition occurs among moderately proficient Tunisian Arabic-French bilinguals only in a bilingual context (Experiment 2) as indexed by the phono-translation interference effect observed. Our findings are in line with the recent hypothesis that lexical selection is a dynamic process modulated by factors like language similarity, language proficiency, and the experimental language context.


Arsenic-induced protein phosphorylation changes in HeLa cells.
Arsenic is well documented as a chemotherapeutic agent capable of inducing cell death while at the same time is considered a human carcinogen and an environmental contaminant. Although arsenic toxicity is well known and has formed an impressive literature over the time, little is known about how its effects are exerted at the proteome level. Protein phosphorylation is an important post-translational modification involved in the regulation of cell signaling and likely is altered by arsenic treatment. Despite the importance of phosphorylation for many regulatory processes in cells, the identification and characterization of phosphorylation, as effected by arsenic through mass spectrometric detection, are not fully studied. Here, we identify phosphorylated proteins, which are related to post-translational modifications after phenylarsine oxide (PAO) inoculation to HeLa cells. PAO was chosen because of its high cytotoxicity, measured earlier in these labs. In this study, size exclusion chromatography coupled to inductively coupled plasma mass spectrometry (SEC-ICP-MS) is used to establish several molecular weight fractions with phosphorylated proteins by monitoring (31)P signal vs. time via ICP-MS. SEC-ICP-MS fractions are collected and then separated by the nano-LC-CHIP/ITMS system for peptide determination. Spectrum Mill and MASCOT protein database search engines are used for protein identification. Several phosphorylation sites and proteins related to post-translational modifications are also identified.


A multilevel simultaneous equations model for within-cluster dynamic effects, with an application to reciprocal parent-child and sibling effects.
There has been substantial interest in the social and health sciences in the reciprocal causal influences that people in close relationships have on one another. Most research has considered reciprocal processes involving only 2 units, although many social relationships of interest occur within a larger group (e.g., families, work groups, peer groups, classrooms). This article presents a general longitudinal multilevel modeling framework for the simultaneous estimation of reciprocal relationships among individuals with unique roles operating in a social group. We use family data for illustrative purposes, but the model is generalizable to any social group in which measurements of individuals in the social group occur over time, individuals have unique roles, and clustering of the data is evident. We allow for the possibility that the outcomes of family members are influenced by a common set of unmeasured family characteristics. The multilevel model we propose allows for residual variation in the outcomes of parents and children at the occasion, individual, and family levels and residual correlation between parents and children due to the unmeasured shared environment, genetic factors, and shared measurement. Another advantage of this method over approaches used in previous family research is it can handle mixed family sizes. The method is illustrated in an analysis of maternal depression and child delinquency using data from the Avon Brothers and Sisters Study.


Effects of mandibular advancement on respiratory resistance.
Mandibular advancing devices are proposed as nonsurgical treatment for certain patients with an obstructive sleep apnoea syndrome. Since they act by increasing the upper airway calibre, the aim of the present study was to investigate the changes in respiratory resistance (Rrs) resulting from mandibular advancement. Rrs was measured at the nose by the forced oscillation technique (4-32 Hz). Ten normal subjects were studied under three conditions: resting mandibular position, passive mandibular advancement steadied by a wax bite, and voluntary advancement, in random order. Respiratory resistance was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression analysis of respiratory resistive impedance versus frequency. R0 (mean+/-SEM=3.5+/-0.2 cmH2O x L(-1) x s in the resting position) decreased significantly with passive advancement (2.9+/-0.2 cmH2O x L(-1) x s, p<0.001), but remained unchanged with voluntary mandibular advancement (3.6+/-0.2 cmH2O x L(-1) s). Similar results were obtained for R16. The results of this study demonstrate that the effects of mandibular advancement on upper airway resistance differ, depending on whether advancement is passive or active, and suggest that in order to simulate the actual effects of therapeutic devices, mandibular advancement should be passive.


Control of ultra-intense single attosecond pulse generation in laser-driven overdense plasmas.
Ultra-intense single attosecond pulse (AP) can be obtained from circularly polarized (CP) laser interacting with overdense plasma. High harmonics are naturally generated in the reflected laser pulses due to the laser-induced one-time drastic oscillation of the plasma boundary. Using two-dimensional (2D) planar particle-in-cell (PIC) simulations and analytical model, we show that multi-dimensional effects have great influence on the generation of AP. Self-focusing and defocusing phenomena occur in front of the compressed plasma boundary, which lead to the dispersion of the generated AP in the far field. We propose to control the reflected high harmonics by employing a density-modulated foil target (DMFT). When the target density distribution fits the laser intensity profile, the intensity of the attosecond pulse generated from the center part of the plasma has a flatten profile within the center range in the transverse direction. It is shown that a single 300 attosecond (1 as = 10(-18)s) pulse with the intensity of 1.4 × 10(21) W cm(-2) can be naturally generated. Further simulations reveal that the reflected high harmonics properties are highly related to the modulated density distribution and the phase offset between laser field and the carrier envelope. The emission direction of the AP generated from the plasma boundary can be controlled in a very wide range in front of the plasma surface by combining the DMFT and a suitable driving laser.


The effect of gender on eye colour variation in European populations and an evaluation of the IrisPlex prediction model.
In two recent studies of Spanish individuals, gender was suggested as a factor that contributes to human eye colour variation. However, gender did not improve the predictive accuracy on blue, intermediate and brown eye colours when gender was included in the IrisPlex model. In this study, we investigate the role of gender as a factor that contributes to eye colour variation and suggest that the gender effect on eye colour is population specific. A total of 230 Italian individuals were typed for the six IrisPlex SNPs (rs12913832, rs1800407, rs12896399, rs1393350, rs16891982 and rs12203592). A quantitative eye colour score (Pixel Index of the Eye: PIE-score) was calculated based on digital eye images using the custom made DIAT software. The results were compared with those of Danish and Swedish population samples. As expected, we found HERC2 rs12913832 as the main predictor of human eye colour independently of ancestry. Furthermore, we found gender to be significantly associated with quantitative eye colour measurements in the Italian population sample. We found that the association was statistically significant only among Italian individuals typed as heterozygote GA for HERC2 rs12913832. Interestingly, we did not observe the same association in the Danish and Swedish population. This indicated that the gender effect on eye colour is population specific. We estimated the effect of gender on quantitative eye colour in the Italian population sample to be 4.9%. Among gender and the IrisPlex SNPs, gender ranked as the second most important predictor of human eye colour variation in Italians after HERC2 rs12913832. We, furthermore, tested the five lower ranked IrisPlex predictors, and evaluated all possible 3(6) (729) genotype combinations of the IrisPlex assay and their corresponding predictive values using the IrisPlex prediction model [4]. The results suggested that maximum three (rs12913832, rs1800407, rs16891982) of the six IrisPlex SNPs are useful in practical forensic genetic casework.


Visualization of coronary wall atherosclerosis in asymptomatic subjects and patients with coronary artery disease using magnetic resonance imaging.
Magnetic resonance imaging (MRI) is sensitive to early atherosclerotic changes such as positive remodeling in patients with coronary artery disease (CAD). We assessed prevalence, quality, and extent of coronary atherosclerosis in a group of healthy subjects compared to patients with confirmed CAD. Twenty-two patients with confirmed CAD (15M, 7F, mean age 60.4 ± 10.4 years) and 26 healthy subjects without history of CAD (11M, 15F, mean age 56.1 ± 4.4 years) underwent MRI of the right coronary artery (RCA) and vessel wall (MR-CVW) on a clinical 1.5T MR-scanner. Wall thickness measurements of both groups were compared. Stenoses of the RCA (both < and ≥50% on CAG) were present in all patients. In 21/22 patients, stenoses detected at MRI corresponded to stenoses detected with conventional angiography. In 19/26 asymptomatic subjects, there was visible luminal narrowing in the MR luminography images. Fourteen of these subjects demonstrated corresponding increase in vessel wall thickness. In 4/26 asymptomatic subjects, vessel wall thickening without luminal narrowing was present. Maximum and mean wall thicknesses in patients were significantly higher (2.16 vs 1.92 mm, and 1.38 vs 1.22 mm, both p<0.05). In this cohort of middle-aged individuals, both patients with stable angina and angiographically proven coronary artery disease, as well as age-matched asymptomatic subjects. exhibited coronary vessel wall thickening detectable with MR coronary vessel wall imaging. Maximum and mean wall thicknesses were significantly higher in patients. The vast majority of asymptomatic subjects had either positive remodeling without luminal narrowing, or non-significant stenosis. ClinicalTrials.gov NCT00456950.


Social Cognition and Behavioral Assessments Improve the Diagnosis of Behavioral Variant of Frontotemporal Dementia in Older Peruvians With Low Educational Levels.
Background: The behavioral variant of frontotemporal dementia (bvFTD), characterized by early behavioral abnormalities and late memory impairment, is a neurodegenerative disorder with a detrimental impact on patients and their caregivers. bvFTD is often difficult to distinguish from other neurodegenerative diseases, such as Alzheimer's disease (AD), using brief cognitive tests. Combining brief socio-cognitive and behavioral evaluations with standard cognitive testing could better discriminate bvFTD from AD patients. We sought to evaluate the diagnostic accuracy of brief socio-cognitive tests that may differentiate bvFTD and AD patients with low educational levels. Methods: A prospective study was performed on 51 individuals over the age of 50 with low educational levels, with bvFTD or AD diagnosed using published criteria, and who were receiving neurological care at a multidisciplinary neurology clinic in Lima, Peru, between July 2017 and December 2020. All patients had a comprehensive neurological evaluation, including a full neurocognitive battery and brief tests of cognition (Addenbrooke's Cognitive Examination version III, ACE-III), social cognition (Mini-social Cognition and Emotional Assessment, Mini-SEA), and behavioral assessments (Frontal Behavioral Inventory, FBI; Interpersonal Reactivity Index-Emphatic Concern, IRI-EC; IRI-Perspective Taking, IRI-PT; and Self-Monitoring Scale-revised version, r-SMS). Receiver operating characteristic (ROC) analysis to calculate the area under the curve (AUC) was performed to compare the brief screening tests individually and combined to the gold standard of bvFTD and AD diagnoses. Results: The AD group was significantly older than the bvFTD group (p < 0.001). An analysis of the discriminatory ability of the ACE-III to distinguish between patients with AD and bvFTD (AUC = 0.85) and the INECO Frontal Screening (IFS; AUC = 0.78) shows that the former has greater discriminatory ability. Social and behavioral cognition tasks were able to appropriately discriminate bvFTD from AD. The Mini-SEA had high sensitivity and high moderate specificity (83%) for discriminating bvFTD from AD, which increased when combined with the brief screening tests ACE-III and IFS. The FBI was ideal with high sensitivity (83%), as well as the IRI-EC and IRI-PT that also were adequate for distinguishing bvFTD from AD. Conclusions: Our study supports the integration of socio-behavioral measures to the standard global cognitive and social cognition measures utilized for screening for bvFTD in a population with low levels of education.


The Body Mass Index of San Francisco Cold-water Swimmers: Comparisons to U.S. National and Local Populations, and Pool Swimmers.
To determine if cold-water swimmers have substantial differences in BMI, which might have a protective effect against heat loss during swims in cold water without wetsuits, and to determine if obesity is more or less prevalent in cold-water swimmers, we compared the body mass index (BMI) values of 103 recreational open-water swimmers (mean age 54.3 ±10.8 years) to data from various population groups. Swimmers swam consistently throughout the winter months, in the San Francisco Bay (water temperature range: 9.6° C [49.3 ° F] to 12.6° C [54.7 ° F]), without wetsuits. After matching for age and sex, the average BMI of cold-water swimmers (25.9 kg/m2) was lower than the corresponding predicted U.S. average BMI (29.2 kg/m2; p<.001), the predicted California state average BMI (28.0 kg/m2; p<.001), and the predicted San Francisco city average BMI (26.6 kg/m2; p=.047). The average BMI value for cold-water swimmers (25.9 kg/m2) was not significantly different from values of North American masters pool swimmers (25.1 kg/m2; p=.15) or international masters pool swimmers (25.3 kg/m2; p=.16). 10.7% of cold-water swimmers were classified as obese (BMI > 30 kg/m2) vs. 35.7%, 25.8%, and 11.8% of the U.S., California, and San Francisco populations, respectively. The lower or similar BMI values of our swimmers suggest that successful recreational swimming in cold water is influenced by factors other than body habitus, such as acclimatization, heat production while swimming, and most importantly, limiting immersion time. The relatively low prevalence of obesity in our swimmers suggests that cold-water swimming could contribute to a healthy lifestyle.


Quantum Chemical Benchmarking, Validation, and Prediction of Acidity Constants for Substituted Pyridinium Ions and Pyridinyl Radicals.
Sensibly modeling (photo)electrocatalytic reactions involving proton and electron transfer with computational quantum chemistry requires accurate descriptions of protonated, deprotonated, and radical species in solution. Procedures to do this are generally nontrivial, especially in cases that involve radical anions that are unstable in the gas phase. Recently, pyridinium and the corresponding reduced neutral radical have been postulated as key catalysts in the reduction of CO2 to methanol. To assess practical methodologies to describe the acid/base chemistry of these species, we employed density functional theory (DFT) in tandem with implicit solvation models to calculate acidity constants for 22 substituted pyridinium cations and their corresponding pyridinyl radicals in water solvent. We first benchmarked our calculations against experimental pyridinium deprotonation energies in both gas and aqueous phases. DFT with hybrid exchange-correlation functionals provide chemical accuracy for gas-phase data and allow absolute prediction of experimental pKas with unsigned errors under 1 pKa unit. The accuracy of this economical pKa calculation approach was further verified by benchmarking against highly accurate (but very expensive) CCSD(T)-F12 calculations. We compare the relative importance and sensitivity of these energies to selection of solvation model, solvation energy definitions, implicit solvation cavity definition, basis sets, electron densities, model geometries, and mixed implicit/explicit models. After determining the most accurate model to reproduce experimentally-known pKas from first principles, we apply the same approach to predict pKas for radical pyridinyl species that have been proposed relevant under electrochemical conditions. This work provides considerable insight into the pitfalls using continuum solvation models, particularly when used for radical species.


Genome-Wide Characterization of Major Intrinsic Proteins in Four Grass Plants and Their Non-Aqua Transport Selectivity Profiles with Comparative Perspective.
Major intrinsic proteins (MIPs), commonly known as aquaporins, transport not only water in plants but also other substrates of physiological significance and heavy metals. In most of the higher plants, MIPs are divided into five subfamilies (PIPs, TIPs, NIPs, SIPs and XIPs). Herein, we identified 68, 42, 38 and 28 full-length MIPs, respectively in the genomes of four monocot grass plants, specifically Panicum virgatum, Setaria italica, Sorghum bicolor and Brachypodium distachyon. Phylogenetic analysis showed that the grass plants had only four MIP subfamilies including PIPs, TIPs, NIPs and SIPs without XIPs. Based on structural analysis of the homology models and comparing the primary selectivity-related motifs [two NPA regions, aromatic/arginine (ar/R) selectivity filter and Froger's positions (FPs)] of all plant MIPs that have been experimentally proven to transport non-aqua substrates, we predicted the transport profiles of all MIPs in the four grass plants and also in eight other plants. Groups of MIP subfamilies based on ar/R selectivity filter and FPs were linked to the non-aqua transport profiles. We further deciphered the substrate selectivity profiles of the MIPs in the four grass plants and compared them with their counterparts in rice, maize, soybean, poplar, cotton, Arabidopsis thaliana, Physcomitrella patens and Selaginella moellendorffii. In addition to two NPA regions, ar/R filter and FPs, certain residues, especially in loops B and C, contribute to the functional distinctiveness of MIP groups. Expression analysis of transcripts in different organs indicated that non-aqua transport was related to expression of MIPs since most of the unexpressed MIPs were not predicted to facilitate the transport of non-aqua molecules. Among all MIPs in every plant, TIP (BdTIP1;1, SiTIP1;2, SbTIP2;1 and PvTIP1;2) had the overall highest mean expression. Our study generates significant information for understanding the diversity, evolution, non-aqua transport profiles and insight into comparative transport selectivity of plant MIPs, and provides tools for the development of transgenic plants.


Environmental Methicillin-resistant Staphylococcus aureus Contamination, Persistent Colonization, and Subsequent Skin and Soft Tissue Infection.
The longitudinal association among persistent Staphylococcus aureus colonization, household environmental contamination, and recurrent skin and soft tissue infection (SSTI) is largely unexplored to date. To identify factors associated with persistent S aureus colonization and recurrent SSTI in households with children with community-associated methicillin-resistant S aureus (MRSA) SSTI. This 12-month prospective cohort study included 150 children with community-associated MRSA SSTI, 542 household contacts, and 154 pets enrolled from January 3, 2012, through October 20, 2015. A total of 5 quarterly home visits were made to 150 households in the St Louis, Missouri, region. Statistical analysis was performed from September 18, 2018, to January 7, 2020. Covariates used in S aureus strain persistence and interval SSTI models included S aureus colonization and contamination measures, personal hygiene and sharing habits, health history, activities external to the home, and household characteristics (eg, cleanliness, crowding, home ownership, and pets). Serial samples to detect S aureus were collected from household members at 3 anatomic sites, from pets at 2 anatomic sites, and from environmental surfaces at 21 sites. Molecular epidemiologic findings of S aureus isolates were assessed via repetitive-sequence polymerase chain reaction. Individual persistent colonization was defined as colonization by an identical strain for 2 consecutive samplings. Longitudinal, multivariable generalized mixed-effects logistic regression models were used to assess factors associated with persistent S aureus personal colonization, environmental contamination, and interval SSTI. Among 692 household members in 150 households, 326 (47%) were male and 366 (53%) were female, with a median age of 14.82 years (range, 0.05-82.25 years). Of 540 participants completing all 5 samplings, 213 (39%) were persistently colonized with S aureus, most often in the nares and with the strain infecting the index patient at enrollment. Nine pets (8%) were persistently colonized with S aureus. Participants reporting interval intranasal mupirocin application were less likely to experience persistent colonization (odds ratio [OR], 0.44; 95% credible interval [CrI], 0.30-0.66), whereas increasing strain-specific environmental contamination pressure was associated with increased individual persistent colonization (OR, 1.17; 95% CrI, 1.06-1.30). Strains with higher colonization pressure (OR, 1.47; 95% CrI, 1.25-1.71) and MRSA strains (OR, 1.57; 95% CrI, 1.16-2.19) were more likely to persist. Seventy-six index patients (53%) and 101 household contacts (19%) reported interval SSTIs. Individuals persistently colonized with MRSA (OR, 1.56; 95% CrI, 1.17-2.11), those with a history of SSTI (OR, 2.55; 95% CrI, 1.88-3.47), and index patients (OR, 1.54; 95% CrI, 1.07-2.23) were more likely to report an interval SSTI. The study findings suggest that recurrent SSTI is associated with persistent MRSA colonization of household members and contamination of environmental surfaces. Future studies may elucidate the effectiveness of specific combinations of personal decolonization and environmental decontamination efforts in eradicating persistent strains and mitigating recurrent SSTIs.


Molecular recognition of β-O-GlcNAc glycopeptides by a lectin-like receptor: binding modulation by the underlying Ser or Thr amino acids.
The binding properties of different carbohydrates and glycopeptides containing the β-O-2-deoxy-2-(N-acetyl)-D-glucosaminyl (β-O-GlcNAc) to a synthetically prepared lectin-like receptor have been analyzed. The study combines the use of NMR spectroscopy experiments with extensive MD simulations in explicit water. Notably, the presence of a key hydrogen bond between the receptor and the OMe group of the β-O-GlcNAc-OMe derivative appears to be responsible for the high selectivity observed for this compound. In addition, to study the effect on the binding of the underlying amino acid, we have prepared different model glycopeptides, which include the non-natural α-methylserine and α-methylthreonine as underlying amino acids. Interestingly, the presence of a methyl group decreases the affinity constant, especially in those cases in which a β-methyl group is present. As a result, the serine-containing glycopeptide exhibited the highest affinity constant of the glycopeptides, and the threonine derivative showed the lowest one. This low selectivity could have its origin in the difficulty to form both specific hydrogen bonds and hydrophobic (CH-π) contacts.


Weight loss before conception: A systematic literature review.
The prevalence of overweight and obesity in women has increased during the last decades. This is a serious concern since a high BMI before conception is an independent risk factor for many adverse outcomes of pregnancy. Therefore, dietary counseling, intended to stimulate weight loss in overweight and obese women prior to conception has recently been recommended. However, dieting with the purpose to lose weight may involve health risks for mother and offspring. We conducted a systematic literature review to identify papers investigating the effects of weight loss due to dietary interventions before conception. The objective of this study is to assess the effect of weight loss prior to conception in overweight or obese women on a number of health-related outcomes in mother and offspring using studies published between January 2000 and December 2011. Our first literature search produced 486 citations and, based on predefined eligibility criteria, 58 were selected and ordered in full text. Two group members read each paper. Fifteen studies were selected for quality assessment and two of them were considered appropriate for inclusion in evidence tables. A complementary search identified 168 citations with four papers being ordered in full text. The two selected studies provided data for overweight and obese women. One showed a positive effect of weight loss before pregnancy on the risk of gestational diabetes and one demonstrated a reduced risk for large-for-gestational-age infants in women with a BMI above 25 who lost weight before pregnancy. No study investigated the effect of weight loss due to a dietary intervention before conception. There is a lack of studies on overweight and obese women investigating the effect of dietary-induced weight loss prior to conception on health-related variables in mother and offspring. Such studies are probably lacking since they are difficult to conduct. Therefore, alternative strategies to control the body weight of girls and women of reproductive age are needed.


Effects of Granulocyte-Macrophage Colony-Stimulating Factor on Neuronal Senescence in Ultraviolet Irradiated Skin.
Ultraviolet (UV) irradiation affects neuronal structures of the skin and accelerates skin aging. Cytokine cascades in keratinocytes after UV irradiation may result in a paracrine inhibitory effect on nerve cells. The purpose of the present study was to determine the direct effect of cytokines induced by UV radiation on nerve cells in terms of neuronal senescence. Our group performed a preliminary study to determine cytokines induced in UV-irradiated keratinocytes. Among 40 cytokines studied, granulocyte-macrophage colony-stimulating factor (GM-CSF) was increased 4-fold in inflammation antibody array. The GM-CSF was added to cultured human neuroblastoma cells. To evaluate the effect of cellular senescence, the authors performed real-time polymerase chain reaction (RT-PCR), western blot, immunocytochemical, and phase-contrast microscopic evaluations. Expression levels of matrix metallopeptidase-9 (MMP-9), nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1), inducible nitric oxide synthase (iNOS), and interleukin β1 (IL-β1) were assessed by RT-PCR. Expression levels of AAP and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) related to formation of beta-amyloid were evaluated by western blot analysis. Expression levels of MMP-9, NF-κB1, iNOS, and IL-β1 after treatment with GM-CSF were significantly higher than those in the control group. Enhanced expression of AAP and BACE1 was also observed in the treatment group. Thus, GM-CSF might have a provocative effect on nerve cells in terms of neuronal senescence.


Measuring success: program fidelity of Queensland's child health home visiting services. A document analysis.
The Family CA.R.E. (Community-based Assistance Resourcing and Education) program was introduced in Queensland two decades ago. It aimed to redress health inequalities for infants from families experiencing specific social stressors. The program has been locally adapted over time and has not been evaluated against the original program. This study assessed the extent to which selected hospital and health services in Queensland, Australia have modified the original Family C.A.R.E. Altheide's model was used to facilitate a critical document analysis of policies and guidelines for adapted Family C.A.R.E. home visiting programs in use by hospital and health services (target n =7). Five of seven eligible services provided service model documentation. There was low alignment with the original Family C.A.R.E. program across four of the five participating services. While the program delivered within Service 4 was highly aligned to the structure and intent of the original model, variation to the program was still evident. Importantly, four of the five participating programs were not collecting evaluation measures. Health services have adapted the original Family C.A.R.E program format to 'fit' the local service environment but have largely failed to collect data to facilitate evaluation. Inability to evaluate the program leads to uncertainty about program success and benefits as well as any unintended consequences for families engaging in unevaluated home visiting programs. This study highlights the importance of monitoring program fidelity and evaluating success given the potential ramifications for this vulnerable cohort and for health service delivery.


Diaphragm myoclonus followed by generalised atonia in a patient with trisomy 4p: unusual semiology in an unusual condition.
In this report, we describe a female patient with trisomy 4p, a rare genetic condition, with unusual seizure semiology. The patient is one of the oldest reported survivors with this condition. This semiology was noted while she was being monitored by inpatient video telemetry. We observed a series of myoclonic shoulder jerks, followed by hiccup-like episodes, and finally an atonic head drop. Corresponding ictal EEG showed semi-rhythmic high-amplitude slow waves with spikes superimposed over the frontotemporal areas. This semiology was confirmed as habitual by her parents. Subsequent hiccup-like episodes had no EEG correlate, and the head drop was again associated with semi-rhythmic high-amplitude slow waves and superimposed spikes, more prominent over the right hemisphere. In addition, we review the several cases in which hiccups have been associated with seizures and how this may relate to the neural pathways involved in the pathophysiology of hiccups. We believe the ictal hiccup-like episodes followed by atonia to be a seizure semiology that has not previously been documented. [Published with video sequence].


Antidepressant use and risk for preeclampsia.
Prior studies suggest that women who use antidepressants during pregnancy have an increased risk for preeclampsia, yet the comparative safety of specific antidepressants remains unclear. US nationwide Medicaid Analytic eXtract (MAX) data have not been used to study medication safety during pregnancy. We identified 100,942 pregnant women with depression from 2000 to 2007 MAX data. We used pharmacy dispensing records to ascertain exposure to selective serotonin reuptake inhibitor (SSRI), serotonin-norepenephrine reuptake inhibitor (SNRI), tricyclic, bupropion, other antidepressant monotherapy or polytherapy, and specific antidepressants, during the second trimester and first half of the third trimester. Relative risks (RRs) and 95% confidence intervals (CIs) were adjusted for delivery year, preeclampsia risk factors, depression severity proxies, other antidepressant indications, other medications, and healthcare utilization. The risk of preeclampsia was 5.4% among women with depression and no antidepressant exposure. Compared with these women, the risk for preeclampsia was higher among those receiving SNRI (RR: 1.52, 95% CI = 1.26-1.83) and tricyclic monotherapy (RR: 1.62, 95% CI = 1.23-2.12), but not SSRI monotherapy (RR: 1.00, 95% CI = 0.93-1.07) or other antidepressants. Compared with women receiving SSRI monotherapy, preeclampsia risk was higher among women with SNRI (RR: 1.54, 95% CI = 1.28-1.86) and tricyclic (RR: 1.64, 95% CI = 1.25-2.16) monotherapy. None of the specific SSRIs was associated with preeclampsia. The RR with venlafaxine was 1.57 (95% CI = 1.29-1.91) and with amitriptyline 1.72 (95% CI = 1.24-2.40). In this population, SNRIs and tricyclics were associated with a higher risk of preeclampsia than SSRIs.


The problem of out-of-hospital cardiac-arrest prevalence of sudden death in Europe today.
In Europe, 40% of all deaths of individuals who are 25-74 years of age are caused by cardiovascular disease. Cardiac disease is the underlying cause in two-thirds of out-of-hospital sudden deaths. The 28-day case fatality rate for the combined population of out-of-hospital coronary artery disease deaths and hospitalized acute myocardial infarction patients is approximately 50% in 29 of the regions included in the World Health Organization (WHO) Monitoring Trends and Determinants in Cardiovascular Disease registry. Of 14,065 patients included in the Swedish Cardiac Arrest Registry, resuscitation procedures were started in 10,966 patients. The remaining 3,099 were considered definitely dead; 70% were witnessed, cardiac arrests and 32.3% had been given bystander cardiopulmonary resuscitation (CPR). The incidence of ventricular tachycardia (VT)/ventricular fibrillation (VF) in all patients was 43%, in witnessed cases 54%, and in nonwitnessed cases, 31%. The initial incidence of VT/VF was calculated to be approximately 60% in the whole population and 80-85% in those with probable cardiac disease. Survival to 1 month was 5.0% in the total population, 9.5% for those with VT/VF on the first electrocardiogram compared with 1.6% for those not in VT/VF. Survival rate was also calculated in relation to delay time to first defibrillation. Survival was 50% when defibrillation was performed immediately and decreased gradually to 0% for those with a delay time of 20 minutes. The survival rate after bystander CPR was 2.6-fold higher than the rate for those where no treatment was given until the ambulance arrived.


Standards of the Polish Ultrasound Society. Ultrasound examination in anesthesiology and intensive care.
This article has been prepared on the basis of the Ultrasonography Standards of the Polish Ultrasound Society (2011) and updated based on the latest findings and reports. Various applications of ultrasonography are used in anesthesiology and intensive therapy both for diagnosis and as a supportive tool during invasive procedures (such as vascular cannulation or regional anesthesia). Ultrasound examinations performed by anesthesiologists in intensive care units are not detailed scans, but they are focused on immediate identification of pathologies that lead to life-threatening conditions. Performing repeated US exams in time intervals enables a physician to monitor the effectiveness of the instituted treatment. Many simplified protocols are used in clinical practice which help to systemize the examination. Focused US examination should be verified by a physician competent in this imaging method as soon as possible. Due to the specificity of anesthesiologists' practice and spatial limitations of operating rooms and intensive care units, portable robust ultrasound equipment with short power-on to scanning time is preferable. A growing number of indications show that ultrasound machine should be equipped with three basic transducers (linear, convex and sector), and in higher-reference centers with a transesophageal probe. The specificity of certain procedures guided by ultrasonography requires adherence to safety measures, e.g. full sterility condition during vein cannulation.


Hyperpolarization-activated cation current contributes to spontaneous network activity in developing neocortical cultures.
The mechanisms underlying spontaneous burst activity (SBA), appearing in networks of embryonic cortical neurons at the end of the first week in vitro, remain elusive. Here we investigated the contribution of the hyperpolarization-activated cation current (I(h)) to SBA in cortical cultures of GAD67-GFP mice. I(h) current could be detected in GFP-positive large GABAergic interneurons (L-INs) and glutamatergic principal neurons (PNs) as early as DIV 5. Under current-clamp conditions, blockers of I(h) current, ZD7288 and Cs⁺, abolished the voltage sag and rebound depolarization. ZD7288 induced a hyperpolarization concomitant with an increase in the membrane input resistance in L-INs and PNs. Voltage-clamp recordings revealed I(h) as slowly activating inward current with a reversal potential close to -50 mV and a mid-activation point around -90 mV. Both, ZD7288 (1-10 μM) and Cs⁺ (1-2 mM) reduced SBA, spontaneous activity-driven Ca²⁺ transients, and frequency as well as amplitude of miniature GABAergic postsynaptic currents. Immunocytochemistry and Western blot demonstrated that HCN1 and HCN2 were the prevalent isoforms of HCN channels expressed in L-INs and PNs. These results suggest an important contribution of HCN channels to the maintenance of SBA in embryonic cortical cultures.


Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis.
The inhA gene has been recently shown to encode a common protein target for isoniazid and ethionamide action in Mycobacterium tuberculosis. In this paper, we demonstrate that the M. tuberculosis InhA protein catalyzes the NADH-specific reduction of 2-trans-enoyl-ACP, essential for fatty acid elongation. This enzyme preferentially reduces long-chain substrates (12-24 carbons), consistent with its involvement in mycolic acid biosynthesis. Steady-state kinetic studies showed that the two substrates bind to InhA via a sequential kinetic mechanism, with the preferred ordered addition of NADH and the enoyl substrate. The chemical mechanism involves stereospecific hydride transfer of the 4S hydrogen of NADH to the C3 position of the 2-trans-enoyl substrate, followed by protonation at C2 of an enzyme-stabilized enolate intermediate. Kinetic and microcalorimetric analysis demonstrates that the binding of NADH to the S94A mutant InhA, known to confer resistance to both isoniazid and ethionamide, is altered. This difference can account for the isoniazid-resistance phenotype, with the formation of a binary InhA-NADH complex required for drug binding. Isoniazid binding to either the wild-type or S94A mutant InhA could not be detected by titration microcalorimetry, suggesting that this compound is a prodrug, which must be converted to its active form.


Effects of Postharvest Onion Curing Parameters on the Development of Sour Skin and Slippery Skin in Storage.
The influence of postharvest curing temperature and duration on development of slippery skin (caused by Burkholderia gladioli pv. alliicola) and sour skin (caused by B. cepacia) in onion (Allium cepa) bulbs during storage was evaluated by inoculating bulbs of the storage cultivars 'Redwing' and 'Vaquero' with each of the pathogens after harvest, curing the bulbs at 25, 30, 35, or 40°C for 2 or 14 days, and storing the bulbs at 5°C for 1, 2, or 3 months. Noninoculated bulbs and bulbs injected with sterile water served as control treatments. The onion bulbs were from drip-irrigated, commercial onion crops grown in the semiarid Columbia Basin of central Washington in 2009 and 2010. Each bulb was cut through the point of inoculation from the neck to the basal plate to assess severity of bulb rot (percentage of cut bulb surface area with bacterial rot symptoms) after 1, 2, or 3 months of storage. Bulb rot severity in the 2009-10 and 2010-11 trials was negligible for noninoculated bulbs (mean of 4.0 and 4.5%, respectively) and bulbs injected with water (6.2 and 10.1%, respectively) compared with bulbs inoculated with B. cepacia (34.6 and 39.8%, respectively) and B. gladioli pv. alliicola (20.7 and 27.4%, respectively). Bulbs inoculated with B. cepacia developed significantly more severe rot than those inoculated with B. gladioli pv. alliicola, even though a 10-fold greater inoculum concentration was used for B. gladioli pv. alliicola, demonstrating the more aggressive nature of B. cepacia compared with B. gladioli pv. alliicola. Severity of bulb decay caused by B. cepacia or B. gladioli pv. alliicola was affected significantly (P < 0.05) by season (trial), cultivar, curing temperature, curing duration, and storage duration, with significant interactions among these factors. In both trials and for both pathogens, bulb rot was significantly more severe the greater the curing temperature and the severity of bulb rot was significantly greater when bulbs were cured for 14 versus 2 days prior to cold storage. Overall, the severity of bulb rot was greater with a longer duration of storage after curing. This increase in bulb rot severity, which resulted from an increase in curing temperature and duration, was significantly greater for Vaquero than Redwing and significantly greater for bulbs inoculated with B. cepacia than B. gladioli pv. alliicola. The results suggest that postharvest curing at temperatures <35°C for a limited duration can significantly reduce the severity of sour skin or slippery skin in storage.


Use of complementary and alternative medicine within Norwegian hospitals.
Over the recent decades complementary and alternative medicine (CAM) use within and outside of the public health care system in Norway has increased. The aim of this study is to describe to what extent CAM is offered in Norwegian hospitals in 2013 and investigate possible changes since 2008. In January 2013 a one-page questionnaire was sent to the medical director of all included hospitals (n = 80). He/she was asked to report whether or not one or more specific CAM therapies were offered in the hospital. Fifty-nine (73.8%) hospitals responded and form the basis for the analyses. CAM was offered in 64.4% of the responding hospitals. No major differences were found between public and private, or between somatic and psychiatric, hospitals. Acupuncture was the most frequent CAM method offered, followed by art- and expression therapy and massage. The proportion of hospitals offering CAM has increased from 50.5% in 2008 to 64.4% in 2013 (p = 0.089). The largest increase was found in psychiatric hospitals where 76.5% of hospitals offered CAM in 2013 compared to 28.6% in 2008 (p = 0.003). A small decrease was found in the proportion of hospitals offering acupuncture between 2008 (41.4%) and 2013 (37.3%). A majority of Norwegian hospitals offer some sort of CAM. The largest increase since 2008 was found in psychiatric hospitals. Psychiatric hospitals seem to have established a practice of offering CAM to their patients similar to the practice in somatic hospitals. This could indicate a shift in the attitude with regard to CAM in psychiatric hospitals.


An office-place stepping device to promote workplace physical activity.
It was proposed that an office-place stepping device is associated with significant and substantial increases in energy expenditure compared to sitting energy expenditure. The objective was to assess the effect of using an office-place stepping device on the energy expenditure of lean and obese office workers. The office-place stepping device is an inexpensive, near-silent, low-impact device that can be housed under a standard desk and plugged into an office PC for self-monitoring. Energy expenditure was measured in lean and obese subjects using the stepping device and during rest, sitting and walking. 19 subjects (27+/-9 years, 85+/-23 kg): 9 lean (BMI<25 kg/m2) and 10 obese (BMI>29 kg/m2) attended the experimental office facility. Energy expenditure was measured at rest, while seated in an office chair, standing, walking on a treadmill and while using the office-place stepping device. The office-place stepping device was associated with an increase in energy expenditure above sitting in an office chair by 289+/-102 kcal/hour (p<0.001). The increase in energy expenditure was greater for obese (335+/-99 kcal/hour) than for lean subjects (235+/-80 kcal/hour; p = 0.03). The increments in energy expenditure were similar to exercise-style walking. The office-place stepping device could be an approach for office workers to increase their energy expenditure. If the stepping device was used to replace sitting by 2 hours per day and if other components of energy balance were constant, weight loss of 20 kg/year could occur.


Event-related clinical distress in college students: Responses to the 2016 U.S. Presidential election.
Objectives: College students have cited the 2016 U.S. presidential election as a significant source of stress. The current study examined the prevalence and demographic correlates of clinically significant election-related avoidance and intrusion symptoms among college students 2-3 months after the election. Participants: College students attending a large public university (N = 769; Mage = 19.19; 48.2% female; 58.4% White) were surveyed in January and February 2017. Methods: Participants completed a validated measure of clinically significant event-related distress symptoms (eg, intrusive thoughts, avoidance) and demographic questions. Results: One out of four students met criteria for clinically significant symptoms related to the election. Regression analyses suggested that sex, political party, religion, and perceived impact of the election on relationships were more useful predictors of stress symptoms than race or social class. Conclusions: The high level of event-related distress is concerning because elevated symptoms of event-related stress are predictive of future distress and subsequent PTSD diagnoses.


Identifying the Best Times for Cognitive Functioning Using New Methods: Matching University Times to Undergraduate Chronotypes.
University days generally start at fixed times in the morning, often early morning, without regard to optimal functioning times for students with different chronotypes. Research has shown that later starting times are crucial to high school students' sleep, health, and performance. Shifting the focus to university, this study used two new approaches to determine ranges of start times that optimize cognitive functioning for undergraduates. The first is a survey-based, empirical model (SM), and the second a neuroscience-based, theoretical model (NM). The SM focused on students' self-reported chronotype and times they feel at their best. Using this approach, data from 190 mostly first and second year university students were collected and analyzed to determine optimal times when cognitive performance can be expected to be at its peak. The NM synthesized research in sleep, circadian neuroscience, sleep deprivation's impact on cognition, and practical considerations to create a generalized solution to determine the best learning hours. Strikingly the SM and NM results align with each other and confirm other recent research in indicating later start times. They add several important points: (1) They extend our understanding by showing that much later starting times (after 11 a.m. or 12 noon) are optimal; (2) Every single start time disadvantages one or more chronotypes; and (3) The best practical model may involve three alternative starting times with one afternoon shared session. The implications are briefly considered.


Metabolic differentiation of neuronal phenotypes by single-cell capillary electrophoresis-electrospray ionization-mass spectrometry.
Single-cell mass spectrometry (MS) is a rapidly emerging field in metabolic investigations. The inherent chemical complexity of most biological samples poses analytical challenges when using MS platforms to measure sample content without prior chemical separation. Here, a single-cell capillary electrophoresis (CE) system was coupled with electrospray ionization (ESI) MS to enable the simultaneous measurement of a vast array of endogenous compounds in over 50 identified and isolated large neurons from the Aplysia californica central nervous system. More than 300 distinct ion signals (m/z values) were detected from a single neuron in the positive ion mode, 140 of which were selected for chemometric data analysis. Metabolic features were evaluated among six different neuron types (B1, B2, left pleural 1 (LPl1), metacerebral cell (MCC), R2, and R15) chosen for their various physiological functions. The results indicated chemical similarities among some neuron types (B1 to B2 and LPl1 to R2) and distinctive features for others (MCC and R15 cells). The quantitative nature of the MS platform allowed the comparison of metabolite levels for specific neurons. The CE-ESI-MS approach for examination of individual nanoliter-volume cells as described herein is readily adaptable to other volume-limited samples.


TBMap: a taxonomic perspective on the phylogenetic database TreeBASE.
TreeBASE is currently the only available large-scale database of published organismal phylogenies. Its utility is hampered by a lack of taxonomic consistency, both within the database, and with names of organisms in external genomic, specimen, and taxonomic databases. The extent to which the phylogenetic knowledge in TreeBASE becomes integrated with these other sources is limited by this lack of consistency. Taxonomic names in TreeBASE were mapped onto names in the external taxonomic databases IPNI, ITIS, NCBI, and uBio, and graph G of these mappings was constructed. Additional edges representing taxonomic synonymies were added to G, then all components of G were extracted. These components correspond to "name clusters", and group together names in TreeBASE that are inferred to refer to the same taxon. The mapping to NCBI enables hierarchical queries to be performed, which can improve TreeBASE information retrieval by an order of magnitude. TBMap database provides a mapping of the bulk of the names in TreeBASE to names in external taxonomic databases, and a clustering of those mappings into sets of names that can be regarded as equivalent. This mapping enables queries and visualisations that cannot otherwise be constructed. A simple query interface to the mapping and names clusters is available at http://linnaeus.zoology.gla.ac.uk/~rpage/tbmap.