Abnormal phasic activity in saliency network, motor areas, and basal ganglia in Parkinson's disease during rhythm perception.
Behavioral studies indicate that persons with Parkinson's disease have complexity dependent problems with the discrimination of auditory rhythms. Furthermore, neuroimaging studies show that rhythm processing activates many brain areas that overlap with areas affected by Parkinson's disease (PD). This study sought to investigate the neural correlates of rhythm processing in PD and healthy controls, with a particular focus on rhythmic complexity. We further aimed to investigate differences in brain activation during initial phases of rhythm processing. Functional magnetic resonance imaging was used to scan 15 persons with Parkinson's disease and 15 healthy controls while they listened to musical rhythms with two different levels of complexity. Rhythmic complexity had no significant effect on brain activations, but patients and controls showed differences in areas related to temporal auditory processing, notably bilateral planum temporale and inferior parietal lobule. We found indications of a particular sequential or phasic activation pattern of brain activity, where activity in caudate nucleus in the basal ganglia was time-displaced by activation in the saliency network-comprised of anterior cingulate cortex and bilateral anterior insula-and cortical and subcortical motor areas, during the initial phases of listening to rhythms. We relate our findings to core PD pathology, and discuss the overall, rhythm processing related hyperactivity in PD as a possible dysfunction in specific basal ganglia mechanisms, and the phasic activation pattern in PD as a reflection of a lack of preparatory activation of task-relevant brain networks for rhythm processing in PD.


Changes of chondrocyte expression profiles in human MSC aggregates in the presence of PEG microspheres and TGF-β3.
Biomaterial microparticles are commonly utilized as growth factor delivery vehicles to induce chondrogenic differentiation of mesenchymal stem/stromal cells (MSCs). To address whether the presence of microparticles could themselves affect differentiation of MSCs, a 3D co-aggregate system was developed containing an equal volume of human primary bone marrow-derived MSCs and non-degradable RGD-conjugated poly(ethylene glycol) microspheres (PEG-μs). Following TGF-β3 induction, differences in cell phenotype, gene expression and protein localization patterns were found when compared to MSC aggregate cultures devoid of PEG-μs. An outer fibrous layer always found in differentiated MSC aggregate cultures was not formed in the presence of PEG-μs. Type II collagen protein was synthesized by cells in both culture systems, although increased levels of the long (embryonic) procollagen isoforms were found in MSC/PEG-μs aggregates. Ubiquitous deposition of type I and type X collagen proteins was found in MSC/PEG-μs cultures while the expression patterns of these collagens was restricted to specific areas in MSC aggregates. These findings show that MSCs respond differently to TGF-β3 when in a PEG-μs environment due to effects of cell dilution, altered growth factor diffusion and/or cellular interactions with the microspheres. Although not all of the expression patterns pointed toward improved chondrogenic differentiation in the MSC/PEG-μs cultures, the surprisingly large impact of the microparticles themselves should be considered when designing drug delivery/scaffold strategies.


Data and performance of an active-set truncated Newton method with non-monotone line search for bound-constrained optimization.
In this data article, we report data and experiments related to the research article entitled "A Two-Stage Active-Set Algorithm for Bound-Constrained Optimization", by Cristofari et al. (2017). The method proposed in Cristofari et al. (2017), tackles optimization problems with bound constraints by properly combining an active-set estimate with a truncated Newton strategy. Here, we report the detailed numerical experience performed over a commonly used test set, namely CUTEst (Gould et al., 2015). First, the algorithm ASA-BCP proposed in Cristofari et al. (2017) is compared with the related method NMBC (De Santis et al., 2012). Then, a comparison with the renowned methods ALGENCAN (Birgin and Martínez et al., 2002) and LANCELOT B (Gould et al., 2003) is reported.


The QIBA Profile for FDG PET/CT as an Imaging Biomarker Measuring Response to Cancer Therapy.
The Quantitative Imaging Biomarkers Alliance (QIBA) Profile for fluorodeoxyglucose (FDG) PET/CT imaging was created by QIBA to both characterize and reduce the variability of standardized uptake values (SUVs). The Profile provides two complementary claims on the precision of SUV measurements. First, tumor glycolytic activity as reflected by the maximum SUV (SUVmax) is measurable from FDG PET/CT with a within-subject coefficient of variation of 10%-12%. Second, a measured increase in SUVmax of 39% or more, or a decrease of 28% or more, indicates that a true change has occurred with 95% confidence. Two applicable use cases are clinical trials and following individual patients in clinical practice. Other components of the Profile address the protocols and conformance standards considered necessary to achieve the performance claim. The Profile is intended for use by a broad audience; applications can range from discovery science through clinical trials to clinical practice. The goal of this report is to provide a rationale and overview of the FDG PET/CT Profile claims as well as its context, and to outline future needs and potential developments.


Detection of Identical Isolates of Enterococcus faecalis from the Blood and Oral Mucosa in a Patient with Infective Endocarditis.
The detection of infective endocarditis (IE) of oral origin has been previously discussed. However, there are few reports confirming this infection using molecular biological techniques. We herein describe the case of a 67-year-old man who developed IE. Blood culture samples and strains obtained from the gingival and buccal mucosa showed 100% identity to Enterococcus faecalis JCM 5803 on sequencing of 16S rRNA gene fragments. A random amplification of polymorphic DNA (RAPD) analysis showed the same pattern for these samples, thus confirming the identity of E. faecalis isolates in the blood and oral mucosa. Our observations provide novel information regarding the level of identity between IE pathogens and oral bacteria.


Hypatulins A and B, Meroterpenes from Hypericum patulum.
Two novel prenylated benzophenone related meroterpenes, hypatulins A (1) and B (2), were isolated from the leaves of Hypericum patulum. The structures of 1 and 2 were assigned by spectroscopic analysis, chemical conversion, and calculations of the ECD (electron circular dichroism) spectra. Hypatulin A (1) had a unique densely substituted tricyclic octahydro-1,5-methanopentalene core, while hypatulin B (2) possessed a bicyclo[3.2.1]octane moiety. Hypatulin A (1) exhibited antimicrobacterial activity against Bacillus subtilis. A possible biogenetic pathway of the new meroterpenes 1 and 2 from a prenylated benzophenone was presented.


A new digital approach for measuring dentin translucency in forensic age estimation.
Assessment of age from the dentition constitutes an important step in constructing an identity profile of the decedent. Dentinal translucency is one of the morpho-histologic parameters considered best for dental age estimation, not only in terms of accuracy but also simplicity. By convention, translucency has been measured using calipers. Computer-based methods have been proposed for the same, although these required the use of custom-built software programs. The present study describes a method to measure translucency on sectioned teeth using commercially available computer hardware and software. Translucency measurements on 81 tooth sections were obtained using the digital method and compared with those obtained using a caliper. Correlation coefficients of translucency measurements to age were statistically significant for both methods (P < 0.001) and marginally higher for the digital approach (r = 0.49). Application of linear regression equations derived from both methods on an independent sample (n = 15) revealed better ability of the digital method to assess age-60% of age estimates were within +/-5 years of the actual age as against 40% for caliper-based method. The superior results using the digital method are attributed to refined measurements obtained under magnification and the "touch-free" approach of measuring translucency on digital images of thin tooth sections. Moreover, the computer hardware and software used in the present study are ubiquitous and easy to use. Considering these advantages, the report recommends the use of the digital method to assess translucency for age estimation.


Stormwater nutrient attenuation in a constructed wetland with alternating surface and subsurface flow pathways: Event to annual dynamics.
Among different Water Sensitive Urban Design (WSUD) options, constructed wetlands (CWs) are widely used to protect and support downstream urban waterways from stormwater nutrients. This analysis assessed the nutrient attenuation ability of a novel CW in Western Australia that combined multiple alternating surface flow (SF) and laterite-based subsurface flow (SSF) compartments within a parkland context to improve the urban landscape and amenity. The CW was designed to maximise nutrient reduction despite experiencing a large range of hydrologic conditions, from low transit time nutrient-rich pulses during the wet periods to prolonged low to zero flow conditions during the dry periods. The CW design was further complicated by the possibility of ungauged water inputs after wet antecedent conditions, seasonal macrophyte senescence and a recirculation system to maintain flow during the dry periods. From analysis of data over a range of time scales, we determined that overall the CW attenuated up to 62% total nitrogen (TN) and 99% total phosphorus (TP) loads during dry weather conditions, and 54-76% TN and 27-68% TP during episodic flow pulses. N species attenuation was dominant in the SF compartments, while P species were attenuated mostly within the SSF compartments. Nutrient accumulation in the sediments, and above and below ground biomass of the macrophytes were found to increase during the early stages of operation, suggesting the system reached equilibrium within four years. Further, by comparing trends in nutrient attenuation within the context of diel changes in high frequency oxygen data from different compartments, it was demonstrated that changes in dissolved oxygen were related to changes in nutrient concentration across the CW, although interpretation of this was complicated by changing hydro-climatological conditions. The implementation of this CW concept in a highly seasonal Mediterranean climate demonstrates that urban liveability and environmental health can both be improved through careful design.


Systemic, prophylactic and local applications of antimicrobials in endodontics: an update review.
Antibiotics were first discovered in the late 1920s but were not routinely used clinically until the early 1940s during the Second World War. They can be used as an adjunct to endodontic treatment in a number of ways-systemically, prophylactically and locally. There are few real indications for the systemic use of antibiotics in conjunction with endodontic treatment. They are only needed when the body's efforts at fighting bacteria are failing. Use of antibiotics to prevent infection (antibiotic prophylaxis) may prevent some case of bacterial endocarditis. Therefore, prophylaxis is recommended for individuals in high-risk and moderate-risk categories. Another mode of application of antibiotics is local application as intracanal medicaments and root canal irrigants.


Association of paternal alcohol use with gestational age and birth weight.
Paternal alcohol use has been associated with a number of adverse reproductive outcomes in laboratory animals and there is one epidemiologic report of a detrimental effect on infant birth weight. To expand the epidemiologic evidence, data from the Child Health and Development Studies were analyzed. Data collected from the onset of prenatal care in 10,232 women enrolled in the Kaiser Foundation Health Plan and residing in the San Francisco East Bay area between June 1959 and September 1966 were available, including information on the mother's report of paternal alcohol consumption and a number of potential confounders. Pregnancy outcomes included preterm delivery (< 37 weeks completed gestation), moderately low birth weight (1,501-2,500 g), very low birth weight (< or = 1,500 g), small-for-gestational-age (< 10th percentile of weight for gestational age), and mean birth weight. Paternal alcohol use, analyzed in intervals from 0 to 2.0 or more drinks per day, showed no association with any of the outcomes of interest. Adjusted prevalence odds ratios ranged from 0.7 to 1.5, with no indication of a monotonic dose-response gradient. Mean birth weight was also virtually unrelated to paternal alcohol use. Compared with the earlier report, this population had a very modest level of alcohol consumption. Nonetheless, within the range that was studied there appears to be no association between paternal alcohol use and birth outcome.


Occupational Engagement in Low-Income Latina Breast Cancer Survivors.
This qualitative study examined the experience of occupational engagement in low-income Latina breast cancer survivors and suggests the potential for occupational therapy practitioners to improve health outcomes in this vulnerable and underserved population. Semistructured interviews were conducted with 9 participants. Inductive analysis was used to code for themes and patterns related to occupational engagement and quality of life (QOL). Lack of occupational engagement negatively affected QOL, but participation in occupations such as religious activity and caregiving promoted well-being. Financial concerns and communication barriers decreased QOL. Breast cancer can have a negative impact on occupational engagement in low-income Latina breast cancer survivors; however, some occupations may increase QOL. Socioeconomic status and cultural values influence occupational engagement and QOL. Occupational therapy practitioners can improve health outcomes in this population through awareness of relevant sociocultural factors and attention to appropriate patient communication.


Translational maintenance of frame: mutants of Saccharomyces cerevisiae with altered -1 ribosomal frameshifting efficiencies.
A special site on the (+) strand of the L-A dsRNA virus induces about 2% of ribosomes translating the gag open reading frame to execute a -1 frameshift and thus produce the viral gag-pol fusion protein. Using constructs in which a -1 ribosomal frameshift at this site was necessary for expression of lacZ we isolated chromosomal mutants in which the efficiency of frameshifting was increased. These mutants comprise eight genes, named mof (maintenance of frame). The mof1-1, mof2-1, mof4-1, mof5-1 and mof6-1 strains cannot maintain M1 dsRNA at 30 degrees, but, paradoxically, do not lose L-A. The mof2-1, mof5-1 and mof6-1 strains are temperature sensitive for growth at 37 degrees, and all three show striking cell cycle phenotypes. The mof2-1 strains arrest with mother and daughter cells almost equal in size, mof5-1 arrests with multiple buds and mof6-1 arrests as single large unbudded cells. mof2-1 and mof5-1 strains are also Pet-. The mof mutations show differential effects on various frameshifting signals.


Inspiratory muscle training abolishes the blood lactate increase associated with volitional hyperpnoea superimposed on exercise and accelerates lactate and oxygen uptake kinetics at the onset of exercise.
We examined the effects of inspiratory muscle training (IMT) upon volitional hyperpnoea-mediated increases in blood lactate ([lac(-)](B)) during cycling at maximal lactate steady state (MLSS) power, and blood lactate and oxygen uptake kinetics at the onset of exercise. Twenty males formed either an IMT (n = 10) or control group (n = 10). Prior to and following a 6-week intervention, two 30 min trials were performed at MLSS (207 ± 28 W), determined using repeated 30 min constant power trials. The first was a reference trial, whereas during the second trial, from 20 to 28 min, participants mimicked the breathing pattern commensurate with 90% of the maximal incremental exercise test minute ventilation ([Formula: see text]). Prior to the intervention, the MLSS [lac(-)](B) was 3.7 ± 1.8 and 3.9 ± 1.6 mmol L(-1) in the IMT and control groups, respectively. During volitional hyperpnoea, [Formula: see text] increased from 79.9 ± 9.5 and 76.3 ± 15.4 L min(-1) at 20 min to 137.8 ± 15.2 and 135.0 ± 19.7 L min(-1) in IMT and control groups, respectively; [lac(-)](B) concurrently increased by 1.0 ± 0.6 (+27%) and 0.9 ± 0.7 mmol L(-1) (+25%), respectively (P < 0.05). Following the intervention, maximal inspiratory mouth pressure increased 19% in the IMT group only (P < 0.01). Following IMT only, the increase in [lac(-)](B) during volitional hyperpnoea was abolished (P < 0.05). In addition, the blood lactate (-28%) and phase II oxygen uptake (-31%) kinetics time constants at the onset of exercise and the MLSS [lac(-)](B) (-15%) were reduced (P < 0.05). We attribute these changes to an IMT-mediated increase in the oxidative and/or lactate transport capacity of the inspiratory muscles.


Prostaglandins in experimental syphilis: treponemes stimulate adherent spleen cells to secrete prostaglandin E2, and indomethacin upregulates immune functions.
Incubation of microorganisms with macrophages enhances the production of prostaglandin E2 (PGE2). Previous research had indicated that macrophages from syphilitic rabbits suppressed spleen cell synthesis of interleukin-2 (IL-2); this suppressive activity was reversed by indomethacin. Experiments were designed to further characterize the involvement of prostaglandins in immune processing. When Treponema pallidum was incubated with unfractionated spleen preparations, PGE2 production was accelerated, and within 24 h, pharmacologic concentrations of the prostaglandin were detected. When cytochalasin B was used to block phagocytosis, decreased levels of PGE2 were apparent. Commercial preparations of PGE2, in the range generated by macrophage-treponeme interaction, inhibited concanavalin A-induced IL-2 secretion by splenic cells. T. pallidum stimulated IL-1 production by adherent cells, and indomethacin markedly enhanced this effect. In vivo, indomethacin upregulated immune function. Two groups of rabbits were infected, and one was given daily injections of indomethacin for 18 days. Both groups were treated with penicillin to terminate infections. One week later, rabbits were challenged with viable organisms to determine their immune status. The indomethacin-treated group was more resistant to reinfection. In further research, indomethacin enhanced the immunogenicity of vaccine preparations containing heat-killed T. pallidum. Results are discussed in terms of the role of PGE2 as it impinges on immune functions involving macrophage activation (IL-1 production) and T lymphocyte activation (IL-2 production).


Reasons Lesbian and Bisexual Adolescent Girls Have or Might Have Sex with Females or Males: Implications for Discordance between Sexual Identity and Behaviors and for Prevention of Pregnancy and STIs.
We examined reasons lesbian and bisexual adolescent girls have sex or, if sexually inexperienced, might have sex with girls or boys, and the role of internalized homonegativity in these relations and among lesbians. Girls were recruited online and classified as lesbian (n = 129) or bisexual (n = 193); the classification was validated. Love and pleasure were common reasons for having sex with girls, although more lesbian girls (LG) than bisexual girls (BG) endorsed love. BG, relative to LG, had sex with girls because they were curious or wanted to verify their sexual identity. Love and pleasure were motives for having sex with boys for BG. They were common reasons for potentially having sex with either sex among sexually inexperienced girls, but both were more likely for BG than LG for sex with boys. Internalized homonegativity did not mediate the relation between sexual identity and reasons for sex, but LG just with male partners were more homonegative than LG just with female partners. The findings indicate that LG and BG should not be combined into a single group, provide insights into the discordance between sexual identity and behaviors, and have implications for reducing risk for pregnancy and sexually transmitted infections among sexual minority girls.


Contribution of genetics to ecological restoration.
Ecological restoration of degraded ecosystems has emerged as a critical tool in the fight to reverse and ameliorate the current loss of biodiversity and ecosystem services. Approaches derived from different genetic disciplines are extending the theoretical and applied frameworks on which ecological restoration is based. We performed a search of scientific articles and identified 160 articles that employed a genetic approach within a restoration context to shed light on the links between genetics and restoration. These articles were then classified on whether they examined association between genetics and fitness or the application of genetics in demographic studies, and on the way the studies informed restoration practice. Although genetic research in restoration is rapidly growing, we found that studies could make better use of the extensive toolbox developed by applied fields in genetics. Overall, 41% of reviewed studies used genetic information to evaluate or monitor restoration, and 59% provided genetic information to guide prerestoration decision-making processes. Reviewed studies suggest that restoration practitioners often overlook the importance of including genetic aspects within their restoration goals. Even though there is a genetic basis influencing the provision of ecosystem services, few studies explored this relationship. We provide a view of research gaps, future directions and challenges in the genetics of restoration.


Tick infestation, and udder and teat damage in selected cattle herds of Matabeleland South, Zimbabwe.
A cross-sectional survey was conducted to determine tick infestation, and udder and teat damage in 286 lactating cows and heifers at six properties in the smallholder and commercial sectors in Gwanda district of Matabeleland South Province, Zimbabwe. Eight tick species were identified: Amblyomma hebraeum, Hyalomma truncatum, Hyalomma marginatum rufipes, Rhipicephalus evertsi evertsi, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus appendiculatus, Rhipicephalus zambeziensis and Rhipicephalus simus. Overall, 81.5% of the cattle were tick infested; prevalence of tick-infested cattle was significantly higher on communal land (93.8%) and recently claimed land (85.1%) than on commercial farms. The mean tick load on infested cattle on communal land was significantly higher than in the other two sectors. Although 53% of the sampled cattle had some degree of udder and teat damage, very few farmers (2.6%) treated their cattle for these conditions. Udder damage was ca. two times and three times, respectively, more likely to occur in cattle on communal land compared to cattle on recently claimed land and commercial farms. The occurrence of R. appendiculatus and R. zambeziensis indicate that the cattle population in the study area is at high risk of a theileriosis outbreak, a tick-borne disease that has not been reported from this area.


Comparison of non-invasive ventilation and standard medical therapy in acute hypercapnic respiratory failure: a randomised controlled study at a tertiary health centre in SE Turkey.
This study was designed in a tertiary health centre in south-eastern Turkey to compare the effectiveness of non-invasive ventilation (NIV) plus standard medical therapy (ST) to ST alone, in acute hypercapnic respiratory failure (AHRF) due to chronic obstructive pulmonary disease (COPD) exacerbation. Thirty-four consecutive patients were randomly assigned to receive either NIV plus ST or ST alone. NIV was applied with a simple non-invasive ventilator through a full face mask in the general ward. Initial settings for inspiratory and expiratory positive airway pressures were 9 cm HO2, and 3 cm HO2, respectively. We observed statistically significant improvements in the first hour of NIV regarding respiratory rate (p<0.001), pH (p<0.05), PaO2 (p<0.05), and PaCO2 (p<0.001). PaO2 (p<0.05) showed significant improvement only in the first hour of ST. The intubation rate and duration of hospitalisation in the NIV group were significantly shorter than those in the ST group (p<0.05). We conclude that NIV provides adjunctive therapeutic benefits compared with ST alone, and should be the choice of first step treatment in the AHRF due to COPD exacerbation in the appropriate setting and in selected patients.


National survey on workplace safety and prevention services: regional differences.
Occupational Safety and Health (OSH) Services, with inspections and support activities to workers and to enterprises, have a relevant role in the field of safety and health in the workplace. The aim of this study, part of the INSuLa Project, is to realize a national survey about risk perception of OSH and awareness about OSH issues in the context of the Italian OSH legislative framework (Legislative Decree 81/08 and subsequent modifications and integrations) implementation, with involvement of the OSH Services operators. The Survey involved a representative national sample of the OSH Services operators. After an analysis of background literature and a comparison with Operating Units involved in the Project, an ad hoc questionnaire was developed and administered to the sample to evaluate the topics of the Survey. The study has been conducted on a sample of 678 OSH Services operators. The Survey showed in Italy an important organizational and procedural inhomogeneity perceived by OSH Services operators. This study highlighted the relevance perceived by OSH Services operators to develop a system of safety culture dissemination to reduce accidents at work and improve the management of occupational risks (traditional and emerging).


First fixed-ratio combination of insulin degludec and liraglutide for the treatment of type 2 diabetes.
When oral hypoglycemic agents do not successfully suppress hyperglycemia, the traditional approach has been to add insulin injections. With the coming of glucagon-like peptide 1 (GLP-1) receptor agonists carrying the benefits of weight loss and reduced risk of hypoglycemia, it has been suggested that GLP-1 agents should be used instead. There is equivalent lowering of HbA1c with either treatment. Insulin therapy is associated with hypoglycemia and weight gain while GLP-1 receptor agonists promote weight loss. Gastrointestinal (GI) intolerance is the chief obstacle to GLP-1 treatment. The combined use of basal insulin and GLP-1 receptor agonists results in improved glycemic control and mitigates weight gain. The recent approval of insulin degludec/liraglutide administered in a fixed ratio combination is unique not simply for the additive benefits of the two agents, but because it now permits adjustable dosing of liraglutide together with insulin, providing better glucose control than with either agent alone at lower dose levels. Lower dosage of insulin degludec reduces the risk of hypoglycemia. Liraglutide combats the weight gain that accompanies the introduction of insulin therapy, and a reduced dose of liraglutide induces less GI intolerance. This first combined basal insulin-GLP-1 receptor agonist combination represents a conceptual advance in the treatment of insulin-requiring type 2 diabetes.


Prepregnant overweight and obesity diminish the prolactin response to suckling in the first week postpartum.
The population subgroups with the highest proportion of overweight and obese women often are characterized by the lowest rates of initiation and shortest durations of breastfeeding. We previously documented that these 2 population-level trends may be related. In a population of white women who lived in a rural area, we observed that prepregnant overweight and obesity were associated with failure to initiate and also to sustain lactation. The means by which being overweight or obese negatively affect lactational performance is unknown and likely to be multifactorial in origin, including the simple mechanical difficulties of latching on and proper positioning of the infant. In addition, we have shown that prepregnant body mass index (BMI) is negatively associated with the timing of lactogenesis II, the onset of copious milk secretion. Although the effects of obesity on the prolactin response to infant suckling have never been studied, we postulated that maternal obesity could compromise this important response. We proposed that this might occur because obesity alters the 24-hour spontaneous release of prolactin and also because prolactin secretion is blunted in response to various stimuli among obese subjects. The fall in progesterone concentration that occurs immediately postpartum is the trigger for the onset of copious milk secretion, but maintenance of prolactin and cortisol concentrations is necessary for this trigger to be effective. Adipose tissue concentrates progesterone. We proposed that this additional source of progesterone would lead to consistently higher progesterone concentrations among obese compared with normal-weight women. This, in turn, would lead to a delay in reaching the appropriate concentration to trigger the onset of lactogenesis II. We tested the hypotheses that a reduced prolactin response to suckling and higher-than-normal progesterone concentration in the first week after delivery might be among the means by which maternal overweight could compromise early lactation. We enrolled 40 mothers of term infants from the same population that we studied previously. We measured serum prolactin and progesterone concentrations by radioimmunoassay before and 30 minutes after the beginning of a suckling episode at 48 hours and 7 days after delivery. We used path analysis to develop a parsimonious multivariate prediction of the prolactin response to suckling at 48 hours and 7 days postpartum. As expected, prolactin values decreased from 48 hours to 7 days postpartum. Women who were overweight or obese (using the Institute of Medicine's cutoff for women of a BMI >26 kg/m2) before conception had a lower prolactin response to suckling than normal-weight women at 48 hours but not at day 7. In multivariate analyses, overweight/obesity, primiparity, and birth weight were negatively associated with the prolactin response to suckling at 48 hours. After adjustment for confounding by time since delivery and the duration of the nursing episode, only overweight/obesity remained a significant negative predictor of prolactin response to suckling at day 7. Concentrations of progesterone decreased dramatically from 48 hours to 7 days postpartum but did not differ between normal-weight and overweight/obese women at either time. In addition, the decreases in progesterone concentrations from 48 hours to 7 days postpartum did not differ between the prepregnant BMI groups. The unique and important finding from this study is that overweight/obese women had a lower prolactin response to suckling. This would be expected to compromise the ability of overweight/obese women to produce milk and, over time, could lead to premature cessation of lactation. These findings are important because, during our observation period (just before and after lactogenesis II, the time of onset of copious milk secretion), the prolactin response to suckling is more important for milk production than it is later in lactation. We have previously shown that a high proportion of the overweight and obese women in women in this population who give up on breastfeeding do so at this time. This finding thus provides evidence of a biological basis for this association, and additional study of it is likely to be informative. We postulated that there would be consistently higher progesterone concentrations in the early postpartum period among obese compared with normal-weight women because adipose tissue is an extraplacental source of this hormone. This hypothesis was not supported in this study because there were no significant differences between normal-weight and overweight/obese women in progesterone concentrations at either 48 hours or 7 days postpartum. The values that we observed at these times were similar to those reported by others in the early postpartum period. The findings from this study add plausibility to our observation that initiation, not just duration of breastfeeding, is negatively affected by maternal overweight/obesity. Although women should begin pregnancy at a healthy weight and gain reasonably during gestation, not all will. Pediatricians can help overweight/obese women to succeed at breastfeeding by targeting them for contact with a lactation consultant before discharge from the hospital to be sure that they have received optimal advice on breastfeeding techniques. In addition, early contact with the mother after discharge--by calling her at home to offer her support and counseling for breastfeeding, by scheduling the first pediatric visit earlier than for other patients, or by enlisting the assistance of public health nurses for a home visit if this is possible--would help overweight/obese women to continue to breastfeed. Being overweight or obese is negatively associated with the prolactin response to suckling in the first week postpartum and, thus, may contribute to early lactation failure.


An insight into curcumin-based photosensitization as a promising and green food preservation technology.
Consumer awareness on the side effects of chemical preservatives has increased the demand for natural preservation technologies. An efficient and sustainable alternative to current conventional preservation techniques should guarantee food safety and retain its quality with minimal side effects. Photosensitization, utilizing light and a natural photosensitizer, has been postulated as a viable and green alternative to the current conventional preservation techniques. The potential of curcumin as a natural photosensitizer is reviewed in this paper as a practical guide to develop a safe and effective decontamination tool for industrial use. The fundamentals of the photosensitization mechanism are discussed, with the main emphasis on the natural photosensitizer, curcumin, and its application to inactivate microorganisms as well as to enhance the shelf life of foods. Photosensitization has shown promising results in inactivating a wide spectrum of microorganisms with no reported microbial resistance due to its particular lethal mode of targeting nucleic acids. Curcumin as a natural photosensitizer has recently been investigated and demonstrated efficacy in decontamination and delaying spoilage. Moreover, studies have shown the beneficial impact of an appropriate encapsulation technique to enhance the cellular uptake of photosensitizers, and therefore, the phototoxicity. Further studies relating to improved delivery of natural photosensitizers with inherent poor solubility should be conducted. Also, detailed studies on various food products are warranted to better understand the impact of encapsulation on curcumin photophysical properties, photo-driven release mechanism, and nutritional and organoleptic properties of treated foods.


Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
This article addresses the treatment of VTE disease. We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence. For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C). Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences.


Nigella sativa Supplementation Improves Asthma Control and Biomarkers: A Randomized, Double-Blind, Placebo-Controlled Trial.
Poor compliance with conventional asthma medications remains a major problem in achieving asthma control. Nigella sativa oil (NSO) is used traditionally for many inflammatory conditions such as asthma. We aimed to investigate the benefits of NSO supplementation on clinical and inflammatory parameters of asthma. NSO capsules 500 mg twice daily for 4 weeks were used as a supplementary treatment in a randomized, double-blind, placebo-controlled trial in asthmatics (clinicaltrials.gov: NCT02407262). The primary outcome was Asthma Control Test score. The secondary outcomes were pulmonary function test, blood eosinophils and total serum Immunoglobulin E. Between 1 June and 30 December 2015, 80 asthmatics were enrolled, with 40 patients in each treatment and placebo groups. After 4 weeks, ten patients had withdrawn from each group. Compared with placebo, NSO group showed a significant improvement in mean Asthma Control Test score 21.1 (standard deviation = 2.6) versus 19.6 (standard deviation = 3.7) (p = 0.044) and a significant reduction in blood eosinophils by -50 (-155 to -1) versus 15 (-60 to 87) cells/μL (p = 0.013). NSO improved forced expiratory volume in 1 second as percentage of predicted value by 4 (-1.25 to 8.75) versus 1 (-2 to 5) but non-significant (p = 0.170). This randomized, double-blind, placebo-controlled trial demonstrated that NSO supplementation improves asthma control with a trend in pulmonary function improvement. This was associated with a remarkable normalization of blood eosinophlia. Future studies should follow asthmatics for longer periods in a multicentre trial. Copyright © 2017 John Wiley & Sons, Ltd.


Hearing the shape of the Ising model with a programmable superconducting-flux annealer.
Two objects can be distinguished if they have different measurable properties. Thus, distinguishability depends on the Physics of the objects. In considering graphs, we revisit the Ising model as a framework to define physically meaningful spectral invariants. In this context, we introduce a family of refinements of the classical spectrum and consider the quantum partition function. We demonstrate that the energy spectrum of the quantum Ising Hamiltonian is a stronger invariant than the classical one without refinements. For the purpose of implementing the related physical systems, we perform experiments on a programmable annealer with superconducting flux technology. Departing from the paradigm of adiabatic computation, we take advantage of a noisy evolution of the device to generate statistics of low energy states. The graphs considered in the experiments have the same classical partition functions, but different quantum spectra. The data obtained from the annealer distinguish non-isomorphic graphs via information contained in the classical refinements of the functions but not via the differences in the quantum spectra.


Game-Based Health Education: The Case of Hexacago Health Academy.
It is a well-documented fact that women and minorities are currently underrepresented in STEM higher education degree programs and careers. As an outreach measure to these populations, we established the Hexacago Health Academy (HHA), an ongoing summer program. Structured as an informal learning environment with a strong youth initiated mentoring component, HHA uses game-based learning as both a means of health education and stimulating interest in careers in medicine among adolescents from underrepresented minority populations. In this article, we describe the 2015 session of the Hexacago Health Academy, which focused on the topic of sexual and reproductive health (SRH). The overall structure of HHA, with its dual focus on game design and enabling youth interaction with science and health professionals, is discussed. Qualitative data from the 24 youths that participated in the 2015 summer session was collected. Results indicated that the initial session of HHA succeeded in its goals of developing critical thinking skills among participants, encouraging teamwork, broadening understanding of the health sciences, and encouraging risk-taking in education. The overall potential efficacy of informal learning environments that use game design as a core component to stimulate interest in STEM fields is discussed.


Role of Immunohistochemistry in the Identification of Supratentorial C11ORF95-RELA Fused Ependymoma in Routine Neuropathology.
Ependymomas (EPs) are tumors of the brain and spinal cord constituting ∼10% of the childhood central nervous system neoplasms and about 30% in children aged <3 years. Their anatomic distribution varies according to the age, with those arising in the supratentorial (ST) compartment, spinal cord being more common in older children and adults, and those at the infratentorial location are more common and occurring more frequently in infants and children. Recently, molecular classification of EP subgroups has been proposed and a supratentorial ependymoma subgroup characterized by RELA-fusion genes (ST-EP-RELA) has been established. It would be useful to define a standardized, robust method for the diagnosis of these relevant fusion genes. We used real-time polymerase chain reaction, conventional real-time polymerase chain reaction, and Sanger sequencing to characterize RELA fusion status in formalin-fixed paraffin-embedded samples from 42 ST-EPs (12 adults and 30 pediatric). We tested p65/RELA and L1CAM protein immunohistochemistry for their ability to predict RELA-fusion status. We reviewed clinical data to assess significant associations in this anatomic subgroup. Of the 42 patients, we identified RELA-fusion genes in 17 cases. L1CAM immunostaining displayed 94% sensitivity, 76% specificity, 73% positive predictive value (PPV), 95% negative predictive value (NPV). The p65/RELA immunostaining displayed 100% sensitivity, 92% specificity, 89.5% PPV, 100% NPV. Concordant double immunostaining improves PPV to 92.5% and maintains 100% NPV. Immunohistochemistry using both p65/RELA and L1CAM antibodies is valuable for ST-EP-RELA diagnosis: the negativity with both antibodies consistently predicts the absence of RELA fusions, whereas verification of fusion transcripts by molecular analyses is warranted only in single-positive or double-positive staining cases.


The role of health systems and policy in producing behavior and social change to enhance child survival and development in low- and middle-income countries: an examination of the evidence.
Evidence-based behavior change interventions addressing health systems must be identified and disseminated to improve child health outcomes. Studies of the efficacy of such interventions were identified from systematic searches of the published literature. Two hundred twenty-nine of the initially identified references were judged to be relevant and were further reviewed for the quality and strength of the evidence. Studies were eligible if an intervention addressed policy or health systems interventions, measured relevant behavioral or health outcomes (e.g., nutrition, childhood immunization, malaria prevention and treatment), used at least a moderate quality research design, and were implemented in low- or middle-income countries. Policy or systems interventions able to produce behavior change reviewed included media (e.g., mass media, social media), community mobilization, educational programs (for caregivers, communities, or providers), social marketing, opinion leadership, economic incentives (for both caregiver and provider), health systems strengthening/policy/legislation, and others. Recommendations for policy, practice, and research are given based on fairly strong data across the areas of health service delivery, health workforce, health financing, governance and leadership, and research.


Universal vaccine against respiratory syncytial virus A and B subtypes.
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, young children, and the elderly. Two subtypes of RSV, A and B, circulate alternately at 1-2-year intervals during epidemics. The attachment glycoprotein (G protein) of RSV is one of the major targets for immune responses. In this study, we generated a recombinant fusion protein, GcfAB, which consists of the central regions (a.a. residues 131-230) of the G proteins of both RSV A (A2 strain) and B (B1 strain) subtypes, and investigated immunogenicity, protective efficacy, and immunopathology. We immunized mice with GcfAB plus cholera toxin as a mucosal adjuvant via intranasal (IN) or sublingual (SL) routes. The IN group showed higher levels of RSV G-specific antibody responses, including serum IgG and mucosal IgA, compared with the SL group. On the contrary, more vigorous RSV G-specific CD4+ T-cell responses were elicited in the SL group than in the IN group after RSV-A but not RSV-B viral challenge. Furthermore, the SL group showed more pulmonary eosinophil recruitment and body weight loss than did the IN group after RSV-A challenge. Both IN and SL immunization with GcfAB provided potential protection against both subtypes of infections. Together, these results suggest that vaccination with GcfAB via an IN route could be a universal vaccine regimen preventing both RSV A and B infections.


Influencing factors on the removal of pharmaceuticals from water with micro-grain activated carbon.
The removal efficiency of 6 micro-grain AC (μGAC) was examined for 23 selected pharmaceutical compounds, usually found at trace level in municipal wastewater treatment plant (WWTP) effluents. Two different sets of experiments were carried out using distilled water and a real WWTP secondary effluent in order to understand the adsorption mechanisms of pharmaceuticals, including the role of the presence of background organic matter. Physical and chemical properties of μGACs and target pollutants were checked for their potential to predict the pharmaceutical removal. Textural properties of μGACs, and especially the mesopore volume, seemed to play the most important role during the adsorption without background organic matter whereas the chemistry of the μGACs, such as the presence of surface oxygen groups and the point of zero charge, could have more influence in the experiments with WWTP effluent water. Positively charged molecules are better adsorbed due to the influence of the background organic matter and the presence of oxygenated groups in the surface of the μGACs. The UV254 removal correlated well with the pharmaceutical removal and it is confirmed as an indicator to control the performance of pharmaceuticals adsorption with μGACs in tertiary treatment.


Adiponectin-mediated heme oxygenase-1 induction protects against iron-induced liver injury via a PPARα dependent mechanism.
Protective effects of adiponectin (APN; an adipocytokine) were shown against various oxidative challenges; however, its therapeutic implications and the mechanisms underlying hepatic iron overload remain unclear. Herein, we show that the deleterious effects of iron dextran on liver function and iron deposition were significantly reversed by adiponectin gene therapy, which was accompanied by AMP-activated protein kinase (AMPK) phosphorylation and heme oxygenase (HO)-1 induction. Furthermore, AMPK-mediated peroxisome proliferator-activated receptor-α (PPARα) activation by APN was ascribable to HO-1 induction. Additionally, we revealed direct transcriptional regulation of HO-1 by the binding of PPARα to a PPAR-responsive element (PPRE) by various experimental assessments. Interestingly, overexpression of HO-1 in hepatocytes mimicked the protective effect of APN in attenuating iron-mediated injury, whereas it was abolished by SnPP and small interfering HO-1. Furthermore, bilirubin, the end-product of the HO-1 reaction, but not CO, protected hepatocytes from iron dextran-mediated caspase activation. Herein, we demonstrate a novel functional PPRE in the promoter regions of HO-1, and APN-mediated HO-1 induction elicited an antiapoptotic effect and a decrease in iron deposition in hepatocytes subjected to iron challenge.


Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis.
An updated economic evaluation was conducted to compare the cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic arthritis (PsA) where response to standard treatment has been inadequate. A systematic review was conducted to identify relevant, recently published studies and the new trial data were synthesised, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). A previously developed economic model was updated with the new meta-analysis results and current cost data. The model was adapted to delineate patients by PASI 50%, 75% and 90% response rates to differentiate between psoriasis outcomes. All four licensed TNF-α inhibitors were significantly more effective than placebo in achieving PsARC response in patients with active PsA. Adalimumab, etanercept and infliximab were significantly more effective than placebo in improving HAQ scores in patients who had achieved a PsARC response and in improving HAQ scores in PsARC non-responders. In an analysis using 1,000 model simulations, on average etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option. The economic analysis agrees with the conclusions from the previous models, in that biologics are shown to be cost-effective for treating patients with active PsA compared with the conventional management strategy. In particular, etanercept is cost-effective compared with the other biologic treatments.


Contribution of growth and cell cycle checkpoints to radiation survival in Drosophila.
Cell cycle checkpoints contribute to survival after exposure to ionizing radiation (IR) by arresting the cell cycle and permitting repair. As such, yeast and mammalian cells lacking checkpoints are more sensitive to killing by IR. We reported previously that Drosophila larvae mutant for grp (encoding a homolog of Chk1) survive IR as well as wild type despite being deficient in cell cycle checkpoints. This discrepancy could be due to differences either among species or between unicellular and multicellular systems. Here, we provide evidence that Grapes is needed for survival of Drosophila S2 cells after exposure to similar doses of IR, suggesting that multicellular organisms may utilize checkpoint-independent mechanisms to survive irradiation. The dispensability of checkpoints in multicellular organisms could be due to replacement of damaged cells by regeneration through increased nutritional uptake and compensatory proliferation. In support of this idea, we find that inhibition of nutritional uptake (by starvation or onset of pupariation) or inhibition of growth factor signaling and downstream targets (by mutations in cdk4, chico, or dmyc) reduced the radiation survival of larvae. Further, some of these treatments are more detrimental for grp mutants, suggesting that the need for compensatory proliferation is greater for checkpoint mutants. The difference in survival of grp and wild-type larvae allowed us to screen for small molecules that act as genotype-specific radiation sensitizers in a multicellular context. A pilot screen of a small molecule library from the National Cancer Institute yielded known and approved radio-sensitizing anticancer drugs. Since radiation is a common treatment option for human cancers, we propose that Drosophila may be used as an in vivo screening tool for genotype-specific drugs that enhance the effect of radiation therapy.


APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study.
To examine the prevalence of Alzheimer's disease (AD) and other dementias in relation to age, education, sex, and genotype at APOE. Recent studies suggest age heterogeneity in the risk of AD associated with the APOE genotype and a possible interaction between APOE-epsilon4 and female sex as risk factors. We studied these topics in the 5,677 elderly residents of Cache County, Utah, a population known for long life expectancy and high participation rates. We screened for dementia with a brief cognitive test and structured telephone Dementia Questionnaire, then examined all individuals with apparent cognitive symptoms and a sample of others. We estimated age-specific prevalence of AD and other dementias and used multiple logistic regression models to describe relation of AD prevalence to age, sex, education, and APOE genotype. We found 335 demented individuals, 230 (69%) with definite, probable, or possible AD (positive predictive value versus autopsy confirmation 85%). The adjusted prevalence estimate for AD was 6.5% and for all dementias 9.6%. After age 90, the adjusted prevalence estimate for AD was 28% and for all dementias 38%. Regression models showed strong variation in AD prevalence with age, sex, education, and number of epsilon4 alleles (effect of epsilon2 not significant). Models were improved by a term for age-squared (negative coefficient) and by separate terms for interaction of age with presence of one or two epsilon4 alleles. An association of AD with female sex was ascribable entirely to individuals with epsilon4. In participants with no epsilon4 alleles, the age-specific prevalence of AD reached a maximum and then declined after age 95. In epsilon4 heterozygotes a similar maximum was noted earlier at age 87, in homozygotes at age 73. Female sex was a risk factor for AD only in those with epsilon4. The epsilon4 allele accounted for 70% of the population attributable risk for AD.


Concentration-dependent circularly polarized luminescence (CPL) of chiral N,N'-dipyrenyldiamines: sign-inverted CPL switching between monomer and excimer regions under retention of the monomer emission for photoluminescence.
Herein, an unprecedented switching of circularly polarized luminescence (CPL) is described for chiral 4,6-bis(1-(pyren-1-ylamino)propyl)dibenzo[b,d]furan (1). The CPL band of chiral diamine 1, which contains two pyrene rings, can be switched between the monomer and excimer emission regions under concomitant inversion of the handedness, simply by changing the concentration of the fluorophore. In contrast, the maximum photoluminescence (PL) intensity is always observed in the monomer region, regardless of the concentration. The reversal of the intensity ratio of monomer and excimer emission between PL and CPL was attributed to a stronger CPL (|gem| = ∼3-4 × 10-3) contribution from the minor excimer component, which should exhibit an efficient chiral environment around the dimeric pyrenes.


HIV Prophylaxis in High Risk Newborns: An Examination of Sociodemographic Factors in an Inner City Context.
Background. Perinatal HIV transmission is less than 1% with antiretroviral (ARV) prophylaxis. Transmission risk appears higher in "high risk" dyads, yet this is not well defined, possibly exposing more infants to combination ARV compared with standard care. Objective. To describe characteristics of mother-infant dyads where infants received ARVs and how these characteristics relate to specific ARV regimens. Methods. Retrospective chart review of ARV-receiving newborns at St. Michael's Hospital from 2007 to 2012 (and their mothers). Numerical and categorical variables were analyzed using t-tests/ANOVA F-tests and Fisher's exact tests, respectively. Results. Maternal HIV status at delivery was as follows: 69% positive and 24% unknown. Maternal factors significantly associated with newborn-triple therapy are Canadian origin, substance abuse, unstable housing, lost custody of previous children, and sex work. Neonatal factors are child protective services involvement, NICU, and lengthier admission. Maternal factors associated with monotherapy are African origin, HIV-positive, employment, and education. Further analysis based on maternal presentation at delivery demonstrated unequal distribution of many aforementioned factors. Discussion. This cohort revealed associations between particular factors and newborn-monotherapy or triple therapy that exist, suggesting that sociodemographic factors may influence the choice of ARV regimen. Canadian perinatal HIV transmission guidelines should qualify how to risk stratify newborns and consider use of rapid HIV antibody testing.


BADGES/PINS OF NURSING AND MIDWIFERY SCHOOLS IN SLOVENIA FROM 1925 UNTIL EARLY 1980s.
Many nursing and midwifery schools in many countries around the world awarded or still award graduation badges or pins to their graduates. All graduates from different parts of the former Kingdom of Yugoslavia and later the Republic of Yugoslavia educated in Slovenian healthcare schools received badges from these schools. Some of the graduates later employed in medical institutions across former Yugoslavia wore these badges on their uniforms. The main purpose of this historical research was to establish which Slovenian health care schools awarded the graduation badges and what they looked like. It was also investigated why the badges ceased to be awarded and what motivated Angela Boškin Faculty of Health Care in Jesenice to reintroduce awarding the badges. Due to a lack of written sources, we conducted 393 face to face and telephonic interviews with former badge recipients across Slovenia. Their existing badges were photographed. On the authors' initiative, a private collection of badges was started. It has been established that in the 20th century all Slovenian secondary health schools awarded badges. The Nursing College, Ljubljana also awarded graduation badges. Five different types of badges in many variants were issued. The first badges were awarded to graduates by Slovenian oldest Nursing School, Ljubljana in 1925. The badges ceased to be awarded in the late 1970s and the early 1980s. Some questions about probable reasons for cessation of awarding badges remain unanswered. Less than a fifth of interviewees kept their badges. Graduating nursing badges were reintroduced in Slovenia in 2017 with a new badge which is presented and depicted in this article. The motivation for the reintroduction of graduating badges is also investigated. Unfortunately, many Slovenian nurses and midwives are not sufficiently aware of the meaning and importance of their badges. Although badges are important for professional image and identity of nurses, badges as a symbol of nursing have become almost completely forgotten. Graduation badges are miniature works of art and are proof of the existence and development of Slovenian healthcare schools. Nursing badges present a part of nursing history as well as being our cultural heritage. The badges deserve to be written and talked about and should be displayed in a planned future Slovenian Health Care Museum.


Emotional distress among LGBT youth: the influence of perceived discrimination based on sexual orientation.
The authors evaluated emotional distress among 9th-12th grade students, and examined whether the association between being lesbian, gay, bisexual, and/or transgendered (i.e., "LGBT") and emotional distress was mediated by perceptions of having been treated badly or discriminated against because others thought they were gay or lesbian. Data come from a school-based survey in Boston, Massachusetts (n = 1,032); 10% were LGBT, 58% were female, and ages ranged from 13 to 19 years. About 45% were Black, 31% were Hispanic, and 14% were White. LGBT youth scored significantly higher on the scale of depressive symptomatology. They were also more likely than heterosexual, non-transgendered youth to report suicidal ideation (30% vs. 6%, p < 0.0001) and self-harm (21% vs. 6%, p < 0.0001). Mediation analyses showed that perceived discrimination accounted for increased depressive symptomatology among LGBT males and females, and accounted for an elevated risk of self-harm and suicidal ideation among LGBT males. Perceived discrimination is a likely contributor to emotional distress among LGBT youth.


Light and growth form interact to shape stomatal ratio among British angiosperms.
In most plants, stomata are located only on the abaxial leaf surface (hypostomy), but many plants have stomata on both surfaces (amphistomy). High light and herbaceous growth form have been hypothesized to favor amphistomy, but these hypotheses have not been rigorously tested together using phylogenetic comparative methods. I leveraged a large dataset including stomatal ratio, Ellenberg light indicator value, growth form and phylogenetic relationships for 372 species of British angiosperms. I used phylogenetic comparative methods to test how light and/or growth form influence stomatal ratio and density. High light and herbaceous growth form are correlated with amphistomy, as predicted, but they also interact; the effect of light is pronounced in therophytes (annuals) and perennial herbs, but muted in phanerophytes (shrubs and trees). Furthermore, amphistomy and stomatal density evolve together in response to light. Comparative analyses of British angiosperms reveal two major insights. First, light and growth form interact to shape stomatal ratio; amphistomy is common under high light, but mostly for herbs. Second, coordinated evolution of adaxial stomatal density and light tolerance indicates that amphistomy helps to optimally balance light acquisition with gas exchange. Stomatal ratio may have potential as a functional trait for paleoecology and crop improvement.


Role of proNGF/p75 signaling in bladder dysfunction after spinal cord injury.
Loss of bladder control is a challenging outcome facing patients with spinal cord injury (SCI). We report that systemic blocking of pro-nerve growth factor (proNGF) signaling through p75 with a CNS-penetrating small-molecule p75 inhibitor resulted in significant improvement in bladder function after SCI in rodents. The usual hyperreflexia was attenuated with normal bladder pressure, and automatic micturition was acquired weeks earlier than in the controls. The improvement was associated with increased excitatory input to the spinal cord, in particular onto the tyrosine hydroxylase-positive fibers in the dorsal commissure. The drug also had an effect on the bladder itself, as the urothelial hyperplasia and detrusor hypertrophy that accompany SCI were largely prevented. Urothelial cell loss that precedes hyperplasia was dependent on p75 in response to urinary proNGF that is detected after SCI in rodents and humans. Surprisingly, death of urothelial cells and the ensuing hyperplastic response were beneficial to functional recovery. Deleting p75 from the urothelium prevented urothelial death, but resulted in reduction in overall voiding efficiency after SCI. These results unveil a dual role of proNGF/p75 signaling in bladder function under pathological conditions with a CNS effect overriding the peripheral one.


Subjective Satiety Following Meals Incorporating Rice, Pasta and Potato.
The satiating capacity of carbohydrate staples eaten alone is dependent upon the energy density of the food but relative satiety when starchy staples are incorporated into mixed meals is uncertain. Our aim was to assess the satiating effects of three carbohydrate staples; jasmine rice, penne pasta, and Agria potato, each consumed within a standard mixed meal. Cooked portions of each staple containing 45 g carbohydrate were combined with 200 g of meat sauce and 200 g of mixed vegetables in three mixed meals. The quantities of staple providing 45 g carbohydrate were: Rice, 142 g; pasta, 138 g and potato 337 g. Participants (n = 14) consumed each of the mixed meals in random order on separate days. Satiety was assessed with using visual analogue scales at baseline and for 3 h post meal. In an area-under-the-curve comparison, participants felt less hungry (mean (SD)) following potato 263 (230) than following rice 374 (237) or pasta 444 (254) mm∙min, and felt fuller, more satisfied, and wanted to eat less following the potato compared with the rice and pasta meals (p for all <0.01). The superior satiating effect of potato compared with rice and pasta in a mixed meal was consistent with its lower energy density.


Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study.
To investigate the association between pre- and postdiagnosis physical activity (as well as change in prediagnosis to postdiagnosis physical activity) and mortality among women with breast cancer. This was a prospective observational study of 933 women enrolled onto the Health, Eating, Activity, and Lifestyle Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or September 2004, whichever came first. The primary outcomes measured were total deaths and breast cancer deaths. The primary exposures were physical activity in the year before and 2 years after diagnosis and the pre- to postdiagnosis change in physical activity. Compared with inactive women, the multivariable hazard ratios (HRs) for total deaths for women expending at least 9 metabolic equivalent hours per week (approximately 2 to 3 h/wk of brisk walking) were 0.69 (95% CI, 0.45 to 1.06; P = .045) for those active in the year before diagnosis and 0.33 (95% CI, 0.15 to 0.73; P = .046) for those active 2 years after diagnosis. Compared with women who were inactive both before and after diagnosis, women who increased physical activity after diagnosis had a 45% lower risk of death (HR = 0.55; 95% CI, 0.22 to 1.38), and women who decreased physical activity after diagnosis had a four-fold greater risk of death (HR = 3.95; 95% CI, 1.45 to 10.50). Moderate-intensity physical activity after a diagnosis of breast cancer may improve prognosis.


Seagrass ecosystem multifunctionality under the rise of a flagship marine megaherbivore.
Large grazers (megaherbivores) have a profound impact on ecosystem functioning. However, how ecosystem multifunctionality is affected by changes in megaherbivore populations remains poorly understood. Understanding the total impact on ecosystem multifunctionality requires an integrative ecosystem approach, which is especially challenging to obtain in marine systems. We assessed the effects of experimentally simulated grazing intensity scenarios on ecosystem functions and multifunctionality in a tropical Caribbean seagrass ecosystem. As a model, we selected a key marine megaherbivore, the green turtle, whose ecological role is rapidly unfolding in numerous foraging areas where populations are recovering through conservation after centuries of decline, with an increase in recorded overgrazing episodes. To quantify the effects, we employed a novel integrated index of seagrass ecosystem multifunctionality based upon multiple, well-recognized measures of seagrass ecosystem functions that reflect ecosystem services. Experiments revealed that intermediate turtle grazing resulted in the highest rates of nutrient cycling and carbon storage, while sediment stabilization, decomposition rates, epifauna richness, and fish biomass are highest in the absence of turtle grazing. In contrast, intense grazing resulted in disproportionally large effects on ecosystem functions and a collapse of multifunctionality. These results imply that (i) the return of a megaherbivore can exert strong effects on coastal ecosystem functions and multifunctionality, (ii) conservation efforts that are skewed toward megaherbivores, but ignore their key drivers like predators or habitat, will likely result in overgrazing-induced loss of multifunctionality, and (iii) the multifunctionality index shows great potential as a quantitative tool to assess ecosystem performance. Considerable and rapid alterations in megaherbivore abundance (both through extinction and conservation) cause an imbalance in ecosystem functioning and substantially alter or even compromise ecosystem services that help to negate global change effects. An integrative ecosystem approach in environmental management is urgently required to protect and enhance ecosystem multifunctionality.


Accurate spring constant calibration for very stiff atomic force microscopy cantilevers.
There are many atomic force microscopy (AFM) applications that rely on quantifying the force between the AFM cantilever tip and the sample. The AFM does not explicitly measure force, however, so in such cases knowledge of the cantilever stiffness is required. In most cases, the forces of interest are very small, thus compliant cantilevers are used. A number of methods have been developed that are well suited to measuring low stiffness values. However, in some cases a cantilever with much greater stiffness is required. Thus, a direct, traceable method for calibrating very stiff (approximately 200 N/m) cantilevers is presented here. The method uses an instrumented and calibrated nanoindenter to determine the stiffness of a reference cantilever. This reference cantilever is then used to measure the stiffness of a number of AFM test cantilevers. This method is shown to have much smaller uncertainty than previously proposed methods. An example application to fracture testing of nanoscale silicon beam specimens is included.


Academic Primer Series: Key Papers About Teaching with Technology.
Modern learners have immediate, unlimited access to a wide variety of online resources. To appeal to this current generation of learners, educators must embrace the use of technology. However, educators must balance newer, novel technologies with traditional methods to achieve the best learning outcomes. Therefore, we aimed to review several papers useful for faculty members wishing to incorporate technology into instructional design. We identified a broad list of papers relevant to teaching and learning with technology within the online discussions of the Academic Life in Emergency Medicine (ALiEM) Faculty Incubator. This list was augmented with suggestions by a guest expert (BT) and an open call on Twitter (tagged with the #meded and #FOAMed hashtags) yielding 24 papers. We then conducted a modified three-round Delphi process within the authorship group, including junior and senior faculty members, to identify the most impactful papers. We pared the list of 24 papers to five that were most highly rated. Two were research papers and three were commentaries or editorials. The authorship group reviewed and summarized these papers with specific consideration to their value to junior educators and faculty developers. This is a key reading list for junior faculty members and faculty developers interested in teaching with technology. The commentary contextualizes the importance of these papers for medical educators, to optimize use of technology in their teaching or incorporate into faculty development.


Demographic models of the reproductive process: Past, interlude, and future.
After 30 years of active development, mechanistic models of the reproductive process nearly stopped attracting scholarly interest in the early 1980s. In the following decades, fertility research continued to thrive, relying on solid descriptive work and detailed analysis of micro-level data. The absence of systematic modelling efforts, however, has also made the field more fragmented, with empirical research, theory building, and forecasting advancing along largely disconnected channels. In this paper we outline some of the drivers of this process, from the popularization of user-friendly statistical software to the limitations of early family building models. We then describe a series of developments in computational modelling and statistical computing that can contribute to the emergence of a new generation of mechanistic models. Finally, we introduce a concrete example of this new kind of model, and show how they can be used to formulate and test theories coherently and make informed projections.


Extracting semantically enriched events from biomedical literature.
Research into event-based text mining from the biomedical literature has been growing in popularity to facilitate the development of advanced biomedical text mining systems. Such technology permits advanced search, which goes beyond document or sentence-based retrieval. However, existing event-based systems typically ignore additional information within the textual context of events that can determine, amongst other things, whether an event represents a fact, hypothesis, experimental result or analysis of results, whether it describes new or previously reported knowledge, and whether it is speculated or negated. We refer to such contextual information as meta-knowledge. The automatic recognition of such information can permit the training of systems allowing finer-grained searching of events according to the meta-knowledge that is associated with them. Based on a corpus of 1,000 MEDLINE abstracts, fully manually annotated with both events and associated meta-knowledge, we have constructed a machine learning-based system that automatically assigns meta-knowledge information to events. This system has been integrated into EventMine, a state-of-the-art event extraction system, in order to create a more advanced system (EventMine-MK) that not only extracts events from text automatically, but also assigns five different types of meta-knowledge to these events. The meta-knowledge assignment module of EventMine-MK performs with macro-averaged F-scores in the range of 57-87% on the BioNLP'09 Shared Task corpus. EventMine-MK has been evaluated on the BioNLP'09 Shared Task subtask of detecting negated and speculated events. Our results show that EventMine-MK can outperform other state-of-the-art systems that participated in this task. We have constructed the first practical system that extracts both events and associated, detailed meta-knowledge information from biomedical literature. The automatically assigned meta-knowledge information can be used to refine search systems, in order to provide an extra search layer beyond entities and assertions, dealing with phenomena such as rhetorical intent, speculations, contradictions and negations. This finer grained search functionality can assist in several important tasks, e.g., database curation (by locating new experimental knowledge) and pathway enrichment (by providing information for inference). To allow easy integration into text mining systems, EventMine-MK is provided as a UIMA component that can be used in the interoperable text mining infrastructure, U-Compare.


Ontogeny, pathology, oncology.
This article traces the history of using embryo-derived stem cells for genetic manipulation--first teratocarcinoma stem cells and then embryonic stem cells. It encompasses several decades of research investigating the similarity between cellular mechanisms of normal growth and differentiation in the embryo and abnormal growth and differentiation in neoplasia. The limited developmental potential of teratocarcinoma-derived, embryonal carcinoma (EC) stem cells is contrasted to the totipotentiality displayed by embryonic stem (ES) cells derived directly from early embryos. From early attempts to select mutants in EC cells in culture to the spectacular success of targeting genes in ES cells by homologous recombination, the different lines of developmental, genetic and cancer research have converged to open vast new areas of possibility in genetic manipulation.


On the evolutionary ecology of multidrug resistance in bacteria.
Resistance against different antibiotics appears on the same bacterial strains more often than expected by chance, leading to high frequencies of multidrug resistance. There are multiple explanations for this observation, but these tend to be specific to subsets of antibiotics and/or bacterial species, whereas the trend is pervasive. Here, we consider the question in terms of strain ecology: explaining why resistance to different antibiotics is often seen on the same strain requires an understanding of the competition between strains with different resistance profiles. This work builds on models originally proposed to explain another aspect of strain competition: the stable coexistence of antibiotic sensitivity and resistance observed in a number of bacterial species. We first identify a partial structural similarity in these models: either strain or host population structure stratifies the pathogen population into evolutionarily independent sub-populations and introduces variation in the fitness effect of resistance between these sub-populations, thus creating niches for sensitivity and resistance. We then generalise this unified underlying model to multidrug resistance and show that models with this structure predict high levels of association between resistance to different drugs and high multidrug resistance frequencies. We test predictions from this model in six bacterial datasets and find them to be qualitatively consistent with observed trends. The higher than expected frequencies of multidrug resistance are often interpreted as evidence that these strains are out-competing strains with lower resistance multiplicity. Our work provides an alternative explanation that is compatible with long-term stability in resistance frequencies.


Assessment of Psychopathological Comorbidities in Children and Adolescents With Autism Spectrum Disorder Using the Child Behavior Checklist.
Autism spectrum disorder (ASD) is characterized by psychiatric and behavioral comorbidities. The Child Behavior Checklist (CBCL) provides valid and well-established measures of emotional, behavioral, and social problems in children and adolescents. The aim of the present study was to verify whether emotional, behavioral, and social problems were modulated by ASD symptom severity, cognitive development, gender, and age by analyzing the CBCL in a large group of children and adolescents with ASD. The results show that around 30% of participants with ASD exhibited internalizing problems and only 6% externalizing problems, with males exhibiting more internalizing problems than females. No correlation was found between CBCL scores and indices of ASD severity. However, higher CBCL Total Problems scores were found in older children and in children with lower cognitive abilities. The detection of behavioral and emotional problems allows children with ASD to undergo specific and individualized treatment that takes into account their psychopathological problems.


The importance of peer effects, cigarette prices and tobacco control policies for youth smoking behavior.
This paper expands the youth cigarette demand literature by undertaking an examination of the determinants of smoking among high school students incorporating the importance of peer effects and allowing cigarette prices (taxes) and tobacco control policies to have a direct effect and an indirect effect (via the peer effect) on smoking behavior. To control for the potential endogeneity of our school-based peer measure we implement a two-stage generalized least squares estimator for a dichotomous dependent variable and implement a series of diagnostic tests. The key finding is that peer effects play a significant role in youth smoking decisions: moving a high-school student from a school where no children smoke to a school where one quarter of the youths smoke is found to increase the probability that the youth smokes by about 14.5 percentage points. The results suggest that there is a potential for social multiplier effects with respect to any exogenous change in cigarette taxes or tobacco control policies.


Does stress alter everyday moral decision-making?
Recent studies in the field of neuropsychological decision-making as well as moral psychology emphasize the role of emotions in decision-making. The current study examines whether stress affects moral decision-making. We induced stress in 20 participants with the Trier Social Stress Test (TSST) and also examined 20 participants in a control condition (Placebo TSST). The level of stress was assessed with questionnaires and endocrine markers (salivary cortisol and alpha-amylase). All participants performed a moral decision-making task in which everyday moral dilemmas were described. Dilemmas varied in emotional intensity and each offered a rather egoistic and a rather altruistic option. Results show that groups did not differ significantly in everyday moral decision-making. However, cortisol responses and egoistic decision-making in emotional dilemmas were positively correlated. Our results indicate that stress per se does not cause more egoistic decision-making in the current setting but suggest an association between the individual's cortisol stress response and egoistic decision-making in high-emotional situations.


Distinct functions of two RNA ligases in active Trypanosoma brucei RNA editing complexes.
Trypanosome RNA editing is a unique U insertion and U deletion process that involves cycles of pre-mRNA cleavage, terminal U addition or U removal, and religation. This editing can occur at massive levels and is directed by base pairing of trans-acting guide RNAs. Both U insertion and U deletion cycles are catalyzed by a single protein complex that contains only seven major proteins, band I through band VII. However, little is known about their catalytic functions, except that band IV and band V are RNA ligases and genetic analysis indicates that the former is important in U deletion. Here we establish biochemical approaches to distinguish the individual roles of these ligases, based on their distinctive ATP and pyrophosphate utilization. These in vitro analyses revealed that both ligases serve in RNA editing. Band V is the RNA editing ligase that functions very selectively to seal in U insertion (IREL), while band IV is the RNA editing ligase needed to seal in U deletion (DREL). In combination with our earlier findings about the cleavage and the U-addition/U-removal steps of U deletion and U insertion, these results show that all three steps of these editing pathways exhibit major differences and suggest that the editing complex could have physically separate regions for U deletion and U insertion.


Dimensional representations of DSM-IV personality disorders: relationships to functional impairment.
This study compared three-dimensional representations of DSM-IV personality disorders and standard categories with respect to their associations with psychosocial functioning. Six hundred sixty-eight patients with semistructured interview diagnoses of schizotypal, borderline, avoidant, or obsessive-compulsive personality disorders or with major depressive disorder and no personality disorder completed questionnaires assessing three-factor and five-factor dimensional models of personality. Personality disorder categories, dimensional representations of the categories based on criteria counts, and three- and five-factor personality dimensions were compared on their relationships to impairment in seven domains of functioning, as measured by the Longitudinal Interval Follow-up Evaluation-Baseline Version. Both the categorical and dimensional representations of DSM-IV personality disorders had stronger relationships to impairment in functioning in the domains of employment, social relationships with parents and friends, and global social adjustment and to DSM-IV axis V ratings than the three- and five-factor models. DSM-IV dimensions predicted functional impairment best of the four approaches. Although five-factor personality traits captured variance in functional impairment not predicted by DSM-IV personality disorder dimensions, the DSM-IV dimensions accounted for significantly more variance than the measures of personality. Scores on dimensions of general personality functioning do not appear to be as strongly associated with functional impairment as the psychopathology of DSM personality disorder. A compromise in the ongoing debate over categories versus dimensions of personality disorder might be the dimensional rating of the criteria that comprise traditional categories.


Using sensors to measure activity in people with stroke.
The purpose of this study was to determine the ability of a novel shoe-based sensor that uses accelerometers, pressure sensors, and pattern recognition with a support vector machine (SVM) to accurately identify sitting, standing, and walking postures in people with stroke. Subjects with stroke wore the shoe-based sensor while randomly assuming 3 main postures: sitting, standing, and walking. A SVM classifier was used to train and validate the data to develop individual and group models, which were tested for accuracy, recall, and precision. Eight subjects participated. Both individual and group models were able to accurately identify the different postures (99.1% to 100% individual models and 76.9% to 100% group models). Recall and precision were also high for both individual (0.99 to 1.00) and group (0.82 to 0.99) models. The unique combination of accelerometer and pressure sensors built into the shoe was able to accurately identify postures. This shoe sensor could be used to provide accurate information on community performance of activities in people with stroke as well as provide behavioral enhancing feedback as part of a telerehabilitation intervention.


Antihyperlipidemic agents cause a decrease in von Willebrand factor levels in pediatric patients with familial hyperlipidemia.
Familial hyperlipidemia is a group of genetic disorders with a predisposition to atherosclerosis. Hyperlipidemia causes increased atherosclerotic events through increased endothelial damage. In this report we aimed to measure the plasma fibrinogen and von Willebrand factor antigen (VWf:Ag) levels in pediatric patients with familial hyperlipidemias and to investigate the effects of serum lipid levels and antihyperlipidemic agents on these parameters. Of the 41 patients analyzed, vWf:Ag level was significantly lower in antihyperlipidemic receivers (132 +/- 51%, 102 +/- 19%; p = 0.010). This finding may indicate that early initiation of antihyperlipidemics in patients with familial hyperlipidemias may decrease the risk of future atherosclerotic events through not only decreasing the serum lipid levels, but also decreasing plasma vWf:Ag levels.


Evaporative fractionation of zinc during the first nuclear detonation.
Volatile element and compound abundances vary widely in planets and were set during the earliest stages of solar system evolution. Experiments or natural analogs approximating these early conditions are limited. Using silicate glass formed from arkosic sands during the first nuclear detonation at the Trinity test site, New Mexico, we show that the isotopes of zinc were fractionated during evaporation. The green silicate glasses, termed "trinitite," show +0.5 ± 0.1‰/atomic mass unit isotopic fractionation from ~200 m to within 10 m of ground zero of the detonation, corresponding to an α fractionation factor between 0.999 and 0.9995. These results confirm that Zn isotopic fractionation occurs through evaporation processes at high temperatures. Evidence for similar fractionations in lunar samples consequently implies a volatile-depleted bulk Moon, with evaporation occurring during a giant impact or in a magma ocean.


Effect of Vicia sativa L. on Motility, Mortality and Expression Levels of hsp Genes in J2 Stage of Meloidogyne hapla.
Assuming that the seeds of Vicia sativa L. have a stressful effect on J2 stage Meloidogyne hapla, we undertook research on the effect of these seeds on the motility and mortality of J2 and determined the expression levels of selected hsp genes in J2. The assessment of the effect of V. sativa seeds on the motility of M. hapla specimens consisted of observing the movement of J2 immersed in a seed diffusate or in a tomato root filtrate at temperatures of 10, 17, and 21°C. In J2 treated with V. sativa (cv. Ina) seed diffusates, the expression level of hsp genes was determined by qPCR. J2 exposed to V. sativa diffusates were found to lose their motility, while their mortality did not exceed 30%. J2 in the seed diffusate were characterized by an increase in the expression levels of the Mh-hsp90, Mh-hsp1, and Mh-hsp43 genes. It is suggested that the hsp90 gene may be a potential bioindicator of the environmental impact on Meloidogyne nematodes. The impaired ability to move in J2 of M. hapla is attributable to the occurrence of V. sativa seeds in their habitat. These studies may contribute to developing methods of reducing crop damage caused by M. hapla.


The Canadian cigar and tobacco journal in the forties: a remembrance.
This paper is a period snapshot of the life and times of Canadian smoking culture, filtered through "The Canadian Cigar and Tobacco Journal" (the industry's trade paper) from 1943-1949. "The Journal" provided a vivid portrait of neighbourhood tobacconists, travelling salesman, wholesalers and factory workers, homemakers and entrepreneurs. I discuss the role of Jews in the industry, as manufacturers and retailers. "The Journal" evokes the dangers of the retail trade, such as armed robberies, as well as the dangers of wartime. There is also the parallel danger of tobacco smoking, which, although not explicitly defined as risky behaviour by physicians, nonetheless is apparent to consumers. World War II is a dominant feature of "The Journal," and the celebration of wartime tobacco consumption is epitomized by Winston Churchill and other heroic smokers. Women's increased economic participation during the war years, and postwar demobilization, is reflected in "The Journal." Finally I discuss the growing targeting of children as potential consumers of tobacco.


Continued functioning of the secretory pathway is essential for ribosome synthesis.
To explore the regulatory elements that maintain the balanced synthesis of the components of the ribosome, we isolated a temperature-sensitive (ts) mutant of Saccharomyces cerevisiae in which transcription both of rRNA and of ribosomal protein genes is defective at the nonpermissive temperature. Temperature sensitivity for growth is recessive and segregates 2:2. A gene that complements the ts phenotype was cloned from a genomic DNA library. Sequence analysis revealed that this gene is SLY1, encoding a protein essential for protein and vesicle transport between the endoplasmic reticulum and the Golgi apparatus. In the strain carrying our ts allele of SLY1, accumulation of the carboxypeptidase Y precursor was detected at the nonpermissive temperature, indicating that the secretory pathway is defective. To ask whether the effect of the ts allele on ribosome synthesis was specific for sly1 or was a general result of the inactivation of the secretion pathway, we assayed the levels of mRNA for several ribosomal proteins in cells carrying ts alleles of sec1, sec7, sec11, sec14, sec18, sec53, or sec63, representing all stages of secretion. In each case, the mRNA levels were severely depressed, suggesting that this is a common feature in mutants of protein secretion. For the mutants tested, transcription of rRNA was also substantially reduced. Furthermore, treatment of a sensitive strain with brefeldin A at a concentration sufficient to block the secretion pathway also led to a decrease of the level of ribosomal protein mRNA, with kinetics suggesting that the effect of a secretion defect is manifest within 15 to 30 min. We conclude that the continued function of the entire secretion pathway is essential for the maintenance of ribosome synthesis. The apparent coupling of membrane synthesis and ribosome synthesis suggest the existence of a regulatory network that connects the production of the various structural elements of the cell.


Total hip arthroplasty after operatively treated acetabular fracture: a concise follow-up, at a mean of twenty years, of a previous report.
Acetabular fractures increase the risk of posttraumatic arthritis and thus the risk of total hip arthroplasty (THA). We previously presented the ten-year results of THA performed for posttraumatic arthritis after an acetabular fracture; we now present the twenty-year outcomes. The original publication included sixty-six patients who underwent THA between 1970 and 1993 for posttraumatic arthritis after open reduction and internal fixation (ORIF) of an acetabular fracture. Clinical outcomes, implant survivorship, radiographic results, and complications were evaluated. A total of thirty-six patients had died. The mean Harris hip score was 80 at the latest follow-up. Nineteen acetabular and/or femoral components had been revised: eleven for aseptic loosening, seven for osteolysis, and one for instability. Twenty-year survivorship of the acetabular component was 71% free from revision for aseptic loosening and 57% free from revision for any reason. THA after ORIF of an acetabular fracture was associated with fair implant survivorship at twenty years after surgery. It is possible that newer implants with improved fixation surfaces and bearing materials may enhance long-term results, as the most common reasons for failure at twenty years were aseptic loosening and osteolysis.


(4-{[(Pyridin-4-yl)methyl-idene]amino}-phen-yl)ferrocene.
The asymetric unit of the title compound, [Fe(C5H5)(C17H13N2)], contains two independent mol-ecules whose conformations differ, especially in the 4-{(pyridin-4-yl)methyl-idene]amino}-phenyl unit where one is flipped by almost 180°. The cyclo-penta-dienyl rings of the ferrocene unit also exhibit different staggered conformations: in one mol-ecule the conformation is staggered by 9.43 (2)° and in the other by 24.46 (1)° from an ideal eclipsed geometry. The plane of the benzene ring is tilted away from the ferrocene group in both mol-ecules, with dihedral angles of 6.97 (1) and 10.30 (2)°. The benzene ring is also slightly twisted from the plane of the pyridine ring, with dihedral angles of 5.98 (2) and 6.51 (2)° in the two mol-ecules.


DISC1: Structure, Function, and Therapeutic Potential for Major Mental Illness.
Disrupted in schizophrenia 1 (DISC1) is well established as a genetic risk factor across a spectrum of psychiatric disorders, a role supported by a growing body of biological studies, making the DISC1 protein interaction network an attractive therapeutic target. By contrast, there is a relative deficit of structural information to relate to the myriad biological functions of DISC1. Here, we critically appraise the available bioinformatics and biochemical analyses on DISC1 and key interacting proteins, and integrate this with the genetic and biological data. We review, analyze, and make predictions regarding the secondary structure and propensity for disordered regions within DISC1, its protein-interaction domains, subcellular localization motifs, and the structural and functional implications of common and ultrarare DISC1 variants associated with major mental illness. We discuss signaling pathways of high pharmacological potential wherein DISC1 participates, including those involving phosphodiesterase 4 (PDE4) and glycogen synthase kinase 3 (GSK3). These predictions and priority areas can inform future research in the translational and potentially guide the therapeutic processes.


Assessing the performance of remotely-sensed flooding indicators and their potential contribution to early warning for leptospirosis in Cambodia.
Remote sensing can contribute to early warning for diseases with environmental drivers, such as flooding for leptospirosis. In this study we assessed whether and which remotely-sensed flooding indicator could be used in Cambodia to study any disease for which flooding has already been identified as an important driver, using leptospirosis as a case study. The performance of six potential flooding indicators was assessed by ground truthing. The Modified Normalized Difference Water Index (MNDWI) was used to estimate the Risk Ratio (RR) of being infected by leptospirosis when exposed to floods it detected, in particular during the rainy season. Chi-square tests were also calculated. Another variable-the time elapsed since the first flooding of the year-was created using MNDWI values and was also included as explanatory variable in a generalized linear model (GLM) and in a boosted regression tree model (BRT) of leptospirosis infections, along with other explanatory variables. Interestingly, MNDWI thresholds for both detecting water and predicting the risk of leptospirosis seroconversion were independently evaluated at -0.3. Value of MNDWI greater than -0.3 was significantly related to leptospirosis infection (RR = 1.61 [1.10-1.52]; χ2 = 5.64, p-value = 0.02, especially during the rainy season (RR = 2.03 [1.25-3.28]; χ2 = 8.15, p-value = 0.004). Time since the first flooding of the year was a significant risk factor in our GLM model (p-value = 0.042). These results suggest that MNDWI may be useful as a risk indicator in an early warning remote sensing tool for flood-driven diseases like leptospirosis in South East Asia.