Niche development: the International Foundation for Science and the road to Sweden.
This paper examines the crowded landscape of conferences and organizations within which the International Foundation for Science (IFS) was shaped in the early 1970s. The IFS aimed to support scientists from developing countries, circumventing the bureaucracy of established international organizations such as UNESCO and the Organization for Economic Co-operation and Development (OECD). The new foundation was a potential rival to such institutions, which ironically provided the conditions essential to its emergence. Their conferences, board meetings and assemblies, where scientists and policy makers convened, provided key infrastructure for the development of the IFS. This infrastructure appears simultaneously both as an almost invisible feature of international science policy, and as a political problem. The solution to this problem was Stockholm: a geographical place that was also placeless, occupying both national and international status, desirable in its political, scientific and geographical neutrality. In an organizational context, academies and scientific societies who found their role circumscribed by existing international institutions used the IFS to argue for their particular role and expertise in funding and promoting scientific development. Geographically and politically, neutral Sweden provided a setting which was located between East and West, and which added to the country's own reputation for championing the causes of developing nations.


Characterization of biological processes through automated image analysis.
The systems-level analysis of complex biological processes requires methods that enable the quantification of a broad range of phenotypical alterations, the precise localization of signaling events, and the ability to correlate such signaling events in the context of the spatial organization of the biological specimen. The goal of this review is to illustrate that, when combined with modern imaging platforms and labeling techniques, automated image analysis methods can provide such quantitative information. The article attempts to review necessary image analysis techniques as well as applications that utilize these techniques to provide the data that will enable systems-level biology. The text includes a review of image registration and image segmentation methods, as well as algorithms that enable the analysis of cellular architecture, cell morphology, and tissue organization. Various methods that enable the analysis of dynamic events are also presented.


Mastery avoidance: An overlooked aspect of medical students' motivation.
Previous research on medical students' motivation mostly overlooked an important concept, namely, mastery-avoidance goals. The mastery-avoidance goal is defined as engaging in a task to avoid losing knowledge or skills that have already been acquired. We aimed to explore the role of mastery-avoidance goals in changes occurring in low frustration tolerance (LFT) levels over a span of one academic year. This approach enables us to understand which type of motivational orientation is expected to explain most adaptive educational outcomes. First year medical students (n = 241) participating in a physician-patient communication course completed the surveys of motivational orientations and LFT at the beginning and at the end of the academic year. A confirmatory factor analysis supported the construct validity of the motivational orientations structure. Cross-lagged analysis using structural equation modelling revealed that the mastery-approach goal was negatively related to the progression of LFT while mastery-avoidance goal was positively related. The findings suggest that what matters is not merely the level of motivation, but rather the type of motivational orientations that students pursue. Encouraging students to improve their current skills, while discouraging competitiveness and reducing fear of losing competence, may enhance the effectiveness of medical training programmes.


Removal of acidic indigo carmine textile dye from aqueous solutions using radiation induced cationic hydrogels.
This study examined the removal of acidic indigo carmine dyes from aqueous solutions using cationic hydrogels. Irradiated hydrogels were investigated as a new sorbent for dye removal from aqueous solution. Poly(N,N-Diethylamino ethyl methacrylate) [poly(DEAEMA)] hydrogels were prepared by radiation polymerisation of N,N-diethylamino ethyl methacrylate [DEAEMA] monomer in the presence of cross-linking agent, ethylene glycol dimethacrylate [EGDMA], and used for the removal of acidic indigo carmine textile dye. The adsorption of dyes was examined using a batch sorption technique. The effects of pH, time and initial dye concentration on the adsorption capacity of hydrogels were investigated. Maximum gelation ratio was 98.2% at irradiation dose of 5.3 kGy. Maximum equilibrium volume swelling, V/V(0), value was 21.3 at pH 2.8. Maximum amount of adsorbed indigo carmine onto hydrogels was 96.7 mg dye/g gel at pH 2.8, 21 h of adsorption time and 120 mg/L initial dye solution. Swelling and adsorption capacity increased with decreasing of pH. Compared with Congo red, amounts of adsorbed indigo carmine are much higher than those of Congo red. Langmuir isotherm model was the best fit for these poly(DEAEMA) hydrogels-indigo carmine systems.


Factors contributing to adolescent obesity.
Obesity in children is a significant public health concern. The prevalence of overweight and obesity in Jordanian children, and adolescents has increased in the last decade. The consequences of obesity to health in childhood and adulthood have both medical, and economic cost to individuals and society. This paper reviews the factors that contribute to adolescent obesity and emphasizes behavioral and environmental factors. An individual's behaviors such as increased consumption of high caloric foods, increased sedentary activity while decreasing physical activity has been identified as key issues in the development of obesity. Additionally, the current environment in homes, schools, and neighborhoods tend to discourage a healthy lifestyle. A comprehensive approach that involves the whole community is the best strategy for preventing adolescent obesity. Nurses are in a unique position to provide leadership in developing programs for healthier lifestyle choices for adolescents' and adoption of these goals into their daily lives.


Large Community Outbreak of Legionnaires Disease Potentially Associated with a Cooling Tower - Napa County, California, 2022.
Legionnaires disease is a serious infection acquired by inhalation of water droplets from human-made building water systems that contain Legionella bacteria. On July 11 and 12, 2022, Napa County Public Health (NCPH) in California received reports of three positive urinary antigen tests for Legionella pneumophila serogroup 1 in the town of Napa. By July 21, six Legionnaires disease cases had been confirmed among Napa County residents, compared with a baseline of one or two cases per year. NCPH requested assistance from the California Department of Public Health (CDPH) and CDC to aid in the investigations. Close temporal and geospatial clustering permitted a focused environmental sampling strategy of high-risk facilities which, coupled with whole genome sequencing results from samples and investigation of water system maintenance, facilitated potential linking of the outbreak with an environmental source. NCPH, with technical support from CDC and CDPH, instructed and monitored remediation practices for all environmental locations that tested positive for Legionella. The investigation response to this community outbreak illustrates the importance of interdisciplinary collaboration by public health agencies, laboratory support, timely communication with the public, and cooperation of managers of potentially implicated water systems. Timely identification of possible sources, sampling, and remediation of any facility testing positive for Legionella is crucial to interrupting further transmission.


Search for an Axionlike Particle in B Meson Decays.
Axionlike particles (ALPs) are predicted in many extensions of the standard model, and their masses can naturally be well below the electroweak scale. In the presence of couplings to electroweak bosons, these particles could be emitted in flavor-changing B meson decays. We report herein a search for an ALP, a, in the reaction B^{±}→K^{±}a, a→γγ using data collected by the BABAR experiment at SLAC. No significant signal is observed, and 90% confidence level upper limits on the ALP coupling to electroweak bosons are derived as a function of ALP mass, improving current constraints by several orders of magnitude in the range 0.175 GeV<m_{a}<4.78 GeV.


Infant joint attention, temperament, and social competence in preschool children.
Infant joint attention has been observed to be related to social-emotional outcomes in at-risk children. To address whether this relation is also evident in typically developing children, 52 children were tested at 12, 15, 24, and 30 months to examine associations between infant joint attention and social outcomes. Twelve-month initiating and responding to joint attention were related to 30-month social competence and externalizing behavior, even when accounting for 15-month temperament ratings, 24-month cognition and language, and demographic variables. These results suggest that, in addition to associations with language and cognition, infant joint attention reflects robust aspects of development that are related to individual differences in the emergence of social and behavioral competence in childhood.


Identification of glucose-fermenting bacteria present in an in vitro model of the human intestine by RNA-stable isotope probing.
16S rRNA-based stable isotope probing (SIP) and nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling were used to identify bacteria fermenting glucose under conditions simulating the human intestine. The TIM-2 in vitro model of the human intestine was inoculated with a GI tract microbiota resembling that of the small intestine, to which subsequently 4, 20 or 40 mM of [U-(13)C]-glucose were added. RNA was extracted from lumen samples after 0 (control), 1, 2 and 4 h and subjected to density-gradient ultracentrifugation. Phylogenetic analysis of unlabeled 16S rRNA revealed a microbial community dominated by lactic acid bacteria and Clostridium perfringens. Distinct (13)C-incorporation into bacterial RNA was only observed for the 40-mM addition. 16S rRNA fingerprinting showed an activity drop of Lactobacillus fermentum after glucose addition, while Streptococcus bovis and C. perfringens were identified as the most active glucose-fermenters. Accordingly, NMR analysis identified lactate, acetate, butyrate and formate as the principal fermentation products, constituting up to 91% of the (13)C-carbon balance. RNA-SIP combined with metabolic profiling allowed us to detect differential utilization of a general model carbohydrate, indicating that this approach holds great potential to identify bacteria involved in the fermentation of dietary relevant oligo- and polymeric carbohydrates in the human intestine.


Antiplatelet versus anticoagulation treatment for patients with heart failure in sinus rhythm.
Morbidity in patients with chronic heart failure is high, and this predisposes them to thrombotic complications, including stroke and thromboembolism, which in turn contribute to high mortality. Oral anticoagulants (e.g. warfarin) and antiplatelet agents (e.g. aspirin) are the principle oral antithrombotic agents. Many heart failure patients with sinus rhythm take aspirin because coronary artery disease is the leading cause of heart failure. Oral anticoagulants have become a standard in the management of heart failure with atrial fibrillation. However, a question remains regarding the appropriateness of oral anticoagulants in heart failure with sinus rhythm. This update of a review previously published in 2012 aims to address this question. To assess the effects of oral anticoagulant therapy versus antiplatelet agents for all-cause mortality, non-fatal cardiovascular events and risk of major bleeding in adults with heart failure (either with reduced or preserved ejection fraction) who are in sinus rhythm. We updated the searches in September 2015 on CENTRAL (The Cochrane Library), MEDLINE and Embase. We searched reference lists of papers and abstracts from cardiology meetings and contacted study authors for further information. We did not apply any language restrictions. Additionally, we searched two clinical trials registers: ClinicalTrials.gov (www.ClinicalTrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal apps.who.int/trialsearch/) (searched in July 2016). We included randomised controlled trials comparing antiplatelet therapy versus oral anticoagulation in adults with chronic heart failure in sinus rhythm. Treatment had to last at least one month. We compared orally administered antiplatelet agents (aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor, dipyridamole) versus anticoagulant agents (coumarins, warfarin, non-vitamin K oral anticoagulants). Two review authors independently assessed trials for inclusion and assessed the risks and benefits of antithrombotic versus antiplatelet therapy using relative measures of effects, such as risk ratios (RR), accompanied with 95% confidence intervals (CI). The data extracted included data relating to the study design, patient characteristics, study eligibility, quality, and outcomes. We used GRADE criteria to assess the quality of the evidence. This update identified one additional study for inclusion, adding data for 2305 participants. This addition more than doubled the overall number of patients eligible for the review. In total, we included four randomised controlled trials (RCTs) with a total of 4187 eligible participants. All studies compared warfarin with aspirin. One RCT additionally compared warfarin with clopidogrel. All included RCTs studied patients with heart failure with reduced ejection fraction.Analysis of all outcomes for warfarin versus aspirin was based on 3663 patients from four RCTs. All-cause mortality was similar for warfarin and aspirin (RR 1.00, 95% CI 0.89 to 1.13; 4 studies; 3663 participants; moderate quality evidence). Oral anticoagulation was associated with a reduction in non-fatal cardiovascular events, which included non-fatal stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism (RR 0.79, 95% CI 0.63 to 1.00; 4 studies; 3663 participants; moderate quality evidence). The rate of major bleeding events was twice as high in the warfarin groups (RR 2.00, 95% CI 1.44 to 2.78; 4 studies; 3663 participants; moderate quality evidence). We generally considered the risk of bias of the included studies to be low.Analysis of warfarin versus clopidogrel was based on a single RCT (N = 1064). All-cause mortality was similar for warfarin and clopidogrel (RR 0.93, 95% CI 0.72 to 1.21; 1 study; 1064 participants; low quality evidence). There were similar rates of non-fatal cardiovascular events (RR 0.85, 95% CI 0.50 to 1.45; 1 study; 1064 participants; low quality evidence). The rate of major bleeding events was 2.5 times higher in the warfarin group (RR 2.47, 95% CI 1.24 to 4.91; 1 study; 1064 participants; low quality evidence). Risk of bias for this study can be summarised as low. There is evidence from RCTs to suggest that neither oral anticoagulation with warfarin or platelet inhibition with aspirin is better for mortality in systolic heart failure with sinus rhythm (high quality of the evidence for all-cause mortality and moderate quality of the evidence for non-fatal cardiovascular events and major bleeding events). Treatment with warfarin was associated with a 20% reduction in non-fatal cardiovascular events but a twofold higher risk of major bleeding complications (high quality of the evidence). We saw a similar pattern of results for the warfarin versus clopidogrel comparison (low quality of the evidence). At present, there are no data on the role of oral anticoagulation versus antiplatelet agents in heart failure with preserved ejection fraction with sinus rhythm. Also, there were no data from RCTs on the utility of non-vitamin K antagonist oral anticoagulants compared to antiplatelet agents in heart failure with sinus rhythm.


Translational regulation of XIAP expression and cell survival during hypoxia in human cholangiocarcinoma.
Tumor progression is promoted by the ability of tumor cells to resist adverse environmental conditions such as hypoxia. We have shown that translational dysregulation contributes to transformed cell growth in malignant cholangiocytes. Translational regulation of gene expression can contribute to an immediate and rapid response to environmental changes such as hypoxia. Thus, our aims were to assess translational mechanisms involved in cell survival during hypoxia and to identify specific translationally regulated proteins involved in the cellular response to hypoxia. Cell viability and apoptosis in response to hypoxia were assessed in human cholangiocarcinoma cells. Translational processes were deregulated by cycloheximide or rapamycin or by targeted deletion of eukaryotic initiation factor (eIF)-4E, a rate-limiting translational initiation factor using small interfering RNA (siRNA). A protein antibody microarray was used to screen for eIF-4E-dependent proteins expressed during hypoxia. Expression of the X-linked inhibitor of apoptosis (XIAP) was decreased using siRNA. Malignant cholangiocytes are resistant to hypoxia-induced apoptosis. Furthermore, cell survival during hypoxia required protein translation. eIF-4E was over expressed in malignant cholangiocytes. Reduction in eIF-4E expression by siRNA decreased tumor cell resistance to hypoxia, increased caspase-3 activation and apoptosis, and decreased cell survival compared with controls. XIAP was identified as a translationally regulated protein expressed during hypoxia. Modulation of XIAP expression by siRNA decreases cell death during hypoxia in vitro and in vivo. Human cholangiocarcinoma cells are highly resistant to hypoxia. Translational regulation of survival proteins such as XIAP is a mechanism mediating cholangiocarcinoma survival during hypoxia.


Distant metastases in ovarian carcinoma.
Distant metastases are unusual at presentation and during the course of ovarian carcinoma. The aim of the present study was to determine the incidence and prognostic factors of distant metastases consistent with stage IV disease in ovarian cancer patients. A retrospective chart review was conducted on 162 patients with epithelial ovarian carcinoma treated at our Unit between 1991 and 2000. Pertinent clinical information, pathologic data, treatment, and prognostic factors for survival following documentation of distant metastatic disease were collected. The significance of the association between metastatic status and various clinical variables was assessed using the standard chi-square test. Survival time was calculated from the time of diagnosis of ovarian cancer and from the time of diagnosis of the distant metastases. A logistic regression procedure was used to estimate the odds of metastatic status given the presence of certain clinical variables. A total of 67 metastatic sites were diagnosed in 50 patients. Thirteen patients (8%) had distant metastatic disease at the time of diagnosis, 37 patients (22%) had distant metastases at the time of recurrent of progressive disease. Site of metastases were: liver, 21; pleura, 11; lung, 8; central nervous system and skin, 7 each; extra-abdominal lymph nodes and spleen, 5 each; bone, 2; and breast, 1. Significant risk factors for the development of distant metastases were stage, grade, and lymph node involvement. Median interval time between diagnosis of ovarian cancer and documentation of metastatic disease was 44 months (range 3-105), and at the time of diagnosis of distant disease, 36 of 50 patients (72%) had other sites of disease (intra-abdominal or extra-abdominal). Median survival from diagnosis of distant disease was 12 months (range 1-58). In univariate analysis performance status (P = 0.03), the presence of other sites of disease (P = 0.04) and interval time between diagnosis of ovarian cancer and documentation of distant metases (P = 0.03) were the only factors significantly associated with survival. Long interval time remained significant for prognosis in multivariate analysis also (P = 0.04). Distant metastasis consistent with stage IV disease is a late complication that occurs in about one third of ovarian cancer patients. Prognosis after documentation of distant metastases is poor. We conclude the most important prognostic factor associated with survival is the interval time between diagnosis of ovarian cancer and documentation of distant metastases.


Reconfigurable moiré nanolaser arrays with phase synchronization.
Miniaturized lasers play a central role in the infrastructure of modern information society. The breakthrough in laser miniaturization beyond the wavelength scale has opened up new opportunities for a wide range of applications1-4, as well as for investigating light-matter interactions in extreme-optical-field localization and lasing-mode engineering5-19. An ultimate objective of microscale laser research is to develop reconfigurable coherent nanolaser arrays that can simultaneously enhance information capacity and functionality. However, the absence of a suitable physical mechanism for reconfiguring nanolaser cavities hinders the demonstration of nanolasers in either a single cavity or a fixed array. Here we propose and demonstrate moiré nanolaser arrays based on optical flatbands in twisted photonic graphene lattices, in which coherent nanolasing is realized from a single nanocavity to reconfigurable arrays of nanocavities. We observe synchronized nanolaser arrays exhibiting high spatial and spectral coherence, across a range of distinct patterns, including P, K and U shapes and the Chinese characters '' and '' ('China' in Chinese). Moreover, we obtain nanolaser arrays that emit with spatially varying relative phases, allowing us to manipulate emission directions. Our work lays the foundation for the development of reconfigurable active devices that have potential applications in communication, LiDAR (light detection and ranging), optical computing and imaging.


The impact of job complexity and performance measurement on the temporal consistency, stability, and test-retest reliability of employee job performance ratings.
Although research has shown that individual job performance changes over time, the extent of such changes is unknown. In this article, the authors define and distinguish between the concepts of temporal consistency, stability, and test-retest reliability when considering individual job performance ratings over time. Furthermore, the authors examine measurement type (i.e., subjective and objective measures) and job complexity in relation to temporal consistency, stability, and test-retest reliability. On the basis of meta-analytic results, the authors found that the test-retest reliability of these ratings ranged from .83 for subjective measures in low-complexity jobs to .50 for objective measures in high-complexity jobs. The stability of these ratings over a 1-year time lag ranged from .85 to .67. The analyses also reveal that correlations between performance measures decreased as the time interval between performance measurements increased, but the estimates approached values greater than zero.


A Replication-Limited Recombinant Mycobacterium bovis BCG vaccine against tuberculosis designed for human immunodeficiency virus-positive persons is safer and more efficacious than BCG.
Tuberculosis is the leading cause of death in AIDS patients, yet the current tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is contraindicated for immunocompromised individuals, including human immunodeficiency virus-positive persons, because it can cause disseminated disease; moreover, its efficacy is suboptimal. To address these problems, we have engineered BCG mutants that grow normally in vitro in the presence of a supplement, are preloadable with supplement to allow limited growth in vivo, and express the highly immunoprotective Mycobacterium tuberculosis 30-kDa major secretory protein. The limited replication in vivo renders these vaccines safer than BCG in SCID mice yet is sufficient to induce potent cell-mediated and protective immunity in the outbred guinea pig model of pulmonary tuberculosis. In the case of one vaccine, rBCG(mbtB)30, protection was superior to that with BCG (0.3-log fewer CFU of M. tuberculosis in the lung [P < 0.04] and 0.6-log fewer CFU in the spleen [P = 0.001] in aerosol-challenged animals [means for three experiments]); hence, rBCG(mbtB)30 is the first live mycobacterial vaccine that is both more attenuated than BCG in the SCID mouse and more potent than BCG in the guinea pig. Our study demonstrates the feasibility of developing safer and more potent vaccines against tuberculosis. The novel approach of engineering a replication-limited vaccine expressing a recombinant immunoprotective antigen and preloading it with a required nutrient, such as iron, that is capable of being stored should be generally applicable to other live vaccine vectors targeting intracellular pathogens.


Alcohol use and related consequences for monoracial and multiracial Native American/American Indian college students.
Native American/American Indian (NA/AI) and Multiracial people (those who claim multiple racial identities) report notably high alcohol use compared to other racial groups in the United States. Nearly half of the NA/AI population is also Multiracial, yet NA/AI and Multiracial college students report different motivations for drinking alcohol. Therefore, it remains unclear if NA/AI individuals who are also Multiracial are at different risk for alcohol use and negative alcohol-related consequences, and if there are distinct patterns of risk factors in these understudied populations. Because college-aged students are at risk for high levels of alcohol use, this exploratory study used the AlcoholEdu for College™ survey to compare the association between initial drinking age, college location (urban vs. rural), and alcohol use motivations and consequences between monoracial NA/AI (N = 2,363) and Multiracial NA/AI college-aged students (N = 6,172). Monoracial NA/AI students reported higher incidences of alcohol use and alcohol-related problems such as blacking out and missing class, compared to Multiracial NA/AI students. Risk factors like earlier age of drinking onset were more strongly associated with negative consequences for monoracial NA/AI students compared to Multiracial NA/AI students. Despite similar levels of Internal Coping motivations for drinking (e.g., to feel more confident or sure of yourself), monoracial NA/AI students reported drinking more than Multiracial students and experienced more negative drinking-related outcomes. These results suggest Multiracial NA/AI students may draw on protective factors not accessible to monoracial NA/AI students, highlighting the need for interventions tailored to students at highest risk. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Association of informal caregiving with body mass index and frequency of sporting activities: evidence of a population-based study in Germany.
While most studies focused solely on the comparison between informal caregivers and non-caregivers, little is known about the relation between caregiving time or caregiving activities and lifestyle factors. Thus, the aim of this study was to examine whether informal caregiving time and type of caregiving activities are associated with body mass index (BMI) and the frequency of sporting activities among informal caregivers. Cross-sectional data were gathered from the German Ageing Survey, a nationally representative study among community-dwelling individuals aged ≥40 that includes a total of n = 1380 people who provide informal care services. Self-reported BMI and self-reported frequency of sporting activities (daily; several times a week; once a week; 1-3 times a month; less often; never) were used as dependent variables. The average time of providing informal care per week as well as four different caregiving activities (help around the house; looking after someone; performing nursing care services; help in another way) were included as independent variables. Multiple ordinal and linear regressions were used to estimate the association between caregiving factors and the frequency of sporting activities and BMI, respectively. Among the 1380 informal caregivers, 65% provided help around the house, 83% looked after people, 28% provided nursing care services, and 68% provided any other help. Bivariate analyses showed that sporting activities and BMI differed by status of providing nursing care services, whereas the other three types of informal caregiving were not associated with BMI nor frequency of sporting activities except for the latter and provision of help around the house. Multiple regressions showed that BMI increased with caregiving time and performing nursing care services, whereas it was not associated with the other three caregiving activities. Likewise, the frequency of sporting activities decreased only with caregiving time and performing nursing care services. The present study revealed that caregiving time and performing nursing care services are associated with a higher BMI and a decreased frequency of sporting activities. As both, a higher BMI and fewer sporting activities are in turn related to various adverse health outcomes, this knowledge should be taken into account when planning informal caregiving.


Cyanobacterial Polyhydroxyalkanoates: A Sustainable Alternative in Circular Economy.
Conventional petrochemical plastics have become a serious environmental problem. Its unbridled use, especially in non-durable goods, has generated an accumulation of waste that is difficult to measure, threatening aquatic and terrestrial ecosystems. The replacement of these plastics with cleaner alternatives, such as polyhydroxyalkanoates (PHA), can only be achieved by cost reductions in the production of microbial bioplastics, in order to compete with the very low costs of fossil fuel plastics. The biggest costs are carbon sources and nutrients, which can be appeased with the use of photosynthetic organisms, such as cyanobacteria, that have a minimum requirement for nutrients, and also using agro-industrial waste, such as the livestock industry, which in turn benefits from the by-products of PHA biotechnological production, for example pigments and nutrients. Circular economy can help solve the current problems in the search for a sustainable production of bioplastic: reducing production costs, reusing waste, mitigating CO2, promoting bioremediation and making better use of cyanobacteria metabolites in different industries.


Larval fish body growth responses to simultaneous browning and warming.
Organisms are facing global climate change and other anthropogenic pressures, but most research on responses to such changes only considers effects of single drivers. Observational studies and physiological experiments suggest temperature increases will lead to faster growth of small fish. Whether this effect of warming holds in more natural food web settings with concurrent changes in other drivers, such as darkening water color ("browning") is, however, unknown. Here, we set up a pelagic mesocosm experiment with large bags in the Baltic Sea archipelago, inoculated with larval Eurasian perch (Perca fluviatilis) and zooplankton prey and varying in temperature and color, to answer the question how simultaneous warming and browning of coastal food webs impact body growth and survival of larval perch. We found that browning decreased body growth and survival of larval perch, whereas warming increased body growth but had no effect on survival. Based on daily fish body growth estimates based on otolith microstructure analysis, and size composition and abundance of available prey, we explain how these results may come about through a combination of physiological responses to warming and lower foraging efficiency in brown waters. We conclude that larval fish responses to climate change thus may depend on the relative rate and extent of both warming and browning, as they may even cancel each other out.


A Trigger Reduction Approach to Treatment of Paradoxical Vocal Fold Motion Disorder in the Pediatric Population.
Paradoxical vocal fold motion disorder (PVFMD), or induced laryngeal obstruction (ILO), is a clinical phenomenon characterized by inappropriate adduction of the true vocal folds during inspiration. The resultant episodes of acute respiratory distress marked by exercise-induced cough, inspiratory stridor, throat tightness, and shortness of breath are often misattributed to asthma despite normal pulmonary function testing results. Although the pathogenesis of the disease remains unclear, the etiology is likely multifactorial with an inflammatory, neurological, and psychiatric basis. Our trigger reduction approach, consisting of a plant-based, Mediterranean-style diet to treat laryngopharyngeal reflux and sinus toilet, aims to dampen the peripheral neuronal hyperexcitability of the laryngopharyngeal tissues that is hypothesized to contribute to this disorder. The primary objective of the present study was to assess for therapeutic efficacy by analyzing pre- and post-treatment subjective scores using four validated indices: Voice Handicap Index (VHI), Reflux Symptom Index (RSI), Dyspnea Index (DI), and Cough Severity Index (CSI). A retrospective chart review of all patients age ≤18 years seen by the senior author between 2012 and 2018 who reported laryngeal spasm (J35.5) as a presenting complaint with no underlying organic diagnosis that otherwise explained the symptom identified the study cohort. Patients were excluded if another cause of their laryngeal spasm was identified or their medical records were incomplete. Of 80 patients, 24 met the criteria. The most frequent presenting symptom was exercise-induced dyspnea (79%). Of the four measured indices, only a change in DI (P = 0.024) met statistical significance. Of 24 patients, 18 (75%) demonstrated a reduction in DI following our treatment protocol. Using reduction in DI as a continuous variable to assess response, the patient cohort experienced a 4.62 (95% confidence interval [CI]: 0.65-8.6) mean point reduction. Using the eight-point reduction (improvement) in DI as an accepted clinical response to treatment, 8 of 24 patients (33%) experienced a clinically relevant response. Changes in CSI (P = 0.059), RSI (P = 0.27), and VHI (P = 0.25) did not meet statistical significance. Of 24 patients, 8 (33%), 11 (46%), and 7 (29%) demonstrated a reduction in CSI, RSI, and VHI following our trigger reduction protocol, respectively. The patient cohort experienced a mean point reduction of 1.8 (95% CI: -0.1 to 3.7), 1.3 (95% CI: -1.1 to 3.7), and 1.3 (95% CI: -1.0 to 3.6) in CSI, RSI, and VHI, respectively. Paradoxical vocal fold motion disorder is a multifactorial disease that poses diagnostic and therapeutic challenges. Early diagnosis and treatment are critical to ensure patient safety, satisfaction, and reduction in health care costs, as mistreatment with asthma pharmacotherapy, intubation, or tracheostomy may exacerbate their dyspnea and lead to preventable hospitalizations. Our results demonstrate that a trigger reduction approach consisting of a plant-based, Mediterranean-style diet and sinus toilet alone may not achieve a clinically meaningful response in the majority of patients. However, given their favorable safety profile, our therapeutic regimen, along with respiratory retraining therapy, may provide symptom relief for selected patients who would otherwise continue to suffer.


Incidental Presacral Myelolipoma Resembling the Liposarcoma: A Case Report and Literature Review.
Presacral myelolipomas are rare, benign, asymptomatic tumors composed of mature adipose tissue and hematopoietic elements, but fewer than 50 cases have been reported in the literature. They are usually discovered incidentally during imaging studies and are often misdiagnosed as liposarcoma, which have a malignant nature, because the imaging findings of myelolipoma can be similar to those of liposarcoma. It is challenging to distinguish presacral myelolipomas from other presacral fat-containing tumors without performing a histological examination. We should consider the possibility of a malignant tumor, and imaging-guided biopsy carries a risk of tumor spread along the biopsy tract. Therefore, surgical management might sometimes be required; however, it is not necessary in all cases. We present an incidentally detected case of presacral myelolipoma that was difficult to differentiate from other malignant tumors in a 71-year-old male.


Rationally designed inhibitor targeting antigen-trimming aminopeptidases enhances antigen presentation and cytotoxic T-cell responses.
Intracellular aminopeptidases endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2), and as well as insulin-regulated aminopeptidase (IRAP) process antigenic epitope precursors for loading onto MHC class I molecules and regulate the adaptive immune response. Their activity greatly affects the antigenic peptide repertoire presented to cytotoxic T lymphocytes and as a result can regulate cytotoxic cellular responses contributing to autoimmunity or immune evasion by viruses and cancer cells. Therefore, pharmacological regulation of their activity is a promising avenue for modulating the adaptive immune response with possible applications in controlling autoimmunity, in boosting immune responses to pathogens, and in cancer immunotherapy. In this study we exploited recent structural and biochemical analysis of ERAP1 and ERAP2 to design and develop phosphinic pseudopeptide transition state analogs that can inhibit this family of enzymes with nM affinity. X-ray crystallographic analysis of one such inhibitor in complex with ERAP2 validated our design, revealing a canonical mode of binding in the active site of the enzyme, and highlighted the importance of the S2' pocket for achieving inhibitor potency. Antigen processing and presentation assays in HeLa and murine colon carcinoma (CT26) cells showed that these inhibitors induce increased cell-surface antigen presentation of transfected and endogenous antigens and enhance cytotoxic T-cell responses, indicating that these enzymes primarily destroy epitopes in those systems. This class of inhibitors constitutes a promising tool for controlling the cellular adaptive immune response in humans by modulating the antigen processing and presentation pathway.


Improvement of stiff-person syndrome symptoms in pregnancy: Case series and literature review.
To describe 2 cases from a single academic institution of improvement in stiff-person syndrome (SPS) symptoms during pregnancy and to review the clinical outcomes of SPS in 6 additional pregnancies described in the literature. Evaluation of clinical symptoms and treatment changes of disease state during pregnancy. Seven patients with 9 pregnancies are described in women with a diagnosis of SPS. Six of 7 (86%) women were positive for glutamic acid decarboxylase (GAD65) antibody. In 5 of 9 (56%) pregnancies, symptomatic medications (antispasmodics) were significantly reduced with stabilization or improvement in symptoms through pregnancy. Nine live, healthy pregnancies resulted. All 7 (100%) women experienced worsening of symptoms after the birth of their children, and symptomatic therapies were resumed and/or increased. The immune pathogenesis of SPS continues to be explored. Immunomodulatory shifts during pregnancy may influence changes of clinical SPS symptoms and provide insight into the unique pathogenesis of SPS. Some women with SPS may be able to reduce symptomatic medications related to clinical improvement during pregnancy. Women with SPS may safely carry pregnancies to term, delivering healthy and unaffected babies.


An optimal permissible source region strategy for multispectral bioluminescence tomography.
Multispectral bioluminescence tomography (BLT) attracts increasing more attention in the area of small animal studies because multispectral data acquisition could help in the 3D location of bioluminescent sources. Generally, BLT problem is ill-posed and a priori information is indispensable to reconstruction bioluminescent source uniquely and quantitatively. In this paper, we propose a spectrally solved bioluminescence tomography algorithm with an optimal permissible source region strategy. Being the most different from earlier studies, an optimal permissible source region strategy which is automatically selected without human intervention is developed to reduce the ill-posedness of BLT and therefore improves the reconstruction quality. Furthermore, both numerical stability and computational efficiency benefit from the strategy. In the numerical experiments, a heterogeneous phantom is used to evaluate the proposed algorithm and the synthetic data is produced by Monte Carlo method for avoiding the inverse crime. The results demonstrate the feasibility and potential of our methodology for reconstructing the distribution of bioluminescent sources.


The effect of clysed and topical epinephrine on intraoperative catecholamine levels.
Epinephrine administration for hemostasis during burn wound excision may produce potential anesthetic risks. Two patient groups were studied to determine the absorption of either topical concentrated epinephrine or exogenously injected dilute epinephrine. For the topical group (10 patients, 10 procedures), excision of wounds under tourniquet was performed, followed by epinephrine (1 mg/10 mL) gauze with pressure wrapping. For the clysis group (9 patients, 12 procedures), donor sites were injected with 0.5 mg epinephrine/1,000 mL lactated Ringer's solution before harvest. Nine intraoperative serum samples were collected and frozen during each procedure for epinephrine and norepinephrine assay. Concentrated epinephrine (67 mL) was topically applied to excise 1,362 cm2. Dilute epinephrine (1,350 mL) was clysed to obtain 1,950 cm2 autograft. No significant increases in the serum catecholamines or changes in the cardiovascular profiles occurred. The administration of either topical or clysed epinephrine during acute burn excision does not cause any side effects for safe anesthetic management; there were no detectable increased plasma levels of epinephrine or norepinephrine. Epinephrine provides the burn surgeon with two safe methods for controlling intraoperative blood loss.


Co-opted Cellular Sac1 Lipid Phosphatase and PI(4)P Phosphoinositide Are Key Host Factors during the Biogenesis of the Tombusvirus Replication Compartment.
Positive-strand RNA [(+)RNA] viruses assemble numerous membrane-bound viral replicase complexes (VRCs) with the help of viral replication proteins and co-opted host proteins within large viral replication compartments in the cytosol of infected cells. In this study, we found that deletion or depletion of Sac1 phosphatidylinositol 4-phosphate [PI(4)P] phosphatase reduced tomato bushy stunt virus (TBSV) replication in yeast (Saccharomyces cerevisiae) and plants. We demonstrate a critical role for Sac1 in TBSV replicase assembly in a cell-free replicase reconstitution assay. The effect of Sac1 seems to be direct, based on its interaction with the TBSV p33 replication protein, its copurification with the tombusvirus replicase, and its presence in the virus-induced membrane contact sites and within the TBSV replication compartment. The proviral functions of Sac1 include manipulation of lipid composition, sterol enrichment within the VRCs, and recruitment of additional host factors into VRCs. Depletion of Sac1 inhibited the recruitment of Rab5 GTPase-positive endosomes and enrichment of phosphatidylethanolamine in the viral replication compartment. We propose that Sac1 might be a component of the assembly hub for VRCs, likely in collaboration with the co-opted the syntaxin18-like Ufe1 SNARE protein within the TBSV replication compartments. This work also led to demonstration of the enrichment of PI(4)P phosphoinositide within the replication compartment. Reduction in the PI(4)P level due to chemical inhibition in plant protoplasts; depletion of two PI(4)P kinases, Stt4p and Pik1p; or sequestration of free PI(4)P via expression of a PI(4)P-binding protein in yeast strongly inhibited TBSV replication. Altogether, Sac1 and PI(4)P play important proviral roles during TBSV replication.IMPORTANCE Replication of positive-strand RNA viruses depends on recruitment of host components into viral replication compartments or organelles. Using TBSV, we uncovered the critical roles of Sac1 PI(4)P phosphatase and its substrate, PI(4)P phosphoinositide, in promoting viral replication. Both Sac1 and PI(4)P are recruited to the site of viral replication to facilitate the assembly of the viral replicase complexes, which perform viral RNA replication. We found that Sac1 affects the recruitment of other host factors and enrichment of phosphatidylethanolamine and sterol lipids within the subverted host membranes to promote optimal viral replication. In summary, this work demonstrates the novel functions of Sac1 and PI(4)P in TBSV replication in the model host yeast and in plants.


Tgamma cells in systemic lupus erythematosus. Variation with disease activity.
Circulating T cells bearing receptors for the Fc portion of IgG (T gamma) were identified by sensitive immunofluorescent techniques with rabbit IgG b4 allotype/anti-b4 complexes. A twofold decrease in both proportion and absolute number of T gamma cells was found in patients with active systemic lupus erythematosus (SLE) relative to values obtained during disease remission. The reduction in T gamma cells was most evident in patients with severe hypocomplementemia. A deficit of T gamma cells in active patients was not demonstrated. The percentage of total T cells rosetting with sheep erythrocytes was reduced in peripheral blood of most patients regardless of disease activity status, but particularly during SLE exacerbation. Cells lacking intrinsic surface immunoglobulin, IgG Fc receptors, and receptors for sheep erythrocytes were increased. These cells, operationally termed null, exhibited an inverse linear relationship with T cells that was not apparent in regression analyses performed against other lymphocyte subpopulations. Such differences were not found for B cells and IgG receptor-bearing non-B/non-T cells which were present in normal proportions in virtually all patients. The origin and functional significance of these unusual lymphocyte subpopulation abnormalities are discussed.


A Bibliometric Analysis of Research on Supported Ionic Liquid Membranes during the 1995-2015 Period: Study of the Main Applications and Trending Topics.
A bibliometric analysis based on Scopus database was performed to identify the global research trends related to Supported Ionic Liquid Membranes (SILMs) during the time period from 1995 to 2015. This work tries to improve the understanding of the most relevant research topics and applications. The results from the analysis reveal that only after 2005 the research efforts focused on SILMs became significant, since the references found before that year are scarce. The most important research works on the four main application groups for SILMs defined in this work (carbon dioxide separation, other gas phase separations, pervaporation and liquid phase separations) were summarized in this paper. Carbon dioxide separation appeared as the application that has received by far the most attention according to the research trends during the analysed period. Comments about other significant applications that are gaining attention, such as the employment of SILMs in analytical tasks or their consideration for the production of fuel cells, have been included.


Effects of steroid 5alpha-reductase inhibitor ONO-9302 and anti-androgen allylestrenol on the prostatic growth, and plasma and prostatic hormone levels in rats.
ONO-9302 [epristeride; (-)-17beta-(tert-butylcarbamoyl)androsta-3,5-diene-3-carboxy lic acid] is a novel inhibitor of steroid 5alpha-reductase. We studied in vitro and in vivo effects of ONO-9302 on the rat prostatic tissue in comparison with those of the anti-androgen allylestrenol. ONO-9302 inhibited the rat prostatic enzyme with an IC50 value of 11 nM, whereas allylestrenol was about 80,000-fold less potent. The growth of ventral prostate, which was induced by the subcutaneous injection of testosterone propionate in the castrated rats, was significantly reduced by ONO-9302 at oral doses of 1-100 mg/kg/day. Allylestrenol showed a significant effect only at a dose of 100 mg/kg/day. In mature male rats, ONO-9302 significantly reduced the ventral prostate weight at doses of 10-100 mg/kg/day and decreased prostatic 5alpha-dihydrotestosterone (DHT) content associated with a rise in testosterone (T) content at doses of 0.1-100 mg/kg/day. Plasma hormone levels (i.e., T, DHT, luteinizing hormone (LH) and follicle stimulating hormone (FSH)) were not altered significantly. Allylestrenol significantly reduced the ventral prostate weight at doses of 10-100 mg/kg/day. However, unlike ONO-9302, allylestrenol reduced both the prostatic DHT and T contents and also lowered plasma T, DHT, LH and FSH levels at a dose of 30 mg/kg/day. These results suggest that ONO-9302 reduces the prostatic growth by inhibiting the conversion of T to DHT in the prostate without lowering blood T level unlike anti-androgen drugs.


The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest.
The aim of this study was to determine whether the type 2 diabetes-associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest. A total of 38 healthy young Caucasian men were studied before and after bed rest using the hyperinsulinemic-euglycemic clamp technique combined with indirect calorimetry preceded by an intravenous glucose tolerance test. The TCF7L2 rs7903146 was genotyped using allelic discrimination performed with an ABI 7900 system. The genetic analyses were done assuming a dominant model of inheritance. The first-phase insulin response (FPIR) was significantly lower in carriers of the T-allele compared with carriers of the CC genotype before bed rest, with and without correction for insulin resistance. The incremental rise of FPIR in response to insulin resistance induced by bed rest was lower in carriers of the T-allele (P < 0.001). Fasting plasma glucagon levels were significantly lower in carriers of the T-allele before and after bed rest. While carriers of the CC genotype developed increased hepatic insulin resistance, the TCF7L2 rs7903146 did not influence peripheral insulin action or the rate of lipolysis before or after bed rest. Healthy carriers of the T-allele of TCF7L2 rs7903146 exhibit a diminished increase of insulin secretion in response to intravenous glucose to compensate for insulin resistance as induced by bed rest. Reduced paracrine glucagon stimulation may contribute to the impairment of beta-cell function in the carriers TCF7L2 rs7903146 T-allele associated with increased risk of type 2 diabetes.


RIBONUCLEIC ACIDS OF BACILLUS SUBTILIS SPORES AND SPORULATING CELLS.
Doi, Roy H. (Syracuse University, Syracuse N.Y.), and Richard T. Igarashi. Ribonucleic acids of Bacillus subtilus spores and sporulating cells. J. Bacteriol. 87:323-328. 1964.-The ribonucleic acids (RNA) of Bacillus subtilis spores were analyzed for their size and base composition. Soluble and ribosomal RNA identical to those found in vegetative cells were present in spores. A base ratio difference was observed between the 16s and 23s ribosomal RNA. The 16s RNA had a higher cytidylate and lower adenylate base composition. The ratio of soluble of ribosomal RNA in spores was 30%, in contrast to 15% in vegetative cells, and may be related to their difference in biosynthetic activity. Although active synthesis of informational RNA occurred prior to endospore formation, no detectable level of informational RNA was found in spores. The informational RNA was shown to have the same base composition as that of B. subtilis deoxyribonucleic acid. The compositional difference between spore and vegetative cell RNA appeared to be strictly quantitative.


Anandamide suppresses proliferation and cytokine release from primary human T-lymphocytes mainly via CB2 receptors.
Anandamide (AEA) is an endogenous lipid mediator that exerts several effects in the brain as well as in peripheral tissues. These effects are mediated mainly by two types of cannabinoid receptors, named CB(1)R and CB(2)R, making AEA a prominent member of the "endocannabinoid" family. Also immune cells express CB(1) and CB(2) receptors, and possess the whole machinery responsible for endocannabinoid metabolism. Not surprisingly, evidence has been accumulated showing manifold roles of endocannabinoids in the modulation of the immune system. However, details of such a modulation have not yet been disclosed in primary human T-cells. In this investigation we used flow cytometry and ELISA tests, in order to show that AEA suppresses proliferation and release of cytokines like IL-2, TNF-alpha and INF-gamma from activated human peripheral T-lymphocytes. However, AEA did not exert any cytotoxic effect on T-cells. The immunosuppression induced by AEA was mainly dependent on CB(2)R, since it could be mimicked by the CB(2)R selective agonist JWH-015, and could be blocked by the specific CB(2)R antagonist SR144528. Instead the selective CB(1)R agonist ACEA, or the selective CB(1)R antagonist SR141716, were ineffective. Furthermore, we demonstrated an unprecedented immunosuppressive effect of AEA on IL-17 production, a typical cytokine that is released from the unique CD4+ T-cell subset T-helper 17. Overall, our study investigates for the first time the effects of the endocannabinoid AEA on primary human T-lymphocytes, demonstrating that it is a powerful modulator of immune cell functions. In particular, not only we clarify that CB(2)R mediates the immunosuppressive activity of AEA, but we are the first to describe such an immunosuppressive effect on the newly identified Th-17 cells. These findings might be of crucial importance for the rational design of new endocannabinoid-based immunotherapeutic approaches.


Effect of antenatal zinc supplementation on impetigo in infants in Bangladesh.
We sought to determine the effects of maternal zinc supplementation on skin infections among infants in poor urban areas of Dhaka, Bangladesh. A double-blind, placebo-controlled, randomized trial was conducted among 199 and 221 Bangladeshi infants whose mothers were administered 30 mg daily of zinc or placebo, respectively. The mothers received zinc supplementation from 12-16 weeks' gestation until delivery, and the infants were followed up until 6 months of age. Among the infants of mothers who received zinc supplementation during the antenatal period, 10.6% had at least 1 episode of impetigo compared with 19.6% of the infants of mothers in the placebo group (P = 0.01). Infants in the treatment group had a 54% reduction in incidence rate of episodes of impetigo when compared with infants in the placebo group (P = 0.01). The effect of zinc supplementation was more pronounced among male infants (64% reduction) and intrauterine growth restricted and low birth weight infants (73% reduction) and among infants of mothers with increased parity (60% reduction) or decreased socioeconomic status (71% reduction).


Effects of sleep inertia after daytime naps vary with executive load and time of day.
The effects of executive load on working memory performance during sleep inertia after morning or afternoon naps were assessed using a mixed design with nap/wake as a between-subjects factor and morning/afternoon condition as a within-subject factor. Thirty-two healthy adults (mean 22.5 ± 3.0 years) attended two laboratory sessions after a night of restricted sleep (6 hrs), and at first visit, were randomly assigned to the Nap or Wake group. Working memory (n-back) and subjective workload were assessed approximately 5 and 25 minutes after 90-minute morning and afternoon nap opportunities and at the corresponding times in the Wake condition. Actigraphically assessed nocturnal sleep duration, subjective sleepiness, and psychomotor vigilance performance before daytime assessments did not vary across conditions. Afternoon naps showed shorter EEG assessed sleep latencies, longer sleep duration, and more Slow Wave Sleep than morning naps. Working memory performance deteriorated, and subjective mental workload increased at higher executive loadings. After afternoon naps, participants performed less well on more executive-function intensive working memory tasks (i.e., 3-back), but waking and napping participants performed equally well on simpler tasks. After some 30 minutes of cognitive activity, there were no longer performance differences between the waking and napping groups. Subjective Task Difficulty and Mental Effort requirements were less affected by sleep inertia and dissociated from objective measures when participants had napped in the afternoon. We conclude that executive functions take longer to return to asymptotic performance after sleep than does performance of simpler tasks which are less reliant on executive functions.


Diagnosis of gastric prepyloric and antral lesions: comparison of fiberendoscopy and gastric biopsy with radiology.
Fibergastroscopy and direct-vision gastric biopsy were performed in 47 patients who had a prepyloric or antral gastric lesion on barium meal (single-contrast) examination. Of 27 cases with a radiological diagnosis of prepyloric or antral ulceration, five cases (18.5%) had evidence of ulceration, 12 cases (44.4%) had acute or chronic gastritis and eight cases (29.6%) had normal gastric mucosa, on fibergastroscopy. Multiple gastric biopsy confirmed the presence of acute-on-chronic gastritis (ACG), chronic gastritis (CG) and chronic atrophic gastritis (CAG), with or without intestinal metaplasia (IM) or epithelial atypia (Aty), in 24 cases (89%). Normal gastric mucosa was found in three cases (11%) and malignancy in none. Of 15 cases with a radiological diagnosis of prepyloric or antral malignancy, only three cases (20%) had evidence of adenocarcinoma on endoscopy and biopsy. One case had rounded nodules seen on endoscopy and gastric biopsies showed malignant lymphoma. In two cases with endoscopic suspicion of malignancy, gastric biopsies showed ACG in one and CAG in the other. Gastric biopsies showed histological changes of CG (+/- IM) or CAG (+/- IM) in 11 cases (73%). In five cases with a radiological diagnosis of various prepyloric or antral lesions, endoscopy and biopsy revealed CG (+/- IM) in all and malignancy in none. It is concluded that fiberendoscopy and gastric biopsy are superior to the single-contrast barium meal in the diagnosis of prepyloric or antral gastric lesions. Direct-vision gastric biopsy should be done in all cases since it increased the diagnostic accuracy of fiberendoscopy.


Delivery of a foreign epitope by sharing amino acid residues with the carrier matrix.
A broad range of structural viral proteins has the ability to assemble into virus-like particles (VLPs). Under the condition that modified subunits are still competent to assemble into VLPs, they are epitope delivery platforms suitable for vaccination purposes. The insertion of foreign sequences can be detrimental for the formation of chimeric VLPs as a result of misfolded subunit proteins. Hence, a strategy was adopted to screen for locations allowing the use of shared residues between the wildtype subunit sequence and the foreign insert. The insertion of a cysteine-containing sequence of hepatitis C virus (HCV) envelope protein 2 (E2) without adding an additional cysteine residue retained the ability of recombinant small hepatitis B surface antigen (HBsAg-S) to form secretion competent VLPs. A cysteine residue shared by the insert and the template protein avoided the formation of non-native disulfide bonds, and allowed the formation of VLPs. The chimeric HBsAg-S VLPs were similar to wildtype VLPs in density exposing the inserted foreign epitope and being immunogenic. Overall, the use of shared sequences between the insert and the subunit will facilitate the design of chimeric VLPs carrying multiple epitopes.


Quality improvement opportunities in gynecologic cytologic-histologic correlations: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 4.
Cytopathology experts, interested stakeholders, and representatives from the College of American Pathologists, the Centers for Disease Control and Prevention, the American Society of Cytopathology, the Papanicolaou Society of Cytopathology, the American Society for Clinical Pathology, and the American Society of Cytotechnology convened the Gynecologic Cytopathology Quality Consensus Conference to present preliminary consensus statements developed by working groups, including the Cytologic-Histologic Correlations Working Group 4, using results from surveys and literature review. Conference participants voted on statements, suggested changes where consensus was not achieved, and voted on proposed changes. To document existing practices in gynecologic cytologic-histologic correlation, to develop consensus statements on appropriate practices, to explore standardization, and to suggest improvement in these practices. The material is based on survey results from 546 US laboratories, review of the literature from 1988 to 2011, and the College of American Pathologists Web site for consensus comments and additional survey questions. Cytologic-histologic correlations can be performed retrospectively, during initial case review, or both. At minimum, all available slides should be reviewed for a high-grade squamous intraepithelial lesion Papanicolaou test with negative biopsies. The preferred monitor for correlations is the positive predictive value of a Papanicolaou test. Laboratories should design cytologic-histologic correlation programs to explore existing or perceived quality deficiencies.


Detection of Tetracycline Resistance Genes in European Hedgehogs (Erinaceus europaeus) and Crested Porcupines (Hystrix cristata).
Relatively little is known regarding the role of wildlife in the development of antibiotic resistance. Our aim was to assess the presence of the tetracycline resistance genes, tet(A), tet(B), tet(C), tet(D), tet(E), tet(G), tet(K), tet(L), tet(M), tet(O), tet(P), tet(Q), tet(S), and tet(X), in tissue samples of 14 hedgehogs (Erinaceus europaeus) and 15 crested porcupines (Hystrix cristata) using PCR assays. One or more tet genes were found in all but three hedgehogs and one crested porcupine. Of the 14 tetracycline resistance genes investigated, 13 were found in at least one sample; tet(G) was not detected. We confirmed the potential role of wild animals as bioindicators, reservoirs, or vectors of antibiotic-resistant bacteria in the environment.


Label-free biosensing with lipid-functionalized gold nanorods.
The fabrication of a label-free mass spectrometry and optical detection-based biosensor platform for the detection of low-abundance lipophilic analytes in complex mixtures is described. The biosensor consists of a lipid layer partially tethered to the surface of a gold nanorod. The effectiveness of the biosensor is demonstrated for the label-free detection of a lipophilic drug in aqueous solution and a lipopeptide in serum.


Synthesis of new selective cytotoxic ricinine analogues against oral squamous cell carcinoma.
Sixteen new analogues were synthesized from ricinine and tested alongside with seven known analogues for their cytotoxic activity against oral cancer (SAS cells) and normal epithelial cells (L132 cells). In contrast to 5-FU, the synthesized ricinine analogues did not show toxicity to normal cells. However, some of them inhibited the proliferation of oral cancer cells at 25 µM as evident from the MTT assay results. Ricinine analogue (19) was shown to be the most active derivative (69.22% inhibition). Potential targets involved in the oral cancer inhibitory activity of compound 19 were investigated using in-silico studies and western blot analysis. PTP1B was predicted to be a target for ricinine using reverse docking approach. This prediction was confirmed by western blot analysis that revealed the downregulation of PTP1B protein by compound 19. Moreover, it showed downregulation of COX-2 which is also extensively expressed in oral cancer.


Intestinal fluid absorption in spontaneously hypertensive rats.
A comparison has been made of intestinal fluid absorption between male Okamoto spontaneously hypertensive rats (s.h.r.) and normotensive male Wistar controls. S.h.r. show enhanced fluid absorption both in hypertensive adults and in young s.h.r. before hypertension has developed. Several potential causes for increased fluid transport in s.h.r. were tested using pharmacological antagonists. It is unlikely that enhanced fluid absorption is due to high sympathetic nervous activity, the renin-angiotensin system or is secondary to hypertension. Intestine from s.h.r. have a high short-circuit current indicating a change in ion pump activity. These results are discussed in relation to the possible causes of increased fluid (ion) transport by the intestine of s.h.r.


Brugia pahangi: effects of protective resistance on lymphatic lesions and granulomatous inflammation in infected jirds (Meriones unguiculatus).
Effects of protective resistance on lymphatic lesions and granulomatous inflammation in infected jirds (Meriones unguiculatus). Experimental Parasitology 77, 395-404. The hypothesis that protective immune responses play a role in the induction of filarial-associated lymphatic lesions was tested in jirds immunized twice with 75 Brugia pahangi radiation-attenuated third-stage larvae. Lymphatic lesions and granulomatous reactivity were compared in immunized, infected, and naive jirds at both acute and chronic periods following challenge with 100 third-stage larvae. Challenge worm burdens were reduced in immunized jirds at both infection periods. The ratio of lymph thrombi to lymphatic worms, an indicator of lymphatic lesion severity, was significantly greater in immunized jirds than in nonimmunized-challenged jirds during acute but not chronic infections. Parasite-specific-granulomatous hypersensitivity was assessed by measurements of granuloma areas around B. pahangi-soluble adult worm antigen-coated sepharose beads embolized in the lungs prior to necropsy. Marked granulomatous inflammatory responses seen during the acute period in both immunized-challenged and nonimmunized-challenged jirds were significantly reduced in similar jirds during chronic periods. Jirds with existing B. pahangi infections were not resistant to homologous challenge infection and had fewer lymphatic lesions and reduced granulomatous inflammatory responses to soluble adult worm antigen compared to previously naive jirds at acute periods postchallenge. These data suggest that protective immune responses increase the severity of filariae-induced lymphatic inflammation. The subsequent modulation of these lesions is probably associated with parasites that survived the protective immune response.


A novel single point mutation of the LYST gene in two siblings with different phenotypic features of Chediak Higashi syndrome.
Chediak Higashi syndrome (CHS) is an autosomal-recessive disorder characterized by oculocutaneous albinism, recurrent infections and a progressive primary neurological disease. Here, we describe two siblings with CHS due to a novel homozygous R1836X mutation in the LYST gene associated with loss of NK cell degranulation and cytotoxicity. While one sibling was born with fair skin and hair and died of hemophagocytic lymphohistiocytosis (HLH) at 5 months of age, the other sibling had dark black hair and skin and developed HLH at the age of 4 years.


Relationship between antiretroviral plasma concentration and emergence of HIV-1 resistance mutations at treatment failure.
The relationship between antiretroviral pharmacokinetic exposure and acquisition of human immunodeficency virus-1 (HIV-1) drug resistance mutations (DRM) is not fully understood. The aim of this study was to investigate whether antiretroviral plasma concentration could predict the emergence of DRM at treatment failure. The study cohort comprised retrospectively selected patients with failing antiretroviral regimens for whom a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) trough concentration measurement (TDM) had been obtained before failure, a genotypic resistance test (GRT1) had been performed before the TDM, and a genotypic resistance test (GRT2) had been performed at therapeutic failure. Drug levels were classified as undetectable/detectable or subtherapeutic/therapeutic according to limits of quantification of a high-performance liquid chromatography-ultraviolet assay or pre-defined efficacy thresholds, respectively. The number of DRM acquired at treatment failure was evaluated by comparing the results of the GRT2 and GRT1. A total of ten and 57 failure episodes occurred among our patients on NNRTI-based and PI-based regimens, respectively, and included in the evaluation. PI concentration was subtherapeutic in 28.1% of patients, among which the levels were undetectable in 21.1%. Twenty-five (43.9%) patients acquired at least one new PI-DRM according to the GRT2. Patients with undetectable PI levels showed a lower emergence of PI-DRM (minor + major) than those with detectable levels (8.3 vs. 53.3%, p = 0.007). Multivariate analysis confirmed that undetectable PI levels were independent negative predictors of DRM selection. NNRTI measurements were subtherapeutic in 2/10 (20%) patients. NNRTI-DRM were acquired by all patients regardless of NNRTI levels. A PI measurement showing undetectable drug levels prior to treatment failure predicted the lack of emergence of PI-DRM at failure. These results suggest that PI levels can help clinicians interpret the reasons for treatment failure and guide the type of interventions needed.


Substring selection for biomedical document classification.
Attribute selection is a critical step in development of document classification systems. As a standard practice, words are stemmed and the most informative ones are used as attributes in classification. Owing to high complexity of biomedical terminology, general-purpose stemming algorithms are often conservative and could also remove informative stems. This can lead to accuracy reduction, especially when the number of labeled documents is small. To address this issue, we propose an algorithm that omits stemming and, instead, uses the most discriminative substrings as attributes. The approach was tested on five annotated sets of abstracts from iProLINK that report on the experimental evidence about five types of protein post-translational modifications. The experiments showed that Naive Bayes and support vector machine classifiers perform consistently better [with area under the ROC curve (AUC) accuracy in range 0.92-0.97] when using the proposed attribute selection than when using attributes obtained by the Porter stemmer algorithm (AUC in 0.86-0.93 range). The proposed approach is particularly useful when labeled datasets are small.


Treatment Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors.
Recent classification of neuroendocrine neoplasms has defined well-differentiated high-grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well-described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens. This was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients' demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression-free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Treatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki-67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum-etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96-16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months. Among patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short-lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy. High-grade well-differentiated neuroendocrine tumors (NET G3) are considered a different entity from low-grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well-differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors.


HuD regulates coding and noncoding RNA to induce APP→Aβ processing.
The primarily neuronal RNA-binding protein HuD is implicated in learning and memory. Here, we report the identification of several HuD target transcripts linked to Alzheimer's disease (AD) pathogenesis. HuD interacted with the 3' UTRs of APP mRNA (encoding amyloid precursor protein) and BACE1 mRNA (encoding β-site APP-cleaving enzyme 1) and increased the half-lives of these mRNAs. HuD also associated with and stabilized the long noncoding (lnc)RNA BACE1AS, which partly complements BACE1 mRNA and enhances BACE1 expression. Consistent with HuD promoting production of APP and APP-cleaving enzyme, the levels of APP, BACE1, BACE1AS, and Aβ were higher in the brain of HuD-overexpressing mice. Importantly, cortex (superior temporal gyrus) from patients with AD displayed significantly higher levels of HuD and, accordingly, elevated APP, BACE1, BACE1AS, and Aβ than did cortical tissue from healthy age-matched individuals. We propose that HuD jointly promotes the production of APP and the cleavage of its amyloidogenic fragment, Aβ.


Plasma ghrelin and oxyntomodulin concentrations in lactating dairy cows receiving abomasal soybean oil, corn starch, and casein infusions.
The effects of increased postruminal supply of casein, corn starch, and soybean oil on plasma concentrations of the gastrointestinal hormones ghrelin and oxyntomodulin (OXM) were investigated. Four mid-lactation Holstein cows were used in a 4 x 4 Latin square. Treatments were continuous abomasal infusions (23 h/d) for 7 d of water, soybean oil (500 g/d), corn starch (1100 g/d), or casein (800 g/d). Jugular vein plasma was obtained every 30 min for 7h on days 1 and 7. Soybean oil and casein infusion decreased preprandial plasma ghrelin concentration by approximately 20% on both d (time-by-treatment P<0.10); however, dry matter intake (DMI) was depressed only after 7 d of oil infusion. Infusion of soybean oil, corn starch, or casein did not change the plasma OXM concentration (P>0.20). The present data indicate that plasma ghrelin concentration is depressed immediately before feeding by the postruminal infusion of soybean oil and casein, but it is not affected during the postprandial period. Plasma ghrelin concentration was not altered (P>0.20), pre- or postfeeding, by increased postruminal supply of corn starch. In addition, plasma OXM concentration did not respond (P>0.20) to postruminal nutrient infusion. In conclusion, a decrease in DMI when fat is infused could be partially explained by the decrease in prefeeding plasma ghrelin concentration, but a decrease in prefeeding plasma ghrelin concentration is not always associated with a decrease in DMI, as observed for the infusion of casein. Plasma OXM concentration was not affected by postruminal infusion of macronutrients.


Role of Positive Emotions in Takotsubo Cardiomyopathy.
Takotsubo Cardiomyopathy, also known as "broken heart syndrome," is a transient cardiac condition characterized by sudden left ventricular dysfunction, often triggered by emotional stress or significant life events. While research has predominantly focused on the impact of negative emotions and emotional stressors, there is a growing interest in understanding the role of positive emotions in this unique cardiac syndrome. This narrative review explores the emerging research on positive emotions and Takotsubo Cardiomyopathy. It provides an overview of studies investigating the relationship between positive emotions and the condition, highlighting key findings and observations. Positive emotions, such as joy, happiness, gratitude, and optimism, have been associated with improved emotional well-being, better-coping mechanisms, and potential cardiovascular protection. Some studies suggest that individuals experiencing higher levels of positive emotions may have a reduced risk of developing Takotsubo Cardiomyopathy. However, the research in this area is still limited, with small sample sizes and challenges in quantifying positive emotions. Additionally, the interplay between positive and negative emotions requires further exploration to fully understand their impact on cardiovascular health. Despite these limitations, harnessing positive emotions in cardiac care holds promise for enhancing patient outcomes and emotional well-being. Integrating positive psychology into clinical practice and cardiac rehabilitation may lead to more holistic and patient-centered approaches to cardiovascular care. Further longitudinal studies, interventional trials, and mechanistic investigations are needed to strengthen the evidence base and identify potential therapeutic perspectives. As research progresses, addressing these gaps will provide valuable insights into the complex relationship between emotions and cardiovascular health, benefiting patients affected by Takotsubo Cardiomyopathy and other cardiovascular conditions.


Pulmonary injury from proton and conventional radiotherapy as revealed by CT.
Although radiation therapy is used in early-stage inoperable lung cancer, it often results in injury to functional lung tissue. A study was undertaken to determine the frequency and severity of pulmonary injury revealed by CT in patients who had undergone conformal proton (to a limited volume) radiation therapy. We compared these findings with those from a group of patients who had undergone a combination of photon and conformal proton (to a larger volume) radiation therapy. Proton radiation therapy was associated with a lower frequency of pulmonary injury than the combined regimen. Injury correlated well with the volume of normal lung that was irradiated. Conformal proton radiation therapy appears to be able to reduce the incidence and severity of pulmonary injury revealed by CT.


Hierarchical temporal prediction captures motion processing along the visual pathway.
Visual neurons respond selectively to features that become increasingly complex from the eyes to the cortex. Retinal neurons prefer flashing spots of light, primary visual cortical (V1) neurons prefer moving bars, and those in higher cortical areas favor complex features like moving textures. Previously, we showed that V1 simple cell tuning can be accounted for by a basic model implementing temporal prediction - representing features that predict future sensory input from past input (Singer et al., 2018). Here, we show that hierarchical application of temporal prediction can capture how tuning properties change across at least two levels of the visual system. This suggests that the brain does not efficiently represent all incoming information; instead, it selectively represents sensory inputs that help in predicting the future. When applied hierarchically, temporal prediction extracts time-varying features that depend on increasingly high-level statistics of the sensory input.


[Vascularization patterns in focal liver lesions: comparison of plain and signal-enhanced amplitude-modulated color duplex ultrasonography].
Morphology of focal liver lesions was studied by power Doppler. Plain images and images after i.v. application of galactose-based microbubbles (Levovist, Schering AG) were compared. 21 patients with focal liver lesions were studied by power Doppler before and after application of the signal enhancer. In lesions that showed short pulsations in plain studies, vascular structures were visible after application of the signal enhancer. In hepatocellular carcinomas, multiple arteries with small diameter became visible. Peripheral veins were detected in metastases. A large feeding artery was detected in 1/2 haemangiomas with flow and in a focal nodular hyperplasia. In comparison to plain amplitude-modulated colour-coded duplex ultrasound, vascular patterns of focal liver lesions were more clearly visible after injection of a signal-enhancer.


Caring for a relative with chronic fatigue syndrome: difficulties, cognition and acceptance over time.
The present study explored the difficulties experienced by carers of chronic fatigue syndrome (CFS) sufferers, their cognitions, and their efforts to accept the illness. Semi-structured interviews were conducted with 17 carers to study these issues, retrospectively, over three stages: before the diagnosis of CFS, shortly after the diagnosis, and at present. Surprisingly, the results suggested that carers, several of them absent from home during the day, felt that their lives were only minimally constrained by the illness. Nevertheless, all carers reported specific coping efforts to manage both the illness and their own distress, and indicated that they learned to accept the illness over time. However, acceptance appeared to be a form of resignation rather than a positive appreciation of the illness. In light of the uncertainties surrounding the origin of CFS and carers' apparent confusion, the results obtained in the present study are significant in that they increase our understanding of CFS carers' quality of life, their efforts to cope with the illness, and the physical and emotional help they may provide to the sufferer. Such information can be usefully employed in the increasing development of counselling interventions and instrumental support networks that involve both sufferers and their carers.


A fluorescent glycolipid-binding peptide probe traces cholesterol dependent microdomain-derived trafficking pathways.
The uptake and intracellular trafficking of sphingolipids, which self-associate into plasma membrane microdomains, is associated with many pathological conditions, including viral and toxin infection, lipid storage disease, and neurodegenerative disease. However, the means available to label the trafficking pathways of sphingolipids in live cells are extremely limited. In order to address this problem, we have developed an exogenous, non-toxic probe consisting of a 25-amino acid sphingolipid binding domain, the SBD, derived from the amyloid peptide Abeta, and conjugated by a neutral linker with an organic fluorophore. The current work presents the characterization of the sphingolipid binding and live cell trafficking of this novel probe, the SBD peptide. SBD was the name given to a motif originally recognized by Fantini et al in a number of glycolipid-associated proteins, and was proposed to interact with sphingolipids in membrane microdomains. In accordance with Fantini's model, optimal SBD binding to membranes depends on the presence of sphingolipids and cholesterol. In synthetic membrane binding assays, SBD interacts preferentially with raft-like lipid mixtures containing sphingomyelin, cholesterol, and complex gangliosides in a pH-dependent manner, but is less glycolipid-specific than Cholera toxin B (CtxB). Using quantitative time-course colocalization in live cells, we show that the uptake and intracellular trafficking route of SBD is unlike that of either the non-raft marker Transferrin or the raft markers CtxB and Flotillin2-GFP. However, SBD traverses an endolysosomal route that partially intersects with raft-associated pathways, with a major portion being diverted at a late time point to rab11-positive recycling endosomes. Trafficking of SBD to acidified compartments is strongly disrupted by cholesterol perturbations, consistent with the regulation of sphingolipid trafficking by cholesterol. The current work presents the characterization and trafficking behavior of a novel sphingolipid-binding fluorescent probe, the SBD peptide. We show that SBD binding to membranes is dependent on the presence of cholesterol, sphingomyelin, and complex glycolipids. In addition, SBD targeting through the endolysosomal pathway in neurons is highly sensitive to cholesterol perturbations, making it a potentially useful tool for the analysis of sphingolipid trafficking in disease models that involve changes in cholesterol metabolism and storage.


Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and In Vivo Evaluation.
Although high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited commercially available UCAs for high-frequency CEUS (hfCEUS) is largely unknown, while shell properties have been shown to be an important factor for their performance. The aim of our study was to produce UCAs in-house for hfCEUS. Twelve different UCA formulations A-L were made by either sonication or mechanical agitation. The gas core consisted of C4F10 and the main coating lipid was either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC; A-F formulation) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC; G-L formulation). Mechanical agitation resulted in UCAs with smaller microbubbles (number weighted mean diameter ~1 [Formula: see text]) than sonication (number weighted mean diameter ~2 [Formula: see text]). UCA formulations with similar size distributions but different main lipid components showed that the DPPC-based UCA formulations had higher nonlinear responses at both the fundamental and subharmonic frequencies in vitro for hfCEUS using the Vevo2100 high-frequency preclinical scanner (FUJIFILM VisualSonics, Inc.). In addition, UCA formulations F (DSPC-based) and L (DPPC-based) that were made by mechanical agitation performed similar in vitro to the commercially available Target-Ready MicroMarker (FUJIFILM VisualSonics, Inc.). UCA formulation F also performed similar to Target-Ready MicroMarker in vivo in pigs with similar mean contrast intensity within the kidney ( n = 7 ), but formulation L did not. This is likely due to the lower stability of formulation L in vivo. Our study shows that DSPC-based microbubbles produced by mechanical agitation resulted in small microbubbles with high nonlinear responses suitable for hfCEUS imaging.


Application of Bayesian decision-making to laboratory testing for Lyme disease and comparison with testing for HIV.
In this study, Bayes' theorem was used to determine the probability of a patient having Lyme disease (LD), given a positive test result obtained using commercial test kits in clinically diagnosed patients. In addition, an algorithm was developed to extend the theorem to the two-tier test methodology. Using a disease prevalence of 5%-75% in samples sent for testing by clinicians, evaluated with a C6 peptide enzyme-linked immunosorbent assay (ELISA), the probability of infection given a positive test ranged from 26.4% when the disease was present in 5% of referrals to 95.3% when disease was present in 75%. When applied in the case of a C6 ELISA followed by a Western blot, the algorithm developed for the two-tier test demonstrated an improvement with the probability of disease given a positive test ranging between 67.2% and 96.6%. Using an algorithm to determine false-positive results, the C6 ELISA generated 73.6% false positives with 5% prevalence and 4.7% false positives with 75% prevalence. Corresponding data for a group of test kits used to diagnose HIV generated false-positive rates from 5.4% down to 0.1% indicating that the LD tests produce up to 46 times more false positives. False-negative test results can also influence patient treatment and outcomes. The probability of a false-negative test for LD with a single test for early-stage disease was high at 66.8%, increasing to 74.9% for two-tier testing. With the least sensitive HIV test used in the two-stage test, the false-negative rate was 1.3%, indicating that the LD test generates ~60 times as many false-negative results. For late-stage LD, the two-tier test generated 16.7% false negatives compared with 0.095% false negatives generated by a two-step HIV test, which is over a 170-fold difference. Using clinically representative LD test sensitivities, the two-tier test generated over 500 times more false-negative results than two-stage HIV testing.


General Copper-Catalyzed Coupling of Alkyl-, Aryl-, and Alkynylaluminum Reagents with Organohalides.
We report the first example of a very general Cu-catalyzed cross-coupling of organoaluminum reagents with organohalides. The reactions proceed for the couplings of alkyl-, aryl-, and alkynylaluminum reagents with aryl and heteroaryl halides and vinyl bromides, affording the cross-coupled products in good to excellent yields. Both primary and secondary alkylaluminum reagents can be utilized as organometallic coupling partners. These reactions are not complicated by β-hydride elimination, and as a result rearranged products are not observed with secondary alkylaluminum reagents even for couplings with heteroaryl halides under "ligand-free" conditions. Radical clock experiment with a radical probe and relative reactivity study of Ph3Al with two haloarenes, 1-bromonaphthalene and 4-chlorobenzonitrile, having two different redox potentials indicates that the reaction does not involve free aryl radicals and radical anions as intermediates. These results combined with the result of the Hammett plot obtained by reacting Ph3Al with iodoarenes containing p-H, p-Me, p-F, and p-CF3 substituents, which shows a linear curve (R(2) = 0.99) with a ρ value of +1.06, suggest that the current transformation follows an oxidative addition-reductive elimination pathway.


Greek students' attitudes toward physical activity and health-related behavior.
A three-wave study over one year with 882 adolescents, aged 10 to 16 years at the initial testing, examined psychosocial variables regarding four health-related behaviors: exercise, eating fruit, smoking, and drug use. Analysis showed that during the stages of the study, high school students' exercise behavior decreased and their smoking behavior increased as well as their willingness to use drugs. It seems that study of physical education and health education during adolescence must take into account the possible differences in psychosocial variables associated with health-related behaviors as well as the different stages of adolescence.


Cardiogenic Shock due to COVID-19-Related Myocarditis in a 19-Year-Old Autistic Patient.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mainly responsible for respiratory involvement but cardiac complications are also reported. Nevertheless, potential life-threatening conditions in young people have not been described. A 19-year-old male autistic patient was admitted with fever and cough. The chest radiography showed viral pneumonia and the nasopharyngeal swab detected SARS-CoV-2. He rapidly developed hypotension, oliguria and increased myocardial injury markers and was treated with adrenaline, antiviral drugs and mechanical ventilation. Echocardiography revealed diffuse myocardial hypo-akinesia and decreased left ventricular ejection fraction (LVEF). After several days of treatment, the patient was weaned off mechanical ventilation, LVEF recovered to 50% and laboratory tests showed a decrease of markers of myocardial injury. Coronavirus disease 2019 (COVID-19) can therefore severely affect myocardium with life-threatening complications and even young people can be involved.


Quantitative determination of contributions to the thermoelectric power factor in Si nanostructures.
We report thermoelectric measurements on a silicon nanoribbon in which an integrated gate provides strong carrier confinement and enables tunability of the carrier density over a wide range. We find a significantly enhanced thermoelectric power factor that can be understood by considering its behavior as a function of carrier density. We identify the underlying mechanisms for the power factor in the nanoribbon, which include quantum confinement, low scattering due to the absence of dopants, and, at low temperatures, a significant phonon-drag contribution. The measurements set a target for what may be achievable in ultrathin nanowires.


Remembering words in context as predicted by an associative read-out model.
Interactive activation models (IAMs) simulate orthographic and phonological processes in implicit memory tasks, but they neither account for associative relations between words nor explicit memory performance. To overcome both limitations, we introduce the associative read-out model (AROM), an IAM extended by an associative layer implementing long-term associations between words. According to Hebbian learning, two words were defined as "associated" if they co-occurred significantly often in the sentences of a large corpus. In a study-test task, a greater amount of associated items in the stimulus set increased the "yes" response rates of non-learned and learned words. To model test-phase performance, the associative layer is initialized with greater activation for learned than for non-learned items. Because IAMs scale inhibitory activation changes by the initial activation, learned items gain a greater signal variability than non-learned items, irrespective of the choice of the free parameters. This explains why the slope of the z-transformed receiver-operating characteristics (z-ROCs) is lower one during recognition memory. When fitting the model to the empirical z-ROCs, it likewise predicted which word is recognized with which probability at the item-level. Since many of the strongest associates reflect semantic relations to the presented word (e.g., synonymy), the AROM merges form-based aspects of meaning representation with meaning relations between words.


Teaching ethics of psychopharmacology research in psychiatric residency training programs.
American psychiatric residency training programs are now required to teach principles of research ethics. This task is especially pressing in light of evolving guidelines pertaining to human subjects, including psychiatric patients, especially when psychopharmacology is involved. Residents need to understand principles of research ethics and implications of roles of psychiatrists as investigators and clinicians. We consider major contemporary ethical issues in clinical psychiatric research, with an emphasis on psychopharmacology, and implications of addressing them within residency training programs. We reviewed recent literature on ethical issues in clinical research and on medical education in bioethics. This report considers: (1) an overview of current training; (2) perceived needs and rationales for training in research ethics, (3) recommended educational content and methods; (4) issues that require further study (including demonstration of acquired knowledge, practice issues, and the treatment versus-investigation misconception); and (5) conclusions. Recommended components of residency training programs include basic ethical principles; scientific merit and research design; assessment of risks and benefits; selection and informed consent of patient-subjects; and integrity of the clinical investigator, including definition of roles, conflicts-of-interest, and accountability. Evaluation of educational effectiveness for both trainees and faculty is a recommended component of such programs. We recommend that psychiatric training include education about ethical aspects of clinical research, with a particular emphasis on psychopharmacology. These activities can efficiently be incorporated into teaching of other aspects of bioethics, research methods, and psychopharmacology. Such education early in professional development should help to clarify roles of clinicians and investigators, improve the planning, conduct and reporting of research, and facilitate career development of much-needed clinical investigators in psychiatry.


Economic and practical aspects of thromboprophylaxis with unfractionated and low-molecular-weight heparins in hospitalized medical patients.
Acutely ill medical patients are at significant risk of developing venous thromboembolic (VTE) complications during or after their hospitalization. Venous thromboembolic events, such as proximal deep vein thrombosis (DVT) or pulmonary embolism (PE), place a high and unacceptable burden on health care resources, up to US$1.5 billion annually in the United States. However, the burden of VTE can be reduced by use of appropriate thromboprophylaxis. Prophylaxis of VTE with either a low-dose unfractionated heparin (UFH) or a low-molecular-weight heparin (LMWH) in medical inpatients is effective, well tolerated and cost-effective, compared with no prophylaxis. Low-molecular-weight heparins have a number of practical benefits over UFH, including once-daily subcutaneous injection and the potential to be used in the outpatient setting. These clinical advantages could translate to improved patient adherence to therapy and provide economic benefits, where LMWHs are more cost-effective compared with UFH.