Practice management performance indicators in academic radiology departments.
To determine the management performance indicators most frequently utilized in academic radiology departments in the United States. This investigation met the criteria for an exemption from institutional review board approval. A cross-sectional study in which a validated national survey was sent to members of the Society of Chairmen of Academic Radiology Departments (SCARD) was conducted. The survey was designed to examine the following six categories of 28 performance indicators: (a) general organization, (b) volume and productivity, (c) radiology reporting, (d) access to examinations, (e) customer satisfaction, and (f) finance. A total of 158 variables were included in the analysis. Summary statistics, the chi(2) test, rank correlation, multiple regression analysis, and analysis of variance were used. A response rate of 42% (55 of 132 SCARD members) was achieved. The mean number of performance indicators used by radiology departments was 16 +/- 6.35 (standard deviation). The most frequently utilized performance indicators were as follows: (a) productivity, in terms of examination volume (78% [43 departments]) and examination volume per modality (78% [43 departments]); (b) reporting, in terms of report turnaround (82% [45 departments]) and transcription time (71% [39 departments]); (c) access, in terms of appointment access to magnetic resonance imaging (80% [44 departments]); (d) satisfaction, in terms of number of patient complaints (84% [46 departments]); and (e) finance, in terms of expenses (67% [37 departments]). Regression analysis revealed that the numbers of performance indicators in each category were statistically significant in predicting the total number of performance indicators used (P < .001 for all). Numbers of productivity and financial indicators were moderately correlated (r = 0.51). However, there were no statistically significant correlations between the numbers of performance indicators used and hospital location, hospital size, or department size (P > .4 for all). Assessing departmental performance with a wide range of management indicators is not yet an established and standardized practice in academic radiology departments in the United States. Among all indicators, productivity indicators are the most frequently used.


Copper in parasitic protists - a hitherto neglected virulence factor.
Copper plays a fundamental role in aerobic metabolism, but its role is double-edged, given its toxicity. Our understanding of copper metabolism in parasites remains rudimentary, despite its significance in virulence. Here we discuss how parasitic protists control copper homeostasis and show the potential key players identified by our bioinformatic analysis.


In vitro evaluation of the antimicrobial activity of a new resin-based endodontic sealer against endodontic pathogens.
The purpose of this study was to compare the antimicrobial activities of a new resin-based SuperBond (SB) Sealer and five other sealers/cements against endodontic pathogens. The antimicrobial activities of SB Sealer, Sealapex, AH plus, Roeko Seal Automix, Canals N, and ProRoot mineral trioxide aggregate (MTA) were examined using a double-layered method. The microorganisms Staphylococcus aureus, Enterococcus faecalis, Candida albicans, Streptococcus mutans, and Streptococcus sanguinis were used. Live microorganisms were stained using triphenyltetrazolium chloride, and the zones of inhibition of microorganism growth were measured. The antimicrobial activity of SB Sealer was significantly lower than that of the other sealers, except for Pro Root MTA, against S. aureus, C. albicans, S. mutans, and S. sanguinis, but no activity against E. faecalis was detected. On the other hand, AH plus exhibited the highest antimicrobial activity. Pro Root MTA showed no antimicrobial activity against any of the microorganisms tested. SB Sealer offered no antimicrobial advantage over the other sealers tested except for Pro Root MTA.


Transcriptome sequencing of field pea and faba bean for discovery and validation of SSR genetic markers.
Field pea (Pisum sativum L.) and faba bean (Vicia faba L.) are cool-season grain legume species that provide rich sources of food for humans and fodder for livestock. To date, both species have been relative 'genomic orphans' due to limited availability of genetic and genomic information. A significant enrichment of genomic resources is consequently required in order to understand the genetic architecture of important agronomic traits, and to support germplasm enhancement, genetic diversity, population structure and demographic studies. cDNA samples obtained from various tissue types of specific field pea and faba bean genotypes were sequenced using 454 Roche GS FLX Titanium technology. A total of 720,324 and 304,680 reads for field pea and faba bean, respectively, were de novo assembled to generate sets of 70,682 and 60,440 unigenes. Consensus sequences were compared against the genome of the model legume species Medicago truncatula Gaertn., as well as that of the more distantly related, but better-characterised genome of Arabidopsis thaliana L.. In comparison to M. truncatula coding sequences, 11,737 and 10,179 unique hits were obtained from field pea and faba bean. Totals of 22,057 field pea and 18,052 faba bean unigenes were subsequently annotated from GenBank. Comparison to the genome of soybean (Glycine max L.) resulted in 19,451 unique hits for field pea and 16,497 unique hits for faba bean, corresponding to c. 35% and 30% of the known gene space, respectively. Simple sequence repeat (SSR)-containing expressed sequence tags (ESTs) were identified from consensus sequences, and totals of 2,397 and 802 primer pairs were designed for field pea and faba bean. Subsets of 96 EST-SSR markers were screened for validation across modest panels of field pea and faba bean cultivars, as well as related non-domesticated species. For field pea, 86 primer pairs successfully obtained amplification products from one or more template genotypes, of which 59% revealed polymorphism between 6 genotypes. In the case of faba bean, 81 primer pairs displayed successful amplification, of which 48% detected polymorphism. The generation of EST datasets for field pea and faba bean has permitted effective unigene identification and functional sequence annotation. EST-SSR loci were detected at incidences of 14-17%, permitting design of comprehensive sets of primer pairs. The subsets from these primer pairs proved highly useful for polymorphism detection within Pisum and Vicia germplasm.


Responses to ionizing radiation mediated by inflammatory mechanisms.
Since the early years of the twentieth century, the biological consequences of exposure to ionizing radiation have been attributed solely to mutational DNA damage or cell death induced in irradiated cells at the time of exposure. However, numerous observations have been at variance with this dogma. In the 1950s, attention was drawn to abscopal effects in areas of the body not directly irradiated. In the 1960s reports began appearing that plasma factors induced by irradiation could affect unirradiated cells, and since 1990 a growing literature has documented an increased rate of DNA damage in the progeny of irradiated cells many cell generations after the initial exposure (radiation-induced genomic instability) and responses in non-irradiated cells neighbouring irradiated cells (radiation-induced bystander effects). All these studies have in common the induction of effects not in directly irradiated cells but in unirradiated cells as a consequence of intercellular signalling. Recently, it has become clear that all the various effects demonstrated in vivo may reflect an ongoing inflammatory response to the initial radiation-induced injury that, in a genotype-dependent manner, has the potential to contribute primary and/or ongoing damage displaced in time and/or space from the initial insult. Importantly, there is direct evidence that non-steroidal anti-inflammatory drug treatment reduces such damage in vivo. These new findings highlight the importance of tissue responses and indicate additional mechanisms of radiation action, including the likelihood that radiation effects are not restricted to the initiation stage of neoplastic diseases, but may also contribute to tumour promotion and progression. The various developments in understanding the responses to radiation exposures have implications not only for radiation pathology but also for therapeutic interventions.


CD3+4-8-WT31-(T cell receptor gamma+) cells and other unusual phenotypes are frequently detected among spontaneously interleukin 2-responsive T lymphocytes present in the joint fluid in juvenile rheumatoid arthritis. A clonal analysis.
T lymphocytes (E rosetting cells) isolated from the joint fluid of four patients with juvenile rheumatoid arthritis (JRA) were first analyzed for surface antigen expression. Approximately 15% of cells were CD25+ (interleukin, IL, 2 receptor positive), in addition, a remarkable proportion of cells expressed the CD2+3- phenotype. CD3+ cells outnumbered the sum of CD4+ and CD8+ cells as well as the cells reactive with the WT31 monoclonal antibody (which recognizes a framework determinant of the alpha/beta T cell receptor). Purified T cells were cloned under culture conditions (1% phytohemagglutinin, PHA plus IL2) which allow clonal expansion of most peripheral blood T lymphocytes. Under these conditions proliferating cells ranged from 25 to 65%; clones (derived from microcultures containing 0.5 or 0.25 cells/well) were tested for cytolytic activity against P815 cells (in the presence of PHA) or against the natural killer (NK)-sensitive K562 target cells. Fifty-four percent and 73% of clones obtained from the two patients with the polyarticular form of the disease displayed cytolytic activity in the lectin-dependent assay. Cytolytic clones were 22 and 29% in the two patients with single joint involvement. About half of all cytolytic clones displayed NK-like activity. Surface antigen analysis revealed that, in addition to conventional CD3+4+8- and CD3+4-8+, a noticeable fraction of clones (50/202) displayed unusual surface phenotypes. In particular, 33/50 coexpressed CD4 and CD8 antigens; 7/50 were CD2+3-4-8- and displayed NK-like activity; 10/50 expressed CD3 but lacked both CD4 and CD8 antigen and did not react with the WT31 monoclonal antibody. In order to allow selective growth of IL2-responsive cells, T lymphocytes were also cloned directly in IL2. As much as 57% of all clones thus obtained (48/84) displayed cytolytic activity. Moreover, about half expressed unusual surface phenotypes including CD2+3-4-8-, CD3+4+8+ and CD3+4-8-WT31-. Given the accumulation at the site of the joint involvement of unusual T cells, most of which displayed cytolytic activity and were likely to represent cells activated in vivo (IL2 responsive), one may speculate that these cells may be involved in the injury process.


Differential expression of microRNAs among cell populations in the regenerating adult mouse olfactory epithelium.
Despite a robust capacity for adult neurogenesis in the olfactory epithelium (OE), olfactory sensory losses are common. Identification of mechanisms regulating adult OE neurogenesis is, therefore, of interest. MicroRNAs (miRNAs) are broadly important in regulating vertebrate neurodevelopment, and are required in embryonic olfactory differentiation. We report here that a panel of miRNAs is differentially expressed by either progenitor or progeny cells in the regenerating mouse OE. Progenitor cells were purified from lesioned OE based on c-Kit expression, and miRNA expression was assayed in c-Kit (+) and c-Kit (-) cell populations. 28 miRNAs were significantly downregulated by at least 4 fold in the c-Kit (+) fraction, which marks the globose basal progenitor cell population. In addition, 10 miRNAs were upregulated in these basal cells. MiR-486, the most strongly downregulated miRNA identified, was further characterized to verify results. MiR-486 expression was confirmed in the c-Kit (-) OE layers using in situ hybridization. As a functional assay, over-expression of miR-486 in purified c-Kit (+) basal cell cultures resulted in a reduction in neurogenesis, consistent with a possible negative feedback regulatory model. Our data provide new insights regarding miRNA expression and function during adult OE neurogenesis, and identify candidate miRNAs warranting further study.


Emergence of a unique SARS-CoV-2 Delta sub-cluster harboring a constellation of co-appearing non-Spike mutations.
Accumulation of diverse mutations across the structural and nonstructural genes is leading to rapid evolution of SARS-CoV-2, altering its pathogenicity. We performed whole genome sequencing of 239 SARS-CoV-2 RNA samples collected from both adult and pediatric patients across eastern India (West Bengal), during the second pandemic wave in India (April-May 2021). In addition to several common spike mutations within the Delta variant, a unique constellation of eight co-appearing non-Spike mutations was identified, which revealed a high degree of positive mutual correlation. Our results also demonstrated the dynamics of SARS-CoV-2 variants among unvaccinated pediatric patients. 41.4% of our studied Delta strains harbored this signature set of eight co-appearing non-Spike mutations and phylogenetically out-clustered other Delta sub-lineages like 21J, 21A, or 21I. This is the first report from eastern India that portrayed a landscape of co-appearing mutations in the non-Spike proteins, which might have led to the evolution of a distinct Delta subcluster. Accumulation of such mutations in SARS-CoV-2 may lead to the emergence of "vaccine-evading variants." Hence, monitoring of such non-Spike mutations will be significant in the formulation of any future vaccines against those SARS-CoV-2 variants that might evade the current vaccine-induced immunity, among both the pediatric and adult populations.


Context effects in survey ratings of health, symptoms, and satisfaction.
Survey self-reports of health status, symptoms (pain and fatigue), and life satisfaction often serve as outcomes in clinical trials. Prior studies have shown, however, that such reports can be subject to context effects, which could threaten their validity. We examined the impact of 2 context effects: the effect of the reporting period associated with a question (No Period Specified; Last Month; Right Now) and the effect of whom the respondent compared themselves to in answering a question (None Specified; Compared with Others in the US; Compared with 20-Year-Olds). One thousand four hundred seventy-one community adults aged 20 through 70 years, who were members of an internet panel, responded to 1 of 9 questionnaires formed by crossing the 2 context variables. A significant effect of Reporting Period was observed indicating that higher levels of Pain and Fatigue were associated with the 1-Month reporting period. When no reporting period was specified, symptom levels were equivalent to the Right Now levels of symptoms. Reporting Period had no effect on the other outcomes. Educational level did not interact with these main effects, with 1 exception. None of the predicted effects were found for Comparison Group, although Pain was significantly associated with this factor. Reporting period in survey questions is a factor that influences responses and should be considered by survey researchers in their study designs.


Immediate transfection of patient-derived leukemia: a novel source for generating cell-based vaccines.
The production of cell-based cancer vaccines by gene vectors encoding proteins that stimulate the immune system has advanced rapidly in model systems. We sought to develop non-viral transfection methods that could transform patient tumor cells into cancer vaccines, paving the way for rapid production of autologous cell-based vaccines. As the extended culture and expansion of most patient tumor cells is not possible, we sought to first evaluate a new technology that combines electroporation and chemical transfection in order to determine if plasmid-based gene vectors could be instantaneously delivered to the nucleus, and to determine if gene expression was possible in a cell-cycle independent manner. We tested cultured cell lines, a primary murine tumor, and primary human leukemia cells from diagnostic work-up for transgene expression, using both RFP and CD137L expression vectors. Combined electroporation-transfection directly delivered plasmid DNA to the nucleus of transfected cells, as demonstrated by confocal microscopy and real-time PCR analysis of isolated nuclei. Expression of protein from plasmid vectors could be detected as early as two hours post transfection. However, the kinetics of gene expression from plasmid-based vectors in tumor cell lines indicated that optimal gene expression was still dependent on cell division. We then tested to see if pediatric acute lymphocytic leukemia (ALL) would also display the rapid gene expression kinetics of tumor cells lines, determining gene expression 24 hours after transfection. Six of 12 specimens showed greater than 17% transgene expression, and all samples showed at least some transgene expression. Given that transgene expression could be detected in a majority of primary tumor samples analyzed within hours, direct electroporation-based transfection of primary leukemia holds the potential to generate patient-specific cancer vaccines. Plasmid-based gene therapy represents a simple means to generate cell-based cancer vaccines and does not require the extensive infrastructure of a virus-based vector system.


Deactivation kinetics of immobilized alpha-chymotrypsin subpopulations.
Electron paramagnetic resonance (EPR) spectroscopy has been applied in concert with measurements of catalytic activity and the quantity of active immobilized protein to study the deactivation in 50% n-propanol of alpha-chymotrypsin immobilized on CNBr-Sepharose 4B. These analyses focus on the behavior of two distinct active forms of immobilized enzyme, designated here A and B, identified in previous studies. Raw data provided by EPR spectroscopy clearly show that the relative quantities of active chymotrypsin-A and active chymotrypsin-B change as a result of exposure to alcohol, with the relative quantity of the B form increasing with time. These and additional results provide evidence that the distribution of A and B forms is a function of active enzyme loading but independent of the means used to obtain the loading. Different kinetic models in conjunction with experimental observations consistently indicate that the activity of enzyme form B, by far the more active enzyme form, does not change significantly during the initial 60 min of catalyst deactivation but then decreases appreciably.


Detecting horizontal gene transfer: a probabilistic approach.
Horizontal gene transfer (HGT) is the event of a DNA sequence being transferred between species not by inheritance. HGT is a crucial factor in prokaryotic evolution and is a significant source for genomic novelty resulting in antibiotic resistance or the outbreak of virulent strains. Detection of HGT and the mechanisms responsible and enabling it, is hence of prime importance.Existing algorithms rely on a strong phylogenetic signal distinguishing the transferred sequence from its recipient genome. Closely related species pose an even greater challenge as most genes are very similar and therefore, the phylogenetic signal is weak anyhow. Notwithstanding, the importance of detecting HGT between such organisms is extremely high for the role of HGT in the emergence of new highly virulent strains. In a recent work we devised a novel technique that relies on loss of synteny around a gene as a witness for HGT. We used a novel heuristic for synteny measurement, SI (Syntent Index), and the technique was tested on both simulated and real data and was found to provide a greater sensitivity than other HGT techniques. This synteny-based approach suffers low specificity, in particular more closely related species. Here we devise an adaptive approach to cope with this by varying the criteria according to species distance. The new approach is doubly adaptive as it also considers the lengths of the genes being transferred. In particular, we use Chernoff bound to decree HGT both in simulations and real bacterial genomes taken from EggNog database. Here we show empirically that this approach is more conservative than the previous χ2 based approach and provides a lower false positive rate, especially for closely related species and under wide range of genome parameters.


Crafting the self: older persons' narratives of occupational identity.
This study aimed to examine how engagement in creative occupations informed six older retired people's occupational identities. Occupational narratives were gathered from in-depth interviews with 6 participants (75 years of age or older) who had extended experience of participation in creative occupations. A process of narrative-type inquiry produced summarized, chronological stories for each participant. Subsequently, a process of paradigmatic-type narrative analysis produced thematic categories related to how a sense of self is associated with creative occupational engagement in later life. Four themes derived from data analysis included the relevance of relational practices, changing self-awareness, enduring qualities, and reflective processes to the formation of a sense of self. This study adds to an understanding of how leisure occupations maintained across the life cycle contribute to building an occupational identity.


Health care systems in Sweden and China: Legal and formal organisational aspects.
Sharing knowledge and experience internationally can provide valuable information, and comparative research can make an important contribution to knowledge about health care and cost-effective use of resources. Descriptions of the organisation of health care in different countries can be found, but no studies have specifically compared the legal and formal organisational systems in Sweden and China. To describe and compare health care in Sweden and China with regard to legislation, organisation, and finance. Literature reviews were carried out in Sweden and China to identify literature published from 1985 to 2008 using the same keywords. References in recent studies were scrutinized, national legislation and regulations and government reports were searched, and textbooks were searched manually. The health care systems in Sweden and China show dissimilarities in legislation, organisation, and finance. In Sweden there is one national law concerning health care while in China the law includes the "Hygienic Common Law" and the "Fundamental Health Law" which is under development. There is a tendency towards market-orientated solutions in both countries. Sweden has a well-developed primary health care system while the primary health care system in China is still under development and relies predominantly on hospital-based care concentrated in cities. Despite dissimilarities in health care systems, Sweden and China have similar basic assumptions, i.e. to combine managerial-organisational efficiency with the humanitarian-egalitarian goals of health care, and both strive to provide better care for all.


Targeting sources of drought tolerance within an Avena spp. collection through multivariate approaches.
In this study, we find and characterize the sources of tolerance to drought amongst an oat (Avena sativa L.) germplasm collection of 174 landraces and cultivars. We used multivariate analysis, non-supervised principal component analyses (PCA) and supervised discriminant function analyses (DFA) to suggest the key mechanism/s responsible for coping with drought stress. Following initial assessment of drought symptoms and area under the drought progress curve, a subset of 14 accessions were selected for further analysis. The collection was assessed for relative water content (RWC), cell membrane stability, stomatal conductance (g (1)), leaf temperature, water use efficiency (WUE), lipid peroxidation, lipoxygenase activity, chlorophyll levels and antioxidant capacity during a drought time course experiment. Without the use of multivariate approaches, it proved difficult to unequivocally link drought tolerance to specific physiological processes in the different resistant oat accessions. These approaches allowed the ranking of many supposed drought tolerance traits in the order of degree of importance within this crop, thereby highlighting those with a causal relationship to drought stress tolerance. Analyses of the loading vectors used to derive the PCA and DFA models indicated that two traits involved in water relations, temperature and RWC together with the area of drought curves, were important indicators of drought tolerance. However, other parameters involved in water use such as g (1) and WUE were less able to discriminate between the accessions. These observations validate our approach which should be seen as representing a cost-effective initial screen that could be subsequently employed to target drought tolerance in segregating populations.


Cost-effectiveness ratios: in a league of their own.
There is an increasing tendency for papers appearing in the medical literature to propose or use league tables of cost-effectiveness ratios as a means of comparing health-care interventions. In this paper we identify what the information in cost-effectiveness league tables tells us and how this is inadequate and inappropriate for addressing questions about improving efficiency in the use of resources at either the broad system level or at the individual care-group level. We present an alternative approach which provides decision makers with a practical way of deciding whether the adoption of a particular programme represents an unambiguous improvement in economic efficiency.


Mycobacterium tuberculosis polyclonal infections and microevolution identified by MIRU-VNTRs in an epidemiological study.
The advent of molecular typing using MIRU-VNTR mini-satellites has largely facilitated tuberculosis (TB) molecular epidemiological studies. Apart from detecting the chains of transmission and risk factors, these markers have also allowed to study the phenomena of mixed strain infections versus microevolutionary events. An initial set of Mycobacterium tuberculosis strains (n=161) genotyped using spoligotyping and MIRU-VNTRs in Guyana and Suriname was evaluated for indications mixed strain infections (characterized by the detection of double alleles in 2 or more MIRU loci) versus "in-patient" microevolutionary events (characterized by the detection of double alleles in a single locus). The present study hereby reports evidence of microevolution in 3.7% (n=6/161) of the studied population, vs. 0.6% (n=1/161) for mixed infection. The strains belonged to three different spoligotyping-based lineages, namely the T (SITs 44, 53, and 1081), Haarlem (SIT47), and EAI (SITs 72 and 349) lineages, while 1 isolate (SIT237) could not be assigned to any lineage. By comparing these results on microevolutionary cases (n=6) to 112,000 strains present in the SITVIT2 database, evidence is presented that in 2/6 cases (each case corresponding to 2 patterns due to MIRU double bands), one of the patterns corresponded to a shared type found exclusively in Suriname or Guyana. Phylogenetic analysis showed that no spoligotyping lineage in particular was more prone to microevolutionary events in this study's sample. Overall, the observations fortify the awareness regarding the existence of microevolution and polyclonal TB infections which has important implications for patient care.


Is there convergence of gut microbes in blood-feeding vertebrates?
Animal microbiomes play an important role in dietary adaptation, yet the extent to which microbiome changes exhibit parallel evolution is unclear. Of particular interest is an adaptation to extreme diets, such as blood, which poses special challenges in its content of proteins and lack of essential nutrients. In this study, we assessed taxonomic signatures (by 16S rRNA amplicon profiling) and potential functional signatures (inferred by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)) of haematophagy in birds and bats. Our goal was to test three alternative hypotheses: no convergence of microbiomes, convergence in taxonomy and convergence in function. We find a statistically significant effect of haematophagy in terms of microbial taxonomic convergence across the blood-feeding bats and birds, although this effect is small compared to the differences found between haematophagous and non-haematophagous species within the two host clades. We also find some evidence of convergence at the predicted functional level, although it is possible that the lack of metagenomic data and the poor representation of microbial lineages adapted to haematophagy in genome databases limit the power of this approach. The results provide a paradigm for exploring convergent microbiome evolution replicated with independent contrasts in different host lineages. This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.


Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD(+) Depletion in Human Astroglial Cells.
Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD(+) levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM) for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose) polymer production. Significant decreases in total NAD(H) and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM) decreased levels of NAD(H) in primary human astrocytes. NAD(H) depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H)]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene.


Figures of merit for surface plasmon waveguides.
Three figures of merit are proposed as quality measures for surface plasmon waveguides. They are defined as benefit-to-cost ratios where the benefit is confinement and the cost is attenuation. Three different ways of measuring confinement are considered, leading to three figures of merit. One of the figures of merit is connected to the quality factor. The figures of merit were then used to assess and compare the wavelength response of hree popular 1-D surface plasmon waveguides: the single metal-dielectric interface, the metal slab bounded by dielectric and the dielectric slab bounded by metal. Closed form expressions are given for the figures of merit of the single metal-dielectric interface.


Health Information Seeking and Technology Use Among Veterans With Spinal Cord Injuries and Disorders.
Access to health information is crucial to persons living with a spinal cord injury or disorder (SCI/D). Although previous research has provided insights on computer and Internet use among persons with SCI/D, as well as how and where persons with SCI/D gather health information, few studies have focused on U.S. veterans with SCI/D. To characterize health information seeking among veterans with SCI/D and to examine the association between technology use and the characteristics of veterans with SCI/D. Cross-sectional. Veterans Health Administration (VHA). Sample of 290 veterans with SCI/D who utilize services at 2 VHA SCI/D Centers. Postal mail survey. Extent of computer, Internet, and text messaging use, information source use, and e-Health literacy rates. The survey response rate was 38%. The majority of respondents were male (97.2%), younger than 65 years (71.0%), and white (71.7%). Of the respondents, 64.8% indicated that they use a computer, 62.9% reported use of the Internet, and 26.2% reported use of text messaging. The mean overall e-Health Literacy Scale score was 27.3 (standard deviation = 7.2). Similar to findings reported in studies focused outside the veteran population, the most frequent source that veterans turned to for information about SCI/D was a health professional (85.1%); this was also the most frequent source that veterans indicated they would turn to first to get information about SCI/D (75.9%). Other frequently reported sources of information included other persons with SCI/D (41.0%), Internet resources (31.0%), and family and friends (27.9%). Fairly high levels of computer and Internet use exist among veterans with SCI/D. Veterans with SCI/D also have a strong preference for people-particularly health professionals, and to a lesser extent peers and family and friends-as sources of information about SCI/D. These findings highlight the importance of combining technology and human interaction to meet the information needs of this population.


Prevalence and patterns of cooking dinner at home in the USA: National Health and Nutrition Examination Survey (NHANES) 2007-2008.
To measure the prevalence of cooking dinner at home in the USA and test whether home dinner preparation habits are associated with socio-economic status, race/ethnicity, country of birth and family structure. Cross-sectional analysis. The primary outcome, self-reported frequency of cooking dinner at home, was divided into three categories: 0-1 dinners cooked per week ('never'), 2-5 ('sometimes') and 6-7 ('always'). We used bivariable and multivariable regression analyses to test for associations between frequency of cooking dinner at home and factors of interest. The 2007-2008 National Health and Nutrition Examination Survey (NHANES). The sample consisted of 10 149 participants. Americans reported cooking an average of five dinners per week; 8 % never, 43 % sometimes and 49 % always cooked dinner at home. Lower household wealth and educational attainment were associated with a higher likelihood of either always or never cooking dinner at home, whereas wealthier, more educated households were more likely to sometimes cook dinner at home (P < 0·05). Black households cooked the fewest dinners at home (mean = 4·4, 95 % CI 4·2, 4·6). Households with foreign-born reference persons cooked more dinners at home (mean = 5·8, 95 % CI 5·7, 6·0) than households with US-born reference persons (mean = 4·9, 95 % CI 4·7, 5·1). Households with dependants cooked more dinners at home (mean = 5·2, 95 % CI 5·1, 5·4) than households without dependants (mean = 4·6, 95 % CI 4·3, 5·0). Home dinner preparation habits varied substantially with socio-economic status and race/ethnicity, associations that likely will have implications for designing and appropriately tailoring interventions to improve home food preparation practices and promote healthy eating.


The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). It affects more than two million people worldwide, mainly young adults, and may lead to progressive neurological disability. Chemokines and their receptors have been shown to play critical roles in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine disease model induced by active immunization with myelin proteins or transfer of encephalitogenic CD4⁺ T cells that recapitulates clinical and neuropathological features of MS. Chemokine ligand-receptor interactions orchestrate leukocyte trafficking and influence multiple pathophysiological cellular processes, including antigen presentation and cytokine production by dendritic cells (DCs). The C-C class chemokines 17 (CCL17) and 22 (CCL22) and their C-C chemokine receptor 4 (CCR4) have been shown to play an important role in homeostasis and inflammatory responses. Here, we provide an overview of the involvement of CCR4 and its ligands in CNS autoimmunity. We review key clinical studies of MS together with experimental studies in animals that have demonstrated functional roles of CCR4, CCL17, and CCL22 in EAE pathogenesis. Finally, we discuss the therapeutic potential of newly developed CCR4 antagonists and a humanized anti-CCR4 antibody for treatment of MS.


Total Body Irradiation in Haematopoietic Stem Cell Transplantation for Paediatric Acute Lymphoblastic Leukaemia: Review of the Literature and Future Directions.
Total body irradiation (TBI) has been a pivotal component of the conditioning regimen for allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) in very-high-risk acute lymphoblastic leukaemia (ALL) for decades, especially in children and young adults. The myeloablative conditioning regimen has two aims: (1) to eradicate leukaemic cells, and (2) to prevent rejection of the graft through suppression of the recipient's immune system. Radiotherapy has the advantage of achieving an adequate dose effect in sanctuary sites and in areas with poor blood supply. However, radiotherapy is subject to radiobiological trade-offs between ALL cell destruction, immune and haematopoietic stem cell survival, and various adverse effects in normal tissue. To diminish toxicity, a shift from single-fraction to fractionated TBI has taken place. However, HSCT and TBI are still associated with multiple late sequelae, leaving room for improvement. This review discusses the past developments of TBI and considerations for dose, fractionation and dose-rate, as well as issues regarding TBI setup performance, limitations and possibilities for improvement. TBI is typically delivered using conventional irradiation techniques and centres have locally developed heterogeneous treatment methods and ways to achieve reduced doses in several organs. There are, however, limitations in options to shield organs at risk without compromising the anti-leukaemic and immunosuppressive effects of conventional TBI. Technological improvements in radiotherapy planning and delivery with highly conformal TBI or total marrow irradiation (TMI), and total marrow and lymphoid irradiation (TMLI) have opened the way to investigate the potential reduction of radiotherapy-related toxicities without jeopardising efficacy. The demonstration of the superiority of TBI compared with chemotherapy-only conditioning regimens for event-free and overall survival in the randomised For Omitting Radiation Under Majority age (FORUM) trial in children with high-risk ALL makes exploration of the optimal use of TBI delivery mandatory. Standardisation and comprehensive reporting of conventional TBI techniques as well as cooperation between radiotherapy centres may help to increase the ratio between treatment outcomes and toxicity, and future studies must determine potential added benefit of innovative conformal techniques to ultimately improve quality of life for paediatric ALL patients receiving TBI-conditioned HSCT.


Epigenetic roles of PIWI‑interacting RNAs (piRNAs) in cancer metastasis (Review).
P‑element‑induced wimpy testis (PIWI)‑interacting RNAs (piRNAs) are epigenetic‑related short ncRNAs that participate in chromatin regulation, transposon silencing, and modification of specific gene sites. These epigenetic factors or alterations are also involved in the growth of a variety of human cancers, including lung, breast, and colon cancer. Accumulating evidence has revealed that tumor metastasis and invasion involve genetic and epigenetic factors. Cancer metastasis is characterized by epigenetic alterations including DNA methylation and histone modification. Changes in DNA methylation, H3K9me3 heterochromatin and transposable elements have been detected in several cancers. piRNAs may function in gene silencing and gene modification upstream or downstream of oncogenes in cancer cell lines or cancer tissues. In addition to piRNAs, PIWI proteins can be used as biomarkers for prognosis, diagnosis and clinical evaluation and may be factors in cancer metastasis. Here, we elucidated the possible mechanisms by which piRNAs regulate cancer metastasis, including but not restricted to influencing DNA and histone methylation and transposable elements.


Stunted from the start: Early life weather conditions and child undernutrition in Ethiopia.
This paper examines the relationship between weather conditions and child nutrition in Ethiopia. We link data from four rounds of the Ethiopia Demographic and Health Survey to high-resolution climate data to measure exposure to rainfall and temperature in utero and during early life. We then estimate a set of multivariate regression models to understand how weather conditions impact child stunting, an indicator of sustained early life undernutrition. We find that greater rainfall during the rainy seasons in early life is associated with greater height for age. In addition, higher temperatures in utero, particularly during the first and third trimesters, and more rainfall during the third trimester, are positively associated with severe stunting, though stunting decreases with temperature in early life. We find potential evidence for a number of pathways underlying the weather-child nutrition relationship including agricultural livelihoods, heat stress, infectious disease transmission, and women's time use during pregnancy. These findings illuminate the complex pathways through which climate change may influence child health and should motivate additional research focused on identifying the causal mechanisms underlying these links.


Vortioxetine promotes early changes in dendritic morphology compared to fluoxetine in rat hippocampus.
Preclinical studies reveal that the multimodal antidepressant vortioxetine enhances long-term potentiation and dendritic branching compared to a selective serotonin reuptake inhibitor (SSRI). In the present study, we investigated vortioxetine׳s effects on spines and dendritic morphology in rat hippocampus at two time points compared to the SSRI, fluoxetine. Rats were dosed for 1 and 4 weeks with vortioxetine and fluoxetine at doses relevant for antidepressant activity. Dendritic morphology of pyramidal neurons (i.e., dendritic length, dendritic branch, spine number and density, and Sholl analysis) was examined in Golgi-stained sections from hippocampal CA1. After 1 week of treatment, vortioxetine significantly increased spine number (apical and basal dendrites), spine density (only basal), dendritic length (only apical), and dendritic branch number (apical and basal), whereas fluoxetine had no effect. After 4 weeks of treatment, vortioxetine significantly increased all measures of dendritic spine morphology as did fluoxetine except for spine density of basal dendrites. The number of intersections in the apical and basal dendrites was also significantly increased for both treatments after 4 weeks compared to control. In addition, 4 weeks of vortioxetine treatment, but not fluoxetine, promoted a decrease in spine neck length. In conclusion, 1-week vortioxetine treatment induced changes in spine number and density and dendritic morphology, whereas an equivalent dose of fluoxetine had no effects. Decreased spine neck length following 4-week vortioxetine treatment suggests a transition to mature spine morphology. This implies that vortioxetine׳s effects on spine and dendritic morphology are mediated by mechanisms that go beyond serotonin reuptake inhibition.


Variation in the THC content in illicitly imported Cannabis products--Part II.
The tetrahydrocannabinol (THC) contents of 220 samples of fresh illicit Cannabis products seized on entry into the United Kingdom of Great Britain and Northern Ireland over the period 1979-1981 have been determined by gas chromatography. During that period there was a general increase in the quality of both cannabis and cannabis resin, but with wide variations in THC contents both within and between countries. Some very high quality samples of cannabis, cannabis resin and cannabis oil from the Indian sub-continent have been analysed. There have been considerable changes in the number of fresh samples from several countries, compared with the previous survey. Fresh cannabis oil samples were very rare during the period covered by this survey.


[Change in mortality of gastric cancer from 1963 to 1981 in Shanghai urban residents].
Data of gastric cancer in Shanghai urban residents from 1963 to 1981 collected by Shanghai Cancer Registry are analysed as to the change in mortality with time. Results show that the crude mortality, both in male and female, was increasing from 1963 to 1977 and levels off after 1978. In contrast, the adjusted and truncated mortalities of the world population show a gradual decreasing pattern which has become more obvious after 1978. As compared to that of 1964 to 1966, the annual average adjusted mortality from 1979 to 1981 had decreased by 10.9% in the male and 18.2% in the female. In the female, rates of the various age groups declined while, in the male, it had decreased only in those under 69 of age while the rate of over 70 was still increasing. Factors which interfere with the time trend are elucidated and discussed.


Simulating real-life exposures to uncover possible risks to human health: A proposed consensus for a novel methodological approach.
In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.


Association of Cereal, Gluten, and Dietary Fiber Intake With Islet Autoimmunity and Type 1 Diabetes.
Dietary proteins, such as gluten, have been suggested as triggers of the disease process in type 1 diabetes (T1D). To study the associations of cereal, gluten, and dietary fiber intake with the development of islet autoimmunity (IA) and T1D. The prospective birth cohort Finnish Type 1 Diabetes Prediction and Prevention Study recruited children with genetic susceptibility to type 1 diabetes from September 1996 to September 2004 from 2 university hospitals in Finland and followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Altogether 6081 infants (78% of those invited) participated in the study. Dietary data were available for 5714 children (94.0%) and dietary and IA data were available for 5545 children (91.2%), of whom 3762 (68%) had data on islet autoantibodies up to age 6 years. Information on T1D was available for all children. Data were analyzed in 2018 and end point data were updated in 2015. Each child's intake of cereals, gluten, and dietary fiber was calculated from repeated 3-day food records up to 6 years. Islet autoimmunity was defined as repeated positivity for islet cell antibodies and at least 1 biochemical autoantibody of 3 analyzed, or T1D. Data on the diagnosis of T1D were obtained from Finnish Pediatric Diabetes Register. Of 5545 children (2950 boys [53.2%]), 246 (4.4%) developed IA and of 5714 children (3033 boys [53.1%]), 90 (1.6%) developed T1D during the 6-year follow-up. Based on joint models, the intake of oats (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13), wheat (HR, 1.09; 95% CI, 1.03-1.15), rye (HR, 1.13; 95% CI, 1.03-1.23), gluten-containing cereals (HR, 1.07; 95% CI, 1.03-1.11), gluten without avenin from oats (HR, 2.23; 95% CI, 1.40-3.57), gluten with avenin (HR, 2.06; 95% CI, 1.45-2.92), and dietary fiber (HR, 1.41; 95% CI, 1.10-1.81) was associated with the risk of developing IA (HRs for 1 g/MJ increase in intake). The intake of oats (HR, 1.10; 95% CI, 1.00-1.21) and rye (HR, 1.20; 95% CI, 1.03-1.41) was associated with the risk of developing T1D. After multiple testing correction, the associations with IA remained statistically significant. A high intake of oats, gluten-containing cereals, gluten, and dietary fiber was associated with an increased risk of IA. Further studies are needed to confirm or rule out the findings and study potential mechanisms.


Thermosensitive behavior in cell culture media and cytocompatibility of a novel copolymer: poly(N-isopropylacrylamide-co-butylacrylate).
Cell sheet technology is a promising step forward in tissue engineering. Cell sheets are usually generated using Poly(N-isopropylacrylamide) hydrogels due to their swelling change around the lower critical solution temperature (LCST). Nevertheless, LCST can be affected by cell culture medium components and therefore it is necessary to ensure that the polymer preserves its thermosensitivity under these conditions. We propose a novel thermosensitive crosslinked-copolymer: Poly(N-isopropylacrylamide-co-butylacrylate). This copolymer is shown to be cytocompatible and thermosensitive under cell culture medium conditions, and besides, it can be synthesized inexpensively. Thermosensitivity was investigated by determining the LCST with differential scanning calorimetry and swelling/ratio measurements. Cytocompatibility and capacity to deliver cell sheets were studied employing 3T3 and human oral epithelial cells. In conclusion, we obtained a thermosensitive copolymer that allows cell sheet formation/detachment by using a simple and low-cost polymerization method. Furthermore, crosslinking allows easy manipulation of cell sheets growing on the copolymer for potential in situ applications.


Diversity and activity of methanotrophs in alkaline soil from a Chinese coal mine.
Culture-independent molecular biological techniques, including 16S rRNA gene and functional gene clone libraries and microarray analyses using pmoA (encoding a key subunit of particulate methane monooxygenase), were applied to investigate the methanotroph community structure in alkaline soil from a Chinese coal mine. This environment contained a high diversity of methanotrophs, including the type II methanotrophs Methylosinus/Methylocystis, type I methanotrophs related to Methylobacter/Methylosoma and Methylococcus, and a number of as yet uncultivated methanotrophs. In order to identify the metabolically active methane-oxidizing bacteria from this alkaline environment, DNA stable isotope probing (DNA-SIP) experiments using (13)CH(4) were carried out. This showed that both type I and type II methanotrophs were active, together with methanotrophs related to Methylocella, which had previously been found only in acidic environments. Methylotrophs, including Methylopila and Hyphomicrobium, were also detected in soil DNA and after DNA-SIP experiments. DNA sequence information on the most abundant, active methanotrophs in this alkaline soil will facilitate the design of oligonucleotide probes to monitor enrichment cultures when isolating key alkaliphilic methanotrophs from such environments.


Clinical validation of the self-reported Glasgow Antipsychotic Side-effect Scale using the clinician-rated UKU side-effect scale as gold standard reference.
Antipsychotics are key for the treatment of psychotic and several non-psychotic disorders. Unfortunately, antipsychotic medications are associated with side effects, which may reduce quality of life and treatment adherence. Therefore, regular screening of antipsychotic side effects is essential. The Glasgow Antipsychotic Side-effect Scale is a patient self-report scale developed for this purpose. However, the Glasgow Antipsychotic Side-effect Scale has only been validated against another self-report side effect measure, which is suboptimal. We aimed to validate the Glasgow Antipsychotic Side-effect Scale using the clinician-rated Udvalg for Kliniske Undersøgelser side-effect rating scale as the gold standard reference. 81 antipsychotic-treated outpatients with schizophrenia-spectrum disorders (age = 42±13 years; males = 43%, schizophrenia = 77%, illness duration: median = 11 years) completed the Glasgow Antipsychotic Side-effect Scale and were subsequently scored on the Udvalg for Kliniske Undersøgelser by trained raters. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for paired Glasgow Antipsychotic Side-effect Scale and Udvalg for Kliniske Undersøgelser items. Sensitivity of Glasgow Antipsychotic Side-effect Scale items ranged from 33-96%, with 19 (86%) having >75% sensitivity. Lowest sensitivity emerged for "nocturnal enuresis" (33%), "galactorrhea" (50%) and "hyperkinesia" 14-99%, with 14 items (64%) having >75% specificity, being lowest for "asthenia" (14%), "polyuria/polydipsia" (35%), "sedation" (41%), "akathisia" (53%), "dystonia" (65%), "hyperkinesia" (68%), "hypokinesia" (70%) and "accommodation" (70%). Positive predictive value ranged from 7-85%, with six items (27%) having a positive predictive value >75%. Negative predictive value ranged from 40-98%, with 21 items (95%) having a negative predictive value >75%. The mean time to complete the Glasgow Antipsychotic Side-effect Scale was 4±2 minutes. The Glasgow Antipsychotic Side-effect Scale demonstrated satisfactory validity as a self-rated tool for antipsychotic side effects and may aid measurement-based care and decision-making.


Dietary Patterns Based on Estimated Glomerular Filtration Rate and Kidney Function Decline in the General Population: The Lifelines Cohort Study.
No specific dietary patterns have been established that are linked with loss of kidney function. We aimed to identify an estimated glomerular filtration rate-based dietary pattern (eGFR-DP) and to evaluate its association with eGFR decline and chronic kidney disease (CKD) incidence in the general population. We included 78,335 participants from the Lifelines cohort in the Northern Netherlands. All participants had an eGFR >60 mL/min/1.73 m2 at baseline and completed a second visit five years later. The eGFR-DP was constructed at baseline using a 110-item food frequency questionnaire by reduced rank regression, stratified by sex. Logistic regression was performed to evaluated the association between the eGFR-DP score and either a ≥20% eGFR decline or incident CKD. Among women, eGFR-DP were characterized by high consumption of egg, cheese, and legumes and low consumption of sweets, white meat, and commercially prepared dishes. In men, eGFR-DP were characterized by high consumption of cheese, bread, milk, fruits, vegetables, and beer and low consumption of white and red meat. A higher eGFR-DP score was associated with a lower risk of a ≥20% eGFR decline (OR 4th vs. 1st quartile, women: 0.79 [95% CI: 0.73-0.87]; men: 0.67 [0.59-0.76]). The association between the eGFR-DP score and CKD incidence was lost upon adjustment for baseline eGFR. Our results provide support for dietary interventions to prevent kidney function decline in the general population.


[Melatonin and metabolic syndrome: is there an association?].
The basis for the current view of the mechanisms for regulating metabolic processes is the hypothesis proposed by the United Kingdom scientists E. Scott and P. Grant that evolutionary fixed adaptation to seasonal environmental changes is impaired. Under the hypothesis, impairment in seasonal and circadian rhythms is the key condition for the occurrence of obesity, arterial hypertension (AH), and type 2 diabetes mellitus. The diseases of civilization, namely obesity, insulin resistance, and AH, are a direct result of chronic metabolic disturbance due to light pollution.


Independently silencing two photosynthetic proteins in Nicotiana attenuata has different effects on herbivore resistance.
Insect attack frequently down-regulates photosynthetic proteins. To understand how this influences the plant-insect interaction, we transformed Nicotiana attenuata to independently silence ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPCase) activase (RCA) and RuBPCase and selected lines whose photosynthetic capacity was similarly reduced. Decreases in plant growth mirrored the decreases in photosynthesis, but the effects on herbivore performance differed. Both generalist (Spodoptera littoralis) and specialist (Manduca sexta) larvae grew larger on RCA-silenced plants, which was consistent with decreased levels of trypsin protease inhibitors and diterpene glycosides and increased levels of RuBPCase, the larvae's main dietary protein. RCA-silenced plants were impaired in their attack-elicited jasmonate (JA)-isoleucine (Ile)/leucine levels, but RuBPCase-silenced plants were not, a deficiency that could not be restored by supplementation with Ile or attributed to lower transcript levels of JAR4/6, the key enzyme for JA-Ile conjugation. From these results, we infer that JA-Ile/leucine signaling and the herbivore resistance traits elicited by JA-Ile are influenced by adenylate charge, or more generally, carbon availability in RCA- but not RuBPCase-silenced plants. Growth of generalist larvae on RuBPCase-silenced plants did not differ from growth on empty vector controls, but the specialist larvae grew faster on RuBPCase-silenced plants, which suggests that the specialist can better tolerate the protein deficiency resulting from RuBPCase silencing than the generalist can. We conclude that the plant-herbivore interaction is more influenced by the particular mechanisms that reduce photosynthetic capacity after herbivore attack than by the magnitude of the decrease, which highlights the value of understanding defense mechanisms in evaluating growth-defense tradeoffs.


Arsenic exposure to mouse visceral leishmaniasis model through their drinking water linked to the disease exacerbation via modulation in host protective immunity: a preclinical study.
A large body of evidence has shown a direct link between arsenic exposure and drug resistance to Leishmania parasites against antimonial preparations in visceral leishmaniasis (VL) hyper-endemic regions, especially in India and its sub-continent. However, the implicated roles of arsenic on the VL host, pathophysiological changes, and immune function have not yet been clarified, particularly at the reported concentration of arsenic in the VL hyper-endemic area of Bihar, India. Herein, we exposed the mouse VL model to arsenic (0.5 mg/L to 2 mg/L) through their drinking water and analyzed its effect on T cells proliferation, Th1/Th2-mediators, MAPK signaling cascade, and parasite load in preclinical models. Coherently, the parasite count in Giemsa stained spleen imprint has been investigated and found significant positive associations with levels of arsenic exposure. The liver and kidney function tests (AST, ALT, ALP, BUN, Creatinine, Urea, etc.) are apparent to hepatonephric toxicity in arsenic exposed VL mice compared to unexposed. This observation appears to be consistent with the up-regulated expression of immune regulatory Th2 mediators (IL-4, IL-10, TGF-β) and down-regulated expression of Th1 mediators (IL-12, IFN-γ, TNF-α) with a suppressed leishmanicidal function of macrophage (ROS, NO, iNOS). We also established that arsenic exposure modulated the host ERK-1/2 and p38 MAPK signaling cascade, limited T lymphocyte proliferation, and a lower IgG2a/IgG1 ratio to favor the Leishmania parasite survival inside the host. This study suggests that the contorted Th1-subtype and exacerbated Th2-subtype immune responses are involved in the increased susceptibility and pathogenesis of Leishmania parasite among subjects/individuals regularly exposed to arsenic.


Headache as a Symptom of COVID-19: Narrative Review of 1-Year Research.
Headache is a common symptom of COVID-19 with emerging literature being published on the subject. Although it may seem unspecific, scientific evidence has allowed a better definition of this headache type, revealing relevant associations with other COVID-19 symptoms and prognoses. We therefore sought to highlight the most remarkable findings concerning headache secondary to COVID-19, specifically focusing on epidemiology, characteristics, pathophysiology, and treatments. The real prevalence of headache as a symptom of COVID-19 is still unclear ranging from 10 to 70%. Headache mainly has a tension-type-like phenotype, although 25% of individuals present with migraine-like features that also occur in patients without personal migraine history. This finding suggests that a likely pathophysiological mechanism is the activation of the trigeminovascular system. SARS-CoV-2 neurotropism can occur by trans-synaptic invasion through the olfactory route from the nasal cavity, leading to anosmia which has been associated with headache. SARS-CoV-2 protein has been found not only in olfactory mucosa and bulbs but also in trigeminal branches and the trigeminal ganglion, supporting this hypothesis. However, other mechanisms such as brain vessels inflammation due to SARS-CoV-2 damage to the endothelium or systemic inflammation in the context of cytokine storm cannot be ruled out. Interestingly, headache has been associated with lower COVID-19 mortality. No specific treatment for COVID-19 headache is available at present. Studies show that investigating COVID-19 headache represents an opportunity not only to better understand COVID-19 in general but also to advance in the knowledge of both secondary and primary headaches. Future research is therefore warranted.


Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study.
To investigate the efficacy (prognosis, coagulation/inflammation biomarkers) and safety (bleeding events) of different anticoagulation dosages in COVID-19 inpatients. COVID-19 inpatients (Athens, Greece) were included. The "Enhanced dose THRomboprophylaxis in Admissions (ETHRA)" protocol was applied in certain Departments, suggesting the use of intermediate anticoagulation dosage. The primary endpoint was a composite of intubation/venous thromboembolism/death. Inflammation/coagulation parameters were assessed. Among 127 admissions, 95 fulfilled the inclusion criteria. Twenty-one events (4 deaths, 17 intubations) were observed. Regression analysis demonstrated significant reduction of events with intermediate or therapeutic dosage [HR=0.16 (95%CI=0.05-0.52) p=0.002; HR=0.17 (0.04-0.71) p=0.015, respectively]. D-Dimer values were higher in those who met the composite endpoint. Intermediate dosage treatment was associated with decreased values of ferritin. Three patients (3%) had minor hemorrhagic complications. Anticoagulation treatment (particularly intermediate dosage) appears to have positive impact on COVID-19 inpatients' prognosis by inhibiting both coagulation and inflammatory cascades.


Power Analysis and Effect Size in Mixed Effects Models: A Tutorial.
In psychology, attempts to replicate published findings are less successful than expected. For properly powered studies replication rate should be around 80%, whereas in practice less than 40% of the studies selected from different areas of psychology can be replicated. Researchers in cognitive psychology are hindered in estimating the power of their studies, because the designs they use present a sample of stimulus materials to a sample of participants, a situation not covered by most power formulas. To remedy the situation, we review the literature related to the topic and introduce recent software packages, which we apply to the data of two masked priming studies with high power. We checked how we could estimate the power of each study and how much they could be reduced to remain powerful enough. On the basis of this analysis, we recommend that a properly powered reaction time experiment with repeated measures has at least 1,600 word observations per condition (e.g., 40 participants, 40 stimuli). This is considerably more than current practice. We also show that researchers must include the number of observations in meta-analyses because the effect sizes currently reported depend on the number of stimuli presented to the participants. Our analyses can easily be applied to new datasets gathered.


Application of bioelectrical impedance analysis in prediction of light kid carcass and muscle chemical composition.
Carcass data were collected from 24 kids (average live weight of 12.5±5.5 kg; range 4.5 to 22.4 kg) of Jarmelista Portuguese native breed, to evaluate bioelectrical impedance analysis (BIA) as a technique for prediction of light kid carcass and muscle chemical composition. Resistance (Rs, Ω) and reactance (Xc, Ω), were measured in the cold carcasses with a single frequency bioelectrical impedance analyzer and, together with impedance (Z, Ω), two electrical volume measurements (VolA and VolB, cm2/Ω), carcass cold weight (CCW), carcass compactness and several carcass linear measurements were fitted as independent variables to predict carcass composition by stepwise regression analysis. The amount of variation explained by VolA and VolB only reached a significant level (P<0.01 and P<0.05, respectively) for muscle weight, moisture, protein and fat-free soft tissue content, even so with low accuracy, with VolA providing the best results (0.326⩽R 2⩽0.366). Quite differently, individual BIA parameters (Rs, Xc and Z) explained a very large amount of variation in dissectible carcass fat weight (0.814⩽R 2⩽0.862; P<0.01). These individual BIA parameters also explained a large amount of variation in subcutaneous and intermuscular fat weights (respectively 0.749⩽R 2⩽0.793 and 0.718⩽R 2⩽0.760; P<0.01), and in muscle chemical fat weight (0.663⩽R 2⩽0.684; P<0.01). Still significant but much lower was the variation in muscle, moisture, protein and fat-free soft tissue weights (0.344⩽R 2⩽0.393; P<0.01) explained by BIA parameters. Still, the best models for estimation of muscle, moisture, protein and fat-free soft tissue weights included Rs in addition to CCW, and accounted for 97.1% to 99.8% (P<0.01) of the variation observed, with CCW by itself accounting for 97.0% to 99.6% (P<0.01) of that variation. Resistance was the only independent variable selected for the best model predicting subcutaneous fat weight. It was also selected for the best models predicting carcass fat weight (combined with carcass length, CL; R 2=0.943; P<0.01) and intermuscular fat weight (combined with CCW; R 2=0.945; P<0.01). The best model predicting muscle chemical fat weight combined CCW and Z, explaining 85.6% (P<0.01) of the variation observed. These results indicate BIA as a useful tool for prediction of light kids' carcass composition.


Outcome of expandable prostheses in children.
Expandable prostheses offer the advantages of limb-salvage and limb-length equality at skeletal maturity. However, what is the cost for achieving that goal, and in how many children this is achieved? We present 32 children (16 boys and 16 girls; mean age, 9 y) with bone sarcomas of the femur treated with limb salvage using expandable prostheses. The Kotz Growing prosthesis and the noninvasive Repiphysis and Stanmore expandable prostheses were used. The mean follow-up was 49 months. Survival analysis of the children and primary implants and functional evaluation were performed. Survival of the children was 94% and 84% at 48 and 72 months. Survival of the primary prostheses was 78% and 66% at 48 and 72 months; survival was significantly higher only for the Kotz when compared with the Repiphysis prostheses (P=0.026). The rate of implant-related complications was 51.3%; 9 prostheses (23%) were revised because of aseptic loosening, infection, and breakage. A mean total lengthening of 28 mm (4 to 165 mm) was achieved by 84 procedures (2.6 procedures/patient). Three of the 9 children who reached skeletal maturity had limb-length equality and 6 discrepancy of 15 to 30 mm. The mean Musculoskeletal Tumor Society score was excellent (79%) without a significant difference between the type of prostheses (P=0.934). The Kotz Growing prosthesis, although it requires an open lengthening procedure, has shown higher survival when compared with the noninvasive Repiphysis prosthesis. However, the total lengthening remains small, and the complications rates are high even with the noninvasive prostheses.


Long noncoding RNA SNHG16 silencing inhibits the aggressiveness of gastric cancer via upregulation of microRNA-628-3p and consequent decrease of NRP1.
MicroRNA-628-3p (miR-628) has been reported to play important roles in the progression of multiple human cancer types. Nonetheless, whether the expression profile of miR-628 is altered in gastric cancer remains unclear and whether its aberrant expression plays a crucial part in the aggressiveness of gastric cancer is yet to be determined. Therefore, in this study, we systematically investigated the involvement of miR-628 in gastric cancer progression. MiR-628 expression in gastric cancer tissues and cell lines were determined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A CCK-8 assay, flow-cytometric analysis, Transwell assays, and a xenograft model experiment were performed to evaluate the influence of miR-628 overexpression on gastric cancer cells. Notably, the mechanisms underlying the tumor-suppressive activity of miR-628 in gastric cancer cells were explored by bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blotting. MiR-628 expression was low in gastric cancer tissue samples and cell lines. The low expression of miR-628 was closely associated with the lymph node metastasis, invasive depth and TNM stage among patients with gastric cancer. Further clinical analysis indicated that patients with gastric cancer underexpressing miR-628 had a worse prognosis than did the patients with high miR-628 expression in the tumor. Overexpressed miR-628 restrained proliferation, migration, and invasion; induced apoptosis; and impaired tumor growth of gastric cancer cells. In addition, neuropilin 1 (NRP1) mRNA was validated as the direct target of miR-628 in gastric cancer. Long noncoding RNA small nucleolar RNA host gene 16 (SNHG16) was demonstrated to sponge miR-628 in gastric cancer. Moreover, miR-628 knockdown abrogated the influence of SNHG16 silencing on gastric cancer cells. Our findings elucidate how the SNHG16-miR-628-NRP1 pathway serves as a regulatory network playing crucial roles in gastric cancer progression, suggesting that this pathway may be a novel target of anticancer therapy.


Changes in T-cell subsets and clonal repertoire during chemoimmunotherapy with pembrolizumab and paclitaxel or capecitabine for metastatic triple-negative breast cancer.
Chemoimmunotherapy is a standard treatment for triple-negative breast cancer (TNBC), however, the impacts of different chemotherapies on T-cell populations, which could correlate with clinical activity, are not known. Quantifying T-cell populations with flow cytometry and T-cell receptor (TCR) immunosequencing may improve our understanding of how chemoimmunotherapy affects T-cell subsets, and to what extent clonal shifts occur during treatment. TCR immunosequencing of intratumoral T cells may facilitate the identification and monitoring of putatively tumor-reactive T-cell clones within the blood. Blood and tumor biopsies were collected from patients with metastatic TNBC enrolled in a phase Ib clinical trial of first or second-line pembrolizumab with paclitaxel or capecitabine. Using identical biospecimen processing protocols, blood samples from a cohort of patients treated for early-stage breast cancer were obtained for comparison. Treatment-related immunological changes in peripheral blood and intratumoral T cells were characterized using flow cytometry and TCR immunosequencing. Clonal proliferation rates of T cells were compared based on intratumoral enrichment. When combined with pembrolizumab, paclitaxel and capecitabine resulted in similar time-dependent lymphodepletions across measured peripheral T-cell subsets. Their effects were more modest than that observed following curative-intent dose-dense anthracycline and cyclophosphamide (ddAC) (average fold-change in CD3+ cells, capecitabine: -0.42, paclitaxel: -0.56, ddAC: -1.21). No differences in T-cell clonality or richness were observed following capecitabine or paclitaxel-based treatments. Regression modeling identified differences in the emergence of novel T-cell clones that were not detected at baseline (odds compared with ddAC, capecitabine: 0.292, paclitaxel: 0.652). Pembrolizumab with paclitaxel or capecitabine expanded T-cell clones within tumors; however, these clones did not always expand within the blood. Proliferation rates within the blood were similar between clones that were enriched and those that were not enriched within tumors. Chemoimmunotherapy for metastatic TNBC with pembrolizumab and capecitabine or paclitaxel resulted in similar peripheral T-cell subset lymphodepletion without altering T-cell clonal diversity. Regression modeling methods are applicable in immune monitoring studies, such as this to identify the odds of novel T-cell clones emerging during treatment, and proliferation rates of tumor-enriched T-cell clones.


Is caregiving hazardous to one's physical health? A meta-analysis.
Caring for a family member with dementia is generally regarded as a chronically stressful process, with potentially negative physical health consequences. However, no quantitative analysis has been conducted on this literature. The authors combined the results of 23 studies to compare the physical health of caregivers with demographically similar noncaregivers. When examined across 11 health categories, caregivers exhibited a slightly greater risk for health problems than did noncaregivers. However, sex and the health category assessed moderated this relationship. Stronger relationships occurred with stress hormones, antibodies, and global reported health. The authors argue that a theoretical model is needed that relates caregiver stressors to illness and proffers moderating roles for vulnerabilities and resources and mediating roles for psychosocial distress and health behaviors.


Engaging community health workers in maternal and infant death identification in Khayelitsha, South Africa: a pilot study.
Engaging community health workers in a formalised death review process through verbal and social autopsy has been utilised in different settings to estimate the burden and causes of mortality, where civil registration and vital statistics systems are weak. This method has not been widely adopted. We piloted the use of trained community health workers (CHW) to investigate the extent of unreported maternal and infant deaths in Khayelitsha and explored requirements of such a programme and the role of CHWs in bridging gaps. This was a mixed methods study, incorporating both qualitative and quantitative methods. Case identification and data collection were done by ten trained CHWs. Quantitative data were collected using a structured questionnaire. Qualitative data were collected using semi-structured interview guides for key informant interviews, focus group discussions and informal conversations. Qualitative data were analysed thematically using a content analysis approach. Although more than half of the infant deaths occurred in hospitals (n = 11/17), about a quarter that occurred at home (n = 4/17) were unreported. Main causes of deaths as perceived by family members of the deceased were related to uncertainty about the quality of care in the facilities, socio-cultural and economic contexts where people lived and individual factors. Most unreported deaths were further attributed to weak facility-community links and socio-cultural practices. Fragmented death reporting systems were perceived to influence the quality of the data and this impacted on the number of unreported deaths. Only two maternal deaths were identified in this pilot study. CHWs can conduct verbal and social autopsy for maternal and infant deaths to complement formal vital registration systems. Capacity development, stakeholder's engagement, supervision, and support are essential for a community-linked death review system. Policymakers and implementers should establish a functional relationship between community-linked reporting systems and the existing system as a starting point. There is a need for more studies to confirm or build on our pilot findings.


Biomolecular dynamics in the 21st century.
The relevance of motions in biological macromolecules has been clear since the early structural analyses of proteins by X-ray crystallography. Computer simulations have been applied to provide a deeper understanding of the dynamics of biological macromolecules since 1976, and are now a standard tool in many labs working on the structure and function of biomolecules. In this mini-review we highlight some areas of current interest and active development for simulations, in particular all-atom molecular dynamics simulations.


Metal ions bound to the human milk immunoglobulin A: metalloproteomic approach.
The presence of calcium, iron, and zinc bound to human milk secretory IgA (sIgA) was investigated. The sIgA components were first separated by two-dimensional polyacrylamide gel electrophoresis and then identified by electrospray ionization-tandem mass spectrometry (ESI MS MS). The metal ions were detected by flame atomic absorption spectrometry after acid mineralization of the spots. The results showed eight protein spots corresponding to the IgA heavy chain constant region. Another spot was identified as the transmembrane secretory component. Calcium was bound to both the transmembrane component and the heavy chain constant region, while zinc was bound to the heavy chain constant region and iron was not bound with the identified proteins. The association of a metal ion with a protein is important for a number of reasons, and therefore, the findings of the present study may lead to a better understanding of the mechanisms of action and of additional roles that sIgA and its components play in human milk.


Shuttle-cargo fusion molecules of transport peptides and the hD2/3 receptor antagonist fallypride: a feasible approach to preserve ligand-receptor binding?
To determine if the conjugation of a small receptor ligand to a peptidic carrier to potentially facilitate transport across the blood-brain barrier (BBB) by "molecular Trojan horse" transcytosis is feasible, we synthesized several transport peptide-fallypride fusion molecules as model systems and determined their binding affinities to the hD2 receptor. Although they were affected by conjugation, the binding affinities were found to be still in the nanomolar range (between 1.5 and 64.2 nM). In addition, homology modeling of the receptor and docking studies for the most potent compounds were performed, elucidating the binding modes of the fusion molecules and the structure elements contributing to the observed high receptor binding. Furthermore, no interaction between the hybrid compounds and P-gp, the main excretory transporter of the BBB, was found. From these results, it can be inferred that the approach to deliver small neuroreceptor ligands across the BBB by transport peptide carriers is feasible.


Computational Modeling of Voice Production Using Excised Canine Larynx.
A combined experimental-numerical work was conducted to comprehensively validate a subject-specific continuum model of voice production in larynx using excised canine laryngeal experiments. The computational model is a coupling of the Navier-Stokes equations for glottal flow dynamics and a finite element model of vocal fold dynamics. The numerical simulations employed a cover-body vocal fold structure with the geometry reconstructed from magnetic resonance imaging scans and the material properties determined through an optimization-based inverse process of experimental indentation measurement. The results showed that the simulations predicted key features of the dynamics observed in the experiments, including the skewing of the glottal flow waveform, mucosal wave propagation, continuous increase of the divergent angle and intraglottal swirl strength during glottal closing, and flow recirculation between glottal jet and vocal fold. The simulations also predicted the increase of the divergent angle, glottal jet speed, and intraglottal flow swirl strength with the subglottal pressure, same as in the experiments. Quantitatively, the simulations over-predicted the frequency and jet speed and under-predicted the flow rate and divergent angle for the larynx under study. The limitations of the model and their implications were discussed.


Coiled coils: attractive protein folding motifs for the fabrication of self-assembled, responsive and bioactive materials.
The coiled coil is a superhelical protein structural motif that consists of two or more alpha-helical peptides that are wrapped around each other in superhelical fashion. Coiled coils are amongst the most ubiquitous folding motifs found in proteins and have not only been identified in structural proteins but also play an important role in various intracellular regulation processes as well as membrane fusion. The aim of this critical review is to highlight the potential of coiled coil peptide sequences for the development of self-assembled, responsive and/or bioactive materials. After a short historical overview outlining the discovery of this protein folding motif, the article will briefly discuss naturally occurring coiled coils. After that, the basic rules, which have been established to date for the design of coiled coils will be briefly summarized followed by a presentation of several classes of coiled coils, which may represent interesting candidates for the development of novel self-assembled, responsive and/or bioactive materials. This critical review will end with a section that summarizes the different coiled coil based (hybrid) materials that have been reported to date and which hopefully will help to stimulate further work to explore the full potential of this unique class of protein folding motifs for the development of novel self-assembled, responsive and/or bioactive materials (212 references).


PAMP-INDUCED SECRETED PEPTIDE 3 modulates immunity in Arabidopsis.
Small post-translationally modified peptides are important signalling components of plant defence responses against phytopathogens, acting as both positive and negative modulators. PAMP-INDUCED SECRETED PEPTIDE (PIP) 1 and 2 have been shown to amplify plant immunity. Here we investigate the role of the related peptide PIP3 in the regulation of immune response in Arabidopsis. Treatment with synthetic PIP peptides led to similar transcriptome reprogramming, indicating an effect on innate immunity-related processes and phytohormones, including jasmonic acid (JA) biosynthesis and signalling. PIP3 overexpressing (OX) plants showed enhanced growth inhibition in response to flg22 exposure. In addition, flg22-induced production of reactive oxygen species and callose deposition was significantly reduced in PIP3-OX plants. Interestingly, PIP3-OX plants showed increased susceptibility toward both Botrytis cinerea and the biotrophic pathogen Pseudomonas syringae. Expression of both JA and salicylic acid (SA) biosynthesis and signalling genes was more induced during B. cinerea infection in PIP3-OX plants compared with wild-type plants. Promoter and ChIP-seq analyses indicated that the transcription factors WRKY18, WRKY33, and WRKY40 cooperatively act as repressors for PIP3. The results point to a fine-tuning role for PIP3 in modulation of immunity through the regulation of SA and JA biosynthesis and signalling pathways in Arabidopsis.


Adrenergic and cholinergic regulation of in vitro melatonin release during ontogeny in the pineal gland of Long Evans rats.
Melatonin, produced by the pineal gland, plays an important role in a great variety of neuroendocrine functions. The rhythmic release of melatonin by the mammalian pineal gland is regulated by norepinephrine (NE) acting via alpha- and beta-adrenergic receptors utilizing distinct signal transduction pathways. Acetylcholine has been demonstrated to exert various effects in the mammalian pineal gland, including an inhibitory action on the NE-induced stimulation of melatonin production. However, data obtained by different laboratories on the interaction of adrenergic receptors are not consistent and whether muscarinic and/or nicotinic receptors participate in the various effects of acetylcholine is still contradictory. To investigate noradrenergic as well as cholinergic mechanisms during ontogeny, we have investigated in vitro melatonin release from isolated pineal glands of Long Evans rats of different ages. NE as well as the beta-adrenergic receptor agonist isoproterenol (ISO) significantly elevated the melatonin release in pineal glands from postnatal week 2 on. In pineal glands originating from 2- to 4-week-old rats, simultaneous activation of alpha- and beta-adrenergic receptors by ISO and the alpha-adrenergic receptor agonist methoxamine (MET) or NE resulted in significantly weaker stimulation of melatonin production than beta-receptor activation alone. Acetylcholine evoked a significant increase in melatonin release in pineal glands from 2- to 4-week-old rats. In pineal glands from 8- to 20-week-old animals, ISO, ISO + MET or NE stimulated pineal melatonin release to comparable maxima, whereas acetylcholine was without effect. Our data indicate (1) that the adrenergic stimulation of pineal melatonin production in Long Evans rats is dominated by a beta-adrenergic mechanism, (2) that additional alpha-adrenergic receptor activation is inhibitory and (3) dependent on the developmental status of the animal, and (4) that acetylcholine acting via muscarinic receptors has the capacity to stimulate melatonin release during early ontogeny. These data suggest that the melatonin-generating system of the pineal gland of Long Evans rats undergoes substantial functional changes during early postnatal development, including adrenergic as well as cholinergic mechanisms.


Global Transcriptomic Analyses Reveal Genes Involved in Conceptus Development During the Implantation Stages in Pigs.
Prenatal mortality remains a significant concern to the pig farming industry around the world. Spontaneous fetal loss ranging from 20 to 45% by term occur after fertilization, with most of the loss happening during the implantation period. Since the factors regulating the high mortality rates of early conceptus during implantation phases are poorly understood, we sought to analyze the overall gene expression changes during this period, and identify the molecular mechanisms involved in conceptus development. This work employed Illumina's next-generation sequencing (RNA-Seq) and quantitative real-time PCR to analyze differentially expressed genes (DEGs). Soft clustering was subsequently used for the cluster analysis of gene expression. We identified 8236 DEGs in porcine conceptus at day 9, 12, and 15 of pregnancy. Annotation analysis of these genes revealed rRNA processing (GO:0006364), cell adhesion (GO:1904874), and heart development (GO:0007507), as the most significantly enriched biological processes at day 9, 12, and 15 of pregnancy, respectively. In addition, we found various genes, such as T-complex 1, RuvB-like AAA ATPase 2, connective tissue growth factor, integrins, interferon gamma, SLA-1, chemokine ligand 9, PAG-2, transforming growth factor beta receptor 1, and Annexin A2, that play essential roles in conceptus morphological development and implantation in pigs. Furthermore, we investigated the function of PAG-2 in vitro and found that PAG-2 can inhibit trophoblast cell proliferation and migration. Our analysis provides a valuable resource for understanding the mechanisms of conceptus development and implantation in pigs.


Research applications of selected 123I-labeled neuroreceptor SPECT imaging ligands.
Neuroreceptor imaging is a promising area of brain imaging used to investigate various neurodegenerative and neuropsychiatric disorders. In the research setting, radiopharmaceuticals targeted to specific areas of the brain are used along with SPECT to assess and analyze functional mechanisms within brain structures. Utilization of the data that are collected from these studies may aid in the development of drug therapies that can be used to relieve symptoms or delay progression of certain disease states. After reading this article, the nuclear medicine technologist should be able to identify and describe the role of structures in the brain, identify various radiopharmaceuticals used and the disease states they demonstrate, and become familiar with the drugs used in treatment of these disorders.


Poor prognosis of young adults with type 1 diabetes: a longitudinal study.
To determine the role of early behavioral and psychological factors on later outcomes in young adults with childhood- or adolescent-onset type 1 diabetes. We conducted a longitudinal cohort study of patients recruited from the register of the young adult outpatient diabetes clinic, Oxford, U.K. A total of 113 individuals (51 male subjects) aged 17-25 years completed assessments, and 87 (77%) were reinterviewed as older adults (aged 28-37 years). Longitudinal assessments were made of glycemic control (HbA(1c)) and complications. Psychological state at baseline was assessed using the Present State Examination and self-report Symptom Checklist, with corresponding interview schedules administered at follow-up. There was no significant improvement between baseline and follow-up in mean HbA(1c) levels (8.5 vs. 8.6% in men, 9.3 vs. 8.7% in women). The proportion of individuals with serious complications (preproliferative or laser-treated retinopathy, proteinuria or more severe renal disease, peripheral neuropathy, and autonomic neuropathy) increased from 3-37% during the 11-year period. Women were more likely than men to have multiple complications (23 vs. 6%, difference 17%, 95% CI 4-29%, P = 0.02). Psychiatric disorders increased from 16 to 28% (20% in men, 36% in women at follow-up, difference NS), and 8% had psychiatric disorders at both assessments. Baseline psychiatric symptom scores predicted follow-up scores (beta = 0.32, SE [beta] 0.12, P = 0.008, 95% CI 0.09-0.56) and recurrent admissions with diabetic ketoacidosis (odds ratio 9.1, 95% CI 2.9-28.6, P < 0.0001). The clinical and psychiatric outcome in this cohort was poor. Psychiatric symptoms in later adolescence and young adulthood appeared to predict later psychiatric problems.


Prenatal diagnosis of pulmonary atresia: impact on clinical presentation and early outcome.
The impact of prenatal diagnosis on morbidity and mortality for certain types of congenital heart disease (obstructive left heart lesions and transposition of the great arteries) is well established. No data are available for lesions with duct dependent pulmonary flow. We aimed to assess the impact of prenatal diagnosis of pulmonary atresia on clinical presentation and neonatal outcome. Fifty-eight newborns with pulmonary atresia presenting to our centre were identified retrospectively between 1997 and 2004 (prenatal diagnosis n = 37, postnatal n = 21). Anatomical sub-types included intact ventricular septum (PAIVS, n = 33) and ventricular septal defect (PAVSD, n = 25); those with more complex anatomy were excluded. After adjusting for anatomical sub-type, postnatally diagnosed infants were significantly more hypoxic at presentation (mean oxygen saturation 65% vs 84%). However, they presented early (median age 1 day) and prostaglandin E was initiated promptly (median 3 hours) with rapid improvement of oxygen saturations (interaction p<0.001). This resulted in no appreciable differences in terms of pH, base deficit, blood pressure or heart rate between the groups by the time of the first catheter/surgical intervention. Postnatal infants did not differ in terms of length of intensive care unit (p = 0.18) or hospital stay (p = 0.86), incidence of complications (p = 0.72), or mortality (p = 0.77). Multivariable analysis revealed a positive association between occurrence of complications and both degree of cyanosis at presentation (rather than postnatal diagnosis per se) and anatomy (PAIVS). Postnatal diagnosis of pulmonary atresia is associated with greater cyanosis at presentation. However this does not translate into greater neonatal morbidity or mortality provided that early recognition and prompt initiation of prostaglandin E therapy occur.


Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA.
Aryl hydrocarbon receptor (AhR) has been shown to have profound influence on T cell differentiation, and use of distinct AhR ligands has shown that whereas some ligands induce regulatory T cells (Tregs), others induce Th17 cells. In the present study, we tested the ability of dietary AhR ligands (indole-3-carbinol [I3C] and 3,3'-diindolylmethane [DIM]) and an endogenous AhR ligand, 6-formylindolo(3,2-b)carbazole (FICZ), on the differentiation and functions of Tregs and Th17 cells. Treatment of C57BL/6 mice with indoles (I3C or DIM) attenuated delayed-type hypersensitivity (DTH) response to methylated BSA and generation of Th17 cells while promoting Tregs. In contrast, FICZ exacerbated the DTH response and promoted Th17 cells. Indoles decreased the induction of IL-17 but promoted IL-10 and Foxp3 expression. Also, indoles caused reciprocal induction of Tregs and Th17 cells only in wild-type (AhR(+/+)) but not in AhR knockout (AhR(-/-)) mice. Upon analysis of microRNA (miR) profile in draining lymph nodes of mice with DTH, treatment with I3C and DIM decreased the expression of several miRs (miR-31, miR-219, and miR-490) that targeted Foxp3, whereas it increased the expression of miR-495 and miR-1192 that were specific to IL-17. Interestingly, treatment with FICZ had precisely the opposite effects on these miRs. Transfection studies using mature miR mimics of miR-490 and miR-1192 that target Foxp3 and IL-17, respectively, or scrambled miR (mock) or inhibitors confirmed that these miRs specifically targeted Foxp3 and IL-17 genes. Our studies demonstrate, to our knowledge for the first time, that the ability of AhR ligands to regulate the differentiation of Tregs versus Th17 cells may depend on miR signature profile.


[Integrated project of personalisation school curricula and training].
To strengthen the motivation to study, promote awareness of their attitudes and actions of orientation / re-orientation to the profession, making the learning experience more stimulating and training in order to staunch the sharp drop-out affecting the school. The project, coordinated by psychologists, involved the administration of AMOS Test as a tool to detect the variables of interest (self-image, ambitions and motivations, concerns for the future, soft skills etc.) in a sample of students belonging the CFP of Lazio. The sample consisted of 632 students (aged between 14 and 20 years and made up 70.6% of females). The sample is divided between the Agency's structures Formation of the Province of Frosinone: Anagni (7,3%); Cassino (24,7%); Ferentino (10,9%); Frosinone (31,8 %); Pontecorvo (4,1%) and Sora (21,2%) that offer various training courses: a wellness area (81%), electronic / mechanical area (12%), administrative one (7%). Most of the students have poor self-esteem and con dence in their own resources. They have a poor perception of their skills both profes- sionally and personally, have trouble thinking of an ambitious future with a 'negative self-image'. Few have plans for the future and are determined to achieve them and bring them forward, demonstrating uncertainty about future careers. The survey findings emerges the need of the students to have a support not only educational but also cognitive and emotional. Possible proposals for action are: the implementation of techniques such as cooperative learning, action learning, problem solving, the 'activation of a door psychological listening and the like.


Effects of sodium chlorate on toxin production by Escherichia coli O157:H7.
Chlorate kills E. coli O157:H7 and has been proposed as a feed additive to be included in cattle rations immediately prior to slaughter to reduce E. coli O157: H7 populations in the gut. Antibiotic usage is not recommended in cases of E. coil O157:H7-induced hemorrhagic colitis because some antibiotics stimulate increased toxin production. This study was undertaken to determine if chlorate treatment affected toxin production. Pure cultures of E. coil O157:H7 were treated with 1/4 MIC of antibiotics (ampicillin, tetracycline, ceftiofur, gentamicin, monensin, tylosin, penicillin, ciprofloxacin, and novobiocin); toxin production was significantly increased by some antibiotics, but not by chlorate. Studies with mixed fecal bacteria demonstrated that chlorate killed E. coli O157:H7, but again did not stimulate toxin production. Chlorate appears to be an effective method to reduce shiga toxin-producing E. coil (STEC) populations in food animals, but additional studies are warranted before it is used to control infections.