Inter-Comparison Campaign of Solar UVR Instruments under Clear Sky Conditions at Reunion Island (21°S, 55°E).
Measurement of solar ultraviolet radiation (UVR) is important for the assessment of potential beneficial and adverse impacts on the biosphere, plants, animals, and humans. Excess solar UVR exposure in humans is associated with skin carcinogenesis and immunosuppression. Several factors influence solar UVR at the Earth's surface, such as latitude and cloud cover. Given the potential risks from solar UVR there is a need to measure solar UVR at different locations using effective instrumentation. Various instruments are available to measure solar UVR, but some are expensive and others are not portable, both restrictive variables for exposure assessments. Here, we compared solar UVR sensors commercialized at low or moderate cost to assess their performance and quality of measurements against a high-grade Bentham spectrometer. The inter-comparison campaign took place between March 2018 and February 2019 at Saint-Denis, La Réunion. Instruments evaluated included a Kipp&Zonen UVS-E-T radiometer, a Solar Light UV-Biometer, a SGLux UV-Cosine radiometer, and a Davis radiometer. Cloud fraction was considered using a SkyCamVision all-sky camera and the Tropospheric Ultraviolet Visible radiative transfer model was used to model clear-sky conditions. Overall, there was good reliability between the instruments over time, except for the Davis radiometer, which showed dependence on solar zenith angle. The Solar Light UV-Biometer and the Kipp&Zonen radiometer gave satisfactory results, while the low-cost SGLux radiometer performed better in clear sky conditions. Future studies should investigate temporal drift and stability over time.


Epilepsy.
As surgical treatments for adult and pediatric forms of epilepsy have become more refined, methods for noninvasive localization of epileptogenic foci have become increasingly important. Detection of focal brain metabolic or flow abnormalities is now well recognized as an essential step in the presurgical evaluation of many patients with epilepsy. Positron emission tomography (PET) scanning is most beneficial when used in the context of the total clinical evaluation of patients, including scalp EEG, invasive EEG, neuropsychologic testing, etc. Metabolic PET studies also give insight into pathophysiologic mechanisms of epilepsy. The dynamic nature of the interictal hypometabolism observed with 18[F]FDG in some patients suggests that excitatory or inhibitory neurotransmitters and their receptors may be involved. An exciting current application of PET scanning is the use of tracers for neurotransmitter receptors in the study of epilepsy patients. Mu and non-mu opiate receptors have been extensively studied and are beginning to give new insights into this disorder. Increased labeling of mu receptors in temporal neocortex using 11C-carfentanil has been demonstrated and, in some patients, supplements the clinical localization information from 18[F]FDG studies. Increased mu opiate receptor number or affinity is thought to play a role in anticonvulsant mechanisms. Specificity of increased mu receptors is supported by the absence of significant changes in non-mu opiate receptors. Other brain receptors are also of interest for future studies, particularly those for excitatory neurotransmitters. Combined studies of flow, metabolism, and neuroreceptors may elucidate the factors responsible for initiation and termination of seizures, thus improving patient treatment.


Identification of Arx transcriptional targets in the developing basal forebrain.
Mutations in the aristaless-related homeobox (ARX) gene are associated with multiple neurologic disorders in humans. Studies in mice indicate Arx plays a role in neuronal progenitor proliferation and development of the cerebral cortex, thalamus, hippocampus, striatum, and olfactory bulbs. Specific defects associated with Arx loss of function include abnormal interneuron migration and subtype differentiation. How disruptions in ARX result in human disease and how loss of Arx in mice results in these phenotypes remains poorly understood. To gain insight into the biological functions of Arx, we performed a genome-wide expression screen to identify transcriptional changes within the subpallium in the absence of Arx. We have identified 84 genes whose expression was dysregulated in the absence of Arx. This population was enriched in genes involved in cell migration, axonal guidance, neurogenesis, and regulation of transcription and includes genes implicated in autism, epilepsy, and mental retardation; all features recognized in patients with ARX mutations. Additionally, we found Arx directly repressed three of the identified transcription factors: Lmo1, Ebf3 and Shox2. To further understand how the identified genes are involved in neural development, we used gene set enrichment algorithms to compare the Arx gene regulatory network (GRN) to the Dlx1/2 GRN and interneuron transcriptome. These analyses identified a subset of genes in the Arx GRN that are shared with that of the Dlx1/2 GRN and that are enriched in the interneuron transcriptome. These data indicate Arx plays multiple roles in forebrain development, both dependent and independent of Dlx1/2, and thus provides further insights into the understanding of the mechanisms underlying the pathology of mental retardation and epilepsy phenotypes resulting from ARX mutations.


Ptpn22 and Cd2 Variations Are Associated with Altered Protein Expression and Susceptibility to Type 1 Diabetes in Nonobese Diabetic Mice.
By congenic strain mapping using autoimmune NOD.C57BL/6J congenic mice, we demonstrated previously that the type 1 diabetes (T1D) protection associated with the insulin-dependent diabetes (Idd)10 locus on chromosome 3, originally identified by linkage analysis, was in fact due to three closely linked Idd loci: Idd10, Idd18.1, and Idd18.3. In this study, we define two additional Idd loci--Idd18.2 and Idd18.4--within the boundaries of this cluster of disease-associated genes. Idd18.2 is 1.31 Mb and contains 18 genes, including Ptpn22, which encodes a phosphatase that negatively regulates T and B cell signaling. The human ortholog of Ptpn22, PTPN22, is associated with numerous autoimmune diseases, including T1D. We, therefore, assessed Ptpn22 as a candidate for Idd18.2; resequencing of the NOD Ptpn22 allele revealed 183 single nucleotide polymorphisms with the C57BL/6J (B6) allele--6 exonic and 177 intronic. Functional studies showed higher expression of full-length Ptpn22 RNA and protein, and decreased TCR signaling in congenic strains with B6-derived Idd18.2 susceptibility alleles. The 953-kb Idd18.4 locus contains eight genes, including the candidate Cd2. The CD2 pathway is associated with the human autoimmune disease, multiple sclerosis, and mice with NOD-derived susceptibility alleles at Idd18.4 have lower CD2 expression on B cells. Furthermore, we observed that susceptibility alleles at Idd18.2 can mask the protection provided by Idd10/Cd101 or Idd18.1/Vav3 and Idd18.3. In summary, we describe two new T1D loci, Idd18.2 and Idd18.4, candidate genes within each region, and demonstrate the complex nature of genetic interactions underlying the development of T1D in the NOD mouse model.


The utility of 3D-printed airway stents to improve treatment strategies for central airway obstructions.
Airway stents are commonly used in the management of patients suffering from central airway obstruction (CAO). CAO may occur directly from airway strictures, obstructing airway cancers, airway fistulas or tracheobronchomalacia, resulting from the weakening and dynamic collapse of the airway wall. Current airway stents are constructed from biocompatible medical-grade silicone or from a nickel-titanium (nitinol) alloy with fixed geometry. The stents are inserted via the mouth during a bronchoscopic procedure. Existing stents have many shortcomings including the development of obstructing granulation tissue in the weeks and months following placement, mucous build up within the stent, and cough. Furthermore, airway stents are expensive and, if improperly sized for a given airway, may be easily dislodged (stent migration). Currently, in Australia, it is estimated that approximately 12,000 patients will develop CAO annually, many of whom will require airway stenting intervention. Of all stenting procedures, the rate of failure is currently reported to be at 22%. With a growing incidence of lung cancer prevalence globally, the need for updating airway stent technology is now greater than ever and personalizing stents using 3D-printing technology may offer the best chance of addressing many of the current limitations in stent design. This review article will assess what represents the gold standard in stent manufacture with regards to treatment of tracheobronchial CAO, the challenges of current airway stents, and outlines the necessity and challenges of incorporating 3D-printing technology into personalizing airway stents today.


Safe sex and student nurses in rural Australia: nurses' knowledge and practices (Part 2).
In this article, the second in a two-part series on a research study investigating student nurses' knowledge and attitudes to safe sex in a rural university in Australia, the results are revealed. The major findings discussed in this article are focused on sexual preference, the need for safe sex, safe sex practices, the need for educational material regarding safe sex, exploration of sex/sexuality and, the need for study of conflict resolution, negotiation skills, and self esteem building. The article concludes with deliberations on educational recommendations associated with the research.


Comparison of multiple transcriptomes exposes unified and divergent features of quiescent and activated skeletal muscle stem cells.
Skeletal muscle satellite (stem) cells are quiescent in adult mice and can undergo multiple rounds of proliferation and self-renewal following muscle injury. Several labs have profiled transcripts of myogenic cells during the developmental and adult myogenesis with the aim of identifying quiescent markers. Here, we focused on the quiescent cell state and generated new transcriptome profiles that include subfractionations of adult satellite cell populations, and an artificially induced prenatal quiescent state, to identify core signatures for quiescent and proliferating. Comparison of available data offered challenges related to the inherent diversity of datasets and biological conditions. We developed a standardized workflow to homogenize the normalization, filtering, and quality control steps for the analysis of gene expression profiles allowing the identification up- and down-regulated genes and the subsequent gene set enrichment analysis. To share the analytical pipeline of this work, we developed Sherpa, an interactive Shiny server that allows multi-scale comparisons for extraction of desired gene sets from the analyzed datasets. This tool is adaptable to cell populations in other contexts and tissues. A multi-scale analysis comprising eight datasets of quiescent satellite cells had 207 and 542 genes commonly up- and down-regulated, respectively. Shared up-regulated gene sets include an over-representation of the TNFα pathway via NFKβ signaling, Il6-Jak-Stat3 signaling, and the apical surface processes, while shared down-regulated gene sets exhibited an over-representation of Myc and E2F targets and genes associated to the G2M checkpoint and oxidative phosphorylation. However, virtually all datasets contained genes that are associated with activation or cell cycle entry, such as the immediate early stress response genes Fos and Jun. An empirical examination of fixed and isolated satellite cells showed that these and other genes were absent in vivo, but activated during procedural isolation of cells. Through the systematic comparison and individual analysis of diverse transcriptomic profiles, we identified genes that were consistently differentially expressed among the different datasets and shared underlying biological processes key to the quiescent cell state. Our findings provide impetus to define and distinguish transcripts associated with true in vivo quiescence from those that are first responding genes due to disruption of the stem cell niche.


Challenging the moral status of blood donation.
The World Health Organisation encourages that blood donation becomes voluntary and unremunerated, a system already operated in the UK. Drawing on public documents and videos, this paper argues that blood donation is regarded and presented as altruistic and supererogatory. In advertisements, donation is presented as something undertaken for the benefit of others, a matter attracting considerable gratitude from recipients and the collecting organisation. It is argued that regarding blood donation as an act of supererogation is wrongheaded, and an alternative account of blood donation as moral obligation is presented. Two arguments are offered in support of this position. First, the principle of beneficence, understood in a broad consequentialist framework obliges donation where the benefit to the recipient is large and the cost to the donor relatively small. This argument can be applied, with differing levels of normativity, to various acts of donation. Second, the wrongness of free riding requires individuals to contribute to collective systems from which they benefit. Alone and in combination these arguments present moral reasons for donation, recognised in communication strategies elsewhere. Research is required to evaluate the potential effects on donation of a campaign which presents blood donation as moral obligation, but of wider importance is the recognition that other-regarding considerations in relation to our own as well as others' health result in a range not only of choices but also of obligations.


Cancer incidence among pesticide applicators exposed to permethrin in the Agricultural Health Study.
Permethrin is a synthetic pyrethroid insecticide widely used in agriculture, in public health, and in many U.S. homes and gardens. In this study we evaluated the incidence of cancer among pesticide applicators exposed to permethrin in the Agricultural Health Study (AHS). A total of 49,093 pesticide applicators were included in this analysis of the AHS, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed in 1993-1997. Average length of follow-up since applicator enrollment in the cohort was 9.14 years. We used two permethrin exposure metrics: a) lifetime days applicators personally mixed or applied permethrin and b) intensity-weighted lifetime days (lifetime days weighted by estimated intensity of exposure). We used Poisson regression analysis to estimate relative risks (RRs) and 95% confidence intervals (CIs) for malignancies by tertiles of exposure. We found no associations between permethrin and all malignant neoplasms combined, or between permethrin and melanoma, non-Hodgkin lymphoma, leukemia, or cancers of the colon, rectum, lung, or prostate. We found elevated and statistically significant risks for multiple myeloma in the highest tertiles of both lifetime exposure-days (RR = 5.72; 95% CI, 2.76-11.87) and intensity-weighted lifetime exposure-days (RR = 5.01; 95% CI, 2.41-10.42), compared with applicators reporting they never used permethrin; these results are based on only 15 exposed cases. These findings were similar across a variety of alternative exposure metrics, exposure categories, and reference groups. This study found no association with most cancers analyzed. Although the suggested association with multiple myeloma was based on a small number of cases, it warrants further evaluation.


Newly designed 16S rRNA metabarcoding primers amplify diverse and novel archaeal taxa from the environment.
High-throughput studies of microbial communities suggest that Archaea are a widespread component of microbial diversity in various ecosystems. However, proper quantification of archaeal diversity and community ecology remains limited, as sequence coverage of Archaea is usually low owing to the inability of available prokaryotic primers to efficiently amplify archaeal compared to bacterial rRNA genes. To improve identification and quantification of Archaea, we designed and validated the utility of several primer pairs to efficiently amplify archaeal 16S rRNA genes based on up-to-date reference genes. We demonstrate that several of these primer pairs amplify phylogenetically diverse Archaea with high sequencing coverage, outperforming commonly used primers. Based on comparing the resulting long 16S rRNA gene fragments with public databases from all habitats, we found several novel family- to phylum-level archaeal taxa from topsoil and surface water. Our results suggest that archaeal diversity has been largely overlooked due to the limitations of available primers, and that improved primer pairs enable to estimate archaeal diversity more accurately.


Alcohol and public health.
Alcoholic beverages, and the problems they engender, have been familiar fixtures in human societies since the beginning of recorded history. We review advances in alcohol science in terms of three topics: the epidemiology of alcohol's role in health and illness; the treatment of alcohol use disorders in a public health perspective; and policy research and options. Research has contributed substantially to our understanding of the relation of drinking to specific disorders, and has shown that the relation between alcohol consumption and health outcomes is complex and multidimensional. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Treatment research shows that early intervention in primary care is feasible and effective, and a variety of behavioural and pharmacological interventions are available to treat alcohol dependence. This evidence suggests that treatment of alcohol-related problems should be incorporated into a public health response to alcohol problems. Additionally, evidence-based preventive measures are available at both the individual and population levels, with alcohol taxes, restrictions on alcohol availability, and drinking-driving countermeasures among the most effective policy options. Despite the scientific advances, alcohol problems continue to present a major challenge to medicine and public health, in part because population-based public health approaches have been neglected in favour of approaches oriented to the individual that tend to be more palliative than preventative.


A systematic review of integrated working between care homes and health care services.
In the UK there are almost three times as many beds in care homes as in National Health Service (NHS) hospitals. Care homes rely on primary health care for access to medical care and specialist services. Repeated policy documents and government reviews register concern about how health care works with independent providers, and the need to increase the equity, continuity and quality of medical care for care homes. Despite multiple initiatives, it is not known if some approaches to service delivery are more effective in promoting integrated working between the NHS and care homes. This study aims to evaluate the different integrated approaches to health care services supporting older people in care homes, and identify barriers and facilitators to integrated working. A systematic review was conducted using Medline (PubMed), CINAHL, BNI, EMBASE, PsycInfo, DH Data, Kings Fund, Web of Science (WoS incl. SCI, SSCI, HCI) and the Cochrane Library incl. DARE. Studies were included if they evaluated the effectiveness of integrated working between primary health care professionals and care homes, or identified barriers and facilitators to integrated working. Studies were quality assessed; data was extracted on health, service use, cost and process related outcomes. A modified narrative synthesis approach was used to compare and contrast integration using the principles of framework analysis. Seventeen studies were included; 10 quantitative studies, two process evaluations, one mixed methods study and four qualitative. The majority were carried out in nursing homes. They were characterised by heterogeneity of topic, interventions, methodology and outcomes. Most quantitative studies reported limited effects of the intervention; there was insufficient information to evaluate cost. Facilitators to integrated working included care home managers' support and protected time for staff training. Studies with the potential for integrated working were longer in duration. Despite evidence about what inhibits and facilitates integrated working there was limited evidence about what the outcomes of different approaches to integrated care between health service and care homes might be. The majority of studies only achieved integrated working at the patient level of care and the focus on health service defined problems and outcome measures did not incorporate the priorities of residents or acknowledge the skills of care home staff. There is a need for more research to understand how integrated working is achieved and to test the effect of different approaches on cost, staff satisfaction and resident outcomes.


Spread and referral of experimental pain in different jaw muscles.
To test the hypothesis that there would be no differences in perceived pain intensity and spread and referral of pain evoked by injection of a similar amount of hypertonic saline into 6 different jaw-muscle sites in healthy female subjects. A total of 15 healthy women participated in 3 experimental sessions separated by 1 week. In a randomized sequence, the deep layers of the masseter, superficial layers of the masseter, anterior temporalis, lateral pterygoid, medial pterygoid, and anterior digastric muscles were injected with 5.8% hypertonic saline (0.2 mL). The subjects rated the perceived intensity of pain on an electronic 0- to 10-cm visual analog scale (VAS). The distribution of pain was drawn by the subjects on anatomical maps of the face, and a Danish version of the McGill Pain Questionnaire (MPQ) was filled out. All injections were associated with moderate to strong pain intensity (mean peak value: 5.6 to 6.4 cm) with no significant differences between muscle sites (analysis of variance [ANOVA]: P = .520). Pain rating indices derived from the MPQ did not suggest significant differences between muscle sites (ANOVA: P = .898). However, the area of perceived pain differed significantly between muscle sites (ANOVA: P = .038) with the greatest area following the injection into the anterior temporalis muscle (Tukey: P < .05). On direct inspection, the pain maps appeared quite similar, but a new analysis technique based on a center-of-gravity method revealed significantly different coordinates and length of vectors (ANOVA: P < .001) with longer vectors associated with the pain areas in the anterior temporalis muscle compared with the other muscle sites (Tukey: P < .05). All muscles were frequently associated with referral of pain to intraoral structures (40% to 87%), but only pain in the anterior digastric muscle was referred to the tip of the tongue (53%). The data suggest no major differences in pain sensitivity between the examined jaw-muscle sites, but pain in the anterior temporalis muscle spreads to a larger area independent of pain intensity. There are subtle but detectable differences in the location and referral of pain patterns between jaw muscles. This will be helpful in the differential diagnosis of myofascial temporomandibular disorder pain.


Ameloglyphics and predilection of dental caries.
Dental caries is an infectious disease of microbiologic origin resulting in destruction and loss of tooth structure and is related to every speciality of dentistry. Many studies have been carried out to identify the causative factors, methods of prevention, and treatment of dental caries. Ameloglyphics is the study of enamel rod end patterns. These patterns have been found to be unique to individual teeth of the same individual and also to different individuals. A possible correlation between the type of enamel rod end pattern and the occurrence of dental caries might help in predicting caries susceptibility of an individual and implementation of preventive measures. This is a simple and easy method cutting short elaborate methods currently in use and can be invaluable in caries prevention. This study is aimed at ascertaining the possibility of a correlation between enamel rod end patterns and occurrence of dental caries, which might help in identifying predisposition to dental caries. Thirty carious and 30 noncarious teeth were used to obtain enamel rod end patterns. Occurrence of any particular pattern in either of the study groups, which might affect the predisposition of teeth to dental caries was analyzed. No particular rod end pattern was found in teeth affected by dental caries. Also, no particular pattern was found to be unique to teeth not affected by dental caries.


Detection of metastases from head and neck cancers.
Before treatment for head and neck malignancies is begun, a search for distant metastases (DM) is performed. The first objective of this review was to determine the accuracy of liver function tests (LFT), alkaline phosphatase (AP) tests, and chest radiographs (CXR) in detection of DM. Second, an effort was made to identify tumor characteristics which are associated with a higher incidence of DM and therefore justify the use of more precise screening tools. An analysis of 97 patients with noncutaneous squamous cell carcinomas presenting to the Stanford Head and Neck Tumor Board in 1991 revealed 17 DM in 14 patients. There were 10 pulmonary metastases, 5 bone metastases, and 2 hepatic metastases. CXR had a sensitivity of 50% and a specificity of 94% for detection of pulmonary DM. AP tests showed a sensitivity of 20% and a specificity of 98% for detection of bone DM. LFT had a sensitivity of 50% and an 81% specificity for demonstration of hepatic DM. A separate analysis of 79 patients with known DM from two hospitals showed the incidence of DM to be increased in patients who had tumors of advanced stage, advanced T status, and poor histologic differentiation and to also be increased in the presence of local-regional recurrence. There was little association of DM with N status. The sensitivity of CXR and laboratory tests, which are currently used in evaluation for DM at most cancer centers, is disappointing; these tests should be viewed as gross screening examinations. We recommend a chest computed tomography scan in the event of an abnormal CXR, a bone scan in the event of an elevated AP, and either an ultrasound or computed tomography/magnetic resonance imaging scan of the liver when elevated LFT levels are present, depending on tumor stage and differentiation.


Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research.
Cannabidiol (CBD) is a non-intoxicating cannabinoid derived from Cannabis sativa. CBD initially drew scientific interest due to its anticonvulsant properties but increasing evidence of other therapeutic effects has attracted the attention of additional clinical and non-clinical populations, including athletes. Unlike the intoxicating cannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC), CBD is no longer prohibited by the World Anti-Doping Agency and appears to be safe and well-tolerated in humans. It has also become readily available in many countries with the introduction of over-the-counter "nutraceutical" products. The aim of this narrative review was to explore various physiological and psychological effects of CBD that may be relevant to the sport and/or exercise context and to identify key areas for future research. As direct studies of CBD and sports performance are is currently lacking, evidence for this narrative review was sourced from preclinical studies and a limited number of clinical trials in non-athlete populations. Preclinical studies have observed robust anti-inflammatory, neuroprotective and analgesic effects of CBD in animal models. Preliminary preclinical evidence also suggests that CBD may protect against gastrointestinal damage associated with inflammation and promote healing of traumatic skeletal injuries. However, further research is required to confirm these observations. Early stage clinical studies suggest that CBD may be anxiolytic in "stress-inducing" situations and in individuals with anxiety disorders. While some case reports indicate that CBD improves sleep, robust evidence is currently lacking. Cognitive function and thermoregulation appear to be unaffected by CBD while effects on food intake, metabolic function, cardiovascular function, and infection require further study. CBD may exert a number of physiological, biochemical, and psychological effects with the potential to benefit athletes. However, well controlled, studies in athlete populations are required before definitive conclusions can be reached regarding the utility of CBD in supporting athletic performance.


Topological effects on dynamics in complex pulse-coupled networks of integrate-and-fire type.
For a class of integrate-and-fire, pulse-coupled networks with complex topology, we study the dependence of the pulse rate on the underlying architectural connectivity statistics. We derive the distribution of the pulse rate from this dependence and determine when the underlying scale-free architectural connectivity gives rise to a scale-free pulse-rate distribution. We identify the scaling of the pairwise coupling between the dynamical units in this network class that keeps their pulse rates bounded in the infinite-network limit. In the process, we determine the connectivity statistics for a specific scale-free network grown by preferential attachment.


Momentum-Resolved Electronic Structure of the High-T_{c} Superconductor Parent Compound BaBiO_{3}.
We investigate the band structure of BaBiO_{3}, an insulating parent compound of doped high-T_{c} superconductors, using in situ angle-resolved photoemission spectroscopy on thin films. The data compare favorably overall with density functional theory calculations within the local density approximation, demonstrating that electron correlations are weak. The bands exhibit Brillouin zone folding consistent with known BiO_{6} breathing distortions. Though the distortions are often thought to coincide with Bi^{3+}/Bi^{5+} charge ordering, core level spectra show that bismuth is monovalent. We further demonstrate that the bands closest to the Fermi level are primarily oxygen derived, while the bismuth 6s states mostly contribute to dispersive bands at deeper binding energy. The results support a model of Bi-O charge transfer in which hole pairs are localized on combinations of the O 2p orbitals.


Genome-wide researches and applications on Dendrobium.
This review summarizes current knowledge of chromosome characterization, genetic mapping, genomic sequencing, quality formation, floral transition, propagation, and identification in Dendrobium. The widely distributed Dendrobium has been studied for a long history, due to its important economic values in both medicine and ornamental. In recent years, some species of Dendrobium and other orchids had been reported on genomic sequences, using the next-generation sequencing technology. And the chloroplast genomes of many Dendrobium species were also revealed. The chromosomes of most Dendrobium species belong to mini-chromosomes, and showed 2n = 38. Only a few of genetic studies were reported in Dendrobium. After revealing of genomic sequences, the techniques of transcriptomics, proteomics and metabolomics could be employed on Dendrobium easily. Some other molecular biological techniques, such as gene cloning, gene editing, genetic transformation and molecular marker developing, had also been applied on the basic research of Dendrobium, successively. As medicinal plants, insights into the biosynthesis of some medicinal components were the most important. As ornamental plants, regulation of flower related characteristics was the most important. More, knowledge of growth and development, environmental interaction, evolutionary analysis, breeding of new cultivars, propagation, and identification of species and herbs were also required for commercial usage. All of these studies were improved using genomic sequences and related technologies. To answer some key scientific issues in Dendrobium, quality formation, flowering, self-incompatibility and seed germination would be the focus of future research. And genome related technologies and studies would be helpful.


The relationship between antibody to R7V and progression of HIV type 1 infection.
The presence of antibody to R7V (anti-R7VAb), a seven-amino acid sequence derived from beta(2)-microglobulin incorporated into HIV-1 virions from the surface of infected cells, has been proposed as an early marker of nonprogressive HIV-1 infection. The present study was undertaken because no prospective studies have tested this hypothesis. Stored samples collected prospectively from 361 HIV-1 seroconverting men in the Multicenter AIDS Cohort Study (0.44-1.53 years after seroconversion) were assayed for the presence or absence of anti-R7VAb, using a standardized ELISA. Using Cox proportional hazards models, crude and adjusted relative hazards (RH) were determined for the following outcomes: (a) clinically defined AIDS, (b) clinically defined AIDS or CD4 T cell count of <200 cells/microl, and (c) death. A total of 143 (39.6%) men had early anti-R7VAb and 218 (60.4%) did not; 192 (53.2%) developed AIDS. At the visit tested, men with anti-R7VAb had significantly lower CD4 T cell counts and higher plasma HIV-1 viral loads than those without antibody. After adjustment for CD4 T cell count, HIV-1 viral load, CCR5 polymorphism, and use of combined antiretroviral therapy, the presence of anti-R7VAb was associated with a higher risk of progression for all outcomes, but not significantly so. Absence of anti-R7VAb was significantly associated with expression of HLA-B*5701 and -B*2705, two alleles associated with slower progression of HIV-1 disease. The early presence of anti-R7VAb in HIV-1 seroconverters was not associated with slower progression of HIV-1 disease.


Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain.
Prolactin gene expression is negatively regulated by glucocorticoids, and by estrogens when positive estrogen regulatory elements in the prolactin gene are removed. Mutational analysis of estrogen receptor confirms that inhibition is a function of receptor, and that transcriptional activation and inhibition require distinct, separable structural elements. Inhibition is dependent on a 63 amino acid region (amino acids 251-314) distinct from the DNA-binding and steroid-binding domains. The comparable region of glucocorticoid receptor confers inhibitory actions on a hybrid receptor. Multiple, nonoverlapping sequences in the rat prolactin 5'-flanking genomic region that confer inhibition by both steroid hormones contain related cis-active elements that bind a common, tissue-specific positive transcription factor, called Pit-1. Experimental results indicate that positive and negative transcriptional effects of estrogen receptor are mediated by separate functional domains, and suggest the protein-protein interactions between steroid hormone receptors and other transcription factor(s) mediate inhibition.


Mobilizing unused resources: using the placebo concept to enhance cognitive performance.
People have significant psychological resources to improve their well-being and performance, but these resources often go unused and could be better harnessed. In the medical domain, it is well established that these resources can be mobilized under certain conditions, for example in the context of the placebo effect. Here we explored whether the placebo principle can be used to enhance cognitive performance. To do so, we employed a modified placebo induction--a bogus priming method that we told participants would unconsciously enhance their knowledge and that they should hence trust their skills in an upcoming knowledge test. Participant performance was indeed enhanced, compared to a group that did not think the priming process would improve their knowledge. The study documents the relevance of the placebo effect outside the medical and therapeutic setting.


An inter-laboratory study to investigate the impact of the bioinformatics component on microbiome analysis using mock communities.
Despite the advent of whole genome metagenomics, targeted approaches (such as 16S rRNA gene amplicon sequencing) continue to be valuable for determining the microbial composition of samples. Amplicon microbiome sequencing can be performed on clinical samples from a normally sterile site to determine the aetiology of an infection (usually single pathogen identification) or samples from more complex niches such as human mucosa or environmental samples where multiple microorganisms need to be identified. The methodologies are frequently applied to determine both presence of micro-organisms and their quantity or relative abundance. There are a number of technical steps required to perform microbial community profiling, many of which may have appreciable precision and bias that impacts final results. In order for these methods to be applied with the greatest accuracy, comparative studies across different laboratories are warranted. In this study we explored the impact of the bioinformatic approaches taken in different laboratories on microbiome assessment using 16S rRNA gene amplicon sequencing results. Data were generated from two mock microbial community samples which were amplified using primer sets spanning five different variable regions of 16S rRNA genes. The PCR-sequencing analysis included three technical repeats of the process to determine the repeatability of their methods. Thirteen laboratories participated in the study, and each analysed the same FASTQ files using their choice of pipeline. This study captured the methods used and the resulting sequence annotation and relative abundance output from bioinformatic analyses. Results were compared to digital PCR assessment of the absolute abundance of each target representing each organism in the mock microbial community samples and also to analyses of shotgun metagenome sequence data. This ring trial demonstrates that the choice of bioinformatic analysis pipeline alone can result in different estimations of the composition of the microbiome when using 16S rRNA gene amplicon sequencing data. The study observed differences in terms of both presence and abundance of organisms and provides a resource for ensuring reproducible pipeline development and application. The observed differences were especially prevalent when using custom databases and applying high stringency operational taxonomic unit (OTU) cut-off limits. In order to apply sequencing approaches with greater accuracy, the impact of different analytical steps needs to be clearly delineated and solutions devised to harmonise microbiome analysis results.


Current management of pelvic fracture urethral injuries: to realign or not?
The acute management of pelvic fracture urethral injuries (PFUIs) remains a controversial topic. Currently, suprapubic tube (SPT) placement with delayed repair or primary realignment (PR) represents the strategies used to treat patients. While many will advocate the use of one technique over the other, the 2014 American Urological Association (AUA) Guidelines give providers the option for the management PFUI. Current literature evaluates these two interventions, focusing on the incidence of re-stricture formation, erectile dysfunction, and urinary incontinence. Here we perform a comprehensive review of the current management for PFUI, as well as, discuss the limitations of the studies and need for more prospective studies on this debated topic.


Drug Repurposing Screen Identifies Foxo1-Dependent Angiopoietin-2 Regulation in Sepsis.
The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). Research laboratories of Hannover Medical School and Harvard Medical School. Septic patients/C57Bl/6 mice and human endothelial cells. Food and Drug Administration-approved library screening. In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.


[A randomized controlled trials on treatment of cervicogenic sudden hearing loss with chiropractic].
To investigate the clinical effect and safety of chiropractic in treating cervicogenic sudden hearing loss. From January 2011 to October 2013, 90 patients with cervicogenic sudden hearing loss were randomly divided into treatment group and control group according to the random number table produced by SPSS 19.0 software. In the treatment group, there were 17 males and 28 females, aged from 31 to 62 years old with an average of (47.57±9.43) years; course of disease was from 1 to 3 days with an average of (1.43±0.68) days; pure-tone audiometry score was from 46.5 to 77.8 dB with the mean of (61.20±9.83) dB; Northwick Park Neck Pain Questionnaire (NPQ) score was from 17 to 31 scores with an average of (23.46±7.18) scores. In the control group, there were 15 males and 30 females, aged from 28 to 64 years old with an average of (45.77±6.99) years; course of disease was from 1 to 3 days with an average of (1.50±0.73) days; pure-tone audiometry score was from 48.1 to 75.0 dB with the mean of (63.91±8.05) dB; Northwick Park Neck Pain Questionnaire (NPQ) score was from 20 to 29 scores with an average of (25.61±10.43) scores. The patients of control group were treated with dexamethasone intravenous drip of 10 mg, 3 days later, decreased to 5 mg, 3 days again. And with the methycobal intravenous drip of 500 μg, treatment continued for 10 days. The patients of treatment group were treated with chiropractic additionally except for the therapeutic methods of control group. Chiropractic included local muscle loosening, attacking point, bilateral pulling atlanto-axial joint, and continuous treatment for 10 days. The pure-tone audiometry score and NPQ score were compared between two groups after treatment. After the treatment, pure-tone audiometry score and NPQ score in treatment group improved to (40.23± 8.14) dB and (12.70±8.29) scores respectively, which were obviously better than that of control group's (37.70±10.61) dB and (21.24±11.13) scores (P<0.05). Compared with routine method for cervicogenic sudden hearing loss, additional chiropractic can improve hearing and relieve neck pain effectively.


A Comparison Between the Conventional and the Laryngoscope-Assisted Lightwand Intubation Techniques in Patients With Cervical Immobilization: A Prospective Randomized Study.
Positioning of a lightwand in the midline of the oral cavity can be challenging in patients with cervical immobilization. Direct laryngoscopy may permit the lightwand tip to more easily access the glottic opening. We tested our hypothesis that a laryngoscope-assisted lightwand technique allows more successful endotracheal intubation than does a conventional lightwand approach. A total of 162 patients requiring cervical immobilization during intubation for cervical spine surgery were allocated randomly to 2 groups. The conventional lightwand technique (group C, n = 80) or the laryngoscope-assisted lightwand technique (group L, n = 82) was used for endotracheal intubation. In the group L, a Macintosh laryngoscope was inserted into the oral cavity, advanced until the epiglottis tip was visible, but not used to lift the epiglottis tip. The lightwand tip was placed below the epiglottis under direct view of the epiglottis tip. The primary outcome (the initial intubation success rate) and secondary outcomes (intubation time, hemodynamic changes, and postoperative airway complications) were evaluated. The initial intubation success rate was significantly lower (75% vs 89%; relative risk [95% confidence interval]: 1.2 [1.0-1.4]; P = .034) in group C than group L. The intubation time (22 ± 13 vs 24 ± 12 seconds; mean difference [98.33% confidence interval]: 2.4 [-2.3 to 7.2]; P = .217) did not differ between groups. Postoperative sore throat score, incidences of hypertension and tachycardia, postoperative oral mucosal bleeding, and hoarseness also did not differ between groups. Laryngoscope-assisted lightwand intubation did not increase intubation time, and it increased first attempt intubation rates compared with traditional lightwand intubation in patients requiring cervical immobilization for cervical spine surgery.


Exogenous IFN-gamma ex vivo shapes the alloreactive T-cell repertoire by inhibition of Th17 responses and generation of functional Foxp3+ regulatory T cells.
Interferon (IFN)-gamma was originally characterized as a pro-inflammatory cytokine with T helper type 1-inducing activity, but subsequent work has demonstrated that mice deficient in IFN-gamma or IFN-gamma receptor show exacerbated inflammatory responses and accelerated allograft rejection, suggesting that IFN-gamma also has important immunoregulatory functions. Here, we demonstrate that ex vivo IFN-gamma conditioning of CD4 T cells driven by allogeneic immature dendritic cells (DC) results in the emergence of a Foxp3(+) regulatory T-cell (Treg)- dominant population that can prevent allograft rejection. The development of this population involves conversion of non-Treg precursors, preferential induction of activation-induced cell death within the non-Treg population and suppression of Th2 and Th17 responses. The suppressive activity of IFN-gamma is dependent on the transcription factor signal transducer and activator of transcription 1 and is mediated by induced nitric oxide. These data indicate not only how IFN-gamma could be used to shape beneficial immune responses ex vivo for possible cell therapy but also provide some mechanistic insights that may be relevant to exacerbated inflammatory responses noted in several autoimmune and transplant models with IFN-gamma deficiency.


Physician Training and Qualification to Educate Patients on Attention-Deficit/Hyperactivity Disorder Stimulant Diversion and Misuse.
The increased number of adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) in recent years has raised concerns regarding diversion and misuse of prescription stimulant medications. As prescribers of these medications, physicians must be prepared to educate patients on these issues. This is the first study to evaluate physician training and qualification to educate adolescent patients on stimulant diversion and misuse. A questionnaire was developed and mailed to a national sample of child and adolescent psychiatrists (CAPs), child neurologists (CNs), and developmental-behavioral pediatricians (DBPs) in the United States. In addition to descriptive statistics, multivariable regressions (log-binomial and ordinal logistic) were performed to identify differences between subspecialists. The final sample consisted of 826 physicians who currently prescribe stimulants. Only 48% of physicians reported receiving formal training on prescription drug diversion (PDD) in medical school, residency, and/or fellowship. Twenty five percent and 48% of physicians felt inadequately qualified to educate patients on the health and legal consequences, respectively, of stimulant misuse and diversion. CAPs were more likely to have received formal training and felt better qualified to educate patients than CNs and DBPs. Physicians who received formal training were 2.4 times more likely to feel adequately qualified to educate patients on these issues. Only 58% of physicians correctly answered a legal question relating to stimulant diversion. Most physicians have not received formal training on PDD and many feel inadequately qualified to educate patients on the health and legal consequences of stimulant misuse and diversion. Increased training is needed so physicians can effectively educate patients with ADHD.


Responses to symptom induction exercises in panic disorder.
Exposure to panic symptoms (interoceptive exposure) is often included as part of treatment for panic disorder (PD), although little is known about the relative effects of particular symptom induction exercises. This study describes responses of individuals with PD and nonclinical controls to 13 standard symptom induction exercises and 3 control exercises. Generally, individuals with PD responded more strongly to symptom induction exercises than did controls. The exercises producing the most fear included spinning, hyperventilation, breathing through a straw, and using a tongue depressor. This study also reports findings regarding specific symptoms triggered by each exercise, the percentage of participants reporting fear during each exercise, and predictors of fear.


Master key generation to avoid the use of an external reference wave in an experimental JTC encrypting architecture.
In experimental optodigital encrypting architectures, the use of a reference wave is essential. In this contribution, we present an experimental alternative to avoid the reference wave during the encrypting procedure in a joint transform correlator architecture by introducing the concept of a master key. Besides, the master key represents an additional security element for the entire protocol. In our method, the master key is holographically processed and used during the encryption process with the encrypting key. We give the mathematical description for the process in case of a single input object and then we extend it to multiple input objects. We present the experimental demonstration of the proposed method including two examples where this technique is successfully applied for several input objects.


Inhibition of leukocyte-endothelial cell interactions and inflammation by peptides from a bacterial adhesin which mimic coagulation factor X.
Factor X (factor ten) of the coagulation cascade binds to the integrin CD11b/CD18 during inflammation, initiating procoagulant activity on the surface of leukocytes (Altieri, D.C., O.R. Etingin, D.S. Fair, T.K. Brunk, J.E. Geltosky, D.P. Hajjar, and T. S. Edgington. 1991. Science [Wash.DC]. 254:1200-1202). Filamentous hemagglutinin (FHA), an adhesin of Bordetella pertussis also binds to the CD11b/CD18 integrin (Relman D., E. Tuomanen, S. Falkow, D.T. Golenbock, K. Saukkonen, and S.D. Wright. 1990. Cell. 61:1375-1382). FHA and the CD11b/CD18 binding loops of Factor X share amino acid sequence similarity. FHA peptides similar to Factor X binding loops inhibited 125I-Factor X binding to human neutrophils and prolonged clotting time. In addition, ETKEVDG and its Factor X analogue prevented transendothelial migration of leukocytes in vitro and reduced leukocytosis and blood brain barrier disruption in vivo. Interference with leukocyte migration by a coagulation-based peptide suggests a novel strategy for antiinflammatory therapy.


Subjective perceptions to the intravenous "rush" of heroin and cocaine in opioid addicts.
Subjective responses to intravenous heroin and cocaine administration were investigated by questionnaire in a population of 40 male and 29 female confirmed heroin addicts. Responses of males and females were very similar for the heroin rush, ranking pleasure, relaxation, satisfaction, warmth, and thirst highest among 20 feelings surveyed and ranking feelings like sexual orgasm low, only fifteenth out of 20. Responses of males and females for the cocaine rush were similar in that both ranked excitement, pleasure, thirst, strength, and anxiety very high, in the top six responses, and both rated feelings like sexual orgasm relatively low, rank 9 for males and 15 for females. However, male and female responses for cocaine differed in that males ranked power very high, rank 2; and females ranked power relatively low, rank 10; but ranked satisfaction, rank 5; warmth, rank 5; and relaxation, rank 12; much higher than males who ranked them 15, 16, and 17, respectively. Despite the fact that sexual feelings were infrequently identified with rushes, the results best supported an interpretation that the population was largely inorgasmic without drugs, but found attractive orgasmic pleasure in heroin and cocaine. Males and females perceived the cocaine rush differently, but the reason of these differences is uncertain.


Mindfulness-based interventions for youth in the criminal justice system: a review of the research-based literature.
Mindfulness is a technique and sense of being present in the moment that incorporates aspects of acceptance, openness and meditation with the ultimate intention of improving well-being. Research indicates that mindfulness can significantly improve negative personality traits, reduce stress, increase attention, alleviate chronic pain and enhance mental health. Mindfulness-based interventions in correctional facilities have resulted in reduced hostility and improved self-esteem for adults, but less is known about its applicability amongst youth. This article reviews the research-based literature on the use of mindfulness-based interventions for youths (aged 13 to 24 years) involved in the justice system. A total of ten studies were located and synthesised into four themes of stress reduction, self-regulation, anger management and acceptance. The article concludes by considering the methodological rigour of the reviewed studies, providing recommendations for future research and contemplating the positive impact that mindfulness interventions might have on youth in the criminal justice system.


The Senolytic Drug Navitoclax (ABT-263) Causes Trabecular Bone Loss and Impaired Osteoprogenitor Function in Aged Mice.
Senescence is a cellular defense mechanism that helps cells prevent acquired damage, but chronic senescence, as in aging, can contribute to the development of age-related tissue dysfunction and disease. Previous studies clearly show that removal of senescent cells can help prevent tissue dysfunction and extend healthspan during aging. Senescence increases with age in the skeletal system, and selective depletion of senescent cells or inhibition of their senescence-associated secretory phenotype (SASP) has been reported to maintain or improve bone mass in aged mice. This suggests that promoting the selective removal of senescent cells, via the use of senolytic agents, can be beneficial in the treatment of aging-related bone loss and osteoporosis. Navitoclax (also known as ABT-263) is a chemotherapeutic drug reported to effectively clear senescent hematopoietic stem cells, muscle stem cells, and mesenchymal stromal cells in previous studies, but its in vivo effects on bone mass had not yet been reported. Therefore, the purpose of this study was to assess the effects of short-term navitoclax treatment on bone mass and osteoprogenitor function in old mice. Aged (24 month old) male and female mice were treated with navitoclax (50 mg/kg body mass daily) for 2 weeks. Surprisingly, despite decreasing senescent cell burden, navitoclax treatment decreased trabecular bone volume fraction in aged female and male mice (-60.1% females, -45.6% males), and BMSC-derived osteoblasts from the navitoclax treated mice were impaired in their ability to produce a mineralized matrix (-88% females, -83% males). Moreover, in vitro administration of navitoclax decreased BMSC colony formation and calcified matrix production by aged BMSC-derived osteoblasts, similar to effects seen with the primary BMSC from the animals treated in vivo. Navitoclax also significantly increased metrics of cytotoxicity in both male and female osteogenic cultures (+1.0 to +11.3 fold). Taken together, these results suggest a potentially harmful effect of navitoclax on skeletal-lineage cells that should be explored further to definitively assess navitoclax's potential (or risk) as a therapeutic agent for combatting age-related musculoskeletal dysfunction and bone loss.


Judo strategy. The competitive dynamics of Internet time.
Competition on the Internet is creating fierce battles between industry giants and small-scale start-ups. Smart start-ups can avoid those conflicts by moving quickly to uncontested ground and, when that's no longer possible, turning dominant players' strengths against them. The authors call this competitive approach judo strategy. They use the Netscape-Microsoft battles to illustrate the three main principles of judo strategy: rapid movement, flexibility, and leverage. In the early part of the browser wars, for instance, Netscape applied the principle of rapid movement by being the first company to offer a free stand-alone browser. This allowed Netscape to build market share fast and to set the market standard. Flexibility became a critical factor later in the browser wars. In December 1995, when Microsoft announced that it would "embrace and extend" competitors' Internet successes, Netscape failed to give way in the face of superior strength. Instead it squared off against Microsoft and even turned down numerous opportunities to craft deep partnerships with other companies. The result was that Netscape lost deal after deal when competing with Microsoft for common distribution channels. Netscape applied the principle of leverage by using Microsoft's strengths against it. Taking advantage of Microsoft's determination to convert the world to Windows or Windows NT, Netscape made its software compatible with existing UNIX systems. While it is true that these principles can't replace basic execution, say the authors, without speed, flexibility, and leverage, very few companies can compete successfully on Internet time.


[Corneal melting after ocular surgery in patients with auto-immune disorders].
Two women aged 78 and 74 years respectively, both with dry eyes due to underlying auto-immune disorders, presented after uncomplicated cataract surgery with immunostromal corneal ulceration. Intensive topical lubrication combined with systemic immunosuppressants were necessary to control the corneal melt. Dry eyes are a frequently-encountered problem among patients with rheumatoid disorders and increase the risk of corneal melting. Auto-immune related corneal melting can occur spontaneously or after ocular surgery, it threatens visual acuity and ocular integrity and may be associated with systemic vasculitis. When treating patients with rheumatoid disorders, the presence of dry eyes and the accompanying risk of serious complications need to be ascertained. In patients at risk, pre-operative preventive measures to suppress any underlying systemic disorders and improve the ocular environment are necessary. When corneal melting is diagnosed, aggressive topical therapy combined with systemic immunosuppressants is indicated.


Safety of antithrombotic therapy for patients with acute ischemic stroke harboring unruptured intracranial aneurysm.
Background The safety of antithrombotic therapy for patients with acute ischemic stroke harboring unruptured intracranial aneurysms remains unclear. Aims This study was performed to determine whether treatment with antiplatelets, anticoagulants, or intravenous thrombolytic agents is safe for patients with acute ischemic stroke and unruptured intracranial aneurysms. Methods Among 9149 patients with acute ischemic stroke enrolled in the Fukuoka Stroke Registry from June 2007 to December 2014, 8857 patients with data on cerebrovascular imaging and three-month outcomes were included in this study. The frequency of adverse events, including intracranial hemorrhage, symptomatic intracranial hemorrhage, and in-hospital mortality, was compared between patients with and without unruptured intracranial aneurysms. The risk of a poor functional outcome (modified Rankin scale score of ≥3) at three months after stroke onset was estimated after adjusting for confounding factors by logistic regression analysis. Results Unruptured intracranial aneurysms were identified in 412 (4.7%) patients, and the mean diameter was 4.1 ± 3.2 mm. There was no significant difference in the frequency of any adverse events between patients with and without unruptured intracranial aneurysms among the overall patients or patients receiving antiplatelets, anticoagulants, or intravenous thrombolytic agents. The odds ratios of a poor functional outcome were not significantly higher in the presence of unruptured intracranial aneurysms, even in patients undergoing antiplatelet therapy, anticoagulation therapy, or intravenous thrombolysis. Conclusions These findings suggest that unruptured intracranial aneurysms are not associated with increased risks of adverse events or poor functional outcomes even after antithrombotic therapy for acute ischemic stroke. However, accumulation of cases is required to verify these findings.


A blocking ELISA for the detection of specific antibodies to bovine respiratory syncytial virus.
A blocking enzyme-linked immunosorbent assay (ELISA) has been adapted to detect specific antibodies in bovine sera to respiratory syncytial virus using a horseradish peroxidase-labeled monoclonal antibody to the fusion protein of the virus. This assay plus an indirect blocking ELISA and indirect ELISA were used to detect antibodies to the bovine respiratory syncytial virus (BRSV) in 159 field-origin bovine sera. Results of these assays were compared with serum antibody titers measured by the serum neutralization (SN) test. Over a 56-day period, the mean neutralization titers and the mean delta absorbance values for the blocking ELISA, on the same sera, showed similar declines. However, the calculated correlation coefficients between mean SN titer and mean absorbance value for the blocking ELISA of the individual sera ranged from -0.2 to -0.5 depending on the source of sera. Similar values were obtained whether using crude or purified viral antigen in the assays. Corresponding calculated correlation coefficients were generally higher for the indirect blocking ELISA or indirect ELISA than for the blocking ELISA. The blocking ELISA was between 70 and 64% as sensitive as the serum neutralization test with a specificity of 100 or 90% using the crude and purified viral antigen, respectively. The indirect blocking ELISA and indirect ELISA had similar calculated sensitivities and specificities. The blocking ELISA was faster to run than either of the other ELISA's or the neutralization test. Further, nonspecific background absorbance was obviated because the blocking ELISA detects antibodies to 1 specific viral protein, the fusion protein. These studies suggest that the blocking ELISA should be useful as a serological test for BRSV antibodies.


Long-term exposure to microwave radiation provokes cancer growth: evidences from radars and mobile communication systems.
In this review we discuss alarming epidemiological and experimental data on possible carcinogenic effects of long term exposure to low intensity microwave (MW) radiation. Recently, a number of reports revealed that under certain conditions the irradiation by low intensity MW can substantially induce cancer progression in humans and in animal models. The carcinogenic effect of MW irradiation is typically manifested after long term (up to 10 years and more) exposure. Nevertheless, even a year of operation of a powerful base transmitting station for mobile communication reportedly resulted in a dramatic increase of cancer incidence among population living nearby. In addition, model studies in rodents unveiled a significant increase in carcinogenesis after 17-24 months of MW exposure both in tumor-prone and intact animals. To that, such metabolic changes, as overproduction of reactive oxygen species, 8-hydroxi-2-deoxyguanosine formation, or ornithine decarboxylase activation under exposure to low intensity MW confirm a stress impact of this factor on living cells. We also address the issue of standards for assessment of biological effects of irradiation. It is now becoming increasingly evident that assessment of biological effects of non-ionizing radiation based on physical (thermal) approach used in recommendations of current regulatory bodies, including the International Commission on Non-Ionizing Radiation Protection (ICNIRP) Guidelines, requires urgent reevaluation. We conclude that recent data strongly point to the need for re-elaboration of the current safety limits for non-ionizing radiation using recently obtained knowledge. We also emphasize that the everyday exposure of both occupational and general public to MW radiation should be regulated based on a precautionary principles which imply maximum restriction of excessive exposure.


Antibody-mediated disease remission in the mouse model of lyme borreliosis.
In the mouse model of Lyme borreliosis, the host immune response during infection with Borrelia burgdorferi results in the remission of carditis and arthritis, as well as global reduction of spirochete numbers in tissues, without elimination of infection. These events were recapitulated by passive transfer of immune serum from infected immunocompetent mice or T-cell-deficient mice to severe combined immunodeficient (SCID) mice. Previous studies have shown that immune serum is reactive against arthritis-related protein (Arp) and that Arp antiserum induces arthritis remission. However, although immune serum from T-cell-deficient mice induced disease remission, it was not reactive against Arp, suggesting that antibody to another antigen may be responsible. T-cell-deficient mouse immune serum was reactive to decorin binding protein A (DbpA). Therefore, DbpA antiserum was tested to determine its ability to induce disease remission in SCID mice. Antisera to Arp or DbpA induced both carditis and arthritis remission but did not significantly reduce spirochete numbers in tissues, based upon quantitative flaB DNA analysis, nor did treatment affect RNA levels of several genes, including arp and dbpA. Immunohistochemical labeling of spirochetes in hearts and joints during disease remission induced by adoptive transfer of lymphocytes, passive transfer of immune serum, or passive transfer of DbpA antiserum revealed that such treatment resulted in elimination of spirochetes from heart base and synovium but not vascular walls, tendons, or ligaments. These results suggest that Arp and DbpA antibodies may be active as disease-resolving components in immune serum but antibody against other antigens may be involved in reductions of spirochetes in tissues.


Phagocyte-specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease.
Phagocyte-derived S100 proteins are endogenous activators of innate immune responses. S100A12 binds to the receptor for advanced glycation end-products, while complexes of S100A8/S100A9 (myeloid-related proteins, MRP8/14; calprotectin) are ligands of toll-like receptor 4. These S100 proteins can be detected in stool. In the present study we analyse the release of S100A12 and MRP8/14 from intestinal tissue. Specimens from patients with Crohn's disease (CD; n = 30), ulcerative colitis (UC; n = 30), irritable bowel syndrome (IBS; n = 30) or without inflammation (n = 30) were obtained during endoscopy. After 24 h culture, S100A12 and MRP8/14 were analysed in supernatants. Endoscopic, histological, laboratory and clinical disease activity measures were documented. We found an increased spontaneous release of S100A12 from tissue in inflammatory bowel disease (IBD). The release of S100A12 into the supernatants was 28-fold enhanced in inflamed tissue when compared to non-inflamed tissue (mean 46.9 vs. 1.7 ng/ml, p < 0.0001). In active CD, release of S100A12 and MRP8/14 was strongly dependent on localization, with little release from sites of active ileal inflammation compared to colonic inflammation. This difference was more pronounced for S100A12 than for MRP8/14. S100A12 and MRP8/14 provoked up-regulation of adhesion molecules and chemokines on human intestinal microvascular endothelial cells (HIMECs) isolated from normal colonic tissue. The direct release of phagocyte-derived S100 proteins from inflamed tissues may reflect secretion from infiltrating neutrophils (S100A12) and also monocytes or epithelial cells (MRP8/14). Via activation of pattern recognition receptors, these proteins promote inflammation in intestinal tissue. The enhanced mucosal release can explain the correlation of fecal markers with disease activity in IBD.


Increased risk of chronic otitis media in chronic rhinosinusitis patients: a longitudinal follow-up study using a national health screening cohort.
Chronic rhinosinusitis (CRS) and chronic otitis media (COM) share pathophysiological mechanisms such as bacterial infection, biofilm, and persistence of the obstruction state of ventilation routes. However, only a few studies have investigated the relationship between these two diseases nationwide and in the general population. The purpose of this study was to determine whether the incidence of COM in patients with CRS differed from that of a matched control from the national health screening cohort. Data from the Korean Health Insurance Review and Assessment Service-National Patient Samples were collected from 2002 to 2015. Participants who were treated ≥ ≥ ≥2 times and underwent head and neck computed tomography evaluation were selected. A 1:4 matched CRS group (n=8,057) and a control group (n=32,228) were selected. The control group included participants who were never treated with the ICD-10 code J32 from 2002 to 2015. The CRS group included CRS patients with/without nasal polyps. The incidence of COM was significantly higher in the CRS group than in the control group. In a subgroup analysis, the incidence of COM in all age groups and in men and women was significantly higher in the CRS group than in the control group. More, CRS increased the risk of COM. A significant association was observed between CRS and COM. This indicates that CRS patients have a high risk of developing COM.


Diffuse proliferative glomerulonephritis associated with dermatomyositis with nephrotic syndrome.
We described a 44-year-old man developing dermatomyositis (DM) and nephrotic syndrome (NS). Renal biopsy revealed diffuse proliferative glomerulonephritis (DPGN) with depositions of immunoglobulin and complements. A combination therapy of steroid and cyclophosphamide (CTX) was found very effective for the patient. Chronic glomerulonephritis is rare in DM. In our review of related literature, membranous glomerulonephritis (MN) is the main type of glomerular lesion, another type is mesangial proliferative glomerulonephritis (mesPGN). Here we reported a case of DM associated with DPGN developing NS, which was not found in existing literature. Although glomerulonephritis is uncommon in patients with DM, renal pathology is not as simplex as previously thought, and treatment with steroid or/and cytotoxic drugs is favorable for prognosis.


Zwitterionic and biradicaloid heteroatomic cyclopentane derivatives containing different group 15 elements.
The formal cyclopentane-1,3-diyl derivatives [E1(μ-NTer)2({E2C} = NDmp)] (Ter = 2,6-dimesityl-phenyl, Dmp = 2,6-dimethylphenyl) were prepared by 1,1-insertion of CNDmp into the N-E2 bond of [E1(μ-NTer)2E2] (E1 = N, P; E2 = P, As). The insertion does not occur for E1 = E2 = As or E2 = Sb. Dependent on the choice of formal radical centres E, either a biradicaloid or a zwitterion was obtained. The biradicaloid features a P and an As radical center and its biradical character was established by computations as well as characteristic reactivity with respect to the formation of a housane derivative and the activation of molecules bearing multiple bonds, which was demonstrated using the example of PC t Bu. In contrast, the formally N,As- and N,P-centered biradicaloids are better regarded as zwitterionic species in accord with computations and diminished reactivity, as neither housane formation nor activation of multiple bonds could be observed.


CNstream: a method for the identification and genotyping of copy number polymorphisms using Illumina microarrays.
Understanding the genetic basis of disease risk in depth requires an exhaustive knowledge of the types of genetic variation. Very recently, Copy Number Variants (CNVs) have received much attention because of their potential implication in common disease susceptibility. Copy Number Polymorphisms (CNPs) are of interest as they segregate at an appreciable frequency in the general population (i.e. > 1%) and are potentially implicated in the genetic basis of common diseases. This paper concerns CNstream, a method for whole-genome CNV discovery and genotyping, using Illumina Beadchip arrays. Compared with other methods, a high level of accuracy was achieved by analyzing the measures of each intensity channel separately and combining information from multiple samples. The CNstream method uses heuristics and parametrical statistics to assign a confidence score to each sample at each probe; the sensitivity of the analysis is increased by jointly calling the copy number state over a set of nearby and consecutive probes. The present method has been tested on a real dataset of 575 samples genotyped using Illumina HumanHap 300 Beadchip, and demonstrates a high correlation with the Database of Genomic Variants (DGV). The same set of samples was analyzed with PennCNV, one of the most frequently used copy number inference methods for Illumina platforms. CNstream was able to identify CNP loci that are not detected by PennCNV and it increased the sensitivity over multiple other loci in the genome. CNstream is a useful method for the identification and characterization of CNPs using Illumina genotyping microarrays. Compared to the PennCNV method, it has greater sensitivity over multiple CNP loci and allows more powerful statistical analysis in these regions. Therefore, CNstream is a robust CNP analysis tool of use to researchers performing genome-wide association studies (GWAS) on Illumina platforms and aiming to identify CNVs associated with the variables of interest. CNstream has been implemented as an R statistical software package that can work directly from raw intensity files generated from Illumina GWAS projects. The method is available at http://www.urr.cat/cnv/cnstream.html.