Spatial multi-criteria decision analysis for the selection of sentinel regions in tick-borne disease surveillance.

BACKGROUND: The implementation of cost-effective surveillance systems is essential for tracking the emerging risk of tick-borne diseases. In Canada, where Lyme disease is a growing public health concern, a national sentinel surveillance network was designed to follow the epidemiological portrait of this tick-borne disease across the country. The surveillance network consists of sentinel regions, with active drag sampling carried out annually in all regions to assess the density of Ixodes spp. ticks and prevalence of various tick-borne pathogens in the tick population. The aim of the present study was to prioritize sentinel regions by integrating different spatial criteria relevant to the surveillance goals. METHODS: We used spatially-explicit multi-criteria decision analyses (MCDA) to map priority areas for surveillance across Canada, and to evaluate different scenarios using sensitivity analyses. Results were shared with stakeholders to support their decision making for the selection of priority areas to survey during active surveillance activities. RESULTS: Weights attributed to criteria by decision-makers were overall consistent. Sensitivity analyses showed that the population criterion had the most impact on rankings. Thirty-seven sentinel regions were identified across Canada using this systematic and transparent approach. CONCLUSION: This novel application of spatial MCDA to surveillance network design favors inclusivity of nationwide partners. We propose that such an approach can support the standardized planning of spatial design of sentinel surveillance not only for vector-borne disease BDs, but more broadly for infectious disease surveillance where spatial design is an important component.

Trigeminal cold receptors and airflow perception are altered in chronic rhinosinusitis.

BACKGROUND: In chronic rhinosinusitis (CRS), nasal obstruction can often be explained by anatomical deformities, polyps, or congested nasal mucosa. However, in cases with little deformity or inflammation, perceived nasal obstruction may result from reduced airflow perception caused by an alteration of the intranasal trigeminal system. The aim of this study was to assess this association. METHODOLOGY: We performed a prospective case-control study of 15 CRS patients, 18 patients with a deviated nasal septum (DNS) and 16 healthy controls. We assessed olfactory function using the Sniffin' Sticks test and Visual Analog Scales (VAS). We used the Trigeminal Lateralization Task (TLT) with eucalyptol and cinnamaldehyde to examine intranasal trigeminal function. Further, we assessed nasal patency with Peak Nasal Inspiratory Flow and VAS. Finally, we measured protein levels of trigeminal receptors (TRPM8, TRPA1 and TRPV1) and inflammatory markers (IL-13, INF-y and eosinophils) in CRS and DNS patients' mucosal biopsies using Western Blots. RESULTS: CRS patients had significantly lower olfactory function than DNS and healthy controls. They also had significantly lower TLT scores for eucalyptol than both other groups. CRS patients had significantly lower nasal patency than controls; for DNS patients this was limited to subjective measures of nasal patency. In line with this, CRS patients exhibited significantly higher levels of sTRPM8-18 than DNS patients. CONCLUSIONS: Intranasal trigeminal function is decreased in CRS patients, possibly due to the overexpression of short isoforms of TRPM8 receptors.

Estimating migration speed of glass eels during their colonization of a Mediterranean lagoon.

Migration speed can have important evolutionary consequences as it can affect the timing of arrival, remaining energy reserves, and habitat choice. Environmental conditions and individual phenotypic traits can impact the migration speed of individuals. In this way, estimating migration speed is of particular importance, especially for species under strong management strategies and colonizing highly diversified habitats, as is the case for the European eel. However, estimating the migration speed of glass eels, which is the life stage when eels colonize continental habitats, presents challenges due to typically low re-capture probabilities and difficulties in tagging individuals. Using recruitment time series at two sites, one at the sea connection and another inland, we estimated the temporal lag between the two migration peaks to compute migration speed. Because we worked on the Mediterranean coasts and in a lagoon, the weak tidal amplitudes may inhibit individuals from efficiently performing the selective tidal stream transport. We obtained migration speed values coherent with the few values available in the literature for Atlantic estuaries. The values we obtained that are lower than those obtained for Atlantic estuaries are also coherent with the weak tides along the Mediterranean coasts and lead to necessary further studies to understand the migratory behavior of glass eels in such hydro-systems.

Trigeminal impairment in treatment-refractory chronic nasal obstruction.

BACKGROUND: Patients with anatomically unexplained, chronic nasal obstruction (CNO) that is refractory to medical treatment pose a challenge for clinicians. A surgical solution, addressing mechanical obstacles, is unsuited for these patients. CNO may result from disrupted airflow perception due to activation of the intranasal trigeminal system; therefore, aim of this study is to evaluate if intranasal trigeminal function of these CNO patients is decreased. METHODS: In this retrospective cross-sectional study, we compared 143 CNO patients and 58 healthy volunteers, between 18 to 80 years old. We assessed nasal patency by means of rhinomanometry (RM) and measured susceptibility of intranasal trigeminal system by the trigeminal lateralization task (TLT). RESULTS: TLT scores were significantly lower in CNO patients compared to controls (p less than 0.001), but RM scores were not different between groups. Accordingly, TLT allowed to identify CNO patients with an accuracy of the area under the curve (AUC) of 0.78, while the value for RM was at chance (AUC=0.47). CNO patients showed normal reaction to vasoconstrictive agents with significantly lower RM values after Xylomethazoline application. CONCLUSION: Results suggest that reported nasal obstruction in CNO patients without any obvious anatomical obstacle and resistant to medical treatment may be linked to decreased perception of nasal airflow rather than physical obstruction. In this sub-set of CNO patients, trigeminal testing more adequately reflects the reported obstruction than nasal resistance assessment does. In future studies, the relation of the trigeminal status and the subjective sensation of nasal obstruction needs to be addressed with validated patient rated outcome measures (PROMs).

N Increased risk of tick-borne diseases with climate and environmental changes.

Climate warming and other environmental changes have contributed to the expansion of the range of several tick species into higher latitudes in North America. As temperatures increase in Canada, the environment becomes more suitable for ticks and the season suitable for tick activity lengthens, so tick-borne diseases are likely to become more common in Canada. In addition to Lyme disease, four other tick-borne diseases (TBDs) have started to emerge and are likely to increase: Anaplasmosis; Babesiosis; Powassan virus; and Borrelia miyamotoi disease. Increased temperature increases the survival and activity period of ticks, increases the range of both reservoir and tick hosts (e.g. mice and deer) and increases the duration of the season when people may be exposed to ticks. Other ticks and TBDs may spread into Canada as the climate changes. The public health strategies to mitigate the impact of all TBDs include surveillance to detect current and emerging TBDs, and public health actions to prevent infections by modifying environmental and social-behavioral risk factors through increasing public awareness. Clinical care strategies include patient education, early detection, laboratory testing, and treatment.

Using Earth observation images to inform risk assessment and mapping of climate change-related infectious diseases.

The number of human cases of several climate-related infectious diseases, including tick- and mosquito-borne diseases, has increased in Canada and other parts of the world since the end of the last century. Predicting and mapping the risks associated with these diseases using environmental and climatic determinants derived from satellite images is an emerging method that can support research, surveillance, prevention and control activities and help to better assess the impacts of climate change in Canada. Earth observation images can be used to systematically monitor changes in the Earth's surface and atmosphere at different scales of time and space. These images can inform estimation and monitoring of environmental and climatic determinants, and thus disease prediction and risk mapping. The current array of Earth observation satellites provides access to a large quantity and variety of data. These data have different characteristics in terms of spatial, temporal and thematic precision and resolution. The objectives of this overview are to describe how Earth observation images may inform risk assessment and mapping of tick-borne and mosquito-borne diseases in Canada, their potential benefits and limitations, the implications and next steps.

Quebec's Multi-Party Observatory on Zoonoses and Adaptation to Climate Change.

Climate change has been linked with the establishment and geographical expansion of zoonotic diseases, an example of which is the well-documented increase in human cases of Lyme disease in Quebec, Canada. As temperatures continue to increase in Quebec, it is anticipated that several zoonotic diseases will be affected. In response to the growing zoonotic issues facing public health authorities, Quebec's Multi-Party Observatory on Zoonoses and Adaptation to Climate Change (Observatoire multipartite québécois sur les zoonoses et l'adaptation aux changements climatiques) (the Observatory) was founded in 2015 as part of the Quebec government's Climate Change Action Plan (Plan d'action 2013-2020 sur les changements climatiques). The Observatory was designed to bring together agencies involved in formulating public policy and experts from the disciplines of human health, animal health and environmental sciences, in a manner similar to the innovative "One World, One Health" approach. The Observatory provides a platform for knowledge sharing and consensus building among representatives of public policy decision makers and scientists. Its main objectives are to anticipate and prioritize potential issues associated with zoonotic diseases in Quebec, in order to support applicable risk management and climate change adaptation. This article describes what the Observatory is, what it does and outlines its plans for the future.

What is the real number of Lyme disease cases in Canada?

BACKGROUND: Lyme disease is emerging in Canada due to expansion of the range of the tick vector Ixodes scapularis from the United States. National surveillance for human Lyme disease cases began in Canada in 2009. Reported numbers of cases increased from 144 cases in 2009 to 2025 in 2017. It has been claimed that few (< 10%) Lyme disease cases are reported associated with i) supposed under-diagnosis resulting from perceived inadequacies of serological testing for Lyme disease, ii) expectation that incidence in Canadian provinces and neighbouring US states should be similar, and iii) analysis of serological responses of dogs to the agent of Lyme disease, Borrelia burgdorferi. We argue that performance of serological testing for Lyme disease is well studied, and variations in test performance at different disease stages are accounted for in clinical diagnosis of Lyme disease, and in surveillance case definitions. Extensive surveillance for tick vectors has taken place in Canada providing a clear picture of the emergence of risk in the Canadian environment. This surveillance shows that the geographic scope of I. scapularis populations and Lyme disease risk is limited but increasing in Canada. The reported incidence of Lyme disease in Canada is consistent with this pattern of environmental risk, and the differences in Lyme disease incidence between US states and neighbouring Canadian provinces are consistent with geographic differences in environmental risk. Data on serological responses in dogs from Canada and the US are consistent with known differences in environmental risk, and in numbers of reported Lyme disease cases, between the US and Canada. CONCLUSION: The high level of consistency in data from human case and tick surveillance, and data on serological responses in dogs, suggests that a high degree of under-reporting in Canada is unlikely. We speculate that approximately one third of cases are reported in regions of emergence of Lyme disease, although prospective studies are needed to fully quantify under-reporting. In the meantime, surveillance continues to identify and track the ongoing emergence of Lyme disease, and the risk to the public, in Canada.

A per-cent-level determination of the nucleon axial coupling from quantum chromodynamics.

The axial coupling of the nucleon, gA, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of gA makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome1,2: contamination of gA from excited states must be controlled in the calculations and statistical precision must be improved markedly2-10. Here we use an unconventional method 11 inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a gA value of 1.271 ± 0.013, which has a precision of about one per cent.

Estimating the effective number of breeders from single parr samples for conservation monitoring of wild populations of Atlantic salmon Salmo salar.

This study assesses whether the effective number of breeders (Nb ) can be estimated using a time and cost-effective protocol using genetic sibship reconstruction from a single sample of young-of-the-year (YOY) for the purposes of Atlantic salmon Salmo salar population monitoring. Nb was estimated for 10 consecutive reproductive seasons for S. salar in the River Nivelle, a small population located at the rear-edge of the species distribution area in France, chronically under its conservation limit and subjected to anthropogenic and environmental changes. Subsampling of real and simulated data showed that accurate estimates of Nb can be obtained from YOY genotypes, collected at moderate random sampling intensity, achievable using routine juvenile electrofishing protocols. Spatial bias and time elapsed since spawning were found to affect estimates, which must be accounted for in sampling designs. Nb estimated in autumn for S. salar in the River Nivelle was low and variable across years from 23 (95% C.I. 14-41) to 75 (53-101) and was not statistically correlated with the estimated number of returning adults, but it was positively correlated with the estimated number of YOY at age 9 months. Nb was found to be lower for intermediate levels of redd aggregation, suggesting that the strength of the competition between males to access females affects reproductive success variance depending on redd spatial configuration. Thus, environmental factors such as habitat availability and quality for spawning and YOY development predominate over demographic ones (number of returning adults) in driving long-term population viability for S. salar in the River Nivelle. This study showcases Nb as an integrated parameter, encompassing demographic and ecological information about a reproductive event, relevant to the assessment of both short-term effects of management practices and long-term population conservation status.

Evaluating the submission of digital images as a method of surveillance for Ixodes scapularis ticks.

Widespread access to the internet is offering new possibilities for data collection in surveillance. We explore, in this study, the possibility of using an electronic tool to monitor occurrence of the tick vector of Lyme disease, Ixodes scapularis. The study aimed to compare the capacity for ticks to be identified in web-based submissions of digital images/photographs, to the traditional specimen-based identification method used by the provincial public health laboratory in Quebec, Canada. Forty-one veterinary clinics participated in the study by submitting digital images of ticks collected from pets via a website for image-based identification by an entomologist. The tick specimens were then sent to the provincial public health laboratory to be identified by the 'gold standard' method using a microscope. Of the images submitted online, 74·3% (284/382) were considered of high-enough quality to allow identification. The laboratory identified 382 tick specimens from seven different species, with I. scapularis representing 76% of the total submissions. Of the 284 ticks suitable for image-based species identification, 276 (97·2%) were correctly identified (Kappa statistic of 0·92, Z = 15·46, P < 0·001). This study demonstrates that image-based tick identification may be an accurate and useful method of detecting ticks for surveillance when images are of suitable quality.

Elucidating the Mechanism(s) Underlying Antipsychotic and Antidepressant-Mediated Fractures.

Mood spectrum disorders and medications used to treat these disorders, such as atypical antipsychotic drugs (AA), are associated with metabolic and endocrine side effects including obesity, dyslipidemia, hyperglycemia and increased risk of fractures. Antidepressant medications, including selective serotonin reuptake inhibitors (SSRI), have also been reported to increase fracture risk in some patients. The pharmacology underlying the increased risk of fractures is currently unknown. Possible mechanisms include alternations in dopaminergic and/or serotonergic signaling pathways. As these medications distribute to the bone marrow as well as to the brain, it is possible that drug-induced fractures are due to both centrally mediated effects as well as direct effects on bone turnover. Given the growing patient population that is prescribed these medications for both on- and off-label indications, understanding the level of risk and the mechanisms underlying drug-induced fractures is important for informing both prescribing and patient monitoring practices.

Relevance of omental pericellular adipose tissue collagen in the pathophysiology of human abdominal obesity and related cardiometabolic risk.

BACKGROUND: Adipose tissue fibrosis is a relatively new notion and its relationship with visceral obesity and cardiometabolic alterations remains unclear, particularly in moderate obesity. OBJECTIVE: Our objective was to examine if total and pericellular collagen accumulation are relevant for the pathophysiology of visceral obesity and related cardiometabolic risk. SUBJECTS AND METHODS: Surgical omental (OM) and subcutaneous (SC) fat samples were obtained in 56 women (age: 47.2±5.8 years; body mass index (BMI): 27.1±4.4 kg/m2). Body composition and fat distribution were measured by dual-energy X-ray absorptiometry and computed tomography, respectively. Total and pericellular collagen were measured using picrosirius red staining. CD68+ cells (total macrophages) and CD163+ cells (M2-macrophages) were identified using immunohistochemistry. RESULTS: We found that only pericellular collagen percentage, especially in OM fat, was associated with higher BMI, body fat mass and adipose tissue areas as well as lower radiologic attenuation of visceral adipose tissue and altered cardiometabolic risk variables. Strong correlations between peri-adipocyte collagen percentage and total or M2-macrophage percentages were observed in both depots. Total collagen percentage in either compartment was not related to adiposity, fat distribution or cardiometabolic risk. CONCLUSIONS: As opposed to whole tissue-based assessments of adipose tissue fibrosis, collagen deposition around the adipocyte, especially in the OM fat compartment is related to total and regional adiposity as well as altered cardiometabolic risk profile.

Effect of transmembrane pressure control on energy efficiency during skim milk concentration by ultrafiltration at 10 and 50°C.

The efficiency of the ultrafiltration process during skim milk concentration was studied using both dynamic and constant (465 or 672kPa) transmembrane pressure experiments at refrigerated temperature (10°C) and high temperature (50°C). The pilot-scale module was equipped with a 10-kDa polyethersulfone spiral-wound membrane element with a surface area of 2.04m2. Permeation flux, resistance-in-series model, mineral and protein rejection, and energy consumption were studied as a function of temperature and transmembrane pressure applied. Higher permeation flux values were systematically obtained at 50°C. Also, a significant temperature effect was found for calcium rejection, which was lower at 10°C compared with 50°C. Total hydraulic resistance and reversible fouling resistance were higher at 50°C than at 10°C. No change in protein rejection was observed, depending on the operating mode studied. Permeation flux, which was higher at 50°C, had lower pumping energy consumption compared with ultrafiltration at the colder temperature. Also, the low ultrafiltration temperature required a higher total energy consumption to reach the 3.6× retentate compared with ultrafiltration at 50°C. Overall, our study shows that the operating parameters and temperature can be optimized using an energy efficiency ratio.

Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat.

BACKGROUND: To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR). SUBJECTS AND METHODS: Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available. RESULTS: A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (P<1.0 × 10(-6)) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; P=1.10 × 10(-7)), an association that was replicated (P=0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; P=2.42 × 10(-7)). Our sex-specific analyses identified one genome-wide significant (P<5.0 × 10(-8)) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 10(-8) to 1.13 × 10(-8)). The THNSL2 gene previously associated with VAT in women was also replicated (P=0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively. CONCLUSIONS: Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2) previously reported to be associated with abdominal fat in women.

B→πll Form Factors for New Physics Searches from Lattice QCD.

The rare decay B→πℓ^{+}ℓ^{-} arises from b→d flavor-changing neutral currents and could be sensitive to physics beyond the standard model. Here, we present the first ab initio QCD calculation of the B→π tensor form factor f_{T}. Together with the vector and scalar form factors f_{+} and f_{0} from our companion work [J. A. Bailey et al., Phys. Rev. D 92, 014024 (2015)], these parametrize the hadronic contribution to B→π semileptonic decays in any extension of the standard model. We obtain the total branching ratio BR(B^{+}→π^{+}µ^{+}µ^{-})=20.4(2.1)×10^{-9} in the standard model, which is the most precise theoretical determination to date, and agrees with the recent measurement from the LHCb experiment [R. Aaij et al., J. High Energy Phys. 12 (2012) 125].

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Elevated endocan levels and its association with clinical severity in Stevens-Johnson Syndrome and toxic epidermal necrolysis.

AIM: The aim of this study was to determine the levels of endocan and other biomarkers of inflammation in the systemic circulation of three groups of patients: 1) biopsy confirmed Stevens Johnson Syndrome, Toxic Epidermal Necrolysis (SJS/TEN) subjects; 2) patients with allergic skin reactions but biopsy negative for SJS/TEN; and 3) normal controls. Besides, this paper aims to investigate the association of endocan levels with the extent of the skin lesions, the presence of purpura, and the degree of acute renal insufficiency, as well as to investigate endocan as a marker of clinical severity by correlating endocan levels with the SCORTEN results (a prognositic score for SJS/TEN). METHODS: Sixteen patients over the age of 18 years who were referred to Loyola University Medical Center with severe allergic skin reactions were recruited over a two-year period from May 2012 to May 2014. A diagnosis of SJS or TEN was confirmed in 7 subjects by skin biopsy. Citrated plasma samples were assayed for endocan, tumor necrosis factor-α (TNFα), vascular endothelial growth factor (VEGF), and C-reactive protein (CRP). The differences between SJS/TEN subjects, biopsy negative subjects, and normal controls (N.=23) were explored using ANOVA and Tukey's post-hoc test. Associations with other clinical variables were identified using linear and logistic regression. RESULTS: Biopsy positive SJS/TEN subjects and biopsy negative subjects had higher endocan levels than normal controls (SJS/TEN: 3.01 ng/mL [IQR: 2.15-8.11]; biopsy negative: 3.96 ng/mL [IQR: 1.54-4.85]; normal controls: 1.79 ng/mL [IQR: 1.67-1.98]; ANOVA P=0.0038). Endocan levels were more strongly associated with SCORTEN in SJS/TEN subjects than in biopsy negative subjects (R2 SJS/TEN=0.5110; biopsy negative=0.0317). SJS/TEN subjects exhibited significantly higher levels of TNF-α compared to normal controls (P=0.0267). The TNF-α levels were significantly lower compared to biopsy negative subjects (P=0.0052). VEGF levels were also elevated among SJS/TEN and biopsy negative subjects compared to normal controls (SJS/TEN: 12.04 pg/mL: [IQR: 7.64-52.7]; biopsy negative: 10.54 pg/mL [IQR: 4.17-6.46]; normal controls: 4.94 pg/mL [IQR: 4.17-6.46]; ANOVA P<0.0001). There was no significant difference in VEGF levels between SJS/TEN and biopsy negative subjects (P=0.7110). Similarly, CRP levels were elevated among SJS/TEN patients and biopsy negative subjects compared to normal controls (SJS/TEN: 32.09 µg/mL [IQR: 31.49-52.08]; biopsy negative: 83.38 µg/mL [IQR: 44.74-145.38]; healthy normal: 1.08 µg/mL [IQR: 0.73-2.03]; ANOVA P<0.0001). There was no significant difference in CRP levels between SJS/TEN and biopsy negative subjects (P=0.2416). CONCLUSION: To our knowledge, this is the first study to evaluate enodcan, a marker of endothelial dysfunction, in the systemic circulation of SJS/TEN patients. Elevated endocan levels were more strongly associated with disease severity among SJS/TEN subjects than among less severe allergic reactions with skin involvement.

Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy.

OBJECTIVE: While daily intravaginal administration of 0.50% (6.5 mg) dehydroepiandrosterone (DHEA, prasterone) for 12 weeks has shown clinically and statistically significant effects on moderate to severe (MS) dyspareunia as the most bothersome symptom (MBS), the present study analyzes the effect of a reduced dosing regimen on MBS vaginal dryness. METHOD: Daily intravaginal 0.50% prasterone for 2 weeks followed by twice weekly for 10 weeks versus placebo. RESULTS: Maximal beneficial changes in vaginal parabasal and superficial cells and pH were observed at 2 weeks as observed for intravaginal 10 µg estradiol (E2). This was followed by a decrease or lack of efficacy improvement after switching to twice-weekly dosing. The decrease in percentage of parabasal cells, increase in percentage of superficial cells and decrease in vaginal pH were all highly significant (p < 0.0001 to 0.0002 over placebo) at 12 weeks. In parallel, the statistical significance over placebo (p value) on MBS vaginal dryness at 6 weeks was 0.09 followed by an increase to 0.198 at 12 weeks. For MBS dyspareunia, the p value of 0.008 at 6 weeks was followed by a p value of 0.077 at 12 weeks, thus illustrating a decrease of efficacy at the lower dosing regimen. The improvements of vaginal secretions, color, epithelial integrity and epithelial surface thickness were observed at a p value < 0.01 or 0.05 over placebo at 2 weeks, with a similar or loss of statistical difference compared to placebo at later time intervals. No significant adverse event was observed. Vaginal discharge related to the melting of Witepsol was reported in 1.8% of subjects. CONCLUSION: The present data show that daily dosing with 0.50% DHEA for 2 weeks followed by twice-weekly dosing is a suboptimal treatment of the symptoms/signs of vulvovaginal atrophy resulting from a substantial loss of the efficacy achieved at daily dosing.