STING-associated vasculopathy with onset in infancy (SAVI) presenting with skin lesions.

STING-associated vasculopathy with onset in infancy (SAVI) is caused by pathogenic gain-of-function variants in the gene TMEM173 (also named stimulator of interferon genes, STING1). This report details the case of an 11-year-old girl with SAVI who presented with skin-limited symptoms and discusses the phenotype-genotype correlations of the TMEM173 variant present in our patient. Treatment of SAVI focuses on preventing the development or progression of organ damage by reducing systemic inflammation. We summarize the available treatments for this syndrome.

Nonresonant Searches for Axionlike Particles at the LHC.

We propose a new collider probe for axionlike particles (ALPs), and more generally for pseudo-Goldstone bosons: nonresonant searches that take advantage of the derivative nature of their interactions with Standard Model particles. ALPs can participate as off shell mediators in the s channel of 2→2 scattering processes at colliders like the LHC. We exemplify the power of this novel type of search by deriving new limits on ALP couplings to gauge bosons via the processes pp→ZZ, pp→γγ, and pp→jj using run 2 CMS public data, probing previously unexplored areas of the ALP parameter space. In addition, we propose future nonresonant searches involving the ALP coupling to other electroweak bosons and/or the Higgs particle.

Internalizing and externalizing symptoms and suicidal behaviour in young people: a systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To assess internalizing and externalizing symptoms as risk factors for suicidal behaviour and suicide among adolescents and young adults. METHOD: We conducted a systematic review of articles published until January 2017. We identified 26 883 potential papers; 1701 full-text articles were assessed for eligibility, of which 1479 were excluded because of methodological reasons. Diverse meta-analyses were performed for each group of symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CI) or beta coefficients for categorical variables, and effect size (ES) were calculated for continuous variables. RESULTS: Finally, 41 studies were included, involving participants aged 12-26 years for a systematic review, and 24 articles were included for meta-analysis. The meta-analysis showed that youths with any internalizing (ES = 0.93) or externalizing symptoms (ES = 0.76 and OR = 2.59) were more likely to attempt suicide in future. This effect was also seen in depression symptoms (OR = 6.58 and ES = 1.00), legal problems (OR = 3.36), and anxiety (ES = 0.65). CONCLUSION: Reported internalizing and externalizing symptoms are predictors of suicide behaviour in young people; therefore, the detection and management of these symptoms in young populations could be a crucial strategy for preventing suicidality in this group.

Global distribution of white spot syndrome virus genotypes determined using a novel genotyping assay.

White spot disease, caused by infection with white spot syndrome virus (WSSV), is a serious panzootic affecting prawn aquaculture. The disease has spread rapidly around the prawn-culturing regions of the world through a number of previously identified mechanisms. The ability to distinguish and trace strains of WSSV is of great benefit to identify, and then limit, the translocation routes of the disease. Here, we describe a novel genotyping method using 34 short tandem repeat regions of the viral genome concurrently. This technique is highly sensitive to strain differences when compared to previous methods. The efficacy of the described method is demonstrated by testing WSSV isolates from around the globe, showing regional genotypic differences. The differences in the genotypes were used to create a global minimum spanning network, and in most cases the observed relationships were substantiated with verification of transboundary movement. This novel panel of STR markers will provide a valuable epidemiological tool for white spot disease. We have applied this to an outbreak of the disease in Queensland, Australia, that occurred in 2016. While the results indicate that the source of this outbreak currently remains cryptic, the analyses have provided valuable insights with which to further study the origins of the strains involved.

Sexual orientation and suicidal behaviour in adolescents and young adults: systematic review and meta-analysis.

BackgroundResearch suggests that lesbian, gay and bisexual (LGB) adolescents have a higher risk of suicidal behaviours than their heterosexual peers, but little is known about specific risk factors.AimsTo assess sexual orientation as a risk factor for suicidal behaviours, and to identify other risk factors among LGB adolescents and young adults.MethodA systematic search was made of six databases up to June 2015, including a grey literature search. Population-based longitudinal studies considering non-clinical populations aged 12-26 years and assessing being LGB as a risk factor for suicidal behaviour compared with being heterosexual, or evaluating risk factors for suicidal behaviour within LGB populations, were included. Random effect models were used in meta-analysis.ResultsSexual orientation was significantly associated with suicide attempts in adolescents and youths (OR = 2.26, 95% CI 1.60-3.20). Gay or bisexual men were more likely to report suicide attempts compared with heterosexual men (OR = 2.21, 95% CI 1.21-4.04). Based on two studies, a non-significant positive association was found between depression and suicide attempts in LGB groups.ConclusionsSexual orientation is associated with a higher risk of suicide attempt in young people. Further research is needed to assess completed suicide, and specific risk factors affecting the LGB population.

Exposure to violence, a risk for suicide in youths and young adults. A meta-analysis of longitudinal studies.

OBJECTIVE: To assess the association and magnitude of the effect of early exposure to different types of interpersonal violence (IPV) with suicide attempt and suicide death in youths and young adults. METHOD: We searched six databases until June 2015. Inclusion criteria were as follows: (1) assessment of any type of IPV as risk factor of suicide attempt or suicide: (i) child maltreatment [childhood physical, sexual, emotional abuse, neglect], (ii) bullying, (iii) dating violence, and (iv) community violence; (2) population-based case-control or cohort studies; and (3) subjects aged 12-26 years. Random models were used for meta-analyses (Reg: CRD42013005775). RESULTS: From 23 682 articles, 29 articles with 143 730 subjects for meta-analyses were included. For victims of any IPV, OR of subsequent suicide attempt was 1.99 (95% CI: 1.73-2.28); for child maltreatment, 2.25 (95% CI: 1.85-2.73); for bullying, 2.39 (95% CI: 1.89-3.01); for dating violence, 1.65 (95% CI: 1.40-1.94); and for community violence, 1.48 (95% CI: 1.16-1.87). Young victims of IPV had an OR of suicide death of 10.57 (95% CI: 4.46-25.07). CONCLUSION: Early exposure to IPV confers a risk of suicide attempts and particularly suicide death in youths and young adults. Future research should address the effectiveness of preventing and detecting early any type of IPV exposure in early ages.

Sputum periostin in patients with different severe asthma phenotypes.

BACKGROUND: Identifying inflammatory phenotypes is relevant in severe uncontrolled asthma. The aim of this study was to identify the different clinical, inflammatory, functional, and molecular phenotypes in patients with severe asthma and to investigate the potential role of sputum periostin as a biomarker of severe asthma phenotypes. PATIENTS AND METHODS: Sputum induction was performed in 62 patients diagnosed with severe asthma. Skin prick testing, lung function tests, exhaled nitric oxide, hematimetry, and total serum IgE were performed. Periostin was measured in sputum supernatants. RESULTS: Patients with asthma were phenotyped and 80% had late-onset asthma, 50% had fixed airflow obstruction, and 66% showed a Th2-high phenotype. With respect to inflammatory phenotypes, 71% were eosinophilic and 25% mixed granulocytic. Periostin levels were higher in patients with fixed as compared to variable airflow limitation (69.76 vs 43.84 pg/ml, P < 0.05) and in patients with eosinophilic as compared to mixed granulocytic phenotype (61.58 vs 37.31 pg/ml, P < 0.05). There was an inverse correlation between postbronchodilator FEV1 /FVC and periostin levels (-0.276, P < 0.05). CONCLUSION: This study demonstrates the utility of periostin in phenotyping severe asthma. Periostin levels in sputum are associated with persistent airflow limitation in asthma patients with airway eosinophilia despite treatment with high-dose inhaled corticosteroids.

Monitoring and surveillance of antimicrobial resistance in microorganisms associated with aquatic animals.

The World Organisation for Animal Health (OIE) Aquatic Animal Health Code recommends that programmes forthe monitoring and surveillance of antimicrobial resistance in microorganisms associated with aquatic animals be initiated by the appropriate authorities. This paper discusses the classes of bacteria to be studied in such programmes and the methods of sample collection to be employed. It also discusses the susceptibility test protocols appropriate for use in such programmes, the interpretive criteria that should be applied to the data they generate and the form in which the output of such programmes should be reported. The authors argue that it is essential that all monitoring and surveillance programmes should employ standardised and internationally harmonised susceptibility test methods to the greatest extent possible. With respect to bacteria capable of infecting aquatic animals, it is recommended that the set of consensus-based standards and guidelines published by the Clinical and Laboratory Standards Institute be adopted as the basis for international harmonisation of test protocols, as they are significantly more developed than any alternatives. It is further recommended that, for the purpose of evaluating antimicrobial resistance trends, such as emerging resistance, the data generated by these protocols should be interpreted by the application of epidemiological cut-off values. However, as yet, internationally agreed cut-off values have been produced for only one species. Thus, for many species, authorities will be obliged to set their own local and laboratory-specific cut-off values. It is recommended that laboratories use a statistical and standardised method of establishing such local cut-off values. Internationally harmonised standard test protocols and interpretive criteria have, to a large extent, been developed to monitor antimicrobial resistance in bacterial species capable of infecting humans. These methods can also be applied to microorganisms capable of infecting humans that are isolated from aquatic animals reared for human consumption or for sale as companion animals.

Necrosis of ears after use of cocaine probably adulterated with levamisole.

BACKGROUND/AIMS: Levamisole is an anthelminthic drug with immunomodulatory properties that has been found to be an adulterant of cocaine in the last 2 years. It was present at least in 70% of tainted cocaine in the U.S.A. in 2009. METHODS: We present the case of a 40-year-old patient with a history of weekend cocaine use who consulted for bilateral necrotic lesions in the ears that had appeared 3 days after the last use. RESULTS: Levamisole causes a typical clinical picture characterized by bilateral necrosis of the ears, positive perinuclear antineutrophil cytoplasmic antibodies and laboratory findings of antiphospholipid syndrome, such as anticardiolipin antibodies and/or lupus anticoagulant. CONCLUSION: Dermatologists should be aware of this new entity, which is likely to be more and more frequent due to the increasing use of cocaine. Here we describe a clinical case that is likely to be secondary to levamisole-tainted cocaine and review the literature.

Valorisation of Camellia sinensis branches as a raw product with green technology extraction methods.

This work deals with the study of tea stalks from pruning debris using environmental friendly extraction technology to offer new healthy properties. In the manufacturing tea industry, tea trees require to be pruned every year and most of their remains are discarded as a waste with no economic value. Microwave aqueous extraction and pressurized hot water extraction process (autohydrolysis) were used to recover bioactive compounds from the tea branches. Operating at a fixed solid: liquid ratio (1:15), the effect of the maximum heating temperatures from 140 to 220 °C was studied. Liquid extracts were analysed for total phenolic, oligosaccharides, protein, mineral and heavy metals content, as well as for antioxidant capacity. The antitumoral possibilities were also determined for selected samples. The obtained results indicated that both processes could be used as an alternative to recover bioactive compounds from tea wastes, although microwave-assisted extraction allowed saving time when compared with autohydrolysis processing. The temperature exhibited a relevant effect on the total phenolic content and antioxidant capacity, decreasing with the microwave treatment and increasing with the autohydrolysis temperature. The obtained extracts could be adequate for incorporation in food and non-food fields.

Titanium plate removal in orthognathic surgery: prevalence, causes and risk factors. A systematic literature review and meta-analysis.

The purpose of this review was to analyse the prevalence of titanium plate removal in orthognathic surgery, as well as the causes of plate removal, and to determine the associated risk factors. A thorough search of the PubMed, Scopus, Embase, and Web of Science databases was conducted. The inclusion criteria were studies of adult patients who underwent orthognathic surgery in which monocortical titanium plates and screws were placed. Of the 325 references identified, 19 were included in the qualitative synthesis and meta-analysis. Overall, 13.4% (95% confidence interval (CI) 9.6-18.3%) of the patients required the removal of at least one titanium plate; 9.7% (95% CI 6.3-14.6%) of the plates placed were removed. The main causes of removal were infection (6.6%), exposed plate (2.6%), thermal sensitivity (2.1%), palpable plate or screw (2.0%), and pain/tenderness (1.9%). Female sex, smoking, and plates placed in the lower jaw were the main risk factors, with odds ratios of 1.5 (95% CI 1.1-2.0), 2.5 (95% CI 1.4-4.2), and 1.8 (95% CI 1.0-3.2), respectively. In no case was a publication bias problem detected. Fixation using titanium plates has a relatively low prevalence of removal. Infection is the main reason for removal. Female sex and smoking, are the main risk factors for removal. Plates placed in the lower jaw is a non-significant risk factor.

Increased susceptibility of white spot syndrome virus-infected Litopenaeus vannamei to Vibrio campbellii.

The concept of polymicrobial disease is well accepted in human and veterinary medicine but has received very little attention in the field of aquaculture. This study was conducted to investigate the synergistic effect of white spot syndrome virus (WSSV) and Vibrio campbellii on development of disease in specific pathogen-free (SPF) shrimp Litopenaeus vannamei. The juvenile shrimp were first injected with WSSV at a dose of 30 SID(50) shrimp(-1) (SID(50) = shrimp infectious dose with 50% endpoint) and 24 h later with 10(6) colony-forming units (cfu) of V. campbellii shrimp(-1). Controls receiving just one of the pathogens or negative inocula were included. In the treatment with WSSV only, shrimp started to die at 48-108 h post injection (hpi) and cumulative mortality reached 100% at 268-336 hpi. In the treatment with only V. campbellii injection (10(6) cfu shrimp(-1)), cumulative mortality reached 16.7%. Shrimp in the dual treatment died very quickly after V. campbellii injection and 100% cumulative mortality was obtained at 72-96 hpi. When WSSV-injected shrimp were given sonicated V. campbellii instead of live V. campbellii, no synergistic effect was observed. Density of V. campbellii in the haemolymph of co-infected moribund shrimp collected 10 h after V. campbellii injection was significantly higher than in shrimp injected with V. campbellii only (P < 0.01). However, there was no difference in WSSV replication between shrimp inoculated with WSSV only compared with dually inoculated ones. This study revealed that prior infection with WSSV enhances the multiplication and disease inducing capacity of V. campbellii in shrimp.

Virulence of white spot syndrome virus (WSSV) isolates may be correlated with the degree of replication in gills of Penaeus vannamei juveniles.

A standardized inoculation model was used in 2 separate experiments to gauge the virulence of 3 white spot syndrome virus (WSSV) isolates from Thailand and Vietnam (WSSV Thai-1, WSSV Thai-2, and WSSV Viet) in Penaeus vannamei juveniles. Mortality patterns (Expt 1) were compared and WSSV-positive cells quantified (Expt 2) in tissues following intramuscular inoculation of shrimp with the most (WSSV Thai-1) and least (WSSV Viet) virulent isolates as determined by Expt 1. The results of Expt 1 demonstrated that mortalities began at 36 h post inoculation (hpi) for both Thai isolate groups and at 36 to 60 hpi for the Viet isolate group. Cumulative mortality reached 100% 96 to 240 h later in shrimp challenged with the WSSV Viet isolate compared to shrimp challenged with the Thai isolates. WSSV infection was verified in all groups by indirect immunofluorescence. In Expt 2, WSSV-infected cells were quantified by immunohistochemical analysis of both dead and time-course sampled shrimp. WSSV-positive cells were detected in tissues of Thai-1 inoculated dead and euthanized shrimp from 24 hpi onwards and from 36 hpi onwards in shrimp injected with the Viet isolate. Significantly more infected cells were found in tissues of dead shrimp inoculated with the Thai-1 than in Viet isolate-inoculated shrimp. In these experiments, substantial differences in virulence were demonstrated between the WSSV isolates. The Vietnamese isolate induced a more chronic disease and mortality pattern than was found for the Thai isolates, possibly because it infected fewer cells. This difference was most pronounced in gills.

Pathogenesis of a Thai strain of white spot syndrome virus (WSSV) in juvenile, specific pathogen-free Litopenaeus vannamei.

White spot syndrome virus (WSSV) causes disease and mortality in cultured and wild shrimp. A standardized WSSV oral inoculation procedure was used in specific pathogen-free (SPF) Litopenaeus vannamei (also called Penaeus vannamei) to determine the primary sites of replication (portal of entry), to analyze the viral spread and to propose the cause of death. Shrimp were inoculated orally with a low (10(1.5) shrimp infectious dose 50% endpoint [SID50]) or a high (10(4) SID50) dose. Per dose, 6 shrimp were collected at 0, 6, 12, 18, 24, 36, 48 and 60 h post inoculation (hpi). WSSV-infected cells were located in tissues by immunohistochemistry and in hemolymph by indirect immunofluorescence. Cell-free hemolymph was examined for WSSV DNA using 1-step PCR. Tissues and cell-free hemolymph were first positive at 18 hpi (low dose) or at 12 hpi (high dose). With the 2 doses, primary replication was found in cells of the foregut and gills. The antennal gland was an additional primary replication site at the high dose. WSSV-infected cells were found in the hemolymph starting from 36 hpi. At 60 hpi, the percentage of WSSV-infected cells was 36 for the epithelial cells of the foregut and 27 for the epithelial cells of the integument; the number of WSSV-infected cells per mm2 was 98 for the gills, 26 for the antennal gland, 78 for the hematopoietic tissue and 49 for the lymphoid organ. Areas of necrosis were observed in infected tissues starting from 48 hpi (low dose) or 36 hpi (high dose). Since the foregut, gills, antennal gland and integument are essential for the maintenance of shrimp homeostasis, it is likely that WSSV infection leads to death due to their dysfunction.

ALPs effective field theory and collider signatures.

We study the leading effective interactions between the Standard Model fields and a generic singlet CP-odd (pseudo-) Goldstone boson. Two possible frameworks for electroweak symmetry breaking are considered: linear and non-linear. For the latter case, the basis of leading effective operators is determined and compared with that for the linear expansion. Associated phenomenological signals at colliders are explored for both scenarios, deriving new bounds and analyzing future prospects, including LHC and High Luminosity LHC sensitivities. Mono-Z, mono-W, W-photon plus missing energy and on-shell top final states are most promising signals expected in both frameworks. In addition, non-standard Higgs decays and mono-Higgs signatures are especially prominent and expected to be dominant in non-linear realisations.

Longitudinal association between self-injurious thoughts and behaviors and suicidal behavior in adolescents and young adults: A systematic review with meta-analysis.

BACKGROUND: Adolescents with previous self-injurious thoughts and behaviors (SITB) have over 2-fold risk of dying by suicide, higher than older ages. This meta-analysis aims to disentangle the association of each SITB with subsequent suicidal behavior in adolescence/young adulthood, the contribution of each SITB, and the proportion of suicide deaths with no previous suicide attempt. METHODS: We searched 6 databases until June 2015. INCLUSION CRITERIA: 1. Assessment of any previous SITB [a) suicidal thoughts and behaviors (ideation; threat/gesture; plan; attempt); b) non-suicidal thoughts and behaviors (thoughts; threat/gesture; self-injury); c) self-harm] as a risk factor of suicide attempt or suicide death; 2. Case-control or cohort studies; 3. Subjects aged 12-26y. Random effect models, metaregression analyses including mental health and environmental variables, and population attributable risks (PAR)s were estimated. RESULTS: From 23,682 potentially eligible articles, 29 were included in the meta-analysis (1,122,054 individuals). While 68% of all youth suicide deaths had no previous suicide attempt, suicide death was very strongly associated with any previous SITB (OR=22.53, 95%CI: 18.40-27.58). Suicide attempts were also associated with a history of previous SITB (OR=3.48, 95%CI: 2.71-4.43). There were no moderating effects for mental health and environmental features. The PAR of previous SITB to suicide attempts is 26%. LIMITATIONS: There is considerable heterogeneity between the available studies. Due to limitations in the original studies, an over-estimation of the proportion dying at their first attempt cannot be ruled out, since they might have missed unrecognized previous suicide attempts. CONCLUSIONS: Although more than two thirds of suicide deaths in adolescence/young adulthood have occurred with no previous suicidal behavior, previous SITBs have a much higher risk of dying by suicide than previously reported in this age group.

Standardized white spot syndrome virus (WSSV) inoculation procedures for intramuscular or oral routes.

In the past, strategies to control white spot syndrome virus (WSSV) were mostly tested by infectivity trials in vivo using immersion or per os inoculation of undefined WSSV infectious doses, which complicated comparisons between experiments. In this study, the reproducibility of 3 defined doses (10, 30 and 90 shrimp infectious doses 50% endpoint [SID50]) of WSSV was determined in 3 experiments using intramuscular (i.m.) or oral inoculation in specific pathogen-free (SPF) Litopenaeus vannamei. Reproducibility was determined by the time of onset of disease, cumulative mortality, and median lethal time (LT50). By i.m. route, the 3 doses induced disease between 24 and 36 h post inoculation (hpi). Cumulative mortality was 100% at 84 hpi with doses of 30 and 90 SID50 and 108 hpi with a dose of 10 SID50. The LT50 of the doses 10, 30 and 90 SID50 were 52, 51 and 49 hpi and were not significantly different (p > 0.05). Shrimp orally inoculated with 10, 30 or 90 SID50 developed disease between 24 and 36 hpi. Cumulative mortality was 100% at 108 hpi with doses of 30 and 90 SID50 and 120 hpi with a dose of 10 SID50. The LT50 of 10, 30 and 90 SID50 were 65, 57 and 50 hpi; these were significantly different from each other (p < 0.05). A dose of 30 SID50 was selected as the standard for further WSSV challenges by i.m. or oral routes. These standardized inoculation procedures may be applied to other crustacea and WSSV strains in order to achieve comparable results among experiments.

Primary hormone treatment in postmenopausal women with breast cancer.

Clinical benefits of hormone therapy in patients with hormone-sensitive tumors have been clearly established. Postmenopausal women with positive hormone receptors represent the largest group of patients in whom early stage breast cancer is diagnosed. Third-generation aromatase inhibitors (letrozole, anastrozole, and exemestane) are active and well tolerated in postmenopausal women with hormone-sensitive metastasic or locally advanced breast cancer as first or second line treatment. These are also valuable agents in the neoadjuvant setting in postmenopausal women, and even as single treatment in localized breast tumors in women not amenable to surgery.