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the article discusses a study to find influence of pelvic vein reflux in prevalence of haemorrhoids in women and which conclude a relationship between internal Iliac vein reflux and haemorrhoids. It states that association of haemorrhoids with pelvic veins was identified. It mentions that symptomatic haemorrhoids may be a result of untreated reflux. It informs foam sclerotherapy and pelvic vein embolisation as treatment for cause resulting in pelvic vein incompetence.

This study examined the validity of the Klonoff and Landrine Illness-Belief Scale when applied to Latino college students (n = 156; 34% male, 66% female) at high risk for future diabetes onset. Principal factor analysis yielded four significant factors -- emotional, folk beliefs, punitive, gene/hereditary -- which accounted for 64.5% of variance and provided a culturally relevant Latino perspective of the causes of diabetes. Additional analyses by age, gender, immigrant status, and psychological acculturation revealed significant differences by age on the emotional and folk illness factors and a negative correlation between assimilation and endorsement of the emotional factor. The implication of these four illness factors for predicting health-related behaviors and health outcomes among young Latinos was discussed as were recommendations for future research. [ABSTRACT FROM AUTHOR]

There is a lack of questionnaires specifically designed to assess social isolation in adolescents. We developed and validated a self-report measure of social isolation in adolescents, the Social Isolation Questionnaire (QIS). A literature review on social isolation and mental health in adolescents indicated 20 questions to form QIS. Two cross-sectional surveys with 48 and 1135 adolescents, respectively, evaluated the reproducibility and validity of QIS. The Bland-Altman plot did not indicate a systematic difference between measurements 15 days apart. Bartlett's sphericity test verified a correlation between the questions and the Kaiser-Meyer-Olkin test showed good adequacy (.896) to the factor analysis. Exploratory factor analysis suggested the exclusion of three questions (loading factors <0.3), and eigenvalues (4.9-0.8) indicated that the questionnaire should be composed of three factors (dimensions). The Cronbach's alpha indicated high internal consistency of the 17 questions (0.850 overall; Dimensions: 0.815 'feeling of loneliness'; 0.760 'friendship'; and, 0.680 'Family support'). The QIS score ranged from 0 to 131 (maximum social isolation score). The correlation between QIS and depressive symptoms (r = .543) indicated the construct validity of QIS. We evaluated QIS in the Portuguese version, thus translation and cultural adaptation are necessary to evaluate the questionnaire in other settings. We constructed and validated the QIS questionnaire, a self-administered questionnaire to assess social isolation in adolescents, composed of three dimensions; feelings of loneliness, friendship and family support. The QIS questionnaire seems a very promising tool to support practitioners and researchers in assessing social isolation among adolescents., (© 2024 Society for Research on Adolescence.)

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1 . Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF-2 binding elements (FBEs) in its 3ÚTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established 'canonical' FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discovery of the LST-1-FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predicts an expanded regulatory repertoire of different assemblies of PUF-partner complexes in nematode germline stem cells. It also suggests analogous PUF controls may await discovery in other biological contexts and organisms.

In this study, we aimed to compare uterine microbial profiles in postpartum dairy cows, determined by bacteriological culture and next-generation sequencing, using three uterine sampling techniques (swab, cytobrush, and lavage) and induced phases of the estrous cycle (estrus and diestrus). Fifteen healthy postpartum dairy cows at 53 ± 5 days postpartum were enrolled in the study. Uterine samples were collected during a fixed-time artificial insemination protocol. Viable bacteria were aerobically cultured from part of each sample, and bacterial isolates were identified through Sanger sequencing of the 16S rRNA gene. Total genomic DNA was extracted from the remainder of undiluted samples to quantify bacterial load using 16S rRNA qPCR and characterize the microbiome by metagenomic sequencing of the V1-V3 region of the 16S rRNA gene. Microbial profiles and composition were analyzed using the Shannon-Weaver diversity index and principal component analysis, respectively. Out of 87 samples, 88 % (77/87) were culture positive. The proportion of culture-positive uterine samples did not differ between sampling techniques (P = 0.39) or estrous cycle phases (P = 0.99). However, swab, cytobrush, and lavage techniques yielded 1.5, 9 and 9 times greater bacterial loads (P < 0.01), respectively, during diestrus than estrus phase. Moreover, during diestrus phase, the cytobrush method yielded 3 and 6 times more bacteria (P < 0.01) than both the lavage and swab methods. The most abundant bacterial genera identified from both bacteriological culture and metagenomic sequencing were Bacillus and Enterococcus, regardless of sampling technique or phases of the estrous cycle. Bacterial genera in moderate to low abundance through metagenomic sequencing included Streptococcus, Oscillospiraceae, and Lachnospiraceae. Notably, the uterine microbial profiles and composition, determined by metagenomic sequencing, did not differ by sampling techniques (P = 0.55 and P = 0.60, respectively) or estrous cycle phases (P = 0.34 and P = 0.17, respectively). In conclusion, our results suggest that any of the sampling techniques can be reliably used to study the uterine microbiome of healthy cows at random phases of the estrous cycle. However, it is important to consider potential differences in bacterial yield as a confounding factor., Competing Interests: Declaration of competing interests The authors have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Notch signaling regulates stem cells across animal phylogeny. C. elegans Notch signaling activates transcription of two genes, lst-1 and sygl-1 , that encode potent regulators of germline stem cells. The LST-1 protein regulates stem cells in two distinct ways: It promotes self-renewal posttranscriptionally and also restricts self-renewal by a poorly understood mechanism. Its self-renewal promoting activity resides in its N-terminal region, while its self-renewal restricting activity resides in its C-terminal region and requires the Zn finger. Here, we report that LST-1 limits self-renewal by down-regulating Notch-dependent transcription. We detect LST-1 in the nucleus, in addition to its previously known cytoplasmic localization. LST-1 lowers nascent transcript levels at both lst-1 and sygl-1 loci but not at let-858 , a Notch-independent locus. LST-1 also lowers levels of two key components of the Notch activation complex, the LAG-1 DNA binding protein and Notch intracellular domain (NICD). Genetically, an LST-1 Zn finger mutant increases Notch signaling strength in both gain- and loss-of-function GLP-1/Notch receptor mutants. Biochemically, LST-1 co-immunoprecipitates with LAG-1 from nematode extracts, suggesting a direct effect. LST-1 is thus a bifunctional regulator that coordinates posttranscriptional and transcriptional mechanisms in a single protein. This LST-1 bifunctionality relies on its bipartite protein architecture and is bolstered by generation of two LST-1 isoforms, one specialized for Notch downregulation. A conserved theme from worms to human is the coupling of PUF-mediated RNA repression together with Notch feedback in the same protein.

Dysbiosis of the neonatal gut microbiome during early life has been suggested as the missing link that may explain higher rates of certain diseases in caesarean section-delivered infants. Many studies report delivery mode-related dysbiosis in infants due to a lack of maternal vaginal microbiome exposure, prompting interventions to correct the neonatal gut microbiome by transferring these missing microbes after caesarean delivery. The maternal vaginal microbiome is among the first microbial exposures that many infants experience, yet little is known about the extent of direct transmission of maternal vaginal microbes. As part of the Maternal Microbiome Legacy Project, we aimed to determine if maternal vaginal bacteria are vertically transmitted to infants. We employed cpn 60 microbiome profiling, culture-based screening, molecular strain typing, and whole-genome sequencing to determine whether identical maternal vaginal strains were present in infant stool microbiomes. We identified identical cpn 60 sequence variants in both halves of maternal-infant dyads in 204 of 585 Canadian women and their newborn infants (38.9%). The same species of Bifidobacterium and Enterococcus were cultured from maternal and corresponding infant samples in 33 and 13 of these mother-infant dyads, respectively. Pulsed-field gel electrophoresis and whole-genome sequencing determined that near-identical strains were detected in these dyads irrespective of delivery mode, indicating an alternative source in cases of caesarean delivery. Overall, we demonstrated that vertical transmission of maternal vaginal microbiota is likely limited and that transmission from other maternal body sites, such as the gut and breast milk, may compensate for the lack of maternal vaginal microbiome exposure during caesarean delivery. IMPORTANCE The importance of the gut microbiome in human health and disease is widely recognized, and there has been a growing appreciation that alterations in gut microbiome composition during a "critical window" of development may impact health in later life. Attempts to correct gut microbiome dysbiosis related to birth mode are underpinned by the assumption that the lack of exposure to maternal vaginal microbes during caesarean delivery is responsible for dysbiosis. Here, we demonstrate that there is limited transmission of the maternal vaginal microbiome to the neonatal gut, even in cases of vaginal delivery. Furthermore, the presence of identical strains shared between mothers and infants in early life, even in cases of caesarean delivery, highlights compensatory microbial exposures and sources for the neonatal stool microbiome other than the maternal vagina., Competing Interests: The authors declare no conflict of interest.

PUF RNA-binding proteins are conserved stem cell regulators. Four PUF proteins govern self-renewal of Caenorhabditis elegans germline stem cells together with two intrinsically disordered proteins, LST-1 and SYGL-1. Based on yeast two-hybrid results, we previously proposed a composite self-renewal hub in the stem cell regulatory network, with eight PUF partnerships and extensive redundancy. Here, we investigate LST-1-PUF and SYGL-1-PUF partnerships and their molecular activities in their natural context - nematode stem cells. We confirm LST-1-PUF partnerships and their specificity to self-renewal PUFs by co-immunoprecipitation and show that an LST-1(AmBm) mutant defective for PUF-interacting motifs does not complex with PUFs in nematodes. LST-1(AmBm) is used to explore the in vivo functional significance of the LST-1-PUF partnership. Tethered LST-1 requires this partnership to repress expression of a reporter RNA, and LST-1 requires the partnership to co-immunoprecipitate with NTL-1/Not1 of the CCR4-NOT complex. We suggest that the partnership provides multiple molecular interactions that work together to form an effector complex on PUF target RNAs in vivo. Comparison of LST-1-PUF and Nanos-Pumilio reveals fundamental molecular differences, making LST-1-PUF a distinct paradigm for PUF partnerships., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Birth mode has been implicated as a major factor influencing neonatal gut microbiome development, and it has been assumed that lack of exposure to the maternal vaginal microbiome is responsible for gut dysbiosis among caesarean-delivered infants. Consequently, practices to correct dysbiotic gut microbiomes, such as vaginal seeding, have arisen while the effect of the maternal vaginal microbiome on that of the infant gut remains unknown. We conducted a longitudinal, prospective cohort study of 621 Canadian pregnant women and their newborn infants and collected pre-delivery maternal vaginal swabs and infant stool samples at 10-days and 3-months of life. Using cpn 60-based amplicon sequencing, we defined vaginal and stool microbiome profiles and evaluated the effect of maternal vaginal microbiome composition and various clinical variables on the development of the infant stool microbiome. Infant stool microbiomes showed significant differences in composition by delivery mode at 10-days postpartum; however, this effect could not be explained by maternal vaginal microbiome composition and was vastly reduced by 3 months. Vaginal microbiome clusters were distributed across infant stool clusters in proportion to their frequency in the overall maternal population, indicating independence of the two communities. Intrapartum antibiotic administration was identified as a confounder of infant stool microbiome differences and was associated with lower abundances of Escherichia coli , Bacteroides vulgatus , Bifidobacterium longum and Parabacteroides distasonis . Our findings demonstrate that maternal vaginal microbiome composition at delivery does not affect infant stool microbiome composition and development, suggesting that practices to amend infant stool microbiome composition focus factors other than maternal vaginal microbes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dos Santos, Pakzad, Albert, Elwood, Grabowska, Links, Hutcheon, Maan, Manges, Dumonceaux, Hodgson, Lyons, Mitchell-Foster, Gantt, Joseph, Van Schalkwyk, Hill and Money.)

Background: Women living with HIV (WLWH) experience higher rates of human papillomavirus (HPV) infection and cervical cancer than women without HIV. Changes in the vaginal microbiome have been implicated in HPV-related disease processes such as persistence of high-risk HPV infection but this has not been well defined in a population living with HIV., Methods: Four hundred and 20 girls and WLWH, age ≥9, across 14 clinical sites in Canada were enrolled to receive three doses of quadrivalent HPV vaccine for assessment of vaccine immunogenicity. Blood, cervical cytology, and cervico-vaginal swabs were collected. Cervico-vaginal samples were tested for HPV DNA and underwent microbiota sequencing., Results: Principal component analysis (PCA) and hierarchical clustering generated community state types (CSTs). Relationships between taxa and CSTs with HPV infection were examined using mixed-effects logistic regressions, Poisson regressions, or generalized linear mixed-effects models, as appropriate. Three hundred and fifty-six cervico-vaginal microbiota samples from 172 women were sequenced. Human papillomavirus DNA was detected in 211 (59%) samples; 110 (31%) contained oncogenic HPV. Sixty-five samples (18%) were taken concurrently with incident oncogenic HPV infection and 56 (16%) were collected from women with concurrent persistent oncogenic HPV infection., Conclusions: No significant associations between taxa, CST, or microbial diversity and HPV-related outcomes were found. However, we observed weak associations between a dysbiotic microbiome and specific species, including Gardnerella , Porphyromonas , and Prevotella species, with incident HPV infection.

The Mycobacterium ulcerans exotoxin, mycolactone, is responsible for the immunosuppression and tissue necrosis that characterizes Buruli ulcer. Mycolactone inhibits SEC61-dependent co-translational translocation of proteins into the endoplasmic reticulum and the resultant cytosolic translation triggers degradation of mislocalized proteins by the ubiquitin-proteasome system. Inhibition of SEC61 by mycolactone also activates multiple EIF2S1/eIF2α kinases in the integrated stress response (ISR). Here we show mycolactone increased canonical markers of selective macroautophagy/autophagy LC3B-II, ubiquitin and SQSTM1/p62 in diverse disease-relevant primary cells and cell lines. Increased formation of puncta positive for the early autophagy markers WIPI2, RB1CC1/FIP200 and ATG16L1 indicates increased initiation of autophagy. The mycolactone response was SEC61A1-dependent and involved a pathway that required RB1CC1 but not ULK. Deletion of Sqstm1 reduced cell survival in the presence of mycolactone, suggesting this response protects against the increased cytosolic protein burden caused by the toxin. However, reconstitution of baseline SQSTM1 expression in cells lacking all autophagy receptor proteins could not rescue viability. Translational regulation by EIF2S1 in the ISR plays a key role in the autophagic response to mycolactone. Mycolactone-dependent induction of SQSTM1 was reduced in eif2ak3 -/- /perk -/- cells while the p-EIF2S1 antagonist ISRIB reversed the upregulation of SQSTM1 and reduced RB1CC1, WIPI2 and LC3B puncta formation. Increased SQSTM1 staining could be seen in Buruli ulcer patient skin biopsy samples, reinforcing genetic data that suggests autophagy is relevant to disease pathology. Since selective autophagy and the ISR are both implicated in neurodegeneration, cancer and inflammation, the pathway uncovered here may have a broad relevance to human disease. Abbreviations: ATF4: activating transcription factor 4; ATG: autophagy related; BAF: bafilomycin A 1 ; ATG16L1: autophagy related 16 like 1; BU: Buruli ulcer; CQ: chloroquine; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; CALCOCO2: calcium binding and coiled-coil domain 2; DMSO: dimethyl sulfoxide; EIF2S1: eukaryotic translation initiation factor 2 subunit alpha; ER: endoplasmic reticulum; GFP: green fluorescent protein; HDMEC: human dermal microvascular endothelial cells; HFFF: human fetal foreskin fibroblasts; ISR: integrated stress response; ISRIB: integrated stress response inhibitor; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; Myco: mycolactone; NBR1: NBR1 autophagy cargo receptor; NFE2L2: nuclear factor, erythroid 2 like 2; OPTN: optineurin; PFA: paraformaldehyde; PtdIns3P: phosphatidylinositol-3-phosphate; RB1CC1: RB1-inducible coiled coil 1; SQSTM1: sequestosome 1; TAX1BP1: Tax1 binding protein 1; ULK: unc-51 like autophagy activating kinase; UPS: ubiquitin-proteasome system; WIPI: WD repeat domain, phosphoinositide interacting; WT: wild type.

Buruli ulcer (BU) is a neglected tropical disease caused by subcutaneous infection with Mycobacterium ulcerans and its exotoxin mycolactone. BU displays coagulative necrosis and widespread fibrin deposition in affected skin tissues. Despite this, the role of the vasculature in BU pathogenesis remains almost completely unexplored. We hypothesise that fibrin-driven ischemia can be an 'indirect' route to mycolactone-dependent tissue necrosis by a mechanism involving vascular dysfunction. Here, we tracked >900 vessels within contiguous tissue sections from eight BU patient biopsies. Our aim was to evaluate their vascular and coagulation biomarker phenotype and explore potential links to fibrin deposition. We also integrated this with our understanding of mycolactone's mechanism of action at Sec61 and its impact on proteins involved in maintaining normal vascular function. Our findings showed that endothelial cell dysfunction is common in skin tissue adjacent to necrotic regions. There was little evidence of primary haemostasis, perhaps due to mycolactone-dependent depletion of endothelial von Willebrand factor. Instead, fibrin staining appeared to be linked to the extrinsic pathway activator, tissue factor (TF). There was significantly greater than expected fibrin staining around vessels that had TF staining within the stroma, and this correlated with the distance it extended from the vessel basement membrane. TF-induced fibrin deposition in these locations would require plasma proteins outside of vessels, therefore we investigated whether mycolactone could increase vascular permeability in vitro. This was indeed the case, and leakage was further exacerbated by IL-1β. Mycolactone caused the loss of endothelial adherens and tight junctions by the depletion of VE-cadherin, TIE-1, TIE-2 and JAM-C; all Sec61-dependent proteins. Taken together, our findings suggest that both vascular and lymphatic vessels in BU lesions become "leaky" during infection, due to the unique action of mycolactone, allowing TF-containing structures and plasma proteins into skin tissue, ultimately leading to local coagulopathy and tissue ischemia., Competing Interests: The authors have declared that no competing interests exist.

Detection of bacterial DNA within meconium is often cited as evidence supporting in utero colonization. However, many studies fail to adequately control for contamination. We aimed to define the microbial content of meconium under properly controlled conditions. DNA was extracted from 141 meconium samples and subjected to cpn 60-based microbiome profiling, with controls to assess contamination throughout. Total bacterial loads of neonatal meconium, infant stool, and controls were compared by 16S rRNA quantitative PCR (qPCR). Viable bacteria within meconium were cultured, and isolate clonality was assessed by pulsed-field gel electrophoresis (PFGE). Meconium samples did not differ significantly from controls with respect to read numbers or taxonomic composition. Twenty (14%) outliers with markedly higher read numbers were collected significantly later after birth and appeared more like transitional stool than meconium. Total bacterial loads were significantly higher in stool than in meconium, which did not differ from that of sequencing controls, and correlated well with read numbers. Cultured isolates were most frequently identified as Staphylococcus epidermidis, Enterococcus faecalis, or Escherichia coli, with PFGE indicating high intraspecies diversity. Our findings highlight the importance of robust controls in studies of low microbial biomass samples and argue against meaningful bacterial colonization in utero . Given that meconium microbiome profiles could not be distinguished from sequencing controls, and that viable bacteria within meconium appeared uncommon and largely consistent with postnatal skin colonization, there does not appear to be a meconium microbiota. IMPORTANCE Much like the recent placental microbiome controversy, studies of neonatal meconium reporting bacterial communities within the fetal and neonatal gut imply that microbial colonization begins prior to birth. However, recent work has shown that placental microbiomes almost exclusively represent contamination from lab reagents and the environment. Here, we demonstrate that prior studies of neonatal meconium are impacted by the same issue, showing that the microbial content of meconium does not differ from negative controls that have never contained any biological material. Our culture findings similarly supported this notion and largely comprised bacteria normally associated with healthy skin. Overall, our work adds to the growing body of evidence against the in utero colonization hypothesis.

Amplification and sequencing of conserved genetic barcodes such as the cpn60 gene is a common approach to determining the taxonomic composition of microbiomes. Exact sequence variant calling has been proposed as an alternative to previously established methods for aggregation of sequence reads into operational taxonomic units (OTU). We investigated the utility of variant calling for cpn60 barcode sequences and determined the minimum sequence length required to provide species-level resolution. Sequence data from the 5´ region of the cpn60 barcode amplified from the human vaginal microbiome (n = 45), and a mock community were used to compare variant calling to de novo assembly of reads, and mapping to a reference sequence database in terms of number of OTU formed, and overall community composition. Variant calling resulted in microbiome profiles that were consistent in apparent composition to those generated with the other methods but with significant logistical advantages. Variant calling is rapid, achieves high resolution of taxa, and does not require reference sequence data. Our results further demonstrate that 150 bp from the 5´ end of the cpn60 barcode sequence is sufficient to provide species-level resolution of microbiota., Competing Interests: The authors have declared that no competing interests exist.

Currently, a significantly lower temperature (35°C) than initially established (56°C) is indicated as the maximum temperature storage for the commercial reference visceral leishmaniasis (VL) freeze-dried direct agglutination test (FD-DAT). Despite an approximately 50% loss in the number of promastigotes in an FD-DAT batch that expired 7 years earlier, the promastigotes maintained a similar morphology to the equivalent valid batch implying most likely that auto-agglutination, rather than aging, is the main reason for expiry. The substitution of normal saline which was initially recommended for reconstitution, by citrate-saline/formaldehyde (CSF) as an anti-clumping/preservative agent resulted in restoration of validity comparable with that of the freeze-dried original or the liquid direct agglutination test (LQ-DAT) version (Friedman ANOVA test = 1.0588; P = 0.5890). Following a similar reconstitution procedure as for the 7-year expired antigen, using significantly lower promastigote concentration (1.4 × 10 7 /mL) than in the non-expired (9.0 × 10 7 /mL), good reliability for VL detection and stability at 4°C (> 12 months) were achieved. In comparison with the original version using normal saline ($32.0/vial), the cost-effectiveness of the FD-DAT was appreciably improved by the CSF incorporation and lowering of promastigote concentration per unit suspension medium ($12.8/vial). With diagnostic reliability comparable with the full-out titration used, FD-DAT procedure based on single sample dilution at the VL cutoff (1:3,200) permitted the use of significantly smaller antigen volumes (0.1 mL vs. > 1.5 mL), therefore contributing to a further reduction in the application cost. The successful replacement of β-mercaptoethanol (β-ME) by urea ( T = 21.00; P = 0.0868) provided the required safety for the test procedure similar to the widely applied LQ-DAT.

To minimize the chance for future visceral leishmaniasis (VL) epidemics such as the 1988-1991 epidemic in Sudan, several VL detection tools have been introduced. There are many VL diagnostics with excellent sensitivities, specificities, and ease of use reported. However, additional test characteristics should be considered for use in the detection of future VL epidemics. The potential for local production or uninterrupted availability, low production and application costs, and stability at ≥45°C are of the utmost importance. Of the antibody-, antigen-, or DNA-based methods introduced, only a liquid direct agglutination test (LQ-DAT) remains in routine use. The LQ-DAT test may be the ideal diagnostic for detection of VL epidemics due to its low cost ($0.50/patient), stability under frequent and long-duration electric failures, and high level of reproducibility. The improved reliability for VL detection achieved locally through incorporating autochthonous L. donovani strains in antigen processing and precluding toxicants in test execution provides optimal sensitivity and safety for routine and mass application., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: It is not well established whether depression leads to weight loss or weight gain, or whether a relationship exists among depression, social anxiety, and weight status. The aim of this study was to evaluate the synergic association among social anxiety, depressive symptoms, and waist circumference (WC) during adolescence and examine whether depression mediated the relationship between social anxiety and WC., Methods: A cross-sectional study was performed with 1296 adolescents from a northeastern district in Brazil. It was used the Social Anxiety Scale for Adolescents (SAS-A) to evaluate symptoms of social anxiety and the Depression Scale of the Center for Epidemiologic Studies (CES-D) for symptoms of depression. Structural equation modeling was used to determine whether depression, social anxiety, and WC were synergically associated. Analysis was adjusted for sex, age, height, and mother's educational level., Results: Symptoms of social anxiety were directly associated with symptoms of depression and WC, whereas symptoms of depression were not associated with WC., Limitations: This is a cross-sectional study, and so we cannot infer causality in the interpretation of results., Conclusion: Social anxiety was found to be associated with depressive symptoms and WC. General medical doctors and health practitioners who observe overweight adolescents with any symptoms of anxiety might consider a thorough evaluation of the patient's mental health., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: Based on world-wide evaluation, the direct agglutination test (DAT) is now generally acknowledged as one of the leading diagnostics for visceral leishmaniasis (VL). To enhance more routine and mass application, but simultaneously ensure safety to both user and environment, further improvements need to be introduced., Methodology: In the current format, a two-sixfold titre decrease was observed due to using formaldehyde as an antigen preservative in DAT. Successful formaldehyde preservative exclusion was achieved by increasing its concentration to 3 % (wt/vol) for conserving promastigote status after β-mercaptoethanol (β-ME) treatment and repeating exposure of the parasite to the fixative after Coomassie Brilliant Blue staining., Results: Microbial contamination was not observed in any of the antigen aliquots preserved in 0.05 % (wt/vol) sodium dichloroisocyanurate (chlorine) instead of formaldehyde for 6 months or longer. By excluding formaldehyde, restoring the normal antibody level, prior to treatment of sera with β-ME only minimally influenced the test outcome. A comparable successful reduction in non-specific agglutination, as with β-ME, was achieved by incorporating urea (0.3 % wt/vol) in the improved DAT procedure (P=0.646; T=23.0). As with the current procedure, the improved equivalent (formaldehyde and β-ME free) showed good reliability for VL detection (VL - Fr=52.39, W=0.70, P<0.001; and non-VL - Fr=65.97, W=0.83, P<0.001). A much lower cut-off (titre 1 : 400 versus 1 : 3200) for VL diagnosis can be adopted if urea is integrated in the improved procedure., Conclusions: By introducing the modifications mentioned, we think we have succeeded to a reasonable degree in increasing the DAT potential for VL control.

Background Pelvic venous reflux is often treated with pelvic vein embolisation; however, atypical pelvic venous anatomy may provide therapeutic challenges. Methods We retrospectively reviewed seven patient files and reported symptoms, diagnostic imaging, aberrant anatomy and means by which the interventional radiologist successfully completed the procedure. Any follow-up data were included if available. Results Four anatomical abnormalities were found: internal iliac veins draining into the contralateral common iliac vein, duplicated inferior vena cava, reverse-angle renal veins with atypical left ovarian vein drainage and direct drainage of the internal iliac vein to the inferior vena cava. All patients were successfully treated with pelvic vein embolisation. Conclusion Abnormal embryologic development may cause variable pelvic venous anatomy. Knowledge of this will enable interventional radiologists to successfully treat such patients.

Objectives To report on a male cohort with pelvic vein reflux and associated primary and recurrent lower limb varicose veins. Methods Full lower limb duplex ultrasonography revealed significant pelvic contribution in eight males presenting with bilateral lower limb varicose veins. Testicular and internal iliac veins were examined with either one or a combination of computed tomography, magnetic resonance venography, testicular, transabdominal or transrectal duplex ultrasonography. Subsequently, all patients received pelvic vein embolisation, prior to leg varicose vein treatment. Results Pelvic vein reflux was found in 23 of the 32 truncal pelvic veins and these were treated by pelvic vein embolisation. Four patients have since completed their leg varicose vein treatment and four are undergoing leg varicose vein treatments currently. Conclusion Pelvic vein reflux contributes towards lower limb venous insufficiency in some males with leg varicose veins. Despite the challenges, we suggest that pelvic vein reflux should probably be investigated and pelvic vein embolisation considered in such patients.

Background During sclerotherapy, it has been recommended to confirm intravenous placement of the needle by aspirating blood into the sclerosant syringe. This may inactivate some, or all of the sclerosant. Aims To quantify the volume of human blood needed to completely inactivate 1 ml of sodium tetradecyl sulphate, and comparing fresh blood and blood that has been stored in an ethylenediaminetetraacetic acid tube. Methods A series of manual titrations were carried out following a procedure developed at STD Pharmaceutical Products Ltd (Hereford, UK) and listed in the British Pharmacopeia. Three percent of sodium tetradecyl sulphate stock solutions were made with increasing volumes of blood and titrated against benzethonium chloride to determine the active concentration (% w/v) of sodium tetradecyl sulphate remaining in the solution. Results A calculated approximation showed 0.3 ml of blood is required to fully inactivate 1 ml of 3% sodium tetradecyl sulphate when made into a foam. A comparison was made between the use of fresh blood and blood stored in ethylenediaminetetraacetic acid tubes. Blood stored in ethylenediaminetetraacetic acid tubes showed more inactivation of sodium tetradecyl sulphate, but this was not significant at the P ≤ 0.05 level. Conclusion The data from our study have shown that a minimum of 0.3 ml of fresh blood is required to inactivate 1 ml of 3% sodium tetradecyl sulphate as a foam and it is not significantly affected by storing blood in an ethylenediaminetetraacetic acid tube. Our methodology suggests that during foam sclerotherapy treatment, blood should not be aspirated into the syringe to confirm position, and that ultrasound guidance is more appropriate for needle placement.

Background In previous in vitro and ex vivo studies, we have shown increased thermal spread can be achieved with radiofrequency-induced thermotherapy when using a low power and slower, discontinuous pullback. We aimed to determine the clinical success rate of radiofrequency-induced thermotherapy using this optimised protocol for the treatment of superficial venous reflux in truncal veins. Methods Sixty-three patients were treated with radiofrequency-induced thermotherapy using the optimised protocol and were followed up after one year (mean 16.3 months). Thirty-five patients returned for audit, giving a response rate of 56%. Duplex ultrasonography was employed to check for truncal reflux and compared to initial scans. Results In the 35 patients studied, there were 48 legs, with 64 truncal veins treated by radiofrequency-induced thermotherapy (34 great saphenous, 15 small saphenous and 15 anterior accessory saphenous veins). One year post-treatment, complete closure of all previously refluxing truncal veins was demonstrated on ultrasound, giving a success rate of 100%. Conclusions Using a previously reported optimised, low power/slow pullback radiofrequency-induced thermotherapy protocol, we have shown it is possible to achieve a 100% ablation at one year. This compares favourably with results reported at one year post-procedure using the high power/fast pullback protocols that are currently recommended for this device.

The dynamics of the aragonite saturation state (Ω arag ) were investigated in the eutrophic coastal waters of Guanabara Bay (RJ-Brazil). Large phytoplankton blooms stimulated by a high nutrient enrichment promoted the production of organic matter with strong uptake of dissolved inorganic carbon (DIC) in surface waters, lowering the concentrations of dissolved carbon dioxide (CO 2aq ), and increasing the pH, Ω arag and carbonate ion (CO 3 2- ), especially during summer. The increase of Ω arag related to biological activity was also evident comparing the negative relationship between the Ω arag and the apparent utilization of oxygen (AOU), with a very close behavior between the slopes of the linear regression and the Redfield ratio. The lowest values of Ω arag were found at low-buffered waters in regions that receive direct discharges from domestic effluents and polluted rivers, with episodic evidences of corrosive waters (Ω arag <1). This study showed that the eutrophication controlled the variations of Ω arag in Guanabara Bay., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although widely spread throughout Sudan, visceral leishmaniasis (VL) is predominantly endemic in the Gedaref, southern Blue-Nile, and Umrimta areas located in the eastern, southern, and central regions, respectively. Regardless of form (endemic or epidemic), VL occurrence follows similar patterns as all ages and both sexes are affected. From January 2005 to May 2016, we received a total of 563 patients with high suspicion for VL from various endemic areas; 159 were children and adolescents (0.5-18 years) from Umrimta (central Sudan). A significant observation during this 11-year period of uninterrupted monitoring using a standard liquid direct agglutination test (LQ-DAT) version was the exclusive VL occurrence (100%) in the child and adolescent populations of Umrimta when compared with other endemic areas (27.3%-48.0%). Among 12 child and adolescent suspects who initially tested marginal in the standard LQ-DAT, 6 scored unequivocally positive readings both in an improved LQ-DAT version (based on an autochthonous Leishmania donovani strain) and rK28 VL reference test. None of the 4 (2.5%) VL adult suspects (≥19years) referred had positive outcomes in the improved LQ-DAT version or the VL reference freeze-dried direct agglutination and rK28 tests. Further incorporation of antigens derived from autochthonous L. donovani strains from Umrimta (central Sudan) or Gedaref (eastern Sudan) in LQ-DAT significantly increased the agglutination titer levels in the respective VL homologous sera (p=0.0263 T=505 and p=0.2814T=219), suggesting possible antigenic variation within the predominant Sudanese L. donovani complex. Additional research is required to determine characteristics other than the serologically-based ones reported for the L. donovani strain involved., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study examined within-group differences in obesity-related dietary behaviors and the health status of 156 Latino students at-risk for diabetes due to family history. Approximately 58% of students were overweight/obese, with female students reporting a greater risk for diabetes. Consumption of meats, fried potatoes, breads, and tortillas was associated with higher BMI and diabetes risk indices. Differences in dietary behaviors were found based on students' college profile and sociodemographic characteristics. Implications for university-related intervention health initiatives are discussed.

Objectives: Endovenous thermal ablation (EVTA) of varicose veins was introduced in the late 1990s with radiofrequency ablation (RFA) using the VNUS Closure device. The results of the original VNUS Closure device for the abolition of truncal venous reflux at 15 years are reported., Methods: A prospective audit of a group of patients treated with VNUS Closure 15 years previously was carried out, using clinical assessment and duplex ultrasound. A total of 189 patients were treated with VNUS Closure between March 1999 and December 2001 and were invited for clinical assessment (subjective and objective) and duplex ultrasonography (DUS) to assess treatment outcome and de novo disease progression. DUS outcome of the treated vein was graded: 1, complete success (complete atrophy); 2, partial success (> 1 patent section; none giving rise to recurrent varicose veins); 3, partial failure (≥ 1 patent sections giving rise to recurrent varicose veins); 4, complete failure., Results: Fifty-eight patients (91 legs, 101 truncal veins) returned for follow-up DUS, giving a 31.5% response rate (many patients had moved or had died in the 15 years). Two truncal veins had been excluded following treatment elsewhere presumably for partial or complete failure. At a mean of 15.4 years post-procedure, 51 (56%) reported no varicose veins, 58 (100%) that they were pleased that they had the procedure and 57 (98%) that they would recommend the procedure. DUS showed 88% of patients achieved success with no clinical recurrence in the originally treated veins. De novo reflux was identified in 47 of 91 legs (51.6%), showing disease progression in veins that were originally competent., Conclusions: RFA with VNUS Closure achieved excellent long-term technical success in treating venous reflux in truncal veins 15 years post-procedure, demonstrated by DUS. This bodes well for the increased use of EVTA in treating truncal vein reflux., (Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Aims: To investigate the thermal spread achieved in porcine liver when using an optimised radiofrequency ablation protocol and correlate findings with the effects seen in ex vivo great saphenous vein (GSV), in order to justify clinical use with the new treatment protocol., Material and Methods: Porcine liver and GSV sections were treated with radiofrequency-induced thermotherapy (RFiTT) using the following settings: 20 W at 1 s/cm (linear endovenous energy density; LEED 20 J/cm), 18 W at 1 s/cm (LEED 18 J/cm), 18 W at 3 s/cm (LEED 54 J/cm), 6 W interrupted pull-back 6 s stationary every 0.5 cm (LEED 72 J/cm). Thermal spread in the liver was measured via digital imaging. GSV sections were sent to an independent laboratory for histological analysis. Previous work suggests a thermal spread of >0.65 mm in liver correlates with transmural thermoablation of a GSV., Results: Parameters giving a LEED of 72 J/cm produced the best results, with a clear transmural effect in the GSV and maximal thermal spread of 1.65 mm, without excessive thermal damage or carbonisation in the ablation tract., Conclusions: Our porcine liver model correlated well with histological findings and was representative of the thermoablative effects observed in the GSV wall treated with RFiTT. Clinical investigations are now being carried out to investigate the efficacy of this protocol in the clinical setting.

Background: Nonthermal, tumescentless devices are the next generation of minimally invasive devices to treat varicose veins. We aimed to investigate the effects of mechanochemical ablation (MOCA) using ClariVein (Vascular Insights, Quincy, Mass) on ex vivo great saphenous vein with histology and immunofluorescent staining., Methods: Extrafascial great saphenous veins were harvested during surgery for varicose veins and were treated ex vivo for 10 to 11 minutes with either liquid sclerotherapy or the use of ClariVein, with and without 3% sodium tetradecyl sulfate. Veins were sectioned and subjected to hematoxylin and eosin staining and immunofluorescent staining for endothelial and smooth muscle cell markers (CD31 and α-actin) to assess overall damage and cell death in the vein wall compared with control sections., Results: Histologic observations confirmed intimal damage from ClariVein, as has been previously shown; however, medial damage was also evident, which was not observed in control or liquid sclerotherapy sections. Immunofluorescent staining in the three sections studied showed a 42% decrease in CD31 staining and 27% mean reduction in α-actin staining up to a depth of 300 μm with liquid sclerotherapy. This cytotoxic effect was significantly enhanced by MOCA with a reduction in CD31 staining just above 60% and a 46% mean decrease in α-actin staining noted up to a depth of 300 μm. Far greater reductions in staining compared with sclerotherapy were observed up to a depth of 600 μm., Conclusions: MOCA using 3% sodium tetradecyl sulfate increases the penetration of the sclerosant and its effect into the vein wall and shows superior rates of tissue destruction compared with liquid sclerotherapy alone. In this model, it appears not solely to damage the endothelium but also to shear the medial layer, creating small lesions into which sclerosant can flow and exert its cytotoxic effect., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Much less is known about grass-pollen allergens to dogs, when compared with humans. Genetic-based patterns might play an important role in sensitization profiles, conditioning the success of allergen-specific immunotherapy., Aim: Mapping of Dactylis glomerata ( D. glomerata ) and Phleum pratense ( P. pratense ) allergens for grass pollen-sensitized atopic dogs, for better understanding how individual allergograms may influence the response to grass-pollen immunotherapy., Material and Methods: To identify D. glomerata and P. pratense allergoms for dogs, 15 individuals allergic to grass pollen and sensitized to D. glomerata and P. pratense were selected. D. glomerata and P. pratense proteomes were separated by isoelectric focusing (IEF), one-dimensional (1-D) and two-dimensional (2-D) sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Separated proteins were blotted onto Polyvinylidene difluoride (PVDF) membranes and allergens were identified by patient sera IgE in Western Blotting (WB)., Results: In D. glomerata , 17 allergens were identified from IEF and 11 from 1-D SDS-PAGE, while from P. pratense , 18 and 6 allergens were identified, respectively. From 2-D SDS-PAGE 13 spots were identified from D. glomerata and 27 from P. pratense ., Conclusions: Several similarities were found between dog and human D. glomerata and P. pratense sensitization profiles but no relationship between clinical signs and a specific pattern of allergen recognition was observed. Similarities were found in each patient pattern of sensitization between D. glomerata and P. pratense , also suggesting cross-reactive phenomena. Further molecular epidemiology approach is needed to understand the role of the sensitization pattern in allergen-specific immunotherapy effectiveness in grass-pollen allergic dogs., Competing Interests: The authors declare no conflict of interest.

Background Pelvic venous reflux has been proven to contribute to the development of primary and recurrent varicose veins, vulval/labial varicose veins and pelvic congestion syndrome. It is associated with lower limb varicose veins in 20% of patients who have a history of at least one prior vaginal delivery. Pelvic vein embolisation is known to be a safe and effective treatment for the abolition of pelvic venous reflux. However, the effect of a subsequent pregnancy on a previously embolised patient remains largely unknown. This study aims to report the effect of pregnancy on patients that have undergone pelvic vein embolisation. Methods Patients that had previously undergone pelvic vein embolisation for pelvic venous reflux at our unit were sent a questionnaire asking if they had had a pregnancy and subsequently delivered post-embolisation. Patients responding positively were invited to attend our unit for transvaginal duplex ultrasonography of their pelvic veins. Post-pregnancy transvaginal duplex ultrasonography results were compared to pre-embolisation and 6-week post-embolisation scans. Results Eight women, aged 32-48 years (mean 38.8), were retrospectively analysed. Parity prior to embolisation ranged from 1 to 5 (mean 2.8). Initial outcomes at 6 weeks Pelvic venous reflux was completely eliminated in five patients, two patients achieved complete elimination of truncal reflux with very minor vulval reflux and one patient had persistent, mild reflux in the right internal iliac vein. Post-pregnancy outcomes Pelvic venous reflux was completely eliminated in three patients and five patients displayed pelvic venous reflux in at least one truncal vein, with or without concurrent vulval reflux. No patient showed any coil displacement or embolisation as a result of the pregnancy. Conclusions Pregnancy is associated with recurrent reflux in the pelvic veins in women who had previously been treated with coil embolisation. Following recovery from pregnancy, repeat embolisation can eliminate recurrent reflux. Pregnancy appears to be safe following coil embolisation of pelvic veins.

Background: Pelvic venous reflux is known to be associated with lower limb varicose veins in 20% of women with a history of at least one previous vaginal delivery. Pelvic vein embolisation with coils has been shown to be a successful treatment in the short term. The objective of this study was to ascertain the long-term outcomes of pelvic vein embolisation for pelvic venous reflux., Methods: Patients who had undergone pelvic vein embolisation in 2005-2007 were invited back to a specialist vein unit for transvaginal duplex ultrasonography in the summer of 2013. A total of 110 women were contacted. Pre-embolisation transvaginal duplex ultrasonography results were compared to those obtained six weeks post-procedure and at long-term follow-up., Results: Twenty-eight female patients aged 40 to 75 years (mean 53.5) attended (response rate 25.5%), with parity prior to embolisation ranging from 1-5 children (mean 2.8). Mean follow-up time was 7.5 years. Six weeks post-procedure, 25 women had complete or virtual elimination of all reflux, and three had persistent reflux in at least one vein. At long-term follow-up, 11 women had complete elimination of all reflux, seven had elimination of all truncal reflux but minor reflux in vulval veins, six had minor reflux in one truncal vein, and four had significant reflux in one or more truncal veins (one of these gave birth one-year post-pelvic vein embolisation and another had coils removed during gynaecological surgery)., Conclusions: Transjugular pelvic vein embolisation is a durable technique for the abolition of reflux in the pelvic veins and is particularly adept at treating reflux in the ovarian veins., (© The Author(s) 2015.)

A prerequisite for the control of visceral leishmaniasis (VL) is the accessibility to reference diagnostics. The high price of the freeze-dried direct agglutination test (FD-DAT) and the short shelf-life time of the rK39 strip test (rK39) have limited the application of these tests in Sudan. An original liquid DAT (LQ-DAT) with high reproducibility compared with the FD-DAT and rK39 has been routinely produced in our laboratory since 1999. In this study, a 3.4-year-old batch (of more than 90 test batches produced to date) was chosen to validate the diagnostic performance of this test against microscopy, FD-DAT, and rK39 in 96 VL and 42 non-VL serum samples. Relatively higher sensitivity (95/96, 99.0%) was recorded for the LQ-DAT than for the FD-DAT (92/96, 95.8%) and rK39 (76/96, 79.2%), probably because of the use of the endemic autochthonous Leishmania donovani isolate as the antigen. Experience with the LQ-DAT, its low cost of production, ease of providing this test, and diagnostic reliability compared with the FD-DAT suggest that widescale implementation of the LQ-DAT can contribute to sustainable VL control in Sudan., (© The American Society of Tropical Medicine and Hygiene.)

Langerhans cell histiocytosis (LCH) is a neoplastic myeloid disorder with a thus far poorly understood immune component. Tertiary lymphoid structures (TLS) are lymph node-like entities which create an immune-promoting microenvironment at tumor sites. We analyzed the presence and clinical relevance of TLS in n = 104 H&E-stained, therapy-naive LCH lesions of non-lymphoid origin and applied immunohistochemistry to a smaller series. Lymphoid-follicular aggregates were detected in 34/104 (33%) lesions. In line with the lymphocyte recruitment capacity of MECA-79(+) high endothelial venules (HEVs), MECA-79(+)-expressing-LCH lesions (37/77, 48%) contained the most CD3(+) T-lymphocytes (p = 0.003). TLS were identified in 8/15 lesions and contained T-and B-lymphocytes, Follicular Dendritic Cells (FDC), HEVs and the chemokines CXCL13 and CCL21 representing key cellular components and TLS-inducing factors in conventional lymph nodes (LN). Lymphoid-follicular aggregates were most frequently detected in patients presenting with unifocal LCH (24/70, 34%) as compared to patients with poly-ostotic or multi-system LCH (7/30, 23%, p = 0.03). In addition, patients with lymphoid-follicular aggregates-containing lesions had the lowest risk to develop new LCH lesions (p = 0.04). The identification of various stages of TLS formation within LCH lesions may indicate a key role for the immune system in controlling aberrant histiocytes which arise in peripheral tissues.

Objective/background: Traditionally, sclerotherapy has been thought to work by the cytotoxic effect of the sclerosant upon the endothelium alone. However, studies have shown that sclerotherapy is more successful in smaller veins than in larger veins. This could be explained by the penetration of the sclerosant, or its effect, into the media. This study aimed to investigate intimal and medial damage profiles after sclerosant treatment., Methods: Fresh human varicose veins were treated ex vivo with either 1% or 3% sodium tetradecyl sulphate (STS) for 1 or 10 minutes. The effect of the sclerosant on the vein wall was investigated by immunofluorescent labelling of transverse vein sections using markers for endothelium (CD31), smooth muscle (α-actin), apoptosis (p53) and inflammation (intercellular adhesion molecule-1 [ICAM-1]). Polidocanol (POL; 3%) treatment at 10 minutes was similarly investigated., Results: Endothelial cell death was concentration- and time-dependent for STS but incomplete for both sclerosants. Time, but not concentration, significantly affected cell death (p > .001). A 40% and 30% maximum reduction was observed for STS and POL, respectively. Destruction of 20-30% of smooth muscle cells was found up to 250 μm from the lumen after 3% STS treatment for 10 minutes. POL treatment for 10 minutes showed inferior destruction of medial cells. Following STS treatment and 24-hour tissue culture, p53 and ICAM-1 were upregulated to a depth of around 300 μm. This effect was not observed with POL., Conclusion: Inflammatory and apoptotic markers show the same distribution as medial cell death, implying that sclerotherapy with STS works by inducing apoptosis in the vein wall rather than having an effect restricted to the endothelium. Incomplete loss of endothelial cells and penetration of the sclerosant effect up to 250 μm into the media suggest that medial damage is crucial to the success of sclerotherapy and may explain why it is less effective in larger veins., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess the suitability of transvaginal duplex ultrasonography to identify pathological reflux in the ovarian and internal iliac veins in women., Methods: A retrospective study of patients treated in 2011 and 2012 was performed in a specialised vein clinic. Diagnostic transvaginal duplex ultrasonography in women presenting with symptoms or signs of pelvic vein reflux were compared with the outcomes of treatment from pelvic vein embolisation. A repeat transvaginal duplex ultrasonography was performed 6 weeks later by a blinded observer and any residual reflux was identified., Results: Results from 100 sequential patients were analysed. Mean age 44.2 years (32-69) with mode average parity of 3 (0-5 deliveries). Pre-treatment, 289/400 veins were refluxing (ovarian - 29 right, 81 left; internal iliac - 93 right, 86 left). Coil embolisation was successful in 86/100 patients and failed partially in 14/100 - 5 due to failure to cannulate the target vein. One false-positive diagnosis was made., Conclusion: Currently there is no accepted gold standard for pelvic vein incompetence. Comparing transvaginal duplex ultrasonography with the outcome from selectively treating the veins identified as having pathological reflux with coil embolisation, there were no false-negative diagnoses and only one false-positive. This study suggests that transvaginal duplex ultrasonography could be the gold standard in assessing pelvic vein reflux., (© The Author(s) 2014.)

Objective: To analyze the association between physical activity, participation in Physical Education classes, and indicators of social isolation among adolescents., Methods: This was an epidemiological study based on secondary analysis of data from a representative sample of students (14-19 years) from public high schools (n=4,207). Data were collected through the questionnaire Global School-based Student Health Survey. The independent variables were the level of physical activity and enrollment in Physical Education classes, while the dependent variables were two indicators of social isolation (feeling of loneliness and having few friends). Descriptive and inferential procedures were used in the statistical analysis., Results: Most of the adolescents were classified as insufficiently active (65.1%) and reported not attending Physical Education classes (64.9%). Approximately two in each ten participants reported feeling of loneliness (15.8%) and, in addition, about one in each five adolescents reported have only one friend (19.5%). In the bivariate analysis, a significantly lower proportion of individuals reporting social isolation was observed among adolescents who referred higher enrollment in Physical Education classes. After adjustment for confounding variables, binary logistic regression showed that attending Physical Education classes was identified as a protective factor in relation to the indicator of social isolation 'having few friends,' but only for girls., Conclusions: It was concluded that participation in Physical Education classes is associated with reduced social isolation among female adolescents., (Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Langerhans cell histiocytosis (LCH) lesions are characterized by neoplastic CD1a(+)/Langerin(+) histiocytes (LCH-cells) and display many features of chronic inflammation. Cancer cells can escape immune-surveillance through intra-tumoral secretion of immune-suppressive cytokines. We therefore studied by immunohistochemistry the local cytokine milieu and phenotypic characteristics of T-cells and LCH-cells present in LCH lesions collected from 25 therapy naïve patients. LCH biopsies predominantly expressed interleukin-10 (IL-10) (10/25), transforming growth factor-beta (TGF-β) (9/25), or both cytokines (6/25). The absolute number of CD3(+)T-cells and the CD3(+)FOXP3(-) conventional cell (T-CONV) versus the CD3(+)FOXP3(+) regulatory T-cell (T-REG) was comparable for each suppressive cytokine profile (5:1). IL-10-expressing lesions contained, however, a higher proportion of T-CONV expressing the activation markers CD25 98% (38%-100%) and inducible costimulatory molecule (ICOS) 86% (47%-100%) than lesions wherein solely TGF-β was detected (CD25(+) 20% (6%-54%); ICOS(+) 29% (7%-51%)). Virtually all T-REG expressed CD25 and ICOS in IL-10 lesions, whereas TGF-β(+) lesions contained a lower proportion of ICOS(+) T-REG (P=0.05). IL-10(+) lesions contained more LCH-cells expressing high intensity of ICOS ligand (ICOSL) compared with TGF-β(+) lesions (P=0.03). ICOS expression by lesion-infiltrating T-CONV and T-REG positively correlated to the extent of ICOSL expression by LCH-cells (P=0.004). Our study points out that the combined detection of interlesional IL-10 and ICOSL expression by LCH-cells is associated with the highest prevalence of activated T-CONV. Immune profiling of LCH-affected tissues obtained at the time of diagnosis may set the stage for the development of new types of therapies, which aim at local boosting of immune cells that recognize and eliminate neoplastic LCH-cells.

Purpose: Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder characterized by tissue accumulating CD1a + histiocytes which frequently carry somatic mutations. Irrespective of mutation status, these LCH-cells display constitutively active kinases belonging to the MAPK pathway. We evaluated, in retrospect, the contribution of individual components of the MAPK-activating and chemotaxis-promoting TNF-CXCR4-CXCL12 axis to LCH manifestation and outcome., Experimental Design: CXCR4, CXCL12 and TNF protein expression was immunohistochemically analyzed in 70 LCH-affected biopsies. The presence of CXCR4 + CD1a + cells in peripheral blood (PB) and/or bone marrow (BM) samples was evaluated by flowcytometry in 13 therapy-naive LCH-patients., Results: CXCL12 was detected in 68/70 (97%) biopsies. CXCR4 + LCH-cells were present in 50/70 (71%) biopsies; their presence was associated with higher levels of intralesional TNF. Circulating CD1a + CXCR4 + cells were detected in 4/13 (31%) therapy-naïve LCH-patients which displayed BRAF V600E (2/4), MAP2K1 (1/4) or no (1/4) mutations in their tissues. These CD11c co-expressing CD1a + CXCR4 + cells migrated to CXCL12 in chemotaxis assays. Lesional CXCR4 + LCH-cells were detected in 18/20 cases who presented with LCH manifestation at multiple sites and in 5/23 (22%) patients who developed additional lesions after initially presenting with a single lesion. The CXCR4 status at onset proved to be an independent risk factor for LCH reactivation in multivariate analysis (odds ratio 10.4, p = 0.034)., Conclusions: This study provides the first evidence that CXCR4 is involved in the homing and retention of LCH-cells in CXCL12-expressing tissues and qualifies CXCR4 as a candidate prognostic marker for less favorable disease outcome.