bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial organization of Clostridium difficile S-layer biogenesis
Authors: Oatley Peter , Kirk Joseph A. , Ma Shuwen , Jones Simon , Fagan Robert P.
Published: August 2018

Surface layers (S-layers) are protective protein coats which form around all archaea and most bacterial cells. Clostridium difficile is a Gram-positive bacterium with an S-layer covering its peptidoglycan cell wall. The S-layer in C. difficile is constructed mainly of S-layer protein A (SlpA), which is a key virulence factor and an absolute requirement for disease. S-layer biogenesis is a complex multi-step process, disruption of which has severe consequences for the bacterium. We examined the subcellular localization of SlpA secretion and S-layer growth; observing formation of S-layer at specific sites that coincide with cell wall synthesis, while the secretion of SlpA from the cell is relatively delocalized. We conclude that this delocalized secretion of SlpA leads to a pool of precursor in the cell wall which is available to repair openings in the S-layer formed during cell growth or following damage.
Bipolar Switching by HCN Voltage Sensor Underlies Hyperpolarization Activation
Authors: Cowgill John , Klenchin Vadim A. , Alvarez-Baron Claudia , Tewari Debanjan , Blair Alexander , Chanda Baron
Published: August 2018

Despite sharing a common architecture with archetypal voltage-gated ion channels (VGIC), the hyperpolarization- and cyclic AMP-activated ion (HCN) channels open upon hyperpolarization rather than depolarization. The basic motions of voltage sensor and pore gates are conserved implying that these domains are inversely coupled in HCN channels. Using structure-guided protein engineering, we systematically assembled an array of mosaic channels that display the full complement of voltage-activation phenotypes observed in the VGIC superfamily. Our studies reveal that the voltage-sensing S3b-S4 transmembrane segment of the HCN channel has an intrinsic ability to drive pore opening in either direction. Specific contacts at the pore-voltage sensor interface and unique interactions near the pore gate forces the HCN channel into a hERG-like inactivated state, thereby obscuring their opening upon depolarization. Our findings reveal an unexpected common principle underpinning voltage gating in the VGIC superfamily and identify the essential determinants of gating polarity.
A screen for targets of the Drosophila pseudokinase Tribbles identifies Neuralized and Mindbomb, ubiquitin ligases that mediate Notch signaling
Authors: Shipman Anna , Nauman Christopher , Haymans Britney , Silverstein Rachel , Dobens Leonard L.
Published: August 2018

Drosophila Tribbles (Trbl) is the founding member of a family of pseudokinases with conserved roles in antagonizing cell division, tissue growth and cell differentiation. In humans, three Tribbles isoforms serve as adaptor proteins, binding targets such as Cdc25 phosphatase, Akt kinase or the transcription factor C/EBP to block their activity or direct their proteosomal degradation. Mutations in Tribbles family members are associated with susceptibility to diabetes and cancer, notably Notch-induced tumor growth. Trbl misexpression in the fly wing disk leads to a block in mitosis associated with decreased levels of String/Cdc25 and increased levels of Cyclin B leading to reduced overall wing size and reduced trichome density. We show these Trbl growth-restricting phenotypes can be suppressed by manipulating levels of known Trbl targets, and use this sensitized wing system to screen a collection of growth regulating open reading frames (ORFs) to search for enhancers and suppressors affecting cell and tissue size. By precisely measuring morphometric changes in wing phenotypes using a computer-based tool, we detected synthetic interactions with several E3 ubiquitin ligases, and focused our analysis on the Notch pathway components Neuralized (Neur) and Mindbomb1 (Mib1). In the wing, notum and egg chamber epithelia, Trbl misexpression suppressed Neur and Mib1 activities and stabilized the accumulation of both proteins. To understand these interactions, we used yeast two-hybrid assays to show Trbl physically bound to both Neur and Mib1. Our data are consistent with published reports that mammalian Tribbles3 modulates Notch responses by binding and stabilizing Mindbomb and indicate that a wing misexpression approach is useful to identify novel components in a conserved Tribbles signaling pathway.

AUTHOR SUMMARY

Tribbles pseudokinases are adaptor molecules, binding diverse targets regulating cell differentiation, growth and proliferation and directing their proteasomal degradation. To search for novel targets of Drosophila Tribbles, we adopted a wing co-misexpression scheme and measured changes in cell/tissue size to identify enhancers and suppressors of the Tribbles phenotype. We show the Notch pathway components Neuralized and Mindbomb1 E3 ligases act as Tribbles suppressors and demonstrate that Tribbles modulates their levels and activites. Recent demonstration that mammalian Tribbles 3 binds the E3 ligase Mindbomb to promote ligand-mediated Notch activation implies a conserved role for Tribbles family members in Notch activation.
Using three-dimensional regulatory chromatin interactions from adult and fetal cortex to interpret genetic results for psychiatric disorders and cognitive traits
Authors: Giusti-Rodriguez Paola MD , Sullivan Patrick F
Published: August 2018

Genome-wide association studies have identified hundreds of genetic associations for complex psychiatric disorders and cognitive traits. However, interpretation of most of these findings is complicated by the presence of many significant and highly correlated genetic variants located in non-coding regions. Here, we address this issue by creating a high-resolution map of the three-dimensional (3D) genome organization by applying Hi-C to adult and fetal brain cortex with concomitant RNA-seq, open chromatin (ATAC-seq), and ChIP-seq data (H3K27ac, H3K4me3, and CTCF). Extensive analyses established the quality, information content, and salience of these new Hi-C data. We used these data to connect 938 significant genetic loci for schizophrenia, intelligence, ADHD, alcohol dependence, Alzheimer's disease, anorexia nervosa, autism spectrum disorder, bipolar disorder, major depression, and educational attainment to 8,595 genes (with 42.1% of these genes implicated more than once). We show that assigning genes to traits based on proximity provides a limited view of the complexity of GWAS findings and that gene set analyses based on functional genomic data provide an expanded view of the biological processes involved in the etiology of schizophrenia and other complex brain traits.
2,2′-Bipyridin-1-ium hemioxalate oxalic acid monohydrate
Authors: Dziuk Błażej , Jezuita Anna
Published: August 2018

The asymmetric unit of the title compound, C10H9N2
+·0.5C2O4
2−·C2H2O4·H2O, consists of a 2,2′-bipyridinium cation, half an oxalate dianion, one oxalic acid and one water molecule. One N atom in 2,2′-bipyridine is unprotonated, while the second is protonated and forms an N—H...O hydrogen bond. In the crystal, the anions are connected with surrounding acid molecules and water molecules by strong near-linear O—H...O hydrogen bonds. The water molecules are located between the anions and oxalic acids; their O atoms participate as donors and acceptors, respectively, in O—H...O hydrogen bonds, which form sheets arranged parallel to the ac plane.
(Z)-3-[(3,5-Dichloroanilino)methylidene]-5-(4-methylphenyl)furan-2(3H)-one
Authors: Grinev Vyacheslav S. , Osipov Alexander K. , Yegorova Alevtina Yu.
Published: August 2018

The crystal structure of the title compound, C18H13Cl2NO2, at 120 K has triclinic (P\overline{1}) symmetry. The molecule demonstrates non-planarity in the solid state and a Z configuration for the exocyclic C=C bond. The Z form is stabilized by the presence of an intramolecular N—H...O hydrogen bond with an O...H interatomic distance of 2.18 (2) Å.
“Stickiness”: gauging students’ attention to online learning activities
Authors: Robinson Ainslie , Cook David
Published: August 2018

Purpose

Online content developers use the term “stickiness” to refer to the ability of their online service or game to attract and hold the attention of users and create a compelling and magnetic reason for them to return repeatedly (examples include virtual pets and social media). In business circles, the same term connotes the level of consumer loyalty to a particular brand. This paper aims to extend the concept of “stickiness” not only to describe repeat return and commitment to the learning “product”, but also as a measure of the extent to which students are engaged in online learning opportunities.

Design/methodology/approach

This paper explores the efficacy of several approaches to the monitoring and measuring of online learning environments, and proposes a framework for assessing the extent to which these environments are compelling, engaging and “sticky”.

Findings

In particular, the exploration so far has highlighted the difference between how lecturers have monitored the engagement of students in a face-to-face setting versus the online teaching environment.

Practical implications

In the higher education environment where increasingly students are being asked to access learning in the online space, it is vital for teachers to be in a position to monitor and guide students in their engagement with online materials.

Originality/value

The mere presence of learning materials online is not sufficient evidence of engagement. This paper offers options for testing specific attention to online materials allowing greater assurance around engagement with relevant and effective online learning activities.
Populism and Fiscal Illusion
Authors: Davidson Sinclair
Published: August 2018

There is a widespread concern that anti‐elitist or populist opinion is on the rise. The policy concern is that political opportunists would exploit voter rational ignorance for their own cynical purposes. In this article I demonstrate that, in the field of taxation, this sort of behaviour already occurs. Fiscal illusion can be described as deceiving taxpayer‐voters into paying more tax than they would otherwise agree to. Taxpayers are already victims of political opportunism unrelated to the rise of populism.
Top‐Down Constitutional Conventions
Authors: Perry Adam , Tucker Adam
Published: August 2018

Many scholars think that all conventions of the constitution emerge from the bottom up, out of the practices of constitutional actors. Here we develop the first systematic account of conventions that are imposed from the top down, through prescriptions by constitutional actors. We show that ‘top‐down conventions’ (as we term them) can be created through the use of normative rule‐making powers; that powers of the right kind are sometimes conferred by ‘bottom‐up conventions’; that these powers are often exercised; and, as a result, that top‐down conventions are increasingly common. We show, too, that as the formal, systematic, and intentional products of a small number of constitutional actors, top‐down conventions are a potentially illegitimate form of constitutional regulation.
Childhood growth of singletons conceived following in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta‐analysis
Authors: Bay B , Lyngsø J , Hohwü L , Kesmodel US
Published: August 2018

Background

Assisted reproductive techniques are associated with an increased risk of adverse pregnancy outcomes, including low birthweight and intrauterine growth restriction. Yet, the long‐term follow‐up on the growth of these children is limited.

Objective

To systematically review the literature on post‐neonatal height and weight among children conceived following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, compared with that of children born after spontaneous conception.

Search strategy

A systematic computerised literature search using the online databases PubMed, Embase, and Scopus.

Selection criteria

Cohort or case–control studies with an exposed group of singletons conceived following IVF or ICSI along with a control group of spontaneously conceived singletons.

Data collection and analysis

Studies were reviewed by at least two authors. Meta‐analyses were conducted using Cochrane Review Manager. The quality of the studies was assessed with the Newcastle–Ottawa Scale.

Main results

Twenty studies were included, with 13 of these eligible for meta‐analyses. The meta‐analyses compared 3972 children born after IVF/ICSI with 11 012 spontaneously conceived children and revealed no statistically significant difference in child weight [mean difference (MD) in weight of −160 g; 95% confidence interval (95% CI) −360, 3]. When stratifying by age of child at follow‐up, we found a significant lower weight in children aged 0–4 years conceived following IVF/ICSI treatment (MD −180 g; 95% CI −320, −4), but this was no longer significant in children from 5 years of age (MD −160 g; 95% CI −580, 260). The pooled analysis revealed no statistically significant difference in childhood height.

Conclusions

In vitro fertilisation/ICSI was not associated with long‐term weight and height.

Tweetable abstract

Children born following IVF/ICSI do not have impaired long‐term weight or height compared with spontaneously conceived children.
Application of 2012 EULAR/ACR criteria for polymyalgia rheumatica to Korean patients previously classified by Chuang and Hunder criteria or Healey criteria
Authors: Park Eun Seong , Ahn Sung Soo , Jung Seung Min , Song Jungsik , Park Yong‐Beom , Lee Sang‐Won
Published: August 2018

Aim

To apply 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria to Korean patients previously classified as polymyalgia rheumatica (PMR) by Chuang and Hunder criteria or Healey criteria and investigated whether they might be still reclassified as PMR or not.

Methods

We retrospectively reviewed the medical records of 113 previously classified PMR patients. We applied 2012 EULAR/ACR criteria without ultrasonography to PMR patients, and fulfilment required at least 4 points. We evaluated odds ratios (OR) using logistic regression analyses.

Results

The mean age was 61.7 years. Seventy‐one patients (62.8%) fulfilled Chuang and Hunder criteria, and 113 patients (100%) met Healey criteria. When we applied 2012 EULAR/ACR criteria, 98 patients fulfilled essential items (≥50 years, bilateral shoulder aching and abnormal C‐reactive protein or erythrocyte sedimentation rate), and only 80 patients achieved points ≥4. Eight patients fulfilling the criteria exhibited higher frequencies of all the detailed items than those who did not. In multivariate logistic regression analysis, absence of rheumatoid factor or anti‐citrullinated peptide antibodies was the only independent contributing item to the fulfilment of 2012 EULAR/ACR criteria (OR 23.571, 95% CI 6.357‐87.407, P < .001). When we reclassified 33 excluded patients, the most common newly classified disease was generalized osteoarthritis (24.2%), followed by osteoporosis with compression fracture (15.2%).

Conclusion

Eighty of 113 patients (81.6%) previously classified by Chuang and Hunder criteria or Healey criteria fulfilled 2012 EULAR/ACR criteria for PMR.
Vasculitis research: Current trends and future perspectives
Authors: Misra Durga P. , Naidu Godasi S. R. S. N. K. , Agarwal Vikas , Sharma Aman
Published: August 2018

We discuss recent and prospective research in small and large vessel vasculitis. Large cohorts of Takayasu arteritis (TA) have been recently published from across the world, clarifying our understanding of this uncommon disease. Novel open‐ended approaches like large‐scale genotyping, proteomics and metabolomics have helped gain novel insights into TA, giant cell arteritis (GCA) and anti‐neutrophil cytoplasmic antibody‐associated vasculitis (AAV). Recent advances in the imaging of TA and GCA offer promise for earlier diagnosis and better monitoring of response to therapy. Although two randomized controlled trials of abatacept and tocilizumab failed to meet their primary end‐points, successful large‐scale studies of abatacept and tocilizumab in GCA hold promise for better disease control. While cyclophosphamide has revolutionized the management of AAV, increasing use of rituximab as an alternative induction regimen, as well as use of novel approaches involving reduced or no corticosteroid use for AAV and alternative agents such as avacopan (a complement 5a receptor antagonist) hold promise for lesser toxic induction regimens in the future. Increasingly, the risk of cardiovascular events and comorbidities such as osteoporosis are being recognized as factors affecting long‐term prospects of patients with vasculitis. There is a shift in emphasis to utilize patient‐reported outcomes to more accurately gauge the impact of vasculitides and their treatment.
Retention rates of adalimumab, etanercept, and infliximab as first‐ or second‐line biotherapies for spondyloarthritis patients in daily practice in Auvergne (France)
Authors: Soubrier Martin , Pereira Bruno , Fan Angelique , Frayssac Thomas , Couderc Marion , Malochet‐Guinamand Sandrine , Mathieu Sylvain , Tatar Zuzana , Tournadre Anne , Dubost Jean‐Jacques
Published: August 2018

Objective

To compare, in real‐life settings, the retention rates of initial anti‐tumor‐necrosis factor (TNF) treatments (etanercept [ETN], adalimumab [ADA] and infliximab [IFX]) used as first‐line biotherapy for axial spondyloarthritis (axSpA), and evaluate treatment switches to another anti‐TNF inhibitor in the event of treatment failure.

Methods

We analyzed the medical records of all SpA patients (Assessment in Ankylosing Spondylitis International Working Group axial criteria) treated with ETN, IFX or ADA between 2001 and February 2015. Drug retention rates were calculated using the Kaplan‐Meier method and compared by means of the Cox extended model. Sub‐analyses were performed according to discontinuation reasons.

Results

Of the 249 SpA patients analyzed (135 radiographic cases, 114 non‐radiographic), 102 received ETN, 62 ADA, and 85 IFX. In total, 103 discontinued treatment. The retention rates of IFX, ADA and ETN were 67%, 59% and 56% after 3 years; 62%, 42% and 47% after 5 years; 55%, 42% and 24% after 8 years; 53%, 42% and 12% after 10 years, respectively. In multivariate analyses, the predictive factors for retention were: low BASDAI score (hazard ratio [HR]: 1.02 [1.01‐1.04]), high C‐reactive protein levels (HR: 0.98 [0.97‐0.99]), concomitant disease‐modifying therapy (HR: 0.4 [0.21‐0.75]), and radiographic SpA (HR: 1.5 [1.0‐2.52]). In total, 61 patients switched to another anti‐TNF therapy. No difference was observed among the three anti‐TNF therapies regarding median retention duration, although the retention rate proved higher for treatment switches from one monoclonal antibody to another.

Conclusion

The retention rate in SpA patients proved high, with retention for IFX superior to that of ETN.
Efficacy of abatacept tapering therapy for sustained remission in patients with rheumatoid arthritis: Prospective single‐center study
Authors: Yoshida Shuzo , Kotani Takuya , Kimura Yuko , Matsumura Yoko , Yoshikawa Ayaka , Tokai Nao , Ozaki Takuro , Nagai Koji , Takeuchi Toru , Makino Shigeki , Arawaka Shigeki
Published: August 2018

Aim

To investigate whether remission can be sustained for rheumatoid arthritis (RA) patients after tapering abatacept (ABT).

Method

All patients were naïve to biological disease‐modifying anti‐rheumatic drugs (bDMARDs) and in low or moderate Disease Activity Score of 28 joints with C‐reactive protein (DAS)28‐CRP). ABT was administrated intravenously (IV) or subcutaneously (SC) for 36 weeks to patients with RA, who had not previously received bDMARDs. As the ABT tapering protocol, ABT was administrated SC at 125 mg every 2 weeks for 12 weeks in patients with remission. RA disease activity was assessed by DAS28‐CRP and ultrasonography. Remission was assessed by defining it as DAS28‐CRP <2.3.

Results

Of the 51 patients, 84.3% were women (mean age 68.7 ± 10.2 years, mean disease duration 7.7 ± 10.2 years). Twenty‐nine patients achieved remission and a power Doppler (PD) score ≤1 at each joint at 36 weeks, followed by tapering ABT. Of these patients, 25 sustained DAS28‐CRP remission, and DAS28‐CRP was not significantly elevated (1.62 ± 0.41 to 1.69 ± 0.49) at 48 weeks, but the total PD score was significantly elevated (1.52 ± 1.21 to 2.59 ± 2.81 P = 0.049). Longer disease duration, higher DAS28‐CRP at 24 weeks, and higher total PD score at 24 weeks were predictors of an elevated total PD score after tapering ABT therapy.

Conclusion

These findings suggest that ABT tapering is a promising short‐term strategy to sustain remission in patients with RA, and ultrasonography is a useful tool for monitoring disease activity after tapering ABT.
TXNIP regulates AKT‐mediated cellular senescence by direct interaction under glucose‐mediated metabolic stress
Authors: Huy Hangsak , Song Hae Young , Kim Mi Jeong , Kim Won Sam , Kim Dong Oh , Byun Jae‐Eun , Lee Jungwoon , Park Young‐Jun , Kim Tae‐Don , Yoon Suk Ran , Choi Eun‐Ji , Lee Chul‐Ho , Noh Ji‐Yoon , Jung Haiyoung , Choi Inpyo
Published: August 2018

Aging is associated with an inevitable and universal loss of cell homeostasis and restricts an organism's lifespan by an increased susceptibility to diseases and tissue degeneration. The glucose uptake associated with producing energy for cell survival is one of the major causes of ROS production under physiological conditions. However, the overall mechanisms by which glucose uptake results in cellular senescence remain mysterious. In this study, we found that TXNIP deficiency accelerated the senescent phenotypes of MEF cells under high glucose condition. TXNIP‐/‐ MEF cells showed greater induced glucose uptake and ROS levels than wild‐type cells, and N‐acetylcysteine (NAC) treatment rescued the cellular senescence of TXNIP‐/‐ MEF cells. Interestingly, TXNIP‐/‐ MEF cells showed continuous activation of AKT during long‐term subculture, and AKT signaling inhibition completely blocked the cellular senescence of TXNIP‐/‐ MEF cells. In addition, we found that TXNIP interacted with AKT via the PH domain of AKT, and their interaction was increased by high glucose or H2O2 treatment. The inhibition of AKT activity by TXNIP was confirmed using western blotting and an in vitro kinase assay. TXNIP deficiency in type 1 diabetes mice (Akita) efficiently decreased the blood glucose levels and finally increased mouse survival. However, in normal mice, TXNIP deficiency induced metabolic aging of mice and cellular senescence of kidney cells by inducing AKT activity and aging‐associated gene expression. Altogether, these results suggest that TXNIP regulates cellular senescence by inhibiting AKT pathways via a direct interaction under conditions of glucose‐derived metabolic stress.
Laparoscopic versus open repair for small paraumbilical hernia: A retrospective review
Authors: Chung Iris , Cheung Billy HH , Law Tsz Ting , Ng Ka Kin , Ng Lily , Wong Kin Yuen
Published: August 2018

Introduction

The advantages of laparoscopic surgery for ventral hernia repairs are well documented, but its application for small paraumbilical hernias has been less studied. There is no consensus regarding the best technique.

Methods

All patients who had open (suture or mesh) and laparoscopic repair of primary paraumbilical hernia between September 2007 and September 2017 in a single center were identified. Hernial defects of 2 cm or less were included; recurrent hernias were excluded. Primary outcomes included operative time, length of hospital stay, and surgical complications.

Results

Seventy‐seven patients were recruited: 54 (70.1%) had open repair and 23 (29.9%) had laparoscopic repair. Forty‐six patients (85%) in the open group had primary suture repair. The mean operative time was significantly shorter in the open group than in the laparoscopic group (27.2 vs 56.1 min, P < 0.05). The length of hospital stay in the open group was significantly shorter than in the laparoscopic group (0.8 vs 1.4 days, P = 0.00). Early complications rates were similar, with wound complications in 5.6% (3/54) of open repair patients and 4.3% (1/23) of laparoscopic repair patients (P = 1.0). Among open repair patients, 19 patients (35.2%) were successfully discharged within 12 h after operation. Two patients (3.7%) in the open simple suture group developed recurrence, but no recurrence was identified in the laparoscopic group; this was not statistically significant (P = 1.0).

Conclusion

The laparoscopic approach is comparable to the open approach in the repair of small paraumbilical hernias. For small paraumbilical hernias, we recommend that laparoscopic repair be reserved for obese patients or those with suspected multiple hernial defects.
Dichotomous histopathological assessment of ductal carcinomain situof the breast results in substantial interobserver concordance
Authors: Van Bockstal Mieke , Baldewijns Marcella , Colpaert Cécile , Dano Hélène , Floris Giuseppe , Galant Christine , Lambein Kathleen , Peeters Dieter , Van Renterghem Sofie , Van Rompuy Anne‐Sophie , Verbeke Sofie , Verschuere Stephanie , Van Dorpe Jo
Published: August 2018

Aims

Robust prognostic markers for ductal carcinomain situ(DCIS) of the breast require high reproducibility and thus low interobserver variability. The aim of this study was to compare interobserver variability among 13 pathologists, in order to enable the identification of robust histopathological characteristics.

Methods and results

One representative haematoxylin and eosin‐stained slide was selected for 153DCIScases. All pathologists independently assessed nuclear grade, intraductal calcifications, necrosis, solid growth, stromal changes, stromal inflammation, and apocrine differentiation. All characteristics were assessed categorically. Krippendorff's alpha was calculated to assess overall interobserver concordance. Cohen's kappa was calculated for every observer duo to further explore interobserver variability. The highest concordance was observed for necrosis, calcifications, and stromal inflammation. Assessment of solid growth, nuclear grade and stromal changes resulted in lower concordance. Poor concordance was observed for apocrine differentiation. Kappa values for each observer duo identified the ‘ideal’ cut‐off for dichotomisation of multicategory variables. For instance, concordance was higher for ‘non‐high versus high’ nuclear grade than for ‘low versus non‐low’ nuclear grade. ‘Absent/mild’ versus ‘moderate/extensive’ stromal inflammation resulted in substantially higher concordance than other dichotomous cut‐offs.

Conclusions

Dichotomous assessment of the histopathological features ofDCISresulted in moderate to substantial agreement among pathologists. Future studies on prognostic markers inDCISshould take into account this degree of interobserver variability to define cut‐offs for categorically assessed histopathological features, as reproducibility is paramount for robust prognostic markers in daily clinical practice. A new prognostic index forDCISmight be considered, based on two‐tier grading of histopathological features. Future research should explore the prognostic potential of such two‐tier assessment.
Autoimmune skin disease among dermatology outpatients in Botswana: a retrospective review
Authors: Madu Pamela N. , Williams Victoria L. , Noe Megan H. , Omech Bernard G. , Kovarik Carrie L. , Wanat Karolyn A.
Published: August 2018

Background

There is a paucity of data describing autoimmune skin diseases in sub‐Saharan Africa and in HIV positive cohorts. We describe the incidence of autoimmune skin diseases in public dermatology clinics in Botswana.

Methods

New patient records from public dermatology clinics were reviewed retrospectively for the period of September 2008 to December 2015. New diagnoses of cutaneous lupus erythematosus, systemic lupus erythematosus (SLE) with cutaneous involvement, dermatomyositis, systemic sclerosis, lichen sclerosus, bullous pemphigoid, pemphigus foliaceus, pemphigus vulgaris, and pemphigus vegetans were identified. Demographic data were recorded, and incidence was determined.

Results

A total of 262 patients were diagnosed with autoimmune skin disease (4% of all new patients) with an incidence rate of 28.8 (per 1,000,000). Cutaneous lupus was the most common diagnosis with discoid lupus occurring most frequently (12.6). The incidence of systemic sclerosis (2.2), morphea (1.6), lichen sclerosus (1.5), SLE with cutaneous involvement (1.3) and dermatomyositis (1.2) was relatively lower. Bullous pemphigoid was the most common bullous disease (3.8). Pemphigus foliaceus (0.9), pemphigus vulgaris (0.6), and pemphigus vegetans (0.2) were observed at a lower rate. At least 19.8% of these patients were also HIV positive.

Conclusions

The incidence of autoimmune skin diseases in Botswana is lower compared to other published studies in other geographic areas, which may be reflective of a younger population, barriers to access, genetic differences, and a lack of comparative studies in sub‐Saharan Africa. The hygiene hypothesis and helminth infections may also contribute to these differences. Further studies are needed to understand these disorders in this region.
Compositional evaluation of perennial wheatgrass (Thinopyrum intermedium) breeding populations
Authors: Tyl Catrin , Ismail Baraem P.
Published: August 2018

A shift to perennial grain cultivation offers environmental benefits such as reduced soil erosion and nitrogen leaching. Recently, tremendous agronomic accomplishments have been made in domesticating perennial intermediate wheatgrass (Thinopyrum intermedium, IWG). Thirteen IWG breeding populations were evaluated for characteristics relevant to food use, including chemical composition, activity of enzymes responsible for rancidity, content of antioxidants (carotenoids and hydroxycinnamic acids) and in vitro antioxidant activity based on the 2,2‐diphenyl‐1‐picrylhydrazyl and Folin‐Ciocalteu assays. IWG populations had higher insoluble dietary fibre, protein, fat and ash, but less starch than wheat. IWG populations were deficient in high‐molecular weight glutenins yet contained appreciable amounts of gliadins. Some populations exhibited significantly lower lipase activity than wheat, and all had lower lipoxygenase activities. Most IWG populations contained higher levels of antioxidants than wheat. This work provided key phenotypic information for developing IWG lines that combine high fibre, protein and antioxidant contents with minimal rancidity development.
Fabrication andkW‐levelMOPAlaser output of planar waveguideYAG/Yb:YAG/YAGceramic slab
Authors: Jiang Nan , Lin Weiping , Zhao Yu , Wang Juntao , Gao Qingsong , Qu Haiyun , Ge Lin , Xie Tengfei , Liu Qiang , Pan Yubai , Li Jiang
Published: August 2018

Using the tape casting method combined with vacuum sintering and hot isostatic pressing, high‐quality planar waveguideYAG/10 at.%Yb:YAG/YAGceramics were successfully prepared. For the sample presintered at 1750°C for 30 hours and thenHIPed at 1700°C for 3 hours in 200MPa argon, the in‐line transmittance reached 82.5% at 400 nm and the average grain size was ~17.1 μm. The diffusion behaviors of Yb ions across the contact boundary between the claddingYAGlayer and the core Yb:YAGlayer were determined by Fick's second law. Then, a 1030 nm continuous‐wave (CW) Yb:YAGplanar waveguide ceramic laser based on the structure of master oscillator power amplification (MOPA) was realized. After a single‐pass amplification, the maximum output of the ceramic slab (60 × 10 × 1 mm3) reached 1251 W and the corresponding optical‐to‐optical efficiency was 30.0%, which is the highest output power of a Yb:YAGplanar waveguide ceramic laser to the best of our knowledge.
A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas
Authors: Kim Min‐Young , Sikkel Markus B. , Hunter Ross J. , Haywood Guy A. , Tomlinson David R. , Tayebjee Muzahir H. , Ali Rheeda L. , Cantwell Chris D. , Gonna Hanney , Sandler Belinda C. , Lim Elaine , Furniss Guy , Panagopoulos Dimitrios , Begg Gordon , Dhillon Gurpreet , Hill Nicola J. , O’Neill James , Francis Darrel P. , Lim Phang Boon , Peters Nicholas S. , Linton Nick W. F. , Kanagaratnam Prapa
Published: August 2018

Introduction

The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence atrioventricular (AV) dissociation.

Methods and Results

High frequency stimulation was delivered through a Smart‐Touch catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. Three dimensional locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia, or no effect. CARTO maps were exported, registered, and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated (AVD‐GP) effects. There were 10 AVD‐GPs (interquartile range, 11.5) per patient. Eighty percent (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups was very similar. Highest probability of AVD‐GPs (>20%) was identified in: inferoseptal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%).

Conclusion

It is feasible to map the entire left atrium for AVD‐GPs before AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD‐GPs, identified three regions with a higher likelihood for finding AVD‐GPs and these matched the histological descriptions. This approach could be used to better characterize the autonomic network.
Food safety in Brazilian popular public restaurants: Food handlers’ knowledge and practices
Authors: Souza Camila Valdejane Silva de , Azevedo Paulo Roberto Medeiros de , Seabra Larissa Mont'Alverne Jucá
Published: August 2018

This study aims to assess food safety knowledge and practices of food handlers in popular public restaurants in Brazil. A questionnaire has been applied with 70 food handlers in different municipalities, with questions related to food safety knowledge and food safety self‐reported practices, and observed practices. To check hygienic‐sanitary conditions of restaurants, a checklist has been applied. Regarding food safety knowledge, an average of 72.64% of correct answers has been observed. Food safety self‐reported practices presented 80.71% of adequacy, while observed practices were 75.40%. A positive correlation has been observed between food safety knowledge and self‐reported practices of handlers. The observed food safety practice of handlers presented no correlation with food safety knowledge and self‐reported practices. The average adequacy of hygienic‐sanitary conditions was 68.08%, classifying the units as “regular.” Despite satisfactory results related to the handlers' food safety knowledge and practices, the hygienic‐sanitary conditions of the restaurants are of concern.

Practical applications

The Popular Restaurant Program in Brazil aims to provide proper food from a nutritional and hygienic‐sanitary aspect at affordable prices. The assessment of food handlers' food safety knowledge and practices and the assessment of hygienic‐sanitary conditions of these units are key in supporting actions aimed at improving the quality of the meals served, as food handlers are the essential agents in the production of meals and can become a source for food contamination if necessary care is not taken. Therefore, conducting this assessment can be an important tool for quality management in these units and can provide improvements in the process of food handling, in addition to ensuring compliance with the objectives proposed by the Popular Restaurant Program.
PRECAUTIONARY SAVING: A REVIEW OF THE EMPIRICAL LITERATURE
Authors: Lugilde Alba , Bande Roberto , Riveiro Dolores
Published: August 2018

Standard macroeconomic models show that uncertainty plays a significant role in consumption and saving decisions under rather mild conditions, namely the convexity of the marginal utility of consumption. Increased uncertainty generates a positive extra saving, the so‐called ‘precautionary saving’. Although this hypothesis has been tested by a large number of authors, both at macro and micro level, the empirical results are not conclusive, and the main conclusion than can be drawn is that there is neither consensus on the intensity of that motive for saving, nor on the most appropriate measure of uncertainty. This paper provides a comprehensive review of the empirical literature discussing the main controversial issues and the different approaches followed by the studies addressing empirically the test of precautionary saving.
Virucidal, antiviral and immunomodulatory activities of β-escin and Aesculus hippocastanum extract
Authors: Michelini Flavia M , Alché Laura E , Bueno Carlos A
Published: August 2018

Objectives

β-Escin, one of the constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), inhibits NF-κB activation, which plays an important role in HSV-1 replication. The aim was to examine the antiherpetic activity of β-escin and AH, as well as their effect on the activation of NF-κB and AP-1 and cytokine secretion in epithelial cells and macrophages.

Methods

Cell viability was evaluated using MTT assay, and antiviral and virucidal activity was determined by plaque assay. The effect on NF-κB and AP-1 signalling pathways activation was determined by a luciferase reporter assay, and cytokine production was measured by ELISA.

Key findings

β-Escin and AH had virucidal and anti-HSV-1 activities, and the antiviral activity was discovered for other enveloped viruses (VSV and Dengue). Moreover, β-escin and AH significantly reduced NF-κB and AP-1 activation and cytokine production in macrophages stimulated with HSV-1 and TLRs ligands. However, an enhanced activation of these pathways and an increase in the levels of pro-inflammatory cytokines in β-escin and AH-treated HSV-1-infected epithelial cells were found.

Conclusions

This study demonstrates virucidal and broad-spectrum antiviral activities for β escin and AH. Besides, β-escin and AH modulate cytokine production depending on the stimuli (viral or non-viral) and the cell type under study.
Violations of the International Code of Marketing of Breast‐milk Substitutes in Mexico
Authors: Hernández‐Cordero Sonia , Lozada‐Tequeanes Ana Lilia , Shamah‐Levy Teresa , Lutter Chessa , González de Cosío Teresita , Saturno‐Hernández Pedro , Rivera Dommarco Juan , Grummer‐Strawn Laurence
Published: August 2018

This study estimated the prevalence of violations of the International Code of Marketing of Breast‐milk Substitutes (BMS) and subsequent resolutions of the World Health Assembly (Code) at health facilities, points of sale (POS), and on BMS labelling and media in Mexico. We carried out a cross‐sectional survey among 693 mothers with children aged less than 24 months and 48 health providers at public and private health facilities in two states of Mexico. Observational assessment at 20 POS and the health facilities was conducted as well as an analysis of labels on BMS products for sale. Women attending public and private health facilities reported receiving free BMS samples in the previous 6 months (11.1%), and about 80% reported seeing BMS promotion in the mass media. Health providers reported contact with BMS manufacturer representatives in the previous 6 months (15.5%), and only 41.6% of the health providers had knowledge of the Code. BMS promotions were identified at nearly all POS. Analysis of 190 BMS labels showed that 30% included pictures/text idealizing the use of BMS, and all labels incorporated health and nutrition claims. Violations of the Code are prevalent within the health services, POS, and labelling of BMS products. The high percentage of health providers with no knowledge of the Code calls for action at national level to better disseminate and comply with the Code. A transparent, free from commercial influence, and continual monitoring system for Code compliance is needed, including a follow‐up component on sanctions for contraventions of the Code.
The vector ecology of introduced Culex quinquefasciatus populations, and implications for future risk of West Nile virus emergence in the Galápagos archipelago
Authors: Eastwood G. , Cunningham A. A. , Kramer L. D. , Goodman S. J.
Published: August 2018

Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of West Nile virus (WNV) in the U.S.A., was first detected on the Galápagos Islands (Ecuador) in the 1980s. However, little is known of its ecology, distribution or capacity for arbovirus transmission in the Galápagos. We characterize details of lifecycle (including gonotrophic period), temporal abundance, spatial distribution, vector competence and host‐feeding behaviour. Culex quinquefasciatus was detected on five islands of the Galápagos during 2006–2011. A period of 7–14 days was required for egg–adult emergence; water salinity above 5 ppt was demonstrated to hinder larval development. Blood‐meal analysis indicated feeding on reptiles, birds and mammals. Assessment of WNV vector competency of Galápagos C. quinquefasciatus showed a median infectious dose of 7.41 log10 plaque‐forming units per millilitre and evidence of vertical transmission (minimal filial infection rate of 3.7 per 1000 progeny). The distribution of C. quinquefasciatus across the archipelago could be limited by salt intolerance, and its abundance constrained by high temperatures. Feeding behaviour indicates potential to act as a bridge vector for transmission of pathogens across multiple taxa. Vertical transmission is a potential persistence mechanism for WNV on Galápagos. Together, our results can be used for epidemiological assessments of WNV and target vector control, should this pathogen reach the Galápagos Islands.
Salicylic acid activates poplar defense against the biotrophic rust fungusMelampsora larici‐populinavia increased biosynthesis of catechin and proanthocyanidins
Authors: Ullah Chhana , Tsai Chung‐Jui , Unsicker Sybille B. , Xue Liangjiao , Reichelt Michael , Gershenzon Jonathan , Hammerbacher Almuth
Published: August 2018

Poplar trees synthesize flavan‐3‐ols (catechin and proanthocyanidins) as a defense against foliar rust fungi, but the regulation of this defense response is poorly understood. Here, we investigated the role of hormones in regulating flavan‐3‐ol accumulation in poplar during rust infection.

We profiled levels of defense hormones, signaling genes, and flavan‐3‐ol metabolites in black poplar leaves at different stages of rust infection. Hormone levels were manipulated by external sprays, genetic engineering, and drought to reveal their role in rust fungal defenses.

Levels of salicylic acid (SA), jasmonic acid, and abscisic acid increased in rust‐infected leaves and activated downstream signaling, withSAlevels correlating closely with those of flavan‐3‐ols. Pretreatment with theSAanalog benzothiadiazole increased flavan‐3‐ol accumulation by activating theMYB–bHLH–WD40 complex and reduced rust proliferation. Furthermore, transgenic poplar lines overproducingSAexhibited higher amounts of flavan‐3‐ols constitutively via the same transcriptional activation mechanism. These findings suggest a strong association amongSA, flavan‐3‐ol biosynthesis, and rust resistance in poplars. Abscisic acid also promoted poplar defense against rust infection, but likely through stomatal immunity independent of flavan‐3‐ols. Jasmonic acid did not confer any apparent defense responses to the fungal pathogen.

We conclude thatSAactivates flavan‐3‐ol biosynthesis in poplar against rust infection.
Myofibroblastic lesions in the oral cavity: Immunohistochemical and ultrastructural analysis
Authors: Pereira de Oliveira Denise Hélen Imaculada , da Silveira Éricka Janine Dantas , de Souza Lélia Batista , Caro‐Sanchez Claudia Haydee S. , Dominguez‐Malagon Hugo , Mosqueda Taylor Adalberto , Queiroz Lélia Maria Guedes
Published: August 2018

Objective

To immunohistochemically characterize a group of oral myofibroblastic lesions (MLs) and to evaluate the ultrastructural features of myofibroblasts.

Material and Methods

Using a tissue microarray technique (TMA), cases of myofibroma (MF), of nodular fasciitis (NF), of desmoplastic fibroma (DF), and of myofibroblastic sarcoma (MS) from the Universidad Autónoma Metropolitana Xochimilco, and a Private Oral Pathology Service in Mexico City were stained with antibodies against alpha‐smooth muscle actin (α‐SMA), H‐caldesmon, vimentin, desmin, β‐catenin, CD34, anaplastic lymphoma protein kinase (ALK‐1), and Ki‐67.

Results

Nineteen of the 22 MF cases, 2/5 of the NF cases, 1/10 of the DF cases, and 1/2 of the MS cases were positive for α‐SMA. 1/2 of the MS cases were positive for desmin; 6/10 of the DF cases were positive for β‐catenin, and 2 of the MF cases were positive for ALK‐1. All of the MLs were positive for vimentin and negative for H‐caldesmon and CD‐34. The Ki‐67 labeling index in all of the 8/22 MF, 3/5 NF, and 2/2 MS cases was ≥10%. For all of the MLs evaluated, ultrastructural analysis revealed spindle‐shaped cells containing endoplasmic reticulum and peripheral actin filament bundles.

Conclusion

In certain myofibroblastic lesions, the use of auxiliary techniques (such as immunohistochemistry) can be critical for differential diagnosis.
The use of botulinum toxin A to promote wound healing in a recurrent lip fissure
Authors: Farrier J. N. , Beech A. N.
Published: August 2018

During the wound healing process there is an element of contraction and scarring. Lip wounds can be very noticeable to others, making patients self‐conscious. In the lower lip there is an added problem of significant muscular pull similar to a sphincteric system. We demonstrate excellent healing with the injection of Botulinum Toxin A (Botox®) as an adjunct to close surgical excision of a chronic, non‐healing lower lip fissure.