bluuebunny/crossref_metadata_2025 huggingface dataset:
Race and Gender Are Associated with Opioid Dose Reduction Among Patients on Chronic Opioid Therapy
Authors: Buonora Michele , Perez Hector R , Heo Moonseong , Cunningham Chinazo O , Starrels Joanna L
Published: June 2018

Objective

Among patients with chronic pain, risk of opioid use is elevated with high opioid dose or concurrent benzodiazepine use. This study examined whether these clinical factors, or sociodemographic factors of race and gender, are associated with opioid dose reduction.

Design and Setting

A retrospective cohort study of outpatients prescribed chronic opioid therapy between 2007 and 2012 within a large, academic health care system in Bronx, New York, using electronic medical record data. Included patients were prescribed a stable dose of chronic opioid therapy over a one-year “baseline period” and did not have cancer.

Methods

The primary outcome was opioid dose reduction (≥30% reduction from baseline) within two years. Multivariable logistic regression tested the associations of two clinical variables (baseline daily opioid dose and concurrent benzodiazepine prescription) and two sociodemographic variables (race/ethnicity and gender) with opioid dose reduction.

Results

Of 1,097 patients, 463 (42.2%) had opioid dose reduction. High opioid dose (≥100 morphine-milligram equivalents [MME]) was associated with lower odds of opioid dose reduction compared with an opioid dose <100 MME (adjusted odds ratio [AOR] = 0.69, 95% confidence interval [CI] = 0.54–0.89). Concurrent benzodiazepine prescription was not associated with opioid dose reduction. Black (vs white) race and female (vs male) gender were associated with greater odds of opioid dose reduction (AOR = 1.82, 95% CI = 1.22–2.70; and AOR = 1.43, 95% CI = 1.11–1.83, respectively).

Conclusions

Black race and female gender were associated with greater odds of opioid dose reduction, whereas clinical factors of high opioid dose and concurrent benzodiazepine prescription were not. Efforts to reduce opioid dose should target patients based on clinical factors and address potential biases in clinical decision-making.
Immune gene diversity in archaic and present-day humans
Authors: Reher David , Key Felix M. , Andrés Aida M. , Kelso Janet
Published: June 2018

Genome-wide analyses of two Neandertals and a Denisovan have shown that these archaic humans had lower genetic heterozygosity than present-day people. A similar reduction in genetic diversity of protein-coding genes (gene diversity) was found in exome sequences of three Neandertals. Reduced gene diversity, and particularly in genes involved in immunity, may have important functional consequences. In fact, it has been suggested that reduced diversity in immune genes may have contributed to Neandertal extinction. We therefore explored gene diversity in different human groups and at different time points on the Neandertal lineage with a particular focus on the diversity of genes involved in innate immunity and genes of the Major Histocompatibility Complex (MHC).

We find that the two Neandertals and the Denisovan have similar gene diversity, both significantly lower than any present-day human. This is true across gene categories, with no gene set showing an excess decrease in diversity compared to the genome-wide average. Innate immune-related genes show a similar reduction in diversity to other genes, both in present-day and archaic humans. There is also no observable decrease in gene diversity over time in Neandertals, suggesting that there may have been no ongoing reduction in gene diversity in later Neandertals, although this needs confirmation with a larger sample size. In both archaic and present-day humans, genes with the highest levels of diversity are enriched for MHC-related functions. In fact, in archaic humans the MHC genes show evidence of having retained more diversity than genes involved only in the innate immune system.
Demographic response to patch destruction in a spatially structured amphibian population
Authors: Cayuela Hugo , Besnard Aurélien , Quay Ludivine , Helder Rémi , Léna Jean‐Paul , Joly Pierre , Pichenot Julian
Published: June 2018

Economic activities such as logging and mineral extraction can result in the creation of new anthropogenic habitats that host specific biodiversity, including protected species. However, the legislation in many Western European countries requires the rehabilitation of “damaged” areas following logging and mining operations, which can eliminate these early successional habitats. Conservation managers face a dilemma in these situations, but often lack knowledge about the impacts of environmental rehabilitation on the population dynamics of pioneer species and so are unable to take this into account in their actions.

We investigated the demography of a spatially structured population of an endangered amphibian (Bombina variegata) that uses waterbodies created by logging activities as breeding sites. Using capture–recapture (CR) data collected during a 9‐year study period, we examined how the destruction of breeding patches due to environmental rehabilitation affected adult survival and the long‐term population growth rate. For this purpose, we used recently developed capture–recapture multievent models to estimate survival and dispersal rates in the spatially structured population. We then used these estimates to simulate population trajectories and viability depending on differing frequency of breeding patch destruction.

The multievent models revealed that dispersal not resulting from patch loss was relatively high and was sex biased. They also highlighted that patch destruction had a negative impact on adult survival. Moreover, simulations showed that the increase in patch destruction frequency had a strong negative influence on the population growth rate, even when the number of patches remained constant over time. This impact was intensified if female fecundity was also affected.

Synthesis and applications. Our study quantifies for the first time the detrimental effect of habitat rehabilitation on the population dynamics of an endangered, pioneer species. Our results show that this deleterious impact of patch destruction could be reduced by certain management practices, such as avoiding the systematic rehabilitation of the breeding patches and compensating for patch destruction by creating substitute breeding patches.
Demography and social dynamics of an African elephant population 35 years after reintroduction as juveniles
Authors: Kuiper Timothy R. , Druce Dave J. , Druce Heleen C.
Published: June 2018

Given their vulnerability to local extinction, the reintroduction of megafauna species (often long‐lived, ecologically influential and highly social) is an increasingly relevant conservation intervention. Studies that evaluate past megafauna reintroductions are both critical and rare.

Between 1981 and 1996, 12 cohorts of a total of 200 juvenile (<5 years old) African savannah elephants Loxodonta africana africana were reintroduced to Hluhluwe‐iMfolozi Park (HiP), South Africa, after 100 years of absence. Here, we model the population's long‐term growth. We also present data on the current (2016) age class distribution and social dynamics of the population based on a year of intensive vehicle‐based monitoring of 16 collared adult females and their family groups.

Exponential population growth (7.1% annual increase) between 1996 and 2014 suggests reintroduction success but has created concerns about overpopulation (with contraception of females implemented since 2014 to suppress reproduction). The age class distribution has normalized as the juveniles have aged; reproductive females (>10 years old) composed 30% of the population in 2016. The population remains relatively young and forecasts suggest high potential for sustained growth over the next decade.

The first calf was born to a reintroduced female in 1990 and since then mother–calf units have gradually developed into semi‐independent multi‐generation families (7–15 individuals in size in 2016). The size of observed cow–calf groups was highly variable (mean = 21.4 individuals, range: 7–109), with repeat observation of individual collared females revealing fusion and fission among different family groups through time, as is typical of more natural elephant populations.

Synthesis and applications. From an unusual founder population of reintroduced juvenile elephants, we document rapid population growth and the development of normal sociality over 35 years. While this may be an encouragement for megaherbivore reintroductions in general, the potential for exponential population growth must be carefully considered when ecologically influential species are introduced to closed systems. Our study provides key long‐term insights for elephant translocations, which are becoming increasingly necessary due to overpopulation in some areas and local extinction in others.
Megaherbivores may impact expansion of invasive seagrass in the Caribbean
Authors: Christianen Marjolijn J. A. , Smulders Fee O. H. , Engel M. Sabine , Nava Mabel I. , Willis Sue , Debrot Adolphe O. , Palsbøll Per J. , Vonk J. Arie , Becking Leontine E.
Published: June 2018

Our knowledge of the functional role of large herbivores is rapidly expanding, and the impact of grazing on species coexistence and nonnative species expansion has been studied across ecosystems. However, experimental data on large grazer impacts on plant invasion in aquatic ecosystems are lacking.

Since its introduction in 2002, the seagrass species Halophila stipulacea has rapidly expanded across the Eastern Caribbean, forming dense meadows in green turtle (Chelonia mydas)—foraging areas. We investigate the changes in seagrass species coexistence and the impacts of leaf grazing by green turtles on nonnative seagrass expansion in Lac Bay (Bonaire, Caribbean Netherlands).

Green turtle grazing behaviour changed after the introduction of nonnative seagrass to Lac Bay in 2010. Field observations, together with time‐lapse satellite images over the last four decades, showed initiation of new grazing patches (65 ha, an increase of 72%). The sharp border between grazed and ungrazed seagrass patches moved in the direction of shallower areas with native seagrass species that had previously (1970–2010) been ungrazed. Green turtles deployed with Fastloc‐GPS transmitters confirmed high site fidelity to these newly cropped patches. In addition, cafeteria experiments indicated selective grazing by green turtles on native species. These native seagrass species had significantly higher nutritional values compared to the nonnative species. In parallel, exclosure experiments showed that nonnative seagrass expanded more rapidly in grazed canopies compared to ungrazed canopies. Finally, in 6 years from 2011 to 2017, H. stipulacea underwent a significant expansion, invading 20–49 fixed monitoring locations in Lac Bay, increasing from 6% to 20% in total occurrence. During the same period, native seagrass Thalassia testudinum occurrence decreased by 33%.

Synthesis. Our results provide first‐time evidence of large‐scale replacement of native seagrasses by rapidly colonizing Halophila stipulacea in the Caribbean and add a mechanistic explanation for this invasiveness. We conclude that green turtle leaf grazing may modify the rate and spatial extent of this invasive species' expansion, due to grazing preferences, and increased space for settlement. This work shows how large herbivores play an important but unrecognized role in species coexistence and plant invasions of aquatic ecosystems.
Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function
Authors: Abé C. , Rolstad S. , Petrovic P. , Ekman C.‐J. , Sparding T. , Ingvar M. , Landén M.
Published: June 2018

Objective

Frontal cortical abnormalities and executive function impairment co‐occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects.

Method

Using a vertex‐wise whole‐brain analysis, we investigated how cortical integrity, as measured by cortical thickness, correlates with executive performance in patients with bipolar disorder type I, II, and controls (N = 160).

Results

We found focal associations between executive function and cortical thickness in the medial prefrontal cortex in bipolar II patients and controls, but not in bipolar I disorder. In bipolar II patients, we observed additional correlations in lateral prefrontal and occipital regions.

Conclusions

Our findings suggest that bipolar disorder patients show altered structure–function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype‐specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure–function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes.
Cytotoxic, Antiproliferative and Apoptosis‐inducing Activity of L‐Amino Acid Oxidase from Malaysian Calloselasma rhodostoma on Human Colon Cancer Cells
Authors: Zainal Abidin Syafiq Asnawi , Rajadurai Pathmanathan , Chowdhury Md. Ezharul Hoque , Ahmad Rusmili Muhammad Rusdi , Othman Iekhsan , Naidu Rakesh
Published: June 2018

The aim of this study was to investigate the cytotoxic, antiproliferative activity and the induction of apoptosis by L‐amino acid oxidase isolated from Calloselasma rhodostoma crude venom (CR‐LAAO) on human colon cancer cells. CR‐LAAO was purified using three chromatographic steps: molecular exclusion using G‐50 gel filtration resin, ion‐exchange by MonoQ column and desalted on a G25 column. The purity and identity of the isolated CR‐LAAO was confirmed by SDS‐PAGE and LC‐MS/MS. CR‐LAAO demonstrated time‐ and dose‐dependent cytotoxic activity on SW480 (primary human colon cancer cells) and SW620 (metastatic human colon cancer cells) with an EC50 values of 6 μg/ml and 7 μg/ml at 48 hr, respectively. Quantification of apoptotic cells based on morphological features demonstrated significant increase in apoptotic cell population in both SW480 and SW620 cells which peaked at 48 hr. Significant increase in caspase‐3 activity and reduction in Bcl‐2 levels were demonstrated following CR‐LAAO treatment. These data provide evidence on the potential anticancer activity of CR‐LAAO from the venom of C. rhodostoma for therapeutic intervention of human colon cancer.
Drug resistance profiles of mutations in the RET kinase domain
Authors: Liu Xuan , Shen Tao , Mooers Blaine H M , Hilberg Frank , Wu Jie
Published: June 2018

Background and Purpose

Alterations in the tyrosine kinase enzyme RET are found in thyroid and lung cancer. While RET TK inhibitors (TKIs) are used to treat thyroid cancer and are in clinical trials for RET fusion‐positive non‐small cell lung cancer, the impact of mutations in the RET kinase domain on drug sensitivity is largely uncharacterized.

Experimental Approach

We identified and analysed mutations in the RET kinase domain that conferred resistance to the TKIs cabozantinib, lenvatinib, vandetanib and nintedanib using RET kinase‐dependent BaF3/KIF5B‐RET (BaF3/KR) cells. We also examined the sensitivity of RET (M918T), a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B, to these TKIs in the context of BaF3/KR cells.

Key Results

Fourteen mutations were analysed. Pan resistance to the four TKIs was found in six RET kinase domain mutations (L730I, V738A, V804L/M, Y806N, G810S). Seven RET kinase domain mutations (L730V, E732K, A807V, G810A, V871I, M918T, F998V) displayed selective resistance to one or more of these drugs. L730I/V and G810A/S had different drug resistance profiles. V871I, M918T and F998V mutations are located at distant sites away from the TKI binding pocket.

Conclusions and Implications

A panel of TKI‐resistant RET mutations were identified, and their drug sensitivities were cross‐profiled. The results provide a reference for selecting appropriate TKIs to inhibit RET kinase domain mutants. Besides changes in the drug‐interacting residues, mutations at distant sites could exert long‐range effects resulting in TKI resistance. Among the four TKIs analysed here, nintedanib remained unaffected by mutations at the three distant sites.
Phase II trial of biweekly cetuximab and irinotecan as third‐line therapy for pretreated KRAS exon 2 wild‐type colorectal cancer
Authors: Osumi Hiroki , Shinozaki Eiji , Mashima Tetsuo , Wakatsuki Takeru , Suenaga Mitsukuni , Ichimura Takashi , Ogura Mariko , Ota Yumiko , Nakayama Izuma , Takahari Daisuke , Chin Keisho , Miki Yoshio , Yamaguchi Kensei
Published: June 2018

Efficacy and safety of biweekly cetuximab plus irinotecan were evaluated to provide guidance for its use in Japan as third‐line treatment for pretreated metastatic colorectal cancer (mCRC) patients harboring wild‐type KRAS exon 2. Objective response rate (ORR) was used as primary endpoint based on an expected proportion of 0.23 with confidence width of 0.298 (95% CI, 0.105‐0.403), which showed 35 to be the minimal participant number. Forty patients, refractory to first‐ and second‐line chemotherapy containing irinotecan, oxaliplatin, and fluoropyrimidine, were enrolled. ORR and disease control rate were 25.0% (95% CI: 11.5‐38.4) and 72.5% (95% CI: 56.8‐86.4), respectively. Median progression‐free survival (PFS), overall survival (OS), and number of courses were 5.70 months (95% CI: 2.7‐7.9), 15.1 months (95% CI: 11.8‐19.0), and 10.5 (range: 3.0‐31.0), respectively. Grade 3 adverse events were skin toxicity (12.5%), diarrhea (10.0%), neutropenia (5.0%), febrile neutropenia (5.0%), nausea (5.0%), anorexia (5.0%), and fatigue (2.5%). Cmax mean was 723.2 μg/mL after first dose. High area under the curve (AUC)last variance was associated with t1/2 range of 131.2‐1209.6 hours (median, 174.4 hours). Early tumor shrinkage (ETS) and median depth of response were 25.0% and 13.0%, respectively. Mutation frequencies in KRAS exon 3 or 4, NRAS, BRAF, and PIK3CA were 5.5%, 2.7%, 8.3%, and 5.5%, respectively. Multivariate Cox regression analysis assessed whether any gene mutations and ETS are predictors for PFS, and whether performance status, synchronous metastasis, and ETS are predictors for OS. Importantly, the data provide guidance for a biweekly cetuximab plus irinotecan regimen in mCRC patients.
Innate immune response reflects disease activity in eosinophilic granulomatosis with polyangiitis
Authors: Tsurikisawa Naomi , Oshikata Chiyako , Watanabe Maiko , Tsuburai Takahiro , Kaneko Takeshi , Saito Hiroshi
Published: June 2018

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease characterized by allergic granulomatosis, necrotizing vasculitis, and peripheral blood eosinophilia. Interleukin (IL)‐33, thymic stromal lymphopoietin (TSLP), and type 2 innate lymphoid cells (ILC2) are involved in the innate and type 2 immune responses in EGPA. However, the relationships among these molecules and the mechanisms underlying the development of EGPA remain unknown.

Objective

We investigated the relationships among peripheral blood eosinophil count, serum IL‐33 and TSLP concentration, and peripheral blood ILC2 count in patients with EGPA, chronic eosinophilic pneumonia (CEP), or bronchial asthma (BA).

Methods

We recruited 86 patients with EGPA in three groups (remission, relapse, and onset), 25 patients with CEP at active or inactive stages of disease, and 11 patients with BA. In patients with EGPA, CEP, or BA, serum IL‐33, sST2, and TSLP concentrations were determined using ELISA and peripheral blood ILC2 counts (as Lin‐1−CD127+CRTH2+ cells) were determined using flow cytometry.

Results

Peripheral blood eosinophil count or ILC2 count, and serum sST2 or TSLP concentration were higher in patients with EGPA at onset than in those with EGPA at relapse or remission, or in those with BA or CEP. Serum IL‐33 concentration was higher in patients with EGPA at relapse than in those with EGPA at onset or remission, or in those with BA or CEP. In a logistic regression model, EGPA disease activity was correlated with serum IL‐33 concentration and peripheral blood ILC2 count, but not daily systemic and inhaled corticosteroid dose or immunosuppressant use. Eosinophil count was correlated with peripheral blood ILC2 count and serum TSLP concentration, but not serum IL‐33 concentration.

Conclusions

Increased peripheral blood ILC2 count and serum IL‐33 concentration were associated with disease activity in EGPA. Increases in serum IL‐33 concentration may indicate the presence of active vasculitis rather than peripheral or tissue eosinophilia.
Biological effect of the abutment material on the stability of peri‐implant marginal bone levels: A systematic review and meta‐analysis
Authors: Sanz‐Sánchez Ignacio , Sanz‐Martín Ignacio , Carrillo de Albornoz Ana , Figuero Elena , Sanz Mariano
Published: June 2018

Objectives

The primary aim of this systematic review was to evaluate the available evidence on the effect of the abutment material on the stability and health of the peri‐implant hard tissues.

Methods

A protocol was developed to answer the following focused question: “Which is the effect of the abutment material on stability and health of the peri‐implant hard tissues?” Randomized controlled trials (RCTs), controlled clinical trials (CCTs) or prospective case series (CS) with at least 6 months of follow‐up were included, and meta‐analyses were performed to compare abutment materials vs. titanium and to evaluate the impact of various abutment materials on bone changes (primary outcome), probing depth, plaque levels and peri‐implant mucosal inflammation.

Results

Twenty‐nine publications from 33 investigations were included. Results from the meta‐analyses demonstrated no significant differences between the different abutment materials when compared to titanium, in regard to the changes in marginal bone levels (MBLs) (n = 15;WMD = 0.034; 95%CI[−0.04, 0.10];p < 0.339). The meta‐analysis reported a significantly greater increase in bleeding on probing for titanium compared to zirconia abutments (n = 3;WMD = −26.96%; 95%CI[−45.00%, −8.92%];p = 0.003). When evaluating the behaviour of each material different to titanium, there was a significant bone loss over time (n = 31;WMD = 0.261; 95%CI[0.18, 0.35];p < 0.001) for all the individual materials except for titanium nitride.

Conclusions

This systematic review has shown that the abutment material had minimal impact on marginal bone levels when compared to the standard titanium.
Are wildlife escape ramps needed along Australian highways?
Authors: Goldingay Ross L. , Taylor Brendan D. , Parkyn Jonathan L. , Lindsay John M.
Published: June 2018

Road escape ramps are structures developed in the USA to enable large mammals that become trapped on the roadside of a wildlife fence to escape the road and avoid vehicle collision. They are now commonly installed in eastern Australia to enable the Koala (Phascolarctos cinereus) and other fauna to escape through a roadside exclusion fence and return to the forest. We investigated the use of seven of 14 escape ramps over three years on the Oxley Highway at Port Macquarie in New South Wales. The Swamp Wallaby (Wallabia bicolor) was the most frequently detected species, traversing the escape ramps on 502 occasions, followed by bandicoots (Isoodon macrourus and Perameles nasuta) on 148 occasions. Various other species were detected but no Koalas. Swamp Wallabies moved through the escape ramps in the reverse direction (i.e. towards the road) in 53% of detections of that species and bandicoots in 14% of their detections. There was no obvious pattern by these species of proportionately higher use of ramps closer to the end of the exclusion fences. The large number of reverse passages through the escape ramps reveals a poor design of these structures. Trials with taller ramps are required to determine how to minimise reverse passages. Concurrent monitoring of three underpasses detected numerous crossings by large mammals including Swamp Wallabies, and some crossings by Koalas. We believe evidence is needed to demonstrate the necessity for escape ramps along Australian highways.
Allelic and haplotype diversity of HLA‐A, HLA‐B and HLA‐DRB1 gene at high resolution in the Nanning Han population
Authors: Pei YongFeng , Huang HuiNi , Li HengCong , Chen JieRun , Wu GuoGuang
Published: June 2018

The distribution of human leucocyte antigen (HLA) allele and haplotype varied among different ethnic populations. In this study, we investigated the allele and haplotype frequencies of HLA‐A, HLA‐B and HLA‐DRB1 loci in the Nanning Han population who live in Guangxi province of China. We identified 26 HLA‐A, 56 HLA‐B and 31 HLA‐DRB1 alleles in 562 Nanning individuals of Han ethnic group by sequence‐based typing method. Of these, the three most common alleles in HLA‐A, HLA‐B and HLA‐DRB1 loci, respectively, were A*11:01 (32.12%), A*02:07 (12.54%), A*24:02 (12.01%); B*46:01 (14.41%), B*15:02 (13.61%), B*40:01 (11.48%); DRB1*15:01 (14.15%), DRB1*16:02 (11.57%) and DRB1*12:02 (10.14%). With the exception of HLA‐DRB1, the p values of the HLA‐A and HLA‐B loci showed that the HLA allelic distribution in this population was in accordance with Hardy–Weinberg expectation (p > 0.05). A total of 173 HLA~A‐B~DRB1 haplotype with a frequency of >0.1% were presented and the three most common haplotype were HLA‐A*33:03~B*58:01~DRB1*03:01 (6.12%), HLA‐A*11:01~B*15:02~DRB1*12:02 (3.39%) and HLA‐A*11:01~B*15:02~DRB1*15:01 (3.22%). The phylogenetic tree and the principal component analysis suggested that Nanning Han population had a relative close genetic relationship with Chinese Zhuang population and a relative distant genetic relationship with Northern Han Chinese. The information will be useful for anthropological studies, for HLA matching in transplantation and disease association studies in the Chinese population.
A complex interplay between the extracellular matrix and the innate immune response to microbial pathogens
Authors: Tomlin Hannah , Piccinini Anna M.
Published: June 2018

The role of the host extracellular matrix (ECM) in infection tends to be neglected. However, the complex interactions between invading pathogens, host tissues and immune cells occur in the context of the ECM. On the pathogen side, a variety of surface and secreted molecules, including microbial surface components recognizing adhesive matrix molecules and tissue‐degrading enzymes, are employed that interact with different ECM proteins to effectively establish an infection at specific sites. Microbial pathogens can also hijack or misuse host proteolytic systems to modify the ECM, evade immune responses or process biologically active molecules such as cell surface receptors and cytokines that direct cell behaviour and immune defence. On the host side, the ECM composition and three‐dimensional ultrastructure undergo significant modifications, which have a profound impact on the specific signals that the ECM conveys to immune cells at the forefront of infection. Unexpectedly, activated immune cells participate in the remodelling of the local ECM by synthesizing ECM glycoproteins, proteoglycans and collagen molecules. The close interplay between the ECM and the innate immune response to microbial pathogens ultimately affects the outcome of infection. This review explores and discusses recent data that implicate an active role for the ECM in the immune response to infection, encompassing antimicrobial activities, microbial recognition, macrophage activation, phagocytosis, leucocyte population balance, and transcriptional and post‐transcriptional regulation of inflammatory networks, and may foster novel antimicrobial approaches.
Physiological and behavioural responses of grazing dairy cows to an acute metabolic challenge
Authors: Müller Esther , Münger Andreas , Mandel Roi , Eggerschwiler Lukas , Schwinn Ann‐Catherine , Gross Josef J. , Bruckmaier Rupert M. , Hess H. Dieter , Dohme‐Meier Frigga
Published: June 2018

Due to seasonal changes in the quality and quantity of herbage, the nutrient supply to grazing dairy cows is not always sufficient, which may increase their metabolic load. To investigate the temporal pattern of behavioural changes in relation to concomitant metabolic alterations, we subjected 15 multiparous early lactating Holstein dairy cows (24 (SD 7.4) days in milk) to a short‐term metabolic challenge, which we provoked by abruptly withdrawing concentrate for 1 week. Cows grazed full‐time and were supplemented with concentrate in experimental week (EW) 1 and EW 3, whereas concentrate was withdrawn in EW 2. We analysed milk and blood samples to characterise the metabolic changes and found that the total yield of milk and protein decreased (p < 0.05) and fat yield, fat‐to‐protein ratio and acetone content increased (p < 0.05) from EW 1 to EW 2. Plasma glucose and insulin concentrations were lower (p < 0.05), and concentrations of nonesterified fatty acids and beta‐hydroxybutyrate were higher (p < 0.05) in EW 2 compared with EW 1. Apart from ingestive and rumination behaviour and activity, we also monitored the use of an automated brush on pasture. While time spent eating and ruminating increased (p < 0.05) in EW 2 compared with EW 1, time spent idling decreased (p < 0.05). Concomitantly, while time standing and moving increased (p < 0.05) from EW 1 to EW 2, walking time decreased (p < 0.05). The daily proportion of cows using the automated brush decreased (p < 0.05) in EW 2 compared with EW 1, as did the duration of brushing per day. In conclusion, grazing cows experiencing a metabolic challenge try to compensate for the nutrient deficiency by increasing eating time, a behavioural element important for short‐term survival. Due to the strong impact of weather conditions, we cannot currently recommend observation of outdoor brushing activity to address short‐term alterations in the metabolic state of grazing cows.
The effect of dietary corn oil and fish oil supplementation in dogs with naturally occurring gingivitis
Authors: Lourenço Ana L. , Booij‐Vrieling Henriette E. , Vossebeld Carmen B. , Neves António , Viegas Carlos , Corbee Ronald J.
Published: June 2018

The aim of this randomized, double‐blinded, placebo‐controlled study was to evaluate if downregulation of the inflammatory response due to ingestion of high levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can slow down gingivitis development, and thus delay the progression of periodontal disease (PD) in dogs. To this aim, 44 client‐owned adult dogs (>1 and <8 years old) with naturally occurring PD (stages 1 and 2) were submitted to a plaque, gingivitis and calculus scoring followed by a dental cleaning procedure and collection of blood samples. The animals were then fed a canine adult maintenance diet, supplemented with either corn oil (0.00 g EPA and 0.00 g DHA) or fish oil (1.53 g EPA and 0.86 g DHA, both per 1,000 kcal ME) over the following 5 months. At the end of this period, the PD scoring and the blood sampling were repeated. The animals consuming fish oil had higher plasma levels of the longer chain (C ≥ 20) omega 3 fatty acids (p < 0.01) and similar plasma levels of alpha‐linolenic acid (p = 0.53), omega 6 fatty acids (p > 0.63) and C reactive protein (p = 0.28) then the ones consuming corn oil. There were no differences between fish oil and corn oil diet supplementation on plaque (18.2 vs. 17.8,p = 0.78), calculus (10.1 vs. 11.5,p = 0.18) or gingivitis (19.3 vs. 19.0,p = 0.77) indexes. The authors conclude that supplementation with EPA + DHA does not slow down progression of PD in dogs.
Loss of specificity variants of WzxC suggest that substrate recognition is coupled with transporter opening in MOP‐family flippases
Authors: Sham Lok‐To , Zheng Sanduo , Yakhnina Anastasiya A , Kruse Andrew C , Bernhardt Thomas G
Published: June 2018

Bacteria produce a variety of surface‐exposed polysaccharides important for cell integrity, biofilm formation and evasion of the host immune response. Synthesis of these polymers often involves the assembly of monomer oligosaccharide units on the lipid carrier undecaprenyl‐phosphate at the inner face of the cytoplasmic membrane. For many polymers, including cell wall peptidoglycan, the lipid‐linked precursors must be transported across the membrane by flippases to facilitate polymerization at the membrane surface. Flippase activity for this class of polysaccharides is most often attributed to MOP (Multidrug/Oligosaccharidyl‐lipid/Polysaccharide) family proteins. Little is known about how this ubiquitous class of transporters identifies and translocates its cognate precursor over the many different types of lipid‐linked oligosaccharides produced by a given bacterial cell. To investigate the specificity determinants of MOP proteins, we selected for variants of the WzxC flippase involved in Escherichia coli capsule (colanic acid) synthesis that can substitute for the essential MurJ MOP‐family protein and promote transport of cell wall peptidoglycan precursors. Variants with substitutions predicted to destabilize the inward‐open conformation of WzxC lost substrate specificity and supported both capsule and peptidoglycan synthesis. Our results thus suggest that specific substrate recognition by a MOP transporter normally destabilizes the inward‐open state, promoting transition to the outward‐open conformation and concomitant substrate translocation. Furthermore, the ability of WzxC variants to suppress MurJ inactivation provides strong support for the designation of MurJ as the flippase for peptidoglycan precursors, the identity of which has been controversial.
Pathogenesis of primordial odontogenic tumour based on tumourigenesis and odontogenesis
Authors: Mikami Toshinari , Bologna‐Molina Ronell , Mosqueda‐Taylor Adalberto , Ogawa Ikuko , Pereira‐Prado Vanesa , Fujiwara Naoki , Pires Fabio Ramoa , Carlos Roman , Takata Takashi , Takeda Yasunori
Published: June 2018

Objective

Primordial odontogenic tumour (POT) is a rare benign mixed epithelial and mesenchymal odontogenic tumour. POT is composed of dental papilla‐like tissue covered with cuboidal to columnar epithelium that resembles to inner and outer enamel epithelium of the enamel organ without dental hard tissue formation. The aim of this study was to examine pathogenesis of POT based on tumourigenesis and odontogenesis.

Subjects and methods

Six cases of POT were submitted for study. DNA analysis and transcriptome analysis were performed by next‐generation sequencing. Expression of amelogenin, ameloblastin and dentin sialophosphoprotein (DSPP) was examined by immunohistochemistry.

Results

There were no gene mutations detected in any of analysed 151 cancer‐ and 42 odontogenesis‐associated genes. Enamel protein‐coding genes of Amelx, Ambn and Enam, and dentin protein‐coding genes of Col1a1, Dspp, Nes and Dmp1 were expressed, whereas expression of dentinogenesis‐associated genes of Bglap, Ibsp and Nfic was negative or very weak suggesting inhibition of dentin formation in POT after odontoblast differentiation. Immunoreactivity of amelogenin, ameloblastin and DSPP was detected in POT.

Conclusions

Pathogenesis of POT is considered to be genetically different from other odontogenic tumours. It is suggested that inhibition of enamel and dentin formation in POT is due to defects in dentin formation process.
Surgical versus non‐surgical treatment of actinic cheilitis: A systematic review and meta‐analysis
Authors: Carvalho Marianne de Vasconcelos , de Moraes Sandra Lúcia Dantas , Lemos Cleidiel Aparecido Araujo , Santiago Júnior Joel Ferreira , Vasconcelos Belmiro Cavalcanti do Egito , Pellizzer Eduardo Piza
Published: June 2018

Objective

The aim of this systematic review was to compare outcomes between surgical and non‐surgical treatment of actinic cheilitis (AC).

Materials and Methods

A systematic review and meta‐analysis based on the Preferred Reporting Items for Systematic reviews and Meta‐Analyses guideline were performed. A search of PubMed/MEDLINE, Web of Science, and Cochrane Library databases was conducted. Articles were selected based on the inclusion criteria: randomized clinical trials, prospective/retrospective studies, and case series with at least 10 patients, with a minimum follow‐up period of 6 months. A weighted remission rate (RER) and recurrence rate (RR) with a 95% confidence interval was performed. Data analysis was performed using a comprehensive meta‐analysis software.

Results

A total of 283 ACs in 10 studies were included. About 2.5% surgically treated cases underwent malignant transformation. The weighted remission rate was higher for surgical (92.8%) compared to non‐surgical treatment (65.9%). The recurrence rate was lower for surgical (8.4%) compared to non‐surgical treatment (19.2%).

Conclusion

In this systematic review, the surgical treatment was more favorable than non‐surgical for AC. Meanwhile, further studies are needed that should maximize methodological standardization and have greater rigor of the data collection process.
High seroprevalence of dengue virus indicates that dengue virus infections are frequent in central and eastern Sudan
Authors: Adam Awadalkareem , Schüttoff Tom , Reiche Sven , Jassoy Christian
Published: June 2018

Objectives

To determine the seroprevalence of dengue in central and eastern Sudan and the breadth of neutralising antibody responses.

Methods

Blood was drawn from 483 patients with fever who visited outpatient clinics in Port Sudan, Red Sea state, in three towns in Kassala state and in El Obeid, North Kordofan, in December 2012 and January 2013. Sera were tested for dengue virus IgG and IgM by ELISA (Panbio) and sera without serologic evidence of acute infection (IgM negative) were used for the analysis of the seroprevalence. DENV neutralisation tests were performed to determine the specificity of the ELISA and to examine the degree of cross‐neutralisation of multiple DENV serotypes.

Results

Sixty‐seven per cent (302 of 448) of the sera were dengue virus IgG‐positive. The seroprevalence in Port Sudan was 89% (106 of 119 sera), in Kassala 61% (128 of 209) and in North Kordofan 56.7% (68 of 120). Thirty‐one of 32 ELISA‐positive sera neutralised dengue viruses indicating that the ELISA was highly specific. The majority of the sera broadly neutralised all four dengue virus serotypes indicating multiple infections.

Conclusions

The majority of the population in central and eastern Sudan has been infected with dengue viruses, many people repeatedly. The high seroprevalence underscores the need for extended dengue surveillance in Sudan, broad disease awareness in medical institutions and in the population and diagnostic capacity building for severe dengue infections.
Socioeconomic status and cigarette expenditure among US households: results from 2010 to 2015 Consumer Expenditure Survey
Authors: Siahpush Mohammad , Farazi Paraskevi A , Maloney Shannon I , Dinkel Danae , Nguyen Minh N , Singh Gopal K
Published: June 2018

Objectives

To examine (1) the association between household socioeconomic status (SES) and whether a household spends money on cigarettes and (2) socioeconomic variations in proportion of total household expenditure spent on cigarettes among smoking households.

Methods

We pooled data from six consecutive years, 2010–2015, of the Consumer Expenditure Interview Survey. The interviews involved a structured questionnaire about household income, demographics and expenditures including expenditure on cigarettes. Households that reported cigarette expenditure in the previous 3 months were distinguished as smoking households. SES indicators were household poverty status, education and occupation of the head of household. Logistic regression was used to assess the association of household smoking status with SES. Fractional logistic regression was used to assess the association of cigarette expenditure as a proportion of total household expenditure with SES. The analysis sample size was 39 218.

Results

The probability of spending money on cigarettes was higher among lower SES households. Households in poverty compared with those above 300% of poverty threshold had 1.86 (95% CI 1.61 to 2.16), households headed by a person with less than high school education compared with those headed by a person with at least a bachelor’s degree had 3.37 (95% CI 2.92 to 3.89) and households headed by a blue-collar work compared with those headed by a person in a managerial occupation had 1.45 (95% CI 1.26 to 1.66) higher odds of spending money on cigarettes. Similarly, the proportion of total household expenditure spent on cigarettes was higher among lower SES smoking households.

Conclusion

Lower SES households are more likely to spend money on cigarettes and spend a larger proportion of their total expenditure on cigarettes. We recommend strategies effective in reducing smoking among low SES smokers.
Schwannomatosis: a genetic and epidemiological study
Authors: Evans D Gareth , Bowers Naomi L , Tobi Simon , Hartley Claire , Wallace Andrew J , King Andrew T , Lloyd Simon K W , Rutherford Scott A , Hammerbeck-Ward Charlotte , Pathmanaban Omar N , Freeman Simon R , Ealing John , Kellett Mark , Laitt Roger , Thomas Owen , Halliday Dorothy , Ferner Rosalie , Taylor Amy , Duff Chris , Harkness Elaine F , Smith Miriam J
Published: June 2018

Objectives

Schwannomatosis is a dominantly inherited condition predisposing to schwannomas of mainly spinal and peripheral nerves with some diagnostic overlap with neurofibromatosis-2 (NF2), but the underlying epidemiology is poorly understood. We present the birth incidence and prevalence allowing for overlap with NF2.

Methods

Schwannomatosis and NF2 cases were ascertained from the Manchester region of England (population=4.8 million) and from across the UK. Point prevalence and birth incidence were calculated from regional birth statistics. Genetic analysis was also performed on NF2, LZTR1 and SMARCB1 on blood and tumour DNA samples when available.

Results

Regional prevalence for schwannomatosis and NF2 were 1 in 126 315 and 50 500, respectively, with calculated birth incidences of 1 in 68 956 and 1 in 27 956. Mosaic NF2 causes a substantial overlap with schwannomatosis resulting in the misdiagnosis of at least 9% of schwannomatosis cases. LZTR1-associated schwannomatosis also causes a small number of cases that are misdiagnosed with NF2 (1%–2%), due to the occurrence of a unilateral vestibular schwannoma. Patients with schwannomatosis had lower numbers of non-vestibular cranial schwannomas, but more peripheral and spinal nerve schwannomas with pain as a predominant presenting symptom. Life expectancy was significantly better in schwannomatosis (mean age at death 76.9) compared with NF2 (mean age at death 66.2; p=0.004).

Conclusions

Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.
Oral Chlorhexidine Against Ventilator-Associated Pneumonia and Microbial Colonization in Intensive Care Patients
Authors: Kocaçal Güler Elem , Türk Gülengün
Published: June 2018

The aim of this systematic review was to determine the effect of chlorhexidine at different concentration and frequency on ventilator-associated pneumonia and microbial colonization in mechanically ventilated patients. Relevant studies in English language were identified by searching data bases between January 2010 and December 2017. Ten studies met the inclusion criteria. Chlorhexidine with 0.2% concentration was found to be more effective than the control group (placebo dental gel and normal saline) in preventing the development of ventilator-associated pneumonia in three of the eight studies. Twice-daily application was found to be effective reducing the rate of ventilator-associated pneumonia in three studies using 0.2% and 2% chlorhexidine. Microbial colonization was found to be less in 2% chlorhexidine group than herbal mouth wash 0.9% NaCl and 0.2% chlorhexidine in three studies. Chlorhexidine is an effective intervention in oral care for ventilator-associated pneumonia and microbial colonization.
Wege einer Verkehrswende
Authors: Petschow Ulrich , Uhle Christian
Published: June 2018

Einführung in das Schwerpunktthema
Click reactions with functional sphingolipids
Authors: Fink Julian , Seibel Jürgen
Published: June 2018

Sphingolipids and glycosphingolipids can regulate cell recognition and signalling. Ceramide and sphingosine-1-phosphate are major players in the sphingolipid pathways and are involved in the initiation and regulation of signalling, apoptosis, stress responses and infection. Specific chemically synthesised sphingolipid derivatives containing small functionalities like azide or alkyne can mimic the biological properties of natural lipid species, which turns them into useful tools for the investigation of the highly complex sphingolipid metabolism by rapid and selective ‘click chemistry’ using sensitive tags like fluorophores. Subsequent analysis by various fluorescence microscopy techniques or mass spectrometry allows the identification and quantification of the corresponding sphingolipid metabolites as well as the research of associated enzymes. Here we present an overview of recent advances in the synthesis of ceramide and sphingosine analogues for bioorthogonal click reactions to study biosynthetic pathways and localization of sphingolipids for the development of novel therapeutics against lipid-dependent diseases.
On Georgian Preverbs
Authors: Makharoblidze Tamar
Published: June 2018

This paper describes the classification of the functions of preverbs in Georgian and the other Kartvelian languages as a contribution to the typology of this issue. Preverbs have different meanings and activities in different languages. The typological classification of the functions of preverbs reveals the four core functions: spatial, temporal, objective and lexical. This paper discusses verbal argument structure alternations encoded by preverbs. I argue that preverbs affect verbal valency changes and stimulate object role-shifting in Georgian verbs and other Kartvelian languages. I also argue that preverbs have a crucial role in object alternation across the languages.
Mixed Feelings: Attitudes towards English loanwords and their use in South Korea
Authors: Rüdiger Sofia
Published: June 2018

This questionnaire study investigates South Korean students’ attitudes towards English loanwords and their use. Even though English enjoys high prestige in Korean society and is considered a requirement for personal and professional advancement, usage of English loanwords is evaluated predominantly negatively or with mixed feelings. For loanwords that semantically deviate from standard English meanings and thus demonstrate Korean identity (i.e., Konglish loanwords), the evaluations turn even more to the negative. Nevertheless, participants also posit positive aspects of general English and Konglish loanword use and, additionally, put forward a variety of perceived reasons for using English words. This study shows that general positive attitudes related to a language can be reversed or at least modified when it comes to the combination of the prestigious language with the native language.