bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostaglandin E2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin
Authors: Mastalerz Lucyna , Tyrak Katarzyna E. , Ignacak Maria , Konduracka Ewa , Mejza Filip , Ćmiel Adam , Buczek Michał , Kot Adrianna , Oleś Krzysztof , Sanak Marek
Published: November 2018

Background

A special regulatory role for prostaglandin E2 (PGE2) has been postulated in nonsteroidal anti‐inflammatory drug (NSAID)–exacerbated respiratory disease (NERD).

Objective

To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airway PGE2 biosynthesis in induced sputum supernatant (ISS) among subjects with NERD or aspirin‐tolerant asthma with chronic rhinosinusitis with nasal polyposis (ATA‐CRSwNP), as well as healthy controls (HC).

Methods

Induced sputum (IS) was collected from patients with NERD (n = 26), ATA‐CRSwNP (n = 17), and HC (n = 21) at baseline and after aspirin challenge. Sputum differential cell count and IS supernatant (ISS) levels of prostanoids, PGE2, 8‐iso‐PGE2, tetranor‐PGE‐M, 8‐iso‐PGF2α, and leukotriene C4, D4, and E4, were determined using mass spectrometry. Urinary excretion of LTE4 was measured by ELISA.

Results

NERD subjects had elevated sputum eosinophilic count as compared to ATA‐CRSwNP and HC (median NERD 9.1%, ATA‐CRSwNP 2.1%, and HC 0.4%; P < 0.01). Baseline ISS levels of PGE2 were higher in asthmatics as compared to HC at baseline (NERD vs HC P = 0.04, ATA‐CRSwNP vs HC P < 0.05). Post‐challenge ISS levels of PGE2 compared to baseline significantly decreased in NERD and HC (P < 0.01 and P = 0.01), but not in ATA‐CRSwNP. In NERD, a similar decrease in PGE2 as in HC resulted from 2.8 times lower dose of aspirin.

Conclusion

Aspirin‐precipitated bronchoconstriction is associated with a decrease in airway PGE2 biosynthesis. These results support the mechanism of PGE2 biosynthesis inhibition as a trigger for bronchoconstriction in NERD.
Classification of South Brazilian grasslands: Implications for conservation
Authors: Andrade Bianca O. , Bonilha Camila L. , Overbeck Gerhard E. , Vélez‐Martin Eduardo , Rolim Rosângela G. , Bordignon Sérgio Augusto L. , Schneider Angelo A. , Vogel Ely Cleusa , Lucas Dióber B. , Garcia Élen N. , dos Santos Emily D. , Torchelsen Fábio P. , Vieira Mariana S. , Silva Filho Pedro J. S. , Ferreira Pedro M. A. , Trevisan Rafael , Hollas Raquel , Campestrini Sérgio , Pillar Valério D. , Boldrini Ilsi I.
Published: November 2018

Aims

We offer a first classification of South Brazilian grasslands (Campos Sulinos) based on quantitative vegetation data and describing grassland types in terms of dominant and indicator species.

Location

South Brazilian grasslands (Paraná, Santa Catarina, Rio Grande do Sul states).

Methods

We described vegetation plots in 167 sampling units throughout the region using a stratified nested design, totalizing 1,502 1 m² quadrats. We classified vegetation using cluster analysis based on Bray–Curtis dissimilarities, establishing three vegetation types and ten subtypes. We conducted indicator species analysis within the resulting subtypes, and for all possible combinations of subtypes.

Results

In the cluster analyses, a clear separation of poorly drained grasslands from the drier sites appeared. Further, a clear distinction between grasslands in the South Brazilian highland region, situated in the Atlantic Forest biome, and the grasslands of the Pampa biome, to the south, emerged, reflecting climatic and management differences. Highland grasslands showed lower species cover dominance, while in the Pampa, Paspalum notatum clearly was the most important species and the abundance of exotic species was higher.

Conclusions

Our study provides the first classification of South Brazilian grasslands based on quantitative vegetation data recorded in a standardized sampling design. The data support the division of grasslands into the main phytogeographic units of the region (Brazilian biome classification). Grasslands in these two regions also differ in terms of species dominance pattern (higher dominance in Pampa grasslands, likely also due to higher grazing levels) and in terms of conservation state (low presence of exotic species in highland grasslands). Our results are important for conservation policies, which can now consider the presence of different grassland types in different region, but more data will be necessary for a more detailed classification that considers different abiotic features in more detail.
Reproductive biology of the unique mudskipper Periophthalmodon septemradiatus living from estuary to upstream of the Hau River
Authors: Dinh Quang Minh , Tran Lam Thanh , Ngo Nhu Chon , Pham Tram Bich , Nguyen Tien Thi Kieu
Published: November 2018

This study provided new knowledge on reproductive traits of the unique mudskipper Periophthalmodon septemradiatus that is also a potential aquarium pet. Fish specimens were obtained by using fishing rods at the muddy flat in tributaries of the Hau River from August 2017 to July 2018. Data analysis of a collection of 1,504 individuals (930 males and 674 females) showed that the sex ratio of this species was significantly different from the ratio 1:1. As mature gonads were found monthly during the study period, it is suggested that P. septemradiatus is an iteroparous species releasing eggs for a year‐round cycle. The fish length at first mature (Lm) showed an increase from estuary to upstream areas. Male P. septemradiatus had higher Lm values than that of females. Likely, the batch fecundity increased from estuary region (5,916 ± 312 SEM eggs) towards upstream area (11,451 ± 953 SEM eggs). The fish total length and weight values had strong positive relationships with batch fecundity, as shown by high determination values (r2), suggesting that batch fecundity increased with fish size. This study provided more information on reproductive biology of P. septemradiatus, which can be utilized for fish population conservation and artificial reproductive study.
Greening the hospitality industry in the developing world: Analysis of the drivers and barriers
Authors: Mzembe Andrew Ngawenja , Melissen Frans , Novakovic Yvonne
Published: November 2018

The implementation of sustainability agendas in the tourism and hospitality industry in developing countries has received little scholarly attention. Working to fill this gap, this paper provides a holistic analysis of the drivers of, and barriers to, sustainability initiatives in the Malawian hospitality industry. Drawing insights from the resource‐based view and institutional theory, it highlights that tensions between global and local norms and values are as important as tensions between internal organizational factors and the isomorphic forces within the organizational fields for implementing sustainability agendas. The paper further reveals the mediating role played by firm size and ownership. It, thus, makes a contribution to the understanding of the role of business in society by focusing on the complex dynamics associated with the adoption of sustainability agendas in an under‐researched context, and demonstrating how tensions between internal organizational factors and local societal expectations within the host countries can shape the nature and focus of the sustainability agenda itself.
Impact of UGT1A1 genetic polymorphism on toxicity in unresectable pancreatic cancer patients undergoing FOLFIRINOX
Authors: Shirasu Hiromichi , Todaka Akiko , Omae Katsuhiro , Fujii Hirofumi , Mizuno Nobumasa , Ozaka Masato , Ueno Hideki , Kobayashi Satoshi , Uesugi Kazuhiro , Kobayashi Noritoshi , Hayashi Hideyuki , Sudo Kentaro , Okano Naohiro , Horita Yosuke , Kamei Keiko , Yukisawa Seigo , Kobayashi Marina , Fukutomi Akira
Published: November 2018

Studies have indicated an association between UDP‐glucuronosyltransferase‐1A1 (UGT1A1) genetic polymorphisms and irinotecan‐induced toxicity. We undertook this study to investigate the association between UGT1A1 genetic polymorphisms and toxicity in patients treated with the FOLFIRINOX (comprising oxaliplatin, irinotecan, fluorouracil, and leucovorin) chemotherapy regimen in the JASPAC 06 study. Patients screened for UGT1A1*6 and UGT1A1*28, and treated with either the original FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 200 mg/m2, bolus 5‐fluorouracil [5‐FU] 400 mg/m2, and continuous 5‐FU 2400 mg/m2) or a modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 200 mg/m2, and continuous 5‐FU 2400 mg/m2) as first‐line chemotherapy were included. Of 199 patients eligible for this analysis, 79 patients were treated with the original FOLFIRINOX regimen and 120 patients were treated with the modified FOLFIRINOX regimen. In the original FOLFIRINOX group, 54 were UGT1A1 WT, and 25 were UGT1A1 heterozygous type (−/*6, 12 patients; −/*28, 13 patients). In the modified FOLFIRINOX group, 64 were UGT1A1 WT and 56 were UGT1A1 heterozygous type (−/*6, 33 patients; −/*28, 23 patients).

In the original FOLFIRINOX group, the incidence of diarrhea was significantly higher among patients with UGT1A1 heterozygous type than among those with UGT1A1 WT and the incidence of leukopenia and diarrhea was significantly higher among patients with UGT1A1 −/*6 than among those with UGT1A1 −/*28. Patients with UGT1A1 heterozygous type, especially those with UGT1A1 −/*6, tended to show a higher incidence rate of severe adverse events, but this was not statistically significant. However, for patients who received the modified FOLFIRINOX, there was no difference in the frequency of adverse events due to UGT1A1 status. In conclusion, patients with heterozygous UGT1A1 polymorphisms treated with the original FOLFIRINOX regimen experienced severe toxicity more frequently than patients with WT UGT1A1.
Protected areas: A focus on Brazilian freshwater biodiversity
Authors: Azevedo‐Santos Valter M. , Frederico Renata G. , Fagundes Camila K. , Pompeu Paulo S. , Pelicice Fernando M. , Padial André A. , Nogueira Marcos G. , Fearnside Philip M. , Lima Luciano B. , Daga Vanessa S. , Oliveira Fagner J. M. , Vitule Jean R. S. , Callisto Marcos , Agostinho Angelo A. , Esteves Francisco A. , Lima-Junior Dilermando P. , Magalhães André L. B. , Sabino José , Mormul Roger P. , Grasel Daniel , Zuanon Jansen , Vilella Fábio S. , Henry Raoul
Published: November 2018

Brazil has a variety of aquatic ecosystems and rich freshwater biodiversity, but these components have been constantly damaged by the expansion of unsustainable activities. An array of different conservation strategies is needed, especially the creation of protected areas (PAs, hereafter). However, Brazil's PAs are biased towards terrestrial ecosystems and we argue that current PAs have limited efficacy in the protection of freshwater biodiversity. New PAs should better consider aquatic environments, covering entire basins, rivers and other freshwater habitats. We recommend ways to implement these PAs and provide guidance to avoid social impacts. Freshwater systems in Brazil provide essential goods and services but these ecosystems are being rapidly degraded and will be lost if not adequately protected.
Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes
Authors: Cusi Kenneth , Bril Fernando , Barb Diana , Polidori David , Sha Sue , Ghosh Atalanta , Farrell Kristin , Sunny Nishanth E. , Kalavalapalli Srilaxmi , Pettus Jeremy , Ciaraldi Theodore P. , Mudaliar Sunder , Henry Robert R.
Published: November 2018

Aim

To evaluate the impact of the sodium glucose co‐transporter 2 inhibitor canagliflozin on intrahepatic triglyceride (IHTG) accumulation and its relationship to changes in body weight and glucose metabolism.

Materials and methods

In this double‐blind, parallel‐group, placebo‐controlled, 24‐week trial subjects with inadequately controlled type 2 diabetes mellitus (T2DM; HbA1c = 7.7% ± 0.7%) from two centres were randomly assigned (1:1) to canagliflozin 300 mg or placebo. We measured IHTG by proton‐magnetic resonance spectroscopy (primary outcome), hepatic/muscle/adipose tissue insulin sensitivity during a 2‐step euglycaemic insulin clamp, and beta‐cell function during a mixed meal tolerance test. Analyses were per protocol.

Results

Between 8 September 2014‐13 June 2016, 56 patients were enrolled. Canagliflozin reduced HbA1c (placebo‐subtracted change: −0.71% [−1.08; −0.33]) and body weight (−3.4% [−5.4; −1.4]; both P ≤ 0.001). A numerically larger absolute decrease in IHTG occurred with canagliflozin (−4.6% [−6.4; −2.7]) versus placebo (−2.4% [−4.2; −0.6]; P = 0.09). In patients with non‐alcoholic fatty liver disease (n = 37), the decrease in IHTG was −6.9% (−9.5; −4.2) versus −3.8% (−6.3; −1.3; P = 0.05), and strongly correlated with the magnitude of weight loss (r = 0.69, P < 0.001). Body weight loss ≥5% with a ≥30% relative reduction in IHTG occurred more often with canagliflozin (38% vs. 7%, P = 0.009). Hepatic insulin sensitivity improved with canagliflozin (P < 0.01), but not muscle or adipose tissue insulin sensitivity. Beta‐cell glucose sensitivity, insulin clearance, and disposition index improved more with canagliflozin (P < 0.05).

Conclusions

Canagliflozin improves hepatic insulin sensitivity and insulin secretion and clearance in patients with T2DM. IHTG decreases in proportion to the magnitude of body weight loss, which tended to be greater and occur more often with canagliflozin.
Circadian pacemaker neurons of the Madeira cockroach are inhibited and activated by GABAA and GABAB receptors
Authors: Giese Maria , Wei HongYing , Stengl Monika
Published: November 2018

GABA is the most abundant neurotransmitter in the circadian pacemaker circuits of mammals and insects. In the Madeira cockroach the accessory medulla (AME) in the brain′s optic lobes is the circadian clock that orchestrates rest‐activity rhythms in synchrony with light dark cycles. Three prominent GABAergic tracts connect the AME to termination sites of compound eye photoreceptors in the lamina and medulla. Parallel GABAergic light entrainment pathways were suggested to either advance or delay the clock for adjustment to changing photoperiods. In agreement with this hypothesis GABA activated or inhibited AME clock neurons, allowing for the distinction of three different GABA response types. Here, we examined which GABA receptors are responsible for these response types. We found that both ionotropic GABAA receptors and metabotropic GABAB receptors were expressed in AME clock cells. Via different signalling pathways, either one of them could account for all three GABA response types. The muscimol‐dependently activated GABAA receptor formed a chloride channel, while the SKF 97541‐dependently activated GABAB receptor signalled via G‐proteins, apparently targeting potassium channels. Expression of chloride exporters or importers determined whether GABAA receptor activation hyper‐ or depolarized AME neurons. For GABAB receptor responses second messenger gated channels present in the clock cells appeared to decide about the polarity of the GABA response. In summary, circadian clock neurons co‐expressed inhibitory and/or excitatory GABAA and GABAB receptors in various combinations, while cotransporter expression and the set of second messenger gated ion channels present allowed for distinct signalling in different clock neurons.
Ethanol upregulates the P2X7 purinergic receptor in human macrophages
Authors: Le Daré Brendan , Victoni Tatiana , Bodin Aude , Vlach Manuel , Vene Elise , Loyer Pascal , Lagente Vincent , Gicquel Thomas
Published: November 2018

Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome and are involved in many ethanol‐related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis, and certain cancers). We hypothesized that ethanol regulates purinergic receptors and thus modulates the NLRP3 inflammasome's activity. In experiments with monocyte‐derived macrophages, we found that interleukin (IL)‐1β secretion was inhibited after 7 h of exposure (but not 48 h of exposure) to ethanol. The disappearance of ethanol's inhibitory effect on IL‐1β secretion after 48 h was not mediated by the upregulated production of IL‐1β, IL‐1α, IL‐6 or the inflammasome components NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain, and caspase 1. P2X7R expression was upregulated by ethanol, whereas expression of the P2X4 and P2X1 receptors was not. Taken as a whole, our results suggest that ethanol induces NLRP3 inflammasome activation by upregulating the P2X7 receptor. This observation might have revealed a new mechanism for inflammation in ethanol‐related diseases.
Evaluation of microbial toxins, trace elements and sensory properties of a high‐theabrownins instant Pu‐erh tea produced using Aspergillus tubingensis via submerged fermentation
Authors: Wang Qiuping , Šarkanj Bojan , Jurasovic Jasna , Chisti Yusuf , Sulyok Michael , Gong Jiashun , Sirisansaneeyakul Sarote , Komes Draženka
Published: November 2018

Theabrownins (TB) are polymeric phenolic compounds associated with the multiple bioactivities of Pu‐erh tea, a post‐fermented Chinese dark tea. High‐TB instant Pu‐erh tea was produced via a novel submerged fermentation (SF) using Aspergillus tubingensis and compared with samples produced commercially via the conventional solid‐state fermentation (SSF). Viable microorganisms and microbial toxins, especially aflatoxins B1, G1, B2, G2, cyclopiazonic acid, fumonisins B1, B2, B3 and ochratoxin A, were below the detection limit in all samples. Fewer microbial metabolites were found in SF instant tea compared with the SSF teas. Based on an adult consuming 1 g of instant Pu‐erh tea daily, the dietary intake of investigated elements was below the safe limits recommended by various authorities. Tasters viewed the instant tea infusions as very mild, smooth, mellow and full. This suggested that submerged fermentation using A. tubingensis offers a speedy and safe alternative to commercial production of instant Pu‐erh tea.
Non‐canonical activation ofCREBmediates neuroprotection in aCaenorhabditis elegansmodel of excitotoxic necrosis
Authors: Feldmann K. Genevieve , Chowdhury Ayesha , Becker Jessica L. , McAlpin N'Gina , Ahmed Taqwa , Haider Syed , Richard Xia Jian X. , Diaz Karina , Mehta Monal G. , Mano Itzhak
Published: November 2018

Excitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu‐receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingly, signaling downstream of GluRs can also activate neuroprotective pathways. The strongest evidence involves activation of the transcription factorcAMPresponse element‐binding protein (CREB), widely recognized for its importance in synaptic plasticity. Canonical views describeCREBas a phosphorylation‐triggered transcription factor, where transcriptional activation involvesCREBphosphorylation and association withCREB‐binding protein. However, givenCREB's ubiquitous cross‐tissue expression, the multitude of cascades leading toCREBphosphorylation, and its ability to regulate thousands of genes, it remains unclear howCREBexerts closely tailored, differential neuroprotective responses in excitotoxicity. A non‐canonical, alternative cascade for activation ofCREB‐mediated transcription involves theCREBco‐factorcAMP‐regulated transcriptional co‐activator (CRTC), and may be independent ofCREBphosphorylation. To identify cascades that activateCREBin excitotoxicity we used aCaenorhabditis elegansmodel of neurodegeneration by excitotoxic necrosis. We demonstrated thatCREB's neuroprotective effect was conserved, and seemed most effective in neurons with moderate Glu exposure. We found that factors mediating canonicalCREBactivation were not involved. Instead, phosphorylation‐independentCREBactivation in nematode excitotoxic necrosis hinged onCRTC.CREB‐mediated transcription that depends onCRTC, but not onCREBphosphorylation, might lead to expression of a specific subset of neuroprotective genes. Elucidating conserved mechanisms of excitotoxicity‐specificCREBactivation can help us focus on core neuroprotective programs in excitotoxicity.

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Cover Image for this issue: doi:10.1111/jnc.14494.
Menopause is associated with decreased postprandial ghrelin, whereas a history of anorexia nervosa is associated with increased total ghrelin
Authors: Stojiljkovic‐Drobnjak Suzana , Fischer Susanne , Arnold Myrtha , Langhans Wolfgang , Ehlert Ulrike
Published: November 2018

Middle age has been linked with various dysfunctional eating patterns in women. The hormone ghrelin is related to food intake, with plasma levels rising before eating and decreasing immediately afterwards. Animal research has shown that oestradiol is an antagonist of ghrelin. Given that both menopause and anorexia nervosa (AN) are states characterised by reduced oestradiol, the present study aimed to investigate for the first time whether menopausal status and a history of AN are linked with altered ghrelin levels in middle‐aged women. Based on previous research, we hypothesised that (i) post‐menopausal women would demonstrate comparably increased ghrelin after food intake and (ii) women with a history of AN would exhibit increased total ghrelin levels. Healthy, middle‐aged women (n = 57) were recruited. Of the women, 31 were post‐menopausal and 27 had a history of AN. Plasma ghrelin was repeatedly collected before and after a meal standardised in terms of caloric content. Areas under the curves were calculated to indicate total (AUCg) and postprandial ghrelin (AUCi). Menopausal status was linked with postprandial ghrelin (AUCi −1.6 ± 2.2 vs −2.9 ± 2.6; P = 0.058), whereas a history of AN was linked with total ghrelin (AUCg 36.2 ± 5.6 vs 39.0 ± 3.7; P = 0.050). There were no interaction effects (both P > 0.466). A closer examination of the effects revealed that post‐menopausal women showed marginally greater decreases in ghrelin immediately after food intake (P = 0.064) and marginally greater re‐increases after 60 minutes (P = 0.084) compared to pre‐menopausal women. Women with a history of AN had significantly higher total ghrelin compared to women without a history of AN (P = 0.042). Post‐menopause was linked with higher sensitivity of ghrelin to food intake (trend), whereas a history of AN was related to greater total ghrelin. Future research should investigate to what extent the observed alterations in ghrelin may affect dysfunctional eating behaviour during middle age.
The fate of genes that cross species boundaries after a major hybridization event in a natural mosquito population
Authors: Hanemaaijer Mark J. , Collier Travis C. , Chang Allison , Shott Chloe C. , Houston Parker D. , Schmidt Hanno , Main Bradley J. , Cornel Anthony J. , Lee Yoosook , Lanzaro Gregory C.
Published: November 2018

Animal species are able to acquire new genetic material via hybridization and subsequent introgression. However, little is known about how foreign genomic material is incorporated into a population over time and what genes are susceptible to introgression. Here, we follow the closely related mosquito sister speciesAnopheles coluzziiandAnopheles gambiaein a sympatric natural population in Mali at multiple time points spanning a period of 25 years. During this period, we observed the temporary breakdown of mating barriers, which allowed us to explore the fate of alleles that crossed the species boundary in a natural population. Whole genome sequencing of 74 individuals revealed introgression within only 34 genes (0.26% of total genes) fromA. gambiaetoA. coluzzii, the majority contained within a 4 Mb region on the 2L chromosome which includes the insecticide resistance gene (AGAP004707). We designed a genotyping assay to follow 25 of the 34 introgressed alleles over time and found that allA. gambiaealleles, except four, reached a frequency of 50% in theA. coluzziipopulation within 4 years (~50 generations) and increased to ~80% within 6 years (~75 generations). However, the frequency of all introgressed alleles, except three, decreased to ~60% in 2016. This suggests an ongoing process of purifying selection in the population against DNA of foreign ancestry, except for alleles that are under positive selection, resulting in a complex genomic landscape.This study shows that stable introgression is limited to only specific genes even within closely related species.
The biotroph Agrobacterium tumefaciens thrives in tumors by exploiting a wide spectrum of plant host metabolites
Authors: Gonzalez‐Mula Almudena , Lachat Joy , Mathias Léo , Naquin Delphine , Lamouche Florian , Mergaert Peter , Faure Denis
Published: November 2018

Agrobacterium tumefaciens is a niche‐constructing biotroph that exploits host plant metabolites.

We combined metabolomics, transposon‐sequencing (Tn‐seq), transcriptomics, and reverse genetics to characterize A. tumefaciens pathways involved in the exploitation of resources from the Solanum lycopersicum host plant.

Metabolomics of healthy stems and plant tumors revealed the common (e.g. sucrose, glutamate) and enriched (e.g. opines, γ‐aminobutyric acid (GABA), γ‐hydroxybutyric acid (GHB), pyruvate) metabolites that A. tumefaciens could use as nutrients. Tn‐seq and transcriptomics pinpointed the genes that are crucial and/or upregulated when the pathogen grew on either sucrose (pgi, kdgA, pycA, cisY) or GHB (blcAB, pckA, eno, gpsA) as a carbon source. While sucrose assimilation involved the Entner–Doudoroff and tricarboxylic acid (TCA) pathways, GHB degradation required the blc genes, TCA cycle, and gluconeogenesis. The tumor‐enriched metabolite pyruvate is at the node connecting these pathways. Using reverse genetics, we showed that the blc, pckA, and pycA loci were important for aggressiveness (tumor weight), proliferation (bacterial charge), and/or fitness (competition between the constructed mutants and wild‐type) of A. tumefaciens in plant tumors.

This work highlighted how a biotroph mobilizes its central metabolism for exploiting a wide diversity of resources in a plant host. It further shows the complementarity of functional genome‐wide scans by transcriptomics and Tn‐seq to decipher the lifestyle of a plant pathogen.
BK polyomavirus viremia and antibody responses of pediatric kidney transplant recipients in Finland
Authors: Miettinen Jenni , Lautenschlager Irmeli , Weissbach Fabian , Wernli Marion , Auvinen Eeva , Mannonen Laura , Lauronen Jouni , Hirsch Hans H. , Jalanko Hannu
Published: November 2018

Background

BKPyV is an important cause of premature graft failure after KT. Most clinical studies describe BKPyV infection in adult KT patients. We studied the prevalence of post‐transplant BKPyV viremia, serology, and graft function in pediatric KT recipients.

Methods

Forty‐six pediatric patients transplanted between 2009 and 2014 were followed up for BKPyV DNAemia by plasma PCR for median 2.3 (range: 1‐6) years. BKPyV‐specific antibodies were retrospectively analyzed using virus‐like particle ELISA. GFR was measured annually by 51Cr‐EDTA clearance, and serum samples were screened for DSAs by Luminex assay.

Results

BKPyV viremia was demonstrated in nine patients at a median of 6 months post‐KT. Early BKPyV viremia at 3 months post‐KT associated with decreased concomitant GFR and tendency for decreased subsequent graft function. Three of nine patients with BKPyV viremia developed DSA, all against class II antigens. PyVAN developed to four patients and responded to judicious reduction in IS. One graft was lost later due to ABMR. BKPyV‐IgG was found in 18 of 31 patients (58%) tested at transplantation, and seven recipients seroconverted after transplantation with a significant increase in IgG levels with IgM. Finally, BKPyV‐IgG was detectable in 31 of 40 patients (78%) at the end of the study.

Conclusions

Post‐transplant BKPyV viremia in pediatric KT patients may alter graft function and contribute to progression of chronic allograft injury. BKPyV‐IgG predicts past exposure. Low or absent BKPyV‐specific antibody levels were seen pretransplant in 42% of tested patients, but were not predictive of prolonged replication or poor outcome.
The use of quantitative imaging to investigate regulators of membrane trafficking in Arabidopsis stomatal closure
Authors: Bourdais Gildas , McLachlan Deirdre H. , Rickett Lydia M. , Zhou Ji , Siwoszek Agnieszka , Häweker Heidrun , Hartley Matthew , Kuhn Hannah , Morris Richard J. , MacLean Dan , Robatzek Silke
Published: November 2018

Expansion of gene families facilitates robustness and evolvability of biological processes but impedes functional genetic dissection of signalling pathways. To address this, quantitative analysis of single cell responses can help characterize the redundancy within gene families. We developed high‐throughput quantitative imaging of stomatal closure, a response of plant guard cells, and performed a reverse genetic screen in a group of Arabidopsis mutants to five stimuli. Focussing on the intersection between guard cell signalling and the endomembrane system, we identified eight clusters based on the mutant stomatal responses. Mutants generally affected in stomatal closure were mostly in genes encoding SNARE and SCAMP membrane regulators. By contrast, mutants in RAB5 GTPase genes played specific roles in stomatal closure to microbial but not drought stress. Together with timed quantitative imaging of endosomes revealing sequential patterns in FLS2 trafficking, our imaging pipeline can resolve non‐redundant functions of the RAB5 GTPase gene family. Finally, we provide a valuable image‐based tool to dissect guard cell responses and outline a genetic framework of stomatal closure.
Frequent human‐poultry interactions and low prevalence of Salmonella in backyard chicken flocks in Massachusetts
Authors: McDonagh Alyssa , Leibler Jessica H. , Mukherjee Jean , Thachil Anil , Goodman Laura B. , Riekofski Cassidy , Nee Amanda , Smyth Khrysti , Forrester Janet , Rosenbaum Marieke H.
Published: November 2018

The backyard chicken (BYC) movement in the USA has increased human contact with poultry and subsequently, human contact with the pathogen Salmonella. However, to date, there have been few studies assessing prevalence of Salmonella in backyard flocks, despite the known public health risk this zoonotic bacterium poses. The objective of this study was to characterize human‐BYC interactions and assess the prevalence of Salmonella among BYC flocks. We interviewed 50 BYC owners using a structured questionnaire to determine flock and household characteristics that facilitate contact with BYC and that may be associated with Salmonella in the BYC environment. Composite faecal material, cloacal swabs and dust samples from 53 flocks housed on 50 residential properties in the Greater Boston, Massachusetts area were tested for Salmonella using standard culture techniques and confirmed using Matrix‐Assisted Laser Desorption/Ionization‐Time of Flight Mass Spectrometer. Microbroth dilution and whole genome sequencing were used to determine phenotypic and genotypic resistance profiles, respectively, and sequence results were used to determine multilocus sequencing type. No owners self‐reported a diagnosis of salmonellosis in the household. Over 75% of a subset of owners reported that they and their children consider BYC pets. This perception is evident in how owners reported interacting with their birds. Salmonella enterica subspecies enterica serotype Kentucky ST152 (serogroup C)—a strain not commonly associated with human infection—was confirmed in one flock, or 2% of tested flocks, and demonstrated resistance to tetracycline and streptomycin. We detected Salmonella at low prevalence in BYC. Further study of the health effects of exposure to zoonotic gastrointestinal pathogens such as Salmonella among families with BYC is warranted.
Effectiveness of psychological interventions for women with type 2 diabetes who are overweight or obese: a systematic review protocol
Authors: Jesse Cecile D. , Creedy Debra K. , Anderson Debra J.
Published: November 2018

Review objective/question:

The objectives of this review are to:
Frameworks for evaluation of community health centers’ services and outcomes: a scoping review protocol
Authors: Nagel Daniel A. , Keeping-Burke Lisa , Pyrke Ryan J.L. , Pyrke Courtney L.B. , Goudreau Alex , Luke Alison , Wilbur Kimberly A. , Waycott Loretta , Hamilton Catherine
Published: November 2018

Review objectives/question:

The objective of this scoping review is to identify and map the frameworks used to evaluate services and outcomes of community health centers within the broader context of primary health care.

The primary question for this scoping review is: what are the frameworks used to evaluate services and outcomes of community health centers?

Secondary questions for this review are:
Benefits and challenges of serial sports training risk assessment and counselling in kids: the T.R.A.C.K. randomised intervention study
Authors: Kliethermes Stephanie A , Dugas Lara R , LaBella Cynthia R , Alawad Noor , Pasulka Jacqueline , Jayanthi Neeru
Published: November 2018

Background

Published training recommendations exist for youth athletes aimed at reducing injury risk. No studies have assessed the impact of counselling interventions using training recommendations on risk of injury in young athletes.

Objectives

To determine if online training counselling regarding safe sport participation can reduce injury risk in youth athletes and to assess recommendation compliance, including barriers to compliance.

Methods

A multicentre randomised intervention trial was performed at two Midwestern academic institutions with expertise in treating young athletes. Enrolled subjects ages 8–17 completed a baseline risk assessment survey and were randomised to a control or intervention group. Both groups completed exposure surveys every 3 months for 1 year. The intervention group also received online training counselling on safe sport participation every 3 months. Training characteristics including training volume, degree of specialisation and adherence to recommendations were captured. Differences in self-reported injury between groups, compliance to recommendations and barriers to compliance were evaluated.

Results

At baseline, n=357 subjects were enrolled (n=172 control and n=185 intervention). Controls were nearly twice as likely to be injured during the intervention period after controlling for age, sex, baseline injury and level of specialisation. No improvement in recommendation compliance was detected among intervention subjects. Primary barriers to compliance were no prior knowledge of recommendations, personal choice and following coaches’ recommendations.

Conclusions

In this convenience sample of youth athletes, electronic training counselling surrounding safe sports participation was not determined to affect injury risk. Lack of knowledge and adherence to appropriate training recommendations is evident and barriers to compliance exist.
Does test-based prescription of evidence-based treatment for malaria improve treatment seeking and satisfaction? Findings of repeated cross-sectional surveys in Papua New Guinea
Authors: Pulford Justin , Saweri Olga P M , Jeffery Caroline , Siba Peter M , Mueller Ivo , Hetzel Manuel W
Published: November 2018

Introduction

The presumptive treatment of febrile illness with antimalarial medication is becoming less common in low-income and middle-income countries as access to reliable diagnostic tests improves. We explore whether the shift towards test-based antimalarial prescription, and the introduction of highly efficacious artemisinin combination therapies (ACTs), reduces critical delays in seeking treatment for febrile illness or increases patient satisfaction.

Methods

We conducted countrywide repeat, cross-sectional surveys in 118 randomly selected primary healthcare services in Papua New Guinea. The clinical case management of 1765 consecutively presenting febrile patients was observed and exit interviews were completed at discharge. This was done prior to implementation of test-based ACT prescription (2011) and at 12 (2012) and 60  months (2016) postimplementation. We conducted multiple logistic regressions. Treatment response time was dichotomised as <24  hours from symptom onset vs 24+ hours. Satisfaction was dichotomised as a ‘high’ vs ‘low’ rating based on participant response to a visual, 7-point Likert-type scale.

Results

62% (322/517) of febrile patients reported seeking treatment within 24  hours of symptom onset in 2011 compared with 53% (230/434) in 2012 and 42% (339/814) in 2016. Adjusted ORs for reporting a treatment response time <24  hours in the postimplementation surveys were 0.77 (95% CI 0.48 to 1.26) and 0.45 (95% CI 0.31 to 0.65), respectively when compared with the preimplementation period. 53% (230/533) of febrile patients reported ‘high’ satisfaction with the service received in 2011 compared with 32% (143/449) in 2012 and 35% (278/803) in 2016. Adjusted ORs for reporting high satisfaction in the postimplementation surveys were 0.52 (95% CI 0.32 to 0.85) and 0.65 (95% CI 0.39 to 1.10), respectively when compared with the preimplementation period.

Conclusion

Nationwide implementation of test-based ACT prescription in Papua New Guinea has increased the likelihood of critical treatment seeking delays and decreased patient satisfaction with the service received.
Using a mentorship model to localise the Practical Approach to Care Kit (PACK): from South Africa to Ethiopia
Authors: Feyissa Yibeltal Mekonnen , Hanlon Charlotte , Emyu Solomon , Cornick Ruth Vania , Fairall Lara , Gebremichael Daniel , Teka Telahun , Shiferaw Solomon , Walelgne Wubaye , Mamo Yoseph , Segni Hailemariam , Ayehu Temesgen , Wale Meseret , Eastman Tracy , Awotiwon Ajibola , Wattrus Camilla , Picken Sandy Claire , Ras Christy-Joy , Anderson Lauren , Doherty Tanya , Prince Martin James , Tegabu Desalegn
Published: November 2018

The Federal Ministry of Health, Ethiopia, recognised the potential of the Practical Approach to Care Kit (PACK) programme to promote integrated, comprehensive and evidence-informed primary care as a means to achieving universal health coverage. Localisation of the PACK guide to become the ‘Ethiopian Primary Health Care Clinical Guidelines’ (PHCG) was spearheaded by a core team of Ethiopian policy and technical experts, mentored by the Knowledge Translation Unit, University of Cape Town. A research collaboration, ASSET (heAlthSystemsStrEngThening in sub-Saharan Africa), has brought together policy-makers from the Ministry of Health and health systems researchers from Ethiopia (Addis Ababa University) and overseas partners for the PACK localisation process, and will develop, implement and evaluate health systems strengthening interventions needed for a successful scale-up of the Ethiopian PHCG. Localisation of PACK for Ethiopia included expanding the guide to include a wider range of infectious diseases and an expanded age range (from 5 to 15 years). Early feedback from front-line primary healthcare (PHC) workers is positive: the guide gives them greater confidence and is easy to understand and use. A training cascade has been initiated, with a view to implementing in 400 PHC facilities in phase 1, followed by scale-up to all 3724 health centres in Ethiopia during 2019. Monitoring and evaluation of the Ministry of Health implementation at scale will be complemented by indepth evaluation by ASSET in demonstration districts. Anticipated challenges include availability of essential medications and laboratory investigations and the need for additional training and supervisory support to deliver care for non-communicable diseases and mental health. The strong leadership from the Ministry of Health of Ethiopia combined with a productive collaboration with health systems research partners can help to ensure that Ethiopian PHCG achieves standardisation of clinical practice at the primary care level and quality healthcare for all.
Moving from formative research to co-creation of interventions: insights from a community health system project in Mozambique, Nepal and Peru
Authors: Beran David , Lazo-Porras Maria , Cardenas Maria Kathia , Chappuis François , Damasceno Albertino , Jha Nilambar , Madede Tavares , Lachat Sarah , Perez Leon Silvana , Aya Pastrana Nathaly , Pesantes Maria Amalia , Singh Suman Bahadur , Sharma Sanjib , Somerville Claire , Suggs L Suzanne , Miranda J Jaime
Published: November 2018

Different methodological approaches for implementation research in global health focusing on how interventions are developed, implemented and evaluated are needed. In this paper, we detail the approach developed and implemented in the COmmunity HEalth System InnovatiON (COHESION) Project, a global health project aimed at strengthening health systems in Mozambique, Nepal and Peru. This project developed innovative formative research at policy, health system and community levels to gain a comprehensive understanding of the barriers, enablers, needs and lessons for the management of chronic disease using non-communicable and neglected tropical diseases as tracer conditions. After formative research, COHESION adopted a co-creation approach in the planning of interventions. The approach included two interactions with each type of stakeholder at policy, health system and community level in each country which aimed to develop interventions to improve the delivery of care of the tracer conditions. Diverse tools and methods were used in order to prioritise interventions based on support, resources and impact. Additionally, a COHESION score that assessed feasibility, sustainability and scaling up was used to select three potential interventions. Next steps for the COHESION Project are to further detail and develop the interventions propositioned through this process. Besides providing some useful tools and methods, this work also highlights the challenges and lessons learned from such an approach.
Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis
Authors: Cao Wenhong , Wei Wenbin , Wu Qian
Published: November 2018

Objective

To evaluate the ophthalmic phenotypes associated with T-cell immune regulator 1 (TCIRG1) mutations in Chinese patients with infantile malignant osteopetrosis (IMO).

Methods and analysis

27 Chinese TCIRG1-related osteoporosis infants were enrolled using direct DNA sequencing of PCR-amplified exons. 12 cases had frameshift mutation (the frameshift mutation group, group F), and 15 cases had point mutation (the point mutation group, group P). The clinical features of the two groups were compared, including age at onset, gaze qualities, optic atrophy, optic canal stenosis and waveforms of Flash visual-evoked potential (FVEP).

Results

The clinical signs, except age at onset and FVEP, showed statistically significant differences between the two groups. The mean age at onset was 1.8 months in group F and 4.3 months in group P; 22 eyes (92%) with frameshift mutation and 16 (53%) with point mutation had poor gaze qualities, such as nystagmus and/or strabismus; optic atrophy was found in 16 eyes (67%) in group F and 6 (20%) in group P; the average optic canal diameter was 1.45  mm in the frameshift mutation cases, 1.87  mm in other cases; FVEP indicated that the waveforms in 10 eyes (42%) were not elicited in group F, yet five eyes (17%) in group P.

Conclusion

In Chinese TCIRG1-related patients of IMO, the optic canal stenosis and optic atrophy were more serious in cases with frameshift mutations. However, no differences in the conduction block of optic nerve were found between the two groups.
Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink
Authors: Liu Zhiwei , Alsaggaf Rotana , McGlynn Katherine A , Anderson Lesley A , Tsai Huei-Ting , Zhu Bin , Zhu Yue , Mbulaiteye Sam M , Gadalla Shahinaz M , Koshiol Jill
Published: November 2018

Objective

To evaluate the association between statin use and risk of biliary tract cancers (BTC).

Design

This is a nested case–control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders.

Results

We included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (ptrend=0.016) and cumulative dose of statins (ptrend=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007).

Conclusion

Compared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.
Public mobilisation in implementation of smoke-free Beijing: a social media complaint platform
Authors: Zhang Jianshu , Cui Xiaobo , Liu Hui , Han Hongshu , Cao Ruoxiang , Sebrie Ernesto M , Yin Xi
Published: November 2018

In November 2014, Beijing People’s Congress adopted the Beijing Smoking Control Ordinance and a key provision bans smoking in all indoor public places, workplaces and on public transport. To ensure effective implementation of the ordinance, the government calls on the whole society to take part. In response, Beijing Tobacco Control Association, with the support of a local technology company, developed the Beijing Tobacco Control Map, a digital system that enables comprehensive tobacco control information collection, data visualisation and mapping. A key component of the Beijing Tobacco Control Map is the Complaint Map which is generated by the data of reported violations of the smoke-free provisions by the general public through a social media platform. The Complaint Map visually displays the reported violations on a map of Beijing in real time. The general public can access the Complaint Map at any time to see which venues and locations have been reported. It is used by tobacco control volunteers, who are recruited and trained to address complaints and promote compliance. It is also used by the government’s enforcement team for targeted inspections. The Complaint Map has effectively engaged the public and promoted a smoke-free Beijing. Beijing’s innovative and systematic approach that involves the Complaint Map, volunteer management, coordination with the enforcement team, and media exposure can be replicated or adapted in other cities in China and abroad that are implementing smoke-free laws or tobacco control laws in general.