bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential role of ALDH3A2 on the lipid and glucose metabolism regulated by (‐)‐hydroxycitric acid in chicken embryos
Authors: Li Shengnan , Yang Zhongmiao , Zhang Huihui , Peng Mengling , Ma Haitian
Published: May 2019

This study aimed to investigate the effect of (‐)‐hydroxycitric acid ((‐)‐HCA) on lipid and glucose metabolism, and further analyzed these actions whether associated with modulation of aldehyde dehydrogenase 3 family member A2 (ALDH3A2) expression in chicken embryos. Results showed that (‐)‐HCA decreased triglyceride content and lipid droplet counts, while these effects induced by (‐)‐HCA were reversed in chicken embryos pre‐transfected with sh4‐ALDH3A2. (‐)‐HCA decreased malic enzyme, acetyl‐CoA carboxylase, fatty acid synthase, and sterol regulatory element binding protein‐1c mRNA level, while increased carnitine palmitoyl transferase 1A (CPT1A) and peroxisome proliferators‐activated receptor α (PPARα) mRNA level; and the action of (‐)‐HCA on lipid metabolism factors had completely eliminated in embryos pre‐transfected with sh4‐ALDH3A2. Chicken embryos pre‐transfected with sh4‐ALDH3A2 had eliminated the increasing of serum glucose and hepatic glycogen content induced by (‐)‐HCA. (‐)‐HCA decreased phosphofructokinase‐1 and increased G6P, fructose‐1,6‐bisphosphatase, phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate carboxylase mRNA level in chicken embryos. Similarly, the effect of (‐)‐HCA on these key enzyme mRNA level was reversed in embryos pre‐transfected with sh4‐ALDH3A2. Furthermore, (‐)‐HCA increased PPAR‐γ‐coactivator‐1α (PGC‐1α), PPARα, hepatic nuclear factor‐4A, PEPCK, and CPT1A protein level, and these actions of (‐)‐HCA disappeared in embryos pre‐transfected with sh4‐ALDH3A2. These results indicated that (‐)‐HCA reduced fat accumulation and accelerated gluconeogenesis via activation of PGC‐1α signaling pathway, and these effects of (‐)‐HCA might associate with the increasing of ALDH3A2 expression level in chicken embryos.
Thermal stimulation at 39°C facilitates the fusion and elongation of C2C12 myoblasts
Authors: Hayashi Satoko , Yonekura Shinichi
Published: May 2019

The aim of this study was to determine the effect of thermal stimulation at 39°C on the fusion and elongation of skeletal muscle cells. During a 5 day differentiation process of C2C12 cells, nine groups subjected to varying lengths of thermal stimulation at 39°C were established. Afterward, all groups were immunostained using anti‐muscle heavy‐chain antibody to test for myotube formation. Quantification of the myotube area demonstrated a significant increase in the group subjected to thermal stimulation at 39°C during the latter half of the differentiation compared with the control group, but the fusion index was significantly higher in the group that received hyperthermic treatment during the first half of the differentiation period. Moreover, the longitudinal length of myotubes was significantly increased in the groups that were subjected to thermal stimulation at 39°C during the latter half of the differentiation period. The distance between the center of myotubes and the nucleus farthest away from the center was substantially extended in the group receiving thermal stimulation at 39°C only on the fourth day of the differentiation. Together, these results demonstrate that thermal stimulation at 39°C facilitates myoblast fusion and elongation.
Effortless or less effort? Effects of tracks on students’ engagement
Authors: Dockx Jonas , Van den Branden Naomi , De Fraine Bieke
Published: May 2019

Background

It is found that assigning students to a lower track during secondary education negatively affects their academic performance. As an explanation, it is often mentioned that an anti‐school culture in lower tracks undermines students’ effort and involvement.

Aims

This study assessed whether going to a lower track affects student engagement. For if an anti‐school culture is to blame for limiting lower track students’ performance, lower track assignment should reduce engagement.

Sample

A sample of a longitudinal cohort study during secondary education in Flanders (northern Belgium) was used to describe development in engagement with n = 5,417 students in 46 schools. Four tracks were investigated across four school years.

Method

Two main methodological challenges were present in this study, different student intake in each track and many students changing from a higher to lower track over time. Accordingly, we used inverse probability treatment weights with marginal structural mean models to account for different student intake and track changes. A comparison was made per pair of tracks that are hierarchically consecutive by matching students who were comparable across these tracks. Accordingly, there were three pairwise comparisons.

Results

It was never found that being continuously in lower track negatively affects engagement. Only for one pairwise comparison, there was evidence that students who changed from the higher to lower track had lower engagement.

Conclusions

We rejected the hypothesis that lower tracks negatively affect student engagement. This makes the anti‐school culture as an explanation for lower track assignment negatively affecting academic performance implausible.
Allodepleted T‐cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft‐versus‐host disease (GVHD) in the absence of GVHD prophylaxis
Authors: Roy Denis Claude , Lachance Sylvie , Cohen Sandra , Delisle Jean‐Sébastien , Kiss Thomas , Sauvageau Guy , Busque Lambert , Ahmad Imran , Bernard Lea , Bambace Nadia , Boumédine Radia S. , Guertin Marie‐Claude , Rezvani Katayoun , Mielke Stephan , Perreault Claude , Roy Jean
Published: May 2019

Graft‐versus‐host disease (GVHD) is a major cause of transplant‐related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and presents a challenge in haploidentical HSCT. GVHD may be prevented by ex vivo graft T‐cell depletion or in vivo depletion of proliferating lymphocytes. However, both approaches pose significant risks, particularly infections and relapse, compromising survival. A photodepletion strategy to eliminate alloreactive T cells from mismatched donor lymphocyte infusions (enabling administration without immunosuppression), was used to develop ATIR101, an adjunctive therapy for use after haploidentical HSCT. In this phase I dose‐finding study, 19 adults (median age: 54 years) with high‐risk haematological malignancies were treated with T‐cell‐depleted human leucocyte antigen‐haploidentical myeloablative HSCT followed by ATIR101 at doses of 1 × 104–5 × 106 CD3+ cells/kg (median 31 days post‐transplant). No patient received post‐transplant immunosuppression or developed grade III/IV acute GVHD, demonstrating the feasibility of ATIR101 infusion for evaluation in two subsequent phase 2 studies. Additionally, we report long‐term follow ‐up of patients treated with ATIR101 in this study. At 1 year, all 9 patients receiving doses of 0·3–2 × 106 CD3+ cells/kg ATIR101 remained free of serious infections and after more than 8 years, TRM was 0%, relapse‐related mortality was 33% and overall survival was 67% in these patients.
Recommended antibiotic prophylaxis regimen in retrograde intrarenal surgery: evidence from a randomised controlled trial
Authors: Zhao Zhijian , Fan Junhong , Sun Hongling , Zhong Wen , Zhu Wei , Liu Yongda , Wu Wenqi , de la Rosette Jean , del Pilar Laguna Pes Maria , Zeng Guohua
Published: May 2019

Objective

To study the incidence of postoperative systemic inflammatory response syndrome (SIRS) following different antibiotic prophylaxis (ABP) regimens in retrograde intrarenal surgery (RIRS).

Patients and Methods

Single‐centre, randomised, controlled trial (August 2014–September 2017) including 426 patients with renal stones with preoperative sterile urine managed by RIRS (ClinicalTrials.gov NCT02304822). Different ciprofloxacin‐based ABP regimens were used and included a zero dose, single dose (30 min before surgery) or two doses (first dose at 30 min before RIRS and additional dose within 6 h after RIRS). The incidence of SIRS was compared using intention‐to‐treat (ITT) and per‐protocol (PP) analyses.

Results

Each group enrolled 142 patients. In the ITT analysis, a zero dose of ABP was statistically similar to the two ABP regimes for the incidence of SIRS (9.9% vs single dose 4.9%, P = 0.112; vs two doses 4.2%, P = 0.062). There were also no relevant differences across groups in the PP analysis; no urosepsis was recorded. In subgroup analysis with stratification by stone area, the three regimens all had a low and similar incidence of SIRS for stones of ≤200 mm2 in the ITT analysis with a sufficient power value (5.4% vs 6.2% vs 3.6%, P = 0.945 vs single dose and P = 0.553 vs two doses). However, there was a greater chance of SIRS in patients who received no ABP with stones of >200 mm2 (18% vs single dose 4.3%, P = 0.036; vs two doses 5.5%, P = 0.044). Similar trends were seen in the PP analysis.

Conclusions

For patients with preoperative sterile urine, ABP is not strongly recommended in patients with stones of ≤200 mm2, but for stones >200 mm2 single‐dose ABP is still required.
Temporal variation in the influence of forest succession on caterpillar communities: A long‐term study in a tropical dry forest
Authors: Boege Karina , Villa‐Galaviz Edith , López‐Carretero Antonio , Pérez‐Ishiwara Rubén , Zaldivar‐Riverón Alejandro , Ibarra Adolfo , del‐Val Ek
Published: May 2019

Forest succession can influence herbivore communities through changes in host availability, plant quality, microclimate, canopy structure complexity and predator abundance. It is not well known, however, if such influence is constant across years. Caterpillars have been reported to be particularly susceptible to changes in plant community composition across forest succession, as most species are specialists and rely on the presence of their hosts. Nevertheless, in the case of tropical dry forests, plant species have less defined successional boundaries than tropical wet forests, and hence herbivore communities should be able to persist across different successional stages. To test this prediction, caterpillar communities were surveyed during eight consecutive years in a tropical dry forest in four replicated successional stages in Chamela, Jalisco and Mexico. Lepidopteran species richness and diversity were equivalent in mature forests and early successional stages, but a distinctive caterpillar community was found for the recently abandoned pastures. Species composition tended to converge among all four successional stages during the span of eight years. Overall, our results highlight the importance of both primary and secondary forest for the conservation of caterpillar biodiversity at a landscape level. We also highlight the relevance of long‐term studies when assessing the influence of forest succession to account for across year variation in species interactions and climatic factors.

Abstract in French is available with online material.
Impact of climatic and hydrological disturbances on blackwater floodplain forests in Central Amazonia
Authors: Rocha Duarte Neves Juliana , Fernandez Piedade Maria Teresa , Faria de Resende Angélica , Oliveira Feitosa Yuri , Schöngart Jochen
Published: May 2019

Extreme climatic events and anthropic disturbances affect the hydrological regime of Amazonian rivers and connected floodplain forests. This study aims to investigate the impacts of the Balbina hydroelectric power plant on the floodplain forests of the Uatumã River, in the Central Amazon. For this, tree age and diameter increment from the most abundant tree species of three different topographic levels were obtained and analyzed in the affected area downstream of the Balbina dam (Uatumã River) and compared to an undisturbed site (Abacate River, affluent) considering age structure and mean diameter increments between the topographic levels and the two systems. The occurrence of old trees is much lower at the disturbed site compared to the undisturbed system. Especially at the middle topography of the Uatumã site, we observed tree species with high mean diameter increment indicating a strong disturbance. We suggest that the disturbances may be associated with extreme hydro‐climatic events, such as extreme droughts that occurred during the El Niño years 1925/26 and 1982/83 and that these events may increase vulnerability of igapó floodplains to wildfires.

Abstract in Portuguese is available with online material.
Bone loss around oral and orthopedic implants: An immunologically based condition
Authors: Albrektsson Tomas , Becker William , Coli Pierluigi , Jemt Torsten , Mölne Johan , Sennerby Lars
Published: May 2019

Background

Marginal bone resorption has by some been identified as a “disease” whereas in reality it generally represents a condition.

Purpose

The present article is a comparison between oral and orthopedic implants, as previously preferred comparisons between oral implants and teeth seem meaningless.

Materials and Methods

The article is a narrative review on reasons for marginal bone loss.

Results and Conclusions

The pathology of an oral implant is as little related to a tooth as is pathology of a hip arthroplasty to a normally functioning, pristine hip joint. Oral as well as orthopedic implants are recognized as foreign bodies by the immune system and bone is formed, either in contact or distance osteogenesis, to shield off the foreign materials from remaining tissues. A mild immune reaction coupled to a chronic state of inflammation around the implant serve to protect implants from bacterial attacks. Having said this, an overreaction of the immune system may lead to clinical problems. Marginal bone loss around oral and orthopedic implants is generally not dependent on disease, but represents an immunologically driven rejection mechanism that, if continuous, will threaten implant survival. The immune system may be activated by various combined patient and clinical factors or, if rarely, by microbes. However, the great majority of cases with marginal bone loss represents a temporary immune overreaction only and will not lead to implant failure due to various defense mechanisms.
Long‐term evaluation of sound localisation in single‐sided deaf adults fitted with a BAHA device
Authors: Bonne Nicolas‐Xavier , Hanson Jean‐Noël , Gauvrit Fanny , Risoud Michaël , Vincent Christophe
Published: May 2019

Objective

To perform a long‐term evaluation of the localisation capabilities in the horizontal plane of single‐sided deaf patients fitted with a BAHA device.

Design

Single‐centre retrospective study.

Participants

Twenty‐one adults with single‐sided deafness (SSD) with normal hearing in the contralateral ear (pure tone average <20 dB, SDS > 90%) rehabilitated with a Cochlear BAHA device from 2003 to 2012 on the deaf side over a median follow‐up of 8 years.

Outcome measures

The task used in this paper is a sound localisation identification task with a set‐up of seven loudspeakers on a semi‐circular array at 30‐degree intervals performed at three periods: before BAHA, initially and at last follow‐up. Our main criterion of judgement was the root‐mean‐square (RMS) localisation error. In addition, the Bern Benefit in Single‐Sided Deafness Questionnaire (BBSS) was administered.

Results

The mean RMS localisation error was initially estimated at 64° without any rehabilitation (for a chance level RMS estimated at 81°). Initially, with the BAHA device, the RMS localisation error dropped to 51°. At the last follow‐up evaluation, a significant decrease at 23° was noted. Concerning the Bern Questionnaire, 19% of the patients (n = 4) did not report any change (score of 0), 33% (n = 7) are satisfied (score of +1 or +2) and 48% (n = 10) are very satisfied with the BAHA device (score better than +3).

Conclusion

Improvement of sound localisation in the horizontal plane for some SSD patients is likely related to altered processing of monaural spectral cues. The time needed to learn to use the azimuth‐dependent spectral cues takes time. Long‐term follow‐up should be considered for studies investigating sound localisation performance.
Effects of land use, cover, and protection on stream and riparian ecosystem services and biodiversity
Authors: Hanna Dalal E.L. , Raudsepp‐Hearne Ciara , Bennett Elena M.
Published: May 2019

Protected areas are an important part of broader landscapes that are often used to preserve biodiversity or natural features. Some argue that protected areas may also help ensure provision of ecosystem services. However, the effect of protection on ecosystem services and whether protection affects the provision of ecosystem services is known only for a few services in a few types of landscapes. We sought to fill this gap by investigating the effect of watershed protection status and land use and land cover on biodiversity and the provision of ecosystem services. We compared the ecosystem services provided in and around streams in 4 watershed types: International Union for Conservation of Nature category II protected forests, unprotected forests, unprotected forests with recent timber harvesting, and unprotected areas with agriculture. We surveyed 28 streams distributed across these watershed types in Quebec, Canada, to quantify provisioning of clean water, carbon storage, recreation, wild foods, habitat quality, and terrestrial and aquatic biodiversity richness and abundance. The quantity and quality of ecosystem services and biodiversity were generally higher in sites with intact forest—whether protected or not—relative to those embedded in production landscapes with forestry or agriculture. Clean‐water provision, carbon storage, habitat quality, and tree diversity were significantly higher in and around streams surrounded by forest. Recreation, wild foods, and aquatic biodiversity did not vary among watershed types. Although some services can be provided by both protected and unprotected areas, protection status may help secure the continued supply of services sensitive to changes in land use or land cover. Our findings provide needed information about the ecosystem service and biodiversity trade‐offs and synergies that result from developing a watershed or from protecting it.
Renal outcome after simultaneous heart and kidney transplantation
Authors: Toinet Théodore , Dominique Inès , Cholley Irène , Vanalderwerelt Victor , Goujon Anna , Paret Fanny , Bessede Thomas , Delaporte Véronique , Salomon Laurent , Badet Lionel , Boutin Jean‐Michel , Verhoest Gregory , Branchereau Julien , Timsit Marc‐Olivier ,   Renal Transplantation Committee of the French Urological Association (CTAFU)
Published: May 2019

Simultaneous heart‐kidney transplant (HKTx) is a valid treatment for patients with coexisting heart and renal failure. The aim of this study was to assess renal outcome in HKTx and to identify predictive factors for renal loss. A retrospective study was conducted among 73 HKTx recipients: Donors’ and recipients' records were reviewed to evaluate patients’ and renal transplants’ survival and their prognostic factors. The mean follow‐up was 5.36 years. Renal primary non‐function occurred in 2.7%, and complications Clavien IIIb or higher were observed in 67.1% including 16 (22%) postoperative deaths. Five‐year overall survival and renal survival were 74.5% and 69.4%. Among survivors, seven returned to dialysis during follow‐up. The postoperative use of ECMO (HR = 6.04, P = 0.006), dialysis (HR = 1.04/day, P = 0.022), and occurrence of complications (HR = 31.79, P = 0.022) were independent predictors of postoperative mortality but not the history of previous HTx or KTx nor renal function prior to transplantation. History of KTx (HR = 2.52, P = 0.026) and increased delay between the two transplantations (HR = 1.25/hour, P = 0.018) were associated with renal transplant failure. HKTx provides good renal transplant survival and function, among survivors. Early mortality rate of 22% underlines the need to identify perioperative risk factors that would lead to more judicious and responsible allocation of a scarce resource.
Use of sensor‐integrated pump therapy to reduce hypoglycaemia in people with Type 1 diabetes: a real‐world study in the UK
Authors: Choudhary P. , de Portu S. , Arrieta A. , Castañeda J. , Campbell F. M.
Published: May 2019

Aims

To assess the efficacy of insulin pumps with automated insulin suspension systems in a real‐world setting.

Methods

We analysed anonymized data uploaded to CareLink™ by people (n=920) with Type 1 diabetes using the MiniMed Paradigm Veo system and the MiniMed 640G system (Medtronic International Trading Sàrl, Tolochanez, Switzerland) with SmartGuard technology, with or without automated insulin suspension enabled, between February 2016 and June 2018. Users with ≥15 days of sensor data and ≥70% sensor‐wear time were classified as sensor‐augmented pump alone, sensor‐integrated pump with low glucose suspend enabled or sensor‐integrated pump with predictive low glucose management enabled.

Results

The median (25th–75th percentile) system use was 161 (58–348) days. The median time spent with sensor glucose values ≤3 mmol/l was 0.8 (0.3–1.7)% in the sensor‐augmented pump group, 0.3 (0.1–0.7)% in the sensor‐integrated pump with low glucose suspend group, and 0.3 (0.1–0.5)% in the sensor‐integrated pump with predictive low glucose management group. In individuals switching from sensor‐augmented pump to sensor‐integrated pump with low glucose suspend (n=31), there were significant reductions in the monthly rate of hypoglycaemic events <3 mmol/l (rate ratio 0.63, 95% CI 0.45–0.89; P=0.009) and in the percentage of time with glucose values ≤3 mmol/l [sensor‐augmented pump: 0.63% (95% CI 0.34–1.29), sensor‐integrated pump with low glucose suspend: 0.33% (95% CI 0.16–0.64); P=0.001]. The monthly rate of hypoglycaemic events decreased further in individuals (n=139) switching from sensor‐integrated pump with low glucose suspend to sensor‐integrated pump with predictive low glucose management [rate ratio 0.82 (95% CI 0.69–0.98); P<0.0274]. Similar results were seen for events <3.9 mmol/l. There was no difference in median time spent in target glucose range.

Conclusion

Real‐world UK data show that increasing automation of insulin suspension reduces hypoglycaemia exposure in people with Type 1 diabetes.
Understanding of interaction (subgroup) analysis in clinical trials
Authors: Brankovic Milos , Kardys Isabella , Steyerberg Ewout W. , Lemeshow Stanley , Markovic Maja , Rizopoulos Dimitris , Boersma Eric
Published: May 2019

Background

When the treatment effect on the outcome of interest is influenced by a baseline/demographic factor, investigators say that an interaction is present. In randomized clinical trials (RCTs), this type of analysis is typically referred to as subgroup analysis. Although interaction (or subgroup) analyses are usually stated as a secondary study objective, it is not uncommon that these results lead to changes in treatment protocols or even modify public health policies. Nonetheless, recent reviews have indicated that their proper assessment, interpretation and reporting remain challenging.

Results

Therefore, this article provides an overview of these challenges, to help investigators find the best strategy for application of interaction analyses on binary outcomes in RCTs. Specifically, we discuss the key points of formal interaction testing, including the estimation of both additive and multiplicative interaction effects. We also provide recommendations that, if adhered to, could increase the clarity and the completeness of reports of RCTs.

Conclusion

Altogether, this article provides a brief non‐statistical guide for clinical investigators on how to perform, interpret and report interaction (subgroup) analyses in RCTs.
Winning and losing with microbes: how microbially mediated fitness differences influence plant diversity
Authors: Kandlikar Gaurav S. , Johnson Christopher A. , Yan Xinyi , Kraft Nathan J. B. , Levine Jonathan M.
Published: May 2019

Interactions between plants and soil microbes can strongly influence plant diversity and community dynamics. Soil microbes may promote plant diversity by driving negative frequency‐dependent plant population dynamics, or may favor species exclusion by providing one species an average fitness advantage over others. However, past empirical research has focused overwhelmingly on the consequences of frequency‐dependent feedbacks for plant species coexistence and has generally neglected the consequences of microbially mediated average fitness differences. Here we use theory to develop metrics that quantify microbially mediated plant fitness differences, and show that accounting for these effects can profoundly change our understanding of how microbes influence plant diversity. We show that soil microbes can generate fitness differences that favour plant species exclusion when they disproportionately harm (or favour) one plant species over another, but these fitness differences may also favor coexistence if they trade off with competition for other resources or generate intransitive dominance hierarchies among plants. We also show how the metrics we present can quantify microbially mediated fitness differences in empirical studies, and explore how microbial control over coexistence varies along productivity gradients. In all, our analysis provides a more complete theoretical foundation for understanding how plant–microbe interactions influence plant diversity.
Experimental dominant plant removal results in contrasting assembly for dominant and non‐dominant plants
Authors: Arnillas Carlos Alberto , Cadotte Marc W.
Published: May 2019

Understanding why communities appear deterministically dominated by relatively few species is an age‐old debate in ecology. We hypothesised that the dominant and non‐dominant species in a community are governed by different assembly mechanisms where environmental conditions influence dominant species more than non‐dominant species. Further, dominant plants moderate the environment where non‐dominant species thrive, diminishing the influence of environmental filtering and increasing the influence of limiting similarity for non‐dominant species. We tested these hypotheses by removing two dominant species in five temperate meadows. We found that the composition of the non‐dominants diverged while the new dominants converged over time. Phylogenetic analyses suggested that habitat filtering and limiting similarity drove the new dominant species simultaneously. Conversely, non‐dominant community assembly appeared more unpredictable. These suggest that dominant species converged towards a predictable environmentally driven optimum, while non‐dominant species thrive in a moderated habitat, which probably reduced non‐dominant species predictability.
A pericyte‐glia scarring develops at the leaky capillaries in the hippocampus during seizure activity
Authors: Klement Wendy , Blaquiere Marine , Zub Emma , deBock Frederic , Boux Fabien , Barbier Emmanuel , Audinat Etienne , Lerner‐Natoli Mireille , Marchi Nicola
Published: May 2019

Objective

Inflammatory cerebrovascular damage occurs in epilepsy. Here, we tested the hypothesis that a pericyte‐glia scar forms around the outer wall of hippocampal capillaries in a model of temporal lobe epilepsy associated with hippocampal sclerosis. We studied the participation of stromal cells expressing platelet‐derived growth factor receptor beta (PDGFRβ) and extracellular matrix modifications to the perivascular scar during epileptogenesis.

Methods

We used NG2DsRed/C57BL6 mice and induced status epilepticus (SE) followed by epileptogenesis and spontaneous recurrent seizures (SRS) by means of unilateral intrahippocampal injection of kainic acid (KA). For pharmacological assessment, we used organotypic hippocampal cultures (OHCs) where ictal electrographic activity was elicited by KA or bicuculline.

Results

NG2DsRed pericytes, GFAP astroglia, and IBA1 microglia are reactive and converge to form a pericapillary multicellular scar in the CA hippocampal regions during epileptogenesis and at SRS. The capillaries are leaky as indicated by fluorescein entering the parenchyma from the peripheral blood. Concomitantly, PDGFRβ transcript and protein levels were significantly increased. Within the regional scar, a fibrotic‐like PDGFRβ mesh developed around the capillaries, peaking at 1 week post‐SE and regressing, but not resolving, at SRS. Abnormal distribution or accumulation of extracellular matrix collagens III/IV occurred in the CA regions during seizure progression. PDGFRβ/DAPI cells were in direct contact with or adjacent to the damaged NG2DsRed pericytes at the capillary interface, consistent with the notion of stromal cell reactivity or fibroblast formation. Inducing electrographic activity in OHCs was sufficient to augment PDGFRβ reactivity around the capillaries. The latter effect was pharmacologically mimicked by treating OHCs with the PDGFRβ agonist PDGF‐BB and it was diminished by the PDGFRβ inhibitor imatinib.

Significance

The reported multicellular activation and scar are traits of perivascular inflammation and hippocampal sclerosis in experimental epilepsy, with an implication for neurovascular dysfunction. Modulation of PDGFRβ could be exploited to target inflammation in this chronic disease setting.
Stress state and stress‐induced microstructural evolution around the crack tip of G115 steel after dwell‐fatigue crack propagation
Authors: Tang Zhengxin , Jing Hongyang , Xu Lianyong , Zhao Lei , Han Yongdian , Xiao Bo , Zhang Yu , Li Haizhou , Wu Dongquan
Published: May 2019

Many components operate under creep‐fatigue loading causing an increasing need to learn the knowledge about creep‐fatigue crack growth (CFCG). The stress and microstructural evolution around the crack tip of G115 steel after CFCG were investigated. According to the finite element simulations, the variations of equivalent stress and stress triaxiality in the crack tip zone are presented. Furthermore, the evolutions of martensitic laths, dislocations, and precipitates were systematically studied through electron backscatter diffraction and transmission electron microscopy observations. The laths at the crack tip or under a larger hold time are wider than those remote from the crack tip or under a shorter dwell time. Meanwhile, the dislocation densities reduced significantly at the crack tip or under a larger hold time. The different variations of laths' width and dislocation densities resulted from the different stress triaxiality and creep strain. W‐rich Laves and Cu‐rich phases appeared during CFCG. The Laves phase coarsened rapidly because of the stress‐accelerated diffusion.
Drones detect illegal and derelict crab traps in a shallow water estuary
Authors: Bloom Daniel , Butcher Paul A. , Colefax Andrew P. , Provost Euan J. , Cullis Brian R. , Kelaher Brendan P.
Published: May 2019

The issues surrounding illegal, unregulated and unreported fishing, and that of abandoned, lost and discarded fishing gears, leading to ghost fishing, are intensifying. Estuarine crab trapping is likely subject to high levels of illegal and potential ghost fishing, because it also has good economic incentives regarding potential catch, low gear acquisition costs and accessible fishing grounds. To improve the efficiency and effectiveness of fisheries monitoring, control and surveillance operations, the efficacy of small consumer‐grade drones for sighting traps in an estuary in NSW, Australia, was tested. Twelve sets of two flights were undertaken at 20 and 30 m altitude over a 600‐m stretch of estuary for 5 days to quantify the detectability of submerged mesh traps of three different mesh colours. The drone was able to detect the majority of traps efficiently, with depth in relation to water clarity being the main factor affecting detection. In shallow water, detection rates were high for all mesh colours, but in the slightly deeper placements, orange traps were more readily detected. This study demonstrates that drones could be an efficient and reliable tool for rapidly assessing areas for illegal and derelict traps and can be supplemented into land or vessel‐based fisheries operations.
Variation in rate of phenological development and morphology between red clover varieties: Implications for clover proportion and feed quality in mixed swards
Authors: Nadeem Shahid , Steinshamn Håvard , Sikkeland Elin Halvorsen , Gustavsson Anne‐Maj , Bakken Anne Kjersti
Published: May 2019

Red clover (Trifolium pratense) grown in mixtures with grasses often constitutes a lower proportion of total yield in spring than in summer growth. A more even red clover proportion between the harvests would benefit forage quality and management at feeding. We investigated whether inclusion of early versus late‐maturing red clover varieties could reduce this disproportionality. In a two‐year field trial harvested three times per season, each of six red clover varieties was grown in two grass mixtures. Rate of phenological development did not differ during spring growth, but did so in regrowth after first and second cuts. Here, the earliest varieties constituted the highest proportion. At all harvests, the early varieties had lower crude protein concentrations and a higher content of neutral detergent fibre (NDF) and indigestible NDF than the late varieties. Clover proportion was higher in swards with a mixture of timothy and meadow fescue than in swards with perennial ryegrass during the first year and lower in the second year. It is concluded that developmental rate should be explored further as a key character for red clover competiveness in spring growth of rapidly elongating grasses.
Community responses on effective flood dissemination warnings—A case study of the December 2014 Kelantan Flood, Malaysia
Authors: Alias Nor Eliza , Salim Nurul Atika , Taib Shazwin Mat , Mohd Yusof Mohd Badruddin , Saari Radzuan , Adli Ramli Muhammad Wafiy , Othman Ilya K. , Annammala Kogila V. , Yusof Halimah M. , Ismail Norazlina , Yuzir Ali , Blenkinsop Stephen
Published: May 2019

Early flood warnings are important to allow sufficient time for evacuation. Although warning systems are now in place, key questions remain as to their effectiveness in sending information to the public, which may in part depend on the media used. This paper assesses the effectiveness of warnings disseminated to the public for the December 2014 Kelantan Flood, Malaysia. The flood was the worst in decades making it an appropriate case study with which to assess public awareness and perceptions associated with flood warnings and their dissemination. The effectiveness of warnings issued via different media was assessed by questionnaire. Results show that 56% of respondents received warnings prior to the flood, a majority of them through television and information shared among the public. While the preferred medium of warning is not dependent on age, assessment of peoples' response to warnings shows that with increasing age responsiveness to orders and readiness to evacuate decreases. To increase the number of people receiving the warnings, short message service (SMS) communications sent from the authorities to a wider audience may be considered, as information shared among the public is observed to be most effective in reaching the greatest number of people.
Physical Performance in Memory Clinic Patients: The Potential Role of the White Matter Network
Authors: Verwer Jurre H. , Reijmer Yael D. , Koek Huiberdina L. , Biessels Geert Jan ,   On Behalf of the Utrecht Vascular Cognitive Impairment (VCI) Study Group
Published: May 2019

BACKGROUND/OBJECTIVES

Memory clinic patients commonly also have declined physical performance. This may be attributable to white matter injury, due to vascular damage or neurodegeneration. Quantifying white matter injury is made possible by new magnetic resonance imaging (MRI) techniques, including diffusion‐weighted imaging (DWI) of network connectivity. We investigated whether physical performance in memory clinic patients is related to white matter network connectivity.

DESIGN

Observational cross‐sectional study.

SETTING

Memory clinic.

PARTICIPANTS

Patients referred to a memory clinic with vascular brain injury on MRI (n = 90; average age = 72 years; 60% male; 34% with diagnosis Alzheimer disease).

MEASUREMENTS

We reconstructed structural brain networks from DWI with fiber tractography and used graph theory to calculate global efficiency, fractional anisotropy (FA), and mean diffusivity (MD) of the white matter, and nodal strength (mean FA or MD of all white matter tracts connected to a node). Assessment of physical performance included gait speed, chair stand time, and Short Physical Performance Battery (SPPB) score.

RESULTS

Lower global efficiency, lower FA, and higher MD correlated with poorer gait speed, SPPB scores, and chair stand times (R range = 0.23‐0.42). Global efficiency and FA explained 5% to 16% of the variance in gait speed, chair stand times, and SPPB scores, independent of age and sex. Moreover, global efficiency and FA explained an additional 4% to 5% of variance on top of lacunar infarcts and white matter hyperintensities. Regional analyses showed that, in particular, the connectivity strength of prefrontal, occipital, striatal, and thalamic nodes correlated with gait speed.

CONCLUSION

Poorer physical performance is related to disrupted white matter network connectivity in memory clinic patients with vascular brain injury. The associations of these network abnormalities are partially independent of visible vascular injury. J Am Geriatr Soc 67:1880–1887, 2019
Quantitative and qualitative investigation of the stress experiences of intensive care unit patients mechanically ventilated for more than 12 hr
Authors: Takashima Naomi , Yosihno Yasuyo , Sakaki Kosuke
Published: May 2019

Aim

The aim was to qualitatively and quantitatively clarify the stress experiences of patients who were mechanically ventilated in an intensive care unit (ICU) for more than 12 hr.

Methods

The participants were adult patients without cognitive impairment who were mechanically ventilated in a general ICU for more than 12 hr. The Japanese version of the ICU Stressful Experiences Questionnaire (ICU‐SEQJ) survey was performed before subjects were discharged from the ICU to collect narratives about how they felt and what they thought during their ICU stay. The results were analyzed in a collective and complementary way by dividing ICU‐SEQJ scores into quartiles and comparing the first (low stress experience group) and third quartiles (high stress experience group).

Results

A total of 96 subjects were enrolled in the study, with 25 scoring in the high stress experience group and 24 in the low stress experience group. The high stress experience group had significantly longer duration of intubation, higher amounts of analgesics and sedative drugs, higher C‐reactive protein, lower level of deepest sedation and greater absence of medical history than the low stress experience group. Analysis of the subjects’ narratives revealed “Unbearable holistic discomfort”, “Pain of being unable to control myself as before” in the high stress experience group and “Responding by giving meaning” in the low stress experience group.

Conclusions

Nurses must recognize that long intubation hours and invasive procedures are subjective stress experiences that may cause patients to suffer holistic discomfort and lose their sense of control.
Real Estate Prices and Corporate Investment: Theory and Evidence of Heterogeneous Effects across Firms
Authors: FOUGÈRE DENIS , LECAT RÉMY , RAY SIMON
Published: May 2019

In this paper, we investigate the effect of real estate prices on productive investment. We build a theoretical framework of firms' investment with credit rationing and real estate collateral. We show that real estate prices affect firms' borrowing capacities through two channels. An increase in real estate prices raises the value of the firms' pledgeable assets and mitigates the agency problem characterizing the creditor–entrepreneur relationship. It simultaneously cuts the expected profit due to the increase in the cost of inputs. We test our theoretical predictions using a large French database. We do find heterogeneous effects of real estate prices on productive investment depending on the position of the firms in the sectoral distributions of real estate holdings.
Effects of salt‐loading on supraoptic vasopressin neurones assessed by ClopHensorN chloride imaging
Authors: Balapattabi Kirthikaa , Farmer George E. , Knapp Blayne A. , Little Joel T. , Bachelor Martha , Yuan Joseph P. , Cunningham J. Thomas
Published: May 2019

Salt‐loading (SL) impairs GABAA inhibition of arginine vasopressin (AVP) neurones in the supraoptic nucleus (SON) of the hypothalamus. Based on previous studies, we hypothesised that SL activates tyrosine receptor kinase B (TrkB), down‐regulating the activity of K+/Cl− co‐transporter2 (KCC2) and up‐regulating Na+/K+/Cl− co‐transporter1 (NKCC1). These changes in chloride transport would result in increased [Cl−]i in SON AVP neurones. The study combined virally‐mediated chloride imaging with ClopHensorN with a single‐cell western blot analysis. An adeno‐associated virus with ClopHensorN and a vasopressin promoter (AAV2‐0VP1‐ClopHensorN) was bilaterally injected in the SON of adult male Sprague‐Dawley rats that were either euhydrated (Eu) or salt‐loaded (SL) for 7 days. Acutely dissociated SON neurones expressing ClopHensorN were tested for decreases or increases in [Cl−]i in response to focal application of the GABAA agonist muscimol (100 μmol L‐1). SON AVP neurones from Eu rats showed muscimol‐induced chloride influx (P < 0.05;23/35). SON AVP neurones from SL rats either significantly increased chloride efflux (P < 0.05;27/39) or did not change chloride flux (12/39). The SON AVP neurones that responded to muscimol appeared to be viable and expressed KCC2 and β‐actin. Neurones that did not respond during chloride imaging did not show KCC2 and β‐actin protein expression. The KCC2 antagonist (VU0240551,10 μmol L‐1) significantly blocked the chloride influx in cells from Eu rats but did not affect cells from SL rats. A NKCC1 antagonist (bumetanide,10 μmol L‐1) significantly blocked the chloride efflux in cells from SL rats but had no effect on cells from Eu rats. Blocking NKCC1 using bumetanide had less of an effect on the muscimol‐induced Cl− influx in Eu rat neurones compared to the KCC2 antagonist. The TrkB antagonist (AnA‐12) (50 μmol L‐1) and protein kinase inhibitor (K252a) (100 nmol L‐1) each significantly blocked chloride efflux in SON AVP neurones from SL rats. Salt‐loading increases [Cl−]i in SON AVP neurones via a TrKB‐KCC2‐NKCC1‐dependent mechanism in rats.
Efficacy of bioactive peptides loaded on hyaluronic acid microneedle patches: A monocentric clinical study
Authors: Avcil Muhammet , Akman Gokhan , Klokkers Jens , Jeong Dohyeon , Çelik Ayhan
Published: May 2019

Background

Aging skin is a gradual physiological process associated with functional and structural changes of the skin. Both intrinsic and extrinsic factors influence skin aging by the involvement of multiple pathways. Restoring natural skin conditions requires a multi‐targeted approach. Recent developments in both bioactive peptides and microneedle delivery system have presented an opportunity for tackling premature skin aging.

Aims

This study was aimed at evaluating the dermal tolerability and efficacy of hyaluronic acid‐based microneedle patches loaded with bioactives for restoration of the skin properties including hydration, wrinkle reduction, density, and thickness.

Patients/Methods

The test product of HA‐MNs comprises arginine/lysine polypeptide, acetyl octapeptide‐3, palmitoyl tripeptide‐5, adenosine, and seaweed extracts. In the monocentric 12‐week clinical trial, the HA‐MNs patches were applied to the outer corner of the right and left eye and a defined area on the volar forearm on healthy subjects with aged skin. Instrumental analysis of skin properties was determined.

Results

The product was tolerated excellently; none of the subjects reported any primary or cumulative skin reactions. Assessment of measurable skin properties provides insight into the general effectiveness: The fine lines/wrinkles showed 25.8% noticeable decrease; the skin hydration measurements demonstrated 15.4% improvement; the skin density and thickness in the dermis increased 14.2% and 12.9%, respectively.

Conclusions

The composition of the microneedle patches works in a multi‐targeted manner and all ingredients might possibly be acted synergistically for the improvement of skin structure, function, and appearance. The study has demonstrated the overall usefulness of the HA‐MNs with careful formulation for skin care applications.
Modified laparoscopic cervicoisthmic cerclage in early pregnancy for refractory cervical incompetence: A case report
Authors: Seo Kohei , Dohi Satoshi , Ishikawa Tetsuya , Ichizuka Kiyotake , Sekizawa Akihiko , Nagatsuka Masaaki
Published: May 2019

Modified laparoscopic cerclage was developed as an easy laparoscopic approach during pregnancy, with sutures placed lateral to the uterine vessels. To the best of our knowledge, its successful use in the first trimester has not been reported in Japan. Additionally, there are no published data on chronological assessment of feto‐placental circulation using Doppler. Here, we present the case of a 31‐year‐old Japanese woman (gravida 2, para 1) with refractory cervical incompetence who had a history of preterm birth at 32 weeks of gestation and cervical conization. Modified laparoscopic cervicoisthmic cerclage was performed. Doppler findings showed normal feto‐placental circulation before and after the procedure. Her pregnancy progressed uneventfully with no significant feto‐placental circulation or obstetric complications, and the baby showed normal growth. Elective cesarean section was performed at 37 + 0 weeks’ gestation. Modified laparoscopic cervicoisthmic cerclage is suggested as one of the treatment methods for pregnant women with refractory cervical incompetence.
Studies on patients establish Crohn's disease as a manifestation of impaired innate immunity
Authors: Segal A. W.
Published: May 2019

The fruitless search for the cause of Crohn's disease has been conducted for more than a century. Various theories, including autoimmunity, mycobacterial infection and aberrant response to food and other ingested materials, have been abandoned for lack of robust proof. This review will provide the evidence, obtained from patients with this condition, that the common predisposition to Crohn's is a failure of the acute inflammatory response to tissue damage. This acute inflammation normally attracts large numbers of neutrophil leucocytes which engulf and clear bacteria and autologous debris from the inflamed site. The underlying predisposition in Crohn's disease is unmasked by damage to the bowel mucosa, predominantly through infection, which allows faecal bowel contents access to the vulnerable tissues within. Consequent upon failure of the clearance of these infectious and antigenic intestinal contents, it becomes contained, leading to a chronic granulomatous inflammation, producing cytokine release, local tissue damage and systemic symptoms. Multiple molecular pathologies extending across the whole spectrum of the acute inflammatory and innate immune response lead to the common predisposition in which defective monocyte and macrophage function plays a central role. Family linkage and exome sequencing together with GWAS have identified some of the molecules involved, including receptors, molecules involved in vesicle trafficking, and effector cells. Current therapy is immunosuppressant, which controls the symptoms but accentuates the underlying problem, which can only logically be tackled by correcting the primary lesion/s by gene therapy or genome editing, or through the development of drugs that stimulate innate immunity.