bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed‐type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T‐cell reactivity study
Authors: Lin C.‐y. , Wang C.‐W. , Hui C.‐Y. R. , Chang Y.‐C. , Yang C.‐H. , Cheng C.‐Y. , Chen W.‐W. , Ke W.‐M. , Chung W.‐H.
Published: June 2017

Background

Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed‐type hypersensitivity reactions (DHR) induced by PPI, such as Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI‐related DHR, followed up their tolerability to alternative anti‐ulcer agents, and investigated the T‐cell reactivity to PPI in PPI‐related DHR patients.

Methods

We retrospectively analyzed patients with PPI‐related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross‐hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon‐γ to confirm the causalities.

Results

There were 69 cases of PPI‐related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI‐related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross‐hypersensitivity reactions, whereas three patients developed cross‐hypersensitivity reactions to alternative structurally similar PPI. The cross‐reactivity to structurally similar PPI was also observed in LAT assay.

Conclusions

PPIs have the potential to induce life‐threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.
Immediate moxifloxacin hypersensitivity: Is there more than currently meets the eye?
Authors: Van Gasse A. L. , Sabato V. , Uyttebroek A. P. , Elst J. , Faber M. A. , Hagendorens M. M. , Mertens C. , Bridts C. H. , De Clerck L. S. , Ebo D. G.
Published: June 2017

Immediate drug hypersensitivity reactions (IDHR) to moxifloxacin constitute a pathomechanistic conundrum and a diagnostic challenge. Our objective was to study whether simultaneous phenotyping and quantification of histamine release might add to our knowledge about the basophil activation properties of moxifloxacin and constitute a reliable diagnostic aid. Fifteen patients with an IDHR to moxifloxacin and nine moxifloxacin challenged controls were selected. All had a basophil activation test (BAT) with moxifloxacin. Flow cytometric analysis of basophil responses implied labeling for CD63, CD203c, and intracellular histamine. Unlike tolerant challenged controls, basophilic upregulation of CD203c in response to moxifloxacin was observed in seven of 15 patients. Only two of these seven patients demonstrated appearance of CD63 and release of histamine. In the remainder eight patients, no basophil responses were demonstrable. In conclusion, immediate hypersensitivity to moxifloxacin might involve mechanisms difficult to capture by traditional CD63‐/CD203c‐based BAT. Deciphering the complexity of quinolone IDHR seems mandatory.
Archaeomagnetic Dating of Pyrotechnological Contexts: a Case Study for Copper Smelting Sites in the Central Timna Valley, Israel
Authors: Peters I. , Tauxe L. , Ben‐Yosef E.
Published: June 2017

This study is focused on establishing age constraints for several copper slag deposits at the centre of the Timna Valley (Israel) via reconstruction of their ancient geomagnetic intensities as recorded by the individual slag samples at the time of their formation. The results show a correlation between the location of the slag deposits (labelled as individual ‘mounds’ in our survey) and their inferred ages, reflecting varying socio‐economic and political dynamics in the region. While the slag mounds found at the unprotected foothills represent a variety of dates (mostly Early Islamic), the slag mounds on the hilltops are chronologically constrained to the early Iron Age (late 11th to 10th centuries bce), supporting the idea for a need for protection during this period. Furthermore, in comparing the new data with previous archaeomagnetic studies from Timna, we can assert the existence of simultaneous copper production at the archaeological Sites 30, 30a and 34. This gives further support to the claim of intense smelting in the central Timna Valley during the early Iron Age. Finally, this project demonstrates the potential of archaeomagnetic experiments to provide chronological insights, and their particular advantage in addressing pyrotechnology‐related cases.
Dependence at a distance: Labour mobility and the evolution of the single industry town
Authors: Storey Keith , Hall Heather
Published: June 2017

Key Messages

Commute work has created a new settlement phenomenon—resource dependent‐at‐a‐distance communities.

As with traditional single industry towns, dependent‐at‐a‐distance communities are vulnerable during resource downturns.

New policies are required to address the problems faced by dependent‐at‐a‐distance communities.
Modelling the sectoral allocation of labour in open economy models
Authors: Povoledo Laura
Published: June 2017

Indivisible labour is not the only type of non‐convexity affecting labour supply decisions. Another type of non‐convexity arises in economies with sectors whenever individuals can work in only one sector at a time. I introduce this restriction into an open economy model with a tradeable and a non‐tradeable sector, and I use lotteries to convexify the consumption possibilities set. This approach implies that the aggregate elasticity of labour supply becomes infinite. I compare the performance of the model with an analogous model in which the labour supply elasticity is finite. I find that there is a disconnect between the response of wages to monetary shocks and the open economy variables. The labour supply elasticity plays a more important role in the transmission of technology and government expenditure shocks to the real exchange rate and the terms of trade.
Greater physical activity and higher androgen concentrations are independently associated with lower cardiometabolic risk in men
Authors: Chasland Lauren C. , Knuiman Matthew W. , Divitini Mark L. , Chan Yi X. , Handelsman David J. , Naylor Louise H. , Green Daniel J. , Yeap Bu B.
Published: June 2017

Context

Male ageing is associated with lower circulating testosterone (T) and increased incidence of cardiovascular disease (CVD). Whether physical activity (PA) interacts with hormones to modify CVD risk is unclear.

Objective

We assessed whether PA and sex hormone concentrations were independently associated with measures of CVD risk.

Participants

A total of 1649 men.

Methods

Leisure, home, work and total PA were ascertained. At baseline, serum T, dihydrotestosterone (DHT) and oestradiol (E2) were assayed. Men were stratified into high PA+high hormone (H/H); low PA+high hormone (L/H); high PA+low hormone (H/L); and low PA+low hormone (L/L).

Results

Mean age was 49.8 years at outset with 415 CVD events and 127 CVD deaths occurring during 20‐year follow‐up. Men with higher PA and higher T or DHT had lower odds of metabolic syndrome (eg leisure H/H vs L/L odds ratio [OR] 0.17 P<.001 for T, 0.26 P<.001 for DHT). Men with higher PA and E2 had lower risk of metabolic syndrome (eg leisure PA H/H vs L/L OR 0.51, P=.001). Men with higher leisure, work or total PA and higher DHT had the lowest risk of CVD death (eg leisure H/H hazard ratio [HR] 0.55 vs L/L, P=.033). Men with lower leisure, home or work PA and higher E2 were at greater risk of CVD death (eg leisure L/H HR 1.60 vs L/L, P=.039).

Conclusions

Considering T, DHT and E2 in the context of PA better informs consideration of cardiovascular risk. A 2×2 factorial RCT assessing PA and androgens would illuminate the scope for preventing CVD in men.
The relationship between adiposity, bone density and microarchitecture is maintained in young women irrespective of diabetes status
Authors: Abdalrahaman N. , McComb C. , Foster J.E. , Lindsay R.S. , Drummond R. , McKay G.A. , Perry C.G. , Ahmed S.F.
Published: June 2017

Background

The relationship between bone health and adiposity and how it may be affected in people with chronic metabolic conditions is complex.

Methods

Seventeen women with type 1 diabetes mellitus (T1DM) and nine age‐matched healthy women with a median age of 22.6 years (range, 17.4, 23.8) were studied by 3T MRI and MR spectroscopy to assess abdominal adiposity, tibial bone microarchitecture and vertebral bone marrow adiposity (BMA). Additional measures included DXA‐based assessments of total body (TB), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and fat mass (FM).

Results

Although women with T1DM had similar BMI and BMA to the controls, they had higher visceral and subcutaneous adiposity on MRI (P<.05) and total body FM by DXA (P=.03). Overall, in the whole cohort, a clear inverse association was evident between BMA and BMD at all sites (P<.05). These associations remained significant after adjusting for age, BMI, FM and abdominal adiposity. In addition, visceral adiposity, but not subcutaneous adiposity, showed a positive association with BMA (r, .4, P=.03), and a negative association with total body BMD (r, .5, P=.02). Apparent trabecular separation as assessed by MRI showed an inverse association to total body BMD by DXA (r, −.4, P=.04).

Conclusion

Irrespective of the presence of an underlying metabolic condition, young women display a negative relationship between MRI‐measured BMA and DXA‐based assessment of BMD. Furthermore, an association between BMA and visceral adiposity supports the notion of a common origin of these two fat depots.
Contextualizing case reviews: A methodology for developing systemic safeguarding practices
Authors: Firmin Carlene
Published: June 2017

This paper introduces a systemic methodology for reviewing professional responses to abuse between young people. The approach, “contextual case reviewing,” draws upon constructivist structuralism to assess the extent to which safeguarding practices engage with the social and public contexts of abuse. The paper conceptually compares the methodologies of contextual case review and other serious case review methods before drawing upon findings from 2 studies, which used the contextual case review methodology to explore the extrafamilial nature of peer‐on‐peer abuse and the ability of child protection practices to engage with this dynamic. Thematic findings from these studies regarding the practical interpretation of “significant harm” and “capacity to safeguard,” as well as their use within child protection assessments, are used to challenge conclusions of other case reviews, which imply that child protection procedures are sufficient for safeguarding young people. Contextual case reviews suggest that safeguarding practices, and the legislation that underpins them, are culturally, procedurally, and organisationally wedded to the context of the home, whereas insufficiently engaged with extrafamilial contexts of significant harm. The application of these issues require interrogation if social work systems are to provide sufficient mechanisms for safeguarding young people and families at risk of significant harm.
A novel PAX1 null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency
Authors: Paganini I. , Sestini R. , Capone G.L. , Putignano A.L. , Contini E. , Giotti I. , Gensini F. , Marozza A. , Barilaro A. , Porfirio B. , Papi L.
Published: June 2017

Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial anomalies, cup‐shaped low‐set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies, and mild intellectual disability. Autosomal dominant cases are caused by deletions or point mutations of EYA1. A single family with an autosomal recessive form of OFCS and a homozygous missense mutation in PAX1 gene has been described.

We report whole exome sequencing of 4 members of a consanguineous family in which 2 children, showing features of OFCS, expired from severe combined immunodeficiency (SCID). To date, the co‐occurrence of OFCS and SCID has never been reported. We found a nonsense homozygous mutation in PAX1 gene in the 2 affected children. In mice, Pax1 is required for the formation of specific skeletal structures as well as for the development of a fully functional thymus. The mouse model strongly supports the hypothesis that PAX1 depletion in our patients caused thymus aplasia responsible for SCID.

This report provides evidence that bi‐allelic null PAX1 mutations may lead to a multi‐system autosomal recessive disorders, where SCID might represent the main feature.
Peridynamics‐Based Fracture Animation for Elastoplastic Solids
Authors: Chen Wei , Zhu Fei , Zhao Jing , Li Sheng , Wang Guoping
Published: June 2017

In this paper, we exploit the use of peridynamics theory for graphical animation of material deformation and fracture. We present a new meshless framework for elastoplastic constitutive modelling that contrasts with previous approaches in graphics. Our peridynamics‐based elastoplasticity model represents deformation behaviours of materials with high realism. We validate the model by varying the material properties and performing comparisons with finite element method (FEM) simulations. The integral‐based nature of peridynamics makes it trivial to model material discontinuities, which outweighs differential‐based methods in both accuracy and ease of implementation. We propose a simple strategy to model fracture in the setting of peridynamics discretization. We demonstrate that the fracture criterion combined with our elastoplasticity model could realistically produce ductile fracture as well as brittle fracture. Our work is the first application of peridynamics in graphics that could create a wide range of material phenomena including elasticity, plasticity, and fracture. The complete framework provides an attractive alternative to existing methods for producing modern visual effects.
Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial
Authors: Bajestan Mona N. , Rajan Archana , Edwards Sean P. , Aronovich Sharon , Cevidanes Lucia H. S. , Polymeri Angeliki , Travan Suncica , Kaigler Darnell
Published: June 2017

Background

Stem cell therapy with bone marrow‐derived mesenchymal stem cells is a promising tissue engineering strategy to promote regeneration of craniofacial bone.

Purpose

To determine whether cell therapy with ex vivo expanded stem cell populations would be safe and efficacious in the regeneration of large alveolar defects in patients with a history of cleft palate or craniofacial trauma.

Materials and Methods

Eighteen patients (10 patients with traumatic injury and 8 patients with cleft palate) presenting with missing teeth associated with horizontal alveolar bone deficiencies were included in this randomized controlled clinical trial. Patients were randomized to receive either conventional autogenous block grafts or stem cell therapy. After a healing period of 4 months the treated sites were re‐entered and the bone width re‐assessed prior to implant placement. Implant stability was evaluated through torque testing of the implant upon insertion and at 6 months postloading.

Results

The mean gain in bone width was 1.5 ± 1.5 mm in the stem cell therapy group and 3.3 ± 1.4 mm in the control group. Overall, bone gain was higher in trauma patients as compared to patients with cleft palate, for both the control and the stem cell therapy groups. Most postoperative complications were wound dehiscences and incision line openings. Implants were placed successfully in 5 out of 10 patients in the stem cell therapy group and in all 8 patients in the control group. One implant from the control/cleft palate group failed before loading, while the rest of the implants were loaded successfully and remained stable at 6 months. The patients who did not receive implants were re‐treated with autogenous block bone graft.

Conclusion

The ability of stem cells to treat large alveolar defects is safe, yet, their ability to completely reconstitute large alveolar defects is limited. This approach requires further optimization to meet the outcomes seen using current methods to treat large defects, particularly those resultant of cleft palate.
Monitoring, imperfect detection, and risk optimization of a Tasmanian devil insurance population
Authors: Rout Tracy M. , Baker Christopher M. , Huxtable Stewart , Wintle Brendan A.
Published: June 2017

Most species are imperfectly detected during biological surveys, which creates uncertainty around their abundance or presence at a given location. Decision makers managing threatened or pest species are regularly faced with this uncertainty. Wildlife diseases can drive species to extinction; thus, managing species with disease is an important part of conservation. Devil facial tumor disease (DFTD) is one such disease that led to the listing of the Tasmanian devil (Sarcophilus harrisii) as endangered. Managers aim to maintain devils in the wild by establishing disease‐free insurance populations at isolated sites. Often a resident DFTD‐affected population must first be removed. In a successful collaboration between decision scientists and wildlife managers, we used an accessible population model to inform monitoring decisions and facilitate the establishment of an insurance population of devils on Forestier Peninsula. We used a Bayesian catch‐effort model to estimate population size of a diseased population from removal and camera trap data. We also analyzed the costs and benefits of declaring the area disease‐free prior to reintroduction and establishment of a healthy insurance population. After the monitoring session in May–June 2015, the probability that all devils had been successfully removed was close to 1, even when we accounted for a possible introduction of a devil to the site. Given this high probability and the baseline cost of declaring population absence prematurely, we found it was not cost‐effective to carry out any additional monitoring before introducing the insurance population. Considering these results within the broader context of Tasmanian devil management, managers ultimately decided to implement an additional monitoring session before the introduction. This was a conservative decision that accounted for uncertainty in model estimates and for the broader nonmonetary costs of mistakenly declaring the area disease‐free.
Postoperative outcomes and management strategies for coronary artery disease in patients in need of a lung transplantation
Authors: Khandhar Sameer J. , Althouse Andrew D. , Mulukutla Suresh , Kormos Robert , Toma Catalin , Marroquin Oscar , Volz Elizabeth , Tefera Leben , Bermudez Christian
Published: June 2017

Background

Patients requiring lung transplantation (LTx) may also have coronary artery disease (CAD). The peri‐operative management and long‐term outcomes of these patients are not well established.

Methods

Patients referred for LTx from 2008 to 2014 were included in this study. CAD was defined by angiography as no CAD (stenosis <20%), moderate CAD (20%‐69%), and significant CAD (stenosis ≥70%). Revascularization was per recommendations of local heart team. Postoperative cardiovascular outcomes and long‐term survival are reported.

Results

A total of 1493 patients were screened for LTx during this period and 656 received a transplant. Of the patients that underwent LTx, 51% had no CAD, 33% had moderate non‐obstructive CAD, and 16% had obstructive CAD. Forty‐three patients underwent revascularization. There was a no increased risk of peri‐operative cardiovascular events or for adjusted mortality for patients with obstructive CAD (HR=1.24, 95% CI: 0.83‐1.86, P=.290) including those requiring revascularization.

Conclusions

There is a high prevalence of coronary disease in the population of patients with advanced lung disease requiring lung transplantation. Careful evaluation and treatment can allow for patients with all severities of CAD including those requiring revascularization to successfully undergo LTx.
The role of biomechanical anatomical modeling via computed tomography for identification of restrictive allograft syndrome
Authors: Horie Miho , Saito Tomohito , Moseley Joanne , D'Errico Luigia , Salazar Pascal , Nakajima Daisuke , Brock Kristy , Yasufuku Kazuhiro , Binnie Matthew , Keshavjee Shaf , Paul Narinder
Published: June 2017

Chronic lung allograft dysfunction (CLAD) reduces long‐term graft survival. It is important to distinguish CLAD subtypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) as RAS has a worse prognosis and accurate subtyping could facilitate targeted treatments. However, the current diagnosis of CLAD subtypes is based on pulmonary function test (PFT) results that reflect global estimates of lung function; anatomical modeling based on computed tomography (CT) has the potential to provide detailed analysis of global and regional lung function. The purpose of this study is to evaluate the utility of CT‐based anatomical modeling for the identification of RAS. This retrospective study included 51 patients (CLAD: 17 BOS and 17 RAS, control: 17 No‐CLAD). CT data were assessed using a biomechanical model‐based platform (MORFEUS) to characterize changes in lung deformation between baseline and disease onset. Lung deformation demonstrated high sensitivity and specificity (>80%) in differentiating RAS from BOS (P<.0001) and No‐CLAD (P<.0001). There were matching radiological reading and inward deformation abnormalities in 79% of lung sections in patients with RAS. Anatomical modeling is complementary to conventional assessment in the diagnosis of RAS and potentially provides quantitative data that can help in the characterization and detailed assessment of heterogeneous lung parenchymal disease.
Differential UBE2C and HOXA1 expression in melanocytic nevi and melanoma
Authors: Kraft Stefan , Moore Johanna B. , Muzikansky Alona , Scott Kenneth L. , Duncan Lyn M.
Published: June 2017

Background

Recent molecular advances suggest that Spitz nevi and other spitzoid neoplasms are biologically distinct from melanoma and conventional nevi. The ubiquitin ligase UBE2C and the homeobox transcription factor HOXA1 are candidate oncogenes in melanoma.

Methods

Using RNA expression analysis and immunohistochemistry, we evaluated these biomarkers in Spitz nevi (n = 20), melanoma (n = 20), and by immunohistochemistry in conventional nevi (n = 20).

Results

RNA analysis with branched DNA multiplex assay identified upregulation of UBE2C in melanomas vs Spitz nevi (P = .003), whereas HOXA1 was downregulated in melanoma (P < .0001). Immunohistochemical analysis confirmed increased nuclear expression of UBE2C in melanoma (mean = 18% of cells; range 3%‐44%) when compared with Spitz nevi (mean = 9%; range 2%‐28%; P = .001) and conventional nevi (mean = 1.5%; range 0‐9%; P < .0001). Strong UBE2C staining was identified in cells undergoing mitosis. UBE2C RNA and protein detection correlated with mitotic rate (P < .0001). On the other hand, HOXA1 nuclear staining was low in melanoma (mean = 69%; range 5%‐100%) when compared with Spitz nevi (mean = 94%; range 66%‐100%; P = .0024) and conventional nevi (mean = 94%; range 83%‐99%; P = .009).

Conclusions

UBE2C and HOXA1 RNA and protein are differentially expressed in conventional and Spitz nevi and melanoma.
Social inequality in youth violence: The role of heavy episodic drinking
Authors: Norström Thor , Rossow Ingeborg , Pape Hilde
Published: June 2017

Introduction and Aims. Alcohol use is an important risk factor for violence, and violent behaviour is more prevalent in lower socioeconomic status (SES) groups. The aim of this study was to examine whether the SES difference in youth violence can be explained by differential exposure to—and/or differential vulnerability to—heavy episodic drinking (HED). In the latter case, effect modification by impulsivity could be assumed. Design and Methods. We analysed cross‐sectional data from a school survey of 15‐ to 17‐year‐olds in Norway (n = 9853). We employed two measures of low‐SES group. Associations between SES, HED and violence were estimated by Poisson regressions, applying a residual centring procedure to test effect modification. Results. Violent behaviour frequency, HED frequency and impulsivity scores were all elevated in the low‐SES group. The SES difference in violent behaviour was significantly reduced when adjusting for HED. The stronger association between HED and violence in the low, compared with the medium‐SES/high‐SES group, was modified when accounting for impulsivity. Sensitivity analyses suggested robust findings. Discussion and Conclusions. The findings lend support to both the differential exposure hypothesis and to the differential vulnerability hypothesis as well as the hypothesis of an enhancing effect of impulsivity on the HED—violence association. The SES difference in youth violence can be accounted for by: (i) an elevated prevalence of HED in low‐SES groups; and (ii) a stronger than average link between HED and violence in low‐SES groups due to their higher than average impulsivity score. [Norström T, Rossow I, Pape H. Social inequality in youth violence: The role of heavy episodic drinking. Drug Alcohol Rev 2017;00:000‐000]
Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea‐induced hypoglycaemia: A GoDARTS Study
Authors: Dujic Tanja , Zhou Kaixin , Donnelly Louise A. , Leese Graham , Palmer Colin N. A. , Pearson Ewan R.
Published: June 2017

Data on the association of CYP2C9 genetic polymorphisms with sulfonylurea (SU)‐induced hypoglycaemia (SH) are inconsistent. Recent studies showed that variants in the P450 oxidoreductase (POR) gene could affect CYP2C9 activity. In this study, we explored the effects of POR*28 and combined CYP2C9*2 and CYP2C9*3 genotypes on SH and the efficacy of SU treatment in type 2 diabetes. A total of 1770 patients were included in the analysis of SU efficacy, assessed as the combined outcome of the HbA1c reduction and the prescribed SU daily dose. Sixty‐nine patients with severe SH were compared with 311 control patients. The number of CYP2C9 deficient alleles was associated with nearly three‐fold higher odds of hypoglycaemia (OR, 2.81; 95% CI, 1.30‐6.09; P = .009) and better response to SU treatment (β, −0.218; SE, 0.074; P = .003) only in patients carrying the POR*1/*1 genotype. Our results indicate that interaction between CYP2C9 and POR genes may be an important determinant of efficacy and severe adverse effects of SU treatment.
Planktivorous vendace (Coregonus albula) utilise algae‐derived fatty acids for biomass increase and lipid deposition
Authors: Strandberg Ursula , Hiltunen Minna , Taipale Sami J. , Yeung Sean , Kankaala Paula
Published: June 2017

Spatial and seasonal variation in the abundance and composition of phytoplankton and other basal resources (bacteria, terrestrial detritus) influence the availability of essential polyunsaturated fatty acids (PUFA) for upper trophic levels in lake food webs. We studied accumulation, composition and content of fatty acids in planktivorous vendace (Coregonus albula) muscle tissue during the summer feeding period (May to late September) in six boreal lakes. Vendace muscle fatty acid content increased from ~17.7 mg/g DW to ~28.1 mg/g DW from spring to summer, corresponding to a ~59% increase in total fatty acids. PUFA accounted for 45%–65% of all fatty acids, and the most abundant fatty acid was docosahexaenoic acid (DHA, 22:6n‐3). The DHA content remained relatively constant throughout the sampling period (~7–8 mg/g DW), but the proportion of DHA decreased from ~40% in spring to ~30% in summer and autumn. The decrease in DHA proportion was due to accumulation of other fatty acids, primarily C18 PUFA (predominantly synthetised by algae) and monounsaturated fatty acids. A similar fatty acid accumulation pattern was observed in lipid storing copepods, an important prey for planktivorous vendace. The abundance of bacterial and terrestrial biomarker fatty acids in vendace muscle and prey items was low (<5% and <0.1% respectively). The increase in weight and the deposition of internal energy stores in vendace were achieved predominantly by algae‐based food chain. This has ecological implications, as vendace requires sufficient lipid stores for reproduction in autumn and survival over winter.
On the structure and mechanism of two‐pore channels
Authors: Kintzer Alexander F. , Stroud Robert M.
Published: June 2017

In eukaryotes, two‐pore channels (TPC1–3) comprise a family of ion channels that regulate the conductance of Na+ and Ca2+ ions across cellular membranes. TPC1–3 form endolysosomal channels, but TPC3 can also function in the plasma membrane. TPC1/3 are voltage‐gated channels, but TPC2 opens in response to binding endolysosome‐specific lipid phosphatidylinositol‐3,5‐diphosphate (PI(3,5)P2). Filoviruses, such as Ebola, exploit TPC‐mediated ion release as a means of escape from the endolysosome during infection. Antagonists that block TPC1/2 channel conductance abrogate filoviral infections. TPC1/2 form complexes with the mechanistic target of rapamycin complex 1 (mTORC1) at the endolysosomal surface that couple cellular metabolic state and cytosolic nutrient concentrations to the control of membrane potential and pH. We determined the X‐ray structure of TPC1 from Arabidopsis thaliana (AtTPC1) to 2.87Å resolution—one of the two first reports of a TPC channel structure. Here, we summarize these findings and the implications that the structure may have for understanding endolysosomal control mechanisms and their role in human health.
ASIC1A in neurons is critical for fear‐related behaviors
Authors: Taugher R. J. , Lu Y. , Fan R. , Ghobbeh A. , Kreple C. J. , Faraci F. M. , Wemmie J. A.
Published: June 2017

Acid‐sensing ion channels (ASICs) have been implicated in fear‐, addiction‐ and depression‐related behaviors in mice. While these effects have been attributed to ASIC1A in neurons, it has been reported that ASICs may also function in nonneuronal cells. To determine if ASIC1A in neurons is indeed required, we generated neuron‐specific knockout (KO) mice with floxed Asic1a alleles disrupted by Cre recombinase driven by the neuron‐specific synapsin I promoter (SynAsic1a KO mice). We confirmed that Cre expression occurred in neurons, but not all neurons, and not in nonneuronal cells including astrocytes. Consequent loss of ASIC1A in some but not all neurons was verified by western blotting, immunohistochemistry and electrophysiology. We found ASIC1A was disrupted in fear circuit neurons, and SynAsic1a KO mice exhibited prominent deficits in multiple fear‐related behaviors including Pavlovian fear conditioning to cue and context, predator odor‐evoked freezing and freezing responses to carbon dioxide inhalation. In contrast, in the nucleus accumbens ASIC1A expression was relatively normal in SynAsic1a KO mice, and consistent with this observation, cocaine conditioned place preference (CPP) was normal. Interestingly, depression‐related behavior in the forced swim test, which has been previously linked to ASIC1A in the amygdala, was also normal. Together, these data suggest neurons are an important site of ASIC1A action in fear‐related behaviors, whereas other behaviors likely depend on ASIC1A in other neurons or cell types not targeted in SynAsic1a KO mice. These findings highlight the need for further work to discern the roles of ASICs in specific cell types and brain sites.
Thermal buffering capacity of the germination phenotype across the environmental envelope of the Cactaceae
Authors: Seal Charlotte E. , Daws Matthew I. , Flores Joel , Ortega‐Baes Pablo , Galíndez Guadalupe , León‐Lobos Pedro , Sandoval Ana , Ceroni Stuva Aldo , Ramírez Bullón Natali , Dávila‐Aranda Patricia , Ordoñez‐Salanueva Cesar A. , Yáñez‐Espinosa Laura , Ulian Tiziana , Amosso Cecilia , Zubani Lino , Torres Bilbao Alberto , Pritchard Hugh W.
Published: June 2017

Recruitment from seeds is among the most vulnerable stage for plants as global temperatures change. While germination is the means by which the vast majority of the world's flora regenerate naturally, a framework for accurately predicting which species are at greatest risk of germination failure during environmental perturbation is lacking. Taking a physiological approach, we assess how one family, the Cactaceae, may respond to global temperature change based on the thermal buffering capacity of the germination phenotype. We selected 55 cactus species from the Americas, all geo‐referenced seed collections, reflecting the broad environmental envelope of the family across 70° of latitude and 3700 m of altitude. We then generated empirical data of the thermal germination response from which we estimated the minimum (Tb), optimum (To) and ceiling (Tc) temperature for germination and the thermal time (θ50) for each species based on the linearity of germination rate with temperature. Species with the highest Tb and lowest Tc germinated fastest, and the interspecific sensitivity of the germination rate to temperature, as assessed through θ50, varied tenfold. A left‐skewed asymmetry in the germination rate with temperature was relatively common but the unimodal pattern typical of crop species failed for nearly half of the species due to insensitivity to temperature change at To. For 32 fully characterized species, seed thermal parameters correlated strongly with the mean temperature of the wettest quarter of the seed collection sites. By projecting the mean temperature of the wettest quarter under two climate change scenarios, we predict under the least conservative scenario (+3.7°C) that 25% of cactus species will have reduced germination performance, whilst the remainder will have an efficiency gain, by the end of the 21st century.
Sea‐ice loss boosts visual search: fish foraging and changing pelagic interactions in polar oceans
Authors: Langbehn Tom J. , Varpe Øystein
Published: June 2017

Light is a central driver of biological processes and systems. Receding sea ice changes the lightscape of high‐latitude oceans and more light will penetrate into the sea. This affects bottom‐up control through primary productivity and top‐down control through vision‐based foraging. We model effects of sea‐ice shading on visual search to develop a mechanistic understanding of how climate‐driven sea‐ice retreat affects predator–prey interactions. We adapt a prey encounter model for ice‐covered waters, where prey‐detection performance of planktivorous fish depends on the light cycle. We use hindcast sea‐ice concentrations (past 35 years) and compare with a future no‐ice scenario to project visual range along two south–north transects with different sea‐ice distributions and seasonality, one through the Bering Sea and one through the Barents Sea. The transect approach captures the transition from sub‐Arctic to Arctic ecosystems and allows for comparison of latitudinal differences between longitudes. We find that past sea‐ice retreat has increased visual search at a rate of 2.7% to 4.2% per decade from the long‐term mean; and for high latitudes, we predict a 16‐fold increase in clearance rate. Top‐down control is therefore predicted to intensify. Ecological and evolutionary consequences for polar marine communities and energy flows would follow, possibly also as tipping points and regime shifts. We expect species distributions to track the receding ice‐edge, and in particular expect species with large migratory capacity to make foraging forays into high‐latitude oceans. However, the extreme seasonality in photoperiod of high‐latitude oceans may counteract such shifts and rather act as a zoogeographical filter limiting poleward range expansion. The provided mechanistic insights are relevant for pelagic ecosystems globally, including lakes where shifted distributions are seldom possible but where predator–prey consequences would be much related. As part of the discussion on photoperiodic implications for high‐latitude range shifts, we provide a short review of studies linking physical drivers to latitudinal extent.
Influence of cervical, thoracic and lumbar spines, and shoulder girdle range of motion on swallowing function of dependent older adults
Authors: Tashiro Munetsugu , Honda Yasutoshi , Ohkubo Mai , Sugiyama Tetsuya , Ishida Ryo
Published: June 2017

Aim

The present study examined the cervical, thoracic and lumbar spines, and shoulder girdle range of motion (ROM) of dependent older adults to clarify the influence of these variables on swallowing function, in order to evaluate the efficiency of ROM training to maintain older adults’ swallowing function.

Methods

A total of 37 (mean age 86.8 ± 6.2 years; 11 men; 26 women) dependent older adults were included in the study. The level of swallowing function was assessed using the Functional Oral Intake Scale. The following ROM were measured three times to calculate the mean: the cervical spine (flexion, extension, rotation and lateral bending); thoracic and lumbar spines (flexion, extension, rotation and lateral bending); and shoulder girdle (flexion, extension, elevation and depression). In order to compare ROM, the participants showing Functional Oral Intake Scale scores of 7 were classified as dysphagia (−), and those showing scores <7 were included in the dysphagia (+) subgroups.

Results

The dysphagia (+) group showed significantly limited cervical spine (flexion, extension and lateral bending), thoracic and lumbar spines (flexion, extension, rotation and lateral bending), and shoulder girdle (flexion, elevation, and depression) ROM.

Conclusions

Although strict relationships were not clarified, the results of the present study suggested the influence of some joint ROM on swallowing function. This suggests the feasibility of preventing dysphagia among dependent older adults by maintaining and enhancing the elasticity and extensibility of their muscles through cervical, thoracic and lumbar spines, and shoulder girdle ROM training. Geriatr Gerontol Int 2017; 17: 2565–2572.
Fear of falling and gait parameters in older adults with and without fall history
Authors: Makino Keitaro , Makizako Hyuma , Doi Takehiko , Tsutsumimoto Kota , Hotta Ryo , Nakakubo Sho , Suzuki Takao , Shimada Hiroyuki
Published: June 2017

Aim

Fear of falling (FOF) is associated with spatial and temporal gait parameters in older adults. FOF is prevalent among older adults, both those with and without fall history. It is still unclear whether the relationships between FOF and gait parameters are affected by fall history. The aim of the present study was to compare gait parameters by the presence of FOF and fall history.

Methods

A total of 3575 older adults (mean age 71.7 years, 49.7% female) met the inclusion criteria for the present study. We assessed the presence of fall history and FOF by face‐to‐face interview, and gait parameters (gait speed, stride length, step rate, double support time and variation of stride length) at a comfortable speed using a computerized electronic walkway.

Results

Prevalences of fall history and FOF were as follows: non‐fallers without FOF 52.6% (n = 1881); fallers without FOF 6.3% (n = 227); non‐fallers with FOF 34.4% (n = 1229); and fallers with FOF 6.7% (n = 238). Analysis of covariance showed significant differences among the four groups in all gait variables even after adjusting for age, sex and number of medications used. It should be noted that non‐fallers with FOF showed significantly slower gait speed, shorter stride length and longer double support time than did non‐fallers without FOF (P < 0.001).

Conclusions

The present results suggest that spatial and temporal gait parameters are influenced by FOF, even in the absence of fall history. The assessment of FOF might be helpful for better understanding of age‐related changes in gait control. Geriatr Gerontol Int 2017; 17: 2455–2459.
Differences in body composition and physical function related to pure sarcopenia and sarcopenic obesity: A study of community‐dwelling older adults in Japan
Authors: Kera Takeshi , Kawai Hisashi , Hirano Hirohiko , Kojima Motonaga , Fujiwara Yoshinori , Ihara Kazushige , Obuchi Shuichi
Published: June 2017

Aim

We compared skeletal muscle mass and physical function between older adults with sarcopenia and those with sarcopenic obesity.

Methods

Body composition and physical and cognitive function were measured for 1283 community‐dwelling older adults. Participants responded to questionnaires about pain and exercise. The pure sarcopenia group (PS) included individuals with sarcopenia only. The sarcopenic obesity group (SO) included individuals with both sarcopenia and obesity. Groups were compared after adjusting for sex, age and height through propensity score matching.

Results

The PS and SO included 129 and 105 individuals, respectively. Comorbidities were more frequent in the SO (P < 0.001). The SO had higher upper limb muscle mass (P < 0.001), and had lower ratios of lower limb muscle mass to upper limb muscle mass (P < 0.001) and of lower limb muscle mass to weight (P < 0.001). The SO also had poorer grip power (P = 0.007), gait times (usual pace, P = 0.001; maximum speed, P = 0.001), Timed Up and Go test (P < 0.001), and time standing on one foot (P = 0.005) than the PS. The SO had a higher frequency of gonalgia (P = 0.013). After adjusting for covariates, comorbidities, upper limb muscle mass, lower limb muscle mass to upper limb muscle mass ratio, lower limb muscle mass to weight ratio, gait time, Timed Up and Go test, time standing on one foot, and gonalgia differed significantly between the PS and SO.

Conclusions

Sarcopenic obesity decreases the ratio of lower limb muscle mass to weight by increasing weight. It affects physical function in older Japanese adults with low weight. Decreased relative lower limb muscle mass is an important function‐limiting factor in sarcopenic obesity. Geriatr Gerontol Int 2017; 17: 2602–2609.
Clinicopathological findings in female‐to‐male gender‐affirming breast surgery
Authors: East Ellen G , Gast Katherine M , Kuzon William M , Roberts Emily , Zhao Lili , Jorns Julie M
Published: June 2017

Aims

Gender dysphoria is a diagnosis whereby an individual identifies as the opposite gender. The management of patients seeking female‐to‐male (FTM) transition includes hormonal therapy and surgical intervention, including mastectomy. The aim of this study was to characterize the immunohistological findings in resection specimens from FTM patients.

Methods and results

We reviewed 68 cases (67 patients, one with re‐excision) of FTM breast tissue resection by collecting clinical data, reviewing breast imaging and pathology reports (gross fibrous density, specimen weight, and number of cassettes submitted), and reviewing pathology slides [number of tissue pieces submitted, number of terminal duct lobule units (TDLUs), and the presence of histological findings]. Significant histological findings were present in 51 of 68 (75.0%) cases, including one case (1.5%) of flat epithelial atypia. Fibrocystic changes were the most common finding (27/68, 39.7%), followed by gynaecomastoid change, fibrotic stage, (22/68, 32.4%), and fibroadenomatoid change (11/68, 16.2%). Fibrocystic change was associated with increased numbers of TDLUs, and gynaecomastoid change was associated with lower body mass index and decreased numbers of TDLUs. Gynaecomastoid change showed a moderate proportion of luminal epithelial cells with strong‐intensity immunohistochemical staining for oestrogen receptor, progesterone receptor, and androgen receptor, and a three‐layered epithelium demonstrated by the use of cytokeratin 5/6 immunohistochemistry.

Conclusions

We identified gynaecomastoid change at a significantly higher rate than previously reported in female patients. We support the continued gross and histological evaluation of FTM specimens in light of the identification of atypia in one case.
InterPrEP: internet‐based pre‐exposure prophylaxis with generic tenofovir disoproxil fumarate/emtrictabine in London – analysis of pharmacokinetics, safety and outcomes
Authors: Wang X , Nwokolo N , Korologou‐Linden R , Hill A , Whitlock G , Day‐Weber I , McClure MO , Boffito M
Published: June 2017

Objectives

The National Health Service in England (NHS England) does not provide pre‐exposure prophylaxis (PrEP) against HIV, forcing people to purchase generic versions on the internet. However, there are concerns about the authenticity of medicines purchased online. We established an innovative service offering plasma tenofovir (TFV) and emcitrabine (FTC) therapeutic drug monitoring for people buying generic PrEP online, to ensure that drug concentrations in vivo were consistent with those of propriety brands and previously published data.

Methods

TFV/FTC concentrations were measured by ultra‐performance liquid chromatography ultraviolet detection. Evaluation of renal function and testing for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) were also carried out, at baseline and every 3–6 months, with risk reduction advice.

Results

A total of 293 individuals presented having purchased PrEP on the internet: 85% were white, 84% were taking daily PrEP, and 16% were event‐driven. Most were on generic TFV disoproxil fumarate (TDF)/FTC from Cipla Ltd. Median (range) TFV and FTC plasma concentrations were 104 (21–597) ng/mL and 140 (17–1876) ng/mL, respectively. All concentrations were above our established plasma TFV and FTC targets, based on previously published data. Renal function was normal in all evaluable individuals and no new cases of HIV, HBV or HCV infection were seen.

Conclusions

In a population at high risk of HIV acquisition, who cannot yet access PrEP on the NHS, concentrations of TFV and FTC in generic formulations purchased over the internet were similar to (or slightly higher than) those measured in phase I studies with the original formulation from Gilead (Truvada™), which has demonstrated high levels of protection against HIV infection in previous PrEP clinical trials.
Pollen and spores from Lower Cretaceous in Guyang Basin of Inner Mongolia, China and their palaeoclimatic and paleoecological significance
Authors: Jin Peihong , Chen Jingwei , Wang Zixi , Xu Xiaohui , Yang Guolin , Du Baoxia , Sun Bainian
Published: June 2017

Research on the climate and vegetation of the Cretaceous is fundamental to understanding the present environment. The present study focuses on the Lower Cretaceous Guyang Formation (Inner Mongolia), which yields unique macrofossils and diverse palynological assemblages that are used to understand the palaeoecology. In total, 56 genera are identified in the examined assemblage, which are dominated by spores and pollen of pteridophytes and gymnosperms. The gymnosperm pollen is dominated by Taxodiaceae, which belong to Coniferales, and a large proportion of pollen attributable to the Cycadophyta and Ginkgopsida. The pteridophyte spores are dominated by taxa attributable to the Lygodiaceae and Cyatheaceae. Quantitative analysis based on the geographical distribution of modern plant communities and the Sporomorph Ecogroup (SEG) model, the palynomorph associations are used to infer the presence of a closed coniferous forest dominated by Podozamitales, Picea and Podocarpus with understory vegetation comprising ferns prevailed. The fossil palyno flora indicates a warm and humid subtropical climate during Early Cretaceous of Inner Mongolia.