bluuebunny/crossref_metadata_2025 huggingface dataset:
Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures
Authors: Augustin Katrin , Williams Sophie , Cunningham Mark , Devlin Anita M. , Friedrich Maximilian , Jayasekera Ashan , Hussain Mohammed A. , Holliman Damian , Mitchell Patrick , Jenkins Alistair , Chen Philip E. , Walker Matthew C. , Williams Robin S.B.
Published: October 2018

Perampanel is an adjunctive treatment for epilepsy that works through the direct inhibition of AMPA receptors. The same molecular mechanism has recently been shown for a fatty acid, decanoic acid, prescribed in the medium chain triglyceride ketogenic diet for the treatment of patients with drug‐resistant epilepsy. Because each compound has been proposed to act through a distinct AMPA receptor binding site, we predicted that perampanel and decanoic acid would act synergistically against AMPA receptors and, consequently, seizures. Here, we show a synergistic interaction between perampanel and decanoic acid in direct AMPA receptor inhibition, in an ex vivo model of seizure activity, and against seizure‐induced activity in human brain slices. These data support a potential role for combination treatment using perampanel and dietary decanoic acid to provide enhanced seizure control.
Transcranial magnetic stimulation over contralateral primary somatosensory cortex disrupts perception of itch intensity
Authors: Jones Olivia , Schindler Igor , Holle Henning
Published: October 2018

Itch, a complex unpleasant sensation causing the desire to scratch, results from the activity of a network of brain regions. However, the specific functional contributions of individual regions within this network remain poorly understood. We investigated whether contralateral primary and secondary somatosensory cortices (S1, S2) and ipsilateral inferior frontal gyrus (IFG) are critically involved in the cortical processing of acute itch. Continuous theta burst transcranial magnetic stimulation (cTBS) was applied to either S1, S2 or IFG, followed by itch induction using a histamine prick. Results indicate a significant reduction in itch intensity when cTBS was applied to S1. Stimulation of S2 or the IFG was not associated with a significant reduction in itch intensity. The novel finding of an antipruritic effect elicited by disruption of activity in contralateral S1 suggests a causal role of S1 in encoding the sensory‐discriminative aspect of itch and might be important in future studies on brain interventions for the treatment of itch.
The Response of Shallow Groundwater Levels to Soil Freeze–Thaw Process on the Qinghai‐Tibet Plateau
Authors: Dai Licong , Guo Xiaowei , Du Yangong , Zhang Fawei , Ke Xun , Cao Yingfang , Li Yikang , Li Qian , Lin Li , Cao Guangmin
Published: October 2018

The Qinghai‐Tibet plateau has the world's largest area of seasonally frozen ground. Here, shallow groundwater displays behavior that is distinct from that elsewhere in the world. In the present study, we explore the seasonal and interannual variation of the shallow groundwater levels from 2012 to 2016, and attempt to quantitatively evaluate the relative influences of individual driving factors on the shallow groundwater levels based on boosted regression trees. The results show that: (1) on a seasonal scale, the groundwater levels were characterized by a double peak and double valley relationship, while on an interannual scale the groundwater levels showed a slightly downwards trend from 2012 to 2016; and (2) during the frozen period, the seasonal variation of groundwater levels was determined by mean air temperature through its effect on the soil thaw–freeze process, accounting for 53.15% of total variation. Meanwhile, ET0 and rainfall exerted little impact on the seasonal variation of groundwater levels, which might be attributed to the aquitard of frozen soil that impedes the exchange between surface water and groundwater. Moreover, there was a lag between groundwater levels and soil freezing–thawing. During the non‐frozen period, the mean air temperature was again the most important factor impacting the variation of groundwater levels, through its effect on ET0, and accounted for 40.75% of total variation, while rainfall had little effect on groundwater levels when rainfall intensity was less than 12 mm/day. These results will benefit predictions of future trends in groundwater levels within the context of global warming.
Effect of fluorine on the optical properties of BaF2‐BaO‐La2O3‐B2O3 glasses prepared by containerless processing
Authors: Chung Jaeyeop , Yanaba Yutaka , Nakatsuka Yuko , Watanabe Yasuhiro , Inoue Hiroyuki
Published: October 2018

The glass‐forming region of the BaO‐La2O3‐B2O3 ternary system was determined by using a containerless processing. Moreover, we prepared xBaF2‐(35‐x)BaO‐15La2O3‐50B2O3 (x = 0‐35 mol%), xBaF2‐(20‐x)BaO‐20La2O3‐60B2O3 (x = 0‐20 mol%), xBaF2‐(20‐x)BaO‐15La2O3‐65B2O3 (x = 0‐20 mol%) and xBaF2‐(20‐x)BaO‐10La2O3‐70B2O3 (x = 0‐20 mol%) novel oxyfluoride glasses. The glass transition temperature, density, refractive index, and the Abbe number of these glasses were investigated. The effects of the substitution of fluorine for oxygen on the refractive index and Abbe number were discussed on the basis of electronic polarizability and resonance wavelength of oscillator. The refractive indices decreased but Abbe number increased with increasing fluorine concentration because of the decrease in resonance wavelength of oscillator. By substituting fluorine for oxygen, we developed new optical glasses (nd = 1.68‐1.74, vd = 46‐60). The fractions of BO4 unit of oxide and oxyfluoride glasses were analyzed by the 11B NMR. The conversion between BO3 and BO4 units was observed when fluorine is added to oxide glasses because, fluorine bonds with network modifier cations and the available number of network modifiers decrease with increasing fluorine concentration. These results are helpful for designing new optical glasses that are controlled to have relatively high refractive index and lower wavelength dispersion.
Hypoglycemic and hypolipidemic effects of total saponins from Stauntonia chinensis in diabetic db/db mice
Authors: Xu Jing , Wang Sha , Feng Tianhui , Chen Yu , Yang Guangzhong
Published: October 2018

Stauntonia chinensis DC. has been utilised as a traditional herbal medicine for its anti‐hyperglycemic characteristic, which has been associated with triterpene saponins. The goal of the current evaluation was to examine hypoglycemic activity and affiliated mechanism of total saponins from S. chinensis. The chemical composition was analysed by HPLC‐ESI‐MS/MS. The fasting blood glucose, oral glucose tolerance test, insulin tolerance test, insulin and glycogen levels of type 2 diabetic db/db mice administered total saponins were quantified to determine the hypoglycemic effects. The serum lipid profiles were assessed to determine the hypolipidemic effects. Western blotting was used to quantify the protein levels of insulin receptor substrates (IRS)‐1/PI3K/AKT, AMPK/ACC and GLUT4. Twenty triterpene saponins were identified from the total saponins, which exhibited hypoglycemic activities and modulated hyperlipidemia that was associated with type 2 diabetes. The hypoglycemic effects were partly due to the activation of GLUT4, which is regulated by IRS‐1/PI3K/AKT. The activation of the AMPK/ACC signalling pathway may be responsible for the hypolipidemic activity. This study revealed that total saponins from S. chinensis have significant hypoglycemic and hypolipidemic activity in diabetic db/db mice, indicating that these may be utilised in the development of saponins based on S. chinensis for the treatment of type 2 diabetes.
CircRUNX2 through has‐miR‐203 regulates RUNX2 to prevent osteoporosis
Authors: Yin Qudong , Wang Jian , Fu Qiang , Gu Sanjun , Rui Yongjuan
Published: October 2018

Objective

We aimed to discover the molecular mechanism of hsa_circ_0076694 (circRUNX2) on osteogenic differentiation. We also explored the interaction between circRUNX2, miR‐203 and RUNX2.

Methods

Clinical samples obtained from femoral neck fracture patients’ bone tissues were used to collect circRUNX2, miR‐203, and RUNX2 expression data, while their expression changes were observed in human bone mesenchymal stem cells (hBMSCs) during osteogenic differentiation. QRT‐PCR and Western blot were used to analyse levels of RNAs and proteins. Biotin pull down, RIP, RNA FISH, and Dual‐Luciferase Reporter assays demonstrated the relationship between circRUNX2, miR‐203, and RUNX2. ALP and ARS staining were used to measure the degree of osteogenic differentiation under the control of circRUNX2, miR‐203.

Results

CircRUNX2 were down‐regulated in osteoporotic patients’ bone tissues. CircRUNX2 could inhibit miR‐203 expression by sponging miR‐203. MiR‐203 inhibited osteogenic differentiation by targeting the 3′‐UTR of RUNX2 and down‐regulate RUNX2 expression. Overexpression of circRUNX2 promoted the expression of osteogenic differentiation‐related proteins such as RUNX2, OCN, OPN, BSP, and prevented osteoporosis.

Conclusion

circRUNX2 could sponge miR‐203 and enhance RUNX2 expression, thus circRUNX2 prevents osteoporosis and may provide a novel therapeutic strategy for it.
MYC and DNMT3A‐mediated DNA methylation represses microRNA‐200b in triple negative breast cancer
Authors: Pang Yamei , Liu Jian , Li Xiang , Xiao Guodong , Wang Huangzhen , Yang Ganghua , Li Yanbo , Tang Shou‐Ching , Qin Sida , Du Ning , Zhang Henggang , Liu Dapeng , Sun Xin , Ren Hong
Published: October 2018

Triple‐negative breast cancer (TNBC) is the most aggressive breast cancer subtype with a poor prognosis. The microRNA‐200 (miR‐200) family has been associated with breast cancer metastasis. However, the epigenetic mechanisms underlying miR‐200b repression in TNBC are not fully elucidated. In this study, we found that MYC proto‐oncogene, bHLH transcription factor (MYC) and DNA methyltransferase 3A (DNMT3A) were highly expressed in TNBC tissues compared with other breast cancer subtypes, while miR‐200b expression was inhibited significantly. We demonstrated that MYC physically interacted with DNMT3A in MDA‐MB‐231 cells. Furthermore, we demonstrated that MYC recruited DNMT3A to the miR‐200b promoter, resulting in proximal CpG island hypermethylation and subsequent miR‐200b repression. MiR‐200b directly inhibited DNMT3A expression and formed a feedback loop in TNBC cells. MiR‐200b overexpression synergistically repressed target genes including zinc‐finger E‐box‐binding homeobox factor 1, Sex determining region Y‐box 2 (SOX2), and CD133, and inhibited the migration, invasion and mammosphere formation of TNBC cells. Our findings reveal that MYC can collaborate with DNMT3A on inducing promoter methylation and miR‐200b silencing, and thereby promotes the epithelial to mesenchymal transition and mammosphere formation of TNBC cells.
Economic Evaluations of Falls Prevention Programs for Older Adults: A Systematic Review
Authors: Olij Branko F. , Ophuis Robbin H. , Polinder Suzanne , van Beeck Ed F. , Burdorf Alex , Panneman Martien J.M. , Sterke Carolyn Shanty
Published: October 2018

Objectives

To provide a comprehensive overview of economic evaluations of falls prevention programs and to evaluate the methodology and quality of these studies.

Design

Systematic review of economic evaluations on falls prevention programs.

Setting

Studies (N=31) of community‐dwelling older adults (n=25), of older adults living in residential care facilities (n=3), and of both populations (n=3) published before May 2017.

Participants

Adults aged 60 and older.

Measurements

Information on study characteristics and health economics was collected. Study quality was appraised using the 20‐item Consensus on Health Economic Criteria.

Results

Economic evaluations of falls prevention through exercise (n = 9), home assessment (n = 6), medication adjustment (n = 4), multifactorial programs (n = 11), and various other programs (n = 13) were identified. Approximately two‐thirds of all reported incremental cost‐effectiveness ratios (ICERs) with quality‐adjusted life‐years (QALYs) as outcome were below the willingness‐to‐pay threshold of $50,000 per QALY. All studies on home assessment and medication adjustment programs reported favorable ICERs, whereas the results of studies on exercise and multifactorial programs were inconsistent. The overall methodological quality of the studies was good, although there was variation between studies.

Conclusion

The majority of the reported ICERs indicated that falls prevention programs were cost‐effective, but methodological differences between studies hampered direct comparison of the cost‐effectiveness of program types. The results imply that investing in falls prevention programs for adults aged 60 and older is cost‐effective. Home assessment programs (ICERs < $40,000/QALY) were the most cost‐effective type of program for community‐dwelling older adults, and medication adjustment programs (ICERs < $13,000/QALY) were the most cost‐effective type of program for older adults living in a residential care facility. J Am Geriatr Soc 66:2197–2204, 2018.
National Trends in Liver Transplantation in Older Adults
Authors: Haugen Christine E. , Holscher Courtenay M. , Garonzik‐Wang Jacqueline , Pozo Marcos , Warsame Fatima , McAdams‐DeMarco Mara , Segev Dorry L.
Published: October 2018

Objectives

To explore trends in liver transplantation (LT) and outcomes for older recipients for evaluation, counseling, and appropriate referral of this vulnerable group of older adults.

Design

Prospective national cohort study.

Setting

Scientific Registry of Transplant Recipients (January 1, 2003–December 31, 2016).

Participants

Older (aged ≥ 65) deceased donor liver‐only transplant recipients (n=8,627).

Measurements

We evaluated temporal changes in recipient, donor, and transplant characteristics and post‐LT length of stay (LOS), acute rejection, graft loss, and mortality using logistic regression and Cox proportional hazards.

Results

LT in older adults almost quadrupled, from 263 in 2003 (9.5% of total LTs that year) to 1,144 in 2016 (20.7% of total LTs). Recent recipients were more likely to be female and African American and have a higher body mass index and Model for End‐Stage Liver Disease score. Hepatitis C, nonalcoholic steatohepatitis, and hepatocellular carcinoma were the most common indications for LT in recent recipients. Odds of LOS longer than 2 weeks decreased 34% from 2003–06 to 2013–16 (adjusted odds ratio (aOR)=0.66, 95% confidence interval (CI)=0.57–0.76, P < .001), 1‐year acute rejection decreased 30% (aOR=0.70, 95% CI=0.56–0.88, P = .002), all‐cause graft loss decreased 54% (adjusted hazard ratio (aHR)=0.46, 95% CI=0.40–0.52, P < .001), and mortality decreased 57% (aHR=0.43, 95% CI=0.38–0.49, P < .001).

Conclusion

Despite the substantial increase in the number of older adults undergoing LT and the severity of their condition, LOS, rejection, graft loss, and mortality have significantly decreased over time. These trends can help guide appropriate LT referral and counseling in older adults with end‐stage liver disease. J Am Geriatr Soc 66:2321–2326, 2018.
A Planning Checklist for Interprofessional Consultations for Women in Midwifery Care
Authors: Phillippi Julia C. , Holley Sharon L. , Thompson Jennifer L. , Virostko Kate , Bennett Kelly
Published: October 2018

Team‐based, interprofessional models of maternity care can allow women to receive personalized care based on their health needs and personal preferences. However, involvement of multiple health care providers can fragment care and increase communication errors, which are a major cause of preventable maternal morbidity and mortality. In order to improve communication within one health system, a community‐engaged approach was used to develop a planning checklist for the care of women who began care with midwives but developed risks for poor perinatal outcomes. The planning checklist was constructed using feedback from women, nurses, midwives, and physicians in one interprofessional, collaborative network. In feasibility testing during 50 collaborative visits, the planning checklist provided a prompt to generate a comprehensive plan for maternity care and elucidate the rationale for interventions to women and future health care providers. In interviews after implementation of the checklist within a new collaborative format of prenatal physician consultations, women were pleased with the information received, and nurses, midwives, and physicians were positive about improved communication. This tool, developed with stakeholder input, was easy to implement and qualitatively beneficial to satisfaction and health system function. This article details the creation, implementation, and qualitative evaluation of the planning checklist. The checklist is provided and can be modified to meet the needs of other health systems.
Associations of sleep duration and quality with serum and hepatic lipids: The Netherlands Epidemiology of Obesity Study
Authors: Bos Maxime M. , Noordam Raymond , van den Berg Rosa , de Mutsert Renée , Rosendaal Frits R. , Blauw Gerard Jan , Rensen Patrick C. N. , Biermasz Nienke R. , van Heemst Diana
Published: October 2018

Short and long sleep duration and poor sleep quality may affect serum and hepatic lipid content, but available evidence is inconsistent. Therefore, we aimed to investigate the associations of sleep duration and quality with serum and hepatic lipid content in a large population‐based cohort of middle‐aged individuals. The present cross‐sectional study was embedded in the Netherlands Epidemiology of Obesity (NEO) study and consisted of 4260 participants (mean age, 55 years; proportion men, 46%) not using lipid‐lowering agents. Self‐reported sleep duration and quality were assessed using the Pittsburgh Sleep Quality Index questionnaire (PSQI). Outcomes of this study were fasting lipid profile (total cholesterol, low‐density lipoprotein [LDL]‐cholesterol, high‐density lipoprotein [HDL]‐cholesterol and triglycerides), postprandial triglyceride (response) levels, and hepatic triglyceride content (HTGC) as measured with magnetic resonance spectroscopy. We performed multivariable linear regression analyses, adjusted for confounders and additionally for measures that link to adiposity (e.g. body mass index [BMI] and sleep apnea). We observed that relative to the group with median sleep duration (≈7.0 hr of sleep), the group with shortest sleep (≈5.0 hr of sleep) had 1.5‐fold higher HTGC (95% confidence interval [CI]: 1.0‐2.2). The group with PSQI score ≥ 10 had a 1.1‐fold (95% CI: 1.0‐1.2) higher serum triglyceride level compared with the group with PSQI ≤ 5. However, these associations disappeared after adjustment for BMI and sleep apnea. Therefore, we concluded that previously observed associations of shorter sleep duration and poorer sleep quality with an adverse lipid profile, may be explained by BMI and sleep apnea, rather than by a direct effect of sleep on the lipid profile.
Rapid establishment of a flowering cline in Medicago polymorpha after invasion of North America
Authors: Helliwell Emily E. , Faber‐Hammond Joshua , Lopez Zoie C. , Garoutte Aaron , von Wettberg Eric , Friesen Maren L. , Porter Stephanie S.
Published: October 2018

To establish and spread in a new location, an invasive species must be able to carry out its life cycle in novel environmental conditions. A key trait underlying fitness is the shift from vegetative to reproductive growth through floral development. In this study, we used a common garden experiment and genotyping‐by‐sequencing to test whether the latitudinal flowering cline of the North American invasive plant Medicago polymorpha was translocated from its European native range through multiple introductions, or whether the cline rapidly established due to evolution following a genetic bottleneck. Analysis of flowering time in 736 common garden plants showed a latitudinal flowering time cline in both the native and invaded ranges where genotypes from lower latitudes flowered earlier. Genotyping‐by‐sequencing of 9,658 SNPs in 446 individuals revealed two major subpopulations of M. polymorpha in the native range, only one of which is present in the invaded range. Additionally, native range populations have higher genetic diversity than invaded range populations, suggesting that a genetic bottleneck occurred during invasion. All invaded range individuals are closely related to plants collected from native range populations in Portugal and southern Spain, and population assignment tests assigned invaded range individuals to this same narrow source region. Taken together, our results suggest that latitudinal clinal variation in flowering time has rapidly evolved across the invaded range despite a genetic bottleneck following introduction.
Does selection pay off? A cost–benefit comparison of medical school selection and lottery systems
Authors: Schreurs Sanne , Cleland Jennifer , Muijtjens Arno M M , oude Egbrink Mirjam G A , Cleutjens Kitty
Published: October 2018

Context

Resources for medical education are becoming more constrained, whereas accountability in medical education is increasing. In this constrictive environment, medical schools need to consider and justify their selection procedures in terms of costs and benefits. To date, there have been no studies focusing on this aspect of selection.

Objectives

We aimed to examine and compare the costs and benefits of two different approaches to admission into medical school: a tailored, multimethod selection process versus a lottery procedure. Our goal was to assess the relative effectiveness of each approach and to compare these in terms of benefits and costs from the perspective of the medical school.

Methods

The study was conducted at Maastricht University Medical School, at which the selection process and a weighted lottery procedure ran in parallel for 3 years (2011–2013). The costs and benefits of the selection process were compared with those of the lottery procedure over three student cohorts throughout the Bachelor's programme. The extra costs of selection represented the monetary investment of the medical school in conducting the selection procedure; the benefits were derived from the increase in income generated by the prevention of dropout and the reductions in extra costs facilitated by decreases in the repetition of blocks and objective structured clinical examinations.

Results

The tailor‐made selection procedure cost about €139 000 when extrapolated to a full cohort of students (n = 286). The lottery procedure came with negligible costs for the medical school. However, the average benefits of selection compared with the lottery system added up to almost €207 000.

Conclusions

This study not only shows that conducting a cost–benefit comparison is feasible in the context of selection for medical school, but also that an ‘expensive’ selection process can be cost‐beneficial in comparison with an ‘inexpensive’ lottery system. We encourage other medical schools to examine the cost‐effectiveness of their own selection processes in relation to student outcomes in order to extend knowledge on this important topic.
Integrated molecular characterization of IDH‐mutant glioblastomas
Authors: Korshunov A. , Casalini B. , Chavez L. , Hielscher T. , Sill M. , Ryzhova M. , Sharma T. , Schrimpf D. , Stichel D. , Capper D. , Reuss D. E. , Sturm D. , Absalyamova O. , Golanov A. , Lambo S. , Bewerunge‐Hudler M. , Lichter P. , Herold‐Mende C. , Wick W. , Pfister S. M. , Kool M. , Jones D. T. W. , von Deimling A. , Sahm F.
Published: October 2018

Aims

Mutations of isocitrate dehydrogenase (IDH)1/2 affect almost all astrocytomas of WHO grade II and III. A subset of IDH‐mutant astrocytic tumours progresses to IDH‐mutant glioblastoma or presents with the histology of a glioblastoma at first presentation. We set out here to assess the molecular spectrum of IDH‐mutant glioblastomas.

Methods

We performed an integrated molecular analysis of a mono‐centric cohort (n = 97); assessed through genome‐wide DNA methylation analysis, copy‐number profiling and targeted next generation sequencing using a neurooncology‐tailored gene panel.

Results

Of these 97 IDH‐mutant glioblastomas, 68 had a glioblastoma at first presentation (‘de novo’ IDH‐mutant glioblastoma) and 29 emerged from a prior low‐grade lesion (‘evolved’ IDH‐mutant glioblastoma). Unsupervised hierarchical clustering of DNA methylation data disclosed that IDH‐mutant glioblastoma (‘de novo’ and ‘evolved’) formed a distinct group separate from other diffuse glioma subtypes. Homozygous deletions of CDKN2A/B were found to be associated with shorter survival.

Conclusions

This study demonstrates DNA methylation patterns in IDH‐mutant glioblastoma to be distinct from lower‐grade astrocytic counterparts but homogeneous within de novo and evolved IDH‐mutant glioblastomas, and identifies CDKN2A as a marker for possible genetic sub‐stratification.
Determinants of weight loss maintenance: a systematic review
Authors: Varkevisser R. D. M. , van Stralen M. M. , Kroeze W. , Ket J. C. F. , Steenhuis I. H. M.
Published: October 2018

Background

Discerning the determinants of weight loss maintenance is important in the planning of future interventions and policies regarding overweight and obesity. We have therefore systematically synthesized recent literature on determinants of weight loss maintenance for individuals with overweight and obesity.

Methods

With the use of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement, prospective studies were identified from searches in PubMed and PsycINFO from 2006 to 2016. We included articles investigating adults with overweight and obesity undergoing weight loss without surgery or medication. Included articles were scored on their methodological quality, and a best‐evidence synthesis was applied to summarize the results.

Results

Our search resulted in 8,222 articles of which 67 articles were selected. In total, 124 determinants were identified of which 5 were demographic, 59 were behavioural, 51 were psychological/cognitive and 9 were social and physical environmental determinants. We found consistent evidence that demographic determinants were not predictive of weight loss maintenance. Behavioural and cognitive determinants that promote a reduction in energy intake, an increase in energy expenditure and monitoring of this balance are predictive determinants.

Conclusion

This review identifies key determinants in weight loss maintenance. However, more research regarding cognitive and environmental determinants of weight loss maintenance is needed to advance our knowledge on determinants of weight loss maintenance.
Surgical treatment of medication‐related osteonecrosis of the upper jaw: Case series
Authors: Aljohani Suad , Troeltzsch Matthias , Hafner Sigurd , Kaeppler Gabriele , Mast Gerson , Otto Sven
Published: October 2018

Purpose

The management of maxillary medication‐related osteonecrosis of the jaw (MRONJ) is challenging. Therefore, identifying the proper treatment is important. This study aimed to evaluate the surgical treatment of maxillary MRONJ using single‐layer closure with mucoperiosteal flap and double‐layer closure with buccal fat pad flap (BFPF) and mucoperiosteal flap and to find the outcomes after rehabilitation with obturators.

Methods

A retrospective analysis was conducted and included all surgically treated and followed‐up maxillary MRONJ cases in a single center. Demographics and clinical data, stage of MRONJ, surgical treatment, and treatment outcome were collected.

Results

Seventy‐nine lesions were included. Removal of necrotic bone was followed by coverage with mucoperiosteal flap in 60 lesions and BFPF in 14 lesions. Seven lesions (five primarily and two following unsuccessful treatment with BFPF) underwent necrectomy and were reconstructed with obturators. Complete mucosal healing was achieved in 76.7% of the lesions covered with mucoperiosteal flap. BFPF led to complete mucosal healing in 85.7% of the lesions. No complications were observed in the defects rehabilitated with obturators.

Conclusion

Removal of necrotic bone followed by closure with mucoperiosteal flap is reliable for MRONJ treatment. BFPF is effective for closure of MRONJ‐related oroantral communications (OACs).
Environmental heterogeneity amplifies behavioural response to a temporal cycle
Authors: Trevail Alice M. , Green Jonathan A. , Sharples Jonathan , Polton Jeff A. , Arnould Jonathan P. Y. , Patrick Samantha C.
Published: October 2018

Resource acquisition is integral to maximise fitness, however in many ecosystems this requires adaptation to resource abundance and distributions that seldom stay constant. For predators, prey availability can vary at fine spatial and temporal scales as a result of changes in the physical environment, and therefore selection should favour individuals that can adapt their foraging behaviour accordingly. The tidal cycle is a short, yet predictable, temporal cycle, which can influence prey availability at temporal scales relevant to movement decisions. Here, we ask whether black‐legged kittiwakes Rissa tridactyla can adjust their foraging habitat selection according to the tidal cycle using GPS tracking studies at three sites of differing environmental heterogeneity. We used a hidden Markov model to classify kittiwake behaviour, and analysed habitat selection during foraging. As expected for a central‐place forager, we found that kittiwakes preferred to forage nearer to the breeding colony. However, we also show that habitat selection changed over the 12.4‐h tidal cycle, most likely because of changes in resource availability. Furthermore, we observed that environmental heterogeneity was associated with amplified changes in kittiwake habitat selection over the tidal cycle, potentially because environmental heterogeneity drives greater resource variation. Both predictable cycles and environmental heterogeneity are ubiquitous. Our results therefore suggest that, together, predictable cycles and environmental heterogeneity may shape predator behaviour across ecosystems.
Fertility of lactating dairy cows inseminated with sex‐sorted or conventional semen after Ovsynch, Presynch–Ovsynch and Double‐Ovsynch protocols
Authors: Karakaya‐Bilen Ebru , Yilmazbas‐Mecitoglu Gulnaz , Keskin Abdulkadir , Guner Barıs , Serim Enes , Santos José E. P. , Gümen Ahmet
Published: October 2018

Contents

The objective was to compare pregnancy per artificial insemination (P/AI) with conventional (CS) or sex‐sorted semen (SS) in dairy cows subjected to one of the three timed AI protocols. Cows (n = 356) were randomly assigned to synchronization with Ovsynch (OVS), Presynch–Ovsynch (PO) or Double‐Ovsynch (DO) and inseminated on Day 77 ± 3 postpartum with either frozen‐thawed SS (n = 182) or CS (n = 184) of the same bull. More cows were cyclic at the beginning of breeding Ovsynch increased (p < 0.01) with presynchronization and it was greater for DO than PO (OVS = 78.5%, PO = 85.1%, DO = 95.6%). Overall, P/AI for SS and CS increased with presynchronization (p < 0.05) on Days 31 (OVS = 35.5%, PO = 47.1%, DO = 48.3%) and 62 (OVS = 30.1%, PO = 43.8%, DO = 43.9%). Regardless of synchronization treatments, insemination with SS reduced P/AI (p < 0.02) on Days 31 (38.1% vs. 50.6%) and 62 (34.5% vs. 45.6%) compared with CS. No interaction was observed between synchronization treatment and type of semen for P/AI, although in cows receiving CS, P/AI was numerically greatest for PO (OVS = 42.0%, PO = 59.3%, DO = 49.0%), and in cows receiving SS, it was numerically greatest for those inseminated following DO (OVS = 27.9%, PO = 35.5%, DO = 47.6%). Thus, presynchronization improved P/AI in cows inseminated with sex‐sorted or conventional semen.
Predicting response to bronchial thermoplasty in patients with severe uncontrolled asthma: An elusive goal
Authors: Hall Chase S. , Castro Mario
Published: October 2018

See related Article
The Joint Distribution of Net Worth and Pension Wealth in Germany
Authors: Bönke Timm , Grabka Markus M. , Schröder Carsten , Wolff Edward N. , Zyska Lennard
Published: October 2018

The research on wealth inequality has generally focused on real and financial assets, while giving little attention to pension wealth: the present value of future pension entitlements from public and company pension schemes. This is surprising given the important role pension plans play in guaranteeing material security and well‐being for a majority of the population, and suggests that they should be accounted for in peoples’ wealth portfolios. Using novel data from the Socio‐Economic Panel (SOEP), we study the incidence, relevance, and distribution of individual pension wealth, net worth, and augmented wealth (the sum of the two) in Germany. Further, we investigate age‐wealth profiles and differences between East and West Germany.
Lymphocytic choriomeningitis virus meningoencephalitis in a renal transplant recipient following exposure to mice
Authors: Tanveer Farah , Younas Mariam , Fishbain Joel
Published: October 2018

Solid organ transplant recipients (SOTR) are at increased risk for a wide variety of typical and atypical infections as a consequence of impaired cell mediated and humoral immunity. We report a case of meningoencephalitis in a renal transplant recipient caused by lymphocytic choriomeningitis virus (LCMV) acquired by exposure to mice excreta. The clinical course was complicated by the development of hydrocephalus, requiring a ventriculoperitoneal shunt. To our knowledge, this is the first reported case of LCMV infection in a SOTR that was not organ donor derived.
Red blood cell mechanical sensitivity improves in patients with sickle cell disease undergoing chronic transfusion after prolonged, subhemolytic shear exposure
Authors: Simmonds Michael J. , Suriany Silvie , Ponce Derek , Detterich Jon A.
Published: October 2018

Background

Sickle cell disease (SCD) is a genetically inherited hemoglobinopathy in which deoxygenated hemoglobin S polymerizes, leading to stiff red blood cells (RBCs) and inefficient microcirculatory blood flow. Transfusion therapy acts as primary and secondary prevention of ischemic stroke in SCD. Whether blood transfusion alters the mechanical sensitivity (MS) of RBCs to prolonged subhemolytic shear stress (shear) is unknown. We hypothesized that individuals with SCD undergoing chronic blood transfusion would have improved sensitivity to shear, compared with patients not undergoing transfusion therapy.

Study Design and Methods

Blood suspensions from individuals with SCD not receiving (n = 15) and receiving (n = 15) chronic simple transfusion were conditioned to shear (1, 4, 16, 32, and 64 Pa) for various durations (1, 4, 16, 32, and 64 sec), and then deformability of RBCs was immediately measured. Healthy young controls (n = 15) were included for reference. A surface mesh was interpolated using the data to determine the effect of blood transfusion on MS of RBCs.

Results

There was impaired RBC deformability to prolonged supraphysiologic shear in both SCD groups; however, MS improved in transfused patients when exposed to prolonged physiologic shear. Furthermore, in the transfused patients with SCD, the threshold above which subhemolytic damage occurs was similar to controls.

Conclusion

We found that chronic transfusion therapy normalizes the MS threshold above which RBC subhemolytic damage occurs after prolonged shear exposure in SCD. An important and novel finding in transfused patients with SCD was the improvement in RBC deformability in response to prolonged shear exposure over the physiologic range.
Human immunodeficiency virus 1 dual‐target nucleic acid technology improves blood safety: 5 years of experience of the German Red Cross blood donor service Baden‐Württemberg–Hessen
Authors: Hourfar Kai , Eberle Josef , Müller Markus , Micha Nübling C , Chudy Michael , Kress Julia , Gürtler Lutz , Mayr‐Wohlfart Uschi , Schrezenmeier Hubert , Hellmann Inke , Luhm Jürgen , Kraas Sabine , Ringwald Jürgen , Gubbe Knut , Frank Kerstin , Karl Andreas , Tonn Torsten , Jaeger Maike , Sireis Walid , Seifried Erhard , Schmidt Michael
Published: October 2018

BACKGROUND

RNA viruses are associated with a high frequency of mutations because of the missing proofreading function of polymerases, such as reverse transcriptase. Between 2007 and 2010, six blood donations with false‐negative nucleic acid technology (NAT) results were reported in Germany. Therefore, NAT screening in two viral genome regions was introduced by our blood donation service in 2010 on a voluntary basis and became mandatory in Germany since the beginning of 2015.

STUDY DESIGN AND METHODS

Blood donor screening was done using, in parallel, the German Red Cross (GRC) HIV‐1 CE long terminate repeats (LTR) PCR kit and the GRC HIV‐1 gag CE PCR kit. In total, 7 million blood donations were screened during the study period from 2010 to 2014 with the GRC dual‐target human immunodeficiency virus 1 (HIV‐1) NAT system. Additionally, three suspicious specimens were analyzed by four monotargeted NAT assays and by five dual‐target NAT assays.

RESULTS

Three of 7 million donations tested negative using the 5’LTR–polymerase chain reaction, but they were positive if amplification was performed in the gag region. HIV antibodies were detected in all three donations. Nucleic acid sequence analysis identified a deletion of 22 bases within the 5’LTR probe binding region. Three different ltr‐based monotargeted assays missed two donations, except for a low‐reactive result obtained by one of the assays. In total, the detection rates for HIV‐1–positive donations were 37.5% (3/8) for monotargeted assays and 100% (10/10) for dual‐target assays.

CONCLUSION

The current data demonstrate that dual‐target NAT systems reduce the risk of false‐negative HIV‐1 NAT screening results.
Platelet concentrate supernatants alter endothelial cell mRNA and protein expression patterns as a function of storage length
Authors: Sut Caroline , Hamzeh‐Cognasse Hind , Arthaud Charles‐Antoine , Eyraud Marie‐Ange , Chettab Kamel , Dumontet Charles , Laradi Sandrine , Burnouf Thierry , Garraud Olivier , Cognasse Fabrice
Published: October 2018

BACKGROUND

Platelet transfusions are safe but can nevertheless cause serious adverse reactions (SARs). This study investigated the effects of platelet biological response modifiers (BRMs) that accumulate during storage and are commonly associated with transfusion adverse reactions.

STUDY DESIGN AND METHODS

Endothelial cells (ECs), that is, EA.hy926, were exposed in vitro to supernatants of platelet components (PCs) that had been either implicated or not in SARs. The EC Biology RT2 Profiler PCR Array was used at the same time to study 84 genes related to functions of ECs. Soluble cytokines and surface expression of EC markers were determined by Luminex/enzyme‐linked immunosorbent assay technology and flow cytometry, respectively. Apoptosis and scratch wound assays were performed using IncuCyte technology.

RESULTS

In vitro exposure of EA.hy926 monolayers with Day 0, 1‐2, and 3‐4 stored PC supernatants resulted in decreases in surface expression of markers of ECs. There was differential production of soluble BRMs in the tested cell line. Exposure to the supernatants of PCs that had been implicated in SARs showed a significant difference in the expression of the EC surface markers. EC mediators also responded differently when exposed to PC supernatants of different storage times and PCs involved in SARs.

CONCLUSION

PC supernatants collected at Day 1‐2 activate fewer cell lines of ECs compared with supernatants collected at Day 3‐4. Moreover, PC supernatants involved in SARs appear to alter EC activation compared with the control and storage length.
Towards a Durable Polymeric Internal Coating for Diabatic Sections in Wickless Heat Pipes
Authors: Villa Fabio , Marengo Marco , De Coninck Joël
Published: October 2018

Heat pipe characteristics are linked to the surface properties of the diabatic surfaces, and, in the evaporator, surface properties influence both the onset boiling temperature (TONB) and the critical heat flux (CHF). In this work, the effect of surface wettability in pool boiling heat transfer is studied in order to understand if there could be a path to increment heat pipe thermal performance. This work analyzes the effects of surface wettability on boiling (tested fluid is pure water) and proposes a new super-hydrophobic polymeric coating (De Coninck et al., 2017, “Omniphobic Surface Coatings,” Patent No. WO/2017/220591), which can have a very important effect in improving the heat pipe start-up power load and increasing the thermal performance of heat pipes when the flux is lower than the critical heat flux. The polymeric coating is able to reduce the TONB (−11% from 117 °C to about 104 °C) compared with the uncoated surfaces, as it inhibits the formation of a vapor film on the solid–liquid interface, avoiding CHF conditions up to maximum wall temperature (125 °C). This is realized by the creation of a heterogeneous surface with superhydrophobic surface (SHS) zones dispersed on top of a hydrophilic surface (stainless steel surface). The proposed coating has an outstanding thermal resistance: No degradation of SH properties of the coating has been observed after more than 500 thermal cycles.
Estimation of CO2 Diffusivity in Brine by Use of the Genetic Algorithm and Mixed Kernels-Based Support Vector Machine Model
Authors: Feng Qihong , Cui Ronghao , Wang Sen , Zhang Jin , Jiang Zhe
Published: October 2018

Diffusion coefficient of carbon dioxide (CO2), a significant parameter describing the mass transfer process, exerts a profound influence on the safety of CO2 storage in depleted reservoirs, saline aquifers, and marine ecosystems. However, experimental determination of diffusion coefficient in CO2-brine system is time-consuming and complex because the procedure requires sophisticated laboratory equipment and reasonable interpretation methods. To facilitate the acquisition of more accurate values, an intelligent model, termed MKSVM-GA, is developed using a hybrid technique of support vector machine (SVM), mixed kernels (MK), and genetic algorithm (GA). Confirmed by the statistical evaluation indicators, our proposed model exhibits excellent performance with high accuracy and strong robustness in a wide range of temperatures (273–473.15 K), pressures (0.1–49.3 MPa), and viscosities (0.139–1.950 mPa·s). Our results show that the proposed model is more applicable than the artificial neural network (ANN) model at this sample size, which is superior to four commonly used traditional empirical correlations. The technique presented in this study can provide a fast and precise prediction of CO2 diffusivity in brine at reservoir conditions for the engineering design and the technical risk assessment during the process of CO2 injection.
Solid-source doping by using phosphosilicate glass into p-type bulk Si (100) substrate: Role of the capping SiO2 barrier
Authors: Kikuchi Yoshiaki , Peter Antony , Pawlak Bartlomiej Jan , De Keersgieter An , Eyben Pierre , Horiguchi Naoto , Mocuta Anda
Published: October 2018

Systematic experimental studies on phosphorus diffusion from phosphosilicate glass into the p-type bulk Si (100) substrate with different capping barrier layer thicknesses have been conducted. In both 2- and 5-nm phosphosilicate glass conditions, a thicker SiO2 cap showed a lower sheet resistance and a higher retained phosphorus dose in the Si substrate after 1050 °C 4 s rapid thermal annealing as drive-in annealing. However, the sheet resistance of 2-nm phosphosilicate glass with a 10-nm SiO2 cap was lower than that of 5-nm phosphosilicate glass with a 3-nm SiO2 cap due to a higher retained phosphorus dose in the Si substrate. For a higher retained phosphorus dose in the Si substrate using fixed total thickness, 2-nm phosphosilicate glass with 6-nm SiO2 cap is better than 5-nm phosphosilicate glass with 3-nm SiO2 cap since prevention of phosphorus out-diffusion during the drive-in annealing is more important than the total phosphorus dose in phosphosilicate glass. Next, SiO2 cap thickness on 2-nm phosphosilicate glass was split to understand the role of the SiO2 capping layer in detail for scaled devices. 3-nm SiO2 cap could not prevent out-diffusion during the drive-in annealing, and it showed much higher sheet resistance and lower retained phosphorus dose in the Si substrate. The highest retained phosphorus dose in the Si substrate was observed for 6-nm SiO2 cap and resulted in 1.8 × 1014 atoms/cm2 retained phosphorus dose with 96% activation level after 1050 °C 4 s rapid thermal annealing. Thicker SiO2 caps than 6 nm were not beneficial since 10-nm SiO2 cap showed a higher sheet resistance value as well as lower phosphorus activation level (82%) compared to 6-nm SiO2 cap even though both the process conditions showed same phosphorus profiles after the drive-in annealing. That sheet resistance increase with 10-nm SiO2 cap could be caused by heterogeneous surface formation on the Si substrate with a prolonged SiO2 atomic layer deposition process.
Localization of broadband sounds carrying interaural time differences: Effects of frequency, reference location, and interaural coherence
Authors: Buchholz Jörg M. , Le Goff Nicolas , Dau Torsten
Published: October 2018

The auditory processes involved in the localization of sounds in rooms are still poorly understood. The present study investigated the auditory system's across-frequency processing of interaural time differences (ITDs) and the impact of the interaural coherence (IC) of the stimuli in ITD discrimination and localization. First, ITD discrimination thresholds were measured as a function of signal frequency, reference ITD, and IC using critical-band wide noises. The resulting data were fitted with a set of analytical functions and ITD weights were derived using concepts from signal detection theory. Inspired by the weighted-image model [Stern, Zeiberg, and Trahiotis. (1988). J. Acoust. Soc. Am. 84, 156–165], the derived ITD weights were then integrated in a simplified localization model using an optimal combination of ITD information across frequency. To verify this model, a series of localization experiments were conducted using broadband noise in which ITD and IC were varied across frequency. The model predictions were in good agreement with the experimental data, supporting the assumption that the auditory system performs a weighted integration of ITD information across frequency to localize a sound source. The results could be valuable for the design of new paradigms to measure localization in more complex acoustic conditions and may provide constraints for future localization models.
In Vitro
and
In Vivo
Drug-Drug Interaction Study of the Effects of Ivermectin and Oxantel Pamoate on Tribendimidine
Authors: Neodo Anna , Schulz Jessica D. , Huwyler Jörg , Keiser Jennifer
Published: October 2018

Soil-transmitted helminth (STH) infections still remain a major health problem in poor rural settings. The lack of efficacious drugs against all STH species raises interest in drug combinations.
OXA-48-Like-Producing Klebsiella pneumoniae in Southern Spain in 2014–2015
Authors: Machuca Jesús , López-Cerero Lorena , Fernández-Cuenca Felipe , Mora-Navas Laura , Mediavilla-Gradolph Concepción , López-Rodríguez Inmaculada , Pascual Álvaro
Published: October 2018

The aim of this study was to characterize the population structure of 56 OXA-48-like-producing
Klebsiella pneumoniae
isolates, as well as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, recovered in 2014 and 2015 from 16 hospitals in southern Spain. XbaI pulsed-field gel electrophoresis and multilocus sequence typing were performed to assess clonal relatedness.
Utility of Urine Cultures in Predicting Blood Culture Susceptibilities in Patients with Bacteremic Urinary Tract Infection
Authors: Lam Philip W. , Wiggers J. Bradley , Lo Jennifer , MacFadden Derek R. , Daneman Nick
Published: October 2018

In a review of 428 patients with bacteremic urinary tract infections, urine culture susceptibility results accurately predicted blood culture results when the same organism was isolated from both cultures. Early targeted therapy using urine culture results can potentially reduce broad-spectrum antibiotic exposure and its associated adverse effects and the length of hospitalization.