bluuebunny/crossref_metadata_2025 huggingface dataset:
The lipid elongation enzyme ELOVL2 is a molecular regulator of aging in the retina
Authors: Chen Daniel , Chao Daniel L. , Rocha Lorena , Kolar Matthew , Nguyen Huu Viet Anh , Krawczyk Michal , Dasyani Manish , Wang Tina , Jafari Maryam , Jabari Mary , Ross Kevin D. , Saghatelian Alan , Hamilton Bruce A. , Zhang Kang , Skowronska‐Krawczyk Dorota
Published: January 2020

Methylation of the regulatory region of the elongation of very‐long‐chain fatty acids‐like 2 (ELOVL2) gene, an enzyme involved in elongation of long‐chain polyunsaturated fatty acids, is one of the most robust biomarkers of human age, but the critical question of whether ELOVL2 plays a functional role in molecular aging has not been resolved. Here, we report that Elovl2 regulates age‐associated functional and anatomical aging in vivo, focusing on mouse retina, with direct relevance to age‐related eye diseases. We show that an age‐related decrease in Elovl2 expression is associated with increased DNA methylation of its promoter. Reversal of Elovl2 promoter hypermethylation in vivo through intravitreal injection of 5‐Aza‐2’‐deoxycytidine (5‐Aza‐dc) leads to increased Elovl2 expression and rescue of age‐related decline in visual function. Mice carrying a point mutation C234W that disrupts Elovl2‐specific enzymatic activity show electrophysiological characteristics of premature visual decline, as well as early appearance of autofluorescent deposits, well‐established markers of aging in the mouse retina. Finally, we find deposits underneath the retinal pigment epithelium in Elovl2 mutant mice, containing components found in human drusen, a pathologic hallmark of age related macular degeneration. These findings indicate that ELOVL2 activity regulates aging in mouse retina, provide a molecular link between polyunsaturated fatty acids elongation and visual function, and suggest novel therapeutic strategies for the treatment of age‐related eye diseases.
Associations between oral health and depressive symptoms: Findings from the Concord Health and Ageing in Men Project
Authors: Wright Fredrick A. Clive , Takehara Sachiko , Stanaway Fiona F. , Naganathan Vasi , Blyth Fiona M. , Hirani Vasant , Le Couteur David G. , Handelsman David J. , Waite Louise M. , Seibel Markus J , Cumming Robert G.
Published: January 2020

Objective

To investigate whether poorer oral health, tooth loss and lower usage of dental services are associated with depressive symptoms in older Australian men.

Methods

Cross‐sectional study of data collected from participants of the Concord Health and Ageing in Men Project. Depressive symptoms were evaluated by the Geriatric Depression Scale. Chewing capacity was estimated by ability to chew 11 food items.

Results

The prevalence of depressive symptoms was 17.5%. Self‐evaluated oral health, chewing capacity and the number of natural and decayed teeth were associated with depressive symptoms. After adjusting for multiple confounders, chewing capacity (PR 1.93; 95% CI 1.34‐2.79) and decayed teeth (PR 1.68; 95% CI 1.03‐2.75) maintained a significant association with depressive symptoms.

Conclusion

The direction of causality between oral health and depression is unclear; however, oral health may contribute to depression in older Australian men and depressive symptoms may limit chewing capacity and be aggravated by untreated dental decay.
Role of oxytocin in prevention of postpartum hemorrhage in unplanned out‐of‐hospital deliveries treated by emergency medical services
Authors: Klemettilä Emma , Rahkonen Leena , Nuutila Mika , Lääperi Mitja , Harve-Rytsälä Heini
Published: January 2020

Introduction

Intramuscular or intravenous oxytocin is used in out‐of‐hospital emergency care in Finland to prevent postpartum hemorrhage after unplanned out‐of‐hospital deliveries. However, the use of oxytocin by emergency medical services is based on in‐hospital studies. The aim of this study was to determine whether the use of oxytocin is associated with diminished postpartum hemorrhage after unplanned out‐of‐hospital deliveries.

Material and methods

We studied patient records covering all unplanned out‐of‐hospital deliveries in the Helsinki University Hospital area between 1 January 2013 and 31 December 2017 inclusive. Oxytocin was available in ambulances responsible for half of the population of the study area and was not available in ambulances responsible for the other half. The study area corresponded to 25% of all deliveries in Finland. The primary outcome was the estimated total bleeding (mL). Secondary outcomes were (1) the first blood hemoglobin value measured in hospital (g/L), (2) whether blood hemoglobin was measured during the first 24 hours after delivery, (3) the need for red blood cell concentrate, (4) the need for uterotonic or prothrombotic medication in‐hospital during the first 24 hours, (5) the need for any postpartum operation during the first 24 hours and (6) composite outcome combining the secondary outcomes 2‐5.

Results

Of all ambulance responses in the study area, .04% concerned out‐of‐hospital deliveries. There were 216 analyzed out‐of‐hospital deliveries. Altogether, 111 of these occurred in the area with oxytocin available in ambulances and 105 in the area without. Oxytocin was administered in 57 of the 111 deliveries (51%) where it was available. No differences in the primary outcome (P = .548 for oxytocin available vs not available and P = .381 for oxytocin used vs not used) or secondary outcomes were detected between those deliveries where oxytocin was available vs not available or between those where it was used vs not used.

Conclusions

Out‐of‐hospital oxytocin was not associated with diminished postpartum hemorrhage in this study setting. Oxytocin does not seem to be an essential drug for all ambulance units. The in‐hospital use of oxytocin was not evaluated and thus is not disputed by this study.
Intra‐placental arterial Doppler: A marker of fetoplacental vascularity in late‐onset placental disease?
Authors: Higgins Lucy E. , Heazell Alexander E. P. , Simcox Louise E. , Johnstone Edward D.
Published: January 2020

Introduction

Late‐gestation adverse pregnancy outcome is associated with reduced placental villous vascularity but rarely with a frankly abnormal umbilical artery Doppler waveform. The clinical utility of umbilical artery Doppler velocimetry in late gestation is limited by poor understanding of what aspect(s) of placental structure and function the impedance reflects. We hypothesized that placental arterial circulation impedance reflects placental vascularity and arterial function.

Material and methods

This was a secondary analysis of data from the FEMINA2 study, a study of pregnancy outcome after reduced fetal movement. Forty‐three pregnancies that delivered within 7 days of ultrasound assessment were examined. Impedance was quantified by pulsatility index (PI) from umbilical, chorionic plate arteries, and intra‐placental arteries. Site‐specific PI was compared with villous vascularity (CD31 immunostaining) and placental arterial function (wire myography) by regression analysis (P < .01) where factor analysis suggested potential co‐variance (Eigen value > 2).

Results

Pulsatility index decreased with proximity to the placental microvasculature (P < .0001). Intra‐placental artery PI correlated significantly with vessel number (R2 = 0.40, P = .0007). No significant relations between umbilical or chorionic plate artery PI and villous vascularity were found (P ≥ .11 and P ≥ .042). No significant co‐variance was suggested between PI at any Doppler sampling site and ex vivo placental arterial function indices. Measurement reliability (intraclass correlation coefficient) was highest in the umbilical artery (PI 0.75 and 0.50 for intra‐ and interoperator reliability, respectively) and lowest in the intra‐placental arteries (PI 0.55 and 0.41, respectively). Systematic bias in umbilical artery PI was observed between observers, but not at other Doppler sampling sites.

Conclusions

More vascular placentas ex vivo are associated with reduced intra‐placental artery Doppler impedance in utero. Although umbilical (but not intra‐placental) artery Doppler PI is associated with adverse outcome after reduced fetal movement, this predictive ability does not appear to be through assessment of placental vascularity or chorionic plate arterial function. The inferior reliability of intra‐placental artery Doppler, although similar to previously published reliability of umbilical artery Doppler, impairs its ability to detect subtle differences in placental vascularity, and must be significantly improved before it could be considered a clinically useful test.
When is gossiping wrong? The influence of valence and relationships on children’s moral evaluations of gossip
Authors: Caivano Oksana , Leduc Karissa , Talwar Victoria
Published: January 2020

Gossip is a common social activity that children admit to engaging in. Although children disapprove of negative gossip (Kuttler, Parker, & La Greca, 2002,Merrill‐Palmer Quarterly, 48, 105), less is known about how it is perceived morally compared to positive gossip and how this changes developmentally as children enter adolescence. Interestingly, misbehaviours are evaluated differently depending on who commits the act and whom it targets (Slomkowski & Killen, 1992,International Journal of Behavioral Development, 15, 247), but this has not been examined in the context of gossip. This study examined children’s moral evaluations of negative and positive valence gossip and how this changed depending on the listener’s relationship to the sharer and target. Children (N = 134, ages 8–16) completed vignettes, evaluating the sharer’s action from the listener’s perspective, a 2 (valence: negative/positive) × 4 (relationship type: friend/unfamiliar classmate of the sharer and target) design. Additionally, the gossip topic was about the target’s behaviour with consequences for him/herself or another (target behaviour type: individual/relational vignettes). The main findings revealed that negative gossip in the sharer–classmate, target–friend condition was rated most negatively. Furthermore, in the individual vignettes condition, positive gossip in the sharer–friend, target–friend condition was rated more negatively than the sharer–classmate, target–friend condition. Girls rated negative gossip more negatively than boys, and adolescents rated gossip more positively than children. Overall, this research allows us to better understand when gossip is viewed as acceptable or unacceptable during an important developmental period.

Statement of contribution

What is already known on this subject?

Children gossip about others negatively but disapprove of negative gossip.

Children and adolescents evaluate negative and positive behaviour differently.

Children evaluate transgressions differently depending on who commits them and whom the target is.

What does this study add?

Adolescents believe that positive gossip is more socially acceptable compared to children.

Gossip shared by a classmate that targets a friend is rated negatively.

Girls view negative gossip as less acceptable compared to boys.
Some pedagogical observations on using augmented reality in a vocational practicum
Authors: Lester Stan , Hofmann Jens
Published: January 2020

The use of augmented reality (AR) in vocational education and training can still be considered as being in its infancy, although interest in it is growing in response both to its potential for teaching and its adoption as a practical tool in various industry sectors. One example of early‐stage AR use is illustrated from a practicum for training apprentices in the chemical industry; this involves the use of various AR objects for learning a simple production operation. Although this application had been conceived of purely in terms of substitution for existing instructional methods, it also gave learners greater control of the learning process and created opportunities for collaborative learning. Pedagogically, AR can be considered as a mildly disruptive technology that favours learner managed learning, a factor that is aligned with its ability to support localised decision‐making in industry.

Practitioner Notes

What is already known about this topic

Augmented reality (AR) tends to favour exploratory, learner managed and increasingly, collaborative learning.

Evaluations of AR for vocational learning are on balance positive, with improved understanding, fewer errors and faster task completion or improved learning performance all reported.

AR is still in the early stages of adoption in vocational education and training (VET), with trials and small‐scale applications dominating.

What this paper adds

Introducing AR even for simple learning tasks affects the pedagogical approaches that are used.

Effects include greater learner control of the learning process and encouragement of reflection‐in‐action.

Implications for practice and/or policy

AR is a mildly disruptive technology that needs to be considered in terms of its pedagogical implications as well as its effectiveness as a learning tool.

The directions favoured by AR in education and training appear consistent with changing skill and learning demands in industry.
Trajectories of Online Racial Discrimination and Psychological Functioning Among African American and Latino Adolescents
Authors: Tynes Brendesha M. , English Devin , Del Toro Juan , Smith Naila A. , Lozada Fantasy T. , Williams David R.
Published: January 2020

This study investigated trajectories of individual and vicarious online racial discrimination (ORD) and their associations with psychological outcomes for African American and Latinx adolescents in 6th–12th grade (N = 522;Mgrade = 9th) across three waves. Data were analyzed using growth mixture modeling to estimate trajectories for ORD and to determine the effects of each trajectory on Wave 3 depressive symptoms, anxiety, and self‐esteem. Results showed four individual and three vicarious ORD trajectories, with the majority of participants starting out with low experiences and increasing over time. Older African American adolescents and people who spend more time online are at greatest risk for poor psychological functioning.
Nicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice
Authors: Li Cheng‐Cheng , Chen Wei‐Xiang , Wang Jie , Xia Min , Jia Zheng‐Cai , Guo Chao , Tang Xiao‐Qin , Li Ming‐Xi , Yin Yi , Liu Xin , Feng Hua
Published: January 2020

Aims

Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated.

Methods

To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang ‐, and NR was added to the food of the mice for 28 days. Then, short‐term memory, blood‐brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated.

Results

Our data showed that mice infused with Ang ‐ exhibited decreased short‐term memory function and BBB leakage due to decreased claudin‐5 expression and increased caveolae‐mediated endocytosis after 28 days. Furthermore, Ang ‐ decreased the expression of α‐smooth muscle actin (α‐SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD‐related damages induced by Ang ‐ were inhibited by NR administration. Moreover, NR administration significantly reduced glial activation around the vessels.

Conclusion

Our results indicated that NR administration alleviated Ang ‐–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.
Comparison of bowel dysfunction between colorectal cancer survivors and a non‐operative non‐cancer control group
Authors: Keane C. , O’Grady G. , Bissett I. , Woodfield J.
Published: January 2020

Aim

Low anterior resection syndrome (LARS) detrimentally affects quality of life in colorectal cancer survivors. This study assessed the prevalence for LARS in colorectal cancer survivors and the same symptoms in a matched control group.

Method

Validated instruments, the LARS score and Short Form Survey 12, used to collect functional and quality of life outcomes from patients who had undergone distal colorectal resection at Auckland Hospital (2008–2015) or Dunedin Hospital (2008–2017). A matched non‐operative control group was drawn from patients undergoing surveillance colonoscopy.

Results

The response rate was 79%. Cross‐sectional prevalence of major LARS in rectal cancer patients was 52% at a median follow‐up of 52 months. Major LARS prevalence in the sigmoid cancer resection and non‐cancer control groups was similar (25% vs 26%, P = 0.6). On univariate analysis anastomotic height [risk ratio (RR) for low anterior resection 4.6, P < 0.001; ultralow anterior resection RR = 15.5, P < 0.001], radiotherapy (RR = 2.6; P = 0.009), stoma (RR = 3.6; P = 0.001) and J pouch reconstruction (vs straight anastomosis, RR = 4.6; P = 0.008) were associated with major LARS for rectal cancer patients. These factors were not significant when the analysis was stratified for anastomotic height. Despite correlation between LARS and Short Form Survey 12 outcomes (physical ρ = −0.2; mental ρ = −0.2) there was no difference in quality of life outcomes between the groups.

Conclusion

Bowel dysfunction after low anterior resection affects the majority of rectal cancer patients. The high background rate of bowel dysfunction must be considered when assessing the prevalence of LARS.
Co‐overexpression of VEGF and GDNF in adipose‐derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model
Authors: Yang Wende , Chen Zehong , Ma Xiaolei , Ouyang Xi , Fang Jiafeng , Wei Hongbo
Published: January 2020

Objectives

To evaluate the rapid repair potential of adipose‐derived stem cells (ADSCs) co‐overexpressing VEGF and GDNF on bilateral cavernous nerve injury (BCNI) in rat models. Progressive fibrosis of the penis that occurs shortly after BCNI is a key cause of clinical treatment difficulty of erectile dysfunction (ED). Traditional medications are ineffective for ED caused by BCNI. ADSCs have shown therapeutic effects in animal models, but disappointing in clinical treatment suggests that we should explore optimal treatment of it.

Materials and methods

We extracted ADSCs from rat epididymis. Lentiviral transfection was verified by western blot and immunofluorescence. Thirty‐six SD rats (10 weeks old) were randomly divided into six groups (n = 6 per group): sham surgery, and remaining five BCNI groups transplanted PBS or ADSCs which were genetically modified by vehicle, VEGF (ADSC‐V), GDNF (ADSC‐G), or VEGF&GDNF (ADSC‐G&V) around major pelvic ganglion (MPG). We investigated the therapeutic effects of BCNI rat model which is characterized by ED, penile tissue fibrosis and hypoxia, and lack of nitrogen nerves or vascular atrophy.

Results

Erectile function was almost recovered after 2 weeks of transplantation of ADSC‐G&V, promoted cavernous nerve repair, prevented penile fibrosis and preserving the vascular endothelium, which was significant differences amongst ADSC‐V or ADSC‐G. Moreover, GM‐ADSCs were detected in MPG and penis, indicating that their participation in repair of target organs and transverse nerves.

Conclusions

These promising data indicate that ADSCs co‐overexpressed VEGF and GDNF‐induced synergistic effects, make it a potential tool for recovering of erectile function speedily after BCNI.
Effectiveness of a marine conservation education program in Okayama, Japan
Authors: Sakurai Ryo , Uehara Takuro
Published: January 2020

Sustainable management of coastal areas including their natural resources cannot be effectively implemented without the continued involvement of residents who are knowledgeable about the value of conservation. Carrying out long‐term conservation education programs and monitoring the impacts of such program in terms of changing people's awareness and behaviors are critical for conservation to be meaningful and sustainable. This research focused on a marine conservation education program (MCEP) offered at a junior high school in Japan that included collaboration with local fishermen. We aimed to reveal how such continuous and collaborative education program including field experience may change students' awareness and behaviors after several years. We conducted interviews with student participants, comparing their perceptions of when they were first‐graders and third‐graders, and with recent program graduates to understand their perception of the program and knowledge about the local environment. We also conducted surveys with parents and teachers at the junior high school to understand the impacts of the program. A series of studies revealed that the MCEP not only changed students' awareness and behaviors but also affected their parents and teachers.
Domain‐specific contributions of biological sex and sex hormones to what, where and when components of episodic‐like memory in adult rats
Authors: Conner Meagan R. , Adeyemi Oluwadamilola M. , Anderson Brenda J. , Kritzer Mary F.
Published: January 2020

Episodic memory involves the integration and recall of discrete events that include information about what happened, where it happened and when it occurred. Episodic memory function is critical to daily life, and its dysfunction is both a first identifiable indicator and an enduring core feature of cognitive decline in ageing and in neuropsychiatric disorders including Alzheimer's disease and schizophrenia. Available evidence from human studies suggests that biological sex and sex hormones modulate episodic memory function in health and disease. However, knowledge of how this occurs is constrained by the limited availability and underutilization of validated animal models in investigating hormone impacts on episodic‐like memory function. Here, adult female, adult male and gonadally manipulated adult male rats were tested on the what–where–when episodic‐like memory task to determine whether rats model human sex differences in episodic memory and how the hormonal milieu impacts episodic‐like memory processes in this species. These studies revealed salient ways in which rats model human sex differences in episodic memory, including a male advantage in spatial episodic memory performance. They also identified domain‐specific roles for oestrogens and androgens in modulating what, where and when discriminations in male rats that were unlike those engaged in corresponding novel object recognition and novel object location tasks. These studies thus identify rats and the what–where–when task as suitable for investigating the neuroendocrine bases of episodic‐like memory, and provide new information about the unique contributions that sex and sex hormones make to this complex mnemonic process.
Development and validation of genetic markers for sex and cannabinoid chemotype in Cannabis sativa L.
Authors: Toth Jacob A. , Stack George M. , Cala Ali R. , Carlson Craig H. , Wilk Rebecca L. , Crawford Jamie L. , Viands Donald R. , Philippe Glenn , Smart Christine D. , Rose Jocelyn K. C. , Smart Lawrence B.
Published: January 2020

Hemp (Cannabis sativa L.) is an emerging dioecious crop grown primarily for grain, fiber, and cannabinoids. There is good evidence for medicinal benefits of the most abundant cannabinoid in hemp, cannabidiol (CBD). For CBD production, female plants producing CBD but not tetrahydrocannabinol (THC) are desired. We developed and validated high‐throughput PACE (PCR Allele Competitive Extension) assays for C. sativa plant sex and cannabinoid chemotype. The sex assay was validated across a wide range of germplasm and resolved male plants from female and monoecious plants. The cannabinoid chemotype assay revealed segregation in hemp populations, and resolved plants producing predominantly THC, predominantly CBD, and roughly equal amounts of THC and CBD. Cultivar populations that were thought to be stabilized for CBD production were found to be segregating phenotypically and genotypically. Many plants predominantly producing CBD accumulated more than the current US legal limit of 0.3% THC by dry weight. These assays and data provide potentially useful tools for breeding and early selection of hemp.
Caries removal strategies for deep carious lesions in primary teeth: Systematic review
Authors: Aïem Elody , Joseph Clara , Garcia Anaïs , Smaïl‐Faugeron Violaine , Muller‐Bolla Michèle
Published: January 2020

The study aimed to compare the efficacy of three caries removal techniques—complete caries removal (CCR), selective caries removal (SCR), and stepwise caries removal (SWR)—for deep carious lesions in vital temporary teeth by conducting a systematic review and meta‐analysis of randomized controlled trials (RCTs). Electronic databases (PubMed [MEDLINE], Cochrane Library, EMBASE) were searched for corresponding references up to 31 May 2019. Possible outcomes were pulp exposure, pulpo‐periodontal complications, or restorative failures. Three reviewers independently selected studies, extracted data, and assessed the risk of bias using RoB 2. Meta‐analyses for intention‐to‐treat and per‐protocol scenarios were performed using Revman5. Of 1374 potentially eligible articles, ten relevant references corresponding to eight studies were included. Pooled results showed decreased risk of pulp exposure after SCR (OR: 0.10, 95% CI [0.04, 0.25]) or SWR (OR: 0.20, 95% CI [0.09, 0.44]), compared with CCR. There was a higher risk of composite restorative failure (OR: 2.61, 95% CI [1.05, 6.49]) using USPHS criteria, after SCR compared with CCR only in intention‐to‐treat analysis. Risk of clinical or radiographic failure of pulpo‐periodontal complications was unchanged when compared with SCR and CCR or SWR. SCR and SWR may result in lower pulp exposure risk than CCR. RCTs with lower risk of bias, higher power, and longer follow‐up are required to choose between these three caries removal techniques for deep carious lesions in vital temporary teeth.
Atomistic understanding of surface wear process of sodium silicate glass in dry versus humid environments
Authors: Hahn Seung Ho , Liu Hongshen , Kim Seong H. , van Duin Adri C. T.
Published: January 2020

Understanding surface reactions of silicate glass under interfacial shear is critical as it can provide physical insights needed for rational design of more durable glasses. Here, we performed reactive molecular dynamics (MD) simulations with ReaxFF potentials to study the mechanochemical wear of sodium silicate glass rubbed with amorphous silica in the absence and presence of interfacial water molecules. The effect of water molecules on the shear‐induced chemical reaction at the sliding interface was investigated. The dependence of wear on the number of interfacial water molecules in ReaxFF‐MD simulations was in reasonable agreement with the experimental data. Confirming this, the ReaxFF‐MD simulation was used to find further details of atomistic reaction dynamics that cannot be obtained from experimental investigations only. The simulation showed that the severe wear in the dry condition is due to the formation of interfacial Sisubstrate–O–Sicounter_surface bond that convey the interfacial shear stress to the subsurface and the presence of interfacial water reduces the interfacial bridging bond formation. The leachable sodium ions facilitate surface reactions with water‐producing hydroxyl groups and their key role in the hydrolysis reaction is discussed.
Simultaneous multicolour imaging using quantum dot structured illumination microscopy
Authors: ZENG HUI , YANG HUAIDONG , LIU GUOXUAN , ZHANG SICHUN , ZHANG XINRONG , ZHANG YINXIN
Published: January 2020

Multicolour structured illumination microscopy (SIM) is a powerful tool used for the investigation of the dynamic interaction between subcellular structures. Nevertheless, most of the multicolour SIM schemes are currently limited by conventional fluorescent dyes and wavelength‐dependent optical systems, and can only sequentially record images of different colour channels instead of obtaining multicolour datasets simultaneously. To address these issues, we present a novel multicolour SIM scheme referred to as quantum dot structured illumination microscopy (QD‐SIM). QD‐SIM enables simultaneously excitation and collection of multicolour fluorescent signals. We also propose a theoretical analysis of the image formation in two‐dimensional multicolour SIM to help combine the optically sectioned and super‐resolution attributes of SIM. Based on this theory, QD‐SIM enables optically sectioned, super‐resolution, multicolour simultaneous imaging at a single plane.
A simple, versatile and robust centrifugation‐based filtration protocol for the isolation and quantification of α‐synuclein monomers, oligomers and fibrils: Towards improving experimental reproducibility in α‐synuclein research
Authors: Kumar Senthil T. , Donzelli Sonia , Chiki Anass , Syed Muhammed Muazzam Kamil , Lashuel Hilal A.
Published: January 2020

Increasing evidence suggests that the process of alpha‐synuclein (α‐syn) aggregation from monomers into amyloid fibrils and Lewy bodies, via oligomeric intermediates plays an essential role in the pathogenesis of different synucleinopathies, including Parkinson's disease (PD), multiple system atrophy and dementia with Lewy bodies (DLB). However, the nature of the toxic species and the mechanisms by which they contribute to neurotoxicity and disease progression remain elusive. Over the past two decades, significant efforts and resources have been invested in studies aimed at identifying and targeting toxic species along the pathway of α‐syn fibrillization. Although this approach has helped to advance the field and provide insights into the biological properties and toxicity of different α‐syn species, many of the fundamental questions regarding the role of α‐syn aggregation in PD remain unanswered, and no therapeutic compounds targeting α‐syn aggregates have passed clinical trials. Several factors have contributed to this slow progress, including the complexity of the aggregation pathways and the heterogeneity and dynamic nature of α‐syn aggregates. In the majority of experiment, the α‐syn samples used contain mixtures of α‐syn species that exist in equilibrium and their ratio changes upon modifying experimental conditions. The failure to quantitatively account for the distribution of different α‐syn species in different studies has contributed not only to experimental irreproducibility but also to misinterpretation of results and misdirection of valuable resources. Towards addressing these challenges and improving experimental reproducibility in Parkinson's research, we describe here a simple centrifugation‐based filtration protocol for the isolation, quantification and assessment of the distribution of α‐syn monomers, oligomers and fibrils, in heterogeneous α‐syn samples of increasing complexity. The protocol is simple, does not require any special instrumentation and can be performed rapidly on multiple samples using small volumes. Here, we present and discuss several examples that illustrate the applications of this protocol and how it could contribute to improving the reproducibility of experiments aimed at elucidating the structural basis of α‐syn aggregation, seeding activity, toxicity and pathology spreading. This protocol is applicable, with slight modifications, to other amyloid‐forming proteins.

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The efficacy and safety of high‐intensity focused ultrasound on upper arm laxity treatment: Our experience with five patients
Authors: Asiran Serdar Zehra , Tukenmez Demirci Gulsen
Published: January 2020

Background

High‐intensity focused ultrasound is approved by FDA for both upper face and lower face, neck laxity and for decollete rejuvenation. It produces micro‐focused thermal damage on the dermis and superficial muscular aponeurotic system layer at precise depth and with this thermal stimulus the collagen denaturation and subsequent neo‐collagenosis occur. High‐intensity focused ultrasound (HIFU) effects on body laxity has also been used in some studies but it has not been approved yet.

Aims

To find out the efficacy of HIFU for the treatment of upper under arm laxity.

Patients/Methods

We used HIFU device with the new transducers; 13 mm depth 4 MHz and 2J for under arm laxity for 5 patients.

Results

All patients showed a clinical improvement according to the physicians and patients assessment scales. The side effects were mild erythema and edema during the treatment and tenderness which lasted in 10 days. We follow up our patients in a one year period, and there were no side effects.

Conclusion

HIFU can be used for upper arm laxity treatment with the new transducers developed for body areas.
Sanguinarine metabolism and pharmacokinetics study in vitro and in vivo
Authors: Wu Yong , Zhao Na‐Jiao , Cao Yan , Sun Zhuo , Wang Qin , Liu Zhao‐Ying , Sun Zhi‐Liang
Published: January 2020

Sanguinarine (SA) is a benzo[c] phenanthridine alkaloid which has a variety of pharmacological properties. However, very little was known about the pharmacokinetics of SA and its metabolite dihydrosanguinarine (DHSA) in pigs. The purpose of this work was to study the intestinal metabolism of SA in vitro and in vivo. Reductive metabolite DHSA was detected during incubation of SA with intestinal mucosa microsomes, cytosol, and gut flora. After oral (p.o.) administration of SA, the result showed SA might be reduced to DHSA in pig intestine. After i.m. administration, SA and DHSA rapidly increased to reach their peak concentrations (Cmax, 30.16 ± 5.85, 5.61 ± 0.73 ng/ml, respectively) at 0.25 hr. Both compounds were completely eliminated from the plasma after 24 hr. After single oral administration, SA and DHSA rapidly increased to reach their Cmax (3.41 ± 0.36, 2.41 ± 0.24 ng/ml, respectively) at 2.75 ± 0.27 hr. The half‐life (T1/2) values were 2.33 ± 0.11 hr and 2.20 ± 0.12 hr for SA and DHSA, respectively. After multiple oral administration, the average steady‐state concentrations (Css) of SA and DHSA were 3.03 ± 0.39 and 1.42 ± 0.20 ng/ml. The accumulation indexes for SA and DHSA were 1.21 and 1.11. The work reported here provides important information on the metabolism sites and pharmacokinetic character of SA. It explains the reasons for low toxicity of SA, which is useful for the evaluation of its performance.
Diabetes after pregnancy prevention trials: Systematic review for core outcome set development
Authors: O'Reilly Sharleen L. , Leonard Yvonne , Dasgupta Kaberi , Terkildsen Maindal Helle
Published: January 2020

Diabetes prevention intervention studies in women with previous gestational diabetes have increased, but no consensus exists on core outcomes to support comparisons and synthesis of findings. We aimed to systematically catalogue outcomes in diabetes after pregnancy prevention interventions with the goal of developing a core outcome set. Embase, Medline, Cochrane Library, Cochrane Pregnancy and Childbirth Trials Register, and CINAHL were searched from inception to October 2017. Post‐partum lifestyle and diabetes screening intervention studies in women with previous gestational diabetes and/or their families were eligible. No limits were placed on intervention type, duration, or location. Two authors independently screened and performed data extraction on outcomes, measurement tools, and relevant study characteristics. We analysed data from 38 studies (29 randomised controlled trials and 9 pre–post intervention evaluations) comprising 12,509 participants. Most publications (80%) occurred between the years 2012 and 2017. Among 172 outcomes, we identified 36 outcome groups and classified them under three domains: health status (body weight, body composition, diabetes risk, cardiometabolic risk, diabetes development, mental health, pregnancy outcomes, and fitness), health behaviours (dietary, physical activity, diabetes screening, behaviour change, and breastfeeding), and intervention processes (implementation). The health status domain contained the most commonly reported outcomes, but measurement tools were very heterogeneous.

Despite the recent explosion in diabetes after pregnancy prevention studies, large variation in outcomes and measurement methods exists. Research is needed to define a core outcome set to standardise diabetes after pregnancy prevention interventions. The core outcome set should engage a wide group of stakeholders to identify impactful indicators for future trials.
The Humanitarian as Negotiator: Developing Capacity Across the Aid Sector
Authors: Grace Rob
Published: January 2020

This article examines the dynamics at play in ongoing efforts to cultivate negotiation capacity among professionals working in the humanitarian sector. Based on extensive semi‐structured interviews conducted with humanitarian practitioners, this article discusses six particular challenges that aid agencies face. The first is raising awareness across the aid sector that negotiation is a core competency of humanitarian action. The second is grappling with ambiguities around the definition of the term “humanitarian negotiation.” The third is cultivating an appreciation for the holistic range of negotiation capital that is necessary for success. The fourth is navigating the difficulties inherent in the experiential nature of negotiation capacity building. The fifth is discerning which lessons should be learned from past humanitarian negotiation practice. The sixth is mitigating negative unintended effects of directing professional and policy attention toward humanitarian negotiation capacity building. Through this examination, the article aims to assess the landscape of current humanitarian negotiation capacity‐building efforts, as well as the difficulties that humanitarian organizations will likely face on the road ahead.
Behind the Curtain: Syria’s 1979 Mediation in the Yemen Dispute
Authors: Lee Su‐Mi
Published: January 2020

The literature on international mediation emphasizes the crucial role that mediator impartiality and interest play in a mediation's success. Building on this literature and focusing on the case of Syria's role in resolving the Yemen dispute, my research seeks to demonstrate how a mediator's relationship with an external actor can change the level of the mediator's impartiality and interest and, ultimately, the mediation outcome. Syria's first attempt in 1979 to resolve the Yemen dispute through mediation failed, but its second attempt in the same year was successful. This article describes how Syria's relations with the Soviet Union changed the level of Syria's interest and impartiality toward the dispute between North Yemen and South Yemen. It also explores how and why the Soviets clandestinely helped Syria to become an effective mediator for the dispute. Drawing upon the lessons of this case, I discuss how external factors other than a mediator's bilateral relations with the parties can increase the mediator's impartiality and interest in a dispute.
Plant functional groups associate with distinct arbuscular mycorrhizal fungal communities
Authors: Davison John , García de León David , Zobel Martin , Moora Mari , Bueno C. Guillermo , Barceló Milagros , Gerz Maret , León Daniela , Meng Yiming , Pillar Valerio D. , Sepp Siim‐Kaarel , Soudzilovaskaia Nadejda A. , Tedersoo Leho , Vaessen Stijn , Vahter Tanel , Winck Bruna , Öpik Maarja
Published: January 2020

The benefits of the arbuscular mycorrhizal (AM) symbiosis between plants and fungi are modulated by the functional characteristics of both partners. However, it is unknown to what extent functionally distinct groups of plants naturally associate with different AM fungi.

We reanalysed 14 high‐throughput sequencing data sets describing AM fungal communities associating with plant individuals (2427) belonging to 297 species. We examined how root‐associating AM fungal communities varied between plants with different growth forms, photosynthetic pathways, CSR (competitor, stress‐tolerator, ruderal) strategies, mycorrhizal statuses and N‐fixing statuses.

AM fungal community composition differed in relation to all studied plant functional groups. Grasses, C4 and nonruderal plants were characterised by high AM fungal alpha diversity, while C4, ruderal and obligately mycorrhizal plants were characterised by high beta diversity. The phylogenetic diversity of AM fungi, a potential surrogate for functional diversity, was higher among forbs than other plant growth forms. Putatively ruderal (previously cultured) AM fungi were disproportionately associated with forbs and ruderal plants. There was phylogenetic correlation among AM fungi in the degree of association with different plant growth forms and photosynthetic pathways.

Associated AM fungal communities constitute an important component of plant ecological strategies. Functionally different plants associate with distinct AM fungal communities, linking mycorrhizal associations with functional diversity in ecosystems.
Bifocal or Trifocal (Double‐Level) Bone Transport Using Unilateral Rail System in the Treatment of Large Tibial Defects Caused by Infection: A Retrospective Study
Authors: Yushan Maimaiaili , Ren Peng , Abula Abulaiti , Alike Yamuhanmode , Abulaiti Alimujiang , Ma Chuang , Yusufu Aihemaitijiang
Published: January 2020

Objective

The aim of this study is to assess the clinical results of bifocal or trifocal bone transport using unilateral rail system in the treatment of large tibial defects caused by infection.

Methods

There were a total of 37 eligible patients with an average age of 40.11 ± 10.32 years (range, 18–57 years; 28 males and nine females) with large tibial defects due to infection who were admitted to our hospital from June 2006 to June 2016. Among the patients, 21 underwent bifocal bone transport (BF group), and the remaining 16 were treated with trifocal bone transport (TF group). The demographic data (age, sex, interval duration before bone transport, previous operation time), intraoperative outcomes (size and location of the defect, size of soft tissue defect), postoperative variables (lengthening speed, external fixation index, duration of regenerate consolidation and docking union), postoperative bone and functional outcomes evaluated by Association for the Study and Application of the Method of Ilizarov (ASAMI) scoring system, and postoperative complications evaluated by Paley classification (muscle contraction, axial deviation, delayed consolidation, pin problems, repeated fracture, joint stiffness and others) of the two groups were recorded and compared at a minimum follow‐up of 24 months.

Results

The mean duration of follow‐up after removal of fixator was 29.49 ± 4.34 months (range, 24–38 months). There was no statistically significant difference in the demographic data, intraoperative outcomes including size and location of the defect, size of soft tissue defect, as well as postoperative complications. However, postoperative functional result in the TF group were superior to those in the BF group at a minimum follow‐up of 24 months, and lengthening speed, external fixation index (EFI), duration of regenerate consolidation and docking union were significantly reduced in the TF group when compared with the BF group.

Conclusions

Treatment of large tibial defects caused by infection with trifocal bone transport using unilateral rail system could significantly improve postoperative functional recovery and reduce duration of regenerate consolidation and docking union. The present study provides novel insight for the treatment of large tibial defects caused by infection.
Benefits of baked milk oral immunotherapy in French children with cow's milk allergy
Authors: Gruzelle Vianney , Juchet Agnès , Martin‐Blondel Audrey , Michelet Marine , Chabbert‐Broue Anne , Didier Alain
Published: January 2020

Background

Introduction and gradual incremental escalation of a low dose of baked milk may accelerate the resolution of severe cow's milk (CM) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked milk oral immunotherapy (OIT) in children with CM allergy after a low‐dose baked milk oral food challenge (OFC).

Methods

In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 64 children with CM allergy and high milk and casein‐specific IgE levels, who underwent a total of 171 milk OFC. Mean age at 1st OFC was 4.8 years. Mean CM‐specific IgE was 47.9 kUA/L, and mean casein‐specific IgE was 42.3 kUA/L.

Results

Most children were treated with baked milk OIT. Our study shows that 67.2% of the children did not react to 1st low‐dose baked milk OFC (168.6 mg of CM protein). Eighteen percent of children stopped the OIT at home. Finally, desensitization to fresh milk was achieved in 27 children (42.2% of children allergic to CM). Children with lower CM‐specific IgE levels have a significantly higher probability of becoming desensitized to unbaked CM.

Conclusion

Most children with CM allergy and high milk and casein‐specific IgE levels tolerate the introduction of baked milk. However, the occurrence of anaphylactic reactions during OIT remains possible.
Percutaneously Inserted Unilateral Lead Migration Salvaged with a Paddle Electrode
Authors: Oh Byeong Ho , Kim Hyeon Tae , Yim Kyoung Hoon , Park Young Seok
Published: January 2020

Introduction

Lead migration has been regarded as a frequent complication after percutaneous spinal cord stimulation (SCS). Thus far, repeated reinsertion of leads or replacement of paddle electrodes after removing percutaneous leads has been performed, but a salvage surgical technique using the remaining electrode has not been reported. Here, we describe a case in which unilateral lead migration was successfully treated with the insertion of a paddle electrode.

Case Summary

A 44‐year‐old male paraplegic patient with chronic neuropathic pain in the right leg and low back for 7 years underwent a percutaneous spinal cord stimulation procedure 5 times over 2 years because of repeated unilateral lead migration. The left lead underwent repeated migration and was difficult to reinsert due to epidural adhesion. After confirming the position and stimulation area of the remaining lead, we decided to insert another paddle electrode beside the remaining lead. We performed a T10 laminotomy and inserted a paddle electrode on the right side, using it in combination with the previous left lead. After surgery, the patient was satisfied with a wide coverage area.

Discussion

We recommend salvage additional paddle electrode insertion rather than removing both leads during revision SCS. This surgical method increases the possibility of covering the dorsal column (DC) of the spinal cord, is cost effective, and decreases the possibility of failing to cover dorsal column using the paddle electrode during open surgery because the remaining lead’s position and stimulation area guide the insertion of the additional paddle lead.