bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol consumption and sedation are altered in mice lacking the glycine receptor α2 subunit
Authors: San Martin Loreto , Gallegos Scarlet , Araya Anibal , Romero Nicol , Morelli Giovanni , Comhair Joris , Harvey Robert J. , Rigo Jean‐Michel , Brone Bert , Aguayo Luis G.
Published: May 2020

Background and Purpose

The precise mechanism/s of action of ethanol, although studied for many years, are not well understood. Like other drugs of abuse, ethanol affects dopamine levels in the nucleus accumbens (nAc), an important region of the mesolimbic system, causing a reinforcing effect. It has been shown that glycine receptors (GlyRs) present in the nAc are potentiated by clinically relevant concentrations of ethanol, where α1 and α2 are the predominant subunits expressed.

Experimental Approach

Using a combination of electrophysiology and behavioural assays, we studied the involvement of GlyR α2 subunits on the effects of low and high doses of ethanol, as well as on consumption using mice lacking the GlyR α2 subunit (maleGlra2−/Yand femaleGlra2−/−).

Key Results

GlyR α2 subunits exist in accumbal neurons, since the glycine‐evoked currents and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) inGlra2−/Ymice were drastically decreased. In behavioural studies, differences in ethanol consumption and sedation were observed between wild‐type (WT) andGlra2knockout (KO) mice. Using the drinking in the dark (DID) paradigm, we found thatGlra2−/Ymice presented a binge‐like drinking behaviour immediately when exposed to ethanol rather than the gradual consumption seen in WT animals. Interestingly, the effect of knocking outGlra2in female (Glra2−/−) mice was less evident, since WT female mice already showed higher DID.

Conclusion and Implications

The differences in ethanol consumption between WT and KO mice provide additional evidence supporting the conclusion that GlyRs are biologically relevant targets for the sedative and rewarding properties of ethanol.
Extracellular vesicle long non–coding RNA‐mediated crosstalk in the tumor microenvironment: Tiny molecules, huge roles
Authors: Zhang Wei‐long , Liu Yan , Jiang Jian , Tang Ya‐Jie , Tang Ya‐ling , Liang Xin‐hua
Published: May 2020

Emerging evidence has shown that dynamic crosstalk among cells in the tumor microenvironment modulates the progression and chemotherapeutic responses of cancer. Extracellular vesicles comprise a crucial form of intracellular communication through horizontal transfer of bioactive molecules, including long non–coding RNA (lncRNA), to neighboring cells. Three main types of extracellular vesicles are exosomes, microvesicles and apoptotic bodies, exhibiting a wide range of sizes and different biogenesis. Over the last decade, dysregulation of extracellular vesicle lncRNA has been revealed to remodel the tumor microenvironment and induce aggressive phenotypes of tumor cells, thereby facilitating tumor growth and development. This review will focus on extracellular vesicle lncRNA‐mediated crosstalk between tumor cells and recipient cells, including tumor cells as well as stromal cells in the tumor microenvironment, and overview the mechanisms by which lncRNA are selectively sorted into extracellular vesicles, which may pave the way for their clinical application in cancer diagnosis and treatment.
Experience‐Driven Semantic Differentiation: Effects of a Naturalistic Experience on Within‐ and Across‐Domain Differentiation in Children
Authors: Vales Catarina , States Sarah L. , Fisher Anna V.
Published: May 2020

Organized semantic networks reflecting distinctions within and across domains of knowledge are critical for higher‐level cognition. Thus, understanding how semantic structure changes with experience is a fundamental question in developmental science. This study probed changes in semantic structure in 4–6 year‐old children (N = 29) as a result of participating in an enrichment program at a local botanical garden. This study presents the first direct evidence that (a) the accumulation of experience with items in a domain promoted increases in both within‐ and across‐domain semantic differentiation, and that (b) this experience‐driven semantic differentiation generalized to nonexperienced items. These findings have implications for understanding the role of experience in building semantic networks, and for conceptualizing the contribution of enrichment experiences to academic success.
Association of endocrine active environmental compounds with body mass index and weight loss following bariatric surgery
Authors: Deshmukh Harshal , Aylward Lesa L. , Rose Martin , Fernandes Alwyn , Sedman Peter , Thatcher Natalie J. , Atkin Stephen L. , Sathyapalan Thozhukat
Published: May 2020

Introduction

The objective of this study was to study associations of a wide range of halogenated biphenyls, dibenzo‐p‐dioxins, dibenzofurans and diphenylethers with body mass index (BMI) and evaluate changes in their concentration following bariatric surgery.

Methods

Subcutaneous fat, visceral fat and liver tissue samples were collected from 106 patients undergoing Roux‐en‐Y gastric bypass surgery for weight loss or patients who were undergoing abdominal surgery for nonbariatric reasons. We measured concentrations of an extensive panel of chlorinated and brominated biphenyls, dioxins, and furans, and brominated diphenylethers in the samples. We conducted linear regression to examine associations with BMI, adjusting for age and gender. Changes in concentration for indicator chemicals were evaluated in samples collected following bariatric surgery in a small subpopulation.

Results

After adjustments for age and gender and correction for multiple testing, seven ortho‐chlorinated biphenyls, one nonortho‐chlorinated biphenyl, four PCDD/Fs and one ortho‐brominated biphenyl were associated with BMI. The strongest associations between BMI and lipid‐adjusted concentrations were seen with PCB‐105 in subcutaneous fat (beta = 16.838 P‐val = 1.45E‐06) PCB‐126 in visceral fat (beta = 15.067 P‐val = 7.72E‐06) and PCB‐118 (beta = 14.101 P‐val = 2.66E‐05) in liver. The concentrations of sum PCBs, chlorinated toxic equivalent quantity (TEQ's) and brominated compounds increased significantly with weight loss in subcutaneous fat in a group of ten individuals resampled up to five years after bariatric surgery and substantial weight loss.

Conclusion

We show that selected polychlorinated biphenyls PCBs and structurally related polychlorinated dibenzo‐p‐dioxins dibenzofurans (PCDD/Fs) were associated with BMI. Concentrations of these lipophilic compounds in subcutaneous fat increased following bariatric surgery.
Long‐term results of a randomized study comparing parathyroidectomy with cinacalcet for treating tertiary hyperparathyroidism
Authors: Moreno Pablo , Coloma Ana , Torregrosa José V. , Montero Nuria , Francos José , Codina Sergi , Manonelles Anna , Bestard Oriol , García‐Barrasa Arantxa , Melilli Edoardo , Cruzado Josep M.
Published: May 2020

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplantation (KT) and has been associated with renal dysfunction, bone mineral density loss, and increased risk of fracture and cardiovascular events. In a previous 12‐month clinical trial, we demonstrated that subtotal parathyroidectomy was more effective than cinacalcet for controlling hypercalcemia. In the current study, we retrospectively evaluate whether this effect is maintained after 5 years of follow‐up. In total, 24 patients had data available at 5 years, 13 in the cinacalcet group and 11 in the parathyroidectomy group. At 5 years, 7 of 11 patients (64%) in the parathyroidectomy group and 6 of 13 patients (46%) in the cinacalcet group (P = .44) showed normocalcemia. However, recurrence of hypercalcemia was only observed in the cinacalcet group (P = .016). Subtotal parathyroidectomy retained a greater reduction in intact parathyroid hormone (iPTH) compared with cinacalcet group. No differences were observed in kidney function and incidence of fragility fractures between both groups. Cinacalcet was discontinued in 5 out of 13 patients. In conclusion, in kidney transplant patients with tertiary hyperparathyroidism recurrence of hypercalcemia after 5‐year follow‐up is more frequent in cinacalcet than after subtotal parathyroidectomy.
Facing the option for the legalisation of cannabis use and supply in New Zealand: An overview of relevant evidence, concepts and considerations
Authors: Fischer Benedikt , Daldegan‐Bueno Dimitri , Boden Joseph M.
Published: May 2020

Issues

Non‐medical cannabis policies are changing, including towards legalisation‐with‐regulation frameworks. New Zealand will hold a public referendum on cannabis legalisation in 2020. We reviewed data on cannabis use and health/social harms; policy reform options; experiences with and outcomes of reforms elsewhere; and other relevant considerations towards informing policy choices in the upcoming referendum.

Approach

Relevant epidemiological, health, social, criminal justice and policy studies and data were identified and comprehensively reviewed.

Key Findings

Cannabis use is common (including in New Zealand) and associated with risks for health and social harms, mainly concentrated in young users; key harms are attributable to criminalisation. ‘Decriminalisation’ reforms have produced ambivalent results. Existing cannabis legalisation frameworks vary considerably in main parameters. Legalisation offers some distinct advantages, for example regulated use, products and user education, yet outcomes depend on essential regulation parameters, including commercialisation, and policy ecologies. While major changes in use are not observed, legalisation experiences are inconclusive to date, including mixed health and social outcomes, with select harms increasing and resilient illegal markets. It is unclear whether legalisation reduces cannabis exposure or social harms (e.g. from enforcement) for youth.

Implications/Conclusions

No conclusive overall evidence on the outcomes of legalisation elsewhere exists, nor is evidence easily transferable to other settings. Legalisation offers direct social justice benefits for adults, yet overall public health impacts are uncertain. Legalisation may not categorically improve health or social outcomes for youth. Legalisation remains a well‐intended, while experimental policy option towards more measured and sensible cannabis control and overall greater policy coherence, requiring close monitoring and possible adjustments depending on setting‐specific outcomes.
Designing ‘Realistic’ Healthcare Improvement
Authors: Inns Tom , Mountain Rod
Published: May 2020

Realistic Medicine asks that both clinicians and patients pause, reflect, and get back to the basic principles of compassionate care.

A program in Scotland shows what can be accomplished when health care professionals used design principles to improve the experience for patients and caregivers.
Community stakeholders' perspectives on youth mental health in India: Problems, challenges and recommendations
Authors: Dhandapani Vijaya Raghavan , Chandrasekaran Sangeetha , Singh Saurabh , Sood Mamta , Chadda Rakesh K , Shah Jai , Iyer Srividya , Meyer Caroline , Mohan Mohapradeep , Birchwood Max , Madan Jason , Currie Graeme , Ramachandran Padmavati , Rangaswamy Thara , Singh Swaran Preet
Published: May 2020

Background

India has a large youth population whose mental health needs must be addressed. This includes promotion of positive mental health, with early detection and effective intervention for mental health disorders. Understanding the perspectives of community stakeholders working with youth is pivotal to this effort. Current study aimed to bring together a group of community stakeholders (eg, parents, teachers, policy makers) to understand their perspectives on youth mental health problems, challenges in provision of care, and to provide recommendations to address these concerns at national level.

Materials and methods

The study was conducted across two sites in India: Chennai and New Delhi. Three group meetings were conducted involving 52 participants, including governmental, non‐governmental and community representatives working with youth. The proceedings were manually recorded, transcribed, and analyzed using thematic analysis method.

Results

Many youth mental health problems were similar across the two sites. The commonest drivers of mental health problems were reported to be academic pressure, substance use and problematic internet/social media use. Stigma and lack of awareness were identified as the most important challenges acting as barriers to seeking mental health help by youth. Prioritizing youth mental health as a national programmes along with strong political will were the major recommendations suggested by the stakeholders.

Conclusion

Initial findings suggest that prioritizing youth mental health programmes in India would be advantageous. Inclusive and collaborative approach, involving community stakeholders working with youth in providing services that promote mental health and early access to care will help in developing healthy young citizens.
Historic and modern genomes unveil a domestic introgression gradient in a wild red junglefowl population
Authors: Wu Meng Yue , Low Gabriel Weijie , Forcina Giovanni , van Grouw Hein , Lee Benjamin P. Y‐H. , Oh Rachel Rui Ying , Rheindt Frank E.
Published: May 2020

The red junglefowl Gallus gallus is the ancestor of the domestic chicken and arguably the most important bird species on Earth. Continual gene flow between domestic and wild populations has compromised its gene pool, especially since the last century when human encroachment and habitat loss would have led to increased contact opportunities. We present the first combined genomic and morphological admixture assessment of a native population of red junglefowl, sampled from recolonized parts of its former range in Singapore, partly using whole genomes resequenced from dozens of individuals. Crucially, this population was genomically anchored to museum samples from adjacent Peninsular Malaysia collected ~110–150 years ago to infer the magnitude of modern domestic introgression across individuals. We detected a strong feral–wild genomic continuum with varying levels of domestic introgression in different subpopulations across Singapore. Using a trait scoring scheme, we determined morphological thresholds that can be used by conservation managers to successfully identify individuals with low levels of domestic introgression, and selected traits that were particularly useful for predicting domesticity in genomic profiles. Our study underscores the utility of combined genomic and morphological approaches in population management and suggests a way forward to safeguard the allelic integrity of wild red junglefowl in perpetuity.
Age‐dependent expression of cancer‐related genes in a long‐lived seabird
Authors: Meitern Richard , Fort Jérôme , Giraudeau Mathieu , Rattiste Kalev , Sild Elin , Sepp Tuul
Published: May 2020

Studies of model animals like mice and rats have led to great advances in our understanding of the process of tumorigenesis, but this line of study has less to offer for understanding the mechanisms of cancer resistance. Increasing the diversity of nonmodel species from the perspective of molecular mechanisms of natural cancer resistance can lead to new insights into the evolution of protective mechanisms against neoplastic processes and to a wider understanding of natural cancer defense mechanisms. Such knowledge could then eventually be harnessed for the development of human cancer therapies. We suggest here that seabirds are promising, albeit currently completely ignored candidates for studying cancer defense mechanisms, as they have a longer maximum life span than expected from their body size and rates of energy metabolism and may have thus evolved mechanisms to limit neoplasia progression, especially at older ages. We here apply a novel, intraspecific approach of comparing old and young seabirds for improving our understanding of aging and neoplastic processes in natural settings. We used the long‐lived common gulls (Larus canus) for studying the age‐related pattern of expression of cancer‐related genes, based on transcriptome analysis and databases of orthologues of human cancer genes. The analysis of differently expressed cancer‐related genes between young and old gulls indicated that similarly to humans, age is potentially affecting cancer risk in this species. Out of eleven differentially expressed cancer‐related genes between the groups, three were likely artifactually linked to cancer. The remaining eight were downregulated in old gulls compared to young ones. The downregulation of five of them could be interpreted as a mechanism suppressing neoplasia risk and three as increasing the risk. Based on these results, we suggest that old gulls differ from young ones both from the aspect of cancer susceptibility and tumor suppression at the genetic level.
Bidirectional Spillover in the Family across the Transition to Parenthood
Authors: Pu Doris F. , Rodriguez Christina M.
Published: May 2020

Although family systems theory posits reciprocal causality between subsystems of the family, such as intimate partner violence exacerbating harsh parenting and vice versa, longitudinal studies with cross‐lagged models have been used infrequently to test these principles. As guided by the spillover model, this study examined bidirectional associations between couple dysfunction, parent–child aggression risk, and child functioning across the transition to parenthood to determine whether and how disruptions in one subsystem relate to problems in other family subsystems. Participants were 201 first‐time mothers and 151 fathers from a diverse community sample, evaluated during pregnancy, and reassessed two more times through their child's first 18 months of life. Individual and dyadic path model results indicate bidirectional spillover effects between parent–child aggression risk and child functioning for both mothers and fathers, and spillover from parent–child aggression risk to couple dysfunction for mothers but not fathers. However, limited spillover effects were identified between couple functioning and child adjustment, in contrast to previous work. Findings suggest that spillover can happen reciprocally and early in the family, supporting transactional models of behavior and highlighting the need for early family level intervention.
Effect of the plastic pollutant bisphenol A on the biology of aquatic organisms: A meta‐analysis
Authors: Wu Nicholas C. , Seebacher Frank
Published: May 2020

Plastic pollution is a global environmental concern. In particular, the endocrine‐disrupting chemical bisphenol A (BPA) is nearly ubiquitous in aquatic environments globally, and it continues to be produced and released into the environment in large quantities. BPA disrupts hormone signalling and can thereby have far‐reaching physiological and ecological consequences. However, it is not clear whether BPA has consistent effects across biological traits and phylogenetic groups. Hence, the aim of this study was to establish the current state of knowledge of the effect of BPA in aquatic organisms. We show that overall BPA exposure affected aquatic organisms negatively. It increased abnormalities, altered behaviour and had negative effects on the cardiovascular system, development, growth and survival. Early life stages were the most sensitive to BPA exposure in invertebrates and vertebrates, and invertebrates and amphibians seem to be particularly affected. These data provide a context for management efforts in the face of increasing plastic pollution. However, data availability is highly biased with respect to taxonomic groups and traits studies, and in the geographical distribution of sample collection. The latter is the case for both measurements of the biological responses and assessing pollution levels in water ways. Future research effort should be directed towards biological systems, such as studying endocrine disruption directly, and geographical areas (particularly in Africa and Asia) which we identify to be currently undersampled.
Miscanthus sacchriflorus exhibits sustainable yields and ameliorates soil properties but potassium stocks without any input over a 12‐year period in China
Authors: Zhao Chunqiao , Fan Xifeng , Li Xiaona , Hou Xincun , Zhang Weiwei , Yue Yuesen , Zhu Yi , Wang Chao , Zuo Yiling , Wu Juying
Published: May 2020

The perennial C4 Miscanthus spp. is used in China for bio‐fuel production and its ecological functions. However, questions arise as to its economic and environmental sustainability in abandoned farmland where the costs should be very low. Little is known about its yield performance and effects on soil properties when it was harvested annually without any inputs in China. To address these questions, an experiment was implemented for 12 years on annually harvested Miscanthus sacchariflorus planted in 2006 and managed without fertilization, irrigation, or any other inputs. We determined biomass yields each year, biomass allocation, and soil properties before and after its cultivation. Biomass yields of M. sacchariflorus reached a peak value (29.67 t/ha) 3 years after cultivation and was maintained at a stable level (averaged 22.22 t/ha) during 2012–2017. Its root shoot ratio increased due to more biomass allocated below‐ground with time. Long‐term cultivation of M. sacchariflorus increased organic carbon contents, pH (for the absence of fertilization), microbial carbon, nitrogen and phosphorus contents, and soil carbon nitrogen ratios (0–100 cm). Soil bulk density was decreased significantly (p < .05) independent of soil depths. Annual harvest did not reduce total nitrogen and phosphorus, available nitrogen, and potassium, but total the potassium content of soil (0–100 cm). Cultivation of M. sacchariflorus increased available phosphorus contents in 40–100 cm soil and reduced that value in 20–40 cm soil. Biological nitrogen fixation provided ~218.74 kg ha−1 year−1 (1 m depth) nitrogen for the system offsetting nitrogen export by biomass harvest and stabilizing nitrogen levels of soil. In conclusion, M. sacchriflorus exhibited sustainable biomass yields and ameliorated soil properties but the decrease of total potassium contents after 12 years’ cultivation without any input. These conclusions could provide important information timely for the government and encourage farmers to promote large‐scale utilization of M. sacchriflorus on the abandoned farmland in China.
Coping with the COVID‐19 crisis: force majeure and gender performativity
Authors: Hennekam Sophie , Shymko Yuliya
Published: May 2020

This article examines the coping strategies of individuals during the confinement in France using a sensemaking lens. We draw on two studies consisting of 85 qualitative surveys followed by a diary in which 20 individuals wrote about their experiences during the first three weeks of the confinement. We employ an interpretative phenomenological approach to analyse the data. The findings reveal two patterns in the ways men and women cope with their experiences during the COVID‐19 pandemic. The first pattern shows intensification of gender performativity manifested in the reproduction of ‘masculine’ and ‘feminine’ reactions to the crisis. The second pattern detects a tendency towards a gradual deflection from gender performances through mental improvisations that foster new awareness of the crisis presenting an opportunity to transcend traditional gender roles. Our study highlights some potential emancipatory implications the COVID‐19 crisis may have for the practices of ‘doing gender’ and perceptions of work–life balance therefore instigating a transition towards more egalitarian households.
Use of Groundwater Level Fluctuations near an Operating Water Supply Well to Estimate Aquifer Transmissivity
Authors: Pozdniakov Sergey , Ivanov Pavel , Davis Paul , Sizov Nikolay
Published: May 2020

We developed a method to estimate aquifer transmissivity from the hydraulic‐head data associated with the normal cyclic operation of a water supply well thus avoiding the need for interrupting the water supply associated with a traditional aquifer test. The method is based on an analytical solution that relates the aquifer's transmissivity to the standard deviation of the hydraulic‐head fluctuations in one or more observation wells that are due to the periodic pumping of the production well. We analyzed the resulting analytical solution and demonstrated that when the observation wells are located near the pumping well, the solution has a simple, Dupuit like form. Numerical analysis demonstrates that the analytical solution can also be used for a quasi‐periodic pumping of the supply well. Simulation of cyclic pumping in a statistically heterogeneous medium confirms that the method is suitable for analyzing the transmissivity of weakly or moderately heterogeneous aquifers. If only one observation well is available, and the shift in the phase of hydraulic‐head oscillations between the pumping well and the observation well is not identifiable. Prior knowledge of aquifer's hydraulic diffusivity is required to obtain the value of the aquifer transmissivity.
A conducive environment? The role of need support in the higher education workplace and its effect on academics' experiences of research assessment in the UK
Authors: Weinstein Netta , Chubb Jennifer A. , Haddock Geoffrey , Wilsdon James R.
Published: May 2020

Little is known about how researchers in higher education institutions (HEIs) experience and respond to support received from their departments. The present study investigated how support for researchers' autonomy (choice and self‐expression), relatedness (through connections with colleagues) and competence (feeling effective in one's work) influenced their attitudes towards an external assessment of research. To do so, we surveyed 598 academics from four HEIs in the UK about their attitudes towards one such external assessment: the Research Excellence Framework (REF), a nationwide assessment of research quality and the subject of debate about research evaluation. Our findings, drawing on self‐determination theory, show that departments can shape responses to the REF: individuals whose psychological needs were supported by their academic departments held more positive, and less negative, attitudes towards the REF. This occurred both directly and indirectly through researchers' recognition that the REF had a more positive influence on their research activities and outputs.
A comparative study of medical ebook and print book prices
Authors: Watson Erin M.
Published: May 2020

Background

Although most medical libraries buy ebooks, there has been little discussion of the comparative costs of medical ebooks and print books.

Objectives

To determine whether individually purchased medical ebooks cost more or less, on average, than the same titles in print format and, if so, to calculate the price differential.

Methods

The author searched the platform of monograph vendor YBP for the 1095 titles in the ‘Clinical Medicine’ category of Doody’s Core Titles 2018 edition. For each title, the print price and the lowest ebook price were noted; the ratio of ebook price to print book price for each title was then calculated.

Results

On average, ebooks cost 2.20 times more than their print equivalents, though the size of the price differential varied greatly with the publisher. For some publishers, ebooks cost nearly the same amount as print books, while for others, ebooks cost three or even four times as much as the print.

Discussion

The greater price of some ebooks may make them unaffordable for libraries or mean that those titles cannot be purchased as ebooks even when that format would be preferred.

Conclusions

Buying ebooks, at least on a title‐by‐title basis, can be very costly for medical libraries.
Reduced bone resorption and inflammation in apical periodontitis evoked by dietary supplementation with probiotics in rats
Authors: Cosme‐Silva L. , Dal‐Fabbro R. , Cintra L. T. A. , Ervolino E. , Plazza F. , Mogami Bomfim S. , Duarte P. C. T. , Junior V. E. D. S. , Gomes‐Filho J. E.
Published: May 2020

Aim

To evaluate the relationship between systemic administration of probiotics and inflammation/resorption processes associated with apical periodontitis (AP) in a rat model.

Methodology

Twenty‐four male Wistar rats were used. AP was induced in the mandibular left/right first molars. The animals were arranged into three groups: Control, Lactobacillus rhamnosus and L. acidophilus. Probiotics were orally administered via gavage (109 colony‐forming units (CFU) diluted in 5 mL of water) for 30 days during the development of AP. On the 30th day, blood was collected to analyse the calcium, phosphorus and alkaline phosphatase concentrations in plasma. Then, the animals were euthanized and the jaws removed for micro‐computed tomography and immune‐histopathological analysis for receptor activator of NF‐κB ligand (RANKL), osteoprotegerin (OPG) and tartrate‐resistant acid phosphatase (TRAP). After the Shapiro–Wilk test of normality, the Kruskal–Wallis followed by Dunn’s test was performed for nonparametric data, and analysis of variance followed by the Tukey test was performed for parametric data (P < 0.05).

Results

There was no significant difference in the calcium and phosphorus levels in plasma amongst the groups (P > 0.05). The level of alkaline phosphatase was significantly higher in the groups that consumed probiotics (P < 0.05). A significantly lower volume of bone resorption was observed in groups that consumed probiotics (P < 0.05). The inflammatory infiltrates and the immunolabelling for RANKL and TRAP were significantly lower in probiotic groups when compared to the control (P < 0.05). Also, the OPG was significantly more immunolabelled in the L. acidophilus group than in the L. rhamnosus and control groups (P < 0.05).

Conclusion

Probiotic supplementation through gavage (L. rhamnosus and L. acidophilus) had a significant effect on the reduction of inflammation and bone resorption in apical periodontitis development in rats.
A PIK3CA transgenic mouse model with chemical carcinogen exposure mimics human oral tongue tumorigenesis
Authors: Tan Melody T. , Wu Jean G. , Callejas‐Valera Juan Luis , Schwarz Richard A. , Gillenwater Ann M. , Richards‐Kortum Rebecca R. , Vigneswaran Nadarajah
Published: May 2020

Oral cancer causes significant global mortality and has a five‐year survival rate of around 64%. Poor prognosis results from late‐stage diagnosis, highlighting an important need to develop better approaches to detect oral premalignant lesions (OPLs) and identify which OPLs are at highest risk of progression to oral squamous cell carcinoma (OSCC). An appropriate animal model that reflects the genetic, histologic, immunologic, molecular and gross visual features of human OSCC would aid in the development and evaluation of early detection and risk assessment strategies. Here, we present an experimentalPIK3CA + 4NQOtransgenic mouse model of oral carcinogenesis that combines the PIK3CA oncogene mutation with oral exposure to the chemical carcinogen 4NQO, an alternate experimental transgenic mouse model with PIK3CA as well as E6 and E7 mutations, and an existing wild‐type mouse model based on oral exposure to 4NQO alone. We compare changes in dorsal and ventral tongue gross visual appearance, histologic features and molecular biomarker expression over a time course of carcinogenesis. Both transgenic models exhibit cytological and architectural features of dysplasia that mimic human disease and exhibit slightly increased staining for Ki‐67, a cell proliferation marker. The PIK3CA + 4NQO model additionally exhibits consistent lymphocytic infiltration, presents with prominent dorsal and ventral tongue tumours, and develops cancer quickly relative to the other models. Thus, the PIK3CA + 4NQO model recapitulates the multistep genetic model of human oral carcinogenesis and host immune response in carcinogen‐induced tongue cancer, making it a useful resource for future OSCC studies.
Adversity exposure and obesogenic food consumption in young children: The transgenerational role of emotion dysregulation
Authors: Huffhines Lindsay , Gusler Stephanie , Jackson Yo
Published: May 2020

Background

Childhood adversity is linked with unhealthy eating behaviours and obesity, but the mechanisms underlying this association are unclear, specifically the transgenerational behavioural precursors that develop in early childhood.

Objective

To determine whether adversity predicts change in obesogenic food consumption through child emotion dysregulation, and whether caregiver emotion dysregulation modifies this association.

Methods

Participants included 190 low‐income caregiver‐child dyads (mean child age = 4.31 years [SD = 0.85]). Cumulative lifetime adversity exposure was assessed via study‐created measure. The Difficulties with Emotion Regulation Scale and Emotion Regulation Checklist assessed caregiver and child emotion dysregulation, respectively. Children's obesogenic food consumption was assessed at two time points 6 months apart using a caregiver‐report measure: the Children's Eating Habits Questionnaire. Moderated mediation models were tested using autoregressive structural equation modelling.

Results

Cumulative lifetime adversity was associated with child emotion dysregulation only when caregiver emotion dysregulation was high. Child emotion dysregulation in turn was associated with greater obesogenic food consumption 6 months later.

Conclusions

Among young children with caregivers high in emotion dysregulation, cumulative lifetime adversity was linked to an increase in obesogenic food consumption through child emotion dysregulation.
Biophysical defects of an SCN5A V1667I mutation associated with epinephrine‐induced marked QT prolongation
Authors: Nakajima Tadashi , Dharmawan Tommy , Kawabata‐Iwakawa Reika , Tamura Shuntaro , Hasegawa Hiroshi , Kobari Takashi , Kaneko Yoshiaki , Nishiyama Masahiko , Kurabayashi Masahiko
Published: May 2020

Background

The epinephrine infusion test (EIT) typically induces marked QT prolongation in LQT1, but not LQT3, while the efficacy of β‐blocker therapy is established in LQT1, but not LQT3. We encountered an LQT3 family, with an SCN5A V1667I mutation, that exhibited epinephrine‐induced marked QT prolongation.

Methods

Wild‐type (WT) or V1667I‐SCN5A was transiently expressed into tsA‐201 cells, and whole‐cell sodium currents (INa) were recorded using patch‐clamp techniques. To mimic the effects of epinephrine, INa was recorded after the application of protein kinase A (PKA) activator, 8‐CPT‐cAMP (200 μM), for 10 minutes.

Results

The peak density of V1667I‐INa was significantly larger than WT‐INa (WT: 469 ± 48 pA/pF, n = 20; V1667I: 690 ± 62 pA/pF, n = 19, P < .01). The steady‐state activation (SSA) and fast inactivation rate of V1667I‐INa were comparable to WT‐INa. V1667I‐INa displayed a significant depolarizing shift in steady‐state inactivation (SSI) in comparison to WT‐INa (V1/2‐WT: −88.1 ± 0.8 mV, n = 17; V1667I: −82.5 ± 1.1 mV, n = 17, P < .01), which increases window currents. Tetrodotoxin (30 μM)‐sensitive persistent V1667I‐INa was comparable to WT‐INa. However, the ramp pulse protocol (RPP) displayed an increased hump in V1667I‐INa in comparison to WT‐INa. Although 8‐CPT‐cAMP shifted SSA to hyperpolarizing potentials in WT‐INa and V1667I‐INa to the same extent, it shifted SSI to hyperpolarizing potentials much less in V1667I‐INa than in WT‐INa (V1/2‐WT: −92.7 ± 1.3 mV, n = 6; V1667I: −85.3 ± 1.6 mV, n = 6, P < .01). Concordantly, the RPP displayed an increased hump in V1667I‐INa, but not in WT‐INa.

Conclusions

We demonstrated an increase of V1667I‐INa by PKA activation, which may provide a rationale for the efficacy of β‐blocker therapy in some cases of LQT3.
Substitution among milk and yogurt products and the risk of incident type 2 diabetes in the EPIC‐NL cohort
Authors: Stuber J. M. , Vissers L. E. T. , Verschuren W. M. M. , Boer J. M. A. , van der Schouw Y. T. , Sluijs I.
Published: May 2020

Background

Higher dairy consumption has been associated with lower type 2 diabetes (T2D) risk, whereas dairy product subtypes appear to differ in their T2D risk association. We investigated whether replacing one type of milk or yogurt product with another is associated with T2D incidence.

Methods

Participants of the European Prospective Investigation into Cancer and Nutrition‐Netherlands (EPIC‐NL) cohort (n = 35 982) were included in the present study. Information on milk and yogurt consumption at baseline was obtained by a validated food frequency questionnaire. T2D cases were identified by self‐report or linkage to the hospital discharge registry, and validated by consulting the general practitioner. Multivariable Cox proportional hazard models were used to estimate associations.

Results

During a mean of 15 years of follow‐up, 1467 indecent T2D cases were validated. Median total milk and yogurt intake was 1.5 servings (25th percentile to 75th percentile: 0.8–2.4). After adjustment for demographic and cardiovascular risk factors, replacement of one serving (200 g) of whole‐fat milk [hazard ratio (HR) = 0.93, 95% confidence interval (CI) = 0.60–1.44], buttermilk (HR = 0.88, 95% CI = 0.58‐1.34), skimmed milk (HR = 0.87, 95% CI = 0.57–1.32) or skimmed fermented milk (HR = 0.99, 95% CI = 0.63–1.54) with whole‐fat yogurt was not associated with T2D risk. Substitutions among other milk and yogurt products were also not associated with T2D risk. Sensitivity analysis investigating T2D risk halfway follow‐up suggested a lower risk for substitutions with whole‐fat yogurt.

Conclusions

No evidence was found for the association between substitutions among milk and yogurt products and the risk of incident T2D, although we cannot exclude possible attenuation of results as a result of dietary changes over time. This analysis should be repeated in a population with a wider consumption range of whole‐fat yogurt.
Host range and susceptibility to Toxoplasma gondii infection in captive neotropical and Old‐world primates
Authors: Paula Nayara Ferreira de , Dutra Kateanne Silva , Oliveira Ayisa Rodrigues de , Santos Daniel Oliveira dos , Rocha Cláudia Emanuela Viana , Vitor Ricardo Wagner de Almeida , Tinoco Herlandes Penha , Costa Maria Elvira Loyola Teixeira da , Paixão Tatiane Alves da , Santos Renato Lima
Published: May 2020

Background

Toxoplasmosis is an important disease affecting captive non‐human primates. The goal of this study was to assess the seroprevalence and pathological findings of toxoplasmosis in different species of captive primates.

Methods

Six captive neotropical primates died naturally due to Toxoplasma gondii infection and were necropsied. Tissue samples were evaluated by histopathology and immunohistochemistry. Serum samples from 57 captive neotropical and Old‐world primates housed at the Belo Horizonte zoological garden were analyzed by indirect fluorescent antibody test (IFAT), enzyme‐linked immunosorbent assay (ELISA), and indirect hemagglutination assay (IHA).

Results

Neotropical primates had lesions compatible with toxoplasmosis with immunolabeled intralesional T gondii. All Old‐World primates (10/10), but only three neotropical primates (3/47), all belonging to the Sapajus apella species (3/6), were serologically positive.

Conclusions

Our results suggest a higher susceptibility of neotropical primates to toxoplasmosis. However, this study also supports the hypothesis that Sapajus apella may be naturally resistant.
Krapina atlases suggest a high prevalence of anatomical variations in the first cervical vertebra of Neanderthals
Authors: Palancar Carlos A. , García‐Martínez Daniel , Radovčić Davorka , Llidó Susanna , Mata‐Escolano Federico , Bastir Markus , Sanchis‐Gimeno Juan Alberto
Published: May 2020

The first cervical vertebra, atlas, and its anatomical variants have been widely studied in Homo sapiens. However, in Neanderthals, the presence of anatomical variants of the atlas has been very little studied until very recently. Only the Neanderthal group from the El Sidrón site (Spain) has been analysed with regard to the anatomical variants of the atlas. A high prevalence of anatomical variants has been described in this sample, which points to low genetic diversity in this Neanderthal group. Even so, the high prevalence of anatomical variations detected in El Sidrón Neanderthal atlases needs to be confirmed by analysing more Neanderthal remains. In this context, we analysed the possible presence of anatomical variants in the three Neanderthal atlases recovered from the Krapina site (Croatia) within the Neanderthal lineage. Two of the three Krapina atlases presented anatomical variations. One atlas (Krapina 98) had an unclosed transverse foramen and the other (Krapina 99) presented a non‐fused anterior atlas arch. Moreover, an extended review of the bibliography also showed these anatomical variations in other Middle and Upper Pleistocene hominins, leading us to hypothesise that anatomical variations of the atlas had a higher prevalence in extinct hominins than in modern humans.
Making the State Responsible: Intersex Embodiment, Medical Jurisdiction, and State Responsibility
Authors: Garland Fae , Travis Mitchell
Published: May 2020

Through consideration of new developments in the United Kingdom's intersex policy, this article traces the ways in which responsibility is produced, naturalized, and avoided by individuals, institutions, and the state. Jurisdiction is identified as a barrier to the attribution of responsibility that must be overcome to achieve progress in relation to the needs of intersex people. By bringing together jurisdictional analysis and vulnerability theory, this article demonstrates how the state has traditionally abrogated responsibility by compartmentalizing specific practices as governed by medical authority. It highlights that such accounts mask the role of the state in the creation of jurisdiction and the ways in which governance is conducted. Challenging these boundaries allows vulnerability theorists to move the state towards greater levels of responsibility. By combining these theoretical tools, the article enhances the practical utility of vulnerability theory and advances an important agenda for intersex people.
Curcumin alleviates OGD/R-induced PC12 cell damage via repressing CCL3 and inactivating TLR4/MyD88/MAPK/NF-κB to suppress inflammation and apoptosis
Authors: Wang Chao , Yang Yong-Hong , Zhou Liang , Ding Xin-Li , Meng Ying-Chun , Han Ke
Published: May 2020

Objectives

Curcumin presents some therapeutic effects including anti-cancer and anti-inflammation. Herein, we centred on the functional role of curcumin in cerebral ischaemia injury and its potential molecular mechanisms.

Methods

Microarray analysis was used for excavating crucial genes in cerebral ischaemia. PC12 cells were subjected to oxygen–glucose deprivation and reoxygenation (OGD/R) to imitate cerebral ischaemia/reperfusion (I/R) injury in vitro. Cell viability and apoptosis abilities were evaluated by Cell Counting Kit-8 and flow cytometry assays. qRT-PCR, Western blot and enzyme-linked immunosorbent assays were performed to assess the concentrations of related genes.

Key findings

By enquiring GEO dataset, C–C motif chemokine ligand 3 (CCL3) was profoundly upregulated in cerebral I/R injury model. And CCL3 was found to be highly expressed in PC12 cells suffered from OGD/R. Moreover, we found that CCL3 was a potential target of curcumin in cerebral I/R injury. More importantly, the following experiments illustrated that curcumin inhibited the expression of CCL3 in OGD/R model and reduced cell apoptosis and inflammation. Moreover, high expression levels of TLR4, MyD88, p-NF-κB P65, p-P38 MAPK and p-IκBα in OGD/R model were inhibited by curcumin.

Conclusions

Our study manifested that curcumin might be a meritorious drug for the treatment of cerebral ischaemia by acting on CCL3.
A unique record of Cercis from the late early Miocene of interior Asia and its significance for paleoenvironments and paleophytogeography
Authors: Li Xiang‐Chuan , Manchester Steven R. , Wang Qin , Xiao Liang , Qi Tian‐Long , Yao Yun‐Zhi , Ren Dong , Yang Qiang
Published: May 2020

The climatic impacts of the Tibetan Plateau since the Neogene and the phytogeographic pattern changes of formerly widely‐distributed forest communities on the plateau remain poorly constrained. Today, Cercis L. (Fabaceae) is a well‐known arborescent genus typically distributed in subtropical to warm temperate zones of the Northern Hemisphere, and Paleogene fossil occurrences from Eurasia and North America show a long history of the genus in mid‐low latitudes of the Northern Hemisphere. Here, we describe a fossil species, Cercis zekuensis sp. nov. based on well‐preserved fruits from the early Miocene of the northeastern Tibetan Plateau. Detailed morphological comparison (e.g., ventral margin with a veinless wing) of extant and fossil members of Cercis and other genera confirmed validity of the present taxonomic identity. Based on the comparison with extant relatives and their climate preferences, this unexpected occurrence of thermophilic Cercis in northeastern Tibetan Plateau indicates this area had higher temperature and precipitation in the Miocene than today. Integrated with inferred (paleo‐)temperature lapse rates, this indicates a low paleoelevation of less than 2.4 km. In contrast with the present‐day alpine climate here (~3.7 km), such a low elevation facilitated a more favorable habitat with comparatively high biodiversity and warm temperate forests at that time, as were evidenced by co‐occurring megafossils. Moreover, the present existence of Cercis implies the genus was widespread in interior Asia during the early Neogene and shows its modern disjunction or diversification between eastern and central Asia was possibly shaped by the late Cenozoic regional tectonic uplift and consequential environmental deterioration.
Sofosbuvir‐Daclatasvir is suboptimal in patients with genotype 2 chronic hepatitis C infection: real‐life experience from the HEPATHER ANRS CO22 cohort
Authors: de Lédinghen Victor , Lusivika‐Nzinga Clovis , Bronowicki Jean‐Pierre , Zoulim Fabien , Larrey Dominique , Metivier Sophie , Tran Albert , Marcellin Patrick , Samuel Didier , Chazouillères Olivier , Chevaliez Stephane , Dorival Celine , Fontaine Hélène , Pawlotsky Jean‐Michel , Carrat Fabrice , Pol Stanislas ,   The AFEF/ANRS Study Group
Published: May 2020

Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real‐world data available for this regimen. To evaluate the real‐life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1‐1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real‐life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV.