bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitation of glutamate, but not GABA, release in Familial Alzheimer's APP mutant Knock‐in rats with increased β‐cleavage of APP
Authors: Tambini Marc D. , Yao Wen , D'Adamio Luciano 
Published: September 2019

AbstractAmyloid precursor protein (APP) modulates glutamate release via cytoplasmic and intravesicular interactions with the synaptic vesicle release machinery. The intravesicular domain, called ISVAID, contains the BACE1 cleavage site of APP. We have tested the functional significance of BACE1 processing of APP using App‐Swedish (Apps) knock‐in rats, which carry an App mutation that causes familial Alzheimer's disease (FAD) in humans. We show that in Apps rats, β‐cleavage of APP is favored over α‐cleavage. Apps rats show facilitated glutamate, but not GABA, release. Our data support the notion that APP tunes glutamate release, and that BACE1 cleavage of the ISVAID segment of APP facilitates this function. We define this phenomenon as BACE1 on APP‐dependent glutamate release (BAD‐Glu). Unsurprisingly, Apps rats show no evidence of AD‐related pathology at 15 days and 3 months of age, indicating that alterations in BAD‐Glu are not caused by pathological lesions. The evidence that a pathogenic APP mutation causes an early enhancement of BAD‐Glu suggests that alterations of BACE1 processing of APP in glutamatergic synaptic vesicles could contribute to dementia.
Impact of the UK Psychoactive Substances Act on awareness, use, experiences and knowledge of potential associated health risks of novel psychoactive substances
Authors: Deligianni Elena , Daniel Omari J. , Corkery John M. , Schifano Fabrizio , Lione Lisa A. 
Published: September 2019

AimsThe risk of potential harms prompted the UK government to introduce the Psychoactive Substances Act in 2016. The aim of the present study was to evaluate the impact and effectiveness of this new legislation on patterns of novel psychoactive substance (NPS) awareness, use, experiences and risk awareness in a self‐selected sample of UK consumers to inform education and policy.MethodsThe Bristol Online Survey was advertised on the Bluelight drug forum and social media Facebook pages and University email between 7 January and 7 February 2015 (168 responses) and 9 March to 18 September 2017 (726 responses). UK country of residence responses were extracted for analysis (SPSS).ResultsIn a predominantly university‐educated, young (< 25 years) self‐selecting sample, 1 year after introduction of the legislation, NPS use (in males, under 18s, those educated to school/college level, P < .001) has increased, whilst health risk awareness has not changed and remains poor. Users are switching to sourcing NPSs via street dealers (49%) and the darknet (31%) and showing an increase in preference for the herbal NPS Salvia divinorum (P < .05). The main reasons for NPS use remain the influence of friends (69%) in a social setting and to get high (76%) usually in combination with alcohol, cannabis or ecstasy.ConclusionRegulation alone, so far, has not impacted on health risk awareness, NPS drug demand and culture in our UK survey sample. Alongside regulation, NPS health promotion education (particularly in schools, colleges) is needed that addresses resilience and both the risks and beneficial effects of NPS.
Influence of donor type, stem cell source and conditioning on outcomes after haploidentical transplant for lymphoma – a LWP‐EBMT study
Authors: Bazarbachi Ali , Boumendil Ariane , Finel Hervé , Castagna Luca , Dominietto Alida , Blaise Didier , Diez‐Martin Jose L. , Tischer Johanna , Gülbas Zafer , Wallet Hélène L. , Corral Lucia L. , Mohty Mohamad , Koc Yener , Yakoub‐Agha Ibrahim , Schmid Christoph , El Cheikh Jean , Arat Mutlu , Forcade Edouard , Dreger Peter , Rocha Vanderson , García Gonzalo G. , Chalandon Yves , Ferra Christelle , Orvain Corentin , Robinson Stephen , Montoto Silvia , Sureda Anna 
Published: September 2019

SummaryHaploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T‐cell (PTCL; 88), diffuse large B‐cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post‐transplant cyclophosphamide. Median follow‐up of alive patients was 32 months. On multivariate analysis, acute graft‐versus‐host disease (GVHD) grade 2–4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression‐free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor.
Delayed intervention with a novel SGLT2 inhibitor NGI001 suppresses diet‐induced metabolic dysfunction and non‐alcoholic fatty liver disease in mice
Authors: Chiang Hao , Lee Jinq‐Chyi , Huang Hsiu‐Chen , Huang Hsing , Liu Hui‐Kang , Huang Cheng 
Published: September 2019

Background and PurposeNon‐alcoholic fatty liver disease (NAFLD), including non‐alcoholic steatohepatitis, is closely related to metabolic diseases such as obesity and diabetes. Despite an accumulating number of studies, no pharmacotherapy that targets NAFLD has received general approval for clinical use.Experimental ApproachInhibition of the sodium‐glucose cotransporter 2 (SGLT2) is a promising approach to treat diabetes, obesity, and associated metabolic disorders. In this study, we investigated the effect of a novel SGLT2 inhibitor, NGI001, on NAFLD and obesity‐associated metabolic symptoms in high‐fat diet (HFD)‐induced obese mice.Key ResultsDelayed intervention with NGI001 protected against body weight gain, hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia, compared with HFD alone. Adipocyte hypertrophy was prevented by administering NGI001. NGI001 inhibited impaired glucose metabolism and regulated the secretion of adipokines associated with insulin resistance. In addition, NGI001 supplementation suppressed hepatic lipid accumulation and inflammation but had little effect on kidney function. In‐depth investigations showed that NGI001 ameliorated fat deposition and increased AMPK phosphorylation, resulting in phosphorylation of its major downstream target, acetyl‐CoA carboxylase, in human hepatocyte HuS‐E/2 cells. This cascade ultimately led to the down‐regulation of downstream fatty acid synthesis‐related molecules and the up‐regulation of downstream β oxidation‐associated molecules. Surprisingly, NGI001 decreased gene and protein expression of SGLT1 and SGLT2 and glucose uptake in oleic acid‐treated HuS‐E/2 cells.Conclusion and ImplicationsOur findings suggest the novel SGLT2 inhibitor, NGI001 has therapeutic potential to attenuate or delay the onset of diet‐induced metabolic diseases and NAFLD.
Fentanyl depression of respiration: Comparison with heroin and morphine
Authors: Hill Rob , Santhakumar Rakulan , Dewey William , Kelly Eamonn , Henderson Graeme 
Published: September 2019

Background and PurposeFentanyl overdose deaths have reached “epidemic” levels in North America. Death in opioid overdose invariably results from respiratory depression. In the present work, we have characterized how fentanyl depresses respiration, and by comparing fentanyl with heroin and morphine, the active breakdown product of heroin, we have sought to determine the factors, in addition to high potency, that contribute to the lethality of fentanyl.Experimental ApproachRespiration (rate and tidal volume) was measured in awake, freely moving mice by whole body plethysmography.Key ResultsIntravenously administered fentanyl produced more rapid depression of respiration than equipotent doses of heroin or morphine. Fentanyl depressed both respiratory rate and tidal volume. Fentanyl did not depress respiration in μ‐opioid receptor knockout mice. Naloxone, the opioid antagonist widely used to treat opioid overdose, reversed the depression of respiration by morphine more readily than that by fentanyl, whereas diprenorphine, a more lipophilic antagonist, was equipotent in reversing fentanyl and morphine depression of respiration. Prolonged treatment with morphine induced tolerance to respiratory depression, but the degree of cross tolerance to fentanyl was less than the tolerance to morphine itself.Conclusion and ImplicationsWe propose that several factors (potency, rate of onset, lowered sensitivity to naloxone, and lowered cross tolerance to heroin) combine to make fentanyl more likely to cause opioid overdose deaths than other commonly abused opioids. Lipophilic antagonists such as diprenorphine may be better antidotes than naloxone to treat fentanyl overdose.
Marijuana use should not preclude consideration for kidney transplantation
Authors: Fabbri Kassandra R. , Anderson‐Haag Tracy L. , Spenningsby Anne M. , Israni Ajay , Nygaard Rachel M. , Stahler Paul A. 
Published: September 2019

AbstractTransplant eligibility for tobacco and/or marijuana using candidates varies among transplant centers. This study compared the impact of marijuana use and tobacco use on kidney transplant recipient outcomes. Kidney transplant recipients at a single center from 2001 to 2015 were reviewed for outcomes of all‐cause graft loss, infection, biopsy‐proven acute rejection, and estimated glomerular filtration rate between four groups: marijuana‐only users, marijuana and tobacco users, tobacco‐only users, and nonusers. The cohort (N = 919) included 48 (5.2%) marijuana users, 45 (4.8%) marijuana and tobacco users, 136 (14.7%) tobacco users, and 75% nonusers. Smoking status was not significantly associated with acute rejection, estimated glomerular filtration rate or pneumonia within one‐year post‐transplant in an adjusted model. Compared to nonuse, marijuana and tobacco use and tobacco‐only use was significantly associated with increased risk of graft loss (aHR 1.68, P = .034 and 1.52, P = .006, respectively). Patients with isolated marijuana use had similar overall graft survival compared to nonusers (aHR 1.00, P = .994). Marijuana use should not be an absolute contraindication to kidney transplant.
Female false black widow spiders,Steatoda grossa,recognize webs based on physical and chemical cues
Authors: Fischer Andreas , Hung Emmanuel , Gries Gerhard 
Published: September 2019

AbstractFemales of the false black widow,Steatoda grossaCL Koch (Araneae: Theridiidae), invest significant energy and time weaving cobwebs. We tested the hypothesis thatS. grossafemales select sites for their webs based, in part, on the presence of con‐ or heterospecific webs, sensing both physical and chemical web cues. In bioassays, we offered femaleS. grossaa choice between an empty control frame and a frame bearing the web of a conspecific female or that of a female common house spider,Parasteatoda tepidariumCL Koch (Araneae: Theridiidae), recording (1) the time she spent, and (2) the time she spent inactive (a proxy for settling behaviour) on each frame. We also tested the effect of (1) silk micro‐ and macrostructure (wrapped‐up silk or intact web, each semiochemical‐deprived), (2) plastic webs, and (3) silk semiochemical extract on the responses ofS. grossafemales. Females settled on both con‐ and heterospecific webs and chose test stimuli based on their chemical and physical characteristics. Even plastic webs in cobweb‐like arrangement readily prompted settling behaviour by females. Our results suggest that web architecture, rather than web silk, mediates settling responses by femaleS. grossaon pre‐existing webs which may provide structural support for a new web and indicate habitat suitability.
Results of a thinning study in a black stain (Leptographium wageneri)‐infested Jeffrey/ponderosa pine forest in northern California
Authors: Woodruff William , Greenberg David , Cannon Philip 
Published: September 2019

AbstractBlack stain root disease (BSRD) caused byLeptographium wagenerivar.ponderosum(Verticicladiella wageneri) is a destructive disease in many Jeffrey pine (Pinus jeffreyi) and ponderosa pine (P. ponderosa) forests of the western United States. Overcrowding is a pervasive problem in these forests, unless alleviated by thinning. In an overcrowded BSRD‐infested second‐growth Jeffrey/ponderosa pine forest in northern California, a large study (16.2 hr; 40 acres) was designed to determine the impact of thinning to four levels—6.9 m2/ha (30 ft2/acre), 13.8 m2/ha (60 ft2/acre), and 20.7 m2/ha (90 ft2/acre) of basal area and a control with no thinning—on the incidence of BSRD‐caused mortality. Ten years after this experiment was initiated, results indicate that thinning to any of these levels lowered the incidence of BSRD‐caused mortality as compared with BSRD‐caused mortality in unthinned control plots.
Genetic drift in range expansions is very sensitive to density dependence in dispersal and growth
Authors: Birzu Gabriel , Matin Sakib , Hallatschek Oskar , Korolev Kirill S. 
Published: September 2019

AbstractTheory predicts rapid genetic drift during invasions, yet many expanding populations maintain high genetic diversity. We find that genetic drift is dramatically suppressed when dispersal rates increase with the population density because many more migrants from the diverse, high‐density regions arrive at the expansion edge. When density dependence is weak or negative, the effective population size of the front scales only logarithmically with the carrying capacity. The dependence, however, switches to a sublinear power law and then to a linear increase as the density dependence becomes strongly positive. We develop a unified framework revealing that the transitions between different regimes of diversity loss are controlled by a single, universal quantity: the ratio of the expansion velocity to the geometric mean of dispersal and growth rates at expansion edge. Our results suggest that positive density dependence could dramatically alter evolution in expanding populations even when its contribution to the expansion velocity is small.
Genomic analyses reveal selection footprints in rice landraces grown under on‐farm conservation conditions during a short‐term period of domestication
Authors: Cui Di , Lu Hongfeng , Tang Cuifeng , Li Jinmei , A Xinxiang , Yu Tengqiong , Ma Xiaoding , Zhang Enlai , Wang Yanjie , Cao Guilan , Xu Furong , Qiao Yongli , Dai Luyuan , Li Ruiqiang , Tian Shilin , Koh Hee‐Jong , Han Longzhi 
Published: September 2019

AbstractTraditional rice landraces grown under on‐farm conservation conditions by indigenous farmers are extremely important for future crop improvement. However, little is known about how the natural selection and agriculture practices of indigenous farmers interact to shape and change the population genetics of rice landraces grown under on‐farm conservation conditions during the domestication. In this study, we sequenced DNA from 108 core on‐farm conserved rice landraces collected from the ethnic minority regions of Yunnan, China, including 56 accessions collected in 1980 and 52 accessions collected in 2007 and obtained 2,771,245 of credible SNPs. Our findings show that most genetic diversity was retained during the 27 years of domestication by on‐farm conservation. However, SNPs with marked allele frequency differences were found in some genome regions, particularly enriched in genic regions, indicating changes in genic regions may have played a much more prominent role in the short‐term domestication of 27 years. We identified 186 and 183 potential selective‐sweep regions in the indica and japonica genomes, respectively. We propose that on‐farm conserved rice landraces during the short‐term domestication had a highly polygenic basis with many loci responding to selection rather than a few loci with critical changes in response to selection. Moreover, loci affecting important agronomic traits and biotic or abiotic stress responses have been particularly targeted in selection. A genome‐wide association study identified 90 significant signals for six traits, 13 of which were in regions of selective sweeps. Moreover, we observed a number of significant and interesting associations between loci and environmental factors, which implies adaptation to local environment. Our results provide insights into short‐term evolutionary processes and shed light on the underlying mechanisms of on‐farm conservation.
Infection of the equine population by Leishmania parasites
Authors: Mhadhbi M. , Sassi A. 
Published: September 2019

SummaryInfection of equids by Leishmania (L.) parasites was previously described in both the Old and New World, particularly in Central and South America. Equine cutaneous leishmaniasis (CL) is caused by the Leishmania species, L. Viannia (V.) braziliensis and L. infantum, previously identified in humans and other parasite hosts living in the same geographic endemic areas. Sporadic autochthonous clinical cases, with no travel history, were documented in several countries including Germany, Portugal, Spain, Texas and Brazil; L. infantum and L. (Mundinia) martiniquensis were the infectious species. Prevalence of subclinical infections is extremely low and CL is observed in only a small proportion of infected animals with the appearance of single or multiple cutaneous lesions located on the head, external ear, scrotum, legs and the neck. To date, there has been no report of visceral abnormalities. However, the mild clinical profile of the disease and its spontaneous regression may indicate that skin lesions related to Leishmania infection is underdiagnosed. Importantly, although the prevalence of Leishmania infections in the equine population is low, a risk may rise from its potential involvement in the parasite transmission cycles as a source of infection for phlebotomine vectors and susceptible mammalian hosts. This review article summarises our current knowledge of the epidemiology, clinical presentation and diagnosis of Leishmania‐infected equids.
Transient pelvic limb neuropathy following proximal metatarsal and tarsal magnetic resonance imaging in seven horses
Authors: Moreno K. L. , Scallan E. M. , Friedeck W. O. , Simon B. T. 
Published: September 2019

SummaryBackgroundPelvic limb neuropathy is a rare post‐anaesthetic complication. In the authors’ experiences, the incidence of post‐anaesthesia neuropathy is increased following MRI of the proximal metatarsus and tarsal regions when compared with previously reported incidences of post‐anaesthetic neuropathy.ObjectivesThis study reports the incidence, diagnosis, treatment and outcome of seven horses with post‐anaesthesia neuropathy following proximal metatarsal and tarsal MRI.Study designRetrospective case series.MethodsCase record review of horses receiving general anaesthesia for MRI between 1 January 2012 and 31 December 2017.ResultsA total of 1134 MRI procedures were performed and reviewed for analysis. Eight cases of neuropathy were identified in 1088 limb scans (0.74%). Of these cases, one was subsequent to thoracic limb imaging (1/834; 0.12%) and seven were subsequent to imaging of proximal metatarsal and/or tarsal structures (7/181; 3.9%). Following proximal metatarsal and/or tarsal MRI, transient nondependent limb femoral neuropathy developed in six of the seven affected horses, with one additional horse developing peroneal neuropathy of the dependent limb. Recovery of pelvic limb function occurred within 72 h and 9 days in six and one horse, respectively.Main limitationsAnaesthetic protocol and neuropathy treatment for the affected horses were not standardised.ConclusionsThough an uncommon complication in horses, transient neuropathy may occur more frequently following MRI of the proximal metatarsal and tarsal structures when compared with other MRI scans. This may be due to patient positioning and the requirement for limb traction for MRI of more proximal regions. Supportive care facilitates rapid return to function.
The effectiveness of chemical restraint in managing acute agitation and aggression: A systematic review of randomized controlled trials
Authors: Muir‐Cochrane Eimear , Oster Candice , Gerace Adam , Dawson Suzanne , Damarell Raechel , Grimmer Karen 
Published: September 2019

AbstractOne approach to manage people with behaviours of concern including agitated or aggressive behaviours in health care settings is through the use of fast‐acting medication, called chemical restraint. Such management often needs to be delivered in crisis situations to patients who are at risk of harm to themselves or others. This paper summarizes the available evidence on the effectiveness and safety of chemical restraint from 21 randomized controlled trials (RCTs) involving 3788 patients. The RCTs were of moderate to high quality and were conducted in pre‐hospital, hospital emergency department, or ward settings. Drugs used in chemical restraint included olanzapine, haloperidol, droperidol, risperidol, flunitrazepam, midazolam, promethazine, ziprasidone, sodium valproate, or lorazepam. There was limited comparability between studies in drug choice, combination, dose, method of administration (oral, intramuscular, or intravenous drip), or timing of repeat administrations. There were 31 outcome measures, which were inconsistently reported. They included subjective measures of behaviours, direct measures of treatment effect (time to calm; time to sleep), indirect measures of agitation (staff or patient injuries, duration of agitative or aggressive episodes, subsequent violent episodes), and adverse events. The most common were time to calm and adverse events. There was little clarity about the superiority of any chemical method of managing behaviours of concern exhibited by patients in Emergency Departments or acute mental health settings. Not only is more targeted research essential, but best practice recommendations for such situations requires integrating expert input into the current evidence base.
Body fat percentage, obesity, and their relation to the incidental risk of hypertension
Authors: Park Sung Keun , Ryoo Jae‐Hong , Oh Chang‐Mo , Choi Joong‐Myung , Chung Pil‐Wook , Jung Ju Young 
Published: September 2019

AbstractStudies have indicated that increased body fat is associated with cardiovascular risk factors including hypertension. However, there is only limited information about the influence of body fat percentage (BF%) on incident hypertension. In a cohort of Korean genome epidemiology study (KoGES), 4864 non‐hypertensive participants were divided into 5 quintile groups, and followed‐up for 10 years to monitor incident hypertension. Cox proportional hazard model was used to evaluate the hazard ratio (HRs) and 95% confidence interval (CI) for hypertension (adjusted HRs [95% CI]) according to BF% quintile groups. Subgroup analysis was conducted by low or high level of BF% (cutoff: 22.5% in men and 32.5% in women) and low or high level of body mass index (BMI), waist circumference (WC) and waist‐to‐hip ratio (WHR). In adjusted model, compared with BF% quintile 1, the risk of incident hypertension significantly increased over BF% quintile 3 (BF% ≥19.9%) in men (quintile 3:1.42 [1.10‐1.85], quintile 4:1.58 [1.22‐2.05], quintile 5:1.82 [1.40‐2.36]), and quintile 4 (BF% ≥32.5%) in women (quintile 4:1.48 [1.12‐1.94], quintile 5:1.56 [1.20‐2.04]). Subgroup analysis showed that individuals with high BF% were significantly associated with the increased risk of hypertension even in individuals with low BMI, WC, and WHR. The risk of hypertension increased proportionally to BF% over the specific level of BF% in Koreans. Even in non‐obese individuals, increase in BF% was significantly associated with the increased risk of hypertension.