bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Aims

The 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.

Methods

The 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).

Results

In 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.

Conclusion

Regulation 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

Haploidentical 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 Purpose

Non‐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 Approach

Inhibition 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 Results

Delayed 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 Implications

Our 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 Purpose

Fentanyl 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 Approach

Respiration (rate and tidal volume) was measured in awake, freely moving mice by whole body plethysmography.

Key Results

Intravenously 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 Implications

We 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

Transplant 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

Females 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

Black 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

Theory 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

Traditional 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

Infection 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

Background

Pelvic 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.

Objectives

This study reports the incidence, diagnosis, treatment and outcome of seven horses with post‐anaesthesia neuropathy following proximal metatarsal and tarsal MRI.

Study design

Retrospective case series.

Methods

Case record review of horses receiving general anaesthesia for MRI between 1 January 2012 and 31 December 2017.

Results

A 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 limitations

Anaesthetic protocol and neuropathy treatment for the affected horses were not standardised.

Conclusions

Though 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

One 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

Studies 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.
Uridine phosphorylase 1 associates to biological and clinical significance in thyroid carcinoma cell lines
Authors: Guan Yaoyao , Bhandari Adheesh , Zhang Xiaohua , Wang Ouchen
Published: September 2019

Thyroid cancer incidence has been continuity increasing worldwide. Uridine phosphorylase 1 (UPP1) is a protein‐coding gene and has been detected that UPP1 was the higher expression in many solid malignancies, just as head and neck cancers, breast cancer, compared with paired normal tissue. But the act of UPP1 in thyroid cancer is not explicit. In this article, we investigate the function of UPP1 expression in thyroid cancer. The Cancer Genome Atlas (TCGA) unpaired thyroid cancer and normal RNA‐seq data were downloaded, and our paired thyroid cancer and normal samples were analysed by a polymerase chain reaction. The expression of UPP1 was regulated by transfected small interfering RNA, and the function of UPP1 was determined via migration, invasion and cell proliferation assays. Western blot assay was achieved to determine the UPP1 expression correlates with the function of 5‐FU regulate epithelial‐mesenchymal transition. The significant upregulation of UPP1 in thyroid cancer tissues compared with normal thyroid tissues was revealed by our data and TCGA data. UPP1 overexpression was significantly correlated with lymph node metastasis, tumour stage and tumour size. In the cell, experiments showed that UPP1 low expression significantly suppressed the migration, invasion and proliferation. Western blot assay proves the effect of UPP1 expression on 5‐FU regulates epithelial‐mesenchymal transition pathway. UPP1 plays a crucial oncogene in thyroid cancer. Our findings indicate that UPP1 might be a biomarker of thyroid cancer and may act by regulating epithelial‐mesenchymal transition (EMT).
Examining the Precision of Cut Scores Within a Generalizability Theory Framework: A Closer Look at the Item Effect
Authors: Clauser Brian E. , Kane Michael , Clauser Jerome C.
Published: September 2019

An Angoff standard setting study generally yields judgments on a number of items by a number of judges (who may or may not be nested in panels). Variability associated with judges (and possibly panels) contributes error to the resulting cut score. The variability associated with items plays a more complicated role. To the extent that the mean item judgments directly reflect empirical item difficulties, the variability in Angoff judgments over items would not add error to the cut score, but to the extent that the mean item judgments do not correspond to the empirical item difficulties, variability in mean judgments over items would add error to the cut score. In this article, we present two generalizability‐theory–based analyses of the proportion of the item variance that contributes to error in the cut score. For one approach, variance components are estimated on the probability (or proportion‐correct) scale of the Angoff judgments, and for the other, the judgments are transferred to the theta scale of an item response theory model before estimating the variance components. The two analyses yield somewhat different results but both indicate that it is not appropriate to simply ignore the item variance component in estimating the error variance.
Experiences of safety among patients receiving home dialysis therapies
Authors: Virtanen Heli , Tuominen Riitta , Kiukainen Senni , Koskinen Jenni , Koskenniemi Jaana , Laulaja Johanna , Numanovic Vanesa , Leino‐Kilpi Helena
Published: September 2019

Background

Dialysis patients' experience of safety can be seen positively connected with their wellbeing and successful outcomes of their treatment and care. Therefore, it is necessary to identify the factors promoting and weakening the safety experiences and create a basis for empowering interventions.

Objectives

Analyse patients' experiences of safety with dialysis and the factors promoting and weakening their safety.

Methods

A descriptive study design was used. This study analysed Finnish patients' (n = 70) experiences of safety with dialysis and the factors promoting and weakening patients' safety. Data were collected using a questionnaire including one structured question and two open questions.

Findings

The patients experienced their care as safe. Thematic analysis provided three factors promoting patients' safety: certainty of patient's own competence in dialysis self‐management, competence of personnel in dialysis treatment and care, continuity of ensuring patients' state of health, as well as three factors weakening safety: patients' uncertainty of living with chronic kidney disease, insufficient patient education and uncertain realisation of dialysis treatment and care.

Conclusion

This study provided new insight into understanding patients' experiences of safety with dialysis. We show that the factors connected with patients' safety were related to the successful realisation of self‐management, support for the self‐management, and delivery of dialysis treatment and care anticipating high‐level outcomes. In light of this study, there are development needs in dialysis treatment and care as a whole in order to ensure patients' safety.
A Qualitative Investigation of Factors that Influence School Employee Health Behaviors: Implications for Wellness Programming
Authors: Schultz Nicole S. , Chui Kenneth K.H. , Economos Christina D. , Lichtenstein Alice H. , Volpe Stella L. , Sacheck Jennifer M.
Published: September 2019

BACKGROUND

Employee health promotion in the elementary school setting can support students' health and academic success. School employees can serve as role models, yet evidence suggests poor health in this population. We identified factors that influence school employee health behaviors to inform subsequent development of employee wellness programs.

METHODS

Focus groups (10 groups, total N = 62) and interviews (N = 5) were conducted with school employees. Participants were recruited from schools in socioeconomically disadvantaged, racially diverse districts in Massachusetts. We used a socioecological framework to identify multi‐level factors that influence employee health behaviors. Factors were characterized as supports (+) or barriers (−) to health‐promoting behaviors.

RESULTS

Eight themes highlighted the importance of an organizational culture that sustains successful employee wellness programming. Intrapersonal themes included: High Stress (+/−), Desire to Adopt Healthy Behaviors (+), and Sufficient Health Knowledge (+). Interpersonal themes included: Strong Social Network (+) and a Desire to Role Model (+). Organizational themes included: Demanding Job (−), Lack of Wellness Culture (−), and Unhealthy Food (−).

CONCLUSIONS

Our findings suggest that this population would be receptive to wellness programming. Promising strategies include supporting a dedicated wellness champion and creating recognizable top down wellness support for employees.
Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance
Authors: Jiang Dong , Wang Jianghua , Zhao Xuesen , Li Yuxin , Zhang Qun , Song Chuan , Zeng Hui , Wang Xianbo
Published: September 2019

Background

Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug‐resistant hepatitis B virus. Few clinical cases with confirmed TDF‐resistance have been reported to date.

Methods and Results

Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)‐resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52‐fold higher half maximal effective concentration than that of wild‐type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy.

Conclusion

An rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF‐resistant mutant. Our studies provide novel insights into the treatment of NA‐naïve patients as well as patients with TDF resistance.
Exposure to environmental radionuclides is associated with altered metabolic and immunity pathways in a wild rodent
Authors: Kesäniemi Jenni , Jernfors Toni , Lavrinienko Anton , Kivisaari Kati , Kiljunen Mikko , Mappes Tapio , Watts Phillip C.
Published: September 2019

Wildlife inhabiting environments contaminated by radionuclides face putative detrimental effects of exposure to ionizing radiation, with biomarkers such as an increase in DNA damage and/or oxidative stress commonly associated with radiation exposure. To examine the effects of exposure to radiation on gene expression in wildlife, we conducted a de novo RNA sequencing study of liver and spleen tissues from a rodent, the bank vole Myodes glareolus. Bank voles were collected from the Chernobyl Exclusion Zone (CEZ), where animals were exposed to elevated levels of radionuclides, and from uncontaminated areas near Kyiv, Ukraine. Counter to expectations, we did not observe a strong DNA damage response in animals exposed to radionuclides, although some signs of oxidative stress were identified. Rather, exposure to environmental radionuclides was associated with upregulation of genes involved in lipid metabolism and fatty acid oxidation in the livers – an apparent shift in energy metabolism. Moreover, using stable isotope analysis, we identified that fur from bank voles inhabiting the CEZ had enriched isotope values of nitrogen: such an increase is consistent with increased fatty acid metabolism, but also could arise from a difference in diet or habitat between the CEZ and elsewhere. In livers and spleens, voles inhabiting the CEZ were characterized by immunosuppression, such as impaired antigen processing, and activation of leucocytes involved in inflammatory responses. In conclusion, exposure to low dose environmental radiation impacts pathways associated with immunity and lipid metabolism, potentially as a stress‐induced coping mechanism.
Fucoidan affects oral squamous cell carcinoma cell functions in vitro by regulating FLNA‐derived circular RNA
Authors: Zhang Nanyang , Gao Ling , Ren Wenhao , Li Shaoming , Zhang Demeng , Song Xianqin , Zhao Chenyang , Zhi Keqian
Published: September 2019

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types, with a high annual incidence. Although chemotherapy contributes to suppressing OSCC tumorigenesis, the available treatments result in poor prognosis because of local recurrence and regional lymph node metastasis. Thus, it is necessary to discover novel and safe drugs with greater effectiveness and fewer side effects. Fucoidan is a component of the cell wall of brown seaweed that has been shown to produce a wide range of biological activities. The present study aimed to investigate the effectiveness of fucoidan in treating OSCC. In in vitro studies, we found that fucoidan inhibited OSCC growth and suppressed migration and invasion of OSCC cells. In addition, the potential interaction between fucoidan and filamin A (FLNA)–derived circular RNA (circFLNA) was predicted using bioinformatics databases and then confirmed in OSCC samples and cell lines. Indeed, fucoidan increased the expression of circFLNA in OSCC cell lines. Furthermore, both fucoidan and circFLNA could mediate the expression of key proteins related to cell growth, apoptosis, migration, and invasion. In conclusion, our research demonstrated that fucoidan might be considered as a potential natural drug in the treatment of OSCC patients by targeting circFLNA.
Overexpression of a Prefoldin β subunit gene reduces biomass recalcitrance in the bioenergy crop Populus
Authors: Zhang Jin , Xie Meng , Li Mi , Ding Jinhua , Pu Yunqiao , Bryan Anthony C. , Rottmann William , Winkeler Kimberly A. , Collins Cassandra M. , Singan Vasanth , Lindquist Erika A. , Jawdy Sara S. , Gunter Lee E. , Engle Nancy L. , Yang Xiaohan , Barry Kerrie , Tschaplinski Timothy J. , Schmutz Jeremy , Tuskan Gerald A. , Muchero Wellington , Chen Jin‐Gui
Published: September 2019

Prefoldin (PFD) is a group II chaperonin that is ubiquitously present in the eukaryotic kingdom. Six subunits (PFD1‐6) form a jellyfish‐like heterohexameric PFD complex and function in protein folding and cytoskeleton organization. However, little is known about its function in plant cell wall‐related processes. Here, we report the functional characterization of a PFD gene from Populus deltoides, designated as PdPFD2.2. There are two copies of PFD2 in Populus, and PdPFD2.2 was ubiquitously expressed with high transcript abundance in the cambial region. PdPFD2.2 can physically interact with DELLA protein RGA1_8g, and its subcellular localization is affected by the interaction. In P. deltoides transgenic plants overexpressing PdPFD2.2, the lignin syringyl/guaiacyl ratio was increased, but cellulose content and crystallinity index were unchanged. In addition, the total released sugar (glucose and xylose) amounts were increased by 7.6% and 6.1%, respectively, in two transgenic lines. Transcriptomic and metabolomic analyses revealed that secondary metabolic pathways, including lignin and flavonoid biosynthesis, were affected by overexpressing PdPFD2.2. A total of eight hub transcription factors (TFs) were identified based on TF binding sites of differentially expressed genes in Populus transgenic plants overexpressing PdPFD2.2. In addition, several known cell wall‐related TFs, such as MYB3, MYB4, MYB7, TT8 and XND1, were affected by overexpression of PdPFD2.2. These results suggest that overexpression of PdPFD2.2 can reduce biomass recalcitrance and PdPFD2.2 is a promising target for genetic engineering to improve feedstock characteristics to enhance biofuel conversion and reduce the cost of lignocellulosic biofuel production.
Tolerance to ozone might impose restrictions to plant disease management in tomato
Authors: Romero A. M. , Menéndez A. I. , Folcia A. M. , Martínez‐Ghersa M. A.
Published: September 2019

Tropospheric ozone (O3) is considered a major air pollutant having negative effects on plant growth and productivity. Background concentrations are expected to rise in several regions of the world in the next 50 years, affecting plant responses to diseases, thus requiring new management strategies for food production.

The effects of elevated O3 on the severity of a bacterial disease, and the effectiveness of a chemical defence inducer, were examined in two cultivars of tomato, Roma and Moneymaker, which present different tolerance to this pollutant. The two cultivars differ in their ability to produce and accumulate reactive oxygen species (ROS) in leaf tissues. Tomato plants were challenged with a strain of Xanthomonas vesicatoria, Xv9, which is pathogenic on tomato.

Ozone consistently increased severity of the disease by over 40% in both cultivars. In the more tolerant cultivar, O3 pollution increased disease intensity, even after applying a commercially available product to enhance resistance (acibenzolar‐S‐methyl, BTH). In the more susceptible cultivar, level of disease attained depended on the oxidative balance that resulted from other stress factors.

The antioxidant capacity of the plant at the time of infection was relevant for controlling development of the disease. Our results suggest that development of O3 tolerance in commercial crops might impose a penalty cost in terms of disease management under projected higher O3 concentrations.
Effects of maternal lifestyle interventions on child neurobehavioral development: Follow‐up of randomized controlled trials
Authors: Menting Malou D. , van de Beek Cornelieke , Rono Kristiina , Hoek Annemieke , Groen Henk , Painter Rebecca C. , Girchenko Polina , Lahti‐Pulkkinen Marius , Koivusalo Saila B. , Räikkönen Katri , Eriksson Johan G. , Roseboom Tessa J. , Heinonen Kati
Published: September 2019

Obesity is a major public health problem. Children of women who were obese before or during pregnancy are at increased risk for neurobehavioral developmental problems. Whether a maternal lifestyle intervention conducted before and during pregnancy in obese women affects child neurobehavioral development is unknown. This study reports on the follow‐up of a subsample of two randomized controlled trials, the Finnish RADIEL (n = 216) and Dutch LIFEstyle (n = 305) trial. Women with a pre‐pregnancy BMI ≥29 kg/m2 wishing to conceive or who were already pregnant (<20 weeks) were allocated to a lifestyle intervention or to care as usual. Child neurodevelopment was measured with the Ages and Stages Questionnaire and child behavioral problems were measured with the Childhood Behavior Checklist (RADIEL) or the Strengths and Difficulties Questionnaire (LIFEstyle) at age 3‐6 years. We used linear and binary logistic regression analyses to assess the effects of the lifestyle interventions on children's neurobehavioral developmental scores. Follow‐up data was available from 161(38%) RADIEL and 96(32%) LIFEstyle children. Child neurodevelopmental scores did not differ significantly between children in the intervention and the control group (RADIEL:median = 275 vs. 280; LIFEstyle:median = 270 vs 267). Child behavioral problem scores did not differ significantly between children in the intervention and the control group (RADIEL:median = 22 vs. 21; LIFEstyle:median = 8 vs. 8). We did not observe considerable effects of the lifestyle interventions before or during pregnancy in obese women on child neurobehavioral development. With our sample sizes, we were not able to detect subtle differences in neurobehavioral development however.
Ganciclovir‐resistant post‐transplant cytomegalovirus infection due to combined deletion mutation at codons 595‐596 of the UL97 gene
Authors: Leung Po Yee Mia , Tran Thomas , Testro Adam , Paizis Kathy , Kwong Jason , Whitlam John B.
Published: September 2019

The development of antiviral‐resistant cytomegalovirus (CMV) infection complicates the management of transplant recipients. We describe the case of a 65‐year‐old male who developed CMV disease on valganciclovir prophylaxis (donor CMV IgG positive, recipient CMV IgG indeterminate) 30 days after combined liver–kidney transplantation for alcoholic cirrhosis and hepato‐renal syndrome. After an initial complete response to treatment dose oral valganciclovir, he developed recurrent CMV viraemia. Resistance testing revealed a UL97 mutation with in‐frame deletions of codons 595‐596. He was treated successfully with foscarnet and reduction in immunosuppression. This mutation has not been described previously and was suspected to confer ganciclovir resistance. Ganciclovir resistance occurs most commonly due to mutations in the UL97 or UL54 genes, which encode a protein kinase and a DNA polymerase, respectively. The UL97‐encoded protein kinase phosphorylates ganciclovir to ganciclovir triphosphate, which competitively inhibits viral replication. Mutations in the UL97 gene are typically point mutations or deletions. We describe a new mutation, del595‐596 in the CMV UL97 gene, occurring in the context of clinical treatment failure with standard and double‐dose ganciclovir, and successful virological control achieved with foscarnet. This mutation is likely to result in ganciclovir resistance, although recombinant phenotyping is required for confirmation.
Cellulose defects in the Arabidopsis secondary cell wall promote early chloroplast development
Authors: Xu Duorong , Dhiman Ravi , Garibay Adriana , Mock Hans‐Peter , Leister Dario , Kleine Tatjana
Published: September 2019

Lincomycin (LIN)‐mediated inhibition of protein synthesis in chloroplasts prevents the greening of seedlings, represses the activity of photosynthesis‐related genes in the nucleus, including LHCB1.2, and induces the phenylpropanoid pathway, resulting in the production of anthocyanins. In genomes uncoupled (gun) mutants, LHCB1.2 expression is maintained in the presence of LIN or other inhibitors of early chloroplast development. In a screen using concentrations of LIN lower than those employed to isolate gun mutants, we have identified happy on lincomycin (holi) mutants. Several holi mutants show an increased tolerance to LIN, exhibiting de‐repressed LHCB1.2 expression and chlorophyll synthesis in seedlings. The mutations responsible were identified by whole‐genome single‐nucleotide polymorphism (SNP) mapping, and most were found to affect the phenylpropanoid pathway; however, LHCB1.2 expression does not appear to be directly regulated by phenylpropanoids, as indicated by the metabolic profiling of mutants. The most potent holi mutant is defective in a subunit of cellulose synthase encoded by IRREGULAR XYLEM 3, and comparative analysis of this and other cell‐wall mutants establishes a link between secondary cell‐wall integrity and early chloroplast development, possibly involving altered ABA metabolism or sensing.
Transgenic expression of human CD47 reduces phagocytosis of porcine endothelial cells and podocytes by baboon and human macrophages
Authors: Nomura Shunichiro , Ariyoshi Yuichi , Watanabe Hironosuke , Pomposelli Thomas , Takeuchi Kazuhiro , Garcia Gabriela , Tasaki Masayuki , Ayares David , Sykes Megan , Sachs David , Johnson Richard , Yamada Kazuhiko
Published: September 2019

Background

Our initial studies utilizing a galactosyl‐α1‐3‐galactosyltransferase gene knockout (GalTKO) pig‐to‐baboon renal transplant model demonstrated that the early development of nephrotic syndrome has been a significant obstacle to the long‐term survival of baboon recipients. We have recently documented that sphingomyelin phosphodiesterase‐3 (SMPDL3b) and CD80 expressed on podocytes in porcine kidney grafts contribute to this complication. We have hypothesized that one regulator of immune function is CD47 and that incompatibilities in CD47 between pig and baboon could potentially affect macrophage function, increasing the susceptibility of the kidney grafts to immunologically induced injury.

Methods

In order to address this hypothesis in vitro, we isolated and cultured porcine podocytes and ECs from GalTKO alone, human CD47 (hCD47)/hCD55 expressing transgenic (Tg) GalTKO swine, and GalTKO hCD46/hCD55 Tg swine along with baboon or human macrophages.

Results

We found that baboon macrophages phagocytosed porcine ECs in a similar manner to human macrophages, and this response was significantly reduced when porcine ECs and podocytes expressed hCD47/hCD55 but not hCD46/hCD55 without hCD47. Furthermore, masking hCD47 by anti‐hCD47 antibody on hCD47/hCD55Tg ECs restored phagocytosis. These results are consistent with the hypothesis that CD47 incompatibility plays an important role in promoting macrophage phagocytosis of endogenous cells from the transplanted kidney.

Conclusions

The similar levels of phagocytosis of porcine cells by baboon and human macrophages suggest that the expression of hCD47Tg on glomerular cells in donor porcine kidneys may prove to be a key strategy for preventing proteinuria following kidney xenotransplantation in a pig‐to‐human as well as a pig‐to‐baboon model.
Neuromuscular electrical stimulation‐promoted plasticity of the human brain
Authors: Carson Richard G. , Buick Alison R.
Published: September 2019

The application of neuromuscular electrical stimulation (NMES) to paretic limbs has demonstrated utility for motor rehabilitation following brain injury. When NMES is delivered to a mixed peripheral nerve, typically both efferent and afferent fibres are recruited. Muscle contractions brought about by the excitation of motor neurons are often used to compensate for disability by assisting actions such as the formation of hand aperture, or by preventing others including foot drop. In this context, exogenous stimulation provides a direct substitute for endogenous neural drive. The goal of the present narrative review is to describe the means through which NMES may also promote sustained adaptations within central motor pathways, leading ultimately to increases in (intrinsic) functional capacity. There is an obvious practical motivation, in that detailed knowledge concerning the mechanisms of adaptation has the potential to inform neurorehabilitation practice. In addition, responses to NMES provide a means of studying CNS plasticity at a systems level in humans. We summarize the fundamental aspects of NMES, focusing on the forms that are employed most commonly in clinical and experimental practice. Specific attention is devoted to adjuvant techniques that further promote adaptive responses to NMES thereby offering the prospect of increased therapeutic potential. The emergent theme is that an association with centrally initiated neural activity, whether this is generated in the context of NMES triggered by efferent drive or via indirect methods such as mental imagery, may in some circumstances promote the physiological changes that can be induced through peripheral electrical stimulation.

image