bluuebunny/crossref_metadata_2025 huggingface dataset:
Lycorine targets multiple myeloma stem cell‐like cells by inhibition of Wnt/β‐catenin pathway
Authors: Wang Haiqin , Gong Yanfei , Liang Long , Xiao Ling , Yi Hui , Ye Mao , Roy Mridul , Xia Jiliang , Zhou Wen , Yang Chaoying , Shen Xiaokai , Zhang Boxin , Li Zhenzhen , Liu Jing , Zhou Hui , Xiao Xiaojuan
Published: March 2020

Multiple myeloma (MM) is characterised by the proliferation and accumulation of malignant plasma cells in the bone marrow. Despite the progress in treatment over the last few years, MM remains incurable and the majority of patients relapse. MM stem‐like cells (MMSCs) have been considered as the main reason for drug resistance and eventual relapse. Currently, therapeutic agents are not enough to eradicate MMSCs, and finding effective strategies to eradicate MMSCs may improve the outcome of patients. Here we showed that lycorine, a natural compound from the Amaryllidaceae species, effectively inhibits the proliferation of myeloma cells from cell lines or patients, mainly through decreasing ALDH1+ cells. Mechanistically, lycorine decreases the MMSC population through inhibition of the Wnt/β‐catenin pathway by reducing the β‐catenin protein level. Moreover, lycorine could overcome the increasing proportion of ALDH1+ cells caused by bortezomib (BTZ) treatment, and a combination BTZ and lycorine have a synergistic effect on anti‐myeloma cells. Furthermore, we found a similar reduction of MMSC characteristics by lycorine in BTZ‐resistant MM cells and primary CD138+ plasma cells. Collectively, our findings indicate lycorine as a promising agent to target MMSCs to overcome the drug resistance of BTZ, and that, alone or in combination with BTZ, lycorine is a potential therapeutic strategy for MM treatments.
Vascular endothelial growth factor‐loaded poly‐lactic‐co‐glycolic acid nanoparticles with controlled release protect the dopaminergic neurons in Parkinson's rats
Authors: Meng Xian‐Yue , Huang An‐Qi , Khan Afsar , Zhang Li , Sun Xiao‐Qian , Song Hao , Han Jun , Sun Qian‐Ru , Wang Yu‐Dan , Li Xue‐Li
Published: March 2020

Vascular endothelial growth factor (VEGF) had neuroprotective effects on dopaminergic (DA) neurons. In order to overcome the gastrointestinal digestion and bioaccessibility, VEGF was encapsulated with poly‐lactic‐co‐glycolic acid nanospheres (NS) in order to prevent the VEGF degradation until its release. The caudal administration of VEGF and NS encapsulated VEGF at different doses (1.0, 10.0, and 100.0 ng/ml) on the rats with Parkinson's disease lesion was evaluated. Intravenous injected VEGF at the dose of 1 ng/ml displayed the strongest neuroprotective effect than other groups as well as the stereotaxic group. The NS encapsulated with VEGF can pass through blood–brain barrier and protect the DA neurons. There was no significant difference between intravenous injection method and stereotaxic method, while the first method is simpler and convenient. Injection of NS encapsulated with VEGF may become a valuable neurorescuing therapeutic approach for Parkinson's disease.
Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta
Authors: Zhytnik Lidiia , Maasalu Katre , Reimand Tiia , Duy Binh Ho , Kõks Sulev , Märtson Aare
Published: March 2020

Osteogenesis imperfecta (OI) is a rare genetic disorder also known as a “brittle bone disease.” Around 90% of patients with OI harbor loss‐of‐function or dominant negative pathogenic variants in the COL1A1 and COL1A2 genes, which code for collagen type I α1 and α2 chains. Collagen‐related forms of the disorder are classified as Sillence OI types I–IV. OI phenotype expression ranges from mild to lethal. The current study aims to evaluate associations between interfamilial and intrafamilial phenotypic variability and genotype characteristics of patients with collagen‐related OI. The study was based on a systematic review of collagen‐related OI cases from the University of Tartu OI database (n = 137 individuals from 81 families) and the Dalgleish database (n = 479 individuals). Interfamilial variability analysis has shown that 17.74% of all studied OI‐related variants were associated with the same phenotype. The remaining 82.26% of pathogenic variants were associated with variable phenotypes. Additionally, higher interfamilial variability correlated with the COL1A1 gene (P value = 0.001) and dominant‐negative variants (P value = 0.0007). Within intrafamilial variability, 32.81% families had increasing or decreasing OI phenotype severity across generations. Higher intrafamilial variability of phenotypes correlated with the collagen I dominant negative variants (P value = 0.0246). The current study shows that, in line with other phenotype modification factors, OI interfamilial and intrafamilial diversity potential is associated with the genotype characteristics of the OI‐causing pathogenic variants. The results of the current study may advance knowledge of OI phenotype modification as well as assist family planning and the evaluation of disease progression in subsequent generations.
Developing disaster risk reduction skills among informal construction workers in Nepal
Authors: Rose Jo , Chmutina Ksenia
Published: March 2020

Capacity development has become an embedded component of the aid package offered by international organisations responding to humanitarian crises. The effectiveness of capacity development is, however, rarely monitored or examined. What is more, the local context and the learning preferences of trainees appear often to be overlooked. Yet, the informal construction sector is thriving throughout the world. Using a case study of Nepal, where construction and post‐earthquake reconstruction projects are largely delivered by the informal construction sector, this paper analyses, therefore, how and whether informal construction workers successfully develop capacity and utilise trainings to create more disaster‐resilient buildings. It goes on to assess how one can draw on the learning preferences of Nepalese construction workers to improve the effectiveness and the sustainability of capacity development initiatives. Lastly, the paper highlights that training programmes informed by the context and the preferred learning style of disaster‐affected communities promote and sustain capacity development efforts.
The onset speed of hyperglycemia is important to the development of neuropathic hyperalgesia in streptozotocin‐induced diabetic rats
Authors: do Prado Filipe C. , Vieira Willians F. , Fernandes de Magalhães Silviane , Bonet Ivan José Magayewsky , Tambeli Claudia H. , Parada Carlos A.
Published: March 2020

Diabetic neuropathic hyperalgesia is one of the most common diabetes complications. The physiopathological mechanism of hyperalgesia and the reason by which this condition affects only part of the diabetic patients still unclear. We tested whether an adaptation of primary afferent neurons to hyperglycemia could prevent the development of hyperalgesia. Hyperglycemia was induced in male Wistar rats by a daily administration of a low dose of streptozotocin (STZ), during five consecutive days. Glycemia and mechanical nociceptive thresholds were measured at days 0, 3, 7 and 14 after starting the streptozotocin treatment. In parallel, dorsal root ganglia (DRG) neurons were collected from healthy male Wistar rats and cultured in different glucose concentrations (mimicking slow or fast increase of hyperglycemia), and used for calcium imaging and Western blot analyses. Rats with a slow increase of glycemia did not develop hyperalgesia, while rats with a fast increase of glycemia developed hyperalgesia. DRG neurons suddenly incubated in DMEM containing a high glucose concentration showed a significant increase of calcium influx. However, DRG neurons incubated in DMEM and receiving increasing doses of glucose had the same calcium influx observed in control neurons. The activation of AMPK (α1/α2) was greater in L5‐L6 DRG of hyperglycemic and non‐hyperalgesic rats, when compared with hyperglycemic and hyperalgesic rats. Our data suggest that the onset speed of hyperglycemia could be related to the development of diabetic neuropathic hyperalgesia, as a maladaptive consequence associated with low activation of AMPK (α1/α2) in peripheral nociceptive neurons when the glycemia suddenly increases.
IP3R2 null mice display a normal acquisition of somatic and neurological development milestones
Authors: Guerra‐Gomes Sónia , Cunha‐Garcia Daniela , Marques Nascimento Diana Sofia , Duarte‐Silva Sara , Loureiro‐Campos Eduardo , Morais Sardinha Vanessa , Viana João Filipe , Sousa Nuno , Maciel Patrícia , Pinto Luísa , Oliveira João Filipe
Published: March 2020

Astrocytes are key players in the regulation of brain development and function. They sense and respond to the surrounding activity by elevating their intracellular calcium (Ca2+) levels. These astrocytic Ca2+ elevations emerge from different sources and display complex spatio‐temporal properties. Ca2+ elevations are spatially distributed in global (soma and main processes) and/or focal regions (microdomains). The inositol 1,4,5‐trisphosphate receptor type 2 knockout (IP3R2 KO) mouse model lacks global Ca2+ elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP3R2 during development may trigger compensating phenotypes, which could bias the results of experiments using developing or adult mice. To address this issue, we performed a detailed neurodevelopmental evaluation of male and female IP3R2 KO mice, during the first 21 days of life, as well as an evaluation of motor function, strength and neurological reflexes in adult mice. Our results show that male and female IP3R2 KO mice display a normal acquisition of developmental milestones, as compared with wild‐type (WT) mice. We also show that IP3R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP3Rs, we quantified the relative mRNA levels of all 3 subtypes, in brain tissue. We found that, along with the complete deletion of Itpr2, there is no compensatory expression of Itpr1 or Itrp3. Overall, our results show that the IP3R2 KO mouse is a reliable model to study the functional impact of global IP3R2‐dependent astrocytic Ca2+ elevations.
KCNT1‐related epilepsy: An international multicenter cohort of 27 pediatric cases
Authors: Borlot Felippe , Abushama Ahmed , Morrison‐Levy Nadine , Jain Puneet , Puthenveettil Vinayan Kollencheri , Abukhalid Musaad , Aldhalaan Hesham M. , Almuzaini Hanin S. , Gulati Sheffali , Hershkovitz Tova , Konanki Ramesh , Lingappa Lokesh , Luat Aimee F. , Shafi Shatha , Tabarki Brahim , Thomas Maya , Yoganathan Sangeetha , Alfadhel Majid , Arya Ravindra , Donner Elizabeth J. , Ehaideb Salleh N. , Gowda Vykuntaraju K. , Jain Vivek , Madaan Priyanka , Myers Kenneth A. , Otsubo Hiroshi , Panda Prateek , Sahu Jitendra K. , Sampaio Letícia P. B. , Sharma Suvasini , Simard‐Tremblay Elisabeth , Zak Maria , Whitney Robyn
Published: March 2020

Objective

Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1‐related epilepsy and explored genotype‐phenotype correlations associated with frequently encountered variants.

Methods

A cross‐sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.

Results

Twenty‐seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two‐thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray‐white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%‐50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.

Significance

Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence‐based practice is still unavailable.
Rate of dyslipidemia higher among women living with HIV: A comparison of metabolic and cardiovascular health in a cohort to study aging in HIV
Authors: Russell EAB , Albert AYK , Côté HCF , Hsieh AYY , Nesbitt A , Campbell AR , Maan EJ , Brophy J , Pick N , Murray MCM
Published: March 2020

Objectives

Combination antiretroviral therapy has largely restored the lifespan of persons living with HIV. Data suggest early comorbidities of aging in this population. Past studies focused on men; limited data exist regarding the prevalence of dyslipidaemia in women living with HIV (WLWH). We investigated the prevalence of cardiometabolic abnormalities among WLWH and HIV‐negative women in the Children and Women: Antiretrovirals and Markers of Aging (CARMA) cohort, and their relationships to cellular aging markers.

Methods

We conducted a cross‐sectional analysis of nonpregnant female patients (156 WLWH and 133 HIV‐negative controls, aged 12–69 years) enrolled in CARMA between 2013 and 2017. The Framingham risk score (FRS) and the prevalences of hypertension, diabetes, metabolic syndrome and dyslipideamia were determined using self‐report, anthropometrics, chart review and laboratory data. Cellular aging was determined by assessing leukocyte telomere length and blood mitochondrial DNA content. Diagnoses were based on current Canadian guidelines and definitions.

Results

HIV‐infected status was associated with dyslipidaemia [odds ratio (OR) 2.89; 95% confidence interval (CI) 1.69–5.01], but not diabetes, higher FRS, hypertension or metabolic syndrome. The median age was 43.5 [interquartile range (IQR) 36.8–50.9] years in WLWH and 46.2 (IQR 30.3–54.9) years in HIV‐negative controls. WLWH were less likely to be menopausal or use alcohol, and more often had hepatitis C virus infection or a current or past smoking history. Lower mitochondrial DNA content was associated with metabolic syndrome; no other associations were noted between cardiometabolic abnormalities and markers of cellular aging.

Conclusions

Despite their relatively young age, almost two‐thirds of WLWH had dyslipidaemia, a significantly greater proportion than in controls. Strategies to address dyslipidaemia and decrease smoking rates may improve long‐term outcomes among WLWH.
Density dependence in Golden Eagle Aquila chrysaetos fecundity better explained by individual adjustment than territory heterogeneity
Authors: Chambert Thierry , Imberdis Ludovic , Couloumy Christian , Bonet Richard , Besnard Aurélien
Published: March 2020

Density‐dependence effects acting on fecundity can be explained by two competing hypotheses. The individual adjustment hypothesis (IAH) states that, as population density increases, interference among individuals negatively affects their breeding performance. The second hypothesis, the habitat heterogeneity hypothesis (HHH), proposes that, as more individuals occupy the space available, lower quality habitats are increasingly used, causing average population fecundity to decline. In territorial species, it is often predicted that interference mechanisms (IAH) should be of less importance than spatial heterogeneity (HHH). Here, we test this prediction in Golden Eagles, using 35 years of reproduction monitoring data from a population that has been recolonizing the grounds of a French National Park (Ecrins) in the Alps. During the study period, the Eagle population increased from c. 11 to 41 territorial pairs, providing a good opportunity to explicitly assess fecundity across a gradient of densities. Under the IAH, we expect the fecundity of all territories to diminish as density rises. Under strict HHH, older territories should maintain higher fecundity across time, and a positive relationship between fecundity and the seniority of a territory should be observed. A density‐dependent pattern was clearly detected at the population level. At the territory level, the decrease of fecundity was strongly related to population size but not to territory seniority. Fecundity decreased similarly in all territories, suggesting that the IAH better explains the observed pattern. Two alternative mechanisms, related to the IAH, could be at play in this population: (1) negative interference by neighbours and non‐territorial Eagles and (2) the contraction of individual territories over time. Our results provide new insights into density dependence in territorial raptors, suggesting that, in addition to habitat heterogeneity, interference mechanisms might actually also play an important role.
Bacterial cellulose–assisted synthesis of glass‐ceramic scaffolds with TiO2 crystalline domains
Authors: Jinga Sorin‐Ion , Draghici Alina‐Denisa , Mocanu Alexandra , Nicoara Adrian‐Ionut , Iordache Florin , Busuioc Cristina
Published: March 2020

Glass‐ceramic 3D porous structures were obtained by from a polymeric template, which was successively loaded with calcium phosphates, by chemical reaction and a dried gel based on barium and titanium by physical attachment. The resulting composite was subjected to a freeze‐drying procedure in order to maintain the spongy morphology. Under the effect of the subsequent thermal treatment at temperatures above 1000°C, the biocellulose membrane was completely removed, the mineral phases combined with each other through intense diffusion processes, and the mineral scaffolds acquired enough mechanical strength to become self‐sustained. The as‐prepared and thermally treated samples were characterized from physicochemical and biological point of view. The only crystalline phase emerged in the final masses was TiO2, while the microstructure was individualized as peculiar 3D architectures with porous and branched appearance. All prepared materials were proven to be biocompatible with the mesenchymal stem cells, showing no cytotoxic effect and suitability for the field of tissue engineering.
Current approach to diagnosis and management of retroperitoneal fibrosis
Authors: Tanaka Toshiaki , Masumori Naoya
Published: March 2020

Retroperitoneal fibrosis is characterized by fibrotic lesions around the abdominal aorta and common ileac artery causing ureteral obstruction. Secondary retroperitoneal fibrosis is associated with malignant disease, drugs, exposure to radiation and surgery. In contrast, the majority of retroperitoneal fibrosis is classified into idiopathic retroperitoneal fibrosis, for which immunological etiology has been suggested. Recently, idiopathic retroperitoneal fibrosis has been considered to be a spectrum of immunoglobulin G4‐related disease, a systemic inflammatory disease, the concept of which has been developed during the past decade. In the management of retroperitoneal fibrosis, assessment of systemic lesions associated with immunoglobulin G4‐related disease and the exclusion of secondary retroperitoneal fibrosis is mandatory. Histological examination of retroperitoneal lesions is desired for accurate diagnosis and management. Laparoscopic or open biopsy is often beneficial, although it is more invasive than needle biopsy. Treatment for idiopathic retroperitoneal fibrosis consists of meticulous glucocorticoid therapy based on that for immunoglobulin G4‐related disease, which is expected to be highly effective. Ureteral obstruction is usually managed with conservative procedures, such as ureteral stenting or percutaneous nephrostomy. The goal of treatment for retroperitoneal fibrosis should be freedom from the stent/nephrostomy with withdrawal of the glucocorticoid in addition to salvage of renal function; however, conservative management does not always provide favorable outcomes. In contrast, aggressive surgical treatment, such as ureterolysis, can achieve the goal; however, the procedure is associated with high morbidity. Establishment of a consensus about treatment for idiopathic retroperitoneal fibrosis, including the optimal indications for the invasive surgical procedure and conservative management, is desired.
The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo
Authors: He Rui , Li Qin , Shen Wenqi , Wang Tao , Lu Huijuan , Lu Junxi , Lu Fendi , Luo Ming , Zhang Jiankang , Gao Haiwei , Wang Dong , Xing Wanli , Jia Weiping , Liu Fang
Published: March 2020

Cold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high‐voltage and high‐frequency power supply. Eight‐week‐old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low‐dose group), and 180s' CAP (high‐dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound‐healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low‐dose group and high‐dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL‐6, tumour necrosis factor‐α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor‐β in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound‐healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.
Oridonin inhibits the migration and epithelial‐to‐mesenchymal transition of small cell lung cancer cells by suppressing FAK‐ERK1/2 signalling pathway
Authors: Xu Linhao , Bi Yanli , Xu Yizhou , Zhang Zhuocheng , Xu Wenjie , Zhang Sisi , Chen Jian
Published: March 2020

Small cell lung cancer (SCLC) is a severe malignant with high morbidity; however, few effective and secure therapeutic strategy is used in current clinical practice. Oridonin is a small molecule from the traditional Chinese herb Rabdosia rubescens. This study mainly aimed to investigate the role of oridonin on inhibiting the process of H1688, a kind of small cell lung cancer cells from human. Oridonin could suppress H1688 cell proliferation and induce their apoptosis in a high dosage treatment (20 μmol/L). Meanwhile, cell migration was suppressed by oridonin (5 and 10 μmol/L) that did not affect cell proliferation and apoptosis. The expression level of E‐cadherin was significantly increased, and the expression of vimentin, snail and slug was reduced after administration of oridonin. These expression changes were associated with the suppressed integrin β1, phosphorylation of focal adhesion kinase (FAK) and ERK1/2. In addition, oridonin (5 and 10 mg/kg) inhibited tumour growth in a nude mouse model; however, HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment oridonin (10 mg/kg). Furthermore, the concentration of alanine aminotransferase (ALP) was significantly increased and lactate dehydrogenase (LDH) was reduced after oridonin treatment (10 mg/kg). Immunohistochemical analysis further revealed that oridonin increased E‐cadherin expression and reduced vimentin and phospho‐FAK levels in vivo. These findings indicated that oridonin can inhibit the migration and epithelial‐to‐mesenchymal transition (EMT) of SCLC cells by suppressing the FAK‐ERK1/2 signalling pathway. Thus, oridonin may be a new drug candidate to offer an effect of anti‐SCLC with relative safety.
Extracellular vesicle‐mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling
Authors: Lerner Natalie , Schreiber‐Avissar Sofia , Beit‐Yannai Elie
Published: March 2020

Primary open‐angle glaucoma is a leading cause of irreversible blindness, often associated with increased intraocular pressure. Extracellular vesicles (EVs) carry a specific composition of proteins, lipids and nucleotides have been considered as essential mediators of cell‐cell communication. Their potential impact for crosstalk between tissues responsible for aqueous humour production and out‐flow is largely unknown. The study objective was to investigate the effects of EVs derived from non‐pigmented ciliary epithelium (NPCE) primary cells on the expression of Wnt proteins in a human primary trabecular meshwork (TM) cells and define the mechanism underlying exosome‐mediated regulation that signalling pathway. Consistent with the results in TM cell line, EVs released by both primary NPCE cells and NPCE cell line showed diminished pGSK3β phosphorylation and decreased cytosolic levels of β‐catenin in primary TM cells. At the molecular level, we showed that NPCE exosome treatment downregulated the expression of positive GSKβ regulator‐AKT protein but increased the levels of GSKβ negative regulator‐PP2A protein in TM cells. NPCE exosome protein analysis revealed 584 miRNAs and 182 proteins involved in the regulation of TM cellular processes, including WNT/β‐catenin signalling pathway, cell adhesion and extracellular matrix deposition. We found that negative modulator of Wnt signalling miR‐29b was abundant in NPCE exosomal samples and treatment of TM cells with NPCE EVs significantly decreased COL3A1 expression. Suggesting that miR‐29b can be responsible for decreased levels of WNT/β‐catenin pathway. Overall, this study highlights a potential role of EVs derived from NPCE cells in modulating ECM proteins and TM canonical Wnt signalling.
A time‐to‐event analysis on air pollutants with the risk of cardiovascular disease and mortality: A systematic review and meta‐analysis of 84 cohort studies
Authors: Pranata Raymond , Vania Rachel , Tondas Alexander Edo , Setianto Budhi , Santoso Anwar
Published: March 2020

Objective

Air pollution is one of the most substantial problems globally. Aerodynamic toxic of particulate matter with <10 mm in diameter (PM10), or <2.5 mm (PM2.5), as well as nitric dioxide (NO2), have been linked with health issues. We aimed to perform a comprehensive analysis of the time‐to‐event for different types of air pollutants on cardiovascular disease (CVD) events based on cohort studies.

Methods

A comprehensive search on topics that assesses air pollution and cardiovascular disease with keywords up until July 2019 was performed.

Results

There were a total of 28 215 394 subjects from 84 cohorts. Increased PM2.5 was associated with composite CVD [HR 1.10 (1.02, 1.19)], acute coronary events [HR 1.15 (1.12, 1.17)], stroke [HR 1.13 (1.06, 1.19)], and hypertension [HR 1.07 (1.01, 1.14)], all‐cause mortality [HR 1.07 (1.04, 1.09)], CVD mortality [HR 1.10 (1.07, 1.12)], and ischemic heart disease (IHD) mortality [HR 1.11 (1.07, 1.16)]. Association with AF became significant after removal of a study. Increased PM10 was associated with heart failure [HR 1.25 (1.04, 1.50)], all‐cause mortality [HR 1.16 (1.06, 1.27)], CVD mortality [HR 1.17 (1.04, 1.30)], and IHD mortality [HR 1.03 (1.01, 1.05)]. Increased of NO2 was associated with increased composite CVD [HR 1.15 (1.02, 1.29)], atrial fibrillation [HR 1.01 (1.01, 1.02)], acute coronary events [HR 1.08 (1.02, 1.13)], all‐cause mortality [HR 1.23 (1.14, 1.32)], CVD mortality [HR 1.17 (1.10, 1.25)], and IHD mortality [HR 1.05 (1.03, 1.08)].

Conclusion

Air pollutants are associated with an increased incidence of cardiovascular diseases, all‐cause mortality, and CVD mortality.
Trehalose‐6‐phosphate phosphatase E modulates ABA‐controlled root growth and stomatal movement in Arabidopsis
Authors: Wang Wenjing , Chen Qingbin , Xu Shouming , Liu Wen‐Cheng , Zhu Xiaohong , Song Chun‐Peng
Published: March 2020

Trehalose plays important roles in plant growth and stress responses and is synthesized from trehalose‐6‐phosphate by trehalose‐6‐phosphate phosphatase (TPP). Here, we show that trehalose and abscisic acid (ABA) have synergistic effects on root growth and stomatal closure. The Arabidopsis thaliana genome contains ten genes encoding TPPs and the expression level of one, TPPE, and trehalose contents increased in response to ABA. In the presence of ABA, the ABA‐responsive transcription factor ABA RESPONSE ELEMENT BINDING FACTOR2 (ABF2) directly binds to the TPPE promoter to activate its expression. Genetic analysis revealed that TPPE acts downstream of ABF2, which is supported by the findings that TPPE expression and trehalose content are reduced in the abf2 mutant and that a mutation in TPPE abolished the ABA‐sensitive root elongation phenotype of 35S:ABF2 plants. Reactive oxygen species (ROS) accumulation in response to ABA failed to occur in tppe mutant plants, suggesting that TPPE is involved in ABA‐controlled root elongation and stomatal movement by inducing ROS accumulation. This study uncovers a new branch of the ABA signaling pathway and provides a molecular basis for the role of trehalose in plant responses to abiotic stress.
Mineral profiling of muscle and hepatic tissues of Australian Merino, Damara and Dorper lambs: Effect of weight loss
Authors: Ribeiro David Miguel , Scanlon Tim , Kilminster Tanya , Martins Cátia Falcão , Greeff Johan , Milton John , Oldham Chris , Freire João P. B. , Mourato Miguel P. , de Almeida André Martinho
Published: March 2020

Seasonal weight loss (SWL) is a major constraint to extensive animal production systems. The Australian sheep production is based on merino sheep, a European breed not tolerant to SWL. Tolerant alternative breeds such as the fat‐tailed Damara and the Dorper have been increasingly used in Australia and elsewhere, due to their robustness. The aim of this study was to understand the mineral profile of muscle and liver tissues of Australian Merino, Damara and Dorper, when subjected to SWL in order to understand SWL‐tolerance physiology. Twenty‐four lambs were divided randomly between growing (control) and nutritionally restricted groups for each breed. The trial lasted 42 days. Animals were weighed bi‐weekly and at the end of the trial, lambs were slaughtered. Liver and muscle samples were taken immediately after slaughter. Mineral assessment was carried out using inductively coupled plasma–optical emission spectrometry. Analysis of variance showed mineral concentrations were generally increased in the muscle of restricted animals, mainly because of fat tissue mobilization. An increase in Zn and Fe concentrations indicates an increase of enzymatic activity in the liver of restricted sheep as well as differential abundance of Fe‐containing proteins. High concentrations of Cu in the liver of Dorper indicate higher ability to accumulate this element, even under SWL.
Requirements of metabolizable protein by Dorper × thin‐tailed Han crossbred ewe lambs
Authors: Deng Kai‐Dong , Ma Tao , Jiang Cheng‐Gang , Tu Yan , Zhang Nai‐Feng , Liu Jie , Zhao Yi‐Guang , Xu Gui‐Shan , Diao Qi‐Yu
Published: March 2020

The requirement of net protein (NP) and metabolizable protein (MP) by Dorper crossbred ewe lambs grown from 35 to 50 kg of body weight (BW) was assessed by comparative slaughter experiment. Thirty‐five ewe lambs (33.5 ± 0.6 kg BW) of F1 crosses of Dorper × thin‐tailed Han sheep were used: 7 lambs were slaughtered as reference animals at the start of the trial, and the remaining 28 lambs were randomly divided into 4 groups of 7 lambs each. Three of the 4 groups were fed a pelleted mixed diet (concentrate/roughage = 44:56, dry matter basis) for ad libitum intake or 65% or 45% of ad libitum intake, and they were all slaughtered when the lambs that were fed ad libitum reached 50 kg BW. The lambs from the fourth group were also fed ad libitum and slaughtered at 43 kg BW as the intermediate group. The intake of MP by the animals of these 4 groups was estimated, and their total body protein and protein retention were measured. The daily requirements of NP and MP for maintenance were 1.52 and 3.98 g/kg BW0.75, respectively, with a partial efficiency of MP utilization for maintenance of 0.38. The MP requirement for growth ranged from 77.4 to 124.5 g/day for average daily gains from 100 to 250 g BW, and the partial efficiency of MP utilization for growth was 0.66. The Dorper crossbred ewe lambs required more MP for both maintenance and growth in comparison with the recommendations of the US nutritional system.
Association between human cytomegalovirus and periodontitis: A systematic review and meta‐analysis
Authors: Botero Javier Enrique , Rodríguez‐Medina Carolina , Jaramillo‐Echeverry Adriana , Contreras Adolfo
Published: March 2020

Background and objective

Human cytomegalovirus (HCMV) has been associated with periodontitis and apical periodontitis. The objective of this systematic review was to evaluate the association between HCMV and periodontitis, and apical periodontitis of endodontic origin.

Material and methods

A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement guidelines and registered in the International prospective register of systematic reviews (PROSPERO). The search for potential studies was performed in MEDLINE via PubMed, Scopus, and SciELO. A quality assessment of the studies, publication bias analysis, and meta‐analysis was performed. The results are presented in odds ratio with 95% confidence interval with the corresponding Forest plot. Sensitivity analysis was performed to evaluate the consistency of the results.

Results

Thirty‐two studies were included in the quantitative and qualitative analyses. Of these, 26 were in periodontitis patients and 6 in apical periodontitis patients. Forest plot of combined studies revealed significant increased odds for periodontitis when subgingival HCMV was detected (OR 5.31; 95% CI 3.15‐8.97). Sensitivity analysis based on quality of the included studies, showed consistent results. In contrast, the odds ratio for apical periodontitis when HCMV was detected from apical lesions was not statistically significant (OR 3.65; 95% CI 0.49‐27.10).

Conclusions

The results from the meta‐analysis indicate that HCMV is significantly associated with periodontitis. In contrast, HCMV infection is not associated with apical periodontitis.
Effect of 12 weeks continuous positive airway pressure on day and night arterial stiffness and blood pressure in patients with type 2 diabetes and obstructive sleep apnea: A randomized controlled trial
Authors: Krogager Christoffer , Banghøj Anne Margareta , Poulsen Per L. , Kirkegaard Martin G. , Thorsteinsson Birger , Tarnow Lise , Hansen Klavs W. , Laugesen Esben
Published: March 2020

The objective of this study was to evaluate the effect of continuous positive airway pressure treatment on pulse wave velocity and blood pressure in patients with type 2 diabetes and obstructive sleep apnea. A randomized controlled study was performed, including 72 patients with type 2 diabetes and newly diagnosed obstructive sleep apnea recruited from outpatient clinics at three Danish hospitals. The patients were randomized to continuous positive airway pressure for 12 weeks or no continuous positive airway pressure. Office measurements were performed at baseline, 4 weeks and 12 weeks. At baseline and 12 weeks, a 24‐hr measurement of pulse wave velocity and blood pressure was performed. No significant change was observed in the primary outcome variable of carotid‐femoral pulse wave velocity measured with SphygmoCor. With the Mobil‐O‐Graph, changes in office pulse wave velocity between the groups were significant: 0.3 m/s; 95% confidence interval, 0.1–0.6; p = .02. The group receiving continuous positive airway pressure had a larger decrease in pulse wave velocity than controls but none of the changes within the groups were significant. No significant change in ambulatory blood pressure was observed in any of the two groups after 12 weeks. In conclusion, continuous positive airway pressure treatment for 12 weeks does not significantly reduce pulse wave velocity or blood pressure in patients with type 2 diabetes and obstructive sleep apnea.
The neglected importance of floral traits in trait‐based plant community assembly
Authors: E‐Vojtkó Anna , de Bello Francesco , Durka Walter , Kühn Ingolf , Götzenberger Lars
Published: March 2020

Aims

Floral traits are frequently studied in population biology and evolutionary ecology but are rarely considered in functional trait‐based studies focusing on the assembly of communities. We address this gap in trait‐based community assembly by synthesizing the existing literature on processes driving floral and pollination‐related trait patterns at community scales. We highlight limitations of the field due to lack of data and suggest potential directions of future research.

Methods

We conducted a systematic literature search collating studies that investigated floral traits in the context of plant community assembly, which allowed us to synthesize the current state of the art and point out important gaps in our knowledge.

Conclusions

The literature review shows that including pollination‐related traits in community assembly studies can shed new light on species coexistence patterns not accounted for by other types of traits. The synthesis presented here shows the diversity of approaches and existing techniques which can generate a step forward in this open field of research. What currently seems to hinder comprehensive analyses of floral traits at community levels is the lack of data, particularly in existing large repositories for traits worldwide, as well as a gap in linking modern coexistence theory with floral traits.
Everyday peace capture: Nationalism and the dynamics of peace after violent conflict
Authors: Visoka Gëzim
Published: March 2020

Nationalism is arguably one of the most detrimental peace‐breaking factors in conflict‐affected societies. This article examines how ethno‐nationalist elites, subterranean movements, and ordinary people can become blockages to sustainable peace and reconciliation after violent conflict. It argues that peacebuilding and state‐building imposed from outside as conflict transformation approaches without acceptable peace settlement and resolute solution of the disputes among parties in conflict risk enabling the co‐optation of power‐sharing arrangements by ethno‐nationalist elites, contestation of peace and reconciliation by subterranean mono‐ethnic movements, and the occurrence of vernacular peace‐breaking acts. This negative mutation of nationalism not only harms peace, justice, and development but also undermines the rights and needs of distinct identity groups. Under these conditions, escaping the nationalism trap in conflict‐affected societies requires seeking political change through post‐ethnic politics and reconciliation through everyday pacifist acts undertaken by the affected communities themselves. The article draws on Kosovo to illustrate empirically the dynamics of peace‐breaking and practices of everyday nationalism. It seeks to bridge debates on nationalism and post‐conflict peacebuilding and offer alternative pathways for rethinking strategies of peace in divided societies.
Epistemic justice and everyday nationalism: An auto‐ethnography of transnational student encounters in a post‐war memory and reconciliation project in Kosovo
Authors: Luci Nita , Schwandner‐Sievers Stephanie
Published: March 2020

This contribution introduces an exercise in epistemic justice to the study of everyday nationalism in post‐conflict, transnational (local and international) encounters. It explores how everyday nationalism, in often unexpected and hidden ways, underpinned a cocreational, educational project involving several local (Albanian) and international (British based) university students and staff collaborating on the theme of post‐war memory and reconciliation in Kosovo. The set‐up resembled a microcosm of transnational social encounters in project collaborations in which the problem of nationalism, typically, is associated with one side only: here, the Kosovars. Guided by Goffman's (1982) social interactionist framework, the study employs selected participants' paraethnographic and auto‐ethnographic reflections of their project experiences and practices after the event in order to trace the everyday workings of mutual assumptions and constructions of a national self and other for all sides involved. In this, it explores how the project participants' asymmetric positioning within a wider, global context of unequal power relations shaped their vernacular epistemologies of belonging and identity. It thereby excavated what otherwise taken‐for‐granted criteria can become relevant in such local/international social encounters as reflected upon and how the enduring power imbalances underpinning these might best be redressed.
Using document analysis to identify core concepts for dietetics: The first step in promoting conceptual learning
Authors: Tweedie Judith , Palermo Claire , Wright Hattie H. , Pelly Fiona E.
Published: March 2020

Concept‐based approaches to curriculum design have been proposed in nursing and health sciences education to address the issue of content overload in curricula but have not been described in dietetics. This study aimed to identify core concepts for the dietetics discipline in Australia and investigate the commonality and differences in these concepts across different dietetic organizations across the world. This study used document analysis of a purposive sample of international dietetics competency or proficiency standards identified from English‐speaking dietetic organizations worldwide. Content analysis was applied to the performance criteria or equivalent from 10 documents (nine organizations) to identify the most common elements. A total of 1,007 statements were analyzed. Fifty‐six concepts were developed. The four most frequent concepts coded across all statements were “critical thinking,” “communication,” “nutrition and dietetic service,” and “quality assurance and improvement.” There were 55 concepts common to all standards. The concept of “food security” was not present in one of the standards from the United States. The concepts that emerged from this study were common across different English‐speaking dietetic organizations across the world. Small differences on the emphasis of concepts, between different competency standards may reflect the health needs; health, political, economic, and social systems; and the cultural context of a country. Identifying core concepts in dietetics is the first step to help to inform curriculum design, which may address overcrowded curricular and promote conceptual learning.
Association between opioid usage and rectal dysfunction in constipation: A cross‐sectional study of 2754 patients
Authors: Vollebregt Paul F. , Hooper Richard L. , Farmer Adam D. , Miller Jonjo , Knowles Charles H. , Scott S. Mark
Published: March 2020

Background

Opioid use has reached epidemic proportions. In contrast to the known effect of opioids on gut transit, the effect on rectal sensorimotor function has not been comprehensively investigated.

Methods

Cross‐sectional (hypothesis‐generating) study of anorectal physiology studies in 2754 adult patients referred to a tertiary unit (2004‐2016) for investigation of functional constipation (defined by “derived” Rome IV core criteria). Statistical associations between opioid usage, symptoms, and anorectal physiological variables were investigated. Opioids were sub‐classified as prescriptions for mild‐moderate or moderate‐severe pain.

Key Results

A total of 2354 patients (85.5%) were classified as non‐opioid users, 162 (5.9%) as opioid users for mild‐moderate pain, and 238 (8.6%) for moderate‐severe pain. Opioids for moderate‐severe pain were associated with increased symptomatic severity (Cleveland Clinic constipation score 18.5 vs 15.1; mean difference 2.9 [95%‐CI 2.3‐3.6]; P < .001), rectal hyposensitivity (odds ratio 1.74 [95%‐CI 1.23‐2.46]; P = .002), functional evacuation disorders (odds ratio 1.73 [95%‐CI 1.28‐2.34]; P < .001), and delayed whole‐gut transit (odds ratio 1.68 [95%‐CI 1.19‐2.37]; P = .003). Differences in anorectal variables between opioid users for mild‐moderate pain and non‐opioid users were not statistically significant. Hierarchical opioid use (non vs mild‐moderate vs moderate‐severe) was associated with decreasing proportions of patients with no physiological abnormality on testing (40.2% vs 38.1% vs 29.2%) and increasing proportions with both delayed whole‐gut transit and rectal sensorimotor dysfunction (16.6% vs 17.5% vs 28.5%).

Conclusions and Inferences

Opioid use is over‐represented in patients referred for investigation of constipation. Opioids for moderate‐severe pain are associated with rectal sensorimotor abnormalities. Further studies are required to determine whether this association indicates causation.
Effects of substrate mechanics on angiogenic capacity and nitric oxide release in human endothelial cells
Authors: Jannatbabaei Atefeh , Tafazzoli‐Shadpour Mohammad , Seyedjafari Ehsan
Published: March 2020

Loss of vascular elasticity results from progressive degeneration of the extracellular matrix of elastic arteries under the effect of aging and certain diseases, including atherosclerosis. To investigate the influence of vessel wall stiffening on endothelial cell (EC) function, we seeded human umbilical vein ECs onto variably compliant polydimethylsiloxane substrates. When plated on the more compliant substrate, ECs assembled into capillary‐like structures. By contrast, they failed to form a network on stiff substrates, even in the presence of vascular endothelial growth factor (VEGF). Cell proliferation and migration increased with stiffness, while ECs released more nitric oxide (NO) on the soft substrate. Treatment with VEGF increased migration and NO release in a stiffness‐dependent manner. Atomic force microscopy measurement of cell elasticity along with actin fiber analysis revealed that ECs plated on the more compliant surface were mechanically softer, with mostly diffuse actin arrangement. Our results demonstrate that matrix stiffening induces actin reorganizations, reflected by cortical stiffening in ECs, which may lead to a decrease in their angiogenic capacity and NO release. Hence, the mechanical properties of ECs display a prognostic and therapeutic potential and might serve as a reliable biomarker of vascular function.