bluuebunny/crossref_metadata_2025 huggingface dataset:
COX‐2 Inhibition Antagonizes Intra‐Accumbens 2‐Arachidonoylglycerol–Mediated Reduction in Ethanol Self‐Administration in Rats
Authors: Pavon Francisco J. , Polis Ilham , Stouffer David G. , Roberto Marisa , Martin‐Fardon Rémi , Rodriguez de Fonseca Fernando , Parsons Loren H. , Serrano Antonia
Published: September 2020

Background

Ethanol (EtOH) self‐administration is particularly sensitive to the modulation of CB1signaling in the nucleus accumbens (NAc) shell, and EtOH consumption increases extracellular levels of the endogenous cannabinoid CB1receptor agonist 2‐arachidonoyl glycerol (2‐AG) in this brain region. Stimulation of CB1receptor with agonists increases EtOH consumption, suggesting that EtOH‐induced increases in 2‐AG might sustain motivation for EtOH intake.

Methods

In order to further explore this hypothesis, we analyzed the alterations in operant EtOH self‐administration induced by intra‐NAc shell infusions of 2‐AG itself, the CB1inverse agonist SR141716A, the 2‐AG clearance inhibitor URB602, anandamide, and the cyclooxygenase‐2 (COX‐2) inhibitor nimesulide.

Results

Surprisingly, self‐administration of 10% EtOH was dose‐dependently reduced by either intra‐NAc shell SR141716A or 2‐AG infusions. Similar effects were found by intra‐NAc shell infusions of URB602, suggesting again a role for accumbal 2‐AG on the modulation of EtOH intake. Intra‐NAc shell anandamide did not alter EtOH self‐administration, pointing to a specific role for 2‐AG in the modulation of EtOH self‐administration. Finally, the inhibitory effect of intra‐NAc shell 2‐AG on EtOH intake was significantly reversed by pretreatment with nimesulide, suggesting that oxidative metabolites of 2‐AG might mediate these inhibitory effects on operant self‐administration.

Conclusions

We propose that 2‐AG signaling in the NAc exerts an inhibitory influence on EtOH consumption through a non–CB1 receptor mechanism involving the COX‐2 pathway.
Morphologic alterations of the genital mesentery implicated in testis non‐descent in rats prenatally exposed to flutamide
Authors: Mentessidou Anastasia , Salakos Christos , Chrousos George , Kanaka‐Gantenbein Christina , Kostakis Alkiviadis , Mirilas Petros
Published: September 2020

Background

There is an endless debate on whether androgens mediate testis descent through developmental changes in the gubernacular or the cranial suspensory ligament.

Objective

To investigate the relation of any possible morphologic changes in the genital mesentery, that is, the system of genital peritoneal folds including the gubernacular and cranial suspensory ligaments, with the event of testis non‐descent in rats prenatally exposed to the antiandrogen flutamide.

Materials and methods

Time‐pregnant Sprague Dawley rats received flutamide (100 mg/kg/d) or vehicle subcutaneously on gestational days 16‐17. Flutamide‐treated male offspring (n = 67), and vehicle‐treated male (n = 34) and female (n = 28) offspring were surgically explored under microscope on postnatal day 50. Testicular position was examined bilaterally. Dimensions of genital mesentery parts were also assessed bilaterally. Association of flutamide‐induced morphologic changes with descended (n = 61) and undescended (n = 50; 33 cryptorchid and 17 ectopic) testes was investigated with logistic regression analysis.

Results

The male genital mesentery comprised a cranial and a caudal fold converging on the vas deferens. Flutamide resulted in enlarged cranial and reduced caudal folds. Of all flutamide‐induced alterations, the increased length of the posterior fixation of the cranial fold and the decreased length of the gubernacular ligament of the caudal fold were found to independently increase the odds of testis non‐descent. Testicular ectopy, unlike cryptorchidism, was associated with a short gubernacular ligament only. The female genital mesentery consisted of a cranial fold only.

Conclusion

Our findings showed a combined contribution of both cranial and caudal folds of the genital mesentery to testis non‐descent, through an abnormally long mesentery root and an abnormally short gubernacular ligament, respectively. Inhibition of male‐specific development of the genital mesentery with flutamide did not result in a feminized architecture.
Using Messages Targeting Psychological versus Physical Health Benefits to Promote Walking Behaviour: A Randomised Controlled Trial
Authors: Caso Daniela , Carfora Valentina , Capasso Miriam , Oliano Deborah , Conner Mark
Published: September 2020

Background

This study aimed to test the efficacy of a messaging intervention targeting psychological or physical benefits plus goal setting and self‐monitoring strategies to promote walking activity in the university context.

Methods

Two hundred and thirty university students from the University of Naples Federico II were randomly allocated to one of four conditions: physical health messages + self‐monitoring, psychological health (well‐being) messages + self‐monitoring, self‐monitoring, and no messages. All three intervention conditions were exposed to goal setting (doing at least 7,000 steps a day) and participants were required to monitor their daily progress through the specific step counting app. Participants’ walking activity and related psychological variables were assessed at T1 and T2. We ran ANCOVAs and mediation analysis to test our research questions and hypotheses. Analyses were based on theN = 156 who completed all measures at both time points.

Results

Participants in the three experimental (message) conditions reported improvement in psychological variables and behaviour. In particular, the messages focused on the physical health benefits, combined with self‐monitoring, were the most effective.

Conclusions

Our study provides new information on the factors that could be usefully targeted to promote walking activity (i.e. intention, past behaviour, action control, and persuasive messages on the physical benefits of walking).
Beyond rebranding from international to global? Lessons from geographies of global health for global development
Authors: Horner Rory
Published: September 2020

With the potential for a major geographic shift from international to global development as paradigm for development studies and practice, this paper seeks to draw lessons from the closely related field of health as to what a shift from “international” to “global” may involve. In both fields, an earlier “international” framing emerges from a state‐dominated system which, although it superseded prior colonial origins, is outdated vis‐à‐vis an ability to fully reflect the contemporary range of actors and problems in a more interdependent context. Little agreement is present over the definition of global health, where the “global” is deployed in multiple ways and often involving only a modest shift in geographical imaginary from international health. The case highlights the potential of such an “international” to “global” shift being a 21st‐century rebranding, which captures some aspects of change but remains a partial perspective on present challenges that are global in scope. It is concluded that the shift from “international” to “global” in development must go beyond rebranding to address a wider range of 21st‐century development challenges.
Ethnic Identity Politics and the Transformation of the Developmental State: Industrial Structure, Democratic Transition, and Policy Constraints in Taiwan
Authors: He Tian
Published: September 2020

许多研究已经分析了台湾发展型国家的转变。本文认为, 台湾的族群认同政治对台湾发展型国家的转型过程产生了挥之不去的影响。特别是, 那些最近的转变可以追溯到台湾在三个阶段期间的民族认同政治。首先, 由国民党 (KMT) 大陆身份塑造的国家发展战略影响了50年代至70年代形成的台湾战后的产业结构, 进而影响了工商业参与者的政策约束能力。其次, 70年代出现的台湾民族意识促进了台湾在1986年的民主过渡, 从而转变了政府经济政策制定的政治基础。第三, 从2000年初开始, 民族过渡之后产生的两个相互竞争的民族身份 (即中国人和台湾人) 引发的政党政治进一步改变了政治环境, 并对国家的经济决策制定产生影响。
Liraglutide treatment improves endothelial function in the Ldlr−/− mouse model of atherosclerosis and affects genes involved in vascular remodelling and inflammation
Authors: Bjørnholm Katrine Dahl , Skovsted Gry Freja , Mitgaard‐Thomsen Anne , Rakipovski Günaj , Tveden‐Nyborg Pernille , Lykkesfeldt Jens , Povlsen Gro Klitgaard
Published: September 2020

Recent clinical intervention studies have shown that the GLP1 analogue liraglutide lowers cardiovascular risk, but the underlying mechanism has not yet been fully elucidated. This study investigated the effects of liraglutide on endothelial function in the Ldlr−/− mouse model. Mice (n = 12/group) were fed Western diet (WD) or chow for 12 weeks followed by 4 weeks of treatment with liraglutide (1 mg/kg/day) or vehicle subcutaneously. Weight loss, blood lipid content, plaque burden, vasomotor function of the aorta and gene expression pattern in aorta and brachiocephalic artery were monitored. Liraglutide treatment significantly induced weight loss (P < .0001), decreased blood triglycerides (P < .0001) and total cholesterol (P < .0001) in WD‐fed mice but did not decrease plaque burden. Liraglutide also improved endothelium‐mediated dilation of the distal thoracis aorta (P = .0067), but it did not affect phenylephrine or sodium nitroprusside responses. Fluidigm analyses of 96 genes showed significantly altered expression of seven genes related to inflammation, vascular smooth muscle cells and extracellular matrix composition in liraglutide‐treated animals. We conclude that treatment with liraglutide decreased endothelial dysfunction and that this could be linked to decreased inflammation or regulation of vascular remodelling.
Maternal waterpipe tobacco smoke exposure during lactation induces hormonal and biochemical changes in rat dams and offspring
Authors: Al‐Sawalha Nour A. , Gaugazeh Hasanh T. , Alzoubi Karem H. , Khabour Omar F.
Published: September 2020

Waterpipe smoking is common among pregnant and breastfeeding women. Herein, the effects of waterpipe tobacco smoke (WTS) exposure during lactation on milk composition, hormonal levels and biochemical profile in dams and pups were investigated. Lactating Wistar rats were randomly assigned to receive either WTS (2 hours per day) or fresh air (control group). Milk was collected on day 21 and analysed for protein, lactose and total fat. Blood, from dams and pups, was analysed for insulin, glucose, lipid profile, leptin, prolactin and corticosterone. WTS exposure during lactation increased the blood level of HDL and corticosterone in dams (P < .05). However, the level of milk lactose and blood glucose was reduced in dams after the exposure to WTS during lactation (P < .05). WTS during lactation significantly increased levels of triglycerides, LDL and leptin (P < .05), and a trend of increase in blood level of nicotine and prolactin in pups. Levels of other parameters were not affected by WTS exposure in dams and pups. In conclusion, WTS exposure during lactation altered the milk composition and altered lipid profile, glucose homeostasis and hormonal levels in dams and pups. It is necessary to adopt strategies to enhance tobacco cessation during breastfeeding.
Phase II trial of single‐agent panobinostat consolidation improves responses after sub‐optimal transplant outcomes in multiple myeloma
Authors: Mithraprabhu Sridurga , Kalff Anna , Gartlan Kate H. , Savvidou Ioanna , Khong Tiffany , Ramachandran Malarmathy , Cooke Rachel E. , Bowen Kathryn , Hill Geoffrey R. , Reynolds John , Spencer Andrew
Published: September 2020

Panobinostat is a pan‐deacetylase inhibitor that modulates the expression of oncogenic and immune‐mediating genes involved in tumour cell growth and survival. We evaluated panobinostat‐induced post‐transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three‐times weekly (TIW) on alternate weeks of 28‐day cycles commencing 8–12 weeks post‐transplant. Twelve of 25 patients (48%) improved their depth of response after a median (range) of 4·3 (1·9–9·7) months of panobinostat. In responders, T‐lymphocyte histone acetylation increased after both three cycles (P < 0·05) and six cycles (P < 0·01) of panobinostat when compared to baseline, with no differences in non‐responders. The reduction in the proportion of CD127+CD8+ T cells and CD4:CD8 ratio was significantly greater, after three and six cycles of panobinostat compared to pre‐transplant, in non‐responders when compared to responders. Whole marrow RNA‐seq revealed widespread transcriptional changes only in responders with baseline differences in genes involved in ribosome biogenesis, oxidative phosphorylation and metabolic pathways. This study confirmed the efficacy of panobinostat as a single agent in multiple myeloma and established acetylation of lymphocyte histones, modulation of immune subsets and transcriptional changes as pharmacodynamic biomarkers of clinical benefit.
lncRNA PART1 and MIR17HG as ΔNp63α direct targets regulate tumor progression of cervical squamous cell carcinoma
Authors: Liu Hanyuan , Zhu Chenchen , Xu Zhihao , Wang Juan , Qian Lili , Zhou Qingqing , Shen Zhen , Zhao Weidong , Xiao Weihua , Chen Liang , Zhou Ying
Published: September 2020

Cervical cancer (CC) remains one of the leading causes of mortality of female cancers worldwide, with more than 90% being cervical squamous cell carcinoma (CSCC). ΔNp63α is the predominant isoform expressed in cervical epithelial tissues and exerts its antitumor function in CSCC. In this study, we have identified 39 long noncoding RNAs as ΔNp63α targets in CSCC through RNA sequencing and chromatin immunoprecipitation sequencing, in which we further confirmed and focused on the two tumor‐related long noncoding RNAs, PART1 (lncPART1) and MIR17HG (lncMIR17HG). Experiments from stable overexpression/knockdown cell lines revealed that lncPART1 and lncMIR17HG regulated cell proliferation, migration, and invasion. In vivo experiments further showed that lncPART1 suppresses tumor growth in CSCC‐derived tumors. Examinations of clinical tissues indicated that the expression of lncPART1 was positively correlated with ΔNp63α expression, while lncMIR17HG was negatively correlated with ΔNp63α expression, suggesting that ΔNp63α plays a central role via regulating its direct targets in the progression of CSCC. These findings provide novel insights in targeted therapy of cervical cancers.
Tumor suppressive activities of solvatochromic 3,3′‐azadimethylene dinaphthospiropyran in colon cancer model
Authors: Lagisetty Pallavi , Eeda Venkateswararao , Yadav Vivek R. , Nimmo Susan L. , Subramaniam Dharmalingam , Powell Douglas R. , Awasthi Vibhudutta
Published: September 2020

Spiropyrans have been extensively investigated because of their thermo‐ and photochromic characteristics, but their biotherapeutic properties have not been explored much. We report anti‐proliferative properties of a novel 3,3′‐azadimethylene dinaphthospiropyran 11. Dibenzospiropyrans and dinaphthospiropyrans were synthesized by a simple and expedient method using acid‐catalyzed aldol condensation of salicylaldehyde and 2‐hydroxy‐1‐naphthaldehyde, respectively, with cyclic ketones. Together with structural elucidation by 2D NMR and X‐ray crystallography studies, we provide a putative mechanism for their formation. Compound 11 showed solvatochromism and exhibited altered spectral characteristics depending on the pH. In acidic conditions, 11 remains in open form, whereas upon alkalinization it reverts back to closed form. Based on the in vitro anti‐proliferative activity in H441, HCT‐116, MiaPaCa‐2, and Panc‐1 cancer cell lines, 11 was submitted to further investigation. It reduced HCT116 colonosphere formation and demonstrated induction of caspase cascade, suggesting apoptosis. In vitro proliferation assays also suggested that HCl and trifluoroacetate salts of 11 are more effective. Treatment of mice carrying HCT‐116 xenografts with 11 (5 µg/day, intraperitoneal for 3 weeks) suppressed tumor growth by 62%. Overall, the results reveal a new series of structurally complex, but relatively easy to synthesize molecules of which compound 11 represents a lead for anticancer development.
Synthesis, extracorporeal nephrotoxicity, and 3D‐QSAR of andrographolide derivatives
Authors: Gu Lili , Lu Jiaqi , Li Qin , Huang Wenhai , Wu Ningzi , Yu Qingqing , Lu Hong , Zhang Xinyue
Published: September 2020

Andrographolide is a traditional Chinese medicine monomer with many pharmacological activities, but has potential nephrotoxicity. Here, we aim to investigate the relationship between modification of andrographolide structure and its nephrotoxicity. Twenty‐three andrographolide derivatives were synthesized, and their structures were confirmed by1H‐NMR and HRMS. Nephrotoxicity of these compounds against human renal tubular epithelial (HK‐2) cells was evaluated using the MTT assay. The results indicated that most of them had significantly reduced nephrotoxicity, especially compoundsIII,V, andIXc, with IC50values of 1,985, 1,300, and 806.9 μmol/L, respectively, which were obviously superior to andrographolide (IC5030.60 μmol/L). However, compoundsIa–If(IC50values < 30 μmol/L), the 14‐OH derivatives of andrographolide, showed higher nephrotoxicity than that of andrographolide. Three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) models of COMFA and COMSIA were established (COMFA:q2 = 0.639,r2 = 0.951; COMSIA:q2 = 0.569,r2 = 0.857). This model allowed proposing five new compounds with lower theoretical nephrotoxicity, which would be worthwhile to synthesize and evaluate. We believe that predicted models will help us to understand the structural modification requirements of andrographolide to reduce the nephrotoxicity, and further investigations will be needed to determine the mechanism involved in the effect of less nephrotoxic compounds.
Modulation of co‐stimulatory signal from CD2–CD58 proteins by a grafted peptide
Authors: Parajuli Pravin , Sable Rushikesh , Shrestha Leeza , Dahal Achyut , Gauthier Ted , Taneja Veena , Jois Seetharama
Published: September 2020

Peptides were designed to inhibit the protein–protein interaction of CD2 and CD58 to modulate the immune response. This work involved the design and synthesis of eight different peptides by replacing each amino acid residue in peptide 6 with alanine as well as grafting the peptide to the sunflower trypsin‐inhibitor framework. From the alanine scanning studies, mutation at position 2 of the peptide was shown to result in increased potency to inhibit cell adhesion interactions. The most potent peptide from the alanine scanning was further studied for its detailed three‐dimensional structure and binding to CD58 protein using surface plasmon resonance and flow cytometry. This peptide was used to graft to the sunflower trypsin inhibitor to improve the stability of the peptide. The grafted peptide, SFTI‐a1, was further studied for its potency as well as its thermal, chemical, and enzymatic stability. The grafted peptide exhibited improved activity compared to our previously grafted peptide and was stable against thermal and enzymatic degradation.
Design and biological evaluation of phenyl imidazole analogs as hedgehog signaling pathway inhibitors
Authors: Sun Chiyu , Zhang Ying , Wang Han , Yin Zhengxu , Wu Lingqiong , Huang Yanmiao , Zhang Wenhu , Wang Youbing , Hu Qibo
Published: September 2020

The hedgehog (Hh) signaling pathway is involved in diverse aspects of cellular events. Aberrant activation of Hh signaling pathway drives oncogenic transformation for a wide range of cancers, and it is therefore a promising target in cancer therapy. In the principle of association and ring‐opening, we designed and synthesized a series of Hh signaling pathway inhibitors with phenyl imidazole scaffold, which were biologically evaluated in Gli‐Luc reporter assay. Compound 25 was identified to possess high potency with nanomolar IC50, and moreover, it preserved the inhibition against wild‐type and drug‐resistant Smo‐overexpressing cells. A molecular modeling study of compound 25 expounded its binding mode to Smo receptor, providing a basis for the further structural modification of phenyl imidazole analogs.
Intradermal Phleum pratense allergoid immunotherapy. Double‐blind, randomized, placebo‐controlled trial
Authors: Sola Martínez Francisco Javier , Barranco Jiménez Ruth María , Martín García Cristina , Senent Sánchez Carlos , Blanco Guerra Carlos , Fernández‐Rivas Montserrat , Vega Castro Arantza , Dávila González Ignacio , Carbonell Martínez Antonio , Panizo Bravo Carmen , Gómez Torrijos Elisa , Rodríguez Gil David , Palacios Peláez Ricardo
Published: September 2020

Background

In allergology, the intradermal approach is generally used to establish an aetiological diagnosis, with limited experience in specific allergen immunotherapy.

Objective

To evaluate the efficacy and safety of immunotherapy with an allergen extract of glutaraldehyde‐polymerized Phleum pratense, administered intradermally, in patients with rhinoconjunctivitis sensitized to grass pollen.

Methods

Multicentre, randomized, double‐blind, placebo‐controlled clinical trial in patients from 12 to 65 years of age with rhinitis or rhinoconjunctivitis, with or without asthma, due to grass pollen allergy. Patients were divided into three groups and received a total of six doses in a weekly interval, of either placebo; 0.03 or 0.06 μg of protein per dose of P pratense allergoid. The primary objective was to evaluate the combined symptoms and medication consumption score (CSMS). The secondary objectives were symptoms and medication, tolerance to the conjunctival provocation test, specific IgE and IgG4 antibodies and the safety profile according to the WAO scale.

Results

The dose of 0.06 μg of protein proved to be effective versus the placebo by significantly reducing CSMS and increasing tolerance to the allergenic extract in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded.

Conclusion & Clinical Relevance

Intradermal immunotherapy with P pratense allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels.
Effect of long‐term glucocorticoid therapy on cardiac functions in children with congenital adrenal hyperplasia
Authors: Amr Nermine Hussein , Mahmoud Rana Abdelhakim Ahmed , Youssef Omneyia , Toaima Nadin Nabil , Elsedfy Heba
Published: September 2020

Background

Glucocorticoids play an important role in cardiac physiology. Chronic exposure and higher doses may cause adverse effects on the myocardium, especially in young patients receiving long‐term therapy.

Objective

To assess cardiac function in children with congenital adrenal hyperplasia (CAH) and its relation to glucocorticoid dose and therapy duration.

Methods

Forty‐seven patients with CAH due to 21‐hydroxylase deficiency were compared to 47 controls. Patients were subdivided according to treatment duration (Group A: less than 6 years, Group B: more than 6 years). Mean daily glucocorticoid and cumulative glucocorticoid doses were calculated. Echocardiography was performed for patients and controls to evaluate cardiac functions, chamber dimensions and tissue Doppler valvular status.

Results

Compared to controls, patients had cardiac chamber hypertrophy reflected by higher M‐mode dimensions. Patients had lower fractional shortening, defective ventricular relaxation, lower average mitral and tricuspid e´/a´ ratios (e´ early diastolic, a´ late diastolic) as well as s´ (systolic) velocities, higher average mitral E/e ratio and higher left ventricle TDI Tei index (P < .05). Group B had lower average mitral e´/a´ and tricuspid s´ velocities, and higher average mitral E/e ratio (P < .05). Cumulative glucocorticoid dose significantly correlated with different echocardiographic parameters.

Conclusion

Long‐term glucocorticoid therapy even within the recommended therapeutic range adversely affects cardiac functions in children with 21‐hydroxylase deficiency.
The evolution of the nosology of osteogenesis imperfecta
Authors: Chetty Manogari , Roomaney Imaan Amina , Beighton Peter
Published: September 2020

Osteogenesis imperfecta (OI) is a relatively common genetic skeletal disorder with an estimated frequency of 1 in 20 000 worldwide. The manifestations are diverse and although individually rare, the several different forms contribute to the production of a significant number of affected individuals with considerable morbidity and mortality. During the last decade, there have been extensive molecular investigations into the etiology of OI and these advances have direct relevance to the medical management of the disorder, and the purpose of this review is to document the history and evolution of the nosology of OI. The current nosology, based on molecular concepts, which are crucial in the identification of genotype‐phenotype correlations in persons with OI, is also outlined. The successive revisions of the nosology and classification of OI have highlighted the importance of the nomenclature of the condition in order for it to be recognized by clinicians, scientists and patient advocacy groups. In this way, improved counseling of patients and individualized, tailored therapeutic approaches based on the underlying pathophysiology of the individual's type of OI have been facilitated.
Extracellular biofilm matrix leads to microbial dysbiosis and reduces biofilm susceptibility to antimicrobials on titanium biomaterial: An in vitro and in situ study
Authors: Costa Raphael Cavalcante , Souza João Gabriel Silva , Bertolini Martinna , Retamal‐Valdes Belén , Feres Magda , Barão Valentim A. R.
Published: September 2020

Objectives

To test the role of exopolysaccharide (EPS) polymers matrix to modulate the composition/virulence of biofilms growing on titanium (Ti) surfaces, the effect on antibiotic susceptibility, and whether a dual‐targeting therapy approach for disrupted EPS matrix could improve the antimicrobial effect.

Materials and Methods

A microcosm biofilm model using human saliva as inoculum was used, and the microbial composition was assessed by checkerboard DNA–DNA hybridization. EPS‐enriched biofilms virulence was tested using fibroblast monolayer. Povidone‐iodine (PI) was used as EPS‐targeting agent followed by amoxicillin + metronidazole antibiotic to reduce bacterial biomass using an in situ model.

Results

An EPS‐enriched environment, obtained by sucrose exposure, promoted bacterial accumulation and led to a dysbiosis on biofilms, favoring the growth of Streptococcus, Fusobacterium, and Campylobacter species and even strict anaerobic species related to peri‐implant infections, such as Porphyromonas gingivalis and Tannerella forsythia (~3‐fold increase). EPS‐enriched biofilm transitioned from a commensal aerobic to a pathogenic anaerobic profile. EPS increased biofilm virulence promoting higher host cell damage and reduced antimicrobial susceptibility, but the use of a dual‐targeting approach with PI pre‐treatment disrupted EPS matrix scaffold, increasing antibiotic effect on in situ biofilms.

Conclusion

Altogether, our data provide new insights of how EPS matrix creates an environment that favors putative pathogens growth and shed light to a promising approach that uses matrix disruption as initial step to potentially improve implant‐related infections treatment.
Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study
Authors:   EuroSurg Collaborative
Published: September 2020

Aim

Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery.

Method

This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30 days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis.

Results

A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56–1.87, P = 0.932).

Conclusion

In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30 days of surgery compared with reactive insertion.
A colorimetric chemosensor for selective detection of copper ions
Authors: Kim Ahran , Chae Ju Byeong , Rha Chang Joo , Kim Cheal
Published: September 2020

A water‐applicable hexamethylbenzene (HMB) chemosensor, (E)‐2‐((2‐hydroxy‐3‐methoxybenzylidene)amino)benzamide, displayed a selective colour change from colourless to yellow in the existence of copper ions. The detection limit was computed as 1.57 μmol/L, which is substantially lower than the World Health Organisation guideline (31.5 μmol/L) for copper ions. Probe HMB could also sense and quantify copper ions in real water samples. The coordination mode of HMB to copper ions was demonstrated through Job plot, electrospray ionisation mass spectroscopy and proton nuclear magnetic resonance titration, and was also supported by theoretical studies.
H3 relaxin protects against calcium oxalate crystal‐induced renal inflammatory pyroptosis
Authors: Liu Jiannan , Yang Kelaier , Jin Yinshan , Liu Yadong , Chen Yaodong , Zhang Xiaohui , Yu Shiliang , Song Erlin , Chen Song , Zhang Jingbo , Jing Guanhua , An Ruihua
Published: September 2020

Objectives

Calcium oxalate (CaOx) crystals can activate inflammatory cytokines by triggering inflammasomes, which cause damage to the adhered epithelium, a dysfunctional microenvironment and even renal failure. However, a comprehensive and in‐depth understanding of the mechanisms underlying the effects of these crystals on damage and cytokine function in renal tubular epithelial cells (TECs) remains limited and to be explored.

Materials and Methods

We detected the pyroptosis of TECs induced after exposure to CaOx crystals and demonstrated the significance of cytokine activation in the subsequent inflammatory processes through a proteomic study. We then conducted animal and cell experiments to verify relevant mechanisms through morphological, protein, histological and biochemical approaches. Human serum samples were further tested to help explain the pathophysiological mechanism of H3 relaxin.

Results

We verified that crystal‐induced extracellular adenosine triphosphate (ATP) upregulation via the membrane purinergic 2X7 receptor (P2X7R) promotes ROS generation and thereby activates NLRP3 inflammasome‐mediated interleukin‐1β/18 maturation and gasdermin D cleavage. Human recombinant relaxin‐3 (H3 relaxin) can act on the transmembrane receptor RXFP1 to produce cAMP and subsequently improves crystal‐derived damage via ATP consumption. Additionally, endogenous relaxin‐3 was found to be elevated in patients with renal calculus and can thus serve as a biomarker.

Conclusions

Our results provide previously unidentified mechanistic insights into CaOx crystal‐induced inflammatory pyroptotic damage and H3 relaxin‐mediated anti‐inflammatory protection and thus suggest a series of potential therapeutic targets and methods for but not limited to nephrocalcinosis.
Peace in the valley? Qualitative insights on collaborative coexistence from the Wood River Wolf Project
Authors: Martin Jeff Vance
Published: September 2020

Threats posed by wild predators to livestock production have too often resulted in human–wildlife conflict, to the detriment of these keystone species and broader biodiversity conservation. Long‐standard practices of lethal control are increasingly seen as costly, controversial, and ineffective, however, with nonlethal alternatives ever more prominent. In addition to assessing these tools' ecological effectiveness, there remains a key role for the social sciences, particularly qualitative research, in identifying obstacles to and opportunities for the long‐term sustainability and scaling up of these coexistence interventions. The Wood River Wolf Project (WRWP), a collaboration among ranchers, environmental organizations, and government agencies in Blaine County, Idaho, has pursued coexistence between gray wolves and domestic sheep since 2008, demonstrating and developing nonlethal techniques and garnering regional and international attention as a model for collaborative coexistence. Yet the Project has also struggled with changing conditions and internal challenges. Investigation of this prominent effort—its history and practices as well as the broader socio‐political and economic context—highlights the challenges of adaptive governance in the face of reduced capacity and hostile legal‐political contexts, while providing important insights for practitioners and policymakers promoting wildlife coexistence in shared landscapes.
Systematic evaluation of therapeutic effects of stem cell transplantation trials for heart diseases in China
Authors: Que Wan‐Cai , Qiu Hong‐Qiang , Chen Hui‐Yun , Wang Shao‐Zhen , Cheng Yu , Liao Lian‐Ming
Published: September 2020

Background

To systematically assess the quality of reports of clinical trials of stem cell for heart diseases published in Chinese.

Methods

The quality of reports was assessed according to the CONSORT statement and the Jadad score. The association between the CONSORT scores and the reported therapeutic effects was evaluated.

Results

A total of 36 randomized clinical trials were identified, and 1552 patients were included. The mean CONSORT score was 7.06 (SD = 2.99). The proportion of reports with a Jadad score of 3 was 8.33%. The improvement of left ventricular function, myocardial perfusion area, left ventricular diastolic diameter, and cardiac output decreased with the increase in the CONSORT score.

Conclusions

The percentages of high‐quality reports published in Chinese on stem cell therapy for heart diseases are low. Although stem cell transplantation seems promising for heart diseases, high‐quality studies are needed to verify the conclusions．
Acute coronary syndromes in the peri‐operative period after kidney transplantation in United States
Authors: Goyal Abhinav , Lo Kevin Bryan , Chatterjee Kshitij , Mathew Roy O. , McCullough Peter A. , Bangalore Sripal , Rangaswami Janani
Published: September 2020

Introduction

Chronic kidney disease is an independent risk factor for cardiovascular disease. Despite careful preoperative evaluation, there is a risk of acute coronary syndromes after kidney transplant.

Methods

The National Inpatient Sample for the years 2004‐2013 was used for this retrospective cohort study. All adult patients undergoing kidney transplantation were identified using the appropriate ICD‐9‐CM codes. Multivariate logistic regression was used to identify predictors of acute coronary syndromes in the peri‐operative period after kidney transplantation.

Results

A total of 147 431 kidney transplants were performed from 2004 through 2013 in the United States. The average peri‐operative in‐hospital mortality was 0.5%. Acute coronary syndrome occurred in 1.3% patients in the peri‐operative period. Half of patients with acute coronary syndromes had pre‐existing coronary artery disease. The strongest predictors of acute coronary syndromes included older age: 45‐64 years. OR 3.28 95% CI (1.85‐5.83), ≥65 years. OR 4.84 (2.59‐9.05), race: African American, OR 0.66 (0.47‐0.93) and pre‐existing coronary artery disease OR 3.83 (2.84‐5.15). The case fatality rates were 16.9% and 5.3% for STEMI and NSTEMI, respectively. The overall mortality for any ACS event was 7.1%.

Conclusion

Acute coronary syndrome in the immediate peri‐operative period after kidney transplantation is rare but is associated with high rates of mortality.
Comparative cytological and histological assessment of 828 primary soft tissue and bone lesions, and proposal for a system for reporting soft tissue cytopathology
Authors: Köster Jan , Ghanei Iman , Domanski Henryk A.
Published: September 2020

Introduction

The aim of the study was to evaluate the diagnostic utility of fine needle aspiration (FNA) cytology and core needle biopsies (CNBs) in a series of primary soft tissue and bone lesions and to test a possible system for reporting results of FNA cytology of soft tissue lesion.

Methods

This retrospective study encompassed 828 primary soft tissue and bone lesions, analysed with FNA, CNB and/or surgical specimen in order to perform sensitivity/specificity as well as accuracy analyses. The series was then used to test a system for reporting soft tissue cytopathology with six categories and the risk of malignancy in each category was calculated.

Results

With a malignant diagnosis defined as positive test result, FNA and CNB analysis showed sensitivity of 87% and 94%, respectively, and specificity of 89% and 95%, respectively. FNA and CNB analyses identified the correct histopathological entity of the examined lesion in 55% and 66%, respectively. The risk of malignancy within the tested categories was non‐diagnostic 42%, non‐neoplastic 0%, atypia of unknown significance 46%, neoplasm benign 3%, neoplasm of unknown malignant potential 27%, suspicious for malignancy 72% and malignant 97%.

Conclusion

FNA cytology is a suitable tool to determine the malignant potential of a sampled soft tissue/bone lesion but is inferior to CNB in defining the correct entity. A standardised reporting system might improve the clinical management of patients with soft tissue tumours examined primarily by FNA cytology.
Substance use prevalence rates among migrant and native adolescents in Europe: A systematic review
Authors: van Dorp Melissa , Boon Albert , Spijkerman Renske , Los Leontien
Published: September 2020

Issues

Migrant adolescents show specific risk and protective factors associated with substance use, but the extent to which prevalence rates differ between migrant and native‐born youth in Europe remains unclear. The present study aims to provide a comprehensive review of all available substance use prevalence studies on differences in substance use between migrant and native‐born adolescents in Europe.

Approach

In this systematic review, PubMed, Medline and Pre‐Medline, EMBASE and PsycINFO were searched for articles comparing substance use prevalence rates (tobacco, alcohol, illicit drugs) between migrant and native‐born adolescents or young adults aged 11 to 29 years in European countries. The Joanna Briggs Institute prevalence critical appraisal tool was used for quality assessment.

Key Findings

Fifteen studies met the inclusion criteria. The findings unanimously showed lower alcohol use in migrant compared to native‐born adolescents, in particular among migrant adolescents from non‐European countries and/or with a Muslim background. For tobacco and illicit drug use, findings were mixed.

Implications

The results suggest a healthier behaviour profile among migrants than among native‐born adolescents regarding alcohol use. Therefore, it would be beneficial to develop interventions to support migrant communities in maintaining their healthier alcohol use practices upon arrival in the host country.

Conclusion

Compared to native‐born adolescents, migrant adolescents are less likely to use alcohol. The findings on tobacco and illicit drug use were mixed. A European standard for surveys regarding substance use among adolescents is needed to investigate fluctuations, causes, and consequences of substance use differences between migrants and natives at the European level.
Optical coherence tomography for fast bedside imaging, assessment and monitoring of autoimmune inflammatory skin diseases?
Authors: Ha Linh , Hundt Jennifer E.
Published: September 2020

Optical coherence tomography (OCT) is a non‐invasive, high‐resolution imaging technique with a growing impact in dermatology. The principle of OCT is comparable to that of sonography, except that it uses infrared laser light instead of ultrasound waves. It has been clinically demonstrated that OCT is suitable for discriminating between different types of non‐melanoma skin cancer at an early stage of disease. Optical coherence tomography generates two‐ or three‐dimensional images of up to 2 mm penetration depth, a field of view of 6 mm × 6 mm, and an acquisition time of seconds. The resolution capability of OCT is more than 3 to 100 times higher than that of ultrasound imaging. It is of particular interest that the additional information on vasculature provided by OCT angiography enables the assessment and monitoring of inflammatory skin diseases. The use of OCT to locate exact blister levels was demonstrated for diagnosing autoimmune bullous diseases. It is anticipated that detection of subclinical lesions could indicate a relapse of the disease. In the future, this could enable intervention and early treatment. Furthermore, the development of high‐speed OCT could allow fast scanning and bedside imaging of large body sites.
Adherence and persistence among patients with type 2 diabetes initiating dulaglutide compared with semaglutide and exenatide BCise: 6‐month follow‐up from US real‐world data
Authors: Mody Reema , Yu Maria , Nepal Bal , Konig Manige , Grabner Michael
Published: September 2020

Aim

To compare 6‐month adherence, persistence and treatment patterns among patients initiating once‐weekly glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), dulaglutide versus semaglutide, and dulaglutide versus exenatide BCise, using claims from the HealthCore Integrated Research Database.

Materials and methods

Patients aged ≥18 years, with type 2 diabetes, ≥1 claim for dulaglutide, semaglutide or exenatide BCise during the index period February 2018 to December 2018 (index date = earliest GLP‐1RA fill date), no claim for GLP‐1RAs in the 6‐month pre‐index period, and continuous enrolment 6 months pre‐ and post‐index were included. Dulaglutide users were propensity‐matched 1:1 to semaglutide users (3852 pairs) or exenatide BCise users (1879 pairs). The proportions of adherent (proportion of days covered ≥80%) patients were compared using chi‐squared tests. Persistence, measured as days to discontinuation, was analysed using a Cox regression model.

Results

Matched cohorts (dulaglutide:semaglutide and dulagutide:exenatide BCise) were balanced in baseline characteristics and the mean age was 54 and 55 years, respectively, with approximately 51% and 49% women, respectively. At 6 months, significantly more dulaglutide users were adherent than semaglutide (59.7% vs. 42.7%; P <0.0001) or exenatide BCise users (58.1% vs. 40.3%; P <0.0001). Cox regression showed that dulaglutide users were less likely to discontinue therapy than semaglutide (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.66, 0.76) or exenatide BCise users (HR 0.59, 95% CI 0.53, 0.65; P <0.0001, both).

Conclusion

At 6‐month follow‐up, a higher proportion of patients initiating dulaglutide were adherent to and persistent with their treatment, compared to matched patients initiating either semaglutide or exenatide BCise.
Relationship of negative symptom severity with cognitive symptoms and functioning in subjects at ultra‐high risk for psychosis
Authors: Üçok Alp , Direk Nese , Kaya Hatice , Çağlar Nuran , Çıkrıkçılı Uğur , Noyan Handan , Yokuşoğlu Çağdaş , Devrim‐Üçok Müge
Published: September 2020

Aim

Negative symptoms and cognition are related with functioning in schizophrenia. However, it is not clear whether they have a similar effect in individuals at ultra‐high risk (UHR) for psychosis. In this study, we aimed to explore relationship of negative symptoms with cognition and functioning cross‐sectionally in people with UHR for psychosis.

Methods

In total, 107 people participated in this study. We assessed negative symptoms with Scale for Negative Symptoms (SANS). We applied a cognitive battery including seven tests. We evaluated functioning by using Global Assessment of Functioning Scale and work/study status as an indicator of role functioning.

Results

SANS scores were correlated to global functioning cross‐sectionally. SANS total score was correlated to cognitive test scores related to cognitive flexibility and attention. Only Trail Making Test B (TMT B) was negatively correlated to global functioning. SANS‐affective blunting and SANS‐avolition scores were independently related to global functioning. There was a significant indirect effect of the TMT B and composite attention scores on global functioning through negative symptoms indicating a complete mediation.

Conclusion

Our findings suggest that negative symptoms, particularly avolition have an impact on functioning and the association of cognition with functioning was mediated by negative symptoms in UHR.
Grassland ecosystem recovery after soil disturbance depends on nutrient supply rate
Authors: Seabloom Eric W. , Borer Elizabeth T. , Tilman David
Published: September 2020

Human disturbances alter the functioning and biodiversity of many ecosystems. These ecosystems may return to their pre‐disturbance state after disturbance ceases; however, humans have altered the environment in ways that may change the rate or direction of this recovery. For example, human activities have increased supplies of biologically limiting nutrients, such as nitrogen (N) and phosphorus (P), which can reduce grassland diversity and increase productivity. We tracked the recovery of a grassland for two decades following an intensive agricultural disturbance under ambient and elevated nutrient conditions. Productivity returned to pre‐disturbance levels quickly under ambient nutrient conditions, but nutrient addition slowed this recovery. In contrast, the effects of disturbance on diversity remained hidden for 15 years, at which point diversity began to increase in unfertilised plots. This work demonstrates that enrichment of terrestrial ecosystems by humans may alter the recovery of ecosystems and that disturbance effects may remain hidden for many years.
Monitoring with microchips: Microchip‐automated doors as a potential novel method for tracking the survival of released Northern Brown Bandicoots
Authors: Edwards Megan C. , Hoy Julia M. , FitzGibbon Sean I. , Murray Peter J.
Published: September 2020

Monitoring animals after release to the wild is often limited due to financial and logistical constraints. Microchip‐automated technology has the potential to provide data on microchipped animals’ survival after release and allows access to only the intended, microchipped animals. We aimed to determine whether Northern Brown Bandicoot (Isoodon macrourus) trained to use microchip‐automated nest boxes in captivity would continue to use them after release back to the wild. Ten animals were brought into captivity and trained to use the nest boxes in as little as three days and then released back to the wild after approximately three months in captivity. Use of the nest boxes after release was recorded for up to a week. Eight of the ten animals used the nest boxes on the first night, but only two used them more than five days after release. Three of the animals did not use them at all after release. Whilst ongoing utilisation of the nest boxes was generally low, this technology shows great potential for other species that are hollow‐dependent.