Source:Journal of Anxiety Disorders, Volume 50
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Πέμπτη 10 Αυγούστου 2017
Inside front cover
Source:Journal of Anxiety Disorders, Volume 50
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Temperature-dependent performance of competitive native and alien invasive plant species
Source:Acta Oecologica, Volume 84
Author(s): Uhram Song
To assess the likely impacts of environmental change, the responses of two well-known invasive plant species, native Pueraria lobata and alien Humulus japonicus, to differences in growth temperature were studied in South Korea. Habitat preferences, physiological responses such as photosynthetic rates and chlorophyll contents, growth rates, and nutrient contents were quantified for each species. A competition experiment was conducted to evaluate the temperature preferences of the two species. All results indicated that the alien species H. japonicus can take advantage of elevated temperatures (35 °C) to enhance its competitive advantage against the native species P. lobata. While H. japonicus took advantage of elevated temperatures and preferred high-temperature areas, P. lobata showed reduced performance and dominance in high-temperature areas. Therefore, in future, due to global warming and urbanization, there are possibilities that H. japonicus takes advantage of elevated temperature against P. lobata that could lead to increased H. japonicus coverage over time. Therefore, consistent monitoring of both species especially where P. lobata is dominated are required because both species are found in every continents in the world. Controlling P. lobata requires thorough inspection of H. japonicus presence of the habitat in advance to prevent post P. lobata management invasion of H. japonicus.
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Disparities of Trastuzumab Use in Resource‐Limited or Resource‐Abundant Regions and Its Survival Benefit on HER2 Positive Breast Cancer: A Real‐World Study from China
AbstractBackground.Trastuzumab is a key component of therapy for human epidermal growth receptor 2 (HER2) positive breast cancer. Because real‐world data are lacking, the present research was conducted to evaluate the the actual use of and the effectiveness of trastuzumab in the real world in China.Methods.Inpatients with HER2 positive invasive breast cancer from 13 hospitals in Eastern China (2010–2015, n = 1,139) were included in this study. We aimed to assess the actual use of trastuzumab and to evaluate potential efficacy from trastuzumab in real‐world research.Results.Of 1,017 patients with early stage breast cancer (EBC), 40.5% (412/1,017) received trastuzumab therapy. Patients with EBC in resource‐abundant regions (gross domestic product per capita >$15,000 and trastuzumab included in Medicare) are more likely to receive trastuzumab than those in resource‐limited regions (37.3% vs. 13.0%, p < .05). After metastasis, 50.8% (366/720) patients received trastuzumab as their first‐line therapy. More than 10% of patients with metastatic breast cancer (MBC) continued trastuzumab therapy after twice progression in resource‐abundant regions, whereas more than 40% of patients never received any trastuzumab therapy during the whole course of therapy in resource‐limited regions. Overall, the improvement in survival for trastuzumab versus non‐trastuzumab was substantial in EBC (hazard ratio [HR] = 0.609, 95% confidence interval [CI]: 0.505–0.744) and in MBC (HR = 0.541, 95% CI: 0.418–0.606). This association was greater for patients with MBC who had never received trastuzumab (HR = 0.493, 95% CI: 0.372–0.576) than for those who had received adequate trastuzumab therapy in EBC stage (HR = 0.878, 95% CI: 0.506–1.431).Conclusion.This study showed great disparities in trastuzumab use in different regions and different treatment stages. Both EBC and MBC patients can benefit from trastuzumab, as the survival data show; however, when trastuzumab is adequate in the early stage, a further trastuzumab‐based therapy in first‐line treatment of MBC will be ineffective, especially for those with short disease‐free survival, and a second line of anti‐HER2 therapy will be recommended. (Research number: CSCO‐BC RWS 15001).Implications for Practice.This article shows there are huge disparities in the rates of trastuzumab use due to the unreasonable allocation of medical resources in China. The irrational use can be found both in resource‐abundant regions and in resource‐limited regions. Although trastuzumab‐based therapy improved survival, the actual use of trastuzumab in the early stage of breast cancer would influence the subsequent therapeutic effect after metastasis. This finding in real‐world research could give us a chance to consider the optimized scheme of anti‐HER2 therapy after metastasis especially in these regions with limited access to these expensive target drugs.
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Perspectives of Screening‐Eligible Women and Male Partners on Benefits of and Barriers to Treatment for Precancerous Lesions and Cervical Cancer in Kenya
AbstractBackground.Cervical cancer is the leading cause of female cancer mortality in Kenya. Kenya's National Cervical Cancer Prevention Program Strategic Plan outlines efforts to reduce the burden; however, treatment services remain limited. This study identified male and female perspectives regarding benefits, facilitators, and barriers to treatment for precancerous lesions and cervical cancer.Materials and Methods.Ten focus groups were conducted in Nairobi and Nyanza in 2014 with females aged 25–49 years (n = 60) and male partners (n = 40). Participants were divided into groups dependent on screening status, sex, language, and geographic location. Qualitative analytic software was used to analyze transcribed and translated data.Results.Treatment was endorsed as beneficial for the prevention of death and the improvement of wellness, quality of life, symptoms, and family life. Barriers reported by males and females included the following: (a) concerns about side effects; (b) treatment‐related fear and stigma; (c) marital discord; (d) financial and access issues; (e) religious and cultural beliefs; and (f) limited knowledge. Male endorsement of wanting to improve knowledge and communication with their partners, in spite of stigmatizing beliefs and misperceptions regarding females with abnormal screening results or those who have been diagnosed with cancer, was novel.Conclusion.Incorporating qualitative data on benefits of and barriers to treatment for precancerous lesions and cervical cancer into Kenya's national priorities and activities is important. Our findings can be used to inform the development and successful implementation of targeted, region‐specific community outreach and health messaging campaigns focused on alleviating the country's cervical cancer burden.Implications for Practice.This article provides important insight into female and male partner perspectives regarding benefits, facilitators, and barriers to treatment for precancerous lesions and cervical cancer. Our novel research findings can inform the development of targeted community health interventions, educational messages, and resources and aid stakeholders in strengthening strategic plans regarding treatment coverage and cervical cancer prevention. Because several treatment barriers identified in this study are similar to barriers associated with cervical cancer screening in low‐ and middle‐resourced countries, effective messaging interventions could address barriers to receipt of both screening and treatment.
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A Phase I Dose‐Escalation Study of the Safety and Pharmacokinetics of Pictilisib in Combination with Erlotinib in Patients with Advanced Solid Tumors
AbstractBackground.Epidermal growth factor receptor (EGFR) and phosphatidylinositol 3‐kinase (PI3K) are involved in the proliferation and survival of many cancer types. Enhanced antitumor activity may be achieved through combined inhibition of these pathways. We report results for pictilisib (GDC‐0941, a class I pan‐PI3K inhibitor) plus erlotinib (an EGFR tyrosine kinase inhibitor) in patients with advanced solid tumors.Materials and Methods.A 3 + 3 dose‐escalation study was carried out at a starting daily dose of 60 mg pictilisib on days 1–21 of a 28‐day cycle and 150 mg erlotinib from day 2 of cycle 1. The primary objectives of the study were to assess safety and tolerability, identify dose‐limiting toxicities (DLTs), estimate the maximum tolerated dose, and identify the recommended phase II dose (RP2D). Evaluation of a dose‐expansion cohort at the RP2D was performed.Results.Fifty‐seven patients were treated in the study. All patients experienced at least one adverse event (AE). Grade ≥3 AEs, serious AEs, and deaths were reported in 38 (66.7%), 19 (33.3%), and 4 (7.0%) patients, respectively. DLTs occurred in nine patients across eight cohorts and the RP2D was determined to be 340 mg pictilisib on a "5 days on, 2 days off" schedule plus 100 mg erlotinib. Two patients (3.5%) experienced partial response and 19 (33.3%) had stable disease.Conclusion.Combining pictilisib with erlotinib in patients with advanced solid tumors is feasible; however, antitumor activity is limited. Additional studies may identify patients likely to benefit from combined inhibition of EGFR and PI3K pathways.Implications for Practice.Combining drugs targeting different signaling pathways in cancer growth and survival could overcome drug resistance and improve antitumor activity. In this first‐in‐human study for the combination, addition of the PI3K inhibitor pictilisib to the EGFR tyrosine kinase inhibitor erlotinib resulted in toxicity that led to dose and schedule modifications to identify a tolerable recommended phase II dose of 340 mg pictilisib on a "5 days on, 2 days off" schedule plus 100 mg erlotinib daily. The limited antitumor activity observed, however, suggests that additional studies are needed to identify patients most likely to benefit from combined EGFR and PI3K inhibition.
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Relevance of the nucleus of the solitary tract, gelatinous part, in learned preferences induced by intragastric nutrient administration
Source:Appetite, Volume 118
Author(s): María A. Zafra, Antonio D. Agüera, Filomena Molina, Amadeo Puerto
Food preferences have been investigated in Wistar rats utilizing a learned concurrent flavor preference behavioral procedure. Previous studies have demonstrated that the perivagal administration of neurotoxin capsaicin disrupts the learning of preferences induced by intragastric administration of rewarding nutrients (pre-digested milk). The vagus nerve projects almost exclusively towards the nucleus of the solitary tract (NST), a brain medullary gateway for visceral signals. The objective of this study was to investigate the participation of the lateral portion of the dorsomedial region, the gelatinous subnucleus (SolG), in the learning of a concurrent preference task. Results show that unlike neurologically intact animals, which learn this task correctly, animals lesioned in the gelatinous part of NST manifest a disruption of discrimination learning. Thus, intakes of the flavored stimulus paired with predigested liquid diet and of the flavored stimulus paired with physiological saline were virtually identical. However, SolG- and sham-lesioned groups consumed similar total amounts of both flavors. These findings suggest that SolG, as a relay of the vagus nerve, along with its anatomical projection, the external lateral parabrachial subnucleus (LPBe), may constitute an anatomical axis that is important in the induction of concurrent flavor/side preferences. It also appears to be relevant in other behavioral processes that require rapid processing of information from the upper gastrointestinal tract.
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The prevalence of food addiction in a large sample of adolescents and its association with addictive substances
Publication date: 1 November 2017
Source:Appetite, Volume 118
Author(s): Gabry W. Mies, Jorien L. Treur, Junilla K. Larsen, Jutka Halberstadt, Joëlle A. Pasman, Jacqueline M. Vink
The prevalence of overweight and obesity is increasing, due to, among other factors, increased availability of highly palatable food (food high in fat, salt and/or sugar). It has been proposed that certain foods and/or eating behaviours may be addictive, to a degree comparable to substances of abuse. The Yale Food Addiction Scale (YFAS) measures 'food addiction' by translating the diagnostic criteria for substance use disorder to eating behaviour. So far, only a few studies have examined the prevalence of food addiction in children with the YFAS for children (YFAS-C). Large-scale studies, especially among adolescents, are lacking. Adolescence is of particular interest because it is a period wherein unhealthy eating behaviours or addictive tendencies are likely to develop. The current study examines the prevalence of food addiction using the YFAS-C in a large group of Dutch adolescents (N = 2653) aged 14–21 years. With Generalized Estimation Equation (GEE) analysis we tested the relationship between food addiction symptoms and smoking, cannabis use, alcohol use, and sugar intake through drinks, while controlling for gender, age, educational level and weight class. In the total sample 2.6% met the criteria for a food addiction 'diagnosis', and the average symptom count was 1.0 (SD = 1.3, range 0–7). Symptoms of food addiction were positively associated with smoking, alcohol use, cannabis use and sugar intake. We propose that future studies focus on possible genetic/(neuro)biological mechanisms involved in both food addiction and substance use and that longitudinal designs are needed to examine possible causal pathways.
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Rational design of hollow N/Co-doped carbon spheres from bimetal-ZIFs for high-efficiency electrocatalysis
Publication date: 15 December 2017
Source:Chemical Engineering Journal, Volume 330
Author(s): Xiaodong Chen, Kui Shen, Junying Chen, Binbin Huang, Danni Ding, Lei Zhang, Yingwei Li
To explore efficient non-noble metal-based electrocatalysts for oxygen reduction reaction (ORR), herein we developed a facile bottom-up approach for the fabrication of a hollow porous carbon sphere codoped with ultra-small Co nanoparticles and uniform nitrogen distribution (Co-HNCS) via one-step pyrolysis of a core-shell type precursor composing of polystyrene (PS) core and bimetallic ZIF (zeolite imidazolate framework) shell. The bimetallic Co-Zn-ZIFs (BMZIFs) was selected as the sacrifice template due to not only its high nitrogen content and regular porosity but also the superiority that Zn species in BMZIFs can both spatially separate Co species to suppress the aggregation of ultra-small Co NPs and be evaporated to afford extra pores during high-temperature pyrolysis. As expected, by adjusting the starting molar ratio of Zn to Co, we were able to prepare Co-HNCS-x (x represent the molar ratio of Co to total starting metal feeding) that exhibited unique hollow structure with large surface areas, enhanced mass transport, high porosities, tunable particle sizes and graphitization degrees, abundant highly active CoNx sites, and thus significantly improved ORR performance. Particularly, the optimal Co-HNCS-0.2 exhibited the remarkable ORR activity (the onset and half-wave potentials were 0.94 and 0.82Vvs. RHE, respectively) via an efficient four-electron-dominant ORR process in alkaline medium, which outperformed that of commercial Pt/C (20wt%, the onset and half-wave potentials were 0.93 and 0.80Vvs. RHE, respectively) and most of previously reported Co-based catalysts. Moreover, it also displayed much superior stability and tolerance to methanol as compared to Pt/C, further highlighting the merit of this facile synthesis approach. Our findings might inspire new thoughts on the development of precious-metal-free, highly-efficient and cost-effective ORR electrocatalysts derived from MOF.
Graphical abstract
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Effect of solvent on the electronic absorption spectral properties of some mixed β-octasubstituted Zn(II)-tetraphenylporphyrins
Publication date: 15 January 2018
Source:Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 189
Author(s): P. Bhyrappa, M. Sankar
A series of mixed β-octasubstituted Zn(II)-porphyrins, 2,3,12,13-tetra(chloro/cyano/methyl)-5,7,8,10,15,17,18,20-octaphenylporphinato zinc(II), ZnTPP(Ph)4X4 (X=CN, Cl and CH3) have been examined by electronic absorption spectroscopy in various solvents. These Zn(II)-porphyrins exhibited varying degree of red-shift of absorption bands as high as 20–30nm in 'B' band and 50–60nm in longest wavelength band, 'Q(0,0)' band in polar solvents relative to that found in nonpolar solvents. The red-shift of B and Q(0,0) bands showed an unusual trend, ZnTPP(Ph)4(CN)4>ZnTPP(Ph)4(CH3)4>ZnTPP(Ph)4Cl4 but fails to follow an anticipated anodic shift in first porphyrin ring oxidation (vs Ag/AgCl) potential: ZnTPP(Ph)4(CN)4 (1.02V)>ZnTPP(Ph)4Cl4 (0.74V)>ZnTPP(Ph)4(CH3)4 (0.38V). Such a trend suggests the combined effect of non-planarity of the macrocycle and electronic effect of the peripheral substituents. The equilibrium constants for the binding of nitrogenous bases with the Zn(II)-porphyrins showed as high as twenty fold increase for ZnTPP(Ph)4X4 (X=Br and CN) relative to ZnTPP(Ph)4(CH3)4 and follow the order: ZnTPP(Ph)4(CN)4>ZnTPP(Ph)4Br4>ZnTPP(Ph)4(CH3)4≤ZnTPP which is approximately in line with an increase in anodic shift of their first ring redox potentials (ZnTPP(Ph)4(CN)4 (1.02V)>ZnTPP(Ph)4Br4 (0.72V)>ZnTPP (0.84V)>ZnTPP(Ph)4(CH3)4) (0.38V).
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Learning and combining image neighborhoods using random forests for neonatal brain disease classification
Publication date: Available online 9 August 2017
Source:Medical Image Analysis
Author(s): Veronika A. Zimmer, Ben Glocker, Nadine Hahner, Elisenda Eixarch, Gerard Sanroma, Eduard Gratacós, Daniel Rueckert, Miguel Ángel González Ballester, Gemma Piella
It is challenging to characterize and classify normal and abnormal brain development during early childhood. To reduce the complexity of heterogeneous data population, manifold learning techniques are increasingly applied, which find a low-dimensional representation of the data, while preserving all relevant information. The neighborhood definition used for constructing manifold representations of the population is crucial for preserving the similarity structure and it is highly application dependent. The recently proposed neighborhood approximation forests learn a neighborhood structure in a dataset based on a user-defined distance. We propose a framework to learn multiple pairwise distances in a population of brain images and to combine them in an unsupervised manner optimally in a manifold learning step. Unlike other methods that only use a univariate distance measure, our method allows for a natural combination of multiple distances from heterogeneous sources. As a result, it yields a representation of the population that preserves the multiple distances. Furthermore, our method also selects the most predictive features associated with the distances. We evaluate our method in neonatal magnetic resonance images of three groups (term controls, patients affected by intrauterine growth restriction and mild isolated ventriculomegaly). We show that combining multiple distances related to the condition improves the overall characterization and classification of the three clinical groups compared to the use of single distances and classical unsupervised manifold learning.
Graphical abstract
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MiR-let-7a regulates anti-citrullinated protein antibody-induced macrophage activation and correlates with the development of experimental rheumatoid arthritis
Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Wei Zhu, Jianbo Yu, Shou Qiu, Haifeng Liu, Yan Wang, Xiaoyan Xu, Lili Shao, Lingling Zhu, Yan Jiao, Fan Liu, Xiaodong Zhu
Anti-citrullinated protein antibodies (ACPAs) are a key serological marker of rheumatoid arthritis (RA). To investigate whether miR-let7a downregulated ACPA-induced macrophage activation and arthritis, miR-let7a levels were assessed in the synovial fluid from patients with RA or osteoarthritis (OA). In addition, expression of the pro-inflammatory genes HMGA2, PI3K, and IRF5 was examined in ACPA-induced macrophages and a collagen antibody-induced mouse model of arthritis. As expected, miR-let7a expression in synovial fluid macrophages was substantially lower in patients with RA than in those with OA. Moreover, ACPAs treatment (160IU/mL) suppressed miR-let7a expression in macrophages isolated from patients with RA. Mechanistic studies revealed that miR-let7a directly targets HMGA2 to suppress ACPA-induced IRF5 expression through PI3K in macrophages. Further, miR-let7a expression was markedly decreased in swollen ankle tissue and splenocytes isolated from arthritic mice, whereas HMGA2, PI3K, and IRF5 expression positively correlated with disease severity. However, injection miR-let7a agomir was unable to mitigate the development of experimental arthritis in model mice. Collectively, these data demonstrated that miR-let7a directly targets HMGA2 to downregulate ACPAs-induced macrophage activation, and correlated with experimental RA severity.
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Sodium butyrate inhibits the NF-kappa B signaling pathway and histone deacetylation, and attenuates experimental colitis in an IL-10 independent manner
Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Changhyun Lee, Byeong Gwan Kim, Jee Hyun Kim, Jaeyoung Chun, Jong Pil Im, Joo Sung Kim
Butyrate is a bacterial metabolite of dietary fiber in the colon that has been used to treat inflammatory disease. However, the effect of oral supplementation with butyrate on colitis has not been fully explored. We evaluated the effects of and mechanisms underlying oral supplementation with butyrate on experimental murine colitis. In an in vitro study, we found that LPS induced the secretion of cytokines (i.e., IL-8 in COLO 205; TNF-α, IL-6, IL-12, and IL-10 in RAW 264.7; and TNF-α, IL-6 and IL-12 in peritoneal macrophages obtained from IL-10-deficient [IL-10−/−] mice). Butyrate (100μM and 500μM) inhibited pro-inflammatory cytokine production (i.e., IL-8 in COLO205 and TNF-α, IL-6 and IL-12 in macrophages) but promoted anti-inflammatory cytokine (i.e., IL-10) production in RAW264.7 cells. Butyrate attenuated both the LPS-induced degradation/phosphorylation of IκBα and DNA binding of NF-κB and enhanced histone H3 acetylation. To confirm that butyrate played a protective role in colitis, an acute colitis model was induced using dextran sulfate sodium (DSS) and a chronic colitis model was induced in IL-10−/− mice. The administration of oral butyrate (100mg/kg) significantly improved histological scores in both colitis models, including the IL-10−/− mice. In immunohistochemical staining, IκBα phosphorylation was attenuated, and histone H3 acetylation was reversed in the treated colons of both colitis models. Our results indicate that oral supplementation with butyrate attenuates experimental murine colitis by blocking NF-κB signaling and reverses histone acetylation. These anti-colitic effects of butyrate were IL-10-independent. Butyrate may therefore be a therapeutic agent for colitis.
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Pseudomonas aeruginosa-mannose sensitive hemagglutinin injection treated cytokine-induced killer cells combined with chemotherapy in the treatment of malignancies
Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Chaoqi Zhang, Zhen Zhang, Liping Wang, Jiaoling Han, Feng Li, Chunyi Shen, Hong Li, Lan Huang, Xuan Zhao, Dongli Yue, Jianmin Huang, Yan Yan, Yi Zhang
Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) injection serves as immunological adjuvant in clinical treatment of cancer patients. In present study, we investigated whether PA-MSHA injection enhanced the anti-tumor efficacy of CIK cells. Twenty patients with malignancies were enrolled in this retrospective clinical trial. They were divided into two groups: 10 patients received PA-MSHA treated CIK cells transfusion combined with chemotherapy, and other patients accepted CIK cells and chemotherapy. The efficacy of PA-MSHA treated CIK cells was also observed in vitro and in vivo. With PA-MSHA treatment CIK cells exhibited enhanced proliferation but decreased expression of inhibitory cell surface markers such as Tim-3 and PD-1. Particularly in CIK cells, PA-MSHA promoted the extrusion of pro-inflammatory cytokines like IFN-γ. Of 10 patients with PA-MSHA treated CIK cells and chemotherapy, two patients reached partial remissions, 7 patients had stable disease and the other one had progressive disease. Some of these patients experienced fever after cell infusion. 8 patients with CIK cells showed stable disease and 2 patients had progressive disease. Moreover, the side effects were small in patients with CIK treatment. Our data indicated that PA-MSHA improves the functions of CIK cells and shed new light on developing more potent therapeutic approaches for malignancies.
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Comparison of Pharmacokinetics and Safety of a Fixed-Dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects
Source:Clinical Therapeutics
Author(s): Kyoung Lok Min, Min Soo Park, Jina Jung, Min Jung Chang, Choon Ok Kim
PurposeRosuvastatin and ezetimibe are concomitantly used for dyslipidemia treatment. Compared with separate tablets, fixed-dose combination (FDC) tablets of rosuvastatin/ezetimibe could increase patient compliance. The aim of this study was to compare the pharmacokinetic (PK) profiles of an FDC tablet of rosuvastatin/ezetimibe and co-administration of rosuvastatin and ezetimibe as separate tablets in healthy Korean volunteers.MethodsThis trial was a randomized, open-label, single-dose, 2-way crossover study. The healthy subjects received an FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg (test) or co-administration of rosuvastatin 20 mg and ezetimibe 10 mg (reference) in each period (periods 1 and 2), with a 14-day washout period. The blood samples for PK analysis were collected predose and up to 96 hours after administration, and safety was assessed throughout the study.FindingsSixty-four healthy Korean subjects were enrolled, and 57 subjects completed the study. All subjects were men and mean age was 28.52 ± 5.93. The geometric least squares mean ratios (test/reference) and 90% CIs of Cmax and AUC0–last were 101.54% (94.03–109.65) and 97.71% (91.86–103.93) for rosuvastatin, 108.93% (98.55–120.40) and 102.90% (96.72–109.47) for free ezetimibe, and 106.74% (98.18–116.05) and 104.24 % (99.53–109.17) for total ezetimibe. Twenty-four adverse events (AEs) were reported in 22 subjects. Three cases were related to the study drugs; 2 cases were mild, and 1 case was severe. However, all AEs were resolved without any sequelae. In addition, there were no serious AEs throughout the study.ImplicationsThe FDC tablet of rosuvastatin/ezetimibe was well tolerated and resulted in comparable systemic exposure with co-administration of rosuvastatin and ezetimibe. ClinicalTrials.gov identifier: NCT02941848.
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Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain lipids and energy metabolism
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Melissa McDougall, Jaewoo Choi, Kathy Magnusson, Lisa Truong, Robert Tanguay, Maret G. Traber
Zebrafish (Danio rerio) are a recognized model for studying the pathogenesis of cognitive deficits and the mechanisms underlying behavioral impairments, including the consequences of increased oxidative stress within the brain. The lipophilic antioxidant vitamin E (α-tocopherol; VitE) has an established role in neurological health and cognitive function, but the biological rationale for this action remains unknown. In the present study, we investigated behavioral perturbations due to chronic VitE deficiency in adult zebrafish fed from 45 days to 18-months of age diets that were either VitE-deficient (E–) or VitE-sufficient (E+). We hypothesized that E– zebrafish would display cognitive impairments associated with elevated lipid peroxidation and metabolic disruptions in the brain. Quantified VitE levels at 18-months in E– brains (5.7 ± 0.1 nmol/g tissue) were ~20-times lower than in E+ (122.8 ± 1.1; n = 10/group). Using assays of both associative (avoidance conditioning) and non-associative (habituation) learning, we found E– vs E+ fish were learning impaired. These functional deficits occurred concomitantly with the following observations in adult E– brains: decreased concentrations of and increased peroxidation of polyunsaturated fatty acids (especially docosahexaenoic acid, DHA), altered brain phospholipid and lysophospholipid composition, as well as perturbed energy (glucose/ketone), phosphatidylcholine and choline/methyl-donor metabolism. Collectively, these data suggest that chronic VitE deficiency leads to neurological dysfunction through multiple mechanisms that become dysregulated secondary to VitE deficiency. Apparently, the E– animals alter their metabolism to compensate for the VitE deficiency, but these compensatory mechanisms are insufficient to maintain cognitive function.
Graphical abstract
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Structural, tribological, and mechanical properties of the hind leg joint of a jumping insect: Using katydids to inform bioinspired lubrication systems
Publication date: Available online 9 August 2017
Source:Acta Biomaterialia
Author(s): Jun Kyun Oh, Spencer T. Behmer, Richelle Marquess, Cengiz Yegin, Ethan A. Scholar, Mustafa Akbulut
This study investigates the structural properties of the hind leg femur-tibia joint in adult katydids (Orthoptera: Tettigoniidae), including its tribological and mechanical properties. It is of particular interest because the orthopteran (e.g., grasshoppers, crickets, and katydids) hind leg is highly specialized for jumping. We show that the katydid hind leg femur-tibia joint had unique surfaces and textures, with a friction coefficient (μ) at its coupling surface of 0.053 ± 0.001. Importantly, the sheared surfaces at this joint showed no sign of wear or damage, even though it had undergone thousands of external shearing cycles. We attribute its resiliency to a synergistic interaction between the hierarchical surface texture/pattern on the femoral surfaces, a nanograded internal nanostructure of articulating joints, and the presence of lubricating lipids on the surface at the joint interface. The micro/nanopatterned surface of the katydid hind leg femur-tibia joint enables a reduction in the total contact area, and this significantly reduces the adhesive forces between the coupling surfaces. In our katydids, the femur and tibia joint surfaces had a maximum effective elastic modulus (Eeff) value of 2.6 GPa and 3.9 GPa, respectively. Presumably, the decreased adhesion through the reduction of van der Waals forces prevented adhesive wear, while the contact between the softer textured surface and harder smooth surface avoided abrasive wear. The results from our bioinspired study offer valuable insights that can inform the development of innovative coatings and lubrication systems that are both energy efficient and durable.Statement of SignificanceRelative to body length, insects can outjump most animals. They also accelerate their bodies at a much faster rate. Orthopterans (e.g., grasshoppers, crickets, and katydids) have hind legs that are specialized for jumping. Over an individual's lifetime, the hind leg joint endures repeated cycles of flexing and extending, including jumping, and its efficiency and durability easily surpass that of most mechanical devices. Although the efficient functioning of insect joints has long been recognized, the mechanism by which insect joints experience friction/adhesion/wear, and operate efficiently/reliably is still largely unknown. Our study on the structural, tribological, and mechanical properties of the orthopteran hind leg joints reveals the potential of katydid bioinspired research leading to more effective coatings and lubrication systems.
Graphical abstract
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Self-defensive antibiotic-loaded layer-by-layer coatings: imaging of localized bacterial acidification and pH-triggering of antibiotic release
Publication date: Available online 9 August 2017
Source:Acta Biomaterialia
Author(s): Victoria Albright, Iryna Zhuk, Yuhao Wang, Victor Selin, Betsy van de Belt-Gritter, Henk J. Busscher, Henny C. van der Mei, Svetlana Sukhishvili
Self-defensive antibiotic-loaded coatings have shown promise in inhibiting growth of pathogenic bacteria adhering to biomaterial implants and devices, but direct proof that their antibacterial release is triggered by bacterially-induced acidification of the immediate environment under buffered conditions remained elusive. Here, we demonstrate that Staphylococcus aureus and Escherichia coli adhering to such coatings generate highly localized acidification, even in buffered conditions, to activate pH-triggered, self-defensive antibiotic release. To this end, we utilized chemically crosslinked layer-by-layer hydrogel coatings of poly(methacrylic acid) with a covalently attached pH-sensitive SNARF-1 fluorescent label for imaging, and unlabeled-antibiotic (gentamicin or polymyxin B) loaded coatings for antibacterial studies. Local acidification of the coatings induced by S. aureus and E. coli adhering to the coatings was demonstrated by confocal-laser-scanning-microscopy via wavelength-resolved imaging. pH-triggered antibiotic release under static, small volume conditions, yielded high bacterial killing efficiencies for S. aureus and E. coli. Gentamicin-loaded films retained their antibacterial activity against S. aureus under fluid flow in buffered conditions. Antibacterial activity increased with the number of polymer layers in the films. Altogether, pH-triggered, self-defensive antibiotic-loaded coatings become activated by highly localized acidification in the immediate environment of an adhering bacterium, offering potential for clinical application with minimized side-effects.Statement of significancePolymeric coatings that are able to uptake and selectively release antibiotics upon stimulus by adhering bacteria, as a potential way to prevent biomaterial-associated infections, were created in order to understand the fundamental mechanisms behind pH-triggered antibiotic release. Through fluorescent imaging studies, this work importantly shows that adhering bacteria produce highly localized pH changes even in buffer. Accordingly such coatings only demonstrate antibacterial activity by antibiotic release in the presence of adhering bacteria. This is clinically important, because ad libitum releasing antibiotic coatings usually show a burst release and have often lost their antibiotic content when bacteria adhere.
Graphical abstract
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
