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Abdalla Bowirrat,1 Igor Elman,2 Catherine A Dennen,3 Marjorie C Gondré-Lewis,4 Jean Lud Cadet,5 Jag Khalsa,6 David Baron,7 Diwanshu Soni,8 Mark S Gold,9 Thomas J McLaughlin,10 Debasis Bagchi,11 Eric R Braverman,12 Mauro Ceccanti,13 Panayotis K Thanos,14,15 Edward Justin Modestino,16 Keerthy Sunder,17,18 Nicole Jafari,19,20 Foojan Zeine,21,22 Rajendra D Badgaiyan,23 Debmalya Barh,24,25 Milan Makale,26 Kevin T Murphy,27 Kenneth Blum1,7,10,12,18,20,24,28,29 1Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, 40700, Israel; 2Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, 02139, USA; 3Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA; 4Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, DC, 20059, USA; 5Molecular Neuropsychiatry Research Branch, NIH National Institute on Drug Abuse, Bethesda, MD, 20892, USA; 6Department of Microbiology, Immunology and Tropical Medicine, George Washington University, School of Medicine, Washington, DC, USA; 7Division of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA, 91766, USA; 8Western University Health Sciences School of Medicine, Pomona, CA, USA; 9Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA; 10Division of Reward Deficiency Clinics, TranspliceGen Therapeutics, Inc, Austin, TX, USA; 11Department of Pharmaceutical Sciences, Texas Southern University College of Pharmacy, Houston, TX, USA; 12Division of Clinical Neurology, The Kenneth Blum Institute of Neurogenetics & Behavior, LLC, Austin, TX, USA; 13Alcohol Addiction Program, Latium Region Referral Center, Sapienza University of Rome, Roma, 00185, Italy; 14Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, 14203, USA; 15Department of Psychology, State University of New York at Buffalo, Buffalo, NY, 14203, USA; 16Department of Psychology, Curry College, Milton, MA, USA; 17Karma Doctors & Karma TMS, and Suder Foundation, Palm Springs, CA, USA; 18Department of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA; 19Department of Human Development, California State University at Long Beach, Long Beach, CA, USA; 20Division of Personalized Medicine, Cross-Cultural Research and Educational Institute, San Clemente, CA, USA; 21Awareness Integration Institute, San Clemente, CA, USA; 22Department of Health Science, California State University at Long Beach, Long Beach, CA, USA; 23Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY, USA; 24Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Purba Medinipur, WB, 721172, India; 25Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Brazil; 26Department of Radiation Medicine and Applied Sciences, UC San Diego, La Jolla, CA, 92093-0819, USA; 27Department of Radiation Oncology, University of California San Diego, La Jolla, CA, USA; 28Department of Psychiatry, University of Vermont School of Medicine, Burlington, VA, USA; 29Institute of Psychology, ELTE Eötvös Loránd University, Budapest, HungaryCorrespondence: Igor Elman; Kenneth Blum, Email dr.igorelman@gmail.com; drd2gene@gmail.comAbstract: Loneliness, an established risk factor for both, mental and physical morbidity, is a mounting public health concern. However, the neurobiological mechanisms underlying loneliness-related morbidity are not yet well defined. Here we examined the role of genes and associated DNA risk polymorphic variants that are implicated in loneliness via genetic and epigenetic mechanisms and may thus point to specific therapeutic targets. Searches were conducted on PubMed, Medline, and EMBASE databases using specific Medical Subject Headings terms such as loneliness and genes, neuro- and epigenetics, addiction, affective disorders, alcohol, anti-reward, anxiety, depression, dopamine, cancer, cardiovascular, cognitive, hypodopaminergia, medical, motivation, (neuro)psychopathology, social isolation, and reward deficiency. The narrative literature review yielded recursive collections of scientific and clinical evidence, which were subsequently condensed and summarized in the following key areas: (1) Genetic Antecedents: Exploration of multiple genes mediating reward, stress, immunity and other important vital functions; (2) Genes and Mental Health: Examination of genes linked to personality traits and mental illnesses providing insights into the intricate network of interaction converging on the experience of loneliness; (3) Epigenetic Effects: Inquiry into instances of loneliness and social isolation that are driven by epigenetic methylations associated with negative childhood experiences; and (4) Neural Correlates: Analysis of loneliness-related affective states and cognitions with a focus on hypodopaminergic reward deficiency arising in the context of early life stress, eg, maternal separation, underscoring the importance of parental support early in life. Identification of the individual contributions by various (epi)genetic factors presents opportunities for the creation of innovative preventive, diagnostic, and therapeutic approaches for individuals who cope with persistent feelings of loneliness. The clinical facets and therapeutic prospects associated with the current understanding of loneliness, are discussed emphasizing the relevance of genes and DNA risk polymorphic variants in the context of loneliness-related morbidity.Keywords: addiction, affective, alcohol, anti-reward, anxiety, depression, dopamine, cancer, genes, cardiovascular, cognitive, medical, motivation, social isolation, reward deficiency

Recent studies show that hydrogen peroxide free radicals have an important role in the renal damage induced by Gentamicin. Previously we studied the hydrogen peroxide scavenging activity of Eryngium caucasicum. This work was conducted to evaluate the possible renoprotective effect of Eryngium caucasicum against Gentamicin-induced renotoxicity. Extracts at the doses 200 and 400 mg/kg/day for 10 consecutive days, by intraperitoneal route (i.p.) offered renoprotective action by change in the blood urea nitrogen (BUN), serum urea and creatinine. Results show that an extract at 400 mg/kg/ day shows better activity than other tested samples. In conclusion, the extracts showed significant renoprotective activity compared with the control group.

In the present study the cardioprotective effects of curcumin, a herbal polyphenolic compound, against sodium fluoride (NaF)-induced toxicity in rat heart was evaluated. Fifty rats were divided into five experimental groups containing 10 rats each. Group I received standard water and diet and was used as a normal group; groups II and III were pretreated with curcumin intraperitoneally for 7 days prior to NaF intoxication. Group IV was pretreated with vitamin C, a standard antioxidant, intraperitoneally for 7 days prior to NaF intoxication and used as a positive control group. The animals in group V were intoxicated with NaF for the same time and used as a control group. There was a significant increase in lipid peroxidation along with a decrease in superoxide dismutase activity in the homogenates of tissues of the NaF-treated animals. Curcumin pretreatment in animals prior to fluoride intoxication normalized the levels of biochemical parameters measured.

The evolution of coastal wetlands is a complex process which is difficult to forecast, made more complicated by the addition of changing climatic conditions. Here, long term ecological and geomorphological data are coupled to geotechnical measurements at a coastal wetland in North Inlet estuary, South Carolina. The coupled methodology is presented and discussed in context of understanding coastal wetland system evolution in a changing climate. Specifically, the root shear strength of Spartina alterniflora across a range of elevations was investigated using a cone penetrometer test. Elevation, shear strength, and biomass are shown to be critically interconnected. Root strength was shown to decrease with increased inundation time and decreased elevation (i.e., mudflats). Conversely, the data set illustrates the importance of maintaining key elevation ranges in relation to sea‐level to optimize wetland resilience. Plain Language Summary: Coastal wetlands are under increased stress from the effects of climate change. We set out to incorporate measurements from multiple disciplines to better understand how these wetlands evolve under these conditions. The strength (resilience) of the wetlands is directly related to the elevation and vegetation of the wetland. Understanding the relationships we present will assist coastal managers make decisions to better protect coastal wetlands. Key Points: Ecological, geomorphological, and geotechnical properties of wetlands are critically interconnectedCoupling of interdisciplinary data sets is required for prediction of wetland evolution in a changing climate [ABSTRACT FROM AUTHOR]

A well-designed Agricultural Extension System (AES) can facilitate transitions towards sustainable agriculture. However, in most developing countries, AES has failed to promote sustainable agricultural development. The New Agricultural Extension System (NAES) was initiated to facilitate agricultural development in Iran. However, there is still no definite reflection on the influences of NAES on agricultural development. Therefore, this research aimed to evaluate the performance of NAES. To ensure an integrative and holistic analysis of the NAES's performance, the Complexity Theory (CT) and Agricultural Innovation System (AIS) approaches were used. To gather data, survey research was conducted in Fars Province, southern Iran. A multi-stage random sampling was used to identify the designated extension agents. The findings indicated that effective implementation of the NAES needs facilitated interaction through network mediation (X = 71.6), creation of an enabling context for the delivery of extension services (X = 66.6), improved communication and marketing infrastructures (X = 72), development of a value chain (X = 71.4), acceptance of self-organization (X = 67.8) and adoption of complexity-aware management (X = 66). The results also identified the hindering effects of demographic, structural and psychological factors on the practical application of CT and AIS principles. Some recommendations and implications are offered to improve the effectiveness of NAES. [ABSTRACT FROM AUTHOR]

Agriculture is an essential instrument for development, poverty alleviation, and food security in developing countries, such as Iran. The agricultural sector of Iran is dominated by small-scale farming, and the yield of most crops is low. A well-designed and well-functioning agricultural extension system can facilitate the transition toward productive, profitable, and sustainable agriculture. However, the top- down agricultural extension system of Iran has left most smallholder and resource-poor farmers with no access to advisory services, and their problems have remained unresolved. The new agricultural extension system (NAES) was initiated in 2014 to better respond to the problems of smallholder farmers. However, there is still no definite reflection on the influences of the NAES on agricultural development. Therefore, this study aimed to evaluate the performance of the NAES. Also, it purposed to identify the blocking mechanisms hindering the NAES’ function. In this regard, qualitative research was planned and conducted in Fars Province, Southern Iran. The findings revealed that NAES has managed to enhance the availability of extension services for smallholder farmers, improve the productivity and profitability of agriculture, and reduce livelihood vulnerability. However, it has failed in facilitating access to remunerative markets, mobilizing sustainable financial and human resources, and being entirely demand-driven because of financial, physical, institutional, market, natural, informational, capability, and psychological constraints. Some recommendations and implications are offered to improve the effectiveness of the NAES. [ABSTRACT FROM AUTHOR]

Affected by the developed pore water pressure during undrained cyclic shear of saturated soils, granular soil liquefaction is regarded as a common phenomenon that occurs under earthquake loads. This phenomenon causes huge damage to infrastructure. Different reinforcement materials have been successfully implemented with particular attention to the use of waste materials to satisfy design specifications and mitigate the adverse environmental effects. This paper aims to investigate the possibility of using waste plastic fibers as reinforcement materials to mitigate liquefaction potential and pore pressure generation of reinforced sand under cyclic loading. For this purpose, 42 stress-controlled cyclic triaxial tests were conducted on Babolsar sand, reinforced by Poly-Ethylene Terephthalate (PET) and Polypropylene (PP) fibers with the fiber contents of 0.25%, 0.5%, and 1% under the confining pressures of 50, 100, and 200 kPa at Cyclic Stress Ratios (CSR) of 0.2 and 0.35. The obtained results revealed that the addition of these waste plastic fibers could significantly increase the liquefaction resistance of Babolsar sand and that with an increase in the waste content, the number of cycles leading to liquefaction would increase. Addition of wastes decreased the pore water pressure generation, and this effect was more pronounced with an increase in the waste content. [ABSTRACT FROM AUTHOR]

Objective: Aloe vera is a medicinal plant that has been traditionally used to accelerate wound healing. Olive oil is also a natural product that may contribute to wound healing owing to its antimicrobial and anti-inflammatory effects. The present study aimed to evaluate the effect of an Aloe vera-olive oil (AVO) combination cream on the healing process of chronic wounds. Method: In this randomised, double-blind, comparator-controlled, parallel-group trial, patients with chronic wounds were treated with either AVO cream or phenytoin cream as the standard treatment for a period of 30 days. Wound healing was evaluated using Bates-Jensen assessment tool and the severity of pain was assessed using a visual analogue scale (VAS). Results: After initial assessment, 60 patients with chronic wounds (41 with pressure ulcer, 13 with diabetic wounds and 6 with venous ulcers), were recruited and randomised into 2 groups of 30. After 30 days of treatment, significant improvements in the wound size, depth, and edges; necrotic tissue type and amount; exudate type and amount; colour of wound surroundings; and peripheral tissue oedema score were observed in the AVO cream group (p<0.001). The total score of wound healing showed significant improvement with both AVO (p<0.001) and phenytoin (p<0.01) creams, although AVO was more efficacious (p<0.001). Likewise, although both treatments reduced the initial VAS score, the efficacy of AVO was significantly greater (p<0.001). Conclusion: AVO cream significantly accelerates biological healing of chronic wounds and helps to reduce pain severity with a higher efficacy compared with phenytoin cream. Declaration of interest: The authors have no competing interest to declare. [ABSTRACT FROM AUTHOR]

This paper is concerned with the analysis of mixed data with ordinal and continuous outcomes with the possibility of non-ignorable missing outcomes. A copula-based regression model is proposed that accounts for associations between ordinal and continuous outcomes. Our approach entails specifying underlying latent variables for the mixed outcomes to indicate the latent mechanisms which generate the ordinal and continuous variables. Maximum likelihood estimation of our model parameters is implemented using standard software such as function nlminb in R. Results of simulations concern the relative biases of parameter estimates of joint and marginal models using data with non-ignorable outcomes. The proposed methodology is illustrated using a medical data obtained from an observational study on women with three correlated responses, an ordinal response of osteoporosis of the spine and two continuous responses of body mass index and waistline. The effect of the amount of total body calcium (Ca), job status (Job), type of dwelling (Ta) and age on all responses are investigated simultaneously. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to compare the stabilizing effect of four disaccharides alone or in combination on the lactoperoxidase (LP) derived from bovine milk during lyophilization. Sucrose, lactose, maltose, and trehalose at different concentrations (5-500 mM) were used to compare their protective effects on LP activity. The activity of lyophilized and native LP enzyme was evaluated using the procedure of Schindler with slight modifications. The antibacterial activity of the lyophilized enzyme against Pseudomonas aeroginosa, Escherichia coli, and Staphylococcus aureus was also investigated using the antimicrobial effectiveness test. Trehalose at concentration of 500 mM was the most effective cryoprotectant in protecting the enzyme activity. It preserved LP activity for 40 days, while the native enzyme lost its activity after 6 days. Combinations of disaccharides resulted in an increment in the stability of the enzyme, compared to the native enzyme. Combination of 200 mM trehalose and 200 mM sucrose were found most effective cryoprotectant in freeze-drying of LP. The lyophilized LP decreased the growth rate of Ps.aeroginosa, E.coli, and S.aureus between up to 30.8% in 106 cfu/ml and 53.3% in 105 cfu/ml. Antimicrobial efficacy of LP was more pronounced when 105 cfu/ml was used as compared to 106 cfu/ml. [ABSTRACT FROM AUTHOR]