Search Results (19)

Rabbits are commonly used for pharmacokinetic (PK) and toxicokinetic (TK) studies in the research setting, requiring repetitive venipuncture, which can be challenging in this species. The auricular vessels are commonly used for venipuncture in rabbits. The repetitive access of these delicate vessels can lead to trauma such as hematomas causing venipuncture to become more challenging as the study progresses. In turn, this leads to missed time points or insufficient blood samples. Surgical models for chronic vascular access in rabbits are common throughout the industry. Common models include exteriorized vascular catheters and implanted vascular access ports. However, these implants come with their own complications and restrictions when used in rabbits. Therefore, the authors evaluated the use of a vascular access button (VAB), an implant commonly used in small rodents, as a refinement to the current chronic models in use in the industry. Seventeen rabbits were implanted with either single or dual channel VABs. The catheters were implanted in the femoral artery and/or vein and then tunneled subcutaneously to the button on the dorsal thoracic area. Overall, the results were outstanding, and an established model was created. The average patency rate was 316 days with several implants still patent after 2 years. The authors feel the implantation and use of a vascular access button in rabbits for routine PK studies is an excellent refinement. The rabbits tolerate the buttons extremely well with minimal issues. The patency rate is equal to or better than vascular access ports and when used with the tethering system, provides a hands-off method for blood collection and intravenous administration in rabbits during PK studies. Full article

Androgen receptor splice variants (AR-SVs) contribute to the aggressive growth of castration-resistant prostate cancer (CRPC). AR-SVs, including AR-V7, are expressed in ~30% of CRPC, but minimally in treatment-naïve primary prostate cancer (PCa). Compared to Caucasian American (CA) men, African American (AA) men are more likely to be diagnosed with aggressive/potentially lethal PCa and have shorter disease-free survival. Expression of a truncated AR in an aggressively growing patient-derived xenograft developed with a primary PCa specimen from an AA patient led us to hypothesize that the expression of AR-SVs could be an indicator of aggressive growth both in PCa progression and at the CRPC stage in AA men. Tissue microarrays (TMAs) were created from formalin-fixed paraffin-embedded (FFPE) prostatectomy tumor blocks from 118 AA and 115 CA treatment-naïve PCa patients. TMAs were stained with AR-V7-speicifc antibody and with antibodies binding to the N-terminus domain (NTD) and ligand-binding domain (LBD) of the AR. Since over 20 AR-SVs have been identified, and most AR-SVs do not as yet have a specific antibody, we considered a 2.0-fold or greater difference in the NTD vs. LBD staining as indication of potential AR-SV expression. Two AA, but no CA, patient tumors stained positively for AR-V7. AR staining with NTD and LBD antibodies was robust in most patients, with 21% of patients staining at least 2-fold more for NTD than LBD, indicating that AR-SVs other than AR-V7 are expressed in primary treatment-naïve PCa. About 24% of the patients were AR-negative, and race differences in AR expression were not statistically significant. These results indicate that AR-SVs are not restricted to CRPC, but also are expressed in primary PCa at higher rate than previously reported. Future investigation of the relative expression of NTD vs. LBD AR-SVs could guide the use of newly developed treatments targeting the NTD earlier in the treatment paradigm. Full article

The nomenclature used to describe animals working in roles supporting people can be confusing. The same term may be used to describe different roles, or two terms may mean the same thing. This confusion is evident among researchers, practitioners, and end users. Because certain animal roles are provided with legal protections and/or government-funding support in some jurisdictions, it is necessary to clearly define the existing terms to avoid confusion. The aim of this paper is to provide operationalized definitions for nine terms, which would be useful in many world regions: “assistance animal”, “companion animal”, “educational/school support animal”, “emotional support animal”, “facility animal”, “service animal”, “skilled companion animal”, “therapy animal”, and “visiting/visitation animal”. At the International Society for Anthrozoology (ISAZ) conferences in 2018 and 2020, over 100 delegates participated in workshops to define these terms, many of whom co-authored this paper. Through an iterative process, we have defined the nine terms and explained how they differ from each other. We recommend phasing out two terms (i.e., “skilled companion animal” and “service animal”) due to overlap with other terms that could potentially exacerbate confusion. The implications for several regions of the world are discussed. Full article

Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus. Full article

Background and Objectives: African Americans and males have elevated risks of infection, hospitalization, and death from SARS-CoV-2 in comparison with other populations. We report immune responses and renal injury markers in African American male patients hospitalized for COVID-19. Methods: This was a single-center, retrospective study of 56 COVID-19 infected hospitalized African American males 50+ years of age selected from among non-intensive care unit (ICU) and ICU status patients. Demographics, hospitalization-related variables, and medical history were collected from electronic medical records. Plasma samples collected close to admission (≤2 days) were evaluated for cytokines and renal markers; results were compared to a control group (n = 31) and related to COVID-19 in-hospital mortality. Results: Among COVID-19 patients, eight (14.2%) suffered in-hospital mortality; seven (23.3%) in the ICU and one (3.8%) among non-ICU patients. Interleukin (IL)-18 and IL-33 were elevated at admission in COVID-19 patients in comparison with controls. IL-6, IL-18, MCP-1/CCL2, MIP-1α/CCL3, IL-33, GST, and osteopontin were upregulated at admission in ICU patients in comparison with controls. In addition to clinical factors, MCP-1 and GST may provide incremental value for risk prediction of COVID-19 in-hospital mortality. Conclusions: Qualitatively similar inflammatory responses were observed in comparison to other populations reported in the literature, suggesting non-immunologic factors may account for outcome differences. Further, we provide initial evidence for cytokine and renal toxicity markers as prognostic factors for COVID-19 in-hospital mortality among African American males. Full article

The European sheep and goat sector is characterized by low professionalization and management training. Moreover, it is fragmented in terms of production aims and farming systems. Here, iSAGEDSS, a web-based application allowing dairy and meat small ruminant farmers in different countries to make annual management plans by testing future scenarios, is presented. Data were obtained for the meat sheep (United Kingdom and Spain), dairy sheep (France and Greece) and dairy goat production systems (Greece) from partners of the Innovation for Sustainable Sheep and Goat Production in Europe (iSAGE) project. These were used to set default values and ranges for all important farm parameters in each system and country. An algorithm was developed assessing nutritional management and its impact on production and financial performance. Reports focus on profitability, productivity and environmental sustainability. A case study in three dairy sheep farms in Greece was performed. In each case, an evaluation scenario was created using actual farm data that were compared with the estimated ones. Two scenarios testing management decisions for gross margin maximization and milk pricing fluctuations were created. Application results showed high prediction accuracy for gross margin and production estimation (error of circa 9% and 4%, respectively). Moreover, the ability to promote financial, production and grazing management efficiency was demonstrated. Full article

Small-quantity lipid-based nutrient supplements (SQ-LNS) could help prevent malnutrition. Our primary objective was to examine the acceptability and consumption of sweetened and unsweetened versions of SQ-LNS before and after 14-days of repeated exposure. A total of 78 mother-infant dyads recruited from health centers in Morelos, Mexico, were randomized to two groups of SQ-LNS (sweetened, LNS-S; unsweetened, LNS-U). During the study, infants were fed SQ-LNS (20 g) mixed with 30 g of complementary food of the caregiver’s choice. The amount of supplement-food mixture consumed was measured before, during and after a 14-day home exposure period. We defined acceptability as consumption of at least 50% of the offered food mixture. At initial exposure, LNS-U consumption was on average 44.0% (95% CI: 31.4, 58.5) and LNS-S 34.8% (25.3, 44.0); at final exposure, LNS-U and LNS-S consumption were 38.5% (27.8, 54.0) and 31.5% (21.6, 43.0). The average change in consumption did not differ between the groups (2.2 p.p. (−17.2, 24.4)). We conclude that the acceptability of sweetened and unsweetened SQ-LNS was low in this study population. Since consumption did not differ between supplement versions, we encourage the use of the unsweetened version given the potential effects that added sugar may have on weight gain especially in regions facing the double burden of malnutrition. Full article

While forming a minor population in the blood and lymphoid compartments, γδ T cells are significantly enriched within barrier tissues. In addition to providing protection against infection, these tissue-resident γδ T cells play critical roles in tissue homeostasis and repair. γδ T cells in the epidermis and intestinal epithelium produce growth factors and cytokines that are important for the normal turnover and maintenance of surrounding epithelial cells and are additionally required for the efficient recognition of, and response to, tissue damage. A role for tissue-resident γδ T cells is emerging outside of the traditional barrier tissues as well, with recent research indicating that adipose tissue-resident γδ T cells are required for the normal maintenance and function of the adipose tissue compartment. Here we review the functions of tissue-resident γδ T cells in the epidermis, intestinal epithelium, and adipose tissue, and compare the mechanisms of their activation between these sites. Full article

Non-communicable diseases are responsible for 63% of global deaths, with a higher burden in low- and middle-income countries. Hypertension is the leading cause of cardiovascular-disease-related deaths worldwide, and approximately 1.7 million deaths are directly attributable to excess salt intake annually. There has been little research conducted on the level of salt consumption amongst the population of Vanuatu. Based on data from other Pacific Island countries and knowledge of changing regional diets, it was predicted that salt intake would exceed the World Health Organization’s (WHO) recommended maximum of 5 g per day. The current study aimed to provide Vanuatu with a preliminary baseline assessment of population salt intake on Efate Island. A cross-sectional survey collected demographic, clinical, and urine data from participants aged 18 to 69 years in rural and urban communities on Efate Island in October 2016 and February 2017. Mean salt intake was determined to be 7.2 (SD 2.3) g/day from spot urine samples, and 5.9 (SD 3.6) g/day from 24-h urine samples, both of which exceed the WHO recommended maximum. Based on the spot urine samples, males had significantly higher salt intake than females (7.8 g compared to 6.5 g; p < 0.001) and almost 85% of the population consumed more than the WHO recommended maximum daily amount. A coordinated government strategy is recommended to reduce salt consumption, including fiscal policies, engagement with the food industry, and education and awareness-raising to promote behavior change. Full article

Raised blood lipid levels are associated with a risk of a cardiovascular disease (CVD). Moderate reductions in several CVD factors such as total, low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol concentrations may be more effective in reducing overall risk than a major reduction in just one. A blind, randomised controlled trial was conducted with 120 healthy overweight (BMI 25–30) adults aged 25–70 years who were non-smokers, not diabetic and of low risk of cardiovascular disease, as assessed by the Framingham risk equation. Participants consumed 4.5 g PolyGlycopleX (PGX) as softgel capsules (PGXS) or 5 g PGX granules (PGXG) or 5 g rice flour (RF) with meals three times a day for 12 weeks. Total, LDL and non-HDL cholesterol were all significantly reduced (−6%, −5% and −3.5%, respectively) post the PGX granule treatment; however, PGX in softgel capsule form did not affect blood lipid profiles. Daily consumption of PGX granules in overweight low CVD risk adults produced lipid changes indicating a CVD preventative benefit. Full article

In Vanuatu, mean salt intake exceeds the recommended maximum daily intake, and contributes to the high proportion of deaths attributable to cardiovascular diseases. Understanding salt-related knowledge, attitudes, and behaviors of the Vanuatu population can inform appropriate interventions. This cross-sectional study was conducted as part of the 2016–2017 Vanuatu Salt Survey. In total, 753 participants aged between 18 and 69 years from rural and urban communities on the Island of Efate were included. Demographic and clinical data were collected and a salt-related knowledge, attitudes, and behaviors survey was administered. Knowledge relating to the need to reduce salt consumption was high, but reported behaviors did not reflect this knowledge. A total of 83% of participants agreed that too much salt could cause health problems, and 86% reported that it was “very important” to lower the amount of salt in the diet. However, more than two-thirds of the population reported always/often adding salt to food during cooking/meal preparation and at the table, and always/often consuming processed foods high in salt. Strategic, targeted, and sustained behavior change programs in parallel with interventions to change the food environment to facilitate healthier choices should be key components of a salt reduction program. Actions should implemented as part of a comprehensive strategy to prevent and control non-communicable diseases in Vanuatu. Full article

This study considers whether a relationship exists between response to lithium (Li) exposure and select vegetation indices (VI) determined from reflectance spectra in each of four plant species: Arabidopsis thaliana, Helianthus annuus (sunflower), Brassica napus (rape), and Zea mays (corn). Reflectance spectra were collected every week for three weeks using an ASD FieldSpec Pro spectroradiometer with both a contact probe (CP) and a field of view probe (FOV) for plants treated twice weekly in a laboratory setting with 0 mM (control) or 15 mM of lithium chloride (LiCl) solution. Plants were harvested each week after spectra collection for determination of relevant physical endpoints such as relative water content and chlorophyll content. Mixed effects analyses were conducted on selected endpoints and vegetation indices (VI) to determine the significance of the effects of treatment level and length of treatment as well as to determine which VI would be appropriate predictors of treatment-dependent endpoints. Of the species considered, A. thaliana exhibited the most significant effects and corresponding shifts in reflectance spectra. Depending on the species and endpoint, the most relevant VIs in this study were NDVI, PSND, YI, R₁₆₇₆/R₁₉₃₃, R₇₅₀/R₅₅₀, and R₉₅₀/R₇₅₀. Full article

The debate about the roles of general and specific abilities in predicting important outcomes is a tempest in a ladle because we cannot measure abilities without also measuring skills. Skills always develop through exposure, are specific rather than general, and are executed using different strategies by different people, thus tapping into varied specific abilities. Relative predictive validities of measurement formats depend on the purpose: the more general and long-term the purpose, the better the more general measure. The more specific and immediate the purpose, the better the closely related specific measure. Full article