Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques.

Zika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.

Molecularly barcoded Zika virus libraries to probe in vivo evolutionary dynamics.

Defining the complex dynamics of Zika virus (ZIKV) infection in pregnancy and during transmission between vertebrate hosts and mosquito vectors is critical for a thorough understanding of viral transmission, pathogenesis, immune evasion, and potential reservoir establishment. Within-host viral diversity in ZIKV infection is low, which makes it difficult to evaluate infection dynamics. To overcome this biological hurdle, we constructed a molecularly barcoded ZIKV. This virus stock consists of a "synthetic swarm" whose members are genetically identical except for a run of eight consecutive degenerate codons, which creates approximately 64,000 theoretical nucleotide combinations that all encode the same amino acids. Deep sequencing this region of the ZIKV genome enables counting of individual barcodes to quantify the number and relative proportions of viral lineages present within a host. Here we used these molecularly barcoded ZIKV variants to study the dynamics of ZIKV infection in pregnant and non-pregnant macaques as well as during mosquito infection/transmission. The barcoded virus had no discernible fitness defects in vivo, and the proportions of individual barcoded virus templates remained stable throughout the duration of acute plasma viremia. ZIKV RNA also was detected in maternal plasma from a pregnant animal infected with barcoded virus for 67 days. The complexity of the virus population declined precipitously 8 days following infection of the dam, consistent with the timing of typical resolution of ZIKV in non-pregnant macaques and remained low for the subsequent duration of viremia. Our approach showed that synthetic swarm viruses can be used to probe the composition of ZIKV populations over time in vivo to understand vertical transmission, persistent reservoirs, bottlenecks, and evolutionary dynamics.

Fur, Fin, and Feather: Management of Animal Interactions in Australian Residential Aged Care Facilities.

Animal-assisted interventions (AAI) have been occurring in Australian Residential Aged Care Facilities (RACF) for more than 40 years and may relieve loneliness and improve quality of life. The presence of animals in RACF poses an inherent risk to residents and the animals involved. Little is known about the policies and guidelines for including animals in the Australian RACF. We anticipated that most RACFs would have some policies, but they may lack the detail necessary to keep humans and animals safe. Using an adapted survey, we surveyed and interviewed a small but representative sample of Australian RACF managers. The results demonstrated that RACF did have animal policies; however, the content regarding the need for hand washing, infection prevention, and animal welfare was lacking. Including unregulated family pets in RACF was an unexpected additional risk factor identified during data analysis. There is a need for national guidelines tied to the national aged care policy, which includes training and educational resources for RACF and AAI providers.

Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics.

A dramatic rise in obesity has occurred among humans within the last several decades. Little is known about whether similar increases in obesity have occurred in animals inhabiting human-influenced environments. We examined samples collectively consisting of over 20 000 animals from 24 populations (12 divided separately into males and females) of animals representing eight species living with or around humans in industrialized societies. In all populations, the estimated coefficient for the trend of body weight over time was positive (i.e. increasing). The probability of all trends being in the same direction by chance is 1.2 × 10(-7). Surprisingly, we find that over the past several decades, average mid-life body weights have risen among primates and rodents living in research colonies, as well as among feral rodents and domestic dogs and cats. The consistency of these findings among animals living in varying environments, suggests the intriguing possibility that the aetiology of increasing body weight may involve several as-of-yet unidentified and/or poorly understood factors (e.g. viral pathogens, epigenetic factors). This finding may eventually enhance the discovery and fuller elucidation of other factors that have contributed to the recent rise in obesity rates.

Omega-3 fatty acids. What consumers need to know.

The general public is increasingly aware of the health benefits associated with consumption of omega-3 fatty acids. While evidence of health benefits continues to mount, the underlying science is complex. Omega-3 fatty acids vary in their physiological efficacy. Consumers are typically unaware of differences in the efficacy of different omega-3 fatty acids and this lack of knowledge can result in consumers being misled within the marketplace. There is a need for consumers to be educated about the distinctions between omega-3 fatty acids. In the interim consumers remain at risk of purchasing premium fortified products and supplements that will not correspond to their desired health outcomes. This paper summarises the current understanding of fatty acid physiological metabolism and interaction for the purpose of highlighting this complex and multifaceted concern.

The guidelines and policies that influence the conduct of Animal-Assisted Activities in Residential Aged-Care Facilities: A systematic integrative review.

INTRODUCTION: For some time, Residential Aged Care Facilities (RACF) have incorporated animals into their environment to relieve loneliness and isolation for aged-care residents. However, research examining this practice is not as developed. This paper aims to identify the policies and practices influencing the conduct of Animal-Assisted Activities (AAA) in RACF focusing on the Australian context. METHODS: Peer-reviewed and gray literature were searched using an array of databases including CINAHL; Embase; Medline; Pubmed; Scopus and Web of Science; Google Scholar; PROSPERO, Proquest Dissertations; Theses Global; Animal Studies Repository; Medicine and Health Science Commons; Open Gray and a targeted Google search for relevant Australian Guidelines. Database searches had no time limits. Nine documents published between 1990 and 2018 were identified, appraised and subsequently included in the analysis. RESULTS: Facilities have not developed or implemented core policies; instead, there appears to be a reliance on AAA providers ensuring resident safety. Animal welfare is also identified as an emerging area, warranting further action and policy development. CONCLUSION: The requirement for effective AAA policies for RACF staff continues to be an area of need. Over the last 30 years, the development of policies guiding the provision of animal activities within RACFs has been inconsistent in both content and application, including the implementation of basic hygiene policies. If the international situation is indicative, further work is needed in Australia to develop and enforce infection control, risk management and animal welfare policies in RACF and AAA organizations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration # CRD42020150440.

Effects of sexual activity on several measures of physical performance in young adult males.

BACKGROUND: There has been considerable debate as to whether sexual activity prior to an athletic event can affect physical performance. The goal of the study was to determine if sexual activity the evening before several physical performance tests affected the results compared to the same performance tests after five days of abstinence. METHODS: Ten, monogamous, married young men (28±7 years old, body mass index = 25.5±2.7 kg/m2) underwent a six-physical performance/balance/agility tests (forearm grip strength, balance, lateral movement, reaction time, anaerobic power, and maximal oxygen uptake) on three different days. The first day was a familiarization session, where the subjects familiarized themselves with the performance tests. Then, two randomized, single-blind mornings sessions occurred there was either no sexual intercourse on the five days prior to the tests (control condition) or sexual intercourse on the night before the tests (experimental condition) in a randomized counterbalanced, fashion. The six performance tests were performed in the same order for each of the three sessions. A paired-t-test was used to compare each fitness test between conditions. RESULTS: The results showed that sexual activity had no effect on any of the six physical performance tests. CONCLUSIONS: This suggests that physical performance is unaffected by sexual activity within 24 hours prior to competition in young men.

AAV-delivered eCD4-Ig protects rhesus macaques from high-dose SIVmac239 challenges.

A number of simian and simian human immunodeficiency viruses (SIV and SHIV, respectively) have been used to assess the efficacy of HIV-1 vaccine strategies. Among these, SIVmac239 is considered among the most stringent because, unlike SHIV models, its full genome has coevolved in its macaque host and its tier 3 envelope glycoprotein (Env) is exceptionally hard to neutralize. Here, we investigated the ability of eCD4-Ig, an antibody-like entry inhibitor that emulates the HIV-1 and SIV receptor and coreceptor, to prevent SIVmac239 infection. We show that rh-eCD4-IgI39N expressed by recombinant adeno-associated virus (AAV) vectors afforded four rhesus macaques complete protection from high-dose SIVmac239 challenges that infected all eight control macaques. However, rh-eCD4-IgI39N-expressing macaques eventually succumbed to serial escalating challenge doses that were 2, 8, 16, and 32 times the challenge doses that infected the control animals. Despite receiving greater challenge doses, these macaques had significantly lower peak and postpeak viral loads than the control group. Virus isolated from three of four macaques showed evidence of strong immune pressure from rh-eCD4-IgI39N, with mutations located in the CD4-binding site, which, in one case, exploited a point-mutation difference between rh-eCD4-IgI39N and rhesus CD4. Other escape pathways associated with clear fitness costs to the virus. Our data report effective protection of rhesus macaques from SIVmac239.

Oropharyngeal mucosal transmission of Zika virus in rhesus macaques.

Zika virus is present in urine, saliva, tears, and breast milk, but the transmission risk associated with these body fluids is currently unknown. Here we evaluate the risk of Zika virus transmission through mucosal contact in rhesus macaques. Application of high-dose Zika virus directly to the tonsils of three rhesus macaques results in detectable plasma viremia in all animals by 2 days post-exposure; virus replication kinetics are similar to those observed in animals infected subcutaneously. Three additional macaques inoculated subcutaneously with Zika virus served as saliva donors to assess the transmission risk from contact with oral secretions from an infected individual. Seven naive animals repeatedly exposed to donor saliva via the conjunctivae, tonsils, or nostrils did not become infected. Our results suggest that there is a risk of Zika virus transmission via the mucosal route, but that the risk posed by oral secretions from individuals with a typical course of Zika virus infection is low.Zika virus (ZIKV) is present in body fluids, including saliva, but transmission risk through mucosal contact is not well known. Here, the authors show that oropharyngeal mucosal infection of macaques with a high ZIKV dose results in viremia, but that transmission risk from saliva of infected animals is low.

Infection via mosquito bite alters Zika virus tissue tropism and replication kinetics in rhesus macaques.

Mouse and nonhuman primate models now serve as useful platforms to study Zika virus (ZIKV) pathogenesis, candidate therapies, and vaccines, but they rely on needle inoculation of virus: the effects of mosquito-borne infection on disease outcome have not been explored in these models. Here we show that infection via mosquito bite delays ZIKV replication to peak viral loads in rhesus macaques. Importantly, in mosquito-infected animals ZIKV tissue distribution was limited to hemolymphatic tissues, female reproductive tract tissues, kidney, and liver, potentially emulating key features of human ZIKV infections, most of which are characterized by mild or asymptomatic disease. Furthermore, deep sequencing analysis reveals that ZIKV populations in mosquito-infected monkeys show greater sequence heterogeneity and lower overall diversity than in needle-inoculated animals. This newly developed system will be valuable for studying ZIKV disease because it more closely mimics human infection by mosquito bite than needle-based inoculations.

Food intake in rhesus monkeys following central administration of orexins.

Orexin A has been reported to stimulate food intake in rats while orexin B does not. The purpose of this study was to determine the role of orexin A or orexin B administration on food intake in adult, male rhesus monkeys. Food intake was measured at 2 and 8 h after the morning feeding following central injections of vehicle, orexin A (10, or 20 microg) or orexin B (10, 30, or 100 microg). When compared to vehicle injections, the 10 and 20 microg doses of orexin A decreased food intake at 2 h post-dose by 45% and 64%, respectively. Eight-hour food intake was decreased at only the 20 microg orexin A dose. Orexin B at all doses and time points did not alter food intake when compared to vehicle. These results indicate that orexin A exhibits anorectic activity while orexin B does not affect food intake in the rhesus monkey.

Energy expenditure of rhesus monkeys subjected to 11 years of dietary restriction.

Dietary restriction (DR) is currently the only paradigm that has consistently extended maximal life span and reduced the onset of age-related chronic diseases in all of the nonprimate species tested. Although it is controversial, some investigators have suggested that the underlying mechanisms may be mediated by adaptations in energy expenditure. We evaluated the extent to which DR alters energy metabolism in a unique cohort of rhesus monkeys submitted to DR for 11 yr. Total energy expenditure (doubly labeled water), resting energy expenditure (REE; indirect calorimetry), and nonbasal energy expenditure (calculated by difference) were measured in DR (n = 12) and control (n = 11) animals. Body composition was determined by dual energy x-ray absorptiometry. Both fat mass and fat-free mass were lower in the restricted animals (56 and 12%, respectively). DR induced a 17% lower total energy expenditure that was attributable to a 20% decrease in REE without changes in the nonbasal energy expenditure. Adjusted for fat-free mass, REE was 13% lower with DR (-250 kJ/d). Taken together with a reanalysis of previous DR experiments published in humans, rodents, and monkeys, these results suggest that DR may lower REE independent of the DR-induced changes in body composition. Whether this reduction in REE contributes to the life-extending properties of DR warrants further analysis, but it suggests that the long-standing debate regarding DR effects on metabolic rates may derive from the lack of consensus on how to adjust for body size and composition.

Influences of calorie restriction and age on energy expenditure in the rhesus monkey.

Caloric restriction (CR) is known to retard the aging process, and a marker of aging is decreased energy expenditure (EE). To assess longitudinal effects of CR on EE in rhesus monkeys (Macaca mulatta), data from 41 males (M) and 26 females (F) subjected to 9 or 15 yr of CR were studied. EE and body composition of monkeys 11-28 yr of age were measured using indirect calorimetry and dual X-ray absorptiometry. Total EE (24-h EE) was divided into daytime (day EE), nighttime (night EE), and daytime minus nighttime (D - N EE). M calorie-restricted monkeys showed a lower 24-h EE (means +/- SD = 568 +/- 96 kcal/day, P < 0.0001) than controls (C; 630 +/- 129 kcal/day). Calorie-restricted M had a lower night EE (difference = 36 kcal P < 0.0001) compared with C M, but after adjusting for FFM and FM, night EE was not different between calorie-restricted and C males (P = 0.72). The 24-h EE decreased with age (13 kcal decrease/yr, P < 0.0001), but there was no difference between CR and C. Adjusted for FFM and FM, D - N EE decreased with age (9 kcal/yr, P < 0.0001), with no interaction with age (P = 0.72). The F were compared with age-matched M selected from the male cohort. F had a lower 24-h EE (496 +/- 84 kcal/day) than M (636 +/- 139 kcal/day) (P < 0.0001). Adjusting for FFM and FM, night EE was lower in F compared with M (difference = 18 kcal, P = 0.077). Night EE did not differ between calorie-restricted and C younger monkeys after adjusting for FFM and FM. In conclusion, CR did not alter the age-related decrease in EE with CR.