Sex differences in behavior and glutamic acid decarboxylase in Long Evans rats after prolonged social isolation beginning in adolescence.

Social isolation can have long-term effects on brain development and behavior and increases the risk of developing clinical conditions, including anxiety disorders. One modulator of the stress response is gamma-aminobutyric acid, an inhibitory neurotransmitter synthesized by glutamic acid decarboxylase (GAD). This study examined sex differences in behavior and GAD expression following prolonged social isolation beginning in adolescence in Long Evans rats. Males and females were equally divided into group-housed (GH) and socially isolated conditions on Postnatal Day 28 (n = 8 per group). Beginning 5 weeks later, tests were conducted for anxietylike behaviors (open-field test and elevated plus maze), social interactions (sociability test), and spatial memory (novel object location). Sex differences in behavior were observed, with GH females showing fewer anxietylike behaviors in the open-field test and elevated plus maze and spending more time with objects (sociability task) compared to GH males. Isolation had no effect on males but increased anxiety and reduced neophilic measures in females, removing sex differences. On the sociability task, all groups spent more time with novel rats compared to objects, suggesting social interest was retained after isolation. In the hippocampus, isolation reduced GAD in both sexes, and sex differences were seen (F > M). However, no group differences in behavior were observed in the hippocampal-dependent novel object location task. Our findings suggest that prolonged social isolation beginning in adolescence is anxiogenic for female Long Evans rats. Furthermore, sex and housing impact hippocampal GABA-ergic activity, which may have important implications in the treatment of anxiety disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prenatal exposure to valproic acid and treatment with intranasal oxytocin have sex-specific effects on behavior in Long Evans rats.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social behaviors and communication. In rodents and humans, prenatal exposure to antiepileptic valproic acid is associated with an increased risk for autistic-like characteristics. One potential treatment is oxytocin, a prosocial neuropeptide that can be delivered intranasally. However, the sex-specific effects of valproic acid exposure and intranasal oxytocin treatment on behavior have not been fully explored. Pregnant Long Evans rats were administered valproic acid (500 mg/kg) or saline midday on gestational day 12, and after weaning, male and female pups were assigned to control (saline-saline), valproic acid-saline, or valproic acid-oxytocin groups. Oxytocin (0.8 IU/kg) or saline was delivered intranasally 30-60 min before tests for anxiety-like behaviors (elevated plus maze), social interactions (sociability) and sociosexual behaviors (partner preference, 50 kHz vocalizations and scent marking). Prenatal exposure to valproic acid resulted in sex-specific differences in behavior. When compared to controls, valproic acid males showed enhanced anxiety-like behaviors in adolescence and fewer scent marks in adulthood, while valproic acid females showed reduced sexual (partner) preference as adults. Intranasal oxytocin was anxiolytic for valproic acid males, but moderately anxiogenic for valproic acid females, and in both sexes it surprisingly impaired social interactions in the sociability test. Furthermore, intranasal oxytocin failed to improve sociosexual deficits in valproic acid rats. These findings highlight the importance of conducting preclinical studies in both sexes, and suggest that oxytocin may be an effective treatment in animal models with heightened anxiety-like behaviors.

Cache Valley virus: A scoping review of the global evidence.

Cache Valley virus (CVV) is a mosquito-borne RNA virus detected throughout North America, Central America and parts of South America. A limited number of human case reports have described severe illness. CVV infection has been associated with outbreaks of congenital defects in small ruminants in Canada and the United States. A scoping review was conducted to identify, characterize and summarize research on CVV, and to identify research gaps. A structured search was conducted in eight electronic databases, with additional search verification and grey literature investigation. All captured studies were independently appraised by two reviewers for relevance and data characterization. The review captured 143 relevant studies investigating CVV epidemiology (n = 104), pathogenesis (n = 37), viral characteristics (n = 24), transmission (n = 14), diagnostic test performance (n = 8) and mitigation strategies (n = 2). Evidence of CVV infection was found in mosquito studies (n = 47), and serological evidence of exposure was demonstrated in animals (n = 41), as well as human (n = 20) studies. In sheep, five outbreaks of birth defects following asymptomatic dam CVV infection during the first 50 days of pregnancy were reported. Only six human cases of CVV-associated illness were captured, with case symptoms described as initially non-specific, progressing to more severe clinical signs (e.g., meningitis). No research was identified investigating treatment, societal knowledge and risk perception, economic burden or predictive models related to the impact of climate change on CVV. CVV circulates in mosquito and animal species across a large area of the Americas. Small ruminants are the only animals in which CVV-associated clinical disease has been extensively studied. It is likely that human cases are under-reported or misdiagnosed. Future research should focus on the impact of CVV infection in human and animal populations.

Powassan virus, a scoping review of the global evidence.

BACKGROUND: Powassan virus (POWV), a flavivirus discovered in 1958, causes sporadic but severe cases of encephalitis in humans. Since 2007, the number of human Powassan cases diagnosed each year in the USA has steadily increased. This is in agreement with predictions that Powassan cases may increase in North America as a result of increased exposure to infected ticks. However, the increase may also reflect improved diagnostics and reporting among other factors. METHODS: A scoping review was prioritized to identify and characterize the global literature on POWV. Following an a priori developed protocol, a comprehensive search strategy was implemented. Two reviewers screened titles and abstracts for relevant research and the identified full papers were used to characterize the POWV literature using a predetermined data characterization tool. RESULTS: One hundred and seventy-eight articles were included. The majority of the studies were conducted in North America (88.2%) between 1958 and 2017. Both genotypes of POWV (Powassan lineage 1 and Deer Tick virus) were isolated or studied in vitro, in vectors, nonhuman hosts and human populations. To date, POWV has been reported in 147 humans in North America. The virus has also been isolated from five tick species, and several animals have tested positive for exposure to the virus. The relevant articles identified in this review cover the following eight topics: epidemiology (123 studies), pathogenesis (66), surveillance (33), virus characterization (22), POWV transmission (8), diagnostic test accuracy (8), treatment (4) and mitigation strategies (3). CONCLUSION: The literature on POWV is relatively small compared with other vector-borne diseases, likely because POWV has not been prioritized due to the small number of severe sporadic human cases. With the projected impact of climate change on tick populations, increases in the number of human cases are expected. It is recommended that future research efforts focus on closing some of the important knowledge gaps identified in this scoping review.

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research.

There has been an increasing incidence of Lyme disease (LD) in Canada and the United States corresponding to the expanding range of the Ixodes tick vector and Lyme disease agent (Borrelia burgdorferi sensu stricto). There are many diagnostic tests for LD available in North America, all of which have some performance issues, and physicians are concerned about the appropriate use and interpretation of these tests. The objective of this systematic review is to summarize the North American evidence on the accuracy of diagnostic tests and test regimes at various stages of LD. Included in the review are 48 studies on diagnostic tests used in North America published since 1995. Thirteen studies examined a two-tier serological test protocol vs. clinical diagnosis, 24 studies examined single assays vs. clinical diagnosis, 9 studies examined single immunoblot vs. clinical diagnosis, 7 studies compared culture or PCR direct detection methods vs. clinical diagnosis, 22 studies compared two or more tests with each other and 8 studies compared a two-tiered serological test protocol to another test. Recent studies examining the sensitivity and specificity of various test protocols noted that the Immunetics® C6 B. burgdorferi ELISA™ and the two tier approach have superior specificity compared to proposed replacements, and the CDC recommended western blot algorithm has equivalent or superior specificity over other proposed test algorithms. There is a dramatic increase in test sensitivity with progression of B. burgdorferi infection from early to late LD. Direct detection methods, culture and PCR of tissue or blood samples were not as sensitive or timely compared to serological testing. It was also noted that there are a large number of both commercial (n = 42) and in-house developed tests used by private laboratories which have not been evaluated in the primary literature.

The effects of repeated forced ethanol consumption during adolescence on reproductive behaviors in male rats.

Adolescence is a sensitive period of brain development when changes in hormone levels may have long-lasting effects on synaptic connections and behavior. In humans, alcohol consumption frequently begins during this critical period, although the impact of early exposure has not been fully examined. The current study was designed to investigate short- and long-term effects of repeated forced ethanol consumption during adolescence on emerging reproductive behaviors. Twenty-six young male Long-Evans rats were assigned to ethanol (Young EtOH, n = 12) or water (Young Control, n = 14) groups at postnatal day (P) 32, receiving a modified binge protocol of 3 g/kg of solution via gavage twice per week from P32 to P80. For comparison, another cohort of rats received a similar treatment paradigm in adulthood from P75-P133 (Adult EtOH, n = 8; Adult Control, n = 10). Reproductive behavior was assessed with tests for copulation, partner preference, and 50-kHz vocalizations during forced consumption (intoxication) and again after a 4-5 week period of abstinence. During forced consumption, the Young EtOH group showed significantly longer latencies on copulation tests than Young Controls, but these differences did not persist after abstinence. Different patterns were observed in Adult animals, who only showed significant, delayed impairments in the post-ejaculatory interval. Preference for sexually receptive females increased with sexual experience in both adolescent and adult rats, regardless of treatment during the forced consumption phase. However, after abstinence, the Young EtOH group showed a significantly reduced partner preference compared to the Young Control group, which may indicate long-term effects on sexual motivation. Additionally, during forced consumption the Young EtOH group tended to emit fewer ultrasonic vocalizations, perhaps reflecting impairments in sexual communication. Adult groups showed no differences in partner preference or vocalization tests at any time. Taken together, these findings indicate that repeated, intermittent ethanol exposure may have moderate effects on reproductive behavior that vary as a function of age. After abstinence, differences were only observed in the younger group, suggesting that the adolescent brain and behavior are more sensitive to ethanol exposure than the adult brain for sexual motivation and performance.

A systematic review and meta-analysis of the effectiveness of food safety education interventions for consumers in developed countries.

BACKGROUND: Foodborne illness has a large public health and economic burden worldwide, and many cases are associated with food handled and prepared at home. Educational interventions are necessary to improve consumer food safety practices and reduce the associated burden of foodborne illness. METHODS: We conducted a systematic review and targeted meta-analyses to investigate the effectiveness of food safety education interventions for consumers. Relevant articles were identified through a preliminary scoping review that included: a comprehensive search in 10 bibliographic databases with verification; relevance screening of abstracts; and extraction of article characteristics. Experimental studies conducted in developed countries were prioritized for risk-of-bias assessment and data extraction. Meta-analysis was conducted on data subgroups stratified by key study design-intervention-population-outcome categories and subgroups were assessed for their quality of evidence. Meta-regression was conducted where appropriate to identify possible sources of between-trial heterogeneity. RESULTS: We identified 79 relevant studies: 17 randomized controlled trials (RCTs); 12 non-randomized controlled trials (NRTs); and 50 uncontrolled before-and-after studies. Several studies did not provide sufficient details on key design features (e.g. blinding), with some high risk-of-bias ratings due to incomplete outcome data and selective reporting. We identified a moderate to high confidence in results from two large RCTs investigating community- and school-based educational training interventions on behaviour outcomes in children and youth (median standardized mean difference [SMD] = 0.20, range: 0.05, 0.35); in two small RCTs evaluating video and written instructional messaging on behavioural intentions in adults (SMD = 0.36, 95% confidence interval [CI]: 0.02, 0.69); and in two NRT studies for university-based education on attitudes of students and staff (SMD = 0.26, 95% CI: 0.10, 0.43). Uncontrolled before-and-after study outcomes were very heterogeneous and we have little confidence that the meta-analysis results reflect the true effect. Some variation in outcomes was explained in meta-regression models, including a dose effect for behaviour outcomes in RCTs. CONCLUSIONS: In controlled trials, food safety education interventions showed significant effects in some contexts; however, many outcomes were very heterogeneous and do not provide a strong quality of evidence to support decision-making. Future research in this area is needed using more robust experimental designs to build on interventions shown to be effective in uncontrolled before-and-after studies.

Using participatory epidemiology to assess factors contributing to common enteric pathogens in Ontario: results from a workshop held at the Ontario Veterinary College, University of Guelph, Ontario.

BACKGROUND: Common enteric pathogens that cause gastrointestinal illness are transmitted to humans through food, water or direct contact. This poses a significant concern to public health as enteric pathogens can cause disease in a large number of people, and cost a substantial amount to treat and prevent. In order to gain a better understanding of the occurrence of enteric disease in Ontario, this study explored public health professionals' perceptions of major contributing factors for common enteric pathogens. METHODS: A case study was conducted as part of a two week training workshop in Participatory Epidemiology held at the Ontario Veterinary College, University of Guelph, in May 2013. Eight semi-structured interviews and four focus groups were conducted with representatives from the Public Health Agency of Canada, the University of Guelph, and three health regions in Southern Ontario. Written notes and pictures captured the qualitative information provided. Results were then analyzed using the mixed methods techniques of triangulation, convergence, and paradox. RESULTS: A total of fifty factors that contribute to enteric disease were identified across all interviews and focus groups. These contributing factors were grouped into key themes (travel, food handling, industry (farm-to-fork), water, geography, demographics, and behaviours) and were categorized as either a risk factor or susceptibility factor. Informants emphasized the complex relationships between the identified factors, and highlighted why these complexities make it difficult to determine where and how a person most likely acquired an enteric pathogen. Workshop participants observed differences in the type and quality of information collected during interviews and focus groups; we hypothesize that this may be attributed to the dynamics between group members (i.e. focus group discussions) as opposed to one-on-one interviews. CONCLUSIONS: The information gathered will serve as a starting point to further explore contributing factors for common enteric pathogens. The identified complexities would be best explored by conducting additional surveillance, as well as interviews and focus groups with a more diverse group of stakeholders. This type of qualitative study can enhance knowledge of enteric pathogen surveillance and contribute to the development of resources and initiatives to holistically address the occurrence of gastrointestinal illness.

Comparing the relative amount of testosterone required to restore sexual arousal, motivation, and performance in male rats.

It is well established that male rat reproductive behaviors including sexual arousal, motivation, and performance are dependent on circulating levels of testosterone (T). The present study was designed to (1) compare the relative amount of T required to restore these different aspects of behavior in castrated rats, and (2) create an animal model for clinical populations with sexual impairments. Twenty-nine male Long-Evans rats were tested before and after castration for sexual performance (copulation), motivation (partner preference), and arousal (50 kHz ultrasonic vocalizations; measured together with scent marking). Sexual arousal was also inferred from copulation data. Rats were then assigned to one of four groups, and T was re-introduced via Silastic capsule implants varying in length and content: No T (empty capsules), Low T (2mm capsules), Medium T (5mm capsules), or High T (two 10mm capsules). The highest dose was intended to restore physiological levels. Results indicate that High T is required for 50 kHz vocalizations, while Medium T was sufficient for the restoration of copulation, partner preference, and scent marking. These data suggest that sexual arousal may be most sensitive to reductions in testosterone. The role of T levels in measures of generalized and specific (sexual) arousal is discussed in the context of other reproductive behaviors. Furthermore, because the Low T group showed impairments across all behaviors during post-implant tests, we propose that these animals may provide a good animal model for studying clinical conditions marked by reduced motivation and arousal, including Hypoactive Sexual Desire Disorder.

Microlesions of the ventromedial nucleus of the hypothalamus: effects on sociosexual behaviors in male rats.

Electrolytic microlesions aimed at the dorsomedial portion of the ventromedial nucleus (VMN) of the hypothalamus were generated, and effects on copulation, 50-kHz vocalizations, scent marking, and sexual motivation were measured. Male rats were tested before and after lesions, after castration, and after testosterone replacement. Three control groups were used: One received sham surgery, another received no surgery or testosterone replacement, and a 3rd received lesions primarily outside the VMN. VMN lesions produced impairments in testosterone's ability to restore ultrasonic vocalizations and scent marking, assessed with 2 different test methods. Copulation, sexual motivation, and weight gain were largely unaffected, although some differences were observed in copulatory efficiency. The authors conclude that the integrity of the VMN is important for full expression of sociosexual behaviors in male rats.

The effects of microgravity on the development of surface righting in rats.

The active interaction of neonatal animals with their environment has been shown to be a decisive factor in the postnatal development of sensory systems, which demonstrates a critical period in their maturation. The direct demonstration of such a dependence on the rearing environment has not been demonstrated for motor system function. Nor has the role of gravity in mammalian motor system development been investigated. Here we report the results of two space flight missions examining the effect of removing gravity on the development of surface righting. Since the essential stimulus that drives this synergy, gravitation, was missing, righting did not occur while the animals were in the microgravity environment. We hypothesize that this absence of contextual motor experience arrested the maturation of the motor tactics for surface righting. Such effects were permanent in rats spending 16 days (from postnatal day (P), P14 to P30), but were transient in animals spending nine days (from P15 to P24) in microgravity. Thus, active, contextual interaction with the environment during a critical period of development is necessary for the postnatal maturation of motor tactics as exemplified by surface righting, and such events must occur within a particular time period. Further, Earth's gravitational field is not assumed by the developing motor system. Rather, postnatal motor system development is appropriate to the gravitational field in which the animal is reared.

Androgen receptor blockade in the MPOA or VMN: effects on male sociosexual behaviors.

Previously, our laboratory has shown that androgen receptors in the medial preoptic area (MPOA) and ventromedial nucleus (VMN) are necessary for copulation in male rats. The present study examined whether these receptors are required for other sociosexual behaviors. In Experiment 1, different regions of the VMN were implanted with the antiandrogen hydroxyflutamide (OHF). We found that implants located in anterodorsal portions of the VMN were more effective at inhibiting the restoration of copulation than implants in the posteroventral VMN. In Experiment 2, a second set of male rats was pretested for copulation and other sociosexual behaviors and was castrated. Experimental animals then received Silastic capsules filled with testosterone (T) plus intracranial (IC) implants filled with OHF to selectively block androgen receptors in either the MPOA or VMN. We found that androgen receptor blockade in the MPOA inhibited the restoration of copulation but had no effect on other sociosexual behaviors. OHF directed at the VMN inhibited the restoration of copulation and 50-kHz vocalizations but had no effect on scent marking. Two tests were used to assay sexual motivation: partner preference and conditioned place preference (CPP). Both methods revealed impairments in sexual motivation in the VMN group but not in animals receiving OHF in the MPOA. Taken together, these data suggest that androgen receptors in the MPOA are essential for copulatory performance, while androgen receptors in the VMN are important for copulation, sexual motivation, and androgen-dependent vocalizations.

Effects of testosterone in the VMN on copulation, partner preference, and vocalizations in male rats.

The present study tested whether testosterone propionate (TP) implanted in the ventromedial nucleus (VMN) of the hypothalamus could initiate performance, motivational, or sociosexual components of sexual behavior in castrated male rats. Twenty-seven intact male Long Evans rats were pretested for copulation, partner preference, and 50-kHz vocalization and were subsequently castrated. Approximately 3 weeks after castration, males were retested to confirm that these behaviors had declined, and groups were assigned. Groups 1 and 2 were implanted with bilateral stainless steel cannulae directed at the VMN that were either filled with TP (TVMN group) or remained empty (Blank group). A third group (TSC) was implanted subcutaneously with two 10-mm Silastic capsules filled with testosterone. Restoration of behavior was measured for 2 weeks after implants. We found that copulation and 50-kHz vocalization were not restored by TP in the VMN alone. However, partner preference returned to preoperative levels in both the TVMN and TSC groups, indicating that TP in the VMN was sufficient to restore sexual motivation. Following behavioral testing, prostate glands and seminal vesicles were weighed and confirmed that TP did not leak into the periphery in the TVMN group. Immunostaining for androgen receptors also verified that TP spread was confined to the immediate area surrounding the cannula tip. These results suggest that androgen activation at the VMN is sufficient to induce the motivational components of male sexual behavior, whereas activation of other brain sites is required for copulation and ultrasonic vocalization.