Effects of dominance and female presence on secondary sexual characteristics in male tufted capuchin monkeys (Sapajus apella)

Alpha status may lead to physiological changes that enhance secondary sexual characteristics, which may serve as competitive signals to conspecific males, sexual signals to females, or possibly a combination of both. Here we report measurements of secondary sexual characteristics in captive dominant and subordinate male tufted capuchin monkeys (Sapajus apella) with varying access to females. An adult male (who had previously been subordinate while housed with other males) was paired with an adult female, and then this male-female pair was introduced into a room that housed three other male-male pairs with stable hierarchy arrangements. We analyzed weight, body measurements, facial photographs, and hair cortisol before, during, and after introducing a female into the room. While there were no differences in weight or measurements between alphas and subordinates without physical access to the female prior to or during the female’s presence, we found that direct access to the female resulted in dramatic changes in facial appearance, body size, and testicular volume in the male who was paired with her. Overall, we found little evidence to suggest that alpha males advertise their status within all male groups via sexual secondary characteristics. However, direct physical access to females appears to trigger the development of such characteristics in alpha males. It remains of continued interest to identify the endocrine mechanisms responsible for the development, and possible loss, of secondary sexual characteristics

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Matrilineal behavioral and physiological changes following the death of a non-alpha matriarch in rhesus macaque

In many species, the loss of alpha matriarchs is associated with a number of negative outcomes such as troop fission, eviction, wounding, and reduced vitality. However, whether the dramatic consequences of their loss are due to their role as an old experienced figure or to their alpha status remains unclear. In a retrospective study, we tested that in a semi-free ranging colony of rhesus macaques (Macaca mulatta), the removal of a non-alpha matriarch, who had a large set of kin, led to changes in behavior and physiological stress within her matriline. Following her removal, her matriline increased in aggression, vigilance, and social grooming. Additionally, hierarchical stability, measured by levels of rank changes, decreased within her matriline, and levels of intense aggression by high-ranking animals were more frequent, as well as matrilineal wounding. Although ordinal rank was positively associated with higher chronic hair cortisol concentrations (HCCs) in the months before the matriarch’s removal, following her removal, only those who experienced large increases in rank within her matriline displayed higher HCCs. Changes in matrilineal stability, aggression, behavior, and HCCs within the other two matrilines in the troop were not evident, although caution is needed due to the small sample sizes. We conclude that the removal of the non-alpha matriarch led to matrilineal instability, characterized by higher levels of aggression and subsequent vigilance, rank changes, physiological stress, and grooming. We suggest that non-alpha matriarchs with a large number of kin and social support can be integral to the stability of matrilines.Division of Intramural Research, National Institute of Child Health and Human Development, 1ZIAHD001107- 3

High rates of aggression do not predict rates of trauma in captive groups of macaques

Socially inflicted traumas are a major concern for the management of captive groups of rhesus macaques. Rhesus macaques are the most commonly used nonhuman primate in biomedical research, and social housing is optimal for promoting psychological well-being. However, trauma is frequent due to a strong reliance on aggression to establish and maintain hierarchical relationships. We studied six captive groups of rhesus macaques (Macaca mulatta) that underwent a variety of social perturbations and explored whether rates of aggression mapped onto rates of trauma using a fine-grained analysis that divided both aggression and trauma variables into specific, behaviorally-relevant categories (e.g., severe aggression by adult males relative to lacerations). Results did not show the expected positive relationship between aggression variables and trauma variables. Instead, rates of trauma (i.e., lacerations, moderate-severe trauma, total trauma) were negatively associated with the rate of impartial interventions (i.e., an intervention directed at both targets during an ongoing conflict) during baseline periods. Additionally, rates of trauma (i.e., lacerations, punctures, moderate-severe trauma, total trauma) were negatively associated with rates of total aggression following temporary knockouts of the individuals who commonly intervene impartially (i.e., conflict policers), and punctures and moderate-severe trauma were negatively associated with rates of severe aggression by adult males following permanent knockout of a high-ranked natal male. These results suggest that under homeostatic conditions, impartial interventions serve as a mechanism to reduce socially inflicted trauma but, following social manipulations of high-ranking males, an imbalance emerges. Our results underscore the importance of developing management strategies for rhesus macaque groups that promote internal social mechanisms of social stability such as maintaining conflict policing individuals (i.e., adult males) in social groups

Potential antidepressant overtreatment associated with office use of brief depression symptom measures.

BackgroundUse of brief depression symptom measures for identifying or screening cases may help to address depression undertreatment, but whether it also leads to diagnosis and treatment of patients with few or no symptoms-a group unlikely to have major depression or benefit from antidepressants-is unknown. We examined the associations of use of a brief depression symptom measure with depression diagnosis and antidepressant recommendation and prescription among patients with few or no depression symptoms.MethodsWe conducted exploratory observational analyses of data from a randomized trial of depression engagement interventions conducted in primary care offices in California. Analyses focused on participants scoring <10 on a study-administered 9-item Patient Health Questionnaire (PHQ-9) (completed immediately before an office visit and not disclosed to the provider) with complete chart review data (n = 595). We reviewed visit notes for evidence of practice administration of a brief symptom measure (independent of the trial) and whether the provider (1) diagnosed depression or (2) recommended and/or prescribed an antidepressant.ResultsAmong the 545 patients without a practice-administered measure, 57 (10.5%) had a visit diagnosis of depression; 9 (1.6%) were recommended and another 21 (3.8%) prescribed an antidepressant. Among the 50 patients (8.4% of total sample) with a practice-administered measure, 10 (20%) had a visit diagnosis of depression; 6 (12%) were recommended and another 6 (12%) prescribed an antidepressant. Adjusting for nesting within providers, trial intervention, stratification variables, and sample weighting, use of a brief symptom measure was associated with depression diagnosis (adjusted odds ratio, 3.2; 95% confidence interval, 1.1-9.2) and antidepressant recommendation and/or prescription (adjusted odds ratio, 3.80; 95% confidence interval, 1.0-13.9). Analyses using progressively lower PHQ-9 thresholds (<9 to <5) and examining antidepressant prescription alone yielded consistent findings. Analyses by practice-administered measure (PHQ-9 vs PHQ-2) indicated the study findings were largely associated with PHQ-9 use.ConclusionsThese exploratory findings suggest administration of brief depression symptom measures, particularly the PHQ-9, may be associated with depression diagnosis and antidepressant recommendation and prescription among patients unlikely to have major depression. If these findings are confirmed, researchers should investigate the balance of benefits and risks (eg, overdiagnosis of depression and overtreatment with antidepressants) associated with use of a brief symptom measure

Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment

Objective: We examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520. Design: The present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4-9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured. Results: All patients had 28.9-30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of -1.7 and -3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with <10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL. Conclusions: MD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable. Trial registration number: NCT02065336