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Over one-third of the United States population sleeps less than the recommended 7 hours a night, which increases risk for chronic diseases. The aim of this study was to evaluate the acceptability of sleep extension interventions and preferences in sleep extension interventions among adults with short sleep duration.Participants aged 18 to 65 years with self-reported sleep duration ≤ 6.5 hours completed an online survey including reported sleep behaviors, barriers to adequate sleep, interest in sleep extension interventions, and a sleep disturbance questionnaire. Data were analyzed using chi-square and binary logistic regression.Participants (n = 92; 61 females; mean age = 45.6 years, standard deviation = 13.5) reported an average sleep duration of 5:49 (standard deviation = 0:49). More than half of the participants reported current health comorbidities (64%), including insomnia (n = 12, 13%) and sleep apnea (n = 9, 10%). Many participants (38%) reported sleep disturbance. The most common barrier to adequate sleep included insomnia or other sleep problems (55%). Most respondents (84%) indicated an interest in increasing sleep duration. Of the treatment options suggested, most (84% of those interested) were interested in a wrist-worn device. Participants with insomnia or other sleep disorders were more likely to be interested in extending sleep, (χ² = 12.86, P.001) and in a wrist-worn device (χ² = 5.24, P = .022). Higher Patient-Reported Outcomes Measurement Information System sleep disturbance t scores were also associated with interest in monitoring sleep with a wrist-worn device (b = .18, P.001).Sleep extension interventions using wearable technology are attractive to individuals with short sleep duration, particularly those with greater sleep disturbance and comorbid sleep disorders.Adkins EC, DeYonker O, Duffecy J, Hooker SA, Baron KG. Predictors of intervention interest among individuals with short sleep duration. JClin SleepMed. 2019;15(8):1143-1148.

BACKGROUND Sleep disturbance is a core feature of post-traumatic stress disorder (PTSD). Given the relationship between sleep disturbance and PTSD, there has been a relative paucity of studies examining the potential therapeutic impact of using pharmacotherapy to target sleep disturbance in patients with PTSD. Eszopiclone (ESZ) is a non-benzodiazepine y-aminobutyric acid-A receptor agonist indicated for the treatment of sleep and may affect sleep in patients with PTSD. AIM To evaluate the efficacy of ESZ vs placebo (PBO) for patients with PTSD and insomnia. METHODS The study was a 12-wk, double blind, randomized controlled trial with 3 mg of ESZ (n = 13) or PBO (n = 12). RESULTS Patients in both arms experienced significant improvement in PTSD symptoms as assessed by the Clinician-Administered PTSD Scale for DSM-IV (CAPS): ESZ (t11 = -3.12, P = 0.005) and PBO (t11 = -3.5, P = 0.002) and by self-report with the Short PTSD Rating Interview (ESZ t11 = -3.38, P = 0.003 and PBO t11 = -4.48, P = 0.0005). There were no significant differences between treatments on the CAPS (t22 = -0.13, P = 0.70) or the Short PTSD Rating Interview (t22 = -0.58, P = 0.56). Similarly, both treated groups improved on sleep measures as assessed by the Pittsburgh Sleep Quality Index with PTSD Addendum (PSQI) and on total sleep time (TST) and sleep latency assessed by actigraphy with no significant differences between groups (PSQI t22 = -0.24, P = 0.81; total sleep time t10 = 0.13, P = 0.90 and sleep latency t10 = 0.68, P = 0.50). There was a significant correlation between improvement in sleep and overall improvement in PTSD as measured by change scores on the PSQI and CAPS, r(8) = 0.79, P = 0.01 for ESZ treated subjects, but not for those treated with PBO r(9) = 0.16, P = 0.69. Adverse events of ESZ were consistent with the known profile of the medication including dysgeusia (30%, mild), sedation (20%, mild) and headache (20%, moderate to severe). CONCLUSION Results do not support the hypothesis of a specific positive effect of ESZ compared to PBO for measures of PTSD and associated sleep disturbance.

A 20-y-old male intact white-faced saki monkey (Pithecia pithecia) presented with an acute ocular disease of the right eye. Clinical signs included periocular swelling, conjunctivitis, and anisocoria with a miotic right pupil. Conjunctival swabs were positive for Human herpesvirus 1 (HHV1) according to PCR amplification with sequencing. Initial clinical signs resolved with supportive treatment, and the animal was managed chronically by using acyclovir (5 mg/kg PO twice daily) during flare-ups. After more than 2 y, the progression of clinical disease led to enucleation of the right eye. At 2 mo after surgery, acute presentation of severe neurologic signs, including ataxia and blindness, resulted in euthanasia. Histopathology, PCR analysis, and sequencing results were consistent with viral encephalitis due to HHV1; coinfection with Pithecia pithecia lymphocryptovirus 1 was identified. This report describes the first case of managed HHV1 infection in a platyrrhine primate and the first case of HHV1 in a white-faced saki monkey that was not rapidly fatal.

Orphan drugs (ODs) are intended for the diagnosis, prevention, or treatment of rare diseases. Many cancer subtypes, including all childhood cancers, are defined as rare diseases, and over one-third of ODs are now intended to treat oncology indications. However, market access for oncology ODs is becoming increasingly challenging; ODs are prone to significant uncertainty around their cost-effectiveness, while payers must balance the need for these vital innovations with growing sensitivity to rising costs. The objective of this review was to evaluate different mechanisms that have been introduced to facilitate patient access to oncology ODs in five different countries (Australia, Canada, England, France, and Sweden), using eight oncology ODs and non-orphan oncology drugs as examples of their application. A targeted literature review of health technology assessment (HTA) agency websites was undertaken to identify country-specific guidance and HTA documentation for recently evaluated oncology ODs and non-orphan oncology drugs. None of these countries were found to have explicit HTA criteria for the assessment of ODs, and therefore, oncology ODs are assessed through the usual HTA process. However, distinct and additional processes are adopted to facilitate access to oncology ODs. Review of eight case-study drugs showed that these additional assessment processes were rarely used, and decisions were largely driven by proving cost-effectiveness using standard incremental cost-effectiveness ratio (ICER) thresholds. The predominant implication arising from this study is that application of standard HTA criteria to oncology ODs in many countries fails to take into account any uncertainties around their clinical- and cost-effectiveness, resulting in disparities in HTA reimbursement decisions based on differences in addressing or accepting uncertainty. In order to address this issue, HTA agencies should adopt a more flexible approach to cost-effectiveness, as typified by the Tandvårds-och Läkemedelsförmånsverket in Sweden, which takes into account the small patient numbers involved, limited budget impact, and high unmet medical needs.

Background: College students are increasingly reporting common mental health problems, such as depression and anxiety, and they frequently encounter barriers to seeking traditional mental health treatments. Digital mental health interventions, such as those delivered via the Web and apps, offer the potential to improve access to mental health treatment. Objective: This study aimed to review the literature on digital mental health interventions focused on depression, anxiety, and enhancement of psychological well-being among samples of college students to identify the effectiveness, usability, acceptability, uptake, and adoption of such programs. Methods: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (registration number CRD42018092800), and the search strategy was conducted by a medical research librarian in the following databases: MEDLINE (Ovid), EMBASE (Elsevier), PsycINFO (EbscoHost), the Cochrane Library (Wiley), and Web of Science (Thomson Reuters) from the date of inception to April 2019. Data were synthesized using a systematic narrative synthesis framework, and formal quality assessments were conducted to address the risk of bias. Results: A total of 89 studies met the inclusion criteria. The majority of interventions (71/89, 80%) were delivered via a website, and the most common intervention was internet-based cognitive behavioral therapy (28, 31%). Many programs (33, 37%) featured human support in the form of coaching. The majority of programs were either effective (42, 47%) or partially effective (30, 34%) in producing beneficial changes in the main psychological outcome variables. Approximately half of the studies (45, 51%) did not present any usability or acceptability outcomes, and few studies (4, 4%) examined a broad implementation of digital mental health interventions on college campuses. Quality assessments revealed a moderate-to-severe risk of bias in many of the studies. Conclusions: Results suggest that digital mental health interventions can be effective for improving depression, anxiety, and psychological well-being among college students, but more rigorous studies are needed to ascertain the effective elements of these interventions. Continued research on improving the user experience of, and thus user engagement with, these programs appears vital for the sustainable implementation of digital mental health interventions on college campuses.

This chapter discusses the developmental origin of sex differences in behavior in humans. It focuses on the question, what is the role of genes or sex hormones in the ontogeny of sex differences in human behavior, a process referred to as psychosexual differentiation? The chapter describes most of the existing investigations of the relationship between fetal hormones and human psycho-sexual differentiation. There is evidence that fetal hormones alter brain development with respect to adult performance of sexual behavior in certain mammalian species, and are important in determining sex differences in copulatory pattern. The vast majority of the nonhuman experiments looked solely at copulation, whereas none of the human experiments have done so. The chapter discusses male homosexuality, which is often regarded as a disorder of psychosexual differentiation, and which has sometimes been assumed to be primarily biological in origin. Hormonal theories of homosexuality have been tested in part by looking for evidence that homosexuals have different androgen levels than heterosexuals.

The purpose of this paper was to determine the efficacy and safety of topical tacrolimus, compared to cyclosporine, for treating keratoconjunctivitis sicca (KCS) in dogs. This study was a two-phase, randomized, controlled, masked clinical trial. Phase 1 evaluated ophthalmic 0.03% tacrolimus in normal dogs. Ocular examinations were performed daily. Phase 2 evaluated the efficacy of tacrolimus in treating KCS. Half the dogs received 2% cyclosporine A; the others received 0.03% tacrolimus, both diluted in olive oil. Four ophthalmic examinations were done over 12 weeks. There was no significant difference between groups in phase I. In phase 2, there was no significant difference in Schirmer tear test I (STT) results between the two groups, and both groups had a significant increase in STT over time. Both drugs were effective in increasing the STT in dogs naïve to lacrimostimulants. Tacrolimus was effective in increasing the STT in 4 dogs currently nonresponsive to cyclosporine.

Two hundred and forty-four dogs were evaluated for cataracts at the University of Tennessee from January 2001 to December 2002. Fifty-four canine breeds were affected. Odds ratios for cataracts were significantly higher for six purebred dogs (including the cocker spaniel, miniature schnauzer, toy poodle, Boston terrier, miniature poodle, and bichon frise) compared with mixed-breed dogs. One hundred fifty-nine dogs did not have cataract surgery. The most common reason for dogs not having surgery was retinal degeneration (n=66).

A 10-week-old Labrador Retriever was examined because of a swelling above the left eye. Ophthalmic examination revealed a tubular, light-pink, slightly raised lesion of the left conjunctiva that extended from the limbus to the fornix and into the dorsal eyelid. The lesion affected the entire margin of the dorsal eyelid and extended 2 cm dorsal to the eyelid margin. With compression of the left jugular vein, the exophthalmos worsened immediately and the subconjunctival and eyelid lesion enlarged. Results of ultrasonography, computed tomography, and contrast venography were consistent with a diagnosis of an orbital varix. Coil embolization was elected for treatment of the varix to prevent the pain and morbidity associated with an orbitotomy. Coils were introduced through a 22-gauge IV catheter inserted through the upper eyelid into the varix. The only complication was moderately severe orbital swelling. The owners reported that the lesion had resolved by 2 weeks after coil embolization.

Experiments in which avian embryos are treated with sex steroids or steroid antagonists suggest that sexual differentiation of reproductive behavior (and thus differentiation of the brain mechanisms for such behavior) is controlled by steroids produced by the embryonic gonads. In chickens and Japanese quail, males hatched from eggs treated with estradiol or testosterone during incubation are feminized (demasculinized); they fail to exhibit masculine sexual behavior as adults, and no longer are behaviorally distinguishable from females. Some evidence suggests that testosterone may mimic the feminizing action of estradiol by being converted to an estrogen in the embryonic brain. Genetic female quail exposed to an antiestrogen during embryonic development are masculinized; they exhibit an increased ability to display the masculine copulatory pattern. Thus the behavior of these species is feminized by embryonic exposure to sex steroids, the anhormonal (neutral) sex for behavioral differentiation appears to be the male, and females appear to result from estrogen produced by the embryonic ovaries. In contrast, sex steroid treatment of mammals early in development masculinizes behavior, the female is the neutral sex, and males result from fetal androgen secretion. These opposite patterns of psychosexual differentiation in birds and mammals are correlated with a major difference between the avian and mammalian sex-determining mechanism. Implications for other vertebrates are discussed.

The purpose of this experiment was to study the effects of homologous and heterologous gonadal hormones on sexual and aggressive behavior in a reptilian species. Thirty adult male and thirty adult female lizards (Anolis carolinensis) were divided into 10 groups of six each (five groups per sex) and each group was given one of five treatments: either left intact, sham-castrated and injected with the hormone vehicle, castrated and injected with the hormone vehicle, castrated and injected with estradiol benzoate, or castrated and injected with testosterone propionate. After a week of visual isolation and daily hormone injection, animals were tested four times, twice with a stimulus animal of each sex. Females treated with estrogen were receptive, but did not court. Females treated with androgen were receptive and also courted and pursued stimulus females as frequently as males given androgen. No males in any group were receptive, and thus the female appears to be more capable of heterotypical sexual behavior than the male. Castrated males failed to court. Courtship and pursuit of stimulus females was readily stimulated in males with testosterone, and weakly stimulated by estrogen. Intact males were very aggressive, but lower levels of aggression were independent of gonadal hormones, as was subordination (head-nodding). The results for aggression and subordination are interpreted with reference to naturally-occurring Anolis behavior, and the results for sexual behavior are compared with similar experiments with mammals and birds.

Male Japanese Quail were injected with oil or with one of four dosages of cyproterone acetate for 8 days. Copulatory behavior and cloacal gland size were measured daily. Cyproterone acetate reduced cloacal gland size at all dosages and in two experiments reduced copulation in eight out of 17 males at the two highest dosages. Thus, cyproterone acetate results in reproductive changes in at least two classes of vertebrates, and has behavioral as well as morphological effects. The morphological effects are more striking, however.

Japanese Quail eggs were injected on Day 9 of incubation with the antiestrogen CI-628. When sexually mature, treated and control birds were given exogenous testosterone and tested for sexual behavior. Unlike control females, females treated with CI-628 before hatching displayed the male mating pattern. Males were unaffected by CI-628. Previous research has shown that male quail treated with sex steroids before hatching are permanently feminized behaviorally, and as adults fail to copulate. Normal female quail also fail to show male sexual behavior, even when given exogenous testosterone as adults. These findings suggest that the male quail is the neutral (anhormonal) sex with respect to behavioral sex differentiation, and that estrogen produced by female embryos results in female behavioral differentiation by eliminating the capacity for male sexual behavior.

This experiment compared the reproductive behavior and morphology of female quail exposed to a short photoperiod (8L: 16D) for 3 or 6 weeks with the behavior and morphology of ovariectomized females and females exposed to a long photoperiod (16L: 8D). Birds exposed to 8L: 16D did not differ from ovariectomized birds in behavior or in oviduct weight and appeared to be functionally castrated. Functional castration by a short photoperiod is a convenient research technique.

On the 10th day of incubation, Japanese quail eggs either were injected with testosterone propionate (TP), estradiol benzoate (EB), or oil, or were not injected. When sexually mature, all birds were examined for a variety of sexually dimorphic behavioral and physical characteristics, both masculine and feminine. They were then exposed to a short photoperiod (causing gonadal regression), treated with either TP or EB, and examined again. Either androgen or estrogen administered before hatching demasculinized males, but did not masculinize females or defeminize either sex. In contrast, early sex hormones masculinize and/or or defeminize mammals. This difference is discussed in relation to other differences in avian and mammalian sexuality.

In Experiment 1 male quail ( Coturnix coturnix japonica ) with photically regressed testes were implanted intraperitoneally with Silastic tubing containing either testosterone propionate (TP), testosterone (T), androstenedione (AE), 17α-methyltestosterone (MT), estradiol benzoate (EB), dihydrotestosterone propionate (DHTP), 6α-fluorotestosterone propionate (FTP), fluoxymesterone (FM), or cholesterol (CHOL), or were implanted subcutaneously with pellets of FTP. All steroids except EB and FM stimulated proctodeal gland development, and all except MT, EB, and FM stimulated crowing to a significant extent. When administered as Silastic implants, the only androgens that activated copulation were TP, T, and AE. Subcutaneous pellets of FTP also activated copulation. In Experiment 2 male quail with photically regressed testes were injected with TP, TP + ATD (1,4,6-androstatrien-3,17-dione, an aromatase inhibitor), EB, EB + ATD, or oil. ATD completely blocked TP-stimulated copulation, but had no effect on EB-stimulated copulation. These experiments provide further evidence for an aromatization theory of quail copulation.

Castrated male Japanese quail were injected for 15 days with 1 mg/day of testosterone propionate (TP), testosterone (T), androstenedione (AE), androsterone (AO), 5α-dihydrotestosterone benzoate (5α-DHTB), or 5β-dihydrotestosterone (5β-DHT), or with oil. Copulation was activated to a significant extent only by TP and T. Strutting was activated only by TP, T, and AE. Proctodeal (foam) glands were well-developed in birds injected with TP, T, AE, or 5α-DHTB. Additional data were obtained following implantation of pellets of crystalline T, AE, AO, or 5α-DHT. T pellets activated copulation, but AO and 5α-DHT pellets did not. Effects of AE require further study. These results suggest that conversion of androgen to estrogen is necessary for the activation of copulation in the male quail.

This study investigated the androgen specificity of aggressive and sexual behavior in the lizard Anolis carolinensis and the capacity of females of this species to exhibit male-typical copulation. Gonadectomized males and females were injected with testosterone propionate (TP) or dihydrotestosterone propionate (DHTP) or were implanted with Silastic tubing containing TP or DHTP. Either TP or DHTP activated male-typical sexual behavior in both males and females and activated aggressive behavior in males; DHTP activated aggressive behavior in females. Thus conversion of androgen to estrogen is not essential for these behavior patterns, and endogenous dihydrotestosterone may be important. TP but not DHTP stimulated receptivity in females, suggesting that conversion of testosterone to estrogen may underlie TP-stimulated receptivity. Females treated with TP did not differ from males in their display of male-typical courtship, neck-clasping, and intromission.

This series of experiments sought to determine whether conversion of androgen to estrogen is important in the activation of male sexual behavior in quail by seeing if an antiestrogen will block androgen stimulated copulation in this species. Experiment I compared the ability of two antiestrogens, MER-25 (5 mg/day) and CI-628 (2 mg/day), to block estrogen stimulated characteristics in female quail. Both treatments greatly reduced oviduct growth in “photically castrated” females given estradiol benzoate (EB, 50 μg/day), but only CI-628 reduced receptivity in these birds. In Experiment II surgically castrated males given 50 μg/day EB together with 2 mg/day CI-628 were much less receptive than castrated males given EB alone, and in addition copulated in fewer tests. In Experiments III, IV, and V, castrated males given testosterone propionate (TP) together with CI-628 were compared with males given TP alone. The ability of CI-628 to suppress TP-stimulated copulation increased with increasing CI TP dosage ratio, and at the highest ratio (4:1), CI-628 effectively blocked copulation in five out of seven birds. Those birds that did copulate did so in fewer tests and performed fewer cloacal contact movements. CI-628 had no antiandrogenic effects in these experiments. These results suggest that estrogens may be important active metabolites of testosterone with respect to quail copulation.