A Relational Agent Intervention for Adolescents Seeking Mental Health Treatment: Protocol for a Randomized Controlled Trial.

BACKGROUND: Unmet pediatric mental health (MH) needs are growing as rates of pediatric depression and anxiety dramatically increase. Access to care is limited by multiple factors, including a shortage of clinicians trained in developmentally specific, evidence-based services. Novel approaches to MH care delivery, including technology-leveraged and readily accessible options, need to be evaluated in service of expanding evidence-based services to youths and their families. Preliminary evidence supports the use of Woebot, a relational agent that digitally delivers guided cognitive behavioral therapy (CBT) through a mobile app, for adults with MH concerns. However, no studies have evaluated the feasibility and acceptability of such app-delivered relational agents specifically for adolescents with depression and/or anxiety within an outpatient MH clinic, nor compared them to other MH support services. OBJECTIVE: This paper describes the protocol for a randomized controlled trial evaluating the feasibility and acceptability of an investigational device, Woebot for Adolescents (W-GenZD), within an outpatient MH clinic for youths presenting with depression and/or anxiety. The study's secondary aim will compare the clinical outcomes of self-reported depressive symptoms with W-GenZD and a telehealth-delivered CBT-based skills group (CBT-group). Tertiary aims will evaluate additional clinical outcomes and therapeutic alliance between adolescents in W-GenZD and the CBT-group. METHODS: Participants include youths aged 13-17 years with depression and/or anxiety seeking care from an outpatient MH clinic at a children's hospital. Eligible youths will have no recent safety concerns or complex comorbid clinical diagnoses; have no concurrent individual therapy; and, if on medications, are on stable doses, based on clinical screening and as well as study-specific criteria. RESULTS: Recruitment began in May 2022. As of December 8, 2022, we have randomized 133 participants. CONCLUSIONS: Establishing the feasibility and acceptability of W-GenZD within an outpatient MH clinical setting will add to the field's current understanding of the utility and implementation considerations of this MH care service modality. The study will also evaluate the noninferiority of W-GenZD against the CBT-group. Findings may also have implications for patients, families, and providers looking for additional MH support options for adolescents seeking help for their depression and/or anxiety. Such options expand the menu of supports for youths with lower-intensity needs as well as possibly reduce waitlists and optimize clinician deployment toward more severe cases. TRIAL REGISTRATION: ClinicalTrials.gov NCT05372913; https://clinicaltrials.gov/ct2/show/NCT05372913. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44940.

Educating Nurses During a Pandemic to Manage Mechanically Ventilated Patients.

Providing care for critically ill patients diagnosed with COVID-19 presented a number of challenges. Initially, few treatment strategies were available; however, evidence of pulmonary complications led to patients' need for ventilators. This article describes the rapid development and implementation of a mechanical ventilation cross-training program for acute care nurses.

Testing a Model of Sexual Minority Orientation in Individuals with Typical Development, the Broad Autism Phenotype, and Autism Spectrum Disorder.

Individuals with Autism Spectrum Disorder (ASD) and the Broad Autism Phenotype (BAP) are more likely than individuals with typical development (TD) to report a sexual minority orientation (e.g., Bejerot and Eriksson, PLoS ONE 9:1-9, 2014; DeWinter et al., Journal of Autism and Developmental Disorders 47:2927-2934, 2017; Qualls et al., Journal of Autism and Developmental Disorders 48:3974-3983, 2018). This study operationalized and tested the fit of an existing model of sexual orientation to examine which factors are associated with increased sexual minority orientation (Worthington et al., The Counseling Psychologist 30:496-531, 2002) in individuals with TD, BAP, and ASD. The model was found to have adequate fit, χ2 (130) = 374.04, p < 0.001; RMSEA = 0.07; CFI = 0.95; SRMR = 0.08. Heterosexism was found to be the only predictor of sexual minority orientation and a significant predictor in the BAP and ASD groups, with increased daily heterosexist experiences predicting greater sexual minority orientation in these groups.

Effects of low-to-moderate ethanol consumption on colonic growth and gene expression in young adult and middle-aged male rats.

Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some epidemiological studies have reported that moderate alcohol consumption may not contribute additional risk or may provide a protective effect reducing colorectal cancer risk. Prior research highlights the importance of proliferation, differentiation, and apoptosis as parameters to consider when evaluating colonic cell growth and tumorigenesis. The present study investigated whether chronic low-to-moderate ethanol consumption altered these parameters of colonic cell growth and expression of related genes. Twenty-four nondeprived young adult (109 days old) and 24 nondeprived middle-aged (420 days old) Wistar rats were randomly assigned to an ethanol-exposed or a water control group (n = 12/group). The ethanol group was provided voluntary access to a 20% v/v ethanol solution on alternate days for 13 weeks. Colon tissues were collected for quantitative immunohistochemical analyses of cell proliferation, differentiation and apoptosis using Ki-67, goblet cell and TUNEL, respectively. Gene expression of cyclin D1 (Ccnd1), Cdk2, Cdk4, p21waf1/cip1 (Cdkn1a), E-cadherin (Cdh1) and p53 were determined by quantitative real-time polymerase chain reaction in colonic scraped mucosa. Ethanol treatment resulted in a lower cell proliferation index and proliferative zone, and lower Cdk2 expression in both age groups, as well as trends toward lower Ccnd1 and higher Cdkn1a expression. Cell differentiation was modestly but significantly reduced by ethanol treatment only in older animals. Overall, older rats showed decreases in apoptosis and gene expression of Cdk4, Cdh1, and p53 compared to younger rats, but there was no observed effect of ethanol exposure on these measures. These findings suggest that low-to-moderate ethanol consumption improves at least one notable parameter in colonic tumorigenesis (cell proliferation) and associated gene expression regardless of age, however, selectively decreased cell differentiation among older subjects.

Change in eating pattern as a contributor to energy intake and weight gain during the winter holiday period in obese adults.

BACKGROUND/OBJECTIVES: The winter holiday season in the United States, which spans mid-November to mid-January, contributes to over half of annual body weight gain. Although self-reported data have linked this weight change to both increased energy intake and reduced physical activity, objective techniques have never been used; and thus, the actual cause of holiday weight gain is controversial. Here, we aimed to determine changes in components of energy balance leading to the holiday weight gain. METHODS: Body weight change was compared between the pre-holiday (mid-September to mid-November) and the holiday period (mid-November to early January). Total energy expenditure (TEE) was measured using doubly labeled water during holiday time (early to mid-December). Subjective (ratings) and physiological (appetite-regulating hormones) measures of appetite, eating-away-from-home frequency, and incentive salience of food pictures were also evaluated. RESULTS: In 23 obese adults (87% female), body weight change during the holidays (0.41 ± 0.42 kg) was significantly higher (P = 0.02) than the body weight change during the pre-holiday period (-0.86 ± 0.42 kg). TEE was unchanged during the two periods, suggesting no role of energy expenditure on weight gain. However, participants reported lower satisfaction after a meal pre-load which was significantly correlated with increased body weight during the holiday period. An increase in number of episodes of eating at sit-down restaurants was also reported during that period. Overall, these changing behaviors were supported by a non-significant increase in energy intake (+80 kcal/day, P = 0.07) observed during the study holiday period. CONCLUSION: We conclude that a decrease in energy expenditure does not result in the weight increase, but that increase in food intake is the more likely cause. Our data imply that compromised internal satiety mechanisms in presence of external food cues and diet-related behavioral variables during the holidays may influence weight gain.

Local inhibition of carbonic anhydrase does not decrease sweat rate.

BACKGROUND: The purpose of this study was to measure sweat rate during exercise in the heat after directly inhibiting carbonic anhydrase (CA) in eccrine sweat glands via transdermal iontophoresis of acetazolamide. It was hypothesized that if CA was important for sweat production, local administration of acetazolamide, without the confounding systemic effects of dehydration typically associated with past studies, would have a significant effect on sweat rate during exercise. METHODS: Ten healthy subjects volunteered to exercise in the heat following acetazolamide or distilled water iontophoresis on the forearm. RESULTS: The distilled water iontophoresis site had a mean sweat rate during exercise in the heat of 0.59±0.31 µL/cm2/min, while the acetazolamide iontophoresis site had a mean sweat rate of 0.63±0.36 µL/cm2/min (p>0.05). CONCLUSIONS: The most important finding of the current study was that iontophoresis of acetazolamide did not significantly decrease sweat rate during exercise in the heat. Such results suggest that in past studies it was systemic dehydration, and not CA inhibition at the level of the sweat gland, that caused the reported decreased sweat rate.

Nicotine trained as a negative feature passes the retardation-of-acquisition and summation tests of a conditioned inhibitor.

Nicotine functions as a negative feature in a Pavlovian discriminated goal-tracking task. Whether withholding of responding to the conditional stimulus (CS) reflects nicotine functioning as a conditioned inhibitor is unknown. Accordingly, the present research sought to determine whether nicotine trained as a negative feature passed the retardation-of-acquisition and summation tests, thus characterizing it as a pharmacological (interoceptive) conditioned inhibitor. In the retardation test, rats received either nicotine (0.4 mg/kg) or chlordiazepoxide (5 mg/kg) negative feature training in which the drug state signaled when a 15-sec light CS would not be paired with sucrose; light was paired with sucrose on intermixed saline sessions. Following acquisition of the discrimination, both groups received nicotine CS training in which sucrose was intermittently available on nicotine but not intermixed saline sessions. Acquisition of conditioned responding to the nicotine CS was slower in the nicotine negative feature group than in the chlordiazepoxide negative feature group. In the summation test, rats were assigned to either the nicotine negative feature group or a pseudoconditioning control. In this control, the light CS was paired with sucrose on half the nicotine and half the saline sessions. Both groups also received excitatory training in which a white noise CS was paired with sucrose. The summation test consisted of presenting the white noise in conjunction with nicotine. Conditioned responding evoked by the white noise was decreased in the negative feature but not the pseudoconditioning group. Combined, the results provide the first evidence that an interoceptive stimulus (nicotine) can become a conditioned inhibitor.

Nicotine competes with a visual stimulus for control of conditioned responding.

Environmental stimuli that co-occur with tobacco use come to evoke drug-related conditioned responses (CRs) that appear involved in continued use of nicotine-containing products. In rats, nicotine can serve as a conditional stimulus (CS) for non-drug unconditioned stimuli (USs), prompting the question of whether the nicotine CS can compete with, or overshadow, a non-drug environmental stimulus for control of a CR. In Experiment 1, male Sprague-Dawley rats were assigned to a group [0, 0.01, 0.03, 0.045, or 0.06 mg nicotine (base)/kg/infusion]. During each session, there were 10 intravenous infusions followed by a 30-second houselight to form a compound CS. At light offset there was 4-second access to sucrose. For Experiment 2, groups were nicotine (0.03 mg/kg/infusion) + light compound paired, nicotine + light compound unpaired, nicotine paired and light unpaired, and nicotine unpaired and light paired. Paired stimuli were presented with sucrose similar to Experiment 1. Unpaired stimuli were temporally separated from sucrose. Following acquisition, tests of nicotine and light alone were conducted by intermixing non-reinforced trails into training sessions. Nicotine dose-dependently overshadowed the light CS as shown by reduced light control of conditioned responding with higher doses. The nicotine, light, and nicotine + light compound had to be paired with sucrose to evoke a CR. These results demonstrate nicotine overshadows an exteroceptive visual stimulus. Because exteroceptive stimuli are often the focus of cue-exposure therapy, such competition may help begin to explain the marginal effectiveness of these therapies.

Investigation of endocannabinoid modulation of conditioned responding evoked by a nicotine CS and the Pavlovian stimulus effects of CP 55,940 in adult male rats.

RATIONALE: The cannabinoid CB(1) receptor antagonist/inverse agonist rimonabant (SR 141716) has been shown to block reinforcing and rewarding effects of nicotine. Research has not investigated whether the cannabinoid system is involved in the interoceptive stimulus effects of nicotine functioning as a conditional stimulus (CS). OBJECTIVE: We examined the effects of rimonabant and the CB(1/2) receptor agonist, CP 55,940, on responding evoked by a nicotine CS in rats. Additionally, we determined whether CP 55,940 functioned as a CS or a Pavlovian positive drug feature MATERIALS AND METHODS: Pavlovian discrimination training involved intermixed nicotine (0.2 mg base/kg) and saline sessions with intermittent access to water only on nicotine. Antagonism tests with rimonabant (0.1-3 mg/kg) and substitution tests with CP 55,940 (0.003-0.1 mg/kg) followed. An effective dose of CP 55,940 was tested against the nicotine generalization curve. A separate group received CS training with CP 55,940 (0.01 mg/kg). Two other groups were trained using CP 55,940 (0.01 or 0.03 mg/kg) as a positive drug feature in which a brief light CS signaled access to water only on CP 55,940 sessions. RESULTS: Rimonabant blocked nicotine-evoked responding. CP 55,940 partially substituted for nicotine and enhanced responding to lower nicotine doses. Overall, CP 55,940 did not acquire control of conditioned responding in either Pavlovian drug discrimination task. CONCLUSIONS: The cannabinoid system was involved in the CS effects of nicotine. This finding is counter to the operant drug discrimination research with nicotine as a discriminative stimulus, warranting further research into this possible dissociation.