Delayed yet persistent effects of daily risperidone on activity in developing rats.

Early-life administration of risperidone, the most widely used antipsychotic drug in children, leads to persistently elevated locomotor activity in adult rats. This study determined whether and when elevated locomotor activity emerges during developmental risperidone administration. Developing and adult rats were administered daily injections of risperidone (1.0 and 3.0 mg/kg) or vehicle for 4 weeks beginning at postnatal days 14 and 74, respectively. Starting with the first injection and every 7 days thereafter, locomotor activity was measured immediately after the injection and 20 min before the next day's injection. Activity was also recorded 1 week after the final injection. Risperidone markedly decreased locomotor activity in developing and adult rats immediately after injection. Within 24 h after their first injection, adult rats administered risperidone showed greater activity levels. In contrast, developing rats did not show compensatory hyperactivity until the beginning of the fourth week of risperidone administration. One week after the final risperidone injection, there was no evidence of hyperactivity in the adult rats maintained on risperidone, but developing rats administered risperidone, especially females, showed greater activity levels relative to vehicle-administered controls. In comparison with adult rats, the emergence of compensatory hyperactivity during long-term antipsychotic drug administration is delayed in developing rats, but persists after treatment cessation.

Influence of Pedaling Cadence and Incremental Protocol on the Estimation of EMGFT.

Duff, TM, Fournier, H, Hopp, OB, Ochshorn, E, Sanders, ES, Stevens, RE, and Malek, MH. Influence of pedaling cadence and incremental protocol on the estimation of EMGFT. J Strength Cond Res 30(8): 2206-2211, 2016-Theoretically, the electromyographic fatigue threshold (EMGFT) is the highest exercise intensity that an individual can exercise at indefinitely without an increase in electromyography (EMG) amplitude. This index is estimated from a single incremental test. There are, however, factors that may influence EMG amplitude such as pedaling cadence or the incremental protocol used. The purposes of this study were to determine whether different pedaling cadences and/or incremental protocols influence the estimation of the EMGFT. Eight healthy college-aged men performed incremental cycle ergometry on three separate visits. The participants exercised using the following combinations of pedaling cadences and incremental protocols in random order: 25 W at 70 RPM; 13 W at 70 RPM; and 25 W at 100 RPM. The EMGFT value was determined from the vastus lateralis muscle of each participant for each of the three conditions. Separate 1-way repeated measures analysis of variances were performed to determine mean differences for various outcome indices. The mean maximal power output for the 13 W at 70 RPM condition was significantly lower than the two other conditions. There were, however, no significant mean differences (F (2,14) = 2.03; p = 0.169) for EMGFT between the three conditions. The findings of this study indicated that different pedaling cadences and incremental protocols did not influence the estimation of the EMGFT.

On a need-to-know basis: Young children distinguish conventional and privileged information.

Young children are biased to treat new information communicated to them as conventional, shareable, and known by others in their community. However, some information is privileged in the sense that is not intended to be shared with or known by all. The current study compared judgements regarding sharing conventional versus privileged information. Seventy-four 3- to 5-year-olds and adults responded to vignettes in which a protagonist had to decide whether to share conventional (an object name) or privileged information (surprise). Consistent with our hypothesis, there was no developmental change in sharing judgements for conventional information but a clear decrease with age for sharing privileged information. Nonetheless, even 3-year-olds were more likely to judge that conventional information should be shared more than privileged information, though this difference increased with age. While children overall treat information as shareable, there is an emerging ability to distinguish how conventional versus privileged information should be shared.

Associations between sun exposure, skin pH, and epidermal permeability in pregnancy: A longitudinal observational study.

Little is known about how sun exposure may affect the maternal skin barrier during pregnancy when many hormonal and physiological changes occur. In this longitudinal observational study, 50 pregnant women were recruited at 18-24 weeks' gestation, 25 in summer-autumn, and 25 in winter-spring. At three time points in pregnancy at 18-24, 28-30, and 36-38 weeks' gestation, participants completed a validated sun exposure questionnaire and had skin permeability and surface pH measured on the volar forearm. We identified an association between increased sun exposure and increased skin permeability at 18-24 weeks' gestation (ß = 0.85, p = 0.01). Lower transepidermal water loss (decreased skin permeability), mean = 12.1 (SD = 5.1) at 28-30 weeks' gestation was observed, compared to mean = 12.6 (SD = 4.0) at 18-24 weeks' and mean = 13.7 (SD = 8.5) at 36-38 weeks' gestation (n = 27, ß = -1.83, p = 0.007). Higher skin pH readings, mean = 5.80 (SD = 0.58) were found at 28-30 weeks' gestation, compared to mean = 5.25 (SD = 0.62) at 18-24 weeks' and mean = 5.47 (SD = 0.57) at 36-38 weeks' gestation (n = 27, ß = 0.40, p = 0.004). These gestational fluctuations remained after adjusting for Fitzpatrick skin type, season, and sun exposure. We observed gestational fluctuations in both skin permeability and skin pH, with 28-30 weeks' gestation being a significant point of difference compared to mid- and late-pregnancy periods.

Acceptability of a Text Message-Based Mobile Health Intervention to Promote Physical Activity in Cardiac Rehabilitation Enrollees: A Qualitative Substudy of Participant Perspectives.

BACKGROUND: Mobile health (mHealth) interventions have the potential to deliver longitudinal support to users outside of episodic clinical encounters. We performed a qualitative substudy to assess the acceptability of a text message-based mHealth intervention designed to increase and sustain physical activity in cardiac rehabilitation enrollees. METHODS AND RESULTS: Semistructured interviews were conducted with intervention arm participants of a randomized controlled trial delivered to low- and moderate-risk cardiac rehabilitation enrollees. Interviews explored participants' interaction with the mobile application, reflections on tailored text messages, integration with cardiac rehabilitation, and opportunities for improvement. Transcripts were thematically analyzed using an iteratively developed codebook. Sample size consisted of 17 participants with mean age of 65.7 (SD 8.2) years; 29% were women, 29% had low functional capacity, and 12% were non-White. Four themes emerged from interviews: engagement, health impact, personalization, and future directions. Participants engaged meaningfully with the mHealth intervention, finding it beneficial in promoting increased physical activity. However, participants desired greater personalization to their individual health goals, fitness levels, and real-time environment. Generally, those with lower functional capacity and less experience with exercise were more likely to view the intervention positively. Finally, participants identified future directions for the intervention including better incorporation of exercise physiologists and social support systems. CONCLUSIONS: Cardiac rehabilitation enrollees viewed a text message-based mHealth intervention favorably, suggesting the potentially high usefulness of mHealth technologies in this population. Addressing participant-identified needs on increased user customization and inclusion of clinical and social support is crucial to enhancing the effectiveness of future mHealth interventions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04587882.

Text Messages to Promote Physical Activity in Patients With Cardiovascular Disease: A Micro-Randomized Trial of a Just-In-Time Adaptive Intervention.

BACKGROUND: Text messages may enhance physical activity levels in patients with cardiovascular disease, including those enrolled in cardiac rehabilitation. However, the independent and long-term effects of text messages remain uncertain. METHODS: The VALENTINE study (Virtual Application-supported Environment to Increase Exercise) was a micro-randomized trial that delivered text messages through a smartwatch (Apple Watch or Fitbit Versa) to participants initiating cardiac rehabilitation. Participants were randomized 4× per day over 6-months to receive no text message or a message encouraging low-level physical activity. Text messages were tailored on contextual factors (eg, weather). Our primary outcome was step count 60 minutes following a text message, and we used a centered and weighted least squares mean method to estimate causal effects. Given potential measurement differences between devices determined a priori, data were assessed separately for Apple Watch and Fitbit Versa users over 3 time periods corresponding to the initiation (0-30 days), maintenance (31-120 days), and completion (121-182 days) of cardiac rehabilitation. RESULTS: One hundred eight participants were included with 70 552 randomizations over 6 months; mean age was 59.5 (SD, 10.7) years with 36 (32.4%) female and 68 (63.0%) Apple Watch participants. For Apple Watch participants, text messages led to a trend in increased step count by 10% in the 60-minutes following a message during days 1 to 30 (95% CI, -1% to +20%), with no effect from days 31 to 120 (+1% [95% CI, -4% to +5%]), and a significant 6% increase during days 121 to 182 (95% CI, +0% to +11%). For Fitbit users, text messages significantly increased step count by 17% (95% CI, +7% to +28%) in the 60-minutes following a message in the first 30 days of the study with no effect subsequently. CONCLUSIONS: In patients undergoing cardiac rehabilitation, contextually tailored text messages may increase physical activity, but this effect varies over time and by device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04587882.

A Physical Activity and Diet Just-in-Time Adaptive Intervention to Reduce Blood Pressure: The myBPmyLife Study Rationale and Design.

BACKGROUND: Smartphone applications and wearable devices are promising mobile health interventions for hypertension self-management. However, most mobile health interventions fail to use contextual data, potentially diminishing their impact. The myBPmyLife Study is a just-in-time adaptive intervention designed to promote personalized self-management for patients with hypertension. METHODS AND RESULTS: The study is a 6-month prospective, randomized-controlled, remotely administered trial. Participants were recruited from the University of Michigan Health in Ann Arbor, Michigan or the Hamilton Community Health Network, a federally qualified health center network in Flint, Michigan. Participants were randomized to a mobile application with a just-in-time adaptive intervention promoting physical activity and lower-sodium food choices as well as weekly goal setting or usual care. The mobile study application encourages goal attainment through a central visualization displaying participants' progress toward their goals for physical activity and lower-sodium food choices. Participants in both groups are followed for up for 6 months with a primary end point of change in systolic blood pressure. Exploratory analyses will examine the impact of notifications on step count and self-reported lower-sodium food choices. The study launched on December 9, 2021, with 484 participants enrolled as of March 31, 2023. Enrollment of participants was completed on July 3, 2023. After 6 months of follow-up, it is expected that results will be available in the spring of 2024. CONCLUSIONS: The myBPmyLife study is an innovative mobile health trial designed to evaluate the effects of a just-in-time adaptive intervention focused on improving physical activity and dietary sodium intake on blood pressure in diverse patients with hypertension. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05154929.

Toward consensus-based actions that balance invasive plant management and conservation of at-risk fauna.

Limiting the spread of invasive plants has become a high priority among natural resource managers. Yet in some regions, invasive plants are providing important habitat components to native animals that are at risk of local or regional extirpation. In these situations, removing invasive plants may decrease short-term survival of the at-risk taxa. At the same time, there may be a reluctance to expand invaded habitats to benefit at-risk species because such actions may increase the distribution of invasive plants. Such a dilemma can result in "management paralysis," where no action is taken either to reduce invasive plants or to expand habitats for at-risk species. A pragmatic solution to this dilemma may be to develop an approach that considers site-specific circumstances. We constructed a "discussion tree" as a means of initiating conversations among various stakeholders involved with managing habitats in the northeastern USA to benefit several at-risk taxa, including New England cottontails (Sylvilagus transitionalis). Major components of this approach include recognition that expanding some invaded habitats may be essential to prevent extirpation of at-risk species, and the effective control of invasive plants is dependent on knowledge of the status of invasives on managed lands and within the surrounding landscape. By acknowledging that management of invasive plants is a complex issue without a single solution, we may be successful in limiting their spread while still addressing critical habitat needs.

Marsh migration and beyond: A scalable framework to assess tidal wetland resilience and support strategic management.

Tidal wetlands are critical but highly threatened ecosystems that provide vital services. Efficient stewardship of tidal wetlands requires robust comparative assessments of different marshes to understand their resilience to stressors, particularly in the face of relative sea level rise. Existing assessment frameworks aim to address tidal marsh resilience, but many are either too localized or too general, and few directly translate resilience evaluations to recommendations for management strategies. In response to the deficiencies in existing frameworks, we identified a set of metrics that influence overall marsh resilience that can be assessed at any spatial scale. We then developed a new comprehensive assessment framework to rank relative marsh resilience using these metrics, which are nested within three categories. We represent resilience as the sum of results across the three metric categories: current condition, adaptive capacity, and vulnerability. Users of this framework can add scores from each category to generate a total resilience score to compare across marshes or take the score from each category and refer to recommended management actions we developed based on expert elicitation for each combination of category results. We then applied the framework across the contiguous United States using publicly available data, and summarized results at multiple spatial scales, from regions to coastal states to National Estuarine Research Reserves to finer scale marsh units, to demonstrate the framework's value across these scales. Our national analysis allowed for comparison of tidal marsh resilience across geographies, which is valuable for determining where to prioritize management actions for desired future marsh conditions. In combination, the assessment framework and recommended management actions function as a broadly applicable decision-support tool that will enable resource managers to evaluate tidal marshes and select appropriate strategies for conservation, restoration, and other stewardship goals.

A randomized trial of a mobile health intervention to augment cardiac rehabilitation.

Mobile health (mHealth) interventions may enhance positive health behaviors, but randomized trials evaluating their efficacy are uncommon. Our goal was to determine if a mHealth intervention augmented and extended benefits of center-based cardiac rehabilitation (CR) for physical activity levels at 6-months. We delivered a randomized clinical trial to low and moderate risk patients with a compatible smartphone enrolled in CR at two health systems. All participants received a compatible smartwatch and usual CR care. Intervention participants received a mHealth intervention that included a just-in-time-adaptive intervention (JITAI) as text messages. The primary outcome was change in remote 6-minute walk distance at 6-months stratified by device type. Here we report the results for 220 participants enrolled in the study (mean [SD]: age 59.6 [10.6] years; 67 [30.5%] women). For our primary outcome at 6 months, there is no significant difference in the change in 6 min walk distance across smartwatch types (Intervention versus control: +31.1 meters Apple Watch, -7.4 meters Fitbit; p = 0.28). Secondary outcomes show no difference in mean step counts between the first and final weeks of the study, but a change in 6 min walk distance at 3 months for Fitbit users. Amongst patients enrolled in center-based CR, a mHealth intervention did not improve 6-month outcomes but suggested differences at 3 months in some users.

Understanding Baseline Physical Activity in Cardiac Rehabilitation Enrollees Using Mobile Health Technologies.

BACKGROUND: Baseline physical activity in patients when they initiate cardiac rehabilitation is poorly understood. We used mobile health technology to understand baseline physical activity of patients initiating cardiac rehabilitation within a clinical trial to potentially inform personalized care. METHODS: The VALENTINE (Virtual Application-Supported Environment to Increase Exercise During Cardiac Rehabilitation Study) is a prospective, randomized-controlled, remotely administered trial designed to evaluate a mobile health intervention to supplement cardiac rehabilitation for low- and moderate-risk patients. All participants receive a smartwatch and usual care. Baseline physical activity was assessed remotely after enrollment and included (1) 6-minute walk distance, (2) daily step count, and (3) daily exercise minutes, both over 7 days and for compliant days, defined by >8 hours of watch wear time. Multivariable linear regression identified patient-level features associated with these 3 measures of baseline physical activity. RESULTS: From October 2020 to March 2022, 220 participants enrolled in the study. Participants are mostly White (184 [83.6%]); 67 (30.5%) are female and 84 (38.2%) are >65 years old. Most participants enrolled in cardiac rehabilitation after percutaneous coronary intervention (105 [47.7%]) or coronary artery bypass surgery (39 [17.7 %]). Clinical diagnoses include coronary artery disease (78.6%), heart failure (17.3%), and valve repair or replacement (26.4%). Baseline mean 6-minute walk distance was 489.6 (SD, 143.4) meters, daily step count was 6845 (SD, 3353), and exercise minutes was 37.5 (SD, 33.5). In a multivariable model, 6-minute walk distance was significantly associated with age and sex, but not cardiac rehabilitation indication. Sex but not age or cardiac rehabilitation indication was significantly associated with daily step count and exercise minutes. CONCLUSIONS: Baseline physical activity varies substantially in low- and moderate-risk patients enrolled in cardiac rehabilitation. Future studies are warranted to explore whether personalizing cardiac rehabilitation programs using mobile health technologies could optimize recovery. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04587882.

Analysis of HER2 gene amplification using an automated fluorescence in situ hybridization signal enumeration system.

The HER2 gene, amplified in 10 to 35% of invasive human breast carcinomas, has prognostic and therapeutic implications. Fluorescent in situ hybridization is one method currently used for assessing HER2 status, but fluorescent in situ hybridization involves the time-consuming step of manual signal enumeration. To address this issue, Vysis has developed an automated signal enumeration system, Vysis AutoVysion. A multicenter, blinded study was conducted on 39 formalin-fixed, paraffin-embedded invasive breast carcinoma specimens, including 20 HER2 nonamplified and 19 HER2 amplified (weakly to highly amplified), provided in duplicate to each study site for analysis. Calculation of the HER2/CEP17 ratio and the hands-on time of both manual and automated enumeration approaches were compared. Overall agreement of HER2 classification results (positive and negative) was 92.5% (196 of 212). The Vysis AutoVysion System requires manual enumeration for cases with scanner results within the ratio range of 1.5 to 3.0. When the data in this range are excluded, the agreement between manual and scanner results is 98.8% (169 of 171). The average Vysis AutoVysion System hands-on time per slide was 4.59 versus 7.47 minutes for manual signal enumeration (savings of 2.88 minutes/slide). These data suggest that the Vysis AutoVysion System can correctly classify specimens and may increase the overall efficiency of HER2 testing.

Imbalances of chromosomes 4, 9, and 12 are recurrent in the thecoma-fibroma group of ovarian stromal tumors.

Traditional cytogenetic studies of ovarian stromal tumors are few, although trisomy 12 has been frequently documented with fluorescence in situ hybridization (FISH). In the current study, karyotypic analysis of four ovarian stromal tumors and a review of the literature suggest that numerical abnormalities of chromosomes 4 and 9 might also be important, possibly as secondary changes. To determine the frequency of 4, 9, and 12 aneuploidy in a larger group of ovarian tumors, FISH studies were performed on eight fibromas, three thecomas, one fibrothecoma, and five cellular fibromas. Trisomy 12 was identified in all five cellular fibromas as well as in two fibromas and the fibrothecoma. Gain of chromosome 9 was confined to the cellular fibromas. Loss of chromosomes 4 and/or 9 was prominent in the fibromas. These findings confirm the presence of trisomy 12 as a nonrandom chromosomal abnormality in ovarian stromal tumors. Moreover, these conventional and molecular cytogenetic data indicate that gain of chromosome 9 in addition to gain of chromosome 12 is prominent in cellular fibroma. In contrast, loss of chromosomes 4 and/or 9 are recurrent in fibroma. In summary, imbalances of chromosomes 4 and 9 appear to represent important secondary abnormalities in the thecoma-fibroma ovarian tumor group.

Development and implementation of a public health workforce training needs assessment survey in North Carolina.

Assessing the training needs of local public health workers is an important step toward providing appropriate training programs in emergency preparedness and core public health competencies. The North Carolina Public Health Workforce Training Needs Assessment survey was implemented through the collaboration of several organizations, including the North Carolina Center for Public Health Preparedness at the North Carolina Institute for Public Health, the outreach and service unit of the University of North Carolina School of Public Health, the Office of Public Health Preparedness and Response in the North Carolina Division of Public Health Epidemiology Section, and local health departments across the state.

A brief mental health and substance abuse screener for persons with HIV.

Mental illness and substance abuse are common among HIV-infected individuals and are associated with negative outcomes, including poor medication adherence. Therefore, quick and effective methods for detecting these co-occurring disorders are necessary for health care practitioners. This article reports on the creation and preliminary testing of a brief screening tool, the Substance Abuse and Mental Illness Symptoms Screener (SAMISS). The 13-item screener was developed primarily from existing scales and administered to HIV-infected individuals receiving care at infectious diseases clinics in the Southeast. To assess the validity of the SAMISS, a subset of those who screened positive for both mental illness symptoms and substance use problems (n = 207) were administered the Structured Clinical Interview for DSMIV Disorders (SCID). The positive predictive value of the screener in comparison to the SCID was 98.6% for mental disorders and 98.6% for substance use disorders. The agreement between specific screener symptoms and their corresponding SCID diagnoses was relatively high for alcohol dependence (kappa = 0.50, p < 0.001), drug dependence (kappa = 0.30, p < 0.001), and drug abuse (kappa = 0.42, p <0.001). The finding that the screener is highly predictive of having a general mental disorder and substance use disorder among those screening positive for mental illness symptoms and substance use problems, as well as its brevity and ease of administration, make it a useful tool to detect symptoms of co-occurring disorders so that patients can be referred to mental health and substance abuse specialists. The screener is not a diagnostic instrument and has limited value in predicting specific psychiatric diagnoses.

Early-life risperidone administration alters maternal-offspring interactions and juvenile play fighting.

Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at 1-hour post-injection. At 23 h post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at 1h post-injection. At 23h post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development.

Adult rats treated with risperidone during development are hyperactive.

Risperidone is an antipsychotic drug approved for use in children, but little is known about the long-term effects of early-life risperidone treatment. In animals, prolonged risperidone administration during development increases forebrain dopamine receptor expression immediately upon the cessation of treatment. A series of experiments was performed to ascertain whether early-life risperidone administration altered locomotor activity, a behavior sensitive to dopamine receptor function, in adult rats. One additional behavior modulated by forebrain dopamine function, spatial reversal learning, was also measured during adulthood. In each study, Long-Evans rats received daily subcutaneous injections of vehicle or 1 of 2 doses of risperidone (1.0 and 3.0 mg/kg per day) from postnatal Days 14 to 42. Weight gain during development was slightly yet significantly reduced in risperidone-treated rats. In the first 2 experiments, early-life risperidone administration was associated with increased locomotor activity at 1 week postadministration through approximately 9 months of age, independent of changes in weight gain. In a separate experiment, it was found that the enhancing effect of early-life risperidone on locomotor activity occurred in males and female rats. A final experiment indicated that spatial reversal learning was unaffected in adult rats administered risperidone early in life. These results indicate that locomotor activity during adulthood is permanently modified by early-life risperidone treatment. The findings suggest that chronic antipsychotic drug use in pediatric populations (e.g., treatment for the symptoms of autism) could modify brain development and alter neural set points for specific behaviors during adulthood.

The neurokinin NK2 antagonist, saredutant, ameliorates stress-induced conditions without impairing cognition.

The current work extends our previous findings in stress-related disorders, but also addresses the impact of a neurokinin-2 (NK2) antagonist on cognition. Besides efficacy in mood disorders, an NK2 antagonist may have the potential to lack the disinhibitory components and adverse side effects associated with existing clinical treatments. Saredutant (3-30 mg/kg, per os, p.o.) was tested for anxiolytic-like potential in three mouse models: holeboard, stress-induced hyperthermia (SIH) and four-plate. In the holeboard model saredutant (30 mg/kg) showed a trend to increase head dipping without affecting general activity. In the SIH model, saredutant demonstrated a significant reduction in stress-induced temperature at 30 mg/kg, while the number of punished crossings in the four-plate was increased at all doses tested (3-30 mg/kg). While chlordiazepoxide (CDP) demonstrated anxiolytic-like effects in these models, the adverse side effects of benzodiazepines, such as sedation, disinhibition and cognitive deficits are well-documented. Saredutant produced no detrimental effect in three models of cognition: Morris Water Maze (MWM) in rats, spontaneous alternation in a Y-maze in mice and novel objection recognition in mice. In contrast, the benzodiazepine, diazepam (DZM), produced cognitive impairments. NK2 receptor antagonists like saredutant may therefore yield beneficial effects for mood disorders without the adverse effects of current treatments.