Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal.

BACKGROUND: Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown. METHODS: In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death. RESULTS: A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups. CONCLUSIONS: As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).

Working memory contributions to reinforcement learning impairments in schizophrenia.

Previous research has shown that patients with schizophrenia are impaired in reinforcement learning tasks. However, behavioral learning curves in such tasks originate from the interaction of multiple neural processes, including the basal ganglia- and dopamine-dependent reinforcement learning (RL) system, but also prefrontal cortex-dependent cognitive strategies involving working memory (WM). Thus, it is unclear which specific system induces impairments in schizophrenia. We recently developed a task and computational model allowing us to separately assess the roles of RL (slow, cumulative learning) mechanisms versus WM (fast but capacity-limited) mechanisms in healthy adult human subjects. Here, we used this task to assess patients' specific sources of impairments in learning. In 15 separate blocks, subjects learned to pick one of three actions for stimuli. The number of stimuli to learn in each block varied from two to six, allowing us to separate influences of capacity-limited WM from the incremental RL system. As expected, both patients (n = 49) and healthy controls (n = 36) showed effects of set size and delay between stimulus repetitions, confirming the presence of working memory effects. Patients performed significantly worse than controls overall, but computational model fits and behavioral analyses indicate that these deficits could be entirely accounted for by changes in WM parameters (capacity and reliability), whereas RL processes were spared. These results suggest that the working memory system contributes strongly to learning impairments in schizophrenia.

Reduced susceptibility to confirmation bias in schizophrenia.

Patients with schizophrenia (SZ) show cognitive impairments on a wide range of tasks, with clear deficiencies in tasks reliant on prefrontal cortex function and less consistently observed impairments in tasks recruiting the striatum. This study leverages tasks hypothesized to differentially recruit these neural structures to assess relative deficiencies of each. Forty-eight patients and 38 controls completed two reinforcement learning tasks hypothesized to interrogate prefrontal and striatal functions and their interaction. In each task, participants learned reward discriminations by trial and error and were tested on novel stimulus combinations to assess learned values. In the task putatively assessing fronto-striatal interaction, participants were (inaccurately) instructed that one of the stimuli was valuable. Consistent with prior reports and a model of confirmation bias, this manipulation resulted in overvaluation of the instructed stimulus after its true value had been experienced. Patients showed less susceptibility to this confirmation bias effect than did controls. In the choice bias task hypothesized to more purely assess striatal function, biases in endogenously and exogenously chosen actions were assessed. No group differences were observed. In the subset of participants who showed learning in both tasks, larger group differences were observed in the confirmation bias task than in the choice bias task. In the confirmation bias task, patients also showed impairment in the task conditions with no prior instruction. This deficit was most readily observed on the most deterministic discriminations. Taken together, these results suggest impairments in fronto-striatal interaction in SZ, rather than in striatal function per se.

A case report of retinal dystrophy in patients with PACS1 syndrome.

PACS1 syndrome, also referred to as Schuurs-Hoeijmakers syndrome, is a multisystemic developmental disorder caused by a specific pathogenic variant in the PACS1 (phosphofurin acidic cluster sorting protein 1) gene. Ocular findings in PACS1 syndrome are known to include iris, retina, optic nerve coloboma, myopia, nystagmus, and strabismus. Here, we present the cases of two patients referred to the University of Wisconsin-Madison Department of Ophthalmology and Visual Sciences for ocular evaluation. The first patient is a 14-month-old female who, at 3 months of age, was found to have a depressed rod and cone response on electroretinogram (ERG), consistent with possible retinal dystrophy (RD). This feature has not been previously described in PACS1 syndrome and joins a growing list of calls for expanding the PACS1 phenotype. The second case illustrates a 5-year-old male referred for ocular screening after diagnosing PACS1 syndrome and underwent ERG without abnormal findings. These cases demonstrate the significant variability in the ophthalmic presentation of PACS1 syndrome and the need for early screening. These novel findings may have implications in understanding the mechanism of the PACS1 protein and its role in retinal ciliary phototransduction in photoreceptors.

Combined Motivational Interviewing and Ecological Momentary Intervention to Reduce Hazardous Alcohol Use Among Sexual Minority Cisgender Men and Transgender Individuals: Protocol for a Randomized Controlled Trial.

BACKGROUND: Sexual minority cisgender men and transgender (SMMT) individuals, particularly emerging adults (aged 18-34 years), often report hazardous drinking. Given that alcohol use increases the likelihood of HIV risk behaviors, and HIV disproportionately affects SMMT individuals, there is a need to test interventions that reduce hazardous alcohol use and subsequent HIV risk behaviors among this population. Ecological momentary interventions (EMIs), which use mobile phones to deliver risk reduction messages based on current location and behaviors, can help to address triggers that lead to drinking in real time. OBJECTIVE: This study will test an EMI that uses motivational interviewing (MI), smartphone surveys, mobile breathalyzers, and location tracking to provide real-time messaging that addresses triggers for drinking when SMMT individuals visit locations associated with hazardous alcohol use. In addition, the intervention will deliver harm reduction messaging if individuals report engaging in alcohol use. METHODS: We will conduct a 3-arm randomized controlled trial (N=405 HIV-negative SMMT individuals; n=135, 33% per arm) comparing the following conditions: (1) Tracking and Reducing Alcohol Consumption (a smartphone-delivered 4-session MI intervention), (2) Tracking and Reducing Alcohol Consumption and Environmental Risk (an EMI combining MI with real-time messaging based on geographic locations that are triggers to drinking), and (3) a smartphone-based alcohol monitoring-only control group. Breathalyzer results and daily self-reports will be used to assess the primary and secondary outcomes of drinking days, drinks per drinking day, binge drinking episodes, and HIV risk behaviors. Additional assessments at baseline, 3 months, 6 months, and 9 months will evaluate exploratory long-term outcomes. RESULTS: The study is part of a 5-year research project funded in August 2022 by the National Institute on Alcohol Abuse and Alcoholism. The first 1.5 years of the study will be dedicated to planning and development activities, including formative research, app design and testing, and message design and testing. The subsequent 3.5 years will see the study complete participant recruitment, data collection, analyses, report writing, and dissemination. We expect to complete all study data collection in or before January 2027. CONCLUSIONS: This study will provide novel evidence about the relative efficacy of using a smartphone-delivered MI intervention and real-time messaging to address triggers for hazardous alcohol use and sexual risk behaviors. The EMI approach, which incorporates location-based preventive messaging and behavior surveys, may help to better understand the complexity of daily stressors among SMMT individuals and their impact on hazardous alcohol use and HIV risk behaviors. The tailoring of this intervention toward SMMT individuals helps to address their underrepresentation in existing alcohol use research and will be promising for informing where structural alcohol use prevention and treatment interventions are needed to support SMMT individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576350; https://www.clinicaltrials.gov/study/NCT05576350. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55166.

Influence of Eat, Sleep, and Console on Infants Pharmacologically Treated for Opioid Withdrawal: A Post Hoc Subgroup Analysis of the ESC-NOW Randomized Clinical Trial.

Importance: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. Objective: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. Design, Setting, and Participants: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. Exposure: Opioid treatment for NOWS and the ESC care approach. Main Outcomes and Measures: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. Results: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). Conclusion and Relevance: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. Trial Registration: ClinicalTrials.gov Identifier: NCT04057820.

Retractable Urology Three-Pronged Grasping Forceps for Removal of Large, Non-Magnetic Intraocular Foreign Bodies.

PURPOSE: To demonstrate the use of urology retractable three-pronged grasping forceps in the removal of a large, round, and non-magnetic intraocular foreign body (IOFB) that was difficult to remove with other surgical instruments. METHODS: Extraction of a 3.0 mm lead shot pellet embedded in vitreous hemorrhage was attempted with multiple surgical instruments including an intraocular magnet, IOFB forceps, and two tools designed for urology stone removal: a three-pronged grasping forceps and a nitinol basket extractor. RESULTS: Due to the round and smooth surface, large size, and non-magnetic nature of the IOFB, extraction was challenging and failed with multiple other surgical instruments. The wide and secure grasp of the grasping forceps allowed for swift IOFB extraction without iatrogenic injury to the retina. CONCLUSION: The grasping forceps offer an effective and safe method for removal of large, round, and non-magnetic IOFBs.

Therapeutic Outcomes of Non-Infectious Scleritis Treated with Tumor Necrosis Factor-Alpha Inhibitors.

PURPOSE: We determine the efficacy of tumor necrosis factor-α (TNF) inhibitors in establishing scleritis quiescence. METHODS: We conducted a multicenter retrospective chart review of patients with non-infectious scleritis treated with a TNF inhibitor for at least 6 months. The primary endpoint was scleritis quiescence at 6 months. Secondary endpoints included scleritis quiescence at 12 months, TNF inhibitor effects on concurrent doses of systemic corticosteroids and visual acuity outcomes at 6 and 12 months. RESULTS: At 6 months, 82.2% (37/45) of subjects obtained scleritis quiescence with TNF inhibition. At 12 months, 76.2% (32/42) of subjects remained quiescent. Baseline daily corticosteroid use (21.5 ± 21.6 mg) decreased to 5.4 ± 8.3 mg by 6 months (p < 0.0001) and 2.8 ± 6.1 mg by 12 months (p < 0.001). There was no significant difference between the baseline and 6-month BCVA (p = 0.52). CONCLUSIONS: TNF inhibitors are an effective scleritis therapy with significant systemic corticosteroid sparing effect.

Primary Care Counseling of Parents Regarding Childhood Screen Media Use.

Parental beliefs and motivation are instrumental in improving childhood digital media use (DMU). Parents (n = 611) completed questionnaires about childhood DMU assessing knowledge, interest in counseling, motivation to change, self-efficacy, and beliefs. Less than a third correctly recognized screen time limits. Twenty-seven percent received childhood DMU information from a doctor, while 46% stated they would like such information. Only 2% had a doctor-recommended DMU plan. Interest in DMU topics, motivation to improve, and management self-efficacy were moderate. Top negative beliefs were addiction to DMU (52%), sleep problems (39%), obesity (33%), social skills (33%), and inappropriate content (32%). Differences between age categories existed for social (48%, P = .01) and language (14%, P = .01) concerns (highest for toddlers), attention concerns (27%, P = .02; highest in preschoolers), and depression (13%, P < .001) and low self-esteem (8%, P = .04; highest in teens). Findings support further development of approaches to address DMU, tailored by age-specific common parental views.

The Effectiveness of a Mobile Health Clinic Delivering Mandatory and Elective Middle School Immunizations: A Descriptive Analysis.

INTRODUCTION: Mobile health clinics serve a unique role in which they can offer affordable and adaptable care to the population they serve. The Edward Via College of Osteopathic Medicine (VCOM) mobile clinics began in 2020 as a partnership with the South Carolina Department of Health and Environmental Control (SCDHEC) to address the low vaccination rates that resulted from the COVID-19 pandemic. METHODS:  This study is a descriptive analysis that examines the number of vaccinations of tetanus, diphtheria, and pertussis (Tdap) and human papillomavirus (HPV) at different locations of administration including pediatrician offices, the novel VCOM mobile vaccination clinic, and the Spartanburg Health Department. The variables of interest and the study endpoints focused on Tdap and HPV vaccinations among students aged 11-12 years old in Spartanburg County according to the type of healthcare delivery location. RESULTS: From April to May of 2021, the VCOM mobile clinic was able to administer 279 Tdap vaccines and 189 HPV vaccines to students at local middle schools, which surpasses the number of vaccines administered at other sites from August 2020 to May 2021 when compared individually for both Tdap and HPV vaccinations. CONCLUSIONS: By assessing the total volume of vaccines administered by each group, the VCOM mobile clinic was established as an effective method of delivery and played a crucial role in the vaccination efforts of the Spartanburg community. Mobile medical units should be considered for similar efforts in providing care to resource-limited communities and those with limited access to care.

Spontaneous heterotopic pregnancy successfully treated via laproscopic surgery with subsequent viable intrauterine pregnancy: a case report.

BACKGROUND: Heterotopic pregnancy (HP) refers to the presence of simultaneous pregnancies at two different sites of implantation, one intrauterine and the other extrauterine. The incidence of HP has increased in recent years secondary to a rise in the use of assisted reproductive technologies (ART). CASE: A 34-year-old woman, without risk factors for multiple pregnancies, presented with a spontaneous hypertopic pregnancy to a military facility. The ectopic pregnancy was successfully treated via laparoscopic surgery. She maintained a viable intrauterine pregnancy and was 32 weeks gestation with no complications at the time of submission. DISCUSSION: This case highlights the importance of maintaining a wide differential in a patient who presents with elevated Beta-human Chorionic Gonadotropin Hormone (B-HCG) levels, which continue to rise, as well as signs and symptoms consistent with ectopic pregnancy. CONCLUSION: Currently the rate of ART is rising; therefore, the expected cases of HP will likely continue to rise. At this time, there are no standard protocols for treatment and diagnosis of HP; this is an area that should be further researched in order to provide the best medical care for these women, the intrauterine pregnancy and future fertility.

Objective and subjective measures indicate that orthographically similar words produce a blocking experience.

Memory blocks are a common experience characterised by inappropriate retrieval of information that impairs memory search processes. In five studies, memory blocks were induced via exposure to orthographically similar words (Smith & Tindell, 1997) while participants reported their subjective experiences to determine whether the memory block effect (MBE) paradigm produces a feeling of being blocked. Experiments 1 and 3 provided evidence that the MBE is associated with more blocked experiences. In Experiments 2 and 4 increased blocking experiences correlated with blocked fragments when the experimental manipulation was disguised, which demonstrates that ratings were not contaminated by demand characteristics. Experiment 5 demonstrated that blocking happens even when there is no study list. Collectively, the subjective retrieval ratings and the objective response data provide converging evidence that exposure to orthographically similar words induces a memory block characterised by an ineffective memory search that perseverates on interfering information.

Evaluating the sector-wide implementation of virtual child and youth mental health services in response to the COVID-19 pandemic: Perspectives from service providers, agency leaders and clients.

Background: The COVID-19 pandemic prompted an abrupt shift in the delivery of community-based child and youth mental health services as virtual care was rapidly adopted. The objective of this study was to evaluate the sector-wide transition to virtual care across Ontario, with a focus on implementation facilitators and barriers. Methods: We used a multi-level mixed-methods design where agency leaders, service providers, and clients shared their experiences planning, implementing, and accessing virtual care. In total, 97 agency leaders, and 192 youth and family members responded to the surveys; 13 agency leaders, and 11 service providers participated in interviews or focus groups. Results: Most agencies undertook a similar journey to implement virtual care. Stakeholders described common facilitators such as staff engagement, leadership support, and training activities. Barriers included internet connection issues, lack of resources, and privacy concerns. Service providers innovated as they implemented by partnering with agencies to meet clients' needs, using multiple platforms to engage clients, and altering session duration to reduce fatigue. Clients found virtual care easy to use, felt confident using it, and intend to continue accessing virtual care. Conclusion: Implementation of virtual care during the pandemic was complex and the evaluation involved obtaining perspectives at multiple levels. This research provides a blueprint for evaluations of the implementation of virtual mental health services, particularly in a child/youth context. Virtual care is a viable way to deliver mental health services, however, equity, accessibility, and appropriateness need to be addressed to ensure services are effective for children, youth, and their families. Plain language abstract: Academic literature suggests that using technology to deliver child and youth mental health services is a promising way to enhance access to care and improve engagement for many children and youth. Despite this, the provision of virtual child and youth mental health services in Ontario prior to the COVID-19 pandemic was limited. Efforts that did exist were largely focused on providing care to those in rural and remote areas. The COVID-19 pandemic prompted a rapid shift to virtual care, as most in-person mental health services were suspended. This paper presents new insight into how virtual mental health services were quickly established and used across Ontario from the perspectives of senior leaders, service providers, and clients. Results from this evaluation showed that agencies followed similar steps to prepare to use virtual services. Staff engagement, support from leadership, and opportunities for staff training supported the implementation of virtual care while internet connections issues, lack of resources (like computers or phones), and privacy and safety concerns hindered the implementation. Most youth and family members found virtual services easy to use and intend to continue using them. Most agencies intend to continue to offer virtual services post-pandemic but noted that it was not appropriate or accessible for all clients. This study provides a foundation for additional research to examine situations and conditions that are most conducive to virtual care delivery to address child and youth mental health concerns. These results may encourage agencies to rely more confidently on virtual services as another means to meet clients' needs and preferences.

Redundant visual signals reduce the intensity of alcohol impairment.

BACKGROUND: Humans interact with multiple stimuli across several modalities each day. The "redundant signal effect" refers to the observation that individuals respond more quickly to stimuli when information is presented as multisensory, redundant stimuli (e.g., aurally and visually), rather than as a single stimulus presented to either modality alone. Studies of alcohol effects on human performance show that alcohol induced impairment is reduced when subjects respond to redundant multisensory stimuli. However, redundant signals do not need to involve multisensory stimuli to facilitate behavior as studies have shown facilitating effects by redundant unisensory signals that are delivered to the "same sensory" (e.g., two visual or two auditory signals). METHODS: The current study examined the degree to which redundant visual signals would reduce alcohol impairment and compared the magnitude of this effect with that produced by redundant multisensory signals. On repeated test sessions, participants (n = 20) received placebo or 0.65 g/kg alcohol and performed a two-choice reaction time task that measured how quickly participants responded to four different signal conditions. The four conditions differed by the modality of the target presentation: visual, auditory, multisensory, and unisensory. RESULTS: Alcohol slowed performance in all conditions and reaction times were generally faster in the redundant signal conditions. Both multisensory and unisensory redundant signals reduced the impairing effects of alcohol compared with single signals. CONCLUSIONS: These findings indicate that the ability of redundant signals to counteract alcohol impairment does not require multisensory input. Duplicate signals to the same modality can also reduce alcohol impairment.

Effects of multisensory stop signals on alcohol-induced disinhibition in adults with ADHD.

Multisensory environments facilitate behavioral functioning in humans. The redundant signal effect (RSE) refers to the observation that individuals respond more quickly to stimuli when information is presented as multisensory, redundant stimuli (e.g., aurally and visually) rather than as a single stimulus presented to either modality alone. RSE appears to be because of specialized multisensory neurons in the superior colliculus and association cortex that allow intersensory coactivation between the visual and auditory channels. Our studies show that the disinhibiting effects of alcohol are attenuated when stop signals are multisensory (e.g., Visual + Auditory stop signals) versus unisensory (Roberts, Monem, & Fillmore, 2016). The present study expanded on this research to test the degree to which multisensory stop signals could also attenuate the disinhibiting effects of alcohol in those with attention-deficit hyperactivity disorder (ADHD), a clinical population characterized by poor impulse control. The study compared young adults with ADHD (n = 22) with healthy controls (n = 22) and examined the acute impairing effect of alcohol on response inhibition to stop signals that were presented as a unisensory (visual) stimulus or a multisensory (Visual + Auditory) stimulus. For controls, results showed alcohol impaired response inhibition to unisensory stop signals but not to multisensory stop signals. Response inhibition of those with ADHD was impaired by alcohol regardless of whether stop signals were unisensory or multisensory. The failure of multisensory stimuli to attenuate alcohol impairment in those with ADHD highlights a specific vulnerability that could account for heightened sensitivity to the disruptive effects of alcohol. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Impaired Expected Value Computations in Schizophrenia Are Associated With a Reduced Ability to Integrate Reward Probability and Magnitude of Recent Outcomes.

BACKGROUND: Motivational deficits in people with schizophrenia (PSZ) are associated with an inability to integrate the magnitude and probability of previous outcomes. The mechanisms that underlie probability-magnitude integration deficits, however, are poorly understood. We hypothesized that increased reliance on "valueless" stimulus-response associations, in lieu of expected value (EV)-based learning, could drive probability-magnitude integration deficits in PSZ with motivational deficits. METHODS: Healthy volunteers (n = 38) and PSZ (n = 49) completed a learning paradigm consisting of four stimulus pairs. Reward magnitude (3, 2, 1, 0 points) and probability (90%, 80%, 20%, 10%) determined each stimulus's EV. Following a learning phase, new and familiar stimulus pairings were presented. Participants were asked to select stimuli with the highest reward value. RESULTS: PSZ with high motivational deficits made increasingly less optimal choices as the difference in reward value (probability × magnitude) between two competing stimuli increased. Using a previously validated computational hybrid model, PSZ relied less on EV ("Q-learning") and more on stimulus-response learning ("actor-critic"), which correlated with Scale for the Assessment of Negative Symptoms motivational deficit severity. PSZ specifically failed to represent reward magnitude, consistent with model demonstrations showing that response tendencies in the actor-critic were preferentially driven by reward probability. CONCLUSIONS: Probability-magnitude deficits in PSZ with motivational deficits arise from underutilization of EV in favor of reliance on valueless stimulus-response associations. Confirmed by our computational hybrid framework, probability-magnitude integration deficits were driven specifically by a failure to represent reward magnitude. This work provides a first mechanistic explanation of complex EV-based learning deficits in PSZ with motivational deficits that arise from an inability to combine information from different reward modalities.

Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance.

The heterochromatin protein 1 (HP1) family is involved in various functions with maintenance of chromatin structure. During murine somatic cell reprogramming, we find that early depletion of HP1γ reduces the generation of induced pluripotent stem cells, while late depletion enhances the process, with a concomitant change from a centromeric to nucleoplasmic localization and elongation-associated histone H3.3 enrichment. Depletion of heterochromatin anchoring protein SENP7 increased reprogramming efficiency to a similar extent as HP1γ, indicating the importance of HP1γ release from chromatin for pluripotency acquisition. HP1γ interacted with OCT4 and DPPA4 in HP1α and HP1ß knockouts and in H3K9 methylation depleted H3K9M embryonic stem cell (ESC) lines. HP1α and HP1γ complexes in ESCs differed in association with histones, the histone chaperone CAF1 complex, and specific components of chromatin-modifying complexes such as DPY30, implying distinct functional contributions. Taken together, our results reveal the complex contribution of the HP1 proteins to pluripotency.

Probing the Dynamic Updating of Value in Schizophrenia Using a Sensory-Specific Satiety Paradigm.

It has been proposed that both positive and negative symptoms in schizophrenia (SZ) may derive, at least in part, from a disrupted ability to accurately and flexibly represent the value of stimuli and actions. To assess relationships between dimensions of psychopathology in SZ, and the tendency to devalue food stimuli, on which subjects were fed to satiety, we administered a sensory-specific satiety (SSS) paradigm to 42 SZ patients and 44 controls. In each of 2 sessions, subjects received 16 0.7-ml squirts of each of 2 rewarding foods and 32 squirts of a control solution, using syringes. In between the 2 sessions, each subject was instructed to drink one of the foods until he/she felt "full, but not uncomfortable." At 10 regular intervals, interspersed throughout the 2 sessions, subjects rated each liquid for pleasantness, using a Likert-type scale. Mann-Whitney U-tests revealed group differences in SSS effects. Within-group tests revealed that, while controls showed an effect of satiety that was sensory specific, patients showed an effect of satiety that was not, devaluing the sated and unsated foods similarly. In SZ patients, we observed correlations between the magnitude of SSS effects and measures of both positive and negative symptoms. We argue that the ability to flexibly and rapidly update representations of the value of stimuli and actions figures critically in the ability of patients with psychotic illness to process salient events and adaptively engage in goal-directed behavior.

Delaying Pap test screening in the adolescent population: an evidence-based approach.

Cervical cancer screening guidelines have evolved significantly over the past ten years in the adolescent population. The objective of this article is to review the cervical screening guidelines in the adolescent population as well as examine the evidence and studies that support delaying screening until 21 years old. Delaying HPV and Papanicolaou testing until 21 years old is safe and will not increase cervical cancer rates in the adolescent population.

Development of catecholamine and cortisol stress responses in zebrafish.

Both adrenal catecholamines and steroids are known to be involved in the stress response, immune function, blood pressure and energy homeostasis. The response to stress is characterized by the activation of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary system, though the correlation with activation and development is not well understood. We evaluated the stress response of both cortisol and catecholamines during development in zebrafish. Zebrafish at two different stages of development were stressed in one of two different ways and cortisol and catecholamine were measured. Cortisol was measured by enzyme immune assay and catecholamine was measured by ELISA. Our results show that stress responses are delayed until after the synthesis of both cortisol and catecholamines. These observations suggest that the development of HPA axis may be required for the acquisition of the stress response for cortisol and catecholamines.