Neonatal hyperoxia exposure leads to developmental programming of cardiovascular and renal disease in adult rats.

Premature infants are often exposed to hyperoxia. However, there is limited data regarding the mechanistic underpinnings linking neonatal hyperoxia exposure and its contribution to cardio-renal dysfunction in adults born preterm. Our objective was to determine whether neonatal hyperoxia induces systemic vascular stiffness and cardio-renal dysfunction in adulthood. Newborn rats were randomly assigned to room air (RA) or hyperoxia (85% O2) from postnatal day 1 to 14, then recovered in RA until 1 year of life. Arterial stiffness, cardio-renal histomorphometry, and fibrosis in the aorta, heart, and kidney were assessed. RNA-sequencing (RNA-seq) of the aorta and kidney was also done. Adult rats exposed to neonatal hyperoxia had increased aortic and mesenteric artery stiffness as demonstrated by wire and pressure myography. They also had cardiomyocyte hypertrophy, glomerulomegaly, and tubular injury. Hyperoxia exposure altered the transcriptome profile associated with fibrosis and matrix remodeling in the aorta and kidney. There was also increased TGF-ß1 levels and fibrosis in the aorta, left ventricle, and kidney. In conclusion, neonatal hyperoxia exposure was associated with systemic vascular and cardio-renal alterations in 1-year-old rats. Further studies to determine how targeted therapies could reprogram cardio-renal injury after neonatal hyperoxia exposure are indicated.

Exploring Asymmetric Fine Motor Impairment Trends in Early Parkinson's Disease via Keystroke Typing.

Background: The nQiMechPD algorithm transforms natural typing data into a numerical index that characterizes motor impairment in people with Parkinson's Disease (PwPD). Objectives: Use nQiMechPD to compare asymmetrical progression of PD-related impairment in dominant (D-PD) versus non-dominant side onset (ND-PD) de-novo patients. Methods: Keystroke data were collected from 53 right-handed participants (15 D-PD, 13 ND-PD, 25 controls). We apply linear mixed effects modeling to evaluate participants' right, left, and both hands nQiMechPD relative change by group. Results: The 6-month nQiMechPD trajectories of right (**P = 0.002) and both (*P = 0.043) hands showed a significant difference in nQiMechPD trends between D-PD and ND-PD participants. Left side trends were not significantly different between these two groups (P = 0.328). Conclusions: Significant differences between D-PD and ND-PD groups were observed, likely driven by contrasting dominant hand trends. Our findings suggest disease onset side may influence motor impairment progression, medication response, and functional outcomes in PwPD.

Experiences of Child and Adolescent Psychiatric Patients Boarding in the Emergency Department from Staff Perspectives: Patient Journey Mapping.

Over the past decade, healthcare providers nationwide have contended with a growing boarding crisis as pediatric patients await psychiatric treatment in emergency departments (EDs). COVID-19 has exacerbated this urgent youth mental health crisis, driving EDs to act as crisis units. Journey mapping is a robust methodology with which to examine strengths and challenges in patient care workflows such as boarding and emergency psychiatric care. Psychiatric, emergency medicine, and hospitalist providers serving patients boarding at a northeastern children's hospital participated in semi-structured qualitative interviews. Investigators conducted directed content analysis with an inductive approach to identify facilitators, barriers, and persistent needs of boarding patients, which were summarized in a patient journey map. Findings were presented to participants for feedback and further refinement. Quantitative data showed a three-fold increase in the number of patients who boarded over the past three years and a 60% increase in the average time spent boarding in the ED. Emergent qualitative data indicated three stages in the boarding process: Initial Evaluation, Admitted to Board, and Discharge. Data highlighted positive and negative factors affecting patient safety, availability of beds in pediatric hospital and psychiatric inpatient settings, high patient-provider ratios that limited staffing support, and roadblocks in care coordination and disposition planning. Patient journey mapping provided insight into providers' experiences serving patients boarding for psychiatric reasons. Findings described bright points and pain points at each stage of the boarding process with implications for psychiatric care and systemic changes to reduce boarding volume and length of stay.

A novel framework to estimate cognitive impairment via finger interaction with digital devices.

Measuring cognitive function is essential for characterizing brain health and tracking cognitive decline in Alzheimer's Disease and other neurodegenerative conditions. Current tools to accurately evaluate cognitive impairment typically rely on a battery of questionnaires administered during clinical visits which is essential for the acquisition of repeated measurements in longitudinal studies. Previous studies have shown that the remote data collection of passively monitored daily interaction with personal digital devices can measure motor signs in the early stages of synucleinopathies, as well as facilitate longitudinal patient assessment in the real-world scenario with high patient compliance. This was achieved by the automatic discovery of patterns in the time series of keystroke dynamics, i.e. the time required to press and release keys, by machine learning algorithms. In this work, our hypothesis is that the typing patterns generated from user-device interaction may reflect relevant features of the effects of cognitive impairment caused by neurodegeneration. We use machine learning algorithms to estimate cognitive performance through the analysis of keystroke dynamic patterns that were extracted from mechanical and touchscreen keyboard use in a dataset of cognitively normal (n = 39, 51% male) and cognitively impaired subjects (n = 38, 60% male). These algorithms are trained and evaluated using a novel framework that integrates items from multiple neuropsychological and clinical scales into cognitive subdomains to generate a more holistic representation of multifaceted clinical signs. In our results, we see that these models based on typing input achieve moderate correlations with verbal memory, non-verbal memory and executive function subdomains [Spearman's ρ between 0.54 (P < 0.001) and 0.42 (P < 0.001)] and a weak correlation with language/verbal skills [Spearman's ρ 0.30 (P < 0.05)]. In addition, we observe a moderate correlation between our typing-based approach and the Total Montreal Cognitive Assessment score [Spearman's ρ 0.48 (P < 0.001)]. Finally, we show that these machine learning models can perform better by using our subdomain framework that integrates the information from multiple neuropsychological scales as opposed to using the individual items that make up these scales. Our results support our hypothesis that typing patterns are able to reflect the effects of neurodegeneration in mild cognitive impairment and Alzheimer's disease and that this new subdomain framework both helps the development of machine learning models and improves their interpretability.

Safe Use of Memantine in a Pediatric Patient With Catatonia.

Pediatric catatonia is a complex neuropsychiatric syndrome. Benzodiazepines are standard first-line pharmacotherapy. When benzodiazepines do not provide relief of symptoms, electroconvulsive therapy (ECT) is the most proven effective therapy. However, the use of NMDA antagonists (amantadine and memantine) has been reported effective in adult patients as adjuncts and may provide an alternative treatment modality when ECT is not readily accessible. To the author's knowledge there are no prior case reports of memantine used in pediatric catatonia. This case demonstrates the safe use of memantine as an adjunctive agent in an adolescent with catatonia.

ATP-binding cassette transporters at the zebrafish blood-brain barrier and the potential utility of the zebrafish as an in vivo model.

The brain is protected from toxins by a tightly regulated network of specialized cells, including endothelial cells, pericytes, astrocyes, and neurons, known collectively as the blood-brain barrier (BBB). This selectively permeable barrier permits only the most crucial molecules essential for brain function to enter and employs a number of different mechanisms to prevent the entry of potentially harmful toxins and pathogens. In addition to a physical barrier comprised of endothelial cells that form tight junctions to restrict paracellular transport, there is an active protective mechanism made up of energy-dependent transporters that efflux compounds back into the bloodstream. Two of these ATP-binding cassette (ABC) transporters are highly expressed at the BBB: P-glycoprotein (P-gp, encoded by the ABCB1 gene) and ABCG2 (encoded by the ABCG2 gene). Although a number of in vitro and in vivo systems have been developed to examine the role that ABC transporters play in keeping compounds out of the brain, all have inherent advantages and disadvantages. Zebrafish (Danio rerio) have become a model of interest for studies of the BBB due to the similarities between the zebrafish and mammalian BBB systems. In this review, we discuss what is known about ABC transporters in zebrafish and what information is still needed before the zebrafish can be recommended as a model to elucidate the role of ABC transporters at the BBB.

Psychosocial Background History of Pregnant Women with Opioid Use Disorder: A Prospective Cohort Study.

OBJECTIVE: This study aimed to evaluate the psychosocial background history and confounding social factors in pregnant women with opioid use disorder (OUD). STUDY DESIGN: We performed a prospective observational cohort study of pregnant women from a dedicated obstetrical OUD clinic. Data collection came from extensive interview sessions regarding psychosocial background events and other social factors that might impact prenatal care. RESULTS: From February 1, 2017, through September 30, 2018, 411 pregnant women were evaluated and 294 (72%, 95% confidence interval [CI]: 67-76%) reported abuse of which 217 (53%, 95% CI: 48-58%) involved sexual abuse (prior to the age of 13 years in 54% of cases) and 209 (51%, 95% CI: 46-56%) involved cases of other physical abuse. Only 10% reported habitual opioid use for managing chronic pain. Only 9% had a valid driver's license with access to a car making transportation to office visits difficult. CONCLUSION: A history of abuse (mainly sexual and/or physical) appears to be the main precipitating event leading to OUD in our pregnant population. Transportation was the primary social factor limiting access to prenatal care. For primary prevention to be successful in our region, early identification of young women who have experienced abuse needs to occur followed by psychotherapy health care intervention before opioid drugs are used.

Use of naltrexone in treating opioid use disorder in pregnancy.

BACKGROUND: The mainstay of the management of opioid use disorder in pregnancy is with methadone or buprenorphine medication-assisted treatment. Methadone and buprenorphine are opioid agonist drugs. Naltrexone, an opioid antagonist, is also a medication-assisted treatment option; however, to date, only a few retrospective studies have reported its use in pregnancy. OBJECTIVE: Our study objective was to evaluate prospectively obstetric and newborn outcomes and the maternal/fetal effects of the use of naltrexone as a medication-assisted treatment in pregnant patients with opioid use disorder. STUDY DESIGN: We performed a prospective cohort study collecting data on all pregnant women who were treated with naltrexone medication-assisted treatment compared with pregnant women who were treated with methadone or buprenorphine medication-assisted treatment. Based on a sample size calculation, it was determined that for a power of 90, a minimum of 160 study participants (80 in each group) was needed with an alpha of .01 and an expected 60% rate of newborn infants who were treated for neonatal abstinence syndrome in the methadone or buprenorphine medication-assisted treatment group compared with a 30% rate in the naltrexone medication-assisted treatment group. In a random subset of 20 maternal/newborn dyads, blood levels for naltrexone and 6-beta-naltrexol (an active metabolite) were analyzed at delivery. RESULTS: A total of 230 patients were studied: 121 patients with naltrexone medication-assisted treatment compared with 109 patients with methadone or buprenorphine medication-assisted treatment. No differences between groups were seen regarding demographics, the use of comedications/drugs, or obstetric outcomes. For newborn outcomes, the rate of neonatal abstinence syndrome in neonates >34 weeks gestation was significantly lower in the naltrexone medication-assisted treatment group (10/119 [8.4%] vs 79/105 [75.2%]; P<.0001). Multivariate analysis demonstrated that the only significant factor for the rate of neonatal abstinence syndrome was the form of medication-assisted treatment. Of 87 patients who received naltrexone up to delivery, no neonates experienced symptoms of neonatal abstinence syndrome. No maternal relapses occurred in the 7-day no-treatment window before the initiation of naltrexone therapy. No cases of spontaneous abortion or stillbirth occurred in either group. In 64 patients who started naltrexone therapy at ≥24 weeks gestation, no changes were seen in the fetal heart monitor tracing with drug initiation. The incidence of birth anomalies was no different between the groups. Umbilical cord blood and maternal levels for naltrexone and 6-beta-naltrexol matched; no levels were elevated, and values were undetected if naltrexone was discontinued >60 hours before delivery. CONCLUSION: These study data demonstrate that, in pregnant women who choose to completely detoxify off opioid drugs during gestation, naltrexone, as a continued form of medication-assisted treatment, is a viable option for some pregnant patients who experience opioid use disorder. Naltrexone crosses the placenta, and maternal and fetal levels are concordant. Because naltrexone clears quickly from the maternal circulation, this rapid clearance needs to be addressed with patients. This is important because maternal relapse could occur in a short time-period if the oral drug is discontinued without the knowledge of their healthcare providers. Nonetheless, the drug is well-tolerated by both mother and fetus, and newborn infants do not experience symptoms of neonatal abstinence syndrome if naltrexone medication-assisted treatment is maintained to delivery.

Challenges of managing pediatric mental health crises in the emergency department.

Children with mental health problems are increasingly being evaluated and treated in pediatric clinical settings. This article focuses on the epidemiology, evaluation, and management of the 2 most common pediatric mental health emergencies, suicidal and homicidal/aggressive patients, as well as the equally challenging population of children with autism or other developmental disabilities.

Pediatric mental health emergencies and special health care needs.

Children with mental health problems are increasingly being evaluated and treated by both pediatric primary care and pediatric emergency physicians. This article focuses on the epidemiology, evaluation, and management of the 2 most common pediatric mental health emergencies, suicidal and homicidal/aggressive patients, as well as the equally challenging population of children with autism or other developmental disabilities.