Drug discovery for heart failure targeting myosin-binding protein C.

Cardiac MyBP-C (cMyBP-C) interacts with actin and myosin to fine-tune cardiac muscle contractility. Phosphorylation of cMyBP-C, which reduces the binding of cMyBP-C to actin and myosin, is often decreased in patients with heart failure (HF) and is cardioprotective in model systems of HF. Therefore, cMyBP-C is a potential target for HF drugs that mimic its phosphorylation and/or perturb its interactions with actin or myosin. We labeled actin with fluorescein-5-maleimide (FMAL) and the C0-C2 fragment of cMyBP-C (cC0-C2) with tetramethylrhodamine (TMR). We performed two complementary high-throughput screens (HTS) on an FDA-approved drug library, to discover small molecules that specifically bind to cMyBP-C and affect its interactions with actin or myosin, using fluorescence lifetime (FLT) detection. We first excited FMAL and detected its FLT, to measure changes in fluorescence resonance energy transfer (FRET) from FMAL (donor) to TMR (acceptor), indicating binding. Using the same samples, we then excited TMR directly, using a longer wavelength laser, to detect the effects of compounds on the environmentally sensitive FLT of TMR, to identify compounds that bind directly to cC0-C2. Secondary assays, performed on selected modulators with the most promising effects in the primary HTS assays, characterized the specificity of these compounds for phosphorylated versus unphosphorylated cC0-C2 and for cC0-C2 versus C1-C2 of fast skeletal muscle (fC1-C2). A subset of identified compounds modulated ATPase activity in cardiac and/or skeletal myofibrils. These assays establish the feasibility of the discovery of small-molecule modulators of the cMyBP-C-actin/myosin interaction, with the ultimate goal of developing therapies for HF.

Latent profile analysis reveals overlapping ARFID and shape/weight motivations for restriction in eating disorders.

BACKGROUND: DSM-5 differentiates avoidant/restrictive food intake disorder (ARFID) from other eating disorders (EDs) by a lack of overvaluation of body weight/shape driving restrictive eating. However, clinical observations and research demonstrate ARFID and shape/weight motivations sometimes co-occur. To inform classification, we: (1) derived profiles underlying restriction motivation and examined their validity and (2) described diagnostic characterizations of individuals in each profile to explore whether findings support current diagnostic schemes. We expected, consistent with DSM-5, that profiles would comprise individuals endorsing solely ARFID or restraint (i.e. trying to eat less to control shape/weight) motivations. METHODS: We applied latent profile analysis to 202 treatment-seeking individuals (ages 10-79 years [M = 26, s.d. = 14], 76% female) with ARFID or a non-ARFID ED, using the Nine-Item ARFID Screen (Picky, Appetite, and Fear subscales) and the Eating Disorder Examination-Questionnaire Restraint subscale as indicators. RESULTS: A 5-profile solution emerged: Restraint/ARFID-Mixed (n = 24; 8% [n = 2] with ARFID diagnosis); ARFID-2 (with Picky/Appetite; n = 56; 82% ARFID); ARFID-3 (with Picky/Appetite/Fear; n = 40; 68% ARFID); Restraint (n = 45; 11% ARFID); and Non-Endorsers (n = 37; 2% ARFID). Two profiles comprised individuals endorsing solely ARFID motivations (ARFID-2, ARFID-3) and one comprising solely restraint motivations (Restraint), consistent with DSM-5. However, Restraint/ARFID-Mixed (92% non-ARFID ED diagnoses, comprising 18% of those with non-ARFID ED diagnoses in the full sample) endorsed ARFID and restraint motivations. CONCLUSIONS: The heterogeneous profiles identified suggest ARFID and restraint motivations for dietary restriction may overlap somewhat and that individuals with non-ARFID EDs can also endorse high ARFID symptoms. Future research should clarify diagnostic boundaries between ARFID and non-ARFID EDs.

The potential role of occupational therapy in the treatment of avoidant/restrictive food intake disorder.

Most individuals with avoidant/restrictive food intake disorder (ARFID) never receive treatment, and treatment needs far exceed the current capacity of mental health services. Occupational therapy (OT) focuses on enhancing function in daily activities, including eating and feeding. Given OT's rich history in mental health and pediatric feeding disorder treatment, we spotlight the potential role of OT in ARFID treatment, current knowledge, and opportunities for future research. Through a preliminary exploratory inquiry involving a review of current literature and clinical practice, we investigated OT's current involvement, knowledge, and interprofessional collaborative practice gaps in ARFID treatment. While many occupational therapy practitioners (OTPs) engage in ARFID treatment, interventions lack rigorous evaluation, and there is limited evidence defining OT's distinct role in interprofessional ARFID treatment. OTPs are uniquely positioned to provide interventions for individuals with ARFID across the lifespan, though research is needed to evaluate the efficacy of OT interventions. Future research suggestions include standardizing OT approaches to ARFID treatment and conducting single-case experiments and randomized controlled trials to compare OT approaches with alternative methods. Recommendations to address practice gaps include enhancing ARFID education for OT students and practitioners and fostering a greater understanding of OT's role on the interprofessional team. PUBLIC SIGNIFICANCE: Individuals with ARFID face barriers to eating that impact their health and function. On a multidisciplinary team, OTPs can treat diverse client populations by identifying and addressing barriers to daily participation, such as physical impairments, trauma history, and environmental barriers. More research is needed to evaluate the efficacy of OT practices in ARFID treatment.

Lower region-specific gray matter volume in females with atypical anorexia nervosa and anorexia nervosa.

OBJECTIVE: Few studies have focused on brain structure in atypical anorexia nervosa (atypical AN). This study investigates differences in gray matter volume (GMV) between females with anorexia nervosa (AN) and atypical AN, and healthy controls (HC). METHOD: Structural magnetic resonance imaging data were acquired for 37 AN, 23 atypical AN, and 41 HC female participants. Freesurfer was used to extract GMV, cortical thickness, and surface area for six brain lobes and associated cortical regions of interest (ROI). Primary analyses employed linear mixed-effects models to compare group differences in lobar GMV, followed by secondary analyses on ROIs within significant lobes. We also explored relationships between cortical gray matter and both body mass index (BMI) and symptom severity. RESULTS: Our primary analyses revealed significant lower GMV in frontal, temporal and parietal areas (FDR < .05) in AN and atypical AN when compared to HC. Lobar GMV comparisons were non-significant between atypical AN and AN. The parietal lobe exhibited the greatest proportion of affected cortical ROIs in both AN versus HC and atypical AN versus HC. BMI, but not symptom severity, was found to be associated with cortical GMV in the parietal, frontal, temporal, and cingulate lobes. No significant differences were observed in cortical thickness or surface area. DISCUSSION: We observed lower GMV in frontal, temporal, and parietal areas, when compared to HC, but no differences between AN and atypical AN. This indicates potentially overlapping structural phenotypes between these disorders and evidence of brain changes among those who are not below the clinical underweight threshold. PUBLIC SIGNIFICANCE: Despite individuals with atypical anorexia nervosa presenting above the clinical weight threshold, lower cortical gray matter volume was observed in partial, temporal, and frontal cortices, compared to healthy individuals. No significant differences were found in cortical gray matter volume between anorexia nervosa and atypical anorexia nervosa. This underscores the importance of continuing to assess and target weight gain in clinical care, even for those who are presenting above the low-weight clinical criteria.

Cognitive-behavioral therapy for avoidant/restrictive food intake disorder: A proof-of-concept for mechanisms of change and target engagement.

BACKGROUND: Cognitive-behavioral therapy for avoidant/restrictive food intake disorder (ARFID; CBT-AR) theoretically targets three prototypic motivations (sensory sensitivity, lack of interest/low appetite, fear of aversive consequences), aligned with three modularized interventions. As an exploratory investigation, we: (1) evaluated change in candidate mechanisms in relationship to change in ARFID severity, and (2) tested if assignment (vs. not) to a module resulted in larger improvements in the corresponding mechanism. METHOD: Males and females (N = 42; 10-55 years) participated in an open trial of CBT-AR. RESULTS: Decreases in scaled scores for each candidate mechanism had medium to large correlations with decreases in ARFID severity-sensory sensitivity: -0.7 decrease (r = .42, p = .01); lack of interest/low appetite: -0.3 decrease (r = .60, p < .0001); and fear of aversive consequences: -1.1 decrease (r = .33, p = .05). Linear mixed models revealed significant weekly improvements for each candidate mechanism across the full sample (ps < .0001). There were significant interactions for the sensory and fear of aversive consequences modules-for each, participants who received the corresponding module had significantly larger decreases in the candidate mechanism than those who did not receive the module. DISCUSSION: Sensory sensitivity and fear of aversive consequences improved more if the CBT-AR module was received, but lack of interest/low appetite may improve regardless of receipt of the corresponding module. Future research is needed to test target engagement in CBT-AR with adaptive treatment designs, and to identify valid and sensitive measures of candidate mechanisms. PUBLIC SIGNIFICANCE: The mechanisms through which components of CBT-AR work have yet to be elucidated. We conducted an exploratory investigation to test if assignment (vs. not) to a CBT-AR module resulted in larger improvements in the corresponding prototypic ARFID motivation that the module intended to target. Measures of the sensory sensitivity and the fear of aversive consequences motivations improved more in those who received the corresponding treatment module, whereas the lack of interest/low appetite measure improved regardless of if the corresponding module was received.

Medical Comorbidities, Nutritional Markers, and Cardiovascular Risk Markers in Youth With ARFID.

OBJECTIVE: Avoidant/restrictive food intake disorder (ARFID) is common among populations with nutrition-related medical conditions. Less is known about the medical comorbidity/complication frequencies in youth with ARFID. We evaluated the medical comorbidities and metabolic/nutritional markers among female and male youth with full/subthreshold ARFID across the weight spectrum compared with healthy controls (HC). METHOD: In youth with full/subthreshold ARFID (n = 100; 49% female) and HC (n = 58; 78% female), we assessed self-reported medical comorbidities via clinician interview and explored abnormalities in metabolic (lipid panel and high-sensitive C-reactive protein [hs-CRP]) and nutritional (25[OH] vitamin D, vitamin B12, and folate) markers. RESULTS: Youth with ARFID, compared with HC, were over 10 times as likely to have self-reported gastrointestinal conditions (37% vs. 3%; OR = 21.2; 95% CI = 6.2-112.1) and over two times as likely to have self-reported immune-mediated conditions (42% vs. 24%; OR = 2.3; 95% CI = 1.1-4.9). ARFID, compared with HC, had a four to five times higher frequency of elevated triglycerides (28% vs. 12%; OR = 4.0; 95% CI = 1.7-10.5) and hs-CRP (17% vs. 4%; OR = 5.0; 95% CI = 1.4-27.0) levels. DISCUSSION: Self-reported gastrointestinal and certain immune comorbidities were common in ARFID, suggestive of possible bidirectional risk/maintenance factors. Elevated cardiovascular risk markers in ARFID may be a consequence of limited dietary variety marked by high carbohydrate and sugar intake.

Assessing clinician competence in the delivery of cognitive-behavioural therapy for eating disorders: development of the Cognitive-Behavioural Therapy Scale for Eating Disorders (CBTS-ED).

Evidence-based cognitive-behaviour therapy for eating disorders (CBT-ED) differs from other forms of CBT for psychological disorders, making existing generic CBT measures of therapist competence inadequate for evaluating CBT-ED. This study developed and piloted the reliability of a novel measure of therapist competence in this domain-the Cognitive Behaviour Therapy Scale for Eating Disorders (CBTS-ED). Initially, a team of CBT-ED experts developed a 26-item measure, with general (i.e. present in every session) and specific (context- or case-dependent) items. To determine statistical properties of the measure, nine CBT-ED experts and eight non-experts independently observed six role-played mock CBT-ED therapy sessions, rating the therapists' performance using the CBTS-ED. The inter-item consistency (Cronbach's alpha and McDonald's omega) and inter-rater reliability (ICC) were assessed, as appropriate to the clustering of the items. The CBTS-ED demonstrated good internal consistency and moderate/good inter-rater reliability for the general items, at least comparable to existing generic CBT scales in other domains. An updated version is proposed, where five of the 16 "specific" items are reallocated to the general group. These preliminary results suggest that the CBTS-ED can be used effectively across both expert and non-expert raters, though less experienced raters might benefit from additional training in its use.

Zika Virus Disease and Pregnancy Outcomes in Colombia.

BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

Research Inclusion Across the Lifespan: A Good Start, but There Is More Work to Be Done.

While older adults account for a disproportionate amount of healthcare spending, they are often underrepresented in clinical research needed to guide clinical care. The purpose of this perspective is to make readers aware of new data on age at enrollment for participants included in National Institutes of Health (NIH)-funded clinical research. We highlight key findings of relevance to general internal medicine and suggest ways readers could support the inclusion of older adults in clinical research. Data from the NIH Research Inclusion Statistics Report show that there were 881,385 participants enrolled in all NIH-funded clinical research in 2021, of whom 170,110 (19%) were 65 years and older. However, on average, studies included a far lower percentage of older adults. Additionally, there were many conditions for which overall enrollment rates for older adults were lower than would be expected. For example, while 10% of participants in studies related to diabetes were ≥ 65 years old, older individuals represent 43% of all prevalent diabetes in the USA. Researchers should work with clinicians to advocate for older adults and ensure their participation in clinical research. Best practices and resources for overcoming common barriers to the inclusion of older adults in research could also be disseminated.

The Intersection of Disorders of Gut-Brain Interaction With Avoidant/Restrictive Food Intake Disorder.

High rates of overlap exist between disorders of gut-brain interaction (DGBI) and eating disorders, for which common interventions conceptually conflict. There is particularly increasing recognition of eating disorders not centered on shape/weight concerns, specifically avoidant/restrictive food intake disorder (ARFID) in gastroenterology treatment settings. The significant comorbidity between DGBI and ARFID highlights its importance, with 13% to 40% of DGBI patients meeting full criteria for or having clinically significant symptoms of ARFID. Notably, exclusion diets may put some patients at risk for developing ARFID and continued food avoidance may perpetuate preexisting ARFID symptoms. In this review, we introduce the provider and researcher to ARFID and describe the possible risk and maintenance pathways between ARFID and DGBI. As DGBI treatment recommendations may put some patients at risk for developing ARFID, we offer recommendations for practical treatment management including evidence-based diet treatments, treatment risk counseling, and routine diet monitoring. When implemented thoughtfully, DGBI and ARFID treatments can be complementary rather than conflicting.

Assessment and Treatment of Avoidant/Restrictive Food Intake Disorder.

PURPOSE OF REVIEW: To review the literature pertaining to the assessment and treatment of avoidant/restrictive food intake disorder (ARFID) ten years following its introduction to DSM-5. RECENT FINDINGS: Several structured clinical interviews for assessing ARFID have been developed, each with its own strengths and limitations. There is no clear leading self-report measure for tracking treatment progress and outcome in ARFID. Medical assessment is comprised of examining anthropometrics, vitamin deficiencies, and other comorbidities. To date, several studies have reported on cognitive behavioral therapy, family-based treatment, and other approaches to the treatment of ARFID. These treatments appear promising; however, they rely on data from clinical case series and very small randomized controlled trials. Several promising assessments and treatments for ARFID are in the early stages of research. Yet, controversies remain. These include (a) overlap with criteria for pediatric feeding disorder; (b) the optimal method for assessing nutrient deficiencies; (c) disciplines involved in treatment. Future research innovation is necessary to improve the psychometric properties of ARFID assessments and evaluate treatment efficacy with larger samples and randomized designs.

A proposed trumping scheme for other specified feeding or eating disorder: Comment on Walsh et al., 2023.

The recent systematic review by Walsh, Hagan, & Lockwood (Int J Eat Disord, 2022) highlights the importance of further distinguishing atypical anorexia nervosa (atypical AN) from other feeding and eating disorders. The lack of a trumping scheme within other specified feeding or eating disorder (OSFED) hinders intervention selection in the clinical context and reduces reliability of diagnostic classification in research samples. Thus, we propose a trumping scheme within OSFED that mirrors the existing diagnostic algorithm in the main DSM-5-TR feeding and eating disorders section. According to this scheme, a diagnosis of atypical AN would override all other OSFED subcategories. Subthreshold bulimia nervosa (BN) would trump subthreshold binge-eating disorder (BED) and purging disorder; purging disorder would trump subthreshold BED and night eating syndrome; night eating syndrome would trump subthreshold BED; and subthreshold BED would trump subthreshold avoidant/restrictive food intake disorder (ARFID)-a novel presentation that we propose adding under the OSFED umbrella to parallel the existing subthreshold classifications for the main feeding and eating disorders. We hope this proposed OSFED trumping scheme will improve intervention selection and diagnostic reliability in clinical and research contexts, and serve as a catalyst for future research on these newly recognized-but common and impairing-feeding and eating disorder presentations.

Development of a brief cognitive-behavioral treatment for avoidant/restrictive food intake disorder in the context of disorders of gut-brain interaction: Initial feasibility, acceptability, and clinical outcomes.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) symptoms are common (up to 40%) among adults with disorders of gut-brain interaction (DGBI), but treatments for this population (DGBI + ARFID) have yet to be evaluated. We aimed to identify initial feasibility, acceptability, and clinical effects of an exposure-based cognitive-behavioral treatment (CBT) for adults with DGBI + ARFID. METHODS: Patients (N = 14) received CBT as part of routine care in an outpatient gastroenterology clinic. A two-part investigation of the CBT included a retrospective evaluation of patients who were offered a flexible (8-10) session length and an observational prospective study of patients who were offered eight sessions. Feasibility benchmarks were ≥75% completion of sessions, quantitative measures (for treatment completers), and qualitative interviews. Acceptability was assessed with a benchmark of ≥70% patients reporting a posttreatment satisfaction scores ≥3 on 1-4 scale and with posttreatment qualitative interviews. Mixed model analysis explored signals of improvement in clinical outcomes. RESULTS: All feasibility and acceptability benchmarks were achieved (and qualitative feedback revealed high satisfaction with the treatment and outcomes). There were improvements in clinical outcomes across treatment (all p's < .0001) with large effects for ARFID fear (-52%; Hedge's g = 1.5; 95% CI = 0.6, 2.5) and gastrointestinal-specific anxiety (-42%; Hedge's g = 1.0; 95% CI = 0.5, 16). Among those who needed to gain weight (n = 10), 94%-103% of expected weight gain goals were achieved. DISCUSSION: Initial development and testing of a brief 8-session CBT protocol for DGBI + ARFID showed high feasibility, acceptability, and promising clinical improvements. Findings will inform an NIH Stage 1B randomized control trial. PUBLIC SIGNIFICANCE: While cognitive-behavioral treatments (CBTs) for ARFID have been created in outpatient feeding and eating disorder clinics, they have yet to be developed and refined for other clinic settings or populations. In line with the recommendations for behavioral treatment development, we conducted a two-part investigation of an exposure-based CBT for a patient population with high rates of ARFID-adults with disorders of gut-brain interaction (also known as functional gastrointestinal disorders). We found patients had high satisfaction with treatment and there were promising improvements for both gastrointestinal and ARFID outcomes. The refined treatment includes eight sessions delivered by a behavioral health care provider and the findings reported in this article will be studied next in an NIH Stage 1B randomized controlled trial.

Assessing community response to wildfire smoke: A multimethod study using social media.

OBJECTIVE: The purpose of this study was to assess health-related responses to wildfire smoke on social media. We examined whether seasonal wildfire smoke is an active topic on Twitter, the correlation between fine particulate matter (PM2.5 ) and Twitter search terms, and dimensions of community-level expression to wildfire smoke through tweets. DESIGN: Search terms were identified using a conceptual model developed and refined by healthcare providers and public health experts. Wildfire-related tweets were downloaded from Twitter users in Spokane, Washington during the 2017 and 2018 wildfire seasons. PM2.5 data were correlated with the search terms. A subset of tweets was deductively and then inductively coded to identify perceptions and behavioral responses to wildfire smoke. RESULTS: Seasonal wildfire smoke is an active topic on Twitter. The term "smoke" was strongly correlated with poor air quality and "unhealthy" was moderately correlated. Deductive analyses revealed a multidimensional response to wildfire smoke. Inductive analysis identified new areas of concern, such as pet and animal health. CONCLUSIONS: Social media is a lens through which public health professionals can assess and respond to local community needs. Findings will be used to broaden the conceptual model, enhance ongoing surveillance of community-identified health risks, and communicate protective actions.

A web-based personalized decision support tool for patients diagnosed with ductal carcinoma in situ: development, content evaluation, and usability testing.

PURPOSE: Patients diagnosed with ductal carcinoma in situ (DCIS) face trade-offs when deciding among different treatments, including surgery, radiation, and endocrine therapy. A less chosen option is active monitoring. While evidence from clinical trials is not yet available, observational studies show comparable results for active monitoring and immediate treatment on cancer outcomes in select subgroups of patients. We developed and tested a web-based decision support tool (DST) to help patients explore current knowledge about DCIS and make an informed choice. METHODS: The DST, an interactive web application, was informed by literature reviews and formative work with patients, breast surgeons, and health communication experts. We conducted iterative interviews to evaluate the DST content among women with and without a history of breast cancer, as well as breast cancer experts. For usability testing, we conducted an online survey among women with and without a history of breast cancer. RESULTS: For content evaluation, 5 women with and 10 women without a history of DCIS were interviewed. The sample included 11 White and 4 non-White women, with a mean age of 64 years. The expert sample consisted of 5 attendings and a physician assistant. The feedback was used to add, clarify, or reorganize information in the DST. For usability testing, 22 participants with a mean age of 61 years were recruited including 15 White and 7 Black women and 6 women with a history of DCIS. The mean usability score was 3.7 out of 5. Most participants (86%) found that the DST provided unbiased information about treatments. To improve usability, we reduced the per-page content and added navigation cues. CONCLUSION: Content and usability evaluation showed that the DST helps patients explore trade-offs of active monitoring and immediate treatment. By adopting a personalized approach, the tool will enable informed decisions aligned with patients' values and expectations.

Direct Real-Time PCR for the Detection and Serotyping of Haemophilus influenzae without DNA Extraction.

To monitor the burden and changes in Haemophilus influenzae (Hi) disease, direct real-time PCR (drt-PCR) assays have been developed for Hi detection in monoplex form and its six serotypes in triplex form, directly from cerebrospinal fluid (CSF) specimens. These assays target the phoB gene for the species detection (Hi-phoB) and serotype-specific genes in region II of the capsule biosynthesis locus (Hi-abf and Hi-cde), identified through comparative analysis of Hi and non-Hi whole-genome sequences. The lower limit of detection (LLD) is 293 CFU/mL for the Hi-phoB assay and ranged from 11 to 130 CFU/mL for the triplex serotyping assays. Using culture as a reference method, the sensitivity and specificity of Hi-phoB, Hi-abf, and Hi-cde were 100%. Triplex serotyping assays also showed 100% agreement for each serotype compared to their corresponding monoplex serotyping assay. These highly sensitive and specific drt-PCR assays do not require DNA extraction and thereby reduce the time, cost, and handling required to process CSF specimens. Furthermore, triplex drt-PCR assays combine the detection of three serotypes in a single reaction, further improving testing efficiency, which is critical for laboratories that process high volumes of Hi specimens for surveillance and diagnostic purposes.

A neonatal neuroNICU collaborative approach to neuromonitoring of posthemorrhagic ventricular dilation in preterm infants.

Morbidity and mortality in prematurely born infants have significantly improved due to advancement in perinatal care, development of NeuroNICU collaborative multidisciplinary approaches, and evidence-based management protocols that have resulted from a better understanding of perinatal risk factors and neuroprotective treatments. In premature infants with intraventricular hemorrhage (IVH), the detrimental secondary effect of posthemorrhagic ventricular dilation (PHVD) on the neurodevelopmental outcome can be mitigated by surgical intervention, though management varies considerably across institutions. Any benefit derived from the use of neuromonitoring to optimize surgical timing and technique stands to improve neurodevelopmental outcome. In this review, we summarize (1) the approaches to surgical management of PHVD in preterm infants and outcome data; (2) neuromonitoring modalities and the effect of neurosurgical intervention on this data; (3) our resultant protocol for the monitoring and management of PHVD. In particular, our protocol incorporates cerebral near-infrared spectroscopy (NIRS) and transcranial doppler ultrasound (TCD) to better understand cerebral physiology and to enable the hypothesis-driven study of the management of PHVD. IMPACT: Review of the published literature concerning the use of near-infrared spectroscopy (NIRS) and a cerebral Doppler ultrasound to study the effect of cerebrospinal fluid drainage on infants with posthemorrhagic ventricular dilation. Presentation of our institution's evidence-based protocol for the use of NIRS and cerebral Doppler ultrasound to study the optimal neurosurgical treatment of posthemorrhagic ventricular dilation, an as yet inadequately studied area.

Effects of prenatal alcohol and delta-9-tetrahydrocannabinol exposure via electronic cigarettes on motor development.

BACKGROUND: Prenatal alcohol exposure can lead to a wide range of neurological and behavioral deficits, including alterations in motor domains. However, much less is known about the effects of prenatal cannabis exposure on motor development, despite cannabis being the most consumed illicit drug among women. Cannabis use among pregnant women has become increasingly popular given the widespread perception that consumption is safe during pregnancy. Moreover, alcohol and cannabis are commonly used together, even among pregnant women. Yet few studies have explored the potential consequences of combined prenatal exposure on behavioral domains. METHODS: Using our previously established model, during gestational days 5 to 20, four groups of pregnant Sprague-Dawley rats were exposed to vaporized alcohol, delta-9-Tetrahydrocannabinol (THC) via electronic (e-) cigarettes, the combination of alcohol and THC, or a vehicle. Following birth, offspring were tested on early sensorimotor development, adolescent motor coordination, and adolescent activity levels. RESULTS: Prenatal THC e-cigarette exposure delayed sensorimotor development early in life and impaired motor coordination later in early adolescence; combined prenatal alcohol and THC exposure did not have additive effects on sensorimotor development. However, combined prenatal exposure produced hyperactivity among male offspring. CONCLUSIONS: Prenatal cannabis exposure may lead to impaired motor skills throughout early development and combined exposure with alcohol during gestation may lead to hyperactivity in early adolescence. These findings have important implications for informing pregnant women of the risks to the fetus associated with prenatal cannabis exposure, with and without alcohol, and could influence public policy.

Early developmental alcohol exposure alters behavioral outcomes following adolescent re-exposure in a rat model.

BACKGROUND: Prenatal alcohol exposure alters brain development, affecting cognitive, motor, and emotional domains, and potentially leading to greater alcohol intake during adolescence. The present study investigated whether early alcohol exposure modifies vulnerability to behavioral alterations associated with adolescent alcohol exposure in a rodent model. METHODS: Sprague-Dawley rats received ethanol or sham intubations during two developmental periods: (1) the third trimester equivalent of brain development in humans (postnatal days [PD] 4-9) and (2) adolescence (PD 28-42). Both exposures resulted in blood alcohol concentrations around 200 mg/dl. Subjects were tested in the open field (PD 45-48) and on hippocampal and prefrontal cortical (PFC) dependent tasks: the Morris water maze (PD 52-58) and trace fear conditioning (PD 63-64). RESULTS: Neonatal alcohol exposure reduced forebrain and cerebellar weight, increased open-field activity, and slowed acquisition of trace fear conditioning. Adolescent alcohol exposure did not disrupt learning or significantly induce gross brain pathology, suggesting that 200 mg/dl/day of ethanol disrupts cognitive development during the 3rd trimester equivalent, but not during adolescence. Interestingly, females exposed to alcohol only during adolescence exhibited an increased conditioned fear response and more rapid habituation of locomotor activity in the open field, suggesting alterations in emotional responding. Moreover, subjects exposed to a combination of neonatal and adolescent alcohol exposure spent significantly more time in the center of the open field chamber than other groups. Similarly, males exposed to the combination exhibited less thigmotaxis in the Morris water maze. CONCLUSIONS: These results indicate that combined exposure to alcohol during these two critical periods reduces anxiety-related behaviors and/or increases risk taking in a sex-dependent manner, suggesting that prenatal alcohol exposure may affect risk for emotional consequences of adolescent alcohol exposure.

Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Pediatric Neurogastroenterology Patients.

ABSTRACT: Recent reports document avoidant/restrictive food intake disorder (ARFID) symptoms among 13-40% of adults presenting to neurogastroenterology clinics, but ARFID in pediatrics is understudied. We conducted a retrospective review of charts from 129 consecutive referrals (ages 6-18 years; 57% female) for pediatric neurogastroenterology examination, from January 2016 through December 2018. Eleven cases (8%) met the full criteria for ARFID by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition and 19 cases (15%) had clinically significant avoidant/ restrictive eating behaviors with insufficient information for a definitive ARFID diagnosis. Of patients with ARFID symptoms (n = 30), 20 (67%) cited fear of gastrointestinal symptoms as motivation for their avoidant/ restrictive eating. Compared to patients without ARFID symptoms, patients with ARFID symptoms were older (P  < .001), more likely to be female (51% vs 79%, P  = 0.014), and more frequently presented with eating/weight-related complaints (15% vs 33%, P  = 0.026). This pilot retrospective study showed ARFID symptoms present in 23% of pediatric neurogastroenterology patients; further research is needed to understand risk and maintenance factors of ARFID in the neurogastroenterology setting.