Prazosin use in a patient with rare Neurobeachin gene deletion shows improvement in paranoid behavior: a case report

Background Disruption of the Neurobeachin gene is a rare genetic mutation that has been implicated in the development of autism and enhanced long-term potentiation of the hippocampal CA1 region, causing a heightened conditioned fear response and impaired fear extinction. Prazosin, an alpha-1 receptor antagonist, has been used in patients with posttraumatic stress disorder to mitigate the increased alpha-1 activity involved in fear and startle responses. Here we report a case of a patient with a rare Neurobeachin gene deletion, who demonstrated marked and sustained improvement in paranoid behavior within days of prazosin initiation. Case presentation The patient is a 27-year-old White male with autism spectrum disorder, obsessive–compulsive disorder, and schizophrenia, with a chromosome 13q12 deletion including deletion of the Neurobeachin gene, who presented to the emergency department due to worsening functional status and profound weight loss as a result of only eating prepackaged foods. He had not showered or changed clothes in several months prior to presentation. He was hospitalized in the inpatient psychiatric unit for 2 months before prazosin was initiated. During that time, he demonstrated paranoia as evidenced by heightened sensitivity to doors opening, guarded interactions, and limited communication with providers and other patients. He also exhibited poor grooming habits, with aversion to showering, shaving, and changing clothes. Since initiating prazosin, he has demonstrated a brighter affect, initiates and maintains conversations, showers and changes clothes on a regular basis, and eats a variety of foods. At the time of this report, the patient was discharged to live in an apartment with a caregiver after a 7-month inpatient hospitalization. Conclusions Low-dose prazosin shows rapid and sustained improvement in paranoid behavior in a patient with a rare Neurobeachin gene deletion. Prazosin has a relatively favorable side effect profile with once-daily dosing and low cost. Prazosin may provide clinical improvement in patients with Neurobeachin gene deletions due to its theoretical attenuation in fear response through alpha-1 antagonism.

Framework for Systemic Change in Undergraduate STEM Teaching and Learning

The Framework for Systemic Change in Undergraduate STEM Teaching and Learning provides a change model for improving the quality and effectiveness of STEM teaching and learning at research universities. The Framework recognizes the wider setting in which educational innovations take place — the department, the college, the university and the external environment — and addresses key institutional elements necessary for sustained improvement to undergraduate STEM education.

Lung Recruitment Using High-Frequency Oscillation Volume Guarantee in Preterm Infants with Evolving Bronchopulmonary Dysplasia

<b><i>Background:</i></b> Stepwise lung recruitment maneuvers (LRMs) may be used in ventilated preterm infants. However, its use in high-frequency oscillation with volume guarantee (HFO-VG) is not well studied. <b><i>Methods:</i></b> Preterm infants treated with HFO-VG who had LRMs were identified. Patient and respiratory parameters were recorded. <b><i>Results:</i></b> Ten infants, median GA 25⁺⁶ (IQR 24⁺²–27⁺⁰) weeks, and 21 LRMs were identified. LRMs were performed at a median age of 26 days, with a starting MAP of 16 (14–17) cm H₂O and the highest MAP of 23.5 (22.0–24.8) cm H₂O. Most (76%) resulted in immediate improved SpO₂/FiO_2. There were no sustained differences in median oxygen saturation index (8.4 vs. 9, <i>p</i> = 0.09), SpO₂/FiO₂ (1.8 vs. 1.8, <i>p</i> = 0.8), ∆P (21 vs. 23, <i>p</i> = 0.64), or transcutaneous CO₂ (58 vs. 60, <i>p</i> = 0.84) in 24 h before and after LRMs. <b><i>Conclusions:</i></b> In preterm infants with evolving bronchopulmonary dysplasia, LRMs on HFO-VG did not result in sustained improvement to oxygenation or ventilation.

Time to put a spotlight on out-patient chronotherapy for depression

Summary The challenge of identifying efficacious out-patient treatments for depression is amplified by the increasing desire to find interventions that reduce the time to sustained improvement. One potential but underexplored option is triple chronotherapy (TCT). To date, use of TCT has been largely restricted to specialist units or in-patients. Recent research demonstrates that it may be possible to undertake sleep deprivation in out-patient settings, raising the possibility of delivering TCT to broader populations of individuals with depression. Emerging evidence suggests that out-patient TCT is a high-benefit, low-risk intervention but questions remain about how to target TCT and its mechanisms of action. Like traditional antidepressants, TCT probably acts through several pathways, especially the synchronisation of the ‘master clock’. Availability of reliable and valid methods of out-patient measurement of intra-individual circadian rhythmicity and light exposure are rate-limiting steps in the wider dissemination of TCT.

Long-term follow-up of a randomized clinical trial comparing glycemic excursion minimization (GEM) to weight loss (WL) in the management of type 2 diabetes

IntroductionWe previously reported the physical, psychological and behavioral 3-month post-treatment results of a randomized controlled trial comparing glycemic excursion minimization (GEM) versus conventional weight loss (WL) therapy in the management of type 2 diabetes (T2D). GEM is a paradigm shift in the lifestyle management of T2D that focuses on reducing postnutrient glucose excursions, rather than reducing weight. We now present the 13-month follow-up results.Research design and methodsThe initial study sample of 172 were 30–80 years old, had T2D for ≤10 years, an HbA1c ≥6.8% (51 mmol/mol), and were not using insulin. Participants were randomized to 6 hours of group treatment, either to WL or one of three versions of GEM. GEM groups differed in degree of blood glucose (BG) feedback provided during treatment: no recommended feedback, systematic capillary BG feedback before and after nutrient intake and physical activity, or continuous glucose monitoring. Since these GEM groups did not differ in pre-post improvement they were combined for initial and current analyses. Of those who completed the 3-month postassessment, 100% and 96% of the WL and GEM participants completed the 13-month follow-up assessment.ResultsPre to follow-up within-group comparisons indicated WL participants sustained improvement in body mass index (BMI) (−0.9±1.4, p=0.001). GEM participants continued to benefit in their HbA1c (−0.5±1.4, p<0.001), BMI (−1±1, p<0.001), high-density lipoprotein (p<0.001), reduction of carbohydrate ingestion (p<0.001), self-monitoring of blood glucose satisfaction (p<0.001) and frequency (p<0.001), diabetes knowledge (p<0.001), diabetes empowerment (p<0.001), and both diabetes distress emotional (p=0.009) and regimen (p=0.001) subscales. Forty-two percent and 52% of WL and GEM participants, respectively, were classified as responders (individuals whose A1c dropped by at least −0.5%), with a mean HbA1c reduction of −1.2% and −1.5%. Neither WL nor GEM responders differed from non-responders in baseline demographics, psychological or disease severity variables. While WL responders could not be predicted, 73% of GEM responders were predicted by post minus pretreatment reductions of HbA1c, diabetes medication and BMI.ConclusionsWhile WL sustained improvement in BMI, GEM sustained benefits across a broad range of physical, behavioral and psychological parameters, beneficial for clinicians and adults with T2D. This may be especially relevant for primary care physicians who manage about 90% of patients with T2D.Trial registration numberNCT03196895.