This case study series investigated a new treatment for paradoxical insomnia patients as there is no standard treatment for this patient group at this time. Four paradoxical insomnia patients had a polysomnography (PSG) sleep study, an unsuccessful brief course of behavioral treatment for insomnia, and then a novel sleep education treatment comprising review of their PSG with video and exploration of the discrepancy between their reported and observed sleep experience. Two patients responded well to sleep education, mainly with improved self-reported sleep onset latency, total sleep time, and Insomnia Severity Index scores; and the other two, who exhibited sleep architecture anomalies, were unresponsive. These findings suggest that sleep education holds promise for some paradoxical insomnia patients. Suggestions for future studies are given.

Eye movements during stage 2, 3, and 4 sleep have been associated with the use of several selective serotonin reuptake inhibitor (SSRI) medications. This activity has been postulated to be a serotonin effect. The authors identified all cases of nonrapid eye movement (NREM) eye movements observed over a 36-month period in an accredited hospital-based sleep center and then correlated the findings with the patient's medications. The polysomnogram (PSG) studies of 2,959 consecutive adults were evaluated prospectively to identify all patients with atypical eye movements which occurred during NREM sleep. Standard recording, staging and arousal scoring methods were used. The use of antidepressants and neuroleptic medications was recorded for each patient. Eye movements in NREM sleep were detected in 94 PSGs. Of these, 73 patients (78%) were taking a SSRI at the time of the study, and 6 (6%) had taken a SSRI in the past. Thirty-six percent of patients (73 of 201) taking a SSRI had abnormal NREM eye movements on PSG. Other classes of antidepressants, neuroleptics, and benzodiazepines showed a much lower incidence of NREM eye movements. Mirtazapine was rarely related to NREM eye movements. Clonazepam and zolpidem were not associated with atypical eye movements unless used in combination with SSRI medications. Selective serotonin reuptake inhibitors was associated with atypical NREM eye movements, even when the medication had been discontinued months to years before the PSG. Atypical NREM eye movements appear to be related primarily to serotonin and less prominently to dopaminergic medication effects.

Background: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. Methods: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. Results: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:2²¹ (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (p < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (p < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. Conclusions: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.

The study of human microbiomes has yielded insights into basic science, and applied therapeutics are emerging. However, conflicting definitions of what microbiomes are and how they affect the health of the “host” are less understood. A major impediment towards systematic design, discovery, and implementation of targeted microbiome therapeutics is the continued reliance on taxonomic indicators to define microbiomes in health and disease. Such reliance often confounds analyses, potentially suggesting associations where there are none, and conversely failing to identify significant, causal relationships. This review article discusses recent discoveries pointing towards a molecular understanding of microbiome “dysbiosis” and away from a purely taxonomic approach. We highlight the growing role of systems biological principles in the complex interrelationships between the gut microbiome and host cells, and review current approaches commonly used in targeted microbiome therapeutics, including fecal microbial transplant, bacteriophage therapies, and the use of metabolic toxins to selectively eliminate specific taxa from dysbiotic microbiomes. These approaches, however, remain wholly or partially dependent on the bacterial taxa involved in dysbiosis, and therefore may not capitalize fully on many therapeutic opportunities presented at the bioactive molecular level. New technologies capable of addressing microbiome-associated diseases as molecular problems, if solved, will open possibilities of new classes and categories of targeted microbiome therapeutics aimed, in principle, at all dysbiosis-driven disorders.

Background: Short sleep and obstructive sleep apnea are underrecognized strains on the public health infrastructure. In the United States, over 35% of adults report short sleep and more than 80% of individuals with obstructive sleep apnea remain undiagnosed. The associations between inadequate sleep and cardiometabolic disease risk factors have garnered increased attention. However, challenges persist in modeling sleep-associated cardiometabolic disease risk factors. Objective: This study aimed to report early findings from the Short Sleep Undermines Cardiometabolic Health-Public Health Observational study (SLUMBRx-PONS). Methods: Data for the SLUMBRx-PONS study were collected cross-sectionally and longitudinally from a nonclinical, rural community sample (n=47) in the southeast United States. Measures included 7 consecutive nights of wrist-based actigraphy (eg, mean of 7 consecutive nights of total sleep time [TST7N]), 1 night of sleep apnea home testing (eg, apnea-hypopnea index [AHI]), and a cross-sectional clinical sample of anthropometric (eg, BMI), cardiovascular (eg, blood pressure), and blood-based biomarkers (eg, triglycerides and glucose). Correlational analyses and regression models assessed the relationships between the cardiometabolic disease risk factors and the sleep indices (eg, TST7N and AHI). Linear regression models were constructed to examine associations between significant cardiometabolic indices of TST7N (model 1) and AHI (model 2). Results: Correlational assessment in model 1 identified significant associations between TST7N and AHI (r=–0.45, P=.004), BMI (r=–0.38, P=.02), systolic blood pressure (r=0.40, P=.01), and diastolic blood pressure (r=0.32, P=.049). Pertaining to model 1, composite measures of AHI, BMI, systolic blood pressure, and diastolic blood pressure accounted for 25.1% of the variance in TST7N (R2adjusted=0.25; F2,38=7.37; P=.002). Correlational analyses in model 2 revealed significant relationships between AHI and TST7N (r=–0.45, P<.001), BMI (r=0.71, P<.001), triglycerides (r=0.36, P=.03), and glucose (r=0.34, P=.04). Results from model 2 found that TST7N, triglycerides, and glucose accounted for 37.6% of the variance in the composite measure of AHI and BMI (R2adjusted=0.38; F3,38=8.63; P<.001). Conclusions: Results from the SLUMBRx-PONS study highlight the complex interplay between sleep-associated risk factors for cardiometabolic disease. Early findings underscore the need for further investigations incorporating the collection of clinical, epidemiological, and ambulatory measures to inform public health, health promotion, and health education interventions addressing the cardiometabolic consequences of inadequate sleep. International Registered Report Identifier (IRRID): RR2-10.2196/27139