Keep it simple: A novel technique for measuring airflow using a wireless patch.

OBJECTIVES: Despite the growing use of home sleep testing for obstructive sleep apnea (OSA), there are significant barriers that make it difficult for patients. This study aimed to evaluate a new set of wireless patches for the detection of OSA as compared to polysomnography (PSG) respiratory signals. Safety was also evaluated. METHODS: Patients (n = 25; mean age = 51.3; SD = 15.6) undergoing standard PSG evaluation for OSA wore 2 device patches applied on the chest and abdomen to provide surrogates of respiratory effort and derived airflow. Two sets of respiratory data (with common SpO2 and heart rate as a reference from PSG) were created, one from PSG and one from the device patches. Data were scored by a Registered Polysomnographic Technologist. Linear regression analyses and Bland-Altman plots were used to compare the two derived apnea-hypopnea indices (AHI). Bench testing was performed to determine whether the device patch respiratory signal accuracy remained consistent for different body characteristics. RESULTS: There was a significant correlation for AHI between the device patch and PSG (r = 0.979; P < .001; 95% CI 0.952, 1.00). There were also significant correlations between PSG and the device patch for supine AHI (r = 0.866, P < .001, 95% CI 0.610, 0.965) and nonsupine AHI (r = 0.983; <0.001, 95% CI 0.954, 1.00). No differences in respiratory signal accuracy were found with bench testing comparison groups. CONCLUSIONS: These preliminary results suggest that the device patch may be an effective way to measure respiratory dynamics, including derived airflow, to evaluate OSA. Results show promise as a new innovative method for home sleep testing.

Validation of a novel Psychosis-Implicit Association Test (P-IAT) as a diagnostic support tool.

Despite significant advances in early-intervention services for psychosis, delays in identifying patients continue to impede the delivery of prompt and effective treatments. We sought to develop and preliminarily validate a self-administered psychosis implicit association task (P-IAT) as a screening and diagnostic support tool for identifying individuals with psychotic illness in community settings. The P-IAT is a response latency task, designed to measure the extent to which individuals implicitly associate psychosis-related terms with the "self." The P-IAT was administered to 57 participants across 3 groups: healthy controls (N=19), inpatients hospitalized with active psychosis (N=19), and outpatients with psychotic disorders (N=19). Mean D-scores (the output of the task) differed significantly between the illness groups and healthy controls (Mann-Whitney U=138, p<.001). A receiver operating curve was plotted to assess the performance of D-scores in predicting a psychosis diagnosis, yielding an area under the curve of 0.81. When participant D-scores exceeded -0.24, the test achieved a specificity of 100% (sensitivity: 47%), with all 18 participants scoring above this threshold belonging to the illness groups. The discriminant performance of the P-IAT suggests its potential to augment existing screening instruments and inform referral decision making, particularly in settings with limited access to specialist providers.

Internet Search Activity of Young People With Mood Disorders Who Are Hospitalized for Suicidal Thoughts and Behaviors: Qualitative Study of Google Search Activity.

BACKGROUND: Little is known about the internet search activity of people with suicidal thoughts and behaviors (STBs). This data source has the potential to inform both clinical and public health efforts, such as suicide risk assessment and prevention. OBJECTIVE: We aimed to evaluate the internet search activity of suicidal young people to find evidence of suicidal ideation and behavioral health-related content. METHODS: Individuals aged between 15 and 30 years (N=43) with mood disorders who were hospitalized for STBs provided access to their internet search history. Searches that were conducted in the 3-month period prior to hospitalization were extracted and manually evaluated for search themes related to suicide and behavioral health. RESULTS: A majority (27/43, 63%) of participants conducted suicide-related searches. Participants searched for information that exactly matched their planned or chosen method of attempting suicide in 21% (9/43) of cases. Suicide-related search queries also included unusual suicide methods and references to suicide in popular culture. A majority of participants (33/43, 77%) had queries related to help-seeking themes, including how to find inpatient and outpatient behavioral health care. Queries related to mood and anxiety symptoms were found among 44% (19/43) of participants and included references to panic disorder, the inability to focus, feelings of loneliness, and despair. Queries related to substance use were found among 44% (19/43) of participants. Queries related to traumatic experiences were present among 33% (14/43) of participants. Few participants conducted searches for crisis hotlines (n=3). CONCLUSIONS: Individuals search the internet for information related to suicide prior to hospitalization for STBs. The improved understanding of the search activity of suicidal people could inform outreach, assessment, and intervention strategies for people at risk. Access to search data may also benefit the ongoing care of suicidal patients.

Google search activity in early psychosis: A qualitative analysis of internet search query content in first episode psychosis.

AIM: Manually explore the Google search queries of individuals with first episode psychosis prior to their first hospitalization, in effort to identify common themes and search interests during the period of emerging illness. METHODS: Individuals hospitalized for psychosis between December 2016 and September 2017 provided access to their Google archive data for manual qualitative evaluation of search content. Searches conducted during the 6-month time period prior to the participant's first hospitalization for psychosis were extracted and evaluated for search activity associated with mental health. RESULTS: Of 20 archives reviewed, 15 individuals (75%) searched for information classified by reviewers as related to mental health. Searches with content associated with delusions were found in 15 participant archives (75%). Searches related to negative symptoms including social withdrawal and decline in function were identified in 6 participant's search archives (30%). Four participants (20%) had searches that were associated with thought processes, and 2 participants (10%) searched for information on suicide. Four participants (20%) searched for information related to anxiety, whereas 3 participants (15%) had searches related to depressive symptoms. CONCLUSIONS: Individuals with early psychosis appear to be using the Internet for obtaining information about their early symptoms and experiences prior to their first contact with psychiatric care. Improving our understanding of the ways by which individuals with emerging psychosis search for information about their experiences online may help mental health clinicians tailor online resources in hopes of improving pathways to care and reducing the duration of untreated psychosis.

CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells.

BACKGROUND: CHD8 (chromodomain helicase DNA-binding protein 8), which codes for a member of the CHD family of ATP-dependent chromatin-remodeling factors, is one of the most commonly mutated genes in autism spectrum disorders (ASD) identified in exome-sequencing studies. Loss of function mutations in the gene have also been found in schizophrenia (SZ) and intellectual disabilities and influence cancer cell proliferation. We previously reported an RNA-seq analysis carried out on neural progenitor cells (NPCs) and monolayer neurons derived from induced pluripotent stem (iPS) cells that were heterozygous for CHD8 knockout (KO) alleles generated using CRISPR-Cas9 gene editing. A significant number of ASD and SZ candidate genes were among those that were differentially expressed in a comparison of heterozygous KO lines (CHD8+/-) vs isogenic controls (CHD8+/-), including the SZ and bipolar disorder (BD) candidate gene TCF4, which was markedly upregulated in CHD8+/- neuronal cells. METHODS: In the current study, RNA-seq was carried out on CHD8+/- and isogenic control (CHD8+/+) cerebral organoids, which are 3-dimensional structures derived from iPS cells that model the developing human telencephalon. RESULTS: TCF4 expression was, again, significantly upregulated. Pathway analysis carried out on differentially expressed genes (DEGs) revealed an enrichment of genes involved in neurogenesis, neuronal differentiation, forebrain development, Wnt/ß-catenin signaling, and axonal guidance, similar to our previous study on NPCs and monolayer neurons. There was also significant overlap in our CHD8+/- DEGs with those found in a transcriptome analysis carried out by another group using cerebral organoids derived from a family with idiopathic ASD. Remarkably, the top DEG in our respective studies was the non-coding RNA DLX6-AS1, which was markedly upregulated in both studies; DLX6-AS1 regulates the expression of members of the DLX (distal-less homeobox) gene family. DLX1 was also upregulated in both studies. DLX genes code for transcription factors that play a key role in GABAergic interneuron differentiation. Significant overlap was also found in a transcriptome study carried out by another group using iPS cell-derived neurons from patients with BD, a condition characterized by dysregulated WNT/ß-catenin signaling in a subgroup of affected individuals. CONCLUSIONS: Overall, the findings show that distinct ASD, SZ, and BD candidate genes converge on common molecular targets-an important consideration for developing novel therapeutics in genetically heterogeneous complex traits.

The Entamoeba histolytica Dnmt2 homolog (Ehmeth) confers resistance to nitrosative stress.

Nitric oxide (NO) has antimicrobial properties against many pathogens due to its reactivity as an S-nitrosylating agent. It inhibits many of the key enzymes that are involved in the metabolism and virulence of the parasite Entamoeba histolytica through S-nitrosylation of essential cysteine residues. Very little information is available on the mechanism of resistance to NO by pathogens in general and by this parasite in particular. Here, we report that exposure of the parasites to S-nitrosoglutathione (GSNO), an NO donor molecule, strongly reduces their viability and protein synthesis. However, the deleterious effects of NO were significantly reduced in trophozoites overexpressing Ehmeth, the cytosine-5 methyltransferase of the Dnmt2 family. Since these trophozoites also exhibited high levels of tRNA(Asp) methylation, the high levels suggested that Ehmeth-mediated tRNA(Asp) methylation is part of the resistance mechanism to NO. We previously reported that enolase, another glycolytic enzyme, binds to Ehmeth and inhibits its activity. We observed that the amount of Ehmeth-enolase complex was significantly reduced in GSNO-treated E. histolytica, which explains the aforementioned increase of tRNA methylation. Specifically, we demonstrated via site-directed mutagenesis that cysteine residues 228 and 229 of Ehmeth are susceptible to S-nitrosylation and are crucial for Ehmeth binding to enolase and for Ehmeth-mediated resistance to NO. These results indicate that Ehmeth has a central role in the response of the parasite to NO, and they contribute to the growing evidence that NO is a regulator of epigenetic mechanisms.