The WorkingWell Smartphone App for Individuals with Serious Mental Illnesses: A Proof-of-Concept, Mixed Methods Feasibility Study (Preprint)

Background: The disparities in employment for individuals with serious mental illnesses (SMI) have been well documented, as have the benefits of work. The benefits of mobile technology in providing accessible, in-the-moment support for these individuals has been demonstrated. The WorkingWell mobile app was developed to meet the need for accessible follow-along supports for individuals with SMI in the workplace. Objective: We explore the usability, usage, usefulness and overall feasibility of the WorkingWell mobile app with individuals with SMI receiving community-based services and actively employed. Methods: In this proof-of-concept, mixed methods, two-month feasibility study (N=40), employed individuals with SMI were recruited in mental health agencies. Participants completed surveys regarding background characteristics and cellphone use at enrollment; and responded to interview items regarding app usability, usage and usefulness in technical assistance calls at one, two, four and six weeks of study participation and in the exit interview at 8 weeks. Data on the frequency of app usage were downloaded and monitored on a daily basis. A version of the System Usability Scale (SUS) was administered in the exit interview. Feasibility was determined by the percent of users completing the study. General impressions were obtained from users regarding user support materials, technical assistance, and study procedures. Results: Over half of the participants were male (60%, 24/40). The majority were age 55 or under (70%, 28/40), Caucasian (80%, 32/40), had less than a 4-year college education (78%, 31/40), were employed part-time (98%, 39/40), had been working more than six months (60%, 24/40), and indicated a diagnosis of bipolar, schizoaffective or depressive disorder (84%, 16/25). The vast majority of participants owned cellphones (95%, 38/40), using them multiple times per day (83%, 33/40). Their average rating on SUS usability items was 3.93 (SD = 0.77; range = 1.57 to 5.00), reflecting positive responses. Participants, in general, indicated WorkingWell was “very easy”, “straightforward”, “simple”, and “user-friendly”. Usability challenges were related to personal issues (e.g., memory) or to difficulties with the phone or app. Data on app usage varied considerably. The most frequent navigations were to the home screen, followed by Rate My Day and My Progress, and then by Manage the Moment and Remind Me. The app was described as useful by most study participants; 86% (30/35) agreed the app would help them manage better on the job. Thirty-five of the 40 original participants (87%) completed the study. Conclusions: The WorkingWell app is a feasible approach to providing accessible, as-needed employment support for individuals with SMI. The app would benefit from additional modifications to address recommendations from feasibility testing. Controlled research with larger samples, more diverse in individual characteristics and workplace settings, is essential to demonstrating the effectiveness of the app

Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium.

Long non-coding RNAs (lncRNAs) have emerged recently as key regulatory molecules with diverse roles at almost every level of the regulation of gene expression. The roles of these RNAs in the pathogenesis of cystic fibrosis (CF); a lethal multisystem, autosomal recessive disorder have yet to be explored. Our aim was to examine the expression profile of lncRNA, in the airway epithelium of people with CF. We examined the expression of 30,586 lncRNAs by microarray (Human LncRNA Array v3.0, Arraystar, Inc.), in vivo in bronchial cells isolated from endobronchial brushings obtained from CF and non-CF individuals. In total, we identified 1,063 lncRNAs with differential expression between CF and non-CF individuals (fold change ≥3, p≤0.001). The microarray also contained probes for ∼26,109 protein coding transcripts, of which 720 were differentially expressed between CF and non-CF brush samples (fold change ≥3, p≤0.001). Confirmation of a selection of differentially expressed coding mRNA and lncRNA transcripts such as XIST and TLR8 was achieved using qRT-PCR. Gene ontology bioinformatics analysis highlighted that many processes over-represented in the CF bronchial epithelium are related to inflammation. These data show a significantly altered lncRNA and mRNA expression profile in CF bronchial cells in vivo. Dysregulation of some of these lncRNAs may play important roles in the chronic infection and inflammation that exists in the lungs of people with CF

Secretory leucoprotease inhibitor binds to NF-κB binding sites in monocytes and inhibits p65 binding

Secretory leucoprotease inhibitor (SLPI) is a nonglycosylated protein produced by epithelial cells. In addition to its antiprotease activity, SLPI has been shown to exhibit antiinflammatory properties, including down-regulation of tumor necrosis factor α expression by lipopolysaccharide (LPS) in macrophages and inhibition of nuclear factor (NF)-κB activation in a rat model of acute lung injury. We have previously shown that SLPI can inhibit LPS-induced NF-κB activation in monocytic cells by inhibiting degradation of IκBα without affecting the LPS-induced phosphorylation and ubiquitination of IκBα. Here, we present evidence to show that upon incubation with peripheral blood monocytes (PBMs) and the U937 monocytic cell line, SLPI enters the cells, becoming rapidly localized to the cytoplasm and nucleus, and affects NF-κB activation by binding directly to NF-κB binding sites in a site-specific manner. SLPI can also prevent p65 interaction with the NF-κB consensus region at concentrations commensurate with the physiological nuclear levels of SLPI and p65. We also demonstrate the presence of SLPI in nuclear fractions of PBMs and alveolar macrophages from individuals with cystic fibrosis and community-acquired pneumonia. Therefore, SLPI inhibition of NF-κB activation is mediated, in part, by competitive binding to the NF-κB consensus-binding site

Allelic Ratios and the Mutational Landscape Reveal Biologically Significant Heterozygous SNVs

The issue of heterozygosity continues to be a challenge in the analysis of genome sequences. In this article, we describe the use of allele ratios to distinguish biologically significant single-nucleotide variants from background noise. An application of this approach is the identification of lethal mutations in Caenorhabditis elegans essential genes, which must be maintained by the presence of a wild-type allele on a balancer. The h448 allele of let-504 is rescued by the duplication balancer sDp2. We readily identified the extent of the duplication when the percentage of read support for the lesion was between 70 and 80%. Examination of the EMS-induced changes throughout the genome revealed that these mutations exist in contiguous blocks. During early embryonic division in self-fertilizing C. elegans, alkylated guanines pair with thymines. As a result, EMS-induced changes become fixed as either G→A or C→T changes along the length of the chromosome. Thus, examination of the distribution of EMS-induced changes revealed the mutational and recombinational history of the chromosome, even generations later. We identified the mutational change responsible for the h448 mutation and sequenced PCR products for an additional four alleles, correlating let-504 with the DNA-coding region for an ortholog of a NFκB-activating protein, NKAP. Our results confirm that whole-genome sequencing is an efficient and inexpensive way of identifying nucleotide alterations responsible for lethal phenotypes and can be applied on a large scale to identify the molecular basis of essential genes

Modeling the Mechanism of Action of a DGAT1 Inhibitor Using a Causal Reasoning Platform

Triglyceride accumulation is associated with obesity and type 2 diabetes. Genetic disruption of diacylglycerol acyltransferase 1 (DGAT1), which catalyzes the final reaction of triglyceride synthesis, confers dramatic resistance to high-fat diet induced obesity. Hence, DGAT1 is considered a potential therapeutic target for treating obesity and related metabolic disorders. However, the molecular events shaping the mechanism of action of DGAT1 pharmacological inhibition have not been fully explored yet. Here, we investigate the metabolic molecular mechanisms induced in response to pharmacological inhibition of DGAT1 using a recently developed computational systems biology approach, the Causal Reasoning Engine (CRE). The CRE algorithm utilizes microarray transcriptomic data and causal statements derived from the biomedical literature to infer upstream molecular events driving these transcriptional changes. The inferred upstream events (also called hypotheses) are aggregated into biological models using a set of analytical tools that allow for evaluation and integration of the hypotheses in context of their supporting evidence. In comparison to gene ontology enrichment analysis which pointed to high-level changes in metabolic processes, the CRE results provide detailed molecular hypotheses to explain the measured transcriptional changes. CRE analysis of gene expression changes in high fat habituated rats treated with a potent and selective DGAT1 inhibitor demonstrate that the majority of transcriptomic changes support a metabolic network indicative of reversal of high fat diet effects that includes a number of molecular hypotheses such as PPARG, HNF4A and SREBPs. Finally, the CRE-generated molecular hypotheses from DGAT1 inhibitor treated rats were found to capture the major molecular characteristics of DGAT1 deficient mice, supporting a phenotype of decreased lipid and increased insulin sensitivity

How does social integration influence breast cancer control among urban African-American women? Results from a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Although social integration is a well-established influence on health, less is known about how the specific types of social connection (social roles, social networks, and social support) influence knowledge, attitudes, and practices for specific prevention goals, and how to utilize these influences in interventions with priority populations. This research examined the prevalence of social roles, networks and support among 576 urban African-American women age 45–93 in East Baltimore, Maryland, and the association of these social factors with breast cancer related knowledge, attitudes, and practices.</p> <p>Methods</p> <p>Using data from 1997–1998 in-home interviews, we developed indices of six possible social roles, social networks of family, neighborhood and church, and instrumental and emotional social support. In multivariate models adjusting for age, education, and medical care, we examined the association of each social influence on breast cancer knowledge, attitudes, screening recency and intention, and treatment preferences.</p> <p>Results</p> <p>We found substantial variation in social integration among these women, with social integration positively associated with overall health and well-being. Social roles and networks were positively associated with screening knowledge, and emotional support and church networks were positively associated with attitudes conducive to early detection and treatment. In regard to screening behaviors, family networks were associated with both screening recency and intention. Women with greater church networks and emotional support held more conservative attitudes towards lumpectomy, reconstruction, and clinical trials.</p> <p>Conclusion</p> <p>Overall, social integration is a positive influence on breast cancer control and should be utilized where possible in interventions, including identifying surrogate mechanisms for support for subgroups without existing social resources.</p

The link between job satisfaction and organizational commitment:differences between public and private sector employees

Employees in the public and private sectors experience different working conditions and employment relationships. Therefore, it can be assumed that their attitudes toward their job and organizations, and relationships between them, are different. The existing literature has identified the relationship between organizational commitment and job satisfaction as interesting in this context. The present field study examines the satisfaction–commitment link with respect to differences between private and public sector employees. A sample of 617 Greek employees (257 from the private sector and 360 from the public sector) completed standardized questionnaires. Results confirmed the hypothesized relationship differences: Extrinsic satisfaction and intrinsic satisfaction are more strongly related to affective commitment and normative commitment for public sector employees than for private sector ones. The results are discussed, limitations are considered, and directions for future research are proposed

Long-term cognitive effects of human stem cell transplantation in the irradiated brain

PURPOSE: Radiotherapy remains a primary treatment modality for the majority of central nervous system tumors, but frequently leads to debilitating cognitive dysfunction. Given the absence of satisfactory solutions to this serious problem, we have used human stem cell therapies to ameliorate radiation-induced cognitive impairment. Here, past studies have been extended to determine whether engrafted cells provide even longer-term benefits to cognition. MATERIALS AND METHODS: Athymic nude rats were cranially irradiated (10 Gy) and subjected to intrahippocampal transplantation surgery 2 days later. Human embryonic stem cells (hESC) or human neural stem cells (hNSC) were transplanted, and animals were subjected to cognitive testing on a novel place recognition task 8 months later. RESULTS: Grafting of hNSC was found to provide long lasting cognitive benefits over an 8-month post-irradiation interval. At this protracted time, hNSC grafting improved behavioral performance on a novel place recognition task compared to irradiated animals not receiving stem cells. Engrafted hESC previously shown to be beneficial following a similar task, 1 and 4 months after irradiation, were not found to provide cognitive benefits at 8 months. CONCLUSIONS: Our findings suggest that hNSC transplantation promotes the long-term recovery of the irradiated brain, where intrahippocampal stem cell grafting helps to preserve cognitive function

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or long COVID ), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411