Examining the Feasibility, Acceptability, and Effectiveness of Remote Training on Community-Based Participatory Research: Single-Arm Pre-Post Pilot Study.

BACKGROUND: Over the past decade, a growing body of scientific evidence has demonstrated that community engagement in research leads to more relevant research, enhances the uptake of research findings, and improves clinical outcomes. Despite the increasing need for the integration of community engagement methodologies into the scientific inquiry, doctoral and master's level competencies in the field of psychiatry often lack dedicated training or coursework on community engagement methodologies. OBJECTIVE: A total of 13 service users, peer support specialists, caregivers of people with mental health challenges, and scientists (with specialties ranging from basic science to implementation science) aged 18 and older participated in remote training on community-based participatory research. Data were collected at baseline, 2 days, and 3 months. METHODS: A total of 13 service users, peer support specialists, caregivers of people with mental health challenges, and scientists (with specialties ranging from basic science to implementation science) aged 18 and older participated in remote training on community-based participatory research. Data were collected at baseline, 2 days, and 3 months. RESULTS: The pilot study demonstrated that a 3-month remote training on community-based participatory research ("Partnership Academy") was deemed feasible and acceptable by service users, peer support specialists, caregivers of people with mental health challenges, and scientists. Improvements were found in research engagement and the quality of partnership. A marked increase in distrust in the medical system was also found. Groups submitted 4 grant applications and published 1 peer-reviewed journal at a 3-month follow-up. CONCLUSIONS: This pre- and postpilot study demonstrated it is possible to train groups of service users, peer support specialists, caregivers of people with mental health challenges, and scientists in community-based participatory research. These findings provide preliminary evidence that a 3-month remote training on community-based participatory research ("Partnership Academy") is feasible, acceptable, and potentially associated with improvements in research engagement as well as the quality of partnership and output, such as manuscripts and grant applications.

The E3 ligase SMURF1 stabilizes p27 via UbcH7 catalyzed K29-linked ubiquitin chains to promote cell migration SMURF1-UbcH7 K29 ubiquitination of p27 and cell migration.

Ubiquitination is a key regulator of protein stability and function. The multifunctional protein p27 is known to be degraded by the proteasome following K48-linked ubiquitination. However, we recently reported that when the ubiquitin-conjugating enzyme UbcH7 (UBE2L3) is overexpressed, p27 is stabilized, and cell cycle is arrested in multiple diverse cell types including eye lens, retina, HEK-293, and HELA cells. However, the ubiquitin ligase associated with this stabilization of p27 remained a mystery. Starting with an in vitro ubiquitination screen, we identified RSP5 as the yeast E3 ligase partner of UbcH7 in the ubiquitination of p27. Screening of the homologous human NEDD4 family of E3 ligases revealed that SMURF1 but not its close homolog SMURF2, stabilizes p27 in cells. We found that SMURF1 ubiquitinates p27 with K29O but not K29R or K63O ubiquitin in vitro, demonstrating a strong preference for K29 chain formation. Consistent with SMURF1/UbcH7 stabilization of p27, we also found that SMURF1, UbcH7, and p27 promote cell migration, whereas knockdown of SMURF1 or UbcH7 reduces cell migration. We further demonstrated the colocalization of SMURF1/p27 and UbcH7/p27 at the leading edge of migrating cells. In sum, these results indicate that SMURF1 and UbcH7 work together to produce K29-linked ubiquitin chains on p27, resulting in the stabilization of p27 and promoting its cell-cycle independent function of regulating cell migration.

"As soon as I start trusting human beings, they disappoint me, and now I am going to get on an app that someone could hack. I really do not want to take that chance": barriers and facilitators to digital peer support implementation into community mental health centers.

Background: Certified peer support specialists often use technologies such as smartphone applications to deliver digital peer support in community mental health centers. Certified peer support specialists are individuals with a mental health diagnosis, trained and accredited by their state to provide mental health support services. Digital peer support has shown promising evidence of promoting recovery, hope, social support, and medical and psychiatric self-management among patients with a diagnosis of a serious mental illness. Interest in digital peer support as part of the patient experience has grown. Understanding barriers and facilitators to the implementation process of digital peer support into community mental health centers is a critical next step to facilitate uptake. Methods: Semi-structured qualitative interviews were conducted with 27 patient participants (N = 17 persons with serious mental illness; N = 10 certified peer support specialists) from an urban community mental health center. Participants responded to open-ended questions on the barriers and facilitators of engaging with digital peer support technologies within community mental health centers. The interview guide and the responses were categorized according to the Consolidated Framework for Implementation Science Research (CFIR) constructs. Results: Nine barriers and two facilitators were identified for the implementation of digital peer support in community mental health centers. The overarching domains for the identified barriers included (1) intervention characteristics (i.e., adaptability, complexity, and cost), (2) inner settings (i.e., implementation climate, readiness for implementation, and access to knowledge and information), and (3) characteristics of individuals (i.e., knowledge and beliefs about the intervention and other personal attributes). The two facilitators identified included (1) intervention characteristics (i.e., relative advantage) and (2) outer setting (i.e., patient needs and resources). Conclusions: The identified barriers and facilitators represent a starting point for developing or modifying digital peer support technology requirements to ease implementation in community mental health centers. Building technology requirements and implementation processes based on these findings may facilitate uptake of digital peer support technologies by people with serious mental illness and certified peer support specialists in community mental health centers.

Prospective Association Between Video and Computer Game Use During Adolescence and Incidence of Metabolic Health Risks: Secondary Data Analysis.

BACKGROUND: Video and computer games are popular activities, with 72% of adolescents aged 13 to 17 years reporting video game use on either a computer, game console, or portable device. Despite high levels of video and computer game use in adolescence, relatively little scientific literature exists examining the association and effects of video and computer games on adolescents. OBJECTIVE: The objective of this study was to examine the prevalence of video and computer game use among US adolescents and rates of positive screens for obesity, diabetes, high blood pressure (BP), and high cholesterol. METHODS: A secondary data analysis was conducted using the National Longitudinal Study of Adolescent to Adult Health (Add Health) data, including adolescents aged 12 to 19 years between 1994 and 2018. RESULTS: Respondents (n=4190) who played the most video and computer games had a significantly (P=.02) higher BMI and were more likely to self-report having at least one of the evaluated metabolic disorders: obesity (BMI >30 kg/m2), diabetes, high BP (BP >140/90), and high cholesterol (>240). With increased video or computer game use, there was a statistically significant increase in high BP rates in each quartile, with those with more frequent use also having higher rates of high BP. A similar trend was observed for diabetes, though the association did not reach statistical significance. No significant association was observed between video or computer game use and diagnoses of dyslipidemia, eating disorders, or depression. CONCLUSIONS: Frequency of video and computer game use is associated with obesity, diabetes, high BP, and high cholesterol in adolescents aged 12 to 19 years. Adolescents who play the most video and computer games have a significantly higher BMI. They are more likely to have at least one of the evaluated metabolic disorders: diabetes, high BP, or high cholesterol. Public health interventions designed to target modifiable disease states through health promotion and self-management may support the health of adolescents aged 12 to 19 years. Video and computer games can integrate health promotion interventions in gameplay. This is an important area for future research as video and computer games are integrated into the lives of adolescents.

Introduction to the Coproduction of Supervision Standards for Digital Peer Support: Qualitative Study.

BACKGROUND: Digital peer support enhances engagement in mental and physical health services despite barriers such as location, transportation, and other accessibility constraints. Digital peer support involves live or automated peer support services delivered through technology media such as peer-to-peer networks, smartphone apps, and asynchronous and synchronous technologies. Supervision standards for digital peer support can determine important administrative, educative, and supportive guidelines for supervisors to maintain the practice of competent digital peer support, develop knowledgeable and skilled digital peer support specialists, clarify the role and responsibility of digital peer support specialists, and support specialists in both an emotional and developmental capacity. OBJECTIVE: Although digital peer support has expanded recently, there are no formal digital supervision standards. The aim of this study is to inform the development of supervision standards for digital peer support and introduce guidelines that supervisors can use to support, guide, and develop competencies in digital peer support specialists. METHODS: Peer support specialists that currently offer digital peer support services were recruited via an international email listserv of 1500 peer support specialists. Four 1-hour focus groups, with a total of 59 participants, took place in October 2020. Researchers used Rapid and Rigorous Qualitative Data Analysis methods. Researchers presented data transcripts to focus group participants for feedback and to determine if the researcher's interpretation of the data match their intended meanings. RESULTS: We identified 51 codes and 11 themes related to the development of supervision standards for digital peer support. Themes included (1) education on technology competency (43/197, 21.8%), (2) education on privacy, security, and confidentiality in digital devices and platforms (33/197, 16.8%), (3) education on peer support competencies and how they relate to digital peer support (25/197, 12.7%), (4) administrative guidelines (21/197, 10.7%), (5) education on the digital delivery of peer support (18/197, 9.1%), (6) education on technology access (17/197, 8.6%), (7) supervisor support of work-life balance (17/197, 8.6%), (8) emotional support (9/197, 4.6%), (9) administrative documentation (6/197, 3%), (10) education on suicide and crisis intervention (5/197, 2.5%), and (11) feedback (3/197, 1.5%). CONCLUSIONS: Currently, supervision standards from the Substance Abuse and Mental Health Services Administration (SAMHSA) for in-person peer support include administrative, educative, and supportive functions. However, digital peer support has necessitated supervision standard subthemes such as education on technology and privacy, support of work-life balance, and emotional support. Lack of digital supervision standards may lead to a breach in ethics and confidentiality, workforce stress, loss of productivity, loss of boundaries, and ineffectively serving users who participate in digital peer support services. Digital peer support specialists require specific knowledge and skills to communicate with service users and deliver peer support effectively, while supervisors require new knowledge and skills to effectively develop, support, and manage the digital peer support role.

Lived Experience-Led Research Agenda to Address Early Death in People With a Diagnosis of a Serious Mental Illness: A Consensus Statement.

Importance: People with serious mental illness (SMI), defined as a diagnosis of schizophrenia spectrum disorder, bipolar disorder, or disabling major depressive disorder) die approximately 10 to 25 years earlier than the general population. Objective: To develop the first-ever lived experience-led research agenda to address early mortality in people with SMI. Evidence Review: A virtual 2-day roundtable comprising 40 individuals convened on May 24 and May 26, 2022, and used a virtual Delphi method to arrive at expert group consensus. Participants responded to 6 rounds of virtual Delphi discussion via email that prioritized research topics and agreement on recommendations. The roundtable was composed of individuals with lived experience of mental health and/or substance misuse, peer support specialists, recovery coaches, parents and caregivers of people with SMI, researchers and clinician-scientists with and without lived experience, policy makers, and patient-led organizations. Twenty-two of 28 (78.6%) of the authors who provided data represented people with lived experiences. Roundtable members were selected by reviewing the peer-reviewed and gray literature on early mortality and SMI, direct email, and snowball sampling. Findings: The following recommendations are presented in order of priority as identified by the roundtable participants: (1) improve the empirical understanding of the direct and indirect social and biological contributions of trauma on morbidity and early mortality; (2) advance the role of family, extended families, and informal supporters; (3) recognize the importance of co-occurring disorders and early mortality; (4) redefine clinical education to reduce stigma and support clinicians through technological advancements to improve diagnostic accuracy; (5) examine outcomes meaningful to people with an SMI diagnosis, such as loneliness and sense of belonging, and stigma and their complex relationship with early mortality; (6) advance the science of pharmaceuticals, drug discovery, and choice in medication use; (7) use precision medicine to inform treatment; and (8) redefine the terms system literacy and health literacy. Conclusions and Relevance: The recommendations of this roundtable are a starting point for changing practice and highlighting lived experience-led research priorities as an option to move the field forward.

Estimates of Gaps in Supportive Housing Among Racially and Ethnically Diverse Older Adults with Serious Mental Illness in New York City Boroughs: Manhattan, Bronx, and Brooklyn.

OBJECTIVE: This study aimed to estimate gaps in supportive housing services for racially and ethnically diverse older adults with SMI residing in supportive housing. METHODS: This study had a total of 753 respondents split into two diagnostic groups, the Delusional and Psychotic Disorders Group, and the Mood (Affective) Disorder Group. Demographic and primary ICD diagnosis data (F2x and F3x) were extracted from medical records. Three elements were measured: supportive housing service needs, fall prevention, and activities in daily living and instrumental activities in daily living. Descriptive statistics (i.e., frequencies and percentages) were used in assessing the demographic characteristics of the sample. RESULTS: Respondents had reasonable fall prevention measures in place, did not have challenges carrying out activities in daily living or instrumental activities of daily living and did not need homecare services (n = 515, 68.4%). Respondents needed support managing chronic medical conditions (n = 323, ∼43%). Approximately 57% of the total respondents in this study (n = 426) reported the need for hearing, vision, and dental services. Respondents showed high levels of food insecurity (n = 380, 50.5%). CONCLUSIONS: This is the most extensive study of racially and ethnically diverse older adults with SMI residing in supportive housing. Three areas of unmet need were found: accessing hearing, vision, and dental services, managing chronic health conditions, and food insecurity. These findings can be used to develop new research programs addressing the needs of older adults with SMI and improve late-life circumstances for older adults with SMI.

Assessing the Feasibility, Acceptability, and Preliminary Effectiveness of a School-Aged Program that Supports Physical Activity and Wellness.

The prevalence of anxiety symptoms in children and adolescents aged 4 to 18 years has nearly doubled after the first year of the pandemic. However, only one in five adolescents diagnosed with anxiety is treated. We R H.O.P. E. is a school-based mental health program that includes evidence-based principles designed to engage children and adolescents in anxiety treatment, including wellness and emotional regulation, and the emotional CPR method. We R H.O.P. E. augments traditional services provided by school administrators, school social workers, school teachers, and school nurses. The purpose of this study was to examine the feasibility, acceptability, and preliminary effectiveness of We R H.O.P. E.

Can Component Size in Total Knee Arthroplasty Be Predicted Preoperatively?-An Analysis of Patient Characteristics.

Accurately predicting component sizing in total knee arthroplasty (TKA) can ensure appropriate implants are readily available, avoiding complications from malsizing while also reducing cost by improving workflow efficiency through a reduction in instrumentation. This study investigated the utility of demographic variables to reliably predict TKA component sizes. A retrospective chart review of 337 patients undergoing primary TKA was performed. Patient characteristics (age, sex, race, height, weight) were recorded along with implant and shoe size. Correlation between shoe size and TKA component size was assessed using Pearson's correlation coefficient and linear regression analysis using three models: (A) standard demographic variables, (B) shoe size, and (C) combination of both models. Shoe size demonstrated the strongest correlation with femoral anteroposterior (FAP) (p < 0.001) followed by height (p < 0.001). Conversely, height exhibited the strongest correlation with tibial mediolateral (TML) (p < 0.001) followed by shoe size (p < 0.001). Model C was able to correctly predict both the femur and tibia within one and two sizes in 83.09 and 98.14% of cases, respectively. Individually, model C predicted the FAP within one and two sizes in 83.09 and 96.14% of cases, and the TML in 98.81 and 100% of cases, respectively. A patient's shoe size demonstrates a strong correlation to the TKA implant size, and when combined with standard demographic variables the predictive reliability is further increased. Here, we present a predictive model for implant sizing based solely on easily attainable demographic variables, that will be useful for preoperative planning to improve surgical efficiency. LEVEL OF EVIDENCE: II, Diagnostic.

The Intersection of Business Innovation and Scientific Exploration to Address Early Mortality in People With Serious Mental Illness.

This Viewpoint describes how open innovation has been used by communities to support individual and community health and discusses how scientists and clinicians could apply this idea- and resource-sharing strategy to generate breakthrough advances that may extend the life span of people with serious mental illness (SMI).

Investigating the Fidelity of Digital Peer Support: A Preliminary Approach using Natural Language Processing to Scale High-Fidelity Digital Peer Support.

Adults with serious mental illnesses are disproportionately affected by chronic health conditions that are linked to inadequately managed medical and psychiatric illnesses and are associated with poor lifestyle behaviors. Emerging intervention models emphasize the value of peer specialists (certified individuals who offer emotional, social, and practical assistance to those with similar lived experiences) in promoting better illness management and meaningful community rehabilitation. Over the last few years, there has been an increasing uptake in the use of digital services and online platforms for the dissemination of various peer services. However, current literature cannot scale current service delivery approaches through audio recording of all interactions to monitor and ensure fidelity at scale. This research aims to understand the individual components of digital peer support to develop a corpus and use natural language processing to classify high-fidelity evidence-based techniques used by peer support specialists in novel datasets. The research hypothesizes that a binary classifier can be developed with an accuracy of 70% through the analysis of digital peer support data.

Elevated Pre-operative D-Dimer Levels Do Not Impact the Effect of Tranexamic Acid on Revision Total Knee Arthroplasty.

The purpose of this study was to determine if elevated pre-operative D-dimer levels in patients undergoing revision total knee arthroplasty (rTKA) pose an increased risk of: (1) post-operative venous thromboemboli (VTE); (2) intra-operative blood loss; and (3) need for transfusion of blood products. Eighty-nine patients who underwent rTKA by a single surgeon between January 1, 2017, and December 31, 2019, met the inclusion criteria. Elevated pre-operative D-dimer levels did not pose an increased risk of VTE, blood loss, or transfusion of blood products, demonstrating that elevated pre-operative D-dimer is not a contraindication to the use of tranexamic acid for rTKA.

Predicting Nonunions in Ankle Fractures Using Quantitative Tibial Hounsfield Samples From Preoperative Computed Tomography: A Multicenter Matched Case Control Study.

The aim of this study is to use tibial Hounsfield unit measurements from preoperative computed tomography scans of ankle fractures to predict delayed union and nonunion. We hypothesize that patients with lower Hounsfield unit averages, an indirect measure of lower bone mineral density, in the distal tibia are more likely to develop delayed union and nonunion complications after ankle fracture surgery. Patient data from January 2010 to January 2020 were retrospectively analyzed from 2 institutions. Exposure cases of delayed union or nonunion that had preoperative computed tomography were compared to 5 controls matched for sex, age, and classification. 3 measurements were taken from the tibia on axial computed tomography and averaged to create a summative measure for overall bone health. Statistical analysis was used to analyze the relationship between the groups. 19 exposure patients were compared to 95 control patients. There were 16 females and 3 males in the exposure group aged from 30 to 88 years. Average follow-up was 1.6 years. The average exposure and control Hounsfield measurements were 186 (161-210) and 258 (248-269), respectively. Significant differences were found for all measured averages. This is the first study to our knowledge relating preoperative tibial Hounsfield measurements to healing rates of ankle fractures. Measurements taken from any of the 3 sites or the average could be an indicator of overall bone health. Using this technique on preoperative imaging will help surgeons adjust their perioperative planning for patients at higher risk for delayed union and nonunion.

Synthesis of libraries and multi-site mutagenesis using a PCR-derived, dU-containing template.

Directed DNA libraries are useful because they focus genetic diversity in the most important regions within a sequence. Ideally, all sequences in such libraries should appear with the same frequency and there should be no significant background from the starting sequence. These properties maximize the number of different sequences that can be screened. Described herein is a method termed SLUPT (Synthesis of Libraries via a dU-containing PCR-derived Template) for generating highly targeted DNA libraries and/or multi-site mutations wherein the altered bases may be widely distributed within a target sequence. This method is highly efficient and modular. Moreover, multiple distinct sites, each with one or more base changes, can be altered in a single reaction. There is very low background from the starting sequence, and SLUPT libraries have similar representation of each base at the positions selected for variation. The SLUPT method utilizes a single-stranded dU-containing DNA template that is made by polymerase chain reaction (PCR). Synthesis of the template in this way is significantly easier than has been described earlier. A series of oligonucleotide primers that are homologous to the template and encode the desired genetic diversity are extended and ligated in a single reaction to form the mutated product sequence or library. After selective inactivation of the template, only the product library is amplified. There are no restrictions on the spacing of the mutagenic primers except that they cannot overlap.

Adaptation of an NLP system to a new healthcare environment to identify social determinants of health.

Social determinants of health (SDoH) are increasingly important factors for population health, healthcare outcomes, and care delivery. However, many of these factors are not reliably captured within structured electronic health record (EHR) data. In this work, we evaluated and adapted a previously published NLP tool to include additional social risk factors for deployment at Vanderbilt University Medical Center in an Acute Myocardial Infarction cohort. We developed a transformation of the SDoH outputs of the tool into the OMOP common data model (CDM) for re-use across many potential use cases, yielding performance measures across 8 SDoH classes of precision 0.83 recall 0.74 and F-measure of 0.78.

Evaluation of Adjunctive Photobiomodulation (PBMT) for COVID-19 Pneumonia via Clinical Status and Pulmonary Severity Indices in a Preliminary Trial.

PURPOSE: Evidence-based and effective treatments for COVID-19 are limited, and a new wave of infections and deaths calls for novel, easily implemented treatment strategies. Photobiomodulation therapy (PBMT) is a well-known adjunctive treatment for pain management, wound healing, lymphedema, and cellulitis. PBMT uses light to start a cascade of photochemical reactions that lead to local and systemic anti-inflammatory effects at multiple levels and that stimulate healing. Numerous empirical studies of PBMT for patients with pulmonary disease such as pneumonia, COPD and asthma suggest that PBMT is a safe and effective adjunctive treatment. Recent systematic reviews suggest that PBMT may be applied to target lung tissue in COVID-19 patients. In this preliminary study, we evaluated the effect of adjunctive PBMT on COVID-19 pneumonia and patient clinical status. PATIENTS AND METHODS: We present a small-scale clinical trial with 10 patients randomized to standard medical care or standard medical care plus adjunctive PBMT. The PBMT group received four daily sessions of near-infrared light treatment targeting the lung tissue via a Multiwave Locked System (MLS) laser. Patient outcomes were measured via blood work, chest x-rays, pulse oximetry and validated scoring tools for pneumonia. RESULTS: PBMT patients showed improvement on pulmonary indices such as SMART-COP, BCRSS, RALE, and CAP (Community-Acquired Pneumonia questionnaire). PBMT-treated patients showed rapid recovery, did not require ICU admission or mechanical ventilation, and reported no long-term sequelae at 5 months after treatment. In the control group, 60% of patients were admitted to the ICU for mechanical ventilation. The control group had an overall mortality of 40%. At a 5-month follow-up, 40% of the control group experienced long-term sequelae. CONCLUSION: PBMT is a safe and effective potential treatment for COVID-19 pneumonia and improves clinical status in COVID-19 pneumonia.

Reconciliation Between Lateral X-ray and Axial Computed Tomography Regarding Posterior Malleolus Fracture Anatomy and Medial Malleolus Involvement: A Pilot Study.

Configuration of a posterior malleolus fracture has significant variation based on mechanism of injury and concomitant ankle injuries. Radiographs obtained during early workup of ankle trauma play a pivotal role in closed reduction, surgical planning and preoperative management. Preoperative computed tomography helps distinguish fracture pathoanatomy. The purpose of this study is to relate measurements from traditional lateral radiographs with measurements on axial computed tomography. Imaging from a total of 22 patients treated at our institution from January 2008 to 2018 were evaluated. Two raters measured posterior malleolus fracture height and articular surface length on lateral radiographs, as well as medial-lateral width and anterior-posterior depth on axial computed tomography using calibrated imaging software. Posterior malleolar fractures with medial extension were recorded. Pearson correlations were calculated for all pairwise combinations of measurements. Lateral height and axial width were positively correlated. There was found to be an association between taller lateral height, and separately, wider axial width with presence of medial extension. Based on the correlations found between the measurements as well as the independent associations found with presence of medial extension, we suggest posterior-medial incision be evaluated as a potential approach in taller fractures as noted on lateral radiograph.

New activators of eIF2α Kinase Heme-Regulated Inhibitor (HRI) with improved biophysical properties.

Heme-regulated inhibitor (HRI), a eukaryotic translation initiation factor 2 alpha (eIF2α) kinase, is critically important for coupling protein synthesis to heme availability in reticulocytes and adaptation to various environmental stressors in all cells. HRI modifies the severity of several hemoglobin misfolding disorders including ß-thalassemia. Small molecule activators of HRI are essential for studying normal- and patho-biology of this kinase as well as for the treatment of various human disorders for which activation of HRI or phosphorylation of eIF2α may be beneficial. We previously reported development of 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) as specific HRI activators and demonstrated their potential as molecular probes for studying HRI biology and as lead compounds for treatment of various human disorders. To develop more druglike cHAUs for in vivo studies and drug development and to expand the chemical space, we undertook bioassay guided structure-activity relationship studies replacing cyclohexyl ring with various 4-6-membered rings and explored further substitutions on the N-phenyl ring. We tested all analogs in the surrogate eIF2α phosphorylation and cell proliferation assays, and a subset of analogs in secondary mechanistic assays that included endogenous eIF2α phosphorylation and expression of C/EBP homologous protein (CHOP), a downstream effector. Finally, we determined specificity of these compounds for HRI by testing their anti-proliferative activity in cells transfected with siRNA targeting HRI or mock. These compounds have significantly improved cLogPs with no loss of potencies, making them excellent candidates for lead optimization for development of investigational new drugs that potently and specifically activate HRI.

AMi: a GUI-based, open-source system for imaging samples in multi-well plates.

Described here are instructions for building and using an inexpensive automated microscope (AMi) that has been specifically designed for viewing and imaging the contents of multi-well plates. The X, Y, Z translation stage is controlled through dedicated software (AMiGUI) that is being made freely available. Movements are controlled by an Arduino-based board running grbl, and the graphical user interface and image acquisition are controlled via a Raspberry Pi microcomputer running Python. Images can be written to the Raspberry Pi or to a remote disk. Plates with multiple sample wells at each row/column position are supported, and a script file for automated z-stack depth-of-field enhancement is written along with the images. The graphical user interface and real-time imaging also make it easy to manually inspect and capture images of individual samples.