Machine learning-assisted high-content imaging analysis of 3D MCF7 microtissues for estrogenic effect prediction.

Endocrine-disrupting chemicals (EDCs) pose a significant threat to human well-being and the ecosystem. However, in managing the many thousands of uncharacterized chemical entities, the high-throughput screening of EDCs using relevant biological endpoints remains challenging. Three-dimensional (3D) culture technology enables the development of more physiologically relevant systems in more realistic biochemical microenvironments. The high-content and quantitative imaging techniques enable quantifying endpoints associated with cell morphology, cell-cell interaction, and microtissue organization. In the present study, 3D microtissues formed by MCF-7 breast cancer cells were exposed to the model EDCs estradiol (E2) and propyl pyrazole triol (PPT). A 3D imaging and image analysis pipeline was established to extract quantitative image features from estrogen-exposed microtissues. Moreover, a machine-learning classification model was built using estrogenic-associated differential imaging features. Based on 140 common differential image features found between the E2 and PPT group, the classification model predicted E2 and PPT exposure with AUC-ROC at 0.9528 and 0.9513, respectively. Deep learning-assisted analysis software was developed to characterize microtissue gland lumen formation. The fully automated tool can accurately characterize the number of identified lumens and the total luminal volume of each microtissue. Overall, the current study established an integrated approach by combining non-supervised image feature profiling and supervised luminal volume characterization, which reflected the complexity of functional ER signaling and highlighted a promising conceptual framework for estrogenic EDC risk assessment.

Development of a human liver microphysiological co-culture system for higher throughput chemical safety assessment.

Chemicals in the systemic circulation can undergo hepatic xenobiotic metabolism, generate metabolites and exhibit altered toxicity compared to their parent compounds. This paper describes a two-chamber liver-organ co-culture model in a higher-throughput 96-well format for the determination of toxicity on target tissues in the presence of physiologically relevant human liver metabolism. This two-chamber system is a hydrogel formed within each well consisting of a central well (target tissue) and an outer ring-shaped trough (human liver tissue). The target tissue chamber can be configured to accommodate a three-dimensional (3D) spheroid-shaped microtissue, or a two-dimensional (2D) cell mono-layer. Culture medium and compounds freely diffuse between the two chambers. Human differentiated HepaRGTM liver cells are used to form the 3D human liver microtissues, which displayed robust protein expression of liver biomarkers (albumin, asialoglycoprotein receptor, Phase I cytochrome P450 (CYP3A4) enzyme, multidrug resistance-associated protein 2 transporter, and glycogen), and exhibited Phase I/II enzyme activities over the course of 17 days. Histological and ultrastructural analyses confirmed that the HepaRG microtissues presented a differentiated hepatocyte phenotype, including abundant mitochondria, endoplasmic reticulum and bile canaliculi. Liver microtissue zonation characteristics could be easily modulated by maturation in different media supplements. Furthermore, our proof-of-concept study demonstrated the efficacy of this co-culture model in evaluating testosterone-mediated androgen receptor responses in the presence of human liver metabolism. This liver-organ co-culture system provides a practical, higher-throughput testing platform for metabolism-dependent bioactivity assessment of drugs/chemicals, to better recapitulate the biological effects and potential toxicity of human exposures.

In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes.

Septic arthritis as a complication of orthopaedic joint surgery can have catastrophic outcomes for patients. To minimise infection risk associated with elective orthopaedics, topical vancomycin during surgery has become increasingly common. Evidence suggests that high concentrations of vancomycin, following direct application of the drug to the joint, are toxic towards various local cell types in the joint, including chondrocytes. However, the mechanism of this vancomycin tissue toxicity is yet to be determined. The aim of this study was to evaluate the toxicity of vancomycin on chondrocytes and the mechanisms of cell death involved. Human primary knee chondrocytes were exposed to vancomycin (1.25-10 mg/mL) for 24 h and their viability assessed using the resazurin reduction assay in vitro. Specific cell death mechanisms and their contributors, including reactive oxygen species (ROS) production and apoptosis, were measured. This study showed that high concentrations of vancomycin (5 and 10 mg/mL) were toxic towards human primary knee chondrocyte cells, while lower concentrations (1.25 and 2.5 mg/mL) were not. Cell death studies found that this occurred through an apoptotic pathway. This study provides additional support that vancomycin in high doses is toxic towards chondrocytes and preliminary evidence that this toxicity occurs via apoptotic cell death mechanisms.

Machine Learning-Assisted High-Content Imaging Analysis of 3D MCF7 Microtissues for Estrogenic Effect Prediction.

Endocrine-disrupting chemicals (EDCs) pose a significant threat to human well-being and the ecosystem. However, in managing the many thousands of uncharacterized chemical entities, the high-throughput screening of EDCs using relevant biological endpoints remains challenging. Three-dimensional (3D) culture technology enables the development of more physiologically relevant systems in more realistic biochemical microenvironments. The high-content and quantitative imaging techniques enable quantifying endpoints associated with cell morphology, cell-cell interaction, and microtissue organization. In the present study, 3D microtissues formed by MCF-7 breast cancer cells were exposed to the model EDCs estradiol (E2) and propyl pyrazole triol (PPT). A 3D imaging and image analysis pipeline was established to extract quantitative image features from estrogen-exposed microtissues. Moreover, a machine-learning classification model was built using estrogenic-associated differential imaging features. Based on 140 common differential image features found between the E2 and PPT group, the classification model predicted E2 and PPT exposure with AUC-ROC at 0.9528 and 0.9513, respectively. Deep learning-assisted analysis software was developed to characterize microtissue gland lumen formation. The fully automated tool can accurately characterize the number of identified lumens and the total luminal volume of each microtissue. Overall, the current study established an integrated approach by combining non-supervised image feature profiling and supervised luminal volume characterization, which reflected the complexity of functional ER signaling and highlighted a promising conceptual framework for estrogenic EDC risk assessment.

The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy.

Pseudomonas aeruginosa (P. aeruginosa) poses a grave clinical challenge due to its multidrug resistance (MDR) phenotype, leading to severe and life-threatening infections. This bacterium exhibits both intrinsic resistance to various antipseudomonal agents and acquired resistance against nearly all available antibiotics, contributing to its MDR phenotype. Multiple mechanisms, including enzyme production, loss of outer membrane proteins, target mutations, and multidrug efflux systems, contribute to its antimicrobial resistance. The clinical importance of addressing MDR in P. aeruginosa is paramount, and one pivotal determinant is the resistance-nodulation-division (RND) family of drug/proton antiporters, notably the Mex efflux pumps. These pumps function as crucial defenders, reinforcing the emergence of extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains, which underscores the urgency of the situation. Overcoming this challenge necessitates the exploration and development of potent efflux pump inhibitors (EPIs) to restore the efficacy of existing antipseudomonal drugs. By effectively countering or bypassing efflux activities, EPIs hold tremendous potential for restoring the antibacterial activity against P. aeruginosa and other Gram-negative pathogens. This review focuses on concurrent MDR, highlighting the clinical significance of efflux pumps, particularly the Mex efflux pumps, in driving MDR. It explores promising EPIs and delves into the structural characteristics of the MexB subunit and its substrate binding sites.

User Experiences in a Digital Intervention to Support Total Skin Self-examination by Melanoma Survivors: Nested Qualitative Evaluation Embedded in a Randomized Controlled Trial.

BACKGROUND: Melanoma is a relatively common cancer type with a high survival rate, but survivors risk recurrences or second primaries. Consequently, patients receive regular hospital follow-up, but this can be burdensome to attend and not optimally timed to detect arising problems. Total skin self-examination (TSSE) supports improved clinical outcomes from melanoma via earlier detection of recurrences and second primaries, and digital technology has the potential to support TSSE. Recent research with app-based interventions aimed at improving the well-being of older adults has found that they can use the technology and benefit from it, supporting the use of digital health care in diverse demographic groups. Thus, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) digital health care intervention was developed. The intervention provided melanoma survivors with a monthly prompt to perform a TSSE as well as access to a dermatology nurse who provided them with feedback on photographs and descriptions of their skin. OBJECTIVE: We aimed to explore participants' attitudes, beliefs, and experiences regarding TSSE practices. Furthermore, we explored how participants experienced technology and how it influenced their practice of TSSE. Finally, we explored the practical and technical experiences of ASICA users. METHODS: This was a nested qualitative evaluation within a dual-center randomized controlled trial of the ASICA intervention. We conducted semistructured telephone interviews with the participants during a randomized controlled trial. The participants were purposively sampled to achieve a representative sample with representative proportions by age, sex, and residential geography. Interviews were transcribed verbatim and analyzed using a framework analysis approach applied within NVivo 12. RESULTS: A total of 22 interviews were conducted with participants from both groups. In total, 40% (9/22) of the interviewed participants were from rural areas, and 60% (13/22) were from urban areas; 60% (13/22) were from the intervention group, and 40% (9/22) were from the control group. Themes evolved around skin-checking behavior, other people's input into skin checking, contribution of health care professionals outside ASICA and its value, ideas around technology, practical experiences, and potential improvements. ASICA appeared to change participants' perceptions of skin checking. Users were more likely to report routinely performing TSSE thoroughly. There was some variation in beliefs about skin checking and using technology for health care. Overall, ASICA was experienced positively by participants. Several practical suggestions were made for the improvement of ASICA. CONCLUSIONS: The ASICA intervention appeared to have positively influenced the attitudes and TSSE practices of melanoma survivors. This study provides important qualitative information about how a digital health care intervention is an effective means of prompting, recording, and responding to structured TSSE by melanoma survivors. Technical improvements are required, but the app offers promise for technologically enhanced melanoma follow-up in future. TRIAL REGISTRATION: ClinicalTrials.gov NCT03328247; https://clinicaltrials.gov/ct2/show/NCT03328247?term=ASICA&rank=1. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3453-x.

Involvement of indoleamine 2, 3-dioxygenase (IDO) and brain-derived neurotrophic factor (BDNF) in the neuroprotective mechanisms of ferulic acid against depressive-like behaviour.

OBJECTIVE: Ferulic acid (FA) is a common food ingredient that is abundantly present in various routinely consumed food and beverages. Like many cinnamic acid derivatives, FA produces wide-ranging effects in a dose-dependent manner and various studies link FA consumption with reduced risk of depressive disorders. The aim of this study was to exploit the neuroprotective mechanisms of FA including indoleamine 2,3-dioxygenase (IDO), brain-derived neurotrophic factor (BDNF), and other pro-inflammatory cytokines by employing lipopolysaccharide (LPS)-induced depressive-like behaviour model. METHODS: C57BL/6J male mice were divided into 4 groups consisting of saline (SAL), LPS, FA and Imipramine (IMI). Animals were pretreated orally with FA (10 mg/kg) and IMI (10 mg/kg) for 21 days once daily and all groups except SAL were challenged with LPS (0.83 mg/kg) intraperitoneally on day 21. RESULTS: LPS administration produced a biphasic change in the behaviour of the animals where the animals lost a significant weight and express high immobility time at 24 h. Proinflammatory cytokines including, TNF-α, IL-6, IL-1ß, and IFN-γ were significantly increased along with increased lipid peroxidation and reduced BDNF. Furthermore, the increased kynurenine to tryptophan ratio was indicative of elevated IDO activity. CONCLUSION: The results of this study emphasise that low dose of FA is effective in attenuating depressive-like behaviour by modulating IDO, BDNF and reducing neuroinflammation.

A novel co-culture model of human prostate epithelial and stromal cells for androgenic and antiandrogenic screening.

The risk assessment of endocrine-disrupting chemicals (EDCs) greatly relies on in vitro screening. A 3-dimensional (3D) in vitro prostate model that can reflect physiologically-relevant prostate epithelial and stromal crosstalk can significantly advance the current androgen assessment. This study built a prostate epithelial and stromal co-culture microtissue model with BHPrE and BHPrS cells in scaffold-free hydrogels. The optimal 3D co-culture condition was defined, and responses of the microtissue to androgen (dihydrotestosterone, DHT) and anti-androgen (flutamide) exposure were characterized using molecular and image profiling techniques. The co-culture prostate microtissue maintained a stable structure for up to seven days and presented molecular and morphological features of the early developmental stage of the human prostate. The cytokeratin 5/6 (CK5/6) and cytokeratin 18 (CK18) immunohistochemical staining indicated epithelial heterogeneity and differentiation in these microtissues. The prostate-related gene expression profiling did not efficiently differentiate androgen and anti-androgen exposure. However, a cluster of distinctive 3D image features was identified and could be applied in the androgenic and anti-androgenic effect prediction. Overall, the current study established a co-culture prostate model that provided an alternative strategy for (anti-)androgenic EDC safety assessment and highlighted the potential and advantage of utilizing image features to predict endpoints in chemical screening.

Increased Risk of Venous Thromboembolism in Patients With Amyotrophic Lateral Sclerosis: Results From a US Insurance Claims Database Study.

Background and Objectives: Reduced mobility in patients with amyotrophic lateral sclerosis (ALS) is hypothesized to increase the risk of venous thromboembolism (VTE). A few small, single-center studies have investigated the risk of VTE in patients with ALS. Given the high morbidity and mortality associated with VTE, further understanding of the risk in patients with ALS may inform clinical care. The objective of this study was to investigate the incidence of VTE in patients with ALS compared with controls without ALS. Methods: Patients were identified from a US health insurance claims database, Optum's deidentified Clinformatics Data Mart Database, between 2004 and 2019. ALS cases were defined as patients aged 18 years or older with (1) 2 or more ALS claims at least 27 days apart including at least 1 claim from a neurologist visit or (2) 1 or more ALS claims and a prescription for riluzole or edaravone. Each ALS case was matched on age and sex to 5 controls without ALS. VTE was defined as at least 1 claim for VTE and at least 1 anticoagulant prescription or VTE-related procedure within 7 days before and 30 days after a VTE claim date. Incidence rates were reported per 1,000 person-years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model. Results: Among 4,205 ALS cases and 21,025 controls, incident VTE occurred in 132 ALS cases (3.1%) and 244 controls (1.2%). Incidence rates of VTE were 19.9 per 1,000 person-years (95% CI 16.7-23.6) in ALS cases compared with 6.0 per 1,000 person-years (95% CI 5.0-7.1) in controls. ALS cases were about 3 times more likely to develop VTE (HR 3.3, 95% CI 2.6-4.0), with similar results among men and women. The median time to first VTE was 10 months from the initial ALS claim in ALS cases. Discussion: Consistent with previous smaller studies, a higher incidence rate of VTE was observed in a large sample of patients with ALS from across the United States, as compared to matched controls. The markedly increased risk underscores the importance of preventive efforts and careful monitoring for VTE in patients with ALS and may have implications for the management of ALS.

Amoxicillin-clavulanate induced DRESS syndrome masquerading as red man syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction carrying a mortality rate of up to 10%. We present a rare case of DRESS syndrome induced by amoxicillin-clavulanate, initially masquerading as red man syndrome. A 32-year-old male was admitted with flu-like symptoms and a maculopapular rash on the trunk and face that was exacerbated with vancomycin infusion, concerning for red man syndrome. He was receiving systemic antibiotics (vancomycin, ceftriaxone, and metronidazole) for infective endocarditis and previously took amoxicillin-clavulanate for a dental abscess. Despite the discontinuation of vancomycin, the exanthem continued to worsen, extending to involve >50% of his body surface area. Eosinophilia, hepatosplenomegaly, and acute kidney and liver injuries prompted consideration of DRESS syndrome. All antibiotics were discontinued, and systemic glucocorticoids were initiated. Punch biopsy revealed interface dermatitis with eosinophilic infiltrates; a high RegiSCAR score confirmed the diagnosis of DRESS. Amoxicillin-clavulanate was flagged as a severe allergy and deemed the culprit owing to the timing of exposure and personal/family history of hypersensitivity.

Interaction between mono-(2-ethylhexyl) phthalate and retinoic acid alters Sertoli cell development during fetal mouse testis cord morphogenesis.

Phthalic acid esters (phthalates) are a class of industrial chemicals that cause developmental and reproductive toxicity, but there are significant gaps in knowledge of phthalate toxicity mechanisms. There is evidence that phthalates disrupt retinoic acid signaling in the fetal testis, potentially disrupting control of spatial and temporal patterns of testis development. Our goal was to determine how a phthalate would interact with retinoic acid signaling during fetal mouse testis development. We hypothesized that mono-(2-ethylhexyl) phthalate (MEHP) would exacerbate the adverse effect of all-trans retinoic acid (ATRA) on seminiferous cord development in the mouse fetal testis. To test this hypothesis, gestational day (GD) 14 C57BL/6 mouse testes were isolated and cultured on media containing MEHP, ATRA, or a combination of both compounds. Cultured testes were collected for global transcriptome analysis after one day in culture and for histology and immunofluorescent analysis of Sertoli cell differentiation after three days in culture. ATRA disrupted seminiferous cord morphogenesis and induced aberrant FOXL2 expression. MEHP alone had no significant effect on cord development, but combined exposure to MEHP and ATRA increased the number of FOXL2-positive cells, reduced seminiferous cord number, and increased testosterone levels, beyond the effect of ATRA alone. In RNA-seq analysis, ATRA treatment and MEHP treatment resulted in differential expression of genes 510 and 134 genes, respectively, including 70 common differentially expressed genes (DEGs) between the two treatments, including genes with known roles in fetal testis development. MEHP DEGs included RAR target genes, genes involved in angiogenesis, and developmental patterning genes, including members of the homeobox superfamily. These results support the hypothesis that MEHP modulates retinoic acid signaling in the mouse fetal testis and provide insight into potential mechanisms by which phthalates disrupt seminiferous cord morphogenesis.

The Achieving Self-directed Integrated Cancer Aftercare Intervention for Detection of Recurrent and Second Primary Melanoma in Survivors of Melanoma: Pilot Randomized Controlled Trial.

BACKGROUND: Melanoma is common with increasing incidence. Guidelines recommend monthly total skin self-examinations (TSSEs) by survivors to detect recurrent and new primary melanomas. TSSE is underperformed despite evidence of benefit. OBJECTIVE: This study compares the effect on psychological well-being and TSSE practice of a self-directed digital intervention with treatment as usual in patients treated for a first stage 0 to IIC primary cutaneous melanoma within the preceding 60 months. METHODS: This randomized clinical trial was conducted at 2 UK National Health Service hospitals (Aberdeen Royal Infirmary, Grampian, and Addenbrooke's, Cambridge). Adults (≥18 years) diagnosed with a first 0 to IIC primary cutaneous melanoma were randomized to receive Achieving Self-directed Integrated Cancer Aftercare (ASICA), a tablet-based intervention prompting and supporting TSSE in survivors of melanoma, or to usual care. The hypothesis was that ASICA would increase TSSE practice in users affected by melanoma and compared with controls without affecting psychological well-being. The main primary outcomes were melanoma worry (Melanoma Worry Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and quality of life (EQ-5D-5L) as well as secondary outcomes collected using postal questionnaires 3, 6, and 12 months following randomization. RESULTS: A total of 240 recruits were randomized (1:1) into the ASICA (n=121, 50.4%) or control (n=119, 49.6%) groups. There were no significant differences between groups for melanoma worry at 12 months (mean difference: 0.12, 95% CI -0.6 to 0.84; P=.74), 3 months (0.23, 95% CI -0.31 to 0.78; P=.40), or 6 months (-0.1, 95% CI -0.7 to 0.51; P=.76). The ASICA group had lower anxiety scores at 12 months (-0.54, 95% CI -1.31 to 0.230; P=.17), 3 months (-0.13, 95% CI -0.79 to 0.54; P=.71), and significantly at 6 months (-1.00, 95% CI -1.74 to -0.26; P=.009). Depression scores were similar, being lower at 12 months (-0.44, 95% CI -1.11 to 0.23; P=.20) and 3 months (-0.24, 95% CI -0.84 to 0.35; P=.42) but only significantly lower at 6 months (-0.77, 95% CI -1.41 to -0.12; P=.02). The ASICA group had significantly higher quality of life scores at 12 months (0.044, 95% CI 0.003-0.085; P=.04) and 6 months (0.070, 95% CI 0.032-0.107; P<.001) and nonsignificantly at 3 months (0.024, 95% CI -0.006 to 0.054; P=.11). ASICA users reported significantly more regular (>5) TSSEs during the study year and significantly higher levels of self-efficacy in conducting TSSE. They also reported significantly higher levels of planning and intention to perform TSSE in the future. CONCLUSIONS: Using ASICA for 12 months does not increase melanoma worry, can reduce anxiety and depression, and may improve quality of life. ASICA has the potential to improve the well-being and vigilance of survivors of melanoma and enable the benefits of regular TSSE. TRIAL REGISTRATION: ClinicalTrials.gov NCT03328247; https://clinicaltrials.gov/ct2/show/NCT03328247. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3453-x.

How does social context influence appraisal and help-seeking for potential cancer symptoms in adults aged 50 and over? A qualitative interview study.

OBJECTIVE: To investigate how social context and social network activation influence appraisal and help-seeking for symptoms potentially indicative of cancer. METHODS: Semi-structured telephone interview study. Community dwelling adults who had experienced at least one symptom potentially indicative of cancer within the last month were sampled from a national symptom survey. RESULTS: Thirty-four interviews were conducted. Participants looked to peers and wider society to judge whether symptoms might be normal for their age. Involvement of others in symptom appraisal promoted an active management strategy, such as contacting a healthcare professional or trying a medication. There were practical, emotional, attitudinal, normative and moral barriers to involving others. Cancer narratives from significant others, public health campaigns and the media influenced symptom appraisal. Participants held mental representations of types of people who get cancer, for example, smokers and unfit people. This had two consequences. First, participants did not identify themselves as a candidate for cancer; impeding help-seeking. Second, social judgements about lifestyle introduced stigma. CONCLUSION: Involving friends/family in symptom appraisal facilitates help-seeking but barriers exist to involving others. Campaigns to promote earlier cancer diagnosis should incorporate age-appropriate narratives, address misconceptions about 'types' of people who get cancer and tackle stigma about lifestyle factors.

Provision of externally accredited immunisation certification within an Australian Professional Pharmacy University programme: a survey of graduates on benefits and outcomes.

OBJECTIVES: In Australia, pharmacists may become authorised immunisers by obtaining additional credentialling from certified providers. Some Australian Universities are providing externally accredited immunisation training to final year pharmacy students. Student satisfaction has been demonstrated, but graduate views on benefits and outcomes are yet to be determined. The aim of this study was to evaluate graduates' perceptions of providing an accredited immunisation certification during their University pharmacy programme. METHODS: A survey was sent to Griffith University pharmacy graduates of 2016-2020 inclusive. Respondents who completed the accredited immunisation training at University were asked to rank their agreement with five statements on a five-point Likert scale (1 = Strongly Disagree, 5 = Strongly Agree). Further information, including free-text responses, was collected on current area of practice and involvement in vaccinations. KEY FINDINGS: Of the 46 graduates who completed the survey, 42 (91.3%) completed the accredited immunisation training at University. Statements that the accredited immunisation training was considered a valuable additional offering to the pharmacy programme and the time commitment was worthwhile resulted in a mean agreement of 4.74 ± 0.73 and 4.64 ± 0.76, respectively. The majority of respondents (n = 27, 58.7%) were providing immunisations on a daily, weekly or monthly basis with over half reporting becoming more actively involved in immunisation due to COVID-19. CONCLUSIONS: Pharmacy graduates valued completing an externally accredited immunisation training within their University programme and reported benefits to their employability and current roles. Incorporating externally accredited training into the curriculum can ensure graduates are prepared and skilled in continually expanding roles for pharmacists.

Factors that predict NCLEX-RN success at a Historically Black College and University: A four-year retrospective study.

INTRODUCTION: Ensuring NCLEX-RN success for graduates of Historically Black Colleges and Universities (HBCUs) is integral to increasing Blacks and other racial/ethnic minorities underrepresented as registered nurses (RNs). PURPOSE: To examine the association between program type (traditional (TBSN) and accelerated Bachelor of Science [ABSN]) and first-time NCLEX-RN exam outcome. METHODS: A retrospective descriptive design was used. TBSN and ABSN students (n = 465) who graduated between 2015-2018 at an HBCU were examined. RESULTS: First-time pass rates for the total sample was 91.58%. Differences were observed between program type in 10 nursing courses for both programs, with Child Health being the only course predicting NCLEX-RN in both programs. In a multivariate logistic regression model, male students were 69% less likely to pass NCLEX-RN exam on first attempt compared to females, AOR = 0.31, p = 0.005. CONCLUSION: HBCUs can successfully prepare a diverse population of BSN graduates who pass NCLEX-RN on first attempt. Increased understanding of factors that decrease NCLEX-RN success of males is a prerequisite to development of strategies to ensure that all students have positive outcomes. There is also a need to understand differential relationships between nursing course grades and NCLEX-RN success among students enrolled in TBSN versus ABSN paths.

Comparative All-Cause Mortality Among a Large Population of Patients with Spinal Muscular Atrophy Versus Matched Controls.

INTRODUCTION: There is little information about survival of spinal muscular atrophy (SMA) patients into adulthood, in particular from population-based samples. We estimated and compared age-specific, all-cause mortality rates in patients with SMA and matched controls in a large, retrospective cohort study using electronic health records (EHRs) from the pre-treatment era. METHODS: The US Optum® de-identified EHR database contains EHRs for ~ 104 million persons (study period: January 1, 2007-December 22, 2016). SMA cases were identified by one or more International Classification of Diseases, Ninth/Tenth Edition codes for SMA. Controls with no SMA diagnosis code were matched 10:1 to SMA cases based on birth year, gender, and first diagnostic code date. For both groups, ≥ 1 month of observation and (if deceased) a valid date of death were required for inclusion. Age-specific mortality rates per person-year (PY) and hazard ratios were calculated. RESULTS: Five thousand one hundred seventy-nine SMA cases and 51,152 controls were analyzed. The overall hazard ratio comparing cases with controls was 1.76 (95% CI 1.63-1.90). In patients with SMA type III diagnostic codes only, the all-age mortality rate was 1059/100,000 PYs in cases and 603/100,000 PYs in controls. In older age groups (13-20, 21-30, 31-40, 41-50, 51-60, and > 60 years), age-specific mortality rates for cases consistently exceeded those of controls. Limitations of this study included the inability to confirm the SMA diagnosis or SMA type by genetic or clinical confirmation. CONCLUSION: Patients with SMA of all ages, including adults and type III patients, had a higher all-cause mortality rate as compared to age-matched controls during the pre-treatment era.

Remedial effects of caffeine against depressive-like behaviour in mice by modulation of neuroinflammation and BDNF.

Objective: Caffeine (CAF) is one of the most commonly consumed nutritional stimulant in beverages. Interestingly, CAF produces varied effects in a dose-dependent manner, and that makes it one of the most controversial nutritional ingredients. Various studies have linked CAF consumption and reduced risk of depressive disorders. The aim of this study was to investigate the effect of CAF on lipopolysaccharide (LPS)-induced neuroinflammation and depressive-like behaviour.Methods: C57BL/6J male mice were divided into four groups consisting of saline (SAL), LPS, CAF and Imipramine (IMI). Animals were pretreated orally with CAF (10 mg/kg) and IMI (10 mg/kg) for 14 days once daily and all groups except SAL were challenged with LPS (0.83 mg/kg) intraperitoneally on day 14.Results: LPS produced a biphasic behavioural response with a significantly high immobility time and weight loss after 24 h. The brain cytokines (TNF-α, IL-6, IL-1ß, and IFN-γ) levels were remarkably high, along with increased lipid peroxidation and reduced Brain Derived Neurotrophic Factor (BDNF). These biochemical and behavioural changes were significantly alleviated by CAF and IMI chronic treatment.Conclusion: The results of this study implicate that mild-moderate consumption of CAF could impart anti-inflammatory properties under neuroinflammatory conditions by modulating the cytokine and neurotrophic mechanisms.

Practical Strategies and Tools for Use by Occupational and Environmental Medicine Departments During COVID-19 Pandemic Surges.

OBJECTIVES: Occupational and environmental medicine (OEM) departments in healthcare institutions can be quickly overwhelmed when COVID-19 infection rates rapidly and simultaneously increase in the workforce and the patients served. Our goal is to present a detailed toolkit of practical approaches for use by front-line OEM specialists to address workforce management tasks during pandemic surges. METHODS: Specific focus is on tasks related to employee symptom triage, exposure risk assessment, workplace contact tracing, and work restrictions. RESULTS: Tools include strategies used by customer call centers, two decision support algorithms (exposure due to cohabitation or non-cohabitation), a color-coded employee case tracking tool, a contact tracing protocol, and documentation templates that serve as memory aids for encounters. CONCLUSIONS: These tools are created with commonly used software. Implementation is feasible in most front-line OEM settings, including those with limited resources.