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Mental health issues are a growing concern in the workplace, linked to negative outcomes including reduced productivity, increased absenteeism, and increased turnover. Employer-sponsored mental health benefits that are accessible and proactive may help address these concerns. The aim of this retrospective cohort study was to evaluate the impact of a digital mental health benefit (Spring Health) on frontline healthcare service workers' clinical and workplace outcomes. The benefit was sponsored by a national health services company from 2021–2022 and included mental health screening, care navigation, psychotherapy and/or medication management. We hypothesized program use would be associated with improvements in depression and anxiety symptoms, and increased productivity and retention. Participants were employees enrolled in the benefit program, had at least moderate anxiety or depression, at least 1 treatment appointment, and at least 2 outcome assessments. Clinical improvement measures were PHQ-9 scale (range, 0–27) for depression and GAD-7 scale (range, 0–21) for anxiety; workplace measures were employee retention and the Sheehan Disability Scale (SDS) for functional impairment. A total of 686 participants were included. Participants using the mental health benefit had a 5.60 point (95% CI, 4.40–6.79, d = 1.28) reduction in depression and a 5.48 point (95% CI, 3.88–7.08, d = 1.64) reduction in anxiety across 6 months. 69.9% (95% CI, 61.8%–78.1%) of participants reliably improved (≥5 point change) and 84.1% (95% CI, 78.2%–90.1%) achieved reliable improvement or recovery (<10 points). Participants reported 0.70 (95% CI, 0.26–1.14) fewer workdays per week impacted by mental health issues, corresponding to $3,491 (95% CI, $1305–$5677) salary savings at approximately federal median wage ($50,000). Furthermore, employees using the benefit were retained at 1.58 (95% CI, 1.4–1.76) times the rate of those who did not. Overall, this evaluation suggests that accessible, proactive, and comprehensive mental health benefits for frontline health services workers can lead to positive clinical and workplace outcomes. [ABSTRACT FROM AUTHOR]

A digital Diabetes Prevention Program (dDPP) was effective in reducing the risk of diabetes in a workforce population. All modifiable components of a validated diabetes risk score (diastolic BP, systolic BP, BMI, fasting glucose, HDL-cholesterol, triglycerides) improved after the first year of the dDPP compared to the year prior. Objective: We asked whether the estimated 8-year risk of diabetes could be reduced within the first 2 years of a digital Diabetes Prevention Program (dDPP) in a workforce population. Methods: Employees and spouses were eligible if they had prediabetes-range fasting glucose or hemoglobin A1c and body mass index ≥25 kg/m2. Diabetes risk was assessed using the Framingham diabetes risk score in the year before and the 2 years after dDPP initiation. Results: Among participants completing at least nine dDPP lessons (n = 286), diabetes risk decreased 5.3% the year after dDPP initiation, after a 5.4% increase the year before initiation (difference in differences, −10.6%; 95% confidence interval, −13.4% to −7.9%; P < 0.001), with risk maintained at reduced levels after the second year of the program. Conclusion: This dDPP reduced the estimated 8-year risk of diabetes over the first 2 years of the program. [ABSTRACT FROM AUTHOR]

Abstract Background The lipocalin (LCN) family of structurally conserved hydrophobic ligand binding proteins is represented in all major taxonomic groups from prokaryotes to primates. The importance of lipocalins in reproduction and the similarity to known epididymal lipocalins prompted us to characterize the novel human epididymal LCN6. Methods and Results LCN6 cDNA was identified by database analysis in a comprehensive human library sequencing program. Macaca mulatta (rhesus monkey) cDNA was obtained from an epididymis cDNA library and is 93% homologous to the human. The gene is located on chromosome 9q34 adjacent LCN8 and LCN5. LCN6 amino acid sequence is most closely related to LCN5, but the LCN6 beta-barrel structure is best modeled on mouse major urinary protein 1, a pheromone binding protein. Northern blot analysis of RNAs isolated from 25 human tissues revealed predominant expression of a 1.0 kb mRNA in the epididymis. No other transcript was detected except for weak expression of a larger hybridizing mRNA in urinary bladder. Northern hybridization analysis of LCN6 mRNA expression in sham-operated, castrated and testosterone replaced rhesus monkeys suggests mRNA levels are little affected 6 days after castration. Immunohistochemical staining revealed that LCN6 protein is abundant in the caput epithelium and lumen. Immunofluorescent staining of human spermatozoa shows LCN6 located on the head and tail of spermatozoa with the highest concentration of LCN6 on the post-acrosomal region of the head, where it appeared aggregated into large patches. Conclusions LCN6 is a novel lipocalin closely related to Lcn5 and Lcn8 and these three genes are likely products of gene duplication events that predate rodent-primate divergence. Predominant expression in the epididymis and location on sperm surface are consistent with a role for LCN6 in male fertility.

Objective: Evaluate the effect of a digital Diabetes Prevention Program (dDPP) on chronic disease risk factors in a workplace population. Methods: dDPP participants were employees and spouses with BMI ≥ 24kg/m² and prediabetes or diabetes (n = 84). Annual change in risk factors before and after dDPP were assessed in the dDPP group and in a retrospectively identified matched control group drawn from those who participated in a dDPP after the conclusion of this study (n = 252). Results: In the dDPP group, body weight, BMI, fasting glucose, triglycerides, total cholesterol and LDL-cholesterol decreased in the post-dDPP period compared with the pre-dDPP period (P<0.05). In the control group, no difference between the annual change before and after dDPP was observed (P > 0.37). Conclusion: The dDPP was effective in reducing risk factors for chronic disease in a workplace setting. [ABSTRACT FROM AUTHOR]

Background: The number of pulmonary nodules detected in the US is expected to increase substantially following recent recommendations for nationwide CT-based lung cancer screening. Given the low specificity of CT screening, non-invasive adjuvant methods are needed to differentiate cancerous lesions from benign nodules to help avoid unnecessary invasive procedures in the asymptomatic population. We have constructed a serum-based multi-biomarker panel and assessed its clinical accuracy in a retrospective analysis of samples collected from participants with suspicious radiographic findings in the Prostate, Lung, Chest and Ovarian (PLCO) cancer screening trial. Methods: Starting with a set of 9 candidate biomarkers, we identified 8 that exhibited limited pre-analytical variability with increasing clotting time, a key pre-analytical variable associated with the collection of serum. These 8 biomarkers were evaluated in a training study consisting of 95 stage I NSCLC patients and 186 smoker controls where a 5-biomarker pulmonary nodule classifier (PNC) was selected. The clinical accuracy of the PNC was determined in a blinded study of asymptomatic individuals comprising 119 confirmed malignant nodule cases and 119 benign nodule controls selected from the PLCO screening trial. Results: A PNC comprising 5 biomarkers: CEA, CYFRA 21-1, OPN, SCC, and TFPI, was selected in the training study. In an independent validation study, the PNC resolved lung cancer cases from benign nodule controls with an AUC of 0.653 (p < 0.0001). CEA and CYFRA 21-1, two of the markers included in the PNC, also accurately distinguished malignant lesions from benign controls. Conclusions: A 5-biomarker blood test has been developed for the diagnostic evaluation of asymptomatic individuals with solitary pulmonary nodules. [ABSTRACT FROM AUTHOR]

Background: Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging. Results: We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21-1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775). Conclusions: Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses. [ABSTRACT FROM AUTHOR]

Background: The lipocalin (LCN) family of structurally conserved hydrophobic ligand binding proteins is represented in all major taxonomic groups from prokaryotes to primates. The importance of lipocalins in reproduction and the similarity to known epididymal lipocalins prompted us to characterize the novel human epididymal LCN6. Methods and Results: LCN6 cDNA was identified by database analysis in a comprehensive human library sequencing program. Macaca mulatta (rhesus monkey) cDNA was obtained from an epididymis cDNA library and is 93% homologous to the human. The gene is located on chromosome 9q34 adjacent LCN8 and LCN5. LCN6 amino acid sequence is most closely related to LCN5, but the LCN6 beta-barrel structure is best modeled on mouse major urinary protein 1, a pheromone binding protein. Northern blot analysis of RNAs isolated from 25 human tissues revealed predominant expression of a 1.0 kb mRNA in the epididymis. No other transcript was detected except for weak expression of a larger hybridizing mRNA in urinary bladder. Northern hybridization analysis of LCN6 mRNA expression in sham-operated, castrated and testosterone replaced rhesus monkeys suggests mRNA levels are little affected 6 days after castration. Immunohistochemical staining revealed that LCN6 protein is abundant in the caput epithelium and lumen. Immunofluorescent staining of human spermatozoa shows LCN6 located on the head and tail of spermatozoa with the highest concentration of LCN6 on the post-acrosomal region of the head, where it appeared aggregated into large patches. Conclusions: LCN6 is a novel lipocalin closely related to Lcn5 and Lcn8 and these three genes are likely products of gene duplication events that predate rodent-primate divergence. Predominant expression in the epididymis and location on sperm surface are consistent with a role for LCN6 in male fertility. [ABSTRACT FROM AUTHOR]

Background: A digital Diabetes Prevention Program (dDPP) has been shown to reduce the 8-year risk of diabetes in the first year of implementation in a workforce setting. We asked whether the dDPP reduced the risk of diabetes in a second year. Methods: Individuals were included in the study if they (i) participated in an employer-sponsored wellness program with year-end biometric screening for 4 consecutive years (2016 to 2019), (ii) had prediabetes-range fasting glucose (100 to 125 mg/dL) or Hb1Ac (5.7% to 6.4%), (iii) a BMI ≥25 kg/m2 at the end of 2017, and (iv) completed ≥9 lessons in a dDPP initiated at the beginning of 2018. In the first year of the dDPP, individuals participated in weekly online lessons. In the second year, no new content was introduced, but individuals had access to lessons delivered in year 1. Results: The baseline characteristics from the 2017 year-end screen are provided (Table). On average, participants (n=401) completed 25.1 lessons (SD: 12.3). In the second year of intervention, levels of BMI, fasting glucose, triglycerides and HDL-C, all components of the 8-year diabetes risk score, improved relative to changes observed in the year before intervention. The 8-year risk of developing diabetes was also reduced (Table). Conclusions: The risk of developing type 2 diabetes was reduced in the second year of a dDPP. Disclosure: C.E. Birse: Employee; Self; Quest Diagnostics. M.S. Fragala: Employee; Self; Quest Diagnostics. A.R. Arellano: None. L.A. Bare: Employee; Self; Quest Diagnostics. C. Castro Sweet: Employee; Self; Omada Health. R.J. Lagier: Employee; Self; Quest Diagnostics. Employee; Spouse/Partner; Thermo Fisher Scientific. [ABSTRACT FROM AUTHOR]

Background: Digital behavioral counseling has previously been shown to reduce levels of risk factors for diabetes including fasting glucose and HbA1c. We asked whether the 8-year risk of developing diabetes could be reduced within the first year of a digital counseling program. Methods: Individuals were included in the study if they (i) participated in an employer-sponsored wellness program with year-end biometric screening for 3 consecutive years (2016, 2017, and 2018), (ii) had prediabetes-range fasting glucose (100 to 125 mg/dL) or Hb1Ac (5.7% to 6.4%), (iii) a BMI ≥25 kg/m2 at the end of 2017, and (iv) completed at least 9 lessons in a digital behavioral counseling program initiated at the beginning of 2018. Paired t-Tests were used to assess changes in yearly trajectories of diabetes risk factors before and after intervention (Table). Results: The baseline characteristics of the cohort at the 2017 year-end screen are provided (Table). On average, participants (n=460) were engaged in the counseling program for 9.1 months (SD: 1.2) and completed 25.1 lessons (SD: 12.3). After participation, levels of all biometric variables included in the 8-year risk model* shifted in a favorable direction; the 8-year risk of developing diabetes was reduced (Table). Conclusions: Digital behavioral counseling was effective in reducing risk factors and the 8-year risk of diabetes during the first year of the program. Disclosure: C.E. Birse: Employee; Self; Quest Diagnostics. Stock/Shareholder; Self; Quest Diagnostics. M.S. Fragala: Employee; Self; Quest Diagnostics. A. Satish: None. K.C. McNamara: Employee; Self; Omada Health, Inc. C.M. Castro Sweet: Employee; Self; Omada Health, Inc. R.J. Lagier: Employee; Self; Quest Diagnostics. [ABSTRACT FROM AUTHOR]

Obesity is a major risk factor for a number of disorders ranging from type II diabetes to cardiovascular disease, however, the molecular basis for these associations has not been be fully clarified. A number of adipokines, cytokines expressed exclusively or at an elevated level in adipose tissue, have been identified that play key roles in regulating energy homeostasis by affecting insulin sensitivity, glucose and lipid metabolism and satiety. Dysregulated expression of adipokines may link obesity with its related metabolic disorders. We have developed a proteomics platform that enables the direct identification and functional characterization of adipokines from cells derived from human subcutaneous and visceral adipose depots. Adipocytes isolated from different fat depots (subcutaneous and visceral) from subjects with a spectrum of BMI (19-42) and diabetic progression, were subjected to Mass Spectrometric (MS) analyses. Preadipocytes isolated from adipose tissue were differentiated for 2 weeks, before being incubated in conditioned medium. Secreted and shed proteins released into the medium were labeled with ICAT and digested with trypsin. The cysteine-containing peptides were subjected to Liquid Chromatography (LC) / MS analysis. Peptide maps representing different adipocyte populations were compared and candidates that were differentially expressed were selected. Sequence-composition was resolved through tandem MS and database search. The functionality of a number of these adipokines was evaluated in a series of RNAi-based assays, established in human adipocytes, to determine the possible involvement of these secreted proteins in key metabolic transitions including: lipolysis and glucose uptake. Our systematic proteomic analysis has resulted in the identification of > 20 adipokines. A number of previously characterized secreted proteins, including visfatin and complement C1r were identified. In addition, a number of novel candidates that included: a protease inhibitor, a hydrolase and a molecule involved in cell-adhesion, were also resolved. Interestingly, subsequent comparison of the MS maps within the adipocyte samples revealed significant differences in expression of secreted / shed proteins isolated from: (i) subcutaneous and visceral depots, (ii) lean and obese subjects and (iii) normal and diabetic patients. [ABSTRACT FROM AUTHOR]