Pandemic-Induced Telework Challenges and Strategies.

Prior to the COVID-19 pandemic, telework was an established discretionary practice with a considerable amount of research. However, the COVID-19 pandemic forced people who had never worked from home before to do so. Our two-wave descriptive investigation provides a historical snapshot of what approximately 400 teleworkers experienced in the first two to three months of the pandemic. We explored how this experience differed for those who had previously teleworked, those who had children in their home, and those who had supervisory responsibilities. The data exposed telework challenges and pandemic-specific challenges. The results support job crafting theories that teleworkers proactively implement strategies to adjust their boundaries and relationships to meet their need (Biron et al., Personnel Review, 2022). The data also revealed that employees were still struggling two months later, despite implementing strategies like self-care, taking breaks, and psychological reframing. This research provides detailed evidence of how pandemic-induced telework is not the same as traditional telework and some initial evidence of the pandemic-induced telework adjustment time period. Supplementary Information: The online version contains supplementary material available at 10.1007/s41542-023-00151-1.

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

An Alpha, Beta and Gamma Approach to Evaluating Occupational Health Organizational Interventions: Learning from the Measurement of Work-Family Conflict Change.

Given the rapid growth of intervention research in the occupational health sciences and related fields (e.g. work-family), we propose that occupational health scientists adopt an "alpha, beta, gamma" change approach when evaluating intervention efficacy. Interventions can affect absolute change in constructs directly (alpha change), changes in the scales used to assess change (beta change) or redefinitions of the construct itself (gamma change). Researchers should consider the extent to which they expect their intervention to affect each type of change and select evaluation approaches accordingly. We illustrate this approach using change data from groups of IT professionals and health care workers participating in the STAR intervention, designed by the Work Family Health Network. STAR was created to effect change in employee work-family conflict via supervisor family-supportive behaviors and schedule control. We hypothesize that it will affect change via all three change approaches-gamma, beta, and alpha. Using assessment techniques from measurement equivalence approaches, we find results consistent with some gamma and beta change in the IT company due to the intervention; our results suggest that not accounting for such change could affect the evaluation of alpha change. We demonstrate that using a tripartite model of change can help researchers more clearly specify intervention change targets and processes. This will enable the assessment of change in a way that has stronger fidelity between the theories used and the outcomes of interest. Our research has implications for how to assess change using a broader change framework, which employs measurement equivalence approaches in order to advance the design and deployment of more effective interventions in occupational settings. Supplementary Information: The online version contains supplementary material available at 10.1007/s41542-022-00122-y.

A Taxonomy of Employee Motives for Telework.

This qualitative research contributes to the telework research literature by identifying and categorizing employee motives for teleworking. Motives for telework contextualize teleworking behavior, represent proximal telework outcomes, and serve as potential boundary conditions for telework-outcome relationships. Role identity theory (Burke & Tully Social Forces, 55(4), 881-897, 1977) and the uncertainty-reduction hypothesis (Hogg & Terry Academy of Management Review, 25, 121-140, 2000) suggest that motives may be driven by role salience and the ability to meet work and nonwork demands. In this research, we sought to identify a comprehensive list of motives as well as reconcile the wide range of categories and labels given to telework motives in the literature. We asked two independent samples of workers comprised of two subsamples of teleworkers (n 1 = 195; n 2 = 97) and a subsample of nonteleworkers (n 3 = 947) why they telework or would like to telework. A total of 2504 reasons were gathered across the three subsamples. Most respondents reported multiple reasons, especially when encouraged to list all of their reasons. After distinguishing preconditions from motives to telework, ten categories emerged from the qualitative data with "avoid commute" emerging as the most frequently reported motive. Other frequently reported motives included "tend to family demands" and "productivity." Additional motives are discussed along with implications for telework research and policy development and implementation.

Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?

Extracellular ATP functions as a signaling messenger through its actions on purinergic receptors, and is known to be involved in numerous physiological and pathophysiological processes throughout the body, including in the lungs and airways. Consequently, purinergic receptors are considered to be promising therapeutic targets for many respiratory diseases, including asthma. This review explores how online bioinformatics resources combined with recently generated datasets can be utilized to investigate purinergic receptor gene expression in tissues and cell types of interest in respiratory disease to identify potential therapeutic targets, which can then be investigated further. These approaches show that different purinergic receptors are expressed at different levels in lung tissue, and that purinergic receptors tend to be expressed at higher levels in immune cells and at more moderate levels in airway structural cells. Notably, P2RX1, P2RX4, P2RX7, P2RY1, P2RY11, and P2RY14 were revealed as the most highly expressed purinergic receptors in lung tissue, therefore suggesting that these receptors have good potential as therapeutic targets for asthma and other respiratory diseases.

Targeting Novel Sodium Iodide Symporter Interactors ADP-Ribosylation Factor 4 and Valosin-Containing Protein Enhances Radioiodine Uptake.

The sodium iodide symporter (NIS) is required for iodide uptake, which facilitates thyroid hormone biosynthesis. NIS has been exploited for over 75 years in ablative radioiodine (RAI) treatment of thyroid cancer, where its ability to transport radioisotopes depends on its localization to the plasma membrane. The advent of NIS-based in vivo imaging and theranostic strategies in other malignancies and disease modalities has recently increased the clinical importance of NIS. However, NIS trafficking remains ill-defined. Here, we used tandem mass spectrometry followed by coimmunoprecipitation and proximity ligation assays to identify and validate two key nodes-ADP-ribosylation factor 4 (ARF4) and valosin-containing protein (VCP)-controlling NIS trafficking. Using cell-surface biotinylation assays and highly inclined and laminated optical sheet microscopy, we demonstrated that ARF4 enhanced NIS vesicular trafficking from the Golgi to the plasma membrane, whereas VCP-a principal component of endoplasmic reticulum (ER)-associated degradation-governed NIS proteolysis. Gene expression analysis indicated VCP expression was particularly induced in aggressive thyroid cancers and in patients who had poorer outcomes following RAI treatment. Two repurposed FDA-approved VCP inhibitors abrogated VCP-mediated repression of NIS function, resulting in significantly increased NIS at the cell-surface and markedly increased RAI uptake in mouse and human thyroid models. Collectively, these discoveries delineate NIS trafficking and highlight the new possibility of systemically enhancing RAI therapy in patients using FDA-approved drugs. SIGNIFICANCE: These findings show that ARF4 and VCP are involved in NIS trafficking to the plasma membrane and highlight the possible therapeutic role of VCP inhibitors in enhancing radioiodine effectiveness in radioiodine-refractory thyroid cancer.

Dimerization of the Sodium/Iodide Symporter.

Background: The ability of thyroid follicular epithelial cells to accumulate iodide via the sodium/iodide symporter (NIS) is exploited to successfully treat most thyroid cancers, although a subset of patients lose functional NIS activity and become unresponsive to radioiodide therapy, with poor clinical outcome. Our knowledge of NIS regulation remains limited, however. While numerous membrane proteins are functionally regulated via dimerization, there is little definitive evidence of NIS dimerization, and whether this might impact upon radioiodide uptake and treatment success is entirely unknown. We hypothesized that NIS dimerizes and that dimerization is a prerequisite for iodide uptake. Methods: Coimmunoprecipitation, proximity ligation, and Förster resonance energy transfer (FRET) assays were used to assess NIS:NIS interaction. To identify residues involved in dimerization, a homology model of NIS structure was built based on the crystal structure of the dimeric bacterial protein vSGLT. Results: Abundant cellular NIS dimerization was confirmed in vitro via three discrete methodologies. FRET and proximity ligation assays demonstrated that while NIS can exist as a dimer at the plasma membrane (PM), it is also apparent in other cellular compartments. Homology modeling revealed one key potential site of dimeric interaction, with six residues <3Å apart. In particular, NIS residues Y242, T243, and Q471 were identified as critical to dimerization. Individual mutation of residues Y242 and T243 rendered NIS nonfunctional, while abrogation of Q471 did not impact radioiodide uptake. FRET data show that the putative dimerization interface can tolerate the loss of one, but not two, of these three clustered residues. Conclusions: We show for the first time that NIS dimerizes in vitro, and we identify the key residues via which this happens. We hypothesize that dimerization of NIS is critical to its trafficking to the PM and may therefore represent a new mechanism that would need to be considered in overcoming therapeutic failure in patients with thyroid cancer.

Caring for the elderly at work and home: Can a randomized organizational intervention improve psychological health?

Although job stress models suggest that changing the work social environment to increase job resources improves psychological health, many intervention studies have weak designs and overlook influences of family caregiving demands. We tested the effects of an organizational intervention designed to increase supervisor social support for work and nonwork roles, and job control in a results-oriented work environment on the stress and psychological distress of health care employees who care for the elderly, while simultaneously considering their own family caregiving responsibilities. Using a group-randomized organizational field trial with an intent-to-treat design, 420 caregivers in 15 intervention extended-care nursing facilities were compared with 511 caregivers in 15 control facilities at 4 measurement times: preintervention and 6, 12, and 18 months. There were no main intervention effects showing improvements in stress and psychological distress when comparing intervention with control sites. Moderation analyses indicate that the intervention was more effective in reducing stress and psychological distress for caregivers who were also caring for other family members off the job (those with elders and those "sandwiched" with both child and elder caregiving responsibilities) compared with employees without caregiving demands. These findings extend previous studies by showing that the effect of organizational interventions designed to increase job resources to improve psychological health varies according to differences in nonwork caregiving demands. This research suggests that caregivers, especially those with "double-duty" elder caregiving at home and work and "triple-duty" responsibilities, including child care, may benefit from interventions designed to increase work-nonwork social support and job control. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Managing the cancer-work interface: the effect of cancer survivorship on unemployment.

OBJECTIVE: This study assessed differences in employment outcomes among cancer survivors using data from a nationally representative sample. METHODS: The 2011 Medical Expenditure Panel Survey (MEPS) data and the 2011 MEPS Experiences with Cancer Survivorship Supplement representing 3,360,465 people in the US population were analyzed to evaluate factors associated with unemployment among cancer survivors during the 5 years following diagnosis and treatment. The sample included adults 1) diagnosed with cancer within 5 years prior to survey completion and 2) engaged in paid employment since diagnosis. Individuals diagnosed with nonmelanoma skin cancer (n=33) were excluded from analyses. RESULTS: Data of 221 cancer survivors were used to identify factors associated with employment status at the time respondents were employed (n=155) vs unemployed (n=66). Results of bivariate analyses indicated that unemployed survivors were older, more likely to be women, more likely to be uninsured at the time of cancer diagnosis, and to report lower incomes than cancer survivors who continue to be employed. Unemployed survivors were more likely than employed survivors to have had anxiety about being forced to retire or quit early when they were employed because of cancer and to report cancer-related interference with physical and mental aspects of their job tasks; unemployed survivors also took less paid time off and were less likely to change to a flexible job schedule when they were employed. In multiple logistic regression analyses, worry about being forced to retire (protective), worry that cancer recurrence will interfere with home or work responsibilities (risk), and change to a flexible work schedule (risk) following cancer diagnosis were associated with unemployment after controlling for demographic differences between employed and unemployed cancer survivors. CONCLUSION: Findings of this study highlight the extent to which the challenges of managing the cancer-work interface create challenges to employment among cancer survivors and may lead to long-term unemployment among cancer survivors. Future studies should evaluate the strategies that the survivors could use to manage the cancer-work interface during cancer treatment to attain medical, psychological, social, and employment outcomes.

PTTG and PBF Functionally Interact with p53 and Predict Overall Survival in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and poses a significant health burden due to its rising incidence. Although the proto-oncogene pituitary tumor-transforming gene 1 (PTTG) predicts poor patient outcome, its mechanisms of action are incompletely understood. We show here that the protein PBF modulates PTTG function, is overexpressed in HNSCC tumors, and correlates with significantly reduced survival. Lentiviral shRNA attenuation of PTTG or PBF expression in HNSCC cells with either wild-type or mutant p53, and with and without HPV infection, led to dysregulated expression of p53 target genes involved in DNA repair and apoptosis. Mechanistically, PTTG and PBF affected each other's interaction with p53 and cooperated to reduce p53 protein stability in HNSCC cells independently of HPV. Depletion of either PTTG or PBF significantly repressed cellular migration and invasion and impaired colony formation in HNSCC cells, implicating both proto-oncogenes in basic mechanisms of tumorigenesis. Patients with HNSCC with high tumoral PBF and PTTG had the poorest overall survival, which reflects a marked impairment of p53-dependent signaling.Significance: These findings reveal a complex and novel interrelationship between the expression and function of PTTG, PBF, and p53 in human HNSCC that significantly influences patient outcome. Cancer Res; 78(20); 5863-76. ©2018 AACR.

Haemoptysis in pregnancy caused by a well-differentiated fetal adenocarcinoma: a case report.

INTRODUCTION: Haemoptysis in pregnancy is frequently assumed to be caused by a pulmonary embolism. However, it can also be an indicator of serious pathology. CASE PRESENTATION: We report the case of a 27-year-old Caucasian woman who presented with haemoptysis in pregnancy that was discovered to be caused by a well-differentiated fetal adenocarcinoma of the lung. CONCLUSION: This case demonstrates the importance of establishing an accurate diagnosis when a pregnant woman presents with haemoptysis and that more serious pathology should be considered if the clinical symptoms persist and/or the presumed diagnosis of pulmonary embolism is not confirmed.