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Inflammatory markers in world trade center workers with asthma: Associations with post traumatic stress disorder

by Juan P. Wisnivesky, Nikita Agrawal, Jyoti Ankam, Adam Gonzalez, Alex Federman, Steven B. Markowitz, Janette M. Birmingham, Paula J. Busse

Background

Post-traumatic stress disorders (PTSD) is associated with worse asthma outcomes in individuals exposed to the World Trade Center (WTC) site.

Research question

Do WTC workers with coexisting PTSD and asthma have a specific inflammatory pattern that underlies the relationship with increased asthma morbidity?

Study design and methods

We collected data on a cohort of WTC workers with asthma recruited from the WTC Health Program. Diagnosis of PTSD was ascertained with a Structured Clinical Interview for DSM-5 (Diagnostic and Statistical Manuel of Mental Disorders) and the severity of PTSD symptoms was assessed with the PTSD Checklist 5. We obtained blood and sputum samples to measure cytokines levels in study participants.

Results

Of the 232 WTC workers with diagnosis of asthma in the study, 75 (32%) had PTSD. PTSD was significantly associated with worse asthma control (p = 0.002) and increased resource utilization (p = 0.0002). There was no significant association (p>0.05) between most blood or sputum cytokines with PTSD diagnosis or PCL-5 scores both in unadjusted and adjusted analyses.

Interpretation

Our results suggest that PTSD is not associated with blood and sputum inflammatory markers in WTC workers with asthma. These findings suggest that other mechanisms likely explain the association between PTSD and asthma control in WTC exposed individuals.

Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel

by Ashley M. Brooks, Andrea Vornoli, Ramesh C. Kovi, Thai Vu T. Ton, Miaofei Xu, Ahmed Mashal, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Daniele Mandrioli, Fiorella Belpoggi, Arun R. Pandiri

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

AGO2-RIP-Seq reveals miR-34/miR-449 cluster targetome in sinonasal cancers

by Marco Tomasetti, Federica Monaco, Corrado Rubini, Marzia Rossato, Concetta De Quattro, Cristina Beltrami, Giacomo Sollini, Ernesto Pasquini, Monica Amati, Gaia Goteri, Lory Santarelli, Massimo Re

Sinonasal tumours are heterogeneous malignancies, presenting different histological features and clinical behaviour. Many studies emphasize the role of specific miRNA in the development and progression of cancer, and their expression profiles could be used as prognostic biomarkers to predict the survival. Recently, using the next-generation sequencing (NGS)-based miRNome analysis the miR-34/miR-449 cluster was identified as miRNA superfamily involved in the pathogenesis of sinonasal cancers (SNCs). In the present study, we established an Argonaute-2 (AGO2): mRNA immunoprecipitation followed by high-throughput sequencing to analyse the regulatory role of miR-34/miR-449 in SNCs. Using this approach, we identified direct target genes (targetome), which were involved in regulation of RNA-DNA metabolic, transcript and epigenetic processes. In particular, the STK3, C9orf78 and STRN3 genes were the direct targets of both miR-34c and miR-449a, and their regulation are predictive of tumour progression. This study provides the first evidence that miR-34/miR-449 and their targets are deregulated in SNCs and could be proposed as valuable prognostic biomarkers.

Primary care system-level training and support programme for the secondary prevention of domestic violence and abuse: a cost-effectiveness feasibility model

Por: Cochrane · M. · Szilassy · E. · Coope · C. · Emsley · E. · Johnson · M. · Feder · G. · Barbosa · E. C.
Objectives

This study aimed to evaluate the prospective cost-effectiveness of the Identification and Referral to Improve Safety plus (IRIS+) intervention compared with usual care using feasibility data derived from seven UK general practice sites.

Method

A cost–utility analysis was conducted to assess the potential cost-effectiveness of IRIS+, an enhanced model of the UK’s usual care. IRIS+ assisted primary care staff in identifying, documenting and referring not only women, but also men and children who may have experienced domestic violence/abuse as victims, perpetrators or both. A perpetrator group programme was not part of the intervention per se but was linked to the IRIS+ intervention via a referral pathway and signposting. A Markov model was constructed from a societal perspective to estimate mean incremental costs and quality-adjusted life years (QALYs) of IRIS+ compared with to usual care over a 10-year time horizon.

Results

The IRIS+ intervention saved £92 per patient and produced QALY gains of 0.003. The incremental net monetary benefit was positive (£145) and the IRIS+ intervention was cost-effective in 55% of simulations at a cost-effectiveness threshold of £20 000 per QALY.

Conclusion

The IRIS+ intervention could be cost-effective or even cost saving from a societal perspective in the UK, though there are large uncertainties, reflected in the confidence intervals and simulation results.

Impact of heat on mental health emergency visits: a time series study from all public emergency centres, in Curitiba, Brazil

Por: Corvetto · J. F. · Federspiel · A. · Sewe · M. O. · Müller · T. · Bunker · A. · Sauerborn · R.
Objectives

Quantify the risk of mental health (MH)-related emergency department visits (EDVs) due to heat, in the city of Curitiba, Brazil.

Design

Daily time series analysis, using quasi-Poisson combined with distributed lag non-linear model on EDV for MH disorders, from 2017 to 2021.

Setting

All nine emergency centres from the public health system, in Curitiba.

Participants

101 452 EDVs for MH disorders and suicide attempts over 5 years, from patients residing inside the territory of Curitiba.

Main outcome measure

Relative risk of EDV (RREDV) due to extreme mean temperature (24.5°C, 99th percentile) relative to the median (18.02°C), controlling for long-term trends, air pollution and humidity, and measuring effects delayed up to 10 days.

Results

Extreme heat was associated with higher single-lag EDV risk of RREDV 1.03(95% CI 1.01 to 1.05—single-lag 2), and cumulatively of RREDV 1.15 (95% CI 1.05 to 1.26—lag-cumulative 0–6). Strong risk was observed for patients with suicide attempts (RREDV 1.85, 95% CI 1.08 to 3.16) and neurotic disorders (RREDV 1.18, 95% CI 1.06 to 1.31). As to demographic subgroups, females (RREDV 1.20, 95% CI 1.08 to 1.34) and patients aged 18–64 (RREDV 1.18, 95% CI 1.07 to 1.30) were significantly endangered. Extreme heat resulted in lower risks of EDV for patients with organic disorders (RREDV 0.60, 95% CI 0.40 to 0.89), personality disorders (RREDV 0.48, 95% CI 0.26 to 0.91) and MH in general in the elderly ≥65 (RREDV 0.77, 95% CI 0.60 to 0.98). We found no significant RREDV among males and patients aged 0–17.

Conclusion

The risk of MH-related EDV due to heat is elevated for the entire study population, but very differentiated by subgroups. This opens avenue for adaptation policies in healthcare: such as monitoring populations at risk and establishing an early warning systems to prevent exacerbation of MH episodes and to reduce suicide attempts. Further studies are welcome, why the reported risk differences occur and what, if any, role healthcare seeking barriers might play.

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