Application of single cell multiomics points to changes in chromatin accessibility near calcitonin receptor like receptor and a possible role for adrenomedullin in the post-shock lung.

Introduction: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a commonly occurring sequelae of traumatic injury resulting from indirect insults like hypovolemic shock and/or extrapulmonary sepsis. The high lethality rate associated with these pathologies outlines the importance of clarifying the "priming" effects seen in the post-shock lung microenvironment, which are understood to bring about a dysregulated or overt immune response when triggered by a secondary systemic infectious/septic challenge culminating in ALI. In this pilot project, we test the hypothesis that application of a single cell multiomics approach can elucidate novel phenotype specific pathways potentially contributing to shock-induced ALI/ARDS. Methods: Hypovolemic shock was induced in C57BL/6 (wild-type), PD-1, PD-L1, or VISTA gene deficient male mice, 8-12 weeks old. Wild-type sham surgeries function as negative controls. A total of 24-h post-shock rodents were sacrificed, their lungs harvested and sectioned, with pools prepared from 2 mice per background, and flash frozen on liquid nitrogen. N = 2 biological replicates (representing 4 mice total) were achieved for all treatment groups across genetic backgrounds. Samples were received by the Boas Center for Genomics and Human Genetics, where single cell multiomics libraries were prepared for RNA/ATAC sequencing. The analysis pipeline Cell Ranger ARC was implemented to attain feature linkage assessments across genes of interest. Results: Sham (pre-shock) results suggest high chromatin accessibility around calcitonin receptor like receptor (CALCRL) across cellular phenotypes with 17 and 18 feature links, exhibiting positive correlation with gene expression between biological replicates. Similarity between both sample chromatin profiles/linkage arcs is evident. Post-shock wild-type accessibility is starkly reduced across replicates where the number of feature links drops to 1 and 3, again presenting similar replicate profiles. Samples from shocked gene deficient backgrounds displayed high accessibility and similar profiles to the pre-shock lung microenvironment. Conclusion: High pre-shock availability of DNA segments and their positive correlation with CALCRL gene expression suggests an apparent regulatory capacity on transcription. Post-shock gene deficient chromatin profiles presented similar results to that of pre-shock wild-type samples, suggesting an influence on CALCRL accessibility. Key changes illustrated in the pre-ALI context of shock may allow for additional resolution of "priming" and "cellular pre-activation/pre-disposition" processes within the lung microenvironment.

Current Impact and Long-Term Influence of the COVID-19 Pandemic on Iraqi Healthcare Systems: A Case Study.

Decades of wars, sanctions, and internal conflicts have compromised Iraq's health system, which once was the best system in the region. National and international efforts to revitalize the system have been successful to some extent; however, significant challenges still exist. The COVID-19 pandemic has exposed new vulnerabilities and exacerbated the existing ones, affecting the quality and the quantity of the health services delivered. This case study explored the baseline function of Iraq's health system within the context of the World Health Organization (WHO) health system framework. The paper also examined the country's response to the COVID-19 pandemic and some of its impacts. Results show that the system was not functioning optimally nor was it prepared to address the immediate impact of the current pandemic and other emerging public health issues. While mitigating the pandemic's short-term and long-term impacts are essential, it should not divert the focus from restructuring and strengthening the health system. Iraq may need to prioritize the health information system and leadership/governance as they provide the basis for health policies and regulations for all other health system building blocks.

Predictors of Vaccine Uptake among Migrants in the United States: A Rapid Systematic Review.

Evaluating challenges to vaccine uptake in non-US-born individuals is necessary for increasing national vaccination rates. This rapid review was conducted to investigate predictors of vaccine utilization among US migrants. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist was utilized, along with the Rayyan webtool, to facilitate the process of identifying primary research articles. Data were independently extracted by using a piloted, customized form. This was tabulated and the results were reported. Of the 186 abstracts reviewed, nine articles were included. Populations included in this review were refugees (n = 1), undocumented migrants (n = 1), migrants crossing the US-Mexico border (n = 2), Blacks (n = 1), and US-born vs. non-US-born adults (n = 1). Three studies focused on "foreign-born" children. The vaccines included in the literature reviewed were both combined series and individual, with one study addressing immunization instead of specific vaccines. Detailed characteristics of these studies and their quality evaluations were also reported. This review identified gaps in research regarding immunization among different migrant groups. Multilevel interventions should be considered to leverage the existing facilitators and address the known modifiable barriers to creating an accessible and supportive environment for marginalized populations.

A Customized Electronic Health Record-Based Tool Highlights and Addresses Gaps in Patient Safety.

The authors present a tool to improve gaps in patient safety using the electronic health record. The tool integrates gap identification, passive alerts, and actions into a single interface embedded within clinicians' workflow. The tool was developed to address venous thromboembolism prophylaxis, prevention of hypo- and hyperglycemia, code status documentation, bowel movement frequency, and skilled nursing facility transitions. Alerts and actions during silent and live periods were retrospectively analyzed. The most prevalent safety gaps were lack of venous thromboembolism prophylaxis (40.4% of alerts), constipation (19.3%), and lack of code status (18.4%). Disparities in safety gaps were present by patient race, sex, and socioeconomic status. Usability testing showed positive feedback without significant alert burden. Thus, a safety gap tool was successfully built to study and address patient safety issues. The tool's strengths are its integration within the electronic health record, ease of use, customizability, and scalability.

Prediction of Moderate to Severe Obstructive Sleep Apnea Using Neck Computed Tomography With Computational Fluid Dynamics Study.

BACKGROUND: Moderate to severe obstructive sleep apnea (OSA) is associated with cardiovascular disease. Polysomnography is time intensive and difficult to access for diagnosis of OSA. Neck computed tomography (CT) provides upper airway delineation but not diagnostic criteria for moderate to severe OSA. We explored neck CT with computational fluid dynamics (CFD) study for airway pressure and airflow velocity to predict moderate to severe OSA. METHODS: Enrolled from February 1, 2020, to June 30, 2021, patients with OSA with overnight oxygen desaturation (sPO2 <90%) received awake neck CT with a CFD study of their airway pressure and airflow velocity. CTL12 and CTL34 were defined as airflow velocity <3 and ≥3 m/s, respectively, and airway pressure <10 and ≥10 pa, respectively, in the narrowest upper airway. RESULTS: Sixty-two patients (42 male and 20 female; mean age: 50.4 ± 14.6 years) were included; 12 and 50 patients had mild OSA and moderate to severe OSA, respectively. The minimum sPO2 in the supine position was 80.7 ± 9.1%. The total time of sPO2 <90% at overnight oximetry was 29.3 ± 51.1 min. Most (85.5%) neck CT examinations with CFD study presented CTL34. Patients with CTL34 had a lower minimum sPO2 in the supine position (78.4 vs. 88.1%, P = 0.004) and longer duration of sPO2 <90% at overnight oximetry (33.9 vs. 1.9 min, P = 0.001) than those with CTL12. The values of the area under the receiver operating characteristic curves of airway pressure and of airflow velocity at the narrowest upper airway were 0.788 and 0.733, respectively. CONCLUSION: Neck CT with CFD study of airway pressure and airflow velocity may provide a quick prediction of moderate to severe OSA.

External Validation of a Nomogram to Predict Survival and Benefit of Concurrent Chemoradiation for Stage II Nasopharyngeal Carcinoma.

A nomogram was recently published by Sun et al. to predict overall survival (OS) and the additional benefit of concurrent chemoradiation (CCRT) vs. radiotherapy (RT) alone, in stage II NPC treated with conventional RT. We aimed to assess the predictors of OS and to externally validate the nomogram in the IMRT era. We analyzed stage II NPC patients treated with definitive RT alone or CCRT between 2001 and 2011 under the territory-wide Hong Kong NPC Study Group 1301 study. Clinical parameters were studied using the Cox proportional hazards model to estimate OS. The nomogram by Sun et al. was applied with 1000 times bootstrap resampling to calculate the concordance index, and we compared the nomogram predicted and observed 5-year OS. There were 482 patients included. The 5-year OS was 89.0%. In the multivariable analysis, an age > 45 years was the only significant predictor of OS (HR, 1.98; 95%CI, 1.15-3.44). Other clinical parameters were insignificant, including the use of CCRT (HR, 0.99; 95%CI, 0.62-1.58). The nomogram yielded a concordance index of 0.55 (95% CI, 0.49-0.62) which lacked clinically meaningful discriminative power. The nomogram proposed by Sun et al. should be interpreted with caution when applied to stage II NPC patients in the IMRT era. The benefit of CCRT remained controversial.

Risk of Inflammatory Bowel Disease Following Appendectomy in Adulthood.

Background: The appendix has a complicated immune function, and appendectomy may derange the immune system. Studies on the relationship between appendectomy and subsequent inflammatory bowel disease (IBD) have been inconsistent. We conducted a nationwide cohort study consisting of individuals who underwent appendectomy to evaluate the incidence and risk of ulcerative colitis (UC) and Crohn's disease (CD). Methods: We identified patients aged >20 years who underwent appendectomy between 2000 and 2012 from inpatient claims of the National Health Insurance Research Database (NHIRD) and assigned them to the appendectomy cohort. Then, we randomly selected patients without appendectomy in the NHIRD and assigned them to the comparison cohort in a frequency-matched 1:1 ratio based on sex, age, and index year. We tracked down all participants until IBD diagnosis, death, or the end of 2013. Cox models were used to estimate the hazard ratio (HR), and 95% confidence intervals (CIs) were used to compare the IBD risk between the appendectomy and comparison cohorts. Results: The appendectomy and comparison cohorts in the study consisted of 246 562 patients each. The appendectomy cohort exhibited a 2.23- and 3.48-fold higher risk of UC (adjusted HR = 2.23, 95% CI = 1.59-3.12) and CD (adjusted HR = 3.48, 95% CI = 2.42-4.99), respectively, than did the comparison cohort. UC and CD risks significantly increased in the appendectomy cohort regardless of whether appendicitis was present. Conclusions: Our study suggests that appendectomy increases UC and CD risks irrespective of appendicitis.

CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation.

Factors that underlie the clustering of metabolic syndrome traits are not fully known. We performed whole-exome sequence analysis in kindreds with extreme phenotypes of early-onset atherosclerosis and metabolic syndrome, and identified novel loss-of-function mutations in the gene encoding the pancreatic elastase chymotrypsin-like elastase family member 2A (CELA2A). We further show that CELA2A is a circulating enzyme that reduces platelet hyperactivation, triggers both insulin secretion and degradation, and increases insulin sensitivity. CELA2A plasma levels rise postprandially and parallel insulin levels in humans. Loss of these functions by the mutant proteins provides insight into disease mechanisms and suggests that CELA2A could be an attractive therapeutic target.