Biomarkers for Biodosimetry and Their Role in Predicting Radiation Injury.

Radiation-related normal tissue injury sustained during cancer radiotherapy or in a radiological or mass casualty nuclear incident is a major health concern. Reducing the risk and mitigating consequences of radiation injury could have a broad impact on cancer patients and citizens. Efforts to discover biomarkers that can determine radiation dose, predict tissue damage, and aid medical triage are underway. Exposure to ionizing radiation causes changes in gene, protein, and metabolite expression that needs to be understood to provide a holistic picture for treating acute and chronic radiation-induced toxicities. We present evidence that both RNA (mRNA, microRNA, long noncoding RNA) and metabolomic assays may provide useful biomarkers of radiation injury. RNA markers may provide information on early pathway alterations after radiation injury that can predict damage and implicate downstream targets for mitigation. In contrast, metabolomics is impacted by changes in epigenetics, genetics, and proteomics and can be considered a downstream marker that incorporates all these changes to provide an assessment of what is currently happening within an organ. We highlight research from the past 10 years to understand how biomarkers may be used to improve personalized medicine in cancer therapy and medical decision-making in mass casualty scenarios.

Emergency medicine resident perspectives on well-being during COVID-19: a qualitative study.

BACKGROUND: Emergency medicine (EM) clinician well-being has been negatively impacted throughout the COVID-19 pandemic. Resident physicians are particularly vulnerable yet less is known about their perspectives. METHODS: The objective of this study was to use qualitative methods to understand EM residents' perspectives on well-being during COVID-19. EM residents at an urban, academic institution in the USA were recruited via email and participated in virtual, semi-structured interviews between November 2020 and February 2021. Interviews were conducted by a trained qualitative researcher, recorded, transcribed and de-identified by a third party vendor. All transcripts were double coded by two trained study team members using thematic analysis to identify the themes and interviews were stopped when no new themes emerged. RESULTS: Seventeen semi-structured interviews were conducted until thematic saturation was reached with residents in their first 4 years of training: 6 postgraduate year (PGY)-1 (35%), 6 PGY-2 (35%), 2 PGY-3 (12%) and 3 PGY-4 (18%). Five themes were identified: (1) isolation from peers in training contrasting with a collective call to action, (2) desire for increased acknowledgement and structured leadership support, (3) concerns about personal needs and safety within the clinical environment, (4) fear of missed educational opportunities and lack of professional development and (5) need for enhanced mental and physical health resources. CONCLUSIONS: This qualitative study elucidated factors inside and outside of the clinical environment which impacted EM resident well-being. The findings suggest that programme and health system leadership can focus on supporting peer-to-peer and faculty connections, structured guidance and mentorship on resident career development and develop programmes which bolster resident on-shift support and acknowledgement. These lessons can be used by training programmes to better support residents, but the generalisability is limited due to the single-centre design and participation.

Ab Initio Prediction of Excited-State and Polaron Effects in Transient XUV Measurements of α-Fe2O3.

Transient X-ray and extreme ultraviolet (XUV) spectroscopies have become invaluable tools for studying photoexcited dynamics due to their sensitivity to carrier occupations and local chemical or structural changes. One of the most studied materials using transient XUV spectroscopy is α-Fe2O3 because of its rich photoexcited dynamics, including small polaron formation. The interpretation of carrier and polaron effects in α-Fe2O3 is currently carried out using a semi-empirical method that is not transferrable to most materials. Here, an ab initio, Bethe-Salpeter equation (BSE) approach is developed that can incorporate photoexcited-state effects into arbitrary material systems. The accuracy of this approach is proven by calculating the XUV absorption spectra for the ground, photoexcited, and polaron states of α-Fe2O3. Furthermore, the theoretical approach allows for the projection of the core-valence excitons and different components of the X-ray transition Hamiltonian onto the band structure, providing new insights into old measurements. From this information, a physical intuition about the origins and nature of the transient XUV spectra can be built. A route to extracting electron and hole energies is even shown possible for highly angular momentum split XUV peaks. This method is easily generalized to K, L, M, and N edges to provide a general approach for analyzing transient X-ray absorption or reflection data.

High risk and low prevalence diseases: Serotonin syndrome.

INTRODUCTION: Serotonin syndrome is a rare, frequently misdiagnosed, serious condition with high morbidity. OBJECTIVE: This review highlights the pearls and pitfalls of serotonin syndrome, including diagnosis, initial resuscitation, and management in the emergency department (ED) based on current evidence. DISCUSSION: Serotonin syndrome is a potentially deadly toxidrome marked by excess serotonin receptor activity or neurotransmission. Features of serotonin syndrome include 1) neuromuscular excitation such as tremor, hyperreflexia, and clonus; 2) autonomic dysfunction such as tachycardia, hypertension/hypotension, and hyperthermia; and 3) altered mental status such as agitation, delirium, and coma. Although serotonin syndrome may be more obvious in patients who have overdosed on serotonergic agents such as serotonin reuptake inhibitors (SSRIs), multiple other medications may also cause serotonin syndrome. Alternative diagnoses such as sepsis, neuroleptic malignant syndrome, and decompensated hyperthyroidism should be considered. The primary components of therapy include stopping the offending agent and supportive care, which focuses on agitation control, monitoring for and treating hyperthermia, and managing autonomic instability. CONCLUSIONS: An understanding of serotonin syndrome can assist emergency clinicians in diagnosing and managing this disease.

Health of Asylees Compared to Refugees in the United States Using Domestic Medical Examination Data, 2014-2016: A Cross-Sectional Analysis.

BACKGROUND: Between 2008 and 2018, persons granted asylum (asylees) increased by 168% in the United States. Asylees are eligible for many of the same domestic benefits as refugees under the US Refugee Admissions Program (USRAP), including health-related benefits such as the domestic medical examination. However, little is known about the health of asylees to guide clinical practice. METHODS: We conducted a retrospective cross-sectional analysis of domestic medical examination data from 9 US sites from 2014 to 2016. We describe and compare demographics and prevalence of several infectious diseases such as latent tuberculosis infection (LTBI), hepatitis B and C virus (HBV, HCV), and select sexually transmitted infections and parasites by refugee or asylee visa status. RESULTS: The leading nationalities for all asylees were China (24%) and Iraq (10%), while the leading nationalities for refugees were Burma (24%) and Iraq (19 %). Approximately 15% of asylees were diagnosed with LTBI, and 52% of asylee adults were susceptible to HBV infection. Prevalence of LTBI (prevalence ratio [PR] = 0.8), hepatitis B (0.7), hepatitis C (0.5), and Strongyloides (0.5) infections were significantly lower among asylees than refugees. Prevalence of other reported conditions did not differ by visa status. CONCLUSIONS: Compared to refugees, asylees included in our dataset were less likely to be infected with some infectious diseases but had similar prevalence of other reported conditions. The Centers for Disease Control and Prevention's Guidance for the US Domestic Medical Examination for Newly Arrived Refugees can also assist clinicians in the care of asylees during the routine domestic medical examination.

Dienolate Annulation Approach for Assembly of Densely Substituted Aromatic Architectures.

The efficient assembly of complex aromatic structures from simple acyclic building blocks is reported. An anion-cascade union of an enoate and a conjugated imine affords cyclohexenone products, which are readily aromatized to phenols. By engaging the intermediate cyclohexenones with Grignard reagents, a facile addition/elimination proceeds yielding chiral cyclohexadienes, which are then aromatized. In a complementary approach, the cyclohexenone products are converted into enol triflates, which provides a gateway to diverse aromatic architectures following cross-couplings and aromatization steps.

Cerebral venous thrombosis: Diagnosis and management in the emergency department setting.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon neurologic emergency associated with significant morbidity and mortality that can be difficult to differentiate from other conditions. It is important for the emergency clinician to be familiar with this disease as it requires a high index of suspicion, and early diagnosis and management can lead to improved outcomes. OBJECTIVE: This narrative review provides an evidence-based update concerning the presentation, evaluation, and management of CVT for the emergency clinician. DISCUSSION: CVT is due to thrombosis of the cerebral veins resulting in obstruction of venous outflow and increased intracranial pressure. Early recognition is important but difficult as the clinical presentation can mimic more common disease patterns. The most common patient population affected includes women under the age of 50. Risk factors for CVT include pregnancy, medications (oral contraceptives), inherited thrombophilia, prior venous thromboembolic event, malignancy, recent infection, and neurosurgery. CVT can present in a variety of ways, but the most common symptom is headache, followed by focal neurologic deficit, seizure, and altered mental status. Imaging studies such as computed tomography (CT) venography or magnetic resonance (MR) venography should be obtained in patients with concern for CVT, as non-contrast CT will be normal or have non-specific findings in most patients. Treatment includes anticoagulation, treating seizures and elevated ICP aggressively, and neurosurgical or interventional radiology consultation in select cases. CONCLUSIONS: CVT can be a challenging diagnosis. Knowledge of the risk factors, patient presentation, evaluation, and management can assist emergency clinicians.

Reversible cerebral vasoconstriction syndrome: A narrative review for emergency clinicians.

INTRODUCTION: Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a rare cause of severe headache that can mimic other causes of sudden, severe headache and result in frequent emergency department (ED) visits. OBJECTIVE: This narrative review provides an evidence-based update concerning the presentation, evaluation, and management of RCVS for the emergency clinician. DISCUSSION: RCVS can present as recurrent, severe headaches that may be maximal in onset, known as a thunderclap headache. Distinguishing from other causes of thunderclap headache such as aneurysmal subarachnoid hemorrhage, cerebral venous thrombosis, and posterior reversible encephalopathy syndrome is challenging. Risk factors for RCVS include use of vasoactive substances, exertion, coughing, showering, sexual activity, and cervical artery dissection. Diagnosis relies on clinical features and imaging. Cerebral catheter digital subtraction angiography (DSA) is considered the gold standard imaging modality; however, computed tomography angiography or magnetic resonance angiography are reliable non-invasive diagnostic modalities. Treatment focuses on avoiding or removing the offending agent, administration of calcium channel blockers such as nimodipine, and reversing anticoagulation if bleeding is present. Although most cases have a benign course and resolve within 3 months, focal subarachnoid hemorrhage, intracerebral hemorrhage, permanent neurologic disability, or death can occur in a minority of cases. CONCLUSIONS: Diagnosis and appropriate management of RCVS can be aided by understanding key aspects of the history and examination. The emergency clinician can then obtain indicated imaging, confirming the diagnosis and allowing for appropriate management.

Understanding Gut Feelings: Transformations in Coping With Inflammatory Bowel Disease Among Young Adults.

Past studies have revealed a dizzying array of coping techniques employed by persons living with inflammatory bowel disease (IBD). Unfortunately, research has provided little insight into when and why individuals adopt or abandon particular coping strategies. Using a retrospective narrative approach, we explored how participants made sense of changes in their approach to coping over time. Shifts in coping strategies were associated with particular illness experiences that wrought new understandings of IBD and novel identity challenges. They followed a common processual form and were marked by a movement away from techniques of purification, normalization, and banalization toward the development of a more communicative body. This was accompanied by notable shifts in identity work. Notably, participants moved from a preoccupation with maintaining continuity and sameness to permitting their extraordinary bodies to occupy a place in their public and personal identities. Implications of this process for theory and practice are discussed.

Health screenings administered during the domestic medical examination of refugees and other eligible immigrants in nine US states, 2014-2016: A cross-sectional analysis.

BACKGROUND: Refugees and other select visa holders are recommended to receive a domestic medical examination within 90 days after arrival to the United States. Limited data have been published on the coverage of screenings offered during this examination across multiple resettlement states, preventing evaluation of this voluntary program's potential impact on postarrival refugee health. This analysis sought to calculate and compare screening proportions among refugees and other eligible populations to assess the domestic medical examination's impact on screening coverage resulting from this examination. METHODS AND FINDINGS: We conducted a cross-sectional analysis to summarize and compare domestic medical examination data from January 2014 to December 2016 from persons receiving a domestic medical examination in seven states (California, Colorado, Minnesota, New York, Kentucky, Illinois, and Texas); one county (Marion County, Indiana); and one academic medical center in Philadelphia, Pennsylvania. We analyzed screening coverage by sex, age, nationality, and country of last residence of persons and compared the proportions of persons receiving recommended screenings by those characteristics. We received data on disease screenings for 105,541 individuals who received a domestic medical examination; 47% were female and 51.5% were between the ages of 18 and 44. The proportions of people undergoing screening tests for infectious diseases were high, including for tuberculosis (91.6% screened), hepatitis B (95.8% screened), and human immunodeficiency virus (HIV; 80.3% screened). Screening rates for other health conditions were lower, including mental health (36.8% screened). The main limitation of our analysis was reliance on data that were collected primarily for programmatic rather than surveillance purposes. CONCLUSIONS: In this analysis, we observed high rates of screening coverage for tuberculosis, hepatitis B, and HIV during the domestic medical examination and lower screening coverage for mental health. This analysis provided evidence that the domestic medical examination is an opportunity to ensure newly arrived refugees and other eligible populations receive recommended health screenings and are connected to the US healthcare system. We also identified knowledge gaps on how screenings are conducted for some conditions, notably mental health, identifying directions for future research.

Health of Special Immigrant Visa holders from Iraq and Afghanistan after arrival into the United States using Domestic Medical Examination data, 2014-2016: A cross-sectional analysis.

BACKGROUND: Since 2008, the United States has issued between 2,000 and 19,000 Special Immigrant Visas (SIV) annually, with the majority issued to applicants from Iraq and Afghanistan. SIV holders (SIVH) are applicants who were employed by, or on behalf of, the US government or the US military. There is limited information about health conditions in SIV populations to help guide US clinicians caring for SIVH. Thus, we sought to describe health characteristics of recently arrived SIVH from Iraq and Afghanistan who were seen for domestic medical examinations. METHODS AND FINDINGS: This cross-sectional analysis included data from Iraqi and Afghan SIVH who received a domestic medical examination from January 2014 to December 2016. Data were gathered from state refugee health programs in seven states (California, Colorado, Illinois, Kentucky, Minnesota, New York, and Texas), one county, and one academic medical center and included 6,124 adults and 4,814 children. Data were collected for communicable diseases commonly screened for during the exam, including tuberculosis (TB), hepatitis B, hepatitis C, malaria, strongyloidiasis, schistosomiasis, other intestinal parasites, syphilis, gonorrhea, chlamydia, and human immunodeficiency virus, as well as elevated blood lead levels (EBLL). We investigated the frequency and proportion of diseases and whether there were any differences in selected disease prevalence in SIVH from Iraq compared to SIVH from Afghanistan. A majority of SIV adults were male (Iraqi 54.0%, Afghan 58.6%) and aged 18-44 (Iraqi 86.0%, Afghan 97.7%). More SIV children were male (Iraqi 56.2%, Afghan 52.2%) and aged 6-17 (Iraqi 50.2%, Afghan 40.7%). The average age of adults was 29.7 years, and the average age for children was 5.6 years. Among SIV adults, 14.4% were diagnosed with latent tuberculosis infection (LTBI), 63.5% were susceptible to hepatitis B virus (HBV) infection, and 31.0% had at least one intestinal parasite. Afghan adults were more likely to have LTBI (prevalence ratio [PR]: 2.0; 95% confidence interval [CI] 1.5-2.7) and to be infected with HBV (PR: 4.6; 95% CI 3.6-6.0) than Iraqi adults. Among SIV children, 26.7% were susceptible to HBV infection, 22.1% had at least one intestinal parasite, and 50.1% had EBLL (≥5 mcg/dL). Afghan children were more likely to have a pathogenic intestinal parasite (PR: 2.7; 95% CI 2.4-3.2) and EBLL (PR: 2.0; 95% CI 1.5-2.5) than Iraqi children. Limitations of the analysis included lack of uniform health screening data collection across all nine sites and possible misclassification by clinicians of Iraqi and Afghan SIVH as Iraqi and Afghan refugees, respectively. CONCLUSION: In this analysis, we observed that 14% of SIV adults had LTBI, 27% of SIVH had at least one intestinal parasite, and about half of SIV children had EBLL. Most adults were susceptible to HBV. In general, prevalence of infection was higher for most conditions among Afghan SIVH compared to Iraqi SIVH. The Centers for Disease Control and Prevention (CDC) Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees can assist state public health departments and clinicians in the care of SIVH during the domestic medical examination. Future analyses can explore other aspects of health among resettled SIV populations, including noncommunicable diseases and vaccination coverage.

Innovative Technology Using Virtual Reality in the Treatment of Pain: Does It Reduce Pain via Distraction, or Is There More to It?

Objective: Virtual reality (VR) is an exciting new technology with almost endless possible uses in medicine. One area it has shown promise is pain management. This selective review focused on studies that gave evidence to the distraction or nondistraction mechanisms by which VR leads to the treatment of pain. Methods: The review looked at articles from 2000 to July 29, 2016, focusing on studies concerning mechanisms by which virtual reality can augment pain relief. The data was collected through a search of MEDLINE and Web of Science using the key words of "virtual reality" and "pain" or "distraction." Results: Six studies were identified: four small randomized controlled studies and two prospective/pilot studies. The search results provided evidence that distraction is a technique by which VR can have benefits in the treatment of pain. Both adult and pediatric populations were included in these studies. In addition to acute pain, several studies looked at chronic pain states such as headaches or fibromyalgia. These studies also combined VR with other treatment modalities such as biofeedback mechanisms and cognitive behavioral therapy. Conclusions: These results demonstrate that in addition to distraction, there are novel mechanisms for VR treatment in pain, such as producing neurophysiologic changes related to conditioning and exposure therapies. If these new mechanisms can lead to new treatment options for patients with chronic pain, VR may have the ability to help reduce opioid use and misuse among chronic pain patients. More studies are needed to reproduce results from prospective/pilot studies in large randomized control studies.

New Class of Anion-Accelerated Amino-Cope Rearrangements as Gateway to Diverse Chiral Structures.

We report useful new lithium-assisted asymmetric anion-accelerated amino-Cope rearrangement cascades. A strategic nitrogen atom chiral auxiliary serves three critical roles, by (1) enabling in situ assembly of the chiral 3-amino-1,5-diene precursor, (2) facilitating the rearrangement via a lithium enolate chelate, and (3) imparting its influence on consecutive inter- or intramolecular C-C or C-X bond-forming events via resulting chiral enamide intermediates or imine products. The mechanism of the amino-Cope rearrangement was explored with density functional theory. A stepwise dissociation-recombination mechanism was found to be favored. The stereochemistry of the chiral auxiliary determines the stereochemistry of the Cope product by influencing the orientation of the lithium dienolate and sulfinylimine fragments in the recombination step. These robust asymmetric anion-accelerated amino-Cope enabled cascades open the door for rapid and predictable assembly of complex chiral acyclic and cyclic nitrogen-containing motifs in one pot.

Increasing Hepatitis B Vaccine Prevalence Among Refugee Children Arriving in the United States, 2006-2012.

OBJECTIVES: To determine whether the addition of hepatitis B virus (HBV) vaccine to national immunization programs improved vaccination rates among refugee children, a marginalized population with limited access to care. METHODS: The sample included 2291 refugees younger than 19 years who completed HBV screening after arrival in the United States. Children were categorized by having been born before or after the addition of the 3-dose HBV vaccine to their birth country's national immunization program. The outcome was serological evidence of immunization. RESULTS: The odds of serological evidence of HBV immunization were higher for children born after the addition of HBV vaccine to their birth country's national immunization program (adjusted odds ratio = 2.54; 95% confidence interval = 2.04, 3.15). CONCLUSIONS: National HBV vaccination programs have contributed to the increase in HBV vaccination coverage observed among US-bound refugee children. PUBLIC HEALTH IMPLICATIONS: Ongoing public health surveillance is needed to ensure that vaccine rates are sustained among diverse, conflict-affected, displaced populations.

Health Profiles of Newly Arrived Refugee Children in the United States, 2006-2012.

OBJECTIVES: We conducted a large-scale study of newly arrived refugee children in the United States with data from 2006 to 2012 domestic medical examinations in 4 sites: Colorado; Minnesota; Philadelphia, Pennsylvania; and Washington State. METHODS: Blood lead level, anemia, hepatitis B virus (HBV) infection, tuberculosis infection or disease, and Strongyloides seropositivity data were available for 8148 refugee children (aged < 19 years) from Bhutan, Burma, Democratic Republic of Congo, Ethiopia, Iraq, and Somalia. RESULTS: We identified distinct health profiles for each country of origin, as well as for Burmese children who arrived in the United States from Thailand compared with Burmese children who arrived from Malaysia. Hepatitis B was more prevalent among male children than female children and among children aged 5 years and older. The odds of HBV, tuberculosis, and Strongyloides decreased over the study period. CONCLUSIONS: Medical screening remains an important part of health care for newly arrived refugee children in the United States, and disease risk varies by population.

The Prescription Opioid Epidemic: Social Media Responses to the Residents' Perspective Article.

In June 2014, Annals of Emergency Medicine collaborated with the Academic Life in Emergency Medicine (ALiEM) blog-based Web site to host an online discussion session featuring the Annals Residents' Perspective article "The Opioid Prescription Epidemic and the Role of Emergency Medicine" by Poon and Greenwood-Ericksen. This dialogue included a live videocast with the authors and other experts, a detailed discussion on the ALiEM Web site's comment section, and real-time conversations on Twitter. Engagement was tracked through various Web analytic tools, and themes were identified by content curation. The dialogue resulted in 1,262 unique page views from 433 cities in 41 countries on the ALiEM Web site, 408,498 Twitter impressions, and 168 views of the video interview with the authors. Four major themes about prescription opioids identified included the following: physician knowledge, inconsistent medical education, balance between overprescribing and effective pain management, and approaches to solutions. Free social media technologies provide a unique opportunity to engage with a diverse community of emergency medicine and non-emergency medicine clinicians, nurses, learners, and even patients. Such technologies may allow more rapid hypothesis generation for future research and more accelerated knowledge translation.

Outbreak of Neisseria meningitidis capsular group W among scouts returning from the World Scout Jamboree, Japan, 2015.

The 23rd World Scout Jamboree was held in Japan from 28 July to 8 August 2015 and was attended by over 33,000 scouts from 162 countries. An outbreak of invasive meningococcal disease capsular group W was investigated among participants, with four confirmed cases identified in Scotland, who were all associated with one particular scout unit, and two confirmed cases in Sweden; molecular testing showed the same strain to be responsible for illness in both countries. The report describes the public health action taken to prevent further cases and the different decisions reached with respect to how wide to extend the offer of chemoprophylaxis in the two countries; in Scotland, chemoprophylaxis was offered to the unit of 40 participants to which the four cases belonged and to other close contacts of cases, while in Sweden chemoprophylaxis was offered to all those returning from the Jamboree. The report also describes the international collaboration and communication required to investigate and manage such multinational outbreaks in a timely manner.

An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 2015.

The 23rd World Scout Jamboree in 2015 took place in Japan and included over 33,000 scouts from 162 countries. Within nine days of the meeting ending, six cases of laboratory-confirmed invasive serogroup W meningococcal disease occurred among scouts and their close contacts in Scotland and Sweden. The isolates responsible were identical to one-another by routine typing and, where known (4 isolates), belonged to the ST-11 clonal complex (cc11) which is associated with large outbreaks and high case fatality rates. Recent studies have demonstrated the need for high-resolution genomic typing schemes to assign serogroup W cc11 isolates to several distinct strains circulating globally over the past two decades. Here we used such schemes to confirm that the Jamboree-associated cases constituted a genuine outbreak and that this was due to a novel and rapidly expanding strain descended from the strain that has recently expanded in South America and the United Kingdom. We also identify the genetic differences that define the novel strain including four point mutations and three putative recombination events involving the horizontal exchange of 17, six and two genes, respectively. Noteworthy outcomes of these changes were antigenic shifts and the disruption of a transcriptional regulator.