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Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (RNA Pol II). While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22) function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16) was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq). The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq), we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production. IMPORTANCE HSV-1 interacts with many cellular proteins throughout productive infection. Here, we demonstrate the interaction of a viral protein, ICP22, with a subset of cellular proteins known to be involved in transcription elongation. We determined that ICP22 is required to recruit the FACT complex and other transcription elongation factors to viral genomes and that in the absence of ICP22 viral transcription is globally reduced late in productive infection, due to an elongation defect. This insight defines a fundamental role of ICP22 in HSV-1 infection and elucidates the involvement of cellular factors in HSV-1 transcription. HSV-1 interacts with many cellular proteins throughout productive infection. Here, we demonstrate the interaction of a viral protein, ICP22, with a subset of cellular proteins known to be involved in transcription elongation. We determined that ICP22 is required to recruit the FACT complex and other transcription elongation factors to viral genomes and that in the absence of ICP22 viral transcription is globally reduced late in productive infection, due to an elongation defect. This insight defines a fundamental role of ICP22 in HSV-1 infection and elucidates the involvement of cellular factors in HSV-1 transcription.

Extracellular vesicles (EVs) are important players in autoimmune diseases, both in disease pathogenesis and as potential treatments. EVs can transport autoimmune triggers throughout the body, facilitating the process of antigen presentation. Understanding the link between cellular stress and EV biogenesis and intercellular trafficking will advance our understanding of autoimmune diseases. In addition, EVs can also be effective treatments for autoimmune diseases. The diversity of cell types that produce EVs leads to a wide range of molecules to be present in EVs, and thus EVs have a wide range of physiological effects. EVs derived from dendritic cells or mesenchymal stem cells have been shown to reduce inflammation. Since many autoimmune treatments are focused only on symptom management, EVs present a promising avenue for potential treatments. This review looks at the different roles EVs can play in autoimmune diseases, from disease pathology to diagnosis and treatment. We also overview various methodologies in isolating or generating EVs and look to the future for possible applications of EVs in autoimmune diseases.

Foreign body aspiration (FBA) is a rare, but potentially fatal condition frequently seen in the emergency department. Bronchoscopy plays a major role in its diagnosis and treatment. In patients with laryngectomy, the strategies for airway maintenance and foreign body retrieval are limited. We describe management of a patient with laryngectomy presenting with aspiration of a tracheoesophageal voice prosthesis (TEP). The TEP was not initially seen in chest radiography; however, computed tomography showed it within the right lower bronchus. Successful extraction of the TEP was achieved through bronchoscopy with forceps and retrieval basket. Otolaryngology placed a larger TEP and secured it with sutures. TEP migration is rare, but represents a risk for FBA. Initial imaging in the emergency department can be misleading, requiring a high degree of suspicion, as the TEP device may not be seen in standard chest radiography. Flexible bronchoscopy under moderate sedation in conjunction with forceps and retrieval basket may be appropriate for treatment of FBA in patients with laryngectomy and can be performed in the emergency department, preventing hospital admission.

Elemental iron powders are used as food fortificants to reduce the incidence of iron deficiency anemia. However, many commercially available iron powders are relatively untested in vivo. The purpose of this study was to determine the hemoglobin regeneration efficiency (HRE) and relative iron bioavailability (RBV) of an electrolytic elemental iron powder (EIP), by treating anemic rats with 14 d iron repletion diets fortified with four different concentrations (12, 24, 36, or 48 mg iron/kg diet) of EIP and bakery-grade ferrous sulfate monohydrate (FS; FeSO4•H2O), or no added iron (control); n = 9–12/group. The HRE of FS was significantly higher (p ≤ 0.05) than EIP at each concentration of dietary iron tested. For EIP, the HREs (ratios) of diets containing 12, 24, 36, and 48 mg iron/kg were 0.356, 0.205, 0.197, and 0.163, respectively. For both EIP and FS, HRE was inversely associated with increasing dietary iron. The RBVs (%) of iron from EIP in diets at 12, 24, 36, and 48 mg iron/kg as compared to FS were 64.5, 59.1, 50.6, and 54.3%, respectively. Overall, findings show that at the concentrations of iron tested, EIP has RBVs greater than 50% and is an effective fortification agent to replenish hemoglobin and correct iron deficiency anemia.

Introduction Sexually transmitted infections (STIs) are frequently tested for and treated in the emergency department (ED). Age, race, and number of sexual partners are known risk factors for STIs. The objective of the current study was to examine marital status as it relates to testing and treating for STIs in the ED. Methods A database of 75,000 ED patient encounters from a single healthcare system in northeast Ohio between April 18, 2014, and March 7, 2017, was examined. All patients in the dataset underwent a urinalysis and urine culture or received STI testing in the ED. We performed Chi-square and multivariable regression analysis to examine the relationships between the patient's marital status and testing and treatment for STIs performed in the ED. Results There were 20,965 patient encounters where STI testing was performed and was analyzed. Patients were 9.1% (N=1,912) married, 86.6% (N=18,149) single, 4.0% (N=837) were neither married nor single, and 0.3% (N=67) with an unknown marital status. There were 7.1% (19/267) and 4.9% (12/267) of tested married men who were infected with gonorrhea and chlamydia, respectively, whereas only 0.4% (6/1,583) and 2.2% (35/1,588) of tested married women were infected with gonorrhea and chlamydia, respectively. Single men and women were both significantly more likely to have a positive test for gonorrhea and chlamydia compared to married men and women, respectively (P<0.001). Married men and women, compared to single men and women, respectively, were more likely to be given antibiotics for gonorrhea and chlamydia in the ED when the infection was present and not be given antibiotics for the infections when testing was negative (P<0.001). Single women (9.1%; 1,291/14,258) were more likely than married women (4.9%; 75/1,534) to have a positive test for trichomonas, but there were no significant differences between married (1.0%; 1/100) and single men (0.7%; 6/893). Conclusion Even when accounting for age and race, marital status can help predict infection with gonorrhea and chlamydia in the ED. The marital status could be considered by clinicians when risk stratifying patients regarding testing and treating for the diseases in the ED. Gonorrhea and chlamydia are much more common in single men and women and much less common in married persons. However, married men tested for gonorrhea and chlamydia were more than twice as likely to test positive for infection than married women. Married men and women were both more likely to be appropriately treated with antibiotics for gonorrhea and chlamydia in the ED (i.e., testing negative for infection and not receiving antibiotics or testing positive and receiving antibiotics) compared to non-married men and women. While trichomonas was more common in single women than married women, the infection was less common in men, and both married men and single men had similar rates of testing positive for the infection.

The long noncoding RNA NEAT1 is known to be heavily dysregulated in many cancers. A single exon gene produces two isoforms, NEAT1_1 and NEAT1_2, through alternative 3′-end processing. As the longer isoform, NEAT1_2 is an essential scaffold for nuclear paraspeckle formation. It was previously thought that the short NEAT1_1 isoform only exists to keep the NEAT1 locus active for rapid paraspeckle formation. However, a recent glycolysis-enhancing function for NEAT1_1, contributing to cancer cell proliferation and the Warburg effect, has been demonstrated. Previous studies have mainly focused on quantifying total NEAT1 and NEAT1_2 expression levels. However, in light of the NEAT1_1 role in cancer cell metabolism, the contribution from specific NEAT1 isoforms is no longer clear. Here, the roles of NEAT1_1 and NEAT1_2 in metabolism and cancer progression are discussed.

Neurological complications, including encephalopathy and stroke, occur in a significant proportion of COVID-19 cases but viral protein is seldom detected in the brain parenchyma. To model this situation, we developed a novel low-inoculum K18-hACE2 mouse model of SARS-CoV-2 infection during which active viral replication was consistently seen in mouse lungs but not in the brain. We found that several mediators previously associated with encephalopathy in clinical samples were upregulated in the lung, including CCL2, and IL-6. In addition, several inflammatory mediations, including CCL4, IFNγ, IL-17A, were upregulated in the brain, associated with microglial reactivity. Parallel in vitro experiments demonstrated that the filtered supernatant from SARS-CoV-2 virion exposed brain endothelial cells induced activation of uninfected microglia. This model successfully recreates SARS-CoV-2 virus-associated para-infectious brain inflammation which can be used to study the pathophysiology of the neurological complications and the identification of potential immune targets for treatment.

AimsThe poster will discuss our Quality Improvement project around improving access to mental health assessments for asylum seekers and refugees and why this model of care proved to be useful in reducing barriers to accessing specialist mental health services for these patients.The clinic was launched as part of the Advancing Mental Health Equality (AMHE) Collaborative, which is a 3-year programme run by the National Collaborating Centre for Mental Health at the Royal College of Psychiatrists, and Norfolk and Suffolk NHS Foundation Trust (NSFT) was one of the organisations that signed up to this initiative.MethodsThe clinic was named SHIFA, which stands for (Supporting Holistic and Integrated Forced Migrants Assessments). SHIFA means ‘Healing’ in Arabic, Turkish, Urdu, Kurdish and Pashtu (languages spoken by many patients accessing this clinic) and the name was selected in collaboration with staff and service users.What are the objectives of the SHIFA clinic?• To offer a trauma-informed approach to the assessment of forced migrants. This is an essential objective of the SHIFA clinic as the trauma-informed approaches are guided by trust, rapport and offering person-centred care.• Reduce barriers to mental health care for people seeking asylum, refugees and people forced to migrate.• Work collaboratively across the systems to bridge the gap among different services to improve the person-centred and continuity of care and avoid the re-traumatising effect of re-telling their stories.• Co-production and putting the voice of our service users and carers at the heart of everything we do.• Share learning and embed inclusive practice within the mental health services in NSFT and other organisations.ResultsWe will provide data on patients seen in the clinic, the diagnosis and treatment. We will also give examples of the feedback we received from professionals and service users and why this model successfully provided collaborative and joint working opportunities with various services working with these patients.ConclusionThe QI project represented in this clinic has provided a local solution to meeting the needs of forced migrants in our community, reducing mental health inequalities. It ran without funding initially and was successful in receiving funding due to the clear difference it made in providing good quality care for these patients.Similar projects can be easily implemented in various mental health trusts.

Receiving a diagnosis of pediatric cancer has the potential to profoundly alter the lives of children and their families as one considers the immense physical and psychological pain, uncertainty, and fear that may lie ahead. As such, pediatric cancer patients may be at higher risk for developing psychiatric symptoms. Previous research has demonstrated that family cohesion can be a strong protective factor against the development of mental health challenges in the pediatric cancer population. Thus, this pilot study aimed to expand on prior psycho-oncology research. The current study analyzed the association between family cohesion and psychosocial functioning within pediatric cancer patients. It was hypothesized that family cohesion would be negatively associated with psychosocial difficulties, indicating that if participants reported strong family cohesion, they would report low levels of psychosocial dysfunction. The study also examined the association between family cohesion and time since diagnosis, hypothesizing that time since diagnosis would enhance family cohesion. Pediatric patients (N = 21) diagnosed with cancer in the past three years were recruited online through the Bass Center for Childhood Cancer and Blood Diseases at Stanford Children’s Hospital. Participants completed measures assessing psychosocial functioning and family cohesion. Family cohesion was not significantly related to psychosocial functioning or time since diagnosis. The current study’s sample demonstrated healthy family cohesion and psychosocial functioning in the face of adversity. This finding highlights the capacity of children, adolescents, and young adults to change, adapt, and maintain psychosocial strengths during and after their cancer journey. Future research should explore diverse family dynamics and contexts, examining how each is associated with psychosocial functioning in pediatric cancer patients.