Sarah M

Human Cytomegalovirus (HCMV) is the leading infectious congenital infection globally and the most common viral infection in transplant recipients, therefore identifying a vaccine for HCMV is a top priority. Humoral immunity is a correlate of protection for HCMV infection. The most effective vaccine tested to date, which achieved 50% reduction in acquisition of HCMV, was comprised of the glycoprotein B protein given with an oil-in-water emulsion adjuvant MF59. We characterize gB-specific monoclonal antibodies isolated from individuals vaccinated with a disabled infectious single cycle (DISC) CMV vaccine, V160, and compare these to the gB-specific monoclonal antibody repertoire isolated from naturally-infected individuals. We find that vaccination with V160 resulted in gB-specific antibodies that bound homogenously to gB expressed on the surface of a cell in contrast to antibodies isolated from natural infection which variably bound to cell-associated gB. Vaccination resulted in a similar breadth of gB-specific antibodies, with binding profile to gB genotypes 1–5 comparable to that of natural infection. Few gB-specific neutralizing antibodies were isolated from V160 vaccinees and fewer antibodies had identifiable gB antigenic domain specificity compared to that of naturally-infected individuals. We also show that glycosylation of gB residue N73 may shield binding of gB-specific antibodies.

By making individuals responsible for reducing pollution and greenhouse gas emissions, the oil industry is deflecting responsibility for making profound changes in their production practices.

A cell-based phenotypic screen led to the discovery of compounds called NVS-STGs, which bind to the N-terminal domain of STING and act as a molecular glue to induce higher-order oligomerization and activation.

Introduction: The pediatric population undergoes tracheostomy for a variety of reasons. For a child and their family, having a tracheostomy means learning a new way of life and facing several social, psychological, medical, and economic challenges. Our analysis of the literature indicates that this is the first study of its kind, using the Pediatric Tracheotomy Health Status Instrument (PTHSI) tool to assess the quality of life (QoL) following tracheostomy in pediatric patients and their caregivers in the Kingdom of Saudi Arabia (KSA).Methods: This was a descriptive cross-sectional study for tracheostomized children's QoL evaluation. The medical records of the Maternity and Children Hospital, Dammam, KSA, were used to identify the patients and their caregivers. A higher score on the validated PTHSI indicated a better result.Results: From a total of 56 patients, 24 were included in this study. Based on the PTHSI tool, the overall mean score was 93.3/150 (62.28%) and this indicated a good QoL score. Analysis of the correlation between the PTHSI score and other variables indicated no association between the total PTHSI score and the age or gender of the patient or the duration of the tracheostomy (p-value > 0.05). However, we found families of children with major medical comorbidities had lower scores (p-value = 0.03) and their QoL was affected much more than families of patients who did not have major medical comorbidities.Conclusion: Tracheostomy care for pediatric patients can significantly affect the QoL of patients and their families. Our findings using the validated PTHSI tool showed poorer QoL compared to other studies, suggesting the need for future home care training programs to support tracheostomized children and their families, particularly those with comorbidities, who tend to have lower QoL scores and require more organized support.

Assessing whether observed association of anxiety, depression indicators with opioid consumption 72 hours after elective spine surgery varies by sex in seniors.

Abstract. Purpose: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single cell RNA sequencing has uncovered the co-existence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach. Experimental Design: We performed subtyping on a single cell RNA sequencing dataset containing 18 human PDAC samples to identify multiple intermediary subtypes. We generated patient-derived PDAC organoids for functional studies. We compared single cell profiling of matched blood and tumor samples to measure changes in the local and systemic immune microenvironment. We then leveraged longitudinally patient-matched blood to follow individual patients over the course of chemotherapy. Results: We identified a cluster of KRT17-high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines. The proportion of KRT17High/CXCL8+ cells in patient tumors correlated with intra-tumoral myeloid abundance, and, interestingly, high pro-tumor peripheral blood granulocytes, implicating local and systemic roles. Patient-derived organoids maintained KRT17High/CXCL8+cells and induced myeloid cell migration in an CXCL8-dependent manner. In our longitudinal studies, plasma CXCL8 decreased following chemotherapy in responsive patients, while CXCL8 persistence portended worse prognosis. Conclusions: Through single cell analysis of PDAC samples we identified KRT17High/CXCL8+ cancer cells as an intermediary subtype, marked by a unique cytokine profile and capable of influencing myeloid cells in the tumor microenvironment and systemically. The abundance of this cell population should be considered for patient stratification in precision immunotherapy.

Warm Atlantic waters entering the southern Nordic Sea via the Iceland-Faroe Atlantic inflow helped maintain seasonal open waters and contributed to Fennoscandian Ice Sheet growth at the onset of Last Glacial Maximum, according to a network of marine sediment records and numerical model output.

Physiological stress levels in response to sexual behavior stigma among men who have sex with men (MSM) in the United States (US) are understudied. The current study aims to explore the relationship between sexual behavior stigma and salivary cortisol both overall and stratified by race/ethnicity. If such an association exists, it may suggest that sexual behavior stigma can be physiologically measured or indicated by the presence of heightened salivary cortisol. A subsample of 667 MSM participants from the 2019 American Men’s Internet Survey (AMIS; N = 10,129) submitted morning (AM) and evening (PM) saliva cortisol samples using at-home mail-in collection kits. Average daily cortisol and daily cortisol change were calculated; simple linear regressions estimated associations between cortisol measures and sexual behavior stigma characterized in four different ways (ever and recent experience of individual stigma items; average ever and recent experience of three stigma scales: stigma from family and friends, anticipated healthcare stigma, general social stigma). Participants reported a mean age of 36.0 years (SD = 14.9), with most being non-Hispanic white (n = 480, 72.0%), Hispanic (n = 164, 12.3%), or Black/African American (n = 146, 10.9%), and identified as homosexual/gay (n = 562, 84.3%). Reporting ever experiencing healthcare providers gossiping was significantly associated with higher PM cortisol (β = 0.12, p = 0.001) and higher average daily cortisol (β = 0.11, p = 0.004), while reporting ever experiencing police refusing to protect was associated with higher AM cortisol (β = 0.08, p = 0.03) and higher average daily cortisol (β = 0.09, p = 0.02). Recent experiences of stigma were not significant predictors of any measure of cortisol. Measures of salivary cortisol may be used to characterize sexual behavior stigma among MSM populations, however more insight is needed to determine its exact relationship and strength.

Transparency and accessibility are keys to avoiding surprise charges and ensuring patient satisfaction

Abstract Introduction Children living in poverty are at an increased risk for maltreatment.