Search

Background The 2022–2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. Methods Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022–2023 season against influenza A–associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022 to March 2023 among adults (aged ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test positive by molecular assay) and controls (influenza test negative), applying inverse-propensity-to-be-vaccinated weights. Results The analysis included 85 389 ED/UC ARI encounters (17.0% influenza A positive; 37.8% vaccinated overall) and 19 751 hospitalizations (9.5% influenza A positive; 52.8% vaccinated overall). VE against influenza A–associated ED/UC encounters was 44% (95% confidence interval [CI], 40%–47%) overall and 45% and 41% among adults aged 18–64 and ≥65 years, respectively. VE against influenza A–associated hospitalizations was 35% (95% CI, 27%–43%) overall and 23% and 41% among adults aged 18–64 and ≥65 years, respectively. Conclusions VE was moderate during the 2022–2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources. [ABSTRACT FROM AUTHOR]

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain. Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition. Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7 days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain. Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO. [ABSTRACT FROM AUTHOR]

Background During the 2022–2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010–2011. Influenza A/H3N2 infections were predominant. Methods We analyzed acute respiratory illness (ARI)–associated emergency department or urgent care (ED/UC) encounters or hospitalizations at 3 health systems among children and adolescents aged 6 months–17 years who had influenza molecular testing during October 2022–March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A–positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models. Results Overall, 13 547 of 44 787 (30.2%) eligible ED/UC encounters and 263 of 1862 (14.1%) hospitalizations were influenza-A–positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44–52%) overall, 53% (95% CI, 47–58%) among children aged 6 months–4 years, and 38% (95% CI, 30–45%) among those aged 9–17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6–61%) overall, 56% (95% CI, 23–75%) among children ages 6 months–4 years, and 46% (95% CI, 2–70%) among those 5–17 years. Conclusions During the 2022–2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE, 40–48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents. [ABSTRACT FROM AUTHOR]

Context: Collegiate athletes who are deaf or hard-of-hearing (D/HoH) are diagnosed with concussions at a similar rate as athletes who are hearing; however, little evidence exists on knowledge and attitudes of athletes who are D/HoH toward concussions. This study aimed to examine differences in knowledge of and attitudes toward concussions between athletes who are D/HoH and athletes who are hearing. Design: Cross-sectional research design. Methods: Of the 310 athletes who are D/HoH and 430 athletes who are hearing that were invited to participate, 90 athletes who are D/HoH, and 72 athletes who are hearing completed the survey. The Rosenbaum Concussion Knowledge and Attitudes Survey was used to quantify knowledge of and attitude toward concussions. The Rosenbaum Concussion Knowledge and Attitudes Survey consists of the concussion knowledge index (CKI) and the concussion attitudes index (CAI) subscales. Linear regressions were run to test the association of hearing status with CKI and CAI scores. Pearson correlations were performed to determine relationships between CKI and CAI for athletes who are D/HoH and athletes who are hearing. Alpha level was set a priori at P ≤.05. Results: Athletes who are hearing demonstrated a higher CKI component score (19.58 [2.19]) compared to athletes who are D/HoH (16.14 [3.31]; P <.001). There were no statistical differences in CAI between hearing groups (hearing: 57.18 [8.73], D/HoH: 55.97 [9.92]; P =.41). There was a moderate positive correlation between CKI and CAI (r =.58) for athletes who are D/HoH, while a weak positive correlation (r =.30) for athletes who are hearing was observed. Conclusions: Athletes who are D/HoH have poorer knowledge of concussions but similar attitudes toward concussion as that of athletes who are hearing. Current concussion educational interventions are in written or spoken form which may not be inclusive to athletes who are D/HoH. Health care professionals should consider an athlete's preferred communication mode to improve the efficiency and effectiveness of education. [ABSTRACT FROM AUTHOR]

Background Following historically low influenza activity during the 2020–2021 season, the United States saw an increase in influenza circulating during the 2021–2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. Methods We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. Results In total, 86 732 ED/UC ARI-associated encounters (7696 [9%] cases) and 16 805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%–29%) and 25% (95% CI, 11%–37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, −5% to 17%) or with immunocompromising conditions (4%; 95% CI, −45% to 36%). Conclusions During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE. [ABSTRACT FROM AUTHOR]

The article offers information about the durability of bivalent messenger RNA COVID-19 vaccines in preventing COVID-19-associated hospitalization and critical illness among adults with and without immunocompromising conditions. It mentions the implications for public health practice include the recommendation for adults to stay updated with COVID-19 vaccines and the availability of optional additional bivalent vaccine doses for older adults and those with immunocompromising conditions.

Background Coronavirus disease 2019 (COVID-19) vaccination coverage remains lower in communities with higher social vulnerability. Factors such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure risk and access to healthcare are often correlated with social vulnerability and may therefore contribute to a relationship between vulnerability and observed vaccine effectiveness (VE). Understanding whether these factors impact VE could contribute to our understanding of real-world VE. Methods We used electronic health record data from 7 health systems to assess vaccination coverage among patients with medically attended COVID-19-like illness. We then used a test-negative design to assess VE for 2- and 3-dose messenger RNA (mRNA) adult (≥18 years) vaccine recipients across Social Vulnerability Index (SVI) quartiles. SVI rankings were determined by geocoding patient addresses to census tracts; rankings were grouped into quartiles for analysis. Results In July 2021, primary series vaccination coverage was higher in the least vulnerable quartile than in the most vulnerable quartile (56% vs 36%, respectively). In February 2022, booster dose coverage among persons who had completed a primary series was higher in the least vulnerable quartile than in the most vulnerable quartile (43% vs 30%). VE among 2-dose and 3-dose recipients during the Delta and Omicron BA.1 periods of predominance was similar across SVI quartiles. Conclusions COVID-19 vaccination coverage varied substantially by SVI. Differences in VE estimates by SVI were minimal across groups after adjusting for baseline patient factors. However, lower vaccination coverage among more socially vulnerable groups means that the burden of illness is still disproportionately borne by the most socially vulnerable populations. [ABSTRACT FROM AUTHOR]

The article reports that the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the U.S., with further Omicron sublineage diversification through November 2022. It mentions that the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose as compared with no previous vaccination and previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses.

ECMO plays a crucial role in treating severe respiratory and cardiac failure in pediatric patients. However, its impact on the regulation of erythropoietin (EPO) and erythropoiesis remains poorly understood. Factors such as improved oxygenation, inflammation, and hemodilution associated with ECMO treatment may influence EPO production and erythropoiesis. This study aimed to examine the effects of ECMO on EPO regulation and erythropoiesis in pediatric patients.This retrospective study serially quantified EPO serum levels, measured markers of erythropoiesis, and tabulated clinical outcomes of pediatric ECMO patients. Descriptive statistics and Pearson correlation coefficients were used to identify associations between biomarkers and clinical care parameters.Preliminary findings suggest a disconnection between elevated EPO levels and reduced markers of erythropoiesis or iron metabolism, indicating ineffective erythropoiesis. Patients receiving more than 10 mL/kg/day of RBC transfusions had higher reticulocyte counts. Non-survivors had sustained elevations of EPO serum levels but reduced erythropoietic activity.In ECMO-treated pediatric patients, ineffective erythropoiesis is a significant concern and may be associated with higher mortality rates. Understanding the mechanisms behind this pathology could better inform clinical approaches and optimize management strategies. Further research is imperative to uncover the factors resulting in ineffective erythropoiesis in these patients and to develop targeted interventions. [ABSTRACT FROM AUTHOR]

Infants undergoing ECMO may have elevated serum ferritin and iron levels, raising concerns about iron overload. Recent studies question the utility of these markers for acute vs. chronic iron overload during ECMO. This study evaluates iron content and localization in autopsy tissues from deceased infants who received or were considered for ECMO.This retrospective single-center case-control study analyzed paraffin-embedded tissues from the basal ganglia, liver, spleen, pancreas, and kidney. Tissue sections were stained to quantify iron deposition and an independent pathologist reviewed samples for iron accumulation.Eighteen deceased infants' tissues were analyzed: nine underwent ECMO, and nine were considered for it. Both groups showed multi-organ iron accumulation with no significant difference between ECMO and non-ECMO cohorts. Red blood cell transfusions were linked to increased iron content in adrenal (p = 0.004), hepatic (p = 0.042), and splenic (p = 0.013) tissues.ECMO exposure alone does not independently increase iron content in infants' organs. Multi-organ iron accumulation in both groups suggests iron deposition in critically ill pediatric patients irrespective of ECMO exposure. Further research is needed to understand the mechanisms and implications. [ABSTRACT FROM AUTHOR]

Aim: Parenting stress is associated with less optimal outcomes for children. Risk factors contributing to parenting stress in healthy toddlers have received little empirical attention. This study sought to determine the factors that are associated with parenting stress in parents of 18‐month‐old children. Methods: We analysed cross‐sectional survey data from a prospective cohort study focused on parent–child mealtime interactions. Families with an 18‐month‐old child were recruited in Columbus, Ohio, USA, between December 2017 and May 2019. Adjusted stepwise linear regression models estimated associations between child factors (e.g., temperament), parental factors (e.g., depressive symptoms), quality of romantic relationship factors (e.g., adult attachment style) and home environment factors (e.g., household income) and parenting stress (Parental Distress subscale of the Parenting Stress Index‐4 Short Form). Results: The 299 children included 129 (43%) females. Parents were on average 30.6 (SD 6.1) years old and included a diverse racial/ethnic cohort. Mean Parental Distress score was 24.3 (SD 6.8; score range 12–60). Higher Parental Distress scores were associated with greater parental depressive symptoms (B = 5.1 [95% CI: 2.4, 7.7]) and avoidant (B = 2.8 [95% CI: 0.9, 4.6]) attachment style. Other child, parental and home environment factors did not demonstrate statistically significant relationships with parental distress in the final model. Conclusion: Our findings align with recommendations for paediatric providers to screen for parenting stress and mental health. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor DNA (ctDNA) offers minimally invasive means to repeatedly interrogate tumor genomes, providing opportunities to monitor clonal dynamics induced by metastasis and therapeutic selective pressures. In metastatic cancers, ctDNA profiling allows for simultaneous analysis of both local and distant sites of recurrence. Despite the promise of ctDNA sampling, its utility in real-time genetic monitoring remains largely unexplored. Methods: In this exploratory analysis, we characterize high-frequency ctDNA sample series collected over narrow time frames from seven patients with metastatic triple-negative breast cancer, each undergoing treatment with Cabozantinib, a multi-tyrosine kinase inhibitor (NCT01738438, https://clinicaltrials.gov/ct2/show/NCT01738438). Applying orthogonal whole exome sequencing, ultra-low pass whole genome sequencing, and 396-gene targeted panel sequencing, we analyzed 42 plasma-derived ctDNA libraries, representing 4–8 samples per patient with 6–42 days between samples. Integrating tumor fraction, copy number, and somatic variant information, we model tumor clonal dynamics, predict neoantigens, and evaluate consistency of genomic information from orthogonal assays. Results: We measured considerable variation in ctDNA tumor faction in each patient, often conflicting with RECIST imaging response metrics. In orthogonal sequencing, we found high concordance between targeted panel and whole exome sequencing in both variant detection and variant allele frequency estimation (specificity = 95.5%, VAF correlation, r = 0.949), Copy number remained generally stable, despite resolution limitations posed by low tumor fraction. Through modeling, we inferred and tracked distinct clonal populations specific to each patient and built phylogenetic trees revealing alterations in hallmark breast cancer drivers, including TP53, PIK3CA, CDK4, and PTEN. Our modeling revealed varied responses to therapy, with some individuals displaying stable clonal profiles, while others showed signs of substantial expansion or reduction in prevalence, with characteristic alterations of varied literature annotation in relation to the study drug. Finally, we predicted and tracked neoantigen-producing alterations across time, exposing translationally relevant detection patterns. Conclusions: Despite technical challenges arising from low tumor content, metastatic ctDNA monitoring can aid our understanding of response and progression, while minimizing patient risk and discomfort. In this study, we demonstrate the potential for high-frequency monitoring of evolving genomic features, providing an important step toward scalable, translational genomics for clinical decision making. [ABSTRACT FROM AUTHOR]

Abstract Objective Uterine carcinosarcoma (UCS) is a rare and aggressive form of uterine cancer. It is bi-phasic, exhibiting histological features of both malignant epithelial (carcinoma) and mesenchymal (sarcoma) elements, reflected in ambiguity in accepted treatment guidelines. We sought to study the genomic and transcriptomic profiles of these elements individually to gain further insights into the development of these tumors. Methods We macro-dissected carcinomatous, sarcomatous, and normal tissues from formalin fixed paraffin embedded uterine samples of 10 UCS patients. Single nucleotide polymorphism microarrays, targeted DNA sequencing and whole-transcriptome RNA-sequencing were performed. Somatic chromosomal alterations (SCAs), point mutation and gene expression profiles were compared between carcinomatous and sarcomatous components. Results In addition to TP53 , other recurrently mutated genes harboring putative driver or loss-of-function mutations included PTEN , FBXW7 , FGFR2 , KRAS , PIK3CA and CTNNB1 , genes known to be involved in UCS. Intra-patient somatic mutation and SCA profiles were highly similar between paired carcinoma and sarcoma samples. An epithelial-mesenchymal transition (EMT) signature tended to differentiate components, with EMT-like status more common in advanced-stage patients exhibiting higher inter-component SCA heterogeneity. Conclusions From DNA analysis, our results indicate a monoclonal disease origin for this cohort. Yet expression-derived EMT statuses of the carcinomatous and sarcomatous components were often discrepant, and advanced cases displayed greater genomic heterogeneity. Therefore, separately-profiled components of UCS tumors may better inform disease progression or potential. Highlights • UCS genomic profiling of distinct carcinoma and sarcoma components reveals deep similarities and implies monoclonal origin. • An EMT-like gene expression signature was observed in samples from advanced stage UCS patients. • Higher levels of genomic inter-component heterogeneity was associated with greater predicted metastatic potential. • Component-specific profiling may provide a means of refining clinical staging for UCS patients. [ABSTRACT FROM AUTHOR]

Certain regions on the surfaces of developing pollen grains exhibit very limited deposition of pollen wall exine. These regions give rise to pollen apertures, which are highly diverse in their patterns and specific for individual species. Arabidopsis thaliana pollen develops three equidistant longitudinal apertures. The precision of aperture formation suggests that, to create them, pollen employs robust mechanisms that generate distinct cellular domains. To identify players involved in this mechanism, we screened natural Arabidopsis accessions and discovered one accession, Martuba, whose apertures form abnormally due to the disruption of the protein kinase D6PKL3. During pollen development, D6PKL3 accumulates at the three plasma membrane domains underlying future aperture sites. Both D6PKL3 localization and aperture formation require kinase activity. Proper D6PKL3 localization is also dependent on a polybasic motif for phosphoinositide interactions, and we identified two phosphoinositides that are specifically enriched at the future aperture sites. The other known aperture factor, INAPERTURATE POLLEN1, fails to aggregate at the aperture sites in d6pkl3 mutants, changes its localization when D6PKL3 is mislocalized, and, in turn, affects D6PKL3 localization. The discovery of aperture factors provides important insights into the mechanisms cells utilize to generate distinct membrane domains, develop cell polarity, and pattern their surfaces. [ABSTRACT FROM AUTHOR]

The article presents the results of the survey of the American Society of Health-System Pharmacists (ASHP) Section of Ambulatory Care Practitioners Section Advisory Group (SAG) on Compensation and Practice Sustainability. Topics include pharmacist integration into team-based ambulatory care practice models, the importance of cooperation and participation, and the need for supportive practice partners. Also discussed was the value of documenting services and outcomes.

Abnormally high serum ferritin levels have been reported during pediatric ECMO, attributed to frequent red blood cell transfusion and suggestive of iron overload. However, the utility of ferritin for diagnosing iron overload is complicated by its response as an acute-phase reactant. In this study, we aimed to assess the utility of ferritin for diagnosing ECMO-related iron overload, with secondary aims of understanding its relationship with inflammation and erythropoiesis. Ferritin was elevated in all pediatric ECMO runs (median 459 ng/ml, IQR = 327.3–694.4). While intermittent elevations in serum iron were observed, all normalized prior to decannulation. Unreported previously, erythropoietin (EPO) remained well above normative values prior to and throughout ECMO runs, despite frequent transfusion and exposure to hyperoxia. Ferritin correlated poorly with serum iron [r(80) = 0.05, p = 0.65], but correlated well with IL-6 [r(76) = 0.48, p < 0.001] and EPO [r(81) = 0.55, p < 0.001]. We suggest that serum ferritin is a poor biomarker of iron overload in ECMO patients, and that future investigation into its relationship with EPO is warranted. • Abnormally high serum ferritin levels have been reported during pediatric ECMO • Elevated ferritin levels were initially reported to reflect iron overload due to red blood cell transfusion • Elevations in serum ferritin appears to greatly correlate with markers of acute inflammation rather than iron sufficiency • Ferritin, an acute-phase reactant, might not accurately reflect iron status • We suggest alternative evaluations to examine the possibility of iron overload in ECMO patients [ABSTRACT FROM AUTHOR]

Background: Disproportionate access to healthcare services among the Lesbian, Gay, Bisexual, Transgender, Queer or Questioning and others (LGBTQ+) population can be partially attributed to the lack of cultural competence among healthcare providers. The aim of this study was to evaluate the impact of an interprofessional model in improving cultural competence and clinical preparedness among dental and pharmacy students for providing LGBTQ+ specific care. Methodology: This study is a retrospective observational study which used a novel interprofessional model of three different LGBTQ+ focused educational interventions within a group of dental and pharmacy students. The study used pre- and post-surveys, Assessment of Interprofessional Team Collaboration Scale (AITCS-II) and the Team Observed Structured Clinical Encounter (TOSCE) evaluations to assess the effectiveness of the interventions. Descriptive statistics, Fisher's exact test, Wilcoxon signed-rank test, Welch test, Kruskal-Wallis Test, and pairwise Wilcox Test were employed to analyze quantitative data while qualitative insights were gathered from evaluator comments and student feedback. Results: The study evaluated cultural competence among 154 dental and pharmacy students revealing improved cultural humility post-intervention, particularly for dental students although not statistically significant (p>0.05). Students participating in multiple interventions had higher mean scores, but the differences were not significant (p>0.05). Significant differences were found among interprofessional teams of students in the domains of roles and responsibilities (p = 0.039) and patient centered approach (p = 0.039). No significant differences were found in individual scores participation in the teams (p = 0.018). Students also provided positive feedback on the program's impact on their understanding of LGBTQ+ health issues and inclusive care. Conclusion: This program was a novel intervention aimed at improving cultural competence for health professional students in an interprofessional environment Further research in the direction can be useful in creating replicable programs. [ABSTRACT FROM AUTHOR]

Background Lower respiratory tract infection (LRTI) is the leading cause of pediatric hospitalizations in the United States, with significant morbidity and mortality. Native American children are at increased risk for severe illness during LRTI. Yet, the reasons for this increased risk are poorly understood. Socio-economic status and/or a genetic predisposition have been postulated as possible causes. In addition, the spectrum of LRTI presentations has not been adequately described in this patient population. The objective of this study was to define the clinical presentations of LRTI and highlight the differences between Native American and non-native American previously healthy patients under the age of 24 months. Methods We performed a retrospective chart review during the 2017–2018 respiratory season. We reviewed 357 medical records, and included 192 patients in the analysis that were full term, previously healthy, and met our inclusion criteria. We recorded demographic information, clinical and laboratory data, and outcomes. Results Of 192 patients, 39 were Native American and 153 were non-native American. We found no differences in gestational age, gender or age (median age was 5 and 7 months, respectively) between groups. We found no difference in rates of vaccination, upper respiratory symptoms, cough, wheezing, crackles, increased work of breathing or peripheral white blood cell count at presentation. In addition, we found no differences in antibacterial use or length of antimicrobial therapy during hospitalization. Native American children had a statistically significant higher length of hospitalization (P = 0.01) as well as days of oxygen supplementation (mean 4.9 vs. 3 days; P = 0.006) compared with non-native Americans. Furthermore, Native American children had a significantly higher percentage of PICU admissions (28% vs. 10.4%; P = 0.008) as well as intubation rate (26% vs. 8%; P = 0.04) compared with non-native Americans. Conclusion Native American children had increased length of hospitalization associated with severe illness including longer oxygen supplementation, higher PICU admission rate and need for mechanical ventilatory support. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: Women involved in repetitive, fatiguing, jobs develop more neck and/or shoulder musculoskeletal disorders than men. Sex differences in the pain response to exercise could contribute to the higher prevalence of neck/shoulder musculoskeletal disorders in women. The objective of this study was to assess sex differences in pain sensitivity following a fatiguing upper limb task. Relationships between measures of fatigue and of the sensitivity to nociceptive and to non-nociceptive stimulations were also explored. Methods: Thirty healthy adults (15 women) performed a fatiguing repetitive pointing task with their dominant arm. Upper limb electromyography was recorded from the dominant upper trapezius, anterior deltoid and bicep brachii and from the contralateral tibialis anterior. Before and immediately after the repetitive pointing task, pressure pain and light touch sensitivity thresholds were measured over the same muscles. Results: Electromyographic signs of fatigue were observed only in the anterior deltoid and biceps brachii muscles. Pressure pain thresholds over both muscles increased slightly (effect size ≤ 0.34), but no changes occurred over the upper trapezius and the tibialis anterior. Light touch thresholds increased moderately to importantly after the repetitive pointing task over all four muscles (effect sizes = 0.58 to 0.87). No sex differences were observed in any sensory variable. Moreover, no or weak correlations (r = -0.27 to 0.39) were observed between electromyographical signs of fatigue, light touch threshold and pressure pain threshold variables. Conclusions: We observed sex-independent effects of a repetitive upper limb task on the sensitivity to painful and to nonpainful stimuli. Moreover, the hypoalgesia induced by the repetitive pointing task was weak and localized, and did not directly correlate with the induced muscle fatigue. Results suggest that fatigue-related changes in the sensitivity to noxious and innocuous stimuli could not explain women's greater prevalence of neck/shoulder musculoskeletal disorders. [ABSTRACT FROM AUTHOR]

Objective: Our pilot study tests whether university counseling centers (UCC) can apply the concept of cluster analysis, and geospatial analysis to identify clusters of "hot spots". Participants: Study participants were university students who received services from a large mid-western UCC between August 2015 and July 2016. The study was approved by the University's Institutional Review Board (IRB). Data collected include demographics, address, educational level and declared major. Methods: Data analysis, conducted using SYSTAT 13.1, IBM SPSS Statistics, ArcGIS Desktop and 10.2, ArcOnline, Microsoft excel to clean and analyze demographic data. Analysis included optimized cluster analysis with a p-value < 0.05 as statistically significant. Results: 927 participants, average age was 21.6. We identified "hotspots" using cluster analysis based on age, address, and country of origin. Conclusions: Our study shows that UCCs can apply cluster analysis, and geospatial analysis to identify clusters of "hot spots" to target risk populations. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC is associated with distinct sociodemographic features. We hypothesized that rapid versus late relapse in TNBC is also defined by distinct clinical and genomic features of primary tumors.Methods: Using three publicly-available datasets, we identified 453 patients diagnosed with primary TNBC with adequate follow-up to be characterized as 'rapid relapse' (rrTNBC; distant relapse or death ≤2 years of diagnosis), 'late relapse' (lrTNBC; > 2 years) or 'no relapse' (nrTNBC: > 5 years no relapse/death). We explored basic clinical and primary tumor multi-omic data, including whole transcriptome (n = 453), and whole genome copy number and mutation data for 171 cancer-related genes (n = 317). Association of rapid relapse with clinical and genomic features were assessed using Pearson chi-squared tests, t-tests, ANOVA, and Fisher exact tests. We evaluated logistic regression models of clinical features with subtype versus two models that integrated significant genomic features.Results: Relative to nrTNBC, both rrTNBC and lrTNBC had significantly lower immune signatures and immune signatures were highly correlated to anti-tumor CD8 T-cell, M1 macrophage, and gamma-delta T-cell CIBERSORT inferred immune subsets. Intriguingly, lrTNBCs were enriched for luminal signatures. There was no difference in tumor mutation burden or percent genome altered across groups. Logistic regression mModels that incorporate genomic features significantly outperformed standard clinical/subtype models in training (n = 63 patients), testing (n = 63) and independent validation (n = 34) cohorts, although performance of all models were overall modest.Conclusions: We identify clinical and genomic features associated with rapid relapse TNBC for further study of this aggressive TNBC subset. [ABSTRACT FROM AUTHOR]

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged =6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged =18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged =6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses =2 months after the last recommended COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Background: Although psychiatric disorders have been associated with reduced immune responses to other vaccines, it remains unknown whether they influence COVID‐19 vaccine effectiveness (VE). This study evaluated risk of COVID‐19 hospitalization and estimated mRNA VE stratified by psychiatric disorder status. Methods: In a retrospective cohort analysis of the VISION Network in four US states, the rate of laboratory‐confirmed COVID‐19‐associated hospitalization between December 2021 and August 2022 was compared across psychiatric diagnoses and by monovalent mRNA COVID‐19 vaccination status using Cox proportional hazards regression. Results: Among 2,436,999 adults, 22.1% had ≥1 psychiatric disorder. The incidence of COVID‐19‐associated hospitalization was higher among patients with any versus no psychiatric disorder (394 vs. 156 per 100,000 person‐years, p < 0.001). Any psychiatric disorder (adjusted hazard ratio [aHR], 1.27; 95% CI, 1.18–1.37) and mood (aHR, 1.25; 95% CI, 1.15–1.36), anxiety (aHR, 1.33, 95% CI, 1.22–1.45), and psychotic (aHR, 1.41; 95% CI, 1.14–1.74) disorders were each significant independent predictors of hospitalization. Among patients with any psychiatric disorder, aHRs for the association between vaccination and hospitalization were 0.35 (95% CI, 0.25–0.49) after a recent second dose, 0.08 (95% CI, 0.06–0.11) after a recent third dose, and 0.33 (95% CI, 0.17–0.66) after a recent fourth dose, compared to unvaccinated patients. Corresponding VE estimates were 65%, 92%, and 67%, respectively, and were similar among patients with no psychiatric disorder (68%, 92%, and 79%). Conclusion: Psychiatric disorders were associated with increased risk of COVID‐19‐associated hospitalization. However, mRNA vaccination provided similar protection regardless of psychiatric disorder status, highlighting its benefit for individuals with psychiatric disorders. [ABSTRACT FROM AUTHOR]

Diet is a key lifestyle component that influences metabolic health through several factors, including total energy intake and macronutrient composition. While the impact of caloric intake on gene expression and physiological phenomena in various tissues is well described, the influence of dietary macronutrient composition on these parameters is less well studied. Here, we use the Nutritional Geometry framework to investigate the role of macronutrient composition on metabolic function and gene regulation in adipose tissue. Using ten isocaloric diets that vary systematically in their proportion of energy from fat, protein, and carbohydrates, we find that gene expression and splicing are highly responsive to macronutrient composition, with distinct sets of genes regulated by different macronutrient interactions. Specifically, the expression of many genes associated with Bardet-Biedl syndrome is responsive to dietary fat content. Splicing and expression changes occur in largely separate gene sets, highlighting distinct mechanisms by which dietary composition influences the transcriptome and emphasizing the importance of considering splicing changes to more fully capture the gene regulation response to environmental changes such as diet. Our study provides insight into the gene regulation plasticity of adipose tissue in response to macronutrient composition, beyond the already well-characterized response to caloric intake. A Nutritional Geometry study in mice identifies complex gene regulatory responses to differences in dietary macronutrient contribution including differential splicing of thousands of genes, most of which did not undergo gene expression changes. [ABSTRACT FROM AUTHOR]

Test-negative-design COVID-19 vaccine effectiveness (VE) studies use symptomatic SARS-CoV-2-positive individuals as cases and symptomatic SARS-CoV-2-negative individuals as controls to evaluate COVID-19 VE. To evaluate the potential bias introduced by the correlation of COVID-19 and influenza vaccination behaviors, we assessed changes in estimates of VE of bivalent vaccines against COVID-19-associated hospitalizations and emergency department/urgent care (ED/UC) encounters when considering influenza vaccination status or including or excluding influenza-positive controls using data from the multi-state VISION vaccine effectiveness network. Analyses included encounters during October 2022 – February 2023, a period of SARS-CoV-2 and influenza cocirculation. When considering influenza vaccination status or including or excluding influenza-positive controls, COVID-19 VE estimates were robust, with most VE estimates against COVID-19-associated hospitalization and ED/UC encounters changing less than 5 percentage points. Higher proportions of influenza-positive patients among controls, influenza vaccination coverage, or VE could impact these findings; the potential bias should continue to be assessed. [ABSTRACT FROM AUTHOR]

PURPOSE: In metastatic triple-negative breast cancer (mTNBC), consistent biomarkers of immune checkpoint inhibitor (ICI) therapy benefit remain elusive. We evaluated the immune, genomic, and transcriptomic landscape of mTNBC in patients treated with ICIs. METHODS: We identified 29 patients with mTNBC treated with pembrolizumab or atezolizumab, either alone (n = 9) or in combination with chemotherapy (n = 14) or targeted therapy (n = 6), who had tumor tissue and/or blood available before ICI therapy for whole-exome sequencing. RNA sequencing and CIBERSORTx-inferred immune population analyses were performed (n = 20). Immune cell populations and programmed death-ligand 1 expression were assessed using multiplexed immunofluorescence (n = 18). Clonal trajectories were evaluated via serial tumor/circulating tumor DNA whole-exome sequencing (n = 4). Association of biomarkers with progression-free survival and overall survival (OS) was assessed. RESULTS: Progression-free survival and OS were longer in patients with high programmed death-ligand 1 expression and tumor mutational burden. Patients with longer survival also had a higher relative inferred fraction of CD8+ T cells, activated CD4+ memory T cells, M1 macrophages, and follicular helper T cells and enrichment of inflammatory gene expression pathways. A mutational signature of defective repair of DNA damage by homologous recombination was enriched in patients with both shorter OS and primary resistance. Exploratory analysis of clonal evolution among four patients treated with programmed cell death protein 1 blockade and a tyrosine kinase inhibitor suggested that clonal stability post-treatment was associated with short time to progression. CONCLUSION: This study identified potential biomarkers of response to ICIs among patients with mTNBC: high tumor mutational burden; presence of CD8+, CD4 memory T cells, follicular helper T cells, and M1 macrophages; and inflammatory gene expression pathways. Pretreatment deficiencies in the homologous recombination DNA damage repair pathway and the absence of or minimal clonal evolution post-treatment may be associated with worse outcomes. In patients with mTNBC, responses to ICI-containing therapies were associated with high TMB; the presence of CD8+, CD4 memory T cells, follicular helper T cells, and M1 macrophages; and inflammatory gene expression pathways. [ABSTRACT FROM AUTHOR]

Abstract: Background: Some conventional therapies for type 2 diabetes mellitus (T2DM) fail to address the progressive nature of the disease, and as a result, they may become ineffective in maintaining normoglycemia. Antihyperglycemic agents have been developed to target incretin hormones, specifically glucagon-like peptide (GLP)-1. Incretin analogues and agents that delay GLP-1 degradation, the dipeptidyl peptidase (DPP)-4 inhibitors, offer mechanisms of action that may improve T2DM management. Saxagliptin was approved by the US Food and Drug Administration in July 2009 and by the European Medicines Evaluation Agency in October 2009 for use as monotherapy or in combination regimens for the treatment of T2DM. Objective: The aim of this article was to review the mechanism of action, pharmacology, clinical efficacy, and tolerability associated with the use of saxagliptin in patients with T2DM. Methods: MEDLINE, BIOSIS, International Pharmaceutical Abstracts, and Google Scholar were searched for English-only clinical trials and therapeutic reviews published between 1966 and June 15, 2011 (search term: saxagliptin). Additional trials and reviews were identified from the reference lists of published articles. Results: Findings on efficacy and tolerability were obtained from 11 completed Phase III clinical trials. In trials in saxagliptin-naive patients, changes from baseline in glycosylated hemoglobin (HbA1c) ranged from –0.72% to –0.90% in the saxagliptin treatment arms compared with –0.27% with placebo (all, P < 0.007). When saxagliptin was used in combination with metformin for 24 weeks, the adjusted mean reductions from baseline in HbA1c and the proportions of patients achieving target HbA1c (<7.0%) were significantly greater with saxagliptin + metformin compared with monotherapy with either drug (all, P ≤ 0.0001). When saxagliptin was used in combination with a sulfonylurea or a thiazolidinedione, the changes in HbA1c ranged from –0.54% to –0.64% and –0.66% to –0.94%, respectively, in a dose-dependent manner (P ≤ 0.0007 vs monotherapies). Based on changes in HbA1c, saxagliptin + metformin was reported to be noninferior to sitagliptin + metformin (–0.52% and –0.62%, respectively; difference, 0.09% [95% CI, –0.01% to 0.20%]). Saxagliptin was reported to have been well tolerated, with the most common adverse events being upper respiratory infection, urinary tract infection, headache, and nasopharyngitis. A systematic review of cardiovascular events in pooled trial results of saxagliptin use reported no increased cardiovascular risk compared with metformin, glyburide, or placebo (relative risk, 0.24 [0.09–0.63]). Conclusions: Saxagliptin, used as monotherapy and in combination regimens, has been associated with significant reductions in HbA1c and significant increases in the rate of achieving target HbA1c in patients with T2DM. It has been reported to be well tolerated compared with other oral antihyperglycemic agents. Based on the findings from the studies in this review, the primary role of saxagliptin is expected to be in combination therapy with other antihyperglycemic agents. [Copyright &y& Elsevier]

Telomere length has garnered interest due to the potential role it may play as a biomarker for the cellular aging process. Telomere measurements obtained from blood-derived DNA are often used in epidemiological studies. However, the invasive nature of blood draws severely limits sample collection, particularly with children. Buccal cells are commonly sampled for DNA isolation and thus may present a non-invasive alternative for telomere measurement. Buccal and leukocyte derived DNA obtained from samples collected at the same time period were analyzed for telomere repeat mass (TRM). TRM was measured in buccal-derived DNA samples from individuals for whom previous TRM data from blood samples existed. TRM measurement was performed by qPCR and was normalized to the single copy 36B4 gene relative to a reference DNA sample (K562). Correlations between TRM from blood and buccal DNA were obtained and also between the same blood DNA samples measured in separate laboratories. Using the classical twin design, TRM heritability was estimated (N = 1892, MZ = 1044, DZ = 775). Buccal samples measured for TRM showed a significant correlation with the blood-1 (R = 0.39, p < 0.01) and blood-2 (R = 0.36, p < 0.01) samples. Sex and age effects were observed within the buccal samples as is the norm within blood-derived DNA. The buccal, blood-1, and blood-2 measurements generated heritability estimates of 23.3%, 47.6% and 22.2%, respectively. Buccal derived DNA provides a valid source for the determination of TRM, paving the way for non-invasive projects, such as longitudinal studies in children. [ABSTRACT FROM AUTHOR]

DNA methylation is one of the most extensively studied epigenetic marks in humans. Yet, it is largely unknown what causes variation in DNA methylation between individuals. The comparison of DNA methylation profiles of monozygotic (MZ) twins offers a unique experimental design to examine the extent to which such variation is related to individual-specific environmental influences and stochastic events or to familial factors (DNA sequence and shared environment). We measured genome-wide DNA methylation in buccal samples from ten MZ pairs (age 8-19) using the Illumina 450k array and examined twin correlations for methylation level at 420,921 CpGs after QC. After selecting CpGs showing the most variation in the methylation level between subjects, the mean genome-wide correlation (rho) was 0.54. The correlation was higher, on average, for CpGs within CpG islands (CGIs), compared to CGI shores, shelves and non-CGI regions, particularly at hypomethylated CpGs. This finding suggests that individual-specific environmental and stochastic influences account for more variation in DNA methylation in CpG-poor regions. Our findings also indicate that it is worthwhile to examine heritable and shared environmental influences on buccal DNA methylation in larger studies that also include dizygotic twins. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We evaluated the clinical relevance of catenins, cadherins and cell cycle regulators in stage IV or recurrent endometrial carcinoma in a multi-center phase II trial (GOG protocol #119). Methods: Tissue microarrays of metastatic or recurrent (n=42) tumor were developed and immunohistochemistry was performed. Average expression (percent staining x intensity) was assessed in tumor epithelium (E) and stroma (S) and categorized into tertiles (T1, T2, T3) for E-cadherinE, N-cadherinE, alpha-cateninE, beta-cateninE, gamma-cateninE, p120-cateninE and Ki-67E; as negative, below median or above median for p16E, p27E and CD44S; or as negative or positive for p53E, Ki-67S and APCS (adenomatous polyposis coli). End points included response and survival. Results: E-cadherin E , p16 E , and p53 E varied by race (p=0.003, p=0.024, p=0.002,) and N-cadherin E , Ki-67 E , p16 E and p27 E by tumor type (p=0.015, p=0.011, p=0.005, p=0.021). Correlations were observed among E-cadherin E with p120 E (r=0.66), p53 E (r=−0.32), alpha-catenin E (r=0.52), beta-catenin E (r=0.58), and gamma-catenin E (r=0.58). High E-cadherin E (T2 or T3) versus low (T1) expression was associated with better survival in unadjusted (hazard ratio [HR]=0.14, 95% confidence interval [CI]=0.06–0.37 or HR=0.17, 95% CI=0.07–0.42) and adjusted models (HR=0.18, 95% CI=0.05–0.59 or HR=0.22, 95% CI=0.07–0.70). High p16 E versus negative expression was associated with worse survival in unadjusted (HR=3.87, 95% CI=1.74-8.61) and adjusted (HR=4.18, 95% CI=1.28–13.6) models. Positive versus negative expression of p53 E was associated with worse survival in unadjusted (HR=2.31, 95% CI=1.16–4.60) but not adjusted models. Conclusions: E-cadherin E and p16 E appear to be clinically relevant, independent prognostic factors in stage IV or recurrent endometrial cancers treated with Tamoxifen and Medroxyprogesterone acetate, and merit further study. [Copyright &y& Elsevier]