For trophically transmitted parasites that manipulate the phenotype of their hosts, whether the parasites do or do not experience resource competition depends on such factors as the size of the parasites relative to their hosts, the intensity of infection, the extent to which parasites share the cost of defending against the host's immune system or manipulating their host, and the extent to which parasites share transmission goals. Despite theoretical expectations for situations in which either no, or positive, or negative density-dependence should be observed, most studies document only negative density-dependence for trophically transmitted parasites. However, this trend may be an artifact of most studies having focused on systems in which parasites are large relative to their hosts. Yet, systems are common where parasites are small relative to their hosts, and these trophically transmitted parasites may be less likely to experience resource limitation. We looked for signs of density-dependence in Euhaplorchis californiensis (EUHA) and Renicola buchanani (RENB), two manipulative trematode parasites infecting wild-caught California killifish (Fundulus parvipinnis). These parasites are small relative to killifish (suggesting resources are not limiting), and are associated with changes in killifish behavior that are dependent on parasite-intensity and that increase predation rates by the parasites' shared final host (indicating the possibility for cost sharing). We did not observe negative density-dependence in either species, indicating that resources are not limiting. In fact, observed patterns indicate possible mild positive density-dependence for EUHA. Although experimental confirmation is required, our findings suggest that some behavior-manipulating parasites suffer no reduction in size, and may even benefit when "crowded" by conspecifics.
Human papillomavirus (HPV), most commonly HPV16, causes a growing subset of head and neck squamous cell carcinomas (HNSCCs), including the overwhelming majority of oropharynx squamous cell carcinomas in many developed countries. Circulating biomarkers for HPV‐positive HNSCC may allow for earlier diagnosis, with potential to decrease morbidity and mortality. This case‐control study evaluated whether circulating tumor HPV DNA (ctHPVDNA) is detectable in prediagnostic plasma from individuals later diagnosed with HPV‐positive HNSCC. Cases were participants in a hospital‐based research biobank with archived plasma collected ≥6 months before HNSCC diagnosis, and available archival tumor tissue for HPV testing. Controls were biobank participants without cancer or HPV‐related diagnoses, matched 10:1 to cases by sex, race, age and year of plasma collection. HPV DNA was detected in plasma and tumor tissue using a previously validated digital droplet PCR‐based assay that quantifies tumor‐tissue‐modified viral (TTMV) HPV DNA. Twelve HNSCC patients with median age of 68.5 years (range, 51‐87 years) were included. Ten (83.3%) had HPV16 DNA‐positive tumors. ctHPV16DNA was detected in prediagnostic plasma from 3 of 10 (30%) patients with HPV16‐positive tumors, including 3 of 7 (43%) patients with HPV16‐positive oropharynx tumors. The timing of the plasma collection was 19, 34 and 43 months before cancer diagnosis. None of the 100 matched controls had detectable ctHPV16DNA. This is the first report that ctHPV16 DNA is detectable at least several years before diagnosis of HPV16‐positive HNSCC for a subset of patients. Further investigation of ctHPV16DNA as a biomarker for early diagnosis of HPV16‐positive HNSCC is warranted.
Micro(mi)RNA-based post-transcriptional regulatory mechanisms have been broadly implicated in the assembly and modulation of synaptic connections required to shape neural circuits, however, relatively few specific miRNAs have been identified that control synapse formation. Using a conditional transgenic toolkit for competitive inhibition of miRNA function in Drosophila, we performed an unbiased screen for novel regulators of synapse morphogenesis at the larval neuromuscular junction (NMJ). From a set of ten new validated regulators of NMJ growth, we discovered that miR-34 mutants display synaptic phenotypes and cell type-specific functions suggesting distinct downstream mechanisms in the presynaptic and postsynaptic compartments. A search for conserved downstream targets for miR-34 identified the junctional receptor CNTNAP4/Neurexin-IV (Nrx-IV) and the membrane cytoskeletal effector Adducin/Hu-li tai shao (Hts) as proteins whose synaptic expression is restricted by miR-34. Manipulation of miR-34, Nrx-IV or Hts-M function in motor neurons or muscle supports a model where presynaptic miR-34 inhibits Nrx-IV to influence active zone formation, whereas, postsynaptic miR-34 inhibits Hts to regulate the initiation of bouton formation from presynaptic terminals.
Objectives/Hypothesis To characterize self‐reported cancer‐related activity limitations among a broad population of head and neck (HNC) survivors and identify sociodemographic factors associated with these limitations. Study Design Cross‐sectional analysis of data from the National Health Interview Survey. Methods The study population included individuals who completed the National Health Interview Survey (NHIS) from 1997 to 2018 and self‐reported a cancer diagnosis. Data regarding activity limitations, cancer history, mental health, and demographics were extracted from the NHIS. Poisson regression was used to evaluate associations between demographics and cancer‐related limitations, and a descriptive analysis was performed to identify the most common types of cancer‐related limitations experienced by HNC survivors. Results Individuals with HNC were more than twice as likely to report having a disability caused by cancer when compared to individuals with other cancers (24% vs. 11%, P < .001). Cancer‐related disability was highest among HNC survivors who were Black (adjusted prevalence ratio (aPR) = 1.57, 95% CI = 1.13–2.18), were aged 50 to 64 (aPR = 1.74, 95% CI = 1.1–2.74), had high school or lower education (aPR = 2.40, 95% CI = 1.07–5.37), and had Medicaid insurance (aPR = 2.58, 95% CI = 1.62–4.10). Among HNC patients who reported a cancer‐related limitation, the most common limitations included difficulty working (78%), going out (51%), and socializing (42%). Conclusions Cancer‐related activity limitations are more common among HNC survivors compared to survivors of other cancers, and disproportionately affect socioeconomically disadvantaged HNC survivors. Clinicians should be aware of the limitations experienced by HNC survivors to provide counseling and resources to help patients cope with these limitations. Level of Evidence 3 Laryngoscope, 132:593–599, 2022
Objective To describe baseline technology use within the head and neck cancer (HNC) population prior to the COVID-19 pandemic. Study Design Cross-sectional analysis of National Health Interview Survey (NHIS) data. Setting The NHIS is a survey of population health administered in person annually to a nationally representative sample of noninstitutionalized US residents via a complex clustered sampling design. Methods Data regarding technology use, cancer history, and demographics were extracted from the NHIS. The study population comprised individuals who completed the NHIS Sample Adult survey from 2012 to 2018 and self-reported a cancer diagnosis. Poisson regression was used to evaluate associations between demographics and general or health-related technology use and prevalence ratios reported. Results Patients with HNC were less likely to use general technology (computers, internet, or email) when compared with other patients with cancer (60% vs 73%, P < .001), although this difference was not statistically significant after controlling for sociodemographic factors. Among patients with HNC, older age, lower education, and lower income were negatively associated with general technology use (adjusted prevalence ratio [aPR], 0.71 [95% CI, 0.59-0.87] for age 65-79 years vs <50 years; aPR, 0.66 [95% CI, 0.51-0.85] for high school vs master; aPR, 0.66 [95% CI, 0.48-0.91] for income 100%-200% vs >400% federal poverty level). Older age and lower education were negatively associated with health-related technology use (aPR, 0.46 [95% CI, 0.32-0.67] for age 65-79 years vs <50 years; aPR, 0.47 [95% CI, 0.30-0.74] for high school vs master). Conclusion Socioeconomic disparities exist in technology use rates among patients with HNC. Access to technology may pose a barrier to telehealth visits for many patients with HNC due to the unique socioeconomic demographics of this patient population.
Background: The impact of safety-net status, case volume, and outcomes among geriatric head and neck cancer patients is unknown.Methods: Chi-square tests and Student's t tests to compare head and neck surgery outcomes of elderly patients between safety-net and non-safety-net hospitals. Multivariable linear regressions to determine predictors of outcome variables including mortality index, ICU stays, 30-day readmission, total direct cost, and direct cost index.Results: Compared with non-safety-net hospitals, safety-net hospitals had a higher average mortality index (1.04 vs. 0.32, p = 0.001), higher mortality rate (1% vs. 0.5%, p = 0.002), and higher direct cost index (p = 0.001). A multivariable model of mortality index found the interaction between safety-net status and medium case volume was predictive of higher mortality index (p = 0.006). Conclusion:Safety-net status is correlated with higher mortality index and cost in geriatric head and neck cancer patients. The interaction between medium volume and safety-net status is independently predictive of higher mortality index.case volume, disparities, head and neck cancer, health disparities, safety-net hospital, socioeconomic status | INTRODUCTIONHead and neck cancer patients represent a socioeconomically vulnerable population. On average, head and neck cancer patients have lower incomes and lower educational attainment compared with patients with other cancers. [1][2][3] The outcomes of head and neck cancer patients are associated with many social and structural determinants of health, including race and ethnicity, socioeconomic status, education level, insurance status, and access to care. 4,5 The intersection of these sociodemographic factors further compounds disparities in cancer outcomes. For instance, Black patients are more likely to be impoverished, uninsured, and less educated-all of these factors contribute to a higher likelihood of advanced disease presentation and decreased survival. 4,6 Safety-net hospitals are important providers of care for patients of racial and ethnic minority backgrounds and low socioeconomic status, who are more likely to be under-or uninsured. 5,7 These hospitals are tasked with caring for a socially and medically complex patient
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