Characterization of Oral Cavity and Oropharyngeal Cancer in the Texas Rio Grande Valley

Background: Cancers of the oral cavity (OC) and oropharynx (OP) account for 3% of cancers diagnosed in the United States each year. A primary cause of death among the Hispanic population in the United States is cancer, accounting for 20% of annual mortality. The Rio Grande Valley (RGV) is a medically-underserved area of South Texas with a large Hispanic population facing health disparities. In this study, we examine the incidence and mortality of OC and OP cancer in the RGV. Methods: CDC population-level incidence and mortality rate per 100,000 of OC/OP cancer among patients in the RGV counties of Hidalgo and Cameron County between 2014-2018 compared to Texas and national incidence data was used. Results: Age-adjusted incidence and 95% confidence interval of OC/OP cancer in the RGV from 2014-2018 is 7.3 [6.6, 8.0], as compared to 11.2 [11.0, 11.3] in Texas, and 11.9 [11.8, 12.0] in the United States. Rates of OC/OP cancer among RGV Hispanics was 6.7 [6.0, 7.5] as compared to 6.8 [6.5, 7.1] in Texas and 6.9 [6.8, 7.0] nationally. Mortality rate in these cancers in the RGV is 1.8 [1.5, 2.2] compared to 2.5 [2.4, 2.5] in Texas. Conclusion: OC/OP cancer rates are prevalent in the Rio Grande Valley but there may be an under-reporting of data. Of note, cancer cases could not be separated by subsite (OC vs. OP) due to the method of reporting to the database. The rising rates nationally may pose a larger problem to the RGV due to cancer health disparities and inequities

Characterization of Oral Cavity and Oropharyngeal Cancer in the Texas Rio Grande Valley

Cancers of the oral cavity (OC) and oropharynx (OP) account for 3% of cancers diagnosed in the United States each year. A primary cause of death among the Hispanic population in the United States is cancer, accounting for 20% of annual mortality. The Rio Grande Valley (RGV) is a medically-underserved area of South Texas with a large Hispanic population facing health disparities. In this study, we examine the incidence and mortality of OC and OP cancer in the RGV. CDC population-level incidence and mortality rate per 100,000 of OC/OP cancer among patients in the RGV counties of Hidalgo and Cameron County between 2014-2018 compared to Texas and national incidence data was used. Starr and Willacy County data was omitted due to case rates below the reporting threshold. Age-adjusted incidence and 95% confidence interval of OC/OP cancer in the RGV from 2014-2018 is 7.3 [6.6, 8.0], as compared to 11.2 [11.0, 11.3] in Texas, and 11.9 [11.8, 12.0] in the United States. Rates of OC/OP cancer among RGV Hispanics was 6.7 [6.0, 7.5] as compared to 6.8 [6.5, 7.1] in Texas and 6.9 [6.8, 7.0] nationally. Mortality rate in these cancers in the RGV is 1.8 [1.5, 2.2] compared to 2.5 [2.4, 2.5] in Texas. OC/OP cancer rates are prevalent in the Rio Grande Valley but there may be an under-reporting of data. Of note, cancer cases could not be separated by subsite (OC vs. OP) due to the method of reporting to the database. The rising rates nationally may pose a larger problem to the RGV due to cancer health disparities and inequities

Propranolol for Treatment of Infantile Hemangioma: Efficacy and Effect on Pediatric Growth and Development

Purpose. Propranolol has been successful in treating problematic infantile hemangiomas (IH) but concerns regarding its effect on normal growth and development have been raised. This study examines physical growth, developmental milestones, and human growth hormone (hGH) levels in infants receiving propranolol for problematic IH. Method. Monthly heights and weights of children undergoing propranolol therapy for IH were prospectively collected and tabulated. Data analysis and comparison to World Health Organization (WHO) weight-for-age and weight-to-length z-scores was performed. Questionnaires regarding milestones, efficacy, and guardian satisfaction were performed, and a combination of both chart results and phone conducted surveys was tabulated. Serum from a small representative cohort of age-matched children with IH treated and not treated with propranolol was collected. Results. A total of 185 children receiving propranolol therapy between 2008 and 2013 for IH were assigned to this study. The children were divided into two cohorts based on the presence of comorbidities or risk factors that may affect growth and development (n = 142 no comorbidities, n = 43 with comorbidities). Neither cohort demonstrated deviation from normal weight in comparison to WHO normative data. There was a significant deviation for BMI-for-age and weight-for-age z-scores in our population, especially in patients on propranolol for more than 7 months. Based on data from participants, via either completed questionnaires or chart results, most children met their developmental milestones at or before target ages, regardless of the presence of comorbidities. Eighty percent of guardians noticed clinical improvement of the IH, with 91% either happy about or neutral to using the medication. hGH levels were higher in patients receiving propranolol therapy, but not significantly different. Conclusion. Propranolol therapy is effective and well tolerated in the treatment of infantile hemangiomas. This study suggests that propranolol does not impair growth and has no impact on normal pediatric development

Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus

Over the past decade, there has been a change in the epidemiology of oral cavity squamous cell cancer (OC-SCC). Many new cases of OC-SCC lack the recognized risk factors of smoking, alcohol and human papilloma virus. The aim of this study was to determine if the oral microbiome may be associated with OC-SCC in nonsmoking HPV negative patients. We compared the oral microbiome of HPV-negative nonsmoker OC-SCC(n = 18), premalignant lesions(PML) (n = 8) and normal control patients (n = 12). Their oral microbiome was sampled by oral wash and defined by 16S rRNA gene sequencing. We report that the periodontal pathogens Fusobacterium, Prevotella, Alloprevotella were enriched while commensal Streptococcus depleted in OC-SCC. Based on the four genera plus a marker genus Veillonella for PML, we classified the oral microbiome into two types. Gene/pathway analysis revealed a progressive increase of genes encoding HSP90 and ligands for TLRs 1, 2 and 4 along the controls→PML → OC-SCC progression sequence. Our findings suggest an association between periodontal pathogens and OC-SCC in non smoking HPV negative patients

Taking the Long View: What Does a Child Focus Add to Social Protection?

Recognising that many indicators of vulnerability among children, such as malnutrition or poor educational performance, might reflect intergenerational problems has profound implications for the design and implementation of social protection programmes. Treating the symptoms of these problems is of course essential: a malnourished child needs immediate nutritional support and a child who is failing at school needs special attention. But the argument of this paper is that ‘taking the long view’ is imperative if the reasons why children are malnourished, or failing, are to be correctly identified and adequately addressed. Importantly, the analysis implies directing interventions not exclusively at the children who are at risk, but at others in society who are responsible for the care of children

Recognition of dance-like actions: memory for static posture or dynamic movement?

Dance-like actions are complex visual stimuli involving multiple changes in body posture across time and space. Visual perception research has demonstrated a difference between the processing of dynamic body movement and the processing of static body posture. Yet, it is unclear whether this processing dissociation continues during the retention of body movement and body form in visual working memory (VWM). When observing a dance-like action, it is likely that static snapshot images of body posture will be retained alongside dynamic images of the complete motion. Therefore, we hypothesized that, as in perception, posture and movement would differ in VWM. Additionally, if body posture and body movement are separable in VWM, as form- and motion-based items, respectively, then differential interference from intervening form and motion tasks should occur during recognition. In two experiments, we examined these hypotheses. In Experiment 1, the recognition of postures and movements was tested in conditions in which the formats of the study and test stimuli matched (movement-study to movement-test, posture-study to posture-test) or mismatched (movement-study to posture-test, posture-study to movement-test). In Experiment 2, the recognition of postures and movements was compared after intervening form and motion tasks. These results indicated that (1) the recognition of body movement based only on posture is possible, but it is significantly poorer than recognition based on the entire movement stimulus, and (2) form-based interference does not impair memory for movements, although motion-based interference does. We concluded that, whereas static posture information is encoded during the observation of dance-like actions, body movement and body posture differ in VWM

DNA Specificity Determinants Associate with Distinct Transcription Factor Functions

To elucidate how genomic sequences build transcriptional control networks, we need to understand the connection between DNA sequence and transcription factor binding and function. Binding predictions based solely on consensus predictions are limited, because a single factor can use degenerate sequence motifs and because related transcription factors often prefer identical sequences. The ETS family transcription factor, ETS1, exemplifies these challenges. Unexpected, redundant occupancy of ETS1 and other ETS proteins is observed at promoters of housekeeping genes in T cells due to common sequence preferences and the presence of strong consensus motifs. However, ETS1 exhibits a specific function in T cell activation; thus, unique transcriptional targets are predicted. To uncover the sequence motifs that mediate specific functions of ETS1, a genome-wide approach, chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq), identified both promoter and enhancer binding events in Jurkat T cells. A comparison with DNase I sensitivity both validated the dataset and also improved accuracy. Redundant occupancy of ETS1 with the ETS protein GABPA occurred primarily in promoters of housekeeping genes, whereas ETS1 specific occupancy occurred in the enhancers of T cell–specific genes. Two routes to ETS1 specificity were identified: an intrinsic preference of ETS1 for a variant of the ETS family consensus sequence and the presence of a composite sequence that can support cooperative binding with a RUNX transcription factor. Genome-wide occupancy of RUNX factors corroborated the importance of this partnership. Furthermore, genome-wide occupancy of co-activator CBP indicated tight co-localization with ETS1 at specific enhancers, but not redundant promoters. The distinct sequences associated with redundant versus specific ETS1 occupancy were predictive of promoter or enhancer location and the ontology of nearby genes. These findings demonstrate that diversity of DNA binding motifs may enable variable transcription factor function at different genomic sites

High Prevalence of Respiratory Ciliary Dysfunction in Congenital Heart Disease Patients With Heterotaxy

Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. Although this finding is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus, airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients

Nef Decreases HIV-1 Sensitivity to Neutralizing Antibodies that Target the Membrane-proximal External Region of TMgp41

Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs) that target the membrane proximal external region (MPER) of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly discovered activity for Nef has important implications for anti-HIV-1 immunity and AIDS pathogenesis