Spatial and Temporal Trends in Travel for COVID-19 Vaccinations

Highlights : Disparities in distances people traveled for vaccinations by demographics exist. Males and White people traveled longer distances for vaccination appointments. Travel distances of over 10 miles for vaccination likely required motorized transportation. Introduction: Understanding spatial and temporal trends in travel for COVID-19 vaccinations by key demographic characteristics (i.e., gender, race, age) is important for ensuring equitable access to and increasing distribution efficiency of vaccines and other health services. The aim of this study is to examine trends in travel distance for COVID-19 vaccinations over the course of the vaccination rollout in North Carolina. Methods: Data were collected using electronic medical records of individuals who had first- or single-dose COVID-19 vaccination appointments through UNC Health between December 15, 2020, and August 31, 2021 (N = 204,718). Travel distances to appointments were calculated using the Euclidean distance from individuals’ home ZIP code centroids to clinic addresses. Descriptive statistics and multivariable regression models with individuals’ home ZIP codes incorporated as fixed effects were used to examine differences in travel distances by gender, race, and age. Results: Males and White individuals traveled significantly farther for vaccination appointments throughout the vaccination rollout. On average, females traveled 14. 4 miles, 3.5% shorter distances than males; Black individuals traveled 13.6 miles, 10.0% shorter distances than White individuals; and people aged 65 and older traveled 14.5 miles, 2.6% longer distances than younger people living in the same ZIP code. Conclusions: Controlling for socioeconomic status and spatial proximity to vaccination clinics at the ZIP code level, males and White individuals traveled longer distances for vaccination appointments, demonstrating more ability to travel for vaccinations. Results indicate a need to consider differential ability to travel to vaccinations by key demographic characteristics in COVID-19 vaccination programs and future mass health service delivery efforts

Transportation barriers to care among frequent health care users during the COVID pandemic

Background: Transportation problems are known barriers to health care and can result in late arrivals and delayed or missed care. Groups already prone to greater social and economic disadvantage, including low-income individuals and people with chronic conditions, encounter more transportation barriers and experience greater negative health care consequences. Addressing transportation barriers is important not only for mitigating adverse health care outcomes among patients, but also for avoiding additional costs to the health care system. In this study, we investigate transportation barriers to accessing health care services during the COVID-19 pandemic among high-frequency health care users. Methods: A web-based survey was administered to North Carolina residents aged 18 and older in the UNC Health system who were enrolled in Medicaid or Medicare and had at least six outpatient medical appointments in the past year. 323 complete responses were analyzed to investigate the prevalence of reporting transportation barriers that resulted in having arrived late to, delayed, or missed care, as well as relationships between demographic and other independent variables and transportation barriers. Qualitative analyses were performed on text response data to explain transportation barriers. Results: Approximately 1 in 3 respondents experienced transportation barriers to health care between June 2020 and June 2021. Multivariate logistic regressions indicate individuals aged 18–64, people with disabilities, and people without a household vehicle were significantly more likely to encounter transportation barriers. Costs of traveling for medical appointments and a lack of driver or car availability emerged as major transportation barriers; however, respondents explained that barriers were often complex, involving circumstantial problems related to one’s ability to access and pay for transportation as well as to personal health. Conclusions: To address transportation barriers, we recommend more coordination between transportation and health professionals and the implementation of programs that expand access to and improve patient awareness of health care mobility services. We also recommend transportation and health entities direct resources to address transportation barriers equitably, as barriers disproportionately burden younger adults under age 65 enrolled in public insurance programs

HSP 27 aspossible prognostic factor in patients with oral squamous cell carcinoma.

Summary. HSP27 belongs to the Heat shock protein (HSP) family, which plays essential functions in cells under physiological conditions and prevents stressinduced cellular damage. The aim of this study was to investigate the biological role of HSP27 in oral tumorigenesis. Materials and methods: Seventy-nine cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analysed for HSP27 expression by immunohistochemistry. Moreover, the western blot analysis was performed on two cases of normal mucosa and five cases of OSCC. Results: Normal oral mucosa showed a suprabasal expression of HSP27. Twenty-four cases of SCC (30.7%) showed a diffuse staining for HSP27, and 48 cases (60.3%) showed instead a decrease in staining, which was diffuse, homogeneous, or with alternation of positive and negative areas in a single tumor (“mosaic” pattern). Only 7 cases of OSCC (7.5%) were completely negative for HSP27. Frequency of lymph node metastases was higher in HSP27-negative tumours (3/7, 42.8%) than in HSP-reduced (16/48, 33.3%) or positive ones (5/26, 19.2%). Regard staging, stages I and II had a higher score than stages III and IV (stage I > stage II > stage III > stage IV). There was also a statistically significant correlation between HSP27 expression and grade: HSP27 expression was reduced in poorly differentiated tumours (P < 0.05). When analysed for prognostic significance, patients with negative/reduced HSP27 expression had poorer survival rates than the group with positive HSP27 expression (P < 0.05). The statistical analysis of these findings showed no significant correlation between HSP27 expression, sex, and tumour size. Conclusion: Cases with reduced expression were more aggressive and poorly differentiated. These data suggest that HSP27 expression may be useful in order to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers

DRD1 and DRD2 Receptor Polymorphisms: Genetic Neuromodulation of the Dopaminergic System as a Risk Factor for ASD, ADHD and ASD/ADHD Overlap

The dopaminergic system (DS) is one of the most important neuromodulator systems involved in complex functions that are compromised in both autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), conditions that frequently occur in overlap. This evidence suggests that both disorders might have common neurobiological pathways involving the DS. Therefore, the aim of this study was to examine the DRD1 and DRD2 dopamine receptor single nucleotide polymorphisms (SNPs) as potential risk factors for ASD, ADHD, and ASD/ADHD overlap. Genetic data were obtained from four groups: 75 ASD patients, 75 ADHD patients, 30 patients with ASD/ADHD overlap, and 75 healthy controls. All participants were between 2 and 17 years old. We compared the genotypic and allelic frequency of 18 SNPs among all of the study groups. Moreover, in the case of statistically significant differences, odds ratios (OR) were obtained to evaluate if the presence of SNPs might be a risk factor of developing a specific clinical phenotype. This study found that DRD1 and DRD2 receptors SNPs might be considered as potential risk factors for ASD and ADHD. However, only DRD2-12 (rs7131465) was significantly associated with a higher risk for the ASD/ADHD overlap. These data support the hypothesis of the genetic neuromodulation of the DS in the neurobiology of these conditions

Spatial and Temporal Trends in Travel for COVID-19 Vaccinations

Introduction: Understanding spatial and temporal trends in travel for COVID-19 vaccinations by key demographic characteristics (i.e., gender, race, age) is important for ensuring equitable access to and increasing distribution efficiency of vaccines and other health services. The aim of this study is to examine trends in travel distance for COVID-19 vaccinations over the course of the vaccination rollout in North Carolina. Methods: Data were collected using electronic medical records of individuals who had first- or single-dose COVID-19 vaccination appointments through UNC Health between December 15, 2020, and August 31, 2021 (N = 204,718). Travel distances to appointments were calculated using the Euclidean distance from individuals’ home ZIP code centroids to clinic addresses. Descriptive statistics and multivariable regression models with individuals’ home ZIP codes incorporated as fixed effects were used to examine differences in travel distances by gender, race, and age. Results: Males and White individuals traveled significantly farther for vaccination appointments throughout the vaccination rollout. On average, females traveled 14. 4 miles, 3.5% shorter distances than males; Black individuals traveled 13.6 miles, 10.0% shorter distances than White individuals; and people aged 65 and older traveled 14.5 miles, 2.6% longer distances than younger people living in the same ZIP code. Conclusions: Controlling for socioeconomic status and spatial proximity to vaccination clinics at the ZIP code level, males and White individuals traveled longer distances for vaccination appointments, demonstrating more ability to travel for vaccinations. Results indicate a need to consider differential ability to travel to vaccinations by key demographic characteristics in COVID-19 vaccination programs and future mass health service delivery efforts

A Model for Damage Load and Its Implications for the Evolution of Bacterial Aging

Deleterious mutations appearing in a population increase in frequency until stopped by natural selection. The ensuing equilibrium creates a stable frequency of deleterious mutations or the mutational load. Here I develop the comparable concept of a damage load, which is caused by harmful non-heritable changes to the phenotype. A damage load also ensues when the increase of damage is opposed by selection. The presence of a damage load favors the evolution of asymmetrical transmission of damage by a mother to her daughters. The asymmetry is beneficial because it increases fitness variance, but it also leads to aging or senescence. A mathematical model based on microbes reveals that a cell lineage dividing symmetrically is immortal if lifetime damage rates do not exceed a threshold. The evolution of asymmetry allows the lineage to persist above the threshold, but the lineage becomes mortal. In microbes with low genomic mutation rates, it is likely that the damage load is much greater than the mutational load. In metazoans with higher genomic mutation rates, the damage and the mutational load could be of the same magnitude. A fit of the model to experimental data shows that Escherichia coli cells experience a damage rate that is below the threshold and are immortal under the conditions examined. The model estimates the asymmetry level of E. coli to be low but sufficient for persisting at higher damage rates. The model also predicts that increasing asymmetry results in diminishing fitness returns, which may explain why the bacterium has not evolved higher asymmetry

Survivin promoter -31G/C polymorphism in oral cancer cell lines.

Survivin (SVV) is a protein that belongs to the inhibitor of apoptosis proteins (IAP) family and is involved in the G2/M phase progression of the cell cycle as a spindle-associated molecule. The biological features of this protein are well documented and its activity appears to be involved in mitochondria-dependent and -independent antiapoptotic pathways. Overexpression of SVV at the transcriptional and translational level has been associated with cancer, a multifactorial disorder in which the occurrence of a -31G to C polymorphism in the promoter region may significantly contribute to the development of this pathology. To verify this hypothesis, the occurrence of a single nucleotide polymorphism (SNP) in cis-acting cell cycle-dependent elements (CDEs) and in cell cycle homology regions (CHRs) of the survivin TATA-less promoter was investigated. A total of 23 oral squamous cell carcinoma (OSCC) cell lines and normal epithelium-derived normal human epidermal keratinocyte (NHEK) cell lines were analyzed by RFLP and direct DNA sequencing of their promoter region. Furthermore, survivin expression at the transcriptional and translational levels was evaluated in these cells by RT-PCR and Western blotting, respectively. The findings indicate that the presence of a G or C allele is not directly correlated to survivin expression, at the mRNA or at the protein level, at least in the OSCC lines analyzed in this study

Compensatory Evolution of pbp Mutations Restores the Fitness Cost Imposed by β-Lactam Resistance in Streptococcus pneumoniae

The prevalence of antibiotic resistance genes in pathogenic bacteria is a major challenge to treating many infectious diseases. The spread of these genes is driven by the strong selection imposed by the use of antibacterial drugs. However, in the absence of drug selection, antibiotic resistance genes impose a fitness cost, which can be ameliorated by compensatory mutations. In Streptococcus pneumoniae, β-lactam resistance is caused by mutations in three penicillin-binding proteins, PBP1a, PBP2x, and PBP2b, all of which are implicated in cell wall synthesis and the cell division cycle. We found that the fitness cost and cell division defects conferred by pbp2b mutations (as determined by fitness competitive assays in vitro and in vivo and fluorescence microscopy) were fully compensated by the acquisition of pbp2x and pbp1a mutations, apparently by means of an increased stability and a consequent mislocalization of these protein mutants. Thus, these compensatory combinations of pbp mutant alleles resulted in an increase in the level and spectrum of β-lactam resistance. This report describes a direct correlation between antibiotic resistance increase and fitness cost compensation, both caused by the same gene mutations acquired by horizontal transfer. The clinical origin of the pbp mutations suggests that this intergenic compensatory process is involved in the persistence of β-lactam resistance among circulating strains. We propose that this compensatory mechanism is relevant for β-lactam resistance evolution in Streptococcus pneumoniae

Small Molecule Control of Virulence Gene Expression in Francisella tularensis

In Francisella tularensis, the SspA protein family members MglA and SspA form a complex that associates with RNA polymerase (RNAP) to positively control the expression of virulence genes critical for the intramacrophage growth and survival of the organism. Although the association of the MglA-SspA complex with RNAP is evidently central to its role in controlling gene expression, the molecular details of how MglA and SspA exert their effects are not known. Here we show that in the live vaccine strain of F. tularensis (LVS), the MglA-SspA complex works in concert with a putative DNA-binding protein we have called PigR, together with the alarmone guanosine tetraphosphate (ppGpp), to regulate the expression of target genes. In particular, we present evidence that MglA, SspA, PigR and ppGpp regulate expression of the same set of genes, and show that mglA, sspA, pigR and ppGpp null mutants exhibit similar intramacrophage growth defects and are strongly attenuated for virulence in mice. We show further that PigR interacts directly with the MglA-SspA complex, suggesting that the central role of the MglA and SspA proteins in the control of virulence gene expression is to serve as a target for a transcription activator. Finally, we present evidence that ppGpp exerts its effects by promoting the interaction between PigR and the RNAP-associated MglA-SspA complex. Through its responsiveness to ppGpp, the contact between PigR and the MglA-SspA complex allows the integration of nutritional cues into the regulatory network governing virulence gene expression

The Minimal Proteome in the Reduced Mitochondrion of the Parasitic Protist Giardia intestinalis

The mitosomes of Giardia intestinalis are thought to be mitochondria highly-reduced in response to the oxygen-poor niche. We performed a quantitative proteomic assessment of Giardia mitosomes to increase understanding of the function and evolutionary origin of these enigmatic organelles. Mitosome-enriched fractions were obtained from cell homogenate using Optiprep gradient centrifugation. To distinguish mitosomal proteins from contamination, we used a quantitative shot-gun strategy based on isobaric tagging of peptides with iTRAQ and tandem mass spectrometry. Altogether, 638 proteins were identified in mitosome-enriched fractions. Of these, 139 proteins had iTRAQ ratio similar to that of the six known mitosomal markers. Proteins were selected for expression in Giardia to verify their cellular localizations and the mitosomal localization of 20 proteins was confirmed. These proteins include nine components of the FeS cluster assembly machinery, a novel diflavo-protein with NADPH reductase activity, a novel VAMP-associated protein, and a key component of the outer membrane protein translocase. None of the novel mitosomal proteins was predicted by previous genome analyses. The small proteome of the Giardia mitosome reflects the reduction in mitochondrial metabolism, which is limited to the FeS cluster assembly pathway, and a simplicity in the protein import pathway required for organelle biogenesis