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1.
PLoS One ; 19(5): e0303280, 2024.
Article in English | MEDLINE | ID: mdl-38768115

ABSTRACT

BACKGROUND: Access to breast screening mammogram services decreased during the COVID-19 pandemic. Our objectives were to estimate: 1) the COVID-19 affected period, 2) the proportion of pandemic-associated missed or delayed screening encounters, and 3) pandemic-associated patient attrition in screening encounters overall and by sociodemographic subgroup. METHODS: We included screening mammogram encounter EPIC data from 1-1-2019 to 12-31-2022 for females ≥40 years old. We used Bayesian State Space models to describe weekly screening mammogram counts, modeling an interruption that phased in and out between 3-1-2020 and 9-1-2020. We used the posterior predictive distribution to model differences between a predicted, uninterrupted process and the observed screening mammogram counts. We estimated associations between race/ethnicity and age group and return screening mammogram encounters during the pandemic among those with 2019 encounters using logistic regression. RESULTS: Our analysis modeling weekly screening mammogram counts included 231,385 encounters (n = 127,621 women). Model-estimated screening mammograms dropped by >98% between 03-15-2020 and 05-24-2020 followed by a return to pre-pandemic levels or higher with similar results by race/ethnicity and age group. Among 79,257 women, non-Hispanic (NH) Asians, NH Blacks, and Hispanics had significantly (p < .05) lower odds of screening encounter returns during 2020-2022 vs. NH Whites with odds ratios (ORs) from 0.70 to 0.91. Among 79,983 women, those 60-69 had significantly higher odds of any return screening encounter during 2020-2022 (OR = 1.28), while those ≥80 and 40-49 had significantly lower odds (ORs 0.77, 0.45) than those 50-59 years old. A sensitivity analysis suggested a possible pre-existing pattern. CONCLUSIONS: These data suggest a short-term pandemic effect on screening mammograms of ~2 months with no evidence of disparities. However, we observed racial/ethnic disparities in screening mammogram returns during the pandemic that may be at least partially pre-existing. These results may inform future pandemic planning and continued efforts to eliminate mammogram screening disparities.


Subject(s)
Breast Neoplasms , COVID-19 , Early Detection of Cancer , Mammography , Humans , COVID-19/epidemiology , Female , Middle Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/diagnostic imaging , Mammography/statistics & numerical data , Early Detection of Cancer/statistics & numerical data , Aged , Adult , Academic Medical Centers , Midwestern United States/epidemiology , Pandemics , SARS-CoV-2 , Bayes Theorem , Mass Screening/statistics & numerical data
2.
Pediatr Blood Cancer ; 71(5): e30861, 2024 May.
Article in English | MEDLINE | ID: mdl-38235939

ABSTRACT

BACKGROUND: Medicaid-associated disparities in childhood and adolescent (pediatric) cancer diagnosis stage and survival have been reported. However, a key limitation of prior studies is the assessment of health insurance at a single time point. To evaluate Medicaid-associated disparities more robustly, we used Surveillance, Epidemiology, and End Results (SEER)-Medicaid linked data to examine diagnosis stage and survival disparities in those (i) Medicaid-enrolled and (ii) with discontinuous and continuous Medicaid enrollment. METHODS: SEER-Medicaid linked data from 2006 to 2013 were obtained on cases diagnosed from 0 to 19 years. Medicaid enrollment was classified as enrolled versus not enrolled, with further classifications as continuous when enrolled 6 months before through 6 months after diagnosis, and discontinuous when not enrolled continuously for this period. We used multinomial logistic and Cox proportional hazards regression models to determine associations between enrollment measures, diagnosis stage, and cancer death adjusted for covariates. RESULTS: Among 21,502 cases, a higher odds of distant stage diagnoses were observed in association with Medicaid enrollment (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.48-1.65), with the highest odds for discontinuous enrollment (OR = 2.0, 95% CI: 1.86-2.15). Among 30,654 cases, any Medicaid enrollment, continuous enrollment, and discontinuous enrollment were associated with 1.68 (95% CI: 1.35-2.10), 1.66 (95% CI: 1.35-2.05), and 1.89 (95% CI: 1.54-2.33) times higher hazards of cancer death versus no enrollment, respectively. CONCLUSIONS: Medicaid enrollment, particularly discontinuous enrollment, is associated with a higher  distant stage diagnosis odds and risk of death. This study supports the critical need for consistent health insurance coverage in children and adolescents.


Subject(s)
Medicaid , Neoplasms , Adolescent , United States/epidemiology , Humans , Child , Neoplasms/diagnosis , Neoplasms/therapy , Insurance, Health , Neoplasm Staging , Proportional Hazards Models , Insurance Coverage
3.
PLoS One ; 18(11): e0293288, 2023.
Article in English | MEDLINE | ID: mdl-37922267

ABSTRACT

BACKGROUND: The U.S. Surgeon General and others have emphasized a critical need to address COVID-19 misinformation to protect public health. In St. Louis, MO, we created iHeard STL, a community-level misinformation surveillance and response system. This paper reports methods and findings from its first year of operation. METHODS: We assembled a panel of over 200 community members who answered brief, weekly mobile phone surveys to share information they heard in the last seven days. Based on their responses, we prioritized misinformation threats. Weekly surveillance data, misinformation priorities, and accurate responses to each misinformation threat were shared on a public dashboard and sent to community organizations in weekly alerts. We used logistic regression to estimate odds ratios (ORs) for associations between panel member characteristics and misinformation exposure and belief. RESULTS: In the first year, 214 panel members were enrolled. Weekly survey response rates were high (mean = 88.3% ± 6%). Exposure to a sample of COVID-19 misinformation items did not differ significantly by panel member age category or gender; however, African American panel members had significantly higher reported odds of exposure and belief/uncertain belief in some misinformation items (ORs from 3.4 to 17.1) compared to white panel members. CONCLUSIONS: Our first-year experience suggests that this systematic, community-based approach to assessing and addressing misinformation is feasible, sustainable, and a promising strategy for responding to the threat of health misinformation. In addition, further studies are needed to understand whether structural factors such as medical mistrust underly the observed racial differences in exposure and belief.


Subject(s)
COVID-19 , Communication , Trust , Humans , Black or African American , Cell Phone , COVID-19/epidemiology
4.
Pediatr Blood Cancer ; 70(11): e30636, 2023 11.
Article in English | MEDLINE | ID: mdl-37638808

ABSTRACT

BACKGROUND: Limited research has been conducted on cancer-related emergency department (ED) patterns among pediatric cancer patients, including whether there are differences in the characteristics of individuals who seek ED care for cancer complications. The objectives of this study were to determine whether rates and disposition of cancer-related ED visits and hospital admissions in childhood cancer patients differ by sociodemographic factors. METHODS: A cross-sectional analysis of ED encounters with a cancer diagnosis code among patients aged 0-19 years from the 2019 National Emergency Department Sample (NEDS) was conducted. Weighted logistic regression models were utilized to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a primary cancer-related encounter, and hospital admission overall and by subgroup characteristics. RESULTS: Of the unweighted 6,801,711 ED encounters in children aged 0-19 years, 10,793 were classified as visits by cancer patients. ED encounters of Hispanic versus non-Hispanic White pediatric cancer patients had higher odds of having a cancer-related primary diagnosis (OR = 1.15, 95% CI: 1.04-1.27). ED encounters of non-Hispanic Black pediatric patients and those in the lowest zip code income quartile had higher odds of hospital admission (OR = 1.28, 95% CI: 1.08-1.53; OR = 1.30, 95% CI: 1.15-1.46), while rurality was associated with lower odds of hospital admission (OR = 0.69, 95% CI: 0.57-0.83). CONCLUSION: These results suggest that pediatric cancer patients from certain under-resourced communities are more likely to use the ED for cancer treatment complications, and their encounters are more likely to result in admission to the hospital.


Subject(s)
Emergency Medical Services , Neoplasms , Child , Humans , United States/epidemiology , Cross-Sectional Studies , Emergency Service, Hospital , Hospitalization , Poverty , Neoplasms/epidemiology , Neoplasms/therapy , Retrospective Studies
5.
Prev Med Rep ; 34: 102251, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37234564

ABSTRACT

Studies examining individual-level changes in protective behaviors over time in association with community-level infection and self or close-contact infection with SARS-CoV-2 are limited. We analyzed overall and demographic specific week-to-week changes in COVID-19 protective behaviors and their association with COVID-19 infections (regional case counts and self or close contacts). Data were collected through 37 consecutive weekly surveys from 10/17/2021 - 6/26/2022. Our survey panel included 212 individuals living or working in St. Louis City and County, Missouri, U.S.A. Frequency of mask-wearing, handwashing, physical distancing, and avoiding large gatherings was self-reported (more/the same/less than the prior week). Close contact with COVID-19 was reported if the panel member, their household member, or their close contact tested positive, got sick, or was hospitalized for COVID-19 in the prior week. Regional weekly COVID-19 case counts were matched to the closest survey administration date. We used generalized linear mixed models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations. Evidence for effect modification was assessed using the likelihood ratio test. Increased protective behaviors were positively associated with COVID-19 case counts (ORhighest vs. lowest case count category = 4.39, 95% CI 3.35-5.74) and with participant-reported self or close contacts with COVID-19 (OR = 5.10, 95% CI 3.88-6.70). Stronger associations were found for White vs. Black panel members (p <.0001). Individuals modulated their protective behaviors in association with regional COVID-19 case counts and self or close contact infection. Rapid reporting and widespread public awareness of infectious disease rates may help reduce transmission during a pandemic by increasing protective behaviors.

6.
Integr Comp Biol ; 63(4): 907-921, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37061788

ABSTRACT

Among extant great apes, orangutans are considered the most sexually dimorphic in body size. However, the expression of sexual dimorphism in orangutans is more complex than simply males being larger than females. At sexual maturity, some male orangutans develop cheek pads (flanges), while other males remain unflanged even after becoming reproductively capable. Sometimes flange development is delayed in otherwise sexually mature males for a few years. In other cases, flange development is delayed for many years or decades, with some males even spending their entire lifespan as unflanged adults. Thus, unflanged males of various chronological ages can be mistakenly identified as "subadults." Unflanged adult males are typically described as "female-sized," but this may simply reflect the fact that unflanged male body size has only ever been measured in peri-pubescent individuals. In this study, we measured the skeletons of 111 wild adult orangutans (Pongo spp.), including 20 unflanged males, 45 flanged males, and 46 females, resulting in the largest skeletal sample of unflanged males yet studied. We assessed long bone lengths (as a proxy for stature) for all 111 individuals and recorded weights-at-death, femoral head diameters, bi-iliac breadths, and long bone cross-sectional areas (CSA) (as proxies for mass) for 27 of these individuals, including seven flanged males, three adult confirmed-unflanged males, and three young adult likely-unflanged males. ANOVA and Kruskal-Wallis tests with Tukey and Dunn post-hoc pairwise comparisons, respectively, showed that body sizes for young adult unflanged males are similar to those of the adult females in the sample (all P ≥ 0.09 except bi-iliac breadth), whereas body sizes for adult unflanged males ranged between those of adult flanged males and adult females for several measurements (all P < 0.001). Thus, sexually mature male orangutans exhibit body sizes that range from the female end of the spectrum to the flanged male end of the spectrum. These results exemplify that the term "sexual dimorphism" fails to capture the full range of variation in adult orangutan body size. By including adult unflanged males in analyses of body size and other aspects of morphology, not as aberrations but as an expected part of orangutan variation, we may begin to shift the way that we think about features typically considered dichotomous according to biological sex.

7.
J Mot Behav ; 55(3): 302-312, 2023.
Article in English | MEDLINE | ID: mdl-36990462

ABSTRACT

Traumatic brain injuries can result in short-lived and long-lasting neurological impairment. Identifying the correct recovery timeframe is challenging, as balance-based metrics may be negatively impacted if testing is performed soon after exercise. Thirty-two healthy controls and seventeen concussed individuals performed a series of balance challenges, including virtual reality optical flow perturbation. The control group completed a backpacking protocol to induce moderate fatigue. Concussed participants had lower spectral power in the motor cortex and central sulcus when compared to fatigued controls. Moreover, concussed participants experienced a decrease in overall theta band spectral power while fatigued controls showed an increase in theta band spectral power. This neural signature may be useful to distinguish between concussed and non-concussed fatigued participants in future assessments.


Subject(s)
Brain Concussion , Humans , Exercise , Postural Balance , Cerebral Cortex
8.
J Neurooncol ; 161(1): 117-126, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36609808

ABSTRACT

PURPOSE: Prior research indicates that the volume of central nervous system (CNS) tumor patients seen by a facility is associated with outcomes. However, most studies have focused on short-term survival and specific CNS tumor subtypes. Our objective was to examine whether facility CNS tumor patient volume is associated with longer-term CNS tumor survival overall and by subtype. METHODS: We obtained National Cancer Database (NCDB) data including individuals diagnosed with CNS tumors from 2004 to 2016. Analyses were stratified by age group (0-14, 15-39, 40-64, and ≥ 65 years) and tumor type. We used Cox Proportional Hazards (PH) regression and restricted mean survival time (RMST) analyses to examine associations between survival and facility patient volume percentile category adjusting for potential confounding factors. RESULTS: Our analytic dataset included data from 130,830 individuals diagnosed with malignant first primary CNS tumors. We found a consistently reduced hazard rate of death across age groups for individuals reported by higher vs. lower (> 95th vs. ≤ 70th percentile) volume facilities (hazard ratio (HR)0-14 = 0.78, 95% confidence interval (CI) 0.64-0.95; HR15-39 = 0.87, 95% CI 0.78-0.96; HR40-64 = 0.82, 95% CI 0.76-0.88; HR≥65 = 0.80, 95% CI 0.75-0.86). Significantly longer survival times within 5 years for higher vs. lower volume facilities were observed ranging from 1.20 months (15-39) to 3.08 months (40-64) higher. Associations varied by CNS tumor subtype for all age groups. CONCLUSIONS: These results suggest facility factors influence CNS tumor survival with longer survival for patients reported by higher volume facilities. Understanding these factors will be critical to developing strategies that eliminate modifiable differences in survival times.


Subject(s)
Central Nervous System Neoplasms , Hospitals, High-Volume , Humans , Aged , Proportional Hazards Models , Central Nervous System Neoplasms/therapy , Survival Rate , Databases, Factual , Retrospective Studies
9.
Sci Rep ; 11(1): 19691, 2021 10 04.
Article in English | MEDLINE | ID: mdl-34608185

ABSTRACT

The goal of this study was to quantify the association between sensory integration abilities relevant for standing balance and disease stage in glaucoma. The disease stage was assessed using both functional (visual field deficit) and structural (retinal nerve fiber layer thickness) deficits in the better and worse eye. Balance was assessed using an adapted version of the well-established Sensory Organization Test (SOT). Eleven subjects diagnosed with mild to moderate glaucoma stood for 3 min in 6 sensory challenging postural conditions. Balance was assessed using sway magnitude and sway speed computed based on center-of-pressure data. Mixed linear regression analyses were used to investigate the associations between glaucoma severity and balance measures. Findings revealed that the visual field deficit severity in the better eye was associated with increased standing sway speed. This finding was confirmed in eyes open and closed conditions. Balance was not affected by the extent of the visual field deficit in the worse eye. Similarly, structural damage in either eye was not associated with the balance measures. In summary, this study found that postural control performance was associated with visual field deficit severity. The fact that this was found during eyes closed as well suggests that reduced postural control in glaucoma is not entirely attributed to impaired peripheral visual inputs. A larger study is needed to further investigate potential interactions between visual changes and central processing changes contributing to reduced balance function and increased incidence of falls in adults with glaucoma.


Subject(s)
Glaucoma/diagnosis , Glaucoma/physiopathology , Postural Balance , Adaptation, Physiological , Aged , Aged, 80 and over , Female , Glaucoma/etiology , Humans , Male , Middle Aged , Posture , Severity of Illness Index , Visual Fields
10.
Sci Rep ; 11(1): 10185, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33986319

ABSTRACT

Pronounced temporal and spatial variation in the availability of food resources can produce energetic deficits in organisms. Fruit-dependent Bornean orangutans face extreme variation in fruit availability and experience negative energy and protein balance during episodes of fruit scarcity. We evaluate the possibility that orangutans of different sexes and ages catabolize muscle tissue when the availability of fruit is low. We assess variation in muscle mass by examining the relationship between urinary creatinine and specific gravity and use the residuals as a non-invasive measure of estimated lean body mass (ELBM). Despite orangutans having a suite of adaptations to buffer them from fruit scarcity and associated caloric deficits, ELBM was lower during low fruit periods in all age-sex classes. As predicted, adult male orangutans had higher ELBM than adult females and immatures. Contrary to expectation, flanged and unflanged males did not differ significantly in ELBM. These findings highlight the precarity of orangutan health in the face of rapid environmental change and add to a growing body of evidence that orangutans are characterized by unique metabolic traits shaped by their unpredictable forest environment.


Subject(s)
Creatine/analysis , Muscle, Skeletal/metabolism , Pongo pygmaeus/metabolism , Animals , Behavior, Animal/physiology , Creatine/urine , Ecosystem , Feeding Behavior/physiology , Female , Food Insecurity , Forests , Fruit , Male , Metabolism/physiology , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiology , Pongo/physiology , Pongo pygmaeus/physiology
11.
Sci Total Environ ; 780: 146399, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-33770593

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) make up a large group of persistent anthropogenic chemicals which are difficult to degrade and/or destroy. PFAS are an emerging class of contaminants, but little is known about the long-term health effects related to exposure. In addition, technologies to identify levels of contamination in the environment and to remediate contaminated sites are currently inadequate. In this opinion-type discussion paper, a team of researchers from the University of Connecticut and the University at Albany discuss the scientific challenges in their specific but intertwined PFAS research areas, including rapid and low-cost detection, energy-saving remediation, the role of T helper cells in immunotoxicity, and the biochemical and molecular effects of PFAS among community residents with measurable PFAS concentrations. Potential research directions that may be employed to address those challenges and improve the understanding of sensing, remediation, exposure to, and health effects of PFAS are then presented. We hope our account of emerging problems related to PFAS contamination will encourage a broad range of scientific experts to bring these research initiatives addressing PFAS into play on a national scale.

12.
Sci Rep ; 11(1): 6492, 2021 03 22.
Article in English | MEDLINE | ID: mdl-33753816

ABSTRACT

Zika virus (ZIKV), a flavivirus transmitted primarily by infected mosquitos, can cause neurological symptoms such as Guillian-Barré syndrome and microcephaly. We developed several vaccinia virus (VACV) vaccine candidates for ZIKV based on replication-inducible VACVs (vINDs) expressing ZIKV pre-membrane (prM) and envelope (E) proteins (vIND-ZIKVs). These vIND-ZIKVs contain elements of the tetracycline operon and replicate only in the presence of tetracyclines. The pool of vaccine candidates was narrowed to one vIND-ZIKV containing a novel mutation in the signal peptide of prM that led to higher expression and secretion of E and production of virus-like particles, which was then tested for safety, immunogenicity, and efficacy in mice. vIND-ZIKV grows to high titers in vitro in the presence of doxycycline (DOX) but is replication-defective in vivo in the absence of DOX, causing no weight loss in mice. C57BL/6 mice vaccinated once with vIND-ZIKV in the absence of DOX (as a replication-defective virus) developed robust levels of E-peptide-specific IFN-γ-secreting splenocytes and anti-E IgG titers, with modest levels of serum-neutralizing antibodies. Vaccinated mice treated with anti-IFNAR1 antibody were completely protected from ZIKV viremia post-challenge after a single dose of vIND-ZIKV. Furthermore, mice with prior immunity to VACV developed moderate anti-E IgG titers that increased after booster vaccination, and were protected from viremia only after two vaccinations with vIND-ZIKV.


Subject(s)
Immunogenicity, Vaccine , Vaccines, Virus-Like Particle/immunology , Vaccinia virus/genetics , Zika Virus Infection/prevention & control , Zika Virus/immunology , Animals , Chlorocebus aethiops , Female , HeLa Cells , Humans , Immunoglobulin G/immunology , Interferon-gamma/immunology , Mice , Mice, Inbred C57BL , Spleen/cytology , Spleen/immunology , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/genetics , Vaccinia virus/physiology , Vero Cells , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology , Virus Replication
13.
J Appl Biomech ; 36(4): 244-248, 2020 Aug 01.
Article in English | MEDLINE | ID: mdl-32396870

ABSTRACT

Virtual reality (VR) paradigms have proved to be a valid method to challenge and perturb balance. There is little consensus in the literature on the best protocol design to perturb balance and induce postural sway. Current VR interventions still lack a well-defined standardized metric to generate a virtual environment that can perturb balance in an efficacious, lifelike, and repeatable manner. The objective of this study was to investigate different configurations of amplitude and frequency in an anterior-posterior translation VR environment, that is, lifelike and scaled. Thirteen young adults with no conditions affecting balance were recruited. Balance was challenged by anterior-posterior sinusoidal movement of the lab image within the VR headset. Four different amplitudes of the sinusoidal movement were tested: 1, 5, 10, and 20 cm, with each amplitude being presented at 2 test frequencies : 0.5 and 0.25 Hz. Mean center of pressure velocity was significantly greater than baseline at 0.5 Hz and amplitudes of 10 and 20 cm. Mean center of pressure at approximate entropy was greater than baseline at 0.5 Hz and amplitude of 20 cm. The results suggest that sinusoidal movement of a realistic VR environment produces altered balance compared with baseline quiet standing, but only under specific movement parameters.

14.
Mol Ther Methods Clin Dev ; 17: 731-738, 2020 Jun 12.
Article in English | MEDLINE | ID: mdl-32346550

ABSTRACT

Vaccinia virus (VACV) was successfully used as a vaccine in the smallpox eradication campaign. Since then, it has been widely used in the development of vaccine and therapeutic vectors. However, methods of generating and purifying recombinant VACVs (rVACVs) are often time-consuming, cumbersome, and in some cases require specialized cell lines or equipment. Here, we describe a novel EPPIC (Efficient Purification by Parental Inducer Constraint) platform for the rapid generation of rVACVs using a replication-inducible VACV (vIND) as a parental virus for homologous recombination. Purification of the rVACV from the parental vIND is achieved by two serial passages in the absence of inducer (i.e., parental inducer "constraint") in standard laboratory cell lines, without the need for specialized equipment, within 1 week. We determined the optimal conditions for homologous recombination and serial purification and generated a suite of vIND parental viruses to facilitate customization of the platform. Importantly, the EPPIC platform can be adapted to rapidly generate replication-deficient and replication-competent rVACVs expressing vaccine or therapeutic antigens, with or without screening markers, by simple modifications to a DNA shuttle vector, thus allowing the rapid development, updating, and refinement of personalized or custom vaccines and therapeutic vectors in a matter of days.

15.
PLoS One ; 15(4): e0230711, 2020.
Article in English | MEDLINE | ID: mdl-32240193

ABSTRACT

Vaccinia virus (VACV) has been used extensively as the vaccine against smallpox and as a viral vector for the development of recombinant vaccines and cancer therapies. Replication-competent, non-attenuated VACVs induce strong, long-lived humoral and cell-mediated immune responses and can be effective oncolytic vectors. However, complications from uncontrolled VACV replication in vaccinees and their close contacts can be severe, particularly in individuals with predisposing conditions. In an effort to develop replication-competent VACV vectors with improved safety, we placed VACV late genes encoding core or virion morphogenesis proteins under the control of tet operon elements to regulate their expression with tetracycline antibiotics. These replication-inducible VACVs would only express the selected genes in the presence of tetracyclines. VACVs inducibly expressing the A3L or A6L genes replicated indistinguishably from wild-type VACV in the presence of tetracyclines, whereas there was no evidence of replication in the absence of antibiotics. These outcomes were reflected in mice, where the VACV inducibly expressing the A6L gene caused weight loss and mortality equivalent to wild-type VACV in the presence of tetracyclines. In the absence of tetracyclines, mice were protected from weight loss and mortality, and viral replication was not detected. These findings indicate that replication-inducible VACVs based on the conditional expression of the A3L or A6L genes can be used for the development of safer, next-generation live VACV vectors and vaccines. The design allows for administration of replication-inducible VACV in the absence of tetracyclines (as a replication-defective vector) or in the presence of tetracyclines (as a replication-competent vector) with enhanced safety.


Subject(s)
Genetic Vectors/administration & dosage , Tetracyclines/pharmacology , Vaccinia virus/growth & development , Vaccinia/prevention & control , Virion/growth & development , Virus Replication , Animals , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Vaccines, Synthetic/administration & dosage , Vaccinia/genetics , Vaccinia/virology , Vaccinia virus/drug effects , Vaccinia virus/genetics , Viral Proteins/genetics , Virion/drug effects
16.
Vaccines (Basel) ; 8(1)2020 Feb 28.
Article in English | MEDLINE | ID: mdl-32121277

ABSTRACT

BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) viruses are a major cause of disease and economic loss in pigs worldwide. High genetic diversity among PRRSV strains is problematic for successful disease control by vaccination. Mosaic DNA and vaccinia (VACV) vaccines were developed in order to improve protection against heterologous PRRSV strains. METHODS: Piglets were primed and boosted with GP5-Mosaic DNA vaccine and recombinant GP5-Mosaic VACV (rGP5-Mosaic VACV), respectively. Pigs vaccinated with rGP5-WT (VR2332) DNA and rGP5-WT VACV, or empty vector DNA and empty VACV respectively, served as controls. Virus challenge was given to separate groups of vaccinated pigs with VR2332 or MN184C. Necropsies were performed 14 days after challenge. RESULTS: Vaccination with the GP5-Mosaic-based vaccines resulted in cellular reactivity and higher levels of neutralizing antibodies to both VR2332 and MN184C PRRSV strains. In contrast, vaccination of animals with the GP5-WT vaccines induced responses only to VR2332. Furthermore, vaccination with the GP5-Mosaic based vaccines resulted in protection against challenge with two heterologous virus strains, as demonstrated by the significantly lower viral loads in serum, tissues, porcine alveolar macrophages (PAMs), and bronchoalveolar lavage (BAL) fluids, and less severe lung lesions after challenge with either MN184C or VR2332, which have only 85% identity. In contrast, significant protection by the GP5-WT based vaccines was only achieved against the VR2332 strain. Conclusions: GP5-Mosaic vaccines, using a DNA-prime/VACV boost regimen, conferred protection in pigs against heterologous viruses.

17.
Am J Primatol ; 82(11): e23058, 2020 11.
Article in English | MEDLINE | ID: mdl-31583721

ABSTRACT

The primate adolescent period is characterized by a series of changes in physiology, behavior, and social relationships. Orangutans have the slowest life history and the longest period of dependency of all primates. As members of a semisolitary species with high levels of sexual coercion, adolescent female orangutans face a unique combination of challenges when achieving independence from their mother. This study examined the mating behavior of adolescent female orangutans and compared it with that of adult females to assess whether mating behavior reflects distinct strategies at these different points in the life cycle. Data were collected in Gunung Palung National Park on the island of Borneo over 20 years. Mating events from adolescent (n = 19) and adult females (n = 26) were scored and compared. Adolescent female mating events had significantly higher mating scores (indicating more proceptivity) than those of adult females (ß = 1.948, p = .001). Adolescent females also engaged in elaborate sociosexual interactions with different flanged males, behaviors that were never observed during mating events of adult females. These interactions involved characteristic behavior on the part of both the adolescent females and the flanged males. Given these findings and the documentation of similar accounts of adolescent female-flanged male mating from the island of Sumatra, we propose that adolescent female orangutans display distinctive behavioral repertoires throughout the genus Pongo which serves to overcome male ambivalence toward nulliparous females, establish familiarity, and evaluate coercive tendencies in flanged males. We suggest that these behavioral patterns are an integral part of female social development in a female philopatric, but highly dispersed species where consistent social support is absent after ranging independence is achieved.


Subject(s)
Parity , Pongo pygmaeus/physiology , Sexual Behavior, Animal , Age Factors , Animals , Borneo , Female , Male
18.
Sci Rep ; 9(1): 14168, 2019 Oct 02.
Article in English | MEDLINE | ID: mdl-31578409

ABSTRACT

Glaucoma is the world's leading cause of irreversible blindness, and falls are a major public health concern in glaucoma patients. Although recent evidence suggests the involvements of the brain toward advanced glaucoma stages, the early brain changes and their clinical and behavioral consequences remain poorly described. This study aims to determine how glaucoma may impair the brain structurally and functionally within and beyond the visual pathway in the early stages, and whether these changes can explain visuomotor impairments in glaucoma. Using multi-parametric magnetic resonance imaging, glaucoma patients presented compromised white matter integrity along the central visual pathway and around the supramarginal gyrus, as well as reduced functional connectivity between the supramarginal gyrus and the visual occipital and superior sensorimotor areas when compared to healthy controls. Furthermore, decreased functional connectivity between the supramarginal gyrus and the visual brain network may negatively impact postural control measured with dynamic posturography in glaucoma patients. Taken together, this study demonstrates that widespread structural and functional brain reorganization is taking place in areas associated with visuomotor coordination in early glaucoma. These results implicate an important central mechanism by which glaucoma patients may be susceptible to visual impairments and increased risk of falls.


Subject(s)
Brain/physiopathology , Connectome , Glaucoma/physiopathology , Psychomotor Performance , Brain/diagnostic imaging , Female , Glaucoma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Posture
19.
Sci Rep ; 9(1): 7806, 2019 05 24.
Article in English | MEDLINE | ID: mdl-31127126

ABSTRACT

Infanticide as a male reproductive tactic is widespread across mammals, and is particularly prevalent in catarrhine primates. While it has never been observed in wild orangutans, infanticide by non-sire males has been predicted to occur due to their extremely long inter-birth intervals, semi-solitary social structure, and the presence of female counter-tactics to infanticide. Here, we report on the disappearance of a healthy four-month-old infant, along with a serious foot injury suffered by the primiparous mother. No other cases of infant mortality have been observed at this site in 30 years of study. Using photographic measurements of the injury, and information on the behavior and bite size of potential predators, we evaluate the possible causes of this injury. The context, including the behavior of the female and the presence of a new male at the time of the injury, lead us to conclude that the most likely cause of the infant loss and maternal injury was male infanticide. We suggest that in orangutans, and other species where nulliparous females are not preferred mates, these females may be less successful at using paternity confusion as an infanticide avoidance tactic, thus increasing the likelihood of infanticide of their first-born infants.


Subject(s)
Animals, Wild , Pongo , Aggression , Animals , Animals, Newborn , Animals, Wild/physiology , Behavior, Animal , Female , Male , Pongo/physiology , Reproduction
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