Search Results (29)

Background and Objectives: The imminent threat of antibiotic resistance has spurred studies of nonconventional antimicrobial approaches. Gallium utilization is a promising and emerging approach to treating a variety of resistant bacteria using “Trojan horse” strategies to disrupt iron-dependent processes and biofilms. This study utilized experimental evolution to test the evolvability of gallium resistance in Staphylococcus aureus and resistance traits potentially correlated with metals, antibiotics and polyfluorinated compounds, as well as its genomics foundations. Methods: Whole-genome sequencing was utilized to reveal functional networks of mutations associated with gallium resistance. Additionally, scanning electron microscopy (SEM) observation was utilized to visualize distinct morphological changes on the surface of gallium-resistant populations and compare with the control populations. Results: As demonstrated by these studies, S. aureus evolved resistance to gallium after 20 days of selection. Furthermore, these populations displayed resistance traits correlated with heavy metals and polyfluorinated compounds. In contrast, the gallium-resistant populations were very sensitive to antibiotics. Whole-genome analysis revealed significant polymorphisms in the gallium (III)-resistant populations for example, polymorphisms in staphyloferrinA export MFS transporter/D ornithine citrate ligase (sfaA/sfaD), teichoic acid D Ala esterase (fmtA), DUF3169 family protein (KQ76_RS01520) and adenine phosphoribosyltransferase (KQ76_RS08360), while polymorphisms in the ABC transporter permease subunit (pstC) and acyltransferase family protein (KQ76_RS04365) were unique to the control populations. The polymorphisms directly affected the cells’ morphology. SEM images showed significant external ultrastructural changes in the gallium-selected bacterial cells compared to the control cells. Conclusions: Our study confirmed that using gallium as an antimicrobial can have significant health and environmental implications. Full article

Background: In May 2019, Ulaanbaatar, Mongolia introduced a city-wide raw coal ban (RCB) to improve ambient air quality. Air pollution exposure particularly affects child health and is associated with acute respiratory disease. We assessed the effects of the RCB on air quality and child respiratory health. Methods: An interrupted time-series analysis was conducted on air quality (PM_2.5, PM₁₀, SO₂, CO) and child (<5 y) severe acute respiratory disease, adjusting for coinciding co-events (COVID-19) where necessary. The subgroup analysis focussed on peak pollution months (November–February). Results: PM₁₀ significantly decreased by −34.3 µg/m³ (95% CI −62.9, −5.8, p = 0.02) and PM_2.5 by −17.1 µg/m³ (95% CI −26.3, −7.9, p < 0.01), immediately post-intervention. The subgroup analysis showed SO₂ increased by 81.6 µg/m³ (95% CI 45.2, 117.9, p < 0.01) in the first month and by 4.9 µg/m³ (95% CI 2.6, 7.3, p < 0.01) monthly afterwards. CO increased by 56.1 µg/m³ (95% CI 13.5, 98.7, p = 0.01). Child respiratory health showed no significant change after adjusting for the COVID-19 effect. Discussion: The RCB successfully reduced key pollutants (PM), almost instantly. Long-term increases in SO₂ and CO and limited health effects highlight the need for further air quality improvements. Outputs from Mongolia’s continuous air quality mitigation efforts provide useful insights for countries facing similar challenges. Full article

Background/Objectives: Vaccinating care home staff is essential to protect vulnerable residents by reducing infection risks and creating a safer care environment. However, vaccine hesitancy amongst staff remains a challenge, particularly since the COVID-19 pandemic raised concerns about side effects and vaccination mandates. This study examines how the pandemic influenced flu vaccine hesitancy amongst UK care home staff. Methods: Data were collected from the FluCare trials conducted over the 2021–22 and 2022–23 winter seasons to explore the impact of concurrent mandatory and non-mandatory COVID-19 vaccination policies on flu vaccine uptake. A total of 52 interviews (21 from the feasibility study and 31 from the randomised control trial) were conducted with care home managers and staff. Thematic analysis identified key themes shaping staff attitudes toward flu vaccination. Results: Four central themes emerged regarding the impact of the pandemic on staff attitudes and the contextual influences shaping vaccine hesitance: (i) tension between autonomy and morals in vaccination decisions; (ii) the COVID ‘craze’ and the displacement of the flu vaccine; (iii) the role of the COVID ‘craze’ in staff vaccine fatigue; and (iv) conspiracies, (mis)information, and the significance of trust. Psychosocial theories on decision making and health behaviour were used to further interpret the findings. Conclusions: Our findings suggest that post-COVID-19 interventions in care home setting should address the issues of autonomy, vaccine fatigue, and trust to enhance vaccine uptake. Understanding these factors could support more effective strategies to address hesitancy amongst care home staff in future vaccination campaigns. Full article

Background/Objectives: Adequate folate intake is required in preterm infants for rapid growth and development, but there is little evidence to back recommendations. We aimed to assess folate status in preterm infants at discharge and in early infancy, according to exposure to folate sources, particularly in those exclusively/predominantly breastfed. Methods: A prospective, multicenter, observational cohort study was conducted in the UK, involving 45 preterm infants <33 weeks’ gestational age (GA) exclusively/predominantly fed human milk when approaching NICU (Neonatal Intensive Care Unit) discharge. Serum folate levels were measured near NICU discharge (T1) and at 2–3 months corrected age (T2). Folate status was categorized per WHO (World Health Organization) guidelines: deficiency (<6.8 nmol/L), possible deficiency (6.8–13.4 nmol/L), normal (13.5–45.3 nmol/L), and elevated (>45.3 nmol/L). Nutritional information on feed and supplements was collected from hospital notes and maternal interviews. Results: Thirty-two infants (71%) received parenteral nutrition. Twelve infants (32%) remained exclusively breastfed at T2. No infant from the whole cohort had a serum folate concentration <13.5 nmol/L at either time point. A proportion of infants had serum folate concentrations >45.3 nmol/L: 14/45 (31%) at T1, 19/37 (42%) at T2, and 7/37 (16%) at both time points. Elevated concentrations were seen particularly in infants who received folic acid supplements or nutrition containing folic acid, such as parenteral nutrition and breastmilk fortifiers. Conclusions: Folate deficiency was not observed in this cohort; folate concentrations were high and in line with those observed in healthy term infants. Further research is needed to assess the high folate concentrations in premature babies and whether they may have any adverse clinical impact. Full article

The rise of mRNA as a novel vaccination strategy presents new opportunities to confront global disease. Double-stranded RNA (dsRNA) is an impurity byproduct of the in vitro transcription reaction used to manufacture mRNA that may affect the potency and safety of the mRNA vaccine in patients. Careful quantitation of dsRNA during manufacturing is critical to ensure that residual dsRNA is minimized in purified mRNA drug substances. In this work, we describe the development and implementation of a sandwich Enzyme-Linked Immunosorbent Assay (ELISA) to quantitate nanogram quantities of residual dsRNA contaminants in mRNA process intermediates using readily available commercial reagents. This sandwich ELISA developed in this study follows a standard protocol and can be easily adapted to most research laboratory environments. Additionally, a liquid handler coupled with an automated robotics system was utilized to increase assay throughput, improve precision, and reduce the analyst time requirement. The final automated sandwich ELISA was able to measure <10 ng/mL of dsRNA with a specificity for dsRNA over 2000-fold higher than mRNA, a variability of <15%, and a throughput of 72 samples per day. Full article

Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel^® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos^®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates. Full article

Sleep is often impaired in firefighters due to the psychologically and physiologically intense nature of their work and working shift schedules. Peanut butter is affordable and a substantial source of monounsaturated fatty acids, which may aid sleep health. Thus, this study sought to determine if a daily serving of peanut butter consumed before bedtime for seven weeks altered sleep quality and quantity among full-time firefighters. Forty firefighters (peanut butter group = 20; control group = 20) participated in this eight-week randomized controlled trial. All participants completed a subjective questionnaire on mood, focus, and alertness twice daily and wore an Actigraph wristwatch to measure sleep variables, including latency, efficiency, time in bed, time asleep, wake after sleep onset, number of awakenings, and time spent awake. After a baseline week, the peanut butter group consumed two tablespoons of peanut butter two hours prior to bedtime for seven weeks. Compared to the control group, the peanut butter group did not demonstrate significant changes (p > 0.05) in sleep measures or subjective feelings of mood, focus, or alertness after consuming peanut butter for seven weeks. Therefore, peanut butter as a source of peanuts did not alter sleep quality or quantity in this group of firefighters. Full article

A proliferation of invasive species is displacing native species, occupying their habitats and degrading biodiversity. One of these is the invasive goldenrod (Solidago spp.), characterized by aggressive growth that results in habitat disruption as it outcompetes native plants. This invasiveness also leads to altered soil composition through the release of allelopathic chemicals, complicating control efforts and making it challenging to maintain ecological balance in affected areas. The research goal was to develop methods that allow the analysis of changes in heterogeneous habitats with high accuracy and repeatability. For this reason, we used open source classifiers Support Vector Machine (SVM), Random Forest (RF), and satellite images of Sentinel-2 (free) and PlanetScope (commercial) to assess their potential in goldenrod classification. Due to the fact that invasions begin with invasion footholds, created by small patches of invasive, autochthonous plants and different land cover patterns (asphalt, concrete, buildings) forming heterogeneous areas, we based our studies on field-verified polygons, which allowed the selection of randomized pixels for the training and validation of iterative classifications. The results confirmed that the optimal solution is the use of multitemporal Sentinel-2 images and the RF classifier, as this combination gave F1-score accuracy of 0.92–0.95 for polygons dominated by goldenrod and 0.85–0.89 for heterogeneous areas where goldenrod was in the minority (mix class; smaller share of goldenrod in canopy than autochthonous plants). The mean decrease in the accuracy analysis (MDA), indicating an informativeness of individual spectral bands, showed that Sentinel-2 bands coastal aerosol, NIR, green, SWIR, and red were comparably important, while in the case of PlanetScope data, the NIR and red were definitely the most important, and remaining bands were less informative, and yellow (B5) did not contribute significant information even during the flowering period, when the plant was covered with intensely yellow perianth, and red-edge, coastal aerosol, or green II were much more important. The maximum RF classification values of Sentinel-2 and PlanetScope images for goldenrod are similar (F1-score > 0.9), but the medians are lower for PlanetScope data, especially with the SVM algorithm. Full article

The ability to detect several types of cancer using a non-invasive, blood-based test holds the potential to revolutionize oncology screening. We mined tumor methylation array data from the Cancer Genome Atlas (TCGA) covering 14 cancer types and identified two novel, broadly-occurring methylation markers at TLX1 and GALR1. To evaluate their performance as a generalized blood-based screening approach, along with our previously reported methylation biomarker, ZNF154, we rigorously assessed each marker individually or combined. Utilizing TCGA methylation data and applying logistic regression models within each individual cancer type, we found that the three-marker combination significantly increased the average area under the ROC curve (AUC) across the 14 tumor types compared to single markers (p = 1.158 × 10⁻¹⁰; Friedman test). Furthermore, we simulated dilutions of tumor DNA into healthy blood cell DNA and demonstrated increased AUC of combined markers across all dilution levels. Finally, we evaluated assay performance in bisulfite sequenced DNA from patient tumors and plasma, including early-stage samples. When combining all three markers, the assay correctly identified nine out of nine lung cancer plasma samples. In patient plasma from hepatocellular carcinoma, ZNF154 alone yielded the highest combined sensitivity and specificity values averaging 68% and 72%, whereas multiple markers could achieve higher sensitivity or specificity, but not both. Altogether, this study presents a comprehensive pipeline for the identification, testing, and validation of multi-cancer methylation biomarkers with a considerable potential for detecting a broad range of cancer types in patient blood samples. Full article

The global incidence of sexually transmitted infections (STIs) remains high, with the World Health Organization (WHO) estimating that over 1 million people acquire STIs daily. STIs can lead to infertility, pregnancy complications, and cancers. Co-infections with multiple pathogens are prevalent among individuals with an STI and can lead to heightened infectivity and more severe clinical manifestations. Chlamydia trachomatis (CT) is the most reported bacterial STI worldwide in both men and women, and several studies have demonstrated co-infection of CT with viral and other bacterial STIs. CT is a gram-negative bacterium with a unique biphasic developmental cycle including infectious extracellular elementary bodies (EBs) and metabolically active intracellular reticulate bodies (RBs). The intracellular form of this organism, RBs, has evolved mechanisms to persist for long periods within host epithelial cells in a viable but non-cultivable state. The co-infections of CT with the most frequently reported sexually transmitted viruses: human immunodeficiency virus (HIV), human papillomavirus (HPV), and herpes simplex virus (HSV) have been investigated through in vitro and in vivo studies. These research studies have made significant strides in unraveling the intricate interactions between CT, these viral STIs, and their eukaryotic host. In this review, we present an overview of the epidemiology of these co-infections, while specifically delineating the underlying mechanisms by which CT influences the transmission and infection dynamics of HIV and HSV. Furthermore, we explore the intricate relationship between CT and HPV infection, with a particular emphasis on the heightened risk of cervical cancer. By consolidating the current body of knowledge, we provide valuable insights into the complex dynamics and implications of co-infection involving CT and sexually transmitted viruses. Full article

Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (n = 38), (2) mTBI (n = 25), (3) comorbid PTSD+mTBI (n = 94), and (4) a control group with neither PTSD nor mTBI (n = 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (p = 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (p < 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (p < 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions. Full article

The calcium-sensing receptor (CaSR) is an important regulator of epidermal function. We previously reported that knockdown of the CaSR or treatment with its negative allosteric modulator, NPS-2143, significantly reduced UV-induced DNA damage, a key factor in skin cancer development. We subsequently wanted to test whether topical NPS-2143 could also reduce UV-DNA damage, immune suppression, or skin tumour development in mice. In this study, topical application of NPS-2143 (228 or 2280 pmol/cm²) to Skh:hr1 female mice reduced UV-induced cyclobutane pyrimidine dimers (CPD) (p < 0.05) and oxidative DNA damage (8-OHdG) (p < 0.05) to a similar extent as the known photoprotective agent 1,25(OH)₂ vitamin D3 (calcitriol, 1,25D). Topical NPS-2143 failed to rescue UV-induced immunosuppression in a contact hypersensitivity study. In a chronic UV photocarcinogenesis protocol, topical NPS-2143 reduced squamous cell carcinomas for only up to 24 weeks (p < 0.02) but had no other effect on skin tumour development. In human keratinocytes, 1,25D, which protected mice from UV-induced skin tumours, significantly reduced UV-upregulated p-CREB expression (p < 0.01), a potential early anti-tumour marker, while NPS-2143 had no effect. This result, together with the failure to reduce UV-induced immunosuppression, may explain why the reduction in UV-DNA damage in mice with NPS-2143 was not sufficient to inhibit skin tumour formation. Full article

The gap between how health information is communicated and what people understand and can use to make informed health decisions is called health literacy. This gap was exacerbated by the rapidly changing and excessive volume of information, misinformation, and disinformation during the COVID-19 pandemic. People with lower health literacy may not have understood the importance of COVID-19 vaccination for themselves or for their communities. Our aim was to understand health literacy levels within Fulton County, Georgia, and their relationship to vaccine prevalence. Fulton county residents ages 18 and over (n = 425) completed an on-line Health Literacy Questionnaire. Individual, organizational, functional, interactive, and critical health literacy scales were created. Vaccination prevalence data were collected from the Georgia Vaccine Distribution Dashboard. All data were divided into one of three county areas. There were statistically significant variations in vaccine prevalence χ²(3) = 29.325, p < 0.001 among the three county areas. All levels of health literacy predicted overall county vaccination prevalence F (4,420) = 85.941, p < 0.001, There were significant differences in health literacy levels among two of the three county area pairs; the lowest resourced county area had the lowest vaccination prevalence and health literacy rates. This is the first example of relating direct health literacy measures across a major metropolitan US county with vaccine prevalence data. Full article

Objective: Schizophrenia is a complex functionally debilitating neurodevelopmental disorder, with associated social cognitive impairment. Corpus Callosum (CC) white matter tracts deficits are reported for people with schizophrenia; however, few studies focus on interhemispheric processing relative to social cognition tasks. This study aimed to determine if a relationship between the CC and social cognition exists. Method: In this cross-section study, a sample of n = 178 typical controls and n = 58 people with schizophrenia completed measures of mentalising (Reading the Mind in the Eyes), emotion recognition outcome and reaction time (Emotion Recognition Test), and clinical symptoms (Positive and Negative Symptom Scale), alongside diffusion-based tract imaging. The CC and its subregions, i.e., the genu, body, and splenium were the regions of interest (ROI). Results: Reduced white matter tract integrity was observed in the CC for patients when compared to controls. Patients performed slower, and less accurately on emotion recognition tasks, which significantly and negatively correlated to the structural integrity of the CC genu. Tract integrity further significantly and negatively related to clinical symptomatology. Conclusions: People with schizophrenia have altered white matter integrity in the genu of the CC, compared to controls, which relates to cognitive deficits associated with recognising emotional stimuli accurately and quickly, and severity of clinical symptoms. Full article

Significant changes in the Arctic climate, particularly a rapid decline of September Arctic sea ice has occurred over the past few decades. Though the exact reason for such drastic changes is still unknown, studies suggest anthropogenic drivers, natural variability of the climate system, and a combination of both as reasons. The present study focus on the influence of one of the natural variabilities of the climate system, the teleconnections associated with the Indian Summer Monsoon (ISM), and its relationship to September Arctic sea ice. Using 50 years (1951–2000) of National Center for Environmental Prediction (NCEP)/National Center for Atmospheric Research (NCAR) NCEP/NCAR reanalysis data, APHRODITE precipitation data, Gridded Monthly Sea Ice Extent and Concentration, 1850 Onward, V2, and HadISST sea-ice concentration data, it is shown that during many strong (weak) ISM years, the Arctic sea ice increased (decreased) predominantly over the Chukchi and Beaufort Seas. The ISM plays a significant role in causing a positive (negative) North Atlantic Oscillation (NAO) during strong (weak) ISM years through the monsoon-desert mechanism associated with monsoonal heating. Simultaneously, the NAO during a strong (weak) ISM causes weakening (strengthening) of the Beaufort Sea High (BSH). The strength of the BSH modulates the Arctic atmospheric circulation, advecting cold air and the direction of the transpolar drift stream, both leading to the generation of more (less) sea ice over the Chukchi-Beaufort Sea region during strong (weak) ISM years. The study illustrates a new atmospheric teleconnection between the tropics and the Arctic. Full article