Shiga toxin-producing E. coli (STEC) infections associated with wildlife are increasing globally, highlighting many ‘spillover’ species as important reservoirs for these zoonotic pathogens. A human ...outbreak of STEC serogroup O157 in 2015 in Scotland, associated with the consumption of venison meat products, highlighted several knowledge gaps, including the prevalence of STEC O157 in Scottish wild deer and the potential risk to humans from wild deer isolates. In this study, we undertook a nationwide survey of wild deer in Scotland and determined that the prevalence of STEC O157 in wild deer is low 0.28% (95% confidence interval = 0.06–0.80). Despite the low prevalence of STEC O157 in Scottish wild deer, identified isolates were present in deer faeces at high levels (>104 colony forming units/g faeces) and had high human pathogenic potential based on whole genome sequencing and virulence gene profiling. A retrospective epidemiological investigation also identified one wild deer isolate from this study as a possible source of a Scottish human outbreak in 2017. These results emphasise the importance of food hygiene practices during the processing of wild deer carcasses for human consumption.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited ...online by SPARK. We identified 60 genes with exome-wide significance (P < 2.5 × 10
), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2). The association of NAV3 with autism risk is primarily driven by rare inherited loss-of-function (LoF) variants, with an estimated relative risk of 4, consistent with moderate effect. Autistic individuals with LoF variants in the four moderate-risk genes (NAV3, ITSN1, SCAF1 and HNRNPUL2; n = 95) have less cognitive impairment than 129 autistic individuals with LoF variants in highly penetrant genes (CHD8, SCN2A, ADNP, FOXP1 and SHANK3) (59% vs 88%, P = 1.9 × 10
). Power calculations suggest that much larger numbers of autism cases are needed to identify additional moderate-risk genes.
Long-term (summer 2015–2018 and short-term (summer 2018) water quality monitoring was performed to understand spatial and temporal variations of surface water quality in the Newark Bay Estuary, as ...well as the Upper New York Bay, parts of the Hudson-Raritan Estuary in the New York–New Jersey metropolitan area. Electrical conductivity (EC), pH, temperature, and dissolved oxygen (DO) were measured in the field, while dissolved nitrate, phosphate, and ammonia concentrations were determined in the laboratory. Long-term and short-term water quality monitoring data consistently indicated that nutrients are significantly elevated in the Hackensack River most likely due to sewage effluent from a major sewage treatment plant. Dissolved oxygen levels were sufficiently high in most parts of the estuaries, whereas the Hackensack River showed a sign of hypoxia. Nutrients in the estuaries showed significant temporal variations typically by 2 to 3-fold during the 1-month short-term monitoring period, and were correlated with EC, DO or pH. The effects of combined sewer overflows (CSOs) during wet weather on the water quality of Newark Bay appeared uncertain except for ammonia, but long-term effects of CSOs need to be further investigated because nutrients from CSOs can accumulate in bottom sediments and be remobilized. Frequent water quality monitoring is necessary to better understand the impact of human activities on temporal variations of nutrients in urban estuaries and to efficiently protect coastal ecosystems.
•A sewage treatment plant is a major source of nutrients in the Hackensack River.•The Newark Bay Estuary was relatively oxygenated, except for the Hackensack River.•Nutrients in the estuary showed significant temporal variations over a month.•The long-term effects of combined sewer overflows need to be further investigated.
Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model ...cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.
In this data paper, we describe environmental DNA (eDNA) cytochrome c oxidase (COI) amplicon sequence data from New York City’s Bronx River Estuary. As urban systems continue to expand, describing ...and monitoring their biodiversity is increasingly important for sustainability. Once polluted and overexploited, New York City’s Bronx River Estuary is undergoing revitalization and restoration. To investigate and characterize the area’s diversity, we collected and sequenced river sediment and surface water samples from Hunts Point Riverside and Soundview Parks (n
total
= 48; n
sediment
= 25; n
water
= 23). COI analysis using universal primers mlCOIintF and jgHCO2198 detected 27,328 Amplicon Sequence Variants (ASVs) from 7,653,541 sequences, and rarefaction curves reached asymptotes indicating sufficient sampling depth. Of these, eukaryotes represented 9,841ASVs from 3,562,254 sequences. At the study sites over the sampling period, community composition varied by substrate (river sediment versus surface water) and with water temperature, but not pH. The three most common phyla were Bacillariophyta (diatoms), Annelida (segmented worms), and Ochrophyta (e.g. brown and golden algae). Of the eukaryotic ASVs, we identified 614 (6.2%) to species level, including several dinoflagellates linked to Harmful Algal Blooms such as
Heterocapsa
spp., as well as the invasive amphipod
Grandidierella japonica
. The analysis detected common bivalves including blue (
Mytilus edulis
) and ribbed (
Geukensia demissa
) mussels, as well as soft-shell clams (
Mya arenaria
), in addition to Eastern oysters (
Crassostrea virginica
) that are being reintroduced to the area. Fish species undergoing restoration such as river herring (
Alosa pseudoharengus
,
A. aestivalis
) failed to be identified, although relatively common fish including Atlantic silversides (
Menidia menidia
), menhaden (
Brevoortia tyrannus
), striped bass (
Morone saxatilis
), and mummichogs (
Fundulus heteroclitus
) were found. The data highlight the utility of eDNA metabarcoding for analyzing urban estuarine biodiversity and provide a baseline for future work in the area.
Prostate cancer (PCa) is the most diagnosed cancer in men, accounting for 27% of male new cancer diagnoses in 2022. If organ-confined, removal of the prostate through radical prostatectomy is ...considered curative; however, distant metastases may form resulting in poor patient prognosis. This study sought to determine whether quantitative pathomic features of prostate cancer differ in patients who biochemically recur following surgery. Whole mount prostate histology from 78 patients was analyzed for this study. In total, 614 slides were hematoxylin and eosin (H&E) stained and digitized to produce whole slide images (WSI). Regions of differing Gleason patterns were digitally annotated by a GU-fellowship trained pathologist (KAI), and high-resolution tiles were extracted from each annotated region of interest (ROI) for further analysis. Individual glands within the prostate were identified using automated image processing algorithms, and histomorphometric features were calculated on a per-tile basis as well as across WSI and averaged by patient. Tiles were organized into cancer and benign tissue. Logistic regression models were fit to assess the predictive value of the calculated pathomic features across tile groups and WSI, as well as models using clinical information for comparison. Logistic regression classified each pathomic feature model at accuracies >80% with areas under the curve (AUC) of 0.82, 0.76, 0.75, and 0.72 for all tiles, cancer only, noncancer only, and across WSI. This was comparable to standard clinical information, Gleason Grade Groups, and CAPRA score, which achieved similar accuracies but AUCs of 0.80, 0.77, and 0.70, respectively. This study demonstrates that the use of quantitative pathomic features calculated from digital histology of prostate cancer may provide clinicians with additional information beyond the traditional qualitative pathologist assessment. Further research is warranted to determine possible inclusion in treatment guidance.
Background
Gastroschisis mortality in sub-Saharan Africa (SSA) remains high at 59–100%. Silo inaccessibility contributes to this disparity. Standard of care (SOC) silos cost $240, while median ...monthly incomes in SSA are < $200. Our multidisciplinary American and Ugandan team designed and bench-tested a low-cost (LC) silo that costs < $2 and is constructed from locally available materials. Here we describe in vivo LC silo testing.
Methods
A piglet gastroschisis model was achieved by eviscerating intestines through a midline incision. Eight piglets were randomized to LC or SOC silos. Bowel was placed into the LC or SOC silo, maintained for 1-h, and reduced. Procedure times for placement, intestinal reduction, and silo removal were recorded. Tissue injury of the abdominal wall and intestine was assessed. Bacterial and fungal growth on silos was also compared.
Results
There were no gross injuries to abdominal wall or intestine in either group or difference in minor bleeding. Times for silo application, bowel reduction, and silo removal between groups were not statistically or clinically different, indicating similar ease of use. Microbiologic analysis revealed growth on all samples, but density was below the standard peritoneal inoculum of 10
5
CFU/g for both silos. There was no significant difference in bacterial or fungal growth between LC and SOC silos.
Conclusion
LC silos designed for manufacturing and clinical use in SSA demonstrated similar ease of use, absence of tissue injury, and acceptable microbiology profile, similar to SOC silos. The findings will allow our team to proceed with a pilot study in Uganda.
Newborns exposed to prenatal opioids often experience intense postnatal withdrawal after cessation of the opioid, called neonatal opioid withdrawal syndrome (NOWS), with limited pre- and postnatal ...therapeutic options available. In a prior study in pregnant mice we demonstrated that the peripherally selective opioid antagonist, 6β-naltrexol (6BN), is a promising drug candidate for preventive prenatal treatment of NOWS, and a therapeutic mechanism was proposed based on preferential delivery of 6BN to fetal brain with relative exclusion from maternal brain. Here, we have developed methadone (MTD) treated pregnant guinea pigs as a physiologically more suitable model, enabling detection of robust spontaneous neonatal withdrawal. Prenatal MTD significantly aggravates two classic maternal separation stress behaviors in newborn guinea pigs: calling (vocalizing) and searching (locomotion) - natural attachment behaviors thought to be controlled by the endogenous opioid system. In addition, prenatal MTD significantly increases the levels of plasma cortisol in newborns, showing that cessation of MTD at birth engages the hypothalamic-pituitary-adrenal (HPA) axis. We find that co-administration of 6BN with MTD prevents these withdrawal symptoms in newborn pups with extreme potency (ID50 ∼0.02 mg/kg), at doses unlikely to induce maternal or fetal withdrawal or to interfere with opioid antinociception based on many prior studies in rodents and non-human primates. Furthermore, we demonstrate a similarly high potency of 6BN in preventing opioid withdrawal in adult guinea pigs (ID50 = 0.01 mg/kg). This high potency appears to run counter to our pharmacokinetic studies showing slow 6BN transit of both the placenta and maternal blood brain barrier in guinea pigs, and calls into question the preferential delivery mechanism. Rather, it suggests a novel receptor mechanism to account for the selectively high potency of 6BN to suppress opioid dependence at all developmental stages, even in adults, as compared to its well-established low potency as a classical opioid antagonist. In conclusion, 6BN is an attractive compound for development of a preventive therapy for NOWS.
This study identified a clinically significant subset of patients with glioma with tumor outside of contrast enhancement present at autopsy and subsequently developed a method for detecting ...nonenhancing tumor using radio-pathomic mapping. We tested the hypothesis that autopsy-based radio-pathomic tumor probability maps would be able to noninvasively identify areas of infiltrative tumor beyond traditional imaging signatures.
A total of 159 tissue samples from 65 subjects were aligned to MRI acquired nearest to death for this retrospective study. Demographic and survival characteristics for patients with and without tumor beyond the contrast-enhancing margin were computed. An ensemble algorithm was used to predict pixelwise tumor presence from pathological annotations using segmented cellularity (Cell), extracellular fluid, and cytoplasm density as input (6 train/3 test subjects). A second level of ensemble algorithms was used to predict voxelwise Cell, extracellular fluid, and cytoplasm on the full data set (43 train/22 test subjects) using 5-by-5 voxel tiles from T1, T1 + C, fluid-attenuated inversion recovery, and apparent diffusion coefficient as input. The models were then combined to generate noninvasive whole brain maps of tumor probability.
Tumor outside of contrast was identified in 41.5% of patients, who showed worse survival outcomes (hazard ratio = 3.90, P < .001). Tumor probability maps reliably tracked nonenhancing tumor on a range of local and external unseen data, identifying tumor outside of contrast in 69% of presurgical cases that also showed reduced survival outcomes (hazard ratio = 1.67, P = .027).
This study developed a multistage model for mapping gliomas using autopsy tissue samples as ground truth, which was able to identify regions of tumor beyond traditional imaging signatures.
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