Search Results (145)

White-tailed deer (Odocoileus virginianus) in the wild and on cervid farms have drawn the attention of state wildlife agencies and animal health agencies as Chronic Wasting Disease (CWD) has spread across North America. Deer farm regulations have been implemented to reduce direct contact between wild and farmed cervids; however, evidence suggests that indirect contact to infectious prions passed through the alimentary tracts of scavengers may be an important transmission pathway. The objective of this study was to characterize mammalian scavenger and wild deer activities associated with deer farms and link these activities with site-specific spatial covariates utilizing a network of camera traps, mounted to farm perimeter fences. We monitored each of 14 farms in Minnesota, Wisconsin, and Pennsylvania for two weeks during the summer, with a subset of farms also monitored in the winter and fall. Across all sites and seasons, we captured 749 observations of wildlife. In total, nine species were captured, with wild white-tailed deer accounting for over three quarters of observations. Despite the large number of wild deer observed, we found that interactions between wild and farmed deer at the fence line were infrequent (six direct contacts observed). In contrast, mammalian scavengers were frequently observed inside and outside of the fence. Supplementary cameras placed on deer feeders revealed higher observation rates of scavengers than those placed along fence lines, highlighting the potential for transmission of CWD through indirect contact via scavenger excreta. To evaluate associations between the number of observations of focal species with land-cover characteristics, two mixed-effects regression models were fitted, one model for scavengers and one for wild deer. Contrary to our hypothesis, landscape context did not have a strong impact on wildlife visitation. This suggests that farm location is less important than management practices, highlighting the need for future research into how farming practices impact rates of wildlife visitation onto cervid farms. Full article

Poor health and increased susceptibility to infectious diseases are among the main sources of economic losses in the pig industry worldwide, and they also serve as indicators of compromised animal welfare. However, there is limited information on long-lasting biomarkers of poor health and common infections experienced by piglets early in life. Hair cortisol, dehydroepiandrosterone sulfate (DHEA(S)), and their ratio have been proposed as components of the mammalian stress response due to the activation of the hypothalamus–pituitary–adrenal axis and were investigated in this study using 30 batches of pigs from 16 farms. The research hypothesis was that batches of piglets experiencing clinical syndromes (as indicated by enteric, neurological, cutaneous, and locomotor scores) during suckling would exhibit a different pattern of resilience and allostatic load later in life compared to healthy ones. Hair from 25 gilts per batch were collected at either 3.5 or 9 months of age, and hormone extraction was subsequently performed. The farm of origin and the age of the animals significantly influenced hormone concentrations. Moreover, batches affected by enteric disease showed lower DHEA(S) levels (p < 0.0001; 15.89 vs. 23.51 pg/mg) and higher cortisol/DHEA(S) ratio (p < 0.0001; 82.83 vs. 55.02) than healthy batches. Similar results were observed in batches with a neurological syndrome (DHEA(S): p < 0.0001; 12.91 vs. 19.43; cortisol/DHEA(S) ratio: p < 0.0001; 97.15 vs. 70.26 pg/mg). These results suggest that pig hair biomarkers carry an intrinsic and temporally stable signal related to early life health status. Full article

Coronary artery disease (CAD) is one of the leading causes of death worldwide, significantly contributing to mortality in both developed and developing nations. CAD arises from a combination of risk factors, including atherosclerosis, dyslipidemia, hypertension, diabetes, and smoking. In recent years, growing evidence has suggested a potential link between infectious agents and cardiovascular diseases. Among these, Helicobacter pylori (H. pylori) infection has been hypothesized for over a decade to play a role in the pathogenesis of CAD. This hypothesis is based on the bacterium’s ability to trigger host inflammatory or autoimmune responses, potentially contributing to the progression of atherosclerotic plaques and coronary events. The association between H. pylori infection and CAD is of considerable interest as it opens new avenues for prevention and management strategies in cardiovascular health. Understanding this relationship could lead to innovative approaches to reducing the burden of CAD, particularly in populations with a high prevalence of H. pylori. In this review, we aim to provide a comprehensive overview of the most recent evidence on the involvement of H. pylori in the development and prognosis of CAD. By analyzing and synthesizing current findings, we seek to shed light on unresolved questions and clarify the ambiguous aspects of this potential connection. Our goal is to contribute to a deeper understanding of how H. pylori, may influence cardiovascular disease and to inspire further research in this critical area. Full article

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, as approximately 55 million people worldwide are affected, with a significant tendency to increase. It reveals three main pathological features: amyloid plaques, neurofibrillary tangles, and neuroinflammation, responsible for the neurodegenerative changes that slowly lead to deterioration of personality and cognitive control. Over a century after the first case report, effective treatments remain elusive, likely due to an incomplete understanding of the precise mechanisms driving its pathogenesis. Recent studies provide growing evidence of an infectious aetiology for AD, a hypothesis reinforced by findings that amyloid beta functions as an antimicrobial peptide. Among the microorganisms already associated with AD, Porphyromonas gingivalis (Pg), the keystone pathogen of periodontitis (PeD), has received particular attention as a possible aetiological agent for AD development. Herein, we review the epidemiological and genetic evidence linking PeD and Pg to AD, highlighting the identification of periodontal bacteria in post mortem analysis of AD patients’ brains and identifying putative mechanistic links relevant to the biological plausibility of the association. With the focus on AD research shifting from cure to prevention, the proposed mechanisms linking PeD to AD open the door for unravelling new prophylactic approaches able to reduce the global burden of AD. As hypothesised in this review, these could include a bionanotechnological approach involving the development of an oral nanoparticulate vaccine based on Pg-specific antigens. Such a vaccine could prevent Pg antigens from progressing to the brain and triggering AD pathology, representing a promising step toward innovative and effective AD prevention. Full article

Rift Valley fever phlebovirus (RVFV) is a zoonotic mosquito-borne pathogen endemic to sub-Saharan Africa and the Arabian Peninsula which causes Rift Valley fever in ruminant livestock and humans. Co-infection with divergent viral strains can produce reassortment among the L, S, and M segments of the RVFV genome. Reassortment events can produce novel genotypes with altered virulence, transmission dynamics, and/or mosquito host range. This can have severe implications in areas where RVFV is endemic and convolutes our ability to anticipate transmission and circulation in novel geographic regions. Previously, we evaluated the frequency of RVFV reassortment in a susceptible ruminant host and observed low rates of reassortment (0–1.7%). Here, we tested the hypothesis that reassortment occurs predominantly in the mosquito using a highly permissive vector, Culex tarsalis. Cells derived from Cx. tarsalis or adult mosquitoes were co-infected with either two virulent (Kenya-128B-15 and SA01-1322) or a virulent and attenuated (Kenya-128B-15 and MP-12) strain of RVFV. Our results showed approximately 2% of virus genotypes isolated from co-infected Cx. tarsalis-derived cells were reassortant. Co-infected mosquitoes infected via infectious bloodmeal resulted in a higher percentage of reassortant virus (2–60%) isolated from midgut and salivary tissues at 14 days post-infection. The percentage of reassortant genotypes isolated from the midguts of mosquitoes co-infected with Kenya-128B-15 and SA01-1322 was similar to that of mosquitoes co-infected with Kenya-128B-15 and MP-12- strains (60 vs. 47%). However, only 2% of virus isolated from the salivary glands of Kenya-128B-15 and SA01-1322 co-infected mosquitoes represented reassortant genotypes. This was contrasted by 54% reassortment in the salivary glands of mosquitoes co-infected with Kenya-128B-15 and MP-12 strains. Furthermore, we observed preferential inclusion of genomic segments from the three parental strains among the reassorted viruses. Replication curves of select reassorted genotypes were significantly higher in Vero cells but not in Culex—derived cells. These data imply that mosquitoes play a crucial role in the reassortment of RVFV and potentially contribute to driving evolution of the virus. Full article

Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder, characterized by progressive demyelination and neuronal cell loss in the central nervous system. Many possible causes of MS have been proposed, including genetic factors, environmental triggers, and infectious agents. Recently, Clostridium perfringens epsilon toxin (ETX) has been incriminated in MS, based initially on the isolation of the bacteria from a MS patient, combined with an immunoreactivity to ETX. To investigate a putative causative role of ETX in MS, we analyzed the pattern of antibodies reacting to the toxin using a sensitive qualitative assay. This prospective observational study included one hundred patients with relapsing remitting multiple sclerosis (RRMS), all untreated, and ninety matched healthy controls. By assessing the isotypic pattern and serum concentration of ETX-reacting antibodies, our study shows a predominant IgM response over IgG and IgA antibody responses both in MS patients and controls, and significantly higher levels of IgM reacting to ETX in MS patients compared to the control group. A longitudinal follow-up of ETX-specific antibody response in a subgroup of MS patients did not show any correlation with disease evolution. Overall, these unexpected findings are not compatible with a specific recognition of ETX by serum antibodies from MS patients. They rather argue for a cross immunological reactivity with an antigen, possibly an autoantigen, mimicking ETX. Thus, our data argue against the hypothesis of a causal relationship between C. perfringens ETX and MS. Full article

Understanding people’s face-to-face interactions is crucial for effective infectious disease management. Traditional contact tracing, often relying on interviews or smartphone applications, faces limitations such as incomplete recall, low adoption rates, and privacy concerns. This study proposes utilizing anonymized Call Detail Records (CDRs) as a substitute for in-person meetings. We assume that when two individuals engage in a phone call connected to the same cell tower, they are likely to meet shortly thereafter. Testing this assumption, we evaluated two hypotheses. The first hypothesis—that such co-located interactions occur in a workplace setting—achieved 83% agreement, which is considered a strong indication of reliability. The second hypothesis—that calls made during these co-location events are shorter than usual—achieved 86% agreement, suggesting an almost perfect reliability level. These results demonstrate that CDR-based co-location events can serve as a reliable substitute for in-person interactions and thus hold significant potential for enhancing contact tracing and supporting public health efforts. Full article

Objectives: As one of the important interventions to alleviate anthracycline-related cardiotoxicity (ARC), the safety assessment of dexrazoxane in clinical practice is particularly important. This study aims to evaluate the actual efficacy and potential adverse effects of dexrazoxane in clinical practice by analyzing the reports of adverse events (AEs) related to the combination with dexrazoxane and anthracyclines. Methods: We utilized four disproportionality analysis methods to analyze AE reports of the combination with dexrazoxane and anthracyclines in the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the third quarter of 2014 to the first quarter of 2024. Results: Under the three backgrounds, a large number of preferred terms (PTs) such as cardiac failure disappeared in the combined group, and the PTs with significant signal values were mainly concentrated in infections and infestations. For patients under 18, some PTs associated with infections and infestations disappeared after the combination of the two drugs. Conclusions: Dexrazoxane can effectively alleviate ARC, but it may also increase the risk of infection. For infections and infestations, children under 18 years old are more likely to benefit from the combination therapy. More attention should be paid to infectious AEs in the clinical use of dexrazoxane, though disproportionality analysis is a hypothesis-generating approach. Full article

Background: Cilomilast, a phosphodiesterase-4 (PDE4) selective inhibitor, has anti-inflammatory effects in vitro and in vivo and reduces COPD exacerbations. We tested the hypothesis that cilomilast inhibits virus-induced airway epithelial intercellular adhesion molecule-1 (ICAM-1) expression and inflammatory cytokine/chemoattractants, IL-6, CXCL8, and CCL5 production in vitro. Methods: BEAS-2B bronchial epithelial cells were incubated with 0.5–2 MOI (multiplicity of infection–infectious units/cell) of rhinovirus 16 (RV16). Then, 0.1–10 μM cilomilast or 10 nM dexamethasone, as inhibition control, were added pre- or post-1 h RV16 infection. Supernatant and cells were sampled at 8, 24, 48, and 72 h after infection. Cell surface ICAM-1 expression was detected by immunogold labelling and visualised by high-resolution scanning electron microscopy (HR-SEM), while IL-6, CXCL8, and CCL5 protein release and mRNA expression were measured using an ELISA and RT-PCR. Results: Cilomilast significantly decreased RV16-induced ICAM-1 expression to approximately 45% (p < 0.01). CXCL8 protein/mRNA production was reduced by about 41% (p < 0.05), whereas IL-6 protein/mRNA production was increased to between 41–81% (p < 0.001). There was a trend to reduction by cilomilast of RV16-induced CCL5. Conclusions: Cilomilast has differential effects on RV16-induced ICAM-1 and interleukins, inhibiting virus-induced ICAM-1 expression and CXCL8 while increasing IL-6 production. These in vitro effects may help to explain the beneficial actions of this PDE4 inhibitor in vivo. Full article

Multiple lines of research have led to the hypothesis that antimicrobial peptides (AMPs) are an important component of the innate immune response, playing a vital role in the defense against a wide range of infectious diseases. In this review, we explore the occurrence and availability of antimicrobial proteins and peptides across various species, highlighting their natural abundance and evolutionary significance. The design of AMPs has been driven by the identification of key structural and functional features, which are essential for optimizing their antimicrobial activity and reducing toxicity to host cells. We discuss various approaches, including rational design, high-throughput screening, and computational modeling, that have been employed to develop novel AMPs with enhanced efficacy. A particular focus is given to the identification and characterization of peptide fragments derived from naturally occurring host defense proteins, which offer a promising avenue for the discovery of new AMPs. The incorporation of artificial intelligence (AI) and machine learning (ML) tools into AMP research has further accelerated the identification, optimization, and application of these peptides. This review also discusses the current status and therapeutic potential of AMPs, emphasizing their role in addressing the growing issue of antibiotic resistance. The conclusion highlights the importance of continued research and innovation in AMP development to fully harness their potential as next-generation antimicrobial agents. Full article

Identification of early signatures of immune rejection represents a key challenge in the clinical management of kidney transplant. To address such an issue, we enrolled 53 kidney transplant recipients without signs of graft rejection, no infectious episodes and no change in the immunosuppressive regimen in the last 6 months. An extensive immune profile revealed increased activation of the T cells, a decreased amount and growth ability of the Treg and a higher level of the T_R3-56 regulatory T cell subset, described by us as involved in the preferential control of cytotoxic T lymphocytes. In renal transplant recipients, the high level of the T_R3-56 cells associates with a reduction in both the amount and the growth ability of the Treg. Moreover, when the transplanted subjects were categorised according to their stable or unstable disease status, as defined by changes in serum creatinine ≥0.2 mg/dL in two consecutive detections, a higher T_R3-56 level and defective Treg growth ability were observed to characterise patients with unstable graft control. Further studies are required to substantiate the hypothesis that immune profiling, including T_R3-56 evaluation, might represent a valuable diagnostic tool to identify patients at risk of developing significant anti-donor allo-immune responses. Full article

Mechanisms resulting from the physiological immaturity of the digestive system in children delivered before 32 weeks of gestation and, in particular, different interactions between the microbiome and the body have not been fully elucidated yet. Next-generation sequencing methods demonstrated the presence of bacterial DNA in the placenta and amniotic fluid, which may reflect bacterial populations that initiate intestinal colonization in utero. Numerous studies confirmed the hypothesis stating that intestinal bacteria played an important role in the pathogenesis of necrotizing enterocolitis (NEC) early- and late-onset neonatal sepsis (EONS and LONS). The model and scale of disorders within the intestinal microbiome are the subject of active research in premature infants. Neonatal meconium was primarily used as an indicator defining the environment in utero, as it is formed before birth. Metagenomic results and previous data from microbiological bacterial cultures showed a correlation between the time from birth to sample collection and the detection of bacteria in the neonatal meconium. Therefore, it may be determined that the colonization of the newborn’s intestines is influenced by numerous factors, which may be divided into prenatal, perinatal, and postnatal, with particular emphasis put on the mode of delivery and contact with the parent immediately after birth. Background: The aim of this review was to collect available data on the intrauterine shaping of the fetal microbiota. Methods: On 13 March 2024, the available literature in the PubMed National Library of Medicine search engine was reviewed using the following selected keywords: “placental microbiome”, “intestinal bacteria in newborns and premature infants”, and “intrauterine microbiota”. Results: After reviewing the available articles and abstracts and an in-depth analysis of their content, over 100 articles were selected for detailed elaboration. We focused on the origin of microorganisms shaping the microbiota of newborns. We also described the types of bacteria that made up the intrauterine microbiota and the intestinal microbiota of newborns. Conclusions: The data presented in the review on the microbiome of both term newborns and those with a body weight below 1200 g indicate a possible intrauterine colonization of the fetus depending on the duration of pregnancy. The colonization occurs both via the vaginal and intestinal route (hematogenous route). However, there are differences in the demonstrated representatives of various types of bacteria, phyla Firmicutes and Actinobacteria in particular, taking account of the distribution in their abundance in the individual groups of pregnancy duration. Simultaneously, the distribution of the phyla Actinobacteria and Proteobacteria is consistent. Considering the duration of pregnancy, it may also be concluded that the bacterial flora of vaginal origin dominates in preterm newborns, while the flora of intestinal origin dominates in term newborns. This might explain the role of bacterial and infectious factors in inducing premature birth with the rupture of fetal membranes. Full article

Brucellosis, as an infectious disease that affects both humans and livestock, poses a serious threat to human health and has a severe impact on economic development. Essentially, brucellosis transmission is a kind of study in biological systems, and the epistemic uncertainty existing in the data of confirmed brucellosis cases in China is realized as significant uncertainty that needs to be addressed. Therefore, this paper proposes an uncertain time series model to explore the confirmed brucellosis cases in China. Then, some methods based on uncertain statistics and symmetry of the biological system are applied, including order estimation, parameter estimation, residual analysis, uncertain hypothesis test, and forecast. The proposed model is practically applied to the data of confirmed brucellosis cases in China from January 2017 to December 2020, and the results show that the uncertain model fits the observed data better than the probabilistic model due to the frequency instability inherent in the data of confirmed brucellosis cases. Based on the proposed model and statistical method, this paper develops an approach to rapidly forecast the number of confirmed brucellosis cases in small sample scenarios, which can contribute to epidemic control in real application. Full article

Our survey in the Mediterranean region of Türkiye revealed high prevalence of Babesia aktasi in goats, while no molecular evidence of the parasite was found in sheep grazing in the same pasture. We hypothesized that the parasite may not be infectious to sheep. To test this hypothesis, the present study was designed to evaluate the susceptibility of Akkaraman sheep breed to B. aktasi infection. Fifteen mL of fresh blood infected with B. aktasi was injected into immune-suppressed lambs (n = 5). The recipient lambs were monitored daily for clinical signs of babesiosis over 30 days, and blood was collected for microscopic and molecular diagnostic evaluation. The lambs did not display clinical and parasitological signs of babesiosis. Two out of five recipient lambs were nested PCR-negative for B. aktasi over 30 days post infection. Out of the remaining three lambs, two were PCR positive on the first day, and one recipient was positive until the fourth day post infection. DNA sequencing confirmed that the PCR positivity in the recipient lambs originated from the inoculum. These findings revealed that immune-suppressed sheep do not appear to be susceptible to infection with B. aktasi that is lethal to immune-suppressed indigenous goats. Full article

Computer tomography (CT)-guided percutaneous core biopsies are currently the gold standard in diagnostic procedures for patients with bone lesions of unknown kind. CT-guided biopsies can lead to misdiagnosis or repetition of biopsies in case of small or heterogeneous lesions. We hypothesize that molecular image guidance could be used to optimize the biopsy strategy, by supporting the detection of heterogeneous lesions or lesions without radiographic substrate. To evaluate this hypothesis, we investigated if and how the addition of 2-deoxy-2-¹⁸F-fluoro-D-glucose-positron emission tomography (¹⁸F-FDG-PET)/CT could augment routine CT-guided bone biopsies. To this end, 106 patients who underwent a CT-guided bone biopsy between April 2019 and April 2020, obtained from either a vertebral or peripheral bone, were included. Patients were divided into 2 groups: 36 patients received an ¹⁸F-FDG-PET/CT scan prior to their CT-guided bone biopsy (PET group), while 70 patients only had a morphological CT scan (CT group). Histopathology was used to categorize biopsies into five subgroups (inconclusive, benign, malignant or infectious disease, or normal tissue). In the PET group, the number of conclusive biopsies was significantly higher compared to the CT group (N = 33/36 (92%) versus N = 53/70 (76%); p < 0.05). Furthermore, the number of first-try biopsies was lower in the PET group compared to the CT group (1.9 vs. 2.54, p = 0.051). In conclusion, ¹⁸F-FDG-PET/CT imaging significantly increased the success rate of first-try CT-guided bone biopsies by showing less inconclusive biopsies and misdiagnosis. Full article