Lesterallen4498

We found the following four antigen-cytokine pairs had a higher weight in the discriminative classifier compared to the standard ESAT-6/CFP-10-induced interferon-

Rv2346/47c- and Rv3614/15c-induced interferon-gamma inducible protein-10; Rv2031c-induced granulocyte-macrophage colony-stimulating factor and ESAT-6/CFP-10-induced tumor necrosis factor-α. 5-FITC A combination of the 10 best antigen-cytokine pairs resulted in area under the curve of 0.92 ± 0.04.

We exploited the use of machine learning algorithms as a key tool to evaluate large immunological datasets. This identified several antigen-cytokine pairs with the potential to improve immunodiagnostic tests for tuberculosis in children.

We exploited the use of machine learning algorithms as a key tool to evaluate large immunological datasets. This identified several antigen-cytokine pairs with the potential to improve immunodiagnostic tests for tuberculosis in children.Human rotavirus (HRV) is the leading worldwide cause of acute diarrhea-related death in children under the age of five. RV infects the small intestine, an important site of colonization by the microbiota, and studies over the past decade have begun to reveal a complex set of interactions between RV and the gut microbiota. RV infection can temporarily alter the composition of the gut microbiota and probiotic administration alleviates some symptoms of infection in vivo, suggesting reciprocal effects between the virus and the gut microbiota. While development of effective RV vaccines has offered significant protection against RV-associated mortality, vaccine effectiveness in low-income countries has been limited, potentially due to regional differences in the gut microbiota. In this mini review, we briefly detail research findings to date related to HRV vaccine cohorts, studies of natural infection, explorations of RV-microbiota interactions in gnotobiotic pig models, and highlight various in vivo and in vitro models that could be used in future studies to better define how the microbiota may regulate RV infection and host antiviral immune responses.

(PA) is one of the most common Gram-negative bacteria causing hospital-acquired pulmonary infection, with high drug resistance and mortality. Therefore, it is urgent to introduce new non-antibiotic treatment strategies. Mesenchymal stem cells (MSCs), as important members of the stem cell family, were demonstrated to alleviate pathological damage in acute lung injury. However, the potential mechanism how MSC alleviate acute lung infection caused by PA remains unclear.

The purpose of this study was to investigate the effects of Adipose-derived mesenchymal stem cells (ASCs) on acute pulmonary infections and the possible mechanisms how ASCs reduce pulmonary inflammation induced by PA.

The therapeutic and mechanistic effects of ASCs on PA pulmonary infection were evaluated respectively in a murine model as well as in an

model stimulated by PA and co-cultured with ASCs.

1. ASCs treatment significantly reduced the bacterial load, inflammation of lung tissue and histopathological damage by PA. 2. link2 PA infec to pulmonary inflammatory damage in mouse; ASCs reduced the activation of NLRC4 inflammasome in macrophages induced by PA infection, thereby increasing the phagocytic ability of macrophages, and ultimately improving lung tissue damage in mouse; ASCs may inhibit NLRC4 inflammasome through the secretion of STC-1.Campylobacter jejuni (CJ) is the most prevalent zoonotic pathogen of chicken meat and related products, which may lead to gastroenteritis and autoimmune diseases in humans. Although controlling this bacterium is important, CJ strains resistance against traditional antibiotic therapy has been increased. Vegetable oils and fats are natural biomaterials explored since the Ancient times, due to their therapeutic properties. Nanotechnology has promoted the miniaturization of materials, improving bioavailability and efficacy, while reducing the toxicity of loaded active molecules. In this work, a screening of 28 vegetable oils was firstly performed, in order to select anti-CJ candidates by the disc diffusion test. Thus, the selected liquid lipids were used as active molecules in nanostructured lipid carriers (NLC) formulations. The three resultant systems were characterized in terms of particle size (~200 nm), polydispersity index (~0.15), and zeta potential (~-35mV), and its physicochemical stability was confirmed for a year, at 25°C. The structural properties of NLC were assessed by infrared (FTIR-ATR) and differential scanning calorimetry (DSC) analyses. The spherical nanoparticle morphology and narrow size distribution was observed by transmission electron microscopy (TEM) and field emission scanning electron (FE-SEM) analyses, respectively. Then, the in vitro antimicrobial activity test determined the minimum inhibitory concentration (MIC) of each formulation against CJ strains, in both free (1-3 mg/ml-1) and sessile (0.78 mg/ml-1) forms. Finally, the in vitro biocompatibility of NLC was demonstrated through cell viability using VERO cell line, in which F6 was found twice less cytotoxic than pure olibanum oil. Considering the abovementioned achieved, F6 formulation is able to be evaluated in the in vivo anti-CJ efficacy assays.Bovine digital dermatitis (BDD) is a common infectious disease of digital skin in cattle and an important cause of lameness worldwide, with limited treatment options. It is of increasing global concern for both animal welfare and food security, imposing a large economic burden on cattle farming industries each year. link3 A polytreponemal etiology has been consistently identified, with three key phylogroups implicated globally Treponema medium, Treponema phagedenis, and Treponema pedis. Pathogenic mechanisms which might enable targeted treatment/therapeutic development are poorly defined. This study used RNA sequencing to determine global differential mRNA expression in primary bovine foot skin fibroblasts following challenge with three representative BDD treponemes and a commensal treponeme, Treponema ruminis. A pro-inflammatory response was elicited by the BDD treponemes, mediated through IL-8/IL-17 signaling. Unexpectedly, the three BDD treponemes elicited distinct mechanisms of pathogenesis. T. phagedenis and Tal unique shared gene targets were identified, particularly RGS16, GRO1, MAFF, and ZC3H12A. The three key BDD Treponema phylogroups elicited both distinct and shared pathogenic mechanisms in bovine foot skin; upregulating inflammation whilst simultaneously suppressing adaptive immunity. The novel gene targets identified here should enable future vaccine/therapeutic approaches.Human Cytomegalovirus (HCMV) infection may result in severe outcomes in immunocompromised individuals such as AIDS patients, transplant recipients, and neonates. To date, no vaccines are available and there are only few drugs for anti-HCMV therapy. Adverse effects and the continuous emergence of drug-resistance strains require the identification of new drug candidates in the near future. Identification and characterization of such compounds and biological factors requires sensitive and reliable detection techniques of HCMV infection, gene expression and spread. In this work, we present and validate a novel concept for multi-reporter herpesviruses, identified through iterative testing of minimally invasive mutations. We integrated up to three fluorescence reporter genes into replication-competent HCMV strains, generating reporter HCMVs that allow the visualization of replication cycle stages of HCMV, namely the immediate early (IE), early (E), and late (L) phase. Fluorescent proteins with clearly distinguishable emission spectra were linked by 2A peptides to essential viral genes, allowing bicistronic expression of the viral and the fluorescent protein without major effects on viral fitness. By using this triple color reporter HCMV, we monitored gene expression dynamics of the IE, E, and L genes by measuring the fluorescent signal of the viral gene-associated fluorophores within infected cell populations and at high temporal resolution. We demonstrate distinct inhibitory profiles of foscarnet, fomivirsen, phosphonoacetic acid, ganciclovir, and letermovir reflecting their mode-of-action. In conclusion, our data argues that this experimental approach allows the identification and characterization of new drug candidates in a single step.Emerging and re-emerging RNA viruses pose significant public health, economic, and societal burdens. Hantaviruses (genus Orthohantavirus, family Hantaviridae, order Bunyavirales) are enveloped, negative-sense, single-stranded, tripartite RNA viruses that are emerging zoonotic pathogens harbored by small mammals such as rodents, bats, moles, and shrews. Orthohantavirus infections cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome in humans (HCPS). Active targeted surveillance has elucidated high-resolution phylogeographic relationships between patient- and rodent-derived orthohantavirus genome sequences and identified the infection source by temporally and spatially tracking viral genomes. Active surveillance of patients with HFRS entails 1) recovering whole-genome sequences of Hantaan virus (HTNV) using amplicon (multiplex PCR-based) next-generation sequencing, 2) tracing the putative infection site of a patient by administering an epidemiological questionnaire, and 3) collecting HTNV-positive rodents using targeted rodent trapping. Moreover, viral genome tracking has been recently performed to rapidly and precisely characterize an outbreak from the emerging virus. Here, we reviewed genomic epidemiological and active surveillance data for determining the emergence of zoonotic RNA viruses based on viral genomic sequences obtained from patients and natural reservoirs. This review highlights the recent studies on tracking viral genomes for identifying and characterizing emerging viral outbreaks worldwide. We believe that active surveillance is an effective method for identifying rodent-borne orthohantavirus infection sites, and this report provides insights into disease mitigation and preparedness for managing emerging viral outbreaks.

To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs).

This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 11 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions.