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PubMed2026

Evaluation of Oxford nanopore sequencing for antimicrobial resistance surveillance in Salmonella: comparison with phenotypic antimicrobial susceptibility in a large-scale study.

UNLABELLED: Salmonella is a major zoonotic foodborne pathogen, and antimicrobial resistance (AMR) in Salmonella presents a significant public health challenge. Compared with conventional antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS) provides a more rapid and comprehensive approach to AMR characterization, thereby informing antimicrobial selection and supporting public health surveillance. In this study, Oxford Nanopore Technology (ONT)-based WGS was performed on 1,490 Salmonella isolates collected through nationwide surveillance in Taiwan in 2025. Genotypic resistance inferred from WGS data was compared with phenotypic AST results to assess the performance of ONT-WGS. Overall, WGS-inferred resistance showed high concordance with phenotypic resistance for most antimicrobials. However, major genotype-phenotype discordance was observed, attributed to four categories: (i) breakpoint-dependent classification, (ii) reduced or absent phenotypic expression of resistance genes, (iii) minimum inhibitory concentration (MIC) modulation by ramAp, and (iv) absence of known AMR determinants. Notable discrepancies included tigecycline resistance without known genetic determinants, nalidixic acid resistance linked to ramAp-mediated MIC elevation, and a high prevalence of colistin resistance (35.7%) in S. Enteritidis, with most resistant isolates lacking identifiable AMR determinants. Additionally, a significant proportion of ESBL- and AmpC-producing isolates were classified as susceptible or intermediate to cefotaxime and ceftazidime under CLSI criteria, highlighting the potential for misclassification and treatment failure. These findings demonstrate that ONT-WGS enables accurate and comprehensive AMR characterization by directly identifying resistance determinants and avoiding potential misclassification associated with breakpoint-based AST interpretations. When interpreted appropriately, WGS can support better antimicrobial selection and serve as a valuable alternative to conventional susceptibility testing. IMPORTANCE: Accurate prediction of antimicrobial resistance is essential for appropriate therapy and effective surveillance of Salmonella. However, discordance between genotype-based predictions and phenotypic antimicrobial susceptibility testing (AST) can complicate clinical interpretation. In this nationwide study of 1,490 Salmonella isolates, we show that Oxford Nanopore Technology-based whole-genome sequencing (ONT-WGS) provides rapid and comprehensive detection of antimicrobial resistance determinants with high concordance to phenotypic AST. We further identify four major mechanisms underlying genotype-phenotype discordance, including breakpoint-dependent classification, reduced or absent phenotypic expression of resistance genes, minimum inhibitory concentration (MIC) modulation by ramAp, and the absence of known AMR determinants. These findings demonstrate how WGS can complement conventional AST, improve interpretation of challenging susceptibility results, and strengthen genomic surveillance of emerging antimicrobial-resistant Salmonella.

Microbial Sensitivity Tests↗
PubMed2004

The epidemiology of non-Hodgkin's lymphoma.

The incidence of non-Hodgkin's lymphoma (NHL) has doubled over the past two decades in the US and most other westernized countries. While improved cancer reporting, changes in lymphoma classification, and increases in AIDS-associated lymphomas have contributed to the startling escalation of disease incidence, these factors are estimated to account for only about 50% of the increase in observed incidence. The elucidation of etiologic factors and their mechanistic role in the pathogenesis of this malignancy are critical to advancements in disease prevention and treatment. Current evidence suggests that factors/conditions that precipitate either chronic antigenic stimulation or immunosuppression may provide a preferential milieu for development of NHL. High rates of lymphoma have been observed among individuals with autoimmune disease, organ transplants, and primary or acquired immunodeficiencies. Ultraviolet radiation, previously demonstrated to have an immunosuppressive effect, has also been suggested as a possible risk factor for NHL. Several pathogens have been linked to the risk of lymphoma, including Epstein-Barr virus, human immunodeficiency virus, human T-cell lymphotropic virus-1, Helicobacter pylori, hepatitis C, and simian virus 40. Whether these microbes are responsible for specific genetic mutations that initiate tumor growth, antigenic stimulation leading to B-cell proliferation, and increased potential of random cell replication errors, or immunosuppression, which thereby promotes tumor growth, has not been clearly delineated. Other exogenous factors which have been implicated in lymphomagenesis are chemicals and agricultural exposures, hair dyes, and blood transfusions. We must build on our current knowledge regarding the etiology of NHL in order that prevention, treatment, and ultimately, cure of this malignancy becomes a reality.

Acquired Immunodeficiency Syndrome↗
PubMed2005

[Cystatins, thyropins and inhibitors homologous to propeptides of cysteine proteases].

Protein inhibitors of proteolytic enzymes play an important role in regulating the activity of endogenous proteases and in host defense mechanisms against pathogens preventing the deleterious effects of exogenous proteases. In recent years a great interest in protein inhibitors of cysteine proteases has increased due to the extensive growth of knowledge about the contribution of cysteine proteases to pathological processes associated with many human diseases, as well as due to prospects for treatment of these disorders which may arise from the thorough understanding of their inhibitory mechanisms. This paper reviews the most important aspects of three families of cysteine protease inhibitors: cystatins, thyropins and inhibitors homologous to propeptides of cysteine proteases. Special attention is given to structural bases of the interactions between the inhibitors and their target enzymes. The paper presents a general characterization of the families according to the MEROPS classification of protease inhibitors, pointing out new members.

Animals↗
PubMed1991

Distribution and transferability of plasmids encoding trimethoprim resistance in urinary pathogens from Greece.

Of 505 strains of Enterobacteriaceae responsible for significant bacteriuria and isolated from hospital patients in two Greek cities in 1989, 151 strains (30%) were resistant to trimethoprim (MIC greater than or equal to 4 mg/L) and 220 (44%) were resistant to sulphamethoxazole (MIC greater than or equal to 64 mg/L); 127 (84%) of the trimethoprim-resistant strains exhibited high-level resistance (MIC greater than 1024 mg/L) and 121 (80%) were additionally resistant to four or more other antibiotics. Plasmids were detected in 141 (93%) of the trimethoprim-resistant strains. Trimethoprim resistance was encoded on self-transmissible plasmids in 79 (52%) of the resistant strains, and in a further seven strains (5%), plasmids coding for trimethoprim resistance could be mobilised by X+ factor. Co-transfer of various other antimicrobial resistances with trimethoprim resistance was observed, tetracycline resistance being the most common. The low degree of linkage observed between trimethoprim resistance and resistance to streptomycin and spectinomycin suggests that Tn7 is relatively uncommon in Greece. Classification of trimethoprim-resistance plasmids on the basis of their antimicrobial-resistance patterns and molecular mass revealed 39 different profiles. Overall, these findings differ from those from other European countries where the prevalence of transferable high-level trimethoprim resistance is low and where chromosomal Tn7-encoded trimethoprim resistance is common.

Bacteriuria↗
PubMed1981

Effect of prophylactic antibiotics in acute nonperforated appendicitis: a prospective, randomized, double-blind clinical study.

A prospective, randomized, double-blind clinical study was performed to determined the efficacy of short-term (24 hr) perioperative antibiotics in preventing septic complications after emergency appendectomy for nonperforated appendicitis. The patients were stratified into three clinical arms: Group I (placebo, n = 45), Group II (cefamandole, n = 46) and Group III (cefamandole plus carbenicillin, n = 45). The three groups of patients were similar in regard to age, sex, duration of operation and pathologic classification of the appendix. The overall incidence of infection in the study was 5.1%. The infection rates in Groups II (2.2%) and III (0%) were significantly lower than Group I (placebo) (13.3%), (p less than 0.05). No difference was observed between cefamandole alone and cefamandole plus carbenicillin. Average postoperative hospital days per patient for each group was: Group I - 3.8 days; Group II - 2.9 days; Group III - 3.1 days. Cost analysis of hospitalization including cost of prophylactic antibiotics revealed a $247.99 per patient saving for Group II versus Group I and $95.53 for Group III versus Group I. Systemic prophylactic antibiotics can successfully reduce septic complications after appendectomy for nonperforated appendicitis, and a single drug (cefamandole) directed at the facultative pathogens is as effective as double drug therapy, which includes specific anaerobic coverage.

Acute Disease↗
PubMed2002

Understanding chronic pelvic pain syndrome.

Patients with non-inflammatory chronic pelvic pain syndrome, the largest group of prostatitis patients according to the US National Institute of Diabetes and Digestive and Kidney Diseases classification, are characterized by the absence of objective findings. Nothing thus links the symptoms of this disease to the prostate or other male organs in particular. For this reason, observations on interstitial cystitis in women are of interest to understand the chronic pelvic pain syndrome. New information from studies on the inflammatory response in expressed prostatic secretion in patients with chronic pelvic pain syndrome and in bladder tissue from patients with interstitial cystitis indicates that complex systems on the cytokine gene expression level may be operating in these diseases. Research findings point to a common denominator at the level of molecular biology that might explain how the symptoms of chronic pelvic pain syndrome and interstitial cystitis can be precipitated by pathogens, inflammatory reactions and even neurological mechanisms. The initial clinical trial reports of drugs that modulate the inflammatory response in interstitial cystitis are met with great interest.

Arylsulfonates↗
PubMed2026

Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options and marked molecular heterogeneity. Despite available antifibrotic therapies, disease progression remains poorly predictable, highlighting the need for improved mechanistic understanding and therapeutic targeting. This review summarizes recent advances in multi-omics research to elucidate the molecular mechanisms underlying IPF and to identify potential biomarkers and pharmacological targets. Multi-omics studies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiome profiling, and single-cell sequencing, have revealed key pathogenic mechanisms in IPF. Genetic susceptibility factors such as MUC5B promoter variants and telomere-related genes contribute to disease risk. Epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNAs, plays a central role in fibrotic remodeling. Transcriptomic and proteomic analyses have identified dysregulated signaling pathways, including TGF-β, mTOR, cellular senescence, and extracellular matrix remodeling. Metabolomic alterations indicate disrupted lipid and amino acid metabolism. Importantly, integration of multi-omics datasets enables the identification of molecular endotypes, candidate biomarkers, and potential therapeutic targets. However, challenges including data integration, tissue heterogeneity, limited cohort size, and the need for functional validation remain important barriers to clinical translation. Continued development of multi-omics approaches may facilitate more accurate disease classification and support the development of personalized therapeutic strategies for IPF.

biomarkers↗
PubMed1997

Genetic diversity and vegetative compatibility among Trichoderma harzianum isolates.

Trichoderma harzianum is the collective name of a set of asexual fungal strains which exhibit heterogeneity in genome structure, DNA sequence and behavior. Contour-clamped homogeneous field (CHEF) electrophoresis of the chromosomes of ten isolates of T. harzianum revealed six clearly distinct electrophoretic karyotypes. Of the ten isolates analyzed, four (GH12, G109, Y and YF) could be classified in a single group with identical karyotypes, while the strains T35 and 315 formed a second group. The genome size characteristic of the different isolates fell into a broad range varying from 29.6 to 56.1 Mb. Gene assignments to the resolved chromosomes showed that all genes analyzed were localized on equivalent chromosomes in the isolates belonging to the same group. Analysis of randomly amplified polymorphic DNAs from the ten isolates confirmed the classification into groups and allowed us to distinguish between isolates T35 and 315, as well as between isolates GH12, G109, Y and YF. Direct confrontation assays using isolates of the same group showed compatible interactions, whereas the same experiment carried out with isolates of different groups showed an incompatible interaction characterized by an area of cell damage. Microscopic observation of the compatible interactions showed hyphal fusions between the isolates, similar to those described for vegetative compatible groups in other fungi. The molecular karyotypes correlated well with the compatibility of the isolates. In addition, we have evaluated both electrophoretic karyotype and randomly amplified polymorphic DNAs analysis as criteria for grouping isolates within the genus according to their capacity for biocontrol of plant pathogens.

Antibiosis↗
PubMed2025

Optical genome mapping improves clinical interpretation of constitutional copy-number gains and reduces their VUS burden.

PURPOSE: Genomic structure of copy-number gains is critical for their clinical interpretation but cannot be determined by chromosomal microarray (CMA) analysis, which does not provide information about chromosomal location and orientation of multiplied regions. We thus hypothesized that in CMA testing gains have higher probability than losses to be classified as variants of uncertain significance (VUS) and that structural information from optical genome mapping (OGM) may improve their interpretation. METHODS: Using a χ2 test, we assessed the association between classification of copy-number variants as VUS and their type (gains vs losses) in a cohort of 4073 CMA cases. Thirty-three VUS gains involving disease-associated genes were characterized by OGM to evaluate if OGM data enable their more conclusive clinical interpretation. RESULTS: The proportion of variants reported as VUS compared with likely pathogenic/pathogenic was significantly higher for gains than losses, confirming their increased VUS burden. OGM successfully determined genomic structure for all 33 copy-number gains, showing that 26 of 33 were tandem duplications and 7 of 33 were complex rearrangements. Structural information facilitated clinical interpretation in majority of the cases; it supported benign nature for 27 of 33 gains and was inconclusive or supported pathogenic role for 6 of 33. An estimated 20% of reported VUS gains would not have been reportable if we had OGM data. CONCLUSION: We illustrate a specific advantage of OGM compared with CMA: in addition to detecting both copy-number variants and balanced rearrangements, OGM improves clinical interpretation of copy-number gains by providing structural information and is thus expected to significantly decrease their VUS burden.

Humans↗
PubMed1997

Cartilage markers in synovial fluid in symptomatic knee osteoarthritis.

OBJECTIVE: To investigate if the relative content of aggrecan and cartilage oligomeric matrix protein (COMP) in synovial fluid lavage samples differs between individuals with knee pain with or without evidence of radiological knee osteoarthritis (joint space narrowing). METHODS: In a community based cohort of 204 individuals aged 35-54 years with chronic (> 3 months duration) knee pain, a subgroup of 45 subjects with radiographic osteoarthritis, grade I according to the Ahlbäck classification, was randomly chosen; 45 individuals, age and sex matched from the same cohort with chronic knee pain but with normal radiographs, served as controls, Knee joint fluid was obtained by a standardised lavage procedure. The concentrations of aggrecan core protein epitopes and a cartilage matrix protein (COMP) were determined by immunoassays and the aggrecan/COMP concentration ratio was calculated. RESULTS: The aggrecan/COMP ratio was higher (P < 0.001) in the group with radiographic osteoarthritis than in the control group. CONCLUSIONS: The higher aggrecan/COMP ratios in osteoarthritis could reflect increased cartilage matrix turnover in osteoarthritis with predominant release of aggrecan fragments. Synovial fluid analysis of cartilage markers holds promise as a useful means of monitoring changes in the cartilage turnover in studies of pathogenic mechanisms in osteoarthritis.

Adult↗
PubMedDate not supplied

Diminished interferon-gamma production in gastric mucosa T lymphocytes after H. pylori eradication in duodenal ulcer patients.

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infects an estimated 50% of the world population; however, only a small proportion of individuals develop clinical symptoms of gastritis, peptic ulceration or gastric cancer. The variations in disease presentation may be due to differences in bacterial virulence and/or immune response to the pathogen. In a previous study we reported an increased expression of the IL-2 receptor in duodenal ulcer (DU) patients. The present study examines the expression of IL-2 receptor and intracellular lymphokine production in gastric mucosa infiltrating T lymphocytes in DU patients before and after H. pylori eradication. METHODOLOGY: T lymphocytes were isolated from gastric mucosa biopsies by using mechanical and enzymatic tissue desegregation. Ficoll-purified lymphocytes were incubated with monoclonal antibodies and analyzed by using 4-color flow cytometry analysis for the IL-2 receptor (CD25) and intracellular interferon-gamma (IFN-gamma) and IL-4 expression. Lymphocytes from 24 H. pylori-infected patients with severe gastric mucosa infiltration (G2 and G3 histological type in Sydney classification) were analyzed. RESULTS: We demonstrated a significant decrease in IL-2 receptor expression on gastric mucosa T cells 3 and 12 months after eradication of H. pylori. We also demonstrated a diminished IFN-gamma production 3 and 12 months after H. pylori eradication. CONCLUSIONS: Our results suggest that cellular immune activation in gastric mucosa is reversibly dependent on the presence of H. pylori.

Amoxicillin↗
PubMed2000

Treatment of glomerular diseases: ANCA-negative RPGN.

Classification of rapidly progressive glomerulonephritis (RPGN) has evolved over the last decade into a variety of categories, some are which are more amenable to treatment than others. The advent of testing for antineutrophilic cytoplasmic antibody (ANCA) has further defined RPGN and aided in the diagnosis and treatment of these diseases. Although RPGN has traditionally carried a poor prognosis, this has been markedly improved by early diagnosis and intervention with aggressive therapy. The current chapter provides an oversight of ANCA-negative RPGN, and delineates an approach to diagnosis and therapy of various subtypes of this entity. Although current therapeutic options still encompass broad-spectrum immunosuppressive modalities, the future holds great hope for specific directed interventions at discrete points in the pathogenic progress. This offers the possibility of abrogation of the immune response leading to RPGN with less toxic general side effects then with treatments currently used. The next millennium will be marked by improved prognosis for ANCA-negative glomerulonephritis compared with that observed with this devastating disease in past decades.

Algorithms↗
PubMedDate not supplied

[Nocardia isolated from the respiratory tract].

Twelve strains of Nocardia isolated from sputa, bronchial washings and pleural fluids, were studied. The classification was based on the following characteristics: a) acid-fastness; 2) ability to disolve crystals of tyrosine and xantine; 3) hydrolysis of casein; 4) growth in dilute gelatin medium (0.4%) and 5) galactose acidification. Direct cultivation of the clinical material in Czapek liquid culture medium without carbon source and containing a paraffin rod (pariffin-bait technic), as well as the routin T.B. sputum digestion and concentration with NaOH solution followed by its cultivation in Loewenstein's medium, were employed for the isolation of Nocardia. The sensitivity of the strains to tuberculostatic drugs was investigated using the Canetti's method, as was the ability to growth in Sabouraud and lactrimel culture media supplemented with 100 mug/ml of rifamycin. Finally the pathogenicity test was carried out by intraperitoneal and intramuscular inoculation in guinea-pigs. All the strains were classified as Nocardia asteroides. Seven starins were isolated from patiens with lung conditions of no nocardial etiology. The diagnosis of nocardiosis of the lung was demonstrated in the remaining five patiens by microscopical observation of Nocardia in clinical specimens, by the repeated cultures obtained from these materials and, finally, by the fact that an improvement of the clinical symptomatology was obtained by sulfa administration.

Anti-Bacterial Agents↗
PubMed2002

Diffuse large B-cell lymphoma: one or more entities? Present controversies and possible tools for its subclassification.

Diffuse large B-cell lymphoma (DLBCL) is the commonest type of lymphoid tumour world-wide. This category was included both in the REAL and WHO Classification aiming to lump together all malignant lymphomas characterized by the large size of the neoplastic cells, B-cell derivation, aggressive clinical presentation, and the need for highly effective chemotherapy regimens. These tumours are detected as primary or secondary forms both at the nodal and extranodal levels, in immunocompetent hosts as well as in patients with different types of immunosuppression. They display a significant variability in terms of cell morphology and clinical findings, which justifies the identification of variants and subtypes. Among the latter, the primary mediastinal one does actually correspond to a distinct clinicopathological entity. Immunophenotypic, tissue microarray and molecular studies underline the extreme heterogeneity of DLBCLs and suggest a subclassification of the tumour, based on the identification of different pathogenic pathways, which might have much greater relevance than pure morphology for precise prognostic previsions and adoption of ad hoc therapies. The more recent acquisitions on the pathobiology of DLBCLs are reviewed in the light of the authors' experience, aiming to contribute to the existing debate on the topic.

Animals↗
PubMed1994

Histological and immunohistological classification of canine glomerular disease.

A histological and immunohistological study of the kidneys of 115 dogs, with and without clinical signs of spontaneous renal disease, was performed to prove the applicability of the WHO criteria for the classification of human glomerulopathy. Aside from the morphological investigation of paraffin and resin semithin sections, deposits of immunoglobulins, the complement component C3, and fibrinogen were observed immunoenzymatically in paraffin-embedded tissue specimens. From this, eight different types of glomerular lesions with various frequencies were identified: minor glomerular abnormalities (28 cases), focal and segmental hyalinosis and sclerosis (12 cases), focal glomerulonephritis (GN; 18 cases), diffuse membranous GN (nine cases), diffuse mesangial proliferative GN (2 cases), diffuse endocapillary proliferative GN (five cases), diffuse mesangiocapillary GN (25 cases), diffuse sclerosing GN (11 cases) und unclassified GN (two cases). In one case, renal dysplasia was diagnosed and two dogs did not present glomerular alterations. The results are discussed with regard to human glomerular diseases and pathogenic mechanisms.

Animals↗
PubMed1999

Initial report of primary sinusitis caused by an atypical pathogen (Mycobacterium chelonae) in an immunocompetent adult.

Primary sinonasal infections caused by atypical mycobacteria are rare. In fact, only four examples of a primary nontuberculous mycobacterial etiology of paranasal sinusitis have been cited in the literature. The patients in all these cases were infected with the human immunodeficiency virus and, by definition, they all had acquired immunodeficiency syndrome. We present a report of an immunocompetent adult with a history of chronic sinusitis who consistently and repeatedly manifested a fast-growing, nonpigmented, atypical mycobacterium of the Runyon group IV category: Mycobacterium chelonae. The patient was successfully treated over a 3-year period with a combination of antimicrobial agents, multiple limited endoscopic sinus surgeries, and eventually a total globe-sparing maxillectomy. At this time, the patient is disease-free and has received no further treatment. This case represents the first report of an immunocompetent adult host with a primary atypical mycobacterial infection of the paranasal sinuses. It also demonstrates the multimodal nature of the treatment of atypical mycobacterial infections. We also discuss the Byzantine classification scheme relative to atypical mycobacteria, the disease process in the immunocompromised host, and the various treatment options.

Adult↗
PubMed1991

Identification of two new antigenic subgroups within the genus Mobiluncus.

Classifications of 48 atypical clinical isolates of Mobiluncus spp. were determined on the basis of biochemical reactions, morphology, antigenic profiles, and DNA hybridization studies. Two new subgroups with unique antigenic profiles are described. Like typical Mobiluncus species, the antigenic variant of M. mulieris is associated with bacterial vaginosis. The atypical isolates of M. curtisii were frequently recovered from women with normal vaginal flora and were also recovered from sterile body sites. These isolates may be incorrectly identified if current biochemical and morphological criteria are used for identification. Gram stain morphology, however, correctly identifies these isolates to the species level. The characterization of these atypical isolates has important implications for future investigations in which serological methods are used for diagnosis, epidemiology, and determination of pathogenicity of Mobiluncus spp.

Antigenic Variation↗
PubMed1989

Disorders of arousal and the relaxation response: speculations on the nature and treatment of stress-related diseases.

The classification of diseases represents an important, yet often enigmatic, process. This is especially true in the case of stress-related diseases. Until the 1980s, stress-related diseases were categorized on the basis of the target organ system affected. A merger of 20 years of clinical data with research and theoretical formulations from the neurosciences gave us the opportunity to reformulate, or at least add a fresh perspective to, the understanding of the nature and treatment of stress-related diseases. Based upon over two decades of research and clinical trials, one such reformulation is presented here. It is contended that many psychiatric and somatic stress-related diseases are but manifest variations on a theme of limbicogenic neurological hypersensitivity and resultant pathogenic arousal. The resultant stress-related diseases are, therefore, viewed as "disorders of arousal." From the reformulation offered herein emerges a neurologically-based rationale for the clinical use of the "relaxation response" in the treatment of stress-related diseases.

Arousal↗