Role of the Gastrointestinal Tract Microbiome in the Pathophysiology of Diabetes Mellitus.

The incidence of diabetes mellitus is rapidly increasing throughout the world. Although the exact cause of the disease is not fully clear, perhaps, genetics, ethnic origin, obesity, age, and lifestyle are considered as few of many contributory factors for the disease pathogenesis. In recent years, the disease progression is particularly linked with functional and taxonomic alterations in the gastrointestinal tract microbiome. A change in microbial diversity, referred as microbial dysbiosis, alters the gut fermentation profile and intestinal wall integrity and causes metabolic endotoxemia, low-grade inflammation, autoimmunity, and other affiliated metabolic disorders. This article aims to summarize the role of the gut microbiome in the pathogenesis of diabetes. Additionally, we summarize gut microbial dysbiosis in preclinical and clinical diabetes cases reported in literature in the recent years

Locus Interactions Underlie Seed Yield In Soybeans Resistant to Heterodera glycines

In soybean (Glycine max L. Merr.) combining resistance to cyst nematode (SCN; Heterodera glycines I.) with high seed yieldremains problematic. Molecular markers linked to quantitative trait loci (QTL) have not provided a solution. Sets of markers describing a collection of favorable alleles (linkats) may assist plant breeders seeking to combine both traits. The objective of this analysis was to identify linkats in genomic regions underlying seed yield and root SCN resistance QTL. Used were groups of cultivars selected from a single recombinant inbred (RIL) population derived from \u27Essex\u27 by \u27Forrest\u27 (ExF). The yield was measured at four locations. SCN resistance was determined in greenhouse assays. The mean seed yield was used to define 3 groups (each n = 30), high, medium and low. SCN resistance formed 2 groups (SCN resistant (n = 21) and SCN susceptible (n = 69)). Microsatellite markers (213) alleles were compared with seed yield and root SCN (Hetrodera glycines) resistance using mean analysis. The number, size and position of potential linkats were determined. Loci, genomic regions and linkats associated with seed yield were identified on linkage group (LG) K and with root resistance to SCN e on LG E, G, and D1b+W. A method to identify co-localized genomic regions is presented

The additional value of CT images interpretation in the differential diagnosis of benign vs. malignant primary bone lesions with 18F-FDG-PET/CT

Objective: To evaluate the value of a dedicated interpretation of the CT images in the differential diagnosis of benign vs. malignant primary bone lesions with 18fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). Materials and methods: In 50 consecutive patients (21 women, 29 men, mean age 36.9, age range 11-72) with suspected primary bone neoplasm conventional radiographs and 18F-FDG-PET/CT were performed. Differentiation of benign and malignant lesions was separately performed on conventional radiographs, PET alone (PET), and PET/CT with specific evaluation of the CT part. Histology served as the standard of reference in 46 cases, clinical, and imaging follow-up in four cases. Results: According to the standard of reference, conventional 17 lesions were benign and 33 malignant. Sensitivity, specificity, and accuracy in assessment of malignancy was 85%, 65% and 78% for conventional radiographs, 85%, 35% and 68% for PET alone and 91%, 77% and 86% for combined PET/CT. Median SUVmax was 3.5 for benign lesions (range 1.6-8.0) and 5.7 (range 0.8-41.7) for malignant lesions. In eight patients with bone lesions with high FDG-uptake (SUVmax ≥ 2.5) dedicated CT interpretation led to the correct diagnosis of a benign lesion (three fibrous dysplasias, two osteomyelitis, one aneurysmatic bone cyst, one fibrous cortical defect, 1 phosphaturic mesenchymal tumor). In four patients with lesions with low FDG-uptake (SUVmax < 2.5) dedicated CT interpretation led to the correct diagnosis of a malignant lesion (three chondrosarcomas and one leiomyosarcoma). Combined PET/CT was significantly more accurate in the differentiation of benign and malignant lesions than PET alone (p = .039). There was no significant difference between PET/CT and conventional radiographs (p = .625). Conclusion: Dedicated interpretation of the CT part significantly improved the performance of FDG-PET/CT in differentiation of benign and malignant primary bone lesions compared to PET alone. PET/CT more commonly differentiated benign from malignant primary bone lesions compared with conventional radiographs, but this difference was not significan

Hodgkin's lymphoma in remission after first-line therapy: which patients need FDG-PET/CT for follow-up?

Background: The purpose of the study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) during follow-up of patients with Hodgkin's lymphoma. Patients and methods: Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG-PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence. Results: Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG-PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7-6.6] and symptoms (P 24 months). Conclusions: Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG-PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG-PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG-PET/CT beyond 24 month

Risk-adapted FDG-PET/CT-based follow-up in patients with diffuse large B-cell lymphoma after first-line therapy

Background: The purpose of this study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) during follow-up of patients with diffuse large B-cell lymphoma (DLBCL) being in complete remission or unconfirmed complete remission after first-line therapy. Patients and methods: DLBCL patients receiving FDG-PET/CT during follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in cases of suspected disease recurrence. Results: Seventy-five patients were analyzed and 23 (30%) had disease recurrence. The positive predictive value (PPV) of FDG-PET/CT was 0.85. Patients >60 years [P = 0.036, hazard ratio (HR) = 3.82, 95% confidence interval (CI) 1.02-7.77] and patients with symptoms indicative of a relapse (P = 0.015; HR = 4.1; 95% CI 1.20-14.03) had a significantly higher risk for relapse. A risk score on the basis of signs of relapse, age >60 years, or a combination of these factors identified patients at high risk for recurrence (P = 0.041). Conclusions: FDG-PET/CT detects recurrent DLBCL after first-line therapy with high PPV. However, it should not be used routinely and if only in selected high-risk patients to reduce radiation burden and costs. On the basis of our retrospective data, FDG-PET/CT during follow-up is indicated for patients 60 years with and without clinical signs of relaps

Heterozygous <em>COL17A1 </em>variants are a frequent cause of amelogenesis imperfecta

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.Background: Collagen XVII is most typically associated with human disease when biallelic COL17A1 variants (&gt;230) cause junctional epidermolysis bullosa (JEB), a rare, genetically heterogeneous, mucocutaneous blistering disease with amelogenesis imperfecta (AI), a developmental enamel defect. Despite recognition that heterozygous carriers in JEB families can have AI, and that heterozygous COL17A1 variants also cause dominant corneal epithelial recurrent erosion dystrophy (ERED), the importance of heterozygous COL17A1 variants causing dominant non-syndromic AI is not widely recognised. Methods: Probands from an AI cohort were screened by single molecule molecular inversion probes or targeted hybridisation capture (both a custom panel and whole exome sequencing) for COL17A1 variants. Patient phenotypes were assessed by clinical examination and analyses of affected teeth. Results: Nineteen unrelated probands with isolated AI (no co-segregating features) had 17 heterozygous, potentially pathogenic COL17A1 variants, including missense, premature termination codons, frameshift and splice site variants in both the endo-domains and the ecto-domains of the protein. The AI phenotype was consistent with enamel of near normal thickness and variable focal hypoplasia with surface irregularities including pitting. Conclusion: These results indicate that COL17A1 variants are a frequent cause of dominantly inherited non-syndromic AI. Comparison of variants implicated in AI and JEB identifies similarities in type and distribution, with five identified in both conditions, one of which may also cause ERED. Increased availability of genetic testing means that more individuals will receive reports of heterozygous COL17A1 variants. We propose that patients with isolated AI or ERED, due to COL17A1 variants, should be considered as potential carriers for JEB and counselled accordingly, reflecting the importance of multidisciplinary care

18F-fluoro-deoxy-glucose focal uptake in very small pulmonary nodules: fact or artifact? Case reports

ABSTRACT: BACKGROUND: F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography integrated/combined with computed tomography (PET-CT) provides the best diagnostic results in the metabolic characterization of undetermined solid pulmonary nodules. The diagnostic performance of 18F-FDG is similar for nodules measuring at least 1 cm and for larger masses, but few data exist for nodules smaller than 1 cm. CASE PRESENTATION: We report five cases of oncologic patients showing focal lung 18F-FDG uptake on PET-CT in nodules smaller than 1 cm. We also discuss the most common causes of 18F-FDG false-positive and false-negative results in the pulmonary parenchyma. In patient 1, contrast-enhanced CT performed 10 days before PET-CT did not show any abnormality in the site of uptake; in patient 2, high-resolution CT performed 1 month after PET showed a bronchiole filled with dense material interpreted as a mucoid impaction; in patient 3, contrast-enhanced CT performed 15 days before PET-CT did not identify any nodules; in patients 4 and 5, contrast-enhanced CT revealed a nodule smaller than 1 cm which could not be characterized. The 18F-FDG uptake at follow-up confirmed the malignant nature of pulmonary nodules smaller than 1 cm which were undetectable, misinterpreted, not recognized or undetermined at contrast-enhanced CT. CONCLUSION: In all five oncologic patients, 18F-FDG was able to metabolically characterize as malignant those nodules smaller than 1 cm, underlining that: 18F-FDG uptake is not only a function of tumor size but it is strongly related to the tumor biology; functional alterations may precede morphologic abnormalities. In the oncologic population, especially in higher-risk patients, PET can be performed even when the nodules are smaller than 1 cm, because it might give an earlier characterization and, sometimes, could guide in the identification of alterations missed on CT