Hovgaardstevens3737

The bacterium Listeria monocytogenes ubiquitously occurs in the environment but can cause severe invasive disease in susceptible individuals when ingested. We recently identified the L. monocytogenes genes lieAB and lftRS, encoding a multidrug resistance ABC transporter and a regulatory module, respectively. These genes jointly mediate resistance against aurantimycin, an antibiotic produced by the soil-dwelling species Streptomyces aurantiacus, and thus contribute to the survival of L. monocytogenes in its natural habitat, the soil. Repression of lieAB and lftRS is exceptionally tight but strongly induced in the presence of aurantimycin. Repression depends on LftR, which belongs to subfamily 2 of the PadR-like transcriptional repressors. To better understand this interesting class of transcriptional repressors, we here deduce the LftR operator sequence from a systematic truncation and mutation analysis of the P lieAB promoter. The sequence identified is also present in the P lftRS promoter but not found elsew identify critical elements in the lieAB promoter and its transcriptional regulator LftR that contribute to habitat-specific expression of the lieAB genes. These results further clarify the molecular mechanisms underlying the aurantimycin resistance of L. monocytogenes.We take advantage of a historic collection of 133 Staphylococcus aureus strains accessioned between 1924 and 2016, whose genomes have been long-read sequenced as part of a major National Collection of Type Cultures (NCTC) initiative, to conduct a gene family-wide computational analysis of enterotoxin genes. We identify two novel staphylococcal enterotoxin (pseudo)genes (sel29p and sel30), the former of which has not been observed in any contemporary strain to date. We provide further information on five additional enterotoxin genes or gene variants that either have recently entered the literature or for which the nomenclature or description is currently unclear (selz, sel26, sel27, sel28, and ses-2p). An examination of over 11,000 RefSeq genomes in search of wider support for these seven (pseudo)genes led to the identification of an additional three novel enterotoxin gene family members (sel31, sel32, and sel33) plus two new variants (seh-2p and ses-3p). We cast light on the genomic distribution of the enteroxin genes and the genomic composition of family members. This study further expands knowledge of the staphylococcal enterotoxins while shedding light on their evolution over the last century.

Cholangiocarcinoma (CC) is a rare tumour arising from the biliary tract epithelium. The aim of this study was to perform a genomic characterisation of CC tumours and to implement a model to differentiate extrahepatic (ECC) and intrahepatic (ICC) cholangiocarcinoma.

DNA extracted from tumour samples of 23 patients with CC, namely 10 patients with ECC and 13 patients with ICC, was analysed by array comparative genomic hybridisation. A support vector machine algorithm for classification was applied to the genomic data to distinguish between ICC and ECC. A survival analysis comparing both groups of patients was also performed.

With these whole genome results, we observed several common alterations between tumour samples of the same CC anatomical type, namely gain of Xp and loss of 3p, 11q11, 14q, 16q, Yp and Yq in ICC tumours, and gain of 16p25.3 and loss of 3q26.1, 6p25.3-22.3, 12p13.31, 17p, 18q and Yp in ECC tumours. Gain of 2q37.3 was observed in the samples of both tumour subtypes, ICC and ECC. The developed genomic model comprised four chromosomal regions that seem to enable the distinction between ICC and ECC, with an accuracy of 71.43% (95% CI 43% to 100%). Survival analysis revealed that in our cohort, patients with ECC survived on average 8 months less than patients with ICC.

This genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.

This genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.Whenever tissue sample is not available, non-small cell lung cancer (NSCLC) biomarker testing is performed with liquid biopsy. The Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is a novel target in patients with NSCLC. In this study, 33 NSCLC frozen plasma samples, previously characterised for KRAS mutational status by next generation sequencing (NGS), were processed by the fully automated Idylla KRAS assay. In 30/33 cases, archival matched cell-free DNA (cfDNA) was also directly pipetted in the cartridge. Overall, 30/33 plasma and 28/30 cfDNA samples yielded valid results. In 29/30 of KRAS p.G12C mutant plasma samples and 26/28 of cfDNA, Idylla confirmed the NGS results. In conclusion, the Idylla NSCLC KRAS liquid biopsy assay may represent a reliable tool to assess KRAS p.G12C mutation.

To determine if a simple prewash step added to the processing workflow of tissue procurement by a core needle biopsy device will recover enough cells to expand the laboratory testing armamentarium.

Tissue was obtained from unfixed resection specimens using a core needle device and washed in a buffered solution before fixation. This creates a liquid aliquot from which dislodged cells can be kept and separated from the tissue specimen, the latter of which can then undergo traditional formalin-fixed, paraffin-embedded processing.

Cells dislodged from the tissue during the biopsy procedure are recoverable, are representative of the tissue section and of sufficient quantities for additional laboratory testing.

The core needle biopsy wash is an under-recognised and underutilised approach to extending the diagnostic capabilities of the limited amount of targeted material obtained during this common procedure. The ability to recover supplemental amounts of diagnostic material yields great potential as a substrate for a multitude of current and developing laboratory assays.

The core needle biopsy wash is an under-recognised and underutilised approach to extending the diagnostic capabilities of the limited amount of targeted material obtained during this common procedure. The ability to recover supplemental amounts of diagnostic material yields great potential as a substrate for a multitude of current and developing laboratory assays.

Various approaches have been reported for distinguishing separate primary lung adenocarcinomas from intrapulmonary metastases in patients with two lung nodules. The aim of this study was to determine whether histological assessment is reliable and accurate in distinguishing separate primary lung adenocarcinomas from intrapulmonary metastases using routine molecular findings as an adjunct.

We studied resected tumour pairs from 32 patients with lung adenocarcinomas in different lobes. In 15 of 32 tumour pairs, next-generation sequencing (NGS) for common driver mutations was performed on both nodules. The remainder of tumour pairs underwent limited NGS, or

genotyping. Tumour pairs with different drivers (or one driver/one wild-type) were classified as molecularly unrelated, while those with identical low-frequency drivers were classified as related. Three pathologists independently and blinded to the molecular results categorised tumour pairs as related or unrelated based on histological assessment.

Of 32 pairs, 15 were classified as related by histological assessment, and 17 as unrelated. Of 15 classified as related by histology, 6 were classified as related by molecular analysis, 4 were unrelated and 5 were indeterminate. Of 17 classified as unrelated by histology, 14 were classified as unrelated by molecular analysis, none was related and 3 were indeterminate. Histological assessment of relatedness was inaccurate in 4/32 (12.5%) tumour pairs.

A small but significant subset of two-nodule adenocarcinoma pairs is inaccurately judged as related by histological assessment, and can be proven to be unrelated by molecular analysis (driver gene mutations), leading to significant downstaging.

A small but significant subset of two-nodule adenocarcinoma pairs is inaccurately judged as related by histological assessment, and can be proven to be unrelated by molecular analysis (driver gene mutations), leading to significant downstaging.

Epiploic appendages are fatty peritoneal structures on the external surface of the colon that can infarct and become necrotic in situ or autoamputate.

To describe clinicopathological features of infarcted epiploic appendages (IEAs).

We reviewed 52 IEAs from 49 patients, recording numerous clinical and pathological characteristics, which were compared across attached and loose IEAs.

Twenty-seven IEAs were attached, and 23 were loose; location was unclear in 2. Most were incidental; 3 attached cases caused 'appendagitis'. Most (31, 60%) had a classic 'egg-like' appearance. Common findings included fat necrosis (84%), calcification (67%) and fibrosis (58%). Attached cases had a larger mean size (1.8 cm vs 1.3 cm, p=0.030) and were more often haemorrhagic (37% vs 4%, p=0.0064) and inflamed (67% vs 13%, p=0.0002). Loose cases were more often necrotic (100% vs 74%, p=0.011).

IEAs have different morphology whether they remain attached to peritoneum or become necrotic and detached. Attached cases may cause symptoms.

IEAs have different morphology whether they remain attached to peritoneum or become necrotic and detached. Attached cases may cause symptoms.

Individuals with diabetes require extensive self-management. Little is known about how Hurricane Matthew (Matthew) or Hurricane Florence (Florence) impacted diabetes self-management and outcomes in Robeson County, North Carolina.

Mixed methods were used to assess the impact of hurricanes on diabetes self-management and outcomes. Individuals with diabetes were recruited for focus groups to understand the perceived impact on diabetes self-management. Health care providers were recruited for parallel key informant interviews. selleck compound Mean hemoglobin A1c (HbA1c) and frequency of diabetic ketoacidosis (DKA) from hospital data six months before and after Matthew were compared using Student t-tests.

A demographic breakdown of 34.25% white, 21.70% Black or African American, and 21.38% American Indian or Alaska Native was observed from focus groups. Qualitative results highlight a limited access to a balanced diet and medications. No significant differences were found between mean HbA1c values before and after Matthew (before Matthew mean HbA1c 8.34 ± 1.87%; after Matthew mean HbA1c 8.31 ± 1.93 %;

= .366). The period prevalence (PP) of DKA was higher after Matthew than before (before Matthew 39 cases out of 4,025 visits, PP = .010; after Matthew 87 cases out of 3,779 visits, PP = .023;

<.0001).

Limitations include non-random sampling and limited sample sizes. Also, the cross-sectional panel approach did not follow the same individuals over time.

The period prevalence of DKA was higher in the six-month time period following Matthew compared to before the hurricane. Future interventions may improve outcomes via increased access to foods and medications recommended for those with diabetes.

The period prevalence of DKA was higher in the six-month time period following Matthew compared to before the hurricane. Future interventions may improve outcomes via increased access to foods and medications recommended for those with diabetes.