The concentration of particulate matter in the barn air and its influence on the content of heavy metals in milk

Heavy metals are one of the components of smog, which is mainly the product of burning fossil fuels in residential buildings. These elements, introduced into the body of cattle by inhalation, may enter the milk. The goal of this study was to assess the impact of particulate pollution in the atmospheric air on the concentration of particulate matter in the air of a dairy cattle barn and on the content of selected heavy metals in milk from cows present in the building. Measurements were taken between November and April (148 measurement days). The calculations carried out showed a high correlation (R$_{S}$ = + 0.95) between the concentrations of particulates measured outside and inside the barn, which is indicative of a significant impact of the atmospheric air on the particulate pollution level of the livestock building. The number of days in excess of the daily standard for PM$_{10}$ inside was 51. The conducted analysis of the chemical composition of the milk collected under high particulate pollution (February) showed that the permitted lead level had been exceeded—21.93 µg/kg (norm 20.00 µg/kg)

Biliary Adenofibroma: A Rare Liver Tumor with Transition to Invasive Carcinoma

Biliary adenofibroma is a rare benign liver tumor with potential for malignant transition. It has a bile duct origin characterized by a complex tubulocystic biliary epithelium with fibrous stroma. MRI features may suggest this uncommon entity, and histological findings can be diagnostic. We report a case of biliary adenofibroma with transformation to an intrahepatic cholangiocarcinoma

Innovative thrust vectoring system with moveable jet vanes integrated with a moveable diffuser – Measurement and analysis of selected nozzle performance parameters

The aim of the study described herein was to design, construct and test a demonstrator of a system to control the direction of the resultant thrust vector of a rocket motor to be used in short range anti-tank missiles with a mass of up to 15 kg. The novelty of the system is that the direction of the resultant thrust vector is manipulated by means of moveable jet vanes integrated with a moveable nozzle diffuser through telescopic connectors. The technology demonstrator was built using different materials and different manufacturing processes. The first versions were 3D printed from plastic materials. Minor modifications to the design were made at an early stage. The final version had the main components made of aluminum using CNC machining. The system, with and without jet vanes, was tested on a specially developed test rig equipped with a multi-axis sensor to measure forces and torques. The nozzle performance parameters measured and analyzed in this study were the components of the thrust vector, the moments and the effective vectoring angle. The findings show that the experimental data are in good agreement with the results of earlier simulations and that the demonstrator is fully operational

Clinical variables as indicative factors for endoscopy in adolescents with esophageal atresia

Introduction: Gastro-esophageal reflux disease (GERD) occurs frequently in patients operated for esophageal atresia (EA). Longstanding esophagitis may lead to dysphagia, strictures, columnar metaplasia, and dysplasia with an increased risk of adenocarcinoma. Are clinical factors and non-invasive assessments reliable indicators for follow-up with endoscopy? Material and method: A follow-up study with inclusion of EA adolescents in Norway born between 1996 and 2002 was conducted. Clinical assessment with pH monitoring, endoscopy with biopsies, along with interviews and questionnaires regarding gastroesophageal reflux disease (GERD) and dysphagia were performed. Results: We examined 68 EA adolescents. 62% reported GERD by interview, 22% by questionnaire. 85% reported dysphagia by interview, 71% by questionnaire. 24-hour pH monitoring detected pathological reflux index (RI) (&gt;7%) in 7/59 (12%). By endoscopy with biopsy 62 (92%) had histologic esophagitis, of whom 3 (4%) had severe esophagitis. Gastric metaplasia was diagnosed in twelve (18%) adolescents, intestinal metaplasia in only one (1.5%). None had dysplasia or carcinoma. Dysphagia and GERD were statistically correlated to esophagitis and metaplasia, but none of the questionnaires or interviews alone were good screening instruments with high combined sensitivity and specificity. A compound variable made by simply taking the mean of rescaled RI and dysphagia by interview showed to be the best predictor of metaplasia (85% sensitivity, 67% specificity). Conclusion: The questionnaires and interviews used in the present study were not good screening instruments alone. However, combining dysphagia score by interview and RI may be helpful in assessing which patients need endoscopy with biopsy at each individual follow-up examination.</p

Metody i narzędzia zapisu i udostępniania danych

Praca recenzowana / Peer-reviewed paperPrzekazujemy czytelnikowi kolejną monografię wydaną w ramach serii „Informatyka”, zawierającą publikacje pracowników związanych z Wydziałem Zarządzania i Komunikacji Społecznej Krakowskiej Akademii im. Andrzeja Frycza Modrzewskiego z obszaru problemów optymalizacji, systemów informacyjnych oraz kształcenia zdalnego. Wśród autorów niniejszej publikacji znajdują się głównie pracownicy Studium Informatyki Krakowskiej Akademii i Katedry Informatyki Stosowanej. Opublikowane artykuły są wynikiem współpracy w zespołach z pracownikami innych krakowskich uczelni. Tematyka monografii koncentruje się na metodach optymalizacji, zastosowaniach systemów informatycznych, oraz kształcenia zdalnego. Całość tematyki podzielona jest na trzy wzajemnie powiązane części. Pierwsza część zawiera trzy podrozdziały, w których podjęto kwestie kształcenia zdalnego. Druga część monografii, ujęta w kolejnych trzech podrozdziałach, prezentuje wybrane narzędzia i modele optymalizacji. Ostatnia, trzecia – przedstawia problematykę związaną z zastosowaniem systemów informatycznych w firmie

Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis.

BACKGROUND People with primary sclerosing cholangitis (PSC) have a 20% lifetime risk of biliary tract cancer (BTC). Using whole-exome sequencing, we characterized genomic alterations in tissue samples from BTC with underlying PSC. METHODS We extracted DNA from formalin-fixed, paraffin-embedded tumor and paired nontumor tissue from 52 resection or biopsy specimens from patients with PSC and BTC and performed whole-exome sequencing. Following copy number analysis, variant calling, and filtering, putative PSC-BTC-associated genes were assessed by pathway analyses and annotated to targeted cancer therapies. RESULTS We identified 53 candidate cancer genes with a total of 123 nonsynonymous alterations passing filtering thresholds in 2 or more samples. Of the identified genes, 19% had not previously been implicated in BTC, including CNGA3, KRT28, and EFCAB5. Another subset comprised genes previously implicated in hepato-pancreato-biliary cancer, such as ARID2, ELF3, and PTPRD. Finally, we identified a subset of genes implicated in a wide range of cancers such as the tumor suppressor genes TP53, CDKN2A, SMAD4, and RNF43 and the oncogenes KRAS, ERBB2, and BRAF. Focal copy number variations were found in 51.9% of the samples. Alterations in potential actionable genes, including ERBB2, MDM2, and FGFR3 were identified and alterations in the RTK/RAS (p = 0.036), TP53 (p = 0.04), and PI3K (p = 0.043) pathways were significantly associated with reduced overall survival. CONCLUSIONS In this exome-wide characterization of PSC-associated BTC, we delineated both PSC-specific and universal cancer genes. Our findings provide opportunities for a better understanding of the development of BTC in PSC and could be used as a platform to develop personalized treatment approaches

Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation

Background and aims We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5’-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT). Methods We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n = 158) sampled prior to and serially after LT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n = 51) or with primary biliary cholangitis (PBC) (n = 100), as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT. Results In different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP was associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant recipients with recurrent disease. Conclusions Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation. Impact and implications We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.publishedVersio

Genomic Characterization of Cholangiocarcinoma in Primary Sclerosing Cholangitis Reveals Therapeutic Opportunities

Background and Aims Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) may exceed 20%, and BTC is currently the leading cause of death in patients with PSC. To open new avenues for management, we aimed to delineate clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). Approach and Results We analyzed formalin-fixed, paraffin-embedded tumor tissue from 186 patients with PSC-BTC from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations, and copy number variations, along with histomorphological and immunohistochemical characterization. Regardless of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, such asTP53(35.5%),KRAS(28.0%),CDKN2A(14.5%), andSMAD4(11.3%), as well as potentially druggable mutations (e.g.,HER2/ERBB2). We found a high frequency of nontypical/nonductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%). Conclusions Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC shows a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC.Peer reviewe

Low Concordance Between T-Cell Densities in Matched Primary Tumors and Liver Metastases in Microsatellite Stable Colorectal Cancer

BackgroundThe subtype, density and location of tumor infiltrating T-cells are being explored as prognostic and predictive biomarkers in primary colorectal cancer (pCRC) and colorectal liver metastases (CLM). Very limited data exist comparing findings in pCRC and matched CLM.Patients and methodsFifty-eight patients with available pCRC and matched CLM (57/58 microsatellite stable) were included in this OSLO-COMET substudy. In immunohistochemically stained sections, total (Ttot), helper (TH), cytotoxic (CTL), and regulatory (Treg) T-cells were manually counted in hotspots from the invasive margin (IM), intratumor (IT), and tumor adjacent regions to determine T-cell densities.ResultsA striking accumulation of T-cells was found in IM of both pCRC and CLM with much lower densities in the IT region, exemplified by Ttot of 2838 versus 340 cells/mm2, respectively, in CLM. The correlation at the individual level between T-cell densities in pCRC and corresponding CLM was poor for all regions and T-cell subtypes; for instance, the correlation coefficient (R2) for IM Ttot was 0.07. The IT TH : CTL and Treg : TH ratios were 2.94 and 0.44, respectively, in pCRC, and 1.84 and 0.24, respectively, in CLM.ConclusionThe observed accumulation of T-cells in the IM regions of pCRC and CLM with low penetration to the IT regions, combined with high TH : CTL and Treg : TH ratios, point to the presence of an immune suppressive microenvironment. T-cell densities of CLM differed markedly from the matched pCRC, indicating that to evaluate T-cell biomarkers in metastasis, the commonly available pCRC cannot serve as a surrogate for the metastatic tumor

Banff 2022 liver group meeting report: monitoring long term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participantsincluded hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists.Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimisation and long-term structural changes.Potential revision of the rejection classification scheme to better accommodate and communicate lateT cell-mediated rejection patterns and related structural changes, such as nodular regenerativehyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression tomatch the heterogeneity of patient settings will be central to improving long-term patient survival.Such personalised therapeutics are in turn contingent on better understanding and monitoring ofallograft status within a rational decision-making approach, likely to be facilitated in implementationwith emerging decision support tools. Proposed revisions to rejection classification emerging fromthe meeting include incorporation of interface hepatitis and fibrosis staging. These will be opened toonline testing, modified accordingly and subject to consensus discussion leading up to the next Banffconference