Characterization of ancient ceramic shreds: Insights into firing conditions and manufacturing technology

Four ancient ceramic shreds from the archaeological site Leletepe in the Fizuli region of the Republic of Azerbaijan and two local raw ceramic pastes were characterized by powder X-ray diffraction (PXRD) and thermal analysis (TG-DTG) techniques. XRD analysis of ceramic sherds reveals that all investigated samples contain similar minerals: quartz, feldspar, and clay. Three samples out of four contain calcite. Based on the traditional approach, it has been assumed that the firing process in these samples stopped before 700 °C. The mass loss ratios of samples of ancient ceramics also indicate that reversible dehydroxylation took place in all four samples, thus indicating the initial mild firing conditions. The summary of all the applied methods indicates that the ceramic samples were made using a similar manufacturing technology. According to XRD analysis, samples N1 and N4 contain diopside, and samples N2 and N3 contain maghemite, indicating the different origins of the ceramic shreds. Analysis of the raw ceramic mass also did not reveal the presence of these minerals, which may indicate a discrepancy between the origin of ancient ceramic sherds and modern ones

Spectral Deconvolution of Fossil Tooth Enamel Electron Paramagnetic Resonance Spectrum

In this work the ESR method has been applied to determine the age of fossil tooth enamel found in Mingachevir archeological site (Azerbaijan, Mingachevir). The EPR spectrum of tooth enamel has been deconvoluted into four individual Gaussian lines. Equivalent dose (Absorbed dose in tooth enamel that was historically accumulated due to natural irradiation) calculated using dose-response curves of individual Gaussian lines shows significantly different values. Peak 1 (with g= 2.006848) gives a significantly lower, Peak 4 (with g=2.002942) a significantly higher value of absorbed dose. The use of integrated spectra gives lower absorption dose values than the use of differential spectra

Thermo Luminescence Dating of Pottery Sample from Chukhur Gabala Archaeological Site in Gabala District of Azerbaijan

The age of fragments of the ancient pottery sample from Chukhur Gabala archeological site in Gabala district of Azerbaijan has been estimated by employing Thermoluminescence dating (TL) method. The annual dose rate was obtained using γ-spectrometer with a hyper-pure germanium detector and it was 2.741±0.121 mGy/year. The age of the sample was calculated by an additive dose method as 2230±510 years which are in line with the stratigraphically estimated age of this area

Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so

High endothelial venules are associated with microsatellite instability, hereditary background and immune evasion in colorectal cancer

Background: Microsatellite-unstable (MSI) tumours show a high load of mutational neoantigens, as a consequence of DNA mismatch repair deficiency. Consequently, MSI tumours commonly present with dense immune infiltration and develop immune evasion mechanisms. Whether improved lymphocyte recruitment contributes to the pronounced immune infiltration in MSI tumours is unknown. We analysed the density of high endothelial venules (HEV) and postcapillary blood vessels specialised for lymphocyte trafficking, in MSI colorectal cancers (CRC). Methods: HEV density was determined by immunohistochemical staining of FFPE tissue sections from MSI (n = 48) and microsatellite-stable (MSS, n = 35) CRCs. Associations with clinical and pathological variables were analysed. Results: We found elevated HEV densities in MSI compared with MSS CRCs (median 0.049 vs 0.000 counts/mm2, respectively, p = 0.0002), with the highest densities in Lynch syndrome MSI CRCs. Dramatically elevated HEV densities were observed in B2M-mutant Lynch syndrome CRCs, pointing towards a link between lymphocyte recruitment and immune evasion (median 0.485 vs 0.0885 counts/mm2 in B2M-wild-type tumours, p = 0.0237). Conclusions: Our findings for the first time indicate a significant contribution of lymphocyte trafficking in immune responses against MSI CRC, particularly in the context of Lynch syndrome. High HEV densities in B2M-mutant tumours underline the significance of immunoediting during tumour evolution

Identification and management of Lynch syndrome in the Middle East and North African countries: outcome of a survey in 12 countries

Background: Lynch syndrome (LS), the most common inherited form of colorectal cancer (CRC), is responsible for 3% of all cases of CRC. LS is caused by a mismatch repair gene defect and is characterized by a high risk for CRC, endometrial cancer and several other cancers. Identification of LS is of utmost importance because colonoscopic surveillance substantially improves a patient’s prognosis. Recently, a network of physicians in Middle Eastern and North African (ME/NA) countries was established to improve the identification and management of LS families. The aim of the present survey was to evaluate current healthcare for families with LS in this region. Methods: A questionnaire was developed that addressed the following issues: availability of clinical management guidelines for LS; attention paid to family history of cancer; availability of genetic services for identification and diagnosis of LS; and assessment of knowledge of LS surveillance. Members of the network and authors of recent papers on LS from ME/NA and neighbouring countries were invited to participate in the survey and complete the online questionnaire. Results: A total of 55 individuals were invited and 19 respondents from twelve countries including Algeria, Azerbaijan, Cyprus, Egypt, Iran, Jordan, Kuwait, Lebanon, Morocco, Palestine, Tunisia, and Turkey completed the questionnaire. The results showed that family history of CRC is considered in less than half of the surveyed countries. Guidelines for the management of LS are available in three out of twelve countries. The identification and selection of families for genetic testing were based on clinical criteria (Amsterdam criteria II or Revised Bethesda criteria) in most countries, and only one country performed universal screening. In most of the surveyed countries genetic services were available in few hospitals or only in a research setting. However, surveillance of LS families was offered in the majority of countries and most frequently consisted of regular colonoscopy. Conclusion: The identification and management of LS in ME/NA countries are suboptimal and as a result most LS families in the region remain undetected. Future efforts should focus on increasing awareness of LS amongst both the general population and doctors, and on the improvement of the infrastructure in these countries