Taxonomic and chemical assessment of exceptionally abundant rock mine biofilm

Background An exceptionally thick biofilm covers walls of ancient gold and arsenic Złoty Stok mine (Poland) in the apparent absence of organic sources of energy. Methods and Results We have characterized this microbial community using culture-dependent and independent methods. We sequenced amplicons of the 16S rRNA gene obtained using generic primers and additional primers targeted at Archaea and Actinobacteria separately. Also, we have cultured numerous isolates from the biofilm on different media under aerobic and anaerobic conditions. We discovered very high biodiversity, and no single taxonomic group was dominant. The majority of almost 4,000 OTUs were classified above genus level indicating presence of novel species. Elemental analysis, performed using SEM-EDS and X-ray, of biofilm samples showed that carbon, sulphur and oxygen were not evenly distributed in the biofilm and that their presence is highly correlated. However, the distribution of arsenic and iron was more flat, and numerous intrusions of elemental silver and platinum were noted, indicating that microorganisms play a key role in releasing these elements from the rock. Conclusions Altogether, the picture obtained throughout this study shows a very rich, complex and interdependent system of rock biofilm. The chemical heterogeneity of biofilm is a likely explanation as to why this oligotrophic environment is capable of supporting such high microbial diversity

Characterization of hepatic macrophages and evaluation of inflammatory response in heme oxygenase-1 deficient mice exposed to scAAV9 vectors

Adeno-associated viral (AAV) vectors are characterised by low immunogenicity, although humoral and cellular responses may be triggered upon infection. Following systemic administration high levels of vector particles accumulate within the liver. Kupffer cells (KCs) are liver resident macrophages and an important part of the liver innate immune system. Decreased functional activity of KCs can contribute to exaggerated inflammatory response upon antigen exposure. Heme oxygenase-1 (HO-1) deficiency is associated with considerably reduced numbers of KCs. In this study we aimed to investigate the inflammatory responses in liver and to characterise two populations of hepatic macrophages in adult wild type (WT) and HO-1 knockout (KO) mice following systemic administration of one or two doses (separated by 3 months) of self-complementary (sc)AAV9 vectors. At steady state, the livers of HO-1 KO mice contained significantly higher numbers of monocyte-derived macrophages (MDMs), but significantly less KCs than their WT littermates. Three days after re-administration of scAAV9 we observed increased mRNA level of monocyte chemoattractant protein-1 (Mcp-1) in the livers of both WT and HO-1 KO mice, but the protein level and the macrophage infiltration were not affected. Three days after the 1st and 3 days after the 2nd vector dose the numbers of AAV genomes in the liver were comparable between both genotypes indicating similar transduction efficiency, but the percentage of transgene-expressing MDMs and KCs was higher in WT than in HO-1 KO mice. In the primary culture, KCs were able to internalize AAV9 particles without induction of TLR9-mediated immune responses, but no transgene expression was observed. In conclusion, in vivo and in vitro cultured KCs have different susceptibility to scAAV9 vectors. Regardless of the presence or absence of HO-1 and initial numbers of KCs in the liver, scAAV9 exhibits a low potential to stimulate inflammatory response at the analysed time points

Skuteczność i koszty leczenia raka jajnika w Polsce – ujęcie regionalne

Ovarian cancer (OC) affects over 3 000 women in Poland annually. The efficacy of the therapy remains relatively low due to challenges of systematic improvement in the early detection OC rates. International comparisons indicate a positive correlation between health expenditures and 5-year survival rates of cancer patients. To the best of our knowledge, our study has been the first to present a correlation between the 5-year survival rates (SRs) and the cost of ovarian cancer therapy in particular regions of Poland. Material and methods: The study was based on the National Health Fund (NHF) data, available in the Disease Treatment Registry. The analysis included approximately 13 000 OC patients who started their treatment between 2005 and 2008 to allow for the evaluation of long-term therapy results. The 5-year survival rates were analyzed in relation to average NHF expenditures in various regions of Poland, distinguishing the population of patients aged 45-64 years. Results: The 5-year survival rate in the cohorts diagnosed in 2005 and 2008 changed marginally, from 42% to 43%, maintaining relatively large differences between the regions (from 35% to 53% in patients diagnosed in 2008). The NHF expenditures in particular regions differed significantly: mean cost for the entire treatment cycle ranged from 31.600 PLN do 58.000 PLN per person among patients diagnosed in 2008. No significant correlation between the survival and the cost was found. Conclusions: SRs of OC patients in particular regions of Poland are not correlated with average treatment cost. Thus, the differences in SRs between various regions of Poland have their source in other factors, e.g. clinical stage at diagnosis, or prevailing treatment patterns in the given region. Further studies may decrease regional discrepancies in patient care and SRs in OC subjects.Wstęp: W Polsce na raka jajnika zachorowuje corocznie ponad trzy tysiące kobiet. Ponieważ w praktyce trudno osiągnąć sytuację systematycznego, wczesnego wykrywania tej choroby, skuteczność jej leczenia jest relatywnie niska. Analiza danych zagranicznych pozwala stwierdzić występowanie korelacji wydatków na opiekę zdrowotną z 5-letnim przeżyciem pacjentów leczonych na chorobę nowotworową. W niniejszym opracowaniu, po raz pierwszy w Polsce, zbadano dane w ujęciu wojewódzkim, dotyczące 5-letniego przeżycia chorych na raka jajnika oraz wydatków na ich leczenie. Materiał i metody: W pracy wykorzystano dane pochodzące z Rejestru Leczenia Chorób Narodowego Funduszu Zdrowia. Analizie poddano blisko 13 tys. nowych potwierdzonych przypadków raka jajnika (początek leczenia w latach 2005–2008), aby umożliwić obserwację odległych wyników zastosowanej terapii. Dokonano analizy porównawczej wskaźników 5-letniego przeżycia oraz wydatków na leczenie w całym cyklu terapeutycznym, wyróżniając grupę pacjentek w wieku od 45 do 64 lat. Wyniki: Wartości wskaźników 5-letniego przeżycia pacjentek leczonych na raka jajnika wzrosły średnio w kohortach chorych, zdiagnozowanych w latach 2005–2008, z poziomu 42% do 43%, notując dużą rozpiętość w poszczególnych województwach (35%–53% w grupie pacjentek rozpoczynających leczenie w roku 2008). Znaczne różnice między województwami stwierdzono również w wydatkach na leczenie (31 tys.–58 tys. złotych na osobę w całym cyklu terapeutycznym, w grupie pacjentek rozpoczynających leczenie w roku 2008). Nie zaobserwowano jednak występowania, statystycznie istotnej, korelacji 5-letniego przeżycia chorych na raka jajnika z wydatkami na ich leczenie. Wnioski: Zestawienie wskaźników przeżycia 5-letniego w populacji chorych na raka jajnika ze średnimi wydatkami poszczególnych województw na ich leczenie nie wskazuje występowania istotnej statystycznie korelacji wydatków z efektami leczenia. Wobec tego przyczyn różnic występujących w wynikach leczenia należy szukać gdzie indziej. Być może wiążą się ze stopniem zaawansowania nowotworu w chwili rozpoczęcia leczenia lub z wyborem sposobu leczenia (treatment patterns). Pogłębienie tej analizy oraz identyfikacja i zrozumienie przyczyn występujących różnic mogą prowadzić do zmniejszenia regionalnych nierówności w zakresie wyników leczenia chorych na raka jajnika w Polsce

Suicide inhibition of alpha-oxamine synthases:structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

The suicide inhibition of the α-oxamine synthases by the substrate analog, L-trifluoroalanine was investigated. The inhibition resulted in the formation of a complex with loss of all three fluorine atoms. Decarboxylation and loss of fluoride occurred immediately after aldimine formation. The inherent flexibility could allow the difluorinated intermediate complex to adopt a suitable conformation. Decarboxylation in the normal mechanism occurs after formation of the ketoacid intermediate.link_to_subscribed_fulltex

Post-little ice age glacial geomorphology of contrasting topographic settings at Skálafellsjökull, southeast Iceland

Glacial geomorphological mapping from the southern margin of Skálafellsjökull, southeast Iceland, depicts a topographically diverse mountainside, influencing glacier dynamics, landform formation and glacier retreat since the Little Ice Age maximum in ∼1890. The glacial landforms present are typical of southeast Icelandic temperate glaciers, comprising recessional push moraines, including sawtooth moraines, and associated fluting. Study area A demonstrates an abandoned lobe confined by steep V-shaped topography, displaying moraines and minimal fluting, suggesting low preservation of landforms, and changes in glacier behaviour. At study area B, the sawtooth moraine morphology demonstrates changes in the glacier margin as the ice interacted with a series of topographic benches during active recession. The steep-sided valley at study area C illustrates densely spaced arcuate moraines, reflecting subtle changes in ice elevation. This mapping provides a framework for further investigations into glacier retreat rates and the influence of local topography and climate

ARTICLEAssociation of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Background: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers.Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy.Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)].Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.Peer reviewe

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30-to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 x 10(-31)).Peer reviewe

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years