RESUMO
Several breast cancer susceptibility genes have been discovered, but more are likely to exist. To identify additional breast cancer susceptibility genes, we used the founder population of Poland and performed whole-exome sequencing on 510 women with familial breast cancer and 308 control subjects. We identified a rare mutation in ATRIP (GenBank: NM_130384.3: c.1152_1155del [p.Gly385Ter]) in two women with breast cancer. At the validation phase, we found this variant in 42/16,085 unselected Polish breast cancer-affected individuals and in 11/9,285 control subjects (OR = 2.14, 95% CI = 1.13-4.28, p = 0.02). By analyzing the sequence data of the UK Biobank study participants (450,000 individuals), we identified ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR = 3.28, 95% CI = 1.76-6.14, p < 0.001). Immunohistochemistry and functional studies showed the ATRIP c.1152_1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress. We showed that tumors of women with breast cancer who have a germline ATRIP mutation have loss of heterozygosity at the site of ATRIP mutation and genomic homologous recombination deficiency. ATRIP is a critical partner of ATR that binds to RPA coating single-stranded DNA at sites of stalled DNA replication forks. Proper activation of ATR-ATRIP elicits a DNA damage checkpoint crucial in regulating cellular responses to DNA replication stress. Based on our observations, we conclude ATRIP is a breast cancer susceptibility gene candidate linking DNA replication stress to breast cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias da Mama , Proteínas de Ligação a DNA , Feminino , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Bancos de Espécimes Biológicos , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Dano ao DNA , Proteínas de Ligação a DNA/genética , Polônia/epidemiologia , Proteína de Replicação A/genética , Proteína de Replicação A/metabolismo , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Local adaptation is a key evolutionary process that enhances the growth of plants in their native habitat compared to non-native habitats, resulting in patterns of adaptive genetic variation across the entire geographic range of the species. The study of population adaptation to local environments and predicting their response to future climate change is important because of climate change. RESULTS: Here, we explored the genetic diversity of candidate genes associated with bud burst in pedunculate oak individuals sampled from 6 populations in Poland. Single nucleotide polymorphism (SNP) diversity was assessed in 720 candidate genes using the sequence capture technique, yielding 18,799 SNPs. Using landscape genomic approaches, we identified 8 FST outliers and 781 unique SNPs in 389 genes associated with geography, climate, and phenotypic variables (individual/family spring and autumn phenology, family diameter at breast height (DBH), height, and survival) that are potentially involved in local adaptation. Then, using a nonlinear multivariate model, Gradient Forests, we identified vulnerable areas of the pedunculate oak distribution in Poland that are at risk from climate change. CONCLUSIONS: The model revealed that pedunculate oak populations in the eastern part of the analyzed geographical region are the most sensitive to climate change. Our results might offer an initial evaluation of a potential management strategy for preserving the genetic diversity of pedunculate oak.
Assuntos
Quercus , Humanos , Quercus/genética , Evolução Biológica , Genômica , Florestas , Polônia , Adaptação Fisiológica/genéticaRESUMO
BACKGROUD: Tripartite motif containing 5α protein is a factor contributing to intracellular defense mechanisms against human immunodeficiency virus-1 (HIV-1) infection. The studies of TRIM5 variants effects on the risk of HIV-1 infection and the clinical course of disease provided inconclusive results in different ethnic groups. The aim of this study was to investigate the influence of TRIM5 variants on susceptibility to HIV-1 infection and clinical parameters among Polish HIV-1-infected patients. MATERIALS & METHODS: In our study, we investigated 301 HIV-1-infected patients and 186 age-matched seronegative controls. Seven variants of the TRIM5 gene (rs7127617, rs3824949, rs3740996, rs11601507, rs10838525, rs11038628, and rs28381981) were genotyped using both sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. RESULTS AND CONCLUSIONS: The frequencies of rs7127617 TT genotype and T allele occurrence were lower in HIV-1-infected subjects compared to controls (0.14 vs. 0.26 for T/T genotype and 0.45 vs. 0.54 for T allele), suggesting their possible protective effect (p = 0.005 and p = 0.007, respectively). Heterozygosity and presence of the T allele at rs3740996 were enriched in controls compared to HIV-1-infected group (0.19 vs. 0.12 for C/T genotype and 0.11 vs. 0.07 for T allele; p = 0.03 and p = 0.02, respectively). Moreover, rs3824949 CC genotype carriers had a lower viral load than patients bearing rs3824949 GG/CG genotypes (4.0 vs. 4.6 log copies/mL; p = 0.049); however, none of the variants affected CD4+ cell count. In conclusion, our data confirm the role of TRIM5 variants in the HIV-1 transmission and the clinical course of HIV-1 infection. The presence of rs7127617 TT genotype and T allele seems to protect against HIV-1 transmission in examined population.
Assuntos
Infecções por HIV , HIV-1 , Humanos , Predisposição Genética para Doença , Polônia , Ubiquitina-Proteína Ligases/genética , Infecções por HIV/genética , Genótipo , Proteínas com Motivo Tripartido/genética , Progressão da Doença , Polimorfismo de Nucleotídeo Único , Frequência do Gene , Fatores de Restrição AntiviraisRESUMO
BACKGROUND: Although biobanks have become fundamental to many research centers and contribute to medical development, they generate many ethical and legal issues that may discourage patients from donating. MATERIALS AND METHODS: To understand patients' perception of ethical and legal issues related to biobanks we conducted a survey among 548 Polish patients with cancer. RESULTS: While 93.1% of patients with cancer declared themselves willing to donate biospecimens left over after a medical procedure to a biobank, most opted for one-time consent or study-specific consent, blanket consent being less frequently preferred. Many patients believed that future use of previously collected tissues require second contact. Most patients preferred pseudonymization over anonymization of the data, and supported donors' right to withdraw informed consent at any given moment. Finally, while personal health information was the most expected form of compensation for donation, most patients suggested that all parties, including the biobank concerned, the sponsors of the research, and the donors, should own the rights to cancer tissues donated and profit from the biobank research. Patients' opinions on the ethical and legal issues related to biobank research were associated with age, sex, religiosity, education level, and place of residence. CONCLUSIONS: Since biobanks generate ethical and legal issues related to informed consent, data protection and storage, as well as the sharing of biosamples, tissue ownership, and profit sharing, that may discourage patients from donation, when asking a patient for a donation, healthcare professionals should communicate in a donor-centered manner and address patients' ethical and moral concerns related to donation and offer resources to help manage these concerns.
Assuntos
Bancos de Espécimes Biológicos , Consentimento Livre e Esclarecido , Neoplasias , Humanos , Masculino , Feminino , Polônia , Neoplasias/psicologia , Neoplasias/terapia , Pessoa de Meia-Idade , Bancos de Espécimes Biológicos/ética , Bancos de Espécimes Biológicos/legislação & jurisprudência , Consentimento Livre e Esclarecido/legislação & jurisprudência , Consentimento Livre e Esclarecido/ética , Adulto , Idoso , Inquéritos e Questionários , Percepção , Pesquisa Biomédica/ética , Pesquisa Biomédica/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Doadores de Tecidos/psicologia , Doadores de Tecidos/éticaRESUMO
BACKGROUND/AIMS: Assessment of the levels of vital blood parameters in donors is essential to evaluate their health status, ensure their suitability for donation, preserve the integrity of the circulatory system, and facilitate comprehensive health monitoring. The aim of our study was to analyse the levels of haemoglobin, haematocrit, erythrocyte count, MCV, MCH, and MCHC in 12 groups of first-time donors and experienced donors of both sexes at the John Paul II Regional Blood Donation and Treatment Centre in Slupsk, northern Poland. The donors were divided into three age groups (18-30 years, 31-45 years, and 46-65 years). METHODS: Using MANOVA multivariate significance tests, we examined the main effects of donor-related factors (age, sex, donor stage) on morphological blood parameters to evaluate different haematological parameters, such as Hb, Ht, RBC, MCV, MCH, and MCHC, and identified statistically significant relationships between all variables. RESULTS: The multivariate analysis of these three main factors showed that the variation in haemoglobin (Hb) levels accounted for 46% of the explained dependence in this statistical model. In particular, approximately half of the variability in the multivariate statistical analysis was attributed to the role of Hb and haematocrit (Ht). In addition, the ß-coefficient values for Hb and Ht were statistically higher in relation to donor sex and donor type (single versus repeat). These ß-coefficient values from our data represent the strength and direction of the relationship between the haematological parameters (Hb and Ht) and the specific donor characteristics. A higher ß-coefficient indicates a stronger influence of donor sex and donor type on these parameters, suggesting that these factors contribute significantly to the variation in the Hb and Ht levels. Based on our results, the comprehensive analysis of the entire statistical model of metabolic biomarkers revealed the following hierarchy: Hb > Ht > MCHC > MCV > RBC > MCH. The results obtained showed strong statistical relationships, as indicated by the high values of the key statistical indicators in our analysis. The coefficient of determination (R²) showed that the model explained a significant proportion of the variance in the data, while the F-test statistic confirmed the significance of the predictors. CONCLUSION: These strong statistical dependencies provided a clear justification for selecting this model over others, as it effectively represented the underlying relationships within the data. These statistics help to assess how well the model matches the actual data, thereby helping to reduce the risks associated with blood donation, optimise donor safety, and maintain the quality and efficiency of blood transfusion services.
Assuntos
Doadores de Sangue , Índices de Eritrócitos , Eritrócitos , Hemoglobinas , Humanos , Pessoa de Meia-Idade , Adulto , Masculino , Feminino , Hemoglobinas/análise , Hemoglobinas/metabolismo , Idoso , Hematócrito , Adolescente , Eritrócitos/citologia , Eritrócitos/metabolismo , Polônia , Adulto Jovem , Análise Multivariada , Contagem de EritrócitosRESUMO
Tom Nowakowski is an Assistant Professor at University of California San Francisco (UCSF), where he uses single-cell sequencing technologies to study neurodevelopment. He is also a Chan Zuckerberg Biohub Investigator and a Next Generation Leader at the Allen Institute for Brain Science. We met with Tom over Zoom to hear more about his career, his transition to becoming a group leader and his plans for the future.
Assuntos
Biologia do Desenvolvimento/história , Genética/história , História do Século XXI , Polônia , Estados UnidosRESUMO
BACKGROUND: Knowledge of genetic structure and the factors that shape it has an impact on forest management practices. European ash (Fraxinus excelsior L.) has declined dramatically throughout its range as a result of a disease caused by the fungus Hymenoscyphus fraxineus. Despite the need for conservation and restoration of the species, genetic data required to guide these efforts at the country level are scarce. Thereofore, we studied the chloroplast and nuclear genetic diversity of 26 natural common ash populations (1269 trees) in Poland. RESULTS: Chloroplast polymorphisms grouped the populations into two geographically structured phylogenetic lineages ascribed to different glacial refugia (the Balkans and the Eastern Alps). However, the populations demonstrated high genetic diversity (mean AR = 12.35; mean Ho = 0.769; mean He = 0.542) but low differentiation based on nuclear microsatellites (FST = 0.045). Significant spatial genetic structure, consistent with models of isolation by distance, was detected in 14 out of 23 populations. Estimated effective population size was moderate-to-high, with a harmonic mean of 57.5 individuals per population. CONCLUSIONS: Genetic diversity was not homogeneously distributed among populations within phylogenetic gene pools, indicating that ash populations are not equal as potential sources of reproductive material. Genetic differences among populations could be related to their histories, including founder effects or gene flow between evolutionary lineages (admixture). Our results suggest that ash stands across Poland could be treated as two main management units (seed zones). Therefore, despite the homogenizing effect of pollen gene flow known for this species, the genetic structure should be taken into account in the management of the genetic resources of the common ash. Although ash dieback poses an additional challenge for the management of genetic resources, efforts should be directed towards protecting populations with high genetic diversity within defined phylogenetic units, as they may be an important source of adaptive variation for future stands.
Assuntos
Ascomicetos , Fraxinus , Humanos , Fraxinus/genética , Fraxinus/microbiologia , Polônia , Filogenia , Florestas , Variação GenéticaRESUMO
BACKGROUND: Eliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it. METHODS: Patients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study. RESULTS: In the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy. CONCLUSIONS: In a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.
Assuntos
Antivirais , Hepatite C Crônica , Perda de Seguimento , Humanos , Masculino , Antivirais/uso terapêutico , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Polônia/epidemiologia , Resposta Viral Sustentada , Resultado do Tratamento , Hepacivirus/efeitos dos fármacosRESUMO
Pyruvate kinase (PK) deficiency is a rare autosomal recessive disorder characterized by chronic hemolytic anemia of variable severity. Nine Polish patients with severe hemolytic anemia but normal PK activity were found to carry mutations in the PKLR gene encoding PK, five already known ones and one novel (c.178C > T). We characterized two of the known variants by molecular modeling (c.1058delAAG) and minigene splicing analysis (c.101-1G > A). The former gives a partially destabilized PK tetramer, likely of suboptimal activity, and the c.101-1G > A variant gives alternatively spliced mRNA carrying a premature stop codon, encoding a severely truncated PK and likely undergoing nonsense-mediated decay.
Assuntos
Anemia Hemolítica Congênita não Esferocítica , Mutação , Piruvato Quinase , Erros Inatos do Metabolismo dos Piruvatos , Humanos , Piruvato Quinase/genética , Piruvato Quinase/deficiência , Polônia , Erros Inatos do Metabolismo dos Piruvatos/genética , Masculino , Feminino , Anemia Hemolítica Congênita não Esferocítica/genética , Criança , Pré-Escolar , Modelos Moleculares , Lactente , Adolescente , Códon sem Sentido , Processamento AlternativoRESUMO
OBJECTIVES: To characterize VIM-type metallo-ß-lactamase (MBL)-encoding genomic islands (GIs) in Pseudomonas aeruginosa and P. putida group isolates from Polish hospitals from 2001-2015/16. METHODS: Twelve P. aeruginosa and 20 P. putida group isolates producing VIM-like MBLs were selected from a large collection of these based on epidemiological and typing data. The organisms represented all major epidemic genotypes of these species spread in Poland with chromosomally located blaVIM gene-carrying integrons. The previously determined short-read sequences were complemented by long-read sequencing in this study. The comparative structural analysis of the GIs used a variety of bioinformatic tools. RESULTS: Thirty different GIs with blaVIM integrons were identified in the 32 isolates, of which 24 GIs from 26 isolates were integrative and conjugative elements (ICEs) of the clc family. These in turn were dominated by 21 variants of the GI2/ICE6441 subfamily with a total of 19 VIM integrons, each inserted in the same position within the ICE's Tn21-like transposon Tn4380. The three other ICEs formed a novel ICE6705 subfamily, lacking Tn4380 and having different VIM integrons located in another site of the elements. The remaining six non-ICE GIs represented miscellaneous structures. The presence of various integrons in the same ICE sublineage, and of the same integron in different GIs, indicated circulation and recombination of the integron-carrying genetic platforms across Pseudomonas species/genotypes. CONCLUSIONS: Despite the general diversity of the blaVIM-carrying GIs in Pseudomonas spp. in Poland, a clear predominance of broadly spread and rapidly evolving clc-type ICEs was documented, confirming their significant role in antimicrobial resistance epidemiology.
Assuntos
Ilhas Genômicas , Integrons , Infecções por Pseudomonas , beta-Lactamases , Polônia/epidemiologia , beta-Lactamases/genética , Integrons/genética , Humanos , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas/genética , Pseudomonas/enzimologia , Pseudomonas/isolamento & purificação , Antibacterianos/farmacologia , Genótipo , Testes de Sensibilidade Microbiana , Elementos de DNA Transponíveis/genéticaRESUMO
The human immunodeficiency virus type 1 (HIV-1) A6 sub-subtype is highly prevalent in Eastern Europe. Over the past decade, the dissemination of the A6 lineage has been expanding in Poland. The recent Russian invasion of Ukraine may further escalate the spread of this sub-subtype. While evolutionary studies using viral sequences have been instrumental in identifying the HIV epidemic patterns, the origins, and dynamics of the A6 sub-subtype in Poland remain to be explored. We analyzed 1185 HIV-1 A6 pol sequences from Poland, along with 8318 publicly available sequences from other countries. For analyses, phylogenetic tree construction, population dynamics inference, Bayesian analysis, and discrete phylogeographic modeling were employed. Of the introduction events to Poland, 69.94% originated from Ukraine, followed by 29.17% from Russia. Most A6 sequences in Poland (53.16%) formed four large clades, with their introductions spanning 1993-2008. Central and Southern Polish regions significantly influenced migration events. Transmissions among men who have sex with men (MSM) emerged as the dominant risk group for virus circulation, representing 72.92% of migration events. Sequences from migrants were found primarily outside the large clades. Past migration from Ukraine has fueled the spread of the A6 sub-subtype and the current influx of war-displaced people maintains the growing national epidemic.
Assuntos
Epidemias , Infecções por HIV , HIV-1 , Minorias Sexuais e de Gênero , Masculino , Humanos , Filogenia , Polônia/epidemiologia , Homossexualidade Masculina , HIV-1/genética , Infecções por HIV/epidemiologia , Teorema de BayesRESUMO
Understanding how the infectious disease burden was affected throughout the COVID-19 pandemic is pivotal to identifying potential hot spots and guiding future mitigation measures. Therefore, our study aimed to analyze the changes in the rate of new cases of Poland's most frequent infectious diseases during the entire COVID-19 pandemic and after the influx of war refugees from Ukraine. We performed a registry-based population-wide study in Poland to analyze the changes in the rate of 24 infectious disease cases from 2020 to 2023 and compared them to the prepandemic period (2016-2019). Data were collected from publicly archived datasets of the Epimeld database published by national epidemiological authority institutions. The rate of most of the studied diseases (66.6%) revealed significantly negative correlations with the rate of SARS-CoV-2 infections. For the majority of infectious diseases, it substantially decreased in 2020 (in case of 83%) and 2021 (63%), following which it mostly rebounded to the prepandemic levels and, in some cases, exceeded them in 2023 when the exceptionally high annual rates of new cases of scarlet fever, Streptococcus pneumoniae infections, HIV infections, syphilis, gonococcal infections, and tick-borne encephalitis were noted. The rate of Clostridioides difficile enterocolitis was two-fold higher than before the pandemic from 2021 onward. The rate of Legionnaires' disease in 2023 also exceeded the prepandemic threshold, although this was due to a local outbreak unrelated to lifted COVID-19 pandemic restrictions or migration of war refugees. The influx of war migrants from Ukraine could impact the epidemiology of sexually transmitted diseases. The present analysis indicates that continued efforts are needed to prevent COVID-19 from overwhelming healthcare systems again and decreasing the control over the burden of other infectious diseases. It also identifies the potential tipping points that require additional mitigation measures, which are also discussed in the paper, to avoid escalation in the future.
Assuntos
COVID-19 , Doenças Transmissíveis , Refugiados , Humanos , COVID-19/epidemiologia , Ucrânia/epidemiologia , Polônia/epidemiologia , Refugiados/estatística & dados numéricos , Doenças Transmissíveis/epidemiologia , SARS-CoV-2 , Feminino , Masculino , Pandemias , Adulto , Sistema de Registros , Efeitos Psicossociais da Doença , Conflitos ArmadosRESUMO
Urbanisation has been increasing worldwide in recent decades, driving environmental change and exerting novel selective pressures on wildlife. Phenotypic differences between urban and rural individuals have been widely documented in several taxa. However, the extent to which urbanisation impacts mating strategies is less known. Here, we investigated extra-pair paternity variation in great tits (Parus major) and blue tits (Cyanistes caeruleus) breeding in nestboxes set in a gradient of urbanisation in Warsaw, Poland, over three breeding seasons. Urbanisation was quantified as the amount of light pollution, noise pollution, impervious surface area (ISA) and tree cover within a 100-m radius around each nestbox. We obtained genotypes for 1213 great tits at 7344 SNP markers and for 1299 blue tits at 9366 SNP markers with a genotyping-by-sequencing method, and inferred extra-pair paternity by computing a genomewide relatedness matrix. We report higher extra-pair paternity in blue tits breeding in more urbanised areas, for example, with higher light pollution and ISA, and lower tree cover. However, no such trend was found in great tits. Late-stage survival of individual nestlings in both species was not associated with paternity or urbanisation proxies, thus we were not able to detect fitness benefits or drawbacks of being an extra-pair offspring in relation to urbanisation. Our results contribute to the growing body of knowledge reporting on the effects of urbanisation on avian ecology and behaviour, and confirm species-specific and population-specific patterns of extra-pair paternity variation.
Assuntos
Genótipo , Passeriformes , Polimorfismo de Nucleotídeo Único , Animais , Passeriformes/genética , Passeriformes/fisiologia , Polônia , Polimorfismo de Nucleotídeo Único/genética , Urbanização , Cruzamento , Comportamento Sexual Animal , Reprodução/genética , Masculino , Paternidade , FemininoRESUMO
BACKGROUND: Gallstone disease (GD) is common but remains asymptomatic in most cases. However, gallstones can lead to complications like choledocholithiasis or gallbladder cancer. In this study, we analyse the common genetic risk factor for GD, the p.D19H variant in the sterol transporter ABCG8, in Polish patients with gallstones and gallbladder cancer. METHODS: Three adult cohorts were prospectively recruited: 65 patients with gallbladder cancer, 170 obese individuals scheduled for bariatric surgery and 72 patients who underwent endoscopic retrograde cholangiopancreatography due to recurrent choledocholithiasis. The control cohort consisted of 172 gallstone-free adults. The ABCG8 p.D19H (rs11887534) polymorphism was genotyped using TaqMan assays. RESULTS: The minor allele frequency (MAF) of the ABCG8 p.D19H polymorphism was significantly (p = .02) higher among cases with either gallstones or gallbladder cancer (MAF = 8.4%) as compared to controls (MAF = 4.0%). The highest frequency of the risk allele was detected in patients with gallbladder cancer (18.5%) and obese patients with GD (17.5%), followed by individuals with choledocholithiasis (13.9%). Notably, the p.19H variant was associated with an increased risk of developing gallbladder cancer (OR 2.76, 95% CI 1.16-6.54, p = .01) and an increased risk of GD in obese individuals scheduled for bariatric surgery (OR = 2.70, 95% CI 1.05-6.49, p = .03), but did not significantly affect the risk of choledocholithiasis. CONCLUSIONS: The ABCG8 p.D19H common risk variant increases the risk of developing gallbladder cancer in Central Europeans and enhances the risk of gallstones in the obese. Carriers of the p.D19H variant might benefit from personalized preventive strategies, particularly regarding gallbladder cancer.
Assuntos
Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Neoplasias da Vesícula Biliar , Cálculos Biliares , Obesidade , Humanos , Masculino , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Feminino , Pessoa de Meia-Idade , Cálculos Biliares/genética , Obesidade/genética , Obesidade/complicações , Polônia/epidemiologia , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/epidemiologia , Adulto , Estudos de Casos e Controles , Idoso , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Frequência do Gene , Fatores de Risco , Polimorfismo GenéticoRESUMO
BACKGROUND: Comorbidities in primary care do not occur in isolation but tend to cluster together causing various clinically complex phenotypes. This study aimed to distinguish phenotype clusters and identify the risks of all-cause mortality in primary care. METHODS: The baseline cohort of the LIPIDOGEN2015 sub-study involved 1779 patients recruited by 438 primary care physicians. To identify different phenotype clusters, we used hierarchical clustering and investigated differences between clinical characteristics and mortality between clusters. We then performed causal analyses using causal mediation analysis to explore potential mediators between different clusters and all-cause mortality. RESULTS: A total of 1756 patients were included (mean age 51.2, SD 13.0; 60.3% female), with a median follow-up of 5.7 years. Three clusters were identified: Cluster 1 (n = 543) was characterised by overweight/obesity (body mass index ≥ 25 kg/m2), older (age ≥ 65 years), more comorbidities; Cluster 2 (n = 459) was characterised by non-overweight/obesity, younger, fewer comorbidities; Cluster 3 (n = 754) was characterised by overweight/obesity, younger, fewer comorbidities. Adjusted Cox regression showed that compared with Cluster 2, Cluster 1 had a significantly higher risk of all-cause mortality (HR 3.87, 95% CI: 1.24-15.91), whereas this was insignificantly different for Cluster 3. Causal mediation analyses showed that decreased protein thiol groups mediated the hazard effect of all-cause mortality in Cluster 1 compared with Cluster 2, but not between Clusters 1 and 3. CONCLUSION: Overweight/obesity older patients with more comorbidities had the highest risk of long-term all-cause mortality, and in the young group population overweight/obesity insignificantly increased the risk in the long-term follow-up, providing a basis for stratified phenotypic risk management.
Assuntos
Comorbidade , Fenótipo , Atenção Primária à Saúde , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Atenção Primária à Saúde/estatística & dados numéricos , Análise por Conglomerados , Adulto , Polônia/epidemiologia , Obesidade/epidemiologia , Mortalidade , Modelos de Riscos Proporcionais , Sobrepeso/epidemiologia , Estudos de Coortes , Fatores Etários , Causas de Morte , Índice de Massa Corporal , Fatores de Risco , Hipertensão/epidemiologiaRESUMO
OBJECTIVE: Primary tracheal tumors are very rare and their management is not definitely established. Due to its rarity, providing patient care in terms of optimal management poses a considerable challenge. The purpose of this study was to investigate treatment outcomes in patients with these rare tumors. METHODS: We carried out a retrospective analysis of 89 patients with primary tracheal tumors treated at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, over sixteen years. The study assessed patient demographics, tumor characteristics and treatment. Different treatment options were compared in terms of overall survival, disease-free survival, and progression-free survival. RESULTS: A total of 89 patients were included in the study. In the group presented, 45 patients underwent primary radical treatment and 44 were qualified for palliative treatment. Surgical resection was performed in 13 patients out of radically treated patients. The 5 year OS rates in the group of patients who underwent radical treatment and in the group of patients who underwent palliative treatment were 45.9% and 2.3%, respectively. In the group of patients who underwent radical surgical treatment, the 5 year OS was 76.9% compared to 35.8% in the group of patients who underwent nonsurgical treatment. CONCLUSION: A multidisciplinary team should decide treatment options, including in-depth consideration of surgical treatment options.
Assuntos
Neoplasias da Traqueia , Humanos , Masculino , Neoplasias da Traqueia/terapia , Neoplasias da Traqueia/mortalidade , Neoplasias da Traqueia/patologia , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais , Cuidados Paliativos/métodos , Adulto Jovem , Polônia/epidemiologia , AdolescenteRESUMO
Three new strains of Phaffia rhodozyma yeast have recently been isolated in Poland. The aim of this study was to phenotypically characterize these strains and to compare them with the properties of the reference strain. The potential for carotenoid biosynthesis in these strains was also determined, depending on temperature, carbon, and nitrogen sources in the medium. Phaffia rhodozyma yeasts were also identified by MALDI-TOF MS. There were minor differences in cell morphology among the strains. All strains reproduced asexually by budding and formed spherical chlamydospores. No ability for sexual reproduction was observed. Physiological tests showed minor variations between the reference strain and the isolates, likely due to the geographical specificity of the habitat from which they were originally isolated. Analysis of protein spectra showed that the tested yeast isolates had seven common peaks of different intensities, with masses at 2200, 2369, 3213, 3628, 3776, 3921, and 4710 m/z. Moreover, additional strain-dependent spectra were found. The amount of synthesized carotenoids varied with the carbon and nitrogen sources used, as well as the temperature. The best producer of carotenoids was the P. rhodozyma CMIFS 102 isolate.
Assuntos
Betula , Carotenoides , Polônia , Carotenoides/metabolismo , Betula/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Nitrogênio/metabolismo , Temperatura , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Carbono/metabolismoRESUMO
PURPOSE: Urolithiasis significantly affects patient quality of life, yet the global standard of care predominantly focuses on achieving a stone free status, often ignoring patient reported outcomes. Currently, there are no specific measures available to assess the quality of life in the Polish population suffering from kidney stones. Therefore, this study aimed to develop and validate the Polish version of the Wisconsin Stone Quality of Life Questionnaire. METHODS: The translation of WISQOL was carried out in accordance with the best available guidelines. Patients treated for kidney stones at a tertiary centre were recruited and completed both POL-WISQOL and SF36 questionnaires. Comprehensive analyses were conducted to assess internal consistency, inter-item and inter-domain correlations, as well as convergent and construct validity. Additionally, test-retest reliability was evaluated to ensure the accuracy and stability of the findings. RESULTS: A total of 102 participants fully completed both questionnaires and were included in the analysis. The translated survey demonstrated excellent internal consistency (Cronbach's coefficient 0.967) and significant convergent validity (Spearman's correlation = 0.847, p < 0.001). Furthermore, an ANOVA with Tukey's post hoc analysis revealed a significant decline in WISQOL scores between symptomatic and asymptomatic individuals, thereby confirming tool's construct validity. CONCLUSION: POL-WISQoL turned out to be a valid disease specific health related quality of life measuring tool. Its widespread utilisation has the potential to shift the standard of care towards patient centered outcomes.
Assuntos
Cálculos Renais , Qualidade de Vida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Cálculos Renais/psicologia , Polônia , Traduções , Inquéritos e Questionários , Idoso , Reprodutibilidade dos TestesRESUMO
Today, the biodiversity of endolithic microbial colonisations are only partly understood. In this study, we used a combination of molecular community metabarcoding using the 16S rRNA gene, light microscopy, CT-scan analysis, and Raman spectroscopy to describe gypsum endolithic communities in 2 sites-southern Poland and northern Israel. The obtained results have shown that despite different geographical areas, climatic conditions, and also physical features of colonized gypsum outcrops, both of these sites have remarkably similar microbial and pigment compositions. Cyanobacteria dominate both of the gypsum habitats, followed by Chloroflexi and Pseudomonadota. Among cyanobacteria, Thermosynechococcaceae were more abundant in Israel while Chroococcidiopsidaceae in Poland. Interestingly, no Gloeobacteraceae sequences have been found in Poland, only in Israel. Some of the obtained 16S rRNA gene sequences of cyanobacteria matched previously detected sequences from endolithic communities in various substrates and geographical regions, supporting the hypothesis of global metacommunity, but more data are still needed. Using Raman spectroscopy, cyanobacterial UV-screening pigments-scytonemin and gloeocapsin have been detected alongside carotenoids, chlorophyll a and melanin. These pigments can serve as potential biomarkers for basic taxonomic identification of cyanobacteria. Overall, this study provides more insight into the diversity of cyanobacterial endolithic colonisations in gypsum across different areas.
Assuntos
Sulfato de Cálcio , Cianobactérias , Cianobactérias/genética , Cianobactérias/metabolismo , Cianobactérias/classificação , Sulfato de Cálcio/química , Israel , Polônia , RNA Ribossômico 16S/genética , MicrobiotaRESUMO
PURPOSE: Amongst all etiologic hospital-acquired infection factors, K. pneumoniae strains producing New Delhi metallo-ß-lactamase (KP-NDM) belong to pathogens with the most effective antibiotic resistance mechanisms. Clinical guidelines recommend using ceftazidime/avibactam with aztreonam (CZA + AT) as the preferred option for NDM-producing Enterobacterales. However, the number of observations on such treatment regimen is limited. This retrospective study reports the clinical and microbiological outcomes of 23 patients with KP-NDM hospital-acquired infection treated with CZA + AT at a single center in Poland. METHODS: The isolates were derived from the urine, lungs, blood, peritoneal cavity, wounds, and peritonsillar abscess. In microbiological analysis, mass spectrometry for pathogen identification, polymerase chain reaction, or an immunochromatographic assay for detection of carbapenemase, as well as VITEK-2 system, broth microdilution, and microdilution in agar method for antimicrobial susceptibility tests were used, depending of the pathogens' nature. CZA was administered intravenously (IV) at 2.5 g every eight hours in patients with normal kidney function, and aztreonam was administered at 2 g every eight hours IV. Such dosage was modified when renal function was reduced. RESULTS: KP-NDM was eradicated in all cases. Four patients (17.4%) died: three of them had a neoplastic disease, and one - a COVID-19 infection. CONCLUSION: The combination of CZA + AT is a safe and effective therapy for infections caused by KP-NDM, both at the clinical and microbiological levels. The synergistic action of all compounds resulted in a good agreement between the clinical efficacy of CZA + AT and the results of in vitro susceptibility testing.