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1.
Appl Microbiol Biotechnol ; 108(1): 294, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598011

RESUMO

Understanding the dynamic change in abundance of both fecal and opportunistic waterborne pathogens in urban surface water under different abiotic and biotic factors helps the prediction of microbiological water quality and protection of public health during recreational activities, such as swimming. However, a comprehensive understanding of the interaction among various factors on pathogen behavior in surface water is missing. In this study, the effect of salinity, light, and temperature and the presence of indigenous microbiota, on the decay/persistence of Escherichia coli and Pseudomonas aeruginosa in Rhine River water were tested during 7 days of incubation with varying salinity (0.4, 5.4, 9.4, and 15.4 ppt), with light under a light/dark regime (light/dark) and without light (dark), temperature (3, 12, and 20 °C), and presence/absence of indigenous microbiota. The results demonstrated that light, indigenous microbiota, and temperature significantly impacted the decay of E. coli. Moreover, a significant (p<0.01) four-factor interactive impact of these four environmental conditions on E. coli decay was observed. However, for P. aeruginosa, temperature and indigenous microbiota were two determinate factors on the decay or growth. A significant three-factor interactive impact between indigenous microbiota, temperature, and salinity (p<0.01); indigenous microbiota, light, and temperature (p<0.01); and light, temperature, and salinity (p<0.05) on the decay of P. aeruginosa was found. Due to these interactive effects, caution should be taken when predicting decay/persistence of E. coli and P. aeruginosa in surface water based on a single environmental condition. In addition, the different response of E. coli and P. aeruginosa to the environmental conditions highlights that E. coli monitoring alone underestimates health risks of surface water by non-fecal opportunistic pathogens, such as P. aeruginosa. KEY POINTS: Abiotic and biotic factors interactively affect decay of E. coli and P. aeruginosa E.coli and P.aeruginosa behave significantly different under the given conditions Only E. coli as an indicator underestimates the microbiological water quality.


Assuntos
Escherichia coli , Pseudomonas aeruginosa , Rios , Fezes , Água Doce
2.
Eur J Cancer ; 202: 114025, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38531266

RESUMO

BACKGROUND: Approximately 30% of patients with clinical stage I non-seminoma (CSI-NS) relapse. Current risk stratification is based on lymphovascular invasion (LVI) alone. The extent to which additional tumor characteristics can improve risk prediction remains unclear. OBJECTIVE: To determine the most important prognostic factors for relapse in CSI-NS patients. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study including all patients with CSI-NS diagnosed in Denmark between 2013 and 2018 with follow-up until 2022. Patients were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histological slides from the orchiectomy specimens were retrieved. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Histological slides were reviewed blinded to the clinical outcome. Clinical data were obtained from medical records. The association between prespecified potential prognostic factors and relapse was assessed using Cox regression analysis. Model performance was evaluated by discrimination (Harrell's C-index) and calibration. RESULTS: Of 453 patients included, 139 patients (30.6%) relapsed during a median follow-up of 6.3 years. Tumor invasion into the hilar soft tissue of the testicular hilum, tumor size, LVI and embryonal carcinoma were independent predictors of relapse. The estimated 5-year risk of relapse ranged from < 5% to > 85%, depending on the number of risk factors. After internal model validation, the model had an overall concordance statistic of 0.75. Model calibration was excellent. CONCLUSION AND RELEVANCE: The identified prognostic factors provide a much more accurate risk stratification than current clinical practice, potentially aiding clinical decision-making.


Assuntos
Seminoma , Neoplasias Testiculares , Masculino , Humanos , Prognóstico , Estadiamento de Neoplasias , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Estudos de Coortes , Doença Crônica , Seminoma/cirurgia , Seminoma/patologia , Orquiectomia
3.
Biomedicines ; 12(2)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38398058

RESUMO

The Rh system, including the highly immunogenic D antigen, is one of the clinically most important blood group systems in transfusion medicine. Numerous alleles of the RHD gene are associated with variant RhD phenotypes. In case of Rh incompatibility, some of them can induce hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. Thus, accurate blood group diagnostics are critical for safe transfusion therapy. We characterized phenotypes of four individuals revealing weakened D expression during routine pre-transfusion testing. Standard gel card matrix techniques with monoclonal and polyclonal anti-D antibodies were used for serological typing, complemented using D epitope and antigen density analysis. Genotyping employing PCR with sequence-specific primers, genomic and allele-specific Sanger sequencing and in silico protein analysis were performed. Four novel RHD alleles associated with weak D or partial D phenotypes were identified. One of the mutations is predicted to disrupt the terminal stop codon and result in an elongated translation of the mutant D protein that phenotypically exhibits a loss of D epitopes. Furthermore, a hybrid gene formed with the homologue RHCE gene is described. The presented data enhances the understanding of the Rh system and may contribute to continued advances in blood group diagnostics.

4.
Orthopadie (Heidelb) ; 53(3): 201-208, 2024 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-38349524

RESUMO

BACKGROUND: Unicompartmental knee arthroplasty (UKA), in addition to total knee arthroplasty (TKA), has been shown to be effective in the surgical treatment of knee osteoarthritis with appropriate patient selection. In clinical studies, it has demonstrated superior functional results with lower complication rates. In clinical practice, these advantages must be weighed against the disadvantage of an increased revision rate, especially in younger patients with sports and work activities. OBJECTIVES: The aim of this study was to compare the functional outcome as well as the time to return to daily activities, work, and sports after revision of UKA to TKA with those of primary UKA and primary TKA using a matched-pair analysis. MATERIALS AND METHODS: The study was based on a matched-pair analysis at two defined time points, always comparing 28 patients who underwent either revision of a UKA to a TKA, primary UKA, or primary TKA. Patients completed the Oxford Knee Score, UCLA score, Knee Society score, and WOMAC score during standardized follow-up. In addition, postoperative patient satisfaction and return to activities of daily living, work, and sports were recorded in a standardized manner, and a clinical examination was performed. RESULTS: The four functional scores studied showed a common trend in favor of UKA, followed by primary TKA and revision TKA. The differences between converted UKA and primary TKA were not significant. However, at 3.2 years after the last surgery, the results of the converted UKA were significantly lower than those of the primary UKA. Return to work and sports tended to occur the earliest after UKA, followed by TKA and the revision group. All groups showed a tendency to engage in low-impact sports. CONCLUSION: The functional results of revised UKA were significantly inferior to those of primary UKA based on a 3-year follow-up. Return to work, sports, and activities of daily living tended to take longer after revision than after primary implantation of either a UKA or a TKA.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Esportes , Humanos , Artroplastia do Joelho/efeitos adversos , Volta ao Esporte , Atividades Cotidianas , Osteoartrite do Joelho/cirurgia
5.
J Neurol Sci ; 457: 122893, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38278097

RESUMO

Nodding Syndrome is a poorly understood epilepsy disorder in sub-Saharan Africa. The cause(s) of the disease, risk factors and long-term outcomes are unknown or controversial. The objectives of this study were to describe the long-term clinical course and treatment outcomes of individuals suffering from Nodding Syndrome. In addition, we aimed to provide a comprehensive characterization of the epileptological and social features of patients with Nodding Syndrome. From 11/2014 to 4/2015, we conducted a hospital-based, cross-sectional and observational study in Mahenge, Tanzania. Seventy-eight individuals (female:male ratio: 40:38, age at examination: 21.1 ± 6.39 (SD) years) have been enrolled, of whom 38 (49%) had also been examined in 2005 and in 2009. The 10-year clinical course analysis of this revisited subgroup revealed a calculated case fatality of 0.8-2.3%. Progressive physical or cognitive deterioration has not been observed in any of the 78 individuals and more than half of the people studied (38/69; 55%) managed to live and work independently. 14/78 individuals (18%) were seizure-free, (no head nodding, no other seizure types), 13 of whom were taking antiseizure medication. Phenytoin was more effective against head nodding seizures (14/19 (74%)) than monotherapy with other available antiseizure medication (phenobarbitone 12/25 (48%) and carbamazepine 7/22 (32%), p = 0.02, chi-square test). Our ten-year clinical outcome data show that Nodding Syndrome is not a fatal disease, however, the response to treatment is worse than in epilepsy patients in general. Phenytoin may be more effective than carbamazepine and phenobarbitone, but further studies are needed to confirm this observation.


Assuntos
Epilepsia , Síndrome do Cabeceio , Humanos , Masculino , Feminino , Anticonvulsivantes/uso terapêutico , Fenitoína/uso terapêutico , Síndrome do Cabeceio/tratamento farmacológico , Síndrome do Cabeceio/epidemiologia , Estudos Transversais , Epilepsia/tratamento farmacológico , Fenobarbital/uso terapêutico , Carbamazepina/efeitos adversos , Resultado do Tratamento , Benzodiazepinas/uso terapêutico , Progressão da Doença
6.
Eur Urol Oncol ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38199869

RESUMO

BACKGROUND AND OBJECTIVE: Optimal treatment outcomes in patients with metastatic nonseminoma testicular cancer are achieved with chemotherapy and subsequent surgery in cases with residual tumor. In Denmark, postchemotherapy retroperitoneal lumpectomy (RPLP) is performed in patients with residual tumors >1 cm. There is a need to clarify whether this surgical method provides acceptable treatment results. Our objective was to describe morbidity and oncological outcomes of postchemotherapy RPLP. METHODS: This was a retrospective population-based multicenter study including patients with nonseminoma testicular cancer and postchemotherapy RPLP performed in Denmark between 1990 and 2015. A total of 219 patients were eligible, with median follow-up of 19 yr. Postoperative complications were evaluated according to the Clavien-Dindo classification. The cumulative incidence of recurrence inside or outside the borders of a bilateral surgical template, progression-free survival (PFS), and overall survival estimates were calculated using the Kaplan-Meier method. KEY FINDINGS AND LIMITATIONS: After median follow-up of 19 yr, 31/219 patients (14%) experienced a surgical complication, of which 5% were Clavien-Dindo grade ≥III. In total, 37 patients experienced a recurrence. The 5-yr, 10-yr, and 20-yr cumulative risk of recurrence inside a bilateral template was 4.3%, 5.9%, and 5.9%, respectively. The 10-yr PFS rate was 83% and the 10-yr overall survival rate was 96%. The main limitation of the study is the retrospective design. CONCLUSIONS AND CLINICAL IMPLICATIONS: With few patients experiencing a major postoperative complication and a 10-yr cumulative rate of 5.9% for recurrence inside a bilateral surgical template, postchemotherapy RPLP appears to be a safe alternative to template surgery for disseminated nonseminoma. PATIENT SUMMARY: We looked at minimal surgery to remove tumor tissue remaining after chemotherapy in patients with testicular cancer. We found a low frequency of complications, tumor recurrence, and death.

7.
J Clin Oncol ; 42(1): 81-89, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37683134

RESUMO

PURPOSE: Approximately 20% of patients with clinical stage I seminoma relapse. Tumor size and rete testis invasion have been identified as risk factors for relapse. However, the level of evidence supporting the use of these risk factors in clinical decision making is low. Previous studies have been hampered by selection bias and variable pathology reporting that limit interpretation and generalization of results. We assessed prognostic factors for relapse in an unselected nationwide population-based setting with centralized pathology review. METHODS: Patients with clinical stage I seminoma diagnosed from January 2013 to December 2018 were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histologic slides from the orchiectomy specimens were retrieved and reviewed blinded to the clinical outcome. Clinical data were obtained from medical records with follow-up until July 2022. The association between prespecified potential clinical and histopathologic prognostic factors and relapse was assessed by the use of Cox regression analysis. RESULTS: Of 924 patients included, 148 (16%) patients relapsed during a median follow-up of 6.3 years. Invasion of the testicular hilum (rete testis and hilar soft tissue), lymphovascular invasion, and elevated preorchiectomy levels of ß-human chorionic gonadotropin and lactate dehydrogenase were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 6% in patients with no risk factors to 62% in patients with all four risk factors with tumor extension into the hilar soft tissue of the testicular hilum. After internal model validation, the prognostic model had an overall concordance statistic of 0.70. CONCLUSION: The provided prognostic factors could replace current risk factors in guidelines and be used in future studies investigating risk-adapted follow-up and treatment strategies.


Assuntos
Seminoma , Neoplasias Testiculares , Masculino , Humanos , Prognóstico , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Estadiamento de Neoplasias , Estudos de Coortes , Seminoma/cirurgia , Seminoma/patologia , Estudos Prospectivos , Recidiva Local de Neoplasia/patologia , Doença Crônica , Recidiva
8.
Mol Genet Genomic Med ; 12(1): e2286, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37968878

RESUMO

BACKGROUND: Safe transfusion therapy requires accurate testing of blood donors and recipients to determine their ABO blood group compatibility. Genotyping does not always clarify serological blood typing discrepancies and conventional PCR methods are not suitable to identify ABO haplotypes. Therefore, an allele-specific long-range sequencing-based typing method was established. METHODS: Study samples (n = 100) and six patient samples were ABO phenotyped and screened for specific single nucleotide polymorphisms (SNP) in the ABO gene. Based on identified heterozygous SNPs in intron 1 (12897G>A), 2 (437C>T) or 4 (102C>A, 1511G>T) both ABO alleles were investigated separately using a high-fidelity long-range PCR system and Sanger sequencing. The alleles were correlated to the ABO phenotypes determined. RESULTS: Direct sequencing of allelic PCR products up to 6743 bases has been successful in discriminating common combinations of the ABO*A1.01, ABO*A2.01, ABO*B.01, ABO*O.01.01, ABO*O.01.02 and ABO*O.02.01 alleles. 10 out of 64 haplotypes were found to be not previously described. The uncommon ABO*AW.31.01 and the unusual O alleles ABO*O.05 and ABO*O.02.03 alleles were detected in patient samples, resolving the initial inconclusive serologic ABO typing results. CONCLUSION: This method is an effective tool for analyzing ABO haplotypes. Applicable for ABO molecular diagnostics and immunohematology research it may help to improve pre-transfusion blood type testing.


Assuntos
Sistema ABO de Grupos Sanguíneos , Humanos , Alelos , Haplótipos , Genótipo , Fenótipo , Sistema ABO de Grupos Sanguíneos/genética
9.
Clin Genitourin Cancer ; 22(1): e106-e112.e4, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37673783

RESUMO

INTRODUCTION: Mild Leydig cell insufficiency affects a substantial proportion of testicular cancer survivors. Previous studies have not shown a beneficial effect of testosterone replacement therapy, however, with a pronounced interindividual effect. Thus, biomarkers identifying the subgroups that might benefit are wanted. We aimed to determine if insulin-like factor 3 (INSL3), basal and human chorionic gonadotropin (hCG)-stimulated testosterone can predict the effect of testosterone replacement therapy in testicular cancer survivors with mild Leydig cell insufficiency. PATIENTS AND METHODS: We randomized adult testicular cancer survivors with mild Leydig cell insufficiency 1:1 to 12 months of transdermal testosterone replacement therapy (Tostran gel 2%) or placebo. INSL3, basal, and hCG-stimulated testosterone were measured at baseline. Outcomes (glucose, insulin, HbA1C, lipids, blood pressure, and body composition) were measured at baseline, 6 and 12 months. We applied a linear mixed-effect model comparing patients receiving testosterone with placebo in subgroups by biomarker. RESULTS: We included and randomized 69 patients between October 2016 and February 2018. Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had a -1.7 kg (95% CI: -3.1, -0.4) and -2.0 kg (95% CI: -3.5, -0.6) change in fat mass after 12 months of testosterone replacement therapy compared with placebo. This was not the case in patients with INSL3 and hCG-stimulated testosterone above the median. We did not find any effect of these biomarkers on glucose, insulin, HbA1c, or lipids. CONCLUSION: Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had decreased fat mass after 12 months of testosterone replacement therapy compared with placebo. It should be evaluated in larger trials if these biomarkers can be used as predictive markers identifying testicular cancer patients with mild Leydig cell insufficiency who might benefit from testosterone substitution.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Testosterona , Masculino , Adulto , Humanos , Células Intersticiais do Testículo , Neoplasias Testiculares/tratamento farmacológico , Hemoglobinas Glicadas , Proteínas/farmacologia , Gonadotropina Coriônica , Insulina/uso terapêutico , Insulina/farmacologia , Biomarcadores , Sobreviventes , Glucose/farmacologia , Lipídeos/farmacologia
10.
Pest Manag Sci ; 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38041619

RESUMO

BACKGROUND: Invasive ants, such as Linepithema humile (the Argentine ant), pose a global threat, necessitating a better understanding of their behaviour in order to improve management strategies. Traditional eradication methods, including baiting, have had limited success, but the causes of control failure are not always clear. This study aims to investigate whether ants form associations between food odours and corpses, and subsequently avoid areas or food sources with food odours associated with corpses. We propose that ants may learn to avoid toxic baits in part because of their association with ant corpses, which could have implications for pest control strategies. RESULTS: Ants were tested on a Y-maze after exposure to scented corpses or dummies. 69% (n = 64) of ants avoided branches bearing the scent of scented corpses. Colonies neglected food with corpse-associated odours, with only 42% (n = 273) of foragers feeding from such sources. However, if corpses were produced by feeding ants scented toxicant, focal ants encountering these corpses did not avoid the corpse-associated scent on a Y-maze (53%, n = 65). In dual-feeder tests, ants did not avoid feeding at food sources scented with odours associated with conspecific corpses. CONCLUSION: Conspecific corpses act as a negative stimulus for ants in a foraging situation, potentially causing avoidance of toxic baits. This study suggests adding odours to baits and cycling them to disrupt the bait-corpse association may be helpful. Interestingly, although avoidance of baits was observed, feeding preferences were not significantly affected. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

11.
Eur Urol Oncol ; 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37951820

RESUMO

BACKGROUND: The relapse rate in patients with clinical stage I (CSI) seminomatous germ cell tumor of the testis (SGCTT) who were undergoing surveillance after radical orchidectomy is 4-30%, depending on tumor size and rete testis invasion (RTI). However, the level of evidence supporting the use of both risk factors in clinical decision-making is low. OBJECTIVE: We aimed to identify the most important prognostic factors for relapse in CSI SGCTT patients. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 1016 CSI SGCTT patients diagnosed between 1994 and 2019 with normal postorchidectomy serum tumor marker levels and undergoing surveillance were collected from nine institutions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox proportional hazard regression models were fit to identify the most important prognostic factors. The primary endpoint was the time to first relapse by imaging and/or markers. Relapse probabilities were estimated by the Kaplan-Meier method. RESULTS AND LIMITATIONS: After a median follow-up of 7.7 yr, 149 (14.7%) patients had relapsed. Categorical tumor size (≤2, >2-5, and >5 cm), presence of RTI, and lymphovascular invasion were used to form three risk groups: low (56.4%), intermediate (41.3%), and high (2.3%) risks with 5-yr cumulative relapse probabilities of 8%, 20%, and 44%, respectively. The model outperformed the currently used model with tumor size ≤4 versus >4 cm and presence of RTI (Harrell's C index 0.65 vs 0.61). The low- and intermediate-risk groups were validated successfully in an independent cohort of 285 patients. CONCLUSIONS: The risk of relapse after radical orchidectomy in CSI SGCTT patients under surveillance is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse. PATIENT SUMMARY: The risk of relapse after radical orchidectomy in patients with clinical stage I seminomatous germ cell tumor of the testis is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse.

12.
Sci Rep ; 13(1): 20097, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973837

RESUMO

Quantifying the potential of a braided riverscape to be colonized by a plant species is essential for assessing the ecological state of the river and provides an important basis for nature conservation planning and the implementation of restoration measures. Common connectivity indices are largely unsuitable for describing the situation for the mostly wind-dispersed plant species. Our approach provides a set of comparable metrics that allows the quantification of the colonization potential of riverscapes at the patch and riverscape level. We propose a set of cell-based, spatially explicit measures that can easily be implemented. We demonstrate their application using two typical plant species and three riverscapes with different habitat configurations as examples. Our metrics consider shape, size and the spatial configuration of habitat patches, along with the dispersal characteristics of the respective species. The metrics provide a linear, balanced, and realistic representation of the colonization potential at the cell, patch, and riverscape levels. The results are comparable between different riverscapes and species, can be easily extended and used for further modeling. The metrics provide a valuable tool for the planning and evaluation of conservation, restoration, and reintroduction measures and close the gap between habitat availability analyses and large-scale terrestrial connectivity indices.


Assuntos
Ecossistema , Vento , Rios
13.
ACS Omega ; 8(42): 39830-39846, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37901541

RESUMO

Oil shale deposits of the Late Cretaceous from three boreholes in central Jordan were examined to assess the impact of thermal maturation on the content of nannofossils. Thermal activity has been shown to have a strong effect on organic matter content and composition but its effect on calcareous nannofossil assemblages remains inconclusive. This study aims to determine the impact of thermal maturation on nannofossil assemblages and to compare this to an estimated maturity level based on bulk geochemical analysis. Micropaleontological and geochemical analyses were conducted on 31 samples from three oil shale wells drilled in Attarat Um Ghudran central Jordan. Several types of nannofossil preservation have been recorded, including dissolution, overgrowth, and breakage. In the Jordan oil shale sections, nannofossils exhibit a variety of preservation types, with intense dissolution in the middle part of the study sections. The vast majority of the samples had high TOC enrichment, with 29 samples exceeding values of >10%. Kerogen recovery and quality from the oil shale are very good, with a predominance of fluorescent amorphous organic matter (AOM) and minor algal components. The low fluorescence preservation index (FPI), which is 1 in most of the samples, indicates that alteration occurred due to intense thermal activities in the study interval. The palynomorph and AOM fluorescence, ranging from a spore coloration index (SCI) of 3 to 5, suggest that the studied samples were approaching the oil window. A correlation between the nannofossil preservation and geochemical parameters shows a predominance of poorly preserved nannofossils along with high total organic carbon contents and an elevated hydrogen index (HI). We show that low FPI values and a higher level of maturity are associated with poor nannofossil preservation, suggesting that nannofossils, in conjunction with petrographic analysis of kerogen, could be used as a rapid screening technique for estimating levels of oil-shale maturity. The nature of the tectonism in the study area, including faulting and a metamorphosed zone, enhanced the maturity, which might explain why the nannofossils were so significantly affected.

14.
Cell Mol Life Sci ; 80(11): 333, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37878054

RESUMO

The conserved multiple PDZ-domain containing protein PATJ stabilizes the Crumbs-Pals1 complex to regulate apical-basal polarity and tight junction formation in epithelial cells. However, the molecular mechanism of PATJ's function in these processes is still unclear. In this study, we demonstrate that knockout of PATJ in epithelial cells results in tight junction defects as well as in a disturbed apical-basal polarity and impaired lumen formation in three-dimensional cyst assays. Mechanistically, we found PATJ to associate with and inhibit histone deacetylase 7 (HDAC7). Inhibition or downregulation of HDAC7 restores polarity and lumen formation. Gene expression analysis of PATJ-deficient cells revealed an impaired expression of genes involved in cell junction assembly and membrane organization, which is rescued by the downregulation of HDAC7. Notably, the function of PATJ regulating HDAC7-dependent cilia formation does not depend on its canonical interaction partner, Pals1, indicating a new role of PATJ, which is distinct from its function in the Crumbs complex. By contrast, polarity and lumen phenotypes observed in Pals1- and PATJ-deficient epithelial cells can be rescued by inhibition of HDAC7, suggesting that the main function of this polarity complex in this process is to modulate the transcriptional profile of epithelial cells by inhibiting HDAC7.


Assuntos
Polaridade Celular , Junções Íntimas , Bioensaio , Regulação para Baixo , Histona Desacetilases/genética
15.
Transfus Med Hemother ; 50(4): 294-302, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37767286

RESUMO

Introduction: The coronavirus disease (COVID-19) pandemic gave rise to studies investigating the association of ABO blood group with COVID-19 susceptibility. It is hypothesized that ABO antibodies might play a role in neutralizing SARS-CoV-2. However, ABO antibodies were exclusively analyzed in blood samples. Investigation of ABO antibodies in saliva, an easy-to-obtain surrogate for respiratory secretions, may provide novel insights into mucosal immunity crucial in early defense against respiratory pathogens. Methods: In this study, saliva and serum samples from healthy individuals with known blood groups were investigated using a flow cytometric method for separate anti-A/anti-B IgA, IgM, and IgG class antibody detection. Saliva samples were additionally tested using hemagglutination-based neutral and indirect anti-human globulin test gel cards. This method comparison was complemented by dilution experiments with a high-titer anti-A/anti-B WHO standard. Results: In saliva, IgA was the most abundant ABO antibody class, followed by IgM; IgG was detected only in low levels in all non-AB blood types. In serum, IgM was the predominant ABO antibody class in all non-AB blood types, followed by IgA and IgG, the latter mainly detected in group O individuals. Saliva and serum samples of group O individuals yielded the highest variability of ABO-specific antibody levels. Regardless of sample material and blood type, major interindividual differences in ABO antibody reactivities were recorded. Antibody levels correlated moderately between these two body fluids. There were no significant sex and age-group differences in ABO antibody levels in both serum and saliva. WHO standard dilution experiments yielded technique-specific limits of detection, illustrating the inherent differences of immunofluorescence versus agglutination. Conclusion: For the first time, salivary ABO antibodies were investigated by separate detection of the three most relevant antibody classes IgA, IgM, and IgG in a healthy cohort. This study opens new perspectives regarding mucosal ABO antibody class profiles and their potential influence on respiratory infections.

17.
Water Res ; 244: 120534, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37659177

RESUMO

The removal of micropollutants from wastewater by constructed wetlands (CWs) has been extensively studied and reviewed over the past years. However, most studies do not specifically focus on the removal of micropollutants from the effluent of conventional wastewater treatment plants (WWTP) that still contains micropollutants, but on the removal of micropollutants from raw wastewater. Raw wastewater has a significantly different composition compared to WWTP effluent, which positively or negatively affects micropollutant removal mechanisms. To determine the optimal CW design for post-treatment of WWTP effluent to achieve additional micropollutant removal, this review analyzes the removal of 16 Dutch indicator micropollutants for post-treatment technology evaluation from WWTP effluent by different types of CWs. It was concluded that CW systems with organic enhanced adsorption substrates reach the highest micropollutant removal efficiency as a result of adsorption, but that the longevity of the enhanced adsorption effect is not known in the systems studied until now. Aerobic biodegradation and photodegradation are other relevant removal mechanisms for the studied micropollutants. However, a current knowledge gap is whether active aeration to stimulate the aerobic micropollutant biodegradation results in an increased micropollutant removal from WWTP effluent. Further knowledge gaps that impede the wider application of CW systems for micropollutant removal from WWTP effluent and allow a fair comparison with other post-treatment technologies for enhanced micropollutant removal, such as ozonation and activated carbon adsorption, relate to i) saturation of enhanced adsorption substrate; ii) the analysis of transformation products and biological effects; iii) insights in the relationship between microbial community composition and micropollutant biodegradation; iv) plant uptake and in-plant degradation of micropollutants; v) establishing design rules for appropriate hydraulic loading rates and/or hydraulic retention times for CWs dedicated to micropollutant removal from WWTP effluent; and vi) the energy- and carbon footprint of different CW systems. This review finishes with detailed suggestions for future research directions that provide answers to these knowledge gaps.


Assuntos
Águas Residuárias , Áreas Alagadas , Adsorção , Biodegradação Ambiental , Transporte Biológico
18.
Sci Rep ; 13(1): 13530, 2023 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598245

RESUMO

In the northern forelands of the Alps, farmers report an increase of Jacobaea aquatica in production grasslands. Due to its toxicity, the species affects grassland productivity and calls for costly control measures. We are investigating the extent to which management practices or climatic factors are responsible for the increase of the species and how the situation will change due to climate change. We tested for effects of management intensity, fertilization, agri-environmental measures, and soil disturbance, and modeled the occurrence of the species under rcp4.5 and rcp8.5 scenarios. The main determinants of the occurrence of the species are soil type and summer rainfall. A high risk is associated with wet soils and > 400 mm of rain between June and August; an influence of the management-related factors could not be detected. Under the climate-change scenarios, the overall distribution decreases and shifts to the wetter alpine regions. Thus, the current increase is rather a shift in the occurrence of the species due to the altered precipitation situation. Under future climatic conditions, the species will decline and retreat to higher regions in the Alps. This will decrease the risk of forage contamination for production grassland in the lowlands.


Assuntos
Síndrome Linfoproliferativa Autoimune , Plantas Tóxicas , Pradaria , Chuva , Solo
19.
Pharmaceutics ; 15(8)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37631325

RESUMO

Metformin is the most commonly prescribed glucose-lowering drug for the treatment of type 2 diabetes. The aim of this study was to investigate whether metformin is capable of impeding the oxidation of LDL, a crucial step in the development of endothelial dysfunction and atherosclerosis. LDL was oxidized by addition of CuCl2 in the presence of increasing concentrations of metformin. The extent of LDL oxidation was assessed by measuring lipid hydroperoxide and malondialdehyde concentrations, relative electrophoretic mobilities, and oxidation-specific immune epitopes. Cytotoxicity of oxLDL in the vascular endothelial cell line EA.hy926 was assessed using the alamarBlue viability test. Quantum chemical calculations were performed to determine free energies of reactions between metformin and radicals typical for lipid oxidation. Metformin concentration-dependently impeded the formation of lipid hydroperoxides, malondialdehyde, and oxidation-specific immune epitopes when oxidation of LDL was initiated by addition of Cu2+. The cytotoxicity of oxLDL was reduced when it was obtained under increasing concentrations of metformin. The quantum chemical calculations revealed that only the reaction of metformin with hydroxyl radicals is exergonic, whereas the reactions with hydroperoxyl radicals or superoxide radical anions are endergonic. Metformin, beside its glucose-lowering effect, might be a suitable agent to impede the development of atherosclerosis and associated CVD. This is due to its capability to impede LDL oxidation, most likely by scavenging hydroxyl radicals.

20.
PLoS Negl Trop Dis ; 17(8): e0011503, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37535695

RESUMO

Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, ß-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.


Assuntos
Epilepsia , Volvo Intestinal , Síndrome do Cabeceio , Onchocerca volvulus , Oncocercose , Animais , Humanos , Oncocercose/epidemiologia , Síndrome do Cabeceio/epidemiologia , Síndrome do Cabeceio/etiologia , Volvo Intestinal/complicações , Epilepsia/epidemiologia , Uganda/epidemiologia , Citocinas
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