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Adjuvant immunotherapy has been recently recommended for patients with metastatic ccRCC, but there are no tissue biomarkers to predict treatment response in ccRCC. Potential predictive biomarkers are mainly assessed in primary tumor tissue, whereas metastases remain understudied. To explore potential differences between genomic alterations and immune phenotypes in primary tumors and their matched metastases, we analyzed primary tumors (PTs) of 47 ccRCC patients and their matched distant metastases (METs) by comprehensive targeted parallel sequencing, whole-genome copy number variation (CNV) analysis, determination of microsatellite instability (MSI) and tumor mutational burden (TMB). We quantified the spatial distribution of tumor-infiltrating CD8+ T cells, and co-expression of the T-cell-exhaustion marker TOX by digital immunoprofiling and quantified tertiary lymphoid structures (TLS). Most METs were pathologically "cold". Inflamed, pathologically "hot" PTs were associated with a decreased disease-free survival (DFS), worst for patients with high levels of CD8+TOX+ T cells. Interestingly, inflamed METs showed a relative increase of exhausted CD8+TOX+ T cells and increased accumulative size of TLS compared to PTs. Integrative analysis of molecular and immune phenotypes revealed BAP1 and CDKN2A/B deficiency to be associated with an inflamed immune phenotype. Our results highlight the distinct spatial distribution and differentiation of CD8+ T cells at metastatic sites, and the association of an inflamed microenvironment with specific genomic alterations.
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Opinions on abortion are more polarized than opinions on most other moral issues. Why are some people pro-choice and some pro-life? Religious and political preferences play a role here, but pro-choice and pro-life people may also differ in other aspects. In the current preregistered study (N = 479), we investigated how pro-choice women differ in their moral foundations from pro-life women. When the Moral Foundations Questionnaire (MFQ) was applied (i.e., when declared moral principles were measured), pro-life women scored higher than pro-choice women in loyalty, authority, and purity. However, when women were asked about moral judgments indirectly via more real-life problems from the Moral Foundations Vignettes (MFV), pro-choice women scored higher than pro-life women in emotional and physical care and liberty but lower in loyalty. When we additionally controlled for religious practice and political views, we found no differences between groups in declaring moral foundations (MFQ). However, in the case of real-life moral judgments (MFV), we observed higher care, fairness, and liberty among pro-choice and higher authority and purity among pro-life. Our results show intriguing nuances between women pro-choice and pro-life as we found a different pattern of moral foundations in those groups depending on whether we measured their declared abstract moral principles or moral judgment about real-life situations. We also showed how religious practice and political views might play a role in such differences. We conclude that attitudes to abortion "go beyond" abstract moral principles, and the real-life context matters in moral judgments. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-023-04800-0.
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CD8+ tumor-infiltrating T cells can be regarded as one of the most relevant predictive biomarkers in immune-oncology. Highly infiltrated tumors, referred to as inflamed (clinically "hot"), show the most favorable response to immune checkpoint inhibitors in contrast to tumors with a scarce immune infiltrate called immune desert or excluded (clinically "cold"). Nevertheless, quantitative and reproducible methods examining their prevalence within tumors are lacking. We therefore established a computational diagnostic algorithm to quantitatively measure spatial densities of tumor-infiltrating CD8+ T cells by digital pathology within the three known tumor compartments as recommended by the International Immuno-Oncology Biomarker Working Group in 116 prospective metastatic melanomas of the Swiss Tumor Profiler cohort. Workflow robustness was confirmed in 33 samples of an independent retrospective validation cohort. The introduction of the intratumoral tumor center compartment proved to be most relevant for establishing an immune diagnosis in metastatic disease, independent of metastatic site. Cut-off values for reproducible classification were defined and successfully assigned densities into the respective immune diagnostic category in the validation cohort with high sensitivity, specificity, and precision. We provide a robust diagnostic algorithm based on intratumoral and stromal CD8+ T-cell densities in the tumor center compartment that translates spatial densities of tumor-infiltrating CD8+ T cells into the clinically relevant immune diagnostic categories "inflamed", "excluded", and "desert". The consideration of the intratumoral tumor center compartment allows immune phenotyping in the clinically highly relevant setting of metastatic lesions, even if the invasive margin compartment is not captured in biopsy material.
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Linfócitos T CD8-Positivos , Processamento de Imagem Assistida por Computador , Imunofenotipagem/métodos , Melanoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aprendizado Profundo , Feminino , Humanos , Masculino , Melanoma/imunologia , Pessoa de Meia-IdadeRESUMO
Chloroxylenol (PCMX) is applied as a preservative and disinfectant in personal care products, currently recommended for use to inactivate the SARS-CoV-2 virus. Its intensive application leads to the release of PCMX into the environment, which can have a harmful impact on aquatic and soil biotas. The aim of this study was to assess the mechanism of chloroxylenol biodegradation by the fungal strains Cunninghamella elegans IM 1785/21GP and Trametes versicolor IM 373, and investigate the ecotoxicity of emerging by-products. The residues of PCMX and formed metabolites were analysed using GC-MS. The elimination of PCMX in the cultures of tested microorganisms was above 70%. Five fungal by-products were detected for the first time. Identified intermediates were performed by dechlorination, hydroxylation, and oxidation reactions catalysed by cytochrome P450 enzymes and laccase. A real-time quantitative PCR analysis confirmed an increase in CYP450 genes expression in C. elegans cells. In the case of T. versicolor, spectrophotometric measurement of the oxidation of 2,20-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) showed a significant rise in laccase activity during PCMX elimination. Furthermore, with the use of bioindicators from different ecosystems (Daphtoxkit F and Phytotoxkit), it was revealed that the biodegradation process of PCMX had a detoxifying nature.
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Cunninghamella/metabolismo , Trametes/metabolismo , Xilenos/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Daphnia/efeitos dos fármacos , Daphnia/fisiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica , Lacase/metabolismo , Oxirredução , Testes de Toxicidade , Xilenos/análise , Xilenos/farmacologiaRESUMO
Synthetic materials commonly used in the packaging industry generate a considerable amount of waste each year. Chitosan is a promising feedstock for the production of functional biomaterials. From a biological point of view, chitosan is very attractive for food packaging. The purposes of this study were to evaluate the antibacterial activity of a set of chitosan-metal oxide films and different chitosan-modified graphene (oxide) films against two foodborne pathogens: Campylobacter jejuni ATCC 33560 and Listeria monocytogenes 19115. Moreover, we wanted to check whether the incorporation of antimicrobial constituents such as TiO2, ZnO, Fe2O3, Ag, and graphene oxide (GO) into the polymer matrices can improve the antibacterial properties of these nanocomposite films. Finally, this research helps elucidate the interactions of these materials with eukaryotic cells. All chitosan-metal oxide films and chitosan-modified graphene (oxide) films displayed improved antibacterial (C. jejuni ATCC 33560 and L. monocytogenes 19115) properties compared to native chitosan films. The CS-ZnO films had excellent antibacterial activity towards L. monocytogenes (90% growth inhibition). Moreover, graphene-based chitosan films caused high inhibition of both tested strains. Chitosan films with graphene (GO, GOP, GOP-HMDS, rGO, GO-HMDS, rGOP), titanium dioxide (CS-TiO2 20:1a, CS-TiO2 20:1b, CS-TiO2 2:1, CS-TiO2 1:1a, CS-TiO2 1:1b) and zinc oxide (CS-ZnO 20:1a, CS-ZnO 20:1b) may be considered as a safe, non-cytotoxic packaging materials in the future.
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Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Materiais Biocompatíveis , Quitosana , Microbiologia de Alimentos , Embalagem de Alimentos , Membranas Artificiais , Antibacterianos/química , Antibacterianos/farmacologia , Membrana Externa Bacteriana/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Quitosana/química , Metais/química , PolímerosRESUMO
Previously, we demonstrated the expression of apelin and G-protein-coupled receptor APJ in human placenta cell lines as well as its direct action on placenta cell proliferation and endocrinology. The objective of this study was to examine the effect of apelin on placenta apoptosis in BeWo cells and villous explants from the human third trimester of pregnancy. The BeWo cells and villous explants were incubated with apelin (2 and 20 ng/mL) alone or with staurosporine for 24 to 72 h. First, we analysed the dose- and time-dependent effect of apelin on the expression of apoptotic factors on the mRNA level by real-time PCR and on the protein level using Western blot. Next, we checked caspase 3 and 7 activity by Caspase-Glo 3/7, DNA fragmentation by the Cell Death Detection ELISA kit and oxygen consumption by the MitoXpress-Xtra Oxygen Consumption assay. We found that apelin increased the expression of pro-survival and decreased proapoptotic factors on mRNA and protein levels in both BeWo cells and villous explants. Additionally, apelin inhibited caspase 3 and 7 activity and DNA fragmentation in staurosporine-induced apoptosis as also attenuated oxidative stress by increasing extracellular oxygen consumption. The antiapoptotic effect of apelin in BeWo cells was mediated by the APJ receptor and mitogen-activated protein kinase (ERK1/2/MAP3/1) and protein kinase B (AKT). The obtained results showed the antiapoptotic effect of apelin on trophoblast cells, suggesting its participation in the development of the placenta.
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Apelina/farmacologia , Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Placenta/metabolismo , Terceiro Trimestre da Gravidez , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular , Feminino , Humanos , Gravidez , Proteínas da Gravidez/metabolismoRESUMO
Caring for victims of harassment can be difficult. Different forms exist, some of which are difficult to detect. Every general practitioner must pay attention to the various warning signs that the victim may present. Careful, empathetic listening on the part of the general practitioner is necessary to take care of these victims. An important place in the consultation is the medical report, which can be used later in a legal process. The general practitioner does not work alone, can count on other medical and non-medical partners. Victims of harassment are also supported by various associations.
La prise en charge des victimes de harcèlement peut s'avérer difficile. Différentes formes, dont certaines difficiles à détecter, existent. Chaque médecin de premier recours doit prêter attention aux différents signaux d'alerte et facteurs de risque que peut présenter la victime. Une écoute attentive, empathique de la part du médecin généraliste est nécessaire pour prendre en charge ces victimes. Le constat médical tient une place importante, qui peut servir plus tard dans une démarche judiciaire. Le médecin ne travaillant pas seul peut compter sur d'autres partenaires médicaux et non médicaux. Les victimes de harcèlement sont par ailleurs soutenues par différentes associations.
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Médicos de Atenção Primária , Assédio Sexual , HumanosRESUMO
BACKGROUND: Real time RT-PCR (qPCR) is a useful and powerful tool for quantitative measurement of gene expression. The proper choice of internal standards such as reference genes is crucial for correct data evaluation. In female dogs, as in other species, the reproductive tract is continuously undergoing hormonal and cycle stage-dependent morphological changes, which are associated with altered gene expression. However, there have been few attempts published so far targeted to the dog aimed at determining optimal reference genes for the reproductive organs. Most of these approaches relied on genes previously described in other species. Large-scale transcriptome-based experiments are promising tools for defining potential candidate reference genes, but were never considered in this context in canine research. RESULTS: Here, using available microarray and RNA-seq datasets derived from reproductive organs (corpus luteum, placenta, healthy and diseased uteri) of dogs, we have performed multistudy analysis to identify the most stably expressed genes for expression studies, in each tissue separately and collectively for different tissues. The stability of newly identified reference genes (EIF4H, KDELR2, KDM4A and PTK2) has been determined and ranked relative to previously used reference genes, i.e., GAPDH, ß-actin and cyclophillin A/PPIA, using RefFinder and NormFinder algorithms. Finally, expression of selected target genes (luteal IL-1b and MHCII, placental COX2 and VEGFA, and uterine IGF2 and LHR) was re-evaluated and normalized. All proposed candidate reference genes were more stable, ranked higher and introduced less variation than previously used genes. CONCLUSIONS: Based on our analyses, we recommend applying KDM4A and PTK2 for normalization of gene expression in the canine CL and placenta. The inclusion of a third reference gene, EIF4H, is suggested for healthy uteri. With this, the interpretation of qPCR data will be more reliable, allowing better understanding of canine reproductive physiology.
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Cães/genética , Expressão Gênica , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Animais , Corpo Lúteo/metabolismo , Cães/metabolismo , Feminino , Perfilação da Expressão Gênica/veterinária , Placenta/metabolismo , Gravidez , Análise de Sequência de RNA , Útero/metabolismoRESUMO
AIM OF THE STUDY: To evaluate the immune response rate in children with inflammatory bowel disease (IBD) who received the full hepatitis B vaccination course in infancy. We also evaluated rates of response to booster doses. MATERIAL AND METHODS: Participants were 1- to 18-year-old children with IBD, who received 3 doses of the hepatitis B vaccine in infancy. The study subjects were on no immunosuppressive therapy, on immunomodulators, on biological therapy, or received combo therapy. Anti-hepatitis B surface antibody (anti-HBs) level ≥ 10 mIU/ml was considered to be seroprotective. Patients with anti-HBs level < 10 mIU/ml received 1 or 3 doses of hepatitis B vaccine, and their post-vaccination anti-HBs levels were evaluated. RESULTS: In total, we included 157 subjects, with a median age of 14.5 years. Anti-HBs levels ≥ 10 mIU/ml were found in 84/157 (53.5%) patients and were not associated with age (p = 0.3), sex (p = 0.7), or IBD type (p = 0.9). There was no significant difference in the rate of seroconversion between IBD patients treated with no immunosuppressive drugs, immunomodulators, biologicals, and combo therapy (30.4% vs. 39.3% vs. 2.7% vs. 7.1%, respectively, p = 0.3). After the first and third dose of booster vaccine, anti-HBs levels ≥ 10 mIU/ml were as follows: 92% and 100%, respectively. CONCLUSIONS: The immune response in children with IBD, who received the full series of hepatitis B vaccinations in infancy was inadequate and did not depend on the type of therapy. The booster dose(s) of vaccine could help to protect this group of patients from hepatitis B virus.
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The domestic dog is the only domestic animal species that does not produce steroids in the placenta and instead relies on luteal steroids throughout pregnancy. Nevertheless, the canine placenta is highly responsive to steroids, and withdrawal of progesterone (P4) affects the feto-maternal unit, initializing the parturition cascade. Similar effects can be observed during antigestagen-induced abortion. Here, aiming to provide new insights into mechanisms involved in the termination of canine pregnancy, next generation sequencing (NGS, RNA-seq) was applied. Placental transcriptomes derived from natural prepartum and antigestagen-induced abortions were analyzed and compared with fully developed mid-gestation placentas. The contrast "prepartum luteolysis over mid-gestation" revealed 1973 differentially expressed genes (DEG). Terms associated with apoptosis, impairment of vascular function and activation of signaling of several cytokines (e.g., IL-8, IL-3, TGF-ß) were overrepresented at natural luteolysis. When compared with mid-term, antigestagen treatment revealed 135 highly regulated DEG that were involved in the induced luteolysis and showed similar associations with functional terms and expression patterns as during natural luteolysis. The contrast "antigestagen-induced luteolysis over prepartum luteolysis" revealed that, although similar changes occur in both conditions, they are more pronounced during natural prepartum. Among P4-regulated DEG were those related to immune system and cortisol metabolism. It appears that, besides inducing placental PGF2α output, both natural and induced P4 withdrawal is associated with disruption of the feto-maternal interface, leading to impaired vascular functions, apoptosis and controlled modulation of the immune response. The time-related maturation of the feto-maternal interface needs to be considered because it may be clinically relevant.
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Perfilação da Expressão Gênica , Luteólise , Placenta/metabolismo , Progestinas/antagonistas & inibidores , Animais , Dinoprosta/metabolismo , Cães , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Luteólise/genética , Anotação de Sequência Molecular , Gravidez , Progesterona/metabolismoRESUMO
Staphylococcus aureus infections are common and difficult to treat. The increasing number of drug-resistant staphylococcal infections has created the need to develop new strategies for the treatment of these infections. The synergistic antimicrobial activity of different pharmaceuticals seems to be an interesting alternative. The aim of this study was to assess the synergistic activity of ciprofloxacin and carvedilol against S. aureus strains. The antibacterial potential of ciprofloxacin and carvedilol was evaluated according to the CLSI guidelines. The calcium content in S. aureus cells was measured using flow cytometry and atomic absorption spectroscopy. Moreover, confocal and scanning electron microscopy were used to determine the mechanism of antibacterial synergy of ciprofloxacin and carvedilol. The antibacterial effect of ciprofloxacin was higher in the presence of carvedilol than in S. aureus cultures containing the antibiotic only. A significant increase in S. aureus membrane permeability was also observed. The simultaneous administration of the tested compounds caused damage to S. aureus cells visualized by SEM. Enhancement of the antimicrobial action of ciprofloxacin by carvedilol was correlated with an increase in free calcium content in S. aureus cells, morphological changes to the cells, and a reduction in the ability to form bacterial aggregates.
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Antibacterianos/farmacologia , Carvedilol/farmacologia , Ciprofloxacina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade MicrobianaRESUMO
Effective communication between patients and health professionals is a key component of patient-centred care. Although there is a large body of literature focusing on doctor-patient communication, there has been limited research related to dentist-patient communication, especially presented from the dentists' perspective. The aim of our study was to explore UK dentists' perceptions of communication in their consultations, and the factors they perceive may influence this. We conducted semi-structured interviews with eight dentists in UK dental NHS practices. Thematic analysis revealed three themes ('Treating the whole person', 'Barriers to patient-centred communication' and 'Mutuality of communication'), which reflected the dentists' perceptions of their own communication during consultations, the patients' interaction skills, attitudes (and characteristics that may affect them), and external factors, such as time constraints, that can influence dentist-patients' encounters. These in-depth accounts are valuable, in that we see what dentists perceive is important, obstructive and facilitative. They report using a patient-centred approach in their everyday dental practice; however this is often difficult due to factors such as time constraints. Although they emphasized that the patient has an active role to play in the communication process, it may be the case that they also need to play their part in facilitating this.
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Atitude do Pessoal de Saúde , Comunicação , Relações Dentista-Paciente , Odontólogos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino UnidoRESUMO
OBJECTIVES: Exosomes - microvesicles which are secreted by living cells - can be produced from different cell types and detected in various body fluids. They are the carriers of intercellular information which regulate tumor microenvironment and are considered to be involved in tumor progression and metastasis. Cancer cells can secrete more exosomes than healthy cells, and are expected to be potential tools for tumor diagnosis and treatment. MATERIAL AND METHODS: In this report, we present the results of microparticle analysis in peripheral and uterine blood of patients with endometrial cancer. To the best of our knowledge, this study has been the first to report microvesicle status in peripheral and uterine blood samples. The aim of the study was to determine the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) microparticles. The counting of the selected microparticles in citrate plasma was performed using flow cytometry on the BD Canto II cytometer. RESULTS: We found that the total amount of microparticles in cancer patients was much higher than in healthy controls. Moreover, microparticle count in uterine blood was higher than in peripheral blood of patients with endometrial cancer. We also demonstrated that the amount of microparticles correlates with the histologic grade and clinical stage of the tumor. CONCLUSIONS: The most interesting finding in this work was the high level of TF, CD144 and CD14 MPs in uterine blood samples. Thus we can consider the monocyte-macrophage-derived MPs as a candidate marker of endometrial cancer and maybe very critical part of the endometrial carcinogenesis.
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Plaquetas/metabolismo , Micropartículas Derivadas de Células/metabolismo , Neoplasias do Endométrio/metabolismo , Endométrio/citologia , Biomarcadores/metabolismo , Feminino , Citometria de Fluxo , HumanosRESUMO
Relaxin (RLN) is a key hormone of pregnancy in mammals best known for its involvement in connective tissue remodeling. In the domestic dog, placental RLN is the only known endocrine marker of pregnancy. However, knowledge is sparse regarding the spatio-temporal expression of RLN and its receptors (RXFP1 and RXFP2) in the canine uterus and placenta. Here, their expression was investigated in the pre-implantation uterus and utero-placental compartments (UtPl) at selected time points during gestation: post-implantation, mid-gestation, and at normal and antigestagen-induced luteolysis/abortion. Immunohistochemistry with newly generated, canine-specific antisera, in situ hybridization and semi-quantitative PCR were applied. In compartmentalization studies, placental and endometrial RLN increased continuously toward prepartum. The placental RXFP1 was time-related and highest during post-implantation and decreased together with RXFP2 at prepartum luteolysis. The endometrial levels of both receptors did not vary greatly, but myometrial RXFP2 decreased from mid-gestation to prepartum luteolysis. Antigestagen treatment resulted in suppression of RLN in UtPl and decreased RXFP1 and RXFP2 in the uterus. The placental RLN was localized mainly in the cytotrophoblast. Additionally, RXFP1 stained strongly in placental endothelial cells while RXFP2 was found mainly in maternal decidual cells. Uterine staining for all targets was found in epithelial cellular constituents and in myometrium. Finally, besides its endocrine functions, RLN seems to be involved in auto-/paracrine regulation of utero-placental functions in dogs in a time-dependent manner. New insights into feto-maternal communication was provided, in particular regarding the localization of RXFP2 in the maternal decidual cells, implying functional roles of RLN during the decidualization process.
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Placenta/metabolismo , Relaxina/metabolismo , Útero/metabolismo , Abortivos/farmacologia , Aborto Induzido , Animais , Comunicação Autócrina , Cães , Estrenos/farmacologia , Feminino , Idade Gestacional , Luteólise , Comunicação Parácrina , Placenta/citologia , Placenta/efeitos dos fármacos , Gravidez , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Relaxina/genética , Transdução de Sinais , Útero/citologia , Útero/efeitos dos fármacosRESUMO
OBJECTIVE: The purpose of this research was to assess the dynamics of autonomic nervous system(ANS) and hemodynamic activity changes during uncomplicated pregnancy. METHODS: We enrolled 36 pregnant women (mean age 29 ± 4.8 years) and a control group of 10 non-pregnant women (mean age 25.9 ± 0.88 years). The examination was performed in the 1st, 2nd, and 3rd trimester. Continuous registration of BP, ECG, and cardioimpedance was performed with Task Force Monitor 3040i. ANS activity was measured using the following parameters: HRV, BPV, BRS at rest, and in response to autonomic tests. RESULTS: Compared to the 1st trimester, an increase in HR (73 vs. 92 bpm; p < 0.001) and mean BP (80 vs. 85 mmHg, p < 0.01) was observed in the 3rd trimester. In the 1st trimester, the BRS of pregnant women was insignificantly higher than in the controls (24.8 vs. 22.3 ms/mmHg); subsequently, it decreased significantly, to 13.4 ms/mmHg in the 3rd trimester (p = 0.0004). An increase in nLF (39.57 ± 13.75 vs. 58.73 ± 15.55; p = 0.001) and LF/HF ratio (1.03 ± 0.76 vs. 1.85 ± 0.8; p < 0.00002) was revealed in HRV analysis conducted in the 3rd trimester, as compared to the 1st tri- mester, along with a decrease in nHF (60.43 ± 13.71 vs. 41.26 ± 15.55; p < 0.001). An increase in LF/HF-sBPV (1.05 ± 0.48 vs. 1.58 ± 0.44; p = 0.01) was recorded in BPV analysis at rest in the 3rd trimester as compared to the respective 1st trimester value. CONCLUSION: Our findings suggest that pregnancy is associated with dynamic changes in autonomic balance, namely doubled dominance of the sympathetic component. Hypervolemia seems the major factor responsible for autonomic and hemodynamic changes observed during pregnancy, as it causes an increase in BP and simultaneous decrease in BRS.
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Sistema Nervoso Autônomo/fisiologia , Hemodinâmica/fisiologia , Gravidez/fisiologia , Adulto , Pressão Sanguínea/fisiologia , Cardiografia de Impedância , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Trimestres da Gravidez/fisiologia , Adulto JovemRESUMO
Objectives: Inherited thrombophilia might lead to recurrent pregnancy loss (RPL). The aim of the study was to estimate the prevalence of V coagulation factor polymorphisms related with inherited thrombophilia among women in Malopolska region.Material and methods: Group of 136 women, who experienced at least 2 unexplained, idiopathic pregnancy loss. 106 healthy women having at least one uncomplicated pregnancy and delivered healthy children constituted a control group. Each patient were examined for factor V Leiden (FVL) and mutation 1328 T>C of factor V gene with use of real time PCR and Taq-Man probes.Results: Among patients with RPL inhabiting region of Malopolska compared to control group occurred higher prevalence of FVL and mutation 1328 T>C. There is coincidence of polymorphism 1328 T>C of factor V gene and FVL in group of early and late RPL.Conclusions: TC genotype of 1328 T>C mutation carriers reveal tendency toward RPL below 7 weeks of pregnancy.Based on results of these findings inherited thrombophilia evaluation in patients after two or more RPL should be recommended.
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Aborto Habitual/genética , Fator V/genética , Mutação Puntual/genética , Polimorfismo Genético/genética , Adulto , Feminino , Predisposição Genética para Doença , Humanos , Gravidez , Proteína C/genética , Fatores de Risco , População Branca/genética , Adulto JovemRESUMO
INTRODUCTION: The aim of our study was to assess the morning and evening cortisol plasma levels in women with polycystic ovary syndrome (PCOS). MATERIAL AND METHOD: 95 patients gave their informed consent to participate in the study and were divided into 2 groups. Group A consisted of 40 PCOS patients and group B consisted of 55 women without features of PCOS. Between day 5 and 8 of the menstrual cycle, morning (7 am), fasting blood samples were taken for the assessment of luteinizng hormone (LH), follicle stimulating hormone (FSH), estradiol, cortisol, prolactin, thyreotropin (TSH), testosterone and dehydroepeiandrosterone (DHEAS). Evening (5 pm) blood samples were also taken for the evaluation of plasma cortisol level RESULTS: There were no differences in mean age, body mass index (BMI), FSH, SHBG, PRL, estradiol and TSH levels between group A and group B. Mean plasma LH level was higher in group A compared to group B (10.7 ± 6.8 IU/l vs 6.6 ± 4.5 LU/l, p < 0.02). Mean plasma testosterone and DHEAS levels were also higher in PCOS patients (3.8 ± 0.6 nmol/l vs 1.63 ± 0.6 nmol/l; 427.7 ± 162.9 vs 236.6 ± 97.8 respectively, p < 0.001). Mean evening plasma cortisol level was higher in PCOS patients (11.8 ± 4.1 ug/dl vs 4.7 ± 1.3 ug/dl, p < 0.02). Mean morning plasma cortisol levels did not differ between groups. CONCLUSION: PCOS women showed the increased evening plasma cortisol level with impacted diurnal secretion rate.
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Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hidrocortisona/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/sangue , Prolactina/sangue , Testosterona/sangue , Tireotropina/sangue , Adulto , Índice de Massa Corporal , Ritmo Circadiano/fisiologia , Feminino , Humanos , Adulto JovemRESUMO
BACKGROUND: Single-stranded DNA-binding proteins (SSBs) play essential roles in DNA replication, recombination and repair in Bacteria, Archaea and Eukarya. In recent years, there has been an increasing interest in SSBs, since they find numerous applications in diverse molecular biology and analytical methods. RESULTS: We report the characterization of single-stranded DNA-binding proteins from the psychrophilic bacteria Desulfotalea psychrophila (DpsSSB), Flavobacterium psychrophilum (FpsSSB), Psychrobacter arcticus (ParSSB), Psychrobacter cryohalolentis (PcrSSB), Psychromonas ingrahamii (PinSSB), Photobacterium profundum (PprSSB), and Psychroflexus torquis (PtoSSB). The proteins show a high differential within the molecular mass of their monomers and the length of their amino acid sequences. The high level of identity and similarity in respect to the EcoSSB is related to the OB-fold and some of the last amino acid residues. They are functional as homotetramers, with each monomer encoding one single stranded DNA binding domain (OB-fold). The fluorescence titrations indicated that the length of the ssDNA-binding site size is approximately 30 ± 2 nucleotides for the PinSSB, 31 ± 2 nucleotides for the DpsSSB, and 32 ± 2 nucleotides for the ParSSB, PcrSSB, PprSSB and PtoSSB. They also demonstrated that it is salt independent. However, when the ionic strength was changed from low salt to high, binding-mode transition was observed for the FpsSSB, at 31 ± 2 nucleotides and 45 ± 2 nucleotides, respectively. As expected, the SSB proteins under study cause duplex DNA destabilization. The greatest decrease in duplex DNA melting temperature was observed in the presence of the PtoSSB 17 °C. The SSBs in question possess relatively high thermostability for proteins derived from cold-adapted bacteria. CONCLUSION: The results showed that SSB proteins from psychrophilic microorganisms are typical bacterial SSBs and possess relatively high thermostability, offering an attractive alternative to other thermostable SSBs in molecular biology applications.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Deltaproteobacteria/enzimologia , Flavobacteriaceae/enzimologia , Gammaproteobacteria/enzimologia , Sítios de Ligação , Proteínas de Ligação a DNA/química , Deltaproteobacteria/genética , Flavobacteriaceae/genética , Gammaproteobacteria/genética , Peso Molecular , Multimerização Proteica , Estabilidade Proteica , Homologia de Sequência de Aminoácidos , TemperaturaRESUMO
PURPOSE: Immunoscore (IS) is prognostic in stage III colorectal cancer (CRC) and may predict benefit of duration (6 v 3 months) of adjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. We sought to determine IS prognostic and predictive value in stage-III CRC treated with adjuvant FOLFOX or oral capecitabine and infusional oxaliplatin (CAPOX) in the SCOT and IDEA-HORG trials. METHODS: Three thousand sixty-one cases had tumor samples, of which 2,643 (1,792 CAPOX) were eligible for IS testing. Predefined cutoffs (IS-Low and IS-High) were used to classify cases into two groups for analysis of disease-free survival (3-year DFS) and multivariable-adjusted hazard ratios (mvHRs) by Cox regression. RESULTS: IS was determined in 2,608 (99.5%) eligible cases, with 877 (33.7%) samples classified as IS-Low. IS-Low tumors were more commonly high-risk (T4 and/or N2; 52.9% IS-Low v 42.2% IS-High; P < .001) and in younger patients (P = .024). Patients with IS-Low tumors had significantly shorter DFS in the CAPOX, FOLFOX, and combined cohorts (mvHR, 1.52 [95% CI, 1.28 to 1.82]; mvHR, 1.58 [95% CI, 1.22 to 2.04]; and mvHR, 1.55 [95% CI, 1.34 to 1.79], respectively; P < .001 all comparisons), regardless of sex, BMI, clinical risk group, tumor location, treatment duration, or chemotherapy regimen. IS prognostic value was greater in younger (≤65 years) than older (>65 years) patients in the CAPOX cohort (mvHR, 1.92 [95% CI, 1.50 to 2.46] v 1.28 [95% CI, 1.01 to 1.63], PINTERACTION = .026), and in DNA mismatch repair proficient than deficient mismatch repair disease (mvHR, 1.68 [95% CI, 1.41 to 2.00] v 0.67 [95% CI, 0.30 to 1.49], PINTERACTION = .03), although these exploratory analyses were uncorrected for multiple testing. Adding IS to a model containing all clinical variables significantly improved prediction of DFS (likelihood ratio test, P < .001) regardless of MMR status. CONCLUSION: IS is prognostic in stage III CRC treated with FOLFOX or CAPOX, including within clinically relevant tumor subgroups. Possible variation in IS prognostic value by age and MMR status, and prediction of benefit from extended adjuvant therapy merit validation.