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INTRODUCTION: Both microenvironmental signals from surrounding cells and changes in the genome of leukemic cells play essential role in the development of chronic lymphocytic leukemia. Nurse-like cells (NLCs) are one of the important elements of the microenvironment of CLL cells. The key role in the interactions of leukemic cells with NLCs is played by chemokines, which may interfere with the programmed cell death process in the leukemic lymphocytes. The aim of our study was analysis of selected microenvironmental factors having a potential impact on the leukemic cells survival, as well as their association with clinical, cytogenetic, and molecular parameters. For this study, we selected three types of molecules which can modulate microenvironment: chemokines IL-8 and CCL3 (which are classically secreted to extracellular matrix), soluble forms of adhesion molecules JAG1 and CD163, and secreted form of endogenous protein BIRC5. We assessed their expression in the serum of CLL patients as well as in medium of long-term NLCs cultures. METHODS: Long-term cell culture was prepared from mononuclear cells derived from the blood of 34 patients with CLL. Number of NLCs cells was evaluated, under a light inverted microscope. The concentration of IL-8, CCL3, sBIRC5, sCD163, and sJAG1 in culture medium and serum was assessed by enzyme-linked immunosorbent assays. RESULTS: There were significant differences in the concentration of IL-8, sBIRC5, CCL3, sCD163, and sJAG1 between the patient's blood serum and the culture medium. The concentrations of IL-8, CCL3, and JAG1 were higher in the culture medium, which confirmed the role of the microenvironment in the production of these proteins. In addition, the concentration of CCL3 chemokine in both patient's blood serum and in the culture medium correlated with the number of NLCs and with known prognostic factors in the course of CLL, e.g., Rai stage, WBC, expression of ZAP-70, CD38, and CD5/19. CONCLUSION: The microenvironment of CLL cells, which includes NLCs, plays an important role in the pathogenesis of CLL. The CCL3 chemokine seems to be a good factor representing microenvironment of CLL cells. Chronic lymphocytic leukemia is a complex and very heterogeneous disease; therefore, its progress should be considered both in the context of genetic changes and the interaction with microenvironmental cells.
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Leucemia Linfocítica Crónica de Células B , Humanos , Quimiocina CCL3/genética , Quimiocina CCL3/metabolismo , Ensayo de Inmunoadsorción Enzimática , Interleucina-8 , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/metabolismo , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
This study aimed to evaluate the safety and potential use of soy isoflavones in the treatment of skin problems, difficult-to-heal wounds and postoperative scars in women after the oncological treatment of breast cancer. The effects of different concentrations of genistein as a representative of soy isoflavonoids on MCF-7 tumor cells and BJ skin fibroblasts cultured in vitro were assessed. Genistein affects both healthy dermal BJ fibroblasts and cancerous MCF-7 cells. The effect of the tested isoflavonoid is closely related to its concentration. High concentrations of genistein destroy MCF-7 cancer cells, regardless of the exposure time, with a much greater effect on reducing cancer cell numbers at longer times (48 h). Lower concentrations of genistein (10 and 20 µM) increase the abundance of dermal fibroblasts. However, higher concentrations of genistein (50 µM and higher) are detrimental to fibroblasts at longer exposure times (48 h). Our studies indicate that although genistein shows high potential for use in the treatment of skin problems, wounds and surgical scars in women during and after breast cancer treatment, it is not completely safe. Introducing isoflavonoids to treatment requires further research into their mechanisms of action at the molecular level, taking into account genetic and immunological aspects. It is also necessary to conduct research in in vivo models, which will allow for eliminating adverse side effects of therapy.
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Neoplasias de la Mama , Isoflavonas , Femenino , Humanos , Genisteína/farmacología , Células MCF-7 , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Cicatriz/patología , Fibroblastos , Isoflavonas/farmacología , Isoflavonas/uso terapéuticoRESUMEN
BACKGROUND: The most popular tool used for measuring personality traits is the Five-Factor Model (FFM). It includes neuroticism, extraversion, openness, agreeableness and conscientiousness. Many studies indicated the association of genes encoding neurotransmitter receptors/transporters with personality traits. The relationship connecting polymorphic DNA sequences and FFM features has been described in the case of genes encoding receptors of cannabinoid and dopaminergic systems. Moreover, dopaminergic system receives inputs from other neurotransmitters, like GABAergic or serotoninergic systems. METHODS: We searched PubMed Central (PMC), Science Direct, Scopus, Cochrane Library, Web of Science and EBSCO databases from their inception to November 19, 2020, to identify original studies, as well as peer-reviewed studies examining the FFM and its association with gene polymorphisms affecting the neurotransmitter functions in central nervous system. RESULTS: Serotonin neurons modulate dopamine function. In gene encoding serotonin transporter protein, SLC6A4, was found polymorphism, which was correlated with openness to experience (in Sweden population), and high scores of neuroticism and low levels of agreeableness (in Caucasian population). The genome-wide association studies (GWASs) found an association of 5q34-q35, 3p24, 3q13 regions with higher scores of neuroticism, extraversion and agreeableness. However, the results for chromosome 3 regions are inconsistent, which was shown in our review paper. CONCLUSIONS: GWASs on polymorphisms are being continued in order to determine and further understand the relationship between the changes in DNA and personality traits.
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Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are considered as laboratory markers of inflammation. They can be potentially useful in predicting the course of multiple neoplasms including selected hematological cancers. The aim of the study was to assess the value of NLR and PLR in predicting the effects of therapy and prognosis in multiple myeloma patients treated with thalidomide-based regimen. The study group consisted of 100 patients treated with the first line CTD (cyclophosphamide, thalidomide, and dexamethasone) chemotherapy. The NLR and PLR were calculated before treatment. High NLR was observed in patients with higher stage of the disease, with poor performance status, hypercalcemia, and high CRP. High PLR was associated with low BMI and high CRP. In patients with high NLR, significantly shorter PFS was observed (17 vs. 26 months, p = 0.0405). In addition, high values of NLR and PLR were associated with significantly shorter OS (38 vs. 79 months, p = 0.0010; 40 vs. 78 months, p = 0.0058). Summarizing, NLR and PLR have a significant independent prognostic value for multiple myeloma patients. Furthermore, the NLR can be a predictive marker for the outcome of thalidomide-based chemotherapy.
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Plaquetas/metabolismo , Linfocitos/metabolismo , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Neutrófilos/metabolismo , Talidomida/uso terapéutico , Anciano , Plaquetas/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Recuento de Linfocitos/métodos , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Neutrófilos/efectos de los fármacos , Recuento de Plaquetas/métodos , Pronóstico , Tasa de Supervivencia/tendencias , Talidomida/farmacología , Resultado del TratamientoRESUMEN
MicroRNAs (miRNAs) regulate gene expression; many of them act in the retinal pigment epithelium (RPE), and RPE degeneration is known to be a critical factor in age-related macular degeneration (AMD). Repeated injections with anti-VEGFA (vascular endothelial growth factor A) are the only effective therapy in wet AMD. We investigated the correlation between the expression of 18 miRNAs involved in the regulation of the VEGFA gene in serum of 76 wet AMD patients and 70 controls. Efficacy of anti-VEGFA treatment was evaluated by counting the number of injections delivered up to 12 years. In addition, we compared the relative numbers of deaths in patient with AMD and control groups. We observed a decreased expression of miR-34-5p, miR-126-3p, miR-145-5p and miR-205-5p in wet AMD patients as compared with controls. These miRNAs are involved in the regulation of angiogenesis, cytoprotection and protein clearance. No miRNA was significantly correlated with the treatment outcome. Wet AMD patients had greater mortality than controls, and their survival was inversely associated with the number of anti-VEGFA injections per year. No association was observed between miRNA expression and mortality. Our study emphasizes the need to clarify the role of miRNA regulation in AMD pathogenesis.
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Regulación de la Expresión Génica , Degeneración Macular/genética , MicroARNs/genética , Factor A de Crecimiento Endotelial Vascular/genética , Anciano , Anciano de 80 o más Años , Anticuerpos/inmunología , Anticuerpos/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/metabolismo , Masculino , Factor A de Crecimiento Endotelial Vascular/inmunología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Expression of microRNAs is altered in cancer. Circulating miRNA level assessed in body fluids commonly reflects their expression in tumor cells. In leukemias, however, both leukemic and nonleukemic cells compose circulating miRNA expression profile of peripheral blood. The latter contribution to extracellular miRNA pool may result in specific microenvironmental signaling, which promotes proliferation and survival. In our study, we used qT-PCR to assay peripheral blood serum of 22 chronic lymphocytic leukemia (CLL) patients for the expression of 84 miRNAs associated with activation and differentiation of B and T lymphocytes. Results were analyzed regarding the most important prognostic factors. We have found that the general expression of examined miRNAs in CLL patients was lower as compared to healthy volunteers. Only miR-34a-5p, miR31-5p, miR-155-5p, miR-150-5p, miR-15a-3p, and miR-29a-3p were expressed on a higher level. Alterations of expression observed in CLL patients involved miRNAs associated both with B and T lymphocyte differentiation and activation. The most important discriminating factors for all functional miRNA groups were trisomy 12, CD38 expression, B2M level, WBC, and NOTCH1 gene mutation. Correlation of expression of miRNAs related to T lymphocytes with prognostic factors proves their supportive function in a leukemic microenvironment. Further studies utilizing a larger test group of patients may warrant the identification of circulating miRNAs that are key players in intercellular interactions and should be considered in the design of microenvironment-targeted therapies.
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Linfocitos B/fisiología , Diferenciación Celular/fisiología , Regulación Neoplásica de la Expresión Génica , Leucemia Linfocítica Crónica de Células B/sangre , MicroARNs/sangre , Linfocitos T/fisiología , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Células Cultivadas , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Masculino , MicroARNs/biosíntesis , MicroARNs/genética , Persona de Mediana EdadRESUMEN
Each population may have its own specific characteristics and cultural differences, which can affect perceptions of one's body, obesity, and the development of weight-related biases. The goal of our study is to (I) examine weight biases among incoming nursing students from two distinct cultures; (II) determine whether the cultural differences may be reflected in the levels of fat phobia, attitudes, and behaviors related to overweight and obesity; (III) adapt the Fat Phobia Scale and translate it into Polish. The study includes 119 Nigerian students and 120 Polish students. The following tools are used-ORK-10, ATOP, BAOP, BES and FPh. The results indicates that Nigerian students have significantly (p < 0.01) less knowledge about the risks associated with overweight and obesity. In contrast, they have a significantly (p < 0.01) more positive body image than the Polish students. Among Nigerian students, men have more positive body image in comparison to women (p = 0.01). An inverse relationship is observed in the group of Polish students, among whom women had a more positive body image than men did (p = 0.01). There are no statistically significant differences in fatphobic attitudes among the studied groups. It has been observed, that culture may be related to weight biases.
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Estudiantes de Enfermería , Prejuicio de Peso , Masculino , Humanos , Femenino , Sobrepeso , Polonia/epidemiología , Imagen Corporal , Nigeria/epidemiología , Obesidad/epidemiología , Sesgo , Índice de Masa Corporal , Peso CorporalRESUMEN
Mast cell tumors are a large group of diseases occurring in dogs, cats, mice, as well as in humans. Systemic mastocytosis (SM) is a disease involving the accumulation of mast cells in organs. KIT gene mutations are very often seen in abnormal mast cells. In SM, high KIT/CD117 expression is observed; however, there are usually no KIT gene mutations present. Mastocytoma (MCT)-a form of cutaneous neoplasm-is common in animals but quite rare in humans. KIT/CD117 receptor mutations were studied as the typical changes for human mastocytosis. In 80% of human cases, the KIT gene substitution p.D816H was present. In about 25% of MCTs, metastasis was observed. Changes in the gene expression of certain genes, such as overexpression of the DNAJ3A3 gene, promote metastasis. In contrast, the SNORD93 gene blocks the expression of metastasis genes. The panel of miR-21-5p, miR-379, and miR-885 has a good efficiency in discriminating healthy and MCT-affected dogs, as well as MCT-affected dogs with and without nodal metastasis. Further studies on the pathobiology of mast cells can lead to clinical improvements, such as better MCT diagnosis and treatment. Our paper reviews studies on the topic of mast cells, which have been carried out over the past few years.
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Mastocitosis , MicroARNs , Trastornos Mieloproliferativos , Humanos , Animales , Perros , Ratones , Mastocitos/metabolismo , Mastocitos/patología , Proteínas Proto-Oncogénicas c-kit/genética , Mastocitosis/genética , Mastocitosis/terapia , Mastocitosis/diagnóstico , Pronóstico , MicroARNs/metabolismoRESUMEN
Orthorexia nervosa (ON) is a disorder characterized by dietary restrictions and an obsessive focus on "healthy" eating. The present study analyzes two aspects of ON. One related to the inner experiences of the individual (intrapersonal). The other concerns the impact of ON on interpersonal relationships (interpersonal). The developed scale was named the Intra- and Interpersonal Effects Scale of Orthorexia (IIESO). The analysis showed an average correlation between the INTER and INTRA factors (r = 0.46). Both the INTER and INTRA scales correlated strongly with both subscales of the TOS but weakly with the ORTO-R score. Females obtained higher scores on the INTER scale (p < 0.01), while no differences were shown for the INTRA subscale or the overall scale score (p < 0.01). Subjects using supplements had higher mean scores on the INTER and INTRA subscales and for the total score. Among the analyzed results, the greatest strength effect was shown for the total score on the IIESO scale (INTER+INTRA) and the TOS scale. The questionnaires used to date have not distinguished between behaviors from interpersonal and intrapersonal perspectives. Research on these dimensions could expand our knowledge of the disorder and refine diagnostic criteria.
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Dieta Saludable , Ortorexia Nerviosa , Femenino , Humanos , Suplementos Dietéticos , Relaciones Interpersonales , ConocimientoRESUMEN
Measuring orthorexia nervosa is challenging due to the use of various existing tools and problems with sample representativeness. Another challenge for the Polish population is the adaptation of existing research tools and the evaluation of their relevance and research reliability. Our research aimed to adapt the TOS to the Polish language and measure pathological and nonpathological orthorexic behavior among the Polish population. The adaptation of the PL-TOS has high psychometric value and allows us to assess healthy and nervous orthorexia levels. This scale can be used not only for further research but also for diagnostic purposes in the daily work of clinicians and psychologists. Our results obtained in the present study indicate a correlation between TOS and both the use of supplements and diet. Higher TOS, ORTO_R and KZZJ_Diet Restrictions scores were obtained for individuals using dietary supplements than for those not using dietary supplements. In the future, it is worth conducting research aimed at various risk groups of individuals with orthorexia to confirm the psychometric properties of this adaptation of the TOS.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Ortorexia Nerviosa , Adulto , Humanos , Polonia , Reproducibilidad de los Resultados , Conducta Alimentaria , Conductas Relacionadas con la Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Multiple myeloma (MM) is a malignancy derived from plasma cells. Bortezomib affects the concentration of reduced glutathione (GSH) and the activity of glutathione enzymes. The aim of our study was to analyze deletion (null/present) variants of GSTT1 and GSTM1 genes and their association with the levels of glutathione and its enzymes in bortezomib-treated cell cultures derived from MM patients. MATERIALS AND METHODS: This study included 180 individuals (80 MM patients and 100 healthy blood donors) who were genotyped via multiplex PCR (for the GSTT1/GSTM1 genes). Under in vitro conditions, MM bone marrow cells were treated with bortezomib (1-4 nM) to determine apoptosis (via fluorescence microscopy), GSH concentration, and activity of glutathione enzymes (via ELISA). RESULTS: Bortezomib increased the number of apoptotic cells and decreased the activity of S-glutathione transferase (GST) and glutathione peroxidase (GPx). We found significant differences in GST activity between 1 nM (GSTT1-null vs. GSTT1-present), 2 nM (GSTT1-null vs. GSTT1-present), and 4 nM (GSTM1-null vs. GSTM1-present) bortezomib: 0.07 vs. 0.12, p = 0.02; 0.06 vs. 0.10, p = 0.02; and 0.03 vs. 0.08, p = 0.01, respectively. CONCLUSIONS: Bortezomib affects the activities of GST and GPx. GST activity was associated with GSTT1 and GSTM1 variants but only at some bortezomib doses.
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Mieloma Múltiple , Polimorfismo Genético , Humanos , Bortezomib/farmacología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Glutatión Peroxidasa/genética , Glutatión Transferasa/genética , Glutatión , ApoptosisRESUMEN
Anxiety is one of the psychological factors associated with body weight experienced by people attempting to live up to expectations of an ideal body shape. The stigma of excessive or too low body weight and the stigmatization of people because of it is becoming a widespread problem with negative psychological and social consequences. One effect of the strong social pressure of beauty standards dependent on low body weight is the development of eating disorders and negative societal attitudes toward overweight or obese people. Research conducted to date has mainly focused on one dimension of weight-related anxiety-the fear of getting fat. Ongoing research has also revealed the other side of weight-related anxiety-fear of weight loss. Therefore, the purpose of the present project was to develop a two-dimensional scale to diagnose the level of weight-related anxiety and to preliminarily test the psychometric properties of the emerging constructs. Results: the BMAS-20 weight-related anxiety scale in both Polish and English versions was developed and its psychometric properties were confirmed. The components of body weight-change anxiety that emerged were: anxiety about getting fat and anxiety about losing weight. It was found that both AGF and ALW may have a protective function related to awareness of the negative consequences of poor eating and the health risks associated with it. Above-normal levels of anxiety may be a predictor of psychopathology. Both AGF and ALW are associated with symptoms of depression.
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Imagen Corporal , Obesidad , Humanos , Imagen Corporal/psicología , Obesidad/psicología , Miedo/psicología , Ansiedad/psicología , Sobrepeso/psicología , Delgadez , Índice de Masa Corporal , Peso CorporalRESUMEN
Persistence is defined as, among other ways, the need to achieve the goals and strive for the goal. Persistence can also be considered from the perspective of the resource concept, as a positive factor related to an individual's adaptive behaviour, psychological resilience, and normal self-regulation. In contrast, tendencies behaviourally similar to perseverance, but which may have psychopathological features, are persistence and perfectionism. The main goal of our study was to: (I) Build non-clinical Persistence Scale (PS) in Polish and English; (II) translate in Polish and validate the Persistence, Perfectionism and Perseveration Questionnaire (PPPQ); (III) analyse properties of both scales. METHODS: The study was conducted on a non-clinical group of 306 subjects. The mean age was 27.6 and ranged from 18 to 58 years. The properties of both scales were analysed using the NEO-FFI personality inventory, PSS-10 Perceived stress level scale, The UPPS-P Impulsive Behaviour Scale, the SPSRQ Sensitivity to Punishment and Reward scale, Grit scale and NAS-50 Self-Control Scale. RESULTS: The psychometric features of the scales fulfil the requirements for psychometric tools. The factorial structure of both versions of the PS-20 scale proved to be unifactorial. Openness was the only variable to co-occur with the persistence scales of both the PS-20 and the PPPQ-10, and did not co-occur with scales intended to indicate psychopathology (Perseveration, Perfectionism). Negative correlations occurred with variables describing Persistence with levels of perceived stress, anxiety and depressive symptoms. Impulsivity measured by the SUPPS scale also showed negative correlations with the study variables. CONCLUSIONS: In the present work, we postulate that persistence is an umbrella construct that gathers and integrates many other traits to form a multi-trait persistence. Perseveration should be regarded as an undesirable trait characterising psychopathological behaviour. Desirable and indicative traits of an individual's good functioning are persistence and, to some extent, perfectionism. Individuals with low persistence and high perseveration may be characterised by a repertoire of psychopathological behaviours.
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Multiple myeloma (MM) is a multifactorial genetic disorder caused by interactive effects of environmental and genetic factors. The proper locus of the TP53 gene (17p13.1) and its protein is essential in genomic stability. The most common variant of the TP53 gene-p.P72R (rs1042522)-shows functional variation. The aim of our study was a complex analysis of the TP53 p.P72R variant and TP53 gene expression in relation to chromosomal changes of the TP53 gene locus, as well as MM risk and outcome. Genomic DNA from 129 newly diagnosed MM patients was analyzed by methods of automated DNA sequencing (for TP53 variant analysis) and cIg-FISH (for chromosomal aberrations analysis). RNA was used in real-time PCR to determine the TP53 expression. In MM patients, the TP53 variant was not in Hardy-Weinberg equilibrium. The RR genotype was associated with lower MM risk (OR = 0.44, p = 0.004). A higher number of plasma cells was found in patients with RR genotype in comparison to those with PP + PR genotypes (36.74% vs. 28.30%, p = 0.02). A higher expression of the TP53 gene was observed in PP + PR genotypes vs. RR homozygote (p < 0.001), in smokers vs. non-smokers (p = 0.02). A positive Pearson's correlation was found between the TP53 expression level and the number of plasma cells (r = 0.26, p = 0.04). The presence of chromosome 17 aberrations with or without TP53 locus did not affect the MM risk and outcome. Similar results were observed in the case of TP53 gene expression and the p.P72R variant.
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(1) Background: Chemokines and chemokine receptors play an important role in tumor development. The aim of this study was to check the significance of CCL5 and CCR1 variants with response rate, survival, and the level of regulated on activation, normal T cells expressed and secreted (RANTES/CCL5) in multiple myeloma (MM) patients; (2) Methods: Genomic DNA from 101 newly diagnosed MM patients and 100 healthy blood donors were analyzed by Real-time PCR method (for CCL5 and CCR1 genotyping). In a subgroup of 70 MM patients, serum samples were collected to determine the level of RANTES; (3) Results: multivariate Cox regression showed increased risk of disease relapse or progression (HR = 4.77; p = 0.01) in MM patients with CG + CC genotypes of CCL5 rs2280788. In contrast, CT + TT genotypes of CCL5 rs2107538 were associated withdecreased risk of death (HR = 0.18; p = 0.028) and disease relapse or progression (HR = 0.26; p = 0.01). In MM patients with major genotypes of rs2280789, rs2280788, and rs2107538, higher survival rates were observed in response to treatment with thalidomide and bortezomib. Statistically significant lower RANTES levels were seen in minor genotypes and heterozygotes of CCL5 and CCR1 variants; (4) Conclusions: Major genotypes of CCL5 variants may be independent positive prognostic factors in MM.
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Obesity has reached epidemic proportions. With the increase in the number of obese people, we have also witnessed a rise in the stigmatisation of this population. The aim of our study was to: (I) validate Polish versions of the attitude toward obese people (ATOP) scale, the beliefs about obese persons (BAOP) scale, and translate the obesity risk knowledge scale (ORK-10); (II) analyse the relationship between personality and the knowledge about obesity, as well as attitudes and beliefs towards obese people. METHODS: The translation procedure was based on the principles of intercultural validation scales. The study was conducted on a group of 306 individuals, including 189 females and 117 males. RESULTS: The original three-factor structure of the ATOP scale was confirmed in the Polish version. Factor analysis confirmed the one-factor structure of the BAOP scale in the Polish version. A very strong correlation was found between ATOP/BAOP and ORK-10. The correlation of personality with ATOP/BAOP scales was at a low level. Regression analysis indicated that knowledge of obesity risk predicted ATOP and BAOP by more than 58% and 50%, in turn, personality only 20% and 3.7%, respectively. CONCLUSION: The polish versions of ATOP, BAOP and ORK-10 scales are fully useful measurement tools. The knowledge about obesity risk is associated with beliefs and attitudes about obese people.
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Actitud , Obesidad , Masculino , Femenino , Humanos , Polonia , Encuestas y Cuestionarios , Obesidad/epidemiología , PersonalidadRESUMEN
(1) Background: The aim of our study was the complex assessment of WT1 variants and their expression in relation to chromosomal changes and molecular prognostic markers in acute myeloid leukemia (AML). It is the first multidimensional study in Polish AML patients; (2) Methods: Bone marrow aspirates of 90 AML patients were used for cell cultures (banding techniques and fluorescence in situ hybridization), and to isolate DNA (WT1 genotyping, array comparative genomic hybridization), and RNA (WT1 expression). Peripheral blood samples from 100 healthy blood donors were used to analyze WT1 rs16754; (3) Results: Allele frequency and distribution of WT1 variant rs16754 (A;G) did not differ significantly among AML patients and controls. Higher expression of WT1 gene was observed in AA genotype (of rs16754) in comparison with GA or GG genotypes10,556.7 vs. 25,836.5 copies (p = 0.01), respectively. WT1 mutations were more frequent in AML patients under 65 years of age (p < 0.0001) and affected relapse-free survival (RFS). The presence of NPM1 or CEBPA mutations decreased the risk of WT1 mutation presence, odds ratio (OR) = 0.11, 95% CI 0.02−0.46, p = 0.002 or OR = 0.05, 95% CI 0.006−0.46, p = 0.002, respectively. We observed significantly higher WT1 expression in AML CD34+ vs. CD34−, −20,985 vs. 8304 (p = 0.039), respectively. The difference in WT1 expression between patients with normal and abnormal karyotype was statistically insignificant; (4) Conclusions: WT1 gene expression and its rs16754 variant at diagnosis did not affect AML outcome. WT1 mutation may affect RFS in AML.
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Acute myeloid leukemia (AML) constitutes a group of diseases that are very heterogeneous with regard to clinical course, response to therapy as well as cytogenetic aberrations and gene mutations. Such lesions are of prognostic value. Patients with t(8;21), inv(16)/t(16;16) or t(15;17) have a favorable prognosis. Patients with normal karyotype and aberrations +6, +8 Y, t(9;11) and del(12p) are classified in the group of intermediate prognosis. In the case of patients with complex karyotype or with the aberrations inv(3)/t(3;3), t(6;9), 5, 7, del(5q), del(7q) and 11q23 rearrangements, the prognosis is poor. Unfavorable molecular factors include C-MYC amplification, MLL amplification and rearrangement, FLT3-ITD, WT1 mutation and overexpression of BAALC, ERG or MN1. The changes in miRNA expression may also be important for AML prognosis. That is why the cases with normal karyotype (CN-AML) and cases with complex aberrations remain to be better characterized at the genetic level. Array technology enables the analysis of genomic DNA and gene expression. This approach may be used in the search for new prognostic and predictive markers in AML.
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Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Mutación , Aberraciones Cromosómicas , Humanos , PronósticoRESUMEN
BACKGROUND: Most of the world's population lives in countries in which overweight and obesity kill more people than does underweight. The weight loss process can be supported by mental simulations, which are used to help individuals to effectively strive towards various goals. The aim of this study was to determine the impact of different types of mental simulations on perseverance, resistance to distractors and the ability to inhibit irrelevant thoughts or memories in people with different body mass indexes (BMI). METHODS: The study included 252 participants. They performed process simulations and outcome simulations, using instructions presented to them during the experiment. Perseverance and resistance to distractors were determined using a computer maze-solving task. Two indicators of perseverance were analysed: number of maze tasks solved and total time spent on solving the test. Mean time spent on a single task was used as a measure of resistance to distractors and the ability to inhibit irrelevant thoughts and memories. RESULTS: The results of the analyses showed that the type of mental simulation used had an effect on the indicators of perseverance. Process simulation subjects completed more tasks and spent more time solving the test than outcome simulation subjects. A relationship was found between the subjects' BMI and the investigated indicators. Individuals who were underweight, overweight or obese scored lower on all three indicators compared to subjects with normal BMI. In people with a BMI above normal, mental simulations increased resistance to distractors and the ability to inhibit thoughts sidetracking them from the task at hand. It is possible that increasing the resistance to distractors is responsible for the effectiveness of mental simulations in the weight loss process. CONCLUSION: Our results can be applied in developing interventions for people who suffer from overweight and obesity. Psychological interventions based on mental simulations can be used to assist individuals in physical activity, leading to an improvement in health, but it has to be underlined that the mechanism of their action may vary from person to person.
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Algae are potential and natural source of long-chain polyunsaturated fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The diatom Pinnularia borealis accumulates high levels of EPA and may be considered as a source for commercial production of dietary supplements. In this study we asked the question whether diet supplementation with P. borealis may augment antioxidant defense and ameliorate risk factors for cardiovascular diseases. We fed mice (Mus musculus) with lyophilized diatom solutions of different concentrations (1%, 3%, and 5%) for 7 days. Then we measured glutathione content and the activity of glutathione redox system enzymes, total cholesterol and triacylglycerol concentrations, and malondialdehyde concentration in the liver and kidney. We found that cholesterol and triacylglycerol concentrations in the liver and kidneys were the lowest in mice who were fed with the highest concentration of Pinnularia borealis, suggesting protective properties of algae. Additionally, the lowest concentration of Pinnularia borealis was sufficient to improve antioxidant capacity. Our results suggest that P. borealis may be used as a source for dietary supplements rich in EPA, but the amount supplied to the organism should be limited.