Introduction: The insertion (I allele) deletion (D allele) polymorphism of ACE gene (rs4646994) may influence the etiopathogenesis of multiple myeloma (MM). ACE gene is expressed in bone marrow cells and encodes angiotensin converting enzyme (ACE). It converts angiotensin I to active peptide angiotensin II, which stimulates proliferation of hematopoietic stem cells. This suggests possible association of ACE I/D gene polymorphism with MM. The aim of our study was to check possible impact of this polymorphism on risk of development and outcome of MM, as well as, sensitivity to bortezomib in cell cultures derived from MM patients. Objects and Methods: Genomic DNA from 98 newly diagnosed MM patients and 100 healthy blood donors were analyzed by PCR method. Chromosomal aberrations were detected by use of cIg-FISH. In a subgroup of 40 MM patients nucleated bone marrow cells were treated with bortezomib in vitro. Results: The Hardy-Weinberg equilibrium test showed that genotypic frequencies diverged significantly from the equilibrium. The differences between I and D allele frequencies in control and study population were significant (p=0.046). We observed the association between DD genotype and more than 2-fold risk of MM – OR=2.69; p<0.0001. We did not detect any significant differences among studied genotypes regarding clinical and laboratory parameters. Moreover we did not observe the association between survival of MM patients and I/D genotypes. Bortezomib increased number of apoptotic and necrotic cells, but the only statistically significant differences were observed in the number of viable cells at 1nM between ID and DD genotypes (p=0.026). Conclusion: Presented results confirmed the significant relationship between ACE (I/D) polymorphism and risk of MM development. We did not observe the association of ACE I/D polymorphism with disease outcome and bortezomib in vitro sensitivity.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by the fibrosis of skin, heart, lung, and kidney as well. Excessive activation of fibroblasts is associated with higher expression of Notch1 and/or Notch3 genes. The constitutive expression of NOTCH genes was described in epithelial cells: epidermal keratinocytes, hair follicle cells and sebaceous glands. The NOTCH signalling pathway may be involved in the development of fibrosis, myofibroblast formation and the process of epithelial-mesenchymal transition. Activation of the NOTCH pathway leads to morphological, phenotypic and functional changes in epithelial cells. Furthermore, inhibition of Notch signalling prevent the development of fibrosis in different models, among them, bleomycin-induced fibrosis and in the Task-1 mause model. Molecular mechanisms, including the role of NOTCH signaling pathway, associated with fibrosis in SSc have not been completely recognized.

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.

Oxidative stress and systemic inflammation are closely linked with increased risk of cancer development. Tumor necrosis factor alpha (TNF-α) is one of the pro-inflammatory cytokines. Glutathione S-transferases (GSTs) are enzymes involved in oxidative stress handling. Polymorphisms of genes encoding mentioned molecules may potentially influence the risk and the outcome in neoplastic diseases. Multiple myeloma (MM) is a haematological malignancy characterized by clonal, atypical plasma cell proliferation. In the present study we investigated the association of deletion polymorphisms in GSTT1/GSTM1 genes and single nucleotide polymorphisms (SNPs) in the TNF-α gene at positions -308/-238 with the risk and outcome in MM and sensitivity to bortezomib under in vitro conditions. One hundred newly diagnosed MM patients and 100 healthy blood donors were genotyped by means of multiplex PCR (for GSTs) and PCR-RFLP (for TNF-α). In a subgroup of 50 MM patients, bone marrow cells were treated with bortezomib in vitro. Patients with -238GA+AA or GSTT1-null genotypes had 2.0 (p=0.002) or 2.29 (p=0.013) fold increased risk of MM. The interaction effects and risk of MM were observed in GSTT1/GSTM1-null (OR=2.82, p=0.018), -308/-238GA+AA (OR=5.63, p<0.001), as well as in all combinations of -308 with GSTs. The -308/-238GA+AA genotypes in comparison to GG were associated with earlier MM onset – 61.14 vs. 66.86 years (p=0.009) and 61.72 vs. 66.52 years (p=0.035), respectively. Patients with GSTM1-present had shorter progression-free-survival (15.17 vs. 26.81 months, p=0.003) and overall-survival (22.79 vs. 34.81 months, p=0.039) compared with GSTM1-null. We did not observe relationship between response rate and studied polymorphisms. The in vitro study revealed significantly higher number of apoptotic cells at 12nM of bortezomib in GSTT1-present, GSTM1-null/present, -308GG and -238GG/GA+AA genotypes. Our findings comprise large analysis of studied polymorphisms in MM.

The role of post-therapeutic support after weight loss in obesity treatment is not fully understood. Therefore, weight maintenance after a successful weight loss intervention is not very common, especially in obese individuals. This randomized controlled study was conducted to explore the efficacy of following dietary and psychological support in a group of 36 obese individuals. Participants (22 women, 14 men aged 35.58 ± 9.85 years, BMI 35.04 ± 3.80 kg/m²) who completed a 12-month weight loss phase (balanced energy-restricted diet) were randomly allocated to receive 18-month support (SG) or no additional care (CG). The support phase included some elements of Ten Top Tips (TTT), cognitive behavioral therapy (CBT), motivational interviewing (MI) in combination with nutritional education and assessment of the level of physical activity. The primary outcome was the maintenance of anthropometric parameters at an 18-month follow-up. The secondary outcomes included evaluation of biochemical parameters and single nucleotide polymorphisms (SNPs) in genes connected with obesity. A comparison of SG vs. CG after a 30-month period of the study revealed significant differences in weight changes (−3.83 ± 6.09 vs. 2.48 ± 6.24 kg), Body Mass Index (−1.27 ± 2.02 vs. 0.72 ± 2.12 kg/m²), visceral adipose tissue (−0.58 ± 0.63 vs. 0.45 ± 0.74 L), and waist circumference (−4.83 ± 4.05 vs. 1.83 ± 5.97 cm). Analysis of SNPs (rs9939609 FTO, rs987237 TFAP2B, and rs894160 PLIN1) provided further insight into the potential modulating effect of certain genotypes on weight loss and maintenance and extended the knowledge of the potential benefits of personalized medicine. Post-therapeutical support in current clinical practice may increase the chances of long-term weight loss maintenance in obesity treatment even in patients with a genetic predisposition to excessive weight.

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.