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Aim Hyperglycaemia diagnosed in pregnancy (HiP) is a serious and frequent complication of pregnancy, increasing the risk for adverse maternal and neonatal outcomes. Investigate whether allelic variations of the glucocorticoid receptor are related to an increased risk of HiP. Method The following polymorphisms of the glucocorticoid receptor (GR) were investigated in the cohort study of N = 197 pregnant women with HiP and N = 133 normoglycemic pregnant controls: 646C > G (rs41423247), N363S (rs6195), ER23/22EK (rs6190, rs6189). Results A GG variant of the rs41423247 polymorphism was associated with a significantly higher risk for HiP: OR 1.94 (1.18; 3.18), p = 0.009. The relationship remained significant after controlling for maternal age and prepregnancy BMI: OR 3.09 (1.25; 7.64), p = 0.014. Conclusions The allelic GG variant of the 646C > G (rs41423247) polymorphism is associated with an increased risk for hyperglycaemia in pregnancy.

Making accurate decisions often involves the integration of current and past evidence. Here we examine the neural correlates of conflict and evidence integration during sequential decision making. Female and male human patients implanted with deep-brain stimulation (DBS) electrodes and age- and gender matched healthy controls performed an expanded judgement task, in which they were free to choose how many cues to sample. Behaviourally, we found that while patients sampled numerically more cues, they were less able to integrate evidence and showed suboptimal performance. Using recordings of Magnetoencephalography (MEG) and local field potentials (LFP, in patients) in the subthalamic nucleus (STN), we found that beta oscillations signalled conflict between cues within a sequence. Following cues that differed from previous cues, beta power in the STN and cortex first decreased and then increased. Importantly, the conflict signal in the STN outlasted the cortical one, carrying over to the next cue in the sequence. Furthermore, after a conflict, there was an increase in coherence between the dorsal premotor cortex and subthalamic nucleus in the beta band. These results extend our understanding of cortico-subcortical dynamics of conflict processing, and do so in a context where evidence must be accumulated in discrete steps, much like in real life. Thus, the present work leads to a more nuanced picture of conflict monitoring systems in the brain and potential changes due to disease.Significance StatementDecision-making often involves the integration of multiple pieces of information over time in order to make accurate predictions. We simultaneously recorded whole-head magnetoencephalography and local field potentials from the human subthalamic nucleus in a novel task which required integrating sequentially presented pieces of evidence. Our key finding is prolonged beta oscillations in the subthalamic nucleus, with a concurrent increase in communication with frontal cortex, when presented with conflicting information. These neural effects reflect the behavioural profile of reduced tendency to respond after conflict, as well as relate to suboptimal cue integration in patients, which may be directly linked to clinically reported side-effects of Deep Brain Stimulation such as impaired decision-making and impulsivity.

A few years ago it was shown that disturbed metabolism of the vitamin D/receptor (VD/VDR) complex may be important in the etiology of spontaneous abortion, as well as in the etiology of recurrent miscarriages (RM). The goal of this study was to investigate the association between four maternal VDR polymorphisms as well as haplotypes settings and RM occurrence in a Polish population of women in reproductive age. A total of 230 women were recruited to this study (110 with RM, 120 consecutively recruited age-matched healthy women with at least two full-term pregnancies and with no history of miscarriages). DNA samples were genotyped for VDR polymorphisms: FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236). Significant differences in genotype distributions and allele frequencies between case and control groups were observed in VDR BsmI polymorphism (GG vs. GA and AA, OR = 0.56, p = 0.036 and OR = 1.49, p = 0.035, respectively). The best evidence of an association with RM prevention was observed for the TTGT haplotype, which was more frequent among controls than cases even after permutation test (0.09 vs. 0.017, p = 0.0024). Other haplotypes were also significantly more frequent in the control group: TGT (rs7975232, rs1544410, rs2228570), TG (rs7975232, rs1544410), TTG (rs731236, rs7975232, rs1544410), TT (rs731236, rs7975232). Our research indicated the possible role of VDR BsmI genetic polymorphism in RM etiology, suggesting at the same time the active role of maternal VD metabolism and its influence on pregnancy outcome. The significant influence of several maternal haplotypes was shown to prevent RM occurrence.

The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.

This study was designed to investigate the relationship between the levels of select adipocytokines (adiponectin, visfatin and apelin) and angiotensin in converting enzyme (ACE) gene insertion/deletion (ID) polymorphism in lean women with and without polycystic ovary syndrome (PCOS). The PCOS group (

Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance in normal estrogen and androgen levels in the blood. Androgens influence bone mineral density, body mass composition, muscle mass, mental state, and the regulation of sexual function.. The aim of the study was to assess the effect of estrogen receptor α gene (ESR1) polymorphisms on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group included 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, sRANKL (soluble receptor activator of nuclear factor-kB ligand), osteoprotegerin and 25-OH vitamin D total levels. An analysis of ESR1 gene polymorphisms was performed using the real-time PCR method. A relationship was demonstrated between the concentration of free estradiol (FEI) and the concentration of 17-OH-progesterone, and the ESR1 gene polymorphisms: rs3020314 (p = 0.031, p = 0.026 respectively) and rs1884051 (p = 0.033, p = 0.026 respectively). In conclusion, the ESR gene polymorphisms may be associated with hormonal disturbances in the concentration of estrogens and androgens, in hyperandrogenism in young women which may indirectly affect bone mineral density. However, no statistically significant relationships between the studied polymorphisms and the selected parameters of mineral metabolism have been demonstrated..

Organ transplant is often the treatment of choice as it extends and improves patient life. Immunosuppressive treatment, which prevents acute rejection of the organ, is used in transplant patients to prevent the loss of transplant. The aim of the study was to determine the impact of the CTLA4 (+49A>G, rs231775) and the TGF-β1 (−800G>A, rs1800468) polymorphisms on the therapeutic effect of immunosuppressive drugs (cyclosporine—CsA, tacrolimus—TAC) and the risk of acute rejection in renal transplant patients. The analysis of the CTLA4 +49A>G and the TGF-β1 −800G>A polymorphisms was carried out in 392 patients after kidney transplant using real-time PCR. The CTLA4 +49A>G polymorphism did not affect CsA or TAC dose, ratio of drug concentration to dose (C/D), and blood concentrations. As for the TGF-β1 -800G>A polymorphism, patients with the GA genotype required lower TAC doses compared to the GG genotype (TAC 12 h: 3.63 mg vs 5.3 mg, TAC 24 h: 2.38 mg vs 3.29 mg). Comparing the C/D ratio in both groups (TAC 12 h and TAC 24 h), higher C/D ratio was observed in patients with the GA genotype. These results indicate that patients with the A allele require slightly lower doses of TAC. The results suggest that the TGF-β1 −800 G>A polymorphism may influence the TAC dose, while the +49A>G polymorphism of the CTLA4 gene does not correlate with the dose of CsA or TAC. The analysis of the biochemical parameters of the renal profile showed no impact of the CTLA4 and the TGF-β1 polymorphisms on the risk of organ rejection.

MATERIAL AND METHODS The study included 675 unrelated women (109 women with osteopenia, 333 women with osteoporosis, and 233 healthy women). Genomic DNA was extracted from the blood samples and the CYP19A1 polymorphisms were determined using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Bone mineral density at the lumbar spine (L1-L4) was measured with dual energy X-ray absorptiometry (DEXA). RESULTS The analysis of the CYP19A1 rs749292 polymorphism showed that there were no statistically significant differences in the distribution of genotypes between the study groups with osteoporosis and osteopenia and the control group. However, it was noted that the GG genotype occurred more often in the group with osteopenia (35.8%; OR = 1.44) than in the control group (27.9%). Also, a difference was noted in the distribution of genotypes in women with osteoporosis. In addition, it can be assumed that the G allele may lead to an increased susceptibility to osteopenia and osteoporosis. The analysis of the CYP19A1 rs700518 polymorphism showed that heterozygotes were more common in the group with osteoporosis (58.3%) than in the control group (52.8%). CONCLUSIONS Our results suggest that the rs749292 polymorphism of the CYP19A1 gene may contribute to an elevated risk for fractures in postmenopausal Polish women.

Objectives: 1) to analyse the prevalence of selected candidate genes for type 2 diabetes mellitus polymorphisms (IRS1 G972R; ENPP1 K121Q; ADRB3 W64R) among women with gestational diabetes; and 2) to investigate any association between variants of these genes and risk of neonatal macrosomia. Material and methods: We conducted a prospective observational study of a group of women (N = 140) in singleton pregnancies who delivered at term. Characteristics of the study group at enrolment: age: 32.0 ± 4.9 years; GA: 26.6 ± 7.5 weeks; HbA1c: 5.6 ± 0.6%; fasting blood glucose: 102.3 ± 16.3 mg/dL; insulin treatment (G2DM): 65.7%; chronic hypertension: 11.4%; gestational hypertension: 17.9%; preeclampsia: 1.4%; birth weight: 3590 ± 540 g; birth weight ≥ 4000 g (macrosomia): 18.6%; caesarean section: 44.3%; and female newborns: 57.1%. Results: The maternal metabolic characteristics at the time of booking did not differ between polymorphisms. Macrosomia was insignificantly more frequent in females (22.5%) than in males (13.3%) (p = 0.193). Only maternal height and body weight at the time of booking significantly predicted birth weight (R = 0.27, p = 0.007; R = 0.25, p = 0.005, respectively). IRS1 G972R GR and ENPP1 K121Q KQ polymorphisms were associated with an insignificantly increased risk for macrosomia. Carriers of the heterozygotic variant of the IRS 1 gene were significantly more likely to be diagnosed with GDM/DiP in the first trimester: OR 5.2, 95% CI: 1.4; 19.2; p = 0.014. Conclusions: 1) having similar metabolic characteristics, carriers of specific variants of T2DM candidate genes might be at increased risk of delivery of macrosomic newborns; 2) any association between genetic variants and macrosomia in this population might be gender-specific; and 3) allelic variation in the IRS1 gene is associated with early GDM/DiP.

The UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in the process of estrogen conjugation and elimination. The aim of the study was to analyze whether the UGT1A1 genetic variants are associated with the development of osteopenia and osteoporosis in postmenopausal women. The analysis of the rs4148323 (UGT1A1*6) and rs3064744 (UGT1A1*28) variants in the UGT1A1 gene was conducted using real-time PCR. A significant correlation was observed between the genotypes of the rs3064744 (UGT1A1*28) sequence variant and body mass in women with osteoporosis. The analysis of the Z-score values revealed that women with osteoporosis and carrying the 6/6 variant had the lowest Z-score values as compared to women with the 6/7 and the 7/7 variants (− 1.966 ± 0.242 vs. − 1.577 ± 0.125 and − 1.839 ± 0.233). In addition, the odds ratio for the investigated genotypes (6/6, 6/7, 7/7) indicated an increased risk for osteopenia and osteoporosis in women with the 7/7 homozygous genotype. The analysis of the frequencies of the GG, GA and AA genotypes of the rs4148323 UGT1A1 gene showed no statistically significant differences between the groups. Our analysis revealed that the UGT1A1 rs3064744 variant may affect the risk of developing osteoporosis in postmenopausal Polish women. The UGT1A1 rs4148323 variant is not directly associated with the development of osteopenia and osteoporosis.

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α, IL-1β, IL-6) and vascular effects (hypoxia-inducible factor 1α—HIF-1α, placental growth factor—PIGF, transforming growth factor β—TGF-β, vascular endothelial growth factor—VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1β, IL-6, HIF-1α, TGF-β, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.

Objective: This study aimed to analyse the effect of neuropsychological activation methods on interictal epileptiform discharges, compared to standard activation methods, for both focal and generalized epilepsies. Methods: This was a multicentre, prospective study including 429 consecutive EEG recordings of individuals with confirmed or suspected diagnosis of epilepsy. Neuropsychological activation included reading aloud in foreign and native language, praxis and a letter cancelation task (each with a duration of three minutes). After counting interictal discharges in three-minute time windows, activation and inhibition were assessed for each procedure, accounting for spontaneous fluctuations (95% CI) and compared to the baseline condition with eyes closed. Differences between generalized and focal epilepsies were explored. Results: Interictal epileptiform discharges were present in 59.4% of the recordings. Activation was seen during hyperventilation in 31%, in at least one neuropsychological activation method in 15.4%), during intermittent photic simulation in 13.1% and in the resting condition with eyes open in 9.9%. The most frequent single cognitive task eliciting activation was praxis (10.3%). Lasting activation responses were found in 18–25%. Significant inhibition was found in 88/98 patients with baseline interictal epileptiform discharges, and was not task-specific. Significance: Adding a brief neuropsychological activation protocol to the standard EEG slightly increased its sensitivity in patients with either focal or generalized epilepsy. However, in unselected epilepsy patients, this effect seems only exceptionally to result in ultimate diagnostic gain, compared to standard procedures. From a diagnostic perspective, cognitive tasks should be reserved for patients with a suspicion of cognitive reflex epilepsy/seizures and probably require longer exposure times. Further research is needed to explore potential therapeutic applications of the observed inhibition of interictal epileptiform discharges by cognitive tasks in some patients.

Bacterial infections are the most common cause of purulent soft tissue inflammations in the head and neck area. These bacteria are also responsible for the majority of inflammatory complications after third molar removal. The key to success of antibacterial treatment in both cases is the use of an appropriate antibacterial agent. The aim of the study was to evaluate the susceptibility profile of bacteria isolated from material collected from patients with intraoral odontogenic abscesses. The test material consisted of swabs taken from the odontogenic abscesses, after their incision and drainage. Another swab was collected from the lesion area, 10 days after the initial visit. Results were compared with an identical study conducted on a control group of healthy patients, who had undergone third molar removal. Bacteria identified in this study consisted of aerobic and anaerobic strains, both Gram-positive and Gram-negative. According to the EUCAST guidelines, none of the tested antibiotics was recommended for all identified bacteria. The percentage of bacterial strains sensitive to amoxicillin and clavulanic acid was 78.13% and 81.48% in the study and control groups, respectively, whereas, the percentage of those sensitive to clindamycin was 96.43% and 80.00%, respectively. For Gram-negative aerobic bacteria, gentamicin and ciprofloxacin were among medications affecting all cultured species. 100.00% of strains were found to be susceptible to these antibiotics. Statistically significant relationship between the presence of Gram-negative aerobic strains and the occurrence of complications was found. In the case of the most frequently occurring bacteria in the study, amoxicillin with clavulanic acid and clindamycin were shown to be very effective. In cases of severe purulent odontogenic inflammations, it is recommended to use a combination of antibiotics. Amoxicillin with ciprofloxacin and clindamycin with cefuroxime seem to be the proper choices based on the results of this study.

Genes encoding insulin receptor substrates IRS-1 and IRS-2 perform key functions in the insulin pathway. Numerous authors have suggested that single-nucleotide polymorphism (SNP) changes in the DNA sequence may be associated with the development of obesity, insulin resistance and type 2 diabetes. The Gly972Arg polymorphism of the IRS-1 gene and the Gly1057Asp polymorphism of the IRS-2 gene are believed to be associated with the occurrence of insulin resistance and obesity according to many sources. The aim of our study was to investigate the influence of these polymorphisms on the clinical parameters and to assess their correlations in obese Polish pregnant women. A total of 154 pregnant Caucasian women from the Wielkopolska region were analyzed: 78 diagnosed with overweight or obesity (study group) and 76 with normal body mass (controls). The analysis of the polymorphisms was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. The IRS-2 Gly1057Asp polymorphism revealed no significant correlations with excessive weight gain during pregnancy. The analysis of the IRS-1 Gly972Arg polymorphism showed an association with obesity between the study and control groups (GG-80.77%, GR-17.95%, RR-1.28% vs GG-94.74%, GR-5.26%; p = 0.023). We also observed slightly increased BMI values ​​and higher values ​​of the waist and hip circumference before pregnancy in the case of the IRS-1 Gly972Arg polymorphism. The analysis of the clinical and anthropometric parameters demonstrated no significant relationships between the genotypes of the polymorphic variants of the IRS-1 and IRS-2 genes but suggested an association between the IRS-1 Gly972Arg polymorphism and the risk for obesity.

Background An increased prevalence of allergies and an increased incidence of breast cancer have been observed. The hypothesis that atopy may have a protective effect against the risk of different types of breast cancer was evaluated. Methods In this study, 11,101 patients (11,101 women with a mean age of 55.2±14.7 years) with different types of breast cancer were tested for allergies. Allergies were confirmed based on the retrospective analysis of allergy diagnostic procedures in patients who had been previously diagnosed with breast cancer. The retrospective prevalence rates of active allergic diseases, including allergic rhinitis, bronchial asthma and atopic dermatitis, were assessed. All patients were also analyzed for bronchial asthma and allergic rhinitis according to the relevant guidelines. A group of healthy control patients was used for the comparisons. Results The women with breast cancer had a significantly lower incidence of IgE-mediated allergic diseases than the controls. The odds ratios (ORs) for allergic rhinitis, atopic dermatitis, and bronchial asthma were 0.61 (95% CI: 0.57-0.73), 0.17 (95% CI: 0.11-0.44), and 0.73 (95% CI: 0.65-0.83), respectively. The mean serum concentrations of total IgE were significantly lower in the study population of women with breast cancer than in the patients of the control group (39.2 ± 26.2 kU/L vs. 108.5 ± 38.5 kU/L; p = 0.002). Conclusion Our results suggest that the overall incidence of allergies, especially allergic rhinitis, is lower in patients with certain types of cancer than in individuals who did not have cancer. Further studies are needed to confirm our findings.

BACKGROUND Orthognathic surgery (OGS) is associated with extensive surgical intervention within the soft and hard tissues of the facial region of the skull leading to inflammatory reactions. The presence of postoperative swelling indicates the accumulation of exudate or transudate; both these fluids occur in surgery. Massive swelling is a significant problem, because the tension of tissues intensifies pain sensations. The aim of the study was to evaluate the effectiveness of the kinesio taping method (KT) in patients after orthognathic surgery in the area of the facial skull in terms of eliminating postoperative swelling. MATERIAL AND METHODS The study of the impact of kinesiology tape applied after orthognathic surgery to the craniofacial area on the elimination of swelling was performed in sixteen patients who suffered from this complication after bilateral sagittal split osteotomy. RESULTS The swelling was shown to be reduced after KT; within the same study the differences were statistically significant between the left and right sides and for the same side (p

Population association studies have demonstrated a strong association between ESR2 SNPs and BMD, indicating that ESR2 may influence attainment of bone mass. The aim of the study was to investigate the ESR2 gene, located on chromosome 14q linked with BMD, which demonstrates a correlation with changes in bone mass in healthy Caucasian women. The study included 675 unrelated Polish postmenopausal women, including 109 with osteopenia, 333 with osteoporosis and 233 healthy women. The women were classified into the following groups: osteopenia, osteoporosis and normal T-score. Analysis of genotype frequency for the ESR2 rs1256044 polymorphism revealed no statistically significant differences. No statistically significant differences were noted for the allele frequency. However, it is noticeable that the CT genotype occurred more often in women with osteopenia (50.4%, OR = 1.14) and osteoporosis (54.7%, OR = 1.33) than controls (47.7%). There were statistically significant differences between the clinical parameters and distribution of genotypes in patients with osteopenia but not osteoporosis. ESR2 polymorphisms demonstrate minimal influence on BMD changes in women. Identification of various genes with little impact on BMD, such as ESR2, might help design a screening panel for osteoporosis risk assessment in healthy subjects.

Reward prediction errors (RPEs) and risk preferences have two things in common: both can shape decision making behavior, and both are commonly associated with dopamine. RPEs drive value learning and are thought to be represented in the phasic release of striatal dopamine. Risk preferences bias choices towards or away from uncertainty; they can be manipulated with drugs that target the dopaminergic system. Based on the common neural substrate, we hypothesize that RPEs and risk preferences are linked on the level of behavior as well. Here, we develop this hypothesis theoretically and test it empirically. First, we apply a recent theory of learning in the basal ganglia to predict how RPEs influence risk preferences. We find that positive RPEs should cause increased risk-seeking, while negative RPEs should cause risk-aversion. We then test our behavioral predictions using a novel bandit task in which value and risk vary independently across options. Critically, conditions are included where options vary in risk but are matched for value. We find that our prediction was correct: participants become more risk-seeking if choices are preceded by positive RPEs, and more risk-averse if choices are preceded by negative RPEs. These findings cannot be explained by other known effects, such as nonlinear utility curves or dynamic learning rates., Author summary Many of our decisions are based on expectations. Sometimes, however, surprises happen: outcomes are not as expected. Such discrepancies between expectations and actual outcomes are called prediction errors. Our brain recognizes and uses such prediction errors to modify our expectations and make them more realistic—a process known as reinforcement learning. In particular, neurons that release the neurotransmitter dopamine show activity patterns that strongly resemble prediction errors. Interestingly, the same neurotransmitter is also known to regulate risk preferences: dopamine levels control our willingness to take risks. We theorized that, since learning signals cause dopamine release, they might change risk preferences as well. In this study, we test this hypothesis. We find that participants are more likely to make a risky choice just after they experienced an outcome that was better than expected, which is precisely what our theory predicts. This suggests that dopamine signaling can be ambiguous—a learning signal can be mistaken for an impulse to take a risk.

Colorectal cancer (CRC) is one of the most common malignancies in Poland. Based on the findings of clinical trials, it is safe to conclude that genetic predisposition and environmental factors are the main factors responsible for the formation of colorectal cancer.The NQO1 gene plays an important role in reducing endogenous and exogenous quinones as well as quinone compounds to hydroquinones. It is an enzyme which is a part of the body’s antioxidant defense system. The aim of the study was to evaluate the correlation between the 609C &gt, T polymorphism of the NQO1 gene and colorectal cancer risk in the Polish population. A total of 512 people were recruited for the study, including 279 patients with colorectal cancer, diagnosed at the University Hospital, Pomeranian Medical University in Szczecin. Genomic DNA was isolated from peripheral blood and the analyzed polymorphism was determined by PCR-RFLP. In the present study, we analyzed the clinical valuesand frequency of NQO1 609C &gt, T polymorphism in patients diagnosed with colorectal cancer and controls. In case of the carriers of the TT genotype of the NQO1 polymorphism, an elevated risk for colorectal cancer was observed (OR = 2.96, 95% CI: 1.02–10.40). The analysis of the clinical parameters concerning the location and characteristics of the tumor stage revealed a statistically significant increase in the risk for colorectal cancer in the carriers of the TT genotype of the NQO1 polymorphism.

Objectives: Collagen type I plays an important role in the bone matrix and is encoded by COL1A2 (collagen type I alpha 2) gene that may be a potential candidate for osteoporotic fracture. The aim of this study is to determine whether EcoR I, Del 38 and Pvu II polymorphisms of COL1A2 are associated with the development of osteoporosis and osteopenia in post­menopausal Polish women. Moreover, analysis of relationship between frequency of COL1A2 gene polymorphic variants and clinical parameters of bone turnover and degree of osteoporosis was performed. Material and methods: The study group comprised of women with osteoporosis (n = 90), osteopenia (n = 56) and healthy individuals (n = 56). The EcoR I, Del 38 and Pvu II polymorphisms in COL1A2 gene were detected by PCR-RFLP method. Results: In women with osteoporosis the TT genotype of EcoR I polymorphism had the lowest Z-score value compared to other genotypes (p = 0.034). In case of Del 28 polymorphism, there was a statistically significant correlation between lower BMI values and the DD genotype in women with osteopenia (p = 0.041). There was no statistically significant correlation between polymorphic variants of Del 28 polymorphism and clinical parameters of women with osteoporosis. The analysis of Pvu II polymorphism showed that in women with osteopenia the CC genotype had the lowest body weight compared to other genotypes (p = 0.039). Pvu II polymorphism and clinical parameters in the group of women with osteoporosis had no statistically significant correlations. Conclusions: The analyzed COL1A2 polymorphisms seem to be related to osteoporosis development and their particular clinical parameters. Hence, the COL1A2 polymorphism may be a genetic risk factor related to the development of osteoporosis.

The aim of the study was to determine the MTR (methionine synthase) and MTRR (mehionine synthase reductase) polymorphisms in pregnant women with preeclampsia (PE).The group of 98 women with PE and the group of 120 healthy pregnant women were analyzed. Determination of MTR 2756A G and MTRR 66A G polymorphisms was performed using polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) method.The study did not show any statistically significant differences in frequency of genotypes and alleles of MTR 2756A G polymorphism between PE group and controls. Higher frequency of 66GG genotype and 66G allele of MTRR 66A G polymorphism was observed in the women with PE compared to control group. Moreover, the 66GG genotype correlated with higher doses of methyldopa, lower birth weight and higher placenta weight in women with PE.The obtained results for 66A G polymorphism of MTRR gene suggest the predisposition to PE in carriers of mutated 66GG genotype and - 66G allele.

BACKGROUND Immunosuppressive drugs such as cyclosporine A (CsA) are characterized by a narrow therapeutic range and high interindividual pharmacokinetic variations. Therefore, the effective monitoring of drug serum level is crucial for successful therapy. This variability can be caused by polymorphisms in genes encoding drug transporters and enzymes responsible for biotransformation. The aim of this study was to determine the relationship between CYP3A4*1B and MDR1 polymorphisms and dose requirements to achieve the target therapeutic range for CsA. MATERIAL AND METHODS The study group consisted of 184 patients after kidney transplantation who were treated with immunosuppressive therapy. The MDR1 3435C>T and CYP3A4*1B polymorphisms were determined by the real-time PCR using the LightCycler® 480 device (Roche Diagnostics). RESULTS Patients with the CYP3A4*1/*1 genotype received the lowest mean dose of CsA compared to CYP3A4*1/*1B, and had a higher average drug concentration in the blood. In the case of MDR1 3435C>T polymorphism, we observed that patients with the CC genotype received lower doses of CsA than patients with the CT and TT genotypes. Average drug concentration in the blood was comparable to individuals with different MDR-1 genotypes. Analysis of dependence between both polymorphisms and concentration/dose ratio showed no statistically significant differences. CONCLUSIONS The characterization of CYP3A4*1B and 3435C>T MDR1 polymorphism cannot provide useful guidance for individualizing CsA dosages in renal transplant patients by indicating the optimal dose of these drugs without exposing patients to possible adverse effects associated mainly with nephrotoxicity.

The relationship between the genetic background, adipocytokines, and metabolic state in postmenopausal women has not yet been fully described. The aim of this study was to determine the relationship between PPAR gamma-2 (Pro12Ala, C1431T) and ADRB3 (Trp64Arg) polymorphisms and serum adipocytokines (adiponectin, visfatin, and resistin) and metabolic disorders in 176 postmenopausal women with increased body mass (BMI ≥ 25 kg m(-2)). The distributions of selected alleles and genotype frequencies were determined with the PCR-RFLP method. The bioimpedance method was used to determine nutritional status, and enzyme-linked immunosorbent assays were applied to determine serum concentrations of adipocytokines. Viscerally obese postmenopausal women had higher body mass, body fat content, serum glucose, insulin, total cholesterol, LDL, triglycerides, uric acid, and HOMA-IR and a higher prevalence of the Ala12 allele. In models based on cytokine concentration, higher body mass and glucose concentration (visfatin model, p = 0.008) and higher insulin and triglyceride levels (resistin model, p = 0.002) were observed in visceral fat deposition and this was potentiated by the presence of the T1431 allele. In resistin models, co-existence of Ala12/X polymorphisms with the T1431 allele was associated with higher resistin and triglyceride concentrations (p = 0.045). In postmenopausal women, metabolic parameters are mainly determined by the distribution of body fat, but Ala12/X polymorphism may increase the metabolic disorders and this effect can be enhanced by the T1431 allele.

CelCelem artykułu jest prezentacja przebiegu, wyników i wniosków z przeprowadzonego cyklu zajęć psychoedukacyjnych dla rodzin osób chorych na schizofrenię, leczących się w Szpitalu Specjalistycznym im. dr J. Babińskiego w Krakowie. Artykuł prezentuje projekt o charakterze eksploracyjnym, opierający się na jakościowym podejściu badawczym. Prezentowany program psychoedukacyjny mieści się w systemowym podejściu terapeutycznym, wykorzystującym ujęcie narracyjne.MetodaW projekcie wzięło udział 23 osoby z 16 rodzin, które uczestniczyły w 14 spotkaniach psychoedukacyjnych na przestrzeni 4 miesięcy. Zastosowano różnorodne metody edukacyjne: wykłady, studium przypadku, warsztaty interaktywne, psychorysunek, prezentacje multimedialne, symulacje sytuacji kryzysowych, zajęcia w podgrupach.WynikiPo zakończeniu cyklu spotkań u uczestników nie stwierdzono wyraźnego wzrostu poziomu wiedzy teoretycznej o schizofrenii, odnotowano natomiast spadek subiektywnie odczuwanego poczucia obciążenia chorobą w rodzinie. Mimo że wstępnie jedynie 11% uczestników oczekiwało od grupy wsparcia emocjonalnego, przez 60% badanych wsparcie zostało uznane za najważniejszą korzyść wyniesioną z programu.WnioskiZastosowanie w programie systemowego podejścia narracyjnego spotkało się z pozytywnym przyjęciem i dobrą oceną przez rodziny pacjentów chorujących na schizofrenię. Wydaje się być efektywną alternatywną dla „tradycyjnej” psychoedukacji. Wykorzystanie skutecznych narzędzi szkoleniowych połączone z jednoczesnym zostawieniem dużej przestrzeni do wymiany myśli i doświadczeń sprawdziło się jako dobra forma pomocy rodzinie w kryzysie.

Tumor hypoxia and high activity of hypoxia-inducible factor-1 (HIF-1) correlate with adverse disease outcomes, malignancy, resistance to therapy and metastasis. Nonetheless, recent studies indicate that under certain circumstances, HIF-1 stabilization may exert protective effects and even decrease tumor cell aggressiveness. This study aimed to characterize the potential anticancer effect of molidustat (BAY 85-3934), the prolyl hydroxylase (PHD) inhibitor and HIF-1 stabilizator. We confirmed that molidustat stabilizes HIF-1α and induces the expression of vascular endothelial growth factor (VEGF) in MDA-MB-231 breast cancer cells, to a similar or even greater extent than hypoxia. Interestingly, decreased cell survival and colony formation capabilities, together with S/G2 cell cycle arrest, were observed after treatment with PHD inhibitor. Importantly, molidustat enhanced the effectiveness of the chemotherapeutic drug, gemcitabine, on cancer cells. Finally, the xenograft model revealed decreased tumor growth in vivo after molidustat treatment. Both in vitro and in vivo analysis showed no differences in the angiogenic potential of endothelial cells treated with tumor-conditioned media or vascularization of the MDA-MB-231 xenografts, respectively. In summary, molidustat treatment exhibits an inhibitory effect on breast cancer cell survival, self-renewal capacity and potentiates the efficacy of chemotherapeutic gemcitabine.

Background Major symptoms of chronic obstructive pulmonary disease (COPD) are chronic bronchitis and emphysema leading from lung tissue destruction, that is an effect of an imbalance between metalloproteinases (MMPs) and their tissue inhibitors activity. As potential factor involved in this COPD pathogenesis, MMP-12 is considered. We investigated the role of genetic polymorphism and protein level of MMP-12 in the COPD development among Poles. Methods We analyzed − 82 A > G SNP in the promoter region of MMP-12 gene (rs2276109) among 335 smoked COPD patients and 309 healthy individuals, including 110 smokers. Additionally, 60 COPD patients and 61 controls (23 smokers) were tested for serum levels of MMP-12 using ELISA. All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). Results We observed that -82G allele and -82GG homozygous genotype frequencies of the SNP rs2276109 were significantly lower in COPD patients than in controls (12.5% vs 16.9%, respectively; χ2 = 4.742, p = 0.02 for allele and 0.5% vs 3.9%, respectively; χ2 = 9.0331, p = 0.01 for genotype). Moreover, −82G allele was more frequent in controls smokers than in non-smokers (22.3% vs 14.1%, χ2 = 6.7588, p = 0.01). Serum level of MMP-12 was significantly higher in COPD patients than in controls groups (6.8 ng/ml vs 3.3 ng/ml, respectively; F = 7.433, p

BACKGROUND Postmenopausal osteoporosis is the most common metabolic bone disease among women. The Wnt signaling pathway has been known to be the critical regulator of osteoblastogenesis. Alterations in this mechanism may have consequences for bone remodeling in humans. OBJECTIVES The aim of the study was to evaluate the frequency of genotypes and alleles of single nucleotide polymorphism (SNP) rs4988321 and rs312009 of LRP5 in Polish postmenopausal women with osteopenia (n = 109) and osteoporosis (n = 333). Potential correlations between genetic polymorphisms, bone mineral density (BMD), risk for bone fractures, and other clinical parameters were analyzed. MATERIAL AND METHODS Genomic DNA was extracted from the blood samples and the sequence polymorphisms of LRP5 gene were detected using real-time polymerase chain reaction (RT-PCR) methods with melting curve analysis. We also calculated the odds ratio (OR) for the LRP5 genotypes and the alleles. Then, we evaluated the effect of the LRP5 polymorphism on T-score, Z-score, L2L4AM, L2L4YA, L2L4BMD, body mass index (BMI), and other clinical parameters. RESULTS No statistically significant differences in the distribution of LRP5 rs312009 genotypes between the groups were observed. Furthermore, our findings indicate that there is no correlation between LRP5 genotypes and the clinical characteristics of women with osteopenia/osteoporosis. In contrast, there was an increased value of OR in heterozygotes for rs4988321, both in patients with osteopenia (OR = 1.47) and in those with osteoporosis (OR = 1.33). In our study, we were not able to calculate the OR parameter for the AA genotype due to its low prevalence in the population. CONCLUSIONS Our results suggest that the Val667Met LRP5 (rs312009) polymorphism may contribute to an elevated risk for fractures in postmenopausal Polish women.

Objectives: Cancer is the second most common cause of death, with breast cancer (BC) as the most frequently diagnosed neoplasm among females. The origin of BC is multifactorial and depends on environmental and genetic factors. The disease presents a significant challenge due to its drug resistance and frequent metastasis. Thus, new effective therapies and metastasis prevention are much needed. Rosmarinic acid (RA) is a natural polyphenol which possesses the ability to inhibit BC cell proliferation and demonstrates cytotoxic properties against those cells. In our study, we examined the effect of RA on the expression of ZEB1, MDM2, ABCB1, PTEN and TWIST1 genes in MCF-7 breast cancer cells. Material and methods: MCF-7 cell cultures were treated with 0.2 μM doxorubicin (DOX) and 1.5, 15 or 50 μM of RA. Real-time PCR reaction was performed to analyze gene expression levels. Results: PCR analysis showed a significant increase of the ZEB1 gene expression, which was about 3-fold for DOX 0.2 μM, 9-fold for 0.2 μM DOX + 1.5 μM RA and 0.2 μM DOX + 15 μM RA (p < 0.05), and about 6.5-fold for 0.2 μM DOX + 50 μM RA (p < 0.05). Furthermore, a decrease of the MDM2 gene expression was observed in all of the examined variants and was about 40–75% (p < 0.05). No influence of DOX and RA combined with DOX on the ABCB1, TWIST1 and PTEN genes was found. Conclusions: The results of our study suggest that RA might be used as an adjuvant therapeutic factor in BC treatment.

Summary To optimally balance opposing demands of speed and accuracy during decision-making, we must flexibly adapt how much evidence we require before making a choice. Such adjustments in decision thresholds have been linked to the subthalamic nucleus (STN), and therapeutic STN deep-brain stimulation (DBS) has been shown to interfere with this function. Here, we performed continuous as well as closed-loop DBS of the STN while Parkinson’s disease patients performed a perceptual decision-making task. Closed-loop STN DBS allowed temporally patterned STN stimulation and simultaneous recordings of STN activity. This revealed that DBS only affected patients’ ability to adjust decision thresholds if applied in a specific temporally confined time window during deliberation. Only stimulation in that window diminished the normal slowing of response times that occurred on difficult trials when DBS was turned off. Furthermore, DBS eliminated a relative, time-specific increase in STN beta oscillations and compromised its functional relationship with trial-by-trial adjustments in decision thresholds. Together, these results provide causal evidence that the STN is involved in adjusting decision thresholds in distinct, time-limited processing windows during deliberation., Highlights • We performed temporally patterned stimulation of the subthalamic nucleus in humans • During stimulation, Parkinson’s patients performed a perceptual decision-making task • Stimulation effects on behavior were confined to a short window during deliberation • Here, stimulation affected changes in decision thresholds during difficult decisions, In this article, Herz et al. provide causal evidence that the subthalamic nucleus mediates adjustments of decision thresholds, depending on the difficulty of the decision. This adjustment is processed during a short time window early during deliberation and is related to changes in oscillatory activity of the subthalamic nucleus.

Objective Osteoporosis is a civilization disease, in which the dominant symptoms are the loss of bone mass and disturbances in bone structure. Gremlin-2 is one of the BMP (bone morphogenetic proteins) antagonists and participate in osteogenesis and osteoblast differentiation. The aim of the study was to analyze whether the GREM2 gene polymorphism is significantly more common in postmenopausal women than in healthy women and whether it is a predisposing factor for the osteoporosis development. Study Design The study consisted of 675 unrelated Polish postmenopausal women, including 109 with osteopenia, 333 with osteoporosis and 233 healthy women. The effect of the GREM2 polymorphism on T-score, Z-score, L2L4AM, L2L4YA, L2L4BMD, body mass, BMI, birth weight was statistically evaluated. Results Statistical significance was observed between the TT and TC genotypes and also between TT and CC genotypes in the case of birth weight in the control group and the group of women with osteoporosis. Analysis of body mass in women with osteoporosis showed the statistical significance between genotypes TT and CC, TT and TC. Analysis of the frequencies of TT, TC and CC genotypes of the rs4454537 polymorphism of the GREM2 gene showed no statistical significance between studied groups. Conclusion Our study found that the most frequent genotype in the group of women with osteopenia and osteoporosis was TC while in the group of healthy women the protective TT genotype was dominant. Hence, it can be postulated that the TT genotype is a protective factor against the development of osteoporosis.

During a decision process the evidence supporting alternative options is integrated over time, and the choice is made when the accumulated evidence for one of the options reaches a decision threshold. Humans and animals have an ability to control the decision threshold, i.e. the amount of evidence that needs to be gathered to commit to a choice, and it has been proposed that the subthalamic nucleus (STN) is important for this control. Recent behavioural and neurophysiological data suggest that in some circumstances the decision threshold decreases with time during choice trials, allowing overcoming of indecision during difficult choices. Here we asked whether this within trial decrease of the decision threshold is mediated by the STN, and if it is affected by disrupting information processing in the STN through deep-brain stimulation (DBS). We assessed 13 patients with Parkinson’s disease receiving bilateral STN-DBS six or more months after the surgery, 11 aged-matched controls and 12 young healthy controls. All participants completed a series of decision trials, in which the evidence was presented in discrete time points, which allowed more direct estimation of the decision threshold. The participants differed widely in the slope of their decision threshold ranging from constant threshold within a trial to steeply decreasing. However, the slope of the decision threshold did not depend on whether STN DBS was switched on or off, and did not differ between the patients and controls. Furthermore, there was no difference in accuracy and reaction time between the patients in the on and off stimulation conditions and healthy controls. Previous studies which have reported modulation of the decision threshold by STN DBS or unilateral subthalamotomy in Parkinson’s disease have involved either fast decision-making under conflict or time pressure or in anticipation of high reward. Our findings suggest that in the absence of reward, decision conflict or time pressure for decision-making, the STN does not play a critical role in modulating the within trial decrease of decision thresholds during the choice process.

Chronic obstructive pulmonary disease (COPD) is characterized by a decline of lung function and symptoms such as chronic bronchitis and emphysema leading from lung tissue destruction. Increased activity of matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs) are considered as factors influencing the pathogenesis of COPD. We investigated the role of genetic polymorphism and expression level of MMP-9 and concentration of its complexes with TIMPs in the development of COPD among Polish patients. We analyzed SNP in the promoter region of MMP-9 gene (rs3918242) using PCR-RFLP method among 335 COPD patients and 309 healthy individuals. Additionally, 60 COPD patients and 61 controls were tested for copy number variants (CNV) of MMP-9 (by quantitative real-time PCR) and serum levels of MMP-9 and its complexes with TIMP1 and TIMP2 (using ELISA). All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). We observed that allele and genotype frequencies of the SNP rs3918242, as well as the number of gene copies, were similar in COPD patient and controls groups. Serum levels of MMP-9 and MMP-9/TIMP1 complex were significantly higher in COPD patients in comparison to controls groups, although independently of analyzed gene polymorphisms. Additionally, the significant inverse relationships between parameters of lung function (FEV1% and FEV1/FVC) and proteins level were found in ridge regression models, especially we found that FEV1% decreased when MMP-9 level increased in controls and patients with COPD group. In conclusion, we found that COPD patients were predisposed to produce more MMP-9 and MMP-9/TIMP1 complex than healthy individuals. This phenomenon is probably associated with the disease-related lung environment but not with genetic features of the MMP-9.

Introduction Thanks to new generation sequencing (NGS) and expansion of HLA typing with additional loci, it will be possible to increase the effectiveness of graft survival and to avoid complications related to the immune system. New pharmacogenetic factors are still being researched to develop better immunosuppressive treatment. Material and methods The incidence of polymorphic HLA loci variants was established, based on a high-resolution NGS method in kidney graft recipients. Furthermore, haplotypic analysis between examined loci was conducted to type additional loci that may influence the transplantation result. A total of 120 kidney recipients were enrolled in the study. A commercial DNA extraction kit in Tubes (QIAamp DNA Blood Mini Kit Qiagen, Germany) was used to isolate DNA from the blood. Sequencing library preparation was done with TruSight HLA set. The Conexio computer program was used to analyse the results of HLA typing. Results The patients with alleles A*02:01:01, B*44:02:01, C*03:03:01, C*01:02:01, C*05:01:01, C*07:02:01, DQB1*03:03:02, DQB1*06:04:01, or with haplotypic variation A*25:01:01-B*18:01:01- C*15:01:01 were taking the highest doses of cyclosporine (CsA), in contrast to patients with allele B*18:01:01, DQB1*06:02:01, DQB1*02:02:01, or haplotypic variation A*02:01:01- B*44:02:01-C*01:01:01, who were taking the lowest doses. The highest dose of tacrolimus (TAC) was administered to patients with alleles A*68:01:02, A*29:01:01, B*07:02:01, B*35:02:01, B*38:01:01, DRB1*12:01:01, DQB1*05:03:01, or haplotypic variations A*02:01:01-B*57:01:01-C*07:01:01, A*03:01:01-B*07:02:01-C*13:01:01, A*29:02:01-B*44:03:01- C*07:01:01, and A*01:01:01-B*08:01:01-C*03:01:01. Additionally, it was established that HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DPA1, and HLA-DQA1 show very slight polymorphism, which suggests that there is no need for their typing for transplantation purposes. Moreover, loci HLA-C, HLA-DQB1, and HLA-DPB1, which are not routinely examined in recipient-donor matching, show genetic variability that may increase the risk of transplant rejection or shortened graft life. Conclusions Expanding the qualification procedure to include allele genotyping could allow clinicians to establish immunosuppressive treatment schemes that would be optimally suited for recipients' phenotype.

Memory consolidation underpins adaptive behavior and dopaminergic networks may be critical for prolonged, selective information storage. To understand the time course of the dopaminergic contribution to memory consolidation in humans, here we investigate the effect of dopaminergic medication on recall and recognition in the short and longer term in Parkinson disease (PD). Fifteen people with PD were each tested on or off dopaminergic medication during learning/early consolidation (Day 1) and/or late consolidation (Day 2). Fifteen age-matched healthy participants were tested only once. On Day 1 participants learned new information, and early episodic memory was tested after 30 min. Then on Day 2, recall and recognition were retested after a 24-hr delay. Participants on medication on Day 1 recalled less information at 30 min and 24 hr. In contrast, patients on medication on Day 2 (8–24 hr after learning) recalled more information at 24 hr than those off medication. Although recognition sensitivity was unaffected by medication, response bias was dependent on dopaminergic state: Medication during learning induced a more liberal bias 24 hr later, whereas patients off medication during learning were more conservative responders 24 hr later. We use computational modeling to propose possible mechanisms for this change in response bias. In summary, dopaminergic medication in PD patients during learning impairs early consolidation of episodic memory and makes delayed responses more liberal, but enhances late memory consolidation presumably through a dopamine-dependent consolidation pathway that may be active during sleep.

Objectives The aim of the study was to evaluate the frequency of gene polymorphisms OPG − 163A/G, − 950T/C and 1181G/C, assessing their relations with the clinical parameters of osseous turnover and the degree of postmenopausal osteoporosis. Study design The study included 800 women of postmenopausal (505) and reproductive (295) age from Poland. The postmenopausal group included women with osteoporosis and osteopenia, as well as healthy individuals. All the women of reproductive age were healthy. The frequency of the tested gene polymorphisms was evaluated within the group where BMD (bone mineral density) was marked and also in the control group. Main outcome measures The frequencies of the polymorphisms of OPG genotypes in the women were characteristic of the population. Results OPG − 950T/C polymorphism has been associated with body weight and birth weight. OPG 1181G/C and OPG − 163A/G polymorphisms have been associated not only with body weight and birth weight, but also with reduced bone density and an increased risk of postmenopausal osteoporosis. Conclusions Evaluation of the polymorphism − 950T/C of the OPG gene showed that the CC genotype may appear as an increased risk factor for the faster loss of bone mass and the onset of osteoporosis in Polish postmenopausal women. This polymorphism may be a genetic marker that is responsible for the development of osteoporosis. The homozygous genotypes of polymorphisms 1181G/C and − 163A/G of the OPG gene may play a role in increased risks of osteoporosis and may be linked to the birth weights of women.

Objectives: Osteoporosis is a chronic, generalized bone disease conditioned by many factors among which the genetic background plays the significant role. Bone morphogenetic protein (BMP2), a growth factor belong to superfamily of TNF- proteins, is actively involved in bone tissue metabolism. BMP2 protein shows the osteoinduction potential and regulates growth of cartilage plate, and the same directly influences the process of osteogenesis. The aim: The aim of study was to examine the frequency of genotypes and alleles of 570A>T and 5375G>A of BMP2 gene polymorphisms in population of Polish postmenopausal women, as well as to analyze the relationship between investigated polymorphic variants and bone turnover parameters. Material and methods: Into the study 117 postmenopausal women, Caucasian race (average age 55,1 years) living in Wielkopolska region were classified. The analysis of 570A>T and 5375G>A BMP2 polymorphisms was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) while bone mineral density (BMD) was measured by DEXA method. In the research the chosen clinical and bone turnover parameters were analysed. Results: In both 570A>T and 5375G>A BMP2 polymorphisms the similar frequency of genotypes and alleles in investigated groups of postmenopausal women with osteoporosis, osteopenia and in the group with correct T-score were noted. The analysis do not show the relationship of clinical and bone turnover parameters with particular genotypes of BMP2 polymorphisms in women with osteoporosis, osteopenia and in the group with correct T-score. Conclusions: The research did not confirm directly relationship of 570A>T and 5375G>A BMP2 polymorphisms with osteoporosis development in population of Polish postmenopausal women. The investigation also shows lack of correlation of 570A>T and 5375G>A BMP2 polymorphisms polymorphisms with analysed clinical and bone turnover parameters.

INTRODUCTION Diabetic foot (DF) is a serious complication of diabetes mellitus (DM) that occurs due to neuropathy or atherosclerosis of the lower limbs. Omentin (encoded by the ITLN1 gene) has been implicated as a protective factor in vascular complications of diabetes, likely due to its endothelial vasodilator activity and its anti‑inflammatory actions. However, susceptibility to DF with respect to the allelic variants of the ITLN1 gene has not been studied so far. OBJECTIVES This study aimed to evaluate the association between the rs2274907 allelic variant of the ITLN1 gene and the occurrence of DF in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS The study included 670 individuals: 204 with T2DM and DF (DF group), 299 with T2DM without DF (T2DM group), and 167 healthy controls. RESULTS Ischemic heart disease, retinopathy, nephropathy, neuropathy, obesity, hyperlipidemia, and active smoking were more frequent in the DF group than in the T2DM group. Allele A of the rs2274907 variant was observed more frequently in the DF group compared with healthy controls in an additive model (odds ratio [OR] = 0.7, P = 0.034). This effect was also sex‑specific for males in both the additive and recessive models (OR = 0.6, P = 0.015 and OR = 0.52, P = 0.0017, respectively). However, no differences in the distribution of alleles was observed between the DF and T2DM groups. CONCLUSIONS The rs2274907 variant of the ITLN1 gene is associated with increased prevalence of DF.

The motor symptoms of both Parkinson's disease and focal dystonia arise from dysfunction of the basal ganglia, and are improved by pallidotomy or deep brain stimulation of the Globus Pallidus interna (GPi). However, Parkinson's disease is associated with a greater degree of basal ganglia-dependent learning impairment than dystonia. We attempt to understand this observation in terms of a comparison of the electrophysiology of the output of the basal ganglia between the two conditions. We use the natural experiment offered by Deep Brain Stimulation to compare GPi local field potential responses in subjects with Parkinson's disease compared to subjects with dystonia performing a forced-choice decision-making task with sensory feedback. In dystonic subjects, we found that auditory feedback was associated with the presence of high gamma oscillations nestled on a negative deflection, morphologically similar to sharp wave ripple complexes described in human rhinal cortex. These were not present in Parkinson's disease subjects. The temporal properties of the high gamma burst were modified by incorrect trial performance compared to correct trial performance. Both groups exhibited a robust low frequency response to 'incorrect' trial performance in dominant GPi but not non-dominant GPi at theta frequency. Our results suggest that cellular processes associated with striatum-dependent memory function may be selectively impaired in Parkinson's disease even if dopaminergic drugs are administered, but that error detection mechanisms are preserved.

Summary Introduction Physiotherapeutic methods, used in patients with urinary incontinence, are recommended and acknowledged treatment methods. They include pelvic floor muscle exercises, electrical stimulation, magnetic field, acupuncture, and biofeedback. However, the influence of Kinesio taping (KT) applications is not known. The aim of this work was to assess the influence of the KT method on the number of incontinence incidents in children. Additionally, children included in the research were given a depression level test to assess their mental state and how it is influenced by incontinence. Material and methods The study included 62 children (37 boys and 25 girls), aged 7–14 years, diagnosed as having night urinary incontinence and frequent daytime incontinence (daytime wetting). Study participants were randomly allocated to the research group, in which KT was applied, or the control group in which a placebo was used. The main outcome measure was the number of incontinence incidents. Result The analysis of study results indicated that there was a statistically significant decrease (p Discussion As can be seen from the analysis of the literature on urinary incontinence therapy, several physiotherapeutic methods are described. They are not merely based on a single strategy but include combinations of methods. To our knowledge, the method described in our work is a pioneer method, previously not applied on its own. It is, however, limited by a relatively small number of research participants, although it took 29 months to gather the group for the research. Additionally, the research based on the principle that children with up to threw incontinence episodes per day were given KT applications every 3 days (72 h per session), whereas children with more frequent incontinence episodes were given KT applications every day (24 h per session). It seems that the principle should be that all children are given KT applications with the same frequency. Perhaps it could be interesting to compare the effects between groups with different frequency. Nevertheless, we believe that the results obtained in this research are of interest in the context of possibility to use KT for urinary incontinence in children. Conclusion The KT method may serve as an effective complementary form of physiotherapy for children with urinary incontinence. Download : Download high-res image (289KB) Download : Download full-size image Figure . Daily incontinence results among children in the research and placebo groups.

Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus–response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the ‘normalization term’ in Bayes’ theorem). Here, we test these theories by investigating 22 patients with Parkinson’s disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions—information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined. * Abbreviations : DBS : deep brain stimulation UPDRS : Unified Parkinson’s Disease Rating Scale

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is characterized by anovulation, polycystic ovaries, hyperandrogenism leading to infertility, dermatological and psychological problems, as well as the risk of developing Metabolic Syndrome (MetS) and cardiovascular disease (CVD). The exact cause of PCOS remains unclear. Various biochemical and genetic markers have been implicated in predisposition to PCOS, but no single variant has been associated with the syndrome. Some authors connect hyperhomocysteinemia (HHcy) with MetS and its components. The MTHFR gene C677T polymorphism is a common genetic abnormality leading to hyperhomocysteinemia.The aim of the study was to confirm the existence of a possible correlation between metabolic disturbances in PCOS and the MTHFR C677T polymorphism.A total of 98 patients diagnosed with PCOS according to the Rotterdam criteria and 101 age-matched healthy controls were included in the study. Genotyping of MTHFR C677T was performed by the real time PCR method.Statistically significant differences were observed between those two groups with regard to body mass index (BMI), waist circumference (WC), hip circumference (HC), fasting insulin, total cholesterol (TC), and triglycerides (TG). No significant differences in the prevalence of the genotypes of the MTHFR C677T gene polymorphism were found between the PCOS group and controls. Despite the lack of significant differences, we observed a tendency for a higher prevalence of the TT genotype in the PCOS group (p = 0.06). No statistically significant differences were observed between the PCOS group and the control group in terms of the presence of the MetS components and the predisposition to develop MetS.Our study did not confirm an association between the MTHFR C677T gene polymorphism and the development of MetS in PCOS. Further studies with larger sample size might be useful to determine this association.

Precipitation and inhibition of seizures and epileptic discharges by sensory stimuli are receiving increasing attention because they provide insight into natural seizure generation in human epilepsies and can identify potential nonpharmacological therapies. We aimed to investigate modulation (provocation or inhibition) of epileptiform discharges (EDs) in mesial temporal lobe epilepsy (MTLE) versus idiopathic generalized epilepsy (IGE) by olfactory stimulation (OS) compared with standard provocation methods. The underlying hypothesis was that any response would be more likely to occur in MTLE, considering the anatomical connections of the temporal lobe to the olfactory system. This multicenter, international study recruited patients with either MTLE or IGE who were systematically compared for responses to OS using an EEG/video-EEG protocol including a 30-min baseline, twice 3-min olfactory stimulation with ylang-ylang, hyperventilation, and intermittent photic stimulation. The 95% confidence interval (CI) for the baseline EDs in each patient was calculated, and modulation was assumed when the number of EDs during any 3-min test period was outside this CI. A total of 134 subjects (55 with MTLE, 53 with IGE, and 26 healthy controls) were included. Epileptiform discharges were inhibited during OS in about half the patients with both MTLE and IGE, whereas following OS, provocation was seen in 29.1% of patients with MTLE and inhibition in 28.3% of patients with IGE. Olfactory stimulation was less provocative than standard activation methods. The frequent subclinical modulation of epileptic activity in both MTLE and IGE is in striking contrast with the rarity of reports of olfactory seizure precipitation and arrest. Inhibition during OS can be explained by nonspecific arousal. The delayed responses seem to be related to processing of olfactory stimuli in the temporal lobe, thalamus, and frontal cortex.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. A number of PCOS complications may be associated with the elevated level of angiotensin II and low bradykinin concentrations. The aim of the present study was to investigate the frequencies of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms in women with PCOS and to determine the association between ACE genetic variants and the risk of metabolic and cardiovascular complications in such women. A total of 138 PCOS patients and 110 healthy volunteers were enrolled. Cardiovascular risk was estimated according to the criteria of the American Heart Association and Androgen Excess and PCOS Society. The median average age was 28.5 (26.0‑31.0) and 27.0 (24.0‑30.0) years in the control and PCOS groups, respectively (P=0.004). Anthropometric parameters, including body mass index and waist circumference were significantly higher in the PCOS patients. In the PCOS group, 97 (57.4%) of the subjects were metabolically unhealthy, whereas, in the control group 51 (46.4%) subjects were (P=0.07). The II, ID, and DD genotypes frequencies were 29.1, 44.5, and 26.4% in the controls and 5.0, 37.7, and 57.3% in the PCOS patients. The cardioprotective I allele was observed significantly less frequently in the women with PCOS compared with the controls [odds ratio (OR), 3.27; P=0.0001]. The DD genotype, which is known to increase cardiovascular risk, was more frequently observed in PCOS patients (OR, 3.87; P=0.0003), whereas the cardioprotective II genotype occurred in this group less frequently (OR, 0.4; P=0.06). The results of the present study demonstrated a statistically significant association between the ACE I/D polymorphism and the presence and intensity of metabolic disturbances in women with PCOS.

Objective : To determine the temporal relationship among behavior, eye movements and respiration during absence seizures. Method : This included simultaneous videorecording of a patient's face, EEG and respirogram, in 5 patients with absence seizures. Absence seizures were defined as a sudden lapse of consciousness with impairment of mental functions. Oculomotor phenomena consisted of: eye fluttering, eye deviation (conjugate lateral or upward deflection), and eye-opening. Results : Oculomotor phenomena began 1 2/3–3 s after the onset of the electrographic discharge and ended before the discharge. The most frequent events were eye-opening, stare with or without palpebral myoclonias, and tonic or clonic upward movements. Downward movement or convergence was not observed as well as head version. Respiratory changes (apnea) are the last events to occur. Conclusions : absence seizures were characterized by the onset of a 3/s spike-slow wave discharge followed by oculomotor phenomena and respiratory changes. The time course suggests that epileptic discharges precede and then involve oculomotor and respiratory brainstem centers.

Learning from competitors poses a challenge for existing theories of reward-based learning, which assume that rewarded actions are more likely to be executed in the future. Such a learning mechanism would disadvantage a player in a competitive situation because, since the competitor's loss is the player's gain, reward might become associated with an action the player should themselves avoid. Using fMRI, we investigated the neural activity of humans competing with a computer in a foraging task. We observed neural activity that represented the variables required for learning from competitors: the actions of the competitor (in the player's motor and premotor cortex) and the reward prediction error arising from the competitor's feedback. In particular, regions positively correlated with the unexpected loss of the competitor (which was beneficial to the player) included the striatum and those regions previously implicated in response inhibition. Our results suggest that learning in such contexts may involve the competitor's unexpected losses activating regions of the player's brain that subserve response inhibition, as the player learns to avoid the actions that produced them.

Background The six-minute walk test (6MWT) is considered to be a simple and inexpensive tool for the assessment of functional tolerance of submaximal effort. The aim of this work was 1) to background the nonlinear nature of the energy expenditure process due to physical activity, 2) to compare the results/scores of the submaximal treadmill exercise test and those of 6MWT in pulmonary patients and 3) to develop nonlinear mathematical models relating the two. Methods The study group included patients with the COPD. All patients were subjected to a submaximal exercise test and a 6MWT. To develop an optimal mathematical solution and compare the results of the exercise test and the 6MWT, the least squares and genetic algorithms were employed to estimate parameters of polynomial expansion and piecewise linear models. Results Mathematical analysis enabled to construct nonlinear models for estimating the MET result of submaximal exercise test based on average walk velocity (or distance) in the 6MWT. Conclusions Submaximal effort tolerance in COPD patients can be effectively estimated from new, rehabilitation-oriented, nonlinear models based on the generalized MET concept and the 6MWT.

Summary Perceptual decisions require the accumulation of sensory information to a response criterion. Most accounts of how the brain performs this process of temporal integration have focused on evolving patterns of spiking activity. We report that subthreshold changes in membrane voltage can represent accumulating evidence before a choice. αβ core Kenyon cells (αβc KCs) in the mushroom bodies of fruit flies integrate odor-evoked synaptic inputs to action potential threshold at timescales matching the speed of olfactory discrimination. The forkhead box P transcription factor (FoxP) sets neuronal integration and behavioral decision times by controlling the abundance of the voltage-gated potassium channel Shal (KV4) in αβc KC dendrites. αβc KCs thus tailor, through a particular constellation of biophysical properties, the generic process of synaptic integration to the demands of sequential sampling., Graphical Abstract, Highlights • Synaptic integration can implement a process of bounded evidence accumulation • FoxP acts in αβc Kenyon cells (KCs) to repress the voltage-gated potassium channel Shal • Shal regulates the ability of αβc KCs to summate synaptic inputs over time • Altering Shal currents in αβc KCs changes spike latencies and decision times, How is information integrated to allow perceptual decision-making? FoxP-expressing neurons in fruit flies accumulate sensory evidence as subthreshold voltage changes. The first spike signals that a decision.

Objective Preeclampsia (PE) is a major cause of mortality of mothers, fetuses and newborns around the world. The etiology of preeclampsia has not yet been clarified, but many studies indicate a multifactorial basis of PE. Aldosterone synthase (CYP11B2) is responsible for synthesis of aldosterone responsible for regulating blood pressure. Similarly, natriuretic peptide (ANP) regulates blood pressure through a variety of mechanisms affecting the sodium concentration and the amount of extracellular fluid. Currently, attention is paid to the role of the polymorphisms in the expression level of these genes. The aim of the study was to determine the frequencies of genotypes and alleles for polymorphisms of −344C > T CYP11B2 gene and 2238T > C ANP gene in women with preeclampsia and healthy pregnant women from the Caucasian population. Study design The study included a group of 165 pregnant women (59 women with preeclampsia and 109 healthy pregnant women). DNA was extracted from peripheral blood. Determination of the polymorphism of −344C > T CYP11B2 gene and 2238T > C ANP gene was performed by PCR-RFLP method. Results The results showed that the frequencies of the TC and CC genotypes of 2238T > C polymorphism in ANP gene were significantly higher in patients with PE compared to control group. For −344C > T polymorphism of CYP11B2 gene, the frequency of TT genotype was significantly higher in patients with hypertension than in controls (32.2% vs. 23.58%). Conclusions Our findings showed that gene polymorphism of CYP11B2 (−344C > T) and ANP (2238T > C) may be associated with developing PE during pregnancy.