A phase 2 trial investigating the efficacy and safety of the mPGES-1 inhibitor vipoglanstat in systemic sclerosis-related Raynaud's.

OBJECTIVE: Our objective was to test the hypothesis, in a double-blind, placebo-controlled study that vipoglanstat, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) which decreases prostaglandin E2 (PGE2) and increases prostacyclin biosynthesis, improves RP. METHODS: Patients with systemic sclerosis (SSc) and ≥7 RP attacks during the last screening week prior to a baseline visit were randomised to four weeks treatment with vipoglanstat 120 mg or placebo. A daily electronic diary captured RP attacks (duration and pain) and Raynaud's Condition Score, with change in RP attacks/week as primary end point. Cold challenge assessments were performed at baseline and end of treatment. Exploratory endpoints included patients' and physicians' global impression of change, Assessment of Scleroderma-associated Raynaud's Phenomenon questionnaire, mPGES-1 activity, and urinary excretion of arachidonic acid metabolites. RESULTS: Sixty-nine subjects received vipoglanstat (n = 33) or placebo (n = 36). Mean weekly number of RP attacks (baseline; vipoglanstat 14.4[SD 6.7], placebo 18.2[12.6]) decreased by 3.4[95% CI -5.8;-1.0] and 4.2[-6.5;-2.0] attacks per week (p= 0.628) respectively. All patient reported outcomes improved, with no difference between the groups. Mean change in recovery of peripheral blood flow after cold challenge did not differ between the study groups. Vipoglanstat fully inhibited mPGES-1, resulting in 57% reduction of PGE2 and 50% increase of prostacyclin metabolites in urine. Vipoglanstat was safe and well tolerated. CONCLUSION: Although vipoglanstat was safe, and well tolerated in a dose achieving full inhibition of mPGES-1, it was ineffective in SSc-related RP. Further development and evaluation of vipoglanstat will therefore be in other diseases where mPGES-1 plays a pathogenetic role.

Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial.

BACKGROUND: With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO2) is a candidate drug. METHODS: The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test. RESULTS: Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60-40.90) vs 83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low physical performance compared to norm data. 6MWT 442 (180) (95% CI 358-525) vs 662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there were at least a possible relationship with the study drug, most commonly cough and chest pain/discomfort. CONCLUSIONS: An (unexpectedly) high frequency of AEs was observed but the DSMB assessed HBO2 to have a favourable safety profile. Our data may help other researchers in designing trials. Trial Registration ClinicalTrials.gov: NCT04842448. Registered 13 April 2021, https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30. Registered 21 May 2021, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE.

Universal prevention through a digital health platform reduces injury incidence in youth athletics (track and field): a cluster randomised controlled trial.

OBJECTIVES: To examine whether universal prevention via a digital health platform can reduce the injury incidence in athletics athletes aged 12-15 years and if club size had an influence on the effect of the intervention. METHODS: This was a cluster randomised trial where young athletics athletes were randomised through their club following stratification by club size into intervention (11 clubs; 56 athletes) and control (10 clubs; 79 athletes) groups. The primary endpoint was time from baseline to the first self-reported injury. Intervention group parents and coaches were given access to a website with health information adapted to adolescent athletes and were encouraged to log in and explore its content during 16 weeks. The control group continued training as normal. Training exposure and injury data were self-reported by youths/parents every second week, that is, eight times. The primary endpoint data were analysed using the log-rank test. Cox proportional hazards regression was used to analyse the second study aim with intervention status and club size included in the explanatory models. RESULTS: The proportion of completed training reports was 85% (n=382) in the intervention group and 86% (n=545) in the control group. The injury incidence was significantly lower (HR=0.62; χ2=3.865; p=0.049) in the intervention group. The median time to first injury was 16 weeks in the intervention group and 8 weeks in the control group. An interaction effect between the intervention and stratification factor was observed with a difference in injury risk between athletes in the large clubs in the intervention group versus their peers in the control group (HR 0.491 (95% CI 0.242 to 0.998); p=0.049). CONCLUSIONS: A protective effect against injury through universal access to health information adapted for adolescent athletes was observed in youth athletics athletes. The efficacy of the intervention was stronger in large clubs. TRIAL REGISTRATION NUMBER: NCT03459313.

Survey of patients and parents on the autotransplantation of developing premolars to replace traumatised maxillary incisors.

BACKGROUND/AIM: There is a little research on the experiences and opinions of patients who have had autotransplantation of a tooth. The aim of the study was to assess the satisfaction of patients who underwent the autotransplantation of a developing premolar to replace a traumatised maxillary central incisor. MATERIALS AND METHODS: Eighty patients (with a mean age of 10.7-years) and 32 parents were surveyed with 13 and 7 questions, respectively, to determine their opinions about the surgery, post-operative period, orthodontic and restorative treatment they had received. RESULTS: Patients and their parents were very satisfied with the outcomes of the autotransplantation treatment. The majority of patients and all parents declared that they would choose this treatment again if needed. Patients who already had aesthetic restoration of the transplanted toothscored significantly better in position, similarity to other teeth, alignment and aesthetics, when compared to patients before restoration of the premolar to the shape of incisor. Patients after orthodontic treatment considered the alignment of the transplanted tooth between the adjacent teeth as better when compared to patients before or during their orthodontic treatment. CONCLUSIONS: Autotransplantation of developing premolars to replace traumatized maxillary central incisors proved to be a well-accepted treatment option. A delay of restoration of the transplanted premolars to the shape of the maxillary incisors did not have a negative impact on the satisfaction with the treatment.

Study of the influence of NGF-ß gene overexpression in human mesenchymal stem cells on the expression level of SOX1 and neural pathway genes.

BACKGROUND: Nerve growth factor (NGF) is a protein exhibiting an influence on the neural development and also, its' impact on the stem cells remains a great potential treatment strategy. The influence of its overexpression on the neural pathway differentiation on Wharton's Jelly derived MSC (WJ-MSC) has not been studied so far, but considering the fact that these cells are relatively easy to obtain, using them may indicate an innovative change in stem cell therapies. The aim of this study was to evaluate the effect of NGF overexpression in human mesenchymal stem cells (MSC) on SOX1 and genes related to the neural pathway. METHODS AND RESULTS: The lentiviral transduction was performed in order to obtain the NGF overexpression, as well as RT-PCR to evaluate the expression level SOX1, SOX2, NES, NGF under influence of overexpressed NGF protein in WJ-MSC. During the study we have observed a decrease in SOX1 expression as the marker of neural stem cells. Other than that an increase of SOX2, NES and NGF was noticed, as they all are markers of early-neural as well as already differentiated neural cells. The results show a great potential of using those examined genes' expression as a form of a new stem cell therapy. CONCLUSIONS: The achieved overexpression of NGF in this study, led the modified MSC onto the neural pathway as well as caused a decrease of SOX1 expression and an increase of expression of genes related to neural differentiated cells.

Suicidal thoughts (ideation) among elite athletics (track and field) athletes: associations with sports participation, psychological resourcefulness and having been a victim of sexual and/or physical abuse.

OBJECTIVE: To examine associations between suicidal ideation and sexual and physical abuse among active and recently retired elite athletics (track and field) athletes. METHODS: The study population consisted of all athletes (n=402) selected for a Swedish Athletics team between 2011 and 2017. Data on suicidal ideation, suicidal events (estimated through the 1 year non-sports injury prevalence), lifetime abuse experiences, sociodemographics, sense of coherence and coping strategies were collected using a cross-sectional survey. The data were analysed using binary logistic regression with suicidal ideation and non-sports injury as outcomes. RESULTS: 192 athletes (47.8%) returned data. The prevalence of suicidal ideation was 15.6% (men 17.4%; women 14.2%) and the non-sports injury prevalence was 8.0% (men 11.6%; women 5.7%). Among women, suicidal ideation was associated with having been sexually abused (OR 5.94, 95% CI 1.42 to 24.90; p=0.015) and lower sense of coherence (OR 0.90, 95% CI 0.85 to 0.96; p=0.001) (Nagelkerke R2=0.33). Among men, suicidal ideation was only associated with use of behavioural disengagement for coping (OR 1.51, 95% CI 1.18 to 1.95; p=0.001) (R2 =0.25). Among women, non-sports injury prevalence was associated with having been sexually abused (OR 8.61, 95% CI 1.34 to 55.1; p=0.023) and participating in an endurance event (OR 7.37, 95% CI 1.11 to 48.9; p=0.039 (R2 =0.23), while among men, having immigrant parents (OR 5.67, 95% CI 1.31 to 24.5; p=0.020) (R2 =0.11) was associated with injury outside sports. CONCLUSIONS: About one out of six international athletics athletes reported having experienced suicidal ideation. World Athletics and National Olympic Committees need to include suicide prevention in their athlete protection programmes.

Synergistic Effect of the Long-Term Overexpression of Bcl-2 and BDNF Lentiviral in Cell Protecting against Death and Generating TH Positive and CHAT Positive Cells from MSC.

Mesenchymal stem cells (MSC) are potentially a good material for transplantation in many diseases, including neurodegenerative diseases. The main problem with using them is the low percentage of surviving cells after the transplant procedure and the naturally poor ability of MSC to spontaneously differentiate into certain types of cells, which results in their poor integration with the host cells. The aim and the novelty of this work consists in the synergistic overexpression of two genes, BCL2 and BDNF, using lentiviral vectors. According to our hypothesis, the overexpression of the BCL2 gene is aimed at increasing the resistance of cells to stressors and toxic factors. In turn, the overexpression of the BDNF gene is suspected to direct the MSC into the neural differentiation pathway. As a result, it was shown that the overexpression of both genes and the overproduction of proteins is permanent and persists for at least 60 days. The synergistically transduced MSC were significantly more resistant to the action of staurosporine; 12 days after transduction, the synergistically transduced MSC had a six-times greater survival rate. The overexpression of the Bcl-2 and BDNF proteins was sufficient to stimulate a significant overexpression of the CHAT gene, and under specific conditions, the TH, TPH1, and SYP genes were also overexpressed. Modified MSC are able to differentiate into cholinergic and dopaminergic neurons, and the release of acetylcholine and dopamine may indicate their functionality.

Lifetime history of sexual and physical abuse among competitive athletics (track and field) athletes: cross sectional study of associations with sports and non-sports injury.

OBJECTIVE: To examine associations between lifetime sexual and physical abuse, and the likelihood of injury within and outside sport in athletes involved in competitive athletics. METHODS: A cross sectional study was performed among the top 10 Swedish athletics athletes using 1 year prevalence of sports and non-sports injuries as the primary outcome measure. Associations with sociodemographic characteristics, lifetime abuse history and training load were investigated. Data were analysed using simple and multiple logistic regression models. RESULTS: 11% of 197 participating athletes reported lifetime sexual abuse; there was a higher proportion of women (16.2%) than men (4.3%) (P=0.005). 18% reported lifetime physical abuse; there was a higher proportion of men (22.8%) than women (14.3%) (P=0.050). For women, lifetime sexual abuse was associated with an increased likelihood of a non-sports injury (OR 8.78, CI 2.76 to 27.93; P<0.001). Among men, increased likelihood of a non-sports injury was associated with more frequent use of alcoholic beverages (OR 6.47, CI 1.49 to 28.07; P=0.013), while commencing athletics training at >13 years of age was associated with a lower likelihood of non-sports injury (OR 0.09, CI 0.01 to 0.81; P=0.032). Lifetime physical abuse was associated with a higher likelihood of sports injury in women (OR 12.37, CI 1.52 to 100.37; P=0.019). Among men, athletes with each parents with ≤12 years formal education had a lower likelihood of sustaining an injury during their sports practice (OR 0.37, CI 0.14 to 0.96; P=0.040). CONCLUSIONS: Lifetime sexual and physical abuse were associated with an increased likelihood of injury among female athletes. Emotional factors should be included in the comprehension of injuries sustained by athletes.

[The influence of hydrotherapy and physical training procedures on selected haemodynamic parameters of the circulatory system in patients with atherosclerotic peripheral vascular disease]. / Wplyw zabiegów z zakresu wodolecznictwa i treningu fizycznego na wybrane parametry hemodynamiczne ukladu krazenia u chorych z miazdzycowa choroba naczyn obwodowych.

Currently, the most common cause of death among highly developed countries are cardiovascular diseases. In terms of incidence, they take epidemic proportions. The main cause of the development of cardiovascular disease in 90% of cases is atherosclerotic lesions. The most important complications of atherosclerosis in addition to myocardial infarction and stroke include peripheral arterial disease, including arteries of the lower limbs. It is estimated that 3-10% of the general population suffers from atherosclerotic peripheral vascular disease. In people over 70, the number of patients with peripheral vascular disease increases up to 15-20%. AIM: The aim of the study was to evaluate the influence of vortex massages and physical training on the temperature of lower limbs and selected haemodynamic parameters of the circulatory system in patients with atherosclerotic peripheral vascular disease. MATERIALS AND METHODS: The study included 50 patients, both sexes, aged from 39 to 79 years, with impaired peripheral circulation of the lower limbs. The subjects were randomly divided into two groups. In group I, a series of 10 lower limb massage vortex procedures and an individually selected training including breathing, relaxation and active exercises of the lower limbs were used. In Group II, individually selected training was conducted. Measurements of blood pressure and heart rate (HR) were carried out before and after the series of treatments. The technique of performing the measurements was consistent with the recommendations of the Polish Society of Arterial Hypertension regarding blood pressure measurements. RESULTS: After the end of the series of treatments, in group I there was a statistically significant decrease in systolic blood pressure (SBP) and heart rate (HR). CONCLUSIONS: The applied eddy massage treatments significantly influenced the improvement of the hemodynamic parameters of the cardiovascular system.

[The influence of treatments in the field of hydrotherapy and controlled physical training on the temperature of lower limbs in patients with atherosclerotic peripheral vascular disease]. / Wplyw zabiegów z zakresu wodolecznictwa i treningu fizycznego na temperature konczyn dolnych u chorych z miazdzycowa choroba naczyn obwodowych.

The ever-increasing pace of life, and thus constant stress, poor nutrition and lack of time for physical activity caused the development of many diseases referred to as civilization diseases, i.e., obesity, diabetes, hypertension, metabolic diseases or generalized atherosclerosis. They have a significant impact on the development of pathological changes in all tissues of the human body. AIM: The aim of the study was to evaluate the effect of vaginal massages and controlled physical training on the temperature of lower limbs in patients with atherosclerotic peripheral vascular disease. MATERIALS AND METHODS: The study included 50 patients, women and men, aged from 39 to 79 years, with impaired peripheral circulation of the lower limbs. The subjects were randomly divided into two groups, each of 25 patients. In group I, a series of 10 lower limb massage vortex procedures and an individually selected training including breathing, relaxation and active exercises of the lower limbs were used. In Group II, individually selected training was conducted. The temperature of the lower extremities was measured in all the subjects using an infrared multifunction thermometer (IR). The measurements were carried out before the beginning of the rehabilitation program and after its completion. RESULTS: There was a statistically significant increase of lower limbs' temperature in group I (p <0.001). CONCLUSIONS: The applied vortex massage treatments significantly influenced the improvement of the lower limbs' warmth. Treatments in the field of hydrotherapy have a beneficial effect in the treatment of patients with chronic lower limb ischemia.

Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx®): a placebo-controlled randomised phase II study (PLIANT).

PURPOSE: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC). PATIENT AND METHODS: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible. Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study, as a 5-min infusion 10 min prior to oxaliplatin. Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale. RESULTS: Eleven patients were included in phase I without any detectable toxicity to calmangafodipir. In the phase II study, 173 patients were randomised to placebo (n = 60), calmangafodipir 2 µmol/kg (n = 57) and calmangafodipir 5 µmol/kg (n = 45, initially 10 µmol/kg, n = 11). Calmangafodipir-treated patients (all three doses pooled) had less physician graded neurotoxicity (odds ratio (90% confidence interval one-sided upper level) 0.62(1.15), p = .16), significantly less problems with cold allodynia (mean 1.6 versus 2.3, p < .05) and significantly fewer sensory symptoms in the Leonard scale (cycle 1-8 mean 1.9 versus 3.0, p < .05 and during follow-up after 3 and 6 months, mean 3.5 versus 7.3, p < .01). Response rate, progression-free and overall survival did not differ among groups. CONCLUSIONS: Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes.

Polymorphic Variants of TNFR2 Gene in Schizophrenia and Its Interaction with -308G/A TNF-α Gene Polymorphism.

AIM: Many data showed a role of inflammation and dysfunction of immune system as important factors in the risk of schizophrenia. The TNFR2 receptor is a molecule that adapts to both areas. Tumor necrosis factor receptor 2 (TNFR2) is a receptor for the TNF-α cytokine which is a strong candidate gene for schizophrenia. The serum level of TNFR2 was significantly increased in schizophrenia and associated with more severe symptoms of schizophrenia. METHODS: We examined the association of the three single nucleotide polymorphisms (rs3397, rs1061622, and rs1061624) in TNFR2 gene with a predisposition to and psychopathology of paranoid schizophrenia in Caucasian population. The psychopathology was measured by a five-factor model of the PANSS scale. We also assessed a haplotype analysis with the -308G/A of TNF-α gene. RESULTS: Our case-control study (401 patients and 657 controls) revealed that the genetic variants of rs3397, rs1061622, and rs1061624 in the TNFR2 gene are associated with a higher risk of developing schizophrenia and more severe course in men. However, the genotypes with polymorphic allele for rs3397 SNP are protective for women. The rs1061624 SNP might modulate the appearance of the disease in relatives of people with schizophrenia. The CTGG haplotype build with tested SNPs of TNFR2 and SNP -308G/A of TNF-α has an association with a risk of schizophrenia in Caucasian population depending on sex. Our finding is especially true for the paranoid subtypes of schizophrenia.

[Evaluation of renal function in the course of hypertension in the elderly]. / Ocena funkcji nerek w przebiegu nadcisnienia tetniczego u osób w podeszlym wieku.

Hypertension is one of the most common chronic diseases in Poland. It occurs in all age groups, but most often affects people over 65 years of age. The correct diagnosis of hypertension in older people includes documenting elevated blood pressure values, differentiating disease changes from physiologically related changes to aging, as well as assessing organ related complications. Detection of organ complications is also an important parameter of prognosis assessment. AIM: The aim of the study was evaluation of renal function in the course of hypertension in the elderly. MATERIALS AND METHODS: The study involved 63 women and 17 men, aged from 75 to 93 years, who were diagnosed with arterial hypertension in accordance with the guidelines of the Polish Society of Hypertension. Patients were divided into two groups. The first pair consisted of a group of 1 hypertensive patients (HA) lasting up to 10 years of age over 85 years and a group of 2 patients with HA lasting up to 10 years at the age of 75-85 years. The second pair is group I - patients with HA over 10 years of age over 85 years and group II - patients with HA lasting over 10 years at the age of 75-85. The assessment of glomerular filtration was made using the estimated glomerular filtration rate (GFR), which was calculated according to the mathematical formula of MDRD, while the renal resistance index was assessed using spectral Doppler after visualization of the flow in the renal arteries. RESULTS: The value of glomerular filtration in the examined groups divided by age was 55.1±15 (group 1) and 66.9±16 (group 2). The values of the kidney artery resistance index (depending on age) were in 1 group: 0.61±0.04 vs 0.60±0.05 and in the second group: 0.59±0.06 vs 0.58±0.05. The values of the renal artery resistance index (depending on the duration of HA) were 0.62±0.04 vs 0.61±0.03 (group I) and 0.61±0.04 vs 0.60±0.04 ( group II). CONCLUSIONS: GFR depends on the duration of hypertension. A relationship was found between the value of the kidney artery resistance index and age. There was no significant relationship between the value of the kidney artery resistance index and duration of hypertension.

[Evaluation of the incidence of stroke in the course of hypertension in elderly patients]. / Ocena czestosci wystepowania udaru mózgu w przebiegu nadcisnienia tetniczego u chorych w podeszlym wieku.

One of the more common chronic diseases is hypertension. After 70 years of age, it is found in over 70% of this population. It causes a number of organ complications that cause death. AIM: The aim of the study was to evaluate the prevalence of stroke in hypertension in elderly patients. MATERIALS AND METHODS: The study involved 63 women and 17 men, aged from 75 to 93 years, who were diagnosed with arterial hypertension in accordance with the guidelines of the Polish Society of Hypertension. Patients were divided into two groups. The first pair consisted of a group of 1 hypertensive patients (HA) lasting up to 10 years of age over 85 years and a group of 2 patients with HA lasting up to 10 years at the age of 75-85 years. The second pair is group I - patients with HA over 10 years of age over 85 years and group II - patients with HA lasting over 10 years at the age of 75-85. The test confirming the history of stroke was obtained from medical records. RESULTS: In the study, no significant differences were found in the incidence of stroke between younger patients and those older than 85 years. In the group of patients treated for more than 10 years due to hypertension, the percentage of patients with diagnosed stroke was slightly higher than in patients treated for shorter periods, however these were not statistically significant differences p <0.43. CONCLUSIONS: In the study population, the incidence of stroke was not significantly influenced by the age or duration of hypertension.

[Evaluation of selected results of laboratory blood tests in the course of hypertension in elderly patients]. / Ocena wybranych wyników badan laboratoryjnych krwi w przebiegu nadcisnienia tetniczego u chorych w podeszlym wieku.

Hypertension is one of the most common chronic diseases. The incidence is estimated at about 30% of the general population, with a clear tendency of increasing the frequency with age. AIM: The aim of the study was to assess selected results of laboratory blood tests in the course of hypertension in elderly patients. MATERIALS AND METHODS: The study involved 63 women and 17 men, aged from 75 to 93 years, who were diagnosed with arterial hypertension in accordance with the guidelines of the Polish Society of Hypertension. Patients were divided into two pairs of groups - in terms of the duration of hypertension and the age of the subjects. Blood samples were taken in patients to determine blood counts, glucose, creatinine, total cholesterol, LDL, HDL and triglycerides. In the morphological examination of the blood, the number of leukocytes, erythrocytes and platelets in 1 µl of blood was assessed, as well as the concentration of CRP, ALAT and ASPAT were assessed. RESULTS: In the study, no significant differences were found between the results of selected biochemical tests and peripheral blood morphology between the analyzed subgroups of patients with respect to age and also depending on the duration of hypertension. CONCLUSIONS: Both the older age of patients and the duration of hypertension do not significantly affect the results of selected blood laboratory tests in the study population.

[Assessment of the intima and media of carotid arteries in the course of hypertension in the elderly]. / Ocena kompleksu blony wewnetrznej i srodkowej tetnic szyjnych w przebiegu nadcisnienia tetniczego u osób w podeszlym wieku.

According to the position of the European Society of Hypertension in 2009, the thickening of the inner and middle membrane complex of the carotid arteries (I-M CCA), or the finding of atherosclerotic plaques is associated with high cardiovascular risk. The increase in I-M CCA thickness, assessed within the carotid artery, is considered the initial stage of atherosclerosis. According to the concept of parallel development of atherosclerosis in many arterial areas I-M CCA is a recognized marker of the process involving other arteries, such as coronary arteries, kidney or lower limbs. AIM: The aim of the study was evaluation of the intima and media of carotid arteries - I-M in the course of hypertension in the elderly. MATERIALS AND METHODS: The study involved 63 women and 17 men, aged from 75 to 93 years, who were diagnosed with arterial hypertension in accordance with the guidelines of the Polish Society of Hypertension. Patients were divided into two groups. The first pair consisted of a group of 1 hypertensive patients (HA) lasting up to 10 years of age over 85 years and a group of 2 patients with HA lasting up to 10 years at the age of 75-85 years. The second pair is group I - patients with HA over 10 years of age over 85 years and group II - patients with HA lasting over 10 years at the age of 75-85. Carotid artery examination was performed using the Aloka SSD-1100 ultrasound machine. The measurements were made within the left and right carotid wall of the common carotid artery in the anterior and lateral-posterior projection. The maximum thickness of the inner and middle membranes was measured in three places within two segments of the common carotid artery. RESULTS: It was observed that in the group of patients treated longer due to hypertension, the thickness of the intima-media complex is significantly higher than in patients with shorter duration. Moreover, in the examined group of patients in the analysis of individual correlations, life expectancy was influenced, among others, by significantly on the thickness of I-M CCA. CONCLUSIONS: Both the older age of patients and the longer duration of hypertension caused thickening of the intima-media complex. The duration of hypertension greater than 10 years had a greater impact on the thickness of this complex than the age of the patients.

Association Study of Tumor Necrosis Factor Receptor 1 (TNFR1) Gene Polymorphisms with Schizophrenia in the Polish Population.

Schizophrenia is a devastating mental disorder with undetermined aetiology. Previous research has suggested that dysregulation of proinflammatory cytokines and their receptors plays a role in developing schizophrenia. We examined the association of the three single nucleotide polymorphisms (SNPs; rs4149576, rs4149577, and rs1860545) in the tumor necrosis factor receptor 1 (TNFR1) gene with the development and psychopathology of paranoid schizophrenia in the Polish Caucasian sample consisting of 388 patients and 657 control subjects. The psychopathology was assessed using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). SNPs were genotyped using the TaqMan 5'-exonuclease allelic discrimination assay. The SNPs tested were not associated with a predisposition to paranoid schizophrenia in either the entire sample or after stratification according to gender. However, rs4149577 and rs1860545 SNPs were associated with the intensity of the PANSS excitement symptoms in men, which may contribute to the risk of violent behavior. Polymorphisms in the TNFR1 gene may have an impact on the symptomatology of schizophrenia in men.

The influence of TSA and VPA on the in vitro differentiation of bone marrow mesenchymal stem cells into neuronal lineage cells: Gene expression studies.

INTRODUCTION: Epigenetic mechanisms regulate the transcription of genes, which can affect the differentiation of MSCs. The aim of the current work is to determine how the histone deacetylase inhibitors TSA and VPA affect the expression of neuronal lineage genes in a culture of rat MSCs (rMSCs). MATERIALS AND METHODS: We analyzed the expression of early neuron marker gene (Tubb3), mature neuron markers genes (Vacht, Th, Htr2a) and the oligodendrocyte progenitor marker gene (GalC). Moreover, changes in the gene expression after three different periods of exposure to TSA and VPA were investigated for the first time. RESULTS: After six days of exposition to TSA and VPA, the expression of Tubb3 and GalC decreased, while the expression of Th increased. The highest increase of VAChT expression was observed after three days of TSA and VPA treatment. A decrease in Htr2a gene expression was observed after TSA treatment and an increase was observed after VPA treatment. We also observed that TSA and VPA inhibited cell proliferation and the formation of neurospheres in the rMSCs culture. DISCUSSION: The central findings of our study are that TSA and VPA affect the expression of neuronal lineage genes in an rMSCs culture. After exposure to TSA or VPA, the expression of early neuronal gene decreases but equally the expression of mature neuron genes increases. After TSA and VPA treatment ER of the oligodendrocyte progenitor marker decreased. TSA and VPA inhibit cell proliferation and the formation of neurospheres in rMSCs culture.

[The assessment of risk factors for glucose metabolism disorders]. / The assessment of risk factors for glucose metabolism disorders.

AIM: The aim of the study was to assess risk factors for glucose metabolism disorders. MATERIALS AND METHODS: The study involved 197 people, 92 women and 105 men aged 63.21±8.74 years. In order to assess glucose metabolism disorders, patients were divided into three groups. The first group (DM) consisted of 60 people (16 women and 44 men aged 61.92±8.46 years). These were people with type 2 diabetes. Second group (IFG IGT) consisted of 67 people (35 women and 32 men aged 65±8.5 years). These were people who were diagnosed with impaired fasting glucose or impaired glucose tolerance. The third group, the control one (K) consisted of 70 people (41 women and 29 men aged 62.6±9.06 years). They were healthy individuals. Age, BMI, blood pressure, heart rate, pulse pressure, lipids in the blood serum, serum creatinine, glomerular filtration rate (GFR), the number of pack-years were assessed. Each patient responded to diabetes risk questionnaire. RESULTS: Univariate analyzes showed statistically significant differences between groups due to: systolic blood pressure, heart rate, pulse pressure, total cholesterol, LDL cholesterol, HDL cholesterol, the number of points obtained in diabetes risk questionnaire, serum creatinine and GFR. Multivariate analyzes demonstrated that in IFG IGT group independent risk factors that increased the risk of prediabetes were elevated levels of total cholesterol (OR 1,945, 95%CI [1,195-3,166], p=0,007) and the result of the diabetes risk questionnaire (OR 1,191, 95%CI [1,061-1,337], p=0,003). In diabetes mellitus (DM) group independent risk factors that increased the risk of diabetes were pulse pressure (OR 1,123, 95%CI [1,063-1,188], p<0,001) and the result of the diabetes risk questionnaire. Independent risk factor that lowered the risk of diabetes (OR 0,068, 95%CI [0,018-0,251], p<0,001) and prediabetes (OR 0,324, 95%CI [0,109-0,969], p=0,044) was higher serum HDL cholesterol. CONCLUSIONS: Elevated level of total cholesterol and the result of the diabetes risk questionnaire are independent risk factors that increase the risk of prediabetes. Puls pressure and the result of the diabetes risk questionnaire are independent risk factors that increase the risk of diabetes. Independent risk factor that lowers the risk of glucose metabolism disorders is higher serum HDL cholesterol.

[The evaluation of color vision and its diagnostic value in predicting the risk of diabetic retinopathy in patients with glucose metabolism disorders]. / Ocena widzenia barw i jej wartosc diagnostyczna w przewidywaniu ryzyka wystapienia retinopatii cukrzycowej u chorych z zaburzeniami gospodarki weglowodanowej.

AIM: The aim of the study was to evaluate color vision and its diagnostic value in predicting the risk of diabetic retinopathy in patients with glucose metabolism disorders. MATERIALS AND METHODS: The study involved 197 people, 92 women and 105 men aged 63.21 ± 8.74 years. In order to assess glucose metabolism disorders, patients were divided into three groups. The first group (DM) consisted of 60 people (16 women and 44 men aged 61.92 ± 8.46 years). These were people with type 2 diabetes. Second group (IFG IGT) consisted of 67 people (35 women and 32 men aged 65 ± 8.5 years). These were people who were diagnosed with impaired fasting glucose or impaired glucose tolerance. The third group, the control one (K) consisted of 70 people (41 women and 29 men aged 62.6 ± 9.06 years). They were healthy individuals. In order to assess diabetic retinopathy study population was divided into two groups. The first group (BZ) consisted of 177 patients (84 women and 93 men aged 62.9 ± 8.78 years) without diabetic retinopathy. The second group (NPDR) consisted of 20 patients (8 women and 12 men aged 65.95 ± 8.17 years) with diabetic retinopathy. Glucose metabolism disorders were diagnosed with glucose tolerance test (OGTT). Evaluation of retinopathy was based on eye examination. All patients underwent binocular Farnsworth-Munsell 100 Hue color vision test (test result is a Total Error Score - TES). RESULTS: In the healthy control group (K) there were less patients with diabetic retinopathy (p = 0,0101), and less patients with abnormal color vision test (p = 0,0001) than in other groups. Majority of patients in K group had generalized abnormalities of color vision while other groups demonstrated tritanomalia (p = 0,0018). It was discovered that sTES value adequately distinguishes group K from group IFG, IGT, DM (AUC = 0,673), group K from group DM (AUC = 0,701), and group K from group IFG IGT (AUC = 0,648) sTES does not differentiate groups IGT, IFG and DM (AUC = 0,563). It was shown that in IGT, IFG group sTES was an independent risk factor that increased the risk of prediabetes almost six times (OR 5,924, 95% CI [1,169- 30,036], p = 0,032). In DM group sTES was an independent risk factor, which increased the risk of diabetes more than thirteen times (OR 13,408, 95% CI [2,324-77,345], p = 0,004). Higher values of sTES occurred in patients with retinopathy (NPDR) (p <0,001) and multivariate analyzes demonstrated that sTES ≥1.04 was an independent risk factor that increased the risk of retinopathy over twenty times (OR 21,380, 95% CI [1,101 -89,241], p <0,001). CONCLUSIONS: sTES is an independent risk factor for glucose metabolism disorders that increases the risk of prediabetes almost six times and the risk of diabetes more than thirteen times. sTES ≥1,04 is an independent risk factor for diabetic retinopathy. sTES ≥1,04 increases the risk of diabetic retinopathy over twenty times. The color vision 100 Hue test can be useful in detecting glucose metabolism disorders even before the ophthalmoscopic manifestation of retinopathy. Early detection rises the possibility to prevent or delay the development of diabetes through lifestyle changes and implementation of healthy behaviors.