Changes in spinal curve during dentistry studies measured with a Spinal Mouse device: A five-year prospective study.

INTRODUCTION: Musculoskeletal disorders (MSDs) often arise and develop during dentistry studies. The most affected regions are related to the spine. Possible associations between spinal curve parameters and MSDs have not yet been investigated amongst dentistry students. This longitudinal observational study aimed to determine whether spinal curve changes during dentistry studies, analyse the relationship between objective findings and subjectively declared MSDs and compare spinal curve parameters with those published in the literature. MATERIALS AND METHODS: Seventy-three dentistry students answered a questionnaire on MSDs, and were examined using the Spinal Mouse® device at the beginning, in the middle, and at the end of their 5-year study. RESULTS: The spinal curve exhibited a gender diversity in the lumbar lordosis angle, sacrum inclination, and thoracolumbar ratio. From the first to fifth study year, we observed an increase in the range of motions in the sagittal and frontal planes, an increase in the maximal extent of right lateral inclination, and a decrease in maximal left lateral inclination. Whole-spine backward inclination increased only in women, and forward sacral inclination decreased. No statistically significant relationships were found between the objective findings and subjectively declared MSDs. CONCLUSIONS: The spinal curve shape differed between men and women and changed during dentistry studies. No objective markers or predictors of MSDs were found amongst the dentistry students. These findings can serve as a benchmark for further studies on the association between MSDs and objective findings.

Sex identification in Australian skinks (Egernia stokesii, E. hosmeri, E. striolata) using cloacoscopy.

Thirteen adult healthy captive skinks, six Gidgee spiny-tailed skinks (Egernia stokesii), three Hosmer's spiny-tailed skinks (Egernia hosmeri) and four tree crevice-skinks (Egernia striolata), were submitted to the study. The weight of the animals ranged from 28 g to 146 g. All skinks were explored during their putative mating season, which is December. Lizards were restrained manually and positioned in ventral recumbence. Cloacoscopy was performed with the rigid endoscope, protecting channel, endocamera and recording system Telepack-Pal (Karl Storz Endoskope, Tuttlingen, Germany). While the endoscope was gently introduced into the cloaca and advanced into the coprodeum sterile saline was flushed into the cloaca through the protecting channel. The endoscope was then slowly withdrawn to allow visualization of the main structures of the urodeum and proctodeum. Male skinks are characterized by the presence of urethral papillae and only one horizontal septum which divides the chamber of the urodeum into two subchambers. Female skinks are characterised by the presence of two septa. The central-dorsal fold that divides the urodeum into two pouches in female skinks is absent in males. Cloacoscopy proved an effective method of sex identification and can be considered a valuable method for breeding and conservation in monomorphic skink lizards.

Malignant ovarian dysgerminoma in a 16-year-old leopard gecko (Eublepharis macularius).

The 16-year-old female leopard gecko (Eublepharis macularius) was presented with distended coelom and cachexia. Examination of the faecal sample ruled out the presence of protozoan parasites. A radiographic examination confirmed the presence of radiopaque foreign material in the intestine. The conservative treatment with tramadol, butylscopolamine, famotidine, vitamin B complex, and supportive fluid therapy with Hartmann solution and Duphalyte, was performed for 14 days. Ultrasonographic examination revealed the presence of a large mass adherent to the liver (with hypoechoic regions), a thin-walled cystic structure close to the liver, and coelomic effusion. Surgical exploration revealed a large mass on the right ovary. The unilateral (right) ovariectomy was performed. Histologic examination of the mass revealed dysgerminoma with an invasion of the ovarian bursa and blood vessels. Nine months after the surgery the patient was active and doing well. In reptiles, dysgerminoma is an uncommon type of neoplasia. To the best of our knowledge, this is the first case of dysgerminoma tumour diagnosed intravitally and treated successfully in lizards.

Effect of GnRH agonist (deslorelin) on reproductive activity in captive female veiled chameleons (Chamaeleo calyptratus).

Eighteen 5 months old veiled chameleon females (Chamaeleo calyptratus) were used in the study. Seven females received subcutaneous implants with gonadotropin-releasing hormone agonist (GnRH) deslorelin acetate whereas eleven females were used as control animals without any implants. Females were kept in five terraria, in groups of four females (in 3 terraria) and groups of three females (in 2 terraria), respectively. A minimum of one female with GnRH implants was present in each terrarium. They were kept under standard husbandry conditions. Females of both groups (females with GnRH and controls, respectively) were monitored for three years. No differences between females with GnRH implants and females without GnRH implants were observed with respect to the presence of large ovarian follicles, number of eggs/female, or number of clutches/female. GnRH implants did not prevent spontaneous reproductive activity in any of the 7 females with implants. Ovariectomy was performed in 8 females (4 females with GnRH implants and 4 control females). Ten females (3 females with GnRH implants and 7 control females) had to be euthanised. In 17 of 18 female veiled chameleons of this study histologic examination revealed heterophilic granulomatous oophoritis. The use of GnRH agonist implants did not prove to be an appropriate method for the control of reproductive function in captive female veiled chameleons.

Plasma bile acids in healthy green iguanas and iguanas with chronic liver diseases.

The aim of the study was to establish reference values for plasma bile acid (BA) concentrations in a collection of healthy green iguanas and to compare the results with BA concentrations in iguana patients presented to the clinic with various types of chronic liver diseases, patients with other chronic diseases and healthy iguanas that were presented for routine or pre-surgical health check-up. The concentration of BA was determined using the enzymatic colorimetric method. Mean plasma bile acid concentration in 110 samples from healthy green iguanas fasted for 24 h was higher (15.89 ± 15.61 µmol/l) than plasma bile acid concentration in the same iguanas fasted for 48 h (9.56 ± 8.52 µmol/l) (P < 0.01). The 3α-hydroxy bile acid concentration was significantly altered in 9 patients suffering from chronic liver diseases (diagnosed by histology) (84.85 ± 22.29 µmol/l). BA concentration in one iguana with hepatocellular adenoma (13.0 µmol/l) was within the interval of BA in healthy iguanas. Mean plasma BA concentration in 10 green iguanas that were suffering from various types of chronic diseases, but without any hepatopathy was 7.85 ± 4.86 µmol/l. The mean plasma BA concentration in 18 samples from green iguanas presented to the clinic for routine health check-ups and 17 green iguana females with preovulatory follicle stasis (POFS) syndrome presented for ovariectomy was 11.95 ± 9.43 µmol/l and 12.97 ± 9.06 µmol/l, respectively. The data collected from this study suggest that plasma bile acids are significantly increased in green iguanas suffering from chronic liver diseases.

Analysis of Results of Specific IgE in 100 Atopic Dermatitis Patients with the Use of Multiplex Examination ALEX2-Allergy Explorer.

BACKGROUND AND AIM: Progress in laboratory diagnostics of IgE-mediated allergy is the use of component-resolved diagnosis. Our study analyses the results of specific IgE to 295 allergen reagents (117 allergenic extracts and 178 molecular components) in patients suffering from atopic dermatitis (AD) with the use of ALEX2 Allergy Explorer. METHOD: The complete dermatological and allergological examination, including the examination of the sensitization to molecular components with ALEX2 Allergy Explorer testing, was performed. The statistical analysis of results was performed with these methods: TURF (total unduplicated reach and frequency), best reach and frequency by group size, two-sided tests, Fisher's exact test, and chi-square test (at an expected minimum frequency of at least 5). RESULTS: Altogether, 100 atopic dermatitis patients were examined: 48 men, 52 women, the average age 40.9 years, min. age 14 years, max. age 67 years. The high and very high level of specific IgE was reached in 75.0% of patients to 18 molecular components: from PR-10 proteins (Aln g 1, Bet v 1, Cor a1.0103, Cor a1.0401, Fag s 1), lipocalin (Can f 1), NPC2 family (Der f 2, Der p 2), uteroglobin (Fel d 1), from Alternaria alternata (Alt a 1), Beta expansin (Lol p 1, Phl p 1), molecular components from Timothy, cultivated rye (Secc pollen) and peritrophin-like protein domain Der p 23. The high and very high level of specific IgE to other lipocalins (Fel d 7, Can f 4), to arginine kinase (Bla g 9, German cockroach), and to allergen extracts Art v (mugwort), and Cyn d (Bermuda grass) reached 52.0% of patients. The severity of AD is in significant relation to the sensitization to molecular components of storage mites (Gly d 2, Lep d 2-NPC2 family), lipocalins (Can f 1, Can f 2, Can f 4, and Can f 6), arginine kinase (Asp f 6, Bla g 9, Der p 20, Pen m 2), uteroglobin (Fel d 1, Ory c 3), Mn superoxide dismutase (Mala s 11), PR-10 proteins (Fag s 1, Mal d 1, Cor a 1.0401, Cor a 1.0103), molecular components of the peritrophin-like domain (Der p 21, Der p 23), and to Secc pollen. In the subgroup of patients suffering from bronchial asthma, the significant role play molecular components from house dust mites and storage mites (Lep d 2, Der p 2, Der f 2-NPC2 family), cysteine protease (Der p 1), peritrophin-like protein domain (Der p 21, Der p 23), enolase from Alternaria alternata (Alt a 6), and Beta expansin Phl p 1. CONCLUSION: The results of our study demonstrate the detailed profile of sensitization to allergens reagents (allergen extract and molecular components) in patients with atopic dermatitis. We show the significance of disturbed epidermal barrier, resulting in increased penetration of allergens. We confirmed the significant relationship between the severity of AD, the occurrence of bronchial asthma and allergic rhinitis, and high levels of specific IgE to allergen reagents. Our results may be important for regime measures and immunotherapy; Der p 23 shall be considered as an essential component for the diagnosis and specific immunotherapy of house dust mite allergy.

Quality of life of patients with psoriasis.

OBJECTIVE: The two main aims of our study were to assess the quality of life (QOL) of patients with moderate or severe psoriasis treated by Goeckerman therapy and to compare QOL of our patients on the date of admission and 1 month after their discharge. METHODS: We performed a prospective study on 51 patients treated for chronic plaque psoriasis by Goeckerman regimen (GR). The psoriasis area involvement and severity was measured using the Psoriasis Area and Severity Index (PASI). Patients' health-related QOL was evaluated using Psoriasis Disability Index (PDI). RESULTS: In our study we demonstrated that the QOL of this sample of 51 patients with severe forms of psoriasis was relatively good; an average PDI value on the day of admission was 9.02, which represents a small effect on patient's QOL. We did not find any significant differences in QOL between younger and older respondents or between men and women. Despite good treatment efficiency, we did not find improvement in QOL 1 month after discharge. CONCLUSIONS: The QOL of our patients was relatively good. This could be explained by the fact that our patients have been suffering from psoriasis for many years and have probably adapted to their disease. QOL of our patients was not directly dependent on the extent and intensity of skin changes. Further studies on the connection between psoriasis therapy and patients' QOL are still highly needed.

Effects of Amlodipine on Bone Metabolism in Orchidectomised Spontaneously Hypertensive Rats.

Spontaneously hypertensive rats (SHR) represent a model of essential hypertension. We studied the effect of amlodipine (AML) on bone markers, bone mineral density (BMD), and biomechanical properties of osteopenic bone induced by orchidectomy in male SHR. Rats were allocated to 3 groups and were sacrificed after 12 weeks: sham-operated control; orchidectomised control; and orchidectomised receiving a diet supplemented with AML. Indicators of bone turnover were assessed in bone homogenate, BMD was measured by dual energy X-ray absorptiometry, and the femurs were subjected to biomechanical testing. Long-term AML administration does not have a negative impact on bone metabolism and density in male SHR.

Observational cohort study of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS).

Introduction and Aim: Hepatic encephalopathy (HE) is a common complication of transjugular intrahepatic portosystemic shunting (TIPS). It is associated with a reduced quality of life and poor prognosis. The aim of this study was to compare two groups of patients who did and did not develop overt HE after TIPS. We looked for differences between these groups before TIPS. MATERIALS AND METHODS: A study of 895 patients was conducted based on a retrospective analysis of clinical data. Data was analyzed using Fisher's exact test, Chi-square, Mann Whitney test, unpaired t-test and logistic regression. After the initial analyses, we have looked at a regression models for the factors associated with development of HE after TIPS. RESULTS: 257 (37.9%) patients developed HE after TIPS. Patients' age, pre-TIPS portal venous pressure, serum creatinine, aspartate transaminase, albumin, presence of diabetes mellitus and etiology of portal hypertension were statistically significantly associated with the occurrence of HE after TIPS (p < 0.01). However, only the age, pre-TIPS portal venous pressure, serum creatinine, presence of diabetes mellitus and etiology of portal hypertension contributed to the regression model. Patients age, serum creatinine, presence of diabetes mellitus and portal vein pressure formed the model describing development of HE after TIPS for a subgroup of patients with refractory ascites. CONCLUSION: we have identified, using a substantial sample, several factors associated with the development of HE after TIPS. This could be helpful in further research.

Elution kinetics of vancomycin and gentamicin from carriers and their effects on mesenchymal stem cell proliferation: an in vitro study.

BACKGROUND: Musculoskeletal infections remain a major complication in orthopedic surgery. The local delivery of antibiotics provides the high levels required to treat an infection without systemic toxicity. However, the local toxicity of antibiotic carriers to the mesenchymal stem cells, as a result of both the peak concentrations and the type of carrier, may be significant. METHODS: To address this concern, the elution kinetics of vancomycin and gentamicin from several commercially available antibiotic carriers and several carriers impregnated by a surgeon (10 ml of each sterile carrier were manually mixed with a 500 mg vancomycin and an 80 mg gentamicin solution, and the duration of impregnation was 30 min) were assessed. Moreover, the effects of these antibiotic carriers on stem cell proliferation were investigated. The following two types of stem cells were used: bone marrow and dental pulp stem cells. RESULTS: The high eluted initial concentrations from antibiotic impregnated cancellous allogeneic bone grafts (which may be increased with the addition of fibrin glue) did not adversely affect stem cell proliferation. Moreover, an increased dental pulp stem cell proliferation rate in the presence of antibiotics was identified. In contrast to allogeneic bone grafts, a significant amount of antibiotics remained in the cement. Despite the favorable elution kinetics, the calcium carriers, bovine collagen carrier and freeze-dried bone exhibited decreased stem cell proliferation activity even in lower antibiotic concentrations compared with an allogeneic graft. CONCLUSIONS: This study demonstrated the benefits of antibiotic impregnated cancellous allogeneic bone grafts versus other carriers.

Experience of Czech Children with Alcohol Consumption in Relation to Selected Family Indicators.

OBJECTIVE: The aim of this study is to monitor and analyze the influence of chosen family indicators related to alcohol consumption and experience of drunkenness in a representative sample of Czech children. METHODS: Data for our work were obtained from the Health Behaviour in School Aged Children (HBSC) study - a World Health Organization (WHO) cross national study. The sample consisted of 4,293 children aged 11, 13 and 15 years. Data collection was conducted in June 2010 in 88 randomly selected schools in the Czech Republic using standardized questionnaires. Statistical analysis was performed in the program NCSS 9, methods of descriptive statistics, χ2 test of independence in the contingency tables and logistic regression analysis were used. RESULTS: Regular alcohol consumption (at least weekly) was reported by 7.4% of children aged eleven, 19.3% of children aged thirteen and 38.4% of children aged fifteen years. Drunkenness at least twice in their life was admitted by 3% of children aged eleven, 15% of children aged thirteen and 43% of children aged fifteen years. Both alcohol consumption and drunkenness were significantly associated (p<0.001) with age and gender. Formal structure of family was found to have significant effect on the experience of drunkenness, but no effect on alcohol consumption was recorded. Based on our results, neither the amount of time spent together, nor the children communication with parents had a statistically significant influence on alcohol consumption or drunkenness experience within each family type. However, statistically significant differences were observed between different family types (p<0.001). CONCLUSIONS: These findings indicate a high degree of liberalism of Czech society towards alcohol. It appears that alcohol consumption will remain a serious problem in Czech society, therefore, more attention should be paid to this phenomenon in the future.

The prognostic effect of neoadjuvant chemoradiotherapy on the change of PD-L1 expression in patients with locally advanced rectal adenocarcinoma.

PURPOSE: To evaluate the prognostic effect of neoadjuvant chemoradiotherapy on the change of programmed death ligand 1 (PD-L1) expression in patients with locally advanced rectal adenocarcinoma, by comparing PD-L1 expression in pretreatment biopsies and PD-L1 expression in pathological specimens after neoadjuvant chemoradiotherapy. METHODS: A total of 25 patients with rectal adenocarcinoma were evaluated. Patients were treated by neoadjuvant chemoradiotherapy (radiotherapy:44Gy normofraxionation; chemotherapy: capecitabine 825 mg/m2 in two daily doses). Surgery was performed 6-8 weeks after the chemoradiotherapy completion. PD-L1 expression was determined in endoscopic biopsies and in resected specimens with immunohistochemistry. RESULTS: All 25 patients received radiotherapy without interruption, while concomitant chemotherapy was discontinued prematurely in one patient because of hematological toxicity. In 13 patients sphincter-saving surgery were performed, and 12 patients underwent rectum resection. Downstaging was noticed in 17 patients. Stable disease was found in 5 patients, and progression in 3. The median disease free survival (DFS) was not reached. Three-year DFS was 54.3% (95% CI 34.3-74.2). The median overall survival (OS) was 60 months (95% CI 48-60). Three-year OS was 75 % (95% CI 57.7-92.3). No PD-L1 expression was noticed in pretreatment biopsy and in resected tissue after chemoradiotherapy. CONCLUSION: No prognostic effect of neoadjuvant chemoradiotherapy on the change of PD-L1 expression was demonstrated in patients with locally advanced rectal adenocarcinoma.

Chlorambucil conjugates of dinuclear p-cymene ruthenium trithiolato complexes: synthesis, characterization and cytotoxicity study in vitro and in vivo.

Four diruthenium trithiolato chlorambucil conjugates have been prepared via Steglich esterification from chlorambucil and the corresponding trithiolato precursors. All conjugates are highly cytotoxic towards human ovarian A2780 and A2780cisR cancer cell lines with IC50 values in the nanomolar range. The conjugates exhibit selectivity towards A2780 cells as compared to non-cancerous HEK293 cells, while being only slightly selective for RF24 and A2780cisR cells. In vivo, the conjugate [10]BF4 suppressed the growth of a solid Ehrlich tumor in immunocompetent NMRI mice but did not prolong their overall survival. The reactivity of the chlorambucil conjugates with glutathione, a potential target of the dinuclear ruthenium motive, and with the 2-deoxyguanosine 5'-monophosphate (dGMP-a model target of chlorambucil) was studied by mass spectrometry and NMR spectroscopy. The conjugates did not show catalytic activity for the oxidation of glutathione nor binding to nucleotides, indicating that glutathione oxidation and DNA alkylation are not key mechanisms of action. Four highly cytotoxic diruthenium trithiolato chlorambucil conjugates have been prepared. All conjugates exhibit selectivity towards A2780 cells as compared to HEK293 cells, while being only slightly active in RF24 and A2780cisR cells. In vivo, the best candidate suppressed the growth of a solid Ehrlich tumor in immunocompetent NMRI mice but did not prolong their overall survival.

In-vitro and in-vivo evaluation of the anticancer activity of diruthenium-2, a new trithiolato arene ruthenium complex [(η6-p-MeC6H4Pri)2Ru2(µ-S-p-C6H4OH)3]Cl.

In the present study, we investigated the anticancer action of the trithiolato arene ruthenium complex, [(η-p-MeC6H4Pr)2Ru2(µ-S-p-C6H4OH)3]Cl, named diruthenium-2, both in vitro and in vivo. The mechanism of antiproliferative, cytotoxic, and DNA-damaging activity, and the effect on expressions of cell cycle regulatory proteins were investigated using a WST-1-based proliferation assay, lactate dehydrogenase leakage assay, comet assay, flow cytometry, and western blot analysis. In-vivo anticancer activity was evaluated using Ehrlich tumor-bearing NMRI mice. Diruthenium-2 inhibited the growth of all cancer cell lines used, the most sensitive being gastric (AGS), breast cancer (BT-549, MCF-7, MDA-MB-231), and leukemic (HL-60, MOLT-4) cells. In MCF-7 cells, it caused a G1/S cell cycle arrest, along with an increase in the expression of protein p21 and cyclin B1. We also observed increased levels of MRN complex proteins, which, together with the results from the comet assay, indicate the formation of DNA double-strand breaks. In tumor-bearing mice, diruthenium-2 at doses of 3 and 5 mg/kg inhibits the growth of solid Ehrlich tumor, although weaker than cisplatin. However, it did not prolong the post-therapeutic survival. Our results suggest the in-vitro potential of diruthenium-2 should be further evaluated in studies using other in-vivo models.

Boldine Inhibits Mouse Mammary Carcinoma In Vivo and Human MCF-7 Breast Cancer Cells In Vitro.

Boldine is an aporphine alkaloid widely consumed in the folk medicine of some regions. Its anticancer potential has been shown but not yet elucidated. We compared the antitumor effect of orally and parenterally applied boldine in mice bearing solid Ehrlich tumor. We also explored the effects of boldine on breast adenocarcinoma MCF-7 cells in vitro. Repeated i. p. injections of 30, 60, or 90 mg boldine/kg, either alone or combined with doxorubicin, slowed tumor growth in vivo. The latter two doses also prolonged the post-therapeutic survival of the mice. When fed food supplemented with boldine at a dose of 90 mg/kg, the tumor-bearing mice survived significantly longer, but there was no effect on tumor size. Interestingly, continuous p. o. administration did not produce detectable levels of boldine in plasma or tissue samples, in contrast to high but short-lived concentrations after i. p. injections. There was neither antagonism nor synergism between boldine and doxorubicin, except a possible synergism of i. p. boldine 90 mg/kg combined with doxorubicin when compared with doxorubicin alone.Boldine was cytotoxic to MCF-7 cells and reduced their viability and proliferation in vitro. Exposure to boldine decreased bromodeoxyuridine incorporation and histone H3 phosphorylation but did not induce apoptosis. Boldine treatment resulted in p38, ERK, and JNK activation in the mitogen-activated protein kinase pathway in a dose-dependent manner. Since bioavailability in mice seems to be different from that reported in rats, pharmacokinetic studies in humans are needed to evaluate the role of boldine in the beneficial effects of Boldo infusions.

Comparative study of various subpopulations of cytotoxic cells in blood and ascites from patients with ovarian carcinoma.

AIM OF THE STUDY: A number of observations have indicated that the immune system plays a significant role in patients with epithelial ovarian cancer (EOC). In cases of EOC, the prognostic significance of tumour infiltrating lymphocytes has not been clearly explained yet. The aim is to determine the phenotype and activation molecules of cytotoxic T cell and NK cell subpopulations and to compare their representation in malignant ascites and peripheral blood in patients with ovarian cancer. MATERIAL AND METHODS: Cytotoxic cells taken from blood samples of the cubital vein and malignant ascites were obtained from 53 patients with EOC. Their surface and activation characteristics were determined by means of a flow cytometer. Immunophenotype multiparametric analysis of peripheral blood lymphocytes (PBLs) and tumour infiltrating lymphocytes (TILs) was carried out. RESULTS: CD3(+) T lymphocytes were the main population of TILs (75.9%) and PBLs (70.9%). The number of activating T cells was significantly higher in TILs: CD3(+)/69(+) 6.7% vs. 0.8% (p < 0.001). The representation of (CD3(-)/16(+)56(+)) NK cells in TILs was significantly higher: 11.0% vs. 5.6% (p = 0.041); likewise CD56(bright) and CD-56(bright) from CD56(+) cells were higher in TILs (both p < 0.001). The activation receptor NKG2D was present in 45.1% of TILs vs. 32.3% of PBLs (p = 0.034), but we did not find a significant difference in the numbers of CD56(+)/NKG2D(+) in TILs and PBLs. CONCLUSIONS: These results prove that the characteristics and intensity of anti-tumour responses are different in compared compartments (ascites/PBLs). The knowledge of phenotype and functions of effector cells is the basic precondition for understanding the anti-tumour immune response.

The prognostic significance of tumor epidermal growth factor receptor (EGFR) expression change after neoadjuvant chemoradiation in patients with rectal adenocarcinoma.

AIM OF THE STUDY: The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. MATERIAL AND METHODS: Fifty patients with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m(2) in two daily oral administrations. Surgery was indicated 4-8 weeks from the chemoradiotherapy completion. Epidermal growth factor receptor expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. RESULTS: All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. Four patients have had complete pathologic remission. Twenty-six patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26.1%). A statistically significantly shorter overall survival (p < 0.0001) and disease-free survival (p < 0.0001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR during neoadjuvant chemoradiotherapy was observed. CONCLUSIONS: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma associated with significant shorter overall survival and disease free survival.

The VEGF and BMP-2 levels in patients with ankylosing spondylitis and the relationship to treatment with tumour necrosis factor alpha inhibitors.

INTRODUCTION: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. AIM: The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. METHODS: Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. RESULTS: In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015). CONCLUSION: Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated.

The interaction between NK cells and ILC cells and their subsets in atopic dermatitis patients with and without dupilumab therapy.

BACKGROUND: Natural killer cells (NK) and innate lymphoid cells with their subsets (ILC) are part of the innate immune system. OBJECTIVE: The aim is to evaluate how NK cells and ILC cells interact in atopic dermatitis (AD) patients (with and without dupilumab therapy) compared to control group. MATERIALS AND METHODS: Complete dermatological examination was performed in all patients included in the study (19 AD patients with dupilumab, 17 AD patients without dupilumab). Surface molecules expressed on NK cells and ILC cells were analyzed by flow cytometry. The association between NK cells and total ILC cells, ILC-1, ILC-2, ILC-3, NCR+ILC3, NCR-ILC3 were compared in AD patients and in the control group. The non-parametric Spearman's rank correlation coefficient was used for this statistical analysis. We evaluated the association of parameters with AD severity at the time of treatment.Non-parametric Mann-Whitney, Kolmogorov-Smirnov tests were used. RESULTS: We confirmed the higher association between NK cells and total ILC cells in AD patients without dupilumab therapy (in 30.3 %) and in healthy controls (in 27.2 %); this association is low in AD patients with dupilumab therapy (in 0.1 %). The higher association was confirmed between NK cells and ILCs subsets only in AD patients without dupilumab therapy; in these patients the highest association was confirmed between NK cells and ILC-2 cells (in 38.6 %). No statistically significant difference in the count of NK cells and ILC cells was found between mild and moderate form of AD patients treated with dupilumab. CONCLUSION: Targeting these cell types or the cytokines they produce could represent potential therapeutic strategies for controlling inflammation and alleviating symptoms in AD patients.

DNA damage and arterial hypertension. A systematic review and meta-analysis.

Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.