Correlation between increased maternal body mass index and pregnancy complications.

OBJECTIVE: Obesity in pregnancy carries significant maternal and fetal risk. The aim of this study was to investigate the effect of maternal body mass index on pregnancy outcomes. PATIENTS AND METHODS: The study retrospectively reviewed the clinical outcome of 485 pregnant women who delivered at the Department of Obstetrics and Gynecology, Clinical Centre of Vojvodina, Novi Sad, during the period of three years (2018-2020) and compared them against the body mass index (BMI). Correlation coefficient was calculated for BMI and seven pregnancy complications (hypertensive syndrome, preeclampsia, gestational diabetes mellitus, intrauterine growth restriction, premature rupture of membranes, mode of delivery and postpartum hemorrhage). The collected data were presented in the form of median values and relative numbers (the measure of variability). The implementation of the simulation model and its verification were carried out using a specialized programming language, Python. Statistical models were created where the Chi-square and p-value were as determined for every observed outcome. RESULTS: The average age of the subjects was 35.79 years and average BMI 29.28 kg/m2. A statistically significant correlation was found between the BMI and arterial hypertension, gestational diabetes mellitus, preeclampsia and cesarean section. The correlations between the body mass index and postpartum hemorrhage, intrauterine growth restriction and premature rupture of membranes were not statistically significant. CONCLUSIONS: As high BMI correlates with a number of negative outcomes in pregnancy, weight control before and during pregnancy and proper antenatal and intranatal care are necessary to achieve a favorable pregnancy outcome.

La prostatectomía radical retropúbica abierta es todavía una técnica quirúrgica bien establecida para el tratamiento del cáncer de próstata / Open retropubic radical prostatectomy: Still a well-established surgical technique for prostate cancer management

Introducción Las opciones de tratamiento quirúrgico del cáncer de próstata han experimentado cambios significativos gracias a la expansión de la robótica. Sin embargo, la prostatectomía radical retropúbica abierta (PRA) seguirá realizándose en aquellos entornos con limitaciones económicas o con escaso acceso a la robótica. El objetivo de este estudio fue determinar los resultados oncológicos a largo plazo, clasificar las tasas de complicaciones y examinar las tasas de recuperación temprana de la continencia en pacientes tratados con PRA. Métodos Identificamos a todos los pacientes sometidos a PRA en nuestra institución entre 2000 y 2020. Se utilizó un pad test (prueba de la compresa) estandarizado para determinar las tasas de continencia precoz tras la retirada del catéter; la continencia tardía, alrededor de un año después de la cirugía, se determinó mediante el número de compresas por día. Se utilizó la clasificación de Clavien-Dindo para informar las tasas de complicaciones. Las tasas de supervivencia libre de recidiva bioquímica (RB) y de supervivencia global (SG) se definieron mediante el método de Kaplan-Meier y el análisis log-rank. Se utilizaron modelos multivariantes de regresión de Cox para comprobar el efecto de los distintos factores sobre la recidiva bioquímica. Resultados Se analizaron los datos de 1.095 pacientes. La mediana de seguimiento fue de 93,4 meses. Se encontró una supervivencia global libre de RB a 10años y una SG del 73% y del 82%, respectivamente. Se observó una tasa de complicaciones de Clavien Dindo ≥3 en el 4,8% de los pacientes. La tasa de continencia precoz fue del 81,4% y la tasa de continencia tardía fue del 89,1%. El nivel de PSA preoperatorio, la suma de la puntuación de Gleason, el estadio pT, el estado de los ganglios linfáticos y el estado de los márgenes quirúrgicos fueron predictores independientes de RB (p<0,001). Entre las limitaciones del estudio están su diseño retrospectivo y unicéntrico (AU)

Introduction The surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. Methods We identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan-Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. Results We analyzed 1095 patients. The median follow-up was 93.4months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo ≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89.1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (P<.001). Limitations include retrospective and single centre study design. Conclusions ORP is a surgical procedure that provides excellent oncological- and early continence-rates (AU)

The effect of arsenic, cadmium, mercury, and lead on the genotoxic activity of Boletaceae family mushrooms present in Serbia.

The aim of this study was to determine accumulation of heavy metals and metalloids which are widely distributed in the environment and in food chain using wild edible mushrooms belonging to the Boletaceae family mushrooms. In addition, methanol extracts of mushrooms were tested for in vitro protective effect by the cytochalasin-B blocked micronucleus (CBMN) assay using chromosome aberrations in human peripheral lymphocytes as a model. The genotoxic activity of methanol extracts prepared at 4 different concentrations (1, 2, 3 or 6 µg/ml) was examined using amifostine and mitomycin C as positive controls. Extracts of species B. regius and B. edulis exhibited the greatest reduction in the frequency of micronuclei (MN). Extract of B. regius at concentrations of 2 µg/ml showed the highest decrease in number of MN. In comparison, extract of mushroom B. edulis at a concentration of 3 µg/ml displayed less reduction. However, as heavy metals and metalloids are found in mushrooms, another aim was to examine whether these agents affected genotoxicity. Principal component analysis (PCA) identified clustering differences between control and heavy metals and metalloids groups and might explain the influence of heavy element content and genotoxic activity in mushrooms.

Open retropubic radical prostatectomy: Still a well-established surgical technique for prostate cancer management.

INTRODUCTION: The surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. METHODS: We identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan-Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. RESULTS: We analyzed 1095 patients. The median follow-up was 93.4 months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89,1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (p<0.001, 95% CI). Limitations include retrospective and single center study design. CONCLUSIONS: ORP is a surgical procedure that provides excellent oncological- and early continence-rates.

Proliferative, anti-apoptotic and immune-enhancing effects of L-arginine in culture of skin fibroblasts.

Semi-essential amino acid L-arginine may be of fundamental importance in various intracellular and intercellular pathways related to skin repair and wound healing. Our current study was aimed to explore the effect of L-arginine on skin fibroblast (L929) signaling pathways involved in cell proliferation (Akt-pAkt kinase, Erk/pErk1/2 kinase, JNK/pJNK kinase and pStat-1), apoptosis (Bcl2 and Bax) and immune defense (NF-κB and CD26). Significant upregulation of Erk (p<0.011), pErk (p<0.017) and JNK (p<0.002) was documented, while the rise was not significant for pJNK kinase. The Akt/pAkt signaling pathway did not change significantly for the above-mentioned time and dose, while pStat-1 was significantly down regulated (p<0.011). The exposure of skin fibroblasts to L-arginine increased anti-apoptotic Bcl2/Bax stoichiometry ratio (p<0.05), obtained by calculation of their individual quantities. L-arginine was able to elicit NF-κB signaling through the increase of p65 active subunit level (p<0.004), while CD26 surface antigen level was not significantly changed. In conclusion, the exposure of skin fibroblasts to L-arginine may help in maintaining and stimulating skin fibroblast proliferative, anti-apoptotic and immune defense function. Therefore, the proposed L-arginine dose may be used for tissue regeneration application, which would be of importance in regenerative medicine, skin rejuvenation approaches and wound healing.

Mental health provision in schools: approaches and interventions in 10 European countries.

BACKGROUND: The role of schools in providing community-based support for children's mental health and well-being is widely accepted and encouraged. Research has mainly focused on designing and evaluating specific interventions and there is little data available regarding what provision is available, the focus and priorities of schools and the professionals involved in providing this support. The current study presents these data from schools in 10 European countries. METHODS: Online survey of 1466 schools in France, Germany, Ireland, Netherlands, Poland, Serbia, Spain, Sweden, UK and Ukraine. The participating countries were chosen based on their geographical spread, diversity of political and economic systems, and convenience in terms of access to the research group and presence of collaborators. RESULTS: Schools reported having more universal provision than targeted provision and there was greater reported focus on children who already have difficulties compared with prevention of problems and promotion of student well-being. The most common interventions implemented related to social and emotional skills development and anti-bullying programmes. Learning and educational support professionals were present in many schools with fewer schools reporting involvement of a clinical specialist. Responses varied by country with 7.4-33.5% between-country variation across study outcomes. Secondary schools reported less support for parents and more for staff compared with primary schools, with private schools also indicating more staff support. Schools in rural locations reported less student support and professionals involved than schools in urban locations. CONCLUSION: The current study provides up-to-date and cross-country insight into the approaches, priorities and provision available for mental health support in schools; highlighting what schools prioritise in providing mental health support and where coverage of provision is lacking.

Is there a direct correlation between the duration and the treatment of type 2 diabetes mellitus and hearing loss?

AIM: The aim of the study was to determine the impact of the duration of diabetes and the control of glycemia on the auditory function of patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This prospective study included 80 patients with T2DM (divided depending on when T2DM was diagnosed, and also according to the control of glycemia), and 50 healthy subjects. RESULTS: The hearing threshold in T2DM patients was statistically significantly higher for 1,000 Hz, 2,000 Hz, 4,000 Hz and 8,000 Hz. Absolute latencies of brainstem auditory evoked potentials (BAEP) revealed significant differences between average absolute latencies for waves I, III and V, as well as inter-wave latencies I‒V and I‒III (p <0.001). A statistically significant difference was noted in the presence of transitory otoacoustic emissions (TEOAE) (p <0.001). In T2DM patients with poor glycemic control, where the glycated hemoglobin (HbA1c) is above 7%, the hearing threshold levels were statistically significantly higher in both ears at 8,000 Hz and at 2,000 Hz in the right ear, and the absolute latency of wave V was prolonged in the right ear. There was no evidence that the duration of diabetes significantly affected the auditory threshold, absolute and inter-wave BAEP latencies. CONCLUSION: The patients with T2DM displayed an increased hearing threshold, qualitative changes in BAEP and the absence of TEOAE. The duration of poorly-controlled glycemia had a greater effect on the patients' auditory function than the duration of T2DM. Hippokratia 2016, 20(1): 32-37.

Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease.

Insulin resistance, oxidative stress, and proinflammatory cytokines play a key role in pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the dynamics of oxidative/nitrosative stress in methionine-choline-deficient (MCD) diet -induced NAFLD in mice. Male C57BL/6 mice were divided into following groups: group 1: control group on standard diet; group 2: MCD diet for 2, 4, and 6 weeks (MCD2, MCD4, and MCD6, respectively). After treatment, liver and blood samples were taken for histopathology, alanine- and aspartate aminotransferase, acute phase reactants, and oxidative/nitrosative stress parameters. Liver malondialdehyde level was higher in all MCD-fed groups versus control group (p < 0.01), while nitrites + nitrates level showed a progressive increase. The activity of total superoxide dismutase and its isoenzymes was significantly lower in all MCD-fed groups (p < 0.01). Although catalase activity was significantly lower in MCD-fed animals at all intervals (p < 0.01), the lowest activity of this enzyme was evident in MCD4 group. Liver content of glutathione was lower in MCD4 (p < 0.05) and MCD6 group (p < 0.01) versus control. : Ferritin and C-reactive protein serum concentration were significantly higher only in MCD6 group. Our study suggests that MCD diet induces a progressive rise in nitrosative stress in the liver. Additionally, the most prominent decrease in liver antioxidative capacity is in the fourth week, which implies that application of antioxidants would be most suitable in this period, in order to prevent nonalcoholic steatohepatitis but not the initial NAFLD phase.

Linfangioma cavernoso laringofaríngeo extenso causante de obstrucción de las vías aéreas superiores / Extensive laryngopharyngeal cavernous lymphangioma causing upper airway obstruction

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Unraveling protein stabilization mechanisms: vitrification and water replacement in a glass transition temperature controlled system.

The aim of this study was to elucidate the role of the two main mechanisms used to explain the stabilization of proteins by sugar glasses during drying and subsequent storage: the vitrification and the water replacement theory. Although in literature protein stability is often attributed to either vitrification or water replacement, both mechanisms could play a role and they should be considered simultaneously. A model protein, alkaline phosphatase, was incorporated in either inulin or trehalose by spray drying. To study the storage stability at different glass transition temperatures, a buffer which acts as a plasticizer, ammediol, was incorporated in the sugar glasses. At low glass transition temperatures (<50°C), the enzymatic activity of the protein strongly decreased during storage at 60°C. Protein stability increased when the glass transition temperature was raised considerably above the storage temperature. This increased stability could be attributed to vitrification. A further increase of the glass transition temperature did not further improve stability. In conclusion, vitrification plays a dominant role in stabilization at glass transition temperatures up to 10 to 20°C above storage temperature, depending on whether trehalose or inulin is used. On the other hand, the water replacement mechanism predominantly determines stability at higher glass transition temperatures.

Infrapopliteal run-off and the outcome of femoropopliteal percutaneous transluminal angioplasty.

BACKGROUND: The outcome of percutaneous transluminal angioplasty (PTA) of peripheral arterial lesions is influenced by several factors, including the haemodynamic conditions. Our study tested: (a) whether infrapopliteal run-off after completed PTA influenced the time course of restenosis/reocclusion of the femoropopliteal arterial segment, and (b) whether worsening of infrapopliteal run-off influenced the long-term femoropopliteal patency after PTA. PATIENTS AND METHODS: Among 245 patients treated by femoropopliteal PTA we enrolled 176 patients who consented to regular follow-up. Concomitant infrapopliteal PTA was performed whenever feasible. The technical success of PTA and the patency of calf arteries were assessed by angiography. Infrapopliteal run-off was scored by a modification of the Society for Vascular Surgery criteria. The treated patients' limbs were divided into a group with good infrapopliteal run-off and a group with compromised run-off. Follow-up examination of the femoropopliteal arterial segment was performed by vascular ultrasonography (US) 1, 6 and 12 months after PTA, and an adverse outcome was defined by a > or = 50 % stenosis, i.e., at least doubling of the maximal systolic velocity, or occlusion - evidenced by the absence of flow. The patency of calf arteries was re-assessed by US 12 months after PTA. RESULTS: One month after femoropopliteal PTA 19 / 83 (23 %) of patients with compromised run-off developed the combined end-point of restenosis or reocclusion in comparison to 10 / 93 (11 %) with good run-off (p = 0.03). After 6 months the incidence of restenosis/reocclusion had increased in both groups at an approximately equal rate, but the differences were no longer significant: 39 / 80 (49 %) in the compromised run-off group vs. 36 / 83 (43 %) in the good run-off group after 6 months, p = 0.49, and 42 / 73 (57 %) vs. 38 / 73 (52 %) after 12 months, p = 0.51. However, in patients' limbs with good periprocedural run-off that deteriorated into compromised run-off in the year after PTA, femoropopliteal restenosis/reocclusion occurred more often than in limbs which retained good run-off: 10 / 14 (71 %) vs. 18 / 51 (35 %), p = 0.02. CONCLUSIONS: Compromised postprocedural infrapopliteal run-off predisposes to early restenosis/reocclusion after femoropopliteal PTA. Deterioration of infrapopliteal run-off in the year after femoropopliteal PTA is accompanied by worsening of long-term femoropopliteal patency.

Factors affecting results of treatment of Hypopharyngeal Carcinoma.

OBJECTIVE: A retrospective review of patients with malignant neoplasms of the hypopharynx treated with combined surgery and radiotherapy is presented to highlight the results of treatment and the factors of treatment success for this malignant disease. PATIENTS AND METHODS: Between 1995 and 2004 at the University ORL Clinic Nis 89 patients with malignant neoplasms of hypopharynx (85 males, 4 females, and age ranging from 44 to 77 years) were treated. In the 89 patients (stage I, n=4; stage II, n=3; stage III, n=34; stage IV, n=48), the sites of origin were pyriform sinus (n=75), postcrycoid (n=8), posterior pharyngeal wall (n=3) and superior hypopharynx (n=3). RESULTS: Laryngeal preservation surgery was achieved in 11.2% of patients, while 88.8% had laryngectomy with partial or total pharyngectomy. Pyriform sinus was the most common site of origin of hypopharyngeal carcinoma in 84.3%. Totally 93% of patients had neck metastases, and tumors extended beyond the hypopharynx in 41.6% of patients. TNM stage was highly significant parameter of outcome. Five year survival was 100% for stage I, 66.6% for stage II, 53.9% for stage III, and 33.3% for stage IV. Residual disease (5.6%) and recurrent disease (2.2%) were low. Postoperative fistula developed in 16.8% of patients, and in 60% it was closed successfully using local flaps, while in 40% pectoralis flap was needed. Localization of disease was also an important factor of survival. Retrocrycoid carcinoma resulted in very poor survival rate (12.5%), high residual disease, lymph node metastasis, and pharyngocutaneous fistula formation. CONCLUSION: Localization and TNM stage are highly significant factors for clinical course, treatment, and outcome of hypopharyngeal carcinoma.

TNF-alpha-308 promotor polymorphism in patients with chronic obstructive pulmonary disease and lung cancer.

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are a major cause of morbidity and mortality worldwide. In both diseases airways inflammation plays an important role. Functional promoter polymorphism, at the position -308, of tumor necrosis factor (TNF)-alpha represents attractive potential susceptibilty marker for both diseases. In order to investigate the role of this polymorphism in COPD and LC, a case-control study was performed. The patient groups consisted of 97 subjects with COPD and 70 subjects with LC, while the control group encompassed 102 subjects. Results of our study showed significant decrease of heterozygote for TNF-alpha-308 1/2 gene variant in COPD group in comparison to controls (p=0.043). According to our results heterozygous carriers of TNF-alpha-308 1/2 polymorphism had a2.3-fold decreased risk for COPD development (OR=0.44, 95%CI=0.20-0.97). In patients with lung cancer we also observed a trend of decreased distribution of TNF-alpha-308 1/2 heterozygotes, but statistical significance was not achieved. To our knowledge, this is the first study implicating decreased frequency of TNF-alpha-308 1/2 gene variant in patients with COPD and LC. Although these results need to be confirmed on larger cohort, they represent anew and interesting finding, not reported in other populations tested so far.

HER-2 expression in uterine cervix carcinogenesis.

PURPOSE: To assess the expression and clinical significance of HER-2 protooncogene in the uterine cervix carcinogenesis. PATIENTS AND METHODS: We examined 69 tissue samples of low grade cervical squamous intraepithelial lesions (SIL) (n=16), high grade SIL (n=11) portio vaginalis uteri (PVU) carcinoma in situ (n=11) and PVU invasive carcinoma, stage IA-IIA (n=13; study group) and 18 samples without SIL or malignancy (control group). The expression of HER-2 was detected immunohistochemically using a monoclonal antibody. Fisher's exact test was used to assess statistical significance. By establishing sensitivity and specificity of the test, the level of reliability of these analyses was determined as a possible screening method for early detection of changes in the uterine cervix. RESULTS: Overexpression of HER-2 was found to increase in direct relation to the grade of the cervical lesions. Statistically significant difference was found in the frequency of overexpression in patients with high grade SIL, PVU carcinoma in situ and PVU invasive carcinoma compared with the control group. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be concluded that in patients with HER-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. CONCLUSION: Our results indicate that overexpression of HER-2 oncogene may play an important role in cervical carcinogenesis. However, more extensive series of samples is required to establish the prognostic significance of HER- 2 in cervical carcinogenesis.

Elevated serum dipeptidyl peptidase IV activity in patients with chronic tonsillitis.

BACKGROUND: Palatine tonsils represent the first place of contact for a variety of antigenic substances present in air and food. Upon antigen stimulation, the interactions between T and B lymphocytes in the tonsil are known to depend on the expression of different co-stimulatory molecules, including proteolytic ectoenzymes. Dipeptidyl peptidase IV (DPP IV) and aminopeptidase N (APN), as T lymphocyte co-stimulatory molecules, participate in the regulation of the immune response during inflammation. METHODS: In this study, the serum and lymphocyte enzymatic activity of DPP IV and APN was investigated in 32 patients, 13 with recurrent tonsillitis (RT) and 19 with tonsillar hypertrophy (TH), before and one month after tonsillectomy. The enzymatic activity of DPP IV and APN in tonsillar lymphocytes and serum was determined kinetically at 37 degrees C using Gly-Pro-p-nitroanilide (for DPP IV) and Ala-p-nitroanilide (for APN) as chromogenic substrates. RESULTS: Significantly higher serum DPP IV and APN activities (P<0.001) were found in TH patients compared with those with RT before tonsillectomy. DPP IV activity in TH patients was also elevated compared with the control of the same age (P<0.001), whereas the activity of APN was the same as the control group. The activity of both enzymes was the same as of controls after tonsillectomy. In addition, the results show that DPP IV and APN activities in serum decrease significantly with age. Tonsillar lymphocytes demonstrated a wide range of DPP IV and APN activities without significant differences between the investigated groups. CONCLUSION: An increased serum DPP IV activity was observed in TH patients compared with both RT patients and controls before tonsillectomy. After tonsillectomy, all activities were similar. The results suggest that serum DPP IV activity may have potential as a diagnostic marker for patients with TH.

Analysis of common CFTR polymorphisms 5T, M470V and R75Q in healthy Serbian population.

Three common CFTR polymorphisms, 5T, M470V and R75Q, have been shown to be relatively frequent in Serbian patients with monosymptomatic CF disorders. Since there is a variation in distribution of common polymorphisms among different populations, it was important to compare their frequencies in patients with the frequencies in healthy population in order to assess the possible role of these polymorphisms in the monosymptomatic CF disorders. Samples obtained from 100 healthy Serbian individuals were analyzed for the presence of CFTR 5T, M470V and R75Q variants by PSM, RFLP and DGGE methods, respectively. Allele 5T was present in two individuals, giving the allelic frequency of 1% (2/200 alleles). The frequency obtained for allele M470 was 45% (90/200 alleles), while V470 allele was present with the frequency of 55% (110/200 alleles). Polymorphism R75Q was present in two individuals, with allelic frequency of 1% (2/200 alleles). Our study has shown that the frequencies of two common polymorphisms, 5T and M470V, differ significantly in Serbian population in comparison with other South European populations. Since it appears that Serbian population has a specific distribution of studied CFTR gene variants, it would also be interesting to analyze other common variants of this gene in our population. Such data can also be potentially useful as anthropogenetic markers in population studies.