The effect of laparoscopic pre- and postconditioning on pneumoperitoneum induced injury of the peritoneum.

INTRODUCTION: Pneumoperitoneum, widely used in laparoscopic surgery increases the intraabdominal pressure, leading to hypoperfusion of the abdominal organs, and promoting the buildup of reactive oxygen species(ROS) and inflammatory cytokines which in turn impairs the body postoperatively. Aim of our investigation was to evaluate the potential protective effects of short ischemic episodes on ischemic damages. METHODS: 70 Wistar rats were used, divided into 7 groups: 1st group sham, 2nd group pneumoperitoneum with 5 mmHg, 3rd group preconditioning with 5 mmHg, 4th group: postconditioning with 5 mmHg, 5th group pneumoperitoneum with 10 mmHg, 6th group: preconditioning with 10 mmHg, 7th group postconditioning with 10 mmHg. Pneumoperitoneum was created by Veres needle. Oxidative stress parameters: malondialdehyde (MDA) concentration, reduced glutathione (GSH), sulfhydril (SH-), myeloperoxidase (MPO) levels and superoxide-dismutase (SOD) activity were measured. We measured TNF-α and IL-6 concentrations. We monitored the activation of anti- and proapoptotic common signaling pathways (bax, bcl-2, p53) during the early phase of reperfusion. Histology was made from kidney samples. RESULTS: GSH concentrations were significantly reduced, MDA concentrations were significantly higher in each group compared to the Sham. SOD enzyme: a pressure of 10 mmHg elicited significantly greater damage than 5 mmHg. There was a significantly higher SOD activity in group 10 mmHg IPC compared to 10 mmHg. We found that the expression of bax was considerably higher in the none conditioned groups. Noticeably higher expression of anti-apoptotic bcl-2 level was measured in 10 mmHg IPC and 10 mmHg IPoC groups. In case of p53 expression: significant decrease could be seen in groups 10 mmHg IPC and 10 mmHg IPoC compared to the 10 mmHg group. CONCLUSION: Based on our results, the elevated intraabdominal pressure due to pneumoperitoneum induces oxidative stress, which is dependent on the applied pressure. Mostly precondiotioning - but also postconditioning - reduces surgical stress following laparoscopic procedures. In order to explore its mechanism it requires further investigations.

Enhancement of nutrient removal performance of activated sludge with a novel hybrid biofilm process.

The aim of this study was to investigate the efficacy of a hybrid biofilm pilot-scale treatment plant, designed with a novel configuration by the integration of a fixed-film system, to improve nitrogen removal. The pilot-scale system was established at a wastewater treatment plant in Istanbul and operated based on stream separation following a process consisting of Bio-P and primary sedimentation units in which carbonaceous compounds were entrapped/incorporated in settled biomass. The ammonia-rich supernatant was directed to a moving bed biofilm (MBBR) nitrification tank to obtain an efficient nitrification with the reduced organic loading after the primary sedimentation. The conventional activated sludge process, for which the net specific growth rate ([Formula: see text]) was measured to be 0.26 day-1 at 15 °C, exhibited a low nitrification capacity. However, the pilot-scale hybrid biofilm system secured nitrification performance up to 1.8 gN/m2/day ammonia loading, providing a competitive advantage over the conventional single sludge systems. The proposed hybrid configuration enables removal efficiencies of 80% and 85% for total nitrogen and phosphorus. It was possible to entrap organic matter by mixing 30% of return activated sludge (RAS) with raw wastewater. Simulation-based design study showed that the use of the hybrid biofilm system reduces the environmental footprint and aeration requirement of the nutrient removal by about 50% and 19%, respectively. Economic analyses highlighting the benefit of hybrid biofilm over conventional BNR system are illustrated.

The first biosimilar approved for the treatment of osteoporosis: results of a comparative pharmacokinetic/pharmacodynamic study.

To demonstrate the clinical comparability between RGB-10 (a biosimilar teriparatide) and the originator, a comparative pharmacokinetic trial was conducted. The study was successful in establishing bioequivalence. Marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency in 2017. INTRODUCTION: Teriparatide, the first bone anabolic agent, is the biologically active fragment of human parathyroid hormone. The imminent patent expiry of the originator will open the door for biosimilars to enter the osteology market, thereby improving access to a highly effective, yet prohibitively expensive therapy. METHODS: Subsequent to establishing comparability on the quality and non-clinical levels between RGB-10, a biosimilar teriparatide, and its reference product (Forsteo®), a randomised, double-blind, 2-way cross-over comparative study (duration: four days) was conducted in 54 healthy women (ages: 18 to 55 years) to demonstrate the pharmacokinetic/pharmacodynamic (PK/PD) equivalence and comparable safety of these products. Extents of exposure (AUC0-tlast) and peak exposure (Cmax), as measured by means of ELISA, were evaluated as co-primary PK endpoints, and serum calcium levels, as measured using standard automated techniques, were assessed for PD effects. Safety was monitored throughout the study. RESULTS: The 94.12% CIs for the ratio of the test to the reference treatments, used due to the two-stage design (85.20-98.60% and 85.51-99.52% for AUC0-tlast and Cmax, respectively), fell within the 80.00-125.00% acceptance range. The calcium PD parameters were essentially identical with geometric mean ratios (GMRs) of 99.93% and 99.87% for AUC and Cmax, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference. CONCLUSION: Based on the high level of similarity in the preclinical data and the results of this clinical study, marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency (EMA) in 2017.

Experimental Assessment of the Degradation of "Unbiodegradable" Organic Solids in Activated Sludge.

In current process models activated sludge consists of biodegradable and unbiodegradable organic fractions. Recent evidence suggests that this approach may not be accurate because some of this "unbiodegradable" material may indeed be degradable. To improve sludge production predictions, it is important to know to what extent the "unbiodegradable" organic fraction is degradable. Assuming that volatile suspended solids (VSS) is a measure of the sum of biodegradable and unbiodegradable organic solids and the integral of the oxygen uptake rate (OUR) is representative of the biodegradable organics, the combination of these measurements can be used to predict the change of unbiodegradable organic solids within an aerobic digestion batch experiment. This procedure was used to estimate degradation rates of "unbiodegradable" VSS between 0.006 to 0.029 d(-1). The advantage of the proposed method is that the degradation rate can be determined directly based on measurements and relies on a limited number of assumptions.

Controlled reperfusion decreased reperfusion induced oxidative stress and evoked inflammatory response in experimental aortic-clamping animal model.

UNLABELLED: Revascularization after long term aortic ischaemia in vascular surgery induces reperfusion injury accompanied with oxidative stress and inflammatory responses. The hypothesis of this study was that the aortic occlusion followed by controlled reperfusion (CR) can reduce the ischaemia-reperfusion injury, the systemic and local inflammatory response induced by oxidative stress.Animal model was used. CONTROL GROUP: animals underwent a 4-hour infrarenal aortic occlusion followed by continuous reperfusion. Treated group: animals were treated with CR: after a 4-hour infrarenal aortic occlusion we made CR for 30 minutes with the crystalloid reperfusion solution (blood: crystalloid solution ratio 1:1) on pressure 60 Hgmm. Blood samples were collected different times. The developing oxidative stress was detected by the plasma levels of malondialdehyde, reduced glutathion, thiol groups and superoxide dismutase. The inflammatory response was measured by phorbol myristate acetate-induced leukocyte reactive oxygen species production and detection of change in myeloperoxidase levels. The animals were anaesthetized one week after terminating ligation and biopsy was taken from quadriceps muscle and large parenchymal organs.CR significantly reduced the postischaemic oxydative stress and inflammatory responses in early reperfusion period. Pathophysiological results: The rate of affected muscle fibers by degeneration was significantly higher in the untreated animal group. The infiltration of leukocytes in muscle and parenchymal tissues was significantly lower in the treatedgroup.CR can improve outcome after acute lower-limb ischaemia. The results confirm that CR might be also a potential therapeutic approach in vascular surgery against reperfusion injury in acute limb ischaemia. Supported by OTKA K108596.

Physiological adaptation of growth kinetics in activated sludge.

Physiological adaptation as it occurs in bacterial cells at variable environmental conditions influences characteristic properties of growth kinetics significantly. However, physiological adaptation to growth related parameters in activated sludge modelling is not yet recognised. Consequently these parameters are regarded to be constant. To investigate physiological adaptation in activated sludge the endogenous respiration in an aerobic degradation batch experiment and simultaneous to that the maximum possible respiration in an aerobic growth batch experiment was measured. The activated sludge samples were taken from full scale wastewater treatment plants with different sludge retention times (SRTs). It could be shown that the low SRT sludge adapts by growth optimisation (high maximum growth rate and high decay rate) to its particular environment where a high SRT sludge adapts by survival optimization (low maximum growth rate and low decay rate). Thereby, both the maximum specific growth rate and the decay rate vary in the same pattern and are strongly correlated to each other. To describe the physiological state of mixed cultures like activated sludge quantitatively a physiological state factor (PSF) is proposed as the ratio of the maximum specific growth rate and the decay rate. The PSF can be expressed as an exponential function with respect to the SRT.

A dynamic physicochemical model for chemical phosphorus removal.

A dynamic physico-chemical model for chemical phosphorus removal in wastewater is presented as a tool to optimize chemical dosing simultaneously while ensuring compliant effluent phosphorus concentration. This new model predicts the kinetic and stoichiometric variable processes of precipitation of hydrous ferric oxides (HFO), phosphates adsorption and co-precipitation. It is combined with chemical equilibrium and physical precipitation reactions in order to model observed bulk dynamics in terms of pH. The model is calibrated and validated based on previous studies and experimental data from Smith et al. (2008) and Szabo et al. (2008) as a first step for full-plant implementation. The simulation results show that the structure of the model describes adequately the mechanisms of adsorption and co-precipitation of phosphate species onto HFO and that the model is robust under various experimental conditions.

Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer.

OBJECTIVE: The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues. MATERIALS AND METHODS: Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of BRAF, NRAS, HRAS and KRAS were also tested. RESULTS: CYP24A1 mRNA expression was markedly increased in 52 cases (52%) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level CYP24A1 in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased CYP24A1 expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in CYP27B1 gene expression between neoplastic and normal tissues. CONCLUSIONS: A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.

Comparative statistical analysis of osteoporosis treatment based on Hungarian claims data and interpretation of the results in respect to cost-effectiveness.

UNLABELLED: The efficacy of interventions used in real life for the treatment of osteoporosis has not been evaluated on a national basis. We analysed the database of the single Hungarian health care provider between 2004 and 2010. A marked reduction in fracture incidence and hospitalization was seen, which also proved to be cost-effective. INTRODUCTION: Osteoporosis and its consequences place a significant burden on the health care systems of developed countries. Present therapeutic modalities are effective in reducing the risk of fractures caused by osteoporosis. However, we do not know whether the interventions introduced in the past 15 years have significantly reduced the number of osteoporotic fractures in real life, and if yes, how cost-effectively. METHODS: The database of the National Health Insurance Fund Administration in Hungary was analysed for the period between 2004 and 2010. Two specific patient groups were identified within the population. Patients, who were under osteoporosis treatment in more than 80% of the potential treatment days in three consecutive years (patients with high compliance), were compared with patients where this ratio was under 20% (patients with low compliance). Several statistical comparative models were implemented in order to capture a complete picture on the differences. Because of natural data heterogeneity of administration databases, propensity matching was applied as well. RESULTS: Comparing treated vs. control subjects, patients with high compliance showed a significant decrease in fracture risk and hospitalization, which was more robust after propensity adjustment. On the basis of the observed statistically significant differences, cost-effectiveness analysis was implemented. Utility loss due the observed fractures was compared with the total cost differences of the two arms based on modelling. Our calculations proved the cost-effectiveness of the long-term high compliance in real world settings. CONCLUSION: Our findings infer that the standardized and uniform health care of osteoporotic patients in a country may reduce general fracture incidence and hospitalization in a cost-effective way.

Anaerobic model for high-solids or high-temperature digestion - additional pathway of acetate oxidation.

Current anaerobic digestion models cannot properly simulate processes that are operated under high solids concentrations or high temperatures. A modification to existing models has been implemented by adding important missing degradation pathways, to accommodate these systems without artificially recalibrating the model parameters. Specifically, we implemented the alternate acetate oxidizing mechanism that is more tolerant to ammonia than the standard aceticlastic pathway. Inhibition values were estimated and an empirical function has been used to apply ammonia inhibition. The model also relates metabolic activity to un-ionised species such as undissociated acetic acid as substrate (although not obligatory for all organisms) and unionised ammonia as inhibitor. The model relies on an equilibrium chemistry module (e.g. including the phosphate buffer), resulting in more accurate pH predictions, which is crucial for proper modeling of CO2 and NH3 stripping. Calibration results from three case-studies modeling thermal hydrolysis and subsequent digestion of sludge are presented.

Instrumentation, control and automation in wastewater--from London 1973 to Narbonne 2013.

Key developments of instrumentation, control and automation (ICA) applications in wastewater systems during the past 40 years are highlighted in this paper. From the first ICA conference in 1973 through to today there has been a tremendous increase in the understanding of the processes, instrumentation, computer systems and control theory. However, many developments have not been addressed here, such as sewer control, drinking water treatment and water distribution control. It is hoped that this review can stimulate new attempts to more effectively apply control and automation in water systems in the coming years.

Report on a case of fibrogenesis imperfecta ossium and a possible new treatment option.

Fibrogenesis imperfecta is an extremely rare acquired progressive bone disorder of unknown etiology. In its course, normal bone architecture is replaced at sites by structurally unsound collagen-deficient tissue resulting in a disorganized bone structure and a skeleton that is radically susceptible to deformity and fracture. Herein, we report the case of a patient who had experienced constant bone pain and several spontaneous fractures since 1997. In 10 years' time with the sole exception of his skull, the disease affected the entire skeleton causing a significant decrease in height and progressive disablement. Laboratory findings included elevation of serum alkaline phosphatase and C-terminal telopeptide of type 1 collagen, with normal serum calcium, phosphate, 25-hydroxy-vitamin-D, and parathyroid hormone concentrations. Monoclonal gammopathy was present with no pathological plasma cells in bone marrow. Radiological and histological results were inconclusive suggesting either osteoporosis, osteomalacia, or Paget's disease and later on osteosclerosis. Treatment administered for the abovementioned conditions has proven to be of no effect. The findings eventually raised the possibility of fibrogenesis imperfecta ossium, which was confirmed by polarized light microscopy as well as transmission electron microscopy. The suggested therapy for the disease is melphalan that could not be initiated due to legal restrictions. Steroid monotherapy also reported to be moderately successful in one case resulted in no improvement. Paraproteinemia had been suggested not only to be a characteristic feature but also a possible etiological factor in this condition. In 2012, plasmapheresis was initiated monthly at the beginning, later on biweekly. In response, the patient's symptoms improved dramatically supporting the abovementioned theory.

Long term efficacy of radioiodine treatment in hyperthyroidism.

OBJECTIVES: Radioiodine is the mainstay of the treatment of thyroid hyperfunction. However, it is difficult to apply the appropriate amount of radioidone to achieve optimal efficacy with the least possible adverse effects. Results of the investigation on the efficacy of a relatively new protocol for radioiodine treatment of hyperthyroidism are reported. DESIGN: A retrospective evaluation of data from 326 patients with a mean average follow-up of 5.7 (1.0-11.7) years was performed. 64% of these patients suffered from Graves' disease and 36% had uni- or multinodular toxic goitre. RESULTS: In Graves' disease, the recurrence rate was 5% 1 year after the treatment, and that remained the same after 5 years. In toxic goitre, these rates were 6 and 7%, respectively. After 5 years 70% of the patients with autonomous adenomas were euthyroid, while 78% of the Graves patients developed hypothyroidism and 17% showed euthyroid state. A relationship between the lack of normalisation of thyroid-stimulating hormone levels after radioiodine treatment and the increased recurrence of late hyperthyroidism has also been established in patients with Graves's disease. CONCLUSION: Compared to the available data published in the literature, the success rate of the treatment is fairly high confirming the effectiveness of our protocol.

A new approach to assess the dependency of extant half-saturation coefficients on maximum process rates and estimate intrinsic coefficients.

The Monod equation is often used to describe biological treatment processes and is the foundation for many activated sludge models. The Monod equation includes a "half-saturation coefficient" to describe the effect of substrate limitations on the process rate and it is customary to consider this parameter to be a constant for a given system. The purpose of this study was to develop a methodology, and its use to show that the half-saturation coefficient for denitrification is not constant but is in fact a function of the maximum denitrification rate. A 4-step procedure is developed to investigate the dependency of half-saturation coefficients on the maximum rate and two different models are used to describe this dependency: (a) an empirical linear model and (b) a deterministic model based on Fick's law of diffusion. Both models are proved better for describing denitrification kinetics than assuming a fixed K(NO3) at low nitrate concentrations. The empirical model is more utilitarian whereas the model based on Fick's law has a fundamental basis that enables the intrinsic K(NO3) to be estimated. In this study data was analyzed from 56 denitrification rate tests and it was found that the extant K(NO3) varied between 0.07 mgN/L and 1.47 mgN/L (5th and 95th percentile respectively) with an average of 0.47 mgN/L. In contrast to this, the intrinsic K(NO3) estimated for the diffusion model was 0.01 mgN/L which indicates that the extant K(NO3) is greatly influenced by, and mostly describes, diffusion limitations.

A new interpretation of endogenous respiration profiles for the evaluation of the endogenous decay rate of heterotrophic biomass in activated sludge.

In current activated sludge models aerobic degradation, resulting in loss of activity and mass of activated sludge is expressed with only one process called decay. The kinetics of this process is regarded to be first order and constant with respect to the loading conditions. In this work twelve aerobic digestion batch experiments were conducted for the activated sludge of seven different water resource recovery facilities (WRRFs). An analysis of the obtained respirograms shows three clearly distinguishable phases. The first phase is assumed to be due to the degradation of stored material (X(STOR)) and active biomass simultaneously. The second phase is exclusively due to the degradation of active biomass that is regarded to consist mainly of ordinary heterotrophic biomass (X(OHO)). The first order decay rate is slower than the degradation rate in phase 1 and varies between samples. The decay rate correlates with the activity of the activated sludge expressed as the ratio of initial heterotrophic OUR and the initial organic fraction X(ORG) of the activated sludge. This second phase was detectable until day 5 of most of the experiments. After that time within phase 3 the OUR decrease slows down and the OUR even increased for short intervals. This behaviour is thought to be due to the activity of higher organisms and the adaptation of microorganisms to starvation.

Going for mainstream deammonification from bench to full scale for maximized resource efficiency.

A three-pronged coordinated research effort was undertaken by cooperating utilities at three different experimental scales investigating bioaugmentation, enrichment and performance of anammox organisms in mainstream treatment. Two major technological components were applied: density-based sludge wasting by a selective cyclone to retain anammox granules and intermittent aeration to repress nitrite oxidizers. This paper evaluates process conditions and operation modes to direct more nitrogen to the resource-saving metabolic route of deammonification.

One-lung ventilation does not result in cerebral desaturation during application of lung protective strategy if normocapnia is maintained.

BACKGROUND: Previously a report has suggested that administration of lung protective strategy for one-lung ventilation(OLV) results in oxygen desaturation of the brain parenchyma. The aim of our work was to confirm that the maintenance of normocapnia during protective OLV strategy results in alteration of cerebral blood fl ow and cerebral oxygen saturation as compared to double-lung ventilation. METHODS: Data were obtained from 24 patients undergoing thoracic surgery. Cerebral oxygen saturation (rSO2) was continuously monitored by INVOS 5100C Cerebral Oxymeter System along with measurement of cerebral blood fl ow velocity (MCAV) by transcranial Doppler sonography. Arterial blood samples were taken for blood gas analysis in the awake state, in the supine and lateral decubitus position during double-lung ventilation (DLV), and during OLV. RESULTS: When ventilation was changed from DLV to OLV, no significant change was observed in rSO2. A significant decrease of rSO2 was found compared to the value observed during DLV in lateral decubitus at the time point 60 minutes after the start of OLV. No clinically significant changes in the MCAV was observed throughout the course of the thoracic surgical procedure. CONCLUSIONS: OLV does not result in clinically relevant decreases in cerebral blood fl ow and cerebral oxygen saturation during application of lung protective ventilation if normocapnia is maintained.

New approach to analyze genetic and clinical data in bisphosphonate-induced osteonecrosis of the jaw.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a major complication associated with long-term use of bisphosphonates (BP). We aimed to investigate the effect of CYP2C8 rs1934951 SNP and its relationship to a number of clinical and biochemical factors in 46 Hungarian subjects with bisphosphonate-induced ONJ. METHODS: Blood samples were collected from each subject and genomic DNA was extracted. SNP analysis of CYP2C8 gene was carried out by predesigned TaqMan primer/probe sets. The genetic data together with clinical and biochemical variables were evaluated by chi-square test, logistic regression, and principal component analysis (PCA). RESULTS: The risk of mandibular localization of ONJ was 19.2-fold higher in subjects with AG genotype than in normal GG genotype. PCA revealed strong positive correlations between maxillar localization of ONJ and a group of variables including intravenous BP application and serum lipid markers. Mandibular localization of ONJ was correlated positively with serum calcium, 25-hydroxy-vitamin D and PTH levels, oral BP application, and the length of BP therapy. The degree of the disease and the number of recurrences were correlated with the application of hormone-deprivation therapy for breast cancer patients. CONCLUSION: The statistical approach applying PCA to our data may contribute to the better understanding of factors playing role in the development of bisphosphonate-induced ONJ.

Computed tomographical (CT) anatomy of the thoracoabdominal cavity of the male turkey (Meleagris gallopavo).

In the present work, our goal was to match high-resolution computed tomography (CT) scans with cross-sectional anatomical pictures of the turkey (Meleagris gallopavo). Two male BUT 6 (a commercial line) turkeys were used. CT scans with 1 mm slice thickness were performed. The images covered the trunk from the level of the 9th cervical vertebra to the end of the coccyx. The anatomical sections and the CT scans were matched, and the important structures were identified and labelled on the corresponding pictures. The aim of this study was to create a reference for evaluating CT scans of avian species.

Models for nitrification process design: one or two AOB populations?

Models for engineering design of nitrifying systems use one ammonia oxidizer biomass (AOB) state variable. A simple extension using two AOB populations allows a more accurate prediction of nitrification systems at switching process environments. These two AOB subpopulations are characterized by two different sets of kinetic parameters. Selection pressure and competition between the two functional AOB populations are determined by process conditions as demonstrated by three case studies: Case study I describes dynamics of two AOB populations showing different temperature sensitivities (modified Arrhenius term on growth and decay) when bioaugmented from the warm sidestream treatment environment to the cold mainstream and vice-versa. Case study II investigates competition between fast growing micro-strategists and k-strategists adjusted to low ammonia levels depending on the internal mixed liquor recycle rate (IMLR). Case study III shows that AOB transferred from the waste activated sludge of an SBR to the parallel continuous flow system with different decay kinetics can overgrow or coexist with the original population.