Disrupted Balance of the Oxidant-Antioxidant System in the Pathophysiology of Female Reproduction: Oxidative Stress and Adverse Pregnancy Outcomes.

The significance of oxidative stress in the pathophysiology of male reproductive processes has been closely studied in the last two decades. Recently, it has become clear that oxidative stress can lead to numerous pathological conditions during female reproductive processes as well, contributing to the development of endometriosis, polycystic ovary syndrome and various forms of infertility. During pregnancy, physiological generation of reactive oxygen species (ROS) occurs in association with several developmental processes including oocyte maturation and implantation. An overproduction of ROS can lead to disturbances in fetal development and increases the risk for missed abortion, intrauterine growth restriction, pre-eclampsia, premature delivery and gestational diabetes. Our review focuses on the etiological role of the disrupted oxidant-antioxidant system during human gestation as it relates to adverse pregnancy outcomes.

Multiple In-Mold Sensors for Quality and Process Control in Injection Molding.

The simultaneous improvement of injection molding process efficiency and product quality, as required by Industry 4.0, is a complex, non-trivial task that requires a comprehensive approach, which involves a combination of sensoring and information techniques. In this study, we investigated the suitability of in-mold pressure sensors to control the injection molding process in multi-cavity molds. We have conducted several experiments to show how to optimize the clamping force, switchover, or holding time by measuring only pressure in a multi-cavity mold. The results show that the pressure curves and the pressure integral are suitable for determining optimal clamping force. We also proved that in-channel sensors could be effectively used for a pressure-controlled SWOP. In the volume-controlled method, only the sensors in the cavity were capable of correctly detecting the end of the filling. We proposed a method to optimize the holding phase. In this method, we first determined the integration time of the area under the pressure curve and then performed a model fit using the relationship between the pressure integral and product mass. The saturation curve fitted to the pressure data can easily determine the gate freeze-off time from pressure measurements.

How many brain metastases can be treated with stereotactic radiosurgery before the radiation dose delivered to normal brain tissue rivals that associated with standard whole brain radiotherapy?

INTRODUCTION: Clinical trial data comparing outcomes after administration of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) to patients with brain metastases (BM) suggest that SRS better preserves cognitive function and quality of life without negatively impacting overall survival. Here, we estimate the maximum number of BM that can be treated using single and multi-session SRS while limiting the dose of radiation delivered to normal brain tissue to that associated with WBRT. METHODS: Multiple-tumor SRS was simulated using a Monte Carlo - type approach and a pre-calculated dose kernel method. Tumors with diameters ≤36 mm were randomly placed throughout the contoured brain parenchyma until the brain mean dose reached 3 Gy, equivalent to the radiation dose delivered during a single fraction of a standard course of WBRT (a total dose of 30 Gy in 10 daily fractions of 3 Gy). Distribution of tumor sizes, dose coverage, selectivity, normalization, and maximum dose data used in the simulations were based on institutional clinical metastases data. RESULTS: The mean number of tumors treated, mean volume of healthy brain tissue receiving > 12 Gy (V12) per tumor, and total tumor volume treated using mixed tumor size distributions were 12.7 ± 4.2, 2.2 cc, and 12.9 cc, respectively. Thus, we estimate that treating 12-13 tumors per day over 10 days would deliver the dose of radiation to healthy brain tissue typically associated with a standard course of WBRT. CONCLUSION: Although in clinical practice, treatment with SRS is often limited to patients with ≤15 BM, our findings suggest that many more lesions could be targeted while still minimizing the negative impacts on quality of life and neurocognition often associated with WBRT. Results from this in silico analysis require clinical validation.

Sensitivity study of C/O logging measurements by Monte Carlo method.

Carbon oxygen ratio (C/O) logging has great importance in the accurate determination of hydrocarbon saturation in the reservoir region. This measurement is independent of the salinity of the formation water, unlike alternative logging methods. Analysis of the measurement requires modelling of the time-dependent coupled neutron-gamma field produced by the tool, which is most efficiently done by the Monte Carlo (MC) method. MC simulation can be used to generate the gamma spectrum at the detectors of the probe for a variety of rock physics conditions and borehole environments and thus the C/O can be determined by the processing of the simulated gamma spectrum. The simulation results are used to derive the interpretation diagrams for the basic petrophysical effects and to investigate the role of the side effects. Considering the industrial practice of log evaluation, the resolution and limitations of the method is quantified in the measurement space by defining a goodness factor based on the area of the interpretation chart. The focus of this paper is on detector arrangement, but it also covers the effect of porosity, lithology, and the casing.

Machine Learning in Injection Molding: An Industry 4.0 Method of Quality Prediction.

One of the essential requirements of injection molding is to ensure the stable quality of the parts produced. However, numerous processing conditions, which are often interrelated in quite a complex way, make this challenging. Machine learning (ML) algorithms can be the solution, as they work in multidimensional spaces by learning the structure of datasets. In this study, we used four ML algorithms (kNN, naïve Bayes, linear discriminant analysis, and decision tree) and compared their effectiveness in predicting the quality of multi-cavity injection molding. We used pressure-based quality indexes (features) as inputs for the classification algorithms. We proved that all the examined ML algorithms adequately predict quality in injection molding even with very little training data. We found that the decision tree algorithm was the most accurate one, with a computational time of only 8-10 s. The average performance of the decision tree algorithm exceeded 90%, even for very little training data. We also demonstrated that feature selection does not significantly affect the accuracy of the decision tree algorithm.

Personalized Mass Production by Hybridization of Additive Manufacturing and Injection Molding.

The new trend in the composites industry, as dictated by Industry 4.0, is the personalization of mass production to match every customer's individual needs. Such synergy can be achieved when several traditional manufacturing techniques are combined within the production of a single part. One of the most promising combinations is additive manufacturing (AM) with injection molding. AM offers higher production freedom in comparison with traditional techniques. As a result, even very sophisticated geometries can be manufactured by AM at a reasonable price. The bottleneck of AM is the production rate, which is several orders of magnitude slower than that of traditional plastic mass production technologies. On the other hand, injection molding is a manufacturing technique for high-volume production with little possibility of customization. The customization of injection-molded parts is usually very expensive and time-consuming. In this research, we offered a solution for the individualization of mass production, which includes 3D printing a baseplate with the subsequent overmolding of a rib element on it. We examined the bonding between the additive-manufactured component and the injection-molded component. As bonding strength between the coupled elements is significantly lower than the strength of the material, we proposed five strategies to improve bonding strength. The strategies are optimizing the printing parameters to obtain high surface roughness, creating an infill density in fused filament fabrication (FFF) parts, creating local infill density, creating microstructures, and incorporating fibers into the bonding area. We observed that the two most effective methods to increase bonding strength are the creation of local infill density and the creation of a microstructure at the contact area of FFF-printed and injection-molded elements. This increase was attributed to the porous structures that both methods created. The melt during injection molding flowed into these pores and formed micro-mechanical interlocking.

The role of apoptosis in the complex pathogenesis of the most common obstetrics and gynaecology diseases.

PURPOSE: We aimed to assess the etiological role of apoptotic genes Bcl-2 and Bax in the background of major obstetric and gynaecological diseases. METHODS: Placental tissue samples were collected from 101 pregnancies with intrauterine growth restriction and 104 pregnancies with premature birth with 140 controll samples from term, eutrophic newborns. In addition, gene expression assessment of the genes Bax and Bcl-2 was performed in 101 uterine leiomyoma tissue samples at our disposal with 110 control cases. Gene expression levels were assessed by PCR method. RESULTS: The expression of the Bcl-2 gene was decreased in placental samples with intrauterine growth restriction. Significant overexpression of the proapoptotic Bax gene was detected in samples from premature infants. Antiapoptotic Bcl-2 gene expression was found to be significantly increased in fibroid tissues. CONCLUSION: Apoptosis plays a crucial role in the development of the most common OB/GYN conditions. Decrease in the placental expression of the antiapoptotic gene Bcl-2 may upset the balance of programmed cell death.

Development and Validation of a Test Mold for Thermoplastic Resin Transfer Molding of Reactive PA-6.

Thermoplastic resin transfer molding (T-RTM) is a cutting-edge manufacturing technique for high-volume production of composites with a recyclable thermoplastic matrix. Although a number of reactive thermoplastic matrices as well as industrial manufacturing equipment for T-RTM are commercially available today, the design of a T-RTM mold is still based on the skills and personal experience of the designer. This study summarizes the best knowledge and expertise in mold design and manufacturing and introduces an innovative mold for T-RTM. A concept and basic principles for designing a T-RTM mold are formulated in this study. The mold developed is manufactured and validated.

Survival and early complications of preterm infants with birthweight less than 500 grams during a 10-year period in Hungary.

BACKGROUND: There are limited data available on the survival and early complications of preterm infants with less than 500 g birthweight. To estimate the outcomes for these infants, it is important for caregivers to be aware of perinatal factors that may affect survival. OBJECTIVES: We assessed the mortality and certain early complications of preterm infants born with less than 500 g in Hungary between 2006 and 2015. METHODS: We reviewed data of 486 infants from the database of the Hungarian Central Statistical Office and in parallel of 407 infants from the "NICU database." The study period was divided into two epochs: 2006-2010 and 2011-2015. RESULTS: The survival was 27.1% in the first epoch and 39.1% in the second epoch, and the incidence of early complications was slightly higher in the second epoch. In the surviving group (first and second epoch combined), gestational age (25.1 vs 23.7 weeks), birthweight (458 vs 447 g) antenatal steroid treatment (66.3% vs 52.3%), surfactant therapy (95.1% vs 84.3%), median Apgar scores (6 vs 3 and 8 vs 5 at 1 and 5 minutes, respectively) and proportion of caesarean delivery (89.3% versus 68.5%) were higher than in the non-surviving group (first and second epoch combined). The proportion of multiple births was lower in the surviving group (15.7% vs 33.4%). CONCLUSIONS: Survival of infants with less than 500 g improved between 2006-2010 and 2011-2015 in Hungary. The slightly higher occurrence of early complications might be associated with improving survival.

Modeling the Thermal Conductivity Inhomogeneities of Injection-Molded Particle-Filled Composites, Caused by Segregation.

Many applications require new materials that have good thermal conductivity, are electrical insulators and can be processed easily and with relatively little energy. A new innovative solution for this problem is thermally conductive composites, which can replace metals in many cases. Many papers have focused on the prediction of their thermal conductivity. At the same time segregation has to be taken into account in the case of composites because it affects the distribution of thermally conductive particles, and thus local thermal conductivities. In this paper, we examined and modeled segregation during injection molding and its effect on thermal conductivity. We injection-molded samples from polypropylene with glass beads of different sizes and analyzed their filler content as a function of the flow path. We described the distribution of the filler with a mathematical model. Using this, we created a new, segregation-dependent model that describes the local thermal conductivity of polymer composites as a function of filler content with great accuracy.

A Review of Thermoplastic Resin Transfer Molding: Process Modeling and Simulation.

The production and consumption of polymer composites has grown continuously through recent decades and has topped 10 Mt/year. Until very recently, polymer composites almost exclusively had non-recyclable thermoset matrices. The growing amount of plastic, however, inevitably raises the issue of recycling and reuse. Therefore, recyclability has become of paramount importance in the composites industry. As a result, thermoplastics are coming to the forefront. Despite all their advantages, thermoplastics are difficult to use as the matrix of high-performance composites because their high viscosity complicates the impregnation process. A solution could be reactive thermoplastics, such as PA-6, which is synthesized from the ε-caprolactam (ε-CL) monomer via anionic ring opening polymerization (AROP). One of the fastest techniques to process PA-6 into advanced composites is thermoplastic resin transfer molding (T-RTM). Although nowadays T-RTM is close to commercial application, its optimization and control need further research and development, mainly assisted by modeling. This review summarizes recent progress in the modeling of the different aspects of the AROP of ε-CL. It covers the mathematical modeling of reaction kinetics, pressure-volume-temperature behavior, as well as simulation tools and approaches. Based on the research results so far, this review presents the current trends and could even plot the course for future research.

A Multidisciplinary Team Approach to Brain and Spine Stereotactic Radiosurgery Conferences: A Unique Institutional Model.

OBJECTIVE: The use of multidisciplinary teams (MDTs) comprised of all members of the patient care team is becoming increasingly popular in the field of oncology. We present a single-center experience exploring the utility and uniqueness of an MDT in the care of patients undergoing brain and spine stereotactic radiosurgery (SRS). METHODS: The weekly SRS conference brought together neurosurgeons, radiation oncologists, neuroradiologists, physicists, dosimetrists, therapists, advanced practice providers, and trainees in these fields as well as researchers from a variety of disciplines with a goal of optimizing patient care. A survey of 20 conference attendees from 7 different facets of the MDT was conducted for feedback. RESULTS: The survey results revealed that most respondents believed the SRS conference increased educational opportunities, provided opportunities for research and collaborations, helped streamline patient care, and was beneficial to their practice. CONCLUSIONS: We present our institutional MDT model, a framework and workflow that can be incorporated at other large academic centers. We believe that the SRS conference has educational, academic, and patient care value.

In-Mold Sensors for Injection Molding: On the Way to Industry 4.0.

The recent trend in plastic production dictated by Industry 4.0 demands is to acquire a great deal of data for manufacturing process control. The most relevant data about the technological process itself come from the mold cavity where the plastic part is formed. Manufacturing process data in the mold cavity can be obtained with the help of sensors. Although many sensors are available nowadays, those appropriate for in-mold measurements have certain peculiarities. This study presents a comprehensive overview of in-mold process monitoring tools and methods for injection molding process control. It aims to survey the recent development of standard sensors used in the industry for the measurement of in-mold process parameters, as well as research attempts to develop unique solutions for solving certain research and industrial problems of injection molding process monitoring. This review covers the established process monitoring techniques-direct temperature and pressure measurement with standard sensors and with the newly developed sensors, as well as techniques for the measurement of indirect process parameters, such as viscosity, warpage or shrinkage.

Thermoplastic Overmolding onto Injection-Molded and In Situ Polymerization-Based Polyamides.

We investigated products manufactured by in situ polymerization, which were reinforced with overmolded ribs. We developed our own mold and prototype product for the project. We used three different materials as preform: a material with a magnesium catalyst, manufactured by in situ polymerization, a Brüggemann AP-NYLON-based in situ polymerization material and an injection-molded PA6 (Durethan B30S, Lanxess GmbH) material. The ribs were formed from the same PA6 material (Durethan B30S, Lanxess GmbH). We examined the effect of the different technological parameters through the pull-off of the overmolded ribs. We measured the effect of melt temperature, holding pressure and holding time, and mold temperature. Considering the individual preforms, we pointed out that monomer migration and binding strength are related, which we concluded from the temperature-dependent mass loss of the materials, measured by thermogravimetric analysis (TGA). Finally, we designed a mold suitable for manufacturing overmolded parts. We designed and built pressure and temperature sensors into the mold to examine and analyze pressures and temperatures around the welding zone of the materials.

Trends in Mortality and Morbidity in Infants Under 500 Grams Birthweight: Observations from Our Neonatal Intensive Care Unit (NICU).

BACKGROUND In our previous study, some changes were presented in obstetric care and we studied the morbidity and mortality trends of infants with <500 grams birth weight. Several neonatal protocol changes occurred during the study period. The aim of this study was to analyze the changes in mortality and morbidity of premature infants in light of changing neonatal protocols. MATERIAL AND METHODS We performed a retrospective study of premature infants with <500 grams birth weight, born at our department between 2006 and 2015. We divided the study period into two 5-year epochs and compared mortality and morbidity rates. We calculated the duration of mechanical ventilation and non-invasive respiratory support, and also investigated the potential impact of the differences in clinical practice. RESULTS The survival rate was 30.8% during first epoch, which was significantly lower than the 70.4% survival rate during second epoch. There was no difference in the rate of complications between the 2 epochs. The total number of ventilator and non-invasive ventilation days was significantly lower in the second epoch. CONCLUSIONS We found significant differences in survival rates but no change in the incidence of morbidities between the 2 epochs. Therefore, although the number of neonates surviving with morbidities has increased, so did the number of those with intact survival. The increased survival of infants born with <500 grams birth weight is not associated with increased rate of morbidities. Protocol changes may have contributed to these findings; however, in a retrospective study it is not possible to separate the impact of individual changes.

[Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction]. / A legjelentosebb angiogeneticus gének méhlepényi expressziójának változásai a méhen belüli növekedési visszamaradás hátterében.

Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

Morbidity and mortality trends in very-very low birth weight premature infants in light of recent changes in obstetric care.

OBJECTIVE: In this study, we describe trends in morbidity and mortality of preterm infants with less than 500mg birth weight in the changing landscape of obstetric and neonatal care. STUDY DESIGN: During a ten year study period between 2006 and 2016 we assessed outcome data for all neonates with less than 500mg birth weight born at our Neonatal Intensive Care Unit. We divided study subjects into two groups based on whether their birth date fell in the first half (2006-2010; n=39) versus the second half (2011-2015; n=27) of the study period comparing clinical outcomes in the two groups. We also assessed several clinical parameters for association with postnatal survival by comparing relative frequencies for each clinical parameter among surviving infants versus mortality cases. RESULTS: Survival rate for preterm neonates with less than 500mg birth weight born between 2006 and 2010 was 30.8%. This survival rate rose to 70.4% in the second half of the study period between 2011 and 2015 (p<0.05). Among surviving babies premature birth was found to be predominantly associated with maternal hypertension or intrauterine growth restriction while in those who died premature birth due to premature rupture of membranes and spontaneous preterm labor were significantly more common. All surviving infants with less than 500mg birth weight were born via cesarean section whereas among those who died cesarean section had been performed in only 80% and vaginal delivery in 20% representing a significant difference between the groups (p<0.05). The majority (90.3%) of surviving infants with less than 500mg birth weight had received surfactant therapy while the proportion of neonates receiving surfactant therapy among mortality cases was significantly lower (65.2%; p<0.05). DISCUSSION: Our findings suggest that among premature neonates with less than 500mg birth weight preterm delivery due to premature rupture of membranes and intrauterine infections represents the worse mortality risk. Steroid prophylaxis and measures to prevent and treat intrauterine infections with appropriate use of antibiotics can markedly improve survival in these cases. In premature neonates with less than 500mg birth weight survival is more favorable after cesarean section compared to vaginal delivery.

Enhanced Injection Molding Simulation of Advanced Injection Molds.

The most time-consuming phase of the injection molding cycle is cooling. Cooling efficiency can be enhanced with the application of conformal cooling systems or high thermal conductivity copper molds. The conformal cooling channels are placed along the geometry of the injection-molded product, and thus they can extract more heat and heat removal is more uniform than in the case of conventional cooling systems. In the case of copper mold inserts, cooling channels are made by drilling and heat removal is facilitated by the high thermal conductivity coefficient of copper, which is several times that of steel. Designing optimal cooling systems is a complex process; a proper design requires injection molding simulations, but the accuracy of calculations depends on how precise the input parameters and boundary conditions are. In this study, three cooling circuit designs and three mold materials (Ampcoloy 940, 1.2311 (P20) steel, and MS1 steel) were used and compared using numerical methods. The effect of different mold designs and materials on cooling efficiency were examined using calculated and measured results. The simulation model was adjusted to the measurement results by considering the joint gap between the mold inserts.

Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction.

OBJECTIVE: We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. METHODS: During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. RESULTS: There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2α: 0.92; p < 0.06). Within the IUGR group, no fetal gender-dependent differences were seen in placental PIGF gene expression (Ln2α: 0.72; p = 0.05). Placental PIGF gene activity was significantly lower in fetuses with more severe IUGR versus less severe cases (Ln2α: -1.49; p < 0.03). CONCLUSION: We found no difference in gene expression of PIGF in placental samples obtained from IUGR pregnancies versus normal pregnancy suggesting the absence of a direct role of PIGF gene activity in the development of defective angiogenesis in IUGR during the later stages of gestation. However, in more severe cases of intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.

Rapamycin-Induced Hypoxia Inducible Factor 2A Is Essential for Chondrogenic Differentiation of Amniotic Fluid Stem Cells.

UNLABELLED: Amniotic fluid stem (AFS) cells represent a major source of donor cells for cartilage repair. Recently, it became clear that mammalian target of rapamycin (mTOR) inhibition has beneficial effects on cartilage homeostasis, but the effect of mTOR on chondrogenic differentiation is still elusive. Therefore, the objectives of this study were to investigate the effects of mammalian target of rapamycin complex 1 (mTORC1) modulation on the expression of SOX9 and on its downstream targets during chondrogenic differentiation of AFS cells. We performed three-dimensional pellet culturing of AFS cells and of in vitro-expanded, human-derived chondrocytes in the presence of chondrogenic factors. Inhibition of mTORC1 by rapamycin or by small interfering RNA-mediated targeting of raptor (gene name, RPTOR) led to increased AKT activation, upregulation of hypoxia inducible factor (HIF) 2A, and an increase in SOX9, COL2A1, and ACAN abundance. Here we show that HIF2A expression is essential for chondrogenic differentiation and that AKT activity regulates HIF2A amounts. Importantly, engraftment of AFS cells in cell pellets composed of human chondrocytes revealed an advantage of raptor knockdown cells compared with control cells in their ability to express SOX9. Our results demonstrate that mTORC1 inhibition leads to AKT activation and an increase in HIF2A expression. Therefore, we suggest that mTORC1 inhibition is a powerful tool for enhancing chondrogenic differentiation of AFS cells and also of in vitro-expanded adult chondrocytes before transplantation. SIGNIFICANCE: Repair of cartilage defects is still an unresolved issue in regenerative medicine. Results of this study showed that inhibition of the mammalian target of rapamycin complex 1 (mTORC1) pathway, by rapamycin or by small interfering RNA-mediated targeting of raptor (gene name, RPTOR), enhanced amniotic fluid stem cell differentiation toward a chondrocytic phenotype and increased their engrafting efficiency into cartilaginous structures. Moreover, freshly isolated and in vitro passaged human chondrocytes also showed redifferentiation upon mTORC1 inhibition during culturing. Therefore, this study revealed that rapamycin could enable a more efficient clinical use of cell-based therapy approaches to treat articular cartilage defects.