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Abstract Ring-shaped DNA sliding clamps are essential for DNA replication and genome maintenance. Clamps need to be opened and chaperoned onto DNA by clamp loader complexes (CLCs). Detailed understanding of the mechanisms by which CLCs open and place clamps around DNA remains incomplete. Here, we present a series of six structures of the Escherichia coli CLC bound to an open or closed clamp prior to and after binding to a primer-template DNA, representing the most significant intermediates in the clamp loading process. We show that the ATP-bound CLC first binds to a clamp, then constricts to hold onto it. The CLC then expands to open the clamp with a gap large enough for double-stranded DNA to enter. Upon binding to DNA, the CLC constricts slightly, allowing clamp closing around DNA. These structures provide critical high-resolution snapshots of clamp loading by the E. coli CLC, revealing how the molecular machine works.

This paper questions the side-channel security of central reduction technique, which is widely adapted in efficient implementations of Lattice-Based Cryptography (LBC). We show that the central reduction leads to a vulnerability by creating a strong dependency between the power consumption and the sign of sensitive intermediate values. We exploit this dependency by introducing the novel absolute value prediction function, which can be employed in higher-order non-profiled multi-query Side-Channel Analysis (SCA) attacks. Our results reveal that – compared to classical reduction algorithms – employing the central reduction scheme leads to a two-orders-of-magnitude decrease in the number of required SCA measurements to exploit secrets of masked implementations. We particularly show that our approach is valid for the prime moduli employed by Kyber and Dilithium, the lattice-based post-quantum algorithms selected by NIST. We practically evaluate our introduced approach by performing second-order non-profiled attacks against an open-source masked implementation of Kyber on an ARM Cortex-M4 micro-processor. In our experiments, we revealed the full secret key of the aforementioned masked implementation with only 250 power traces without any forms of profiling or choosing the ciphertexts.

Complete blood count (CBC) is performed using automated hematology analyzers. It is important that CBC results are comparable, reproducible, and reliable. In this study, our aim is to compare the results of Sysmex XN-1000 and Dirui BF-7200 hematology analyzers.

Recombineering is an essential tool for molecular biologists, allowing for the facile and efficient manipulation of bacterial genomes directly in cells without the need for costly and laborious in vitro manipulations involving restriction enzymes. The main workhorses behind recombineering are bacteriophage proteins that promote the single-strand annealing (SSA) homologous recombination pathway to repair double-stranded DNA breaks. While there have been several reviews examining recombineering methods and applications, comparatively few have focused on the mechanisms of the proteins that are the key players in the SSA pathway: a 5′→3′ exonuclease and a single-strand annealing protein (SSAP or “annealase”). This review dives into the structures and functions of the two SSA recombination systems that were the first to be developed for recombineering in E. coli: the RecET system from E. coli Rac prophage and the λRed system from bacteriophage λ. By comparing the structures of the RecT and Redβ annealases, and the RecE and λExo exonucleases, we provide new insights into how the structures of these proteins dictate their function. Examining the sequence conservation of the λExo and RecE exonucleases gives more profound insights into their critical functional features. Ultimately, as recombineering accelerates and evolves in the laboratory, a better understanding of the mechanisms of the proteins behind this powerful technique will drive the development of improved and expanded capabilities in the future.

Teaching computer architecture (Comp-Arch) courses in undergraduate curricula is becoming more of a challenge as most students prefer software-oriented courses. In some computer science/engineering departments, Comp-Arch courses are offered without the lab component due to resource constraints and differing pedagogical priorities. This article demonstrates how students working in teams are motivated to study the Comp-Arch course and how instructors can increase student motivation and knowledge by taking advantage of hands-on practices. The teams are asked to design and implement a 16-bit MIPS-like processor with constraints as a specific instruction set, and limited data and instruction memory. Student projects include following three phases, namely, design, desktop simulator implementation, and verification using hardware description language (HDL). In the design phase, teams develop their Comp-Arch to implement specified instructions. A range of designs resulted, e.g., (a) a processor with extensive user-defined instructions resulting in longer cycle times (b) a processor with a minimal instruction set but with a faster clock cycle time. Next, teams developed a desktop simulator in any programming language to execute instructions on the architecture. Finally, students engage in Verilog Hardware Description Language (HDL) projects to simulate and verify the data-path designed during the initial phase. Student feedback and their current understanding of the project were collected through a questionnaire featuring varying Likert scale questions, some with a ten-point scale, and others with a five-point scale. Results of the survey show that the hands-on approach increases students’ motivation and knowledge in the Comp-Arch course, which is centered around computer system design principles. This approach can also be effectively extended to related courses, such as Microprocessor Design, which delves into the intricacies of creating and implementing microprocessors or central processing units (CPUs) at the hardware level. Furthermore, the present study demonstrates that interactions, specifically through peer reviews and public presentations, between students in each phase increases their knowledge and perspective on designing custom processors.

Objective: This study aimed to determine the serum levels of neopterin, galectin-3, tissue necrosis factor alpha, and interleukin-10 (IL-10) during the interictal and attack periods of patients with migraine. It is hoped that the findings will contribute to the literature on the theory of neurogenic inflammation. Materials and Methods: Eighty patients with migraine (40 attacks and 40 interictal periods) and 30 healthy volunteers were included in the study. Blood samples were taken from the people participating in the study, and serum was obtained under the appropriate conditions. The serum levels of all the parameters were determined using a ELISA kit (Coon Koon, Shanghai, China). The difference between the groups was evaluated using appropriate statistical analysis methods. Results: Galectin-3 and neopterin levels were higher during the attack period compared with the interictal period, and IL-10 and galectin-3 levels were higher during the attack period than in the control group. There was no significant difference in any parameter between the control and interictal period groups. There was a correlation between galectin-3 and neopterin levels in all groups (r = 0.598, P < 0.001). Conclusion: The levels of pro-inflammatory molecules, such as galectin-3 and neopterin, were found to be higher in patients with migraine during attacks, which is consistent with the theory of neurogenic inflammation. It is thought that the increase in IL-10 levels during the attack occurs to limit inflammation. Since the tetrahydrobiopterin pathway plays a role in inflammatory and neuropathic pain, it is thought that high neopterin levels during an attack may be associated with migraine headaches.

Over the past two decades, the gaming industry has rapidly increased its popularity and gained a top spot in the entertainment sector. With this rise, customer relations and churn analysis have become even more prominent in gaming, as digital games are quickly integrated into the industry and fetch high revenues. The esteem for gaming and the revenue of companies has increased, which has made the concept of customer churn more critical. The behavior of most customers in the gaming industry also shows that it is a structure worth analyzing. This study focuses on the player log data of Blade and Soul game over specific periods with machine learning algorithms and tries to answer two business problems. These problems are to predict churners and player survival time, which are modeled as a classification and a regression problem, respectively. Blade and Soul is an MMORPG (massively multiplayer online role-playing game) developed by NCSOFT and widely played in the Far East. The theoretical basis of the study is the provisions of behavioral economics and churn management. For research purposes, the methods and algorithms of machine learning were used. Player log data was collected in 2016 and 2017, then anonymized and released for researchers. The research scope follows the CRISP-DM methodology and explains the process in detail by adhering to this methodology. A set of data consisting of 10,000 players with Test 1, Test 2, and Train were released separately by NCSOFT. Considering player churn and survival times, XGBoost demonstrates the highest effectiveness for classification problem and MLP and GBR for regression problem. The results show churn analysis can help businesses identify trends and patterns in customer behavior, such as when customers are most likely to leave, which features are causing them to leave, and which customer segments are most at risk of churning identifying trends and patterns.

Abstract 3‐Methylglutaconyl‐CoA hydratase deficiency (MGA1) is a defect in leucine catabolism, which causes the accumulation of urinary 3‐methylglutaconate, with or without 3‐hydroxyisovalerate and 3‐methylglutarate. It is an ultra‐rare condition, with

Redβ annealase catalyses single-strand annealing homologous DNA recombination. Here, the authors present a cryo-EM structure of a Redβ annealing intermediate bound to two complementary 27mer oligonucleotides.

Abstract Ornithine transcarbamylase deficiency (OTCD) is an X‐linked urea cycle disorder characterised by reduced or absent OTC enzyme activity, resulting in the accumulation of neurotoxic ammonia. Approximately 80%–90% of the causative variants are identified by Sanger sequencing or multiplex ligation‐dependent probe amplification (MLPA) of the OTC gene. A 23‐year‐old male with biochemical evidence of OTCD was referred for molecular analysis. Initial Sanger sequencing yielded no pathogenic variants. MLPA testing raised suspicion of a mosaic deletion of exon 1; however, high‐resolution microarray did not identify a copy number variant on the X chromosome. Sequencing over the suspected breakpoint detected a hemizygous likely pathogenic promoter variant, c.‐106C > A, which was located within the MLPA probe binding site. Subsequently, historical patients referred to our centre, without a molecular aetiology for their OTCD, were re‐sequenced with these primers and this variant was also identified in two additional unrelated males. All three patients described in this case series have the late‐onset disease. Two presented at 5 years of age with vomiting, whilst the other was managed from birth based on a family history of late‐onset OTCD. One patient required liver transplantation due to recurrent decompensations; the other two are managed with a protein‐restricted diet. All three patients have not sustained any significant neurological insults and are functioning well as adults. These cases support screening of the promoter region within the OTC gene, particularly if a molecular basis has not been elucidated by MLPA or sequencing of the coding regions.

This study was conducted to evaluate whether sildenafil effectively treats necrotizing enterocolitis (NEC).

In this overview, the latest achievements in dietary origins, absorption mechanism, bioavailability assay, health advantages, cutting-edge encapsulation techniques, fortification approaches, and innovative highly sensitive sensor-based detection methods of vitamin B12 (VB12) were addressed. The cobalt-centered vitamin B is mainly found in animal products, posing challenges for strict vegetarians and vegans. Its bioavailability is highly influenced by intrinsic factor, absorption in the ileum, and liver reabsorption. VB12 mainly contributes to blood cell synthesis, cognitive function, and cardiovascular health, and potentially reduces anemia and optic neuropathy. Microencapsulation techniques improve the stability and controlled release of VB12. Co-microencapsulation of VB12 with other vitamins and bioactive compounds enhances bioavailability and controlled release, providing versatile initiatives for improving bio-functionality. Nanotechnology, including nanovesicles, nanoemulsions, and nanoparticles can enhance the delivery, stability, and bioavailability of VB12 in diverse applications, ranging from antimicrobial agents to skincare and oral insulin delivery. Staple food fortification with encapsulated and free VB12 emerges as a prominent strategy to combat deficiency and promote nutritional value. Biosensing technologies, such as electrochemical and optical biosensors, offer rapid, portable, and sensitive VB12 assessment. Carbon dot-based fluorescent nanosensors, nanocluster-based fluorescent probes, and electrochemical sensors show promise for precise detection, especially in pharmaceutical and biomedical applications.

Abstract Smith‐Lemli‐Opitz syndrome (SLOS) is a relatively common genetic cause of developmental delay and may only present in conjunction with 2,3 toe syndactyly. This case series illustrates a milder phenotype of SLOS, where the predominant findings are neurocognitive in the presence of 2,3 toe syndactyly.

Non-coding regions are areas of the genome that do not directly encode protein and were initially thought to be of little biological relevance. However, subsequent identification of pathogenic variants in these regions indicates there are exceptions to this assertion. With the increasing availability of next generation sequencing, variants in non-coding regions are often considered when no causative exonic changes have been identified. There is still a lack of understanding of normal human variation in non-coding areas. As a result, potentially pathogenic non-coding variants are initially classified as variants of uncertain significance or are even overlooked during genomic analysis. In most cases where the phenotype is non-specific, clinical suspicion is not sufficient to warrant further exploration of these changes, partly due to the magnitude of non-coding variants identified. In contrast, inborn errors of metabolism (IEMs) are one group of genetic disorders where there is often high phenotypic specificity. The clinical and biochemical features seen often result in a narrow list of diagnostic possibilities. In this context, there have been numerous cases in which suspicion of a particular IEM led to the discovery of a variant in a non-coding region. We present four patients with IEMs where the molecular aetiology was identified within non-coding regions. Confirmation of the molecular diagnosis is often aided by the clinical and biochemical specificity associated with IEMs. Whilst the clinical severity associated with a non-coding variant can be difficult to predict, obtaining a molecular diagnosis is crucial as it ends diagnostic odysseys and assists in management.

Nowadays, the most critical agriculture-related problem is the harm caused in fruit, vegetable, nut, and flower crops by harmful pests, particularly the Mediterranean fruit fly, Ceratitis capitata, named in short as Medfly. Medfly existence in agricultural fields must be monitored systematically for effective combat against it. Special traps are utilized in the field to catch Medflies which will reveal their presence, and applying pesticides at the right time will help reduce their population. A technologically supported automated remote monitoring system should eliminate frequent site visits as a more economical solution. In this paper, a machine learning system that can detect Medfly images on a picture and count their numbers is developed. A special trap equipped with an integrated camera that can take photos of the sticky band where Medflies are caught daily is utilized. Obtained pictures are then transmitted by an electronic circuit containing a SIM card to the central server where the object detection algorithm runs. This study employs a faster region-based convolutional neural network (Faster R-CNN) model in identifying trapped Medflies. When Medflies or other insects stick on the sticky band of the trap, they continue to spend extraordinary effort trying to release themselves in a panic until they die. Therefore, their shape is badly distorted as their bodies, wings, and legs are all buckled. The challenge here is that the machine learning system should detect these Medflies of distorted shape with high accuracy. Therefore, it is crucial to utilize pictures that contain trapped Medfly images that possess distorted shapes for training and validation. In this paper, the success rate in identifying Medflies when other insects are also present is approximately 94% that is achieved by the machine learning system training process, owing to the considerable amount of purpose-specific photographic data. This rate may be seen as quite favorable when compared to the success rates provided in the literature.

Introduction: Biotinidase synthesis is needed to recycle biotin for essential metabolic reactions. Biotinidase activity is lower than normal levels in advanced liver disease but is higher in hepatic glycogen storage disorders (GSDs), however the cause of this association remains unclear. Methods: In this study, biotinidase activity was measured in plasma samples from 45 individuals with hepatic GSDs; GSDI (a, b; n = 25) and GSD III (a, b; n = 20), complemented by a chart review to associate biotinidase activity levels with clinical laboratory and imaging findings known to be implicated in these GSDs. Results: Our findings showed variation in biotinidase activity levels among subjects with GSD I and III; biotinidase activity correlated positively with hypertriglyceridemia in subjects with GSD I (r = 0.47, P = 0.036) and GSD III (r = 0.58, P = 0.014), and correlated negatively with age (r = −0.50, P = 0.03) in patients with GSD III. Additionally, biotinidase activity was reduced, albeit within the normal range in subjects with evidence of fibrosis/cirrhosis, as compared to subjects with hepatomegaly with or without steatosis (P = 0.002). Discussions: These findings suggest that abnormal lipid metabolism in GSD I and III and progressive liver disease in GSD III may influence biotinidase activity levels. We suggest that a prospective, multi-center, longitudinal study designed to assess the significance of monitoring biotinidase activity in a larger cohort with hepatic GSDs is warranted to confirm this observation. Take-home message: Altered lipid metabolism and advancing liver fibrosis/cirrhosis may influence biotinidase activity levels in patients with hepatic glycogen storage disease. Thus, longitudinal monitoring of biotinidase activity, when combined with clinical and other biochemical findings may be informative.

Gram-positive bacteria contain a transcription factor HelD that is able to remove and recycle stalled transcription complexes. Here the authors provide mechanistic insights into this process by determining the cryo-EM structures of the Bacillus subtilis RNA polymerase (RNAP) elongation complex and the RNAP-HelD transcription recycling complex and propose a model of HelD catalysed transcription recycling.

Objective: To show the effect of the oxidative stress index (OSI) of serum and follicular fluid and ischemia-modified albumin (IMA) levels on embryonic development and pregnancy in cases of unexplained infertility applied with in-vitro fertilization (IVF). Materials and Methods: A total of 80 patients were treated with antagonist protocol in the first cycle of IVF for a diagnosis of unexplained infertility. We recorded demographic data, blood and follicular fluid levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), OSI and IMA. Using ROC analysis for follicular fluid OSI and IMA, patients were grouped according to the cutoff values determined (11.15 and 0.509, respectively). Results: No correlation was detected between serum OSI and IMA values and the implantation rate. In the follicular fluid OSI ≤ 11.15 group (n = 32), beta HCG positivity was seen in 65.6% of patients and live births in 50%. In the IMA ≤ 0.509 group (n = 24), beta HCG positivity was seen in 66.6% and live births in 50%. With respect to follicular fluid OSI and IMA values, the difference in terms of both beta HCG positivity and live birth rates was statistically significant (p = 0.003, p = 0.007, and p = 0.044, p = 0.028, respectively). The BMI value was significantly high in the IMA > 0.509 group (p < 0.05). Conclusions: In cases of unexplained infertility with high BMI, increased IMA but not OSI in follicular fluid during IVF treatment could be related to decreased implantation and live birth rates. Follicular fluid IMA levels below the cutoff value may predict pregnancy success.

Abstract Background and objective: The aim was to investigate the effects of Turkish classical music on pain and oxidative stress in patients undergoing oocyte pick-up. Methods: The study was a randomized, controlled trial. The groups included Group NM (Non-Music), control group; Group PM, which comprised patients who listened to music before the operation; and Group CM, which comprised patients who listened to music both before and during the operation. Blood was drawn prior to the operation to measure the oxidative stress values. Pain, hemodynamic parameters, oxidative stress values were assessed postoperatively. Results: The number of patients requiring additional propofol was higher in Group PM than in Groups NM and CM (p = 0.003). The postoperative Visual Analog Scale (VAS) score were lower in Groups PM and CM than in Group NM (p = 0.001, p = 0.007) in the 1st and 60th minutes. The postoperative VAS score was lower in Group CM than in Group NM (p = 0.045) in the 5th minute. The postoperative additional analgesic requirements were lower in Groups PM and CM than in Group NM (p = 0.045). The postoperative blood glutathione peroxidase values were significantly higher in Groups PM and CM than in Group NM (p = 0.001). The postoperative catalase values were significantly higher in Groups PM and CM than in Group NM (p = 0.008 and p < 0.001). The preoperative malondialdehyde values were significantly lower in Groups PM and CM than in Group NM. The preoperative nitric oxide values were higher in Groups PM and CM than in Group NM (p < 0.001), whereas the postoperative nitric oxide values were lower in Groups PM and CM than in Group NM (p < 0.001). Conclusion: Turkish classical music has beneficial effects on pain and oxidative stress in oocyte pick-up patients.

This study focuses on the relationship between financial ratios and the technology and telecommunication stock returns listed on the Istanbul Stock Exchange. Since technology and telecommunication sector has become an important part of the Turkish economy and is attractive for investors and shareholders, the results play a critical role for all stakeholders. This academic work aims to determine, through the application of panel data analysis, using both the Parks-Kmenta estimator and the Two-way Mixed Effects Model, whether the Price-to-Sales, Earnings per Share (EPS), Debt-to-Equity, and EBITDA Margin financial ratios affect the returns of technology and telecommunication stock returns listed on the Istanbul Stock Exchange. According to empirical findings, Earnings per Share (EPS), EBITDA Margin, and Price-to-Sales ratios have statistically significant effects on technology and telecommunication companies’ stock returns. Higher EPS and EBITDA Margin ratios generate higher returns for the next quarters, and lower Price-to-Sales ratios lead to higher returns for the following periods. Furthermore, the results obtained using the Two-way Mixed Effects Model show that the Debt-to-Equity ratio is negatively related to stock returns.

Choosing the most suitable machine among the machines differ in terms of numerous criteria such as speed, quality, cost and after-sales service is a very complicated and important problem for the firms. Since multiple criteria need to be taken into consideration when making decisions, an effective decision-making process is needed, and multi-criteria decision-making techniques can be used as a solution tool. In this study, it is aimed to solve the machine selection problem of an enterprise which should consider many criteria. The criteria considered in the purchasing, weighted with AHP due to the different priorities of criteria in the eyes of the manager. In order to be able to choose from different alternatives, the most appropriate one was provided with the help of Gray Relational Analysis.

Abstract Background Ketone bodies form a vital energy source for end organs in a variety of physiological circumstances. At different times, the heart, brain and skeletal muscle in particular can use ketones as a primary substrate. Failure to generate ketones in such circumstances leads to compromised energy delivery, critical end-organ dysfunction and potentially death. There are a range of inborn errors of metabolism (IEM) affecting ketone body production that can present in this way, including disorders of carnitine transport into the mitochondrion, mitochondrial fatty acid oxidation deficiencies (MFAOD) and ketone body synthesis. In situations of acute energy deficit, management of IEM typically entails circumventing the enzyme deficiency with replenishment of energy requirements. Due to profound multi-organ failure it is often difficult to provide optimal enteral therapy in such situations and rescue with sodium DL-3-hydroxybutyrate (S DL-3-OHB) has been attempted in these conditions as documented in this paper. Results We present 3 cases of metabolic decompensation, one with carnitine-acyl-carnitine translocase deficiency (CACTD) another with 3-hydroxyl, 3-methyl, glutaryl CoA lyase deficiency (HMGCLD) and a third with carnitine palmitoyl transferase II deficiency (CPT2D). All of these disorders are frequently associated with death in circumstance where catastrophic acute metabolic deterioration occurs. Intensive therapy with adjunctive S DL-3OHB led to rapid and sustained recovery in all. Alternative therapies are scarce in these situations. Conclusion S DL-3-OHB has been utilised in multiple acyl co A dehydrogenase deficiency (MADD) in cases with acute neurological and cardiac compromise with long-term data awaiting publication. The use of S DL-3-OHB is novel in non-MADD fat oxidation disorders and contribute to the argument for more widespread use.

ABSTRACT Purpose: To investigate experimentally the effects of Tropifexor, a farnesoid X receptor agonist, on liver injury in rats with obstructive jaundice. Methods: Forty healthy Wistar albino female rats were divided randomly in selected groups. These groups were the sham group, control group, vehicle solution group, Ursodeoxycholic acid group and Tropifexor group. Experimental obstructive jaundice was created in all groups, except the sham one. In the blood samples obtained, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin and direct bilirubin levels were established and recorded. Additionally, liver malondialdehyde, myeloperoxidase and catalase enzyme activity in the tissue samples were studied. Histopathological analysis was also performed. Results: No statistical difference was found between the control group and the Tropifexor group when AST, ALT and ALP values were compared. However, it was found that the Tropifexor group had statistically significant decreases in the values of GGT, total bilirubin and direct bilirubin (p < 0.05). Additionally, Tropifexor decreased the median values of malondialdehyde and myeloperoxidase, but this difference was not statistically significant compared to the control group. Finally, the Tropifexor group was statistically significant in recurring histopathological liver damage indicators (p < 0.05). Conclusions: Tropifexor reduced liver damage due to obstructive jaundice.

Objective: Autosomal recessive cutis laxa type IIA (ARCL2A) is a rare congenital disorder characterized by loose and elastic skin, growth and developmental delay, and skeletal anomalies. It is caused by biallelic mutations in ATP6V0A2. Those mutations lead to increased pH in secretory vesicles and thereby to impaired glycosyltransferase activity and organelle trafficking. We aimed to identify the genetic and molecular cause of the unexpected hematological findings in a Turkish family. Materials and Methods: We performed clinical, genetic, and histological analyses of a consanguineous family afflicted with wrinkled and loose skin, microcephaly, intellectual disability, cleft lip and palate, downslanting palpebral fissures, ectopia lentis, bleeding diathesis, and defective wound healing. Results: Linkage analysis using SNP genotype data yielded a maximal multipoint logarithm of odds score of 2.59 at 12q24.21-24.32. Exome sequence analysis for the proband led to the identification of novel homozygous frameshift c.2085_2088del (p.(Ser695Argfs*12)) in ATP6V0A2, within the linked region, in the two affected siblings. Conclusion: Our patients do not have gross structural brain defects besides microcephaly, strabismus, myopia, and growth or developmental delay. Large platelets were observed in the patients and unusual electron-dense intracytoplasmic inclusions in fibroblasts and epidermal basal cells were observed in both affected and unaffected family members. The patients do not have any genetic defect in the VWF gene but von Willebrand factor activity to antigen ratios were low. Clinical findings of bleeding diathesis and defective wound healing have not been reported in ARCL2A and hence our findings expand the phenotypic spectrum of the disease.

Background. Pain aggravates the autonomic response to stress and raises neuroendocrine stress hormone levels. We compared the effects of propofol and sevoflurane on postoperative pain and neuroendocrine stress hormones. A prospective, randomized, and controlled trial was conducted with 60 patients. Methods. We randomly allocated patients to groups P (remifentanil/propofol, n = 30) and S (remifentanil/sevoflurane, n = 30). Preoperative blood samples were taken to measure serum adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), glucagon, cortisol, aldosterone, and prostaglandin E2 (PGE2) levels. Intraoperatively and postoperatively, clinical parameters were monitored at different time points. The hormone levels were again measured in the follicular fluid and blood postoperatively. Result. Demographic data were similar. The preoperative serum aldosterone levels were significantly higher in group P (p=0.001). Preoperative and postoperative serum ACTH, glucagon, cortisol, and PGE2 levels were significantly different in group P (p=0.009, p=0.004, p=0.029, and p=0.002); serum ACTH, glucagon, and PGE2 levels increased while serum cortisol levels decreased postoperatively. In group S, serum CRH and aldosterone levels, both increased in the postoperative period compared to the preoperative (p=0.001, p=0.006). Postoperatively, glucagon and PGE2 levels were both higher in group P than group S (p=0.019, p=0.015). In postoperative follicular fluid, glucagon and PGE2 levels were higher in group P, while cortisol levels were higher in group S (p=0.001, p=0.007, and p=0.001). Conclusion. The effects of anesthetic agents were different. In group P, in the preoperative and postoperative evaluation, ACTH, glucagon, and PGE2 increased postoperatively, while cortisol decreased. In group S, aldosterone and CRH increased postoperatively. Glucagon and PG E2 were higher in group P than S, postoperatively.

Objective: The aim of the study was to investigate the protective effect of amifostine against radiotherapy-induced small bowel injury. Materials and Methods: Forty rats were divided equally into four groups as control, irradiation (IR), IR + Amifostine, IR+N-acetyl cysteine (NAC) groups. Caspase-3 expression, villus lengths, and microscopic tissue injury were evaluated histopathologically. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO) and malondialdehyde (MDA) were measured biochemically in jejunum tissue. Pre- and post-radiation weights of the rats were recorded. Results: Caspase-3 was at the highest level in the IR group, at the lowest level in the control and weak in the Amifostine+IR group. The lowest microscopic score was determined in the IR group and the difference between the groups was statistically significant. CAT decreases after IR. However, Amifostine and NAC prevented radiation-induced catalase decline. In Amifostine+IR group, the villus length was significantly longer than that of the IR group. Amifostine was observed to protect against weight loss. Conclusion: The results obtained from this study demonstrate that the administration of Amifostine can substantially reduce apopitosis and support the repair of the structure and function of intestinal tissues which have been damaged by exposure to radiation. These results also suggest that it may be a promising therapeutic agent.

Thanks to the beneficial properties of probiotic bacteria, there exists an immense demand for their consumption in probiotic foods worldwide. Nevertheless, it is difficult to retain a high number of viable cells in probiotic food products during their storage and gastrointestinal transit. Microencapsulation of probiotic bacteria is an effective way of enhancing probiotic viability by limiting cell exposure to extreme conditions via the gastrointestinal tract before releasing them into the colon. This research aims to develop a new coating material system of microencapsulation to protect probiotic cells from adverse environmental conditions and improve their recovery rates. Hence, Lactobacillus rhamnosus was encapsulated with emulsion/internal gelation techniques in a calcium chloride solution. Alginate–probiotic microbeads were coated with xanthan gum, gum acacia, sodium caseinate, chitosan, starch, and carrageenan to produce various types of microcapsules. The alginate+xanthan microcapsules exhibited the highest encapsulation efficiency (95.13 ± 0.44%); they were simulated in gastric and intestinal juices at pH 3 during 1, 2, and 3 h incubations at 37 °C. The research findings showed a remarkable improvement in the survival rate of microencapsulated probiotics under simulated gastric conditions of up to 83.6 ± 0.89%. The morphology, size, and shape of the microcapsules were analyzed using a scanning electron microscope. For the protection of probiotic bacteria under simulated intestinal conditions; alginate microbeads coated with xanthan gum played an important role, and exhibited a survival rate of 87.3 ± 0.79%, which was around 38% higher than that of the free cells (49.4 ± 06%). Our research findings indicated that alginate+xanthan gum microcapsules have a significant potential to deliver large numbers of probiotic cells to the intestines, where cells can be released and colonized for the consumer’s benefit.

As known, marine dredged materials (DMs) are highly nuisance wastes if they are not correctly reused or removed. In this work, the usability of DMs to the technical terms as manufactured topsoil (MT) in the urban landscaping works is discussed. Firstly, the leaching potentials of DMs were determined according to the related legislations to identify their hazardousness features. Secondly, DMs were subject to some treatment stages such as sieving, desalination, organic amelioration via peat and sheep manure, and pH adjustment to turn into an alternative natural soil pursuant to the British Standard in the scope of soil quality improvement studies as there is not any national standard in Turkey for the production of topsoil from different materials. Then, MT mixtures were prepared with washed and unwashed DM, peat and sheep manure in different mixing ratios (v/v); 33%, 50% and 67% DM, respectively. Consequently, high quality grass seed mixtures used for the landscaping applications were monitored for six months. The results demonstrate the availability of DM as alternative MT in the urban landscaping areas. Thus, important data were obtained as to the use of DM at alternative areas such as green city, green roof, shopping centers, organized industry, etc.

Maple syrup urine disease is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase, responsible for degradation of leucine, isoleucine, and valine. Biallelic pathogenic variants in BCKDHA, BCKDHB, or DBT genes result in enzyme deficiency. We report the case of a female infant who presented with mild gross motor delay at 4 months, and seizures with hypoglycaemia at 5 months. Newborn screening returned total leucine/isoleucine at the 99.5th centile of the population; however, as second-tier testing reported minimal alloisoleucine, the results were considered inconsistent with MSUD. Plasma amino acid and urine organic acid analyses at 5 months were, however, consistent with a diagnosis of MSUD. A brain MRI showed bilateral symmetrical T2 hyperintense signal abnormalities involving white matter, globus pallidus, thalamus, brainstem, and dentate nuclei with restricted diffusion. A repeat MRI 10 months post-dietary-intervention showed the resolution of these changes and progression in myelination. Her clinical phenotype, including protein tolerance, correlated with intermediate MSUD. Molecular analysis of all three genes identified two variants of uncertain significance, c.434-15_434-4del and c.365A>G (p. Tyr122Cys) in the DBT gene. The rate of leucine decarboxylation in fibroblasts was reduced, but not to the extent observed in classical MSUD patients, supporting an intermediate form of MSUD. Previously reported mRNA splicing studies supported a deleterious effect of the c.434-15_434-4del variant. This functional evidence and confirmation that the variants were in trans, permitted their reclassification as pathogenic and likely pathogenic, respectively, facilitating subsequent prenatal testing. This report highlights the challenges in identifying intermediate MSUD by newborn screening, reinforcing the importance of functional studies to confirm variant pathogenicity in this era of molecular diagnostics.

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This paper proposes a novel data classification framework, combining sparse auto-encoders (SAEs) and a post-processing system consisting of a linear system model relying on Particle Swarm Optimization (PSO) algorithm. All the sensitive and high-level features are extracted by using the first auto-encoder which is wired to the second auto-encoder, followed by a Softmax function layer to classify the extracted features obtained from the second layer. The two auto-encoders and the Softmax classifier are stacked in order to be trained in a supervised approach using the well-known backpropagation algorithm to enhance the performance of the neural network. Afterwards, the linear model transforms the calculated output of the deep stacked sparse auto-encoder to a value close to the anticipated output. This simple transformation increases the overall data classification performance of the stacked sparse auto-encoder architecture. The PSO algorithm allows the estimation of the parameters of the linear model in a metaheuristic policy. The proposed framework is validated by using three public datasets, which present promising results when compared with the current literature. Furthermore, the framework can be applied to any data classification problem by considering minor updates such as altering some parameters including input features, hidden neurons and output classes.

Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects' cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health.

Background: Smokeless tobacco use is common in various parts of the world. In Turkey a type of smokeless tobacco called “Maras powder” is widely used in southeastern region. Smoking is known to have an adverse effect on nitric oxide and cardiovascular risk factors. The aim of this study was to evaluate whether there is difference between the effects of Maras powder and cigarette smoking on the cardiovascular risk factors and nitric oxide levels.Methods: In the study, participants were 48 Maras powder users, 50 cigarette smokers and 45 nontobacco user subjects. Blood samples were collected and hematological parameters and lipid parameters were measured. Plasma Nitric oxide level was also detected by using the Griess method.Results: Plasma total cholesterol, LDL-cholesterol, triglyceride levels were significantly higher in Maras powder and cigarette smokers group than in the nontobacco user group (pConclusion: We conclude that Maras powder has similar adverse effects on nitric oxide level and cardiovascular risk parameters and thereby it appears to be harmful as cigarette smoking.

PURPOSE: To investigate the protective effect of zofenopril on torsion detorsion-induced biochemical and histopathological changes in experimental testicular ischemia or reperfusion injury in rats.MATERIALS AND METHODS: A total of 35 prepubertal male Wistar-Albino rats were divided into five groups, including 7 rats in each group: Group I (sham, S), sham operation; group II (torsion/detorsion-early orchiectomy, T/D-E), 2 hours ischemia and 4 hours reperfusion; group III (torsion/detorsion-late orchiectomy), T/D-L), 2 hours ischemia and 5 days reperfusion; group IV (zofenopril-early orchiectomy, Z-E), 2 hours ischemia, 4 hours reperfusion, and a single dose of zofenopril; and group V (zofenopril-late orchiectomy, Z-L), 2 hours ischemia, 5 days reperfusion, and 5 doses of zofenopril. We determined the tissue levels of malondialdehyde, nitric oxide, glutathione peroxidase, and superoxide dismutase enzyme activities. Histopathologically, mean seminiferous tubule diameter measurements were used.RESULTS: Malondialdehyde (3.490 ± 0.89 versus 1.729 ± 0.25 in early period; 3.837 ± 1.694 versus 1.694 ± 0.47 in late period) and nitric oxide levels (3.507 ± 0.44 versus 2.853 ± 0.54 in early period; 4.010 ± 0.72 versus 2.446 ± 0.29 in late period) significantly reduced and glutathione peroxidase (0.012 ± 0.001 versus 0.017 ± 0.001 in early period; 0.013 ± 0.002 versus 0.018 ± 0.001 in late period) and superoxide dismutase enzyme activities (58.030 ± 5.97 versus 70.773 ± 3.85 in early period; 57.421 ± 7.81 versus 76.329 ± 4.09 in late period) significantly increased in the testis tissue in zofenopril pretreated groups compared to group T/D both in early and late period (P < .05). The mean seminiferous tubule diameter was significantly better in pretreated group (210.33 ± 17.32) than group T/D (185.02 ± 22.45) only in late period (P < .05), but not in early period (209.38 ± 30.40 versus 208.21 ± 13.57; P > .05).CONCLUSION: Treatment with zofenopril decreased damage in ipsilateral testis caused by ischemia/reperfusion, and clinical application of zofenopril might be a new approach for the treatment of testicular torsion in addition to conventional detorsion.

Due to their low density, high structural strength and energy absorption capacity, aluminum alloys are frequently used in lightweight armor systems such as aeronautics applications, offshore platforms, ship components, bridge decks, etc. Impacts or other types of high-speed loading conditions are thus a relevant issue for several of these applications. In these applications, weight of a structure is an important design criterion. For this reason, it’s known that aluminum alloys are preferred instead of conventional steel or concrete. This wide application area considering behavior of materials subjected to high velocity impact load increases the importance of the investigations about solutions to decrease the penetration depth caused by high velocity impact. In this study, influences of ballistic performance improving techniques e.g. surface coating and adding support on high velocity normal impact resistance of aluminum plates were analyzed and compared experimentally.