A Newborn With Esophageal Atresia, Tracheoesophageal Fistula and Feeding Problems

DergiPark: 584646tmsjAims: Esophageal atresia is the most common congenital malformation of the esophagus. It can be diagnosed in the prenatalperiod, during the delivery or at the neonatal intensive care unit. With the operation, the respiratory system and digestive tractare being corrected to the anatomic position. In this case, we wanted to emphasize that patients with esophageal atresia maycontinue to have functional problems even after successful surgical treatment. Case Report: After preterm delivery, a femalepatient was consulted to Trakya University Department of Pediatric Surgery, at one day of age with the symptom of regurgitationof saliva. There were no abnormalities on physical examination. Due to the inability to pass an orogastric tube to the stomach,esophageal atresia was suspected. Thus, radiocontrast x-ray study was performed: the proximal esophageal pouch was identified,and malformation was diagnosed. After the diagnosis, tracheoesophageal fistula has been ligated. The patient received physicaltherapy after the operation, and she was followed-up for 10 months. A full recovery was observed, and the patient was able toswallow food. Conclusion: Esophageal atresia with distal tracheoesophageal fistula is not an uncommon malformation. Thepatients can have problems with swallowing in their infancy even they are treated surgically in the neonatal period.Keywords: Esophageal atresia, tracheoesophageal fistula, newbor

PiDRAM: A Holistic End-to-end FPGA-based Framework for Processing-in-DRAM

Processing-using-memory (PuM) techniques leverage the analog operation of memory cells to perform computation. Several recent works have demonstrated PuM techniques in off-the-shelf DRAM devices. Since DRAM is the dominant memory technology as main memory in current computing systems, these PuM techniques represent an opportunity for alleviating the data movement bottleneck at very low cost. However, system integration of PuM techniques imposes non-trivial challenges that are yet to be solved. Design space exploration of potential solutions to the PuM integration challenges requires appropriate tools to develop necessary hardware and software components. Unfortunately, current specialized DRAM-testing platforms, or system simulators do not provide the flexibility and/or the holistic system view that is necessary to deal with PuM integration challenges. We design and develop PiDRAM, the first flexible end-to-end framework that enables system integration studies and evaluation of real PuM techniques. PiDRAM provides software and hardware components to rapidly integrate PuM techniques across the whole system software and hardware stack (e.g., necessary modifications in the operating system, memory controller). We implement PiDRAM on an FPGA-based platform along with an open-source RISC-V system. Using PiDRAM, we implement and evaluate two state-of-the-art PuM techniques: in-DRAM (i) copy and initialization, (ii) true random number generation. Our results show that the in-memory copy and initialization techniques can improve the performance of bulk copy operations by 12.6x and bulk initialization operations by 14.6x on a real system. Implementing the true random number generator requires only 190 lines of Verilog and 74 lines of C code using PiDRAM's software and hardware components.Comment: To appear in ACM Transactions on Architecture and Code Optimizatio

Tick bite cases among hazelnut farm workers in Giresun

Ticks are arthropod vectors of many diseases. The prevalence of Lyme disease transmitted by Ixodes is not known in Turkey. The disease is caused by Borrelia species and can also be seen in domestic animals. The aim of this study is to identify the ticks, which are collected from the agricultural workers who admitted to hospitals during the hazelnut harvest season between August and September 2015, at species and genus level and investigate whether these ticks vector of Borrelia spp. Method: In this study, 152 ticks collected from 134 patients were investigated. Of all samples including larvae and nymphs, 95.24% were collected in September. All patients who admitted with complaints of tick bites were agricultural workers collecting nuts in the gardens at sea level. The ticks were identified at species and genus level with stereomicroskop, hemolymph fluid examined directly by dark-field microscope and cultured in the Borellia BarbourStoenner-Kelly (BSK-H) medium. Results: Of all the ticks, 126 (82.9%) were adults, 13 (8.55%) were nymphs and 13 (8.55%) were larvae. Stereoscopic examination of the ticks revealed that 125 (82.2%) of the adults were Ixodes ricinus and 1 (0.65%) was Rhipicephalus sanguineus. All of the 13 nymphs (8.55%) and 13 larvae (8.55%) were identified as Ixodes spp.. All forms of development cycle were detected in the samples and the forms were inconsistent with the expected development cycle. Borrelia spp., the agent of Lyme disease, was investigated in the 146 ticks defined as I. ricinus and Ixodes spp. Borrelia spp were detected by dark field microscope in 3 (2.05%) of the 146 Ixodes and Borrelia spp. were identified in 5 (3.4%) of the cultures. Conclusions: These results demonstrate that Lyme disease can be seen in our region and the most probable vector is Ixodes ricinus

Targeting SARS-CoV-2 Nsp12/Nsp8 interaction interface with approved and investigational drugs: anin silicostructure-based approach

In this study, the Nsp12-Nsp8 complex of SARS-CoV-2 was targeted with structure-based and computer-aided drug design approach because of its vital role in viral replication. Sequence analysis of RNA-dependent RNA polymerase (Nsp12) sequences from 30,366 different isolates were analysed for possible mutations. FDA-approved and investigational drugs were screened for interaction with both mutant and wild-type Nsp12-Nsp8 interfaces. Sequence analysis revealed that 70.42% of Nsp12 sequences showed conserved P323L mutation, located in the Nsp8 binding cleft. Compounds were screened for interface interaction, any with XP GScores lower than -7.0 kcal/mol were considered as possible interface inhibitors. RX-3117 (fluorocyclopentenyl cytosine) and Nebivolol had the highest binding affinities in both mutant and wild-type enzymes, therefore they were selected and resultant protein-ligand complexes were simulated for analysis of stability over 100 ns. Although the selected ligands had partial mobility in the binding cavity, they were not removed from the binding pocket after 100 ns. The ligand RX-3117 remained in the same position in the binding pocket of the mutant and wild-type enzyme after 100 ns MD simulation. However, the ligand Nebivolol folded and embedded in the binding pocket of mutant Nsp12 protein. Overall, FDA-approved and investigational drugs are able to bind to the Nsp12-Nsp8 interaction interface and prevent the formation of the Nsp12-Nsp8 complex. Interruption of viral replication by drugs proposed in this study should be further tested to pave the way forin vivostudies towards the treatment of COVID-19

Evaluation of the potency of FDA-approved drugs on wild type and mutant SARS-CoV-2 helicase (Nsp13)

SARS-CoV-2 has caused COVID-19 outbreak with nearly 2 M infected people and over 100K death worldwide, until middle of April 2020. There is no confirmed drug for the treatment of COVID-19 yet. As the disease spread fast and threaten human life, repositioning of FDA approved drugs may provide fast options for treatment. In this aspect, structure-based drug design could be applied as a powerful approach in distinguishing the viral drug target regions from the host. Evaluation of variations in SARS-CoV-2 genome may ease finding specific drug targets in the viral genome. In this study, 3458 SARS-CoV-2 genome sequences isolated from all around the world were analyzed. Incidence of C17747T and A17858G mutations were observed to be much higher than others and they were on Nsp13, a vital enzyme of SARS-CoV-2. Effect of these mutations was evaluated on protein-drug interactions using in silico methods. The most potent drugs were found to interact with the key and neighbor residues of the active site responsible from ATP hydrolysis. As result, cangrelor, fludarabine, folic acid and polydatin were determined to be the most potent drugs which have potency to inhibit both the wild type and mutant SARS-CoV-2 helicase. Clinical data supporting these findings would be important towards overcoming COVID-19

Targeting SARS-CoV-2 Nsp12/Nsp8 interactioninterface with approved and investigational drugs:an in silico structure-based approach

In this study, the Nsp12–Nsp8 complex of SARS-CoV-2 was targeted with structure-based and com-puter-aided drug design approach because of its vital role in viral replication. Sequence analysis ofRNA-dependent RNA polymerase (Nsp12) sequences from 30,366 different isolates were analysed forpossible mutations. FDA-approved and investigational drugs were screened for interaction with bothmutant and wild-type Nsp12–Nsp8 interfaces. Sequence analysis revealed that 70.42% of Nsp12sequences showed conserved P323L mutation, located in the Nsp8 binding cleft. Compounds werescreened for interface interaction, any with XP GScores lower than 7.0kcal/mol were considered aspossible interface inhibitors. RX-3117 (fluorocyclopentenyl cytosine) and Nebivolol had the highestbinding affinities in both mutant and wild-type enzymes, therefore they were selected and resultantprotein–ligand complexes were simulated for analysis of stability over 100ns. Although the selectedligands had partial mobility in the binding cavity, they were not removed from the binding pocketafter 100ns. The ligand RX-3117 remained in the same position in the binding pocket of the mutantand wild-type enzyme after 100ns MD simulation. However, the ligand Nebivolol folded andembedded in the binding pocket of mutant Nsp12 protein. Overall, FDA-approved and investigationaldrugs are able to bind to the Nsp12–Nsp8 interaction interface and prevent the formation of theNsp12–Nsp8 complex. Interruption of viral replication by drugs proposed in this study should be fur-ther tested to pave the way forin vivostudies towards the treatment of COVID-19

DRAM Bender: An Extensible and Versatile FPGA-based Infrastructure to Easily Test State-of-the-art DRAM Chips

To understand and improve DRAM performance, reliability, security and energy efficiency, prior works study characteristics of commodity DRAM chips. Unfortunately, state-of-the-art open source infrastructures capable of conducting such studies are obsolete, poorly supported, or difficult to use, or their inflexibility limit the types of studies they can conduct. We propose DRAM Bender, a new FPGA-based infrastructure that enables experimental studies on state-of-the-art DRAM chips. DRAM Bender offers three key features at the same time. First, DRAM Bender enables directly interfacing with a DRAM chip through its low-level interface. This allows users to issue DRAM commands in arbitrary order and with finer-grained time intervals compared to other open source infrastructures. Second, DRAM Bender exposes easy-to-use C++ and Python programming interfaces, allowing users to quickly and easily develop different types of DRAM experiments. Third, DRAM Bender is easily extensible. The modular design of DRAM Bender allows extending it to (i) support existing and emerging DRAM interfaces, and (ii) run on new commercial or custom FPGA boards with little effort. To demonstrate that DRAM Bender is a versatile infrastructure, we conduct three case studies, two of which lead to new observations about the DRAM RowHammer vulnerability. In particular, we show that data patterns supported by DRAM Bender uncovers a larger set of bit-flips on a victim row compared to the data patterns commonly used by prior work. We demonstrate the extensibility of DRAM Bender by implementing it on five different FPGAs with DDR4 and DDR3 support. DRAM Bender is freely and openly available at https://github.com/CMU-SAFARI/DRAM-Bender.Comment: To appear in TCAD 202

Three Single Nucleotide Polymorphisms of LOXL1’ in a Turkish Population with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Objectives: To investigate the three single nucleotide polymorphisms (SNPs) (rs3825942, rs1048661, and rs2165241) of the LOXL1 gene in pseudoexfoliation syndrome (XFS) and pseudoexfoliation glucoma (XFG) in the Turkish population. Materials and Methods: DNA was obtained from blood samples of 48 XFS, 58 XFG, and 171 control subjects. Three LOXL1 SNPs (rs3825942, rs1048661, rs2165241) were investigated with real time PCR, a probe-based genotyping method, and melting curve analysis. Results: All three SNPs of LOXL1 were significantly associated with XFS (rs3825942 p=3.54x10-6, odds ratio [OR]=∞; rs1048661 p=0.008, OR=2.18; rs2165241 p=8.69x10-9, OR=4.30) and XFG (rs3825942 p=3.41x10-7, OR=∞; rs1048661 p=1.75x10-5, OR=3.78; rs2165241 p=3.85x10-11 OR=4.90). No significant differences were observed between the XFS and XFG groups for any of the SNPs. The GG genotype of rs3825942 was more valuable for distinguishing pseudoexfoliative cases from healthy individuals. The homozygous TT genotype of rs2165241 was associated with 6-fold increased XFS risk (p=8.15x10-8, OR=6.32) and 7-fold increased XFG risk (p=1.45x10-10 OR=7.95). The GGT haplotype consisting of all three risk alleles was associated with a 7.45-fold higher risk of XFS/XFG (p=8.65x10-14, OR=7.45). Presence of T allele of rs2165241 conferred 3 times higher risk for men than women (p=6.78x10-5, OR=3.202). Conclusion: LOXL1 SNPs are associated with increased risk for pseudoexfoliation in the Turkish population. T allele of rs2165241 was found to be the most important characterized risk factor for our cohort. All SNP distributions were similar to other European and American populations

TuRaN: True Random Number Generation Using Supply Voltage Underscaling in SRAMs

Prior works propose SRAM-based TRNGs that extract entropy from SRAM arrays. SRAM arrays are widely used in a majority of specialized or general-purpose chips that perform the computation to store data inside the chip. Thus, SRAM-based TRNGs present a low-cost alternative to dedicated hardware TRNGs. However, existing SRAM-based TRNGs suffer from 1) low TRNG throughput, 2) high energy consumption, 3) high TRNG latency, and 4) the inability to generate true random numbers continuously, which limits the application space of SRAM-based TRNGs. Our goal in this paper is to design an SRAM-based TRNG that overcomes these four key limitations and thus, extends the application space of SRAM-based TRNGs. To this end, we propose TuRaN, a new high-throughput, energy-efficient, and low-latency SRAM-based TRNG that can sustain continuous operation. TuRaN leverages the key observation that accessing SRAM cells results in random access failures when the supply voltage is reduced below the manufacturer-recommended supply voltage. TuRaN generates random numbers at high throughput by repeatedly accessing SRAM cells with reduced supply voltage and post-processing the resulting random faults using the SHA-256 hash function. To demonstrate the feasibility of TuRaN, we conduct SPICE simulations on different process nodes and analyze the potential of access failure for use as an entropy source. We verify and support our simulation results by conducting real-world experiments on two commercial off-the-shelf FPGA boards. We evaluate the quality of the random numbers generated by TuRaN using the widely-adopted NIST standard randomness tests and observe that TuRaN passes all tests. TuRaN generates true random numbers with (i) an average (maximum) throughput of 1.6Gbps (1.812Gbps), (ii) 0.11nJ/bit energy consumption, and (iii) 278.46us latency

The Relationship Between Serum Asymmetric Dimethylarginine Levels and Cardiovascular Risk Factors in Children with Nephrotic Syndrome

Aim:Nephrotic syndrome is a common type of kidney disease during childhood characterized by proteinuria, edema and hypoalbuminemia. Serum asymmetric dimethylarginine (ADMA) inhibits vascular nitric oxide production and may be an independent risk factor for coronary heart disease. The aim of this study was to investigate the relationship between ADMA and atherosclerotic risk factors in children with nephrotic syndrome.Methods:Forty-one children with nephrotic syndrome and 33 healthy children were included in the study. Patients’ demographic and anthropometric characteristics, biochemical tests, serum homocysteine, ADMA and carotid intima-media thickness (CIMT) were assessed. The patients were divided into three groups: group 1 - steroid-free remission; group 2 - steroid-induced remission, still on steroid therapy; and group 3 - active proteinuria.Results:The patient and control groups were similar in terms of age, sex, weight, height, body mass index, and systolic blood pressure (p>0.05). Diastolic blood pressure was significantly higher in children with nephrosis than in controls. Serum ADMA, homocysteine and CIMT measurements were not different between the two groups (p>0.05). There was a positive correlation between diastolic blood pressure and CIMT measurement in patients. In group 3, ADMA was positively correlated with total cholesterol and low density lipoprotein cholesterol.Conclusion:Children with idiopathic nephrotic syndrome did not show signs of endothelial damage assessed by ADMA and CIMT