Unique Procedure to Remove Pedicle Screw without Compatible Instrumentation: Case Report and Review of Literature.

Introduction: As the number of patients undergoing spine fixation has increased, the requirement for revision surgery has also increased. Difficulty faced while doing revision surgery is mostly in removing polyaxial pedicle screws, especially if we do not have the desired instrumentation. Case Report: A 55-year-old patient previously operated for D12 fracture presented to us with implant failure due to backing out of pedicle screws. Compatible instrumentation to remove the implant was not available as even the cap screw could not be removed due to screwdriver mismatch. Hence, we had to design our own method to address the problem which we did successfully. At present, the patient is on our regular follow-up, is pain free, is able to walk without support, and has not reported any new complaints. Conclusion: Method used in our case simplifies and accelerates the screw removal process and provides guidance to any surgeon who faces a similar problem.

Synergy of waste plastics and natural fibers as sustainable composites for structural applications concerning circular economy.

The increasing demand for shelters, depleting natural resources, concern for plastic waste, and rising awareness for the environment have attracted the contemporary world towards the recycling of waste plastics for the development of an alternative and sustainable building construction material. The plastics suffer due to their poor strength which can be successfully overcome by the reinforcement of natural fibers. The work aimed to develop and investigate the properties of natural fiber-reinforced composites for structural applications such as floor tiles and pavements. The composites were developed by utilizing three different types of waste plastics, namely, low-density polyethylene, high-density polyethylene, and polypropylene with the reinforcement of coconut (cocos nucifera) and Tossa jute (corchorus olitorius) fibers. The evaluation of the density, water absorption, compressive strength, and flexural strength was performed. Moreover, three-body abrasive wear performance was investigated under the conditions of different loads and sliding speeds. The wear mechanism was explored by the morphological analyses of the fractured and worn-out surfaces. The composite HDPE80C20 showed a maximum density of 1.603 g/cm3 and minimum percentage of water absorption to 0.2022. Moreover, the composite attained a maximum compressive and flexural strength of 40.10 and 10.04 (MPa), respectively. The ranges for abrasive wear were found to be 0.002375-0.20015 (cm3) and 0.01987-0.39593 (cm3) under the considered conditions of loads and sliding speeds, respectively. The comparative analysis of the properties suggested the reinforcement of 20 wt% of jute fiber with 80 wt% of high-density polyethylene for the development of composites for structural applications. The study highlighted the potential of waste plastics and natural fibers as value-added products for building construction with relevancy from socio-eco and environmental points of view.

MK2a inhibitor CMPD1 abrogates chikungunya virus infection by modulating actin remodeling pathway.

Chikungunya virus (CHIKV) epidemics around the world have created public health concern with the unavailability of effective drugs and vaccines. This emphasizes the need for molecular understanding of host-virus interactions for developing effective targeted antivirals. Microarray analysis was carried out using CHIKV strain (Prototype and Indian) infected Vero cells and two host isozymes, MAPK activated protein kinase 2 (MK2) and MAPK activated protein kinase 3 (MK3) were selected for further analysis. The substrate spectrum of both enzymes is indistinguishable and covers proteins involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling and transcriptional regulation. Gene silencing and drug treatment were performed in vitro and in vivo to unravel the role of MK2/MK3 in CHIKV infection. Gene silencing of MK2 and MK3 abrogated around 58% CHIKV progeny release from the host cell and a MK2 activation inhibitor (CMPD1) treatment demonstrated 68% inhibition of viral infection suggesting a major role of MAPKAPKs during late CHIKV infection in vitro. Further, it was observed that the inhibition in viral infection is primarily due to the abrogation of lamellipodium formation through modulation of factors involved in the actin cytoskeleton remodeling pathway. Moreover, CHIKV-infected C57BL/6 mice demonstrated reduction in the viral copy number, lessened disease score and better survivability after CMPD1 treatment. In addition, reduction in expression of key pro-inflammatory mediators such as CXCL13, RAGE, FGF, MMP9 and increase in HGF (a CHIKV infection recovery marker) was observed indicating the effectiveness of the drug against CHIKV. Taken together it can be proposed that MK2 and MK3 are crucial host factors for CHIKV infection and can be considered as important target for developing effective anti-CHIKV strategies.

N6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages.

N6-methyladenosine (m6A) is a prevalent RNA modification that plays a key role in regulating eukaryotic cellular mRNA functions. RNA m6A modification is regulated by two groups of cellular proteins, writers and erasers that add or remove m6A, respectively. HIV-1 RNA contains m6A modifications that modulate viral infection and gene expression in CD4+ T cells. However, it remains unclear whether m6A modifications of HIV-1 RNA modulate innate immune responses in myeloid cells that are important for antiviral immunity. Here we show that m6A modification of HIV-1 RNA suppresses the expression of antiviral cytokine type-I interferon (IFN-I) in differentiated human monocytic cells and primary monocyte-derived macrophages. Transfection of differentiated monocytic U937 cells with HIV-1 RNA fragments containing a single m6A-modification significantly reduced IFN-I mRNA expression relative to their unmodified RNA counterparts. We generated HIV-1 with altered m6A levels of RNA by manipulating the expression of the m6A erasers (FTO and ALKBH5) or pharmacological inhibition of m6A addition in virus-producing cells, or by treating HIV-1 RNA with recombinant FTO in vitro. HIV-1 RNA transfection or viral infection of differentiated U937 cells and primary macrophages demonstrated that HIV-1 RNA with decreased m6A levels enhanced IFN-I expression, whereas HIV-1 RNA with increased m6A modifications had opposite effects. Our mechanistic studies indicated that m6A of HIV-1 RNA escaped retinoic acid-induced gene I (RIG-I)-mediated RNA sensing and activation of the transcription factors IRF3 and IRF7 that drive IFN-I gene expression. Together, these findings suggest that m6A modifications of HIV-1 RNA evade innate immune sensing in myeloid cells.

Inadequacy of near-infrared spectroscopy cerebral oximetry monitoring for detecting neurological complication.

Near-infrared spectroscopy (NIRS) cerebral oximetry is an established and standard monitoring modality for surgery under extracorporeal circulation with circulatory arrest. It helps to reduce the neurological complication, but in many instances, it becomes not only technically challenging but also is difficult to interpret and take corrective action based on the NIRS values. In this case study, we aimed to present the inadequacy of cerebral oximetry for detecting neurological complication.

Chikungunya virus nsP1 interacts directly with nsP2 and modulates its ATPase activity.

Chikungunya virus (CHIKV) is a mosquito-borne virus, which has created an alarming threat in the world due to unavailability of vaccine and antiviral compounds. The CHIKV nsP2 contains ATPase, RTPase, helicase and protease activities, whereas, nsP1 is a viral capping enzyme. In alphaviruses, the four non-structural proteins form the replication complex in the cytoplasm and this study characterizes the interaction between CHIKV nsP1 and nsP2. It was observed that, both the proteins co-localize in the cytoplasm and interact in the CHIKV infected cells by confocal microscopy and immunoprecipitation assay. Further, it was demonstrated through mutational analysis that, the amino acids 1-95 of nsP2 and 170-288 of nsP1 are responsible for their direct interaction. Additionally, it was noticed that, the ATPase activity of nsP2 is enhanced in the presence of nsP1, indicating the functional significance of this interaction. In silico analysis showed close (≤1.7 Å) polar interaction (hydrogen bond) between Glu4, Arg7, 96, 225 of nsP2 with Lys256, 206, Val367 and Phe312 of nsP1 respectively. Hence, this investigation provides molecular characterization of CHIKV nsP1-nsP2 interaction which might be a useful target for rational designing of antiviral drugs.

ER stress mediated regulation of miR23a confer Hela cells better adaptability to utilize glycolytic pathway.

Cancer cells exhibit increased dependency on aerobic glycolysis, a phenomenon referred as the "Warburg effect" and therefore, blocking glycolysis by using non-metabolizable analogues of glucose, like 2-Deoxy glucose (2-DG), has been proposed to be of huge therapeutic importance. One of the major drawbacks of using 2-DG as a chemotherapeutic agent is that it can induce ER stress. ER stress is a hall mark in many solid tumors and the unfolded protein response (UPR) associated with it initiates many survival mechanisms in cancer cells. In the present study, we report a novel survival mechanism associated with ER stress, by which the cancer cells become more adapted to aerobic glycolysis. When ER stress was induced in Hela cells by treating them with 2-DG or Thapsigargin (TG) the expression and activity of LDH was significantly up regulated, conferring the cells a greater glycolytic potential. A simultaneous decrease was observed in the expression of miR-23a, which was predicted in silico to have target site on the 3'UTR of LDH A and B mRNAs. miRNA over expression studies and mRNA degradation assays suggest that miR-23a could target LDH A and LDH B mRNAs. Further on the basis of our results and previous scientific reports, we propose that "c-Myc," which is over expressed during ER stress, repress the expression of miR-23a, which in turn regulates the expression of its target genes viz., LDH A and LDH B, thereby making the cells more competent to survive in tumor microenvironment, which requires efficient use of aerobic glycolysis.

MicroRNA106a regulates matrix metalloprotease 9 in a sirtuin-1 dependent mechanism.

Cellular migration is important during many physiological as well as pathological conditions and is regulated very tightly by an intricate network of signaling and effector molecules. One of the important players during cellular migration are matrix metalloproteases and their levels have been reported to be important in determining the cellular migratory properties during metastasis. MMPs and regulators of MMPs therefore, present themselves as potent candidates for manipulation, to control conditions where they get dysregulated. Micro RNAs are a group of micro regulators that can modulate expression of a gene through transcriptional and post transcriptional regulations. Owing to the fact that many microRNAs have already been reported to regulate MMPs and that miR106a, a member of oncomir17 family has been implicated in metastatic conditions, the present study intended to analyze if miR106a can regulate levels of MMP9, an important inducible matrix metalloproteinase. The results of the in vitro experiments demonstrated that under conditions of migration cells showed elevated levels of miR106a, which could regulate the expression of major MMP9 regulator, SIRT-1. Decreased levels of SIRT1thus resulted in an increase in the expression and activity of MMP9. Over expression and mRNA stability studies carried out also suggested regulatory role of miR106a. The overall results thus suggested that the levels of miR106a gets modulated during cellular migration, causing a change in the levels of SIRT-1 mRNA by affecting its stability and the levels of SIRT-1 in turn can regulate the levels of MMP9.

Horizontal transfer of miR-23a from hypoxic tumor cell colonies can induce angiogenesis.

Neo vessel formation by angiogenesis is an important event during many pathological conditions including cancer, where it is indispensable for tumor growth and survival. Although, various pro-angiogenic cytokines and soluble factors, secreted by tumor cells, have been reported to promote angiogenesis, recent studies have shown regulatory role of exosomes, secreted by tumor cells in the process of angiogenesis. These exosomes are capable of carrying nucleic acids, proteins, etc., as their cargo. Under the light of these facts and considering the presence of miRNAs, the non-coding RNAs capable of regulating target gene expression, as one of the major cargos in the exosomes, we investigated, whether exosomes derived from normoxic and hypoxic tumor cell colonies exhibit difference in levels of miR-23∼27∼24 cluster members and if so, to check the significance of their horizontal transfer on the process of angiogenesis. Results of our study showed that exosomes secreted by hypoxic tumor cell colonies possess significantly higher levels of miR23a and can induce angiogenesis. Further, we have shown that exosomes secreted by cells that ectopically over express miR23a is capable of inducing angiogenesis in different angiogenic model systems such as CAM, in ovo Xenograft and HUVEC models systems. Further, mechanistic analysis revealed that miR23a driven regulation of angiogenesis is brought about by down regulation of SIRT1 in the recipient cells. Collectively, the results presented here suggest that exosomal transfer of miR23a from tumor cell colonies can induce the process of angiogenesis by targeting SIRT1 in the recipient endothelial cells.

2-Deoxy Glucose Modulates Expression and Biological Activity of VEGF in a SIRT-1 Dependent Mechanism.

Reprogramming of energy metabolism particularly switching over of cells to aerobic glycolysis leading to accumulation of lactate is a hallmark of cancer. Lactate can induce angiogenesis, an important process underlying tumor growth and metastasis. VEGF is one of the most important cytokines which regulate this process and the present study was designed to examine if blocking glycolytic pathway in tumor cells can affect its angiogenic potency with respect to VEGF. For this, the expression and biological activity of VEGF synthesized and secreted by tumor derived cell lines in the presence or absence of 2-deoxy glucose (2-DG), an inhibitor of glycolysis was determined. The results suggested that inhibition of glycolysis using sub-lethal doses of 2-DG down-regulated the expression of VEGF and also significantly reduced its biological activity. Further mechanistic studies revealed that the down regulation of VEGF gene expression by 2-DG was due to an increase in SIRT-1 activity and the reduced biological activity was found to be due to an increase in the PAR modification of VEGF. Activity of SIRT-1 and PAR modification of VEGF in turn, was found to be correlated to the cellular NAD+ levels. The results presented here therefore suggest that treatment of cancer cells with 2-DG can significantly reduce its overall angiogenic potency through transcriptional and post-translational mechanisms. J. Cell. Biochem. 118: 252-262, 2017. © 2016 Wiley Periodicals, Inc.

Rare Presentation of Pulmonary Alveolar Proteinosis Causing Acute Respiratory Failure.

Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by dysfunctional alveolar macrophages, which ineffectively clear surfactant and typically cause mild hypoxemia. Characteristic Computed Tomography findings are septal reticulations superimposed on ground-glass opacities in a crazy paving pattern, with a clear juxtaposition between affected and unaffected parenchyma. While traditionally PAP was diagnosed via biopsy, bronchoalveolar lavage (BAL) is usually sufficient; the fluid appears milky, and on microscopic examination there are foamy macrophages with eosinophilic granules and extracellular hyaline material that is Periodic Acid-Schiff positive. Standard therapy is whole lung lavage (WLL), although novel treatments are under development. The case presented is a 55-year-old woman with six months of progressive dyspnea, who developed hypoxemic respiratory failure requiring mechanical ventilation; she had typical findings of PAP on imaging and BAL. WLL was ultimately successful in restoring adequate oxygenation. Respiratory failure of this magnitude is a rare finding in PAP.

RFID in healthcare: a Six Sigma DMAIC and simulation case study.

PURPOSE: The purpose of this paper is to develop a business model to generate quantitative evidence of the benefits of implementing radio frequency identification (RFID) technology, limiting the scope to outpatient surgical processes in hospitals. DESIGN/METHODOLOGY/APPROACH: The study primarily uses the define-measure-analyze-improve-control (DMAIC) approach, and draws on various analytical tools such as work flow diagrams, value stream mapping, and discrete event simulation to examine the effect of implementing RFID technology on improving effectiveness (quality and timeliness) and efficiency (cost reduction) of outpatient surgical processes. FINDINGS: The analysis showed significant estimated annual cost and time savings in carrying out patients' surgical procedures with RFID technology implementation for the outpatient surgery processes in a hospital. This is largely due to the elimination of both non-value added activities of locating supplies and equipment and also the elimination of the "return" loop created by preventable post operative infections. Several poka-yokes developed using RFID technology were identified to eliminate those two issues. PRACTICAL IMPLICATIONS: Several poka-yokes developed using RFID technology were identified for improving the safety of the patient and cost effectiveness of the operation to ensure the success of the outpatient surgical process. ORIGINALITY/VALUE: Many stakeholders in the hospital environment will be impacted including patients, physicians, nurses, technicians, administrators and other hospital personnel. Different levels of training of hospital personnel will be required, based on the degree of interaction with the RFID system. Computations of costs and savings will help decision makers understand the benefits and implications of the technology in the hospital environment.

Globalization of health care delivery in the United States through medical tourism.

This study highlights some of the inefficiencies in the U.S. health care system and determines what effect medical tourism has had on the U.S. and global health care supply chains. This study also calls attention to insufficient health communication efforts to inform uninsured or underinsured medical tourists about the benefits and risks and determines the managerial and cost implications of various surgical procedures on the global health care system into the future. This study evaluated 3 years (2005, 2007, and 2011) of actual and projected surgical cost data. The authors selected 3 countries for analysis: the United States, India, and Thailand. The surgeries chosen for evaluation were total knee replacement (knee arthroplasty), hip replacement (hip arthroplasty), and heart bypass (coronary artery bypass graft). Comparisons of costs were made using Monte Carlo simulation with variability encapsulated by triangular distributions. The results are staggering. In 2005, the amount of money lost to India and Thailand on just these 3 surgeries because of cost inefficiencies in the U.S. health care system was between 1.3 to 2 billion dollars. In 2011, because many more Americans are expected to travel overseas for health care, this amount is anticipated to rise to between 20 and 30.2 billion dollars. Therefore, more attention should be paid to health communication efforts that truly illustrate the benefits/risks of medical travel. The challenge of finding reliable data for surgeries performed and associated surgical cost estimates was mitigated by the use of a Monte Carlo simulation of triangular distributions. The implications from this study are clear: If the U.S. health care industry is unable to eliminate waste and inefficiency and thus curb rising costs, it will continue to lose surgical revenue to foreign health providers.

Examining quality and efficiency of the U.S. healthcare system.

PURPOSE: The fundamental concern of this research study is to learn the quality and efficiency of U.S. healthcare services. It seeks to examine the impact of quality and efficiency on various stakeholders to achieve the best value for each dollar spent for healthcare. The study aims to offer insights on quality reformation efforts, contemporary healthcare policy and a forthcoming change shaped by the Federal healthcare fiscal policy and to recommend the improvement objective by comparing the U.S. healthcare system with those of other developed nations. DESIGN/METHODOLOGY/APPROACH: The US healthcare system is examined utilizing various data on recent trends in: spending, budgetary implications, economic indicators, i.e., GDP, inflation, wage and population growth. Process maps, cause and effect diagrams and descriptive data statistics are utilized to understand the various drivers that influence the rising healthcare cost. A proposed cause and effect diagram is presented to offer potential solutions, for significant improvement in U.S. healthcare. FINDINGS: At present, the US healthcare system is of vital interest to the nation's economy and government policy (spending). The U.S. healthcare system is characterized as the world's most expensive yet least effective compared with other nations. Growing healthcare costs have made millions of citizens vulnerable. Major drivers of the healthcare costs are institutionalized medical practices and reimbursement policies, technology-induced costs and consumer behavior. PRACTICAL IMPLICATIONS: Reviewing many articles, congressional reports, internet websites and related material, a simplified process map of the US healthcare system is presented. The financial process map is also created to further understand the overall process that connects the stakeholders in the healthcare system. Factors impacting healthcare are presented by a cause and effect diagram to further simplify the complexities of healthcare. This tool can also be used as a guide to improve efficiency by removing the "waste" from the system. Trend analyses are presented that display the crucial relationship between economic growth and healthcare spending. ORIGINALITY/VALUE: There are many articles and reports published on the US healthcare system. However, very few articles have explored, in a comprehensive manner, the links between the economic indicators and measures of the healthcare system and how to reform this system. As a result of the US healthcare system's complex structure, process map and cause-effect diagrams are utilized to simplify, address and understand. This study linked top-level factors, i.e., the societal, government policies, healthcare system comparison, potential reformation solutions and the enormity of the recent trends by presenting serious issues associated with U.S. healthcare.

Early results of one-level cervical discectomy and fusion with stand-alone cervical cage and bone marrow soaked tricalcium phosphate.

Cervical disc prolapse has been traditionally treated with anterior discectomy and fusion, with good results; however autogenous bone graft and instrumentation remain a limiting factor. To avoid this, a stand-alone cage with bone marrow soaked tricalcium phosphate was used for single level cervical disc disease. Fifteen consecutive patients with single level cervical disc disease operated with the above technique were prospectively followed at six weeks, six and twelve months post-surgery. Clinical improvement was assessed by VAS and Odom's criteria. CT and plain radiography were used to assess fusion. Mean duration of symptoms was 7.2 months (SD: 4.14, range: 1-18 months). Mean preoperative VAS was 7 (SD: 131, range: 5-10) which improved to 1.4 (SD: 0.63, range: 1-3) at 6 weeks post op, 0.93 (SD: 0.80, range: 0-3) at 6 months and 0.80 (SD : 0.77, range : 0-3) at final follow-up. Similarly Odom's criteria were excellent in ten, good in three and satisfactory in 2 patients at six weeks. Results were rated excellent in eleven patients, good and satisfactory in two patients each respectively at six months and final follow-up. All patients had radiological fusion with no sign of cage extrusion. Results with this technique in terms of fusion, pain relief and overall functional outcomes were found to be good in this small patient population and warrant a larger sample size randomized long-term study.

A modified Delphi methodology to conduct a failure modes effects analysis: a patient-centric effort in a clinical medical laboratory.

In this article, we describe the use of an information-gathering tool, the Delphi technique, to overcome issues encountered when conducting a failure modes effects analysis as part of a define, measure, analyze, implement, control study to improve the processes of a clinical medical laboratory. The study was conducted with the goals of reducing medical errors in the total testing process (TTP) in order to improve patient safety, patient satisfaction, and improve the overall quality of the health care services provided by the subject hospital while meeting its Joint Commission (JC) accreditation requirements. The study found that the Delphi technique was very useful in overcoming 4 barriers encountered in conducting a failure modes effects analysis in a hospital's clinical medical laboratory and in achieving those goals.

Modeling hospital surgical delivery process design using system simulation: optimizing patient flow and bed capacity as an illustration.

OBJECTIVES: It is increasingly recognized that hospital operation is an intricate system with limited resources and many interacting sources of both positive and negative feedback. The purpose of this study is to design a surgical delivery process in a county hospital in the U.S where patient flow through a surgical ward is optimized. METHOD: The system simulation modeling is used to address questions of capacity planning, throughput management and interacting resources which constitute the constantly changing complexity that characterizes designing a contemporary surgical delivery process in a hospital. RESULTS: The steps in building a system simulation model is demonstrated using an example of building a county hospital in a small city in the US. It is used to illustrate a modular system simulation modeling of patient surgery process flows. CONCLUSIONS: The system simulation model development will enable planners and designers how they can build in overall efficiencies in a healthcare facility through optimal bed capacity for peak patient flow of emergency and routine patients.

Human Protein Reference Database--2009 update.

Human Protein Reference Database (HPRD--http://www.hprd.org/), initially described in 2003, is a database of curated proteomic information pertaining to human proteins. We have recently added a number of new features in HPRD. These include PhosphoMotif Finder, which allows users to find the presence of over 320 experimentally verified phosphorylation motifs in proteins of interest. Another new feature is a protein distributed annotation system--Human Proteinpedia (http://www.humanproteinpedia.org/)--through which laboratories can submit their data, which is mapped onto protein entries in HPRD. Over 75 laboratories involved in proteomics research have already participated in this effort by submitting data for over 15,000 human proteins. The submitted data includes mass spectrometry and protein microarray-derived data, among other data types. Finally, HPRD is also linked to a compendium of human signaling pathways developed by our group, NetPath (http://www.netpath.org/), which currently contains annotations for several cancer and immune signaling pathways. Since the last update, more than 5500 new protein sequences have been added, making HPRD a comprehensive resource for studying the human proteome.

Eliminating US hospital medical errors.

PURPOSE: Healthcare costs in the USA have continued to rise steadily since the 1980s. Medical errors are one of the major causes of deaths and injuries of thousands of patients every year, contributing to soaring healthcare costs. The purpose of this study is to examine what has been done to deal with the medical-error problem in the last two decades and present a closed-loop mistake-proof operation system for surgery processes that would likely eliminate preventable medical errors. DESIGN/METHODOLOGY/APPROACH: The design method used is a combination of creating a service blueprint, implementing the six sigma DMAIC cycle, developing cause-and-effect diagrams as well as devising poka-yokes in order to develop a robust surgery operation process for a typical US hospital. FINDINGS: In the improve phase of the six sigma DMAIC cycle, a number of poka-yoke techniques are introduced to prevent typical medical errors (identified through cause-and-effect diagrams) that may occur in surgery operation processes in US hospitals. It is the authors' assertion that implementing the new service blueprint along with the poka-yokes, will likely result in the current medical error rate to significantly improve to the six-sigma level. Additionally, designing as many redundancies as possible in the delivery of care will help reduce medical errors. PRACTICAL IMPLICATIONS: Primary healthcare providers should strongly consider investing in adequate doctor and nurse staffing, and improving their education related to the quality of service delivery to minimize clinical errors. This will lead to an increase in higher fixed costs, especially in the shorter time frame. ORIGINALITY/VALUE: This paper focuses additional attention needed to make a sound technical and business case for implementing six sigma tools to eliminate medical errors that will enable hospital managers to increase their hospital's profitability in the long run and also ensure patient safety.