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In this retrospective, single-center study, the records of patients with acute endophthalmitis following intravitreal bevacizumab (IVB) injections during the pre-COVID and COVID-19 eras were reviewed and compared. A total of 28,085 IVB injections were performed during the pre-COVID era; nine eyes of nine patients developed acute post-IVB endophthalmitis in this era, giving an overall incidence of 0.032% (3.2 in 10000 injections). In the COVID era, a total of 10,717 IVB injections were performed; four eyes of four patients developed acute post IVB endophthalmitis in this era, giving an overall incidence of 0.037% (3.7 in 10000 injections). The incidences of post-IVB endophthalmitis during these two eras were not different (P-value = 0.779). The BCVA of the eyes affected during the COVID era showed poor improvement back to baseline values, after three months, even with prompt and maximum treatment. Face masking protocols seem unlikely to increase the risk of post-IVB endophthalmitis.

The current protocols for neuropathic pain management include µ-opioid receptor (MOR) analgesics alongside other drugs; however, there is debate on the effectiveness of opioids. Nevertheless, dose escalation is required to maintain their analgesia, which, in turn, contributes to a further increase in opioid side effects. Finding novel approaches to effectively control chronic pain, particularly neuropathic pain, is a great challenge clinically. Literature data related to pain transmission reveal that angiotensin and its receptors (the AT1R, AT2R, and MAS receptors) could affect the nociception both in the periphery and CNS. The MOR and angiotensin receptors or drugs interacting with these receptors have been independently investigated in relation to analgesia. However, the interaction between the MOR and angiotensin receptors has not been excessively studied in chronic pain, particularly neuropathy. This review aims to shed light on existing literature information in relation to the analgesic action of AT1R and AT2R or MASR ligands in neuropathic pain conditions. Finally, based on literature data, we can hypothesize that combining MOR agonists with AT1R or AT2R antagonists might improve analgesia.

Ageing is a sophisticated process, accompanied by reduction in general physiological capacity and increase in mortality and death, stemming from damage accumulation over time. Various signaling pathways are known to be involved in the functional decrease in various organs in ageing humans. One of the most prominent pathways is DNA damage response (DDR), which is responsible for maintenance of the genomic integrity and stability. Insufficient or dysfunctional DDR signaling and the subsequent accumulation of potential DNA lesions are associated with the initiation/progression of various human pathologies including ageing. As a tumor suppressor gene, with critical functions in the ageing process, p53 is considered as a DDR centerpiece. In this review, we aim to discuss the interactions between p53 and DDR signaling and their contributions in ageing.

Structure of capital is one of the important matters in every company. Choosing an appropriate capital structure is an important matter in determining the value of every company and this structure, is the combination of the company’s supply of the financial resources. Debts and the rights of the stock holder are components of capital structure. Type of debt used in the Company has influence on the company's risk. Some of the companies for the supplying required financial resources use current debts and financial risk is increased naturally, and some of them use non-current debts. Methodology: In this study the effect of operating’s cycle, operating cash flow and inflation during 1385 to 1392 is analyzed. The number of observations of this study including 98 companies and by using OLS method the hypotheses of the study is tested. Results: The results suggest there is a significant relationship between c operating cash flow and time deadline and there is no significant relation between operating cycle and inflation with the time deadline of the debts. Conclusion: Finally, there is a positive relation between operating cycle and debt’s term structure but not significant, and operating cash flow’s coefficient is 0.0893 and there is a significant and positive relation between operating cash flow and debt’s term structure, and there is an opposite relation between them, but it is not significant.

Capital structure is one of the most important topics in any company. Choose an appropriate capital structure is one of the important issues in determining the value of each company and this structure is composition of financing the company. Methodology: In this study, we investigate the effect of operating cash flow on time structure of debts in listed companies in Tehran Stock Exchange within 2006 to 2013. The number of observations in this research are 98 companies. Research data have been collected using informational banks of Stock Exchange and companies and the hypotheses have been tested using OLS method. Results: Given the results of study, there is a significant relationship between operating cash flow and time maturity of debts. Conclusion: Debts and equity are structural components of capital. Type of debt used in the company will be effective on the company's risk ratio. Some of the companies have used the current debts in financing and financial risk of them will be increased naturally and some are more willing to Non-Current debts.

Colorectal cancer is one of the most common cancers among the elderly, which is also seen in the forms of hereditary syndromes occurring in younger individuals. Numerous studies have been conducted to understand the molecular and cellular pathobiology underlying colorectal cancer. These studies have found that cellular signaling pathways are at the core of colorectal cancer pathology. Because of this, new agents have been proposed as possible candidates to accompany routine therapy regimens. One of these agents is melatonin, a neuro-hormone known best for its essential role in upholding the circadian rhythm and orchestrating the many physiologic changes it accompanies. Melatonin is shown to be able to modulate many signaling pathways involved in many essential cell functions, which if deregulated cause an accelerated pace towards cancer. More so, melatonin is involved in the regulation of immune function, tumor microenvironment, and acts as an antioxidant agent. Many studies have focused on the beneficial effects of melatonin in colorectal cancers, such as induction of apoptosis, increased sensitivity to chemotherapy agents and radiotherapy, limiting cellular proliferation, migration, and invasion. The present review aims to illustrate the known significance of melatonin in colorectal cancer and to address possible clinical use.

It has been proposed that changes in microbiota due to nonsteroidal anti-inflammatory drugs (NSAIDs) alter the composition of bile, and elevation of hydrophobic secondary bile acids contributes to small intestinal damage. However, little is known about the effect of NSAIDs on small intestinal bile acids, and whether bile alterations correlate with mucosal injury and dysbiosis. Here we determined the ileal bile acid metabolome and microbiota 24, 48 and 72 h after indomethacin treatment, and their correlation with each other and with tissue damage in rats. In parallel with the development of inflammation, indomethacin increased the ileal proportion of glycine and taurine conjugated bile acids, but not bile hydrophobicity. Firmicutes decreased with time, whereas Gammaproteobacteria increased first, but declined later and were partially replaced by Bilophila, Bacteroides and Fusobacterium. Mucosal injury correlated negatively with unconjugated bile acids and Gram-positive bacteria, and positively with taurine conjugates and some Gram-negative taxa. Strong positive correlation was found between Lactobacillaceae, Ruminococcaceae, Clostridiaceae and unconjugated bile acids. Indomethacin-induced dysbiosis was not likely due to direct antibacterial effects or alterations in luminal pH. Here we provide the first detailed characterization of indomethacin-induced time-dependent alterations in small intestinal bile acid composition, and their associations with mucosal injury and dysbiosis. Our results suggest that increased bile hydrophobicity is not likely to contribute to indomethacin-induced small intestinal damage.

Introduction Tracheal stenosis and tracheobronchomalacia are complicated, patient-specific diseases that can be treated with intraluminal stenting. Most commonly, silicone and metal stents are utilized, however, they pose significant early and late morbidity and are further complicated by growth of the airway in the pediatric population. Given recent improvements in materials science, there is a growing body of evidence suggesting a strong role for bioresorbable intraluminal stents in treating pediatric tracheobronchial obstruction. Methods A PubMed.gov literature search was performed on December 3, 2019 and May 15, 2020, and a 2-researcher systematic review was performed following the PRISMA criteria. The following search query was utilized: (((((((bioresorbable) OR bioabsorbable) OR resorbable) OR absorbable) OR biodegradable AND airway) OR trachea) AND stent. A pooled statistical analysis was performed on all reported pediatric patients using SPSS software. Results 1369 publications were screened and 26 articles with original data were identified. Materials used included polydioxanone (PDO), poly- l -lactic acid (PLLA), polyglycolic acid/poly- l -lactide co-polymer with Proglactin 910 (Vicryl®-PDS®), polycaprolactone (PCL), magnesium alloys, and co-polymers in varying proportions. Twelve articles presented data on human subjects, 8 of which were case series and case reports on pediatric populations using polydioxanone (PDO) stents. Pooled statistical analysis demonstrated an average age of 19 months (range 0.25–144), 56.5% associated with a cardiovascular anomaly, and overall complication rate of 21.7%, with a stent fragment foreign body being the most common (8.7%), followed by significant granulation tissue (4.3%), stent migration (4.3%), and local stenosis (4.3%). Comparative analysis demonstrated short-term improvement (up to 1 month) has a statistically significant association with tracheobronchomalacia versus tracheal stenosis on chi-squared test (p = 0.001). The remaining analyses did not yield statistical significance. Conclusion The reported application of bioresorbable materials as intraluminal airway stents is positive. All comparative animal studies report biocompatibility and fewer morbidities compared to metal and silicone stents, however, in human studies there are concerns over the short interval of degradation and the potential for obstructive foreign bodies in poorly seated stents. Overall, there are clear, reproducible advantages to bioresorbable intraluminal stents in pediatric airway obstruction, as well as common pitfalls, that warrant further research.

The information on data packet loss occurrences in a networked control system (NCS) is useful for improving the control performance and detecting communication failures or cyber-attacks. This study considers the simultaneous estimation of the plant state and packet loss occurrences at each time step. After formulation of the problem, two solutions are proposed. In the first one, an input–output representation of the NCS model is used to design a recursive filter for estimation of the packet loss occurrences. This estimation is then used for state estimation through Kalman filtering. In the second solution, a state–space model of NCS is used to design an estimator for both the plant state and the packet loss occurrences, which employs a Kalman filter. The effectiveness of the proposed solutions is shown during an example, and comparisons are made with another solution based on the interacting multiple model approach to estimation.

There is some recent evidence that cardiac ischemia/reperfusion (I/R) injury induces intestinal damage within days, which contributes to adverse cardiovascular outcomes after myocardial infarction. However, it is not clear whether remote gut injury has any detectable early signs, and whether different interventions aiming to reduce cardiac damage are also effective at protecting the intestine. Previously, we found that chronic treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), limited myocardial infarct size to a comparable extent as cardiac ischemic preconditioning (IPC) in rats subjected to 30-min coronary artery occlusion and 120-min reperfusion. In the present study, we aimed to analyse the early intestinal alterations caused by cardiac I/R injury, with or without the above-mentioned infart size-limiting interventions. We found that cardiac I/R injury induced histological changes in the small intestine within 2 h, which were accompanied by elevated tissue level of COX-2 and showed positive correlation with the activity of matrix metalloproteinase-2 (MMP-2), but not of MMP-9 in the plasma. All these changes were prevented by rofecoxib treatment. By contrast, cardiac IPC failed to reduce intestinal injury and plasma MMP-2 activity, although it prevented the transient reduction in jejunal blood flow in response to cardiac I/R. Our results demonstrate for the first time that rapid development of intestinal damage follows cardiac I/R, and that two similarly effective infarct size-limiting interventions, rofecoxib treatment and cardiac IPC, have different impacts on cardiac I/R-induced gut injury. Furthermore, intestinal damage correlates with plasma MMP-2 activity, which may be a biomarker for its early diagnosis.

There is growing evidence on the role of peripheral µ-opioid receptors (MORs) in analgesia and analgesic tolerance. Opioid analgesics are the mainstay in the management of moderate to severe pain, and their efficacy in the alleviation of pain is well recognized. Unfortunately, chronic treatment with opioid analgesics induces central analgesic tolerance, thus limiting their clinical usefulness. Numerous molecular mechanisms, including receptor desensitization, G-protein decoupling, β-arrestin recruitment, and alterations in the expression of peripheral MORs and microbiota have been postulated to contribute to the development of opioid analgesic tolerance. However, these studies are largely focused on central opioid analgesia and tolerance. Accumulated literature supports that peripheral MORs mediate analgesia, but controversial results on the development of peripheral opioid receptors-mediated analgesic tolerance are reported. In this review, we offer evidence on the consequence of the activation of peripheral MORs in analgesia and analgesic tolerance, as well as approaches that enhance analgesic efficacy and decrease the development of tolerance to opioids at the peripheral sites. We have also addressed the advantages and drawbacks of the activation of peripheral MORs on the sensory neurons and gut (leading to dysbiosis) on the development of central and peripheral analgesic tolerance.

OBJECTIVE To determine and itemize surgical costs associated with the translabyrinthine (TL), retrosigmoid (RS), and middle cranial fossa (MCF) approaches for microsurgical excision of vestibular schwannoma (VS). STUDY DESIGN Retrospective cost analysis study. SETTING Tertiary referral center. PATIENTS Thirty consecutive adult patients underwent microsurgical excision of VS by either TL, RS, or MCF approach (10 per approach). INTERVENTIONS Microsurgical excision of VS by one of the three major approaches. Medical and financial data were collected. MAIN OUTCOME MEASURES Total operating room time (minutes), skin-to-skin time (minutes), operating room cost ($US), and surgical supplies cost ($US). RESULTS The MCF approach was associated with the shortest skin-to-skin time (230.3 min, p

Interneurons operating with glycine neurotransmitter are involved in the regulation of pain transmission in the dorsal horn of the spinal cord. In addition to interneurons, glycine release also occurs from glial cells neighboring glutamatergic synapses in the spinal cord. Neuronal and glial release of glycine is controlled by glycine transporters (GlyTs). Inhibitors of the two isoforms of GlyTs, the astrocytic type-1 (GlyT-1) and the neuronal type-2 (GlyT-2), decrease pain sensation evoked by injuries of peripheral sensory neurons or inflammation. The function of dorsal horn glycinergic interneurons has been suggested to be reduced in neuropathic pain, which can be reversed by GlyT-2 inhibitors (Org-25543, ALX1393). Several lines of evidence also support that peripheral nerve damage or inflammation may shift glutamatergic neurochemical transmission from N-methyl-D aspartate (NMDA) NR1/NR2A receptor- to NR1/NR2B receptor-mediated events (subunit switch). This pathological overactivation of NR1/NR2B receptors can be reduced by GlyT-1 inhibitors (NFPS, Org-25935), which decrease excessive glycine release from astroglial cells or by selective antagonists of NR2B subunits (ifenprodil, Ro 25-6981). Although several experiments suggest that GlyT inhibitors may represent a novel strategy in the control of neuropathic pain, proving this concept in human beings is hampered by lack of clinically applicable GlyT inhibitors. We also suggest that drugs inhibiting both GlyT-1 and GlyT-2 non-selectively and reversibly, may favorably target neuropathic pain. In this paper we overview inhibitors of the two isoforms of GlyTs as well as the effects of these drugs in experimental models of neuropathic pain. In addition, the possible mechanisms of action of the GlyT inhibitors, i.e. how they affect the neurochemical and pain transmission in the spinal cord, are also discussed. The growing evidence for the possible therapeutic intervention of neuropathic pain by GlyT inhibitors further urges development of drugable compounds, which may beneficially restore impaired pain transmission in various neuropathic conditions.

Reduction of the opioid analgesia in diabetic neuropathic pain (DNP) results from µ-opioid receptor (MOR) reserve reduction. Herein, we examined the antinociceptive and antiallodynic actions of a novel opioid agonist 14-O-methymorphine-6-O-sulfate (14-O-MeM6SU), fentanyl and morphine in rats with streptozocin-evoked DNP of 9-12 weeks following their systemic administration. The antinociceptive dose-response curve of morphine but not of 14-O-MeM6SU or fentanyl showed a significant right-shift in diabetic compared to non-diabetic rats. Only 14-O-MeM6SU produced antiallodynic effects in doses matching antinociceptive doses obtained in nondiabetic rats. Co-administered naloxone methiodide (NAL-M), a peripherally acting opioid receptor antagonist failed to alter the antiallodynic effect of test compounds, indicating the contribution of central opioid receptors. Reduction in spinal MOR binding sites and loss in MOR immunoreactivity of nerve terminals in the spinal cord and dorsal root ganglia in diabetic rats were observed. G-protein coupling assay reveals low efficacy character for morphine and high efficacy character for 14-O-MeM6SU or fentanyl at spinal or supraspinal levels (Emax values). Furthermore, at the spinal level only 14-O-MeM6SU showed equal efficacy in G-protein activation in tissues of diabetic- and non-diabetic animals. Altogether, the reduction of spinal opioid receptors concomitant with reduced analgesic effect of morphine may be circumvented by using high efficacy opioids, which provide superior analgesia over morphine. In conclusion, the reduction in the analgesic action of opioids in diabetic neuropathic pain might be a consequence of MOR reduction, particularly in the spinal cord. Therefore, developing opioids of high efficacy might provide analgesia exceeding that of currently available opioids.

Much research has been conducted to discover novel techniques to reverse the process of tumorigenesis and, cure already stablished malignancies. One well-stablished approach has been the use of organic compounds and naturally found agents such as melatonin whose anticancer effects have been shown in multiple studies, signaling a unique opportunity regarding cancer prevention and treatment. Various agents use a variety of methods to exert their anticancer effects. Two of the most important of these methods are interfering with cell signaling pathways and changing cellular functions, such as autophagy, which is essential in maintaining cellular stability against multiple exogenous and endogenous sources of stress, and is a major tool to evade early cell death. In this study, the importance of melatonin and autophagy are discussed, and the effects of melatonin on autophagy, and its contribution in the process of tumorigenesis are then noted.

The present work represents the in vitro (potency, affinity, efficacy) and in vivo (antinociception, constipation) opioid pharmacology of the novel compound 14-methoxycodeine-6-O-sulfate (14-OMeC6SU), compared to the reference compounds codeine-6-O-sulfate (C6SU), codeine and morphine. Based on in vitro tests (mouse and rat vas deferens, receptor binding and [35S]GTP&gamma, S activation assays), 14-OMeC6SU has &micro, opioid receptor-mediated activity, displaying higher affinity, potency and efficacy than the parent compounds. In rats, 14-OMeC6SU showed stronger antinociceptive effect in the tail-flick assay than codeine and was equipotent to morphine, whereas C6SU was less efficacious after subcutaneous (s.c.) administration. Following intracerebroventricular injection, 14-OMeC6SU was more potent than morphine. In the Complete Freund&rsquo, s Adjuvant-induced inflammatory hyperalgesia, 14-OMeC6SU and C6SU in s.c. doses up to 6.1 and 13.2 &micro, mol/kg, respectively, showed peripheral antihyperalgesic effect, because co-administered naloxone methiodide, a peripherally acting opioid receptor antagonist antagonized the measured antihyperalgesia. In addition, s.c. C6SU showed less pronounced inhibitory effect on the gastrointestinal transit than 14-OMeC6SU, codeine and morphine. This study provides first evidence that 14-OMeC6SU is more effective than codeine or C6SU in vitro and in vivo. Furthermore, despite C6SU peripheral antihyperalgesic effects with less gastrointestinal side effects the superiority of 14-OMeC6SU was obvious throughout the present study.

Background: Today, because of increasing immigration and the prevalence of drug-resistant tuberculosis in Iran, identifying intra-community cases is necessary in the country. It will be possible through the use of molecular epidemiologic methods. In this inquiry, in order to determine the role of immigrants in the transmission of specific strains to Iran, the studies have been examined which had been conducted based on molecular epidemiologic methods among Iranians and non-Iranians people. Methods: All studies from 1997 to the end of March 2017 were examined in three databases of PubMed, Scopus, and Google Scholar and finally, 16 studies were selected. Results: The common clustering rate between Iranians and non-Iranians was determined to be 19.8, and the intra-community recent transmission rate was from 0% to 49% with average of 18.1%. The rate of multidrug-resistant tuberculosis (MDR-TB) was 12.5%, which was higher among immigrants, especially Afghans, and a significant number of the strains were Beijing. Conclusions: The studies have shown that migrants, especially Afghans, are more effective in transmitting specific strains of tuberculosis to migratory areas. To control tuberculosis, it is necessary to register of immigrant's health information, while enter to the country, so that, by doing appropriate diagnostic tests, the curing the patients, the transmission of tuberculosis to the country would be prevented.

Maintenance of genome integrity and stability is a critical responsibility of the DNA damage response (DDR) within cells, such that any disruption in this kinase-based signaling pathway leads to development of various disorders, particularly cancer. The tumor suppressor P53-binding protein 1 (53BP1), as one of the main mediators of DDR, plays a pivotal role in orchestrating the choice of double-strand break (DSB) repair pathway and contains interaction surfaces for numerous DSB-responsive proteins. It has been extensively demonstrated that aberrant expression of 53BP1 contributes to tumor occurrence and development. 53BP1 loss of function in tumor tissues is also related to tumor progression and poor prognosis in human malignancies. Due to undeniable importance of this protein in various aspects of cancer initiation/progression, angiogenesis, metastasis and development of drug resistance, as well as its targeting in the treatment of cancer, this review focused on explaining the structure and function of 53BP1 and its contribution to cancer.

Article history: Received October 9, 2012 Received in revised format 29 November 2012 Accepted 27 December 2012 Available online January 3 2013 During the past few years, stock exchange investors confront numerous problems in terms of legal, environmental issues, etc. In this paper, we present an empirical study to detect important issues as barriers for investment in Tehran Stock Exchange. The study has categorized the issues into two groups of real world and legal issues. Since there are different issues involved as major barriers, the study uses analytical hierarchy process to rank them. The study extracts 18 important factors, which influence investors’ participation in Tehran Stock Exchange and using Borda method, prioritize them. The results of the survey indicate that in terms of real issues, Increase in quality of firms Financial Statement is number one priority followed by Increase stock exchange and agents’ proficiency and electronic equipment, Unchangeable investment market rules and bounding organization managers to flow them and Strict supervision on agents’ activities. In terms of legal issues, good supervision of provisions to force firms to reveal information correctly and restrict their secret bargaining is the most important factor followed by Using indirect investment guideline instead of direct investment, Increase in quality of firms’ Financial Statement and Investors’ training toward their rights. © 2013 Growing Science Ltd. All rights reserved.

Prediction of total cost of water helps the Isfahan municipality to optimize the water usage in its 14 urban zone. The total cost of water, basically, depends on different parameters. Generally, the analytically prediction of the total cost is very difficult if not impossible. Thus, applying intelligent systems such as neural network models can be a good alternative. In this paper, using multi-layer perceptron neural network and error back propagation algorithm, the total cost of municipal water in the Isfahan municipality is calculated based on parameters such as per capita population and area of each urban zone. In this paper, a model for simulation and prediction of the annual total cost of water in Isfahan municipality is developed. The simulation model is developed using the regression and the neural network model is built using data from 2004 to 2009. Finally, the neural network method is selected as the main simulation method for forecasting the total cost of water in the 14 urban zones of Isfahan. Key words: Isfahan municipality, regression model, artificial neural networks, forecasting, cost of water, prediction.

Capital market paves the way for developing and creating job and improving level of welfare by directing capitals and savings of people. Economic growth and welfare improvement cannot be achieved in long term without considering investing and main factors existing in the environment. This paper evaluates factors affecting transactors` and managers` decision making for investing. Independent variables include dividend per share (DPS), yield, price trend, market status, consulting and recommendations of brokers, and perceived risk which is considered as features of capitalists. Also, dependent variable contains transactors` and managers` decision making. Statistical population includes all capitalists referred to hall of the Tehran Stock Exchange in 2012. The sample is simply randomized. Data is collected through library and field methods by distributing questionnaires among 130 stock capitalists. Then, the research hypothesis is examined and analyzed using descriptive and inferential statistics with respect to collected data. Finally, the obtained results from distributed questionnaires are analyzed using SPSS software. The results show that capitalists do not rely on the financial statements and financial ratios and the accounting system as a whole, in return, they consider the more tangible criteria such as price trend and market status.