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   Table of Contents - Current issue
July-September 2020
Volume 4 | Issue 3
Page Nos. 179-267

Online since Saturday, September 12, 2020

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Chimeric antigen receptor T-cell therapy in hematopoietic and nonhematopoietic malignancies Highly accessed article p. 179
Faizan Ahmad
Chimeric antigen receptor (CAR) T-cell therapy is an advanced personalized immunotherapy used in the treatment of many cancers. Basically, an immunotherapy uses the body's own immune system to detect and destroy the cancerous cells. The isolated T-cells from patients are genetically engineered to identify and target the elimination of cancer cells. Such T-cells, after genetic modification, are known as CAR-T cells. Most recently, the CAR-T cells are developed which show a remarkable ability to treat leukemia along with combinatorial treatment (e.g., Tisagenlecleucel) and lymphoma (e.g., Axicabtagene and Ciloleucel). Furthermore, these drugs have received FDA regulatory approval in the United States. Hence, more exploratory researches are the need of the hour in the CAR-T cell therapy of solid tumors to make it accessible and affordable for patients. The paper reviews various approaches and advancements of CAR-modified T-cell therapy, its persistence, and homing, along with the concept of universal CAR-T cell development. The usage of genetically engineered T-cells for treating B-cell tumor, especially B-cell acute lymphoblastic leukemia, embodies how encouraging this restorative method can be for treating other nonhematopoietic cancers. Till date, the majority of scientific interventions have been conducted to address the hematopoietic malignancies. This review impels the requirement for directing further research concerning the nonhematopoietic malignancies and adds on more to the current information based on anticancer treatments.
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The hemostatic properties of chitosan in oral surgery p. 186
Rocco Franco, Francesco Gianfreda, Michele Miranda, Alberta Barlattani, Patrizio Bollero
Chitosan (CS) belongs to the natural linear aminopolysaccharide family. It is formed by a repetition of D-glucosamine units (deacetylated units) and a smaller number of N-acetyl-D-glucosamine units. Their distribution is casual. It derives from chitin which is a naturally occurring polysaccharide in the arthropod exoskeleton. CS is a biocompatible material and for this reason it is used in medicine, especially in dentistry. It also has anti-inflammatory and regenerative properties. It is used in conservative dentistry, periodontology, especially in oral surgery. Its antibacterial and hemostatic properties are useful in the surgical treatment of patients on anticoagulant/antiplatelet therapy. The purpose of this work is to analyze through a systematic review of the literature on the use of CS as a local hemostatic.
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Macrolides and COVID-19: An optimum premise Highly accessed article p. 189
Hayder M Al-Kuraishy, Marwa S Al-Naimi, Claire M Lungnier, Ali I Al-Gareeb
The epidemic of coronavirus infection disease 19 (COVID-19), which started in Wuhan City, is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) which binds angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed by the lung epithelial cells. In COVID-19-induced acute respiratory distress syndrome, a hyperinflammatory syndrome with hypercytokinemia leads to acute lung injury and the development of respiratory failure. Macrolides are broad-spectrum, bacteriostatic antibiotics with significant anti-inflammatory and immunomodulatory effects. Different preclinical and clinical studies have shown that macrolides inhibit cytokine release, attenuate the inflammatory response, and improve immunoglobulin response. Azithromycin potentiates the anti-SARS-CoV-2 activity of chloroquine in COVID-19. However, azithromycin alone is effective initially in the management of COVID-19 due to its antiviral and anti-inflammatory activity. The antiviral potential of azithromycin is linked to different mechanisms, including modulation of lysosomal activity and the interaction points between SARS-CoV-2 and ACE2 receptor. Therefore, macrolides, chiefly azithromycin, are an effective drug against COVID-19 through direct antiviral effect or via the modulation of hyperinflammatory status.
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AntiMycobacterial activity of endophytic actinobacteria from selected medicinal plants Highly accessed article p. 193
Alka Ashok, Usha Nandhini, Ayswarya Sreenivasan, Manigundan Kaari, Revathy Kalyanasundaram, Radhakrishnan Manikkam
Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), poses a serious threat to human life. In addition, certain nontuberculous mycobacterial (NTM) species also cause infections in immune suppressed and even in immunocompetent individuals. With this view, the present study investigated the antimycobacterial properties of endophytic actinobacteria using Mycobacterium smegmatis as a surrogate model. Methods: Endophytic actinobacterial cultures were isolated from seven medicinal plants and their antimicrobial activity against two Gram-positive bacteria, three Gram-negative bacteria, fungi, and M. smegmatis was studied. Crude bioactive metabolites from one potential culture EAM4 were tested against Staphylococcus aureus, Escherichia coli, and M. smegmatis by disc-diffusion method, whereas activity against MTB H37Rv was tested by luciferase reporter phage (LRP) assay. The potential actinobacterial culture EAM4 was identified based on their 16S rRNA analysis. Results: Thirty actinobacterial cultures were isolated and were belonged to the genus Streptomyces. Maximum number of actinobacterial strains was isolated from Selaginella stellata (36.6%) and Pilea microphylla (36.6%). Gram-positive pathogens are inhibited by more number of actinobacterial cultures (>90%) than Gram-negative pathogens (50%). Twenty-eight of thirty actinobacterial cultures showed inhibitory activity against M. smegmatis. Bioactive metabolites from the potential culture EAM4 showed better inhibition against the S. aureus, E. coli, and M. smegmatis. In the LRP assay, 79% inhibition was exhibited against the MTB H37Rv. The potential actinobacterial strain EAM4 was identified as Streptomyces sp. based on their 16S rRNA analysis. Conclusion: Findings of the present study revealed that the endophytic cultures of Streptomyces investigated in this study are the promising source for isolating antimycobacterial metabolites effective against TB and nontuberculous mycobacterial pathogens.
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Novel strain of Nocardiopsis sp. CN2 from andaman nicobar islands: Isolation, taxonomy, fermentation, and antiproliferative effect on cervical cancer cells Highly accessed article p. 200
D Chandrakumar, K Manigundan, K Gopalakrishnan, V Karuppiah, N Rajendra Prasad, M Radhakrishnan, K Sivakumar, R Balagurunathan
Background: Cancer continues to be one of the world's deadliest diseases. New antibiotics with unique modes of action are urgently needed and therefore extensive research has been undertaken on novel anti-cancer antibiotics from natural resources. The aim of this present study was undertaken to characterize the marine actinobacterial strain CN2 isolated from Andaman and Nicobar Islands and also to evaluate its antiproliferative activity on HeLa cervical cancer cell line. Methods: Antiproliferative effect of the ethyl acetate extract was evaluated on HeLa cell lines by MTT assay and the oxidative stress was determined by lipid peroxidation and glutathione reductase changes in the antioxidant status. To understand the mode of antiproliferative effect, intracellular ROS levels by DCFH-DA method, mitochondrial membrane potential alterations by Rh-123 staining, oxidative DNA damage by comet assay, and apoptotic morphological changes by AO/EtBr-staining method were studied. Results: Based on the studied phenotypic, chemotaxonomic and molecular characteristics, strain CN2 was identified as Nocardiopsis sp. and it showed 99.9% similarity with N. exhalans (EU570349). However differences observed in certain phenotypic properties between strain CN2 and its close related species N. exhalans evidenced its novelty at strain level. Actinobacterial extract enhanced the ROS level, as evidenced by the increased DCF fluorescence. Further, it altered the mitochondrial membrane potential and increased the oxidative DNA damage and apoptotic morphological changes in HeLa cell lines. Conclusion: This is the first report on antiproliferative activity of the rare actinobacterium, Nocardiopsis sp. from Andaman and Nicobar Islands. Further production, purification and characterization of active metabolite from the ethyl acetate extract will pave the way for promising anticancer drug development.
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Is early diagnosis of chronic obstructive airway disease using spirometry in asymptomatic smokers an effect tool for smoking cessation in the Indian population? A study from Central India p. 209
AK Patra, Rahul Sud, Ipshita Patra, BB Patel, DK Boro
Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in smokers worldwide. A chronic smoker remains asymptomatic for a long time with underlying deteriorating lung function which manifests in later life as COPD. Although there is no screening for the disease, a spirometric evaluation of chronic smokers to detect the early asymptomatic disease and counseling for smoking cessation may slow down further progression of disease. India has a large population of smokers including a sizable number in the defense forces who need to be fighting fit at all times. The data with this regard from Indian scenario are scanty. The present study was carried out with an aim to detect early COPD in chronic smokers and further counsel these individuals to abstain from smoking. This cross-sectional study was done in Air Force Hospital Gorakhpur, India, from August 2014, and 2974 individuals were evaluated and followed. Methods: The individuals were standardized on the basis of personal history including age, number of cigarettes smoking per day, and duration of smoking. The diagnosis of COPD in such individuals was based on the spirometric evaluation which included forced expiratory volume in one sec (FEV1), forced vital capacity (FVC), and FEV1/FVC which were measured at rest and postbronchodilators. The individuals were diagnosed as COPD as per GOLD criteria (Gr C) and nonCOPD (Gr N). Both groups were followed up for 1 year with motivational counseling to stop smoking and spirometry repeated in those who quit smoking completely or partially. Results: COPD was observed in 187 (18.7%) asymptomatic smokers and among these 1.8% having severe COPD. 26% of these patients completely abstained from smoking after diagnosis and counseling and these patients had the least drop in FEV1 after 1 year as compared to partial and nonquitters of smoking. Conclusion: Spirometer for early diagnosis of COPD in asymptomatic nonsmoker is an effective tool. The detection of COPD early paves a way for effective counseling in pursuit for smoking cessation in young adults.
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Determination of serum DNA purity among patients undergoing antiretroviral therapy using NanoDrop-1000 spectrophotometer and polymerase chain reaction p. 214
Samuel Jacob Bunu, Denmo Otele, Tolulope Alade, Robinson Tuemi Dodoru
Background: The study aimed to determine the effects of antiretrovirals on host DNA purity and to qualitatively quantify the DNA primers quality using NanoDrop-1000 spectrophotometer and polymerase chain reaction (PCR). Methods: Serum samples from 50 HIV/AIDS-positive patients who were undergoing antiretroviral therapy were collected at the point of their routine CD4 level checkup. The samples subjected to initial purifications and subsequent qualitative quantification using the NanoDrop-1000 spectrophotometer and PCR analysis. Results: The purity of the DNA from the subject was determined by the NanoDrop-1000 spectrophotometer, and the adequate yield from 1.13 (lowest) to 149 ng/μl (highest) was obtained across the 50 subjects at 260 and 280 nm. The ratio of the absorbance was compared. Thus, DNA products were obtained with high purity, and PCR showed that all patients had the right gene to code for the respective drug-metabolizing enzyme. The NanoDrop-1000 technique and PCR analysis proved to be beneficial in the measurement of both quantity and purity of DNA in the samples. Conclusion: This technique does not only designs better experiments but also ensures improved reporting and significant time- and energy-saving qualitative analysis of DNA and related molecules.
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“Evaluation of salivary levels of heat shock protein 70 using ELISA among nonsmokers, conventional smokers, and reverse smokers”: A prospective study p. 220
Manoj Kumar Bobbili, Swetha Pasupuleti, Ravikanth Manyam
Background: Heat shock response is coordinated by five families of proteins with varying molecular weights known as heat shock proteins (HSP100, 90, 70, 60 and small HSPs). Members of HSP70 family are expressed during tumor cell differentiation, elevated temperatures, necrosis, exposure to nicotine etc., and act as chaperones facilitating newly synthesized proteins through intracellular compartments. Reverse smoking, where intraoral temperature could is very deleterious, well documented to cause malignancies and other pathological change. This present study was conducted to analyze the salivary levels of HSP 70 in conventional, reverse and non-smokers by using ELISA. Materials and Methods: A total of 90 individuals were included in the study comprising of conventional smokers (30), Reverse smokers (30) and non-smokers (30). 2ml of saliva was collected from all the individuals and subjected to centrifuge at 3000 rpm for 20mins. The collected supernatant was subjected to ELISA. Results: Increased salivary levels of HSP70 were observed in controls followed by reverse and conventional smokers (p value 0.000). Post Hoc analysis of HSP70 among conventional and reverse smokers, conventional and non-smokers, reverse and non-smokers was statistically significant between the all groups. Conclusion: Increased salivary HSP70 levels in non-smokers could be because the control group is due to their higher metabolism and possible hormonal imbalance in younger individuals. Reverse smokers had higher levels of salivary HSP70 due to the increased intraoral temperature and oxidative stress caused by the smoke. Hence, Smoking in any form could significantly alter the salivary HSP70 levels.
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Evaluation of pro-inflammatory cytokine level in cases of idiopathic recurrent spontaneous miscarriage in Saudi Arabia p. 225
Poonam Tyagi, Nahed Sail Alharthi
Background: A balanced stimulation and action of T-helper type 2 (Th2) and type 1 (Th1) immune response is required for a successful embryo implantation and positive outcomes of pregnancy while specific pro-inflammatory cytokine levels either belong to Th1 or Th2 profile which may deteriorate the pregnancy causing miscarriage. Methods: This research study comprised two groups: Group I – pregnant women with a history of recurrent spontaneous miscarriage (RSM, n = 50) and Group II – healthy pregnant controls (n = 50). Blood was collected, and serum was analyzed for interleukin (IL)-6, IL-8, IL-12, IL-18, TNF-α, and interferon (IFN)-γ using ELISA kit. Results: Th1 activity (IL-8, IL-12, IL-18, TNF-α, and IFN-γ) was higher in study Group I irrespective of whether continuing their pregnancy or aborting in comparison to Group II controls (P < 0.001). On the other hand, Th2 activity (IL-6) was decreased in Group I patients (P < 0.001) as compared with normal control Group II. Conclusions: Patients with a history of RSM have significantly increased Th1 activity and decrease in Th2 activity in comparison to normal pregnant women without any history of spontaneous miscarriage in their past.
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Antibacterial potential of neem (Azadirachta indica) against uropathogens producing beta-lactamase enzymes: A clue to future antibacterial agent? p. 232
Sameer Singh Faujdar, Dakshina Bisht, Amisha Sharma
Background: Emergence of drug resistance in Gram-negative bacilli due to production of extended-spectrum beta-lactamases (ESBL), metallo-beta-lactamases (MBL), and AmpC beta-lactamase is very common nowadays; therefore, we are left with less choice for antibiotics that is why we are in the need for the new alternatives. Hence, the current study was done to demonstrate antibacterial properties of neem (Azadirachta indica) leaves against ESBL, MBL, and AmpC beta-lactamase-producing Gram-negative uropathogens. Methods: Gram-negative uropathogens (221) were isolated and further tested for beta-lactamase (ESBL, MBL, and AmpC) production. Neem (A. indica) was tested for its antibacterial activity against all uropathogens. Results: Ethanolic extract of neem leaves showed good antibacterial activity against all isolates. Maximum zone of inhibitions and lowest minimum inhibitory concentration and minimum bactericidal concentration values were revealed by Acinetobacter baumannii. Conclusion: Extract of neem leaves at different concentrations showed potential antibacterial activity against both beta-lactamase-producing and nonproducing Gram-negative bacilli.
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Brain natriuretic peptide in patients with acute ischemic stroke: Role of statins p. 239
Hayder M Al-Kuraishy, Ali I Al-Gareeb, Marwa Thaier Naji
Background: Acute ischemic stroke (AIS) is associated with disturbances in brain natriuretic peptide (BNP) serum levels. Therefore, the objective of this study is to illustrate the potential effects of atorvastatin and rosuvastatin on BNP in patients with AIS. Methods: A total of 88 patients with AIS with or without statins therapy compared with 22 healthy controls were recruited. The patients with AIS were divided into: Group A: Patients with AIS on statins therapy (atorvastatin or rosuvastatin), (n = 44) and Group B: Patients with AIS not were on statins therapy (n = 22). Body mass index, blood pressure profile, lipid profile, and serum levels of human BNP were measured. As well, stroke risk score (SRS) was assessed in all involved patients and healthy volunteers. Results: BNP serum level was higher in patients with AIS compared with healthy controls (P = 0.0006). It was higher in patients with AIS not were on statins therapy (29.96 ± 17.21 μg/dL) as compared with patients with AIS on statins therapy (21.66 ± 14.22 μg/dL), P < 0.001. However, BNP serum level was (20.33 ± 6.05 μg/dL) in AIS patients on atorvastatin and (21.51 ± 6.82 μg/dL) AIS patients on rosuvastatin, which was not significantly differed (P = 0.54). Moreover, BNP serum levels were correlated with SRS in patients with AIS on statins therapy (r = 0.42, P= 0.03), but it was highly correlated with SRS in patients with AIS not were on statins therapy (r = 0.89, P < 0.001). Conclusion: BNP serum level is elevated in patients with AIS and correlated significantly with SRS. Statins therapy mainly atorvastatin and rosuvastatin are effective anti-inflammatory agents in the management of AIS through the reduction of BNP serum levels. However, there is no significant difference between the two statins.
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Spectrum of pediatric malignancies in a referral hospital of the eastern region of India p. 246
Senjuti Dasgupta, Sudipta Chakrabarti, Asit Ranjan Deb
Background: Pediatric malignancies are one of the most common causes of childhood morbidity and mortality. The prevalence of different malignancies in the pediatric age group varies from one place to another. The present study was done to find out the occurrence of childhood malignancies in the southern region of West Bengal to compare the patterns of different malignancies with other established epidemiological studies and to search for the specific causes for apparently increased occurrence of childhood malignancies. Methods: A prospective study was conducted for 7 years in which patients with pediatric malignancies were included in the study. The clinicopathological features of each case were analyzed. Results: A total number of 247 cases were included in the study among which 162 were males (65.59%). Children below the age of 5 years accounted for 90 cases (36.58%). Hematological malignancies were found in 122 cases (49.39%), and the rest constituted nonhematological malignancies (125, 50.61%). The most common malignant disorder noted was acute leukemia, constituting about 33.37% of cases (82 cases). The highest occurrence (37.9%) of malignancies was encountered in 5–10 years of age, and the next common (31.7%) was between the age group of 2 and 5 years. The most common malignancies noted in these age groups were acute leukemia, retinoblastoma, Wilm's tumor, and neuroblastoma. Conclusion: Lympho-hematogeneous malignancies were the most common followed by embryonal tumors. Although the occurrence of hematological malignancies was comparable to the similar studies of the developed countries, the corresponding figures of central nervous system tumors were considerably less.
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Pentoxifylline modulation hepatotoxicity and apoptosis induced by nitrosamine in rats p. 251
Mohammad Reza Salahshoor, Cyrus Jalili, Amir Abdolmaleki, Shiva Roshankhah
Background: Pentoxifylline (PEN) is a xanthine derivative with different functional characteristics including dilution of blood and increase in tissue oxygenation rate. Nitrosamines (NITs) are well known as strong carcinogenic agents. This study attempts to show the histopathological and biochemical effects of PEN against hepatotoxicity induced by NIT in rats. Methods: Sixty-four rats were assigned to eight groups including the groups of sham: NIT (40 mg/kg); PEN (25, 50, and 100 mg/kg); and NIT + PEN. Experimental treatments were applied either intraperitoneally (for NIT) or orally (for PEN) daily for 4 weeks. The relative expression level of p53 and Bax genes and hepatocyte apoptotic index were analyzed. Liver malondialdehyde (MDA), tissue ferric-reducing ability of plasma (FRAP), the diameters of hepatocytes (DH) and central hepatic vein (CHV), and biochemical liver function indicators (LFI) were investigated. Griess technique was hired for the determination of the level of serum nitrite oxide (NO). Results and Conclusions: NIT significantly increased the level of apoptotic gens and index, MDA, NO, diameter of CHV and DH, and LFI and decreased the FRAP level compared to the sham group (P < 0.01). All parameters in PEN and PEN + NIT groups significantly reduced (except FRAP level, which was decreased) in compared to the NIT group (P < 0.01) . By summarizing the results of this research, it is concluded that the PEN administration alleviates the hepatotoxicity due to oxidative stress produced by NIT in rats.
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Fenofibrate and Crataegus oxyacantha is an effectual combo for mixed dyslipidemia p. 259
Huda A Rasheed, Nawar R Hussien, Marwa S Al-Naimi, Hayder M Al-Kuraishy, Ali I Al-Gareeb
Background: Dyslipidemia (DL) is a blood lipid disorder characterized by high cholesterol, triglyceride and low density lipoprotein with reduction of high density lipoprotein. Crataegus Oxyacantha hawthorn (COH) is used in treatment of hyperlipidemia , hypertension , angina pectoris and arrhythmia as alternative medicine . The aim of the present study was to evaluate the effect of fenofibrate alone or in combination with Crataegus Oxyacantha on lipid profile in patients with mixed dyslipidemia. Methods: A total number of 64 patients with MD on fenofibrate therapy compared to 24 healthy controls were recruited and randomized into three groups: Group A: (control, n = 24) not received any lipid-lowering agents, Group B: (fenofibrate, n = 30) received fenofibrate 200 mg/day for 10 weeks, and Group C: (combination, n = 34) received fenofibrate 200 mg/day plus C. oxycantha for 10 weeks. The estimation of lipid profile and blood pressure changes were done at baseline and following 10 weeks of therapy. Results: Following 10 weeks of C. oxycantha add on fenofibrate therapy, there was a significant reduction on total cholesterol, triglyceride, non-high-density lipoprotein-cholesterol AI, and low-density lipoprotein plasma levels compared with fenofibrate-treated patients (P < 0.05). Blood pressure profile showed more significant reduction in patients with dyslipidemia (DL) treated with C. oxycantha compared with baseline data and with patients with DL treated with fenofibrate alone (P < 0.05). Fenofibrate plus C. oxycantha showed more significant reduction on high-sensitive C-reactive protein serum levels from 5.28 ± 1.61 mg/dL to 2.74 ± 1.99 mg/dL, P < 0.0001. Conclusion: C. oxycantha synergized the effect of fenofibrate therapy in patients with MD through the improvement of lipid profile and attenuation of endothelial inflammation.
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Coronavirus disease 2019 pandemic: Envisaging capacity building in the field of research to accomplish effective control p. 266
Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava
The coronavirus disease-2019 (COVID-19) pandemic has created a sense of fear and raised major concerns over the preparedness of the national public health authorities to respond to infectious disease outbreaks. Even though, a lot of dimensions pertaining to the disease prevention, control and treatment need to be strengthened to mount an effective response plan against the novel infection, it is extremely essential to invest and make rapid progress in the research and development field to enhance our understanding about the disease. In-fact, multiple number of such projects have been funded in China to gain significant insights about the genomics of the causative virus, antiviral drugs, utility of traditional Chinese therapy, clinical trials, potential vaccines, better diagnostic tools and various animal models. In conclusion, in the global battle against the novel COVID 19 outbreak, the domain of research and development for coming out with better diagnostic tools, potential therapeutic agents, and vaccines need to be strengthened immensely. It is worth realizing that any advancements made in this regard will shape the way the infection will be tackled in the coming days.
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