Search results for: Lokesh Bhatt

Authors: Daniela Prado, Lexi Frankel, Amalia Ardeljan, Lokesh Manjani, Matthew Cardeiro, Omar Rashid

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Background: Clostridium difficile (C. diff) is a gram-positive bacterium that is known to cause life-threatening diarrhea and severe inflammation of the colon. It originates as an alteration of the gut microbiome and can be transmitted through spores. Recent studies have shown a high association between the development of C. diff in cancer patients due to extensive hospitalization. However, research is lacking regarding C. diff’s association in the causation or prevention of cancer. The objective of this study was to therefore assess the correlation between Clostridium difficile infection (CDI) and the incidence of bone cancer. Methods: This retrospective analysis used data provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with C. diff using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Standard statistical methods were used. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 78863 patients in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bone cancer was 659 patients (0.835%) in the C. diff group compared to 1941 patients (2.461%) in the control group. The difference was statistically significant by a P-value < 2.2x10^-16 with an odds ratio (OR)= 0.33 (0.31-0.37) with a 95% confidence interval (CI). Treatment for CDI was analyzed for both C. diff infected and noninfected populations. 91 out of 16,676 (0.55%) patients with a prior C. diff infection and treated with antibiotics were compared to the control group were 275 out of 16,676 (1.65%) patients with no history of CDI and received antibiotic treatment. Results remained statistically significant by P-value <2.2x10-16 with an OR= 0.42 (0.37, 0.48). and a 95% CI. Conclusion: The study shows a statistically significant correlation between C. diff and a reduced incidence of bone cancer. Further evaluation is recommended to assess the potential of C. difficile in reducing bone cancer incidence.

Keywords: bone cancer, colitis, clostridium difficile, microbiome

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Authors: Somya Ranjan Patro, Abhigna Bhatt, Arnab Banerjee

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Inertial amplifier has recently gained increasing attention as a new mechanism for vibration control of structures. Currently, theoretical investigations are undertaken by researchers to reveal its fundamentals and to understand its underline principles in altering the structural response of structures against dynamic loadings. This paper investigates experimental and analytical studies on the dynamic characteristics of hybrid beam inertial amplifier (HBIA). The analytical formulation of the HBIA has been derived by implementing the spectral element method and rigid body dynamics. This formulation gives the relation between dynamic force and the response of the structure in the frequency domain. Further, for validation of the proposed HBIA, the experiments have been performed. The experimental setup consists of a 3D printed HBIA of polylactic acid (PLA) material screwed at the base plate of the shaker system. Two numbers of accelerometers are used to study the response, one at the base plate of the shaker second one placed at the top of the inertial amplifier. A force transducer is also placed in between the base plate and the inertial amplifier to calculate the total amount of load transferred from the base plate to the inertial amplifier. The obtained time domain response from the accelerometers have been converted into the frequency domain using the Fast Fourier Transform (FFT) algorithm. The experimental transmittance values are successfully validated with the analytical results, providing us essential confidence in our proposed methodology.

Keywords: inertial amplifier, fast fourier transform, natural frequencies, polylactic acid, transmittance, vibration absorbers

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Authors: Lokesh Soni, Sushanta Kumar Sethi, Gaurav Manik

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This work attempts to use molecular simulations to create equilibrated structures of a range of commercially used polymers. Generated equilibrated structures for polyvinyl acetate (isotactic), polyvinyl alcohol (atactic), polystyrene, polyethylene, polyamide 66, poly dimethyl siloxane, poly carbonate, poly ethylene oxide, poly amide 12, natural rubber, poly urethane, and polycarbonate (bisphenol-A) and poly ethylene terephthalate are employed to estimate the correct chain length that will correctly predict the chain parameters and properties. Further, the equilibrated structures are used to predict some properties like density, solubility parameter, cohesive energy density, surface energy, and Flory-Huggins interaction parameter. The simulated densities for polyvinyl acetate, polyvinyl alcohol, polystyrene, polypropylene, and polycarbonate are 1.15 g/cm3, 1.125 g/cm3, 1.02 g/cm3, 0.84 g/cm3 and 1.223 g/cm3 respectively are found to be in good agreement with the available literature estimates. However, the critical repeating units or the degree of polymerization after which the solubility parameter showed saturation were 15, 20, 25, 10 and 20 respectively. This also indicates that such properties that dictate the miscibility of two or more polymers in their blends are strongly dependent on the chosen polymer or its characteristic properties. An attempt has been made to correlate such properties with polymer properties like Kuhn length, free volume and the energy term which plays a vital role in predicting the mentioned properties. These results help us to screen and propose a useful library which may be used by the research groups in estimating the polymer properties using the molecular simulations of chains with the predicted critical lengths. The library shall help to obviate the need for researchers to spend efforts in finding the critical chain length needed for simulating the mentioned polymer properties.

Keywords: Kuhn length, Flory Huggins interaction parameter, cohesive energy density, free volume

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Authors: G. C. Jadeja, M. A. Desai, D. R. Bhatt, J. K. Parikh

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Green extraction techniques are fast paving ways into various industrial sectors due to the stringent governmental regulations leading to the banning of toxic chemicals’ usage and also due to the increasing health/environmental awareness. The present work describes the ionic liquids based sonication method for selectively extracting patchoulol from the leaves of patchouli. 1-Butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4) and N,N,N,N’,N’,N’-Hexaethyl-butane-1,4-diammonium dibromide (dicationic ionic liquid - DIL) were selected for extraction. Ultrasound assisted ionic liquid extraction was employed considering concentration of ionic liquid (4–8 %, w/w), ultrasound power (50–150 W for [Bmim]BF4 and 20–80 W for DIL), temperature (30–50 oC) and extraction time (30–50 min) as major parameters influencing the yield of patchoulol. Using the Taguchi method, the parameters were optimized and analysis of variance (ANOVA) was performed to find the most influential factor in the selected extraction method. In case of [Bmim]BF4, the optimum conditions were found to be: 4 % (w/w) ionic liquid concentration, 50 W power, 30 oC temperature and extraction time of 30 min. The yield obtained under the optimum conditions was 3.99 mg/g. In case of DIL, the optimum conditions were obtained as 6 % (w/w) ionic liquid concentration, 80 W power, 30 oC temperature and extraction time of 40 min, for which the yield obtained was 4.03 mg/g. Temperature was found to be the most significant factor in both the cases. Extraction time was the insignificant parameter while extracting the product using [Bmim]BF4 and in case of DIL, power was found to be the least significant factor affecting the process. Thus, a green method of recovering patchoulol is proposed.

Keywords: green extraction, ultrasound, patchoulol, ionic liquids

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Authors: Sarika Singh, Moin Uddin, M. Masroor A. Khan, Aman Sobia Chishti, Sangram Singh, Urooj Hassan Bhatt

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Mentha arvensis L. (Japanese mint) is a perennial plant carrying medicinal, aromatic, antiseptic, and anaesthetic properties. Plant-derived smoke-water (PDSW) plays a significant role in seed germination, seedling growth, and other physiological attributes. To ascertain the effect of PDSW and karrikinolide on Mentha arvensis L., a rhizome-soaking experiment was conducted on Mentha arvensis. Prior to planting, mint rhizomes were soaked for 24 hours with aqueous solutions of various concentrations of PDSW (1:125v/v, 1:250 v/v, 1:500 v/v, and 1:1000 v/v), karrikinolide (10-6M, 10⁻⁷M, 10⁻⁸M, and 10⁻⁹M) using double distilled water as control treatment. Rhizome soaking with 1:500 v/v concentration of PDSW and 10⁻⁸M concentration of KAR1 increased the growth attributes, including plant height, fresh weight, dry, leaf area, and leaf yield per plant of Mentha arvensis. Leaf physiological-parameters, viz. chlorophyll fluorescence, PSII activity, and total chlorophyll and carotenoid content, were also increased as a result of the application of this treatment PDSW (1:500 v/v) and KAR1 (10⁻⁸M). In addition, treatment with 1:500 v/v and 10⁻⁸M significantly increased the essential oil yield and active constituents of Mentha arvensis compared to the control. Results indicated that PDSW, being a cheap source of karrikins, might be successfully used to augment mint essential oil production.

Keywords: active constituents, essential oil, medicinal plant, mentha arvensis L

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Authors: Prachi Bhatt

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Motivated workforce is an important asset of an organisation. Intrinsic motivation is one of the key aspects of people operations and performance. Researches have emphasized the significance of internal factors in individuals’ motivation. In the changing business scenario, it is a challenge for the organizations’ leaders to inspire and motivate their workforce. The present study deals with the intrinsic motivation potential of an individual which govern the innate capability of an individual driving him or her to behave or perform in the changing work environment, tasks, teams. Differences at individual level significantly influence differences in levels of motivation. In the above context, the present research attempts to explore behavioral trait dimensions which influence motivational potential of an individual. The present research emphasizes the significance of intrinsic motivational potential and the significance of exploring the differences in the intrinsic motivational potential levels of individuals at work places. Thus, this paper empirically tests the framework of behavioral traits which affects motivational potential of an individual. With the help of two studies i.e., Study 1 and Study 2, exploratory factor analysis and confirmatory factor analysis, respectively, indicated a reliable measure assessing intrinsic motivational potential of an individual. Given the variety of challenges of motivating contemporary workforce, and with increasing importance of intrinsic motivation, the paper discusses the relevance of the findings and of the measure assessing intrinsic motivational potential. Assessment of such behavioral traits would assist in the effective realization of intrinsic motivational potential of individuals. Additionally, the paper discusses the practical implications and furnishes scope for future research.

Keywords: behavioral traits, individual differences, intrinsic motivational potential, intrinsic motivation, motivation, workplace motivation

Procedia PDF Downloads 171

Authors: Diya Kohli, Amalia Ardeljan, Lexi Frankel, Jose Garcia, Lokesh Manjani, Omar Rashid

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Gonorrhea is the second most common sexually transmitted disease (STDs) in the United States of America. Gonorrhea affects the urethra, rectum, or throat and the cervix in females. Lymphoma is a cancer of the immune network called the lymphatic system that includes the lymph nodes/glands, spleen, thymus gland, and bone marrow. Lymphoma can affect many organs in the body. When a lymphocyte develops a genetic mutation, it signals other cells into rapid proliferation that causes many mutated lymphocytes. Multiple studies have explored the incidence of cancer in people infected with STDs such as Gonorrhea. For instance, the studies conducted by Wang Y-C and Co., as well as Caini, S and Co. established a direct co-relationship between Gonorrhea infection and incidence of prostate cancer. We hypothesize that Gonorrhea infection also increases the incidence of Lymphoma in patients. This research study aimed to evaluate the correlation between Gonorrhea infection and the incidence of Lymphoma. The data for the research was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. This database was utilized to evaluate patients infected with Gonorrhea versus the ones who were not infected to establish a correlation with the prevalence of Lymphoma using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for academic research. Standard statistical methods were applied throughout. Between January 2010 and December 2019, the query was analyzed and resulted in 254 and 808 patients in both the infected and control group, respectively. The two groups were matched by Age Range and CCI score. The incidence of Lymphoma was 0.998% (254 patients out of 25455) in the Gonorrhea group (patients infected with Gonorrhea that was Lymphoma Positive) compared to 3.174% and 808 patients in the control group (Patients negative for Gonorrhea but with Lymphoma). This was statistically significant by a p-value < 2.210-16 with an OR= 0.431 (95% CI 0.381-0.487). The patients were then matched by antibiotic treatment to avoid treatment bias. The incidence of Lymphoma was 1.215% (82 patients out of 6,748) in the Gonorrhea group compared to 2.949% (199 patients out of 6748) in the control group. This was statistically significant by a p-value <5.410-10 with an OR= 0.468 (95% CI 0.367-0.596). The study shows a statistically significant correlation between Gonorrhea and a reduced incidence of Lymphoma. Further evaluation is recommended to assess the potential of Gonorrhea in reducing Lymphoma.

Keywords: gonorrhea, lymphoma, STDs, cancer, ICD

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Authors: Shraddha Srivastava, N. K. Painuly, S. P. Mishra, Navin Singh, Muhsin Punchankandy, Kirti Srivastava, M. L. B. Bhatt

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Various optimization methods used in interstitial brachytherapy are based on dwell positions and dwell weights alteration to produce dose distribution based on the implant geometry. Since these optimization schemes are not anatomy based, they could lead to deviations from the desired plan. This study was henceforth carried out to compare anatomy-based Inverse Planning Simulated Annealing (IPSA) optimization technique with graphical and geometrical optimization methods in interstitial high dose rate brachytherapy planning of cervical carcinoma. Six patients with 12 CT data sets of MUPIT implants in HDR brachytherapy of cervical cancer were prospectively studied. HR-CTV and organs at risk (OARs) were contoured in Oncentra treatment planning system (TPS) using GYN GEC-ESTRO guidelines on cervical carcinoma. Three sets of plans were generated for each fraction using IPSA, graphical optimization (GrOPT) and geometrical optimization (GOPT) methods. All patients were treated to a dose of 20 Gy in 2 fractions. The main objective was to cover at least 95% of HR-CTV with 100% of the prescribed dose (V100 ≥ 95% of HR-CTV). IPSA, GrOPT, and GOPT based plans were compared in terms of target coverage, OAR doses, homogeneity index (HI) and conformity index (COIN) using dose-volume histogram (DVH). Target volume coverage (mean V100) was found to be 93.980.87%, 91.341.02% and 85.052.84% for IPSA, GrOPT and GOPT plans respectively. Mean D90 (minimum dose received by 90% of HR-CTV) values for IPSA, GrOPT and GOPT plans were 10.19 ± 1.07 Gy, 10.17 ± 0.12 Gy and 7.99 ± 1.0 Gy respectively, while D100 (minimum dose received by 100% volume of HR-CTV) for IPSA, GrOPT and GOPT plans was 6.55 ± 0.85 Gy, 6.55 ± 0.65 Gy, 4.73 ± 0.14 Gy respectively. IPSA plans resulted in lower doses to the bladder (D₂

Keywords: cervical cancer, HDR brachytherapy, IPSA, MUPIT

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Authors: Mohd Tariq, Shyamal K. Nandi, Indra D. Bhatt

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Paris polyphylla Smith (Family- Liliaceae; English name-Love apple: Local name- Satuwa) is an important folk medicinal herb of the Indian subcontinent, being a source of number of bioactive compounds for drug formulation. The rhizomes are widely used as antihelmintic, antispasmodic, digestive stomachic, expectorant and vermifuge, antimicrobial, anti-inflammatory, heart and vascular malady, anti-fertility and sedative. Keeping in view of this, the species is being constantly removed from nature for trade and various pharmaceuticals purpose, as a result, the availability of the species in its natural habitat is decreasing. In this context, it would be pertinent to conserve this species and reintroduce them in its natural habitat. Predictive distribution modelling of this species was performed in Western Himalayan Region. One such recent method is Ecological Niche Modelling, also popularly known as Species distribution modelling, which uses computer algorithms to generate predictive maps of species distributions in a geographic space by correlating the point distributional data with a set of environmental raster data. In case of P. polyphylla, and to understand its potential distribution zones and setting up of artificial introductions, or selecting conservation sites, and conservation and management of their native habitat. Among the different districts of Uttarakhand (28°05ˈ-31°25ˈ N and 77°45ˈ-81°45ˈ E) Uttarkashi, Rudraprayag, Chamoli, Pauri Garhwal and some parts of Bageshwar, 'Maximum Entropy' (Maxent) has predicted wider potential distribution of P. polyphylla Smith. Distribution of P. polyphylla is mainly governed by Precipitation of Driest Quarter and Mean Diurnal Range i.e., 27.08% and 18.99% respectively which indicates that humidity (27%) and average temperature (19°C) might be suitable for better growth of Paris polyphylla.

Keywords: biodiversity conservation, Indian Himalayan region, Paris polyphylla, predictive distribution modelling

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Authors: Mahmoud Abdulhamid, Rifan Hardian, Prashant Bhatt, Shuvo Datta, Adrian Ramirez, Jorge Gascon, Mohamed Eddaoudi, Gyorgy Szekely

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Polybenzimidazole (PBI) is a high-performance polymer that exhibits high thermal and chemical stability. However, it suffers from low porosity and low fractional free volume, which hinder its application as separation material. Herein, we demonstrate the molecular engineering of gas separation materials by manipulating a PBI backbone possessing kinked moieties. PBI was selected as it contains NH groups which increase the affinity towards CO₂, increase sorption capacity, and favors CO₂ over other gasses. We have designed and synthesized an intrinsically microporous polybenzimidazole (iPBI) featuring a spirobisindane structure. Introducing a kinked moiety in conjunction with crosslinking enhanced the polymer properties, markedly increasing the gas separation performance. In particular, the BET surface area of PBI increased 30-fold by replacing a flat benzene ring with a kinked structure. iPBI displayed a good CO₂ uptake of 1.4 mmol g⁻¹ at 1 bar and 3.6 mmol g⁻¹ at 10 bar. Gas sorption uptake and breakthrough experiments were conducted using mixtures of CO₂/CH₄ (50%/50%) and CO₂/N₂ (50%/50%), which revealed the high selectivity of CO₂ over both CH₄ and N₂. The obtained CO₂/N₂ selectivity is attractive for power plant flue gas application requiring CO₂ capturing materials. Energy and process simulations of biogas CO₂ removal demonstrated that up to 70% of the capture energy could be saved when iPBI was used rather than the current amine technology (methyl diethanolamine [MDEA]). Similarly, the combination of iPBI and MDEA in a hybrid system exhibited the highest CO₂ capture yield (99%), resulting in nearly 50% energy saving. The concept of enhancing the porosity of PBI using kinked moieties provides new scope for designing highly porous polybenzimidazoles for various separation processes.

Keywords: polybenzimidazole (PBI), intrinsically microporous polybenzimidazole (iPBI), gas separation, pnergy and process simulations

Procedia PDF Downloads 58

Authors: Harshita Raj, Joydeep Ghosh, Rakesh L. Tanna, Prabal K. Chattopadhyay, K. A. Jadeja, Sharvil Patel, Kaushal M. Patel, Narendra C. Patel, S. B. Bhatt, V. K. Panchal, Chhaya Chavda, C. N. Gupta, D. Raju, S. K. Jha, J. Raval, S. Joisa, S. Purohit, C. V. S. Rao, P. K. Atrey, Umesh Nagora, R. Manchanda, M. B. Chowdhuri, Nilam Ramaiya, S. Banerjee, Y. C. Saxena

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Efficient gas fueling is a critical aspect that needs to be mastered in order to maintain plasma density, to carry out fusion. This requires a fair understanding of fuel recycling in order to optimize the gas fueling. In Aditya tokamak, multiple gas puffs are used in a precise and controlled manner, for hydrogen fueling during the flat top of plasma discharge which has been instrumental in achieving discharges with enhanced density as well as energy confinement time. Following each gas puff, we observe peaks in temporal profile of Hα emission, Soft X-ray (SXR) and chord averaged electron density in a number of discharges, indicating efficient gas fueling. Interestingly, Hα temporal profile exhibited an additional peak following the peak corresponding to each gas puff. These additional peak Hα appeared in between the two gas puffs, indicating the presence of a secondary hydrogen source apart from the gas puffs. A thorough investigation revealed that these secondary Hα peaks coincide with Hard X- ray bursts which come from the interaction of runaway electrons with vessel limiters. This leads to consider that the runaway electrons (REs), which hit the wall, in turn, bring out the absorbed hydrogen and oxygen from the wall and makes the interaction of REs with limiter a secondary hydrogen source. These observations suggest that runaway electron induced recycling should also be included in recycling particle source in the particle balance calculations in tokamaks. Observation of two Hα peaks associated with one gas puff and their roles in enhancing and maintaining plasma density in Aditya tokamak will be discussed in this paper.

Keywords: fusion, gas fueling, recycling, Tokamak, Aditya

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Authors: Srishti Bhatt, Vaibhav Bhavsar, Adil Hussain, Aashay Mhaske, S. C. Bali, T. S. Srikanth

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Shape Memory Alloys (SMA) are widely known for their unique shape recovery properties. SMA based actuation systems have high-force to weight ratio, light weight and also bio-compatible material. Which is why they are being used in different fields of aerospace, robotics, automotive and biomedical industries. However, in the automotive industry plenty of patents are available but commercially viable products are very few in market. This could be due to SMA material limitations like small stroke, direct dependability of lifecycle on stroke, pull load of the wire and high cycle time. In automotive sector, SMA being considered as an actuator which is required to have high stroke and constraint arises to accommodate a long length of wire (to compensate maximum 4 % strain as per better fatigue life cycle) not only increases complexity but also adds on the cost. More than 200 different types of actuators are used in an automobile, few of them whose efficiency can highly increase by replacing them with SMA based actuators which include latch lock mechanism, glove box, Head lamp leveling, side mirror and rear mirror leveling, tailgate opener and fuel lid cap actuator. To overcome the limitation of available space for required stroke of an actuator which leads to study the effect of different loading positions on SMA wires, different orientations of SMA wire by using pulleys and lever based systems to achieve maximum stroke. This investigation summarizes the loading under the V shape orientation the required stroke and carrying load capacity in more compact in comparison with straight orientation of wire. Similarly, the U shape orientation its showing higher load carrying capacity but reduced stroke which is aligned with concept of bundled wire method. Life-cycle of these orientations were also evaluated.

Keywords: actuators, automotive, nitinol, shape memory alloy, SMA wire orientations

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Authors: Prashantkumar Waghe, N. Prakash, N. D. Prasada, L. V. Lokesh, M. Vijay Kumar, Vinay Tikare

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Arsenic is a naturally occurring metalloid with potent toxic effects. It is ubiquitous in the environment and released from both natural and anthropogenic sources. It has the potential to cause various health hazards in exposed populations. Arsenic exposure through drinking water is considered as one of the most serious global environmental threats including Southeast Asia. The aim of present study was to evaluate the modulatory role of subacute exposure to sodium (meta) arsenite on the antinociceptive, anti-inflammatory and antipyretic responses mediated by meloxicam in rats. Rats were exposed to arsenic as sodium arsenite through drinking water for 28 days. A single dose of meloxicam (2 mg/kg b. wt.) was administered by oral gavage on the 29th day. The exact time of meloxicam administration depended on the type of test. Rats were divided randomly into 5 groups (n=6). Group I served as normal control and received arsenic free drinking water, while rats in group II were maintained similar to Group I but received meloxicam on 29th day. Groups III, IV and V were pre-exposed to arsenic through drinking water at 0.5, 5.0 and 50 ppm, respectively, for 28 days and was administered meloxicam next day and; pain and inflammation carried out by using formalin-induced nociception and carrageenan-induced inflammatory model(s), respectively by using standard protocol. For assessment of antipyretic effects, one more additional group (Group VI) was taken and given LPS @ 1.8 mg/kg b. wt. for induction of pyrexia (LPS control). Higher dose of arsenic inhibited the meloxicam mediated antinociceptive, anti-inflammatory and antipyretic responses. Further, meloxicam inhibited the arsenic induced level of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 and COX2 mediated prostaglandin E2 in hind paw muscle. These results suggest a functional antagonism of meloxicam by arsenic. This may relate to arsenic mediated local release of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 releases COX2 mediated prostaglandin E2. Based on the experimental study, it is concluded that sub-acute exposure to arsenic through drinking water aggravate pyrexia, inflammation and pain at environment relevant concentration and decrease the therapeutic efficacy of meloxicam at higher level of arsenite exposure. Thus, the observation made has clinical relevance in situations where animals are exposed to arsenite epidemic geographical locations.

Keywords: arsenic, analgesic activity, meloxicam, Wistar rats

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Authors: Showkat Ahmad Bhat, M. S. Bhatt

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The study evaluates the ex-post impact of institutional credit on agricultural output. It first examines the key factors that influence the accessibility of institutional credit by farm households. For quantitative analysis both program participant and non-participant respondents were drawn and cross-sectional survey data were collected from 412 households in Pulwama District of Jammu & Kashmir (India). Propensity Score Matching Method was employed to analyze the impact of the institutional credit on agricultural output. Results show that institutional credit has a positive and significant impact on the agricultural output measured in terms of farm income and crop productivity. To estimate the accessibility of credit, an examination of both demand side and supply side factors were carried out. The demand for credit was measured with respect to respondents who applied for credit. Supply side credit allocation measured in terms of the proportion of ‘credit amount’ farmers obtained. Logit and Two-limit Tobit Regression Models were used to investigate the determinants that influence the accessibility of formal credit for Demand for and supply of credit respectively. The estimated results suggested that the demand for credit is positively and significantly affected by the factors such as: age of the household head, formal education, membership, cash crop grown, farm size and saving account. All the variables were found significantly increasing the household’s likelihood to demand for and supply of credit from banks. However, the impact of these factors varies considerably across the credit markets. Factors which were found negatively and significantly influencing the accessibility of credit were: ‘square of the age’, household assets and rate of interest. The credit constraints analysis suggested that square of the age; household assets and rate of interest were the three most important factors that increased the probability of being constrained. The study finally discusses these results in detail and draws some recommendations.

Keywords: institutional credit, agriculture, propensity score matching logit model, Tobit model

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Authors: Vaibhav D. Bhatt, Anju P. Kunjadia, D. S. Nauriyal, Bhumika J. Joshi, Chaitanya G. Joshi

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Metagenomic analysis of milk samples collected from local cattle breed, kankrej (Bos indicus), Gir (Bos indicus) and Crossbred (Bos indicus X Bos taurus) cattle harbouring subclinical mastitis was carried out by next-generation sequencing (NGS) 454 GS-FLX technology. Around 56 different species including members of Enterobacteriales, Pseudomonadales, Bacillales and Lactobacillales with varying abundance were detected in infected milk. The interesting presence of bacteriophages against Staphylococcus aureus, Escherichia coli, Enterobacter and Yersinia species were observed, especially Enterobacteria and E. coli phages (0∙32%) in Kankrej, Enterobacteria and Staphylococcus phages (1∙05%) in Gir and Staphylococcus phages (2∙32%) in crossbred cattle. NGS findings suggest that phages may be involved in imparting natural resistance of the cattle against pathogens. Further infected milk samples were subjected for bacterial isolation. Fourteen different isolates were identified, and DNA was extracted. Genes (Tet-K, Msr-A, and Mec-A) providing antibiotic resistance to the bacteria were screened by Polymerase Chain Reaction and results were validated with traditional antibiotic assay. Total 3 bacteriophages were isolated from nearby environment of the cattle farm. The efficacy of phages was checked against multi-drug resistant bacteria, identified by PCR. In-vivo study was carried out for phage therapy in mammary glands of female rats “Wister albino”. Mammary glands were infused with MDR isolates for 3 consecutive days. Recovery was observed in infected rats after intramammary infusion of sterile phage suspension. From day 4th onwards, level of C-reactive protein was significant increases up to day 12th . However, significant reduction was observed between days 12th to 18th post treatment. Bacteriophages have significant potential as antibacterial agents and their ability to replicate exponentially within their hosts and their specificity, make them ideal candidates for more sustainable mastitis control.

Keywords: bacteriophages, c-reactive protein, mastitis, metagenomic analysis

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Authors: Kanduru Lokesh, Venkitasamy Kesavan

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The unique structural features of spiro-oxindoles with diverse biological activities have made them privileged structures in new drug discovery. The key structural characteristic of these compounds is the spiro ring fused at the C-3 position of the oxindole core with varied heterocyclic motifs. Structural diversification of heterocyclic scaffolds to synthesize new chemical entities as pharmaceuticals and agrochemicals is one of the important goals of synthetic organic chemists. Nitrogen and oxygen containing heterocycles are by far the most widely occurring privileged structures in medicinal chemistry. The structural complexity and distinct three-dimensional arrangement of functional groups of these privileged structures are generally responsible for their specificity against biological targets. Structurally diverse compound libraries have proved to be valuable assets for drug discovery against challenging biological targets. Thus, identifying a new combination of substituents at C-3 position on oxindole moiety is of great importance in drug discovery to improve the efficiency and efficacy of the drugs. The development of suitable methodology for the synthesis of spiro-oxindole compounds has attracted much interest often in response to the significant biological activity displayed by the both natural and synthetic compounds. So creating structural diversity of oxindole scaffolds is need of the decade and formidable challenge. A general way to improve synthetic efficiency and also to access diversified molecules is through the annulation reactions. Annulation reactions allow the formation of complex compounds starting from simple substrates in a single transformation consisting of several steps in an ecologically and economically favorable way. These observations motivated us to develop the annulation reaction protocol to enable the synthesis of a new class of spiro-oxindole motifs which in turn would enable the enhancement of molecular diversity. As part of our enduring interest in the development of novel, efficient synthetic strategies to enable the synthesis of biologically important oxindole fused spirocarbocyclic systems, We have developed an efficient methodology for the construction of highly functionalized spirocarbocyclic oxindoles through [4+2] annulation of phthalides via Hauser annulation. functionalized spirocarbocyclic oxindoles was accomplished for the first time in the literature using Hauser annulation strategy. The reaction between methyleneindolinones and arylsulfonylphthalides catalyzed by cesium carbonate led to the access of new class of biologically important spiro[indoline-3,2'-naphthalene] derivatives in very good yields. The synthetic utility of the annulated product was further demonstrated by fluorination Using NFSI as a fluorinating agent to furnish corresponding fluorinated product.

Keywords: Hauser-Kraus annulation, spiro carbocyclic oxindoles, oxindole-ester, fluoridation

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Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: Krupali Mehta, Sandip Bhatt, Umesh Trivedi, Bhavesh Bharatiya, Mukesh Ranjan, Atindra D. Shukla

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Owing to the dominating surface forces and large-scale surface interactions, the nano-scale particles face difficulties in getting suspended in various media. Magnetic nanoparticles of iron oxide offer a great deal of promise due to their ease of preparation, reasonable magnetic properties, low cost and environmental compatibility. We intend to modify the surface of magnetic Fe₂O₃ nanoparticles with selected surface modifying agents using simple and effective single-step chemical reactions in order to enhance dispersibility of magnetic nanoparticles in non-polar media. Magnetic particles were prepared by hydrolysis of Fe²⁺/Fe³⁺ chlorides and their subsequent oxidation in aqueous medium. The dried particles were then treated with Octadecyl quaternary ammonium silane (Terrasil™), stearic acid and gallic acid ester of stearyl alcohol in ethanol separately to yield S-2 to S-4 respectively. The untreated Fe₂O₃ was designated as S-1. The surface modified nanoparticles were then analysed with Dynamic Light Scattering (DLS), Fourier Transform Infrared spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermogravimetric Gravimetric Analysis (TGA) and Scanning Electron Microscopy and Energy dispersive X-Ray analysis (SEM-EDAX). Characterization reveals the particle size averaging 20-50 nm with and without modification. However, the crystallite size in all cases remained ~7.0 nm with the diffractogram matching to Fe₂O₃ crystal structure. FT-IR suggested the presence of surfactants on nanoparticles’ surface, also confirmed by SEM-EDAX where mapping of elements proved their presence. TGA indicated the weight losses in S-2 to S-4 at 300°C onwards suggesting the presence of organic moiety. Hydrophobic character of modified surfaces was confirmed with contact angle analysis, all modified nanoparticles showed super hydrophobic behaviour with average contact angles ~129° for S-2, ~139.5° for S-3 and ~151° for S-4. This indicated that surface modified particles are super hydrophobic and they are easily dispersible in non-polar media. These modified particles could be ideal candidates to be suspended in oil-based fluids, polymer matrices, etc. We are pursuing elaborate suspension/sedimentation studies of these particles in various oils to establish this conjecture.

Keywords: iron nanoparticles, modification, hydrophobic, dispersion

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Authors: Shailendra Kumar, Lokesh Kashyap, Puneet Khanna, Nishant Patel, Rakesh Kumar, Arshad Ayub, Kelika Prakash, Yudhyavir Singh, Krithikabrindha V.

Abstract:

Introduction: Spinal anesthesia is considered a standard anesthesia technique for caesarean delivery. The incidence of spinal hypotension during caesarean delivery is 70 -80%. Spinal hypotension may cause cerebral hypoperfusion in the mother, but physiologically cerebral autoregulatory mechanisms accordingly prevent cerebral hypoxia. Cerebral blood flow remains constant in the 50-150 mmHg of Cerebral Perfusion Pressure (CPP) range. Near-infrared spectroscopy (NIRS) is a non-invasive technology that is used to detect Cerebral Desaturation Events (CDEs) immediately compared to other conventional intraoperative monitoring techniques. Objective: The primary aim of the study is to correlate the change in cerebral oxygen saturation using NIRS with respect to a fall in mean blood pressure after spinal anaesthesia and to find out the effects of spinal hypotension on neonatal APGAR score, neonatal acid-base variations, and presence of Postoperative Delirium (POD). Methodology: NIRS sensors were attached to the forehead of all the patients, and their baseline readings of cerebral oxygenation on the right and left frontal regions and mean blood pressure were noted. Subarachnoid block was given with hyperbaric 0.5% bupivacaine plus fentanyl, the dose being determined by the individual anaesthesiologist. Co-loading of IV crystalloid solutions was given to the patient. Blood pressure reading and cerebral saturation were recorded every 1 minute till 30min. Hypotension was a fall in MAP less than 20% of the baseline values. Patients going for hypotension were treated with an IV Bolus of phenylephrine/ephedrine. Umbilical cord blood samples were taken for blood gas analysis, and neonatal APGAR was noted by a neonatologist. Study design: A prospective observational study conducted in a population of Thirty ASA 2 and 3 parturients scheduled for lower segment caesarean section (LSCS). Results: Mean fall in regional cerebral saturation is 28.48 ± 14.7% with respect to the mean fall in blood pressure 38.92 ± 8.44 mm Hg. The correlation coefficient between fall in saturation and fall in mean blood pressure is 0.057, and p-value {0.7} after subarachnoid block. A fall in regional cerebral saturation occurred 2±1 min before a fall in mean blood pressure. Twenty-nine out of thirty patients required vasopressors during hypotension. The first dose of vasopressor requirement is needed at 6.02±2 min after the block. The mean APGAR score was 7.86 and 9.74 at 1 and 5 min of birth, respectively, and the mean umbilical arterial pH of 7.3±0.1. According to DRS-98 (Delirium Rating Scale), the mean delirium rating score on postoperative day 1 and day 2 were 0.1 and 0.7, respectively. Discussion: There was a fall in regional cerebral oxygen saturation, which started before with respect to a significant fall in mean blood pressure readings but was statistically not significant. Maximal fall in blood pressure requiring vasopressors occurs within 10 min of SAB. Neonatal APGAR scores and acid-base variations were in the normal range with maternal hypotension, and there was no incidence of postoperative delirium in patients with post-spinal hypotension.

Keywords: cerebral oxygenation, LSCS, NIRS, spinal hypotension

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Authors: Preeti Virkar, V. P. Uniyal, Vinod Kumar Bhatt

Abstract:

With 50% decline in managed honey bee hives in the continents of Europe and America, farmers and landscape managers are turning to native wild bees for their essential ecosystem services of pollination. Wild bees population are too under danger due to the rapid land use changes from anthropogenic activities. With an escalating population reaching 9.0 billion by 2050, human-induced land use changes are predicted to further deteriorate the habitats of numerous species by the turn of this century. The status of bees are uncertain, especially in the tropical regions of the world, which also questions the crisis of global pollinator decline and their essential services to wild and managed flora. Our investigation collectively compares wild native bee diversity and their status in forests and agroecosystems in Doon Valley landscape, situated at the foothills of Himalayan ranges, Uttarakhand, India. We seek to ask whether (1) natural habitat are refuge to richer and rarer bees communities than the agroecosystems, (2) Are agroecosystems closer to natural habitats similar to them than agroecosystems farther away; hence support richer bee communities and hence, (3) Do polyculture farms support richer bee communities than monoculture. The data was collected using observation and pantrap sampling form February to May, 2012 to 2014. We recorded 43 species of bees in Doon Valley. They belonged to 5 families; Megachilidae, Apidae, Andrenidae, Halictidae and Collitidae. A multinomial model approach was used to classify the bees into 2 habitats, in which forests demonstrated to support greater number of specialist (26%, n= 11) species than agroecosystems (7%, n= 3). The valley had many species categorized as the rare (58%, n= 25) and very few generalists (9%, n=4). A linear regression model run on our data demonstrated higher bee diversity in agro-ecosystems in close proximity to forests (H’ for < 200 m = 1.60) compared to those further away (H’ for > 600 m = 0.56) (R2=0.782, SE=0.148, p value=0.004). Organic agriculture supported significantly greater species richness in comparison to conventional farms (Mann-Whitney U test, n1 = 33, n2 = 35; P = 0.001). Forests ecosystems are refuge to rare specialist groups and support bee communities in nearby agroecosystems. The findings of our investigation demonstrate the importance of natural habitats as a potential refuge for rare native wild bee pollinators. Polyculture in the valley behaves similar to natural habitats and supports diverse bee communities in comparison to conventional monocultures. Our study suggests that the farming communities adopt diverse organic agriculture systems to attract wild pollinators beneficial for better crop production. Forests are sanctuaries for bees to nest, forage, and breed. Therefore, our outcome also suggests landscape managers not only preserve protected areas but also enhance the floral diversity in semi-natural and urban areas.

Keywords: native bees, pollinators, polyculture, agroecosystem, natural habitat, diversity, monoculture, specialists, generalists

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Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen

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Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.

Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease

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Authors: A. Bhatt, C. Bassi, H. Farragher, J. Musk

Abstract:

Background: All medicines placed on the EU market are legally required to be accompanied by labeling and package leaflet, which provide comprehensive information, enabling its safe and appropriate use. Mock-ups with results of assessments using a target patient group must be submitted for a marketing authorisation application. Consumers need confidence in non-prescription, OTC medicines in order to manage their minor ailments and umbrella brands assist purchasing decisions by assisting easy identification within a particular therapeutic area. A number of regulatory agencies have risk management tools and guidelines to assist in developing umbrella brands for OTC medicines, however assessment and decision making is subjective and inconsistent. This study presents an evaluation in the UK following the US FDA warning concerning methaemoglobinaemia following 21 reported cases (11 children under 2 years) caused by OTC oral analgesics containing benzocaine. METHODS: A standard face to face, 25 structured task based user interview testing methodology using a standard questionnaire and rating scale in consumers aged 15-91 years, was conducted independently between June and October 2015 in their homes. Whether individuals could discriminate between the labelling, safety information and warnings on cartons and PILs between 3 different OTC medicines packs with the same umbrella name was evaluated. Each pack was presented with differing information hierarchy using, different coloured cartons, containing the 3 different active ingredients, benzocaine (oromucosal spray) and two lozenges containing 2, 4, dichlorobenzyl alcohol, amylmetacresol and hexylresorcinol respectively (for the symptomatic relief of sore throat pain). The test was designed to determine whether warnings on the carton and leaflet were prominent, accessible to alert users that one product contained benzocaine, risk of methaemoglobinaemia, and refer to the leaflet for the signs of the condition and what to do should this occur. Results: Two consumers did not locate the warnings on the side of the pack, eventually found them on the back and two suggestions to further improve accessibility of the methaemoglobinaemia warning. Using a gold pack design for the oromucosal spray, all consumers could differentiate between the 3 drugs, minimum age particulars, pharmaceutical form and the risk factor methaemoglobinaemia. The warnings for benzocaine were deemed to be clear or very clear; appearance of the 3 packs were either very well differentiated or quite well differentiated. The PIL test passed on all criteria. All consumers could use the product correctly, identify risk factors ensuring the critical information necessary for the safe use was legible and easily accessible so that confusion and errors were minimised. Conclusion: Patients with known methaemoglobinaemia are likely to be vigilant in checking for benzocaine containing products, despite similar umbrella brand names across a range of active ingredients. Despite these findings, the package design and spray format were not deemed to be sufficient to mitigate potential safety risks associated with differences in target populations and contraindications when submitted to the Regulatory Agency. Although risk management tools are increasingly being used by agencies to assist in providing objective assurance of package safety, further transparency, reduction in subjectivity and proportionate risk should be demonstrated.

Keywords: labelling, OTC, risk, user testing

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Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 481

Authors: Kelsi Hagerty, Ami Rosen, Aaliyah Heyward, Nadia Ali, Emily Brown, Erin Demo, Yue Guan, Modele Ogunniyi, Brianna McDaniels, Alanna Morris, Kunal Bhatt

Abstract:

Hereditary transthyretin amyloidosis (hATTR) is a progressive, multi-systemic, and life-threatening disease caused by a disruption in the TTR protein that delivers thyroxine and retinol to the liver. This disruption causes the protein to misfold into amyloid fibrils, leading to the accumulation of the amyloid fibrils in the heart, nerves, and GI tract. Over 130 variants in the TTR gene are known to cause hATTR. The Val122Ile variant is the most common in the United States and is seen almost exclusively in people of African descent. TTR variants are inherited in an autosomal dominant fashion and have incomplete penetrance and variable expressivity. Individuals with hATTR may exhibit symptoms from as early as 30 years to as late as 80 years of age. hATTR is characterized by a wide range of clinical symptoms such as cardiomyopathy, neuropathy, carpal tunnel syndrome, and GI complications. Without treatment, hATTR leads to progressive disease and can ultimately lead to heart failure. hATTR disproportionately affects individuals of African descent; the estimated prevalence of hATTR among Black individuals in the US is 3.4%. Unfortunately, hATTR is often underdiagnosed and misdiagnosed because many symptoms of the disease overlap with other cardiac conditions. Due to the progressive nature of the disease, multi-systemic manifestations that can lead to a shortened lifespan, and the availability of free genetic testing and promising FDA-approved therapies that enhance treatability, early identification of individuals with a pathogenic hATTR variant is important, as this can significantly impact medical management for patients and their relatives. Furthermore, recent literature suggests that TTR genetic testing should be performed in all patients with suspicion of TTR-related cardiomyopathy, regardless of age, and that follow-up with genetic counseling services is recommended. Relatives of patients with hATTR benefit from genetic testing because testing can identify carriers early and allow relatives to receive regular screening and management. Despite the striking prevalence of hATTR among Black individuals, hATTR remains underdiagnosed in this patient population, and germline genetic testing for hATTR in Black individuals seems to be underrepresented, though the reasons for this have not yet been brought to light. Historically, Black patients experience a number of barriers to seeking healthcare that has been hypothesized to perpetuate the underdiagnosis of hATTR, such as lack of access and mistrust of healthcare professionals. Prior research has described a myriad of factors that shape an individual’s decision about whether to pursue presymptomatic genetic testing for a familial pathogenic variant, such as family closeness and communication, family dynamics, and a desire to inform other family members about potential health risks. This study explores these factors through 10 in-depth interviews with patients with hATTR about what factors may be contributing to the underdiagnosis of hATTR in the Black population. Participants were selected from the Emory University Amyloidosis clinic based on having a molecular diagnosis of hATTR. Interviews were recorded and transcribed verbatim, then coded using MAXQDA software. Thematic analysis was completed to draw commonalities between participants. Upon preliminary analysis, several themes have emerged. Barriers identified include i) Misdiagnosis and a prolonged diagnostic odyssey, ii) Family communication and dynamics surrounding health issues, iii) Perceptions of healthcare and one’s own health risks, and iv) The need for more intimate provider-patient relationships and communication. Overall, this study gleaned valuable insight from members of the Black community about possible factors contributing to the underdiagnosis of hATTR, as well as potential solutions to go about resolving this issue.

Keywords: cardiac amyloidosis, heart failure, TTR, genetic testing

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