Herein, a polysaccharide-based hydrogel from seeds of Salvia spinosa (SSH) was evaluated as a pH-responsive, superporous, hemocompatible, non-toxic, and sustained release material. The SSH-based tablets showed pH-dependent swelling (pH 7.4 > 6.8 > 4.5 > 1.2) as well as swelling and de-swelling behavior at pH 7.4 and 1.2, respectively. Sustained release of febuxostat was achieved by mimicking the gastrointestinal tract conditions for 14 h and following the zero-order kinetics and super case-II transport mechanism. Scanning electron microscopy revealed the porous nature of SSH even after compression. SSH was found to be hemocompatible with antioxidant properties. Acute toxicity studies ensured the safety of SSH at a maximum dose level of 2.0 g kg-1 body weight of the animals. SSH was also found as non-irritant to the eye. The histopathology of vital organs did not show any lesions or inflammation. Conclusively, SSH can be considered a safe ingredient for oral, dermal, and ophthalmic formulations.

ABSTRACT Aspergillus fumigatus is a respiratory pathogen, which has the potential to cause brooder pneumonia in poultry chicks and aspergillosis in birds and farmers. Frequent and irrational use of antifungals has led to the development of resistance in the fungal species. The present study aimed to evaluate the antifungal activity of essential oils (EOs) from four different spices against multi-drug resistant (MDR) A. fumigatus isolated from 40 poultry feed samples. Twenty fungal isolates were identified to be A. fumigatus based on the macroscopic and microscopic characteristics, which were confirmed by targeting and amplifying the species-specific rodA gene (313 bp). Five (5/20) isolates were found to be MDR by the disk diffusion method. EOs were tested as an alternative strategy for 5 MDR isolates of A. fumigatus. Clove EO provided better activity by 6 log10 reduction for 30-90 min exposure as compared to other EOs, therefore, shortlisted for well-diffusion and minimum inhibitory concentration (MIC) method. Clove EO provided promising results as compared to fluconazole, amphotericin B, ketoconazole, nystatin and voriconazole as its mean ZOI (39.6 ± 6.34) were better than all other commercial antifungals (p< 0.001). Mean MIC was reported to be 0.195 ± 0.11 µl/ml. Safety testing of the EO produced 74-82% cell viability for the range of 0.390 - 0.097 µl/ml as compared to DMSO. Findings of the present study highlight that clove EO can be source of a good therapeutic agent for infections of MDR isolates of A. fumigatus.

RESUMO Aspergillus fumigatus é um patógeno respiratório, que tem o potencial de causar pneumonia incubadora em pintos e aspergilose em aves e criadores. O uso frequente e irracional de antifúngicos tem levado ao desenvolvimento de resistência nas espécies fúngicas. O presente estudo teve como objetivo avaliar a atividade antifúngica de óleos essenciais (OEs) de quatro diferentes especiarias contra A. fumigatus multirresistente (MDR) isolado de 40 amostras de ração de aves. Vinte isolados fúngicos foram identificados como A. fumigatus com base nas características macroscópicas e microscópicas, que foram confirmadas pelo direcionamento e amplificação do gene rodA espécie-específico (313 pb). Cinco (5/20) isolados foram considerados MDR pelo método de difusão em disco. OEs foram testados como uma estratégia alternativa para 5 isolados MDR de A. fumigatus. Clove EO forneceu melhor atividade por redução de 6 log10 para exposição de 30-90 min em comparação com outros OEs, portanto, pré-selecionado para difusão e método de concentração inibitória mínima (MIC). Clove EO forneceu resultados promissores em comparação com fluconazol, anfotericina B, cetoconazol, nistatina e voriconazol, com ZOI médio (39,6 ± 6,34) melhor do que todos os outros antifúngicos comerciais (p < 0,001). A MIC média foi de 0,195 ± 0,11 µl/ml. O teste de segurança do EO produziu 74-82% de viabilidade celular para a faixa de 0,390 - 0,097 µl/ml em comparação com DMSO. Os resultados do presente estudo destacam que o EO de cravo pode ser fonte de um bom agente terapêutico para infecções de isolados multirresistentes de A. fumigatus.

Abstract Introduction Total thyroidectomy remains highly technical, with a significant risk of recurrent laryngeal nerve (RLN) compromise and hypoparathyroidism. After identifying RLN, at the level of the ligament of Berry, local factors may compel the surgeon to either dissect along the nerve or the thyroid capsule. Objective The objective of the present study is to compare these two approaches in terms of outcomes and complication rates. Methods This is a retrospective analysis from September, 2013 to April 2019 of 511 consecutive patients undergoing thyroidectomy. General demographics and disease parameters were recorded. At the discretion of the surgeon and according to the demands of the local operative factors, the patients either had dissection along the RLN or along the thyroid capsule. Perioperative and postoperative parameters such as blood loss, duration of surgery, hospital stay, pain scores, analgesia requirements and complications were recorded. The groups were compared with the Pearson chi-squared test or with the Fisher exact test. A p-value < 0.05 was considered statistically significant. Results The incidence of transient hypocalcaemia and transient RLN compromise were higher when dissection was performed along the nerve as opposed to the plane along the thyroid capsule. Other parameters including operative time, hospital stay, pain scores, analgesia requirement, wound infection, seroma, hemorrhage, and recurrence did not differ between the groups. Subgroup analysis of the patients who presented with complications showed that local factors, malignancy, and extent of surgery correlated positively with complications when dissected along the RLN. Conclusion Dissection along the capsule of the thyroid during thyroidectomy is a safer plane in terms of low rate of transient RLN injury and hypoparathyroidism as opposed to dissection along the nerve.

Abstract Highly nutritional and functional properties of chia seeds would make it unique than other grains. Considering its known properties chia can be used as an important food ingredient. These are rich in fiber, ash, protein, polyunsaturated fatty acids (PUFA) and antioxidants. Higher proportion of protein having greater biological value with essential amino acids and high dietary fiber content prevents several metabolic disorders and obesity. It is also consist of PUFA helpful in lowering cardiovascular diseases. Rusks were supplemented with chia flour at a rate ranging 5 to 20% with the goal to modify the fiber content, nutritional contents and physicochemical properties. The obtained results were highly significant and showed increasing trend in dietary fiber and PUFA values. Texture values decreased significantly. Sensory evaluation showed significant (p<0.05) differences in color, flavor, texture and overall acceptability. Most acceptable treatment was with 5% chia flour supplementation with a mean score of 8.10. Hence, Chia flour-supplemented rusks up to 5% addition level could be utilized as a convenience food and vehicle of improved nutritional status with health beneficial bioactive compounds. Moreover, supplementation of chia flour led to improvement of functional properties of wheat rusks as a valuable source of dietary fiber and bioactive compounds.

Abstract Food is a basic human right since it is necessary for survival. Unsafe food threatens billions of people throughout the world. Every year, hundreds of thousands of people grow sick and die. Microbial, chemical, personal, and environmental hygiene are all issues that the food chain faces from farm to fork/plate. Human tragedies and economic disasters have been reported in the past as a result of purposeful or inadvertent personal behavior and government inability to ensure food safety and quality. The issue of food safety has gotten a lot of press. As a result, a Food Safety Information Platform (FSIP) based on machine learning and open data with a Chatbot based on cloud computing (MLODCCC) architecture was developed, which includes a nice Facebook hyperlink and chatbot interface for locating trustworthy food safety knowledge. Rumors about the safety of food goods instill fear in people, leading to a broad boycott and, as a result, significant economic loss. This study looked into the function of rumors among friends. The findings suggested that people choose to use news media information in interaction with friends because it is seen to be more reliable than other resources.

RESUMO A presente pesquisa avaliou a mudança espaço-temporal na floresta subtropical do distrito de Malakand através de técnicas de Sensoriamento Remoto e GIS. O principal objetivo era identificar diferentes classes de cobertura terrestre e determinar as mudanças temporais na cobertura florestal na área de estudo. Este estudo foi baseado nas duas diferentes técnicas de classificação da cobertura do solo. Neste estudo, quatro imagens Landsat foram adquiridas com o intervalo de 10 anos, de 1988 a 2018. A classificação de máxima probabilidade e a classificação de distância mínima foram aplicadas passo a passo em todas as quatro imagens. A área total do distrito de Malakand foi registrada como 975,32 km2. Em relação à porcentagem de cobertura de área sábia, a floresta cobriu 22,1 % da área total, enquanto os assentamentos de outras classes, agricultura, terra árida e água cobriram 17,7, 23,3, 33 e 3,9% respectivamente em 1988. Enquanto que em 2018, a porcentagem de cobertura de área razoável abrangia 9,3 % da área total, embora os assentamentos de outras classes, a agricultura, a terra árida e a água tenham coberto 33,8, 22,3, 31,8 e 3,7, respectivamente. A mudança na área florestal ao longo do tempo foi de 60,4 km2 que é igual a 6,2 % durante 1998 a 2008 e finalmente o desmatamento total foi de 124,4 km 2 que é igual a 12,7% de perda de área de floresta perdida de 1998 a 2018. Assim, a área florestal foi mudada para assentamentos e terras áridas de 1988 a 2018. O Índice de Vegetação com Diferença Normalizada (NDVI) foi calculado para 1988, 1998, 2008 e 2018. Com base na análise do NDVI, o desmatamento total ao longo do tempo foi de 166,29 km 2 nos últimos 30 anos (1988-2018) com percentual de desmatamento de 43,66 % de área perdida. As imagens Landsat têm resolução de 30 metros e pequenas mudanças de área florestal não podem ser detectadas pelas imagens Landsat, assim, produtos de alta resolução podem detectar mais desmatamento comparativamente.

ABSTRACT The present research evaluated spatio-temporal change in the sub-tropical forest of district Malakand through Remote Sensing and GIS techniques. The main objective was to identify different land cover classes and to determine temporal changes in forest cover in the study area. This study was based on the two different classification techniques for the land cover classification. In this study, four Landsat images were acquired with the interval of 10 years from 1988 to 2018. The maximum likelihood classification and Minimum distance classification was applied on all the four images step by step. The total area of district Malakand was recorded as 975.32 km2. Regarding percent wise area coverage Forest covered 22.1 % of the total area while other classes' settlements, agriculture, barren land and water have covered 17.7, 23.3, 33 and 3.9 % respectively in 1988. Whereas in 2018, percent wise area coverage forest covered 9.3 % of the total area although other classes' settlements, agriculture, barren land and water have covered 33.8, 22.3, 31.8 and 3.7 respectively. The change in forest area over the time was 60.4 km2 which is equal to 6.2 % during 1998 to 2008 and ultimately overall deforestation was 124.4 km2 which is equal to 12.7 % loss of forest area lost from 1998 to 2018. Thus, the forest area was changed to settlements and barren lands from 1988 to 2018. Normalized Difference Vegetation Index (NDVI) was calculated for 1988, 1998, 2008 and 2018. Based on NDVI analysis, total deforestation over the time was 166.29 km2 in last 30 years (1988-2018) with percent deforestation of 43.66 % area lost. The Landsat images have 30 meters resolution and small forest area changes can not detected by Landsat images, thus high-resolution products can detect more deforestation comparatively.

RESUMEN La presente investigación evaluó el cambio espacio-temporal en el bosque subtropical del distrito de Malakand mediante técnicas de teledetección y SIG. El objetivo principal era identificar las diferentes clases de cobertura del suelo y determinar los cambios temporales de la cobertura forestal en el área de estudio. Este estudio se basó en dos técnicas de clasificación diferentes para la clasificación de la cubierta del suelo. En este estudio, se adquirieron cuatro imágenes Landsat con un intervalo de diez años desde 1988 hasta 2018. La clasificación de máxima verosimilitud y la clasificación de mínima distancia se aplicaron a las cuatro imágenes paso a paso. La superficie total del distrito de Malakand se registró como 975,32 km2. En lo que respecta a la cobertura porcentual de la superficie, el bosque cubrió el 22,1 % de la superficie total, mientras que los asentamientos, la agricultura, las tierras baldías y el agua cubrieron el 17,7, el 23,3, el 33 y el 3,9 % respectivamente en 1988. Durante el año 2018, el bosque cubrió el 9,3 % de la superficie total, así también los asentamientos de otras clases, la agricultura, la tierra estéril y el agua han cubierto el 33,8, 22,3, 31,8 y 3,7 respectivamente. El cambio en la superficie forestal a lo largo del tiempo fue de 60,4 km2, lo que equivale a un 6,2 % durante el período 1998-2008 y, en última instancia, la deforestación global fue de 124,4 km2, lo que equivale a una pérdida del 12,7 % de la superficie forestal perdida entre 1998 y 2018. Por lo tanto, la superficie forestal se transformó en asentamientos y tierras baldías de 1988 a 2018. Se calculó el índice de vegetación de diferencia normalizada (NDVI) para 1988, 1998, 2008 y 2018. Según el análisis del NDVI, la deforestación total a lo largo del tiempo fue de 166,29 km2 en los últimos 30 años (1988-2018), con un porcentaje de deforestación del 43,66 % de superficie perdida. Las imágenes Landsat tienen una resolución de 30 metros y los cambios en las áreas forestales pequeñas no pueden ser detectados por las imágenes Landsat, a diferencia de los productos de alta resolución que pueden detectar más deforestación en comparación.

Resumo: Tanto a hidrólise de proteínas quanto de amido contribui para a mobilização eficaz das reservas para desencadear a germinação das sementes. Estudamos a atividade de enzimas hidrolíticas na germinação de sementes de feijão mungo (Vigna radiata) expostas ao estresse de cádmio a 0, 25, 50, 75, 100 mg.L-1. A exposição ao estresse por Cd diminuiu a taxa de germinação das sementes e as características de crescimento inicial das plântulas, incluindo comprimento de raiz e parte aérea e biomassa fresca e seca da planta em comparação com o controle. Os efeitos adversos do Cd foram mais evidentes no comprimento do caule do que no comprimento da raiz. As atividades de α-amilase e protease de plântulas exibiram reduções significativas com o aumento da dose de Cd. Também observamos redução induzida por Cd em proteínas solúveis totais e açúcares, enquanto a concentração de aminoácidos livres exibiu um aumento. Em síntese, uma diminuição no processo de hidrólise de carboidratos de reserva, proteínas e translocação de reserva prejudicada contribuiu para a inibição da germinação das mudas e características de crescimento inicial.

Abstract: Both protein and starch hydrolysis contribute to the effective mobilization of seed reserves to trigger seed germination. We studied the activities of hydrolytic enzymes in germinating seeds of mung bean (Vigna radiata) exposed to cadmium stress at 0, 25, 50, 75, 100 mg.L-1. Exposure to Cd stress decreased the seed germination rate and early seedling growth traits, including root and shoot length and plant fresh and dry biomass compared to control. The adverse effects of Cd were more prominent in terms of shoot length than root length. Seedling α-amylase and protease activities exhibited significant reductions with increasing Cd dose. We also recorded Cd-induced reduction in total soluble proteins and sugars while the concentration of free amino acids exhibited an increase. Above all, a decrease in the hydrolysis process of reserve carbohydrates, proteins and impaired reserve translocation contributed to the inhibition of seedlings’ germination and early growth traits.

[RESUMO] A nabumetona é usada na redução da dor e inflamação da artrite reumática. No presente estudo, o efeito imunomodulador é investigado em camundongos. O grupo de controle recebeu solução salina via oral como placebo. Nabumetona foi administrada oralmente via gavagem em dois grupos de tratamentos com doses de 14mg/kg.b.w. e 28mg/kgb.w., respectivamente. Foram realizados ensaios de hemaglutinação (HA), placa hemolítica de Jerne e letalidade dos camundongos. No ensaio HA, o grau foi significativamente menor nos grupos de tratamento com nabumetoma (P< 0.001). No ensaio de formação de placa hemolítica de Jerne houve redução significativa (P< 0.001) no número de placas em grupos tratados com nabumetoma comparado ao controle. No ensaio de letalidade dos camundongos houve diferença significativa no grau de mortalidade de camundongos no grupo de controle e grupos tratados com nabumetoma (P< 0.001). Portanto, conclui-se que a Nabumetoma suprime a resposta imune humoral em camundongos.

ABSTRACT Nabumetone is used to reduce the pain and inflammation in rheumatoid arthritis. In the current study, immunomodulatory effect of Nabumetone is investigated in mice. The control group was administered normal saline orally as placebo. Nabumetone was administered orally via gavage in two treatment groups at 14mg/kg.b.w. doses and 28mg/kgb.w., respectively. Haemagglutination (HA) assay, Jerne hemolytic plaque and mice lethality assays were applied. In HA assay, the titer was significantly decreased in Nabumetone treatment groups (P< 0.001). In Jerne hemolytic plaque formation assay, there was a significant reduction (P< 0.001) in number of plaques in Nabumetone treated groups when compared with control. In mice lethality assay, there was a significant difference in mortality ratio of mice in control and Nabumetone treated groups (P< 0.001). Therefore, it is concluded that Nabumetone suppresses the humoral immune response in mice.

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Anesthetics are an indispensable prerequisite for surgical intervention and pharmacological animal studies. The objective of present study was to optimize the dose of ketamine (K) and xylazine (X) along with atropine sulfate (A) in order to achieve surgical tolerance in BALB/c mice. Several doses of ketamine (100, 150, 200 mg/kg) and xylazine (10, 15, 20 mg/kg) were mixed and combination of nine doses (K/X: 100/10, 100/15, 100/20, 150/10, 150/15, 150/20, 200/10,200/15,200/20) were evaluated (n=9 per combination). A constant dose of atropine (0.05 mg/kg) was also used to counter side effect. Time-related parameters were evaluated on the basis of reflexes. KX at dose 200/20 mg/kg produced surgical tolerance in all nine mice with duration 55.00±6.87 minutes. The induction time 0.97±0.09 minutes, sleeping time 90.67±5.81 minutes and immobilization time (102.23±6.83 minutes) were significantly higher than all combination. However, this combination was considered unsafe due to 11 % mortality. While, KX at dose 200/15 mg/kg results in none of the mortality, so was considered as safe. Moreover, this combination produces surgical tolerance in 89 % mice with duration (30.00±7.45 minutes). It was concluded that KX at dose 200/15 mg/kg along with atropine 0.05 mg/kg is safe for performing surgical interventions in BALB/c mice.

The aim of the present research work was to investigate the enzyme inhibitory potential of some new sulfonamides having benzodioxane and acetamide moieties. The synthesis was started by the reaction of N-2,3-dihydrobenzo[1,4]-dioxin-6-amine (1) with 4-methylbenzenesulfonyl chloride (2) in the presence of 10% aqueous Na2CO3 to yield N-(2,3-dihydrobenzo[1,4]-dioxin-6-yl)-4-methylbenzenesulfonamide (3), which was then reacted with 2-bromo-N-(un/substituted-phenyl)acetamides (6a-l) in DMF and lithium hydride as a base to afford various 2-{2,3-dihydro-1,4-benzodioxin-6-yl[(4-methylphenyl)sulfonyl]amino}-N-(un/substituted-phenyl)acetamides (7a-l). All the synthesized compounds were characterized by their IR and 1H-NMR spectral data along with CHN analysis data. The enzyme inhibitory activities of these compounds were tested against a-glucosidase and acetylcholinesterase (AChE). Most of the compounds exhibited substantial inhibitory activity against yeast a-glucosidase and weak against AChE. The in silico molecular docking results were also consistent with in vitro enzyme inhibition data.

Glucuronoxylan hydrogel (GXH) isolated from M. pudica seeds was assessed for acute toxicology in albino mice that were alienated into four groups. Three groups, i.e., II, III and IV received GXH at a dose of 1, 2 and 5 g/kg, respectively while group I was retained untreated and provided routine diet. After administering GXH, mice were examined for vomiting, diarrhea, allergy and tremors for 8 h. All animals were carefully observed for food and water consumption at 1, 2, 3, 7 and 14 day after administering GXH. At the end of studies, blood samples were drawn for investigation of hematological and biochemical parameters. All animals were sacrificed, relative body weight of vital organs was calculated and their histopathology was studied. It was concluded that there was insignificant difference in body weight, behavioral pattern, food and water intake among treated and control groups. Haematology and biochemistry of blood samples from all groups were found analogous. Histopathological evaluation of vital body organs exhibited no lesions in all groups. Ocular, cardiac and dermal safety of GXH was also established on albino rabbits.

ABSTRACT Linseed hydrogel (LSH) was evaluated by acute toxicity for its potential application in oral drug delivery design. White albino mice and rabbits were divided in four groups (I-IV) and different doses of LSH (1, 2 and 5 g/kg body weight) were given except to the control group (I) that was left untreated. Rabbits were monitored for eye irritation, acute dermal toxicity and primary dermal irritation, whereas, body weight, food and water consumption, hematology and clinical biochemistry, gross necropsy and histopathology of vital organs were scrutinized in mice. LSH was considered safe after eye irritation test as no adverse signs or symptoms were seen in the eye. In dermal toxicity and irritation study, skin of treated rabbits was found normal in color without any edema or erythema. After oral administration, there was no sign of any abnormalities in treated group animals (II-IV). The hematology and clinical biochemistry of treated group animals was comparable with the control group. Histopathology of vital organs has not shown any lesion or abnormalities. In the light of these outcomes, it can be concluded that LSH is not a hazardous biomaterial and could be incorporated as an excipient in oral and dermal preparations.

Abstract It is understood that drugs regardless of their order of administration can exhibit drug interactions. Established on the fact that treatment of hypertension may last for decades and prolong usage of multiple drug regimen may induce substantial pathophysiological changes. Hence, This study was designed to evaluate the possible synergistic toxic effects of anti-hypertensive (carvedilol), and anti-inflammatory drug (celecoxib) alone and in combinations. Well-established MTT assay, Single Cell Gel Electrophoresis (SCGE) and Ames assay were employed to evaluate the toxicity at cellular level. Results from MTT assay on Vero cell line revealed that drug combinations have more pronounced anti-proliferative activity with combine IC50 value of 13.7:47.8 µg/mL. Likewise, exposure of peripheral blood mononuclear cells with drug combinations revealed significant (P<0.05) DNA damage (Class 3) in a dose dependent manner at concentrations ≥ 0.78: 2.34 µg/mL. However, carvedilol and celecoxib were non mutagenic against either mutant strain (TA 100 and TA 98) and combinations have also shown mild to moderate mutagenic potential. Nevertheless, upon addition of metabolic activation enzyme, concentration <12.5:37.5 µg/plate exhibited significant (P<0.05) mutagenicity against both tester strains. In conclusion, this study provides additional genotoxicity and mutagenicity data that could be used in considering options for formulating regimens with reduced mutagenic potential.

ABSTRACT Indole-based tetraarylimidazoles were prepared by multicomponent reaction of substituted 2-arylindole-3-carbaldehydes, benzil, substituted anilines and ammonium acetate in acetic acid. The new compounds were evaluated for their antiurease and antioxidant activity. The synthesized compounds exhibited potent antiurease activity.