Renal resistive index by point of care ultrasound to predict sepsis associated acute kidney injury in critically ill children.

BACKGROUND: Sepsis associated acute kidney injury (AKI) is linked with adverse outcomes in the PICU. Doppler-based renal resistive index (RRI) has shown promising results in adults for prediction of AKI. We aimed to explore the performance of RRI in children with sepsis. METHODS: This prospective observational study (March - November 2022) included children aged 1-12 years with sepsis admitted to the PICU. RRI and urine neutrophil gelatinase associated lipocalin (NGAL) were measured within 12 h of admission. Children were followed up for 3 days. AKI (new and persistent) was defined as any child with KDIGO stage 2 or 3 AKI on day 3. RESULTS: We enrolled 90 children but included 79 in final analysis. Two thirds (n = 53, 67%) had septic shock. Median (IQR) age was 6.2 years (4.1-9.2). RRI decreased with increasing age. Twenty-six (33%) children had AKI on day 3. Mean (SD) RRI was higher in the AKI group [0.72 (0.08) vs. 0.65 (0.07), p < 0.001].The area under ROC curve for RRI to detect AKI among the 1-4 year old group was 0.75 (95% CI:0.51, 0.98; p = 0.05) and among the 5-12 year old group was 0.76 (0.62, 0.89; p = 0.001). An RRI 0.71 predicted AKI with 100% sensitivity and 46.2% specificity among the 1-4-year-old group and RRI 0.69 predicted it with 70% sensitivity and 77.5% specificity in the 5-12-year-old group. RRI and eGFR at admission were independent predictors of AKI on multivariable analysis. Urine NGAL 94.8 ng/ml predicted AKI with 76.9% sensitivity and 77.4% specificity and AUROC was 0.74 (0.62, 0.86) among the 1-12-year-old group. CONCLUSIONS: RRI values varied with age. RRI showed good diagnostic accuracy to detect new/persistent AKI on day 3 in children with sepsis; however, it was less precise as an independent predictor.

Augmented mannose-binding lectin levels in primary membranous nephropathy: A pilot study.

There is evidence to suggest that M-type phospholipase A2 (PLA2R) antibodies activate the mannose-binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy-confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow-mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p < .01). MBL levels decreased significantly after immunosuppressive therapy (p = .04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p = .01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients.

The therapeutic potential of typical plant-derived compounds for the management of metabolic disorders.

Obesity and Type 2 diabetes are prevalent metabolic dysfunctions that present significant health challenges worldwide. Available cures for these ailments have constraints with accompanying unwanted effects that persistently exist. Compounds originated from plants have recently been introduced as hopeful remedies to treat metabolic disorders because of their diverse pharmacological activities. This detailed observation gives an introduction into the treatment capacity of plant-derived compounds regarding metabolic syndromes while analyzing various groups alongside their performance in this field despite unique mechanisms designed by nature itself. Interestingly, this study provides some examples including curcumin, resveratrol, quercetin, berberine, epigallocatechin gallate (EGCG), and capsaicin, which highlights potential therapeutic impacts for future testing. However, current clinical trials inspecting human studies investigating efficacies concerning metabolism challenge present limitations. Finally, the review weighs up bad reactions possibly inflicted after administering plant-originated materials though suggestive insights will be provided later. Above all, it outlines the chance to identify novel therapies encapsulated within natural substances based upon recent developments could hold significant promise toward managing misplaced metabolisms globally.

Antimicrobial-Resistant Escherichia coli, Enterobacter cloacae, Enterococcus faecium, and Salmonella Kentucky Harboring Aminoglycoside and Beta-Lactam Resistance Genes in Raw Meat-Based Dog Diets, USA.

The practice of feeding raw meat-based diets to dogs has grown in popularity worldwide in recent years. However, there are public health risks in handling and feeding raw meat-based dog diets (RMDDs) to dogs since there are no pathogen reduction steps to reduce the microbial load, which may include antimicrobial-resistant pathogenic bacteria. A total of 100 RMDDs from 63 suppliers were sampled, and selective media were used to isolate bacteria from the diets. Bacterial identification, antimicrobial susceptibility testing, and whole-genome sequencing (WGS) were conducted to identify antimicrobial resistance (AMR). The primary meat sources for RMDDs included in this study were poultry (37%) and beef (24%). Frozen-dry was the main method of product production (68%). In total, 52 true and opportunistic pathogens, including Enterobacterales (mainly Escherichia coli, Enterobacter cloacae) and Enterococcus faecium, were obtained from 30 RMDDs. Resistance was identified to 19 of 28 antimicrobials tested, including amoxicillin/clavulanic acid (23/52, 44%), ampicillin (19/52, 37%), cephalexin (16/52, 31%), tetracycline (7/52, 13%), marbofloxacin (7/52, 13%), and cefazolin (6/52, 12%). All 19 bacterial isolates submitted for WGS harbored at least one type of AMR gene. The identified AMR genes were found to mediate resistance to aminoglycoside (gentamicin, streptomycin, amikacin/kanamycin, gentamicin/kanamycin/tobramycin), macrolide, beta-lactam (carbapenem, cephalosporin), tetracycline, fosfomycin, quinolone, phenicol/quinolone, and sulfonamide. In conclusion, the results of this study suggest that feeding and handling RMDDs may pose a significant public health risk due to the presence of antimicrobial-resistant pathogens, and further research and intervention may be necessary to minimize these risks.

Lyophilized mixed micelles of exemestane: A novel paradigm to improve its absorption and anticancer activity.

The objective of the present investigation was to prepare and optimize lyophilized mixed micelles (Lyp-EXE-MMs) of exemestane (EXE) with improved solubility, bioavailability, in vivo anticancer activity, and physical stability, by using various cryoprotectants. The prepared lyophilized mixed micelles were characterized by various techniques, including dynamic light scattering, zeta potential, powdered X-ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance (1 H NMR), transmission electron microscopy (TEM), and so on. Thereafter, the lyophilized micelles were evaluated for ex vivo permeation, in vitro drug release and gene/protein expression (RT-PCR and Western blot analysis) in MCF-7 breast cancer cells. The developed formulation was also investigated for its in vivo anticancer study in BALB/c mice with induced breast cancer. The use of trehalose (10% w/w) was proven to be a suitable cryoprotectant for these micelles. Lyp-EXE-MMs were spherical, with a particle size of 42.9 ± 3.8 nm and a polydispersity index of 0.307 ± 0.122. Furthermore, % drug loading and % entrapment efficiency were found to be 5.8 ± 1.4 and 89.1 ± 1.1, respectively. Lyp-EXE-MMs showed sustained release behavior as compared to EXE-suspensions in SGF/SIF (pH 1.2 and 6.8) and phosphate buffer saline (pH 7.4). The micelles induced apoptosis through the regulation of BAX, BCL2, Caspase-3, p53, and CYP19A1 in MCF-7 cells, which was correlated to enhanced ex vivo drug permeation. Animals receiving EXE micelle formulations showed reduced tumor volume and improved survivability and pharmacokinetic parameters as compared to pure EXE. Lyp-EXE-MMs were found to withstand simulated harsh conditions of SGF/SIF during stability studies. The fabricated EXE micellar preparations hold a promising approach for breast cancer treatment.

Ag and Au Nanoparticles as Color Indicators for Monomer/Micelle-Nanoparticle Interactions.

Ag and Au nanoparticles (NPs) were used as color indicators to determine the monomer/micelle adsorption on the NP surface. A simple methodology based on the color change of Ag/Au NPs upon interacting with surface-active molecules was developed. A contrasting color change occurred when NPs interact with the monomer/micelle. This was demonstrated by monitoring the adsorption behavior of a series of Gemini surfactants. UV-visible measurements showed a large change in the intensity and wavelength of Ag/Au NP absorbance upon the surface adsorption of the monomer/micelle of Gemini surfactants. The mechanism of surface adsorption and molecular orientation on the solid-liquid interface of NPs was determined by performing the FT-IR and XPS measurements. Results demonstrated that sharp color changes from yellow to red for Ag NPs and red to purple for Au NPs happened when the Gemini surfactant monomer/micelle adsorbs on the NP surface. This colorimeter-based methodology highlighted the applicability of Ag/Au NPs in complex media where such NPs frequently encounter surface-active molecules.

The Childhood and Adolescent Sleep Evaluation Questionnaire (CASEQ): Development and validation of an ICSD-3-based screening instrument, a community and hospital-based study.

Sleep disorders are common in children and adolescents. Polysomnography is the gold-standard diagnostic method; however, it is a tedious procedure. The objective of the study was to develop a screening questionnaire for sleep problems based on International Classification of Sleep Disorders-3 in children and adolescents, and validate it with clinical evaluation and polysomnography. A questionnaire was developed in English and Hindi with content validation by eight multidisciplinary experts. Respondents were parents of children and adolescents, aged 2-18 years, recruited from a public school and a tertiary care teaching hospital in north India. A subset of these children and adolescents underwent overnight polysomnography and detailed clinical evaluation within 4 weeks of applying the questionnaire. The questionnaire, named Childhood and Adolescent Sleep Evaluation Questionnaire, contains primary questions covering all subgroups of disorders under International Classification of Sleep Disorders-3, and secondary questions on sleep hygiene and comorbidities. The questionnaire was filled by 750 respondents, out of which 100 cases underwent polysomnography and clinical evaluation. The internal consistency in the form of Cronbach's α was 0.8 for the questionnaire. The sensitivity, specificity, positive and negative predictive values for the questionnaire in identifying those with sleep problems compared with detailed clinical and polysomnographic evaluations were 85%, 100%, 100% and 62.5%, respectively. For individual subgroups of disorders, the sensitivity, specificity, positive and negative predictive values varied between 72.7% and 100%, 88.9% and 100%, 62.5% and 100% and 81.6% and 100%, respectively. The Childhood and Adolescent Sleep Evaluation Questionnaire has good psychometric properties, moreover, its simplicity and translatability make it ideal for use at the community and hospital settings.

Primary cutaneous gamma-delta T-cell lymphoma masquerading as leukemia cutis in a patient recently diagnosed with small lymphocytic lymphoma: Clues to the diagnosis.

A 54-year-old man recently diagnosed with small lymphocytic lymphoma (SLL) had waxing and waning, indurated, erythematous plaques on his legs, with leukopenia and anemia disproportionate to the SLL burden in his marrow and pelvic lymph nodes. Punch biopsy of a plaque performed to evaluate for leukemia cutis revealed a lymphocytic lobular-panniculitis-like infiltrate resembling lupus panniculitis, but a preponderance of CD8+/Ki-67+ T-cells surrounding adipocytes raised concern for subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Additional immunohistochemistry (IHC) studies showed that the adipotropic T-cells expressed TCR-gamma, supporting the rare, unexpected diagnosis of Primary cutaneous gamma-delta T-cell lymphoma (PCGDTCL). The patient subsequently met diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). PCGDTCL is an aggressive, HLH-associated lymphoma requiring different management than SPTCL and SLL. This case illustrates how PCGDTCL can co-exist with B-cell lymphoma and resemble panniculitis on biopsies. PCGDTCL and SPTCL should enter the differential diagnosis whenever patients present with the constellation of lobular panniculitis and unexplained cytopenias. In the present case, close clinicopathologic correlation and judicious use of IHC on a small sample allowed for a prompt diagnosis.

In vitro propagation and secondary metabolite production in Gloriosa superba L.

Gloriosa superba L., commonly known as "gloriosa lily," "glory lily," and "tiger claw," is a perennial climber in the Liliaceae family. This plant is used in African and Southeast Asian cultures as an ayurvedic medicinal herb to treat various health conditions. Its main bioactive component is colchicine, which is responsible for medicinal efficacies as well as poisonous properties of the plant. A high market demand, imprudent harvesting of G. superba from natural habitat, and low seed setting have led scientists to explore micropropagation techniques and in vitro optimization of its phytochemicals. Plant growth regulators have been used to induce callus, root, and shoot organogenesis, and somatic embryogenesis in vitro. This review is aimed at presenting information regarding the occurrence, taxonomic description, phytochemistry, micropropagation, in vitro secondary metabolite, and synthetic seed production. The data collected from the existing literature, along with an analysis of individual study details, outcomes, and variations in the reports, will contribute to the development of biotechnological strategies for conservation and mass propagation of G. superba. KEY POINTS: • Latest literature on micropropagation of Gloriosa superba. • Biotechnological production and optimization of colchicine. • Regeneration, somatic embryogenesis, and synthetic seed production.

Recognition of Leaf Disease Using Hybrid Convolutional Neural Network by Applying Feature Reduction.

Agriculture is crucial to the economic prosperity and development of India. Plant diseases can have a devastating influence towards food safety and a considerable loss in the production of agricultural products. Disease identification on the plant is essential for long-term agriculture sustainability. Manually monitoring plant diseases is difficult due to time limitations and the diversity of diseases. In the realm of agricultural inputs, automatic characterization of plant diseases is widely required. Based on performance out of all image-processing methods, is better suited for solving this task. This work investigates plant diseases in grapevines. Leaf blight, Black rot, stable, and Black measles are the four types of diseases found in grape plants. Several earlier research proposals using machine learning algorithms were created to detect one or two diseases in grape plant leaves; no one offers a complete detection of all four diseases. The photos are taken from the plant village dataset in order to use transfer learning to retrain the EfficientNet B7 deep architecture. Following the transfer learning, the collected features are down-sampled using a Logistic Regression technique. Finally, the most discriminant traits are identified with the highest constant accuracy of 98.7% using state-of-the-art classifiers after 92 epochs. Based on the simulation findings, an appropriate classifier for this application is also suggested. The proposed technique's effectiveness is confirmed by a fair comparison to existing procedures.

Screening the elite chemotypes of Gloriosa superba L. in India for the production of anticancer colchicine: simultaneous microwave-assisted extraction and HPTLC studies.

BACKGROUND: Gloriosa superba L. (Colchicaceae) is a high-value medicinal plant indigenous to Africa and Southeast Asia. Its therapeutic benefits are well-established in traditional medicines including Ayurveda. It is well known for its natural bioactive compound colchicine which exhibits a wide range of pharmacological activities i.e. rheumatism, gout and was also introduced into clinical practices. The increasing demand as well as its illegal harvesting has brought this valuable plant under threatened category. METHODS: The present investigation describes a microwave assisted extraction (MAE) strategy coupled with a densitometric-high performance thin layer chromatographic (HPTLC) methodology for the analysis of colchicine from 32 different populations of G. superba. A Box-Behnken statistical design (3 level factor) has been employed to optimize MAE, in which power of microwave, time of irradiation, aqueous ethanol and pH were used as independent variables whereas colchicine was used as the dependent variables. Chromatography was carried out on Silica gel 60 F254 TLC plates with toluene: methanol, 85:15 (v/v) being used as solvent system. Densitometric measurement was performed at λ=254 nm following post-derivatization (10% methanolic sulphuric acid). RESULTS: Optimal conditions for extraction to obtain the maximum colchicine yield was found to be 7.51 mg g- 1 which was very close to be predicted response 7.48 mg g- 1 by maintaining microwave power (460 W), irradiation time (6.4 min), aqueous ethanol-30, pH -3. Colchicine content ranged between 2.12-7.58 mg g- 1 among 32 G. superba populations in which only three chemotypes viz. GS- 1, GS- 3, and GS- 2 collected from West Bengal and Sikkim, respectively exhibited maximum yield of colchicine. CONCLUSION: Therefore, this newly developed optimized MAE coupled with HPTLC densitometry methodology not only quantifies colchicine in order to identify elite chemotypes of G. superba, but it also encourages in selecting high yielding populations of the plants for industrial use and economic boost for the farmers. This validated, simple and reproducible HPTLC protocol is being used for the first time to estimate colchicine from natural populations of G. superba obtained from 32 different geographical regions of India.

Small lymphocytic lymphoma mimicking primary cutaneous marginal zone lymphoma with colonization of germinal center follicles.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is primarily a disease of older adults and is occasionally an incidental finding on skin biopsies accompanying epithelial neoplasms and insect bite reactions. In rare instances, however, it produces leukemic infiltrates showing clinical and histopathologic overlap with primary cutaneous B-cell lymphomas including primary cutaneous marginal zone lymphoma (PCMZL). Even less frequently, such findings serve as the initial disease manifestation. We present an exceptional case of a 61-year-old man with no past medical history whose clinical and histopathologic findings raised consideration for PCMZL with abnormal B-cells colonizing germinal center follicles; however, faint CD5 and CD23 co-expression raised the differential diagnosis of CLL/SLL. In light of an ambiguous clinical presentation with widely distributed papules and plaques, peripheral blood flow cytometry was also performed, revealing high count of CLL-type monoclonal B lymphocytosis. Subsequent workup revealed bone marrow involvement and mesenteric lymphadenopathy, supporting the diagnosis of SLL. Follicular colonization by SLL has not been previously reported. Our case underscores the importance of subtle immunophenotypic clues and correlations with clinical and radiologic findings in the workup of B-cell lymphomas presenting in the skin.

Biotechnological interventions and genetic diversity assessment in Swertia sp.: a myriad source of valuable secondary metabolites.

The genus Swertia (Family: Gentianaceae) has cosmopolitan distribution which is present in almost all the continents except South America and Australia. Swertia genus has been renowned as one of the potent herbal drugs in the British, American, and Chinese Pharmacopeias as well as well-documented in the Indian traditional medicinal systems, viz. Ayurveda, Siddha, and Unani. Many species of this genus have therapeutic properties and have been used traditionally in the treatment of a number of health ailments viz. hepatitis, diabetes, inflammation, bacillary dysentery, cancer, malaria, fever etc. This genus is industrially important medicinal plant that has been used as a principal component in numerous marketed herbal/ polyherbal formulations. Medicinal usage of Swertia is endorsed to the miscellaneous compounds viz. xanthones, irridoids, seco-irridoids, and triterpenoids. A chain of systematic isolation of bio-active compounds and their diverse range of pharmacological effects during last 15-20 years proved this genus as industrially important plant. Due to the various practices of the Swertia species, annual demand is more than 100 tons per year for this important herb which is continuously increasing 10% annually. The market value rises 10% by the year as there is increased demand in national and international market resulted in adulteration of many Swertia spp. due to paucity of agricultural practices, exomorphological, phytochemical, and molecular characterization. Thus, efficient biotechnology methods are prerequisite for the mass production of authentic species, sustainable production of bio-active compounds and ex situ conservation. A chain of systematic biotechnological interventions in Swertia herb during last 20 years cover the assessment of genetic diversity, in vitro sustainable production of bio-active compounds and mass propagation of elite genotypes via direct and indirect organogenesis. This review attempts to present the comprehensive assessment on biotechnological process made in Swertia over the past few years. KEY POINTS: • Critical and updated assessment on biotechnological aspects of Swertia spp. • In vitro propagation and genetic diversity assessment in Swertia spp. • Biosynthesis and sustainable production of secondary metabolites in Swertia spp.

Biotechnological interventions of in vitro propagation and production of valuable secondary metabolites in Stevia rebaudiana.

Plant cell and tissue culture makes provision of a sustainable and nature-friendly strategy for the production of secondary metabolites, and modern progress in gene editing and genome engineering provides novel possibilities to improve both the qualitative and quantitative aspects of such phytochemicals. The ever-expanding quest for plant-based medicine to treat diabetes facilitates large-scale cultivation of Stevia rebaudiana to enhance the yield of its much-coveted low-calorie sweetener glycosides. The potential to process stevia as a "natural" product should enhance the acceptance of steviosides as a natural calorie-free sweetener especially suitable for use in diabetic and weight control drinks and foods. Besides sweetener agents, S. rebaudiana is a potent source of many antioxidant compounds and is used to cure immunodeficiencies, neurologic disorders, inflammation, diabetes mellitus, Parkinson's disease, and Alzheimer's disease. This comprehensive review presents the research outcomes of the many biotechnological interventions implicated to upscale the yield of steviol glycosides and its derivatives in in vitro cell, callus, tissue, and organ cultures with notes on the use of bioreactor and genetic engineering in relation to the production of these valuable compounds in S. rebaudiana. KEY POINTS: • Critical and updated assessment on sustainable production of steviol glycosides from Stevia rebaudiana. • In vitro propagation of S. rebaudiana and elicitation of steviol glycosides production. • Genetic fidelity and diversity assessment of S. rebaudiana using molecular markers.

Statistical interpretation of environmental influencing parameters on COVID-19 during the lockdown in Delhi, India.

The novel coronavirus disease is known as COVID-19, which is declared as a pandemic by the World Health Organization during March 2020. In this study, the COVID-19 connection with various weather parameters like temperature, wind speed, and relative humidity is investigated and the future scenario of COVID-19 is predicted based on the Gaussian model (GM). This study is conducted in Delhi, the capital city of India, during the lowest mobility rate due to strict lockdown nationwide for about two months from March 15 to May 17, 2020. Spearman correlation is applied to obtain the interconnection of COVID-19 cases with weather parameters. Based on statistical analysis, this has been observed that the temperature parameter shows a significant positive trend during the period of study. The number of confirmed cases of COVID-19 is fitted with respect to the number of days by using the Gaussian curve and it is estimated on the basis of the model that maximum cases will go up to 123,886 in number. The maximum number of cases will be observed during the range of 166 ± 36 days. It is also estimated by using the width of the fitted GM that it will take minimum of 10 months for the complete recovery from COVID-19. Additionally, the linear regression technique is used to find the trend of COVID-19 cases with temperature and it is estimated that with an increase in temperature by 1 °C, 30 new COVID-19 cases on daily basis will be expected to observe. This study is believed to be a preliminary study and to better understand the concrete relationship of coronavirus, at least one complete cycle is essential to investigate. The laboratory-based study is essential to be done to support the present field-based study. Henceforth, based on preliminary studies, significant inputs are put forth to the research community and government to formulate thoughtful strategies like medical facilities such as ventilators, beds, testing centers, quarantine centers, etc., to curb the effects of COVID-19.

Allicin Overcomes Hypoxia Mediated Cisplatin Resistance in Lung Cancer Cells through ROS Mediated Cell Death Pathway and by Suppressing Hypoxia Inducible Factors.

BACKGROUND/AIMS: The hypoxic microenvironment in NSCLC has been widely accepted as a contributor to both therapeutic resistance and tumor progression. In this study, we have explored Allicin, a key organosulfur compound present in garlic for its previously unreported effectiveness in the heterogeneous hypoxic tumor microenvironment of NSCLC. METHODS: The effect of Allicin on the viability of NSCLC cells was determined by MTT assay. To determine the migration rate of treated cells compared to the control, scratch and transwell migration assays were performed. Flowcytometry was done to explore cell cycle distribution, apoptosis and ROS production in cells. Fluorescence microscopy was used to examine autophagy and DNA damage in cells. Dot blot was done to check genome wide methylation. RNA expression was detected by RT-PCR and protein expression by western blotting. RESULTS: Allicin significantly decreases cell viability, proliferation and migration of NSCLC cells in both normoxia and hypoxia. It elicits both apoptosis and autophagy pathway in A549 cells by ROS accumulation and facilitating S/G2-M phase arrest in both normoxia as well as hypoxia. We suggest that ROS/MAPK and ROS/JNK signaling pathway together govern the cytotoxic effect of allicin in NSCLC cells. Notably, allicin suppresses the expression of HIF-1α and HIF-2α in hypoxic cells, pointing towards a mechanism of its effectiveness in hypoxia. A long term passive demethylation was observed, with decreased mC and no change in TET expression, thereby ruling out active demethylation by allicin. Furthermore, allicin synergistically enhances growth inhibitory activity of low dose cisplatin to effectively overcome hypoxia induced cisplatin resistance in A549 cells. CONCLUSION: Altogether, our results elucidate a potential use of allicin in sensitizing hypoxic and chemoresistant NSCLC to cisplatin-based chemotherapy and provide new, affordable therapeutic strategy with reduced side effects.

Optimization of salicylic acid and chitosan treatment for bitter secoiridoid and xanthone glycosides production in shoot cultures of Swertia paniculata using response surface methodology and artificial neural network.

BACKGROUND: In this study, response surface methodology (RSM) and artificial neural network (ANN) was used to construct the predicted models of linear, quadratic and interactive effects of two independent variables viz. salicylic acid (SA) and chitosan (CS) for the production of amarogentin (I), swertiamarin (II) and mangiferin (III) from shoot cultures of Swertia paniculata Wall. These compounds are the major therapeutic metabolites in the Swertia plant, which have significant role and demand in the pharmaceutical industries. RESULTS: Present study highlighted that different concentrations of SA and CS elicitors substantially influenced the % yield of (I), (II) and (III) compounds in the shoot culture established on modified ½ MS medium (supplemented with 2.22 mM each of BA and KN and 2.54 mM NAA). In RSM, different response variables with linear, quadratic and 2 way interaction model were computed with five-factor-three level full factorial CCD. In ANN modelling, 13 runs of CCD matrix was divided into 3 subsets, with approximate 8:1:1 ratios to train, validate and test. The optimal enhancement of (I) (0.435%), (II) (4.987%) and (III) (4.357%) production was achieved in 14 days treatment in shoot cultures of S. paniculata elicited by 9 mM and 12 mg L- 1 concentrations (SA) and (CS). CONCLUSIONS: In optimization study, (I) show 0.170-0.435%; (II) display 1.020-4.987% and (III) upto 2.550-4.357% disparity with varied range of SA (1-20 mM) and CS (1-20 mg L- 1). Overall, optimization of elicitors to promote secoiridoid and xanthone glycoside production with ANN modeling (r2 = 100%) offered more significant results as compared to RSM (r2 = 99.8%).

New coumarin-benzotriazole based hybrid molecules as inhibitors of acetylcholinesterase and amyloid aggregation.

A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 µΜ) with mixed type inhibition scenario. Structure-activity relationship revealed that three-carbon alkyl chain connecting coumarin and triazole is well tolerable for inhibitory potential. Hybrids obtained from 4-hydroxycoumarin and 1-benzotriazole were most potent AChE inhibitors. The inhibitory potential of all compounds against butyrylcholinesterase was also evaluated but all showed negligible activity suggesting that the hybrid molecules are selective AChE inhibitors. 13b (most potent AChE inhibitor) also showed copper-induced Aß1-42 aggregation inhibition (34.26% at 50 µΜ) and chelating properties for metal ions (Cu2+, Fe2+, and Zn2+) involved in AD pathogenesis along with DNA protective potential against degenerative actions of OH radicals. Molecular modelling studies confirm the potential of 13b in blocking both PAS and CAS of AChE. In addition, interactions of 13b with Aß1-42 monomer are also streamlined. Therefore, hybrid 13b can act as an effective hit lead molecule for further development of selective AChE inhibitors as multifunctional anti-Alzheimer's agents.

Theoretical model for predicting thermoelectric properties of tin chalcogenides.

The global energy crisis demands the search for new materials for efficient thermoelectric energy conversion. Theoretical predictive modelling with experiments can expedite the global search of novel and ecoconscious thermoelectric materials. The efficiency of thermoelectric materials depends upon the thermoelectric figure of merit (ZT). In this perspective, we discuss the theoretical model to calculate thermoelectric properties. Different scattering mechanisms of electrons and phonons are calculated using a simple model for the fast prediction of thermoelectric properties. Thermoelectric properties based on the simple model have shown more than 90% agreement with the experimental values. Possibility to optimize the figure of merit by alloying, defects, nanostructuring and band convergence is also discussed for layered chalcogenides of tin. In the case of doped materials, ion-impurity scattering is found to be dominating over electron-phonon scattering and the power factor can be optimized by tuning the former scattering rate. For phonon transport, alloy scattering is found to be the most dominating among all other scattering mechanisms. Theoretically, it is found that in the temperature range between 300 K and 800 K, SnSe0.70S0.30 has the highest ZT with an efficiency of 17.20% with respect to Carnot efficiency. There could be 53.8% enhancement of the device efficiency in SnSe0.70S0.30 compared to experimentally reported SnSe0.50S0.50 in the medium temperature range (300 K to 800 K). Possible routes to achieve the best ZT in the medium temperature range are also discussed in this perspective.

Characteristics of 'sawtooth shunt' following anti-vascular endothelial growth factor for aggressive posterior retinopathy of prematurity.

OBJECTIVE: To explore the characteristics of 'sawtooth shunts (STS)' following intravitreal anti-vascular endothelial growth factors (anti-VEGF) for aggressive posterior retinopathy of prematurity (AP-ROP). DESIGN: Prospective observational study. METHODS: In a prospective observational study, 45 eyes of 24 babies receiving intravitreal anti-VEGF for AP-ROP or hybrid ROP were analyzed. Anti-VEGF molecule and doses: bevacizumab (0.62 mg or ½ IVB, n = 30 eyes; 0.25 mg or 1/5IVB, n = 9 eyes; 0.12 mg or 1/10 IVB, n = 1 eye); or ranibizumab (0.25 mg or ½IVR, n = 3 eyes; 0.1 mg or 1/5IVR, n = 2 eyes). They were followed every 1-2 week till disease regression with or without laser treatment. Development of STS, its variants, characteristics, timeline, and final outcomes was analyzed. RESULTS: STS occurred in 26 (57.7%) eyes at 1-6 weeks following anti-VEGF injections and persisted for 1-14 weeks. While the shunt regressed spontaneously in half of the treated eyes (n = 13) with anti-VEGF alone, the other half (n = 13) required additional laser because of either non-compliance (n = 9) or recurrence (n = 4). CONCLUSION: The STS was observed to be an important retinal vascular change seen in infants treated with intravitreal anti-VEGF at half adult doses. It warrants further studies to explore the association between STS and its association with disease recurrence or regression.