Search

The present study employs the Delphi method to devise a consensus-based protocol for utilizing integrated acupuncture in treating medial tibial stress syndrome (MTSS). Twenty acupuncture experts contributed opinions across six key themes, including diagnosis, acupuncture points, additional Traditional Oriental Medicine modalities, treatment rationale, treatment duration/frequency, and integration of yoga/naturopathic therapies. Consensus, defined as a 70% agreement or higher, was reached on all themes, reflecting a collective acknowledgment of the necessity for a holistic approach to MTSS management. The final protocol includes six diagnostic criteria, six acupuncture points, one additional modality, two Traditional Oriental Medicine therapies, four treatment rationales, and six yoga/naturopathic therapies. The present comprehensive protocol offers valuable guidance for healthcare professionals seeking an integrated approach to MTSS management.

Abstract Background Lignin and xylan are important determinants of cell wall structure and lignocellulosic biomass digestibility. Genetic manipulations that individually modify either lignin or xylan structure improve polysaccharide digestibility. However, the effects of their simultaneous modifications have not been explored in a similar context. Here, both individual and combinatorial modification in xylan and lignin was studied by analysing the effect on plant cell wall properties, biotic stress responses and integrity sensing. Results Arabidopsis plant co-harbouring mutation in FERULATE 5-HYDROXYLASE (F5H) and overexpressing Aspergillus niger acetyl xylan esterase (35S:AnAXE1) were generated and displayed normal growth attributes with intact xylem architecture. This fah1-2/35S:AnAXE1 cross was named as hyper G lignin and hypoacetylated (HrGHypAc) line. The HrGHypAc plants showed increased crystalline cellulose content with enhanced digestibility after chemical and enzymatic pre-treatment. Moreover, both parents and HrGHypAc without and after pre-treating with glucuronyl esterase and alpha glucuronidase exhibited an increase in xylose release after xylanase digestion as compared to wild type. The de-pectinated fraction in HrGHypAc displayed elevated levels of xylan and cellulose. Furthermore, the transcriptomic analysis revealed differential expression in cell wall biosynthetic, transcription factors and wall-associated kinases genes implying the role of lignin and xylan modification on cellular regulatory processes. Conclusions Simultaneous modification in xylan and lignin enhances cellulose content with improved saccharification efficiency. These modifications loosen cell wall complexity and hence resulted in enhanced xylose and xylobiose release with or without pretreatment after xylanase digestion in both parent and HrGHypAc. This study also revealed that the disruption of xylan and lignin structure is possible without compromising either growth and development or defense responses against Pseudomonas syringae infection.

Abstract Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i’s) in combination with chemotherapy have shown promising results in preclinical studies but have displayed minimal efficacy with substantial toxicity in clinical trials. To explore combinatorial strategies that can overcome these limitations, we perform an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identify thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a determinant of CHK1i sensitivity. We establish a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR inhibitor auranofin, an approved anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, we show a pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.

Objective: The objectives of this study were to explore the cytotoxic potential of different fractions (Hexane, chloroform, ethyl acetate and methanol) of Plumbago zeylanica L. root powder. Methodology: In this study, PzMH, PzMC, PzME, and PzMM fractions from the root powder of P. zeylanica were obtained through the cold maceration technique. The cytotoxic properties of these fractions on MG-63 cells were assessed using the MTT assay. The most potent fraction was further analyzed to understand its cytotoxic mechanism. To explore its apoptosis-inducing potential, microscopic and flow cytometric studies were conducted. Additionally, western blot analysis was used to examine the expression levels of proteins associated with apoptotic pathways. Results: PzMH showed the highest cytotoxicity against MG-63 osteosarcoma cells, with a GI50 value of 53.07 µg/ml. Flow cytometric studies revealed an upsurge in reactive oxygen species and disruption of mitochondrial membrane potential. The highest concentration of PzMH fraction (183.48 µg/ml) led to 62 % cell population arrest at G0/G1 stage. The anti-apoptotic protein Bcl2 was downregulated, with p53, cleaved-caspase 9, cleaved-caspase3, Bad and Bax expression upregulated. HPLC analysis revealed the presence of lawsone, p-coumaric acid, plumbagin, and 4-hydroxy benzaldehyde, indicating that the quinone-rich fraction of Plumbago zeylanica L. attenuates the proliferation of MG-63 osteosarcoma cells through the Bax/Bcl-2 pathway. Conclusion: To the best of our current knowledge, this marks the first documented case where the hexane fraction enriched with quinones extracted from the roots of P. zeylanica demonstrates its ability to induce apoptosis by influencing the Bax/Bcl2 pathway.

AIM: To investigate the aldose reductase (AR) inhibition capacity of astragalin (AST) against streptozoticin-induced diabetic cataracts (DCs) in rats. METHODS: Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor (AAH) of pH 7.8 at room temperature with cataract-causing substance (55 mmol/L of galactose) and in vivo studies were performed on rats via induction with streptozotocin. AST was administered at different dose levels and scrutinize for DC activity. RESULTS: In diabetic rats, AST improved the body weight, blood insulin, and glucose as well as the levels of galactitol in a dose-dependent way, other biochemical parameters i.e. inflammatory mediators and cytokines, and also suppress AR activity. The level of the antioxidant parameters such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activity were also altered on a diabetic lens after the administration of the AST. CONCLUSION: AST protects against lens opacification to avoid cataracts and polyols formation, indicating that it could be used as a potential therapeutic agent for diabetes.

While BCR::ABL1 tyrosine kinase inhibitors have transformed the treatment paradigm for chronic myeloid leukemia (CML), disease progression and treatment resistance due to BCR::ABL1-dependent and BCR::ABL1-independent mechanisms remain a therapeutic challenge. Natural compounds derived from plants have significantly contributed to cancer pharmacotherapy. This study investigated the efficacy of an active component of Leea indica, a local medicinal plant, in CML. Using high-performance liquid chromatography–electrospray ionization–mass spectrometry, a chemical constituent from L. indica extract was isolated and identified as gallic acid. Commercially obtained gallic acid was used as a chemical standard. Gallic acid from L. indica inhibited proliferation and induced apoptosis in CML cell lines, as did the chemical standard. Furthermore, gallic acid induced apoptosis and decreased the colony formation of primary CML CD34+ cells. The combination of isolated gallic acid or its chemical standard with BCR::ABL1 tyrosine kinase inhibitors resulted in a significantly greater inhibition of colony formation and cell growth compared to a single drug alone. Mechanistically, CML cells treated with gallic acid exhibited the disruption of multiple oncogenic pathways including ERK/MAPK, FLT3 and JAK/STAT, as well as impaired mitochondrial respiration. Rescue studies showed that gallic acid is significantly less effective in inducing apoptosis in mitochondrial respiration-deficient ρ0 cells compared to wildtype cells, suggesting that the action of gallic acid is largely through the inhibition of mitochondrial respiration. Our findings highlight the therapeutic potential of L. indica in CML and suggest that gallic acid may be a promising lead chemical constituent for further development for CML treatment.

Abstract Background Childhood-onset ANCA-associated vasculitides (AAV) are characterized by necrotizing inflammation and include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pediatric data is scare and there have been no prior studies examining the characteristics of pediatric AAV in Central California. Methods This retrospective study comprised AAV patients ≤18 years of age, diagnosed between 2010 and 2021, in Central California. We analyzed initial presentation including demographics, clinical, laboratory characteristics, treatment, and initial outcomes. Results Of 21 patients with AAV, 12 were categorized as MPA and 9 with GPA. Median age at diagnosis was 13.7 years in MPA cohort and 14 years in GPA. MPA cohort were majority females (92% versus 44%). 57% of the cohort were racial/ethnic minority including Hispanics (n = 9), Asians (n = 2), multiracial (n = 1) and 43% were white (n = 9). MPA patients were more frequently Hispanic (67%), meanwhile GPA patients were frequently white (78%). Median duration of symptoms prior to diagnosis was 14 days in MPA cohort and 21 days in GPA cohort. Renal involvement was frequent (100% in MPA and 78% in GPA). GPA cohort had frequent ear, nose and throat (ENT) involvement (89%). All patients were ANCA positive. All Hispanic patients were MPO positive, meanwhile 89% of white patients were PR3 positive. MPA cohort tended towards more severe disease with 67% requiring ICU admission and 50% requiring dialysis. Two deaths were reported in MPA cohort, related to Aspergillus pneumonia and pulmonary hemorrhage. In MPA cohort, 42% received cyclophosphamide in combination with steroids and 42% received rituximab in combination with steroids. GPA patients received cyclophosphamide, either with steroids alone (78%) or in combination with steroids and rituximab (22%). Conclusions Microscopic polyangiitis was the most frequent AAV subtype with female preponderance, shorter duration of symptoms at onset and higher proportion of racial/ ethnic minority patients. Hispanic children demonstrated frequent MPO positivity. Trends towards higher rates of ICU requirement and need for dialysis upon initial presentation was noted in MPA. Patients with MPA received rituximab more frequently. Future prospective studies are needed to understand differences in presentation and outcomes in childhood onset AAV between diverse racial-ethnic groups.

Biallelic mutations in the ACP5 gene cause spondyloenchondrodysplasia with immune dysregulation (SPENCDI). SPENCDI is characterized by the phenotypic triad of skeletal dysplasia, innate and adaptive immune dysfunction, and variable neurologic findings ranging from asymptomatic brain calcifications to severe developmental delay with spasticity. Immune dysregulation in SPENCDI is often refractory to standard immunosuppressive treatments. Here, we present the cases of two patients with SPENCDI and recalcitrant autoimmune cytopenias who demonstrated a favorable clinical response to targeted JAK inhibition over a period of more than 3 years. One of the patients exhibited steadily rising IgG levels and a bone marrow biopsy revealed smoldering multiple myeloma. A review of the literature uncovered that approximately half of the SPENCDI patients reported to date exhibited increased IgG levels. Screening for multiple myeloma in SPENCDI patients with rising IgG levels should therefore be considered.

Abstract Background The rich biodiversity of medicinal plants and their importance as sources of novel therapeutics and lead compounds warrant further research. Despite advances in debulking surgery and chemotherapy, the risks of recurrence of ovarian cancer and resistance to therapy are significant and the clinical outcomes of ovarian cancer remain poor or even incurable. Objective This study aims to investigate the effects of leaf extracts from a medicinal plant Leea indica and its selected phytoconstituents on human ovarian cancer cells and in combination with oxaliplatin and natural killer (NK) cells. Methods Fresh, healthy leaves of L. indica were harvested and extracted in 70% methanol by maceration. The crude extract was partitioned with n-hexane, dichloromethane and ethyl acetate. Selected extracts and compounds were analyzed for their effects on cell viability of human ovarian cancer cells, NK cell cytotoxicity, and stress ligands expression for NK cell receptors. They were also evaluated for their effects on TNF-α and IL-1β production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. Results Leaf extracts of L. indica increased the susceptibility of human ovarian tumor cells to NK cell-mediated cytotoxicity. Treatment of cancer cells with methyl gallate but not gallic acid upregulated the expression of stress ligands. Tumor cells pretreated with combination of methyl gallate and low concentration of oxaliplatin displayed increased levels of stress ligands expression and concomitantly enhanced susceptibility to NK cell-mediated cytolysis. Further, NK cells completely abrogated the growth of methyl gallate-pretreated ovarian cancer cells. The leaf extracts suppressed TNF-α and IL-1β production in human U937 macrophages. Methyl gallate was more potent than gallic acid in down-regulating these cytokine levels. Conclusions We demonstrated for the first time that leaf extracts of L. indica and its phytoconstituent methyl gallate enhanced the susceptibility of ovarian tumor cells to NK cell cytolysis. These results suggest that the combined effect of methyl gallate, oxaliplatin and NK cells in ovarian cancer cells warrants further investigation, for example for refractory ovarian cancer. Our work is a step towards better scientific understanding of the traditional anticancer use of L. indica.

Upcycling glycerol can substantially contribute to circular carbon economy. Here, an amino acid-functionalized graphene organocatalyst with high acidity converts glycerol and biooil wastes into high-value chemicals and fuels, even at low temperatures, advancing the state-of-the-art in sustainable carbon valorization technologies and circular economy.

Context: During pregnancy, poor oral hygiene practices and inadequate attention toward their oral health have an impact on the developing of the fetus and significant adverse pregnancy outcomes. Aims: The study aimed to assess the oral hygiene knowledge and practices among rural and urban pregnant women attending obstetrics and gynecology department in a tertiary care hospital of Ajmer, Rajasthan, India. Settings and Design: This study was a cross-sectional study. A total of 400 samples were selected by convenience sampling technique. Subjects and Methods: A questionnaire containing 12 questions related to knowledge and practices pertaining to the oral health of pregnant women, along with sociodemographic data. Statistical Analysis Used: Data obtained from this questionnaire were collected and analyzed using the SPSS Statistical Package for the Social Sciences. Results: A majority of respondents (74%) of urban areas had good oral hygiene status and of rural areas only (44.50%) had good oral hygiene. Awareness of the connection between pregnancy and oral health among the urban participants was 7.5%, whereas only 4.5% of rural participants were aware of the same. Oral hygiene practice was found to be relatively fair in urban participants compared to rural participants. Dental visits were seen to be higher in urban participants. Conclusion: This study revealed that the knowledge of pregnant women of the rural group about the association of oral hygiene knowledge and practices was poor. Oral hygiene knowledge and practices were significantly associated with education and socioeconomic status. Therefore, pregnant women need to be educated and made aware in both urban and rural areas of oral hygiene knowledge and practices toward oral health to improve adverse pregnancy outcomes.

ObjectivesThe aim of this study is to identify the characteristics of patients who underwent yoga therapy for pain in yoga and naturopathy clinical settings in India.MethodsElectronic medical records of patients who received yoga therapy for pain in three inpatient yoga and naturopathy hospitals were reviewed retrospectively from January 2021 to September 2022. Demographic characteristics and details on pain condition, socioeconomic status, comorbidities, ancillary therapies received, and insurance status were collected. In addition, we prospectively collected data on adherence to yoga practice through a telephonic interview.ResultsA total of 984 patients were identified from a pool of 3,164 patients who received yoga therapy for pain for an average of 9.48 (1.13) days. Patients aged between 8 and 80 underwent therapy for varying pain conditions and diseases that include pain in the extremities, pain due to infection, trauma, degenerative diseases, autoimmune diseases, and spine and neurological diseases. The majority of the patients were females (66.3%), from middle class families (74.8%), and who did not have any insurance coverage (93.8%). Most of the patients were under naturopathy treatment (99.8%), followed by ayurveda (56%), and physiotherapy (49.3%), along with yoga therapy. All patients reported a significant reduction in pain post-integrated yoga therapy (p

Background: Epilepsy is a widespread neurological illness with significant medical, social, and psychological implications. Valproate, Oxcarbazepine, and Levetiracetam are the most regularly used long-term antiepileptic drugs (AEDs) in children today. Objectives: To assess the effect of Valproate, Levetiracetam, and Oxcarbazepine monotherapy on thyroid function of children with epilepsy. Patients and method: This prospective observational study was carried out from May 2019 to December 2020 involving children of age group 1-12 years. Any child with newly diagnosed epilepsy being started on monotherapy with Levetiracetam/Valproate/Oxcarbazepine was included in the study. Their baseline thyroid profile and thyroid function at 6th month and 12th month of starting the antiepileptics were evaluated through Biochemical parameters -T3, T4 & TSH. These values were analyzed and compared by applying paired t-test to determine the effect of antiepileptic therapy on the thyroid function of the study subjects. Results: In the study, a total of 66 study participants were included of which 51 (77.3%) were males and 15 (22.7%) females. Among the study participants, generalized tonic-clonic seizures were seen in 36 (55%) study participants. As an antiepileptic treatment, Valproate was administered to 34 (51.5%), levetiracetam to 24 (36.4%), and oxcarbazepine to 8 (12.1%) of the study participants. Mean values of TSH, total T3, and total T4 scores at baseline were 1.7, 3.04, and 8.05 respectively; at 6 months were 3.17, 3.4, and 1.4 respectively, at 12 months were 4.9, 3.2, and 5.9. A significant increase in TSH and decrease in T4 values as compared to baseline levels was observed after antiepileptic therapy in the target group indicating a suppressive effect on thyroid function. Conclusion: This study has depicted a significant negative effect of anti-epileptic therapy on thyroid function in children.

Flowering in saffron is a highly complex process regulated by the synchronized action of environmental cues and endogenous signals. Hormonal regulation of flowering is a very important process controlling flowering in several plants, but it has not been studied in saffron. Flowering in saffron is a continual process completed in months with distinct developmental phases, mainly divided into flowering induction and flower organogenesis/formation. In the present study, we investigated how phytohormones affect the flowering process at different developmental stages. The results suggest that different hormones differentially affect flower induction and formation in saffron. The exogenous treatment of flowering competent corms with abscisic acid (ABA) suppressed both floral induction and flower formation, whereas some other hormones, like auxins (indole acetic acid, IAA) and gibberellic acid (GA), behaved contrarily at different developmental stages. IAA promoted flower induction, while GA suppressed it; however, GA promoted flower formation, whereas IAA suppressed it. Cytokinin (kinetin) treatment suggested its positive involvement in flower induction and flower formation. The expression analysis of floral integrator and homeotic genes suggests that ABA might suppress floral induction by suppressing the expression of the floral promoter (LFY, FT3) and promoting the expression of the floral repressor (SVP) gene. Additionally, ABA treatment also suppressed the expression of the floral homeotic genes responsible for flower formation. GA reduces the expression of flowering induction gene LFY, while IAA treatment upregulated its expression. In addition to these genes, a flowering repressor gene, TFL1-2, was also found to be downregulated in IAA treatment. Cytokinin promotes flowering induction by increasing the expression levels of the LFY gene and decreasing the TFL1-2 gene expression. Moreover, it improved flower organogenesis by increasing the expression of floral homeotic genes. Overall, the results suggest that hormones differently regulate flowering in saffron via regulating floral integrator and homeotic gene expression.

Abstract Uziflies (Family: Tachinidae) are dipteran endoparasites of sericigenous insects which cause major economic loss in the silk industry globally. Here, we are presenting the first full mitogenome of Blepharipa sp. (Acc: KY644698, 15,080 bp, A + T = 78.41%), a dipteran parasitoid of Muga silkworm (Antheraea assamensis) found in the Indian states of Assam and Meghalaya. This study has confirmed that Blepharipa sp. mitogenome gene content and arrangement is similar to other Tachinidae and Sarcophagidae flies of Oestroidea superfamily, typical of ancestral Diptera. Although, Calliphoridae and Oestridae flies have undergone tRNA translocation and insertion, forming unique intergenic spacers (IGS) and overlapping regions (OL) and a few of them (IGS, OL) have been conserved across Oestroidea flies. The Tachinidae mitogenomes exhibit more AT content and AT biased codons in their protein-coding genes (PCGs) than the Oestroidea counterpart. About 92.07% of all (3722) codons in PCGs of this new species have A/T in their 3rd codon position. The high proportion of AT and repeats in the control region (CR) affects sequence coverage, resulting in a short CR (Blepharipa sp.: 168 bp) and a smaller tachinid mitogenome. Our research unveils those genes with a high AT content had a reduced effective number of codons, leading to high codon usage bias. The neutrality test shows that natural selection has a stronger influence on codon usage bias than directed mutational pressure. This study also reveals that longer PCGs (e.g., nad5, cox1) have a higher codon usage bias than shorter PCGs (e.g., atp8, nad4l). The divergence rates increase nonlinearly as AT content at the 3rd codon position increases and higher rate of synonymous divergence than nonsynonymous divergence causes strong purifying selection. The phylogenetic analysis explains that Blepharipa sp. is well suited in the family of insectivorous tachinid maggots. It's possible that biased codon usage in the Tachinidae family reduces the effective number of codons, and purifying selection retains the core functions in their mitogenome, which could help with efficient metabolism in their endo-parasitic life style and survival strategy.

Background: A successful root canal (RC) treatment depends upon creation of a fluid impervious seal that is commonly built by using a RC sealer along with gutta-percha. The bond strength of the RC sealer is a hallmark as it will minimize the risk of treatment failure by reducing the possibility of filling detachment from dentin. Aim: To evaluate and compare the push-out bond strength of AH-Plus and MTA-Fillapex with Gutta-Percha and Epiphany Self Etch/Resilon system using the Universal Testing Machine. Materials and Method: About 60 mandibular premolars with single canals were prepared apically with Hyflex CM files upto size #30. Out of total, 20 teeth were obturated with AH-Plus/GP (group 1), 20 with MTA-Fillapex/GP (group 2), and other 20 with Epiphany Self Etch/Resilon system (group 3). Teeth were sectioned into three slices of 2 mm each and were subjected to Universal Testing Machine. Statistical Analysis: The data obtained were tabulated and statistically evaluated using SPSS version 21.0 statistical analysis software (IBM, Chicago, Illinois, USA). Results: The mean push-out bond strength was highest for AH–Plus (14.32 MPa) followed by MTA-Fillapex (12.18 MPa) and then Epiphany SE (8.44 MPa). The results were statistically significant. Conclusion: Significantly, higher push out bond strength was displayed by AH-Plus sealer than MTA-Fillapex and least being Epiphany SE sealer. The push out bond strength was significantly highest at apical third and lowest at coronal third.

Background: Cognitive impairment and alexithymia are commonly associated with schizophrenia and alcohol use disorder independently. Both can lead to poor prognosis and recovery. In patients with dual diagnosis, this association can be more prevalent and severe. Materials and Methods: A total of 75 participants were grouped into two (35 each): Group A, a Schizophrenia group and Group B with comorbid alcohol use. Sociodemographic factors, clinical profile, cognitive functions, and alexithymia were compared between the two groups using semi-structured pro forma, Positive and Negative Syndrome Scale, Alcohol Use Disorders Identification Test (AUDIT), Montreal Cognitive Assessment (MoCA) Scale, Toronto Alexithymia Scale (TAS-20) (subcategorized into three subscales (1) “Difficulty describing feelings” (DDF), (2) “Difficulty identifying feeling” (DIF), and (3) “Externally-Oriented Thinking” and Brief Psychiatric Rating Scale. Statistical analysis was performed using the Chi-square tests and t-tests as applicable. P < 0.05 was considered statistically significant. Results: The mean age of the participants was 33.61 (standard deviation [SD]-8.11), mean duration of schizophrenia was 70.8 months (SD-47.5) and mean duration of alcohol consumption was 9.10 years (SD-7.7). MoCA score was significantly lower (mean-21.80, SD-2.98) and TAS total score was significantly higher in Group B (Mean-67.31, SD-8.10). DDF (Mean-19.28, SD-4.02) and DIF scores (Mean-22.86, SD-4.66) were significantly higher in alcohol group compared to nonalcohol group. Furthermore, MoCA score was significantly impaired and TAS total, DDF and DIF scores were significantly higher in participants with AUDIT score >8 (P < 0.05). Lower score on MoCA correlated with the higher score of alexithymia. Conclusion: Cognitive dysfunction and alexithymia were significantly more in patients of schizophrenia with comorbid alcohol use and positively correlated with the severity of alcohol use disorder.

Cancer therapy has achieved new heights with numerous advancements made in this field still, cancer treatment modalities including chemotherapy, radiotherapy, immunotherapy, neoadjuvant therapy, and surgery have limitations in clinics and urges for new therapeutics. Natural products remain the mainstay of chemotherapy since ancient times. Flavonoids are a class of readily available polyphenolic secondary plant metabolites with remarkable anti-cancerous properties. However, poor aqueous solubility, rapid clearance from the blood, and poor bioavailability hinder their clinical use. In this direction, advancements in nanoparticle synthesis and functionalization have produced nanoscale drug delivery agents affording safe and target-specific delivery. Here, we highlight the importance of nanotechnology in safely delivering flavonoids to tumor tissues with high efficiency. We have also described the advancement of flavonoid-loaded nanoparticles either single or in combination with a conventional chemotherapeutic in pre-clinical settings which distinguishes them from other chemotherapeutics. While enormous pre-clinical studies have been published on flavonoid-based nanoparticles the emphasis here is to push these nanomedicines into clinical studies which are likely to influence clinical investigations and their translation for the treatment of cancer patients.

Abstract Autonomic modulation is critical during various physiological activities, including orthostatic stimuli and primarily evaluated by heart rate variability (HRV). Orthostatic stress affects people differently suggesting the possibility of identification of predisposed groups to autonomic dysfunction‐related disorders in a healthy state. One way to understand this kind of variability is by using Ayurvedic approach that classifies healthy individuals into Prakriti types based on clinical phenotypes. To this end, we explored the differential response to orthostatic stress in different Prakriti types using HRV. HRV was measured in 379 subjects(Vata = 97, Pitta = 68, Kapha = 68, and Mixed Prakriti = 146) from two geographical regions(Vadu and Delhi NCR) for 5 min supine (baseline), 3 min head‐up‐tilt (HUT) at 60°, and 5 min resupine. We observed that Kapha group had lower baseline HRV than other two groups, although not statistically significant. The relative change (%Δ1&2) in various HRV parameters in response to HUT was although minimal in Kapha group. Kapha also had significantly lower change in HR, LF (nu), HF (nu), and LF/HF than Pitta in response to HUT. The relative change (%Δ1) in HR and parasympathetic parameters (RMSSD, HF, SD1) was significantly greater in the Vata than in the Kapha. Thus, the low baseline and lower response to HUT in Kapha and the maximum drop in parasympathetic activity of Vata may indicate a predisposition to early autonomic dysfunction and associated conditions. It emphasizes the critical role of Prakriti‐based phenotyping in stratifying the differential responses of cardiac autonomic modulation in various postures among healthy individuals across different populations.

Cancer is one of the leading causes of mortality worldwide. Currently available anticancer therapeutic strategies are not able to improve the survival rate of patients over the past few decades. Research suggests that cancer cells develop multidrug resistance (MDR) against chemotherapeutics that lead to enhanced proliferation, epithelial to mesenchymal transition (EMT), invasion and metastasis. Hence, there is an urgent need for an alternative strategy to treat this disease. Recently, phytochemicals have gained immense attention as a promising anticancer agent by targeting multimodal oncogenic pathways, inducing cell cycle arrest and apoptosis in preclinical studies. However, their clinical application is limited due to poor aqueous solubility, poor bioavailability, low cellular uptake and narrow therapeutic index. Therefore, to address these challenges, phytochemical-based nanomedicine i.e. phytonanomedicine have been developed that can improve pharmacokinetics profile in in vivo systems. In this review, we aim to summarize challenges in cancer treatment and the status of phytonanomedicine for effective cancer treatment in preclinical and clinical studies.

Background and aim: Dengue a worldwide concern for public health has no effective vaccine or drug available for its prevention or treatment. There are billions of people who are at risk of contracting the dengue virus (DENV) infections with only anti-mosquito strategies to combat this disease. Based on the reports, particularly in vitro studies and small animal studies showing anti-viral activity of aqueous extract of Cocculus hirsutus (AQCH), studies were conducted on AQCH tablets as a potential for the treatment of dengue and COVID-19 infections. The current study was part of the research on AQCH tablet formulation and was aimed to evaluate safety and pharmacokinetics in healthy human subjects. Materials and methods: Sixty healthy adult human subjects were divided into 5 groups (cohorts: I to V; n = 12 per cohort) and randomized in the ratio of 3:1 to receive active treatment or placebo in a blinded manner. Five doses 100 mg, 200 mg, 400 mg, 600 mg and 800 mg tablets were administered three times daily at an interval of 8 h for days 01–09 under fasting conditions and a single dose in morning on day 10. Safety assessment was based on monitoring the occurrence, pattern, intensity, and severity of adverse events during study period. Blood samples were collected for measurement of the bio-active marker Sinococuline concentrations by a validated LC-MS/MS method followed by pharmacokinetic evaluation. Results and conclusion: The test formulation was well tolerated in all cohorts. Sinococuline peak plasma concentration (Cmax) and total exposure of plasma concentration (AUC) demonstrated linearity up to 600 mg and saturation kinetics at 800 mg dose. There was no difference observed in elimination half-life for all the cohorts, suggesting absence of saturation in rate of elimination. Dose accumulation was observed and steady state was achieved within 3 days. The information on human pharmacokinetics of AQCH tablets would assist in further dose optimization with defined pharmacokinetic-pharmacodynamic relationship.

Abstract Cerebrovascular lesions seen as white matter hyperintensity in MRI of elderly population caused due to micro-infracts and micro-bleeds contributes to vascular dementia. Such vascular insult caused by impairment in blood flow to specific area in brain involving small vessels can gradually worsen the pathology leading to cognitive deficits. In the present study we developed a transient model of vaso-constriction to study the impact of such pathology by bilateral injection of ET-1 (Endothelin-1; a 21 amino acid vasoconstricting peptide) into lateral ventricles of C57 mice. The impediment in cerebral blood flow decreased CD31 expression in endothelial cells lining the blood vessels around the hippocampal region, leading to memory deficits after 7 days. Activity dependent protein translation, critical for synaptic plasticity was absent in synaptoneurosomes prepared from hippocampal tissue. Further, Akt1- mTOR signaling cascade was downregulated indicating the possible cause for loss of activity dependent protein translation. However, these effects were reversed after 30 days indicating the ephemeral nature of deficits following a single vascular insult. Present study demonstrates that vasoconstriction leading to memory deficit and decline in activity dependent protein translation in hippocampus as a potential molecular mechanism impacting synaptic plasticity.

Introduction: Inflammation and oxidative stress are the main factors ascribed with interruption in the process of renal tissue impairment. The toxicity of different types of nitrosamine is well recognized in animals and humans. Administration of the smallest quantities of diethylnitrosamine or dimethylnitrosamine either orally or parenterally results into renal damage. Therapeutic effects of phytofabricated silver nanoparticles of Carissa carandas aqueous extract has been scrutinised in current study for the assessment of renal cancer activity in animal model. Methodology: Phytofabricated silver nanoparticles were characterized by using different instrumentation. Nephroprotective activity of silver nanoparticles at different doses was evaluated against N-diethylnitrosamine (200 mg/kg b.w., intraperitoneal) in animal model. Serum and renal homogenate were taken to evaluate the renal toxicity markers, oxidative stress, and antioxidant parameter, proinflammatory cytokines and histopathological study. Result: Significant outcomes of silver nanoparticles in dose dependent manner down regulated the elevated serum marker, tumour marker enzymes and histopathology observation of repaired tissue assured the renal cancer activity in animals. In addition, profile of enzymatic and non-enzymatic antioxidant, proinflammatory cytokines and tumour promotion marker also favours the anticancer property of silver nanoparticles. Conclusion: The data of current study reveals silver nanoparticles ameliorates renal oxidative stress and carcinogenesis which was induced by N-diethylnitrosamine and accredited to antioxidant and anticancer activities of phytofabricated nanoparticles by biological approach.

Background: Emesis gravidarum is a common obstetrical problem affecting 50–80% of pregnant women during their first trimester which begins in the morning and frequently continues throughout the day; considered as one of the Vyakta Garbha Lakshana in Ayurveda. If it is not treated effectively in time; it may lead to complications in pregnancy affecting the quality of life and thus the pregnancy outcome. Objective: To evaluate the clinical effectiveness of Bilwa-Lajadi syrup in emesis gravidarum. Material and methods: A single arm open labeled clinical trial was conducted on 30 participants fulfilling the inclusion criteria from OPD and IPD of Prasuti Tantra Evam StreeRoga, Sri Dharmasthala Manjunatheshwara College of Ayurveda and Hospital, Hassan and administered with Bilwa-Lajadi Syrup 20 ml per day in two divided doses, empty stomach before food for 30 days with followed up every 15 days during treatment and 15 days after completion of trial period. Results: The drug showed statistically significant effect in reducing the frequency of vomiting per day, quantity of vomitus, aversion to smell, nausea and anorexia, altered content of vomitus, improved appetite, imparted lightness of body and increased haemoglobin gm%. Conclusion: Thus, early medication with Bilwa-Lajadi syrup and following dietetic regimen played a vital role in relieving the symptoms of emesis gravidarum.

Abstract Background Dysregulation of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) form the basis of immune-mediated inflammatory diseases. Vitex trifolia L. is a medicinal plant growing in countries such as China, India, Australia and Singapore. Its dried ripe fruits are documented in Traditional Chinese Medicine to treat ailments like rhinitis and dizziness. Its leaves are used traditionally to treat inflammation-related conditions like rheumatic pain. Objective This study aimed to investigate the effects of V. trifolia leaf extracts prepared by different extraction methods (Soxhlet, ultrasonication, and maceration) in various solvents on cytokine production in human U937 macrophages, and identify phytoconstituents from the most active leaf extract. Methods Fresh leaves of V. trifolia were extracted using Soxhlet, ultrasonication, and maceration in hexane, dichloromethane, methanol, ethanol or water. Each extract was evaluated for its effects on TNF-α and IL-1β cytokine production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. The most active extract was analyzed and further purified by different chemical and spectroscopic techniques. Results Amongst 14 different leaf extracts investigated, extracts prepared by ultrasonication in dichloromethane and maceration in ethanol were most active in inhibiting TNF-α and IL-1β production in human U937 macrophages. Further purification led to the isolation of artemetin, casticin, vitexilactone and maslinic acid, and their effects on TNF-α and IL-1β production were evaluated. We report for the first time that artemetin suppressed TNF-α and IL-1β production. Gas chromatography-mass spectrometry analyses revealed the presence of eight other compounds. To the best of our knowledge, this is the first report of butylated hydroxytoluene, 2,4-di-tert-butylphenol, campesterol and maslinic acid in V. trifolia leaf extracts. Conclusions In conclusion, leaf extracts of V. trifolia obtained using different solvents and extraction methods were successfully investigated for their effects on cytokine production in human U937 macrophages. The findings provide scientific evidence for the traditional use of V. trifolia leaves (a sustainable resource) and highlight the importance of conservation of medicinal plants as resources for drug discovery. Our results together with others suggest further investigation on V. trifolia and constituents to develop novel treatment strategies in immune-mediated inflammatory conditions is warranted.

Background: Social media like WhatsApp is known to affect relationships of an individual, and busy professionals like doctors appear no bar. The objectives of this study were to analyze the pattern of WhatsApp use in specialist-doctors and to study its effect on their relationships. Materials and Methods: This was a cross-sectional pilot study. Consecutively selected hundred married specialist doctors were assessed using self-reported validated questionnaire including questions related to demographics, WhatsApp use, and effects on relationships in a tertiary care center. Statistical analysis was performed using mean, standard deviation, t-test, and Chi-square test. A value of P < 0.05 was considered statistically significant. Results: Participants of various specialties, with a mean age of 41.5 years reported regular WhatsApp-use (89%) of mean duration 2.5 years with 19% spending> 2 h/day. About 62% reported using WhatsApp during personal time, leading to reduction in time spent with spouse (37%), impairment in household responsibilities (24%), disturbances in social-activities (26%) and craving. About 36% reported negative effects on married life. 21% reported inability to spend quality-time with spouse, 24% had concern about spouse's WhatsApp-use, 25% reported reduced cohesion between them and 22% felt that excessive use can create doubts in spouse's mind. Those aged

Dengue is a serious public health concern worldwide, with ∼3 billion people at risk of contracting dengue virus (DENV) infections, with some suffering severe consequences of disease and leading to death. Currently, there is no broad use vaccine or drug available for the prevention or treatment of dengue, which leaves only anti-mosquito strategies to combat the dengue menace. The present study is an extension of our earlier study aimed at determining the in vitro and in vivo protective effects of a plant-derived phytopharmaceutical drug for the treatment of dengue. In our previous report, we had identified a methanolic extract of aerial parts of Cissampelos pareira to exhibit in vitro and in vivo anti-dengue activity against all the four DENV serotypes. The dried aerial parts of C. pareira supplied by local vendors were often found to be mixed with aerial parts of another plant of the same Menispermaceae family, Cocculus hirsutus, which shares common homology with C. pareira. In the current study, we have found C. hirsutus to have more potent anti-dengue activity as compared with C. pareira. The stem part of C. hirsutus was found to be more potent (∼25 times) than the aerial part (stem and leaf) irrespective of the extraction solvent used, viz., denatured spirit, hydro-alcohol (50:50), and aqueous. Moreover, the anti-dengue activity of stem extract in all the solvents was comparable. Hence, an aqueous extract of the stem of C. hirsutus (AQCH) was selected due to greater regulatory compliance. Five chemical markers, viz., Sinococuline, 20-Hydroxyecdysone, Makisterone-A, Magnoflorine, and Coniferyl alcohol, were identified in fingerprinting analysis. In a test of primary dengue infection in the AG129 mice model, AQCH extract at 25 mg/kg body weight exhibited protection when administered four and three times a day. The AQCH was also protective in the secondary DENV-infected AG129 mice model at 25 mg/kg/dose when administered four and three times a day. Additionally, the AQCH extract reduced serum viremia and small intestinal pathologies, viz., viral load, pro-inflammatory cytokines, and vascular leakage. Based on these findings, we have undertaken the potential preclinical development of C. hirsutus-based phytopharmaceutical, which could be studied further for its clinical development for treating dengue.

Recently, the use of hips of different rose species has increased due to its nutritional and health-promoting benefits. Rose hips contain a rich amount of ascorbic acid, phenolics, and various other bioactive constituents. Based on the distribution and variation in the morphological characters, rose hips of nine accessions belonging to the three species viz. Rosa webbiana Wall. ex Royle, R. moschata Herrm., and R. canina L. were studied. The rose hips were evaluated for moisture, carbohydrates, total protein, crude fat, total phenolic, crude fibers, water-soluble vitamins, fat-soluble vitamins, and mineral contents. An appreciable amount of the studied biochemical parameters with significant variations was observed in the rose hips originated from different regions. Results demonstrated the high nutraceutical potential of these species and indicated that their rose hips could be promoted as a functional food in the region. Furthermore, the phytonutrient-rich composition of the region's rose hips was revealed when the current study's findings were compared to previous studies. Therefore, they may be considered ingredients in food and dietary supplement formulations, phytopharmaceutical sector and can be quickly brought under cultivation. Furthermore, findings based on the scientific evidence indicate that the information on the pharmacological and toxicological of R. webbiana and R. moschata is very scanty or lacking; therefore, needing more research interest.

Abstract Background Exploration of microbes isolated from north western Himalayas for bioactive natural products. Results A strain of Trichoderma lixii (IIIM-B4) was isolated from Bacopa monnieri L. The ITS based rDNA gene sequence of strain IIIM-B4 displayed 99% sequence similarity with different Trichoderma harzianum species complex. The highest score was displayed for Hypocrea lixii strain FJ462763 followed by H. nigricans strain NBRC31285, Trichoderma lixii strain CBS 110080, T. afroharzianum strain CBS124620 and Trichoderma guizhouense BPI:GJS 08135 respectively. Position of T. lixii (IIIM-B4) in phylogenetic tree suggested separate identity of the strain. Microbial dynamics of T. lixii (IIIM-B4) was investigated for small peptides. Medium to long chain length peptaibols of 11 residue (Group A), 14 residue (Group B) and 17 residue (Group C) were identified using Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometer. Optimization is undeniably a desideratum for maximized production of desirable metabolites from microbial strain. Here optimization studies were carried out on T. lixii (IIIM-B4) using different growth media through Intact Cell Mass Spectrometry (ICMS). A multifold increase was obtained in production of 11 residue peptaibols using rose bengal medium. Out of these, one of them named as Tribacopin AV was isolated and sequenced through mass studied. It was found novel as having unique sequence Ac-Gly-Leu-Leu-Leu-Ala-Leu-Pro-Leu-Aib-Val-Gln-OH. It was found to have antifungal activity against Candida albicans (25 μg/mL MIC). Conclusion In this study, we isolated a strain of T. lixii (IIIM-B4) producing medium and long chain peptaibols. One of them named as Tribacopin AV was found novel as having unique sequence Ac-Gly-Leu-Leu-Leu-Ala-Leu-Pro-Leu-Aib-Val-Gln-OH, which had antifungal properties.

Purpose: The aim of this study is to know practice pattern of cataract surgeons when operating on patients, positive for blood-borne viral infections (BBVIs), namely, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. We also studied their awareness, knowledge, and attitude toward universal precautions and guidelines. Methods: The telephonic survey enrolled practicing cataract surgeons, who were interviewed to record responses pertaining to their practice using an open-ended questionnaire. We studied statistical significance of difference of frequency of prick injuries in topical versus peribulbar anesthesia, and phacoemulsification versus manual small incision cataract surgery by employing Chi-square test. Significance of proportion was calculated using z-test. For all statistical calculations, significance level was set at 0.05%. Results: Of 623 ophthalmologists contacted, responses of 479 (79%) ophthalmologists were analyzed. Maximum participants were in private practice (48%). During whole practicing carrier, 313 (65%; 95% confidence interval [CI]: 61–70) participants admitted having suffered injury with needle or sharp instruments; of these, 204 (65%; 95% CI: 60–70) participants did not report their injury. Wearing “double gloves” during cataract surgery was the most common barrier adopted by participants. Conclusion: We found high prevalence of occupational-related sharp injuries among ophthalmologists in this survey. Majority of them were aware of universal precautions, but adherence to postexposure prophylaxis was lacking.

Kawasaki disease is an acute multisystem vasculitis characterized by involvement of medium-sized vessels that mostly affects children under the age of 5 years. The presentation is typically preceded by five or more days of fever with additional clinical findings including rash, peripheral edema, mucositis, conjunctival changes, and unilateral cervical lymphadenopathy. The most feared complication of Kawasaki disease is development of coronary artery aneurysms. Common laboratory abnormalities include normocytic anemia, thrombocytosis, leukocytosis, and elevated inflammatory markers. Immune-mediated cytopenias such as autoimmune hemolytic anemia and thrombocytopenia are rarely seen at presentation in Kawasaki disease. We describe a unique case of a child presenting with autoimmune hemolytic anemia, who sequentially developed immune thrombocytopenia concerning for Evans’ syndrome and eventually diagnosed with Kawasaki Disease with coronary artery dilatation. Characteristic clinical findings including extremity edema, cracked lips, and rash developed later in the course. Our patient was treated with IVIG and steroids with significant clinical improvement and complete resolution of cytopenias and coronary aneurysms on long term follow up. Timely administration of IVIG prevents and minimizes the risk of long term cardiac consequences. Hence a high index of suspicion should be maintained for this relatively common pediatric illness, even in absence of more commonly seen laboratory findings.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has emerged as a global pandemic worldwide. In this study, we used ARTIC primers–based amplicon sequencing to profile 225 SARS-CoV-2 genomes from India. Phylogenetic analysis of 202 high-quality assemblies identified the presence of all the five reported clades 19A, 19B, 20A, 20B, and 20C in the population. The analyses revealed Europe and Southeast Asia as two major routes for introduction of the disease in India followed by local transmission. Interestingly, the19B clade was found to be more prevalent in our sequenced genomes (17%) compared to other genomes reported so far from India. Haplotype network analysis showed evolution of 19A and 19B clades in parallel from predominantly Gujarat state in India, suggesting it to be one of the major routes of disease transmission in India during the months of March and April, whereas 20B and 20C appeared to evolve from 20A. At the same time, 20A and 20B clades depicted prevalence of four common mutations 241 C > T in 5′ UTR, P4715L, F942F along with D614G in the Spike protein. D614G mutation has been reported to increase virus shedding and infectivity. Our molecular modeling and docking analysis identified that D614G mutation resulted in enhanced affinity of Spike S1–S2 hinge region with TMPRSS2 protease, possibly the reason for increased shedding of S1 domain in G614 as compared to D614. Moreover, we also observed an increased concordance of G614 mutation with the viral load, as evident from decreased Ct value of Spike and the ORF1ab gene.

Cardiovascular diseases are the leading cause of death, accounting about 31% deaths globally in 2012. The major risk factors causing cardiovascular diseases are coronary atherosclerosis, hyperlipidemia, myocardial infarction, and stroke. The dominating cause of cardiovascular diseases is accredited to our modern lifestyle and diet. Medicinal plants have been used for the prevention and treatment of cardiovascular diseases from centuries. The in built chirality and chemical space of natural products have been playing an important role in providing leads and templates for pharmacophore synthesis. This review highlights one of the important naturally occurring class saponins and their role in cardioprotection along with structural characteristics and pharmacological effects such as antioxidant, Ca2+ ion regulation, antiapoptotic, antiatherosclerosis, antihyperlipidemic, hypocholesterolemic, angiogenic, vasodilatory, and hypotensive. The characteristic cholesterol lowering, hemolytic, and anticoagulant properties of the saponins prompted us to select as one of the natural products class for cardioprotection. This review covers the most updated information on saponins related to their cardioprotective effects, mechanism of action, bioavailability, and structure activity relationship. Keywords: Bioavailability, Cardioprotective activity, Saponins, Structure activity relationship

Background: Medically ill elderly patients are more prone to develop depression. Stressful life events which the patient experiences as well as the absence of perceived social support all act as risk factors for developing depression. Moreover, if the coping mechanisms are faulty the risk of developing depression increases. Aim: This study was conducted to assess the prevalence of depression in medically ill elderly patients and the risk factors associated with faulty coping mechanisms, perceived social support, and stressful life events. Materials and Methods: This was a cross-sectional study conducted at a tertiary care hospital, wherein 100 patients fulfilling the inclusion and exclusion criteria were chosen. Patients were administered a semi-structured questionnaire to obtain details about sociodemographic profile and diagnosed medical illnesses. Geriatric Depression Scale, Coping Inventory for Stressful Situations, Multidimensional Scale of Perceived Social Support, and Presumptive Stressful Life Event Scale were used. Results: Prevalence of depression was 72% among the medically ill elderly patients. Depressed patients used more of emotion-oriented coping and less of task-oriented and avoidance coping mechanisms the perceived social support in the form of family and friends was significantly less in depressed patients. The more the number of stressful life events experienced by the patients the more depressed they were. Conclusion: Early identification of risk factors and early diagnosis of depression may help us in carrying out timely interventions and thus improve the quality of life of our patients.

The key factor to obtain good yield and high fruit quality in apple (Malus domestica Borkh.) production is tree fertilization. The present study was planned with the objective to investigate the effect of soil applied N sources through foliar Urea sprays on morphometric growth traits, yield and fruit quality of apple cv. Royal Delicious. The trial was carried out on 28-year old trees raised on Crab apple Malus sylvestris (L.) Mill rootstock. Soil application of N sources, viz. Urea, calcium nitrate (CN), N:P:K (19:19:19) + Urea, N:P:K (12:32:16) + Urea and CAN + foliar Urea sprays at the levels of 840, 700 and 560 g N/tree were used. The effect of soil application of N sources and levels along with foliar Urea sprays on growth, production and fruit quality of apple recorded CAN + foliar Urea at 700 g N/ tree as the superior combination for optimum growth, fruit set and yield which was closely followed by CN + foliar Urea and Urea (soil) + Urea (foliar) application at 700 g N/tree. Whereas, fruit quality in terms of fruit size, weight, sugars and total soluble solids were improved with CAN + foliar Urea as well as CN + foliar Urea at 700 g N/tree.

As part of our endeavor to enhance survival of natural product derived drug candidates and to guide the medicinal chemist to design higher probability space for success in the anti cancer drug development area, we embarked on a detailed study of the property space for a collection of natural product derived anti cancer molecules. We carried out a comprehensive analysis of properties for 24 natural products derived anti cancer drugs including clinical development candidates and a set of 27 natural products derived anti cancer lead compounds. In particular, we focused on understanding the interplay among eight physicochemical properties including like partition coefficient (log P), distribution coefficient at pH=7.4 (log D), topological polar surface area (TPSA), molecular weight (MW), aqueous solubility (log S), number of hydrogen bond acceptors (HBA), number of hydrogen bond donors (HBD) and number of rotatable bonds (nRot) crucial for drug design and relationships between physicochemical properties, ADME (absorption, distribution, metabolism, and elimination) attributes, and in silico toxicity profile for these two sets of compounds. This analysis provides guidance for the chemist to modify the existing natural product scaffold or designing of new anti cancer molecules in a property space with increased probability of success and may lead to the identification of druglike candidates with favorable safety profiles that can successfully test hypotheses in the clinic.

Conversational agents are gaining huge popularity in industrial applications such as digital assistants, chatbots, and particularly systems for natural language understanding (NLU). However, a major drawback is the unavailability of a common metric to evaluate the replies against human judgement for conversational agents. In this paper, we develop a benchmark dataset with human annotations and diverse replies that can be used to develop such metric for conversational agents. The paper introduces a high-quality human annotated movie dialogue dataset, HUMOD, that is developed from the Cornell movie dialogues dataset. This new dataset comprises 28,500 human responses from 9500 multi-turn dialogue history-reply pairs. Human responses include: (i) ratings of the dialogue reply in relevance to the dialogue history; and (ii) unique dialogue replies for each dialogue history from the users. Such unique dialogue replies enable researchers in evaluating their models against six unique human responses for each given history. Detailed analysis on how dialogues are structured and human perception on dialogue score in comparison with existing models are also presented.

Over recent years, utilization of green synthesized nanomaterials has been widely growing on human body because of its special properties. With the increasing acceptance of nanoparticle approach for various clinical treatments, the biosafety and toxicological effects on the vital organs such as central nervous system, have received more concern. Main focus of this study was to evaluate acute exposure of n-butanol fraction of Prosopis cineraria (L.) Druce hydroethanolic extract (BuPC) and green synthesized zinc oxide nanoparticles of BuPC (ZnOPC) on spatial cognition behavior, and to assess underlying mechanism by estimation of enzymatic antioxidative status along with acetylcholinesterase (AChE) activity in mice brain. Strongest in vitro antioxidant and AChE inhibitory activity exhibiting fraction, BuPC, was examined for inhibition kinetic study by Lineweaver–Burk and Dixon plots. BuPC was further used for fabrication ZnOPC and characterized by UV-visible spectroscopy, Fourier Transform Infrared (FTIR), Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X ray (EDX), and Dynamic Light Scattering (DLS) analysis. Old male swiss albino mice were randomly divided into seven groups and treated for 21 days. Subsequently spatial memory was determined by two behavioral models [Elevated plus maze (EPM) and Hebbs William maze (HWM)] and supernatant of brain homogenate was analyzed for enzymatic antioxidant level and AChE inhibitory activity. Zinc content of blood plasma and brain was estimated. Results showed prolonged transfer latency (TL) and time taken to reach reward chamber (TRC) by scopolamine was not ameliorated by the ZnOPC group, whereas BuPC group showed significant reduction in scopolamine induced increase in TL and TRC compared to control and scopolamine treated groups. ZnOPC alleviated enzymatic antioxidant activity and AChE as compared to donepezil and BuPC treated groups. Study concludes that ZnOPC attenuated spatial learning and memory by increase in oxidative stress and decrease in AChE activity at both dose levels. Our results suggest that BuPC exhibited a strong neuroprotective effect on cognitive deficit mice and it may be employed as a strong substance for the treatment of dementia whereas the green synthesized ZnOPC was not proficient to reverse the memory impairment induced by scopolamine.

Aim: The aim of this clinical study was to compare the effect of working length (WL) determination using electronic apex locator (EAL) or WL radiograph on the length adequacy of final WL. Materials and Methods: A total of 153 patients with 153 teeth with single canal were randomized into two groups; in Group 1, the WL was determined by WL radiograph; whereas in Group 2, it was determined by the Raypex5 EAL (VDW, Munich, Germany). Length adequacy was assessed in each group for master cone and categorized into short, acceptable, and over cases. Statistical Analysis Used: The data were statistically analyzed using the Pearson chi-square test at a significance level of P < 0.05. Results: There was no statistically significant difference between the groups in the rates of acceptable (Group 1 = 83.1% and Group 2 = 92.1%) and short cases (Group 1 = 3.9% and Group 2 = 5.2%). Over cases in master cone radiography were significantly more in Group 1 (13.1%) than Group 2 (2.6%) (P = 0.017). Conclusion: The results of our study have shown that under clinical condition, success of Raypex5 was comparable to the radiographic WL determination technique in terms of acceptable and short cases. However, there were significantly lesser over cases in EAL group, showing that EALs can avoid the overestimation of WL.

Muga (Antheraea assamensis) is an economically important silkmoth endemic to the states of Assam and Meghalaya in India and is the producer of the strongest known commercial silk. However, there is a scarcity of genomic and proteomic data for understanding the organism at a molecular level. Our present study is on decoding the complete mitochondrial genome (mitogenome) of A. assamensis using next generation sequencing technology and comparing it with other available lepidopteran mitogenomes. Mitogenome of A. assamensis is an AT rich circular molecule of 15,272 bp (A+T content ~80.2%). It contains 37 genes comprising of 13 protein coding genes (PCGs), 22 tRNA and 2 rRNA genes along with a 328 bp long control region. Its typical tRNAMet-tRNAIle-tRNAGln arrangement differed from ancestral insects (tRNAIle-tRNAGln-tRNAMet). Two PCGs cox1 and cox2 were found to have CGA and GTG as start codons, respectively as reported in some lepidopterans. Interestingly, nad4l gene showed higher transversion mutations at intra-species than inter-species level. All PCGs evolved under strong purifying selection with highest evolutionary rates observed for atp8 gene while lowest for cox1 gene. We observed the typical clover-leaf shaped secondary structures of tRNAs with a few exceptions in case of tRNASer1 and tRNATyr where stable DHU and TΨC loop were absent. A significant number of mismatches (35) were found to spread over 19 tRNA structures. The control region of mitogenome contained a six bp (CTTAGA/G) deletion atypical of other Antheraea species and lacked tandem repeats. Phylogenetic position of A. assamensis was consistent with the traditional taxonomic classification of Saturniidae. The complete annotated mitogenome is available in GenBank (Accession No. KU379695). To the best of our knowledge, this is the first report on complete mitogenome of A. assamensis.

Background: Medically ill elderly patients are more prone to develop depression. Faulty coping mechanisms increase the risk of developing depression. Spirituality is known to decrease this risk. Aim: This study was conducted to assess the prevalence of depression in medically ill elderly patients, coping strategies used and spirituality as a way of coping. A comparison was made between coping strategies used by depressed and nondepressed elderly patients with medical illnesses. Materials and Methods: This was a cross-sectional study carried out at a tertiary care hospital. A total of 100 consecutive patients were evaluated on Geriatric Depression Scale, Coping Inventory for Stressful Situations-21, and Spiritual Attitude Inventory. Results: Prevalence of depression was 72% among the medically ill elderly patients. Of those found to have depression, two third had mild depression and one-third had severe depression. On comparing coping and spirituality between depressed and nondepressed patients it was found that non depressed patients had better coping towards stressful situation, they used more of task oriented and avoidance based coping, whereas depressed patients used more of emotion oriented coping. Non-depressed patients were more spiritual when compared to depressed patients. Severity of depression positively correlated with emotion oriented coping mechanisms and it was negatively correlated with task and avoidance oriented coping mechanisms and spirituality in all four domains. Conclusion: The present study shows that 72% of medically ill elderly patients have depression and compared to those with one medical illness, the prevalence of depression is more among those who have 2 or more medical illnesses. Compared with those without depression, patients with depression more often used emotion based coping, less often used task and avoidance coping mechanisms and were less spiritual.

Leea indica (Vitaceae) is a Southeast Asian medicinal plant. In this study, an ethyl acetate fraction of L. indica leaves was studied for its phytoconstituents using high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-microTOF-Q-MS/MS) analysis. A total of 31 compounds of different classes, including benzoic acid derivatives, phenolics, flavonoids, catechins, dihydrochalcones, coumarins, megastigmanes, and oxylipins were identified using LC-MS/MS. Among them, six compounds including gallic acid, methyl gallate, (−)-epigallocatechin-3-O-gallate, myricetin-3-O-rhamnoside, quercetin-3-O-rhamnoside, and 4′,6′-dihydroxy-4-methoxydihydrochalcone 2′-O-β-d-glucopyranoside were isolated and identified by NMR analysis. The LC-MS/MS analysis led to the tentative identification of three novel dihydrochalcones namely 4′,6′-dihydroxy-4-methoxydihydrochalcone 2′-O-rutinoside, 4′,6′-dihydroxy-4-methoxydihydrochalcone 2′-O-glucosylpentoside and 4′,6′-dihydroxy-4-methoxydihydrochalcone 2′-O-(3″-O-galloyl)-β-d-glucopyranoside. The structural identification of novel dihydrochalcones was based on the basic skeleton of the isolated dihydrochalcone, 4′,6′-dihydroxy-4-methoxydihydrochalcone 2′-O-β-d-glucopyranoside and characteristic LC-MS/MS fragmentation patterns. This is the first comprehensive analysis for the identification of compounds from L. indica using LC-MS. A total 24 compounds including three new dihydrochalcones were identified for the first time from the genus Leea.

The present investigation was planned and focused with the objective to compare the effect of nitrogen (N) fertigation and conventional soil fertilization on growth and nutrient dynamics for the establishment of Snow Queen nectarines (Prunus persica var. nucipersica). We determined if the frequency of application of fertigation that could modify cropping behavior of the plantations in integrated horticultural based cropping system under rainfed ecosystem. In the experiment, all plants received the same amount of water with sufficient fertilizer N but the treatment included four fertigation frequencies applied weekly intervals of the recommended dose (RD) of N fertilizers over conventional soil fertilization scheduled at 25% (25% RD-N fertigation), 50% (50% RD-N fertigation), 75% (75% RD-N fertigation) and 100% (100% RD-N fertigation) in the Randomized Block Design replicated thrice. The availability of nutrients at root zone of the trees significantly influenced vegetative growth attributes, the uptake of macro- and micronutrient cations and fruit quality characteristics. Given the fact that all treatments applied with adequate and equal amount of fertilizer and water, however, 75% RD-N fertigation frequency had significantly affected cropping behavior and uptake efficiency both vertically as well as horizontally. The N availability steadily increased with increased depth up to 30 cm after that declined in all the distances at fertigation with 75% RD-N. Highest available P and K in soil was confined to 0-15 cm of soil layer under all fertigation levels and decreased with increase in distance from the emitters and soil depth. With regards to exchangeable Ca and Mg, the contents were decreased in the surface soil than in the subsoil. This superior application also recorded improved vertical and horizontal distribution of available macro- and micronutrient cations in soil, leaf nutrient concentration and fruit quality attributes for growth parameters and fruit quality characteristics which in turn saved 25% of the inorganic fertilizers application.

Imidazoles have occupied a unique position in heterocyclic chemistry, and its derivatives have attracted considerable interests in recent years for their versatile properties in chemistry and pharmacology. Imidazole is nitrogen-containing heterocyclic ring which possesses biological and pharmaceutical importance. Thus, imidazole compounds have been an interesting source for researchers for more than a century. The imidazole ring is a constituent of several important natural products, including purine, histamine, histidine, and nucleic acid. Being a polar and ionisable aromatic compound, it improves pharmacokinetic characteristics of lead molecules and thus is used as a remedy to optimize solubility and bioavailability parameters of proposed poorly soluble lead molecules. There are several methods used for the synthesis of imidazole-containing compounds, and also their various structure reactions offer enormous scope in the field of medicinal chemistry. The imidazole derivatives possess extensive spectrum of biological activities such as antibacterial, anticancer, antitubercular, antifungal, analgesic, and anti-HIV activities. This paper aims to review the biological activities of imidazole during the past years.