Nanoemulsion-Based System as a Novel and Promising Approach for Enhancing the Antimicrobial and Antitumoral Activity of Thymus vulgaris (L.) Oil in Human Hepatocellular Carcinoma Cells.

The utilisation of medicinal plants and their essential oils is receiving more attention due to the ineffectiveness of current therapeutic methods in the treatment of various cancers and the rising incidence of bacterial antibiotic resistance. Thymol, an active ingredient of Thymus vulgaris, is known to have hepatoprotective, antibacterial, and antioxidant properties. To overcome major obstacles to their usage, such as quick oxidation and high volatility, plant essential oils must be administered through a system to improve the delivery of their active pharmaceutical ingredient. The bioavailability of active substances may be enhanced by the colloidal dispersion nanoemulsion. Therefore, this study aims to derive a comparative evaluation of the thyme oil nanoemulsion formulation and the characterisation of its antibacterial and antitumorigenic activities. A nanoemulsion (NE) with a droplet size of 122.2 ± 1.079 nm was discovered to be stable and mono-dispersed for 4 months and inhibited the growth of B. subtilis, E. coli, P. aeruginosa, and S. aureus. It also displayed antitumorigenic capabilities in HepG2 cells by arresting the cell cycle in the G2/M phase and upregulating the gene expression levels of Bcl-2-associated X protein (Bax), Caspase 3, 8, and 9, as well as a concomitant concentration-dependent decrease in B-cell leukaemia/lymphoma 2 protein (BCL2). Along with an increase in inducible nitric oxide synthase (iNOS) levels, upregulation of the expression levels of the reactive oxygen species (ROS), mitogen-activated protein kinase (MAPK), and endoplasmic reticulum (ER) stress pathways was also seen, indicating of ROS formation in the cancer cells.

A critical review on sustainable hazardous waste management strategies: a step towards a circular economy.

Globally, industrialisation and urbanisation have led to the generation of hazardous waste (HW). Sustainable hazardous waste management (HWM) is the need of the hour for a safe, clean, and eco-friendly environment and public health. The prominent waste management strategies should be aligned with circular economic models considering the economy, environment, and efficiency. This review critically discusses HW generation and sustainable management with the strategies of prevention, reduction, recycling, waste-to-energy, advanced treatment technology, and proper disposal. In this regard, the major HW policies, legislations, and international conventions related to HWM are summarised. The global generation and composition of hazardous industrial, household, and e-waste are analysed, along with their environmental and health impacts. The paper critically discusses recently adapted management strategies, waste-to-energy conversion techniques, treatment technologies, and their suitability, advantages, and limitations. A roadmap for future research focused on the components of the circular economy model is proposed, and the waste management challenges are discussed. This review stems to give a holistic and broader picture of global waste generation (from many sources), its effects on public health and the environment, and the need for a sustainable HWM approach towards the circular economy. The in-depth analysis presented in this work will help build cost-effective and eco-sustainable HWM projects.

Use of Complementary and Alternative Medicine in Children with Neuromuscular Disorders Followed at Penn State Health Pediatric Muscular Dystrophy Association Care Center Clinic.

The exact prevalence of complementary and alternative medicine (CAM) use is not known in pediatric patients with neuromuscular diseases followed by any of the 150 Muscular Dystrophy Association (MDA) Care Center Clinics nationwide. This study describes the prevalence and variety of CAM usage in this population, while also assessing the prevalence of caregiver disclosure of CAM use and caregiver perception of provider support for CAM. Fifty-two caregivers of pediatric patients seen at Penn State Health's Pediatric MDA Care Center Clinic completed our online survey. Overall, 19.2% of caregivers reported CAM use by their child. Less than half of caregivers reported discussing CAM use with their child's neurologist (41.5%); however, a majority of respondents reported interest in using CAM for their child in the future (52.8%). Understanding the prevalence of CAM usage and disclosure in pediatric MDA clinics may facilitate safer use of CAM in this community.

Diagnostic Accuracy of Cord Bilirubin to Predict the Need for Phototherapy in Healthy Neonates >35-Week Gestational Age: A Systematic Review and Meta-Analysis.

Objective: Early discharge puts neonates at risk of delayed detection of jaundice and resulting neurological injury. In these neonates, we can use cord bilirubin to make predictions. In this meta-analysis, we assessed the diagnostic accuracy of cord bilirubin in predicting the need for phototherapy (AAP-2004 or NICE-2010 charts). Methods: We searched the databases of PubMed, Embase, Cochrane Library, Google Scholar, and Index Medicus for Southeast Asian Region. We included all observational studies that assessed the diagnostic accuracy of cord bilirubin. A bivariate model was used to pool the data in prespecified range of cord bilirubin levels (<1.5 mg/dl, 1.5-2.0 mg/dl, 2.0-2.5 mg/dl, 2.5-3.0 mg/dl, and >3.0 mg/dl). Data were pooled separately for studies including all neonates (no risk stratification), high-risk neonates (Rh and/or ABO incompatibility only), and low-risk neonates (excluded Rh and ABO incompatibility). Results: Of the 1990 unique records, we studied 153 full texts and included 54 studies in the meta-analysis. For all the three groups of studies, the highest diagnostic odds ratio was noted for a cord bilirubin cut-off of 2.5-3.0 mg/dl (all neonates: 22.5, 95% CI: 21.1, 22.9; high-risk neonates: 75.5, 95% CI: 63, 85.7; low-risk neonates: 91.9; 95% CI: 64, 134.14). Using the same cut-off, the studies including all neonates without risk stratification had a pooled sensitivity of 0.31 (95% CI: 0.18, 0.47) and a pooled specificity of 0.98 (0.96, 0.99) in predicting the need for phototherapy. In studies on high-risk neonates, the pooled sensitivity was 0.8 (0.39, 0.96) and pooled specificity was 0.95 (0.78, 0.99). In studies on low-risk neonates, the pooled sensitivity was 0.74 (0.39, 0.93) and pooled specificity of 0.97 (0.91, 0.99). We noted significant heterogeneity and a high risk of bias in the index test's conduct. Conclusion: A cord bilirubin cut-off of 2.5-3 mg/dl has good diagnostic accuracy in predicting the need for phototherapy in neonates. Registration number: CRD42020196216.

Use of Integrative, Complementary, and Alternative Medicine in Children with Epilepsy: A Global Scoping Review.

(1) Background: Epilepsy is one of the most common chronic neurological disorders in childhood. Complementary and alternative medicine (CAM) use is highly prevalent in patients with epilepsy. Despite CAM's widespread and increasing popularity, its prevalence, forms, perceived benefits, and potential risks in pediatric epilepsy are rarely explored. (2) Methods: We performed a scoping review of the available literature on the use of CAM in pediatric epilepsy. (3) Results: Overall, global cross-sectional studies showed a variable degree of CAM usage among children with epilepsy, ranging from 13 to 44% in prevalence. Popular types of CAMs reported were supplements, cannabis products, aromatherapy, herbal remedies, dietary therapy, massage therapy, and prayer. Families often report that CAM is effective, although there are limited objective measures of this. Potential risks lie in the use of CAM, such as herbal remedies, and/or unregulated, contaminated, or unpurified products. Studies also underscored inadequate patient-physician discussions regarding CAM. (4) Conclusions: A better understanding of this topic would aid clinicians in guiding patients/families on the use of CAM. Further studies on the efficacy of the different types of CAM used, as well as potential side effects and drug interactions are needed.

Melatonin prevents diabetes-induced nephropathy by modulating the AMPK/SIRT1 axis: Focus on autophagy and mitochondrial dysfunction.

Impaired nutrient sensing mechanisms such as AMPK/silent information regulator type 1 (SIRT1) axis and autophagy in renal cells upon chronic diabetic condition accelerate renal injury and upregulating these mechanisms has been reported to prevent renal damage. Melatonin, a neuroendocrine agent, also possess antioxidant and AMPK modulatory effect. In the current study, the protective effect of melatonin against diabetic renal injury was assessed in streptozotocin-induced diabetic nephropathy model and in in vitro model of high-glucose-induced tubular injury. Melatonin (3 and 10 mg/kg) was administered for 28 days after 4 weeks of diabetes induction in Sprague-Dawley rats. For in vitro model, the NRK-52E cells were co-incubated with high glucose and melatonin (25 and 50 µM). Melatonin supplementation abrogated the diabetes-induced renal injury and improved renal function in diabetic rats. Immunoblot analysis of renal tissue lysates revealed improved expression of AMPK, as well as upregulated the expression of nuclear factor erythroid 2-related factor 2, SIRT1, PGC-1α, TFAM and enhanced autophagy upon melatonin treatment in diabetic rats. Likewise, melatonin treatment in high glucose exposed NRK-52E cells improved expression of AMPK, enhanced mitochondrial biogenesis and positively modulated autophagy. However, these effects were repressed upon inhibition of AMPK activity in NRK-52E cells by treatment of Compound-C, suggesting that the protective effects of melatonin were mainly mediated through activation of AMPK. These results suggest that melatonin might mediate the renoprotective effect by upregulating the AMPK/SIRT1 axis, enhancing the autophagy and mitochondrial health in DIabetic Nephropathy.

Gestational Age-Specific Nomogram of Transcutaneous Bilirubin in First 120 h of Life for Term and Late Preterm Indian Neonates.

OBJECTIVE: To create a nomogram based on transcutaneous bilirubin values (TCB) in first week of life for term and late preterm (>34 weeks) neonates. METHODS AND DESIGN: Prospective longitudinal study. SETTING: Four tertiary-care teaching hospitals (one each in eastern and southern India, two in northern India) between February 2019 and March 2020. PARTICIPANTS: A total of 2492 term and late preterm (>34 weeks) neonates. INTERVENTION: Bilirubin was measured by transcutaneous bilirubinometer (Drager JM-105, Germany) in all neonates in pre-specified times of the day, 12 hourly every day since birth till discharge between 48 and 72 h, and data were recorded in epochs of 6 hourly intervals. Post-discharge, all neonates were called for review in next 48 h. OUTCOME MEASURES: Primary-TCB in first week of life. Secondary-factors having significant association with significant hyperbilirubinaemia requiring phototherapy. RESULTS: Total of 2492 neonates (males 1303 and female 1189), with a total of 14 162 TCB recordings were analysed and mean hourly bilirubin (TCB) at hourly intervals till 120 h and then daily bilirubin values on Days 6 and 7 were tabulated. We have constructed hour-specific bilirubin nomogram with percentiles as per gestational age in term and near-term Indian neonates till 120 h of life. Amongst the known risk factors, delayed cord clamping, primipara and breastfeeding jaundice had significant association for hyperbilirubinaemia needing phototherapy. CONCLUSIONS: We have created gestation-specific nomogram of TCB levels in 6 hourly intervals for the first 120 postnatal hours, obtained from a large predominantly breast fed healthy, term and near-term Indian neonates.

Complementary and Alternative Medicine (CAM) use in Children with Epilepsy.

Complementary and alternative medicine (CAM) use by the pediatric population with epilepsy in rural Pennsylvania was studied to characterize the prevalence, perceived effectiveness, and reasons for CAM use. This study additionally assessed the adequacy of parent-physician communication regarding CAM usage. A telephone survey was administered to 200 parents/caregivers of children with epilepsy followed at Hershey Medical Center. Thirteen percent of respondents indicated CAM use by their child. Common types of CAM used were cannabis-related products such as CBD oil and medical marijuana. Forty-eight percent of CAM users chose to initiate CAM owing to dissatisfaction with the outcomes of antiseizure drugs. Fifty-nine percent noticed a decrease in seizure frequency with CAM use, and more than 11% of CAM users reported side effects from CAM. Eighty percent of CAM users had discussions regarding CAM with their child's neurologist. CAM use was found to be associated with increased seizure severity (P = .004) and the prior use of cannabidiol (Epidiolex) (P < .001) or the ketogenic diet (P = .001). Increased seizure severity and the prior use of Epidiolex or the ketogenic diet may be used as predictors for the identification of patients with a higher likelihood of using CAM. Interest in future CAM use, especially cannabis-related products, was expressed in a large percentage of non-CAM users. Given the high parental or caregiver interest in CAM, providers are encouraged to be proactive in initiating discussions about CAM and collaborate with parents/caregivers to ensure the safe usage of CAM among pediatric patients.

Hydrothermal treatment of metal impregnated biomass for the generation of H2 and nanometal carbon hybrids.

The nanocatalyst impregnation onto the biomass matrix has gained importance in enhancing the H2 yield and overcoming the catalyst deactivation problems. In-situ catalytic gasification of Ru/Fe-impregnated sugarcane bagasse and citrus limetta (mosambi peels) were examined and compared with their raw biomass at subcritical and supercritical water conditions. Bagasse having a higher amount of lignocellulosic content produces a maximum yield of H2 over moambi peels. Besides, Ru and Fe nano-metal carbon hybrids with crystalline sizes between 10 and 25 nm were formed during in-situ hydrothermal gasification. The performance of hydrothermal gasification based on hydrogen yield was studied, and it relatively follows the order as temperature, nanoparticle composed, metal loading onto biomass matrix, type of catalyst, and biomass used. At the maximum operating temperature of 600 °C, B: W ratio 1:10 for the resident time of 60 min, highest H2 yield of 12.75 ± 0.17 and 11.20 ± 0.13 mmol/g attained for Ru and Fe impregnated bagasse with the CGE of 72.28 ± 2.17% and 67.08 ± 1.97% respectively. At similar operating conditions, H2 yields of 8.75 ± 0.18 and 8.13 ± 0.16 mmol/g were achieved with the CGE of 62.4 ± 1.91% and 53.7 ± 1.66% for Ru and Fe impregnated mosambi peels, respectively. Based on the H2 and CH4 production, Ru shows the highest performance than Fe catalyst.

Structure-based virtual screening of highly potent inhibitors of the nematode chitinase CeCht1.

Nematode chitinases play vital roles in various physiological processes, including egg hatching, larva moulting, and reproduction. Small-molecule inhibitors of nematode chitinases have potential applications for controlling nematode pests. On the basis of the crystal structure of CeCht1, a representative chitinase indispensable to the eggshell chitin degradation of the model nematode Caenorhabditis elegans, we have discovered a series of novel inhibitors bearing a (R)-3,4-diphenyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one scaffold by hierarchical virtual screening. The crystal structures of CeCht1 complexed with two of these inhibitors clearly elucidated their interactions with the enzyme active site. Based on the inhibitory mechanism, several analogues with improved inhibitory activities were identified, among which the compound PP28 exhibited the most potent activity with a Ki value of 0.18 µM. This work provides the structural basis for the development of novel nematode chitinase inhibitors.

Fabrication of methotrexate-loaded gold nanoconjugates and its enhanced anticancer activity in breast cancer.

Methotrexate (MTX) is known antagonist of folic acid and widely used as an anti-cancer drug. The folate receptor (FR) and reduced folate carrier are mostly responsible for internalization of methotrexate in tumor cells. Mutation in reduced folate carrier (RFC) leads to resistance against MTX in various tumor cell lines including MDA-MB-231 breast cancer cells. To overcome the resistance of MTX, folate receptor targeted nanoparticles have been commonly used for targeting breast tumors. The aim of the study is to determine the ability of methotrexate gold nanoparticles (MTX-GNPs) in the induction of apoptosis and to explore the molecular changes at genomics and proteomics level. Different assays like cell viability assay, cell cycle analysis, apoptosis, real-time PCR and western blot were carried out to evaluate the anti-cancer effect of MTX-Gold NPs on MCF-7 and MDA-MB-231 cells. Our observations demonstrated the decrease in the percent viable cells after the treatment of MTX-GNPs, with an arrest in cell cycle at G0/G1 phase and a significant increase in apoptotic cell population and loss of mitochondrial membrane potential in MCF-7 and MDA-MB-231 cells. Folate receptor targeted MTX-GNPs showed significant cellular uptake in breast cancer cells along with significant down-regulation in expression of anti-apoptotic gene (Bcl-2) and up-regulation in expression of pro-apoptotic genes (Bax, Caspase-3, Caspase-9, APAF-1, p53). These results unveil the increased anti-cancer effect of MTX-GNPs in cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02718-7.

Identification of a Selective RelA Inhibitor Based on DSE-FRET Screening Methods.

Nuclear factor-κB (NF-κB) is an important transcription factor involved in various biological functions, including tumorigenesis. Hence, NF-κB has attracted attention as a target factor for cancer treatment, leading to the development of several inhibitors. However, existing NF-κB inhibitors do not discriminate between its subunits, namely, RelA, RelB, cRel, p50, and p52. Conventional methods used to evaluate interactions between transcription factors and DNA, such as electrophoretic mobility shift assay and luciferase assays, are unsuitable for high-throughput screening (HTS) and cannot distinguish NF-κB subunits. We developed a HTS method named DNA strand exchange fluorescence resonance energy transfer (DSE-FRET). This assay is suitable for HTS and can discriminate a NF-κB subunit. Using DSE-FRET, we searched for RelA-specific inhibitors and verified RelA inhibition for 32,955 compounds. The compound A55 (2-(3-carbamoyl-6-hydroxy-4-methyl-2-oxopyridin-1(2H)-yl) acetic acid) selectively inhibited RelA-DNA binding. We propose that A55 is a seed compound for RelA-specific inhibition and could be used in clinical applications.

Proportionate Postnatal Growth in Preterm Neonates on Expressed Breast Milk Feeding With Selected Fortification.

BACKGROUND: Preterm neonates not fed an exclusive human-milk diet in the neonatal intensive care unit (NICU) show disproportionate postnatal growth. There are scant data on postnatal growth in neonates from India fed an exclusive expressed breast milk (EBM) diet. This study describes the postnatal changes in weight, length, and head circumference in preterm neonates given EBM with selected fortification. METHODS: The study had a prospective observational design. Exclusive EBM feeding, early initiation, and standardized progression of feeds was followed. Fortification of breast milk with human milk fortifier (HMF) or liquid calcium phosphate and multivitamins (CALVIT) or hindmilk (HM) was done based on the gestational age. Monitoring for weight, length, and head circumference was done from admission to discharge. RESULTS: Ninety-three preterm neonates were included in the study, of which 34 (36.6%) were small for gestational age. Thirty-two (34.3%) neonates received EBM with HMF, 35 (35.7%) received EBM fortified with CALVIT and 26 (28%) neonates received HM fortification. There was a significant difference in the change in z-scores from birth to discharge for the weight, length, and head circumference (P = .001). The mean increase in daily weight ranged from 8.8 to 9.5 g/d, whereas weekly change in length was 0.8-0.9 cm/wk, and head circumference was 0.7 cm/wk. CONCLUSION: Postnatal growth of preterm neonates during NICU admission on exclusive EBM feeding with selected fortification resulted in a proportionate increase in weight, length, and head circumference.

Use of Complementary and Alternative Medicine in Children With Tourette Syndrome.

INTRODUCTION: Tourette syndrome is a neuropsychiatric condition defined by motor and phonic tics with onset in childhood. Many families have concerns regarding potential side effects of pharmacologic treatments, and often have difficulty accessing comprehensive behavioral intervention for tics. Patients and caregivers may turn to complementary and alternative medicine (CAM) as they perceive these as "natural" and therefore "safe." Although there are anecdotal reports of an increased use of CAM in Tourette syndrome patients, the exact prevalence is unknown. OBJECTIVE: The purpose of this study was to identify commonly used CAM therapies for children with Tourette syndrome at Penn State Hershey Medical Center. METHODS: A questionnaire was administered to the caregivers of children (<18 years old) via telephone. The data pertaining to demographics, type of CAM use, duration of use, adverse effects, and caregiver's perception of the effectiveness were collected. RESULTS: A total of 110 patients participated in this survey. When inquired about the different CAM methods, 69.1% of the participants reported using 1 or more CAM therapies, and 58% of those who used CAM informed the doctor about their use. Ninety-three percent of those who used CAM therapy reported a decrease in tic frequency. The most commonly used CAM therapies were stress management (44.6%), herbal medicine (18.2%), homeopathy (12.7%), and meditation (9.1%). In total, 46% of the participants said that CAM helped more than medication. CONCLUSION: The majority of patients interviewed were using CAM therapies, and a significant portion reported benefit greater than medication. More than half of all participants discussed CAM therapies with their physicians, and 63% of participants felt that their physicians would support their use of CAM therapies.

Combination of humic acid and clay reduce the ecotoxic effect of TiO2 NPs: A combined physico-chemical and genetic study using zebrafish embryo.

The series of breakthroughs that have occurred within the realm of nanotechnology have been the source of several new products and technological interventions. One of the most salient examples in this regard is the widespread employment of titanium dioxide (TiO2) nanoparticles across a range of consumer goods. Given that waste is generated at every stage of the consumer-product cycle (from production to disposal), many items with TiO2 nanoparticles are likely to end up being discarded into water bodies. In order to understand the interaction of TiO2 NPs with aquatic ecosystem, the ecological fate and toxicity of TiO2 NPs was studied by exposing zebrafish embryos to a combination of abiotic factors (humic acid and clay) to assess its effect on the development of zebrafish embryos. The physiological changes were correlated with genetic marker analysis to holistically understand the effect on embryos development. Derjaguin-Landau-Verwey-Overbeek (DLVO) theory was used to analyze the interaction energy between TiO2 NPs and natural organic matter (NOM) for understanding the aggregation behavior of engineered nanoparticles (ENPs) in media. The study revealed that combination of HA and clay stabilized TiO2 NPs, compared to bare TiO2 and HA or clay alone. TiO2 NPs and TiO2 NPs + Clay significantly altered the expression of genes involved in development of dorsoventral axis and neural network of zebrafish embryos. However, the presence of HA and HA + clay showed protective effect on zebrafish embryo development. The complete system analysis demonstrated the possible ameliorating effects of abiotic factors on the ecotoxicity of ENPs.

Evaluation of Rh-Hemolytic Disease in Neonates and Management with Early Intensive Phototherapy in the Neonatal Intensive Care Unit.

BACKGROUND OF THE STUDY: In neonates with Rh-hemolytic disease, light emitting diode (LED) phototherapy allows delivery of high spectral irradiance (SI). A linear correlation exists between SI and efficacy of phototherapy with no saturation point. There is scant data on evaluation and early phototherapy using LED units in Rh-hemolytic disease. OBJECTIVE: This study aimed to describe the hemoglobin (Hb), hematocrit (Hct), total serum bilirubin (TSB), phototherapy parameters and short-term outcomes in neonates with Rh-hemolytic disease. METHODOLOGY: Maternal parameters for Rh-isoimmunization were recorded and monitoring of fetal anemia by Doppler ultrasound was done. Early intensive phototherapy within 1 h of birth was initiated for cord blood Hb below 13.6 g/dl and/or TSB greater than 2.8 mg/dl. RESULTS: Fifty Rh positive neonates were enrolled of which 11/50 (22%) received intrauterine transfusions. The maximum TSB remained below 18 mg/dl in 42/50 (84%) of neonates. The mean SI on the trunk was 56.260 ± 8.768 µW/cm2/nm and duration of phototherapy was 7 ± 3.29 days (mean ± SD). There was a positive correlation between strength of indirect antiglobulin test and cord blood Hb: correlation coefficient (r) = 0.295; direct antiglobulin test and duration of phototherapy: r = 0.331. Early packed red blood cell (PRBC) transfusion was required in 8/50 (16%) neonates while 20/50 (40%) required late transfusions. CONCLUSION: With a mean SI of 56.260 ± 8.768 µW/cm2/nm on the trunk, TSB remained below 18 mg/dl in majority thereby avoiding exchange transfusion. Early or late PRBC transfusion requirement was 1 (1-2) (median ± interquartile range).

Montmorillonite clay and humic acid modulate the behavior of copper oxide nanoparticles in aqueous environment and induces developmental defects in zebrafish embryo.

Copper oxide nanoparticles (CuO NPs) is one of the most commonly used metal oxide nanoparticles for commercial and industrial products. An increase in the manufacturing and use of the CuO NPs based products has increased the likelihood of their release into the aquatic environment. This has attracted major attention among researchers to explore their impact in human as well as environmental systems. CuO NPs, once released into the environment interact with the biotic and abiotic constituents of the ecosystem. Hence the objective of the study was to provide a holistic understanding of the effect of abiotic factors on the stability and aggregation of CuO NPs and its correlation with their effect on the development of zebrafish embryo. It has been observed that the bioavailability of CuO NPs decrease in presence of humic acid (HA) and heteroagglomeration of CuO NPs occurs with clay minerals. CuO NPs, CuO NPs + HA and CuO NPs + Clay significantly altered the expression of genes involved in development of dorsoventral axis and neural network of zebrafish embryos. However, the presence of HA with clay showed protective effect on zebrafish embryo development. These findings provide new insights into the interaction of NPs with abiotic factors and combined effects of such complexes on developing zebrafish embryos genetic markers.

Azadirachtin inhibits amyloid formation, disaggregates pre-formed fibrils and protects pancreatic ß-cells from human islet amyloid polypeptide/amylin-induced cytotoxicity.

The human islet amyloid polypeptide (hIAPP) or amylin is the major constituent of amyloidogenic aggregates found in pancreatic islets of type 2 diabetic patients that have been associated with ß-cell dysfunction and/or death associated with type 2 diabetes mellitus (T2DM). Therefore, developing and/or identifying inhibitors of hIAPP aggregation pathway and/or compound that can mediate disaggregation of preformed aggregates holds promise as a medical intervention for T2DM management. In the current study, the anti-amyloidogenic potential of Azadirachtin (AZD)-a secondary metabolite isolated from traditional medicinal plant Neem (Azadirachta indica)-was investigated by using a combination of biophysical and cellular assays. Our results indicate that AZD supplementation not only inhibits hIAPP aggregation but also disaggregates pre-existing hIAPP fibrils by forming amorphous aggregates that are non-toxic to pancreatic ß-cells. Furthermore, AZD supplementation in pancreatic ß-cells (INS-1E) resulted in inhibition of oxidative stress; along with restoration of the DNA damage, lipid peroxidation and the associated membrane damage, endoplasmic reticulum stress and mitochondrial membrane potential. AZD treatment also restored glucose-stimulated insulin secretion from pancreatic islets exposed to hIAPP. All-atom molecular dynamics simulation studies on full-length hIAPP pentamer with AZD suggested that AZD interacted with four possible binding sites in the amyloidogenic region of hIAPP. In summary, our results suggest AZD to be a promising candidate for combating T2DM and related amyloidogenic disorders.

A Comprehensive Review of Tourette Syndrome and Complementary Alternative Medicine.

PURPOSE OF REVIEW: Tourette syndrome (TS) is a neuropsychiatric condition defined by both motor and phonic tics over a period of at least 1 year with the onset before 18 years of age. The purpose of this article is to review the use of complementary alternative medicine (CAM) in children and adults with Tourette syndrome with emphasis on recent research. RECENT FINDINGS: Most patients do not tell their physician about the use of CAM unless if specifically asked. Of the studies reviewed, description of the treatment and the frequency of use were most often reported. Few studies examine the role or effectiveness of CAM in the treatment of TS specifically. SUMMARY: Practitioners should be aware of current research regarding various CAM modalities used for TS patients, including efficacy, potential adverse effects, and interactions with medications. Robust data about the use of CAM, efficacy, and potential side effects is lacking and requires further research to clarify optimal use.