Search

Importance: National guidelines recommend cardiac rehabilitation (CR) after cardiac valve surgery, and CR is covered by Medicare for this indication. However, few data exist regarding current CR enrollment after valve surgery., Objective: To characterize CR enrollment after cardiac valve surgery and its association with outcomes, including hospitalizations and mortality., Design, Setting, and Participants: This cohort study of patients undergoing valve surgery was conducted in calendar year 2014, with follow-up through 2015. The study included all fee-for-service Medicare beneficiaries undergoing open cardiac valve surgery in 2014. Patients identified by inpatient diagnosis codes for open aortic, mitral, tricuspid, and pulmonary valve surgery were included. Data analysis occurred from January 2018 to March 2019., Exposures: Logistic regression was used to evaluate sociodemographic and clinical factors associated with CR enrollment., Main Outcomes and Measures: We used Andersen-Gill models to evaluate the association of CR enrollment with 1-year hospitalization risk and Cox regression models to evaluate the association of CR enrollment with 1-year mortality risk., Results: A total of 41 369 Medicare beneficiaries (median [interquartile range] age, 73 [68-79] years; 16 935 [40.9%] female) underwent open valve surgery in the United States in 2014. Fewer than half of patients (17 855 [43.2%]) who had valve surgery enrolled in CR programs. Several racial/ethnic groups had lower odds of enrolling in CR programs after valve surgery compared with white patients, including Asian patients (odds ratio [OR], 0.36 [95% CI, 0.28-0.47]), black patients (OR, 0.60 [95% CI, 0.54-0.67]), and Hispanic patients (OR, 0.36 [95% CI, 0.28-0.46]). Patients undergoing concomitant coronary artery bypass grafting had higher odds of CR enrollment (OR, 1.26 [95% CI, 1.20-1.31]) than those without the concomitant coronary artery bypass graft procedure, as did patients in the Midwest census region (OR, 2.40 [95% CI, 2.28-2.54]) compared with those in the South (reference). Cardiac rehabilitation enrollment was associated with fewer hospitalizations within 1 year of discharge (hazard ratio, 0.66 [95% CI, 0.63-0.69] after multivariable adjustment). Enrollment was also associated with a 4.2% absolute decrease in 1-year mortality risk (hazard ratio, 0.39 [95% CI, 0.35-0.44] after multivariable adjustment)., Conclusions and Relevance: Fewer than half of Medicare beneficiaries undergoing cardiac valve surgery enroll in CR programs, and there are marked racial/ethnic disparities among those that do. Cardiac rehabilitation is associated with decreased 1-year cumulative hospitalization and mortality risk after valve surgery. These results invite further study on barriers to CR enrollment in this population.

Cellulose nanocrystals (CNCs) have received a great amount of attention to the production of micro/nano-platforms for tissue engineering applications. CNCs were extracted from rice husk biomass and characterized by different spectroscopic techniques. The biocompatibility of the extracted CNCs was revealed by the WST-1 assay technique in the presence of human mesenchymal stem cells (hMSCs) after different time intervals. An improvement in the mechanical properties was observed in the fabricated scaffolds (PCL/CNC) compared to PCL scaffolds. Graphene oxide (GO)-coated (PCL/CNC) electrospun scaffolds (GPC) were prepared by the deposition of PCL/CNC composite nanofibers on the surface of GO for tissue engineering. Notably, better cell proliferation and differentiation were observed in the presence of the fabricated scaffolds. This enhancement of the properties of the fabricated scaffolds was due to the presence of conductive GO moieties which facilitated the cellular response. Therefore, the fabricated materials have the potential to be used as a biomaterial for enhanced cell proliferation and osteogenic differentiation., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Nanohybrid scaffolds of chitosan have been designed for controlled drug delivery and bone regeneration. Sulfonated graphene oxide has been used to develop the nanohybrids. Nanohybrid scaffolds show highly hydrophilic character and greater mechanical strength as compared to pure chitosan. Nanohybrid scaffolds show an interconnected uniform porous network structure exhibiting sustained release kinetics of the antibacterial drug, tetracycline hydrochloride. Nanohybrids are found to be highly biocompatible in nature and are able to support and proliferate MG63 osteoblast cells and thereby induce bone tissue regeneration. The in-vivo bone healing study shows that the developed nanohybrid scaffolds have the potential to regenerate the bone faster without any side effects as compared to pure scaffolds. Hence, the developed nanohybrid scaffold has good potential as a controlled drug delivery vehicle and in bone tissue engineering for faster healing.

Type 2 diabetes (T2D) is associated with an increased risk of macro- and microvascular complications, including cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD). Of the currently available glucose-lowering therapies, sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are the only class to target the pathophysiologic increase in renal glucose reabsorption in patients with T2D. In CV outcomes trials of SGLT-2is in patients with T2D and established CVD or varying levels of CV risk, empagliflozin, canagliflozin, and dapagliflozin were associated with significant improvements in the risk of composite CV and renal outcomes compared with placebo that extended beyond their glycemic effects. Real-world observational studies have also reported improvements in CV outcomes with SGLT-2is compared with other glucose-lowering therapy in routine clinical practice. This review describes the pleiotropic effects of SGLT-2is and discusses the potential mechanisms for these effects as well as how they potentially provide benefits beyond glycemic control in patients with T2D. These favorable nonglycemic effects indicate that SGLT-2is may be of particular benefit in patients with diabetic complications, such as CVD, HF, or CKD. Ongoing large randomized trials in specific patient populations, including those with CVD, HF, or CKD (with or without T2D), may help to confirm the benefits of SGLT-2is in these patients and further elucidate the potential mechanisms of their pleiotropic effects. FUNDING: AstraZeneca.

Scaffolds are considered promising materials for tissue engineering applications due to their unique physiochemical properties. The high porosity and adequate mechanical properties of the scaffolds facilitate greater cell adhesion, proliferation, and differentiation. Stem cells are frequently applied in tissue engineering applications due to their excellent potential. It has been noted that cell functions are profoundly affected by the nature of the extracellular matrix (ECM). Naturally derived ECM contains the bioactive motif that also influences the immune response of the organism. The properties of polymer scaffolds mean they can resemble the native ECM and can regulate cellular responses. Various techniques such as electrospinning and 3D printing, among others, are frequently used to fabricate polymer scaffolds, and their cellular responses are different with each technique. Furthermore, enhanced cell viability, as well as the differentiation ability of stem cells on the surface of scaffolds, opens a fascinating approach to the formation of ECM-like environments for tissue engineering applications., Competing Interests: The authors declare no conflict of interest.

The increased incidence of diabetes to the magnitude of a global epidemic is attributed to non-traditional risk factors, including exposure to environmental chemicals. However, the contribution of xenobiotic exposure during the development of an organism to the etiology of diabetes is not fully addressed. Developing stages are more susceptible to chemical insult, but knowledge on the consequence of the same to the onset of diabetes is residual. In this context, by using Drosophila melanogaster having conserved Insulin/Insulin growth factor-like signaling (IIS) as well as glucose homeostasis as a model, we evaluated the potential of developmental exposure to dichlorvos (DDVP, an organophosphorus pesticide) or atrazine (herbicide) to cause diabetes in exposed organisms. Flies exposed to DDVP during their development display insulin deficiency or type 1 diabetes (T1D) while those exposed to atrazine show insulin resistance or type 2 diabetes (T2D), suggesting that exposure to these xenobiotics during organismal development can result in diabetes and that different mechanisms underlie pesticide mediated diabetes. We show that oxidative stress-mediated c-Jun N-terminal kinase (JNK) signaling activation underlies insulin resistance in flies exposed to atrazine during their development while DDVP-mediated T1D involves activation of caspase-mediated cell death pathway. Mitigation of oxidative stress through over-expression of SOD2 in atrazine (20μg/ml) exposed flies, revealed significantly decreased oxidative stress levels and reduced phosphorylation of JNK. Moreover, glucose and Akt phosphorylation levels in SOD2 over-expression flies exposed to atrazine were comparable to those in controls, suggesting restoration in insulin sensitivity. Therefore, exposure to xenobiotics during development is a common risk factor for the development of type 1 or type 2 diabetes. Accordingly, the present study cautions against the use of such diabetogenic pesticides. Also, mitigation of oxidative stress or anti-oxidant supplementation could be a potential therapy for xenobiotic mediated type 2 diabetes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In the original publication of the article, the wrong β-actin blots were pasted in Figs. 1b and 2c. The correct versions of Figs. 1b and 2c are given in this correction.

Fipronil is a highly effective, broad-spectrum insecticide used to control pests, globally. The increased usage has led to contamination of soil, water, fruits, and vegetables. The wide and frequent usage of fipronil across the globe calls for attention regarding risk assessment of undesirable effects on non-target microorganisms. In this context, the present study was carried to understand the impact of fipronil on non-pathogenic Escherichia coli. The non-pathogenic E. coli are important commensal of the intestinal tract of humans and animals and are also indicator organisms in the environment. Our study indicates that exposure of E. coli to fipronil (100 μM concentration) leads to significant reactive oxygen species production, loss of membrane potential and viability. Further, we have witnessed the bioaccumulation and biotransformation of fipronil by E. coli at non-lethal concentrations. The bio-transformed products (fipronil sulfone and fipronil sulfide) are also the major metabolites (along with amide) reported in the feces of the mammals when exposed to fipronil. Thus, there is a possibility that the gut E. coli might play a role in the degradation and thereby removal of fipronil. In addition, the bioaccumulation of fipronil in bacteria is of concern and need to be further explored because it can lead to biomagnification in the higher trophic level and can disturb the ecological balance. In our knowledge, this is the first report on the determination of fipronil and its metabolites in bacteria through GC-MS/MS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Fluorescence probe has attracted significant attention for biomedical imaging in recent years due to their high resolution at the cellular level. Organic-based fluorescent probes with high quantum yield are widely applied in bioimaging, but most of them suffer from a serious obstacle called aggregation-caused quenching in cellular systems. New fluorophore has been designed through functionalization of graphene oxide which emphatically exhibits aggregation-induced emission along with pH-responsive nanoprobe. Significantly higher emission of this material in slightly acidic media helps to detect tumor cell by creating a sharp contrast with the image of normal cells. The reason for pH-induced enhanced emission phenomenon is revealed through aggregation of sulfonated species in acidic media. Furthermore, the biocompatible nature of the newly developed material is found to be suitable for its application in biomedical imaging for cancer detection with better accuracy at lower cost. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1917-1924, 2019., (© 2019 Wiley Periodicals, Inc.)

Human mesenchymal stem cells (hMSCs) have attracted significant attention for tissue engineering because of their ability to differentiate into bone cells, chondrocytes, adipocytes, and muscle cells. Single-walled carbon nanotubes (SWCNTs) have been considered as a potential material for tissue engineering applications due to their unique properties, such as high aspect ratio, excellent electrocatalytic activity, and biocompatibility. Here we prepared exfoliated SWCNTs layers through an ultra-sonication process in the acidic medium and evaluated their cytotoxicity using hMSCs. Improved viability and osteogenesis of hMSCs were observed in the presence of exfoliated SWCNTs. Besides, the higher expression of osteogenic differentiation-related genes in the presence of exfoliated SWCNTs further confirmed their enhanced osteogenic nature. These results indicated the potential of SWCNTs as a biomaterial for tissue engineering applications.

Santonin, a natural product, was aromatized with molecular iodine as the catalyst. The new compound was characterized as ( S)-methyl-2-(7-hydroxy-5,8-dimethylnaphthalen-2-yl) propanoate (2) based on 2D NMR spectroscopic data. Structurally, compound 2 was highly similar to the anti-inflammatory drug naproxen. The new naproxen analogue had significant potency against cyclooxygenase 1 and 2 (IC 50 = 31.0 and 66.1 μM, respectively).

Cellulose-based hydrogels are immensely important for tissue engineering. In this review, we attempt to document the source, nature, and application of cellulose-based hydrogels as an extracellular matrix for tissue growth and regeneration. Hydrogels can be prepared either from native cellulose, including both bacterial and plant sources or from cellulose derivatives, such as methyl cellulose, carboxymethylcellulose, and hydroxypropylmethylcellulose or even metal ions such as silver. Cellulose-polymer composite (polymers that include natural sources including chitosan, starch, alginates, collagen, hyaluronic acid, and chitin) are an attractive, inexpensive, and advantageous structural material that is easy to use. Cellulose-based scaffolding materials are widely used in the regeneration of various tissues, such as bone, cartilage, heart, blood vessel, nerve, and liver, among others. In this review, we discuss the most important applications of cellulosic hydrogels in tissue engineering based on their structural compositions., Competing Interests: Competing interestsThe authors declare no competing interests.

Nanocellulose, derived from cellulose hydrolysis, has unique optical and mechanical properties, high surface area, and good biocompatibility. It is frequently used as a reinforcing agent to improve the native properties of materials. The presence of functional groups in its surface enables the alteration of its behavior and its use under different conditions. Nanocellulose is typically used in the form of cellulose nanocrystals (CNCs), cellulose nanofibers (CNFs), or bacterial nanocellulose (BNC). CNCs and CNFs have a high aspect ratio with typical lengths of ∼100-250 nm and 0.1-2 μm, respectively; BNC is nanostructured cellulose produced by bacteria. Nanohybrid materials are a combination of organic or inorganic nanomaterials with macromolecules forming a single composite and typically exhibit superior optical, thermal, and mechanical properties to those of native polymers, owing to the greater interactions between the macromolecule matrix and the nanomaterials. Excellent biocompatibility and biodegradability make nanocellulose an ideal material for applications in biomedicine. Unlike native polymers, nanocellulose-based nanohybrids exhibit a sustained drug release ability, which can be further optimized by changing the content or chemical environment of the nanocellulose, as well as the external stimuli, such as the pH and electric fields. In this review, we describe the process of extraction of nanocellulose from different natural sources; its effects on the structural, morphological, and mechanical properties of polymers; and its various applications., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Extracorporeal septoplasty is a valuable tool in the armamentarium of the nasal surgeon for the reconstruction of the severely deviated septum. Extracorporeal septoplasty offers the surgeon the opportunity to correct the septum under direct visualization, shape the nasal vault and address the nasal dorsum with the ultimate goal of providing both form and function for the patient with a complex septal deviation. The study was conducted with the aim to measure the outcomes of extracorporeal septoplasty in severely deviated nasal septum, relief of symptoms (nasal obstruction), surgical complications, if any, revision, if any with objective to evaluate the functional outcome and aesthetic aspects of extracorporeal septoplasty. This was a prospective observational study of 35 patients with severe deviated nasal septum with or without external deformity of nose attending the ENT OPD between Jan 2015 and Jan 2016 at Sri Aurobindo Medical College and Post Graduate Institute, Indore (M.P.). In this study, 17 patients (48.57%) shows excellent improvement on VAS scale, out of which 13 patients shows excellent improvement and 4 patients shows good improvement on photographic assessment. 11 patients (31.43%) show good improvement on VAS as well as photographic assessment and 7 patients (20%) show moderate improvement on VAS scale and fair improvement on photographic assessment. Extracorporeal septal reconstruction is an important surgical option for the correction of the markedly deviated nasal septum. Fixation of the straightened and replanted septum at the nasal spine and dorsal septum border with the upper lateral cartilages is essential. Spreader grafts for stabilization of the internal nasal valve and dorsal onlay grafts to prevent dorsal irregularity are strongly encouraged., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.

Prenatal exposure to low doses of lindane, an organochlorine insecticide used in public health and agriculture, induced a persistent increase in the expression of cerebral cytochrome P450s (CYPs) in rat offspring and modify the adult response to a later exposure of xenobiotics. To understand the mechanism involved in the modification of adult response, rat offspring exposed prenatally to lindane (p.o.; 0.25 mg/kg b.wt. from gestation day 5-21) were rechallenged with lindane (p.o.; 5 mg/kg X 5 days) postnatally at 9- or 18- or 27 weeks. The greater magnitude of increase in the expression of cerebral CYPs in rechallenged offspring and decline in the magnitude of increase in CYPs with increasing age correlated with the amount of lindane accumulating in the brain. Significant alterations in the circulatory levels of hormones in the rechallenged offspring suggest that these alterations may partly account for the persistence in the increase in the cerebral CYPs during development. Epigenetic data further revealed alterations in histone H3 acetylation and DNA methylation in promoter regions of cerebral CYPs isolated from rechallenged offspring at 9- or 18- or 27 weeks. Bisulphite sequencing revealing critical CpG methylation changes in the promoter regions in rechallenged offspring at 9 weeks demonstrated imprinting of the cerebral CYPs. Further, a greater magnitude of increase in apoptosis in the brain of rechallenged offspring has suggested that enhanced responsiveness of cerebral CYPs, which may result due to alterations in circulatory hormones, increased accumulation of lindane in the brain and epigenetic regulation of CYPs, is of toxicological relevance., (Copyright © 2019. Published by Elsevier Inc.)

Since the introduction of insulin as a life-saving agent for patients with type 1 diabetes, insulin preparations have evolved to approximate physiologic insulin delivery profiles to meet prandial and basal insulin needs. While prandial insulins are designed to have quick time-action profiles that minimize postprandial glucose excursions, basal insulins are designed to have a protracted time-action profile to facilitate basal glucose control over 24 h. Given that all insulins have the same mechanism of action at the target tissue level, the differences in time-action profiles are achieved through different mechanisms of protraction, resulting in different behaviors in the subcutaneous space and different rates of absorption into the circulation. Herein, we evaluate the differences in basal insulin preparations based on their differential mechanisms of protraction, and the resulting clinical action profiles. Multiple randomized control trials and real-world evidence studies have demonstrated that the newer second-generation basal insulin analogs, insulin glargine 300 units/mL and insulin degludec 100 or 200 units/mL, provide stable glycemic control with once-daily dosing and are associated with a reduced risk of hypoglycemia compared with previous-generation basal insulin analogs insulin glargine 100 units/mL and insulin detemir. These advantages can lead to decreased healthcare resource utilization and cost. With this collective knowledge, healthcare providers and payers can make educated and well-informed decisions when determining which treatment regimen best meets the needs of each individual patient.Funding: Sanofi US, Inc.

Particle-based systems provide a capability for the delivery of imaging and/or therapeutic payloads. We have engineered constructs derived from erythrocytes, and doped with the FDA-approved near infrared dye, indocyanine green (ICG). We refer to these optical particles as NIR erythrocyte-mimicking transducers (NETs). A particular feature of NETs is that their diameters can be tuned from micron- to nano-scale. Herein, we investigated the effects of micron- (≈2.6 μm diameter), and nano- (≈145 nm diameter) sized NETs on their biodistribution, and evaluated their acute toxicity in healthy Swiss Webster mice. Following tail vein injection of free ICG and NETs, animals were euthanized at various time points up to 48 hours. Fluorescence analysis of blood showed that nearly 11% of the injected amount of nano-sized NETs (nNETs) remained in blood at 48 hours post-injection as compared to ≈5% for micron-sized NETs (μNETs). Similarly, at this time point, higher levels of nNETs were present in various organs including the lungs, liver, and spleen. Histological analyses of various organs, extracted at 24 hours post-injection of NETs, did not show pathological alterations. Serum biochemistry profiles, in general, did not show elevated levels of the various analyzed biomarkers associated with liver and kidney functions. Values of various hematological profiles remained within the normal ranges following the administration of μNETs and nNETs. Results of this study suggest that erythrocyte-derived particles can potentially provide a non-toxic platform for delivery of ICG.

Beta-glucan ( β -glucan) is a macromolecule structure where glucose unit has bonded through β -glycosidic bond at 1 and 3 positions. It is well known as a natural immunomodulator without exhibiting any side effects via enhancing immunity. Mushroom contains a large amount of β -glucan and it has anticancerous and antioxidant efficacy. Structure and physical properties of β -glucan are highly influenced by the types of mushroom. In particular, Grifola frondosa has β -1, 3 and β -1, 6 bonds in their structure. It has been noted that β -glucan content also depends upon the size of mushroom particles. The exact content of β -glucan and their immunological activity by a particle size of G. frondosa have yet to be fully elucidated. Herein, β -glucan contents were analyzed according to the particle size of leaf mushroom followed by cell activation and immunoactivity analysis. The highest β -glucan content was observed at a particle size of 20-30 μ m (27.65 ± 0.30 w/w). All samples showed ~ 103% cell activation compared to the control and greater cell activity was observed at higher concentration. The significant increase in cytokines secretion was observed in the presence of 20-30 μ m particle size of G. frondosa compared to the control. This study suggested that 20-30 μ m size is the suitable size of G. frondosa that can be used as a health supplement and food additive to act as an immune booster, hypotensive agent, and hypoglycemic agent.

Stimuli-responsive materials, also known as smart materials, can change their structure and, consequently, original behavior in response to external or internal stimuli. This is due to the change in the interactions between the various functional groups. Graphene, which is a single layer of carbon atoms with a hexagonal morphology and has excellent physiochemical properties with a high surface area, is frequently used in materials science for various applications. Numerous surface functionalizations are possible for the graphene structure with different functional groups, which can be used to alter the properties of native materials. Graphene-based hybrids exhibit significant improvements in their native properties. Since functionalized graphene contains several reactive groups, the behavior of such hybrid materials can be easily tuned by changing the external conditions, which is very useful in biomedical applications. Enhanced cell proliferation and differentiation of stem cells was reported on the surfaces of graphene-based hybrids with negligible cytotoxicity. In addition, pH or light-induced drug delivery with a controlled release rate was observed for such nanohybrids. Besides, notable improvements in antimicrobial activity were observed for nanohybrids, which demonstrated their potential for biomedical applications. This review describes the physiochemical properties of graphene and graphene-based hybrid materials for stimuli-responsive drug delivery, tissue engineering, and antimicrobial applications.

The treatment of type 2 diabetes (T2D) is often complicated by factors such as patient co-morbidities, complex drug-drug interactions, and management of adverse events. In addition, some of these factors are highly dependent on the nature of the treatment regimen and the molecular and physical properties of the drugs being used to treat patients with this disease. This calls for a better understanding of how the properties of individual drugs affect the overall outcome for patients with diabetes. Clinical pharmacology studies to assess the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of new diabetes drugs play an important role in advancing our understanding of the interactions between a drug and the human body. Specific PK and PD techniques such as the glucose clamp test can be applied to assess the properties of drugs used for the treatment of diabetes. Basal insulin analogs are a common treatment option for the maintenance of glycemic control in patients with T2D. These drugs work by mimicking endogenous insulin secretion within the body and provide stable and prolonged insulin action to achieve optimal glucose levels. Insulin glargine 300 U/mL (Gla-300) and insulin degludec (IDeg) 100 U/mL and 200 U/mL represent a new generation of longer-acting basal insulins. These drugs demonstrate improved PK and PD properties compared with previous basal insulins, allowing them to more closely mimic physiological basal insulin secretion. Here we review the methods used to evaluate the PK and PD profiles of Gla-300 and IDeg and describe studies that have investigated the PK/PD properties of these drugs in type 1 diabetes. The aim of this review is to inform primary care physicians of the value and limitations of data from clinical pharmacology studies when prescribing these agents for the management of T2D.

There is a need for the development of liposomes based nanomedicines formulation for better efficacy and safety of the available drugs in the market. Liposomes have various applications in the field of pharmaceutical and medical field for their drug target potential, diagnostic importance and imaging techniques. Natural plant based drugs and their derivatives have been used in the medicine, nutraceuticals, perfumery, cosmetic and beverages industry. More than half of the prescribed drugs in the worldwide are mainly derived from different natural sources. Development of plant derived product is an emerging field of food, pharmaceutical and health industries. Plants belonging to the Gentianaecae family are well known for their bitter taste and Swertia chirata is one of best plants among them. Various active phytochemical of Swertia chirata are bitter secoiridoids like gentiopicroside, amarogentin, swertiamarin, isovitexin and isogentisin. People use different species of Swertia in the form of decoction, infusion, paste and juice for the treatment of fever and enteric diseases. Swertia chirata possesses anticarcinogenic, antioxidative, hypoglycemic, antihepatotoxic, antimalarial, anti-inflammatory and antimicrobial activities. Amarogentin, a bitter secoiridoid glycoside present in Swertia chirata plant is an activator of human bitter taste receptor. Pharmacologically, amarogentin has antibacterial, antihepatitis, anticholinergic and chemopreventive activities, moreover, amarogentin has been proven for their anti-lieshmanial activity. Other studies also suggested that amarogentin acts on liver carcinogenesis, skin carcinogenesis and reduced tumour progression. In the present review, we have collected and compiled the data regarding biological sources, ethnomedicinal uses, phytochemistry, anticancer and anti-infective potential of amarogentin. For better understanding of various aspects of amarogentin, we have also discussed Swertia chirayita in a very concise manner. Further data related to various patents on amarogentin have also been discussed in this manuscript. However, we also admit that new advance biological research will also increase the medicinal and pharmacological value of amarogentin. Information regarding the chemistry of amarogentin, its biological sources, bioavailability as a pharmacological agent for the treatment and management of skin disorders and various forms of cancers will be beneficial to the scientists in the medicinal field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this paper, we show that quantum Hall resistance measurements using two terminals may be as precise as four-terminal measurements when applying superconducting split contacts. The described sample designs eliminate resistance contributions of terminals and contacts such that the size and complexity of next-generation quantized Hall resistance devices can be significantly improved.

Impairment of host immune response in malaria favors bacteremia caused by typhoidal or nontyphoidal serovars of Salmonella enterica. Ofloxacin and Artesunate are the drugs that are clinically proven for treating typhoid and malaria, respectively. The study evaluates the host responses upon treatment with antibiotic (Ofloxacin) and antimalarial (Artesunate) in a standardized mice model harboring coinfection. BALB/c mice (18-22 g) were simultaneously coinfected with Plasmodium yoelii nigeriensis (Pyn) and S. enterica serovar Typhimurium (STm) and then treated with Ofloxacin or/and Artesunate from day 4 to day 7. The bacterial burden, liver function enzymes, oxidative stress, m-RNA expression of Toll-like receptors (TLR-2 and TLR-4), Th1/Th2 cytokines, hemeoxygenase-1, and NFкB were assessed. Ofloxacin treatment failed to counter the bacterial proliferation in Pyn-STm coinfected mice. However, upon controlling parasitemia with antimalarial, the efficacy of Ofloxacin could be regained. Elevated bacterial burden with malaria induces the expression of TLR-2 and TLR-4 triggering intense inflammatory response (NFκB, Th1/Th2 cytokines) in coinfected mice. This results in critical liver damage (ALT, AST, and ALP), oxidative stress (lipid peroxidation, total GSH, catalase, and super oxide dismutase), and hemeoxygenase-1 (HO-1). The study concludes that malaria infection aggravates the secondary infection of Salmonella serovars and the control of septicemia is critical in recovery of the coinfected subject.

Background: To study the association between kidney injury biomarkers and urinary OH-PAH metabolites in kitchen workers, with microalbuminuria., Methods: A cross-sectional pilot study was conducted among 120 male kitchen workers in a mega kitchen located at Coimbatore, India. Personal and sub-clinical details of study subjects were collected using a questionnaire. Albumin, creatinine, and albumin-creatinine ratio (ACR) were measured using urine dipstick test for the determination of microalbuminuria. Urinary hydroxylated PAHs metabolites (1-NAP, 9-HF, 3-HF, 2-HF, 9-PHN, and 1-OHP) were measured using GC-MS/MS and urinary kidney biomarkers (uNGAL, uCyst-C, uKIM-1, uOPN, and uTIMP-1) were measured using Multiplex Reader., Results: Concentrations of urinary PAHs metabolites (1-NAP, 3-HF, 2-HF, 9-PHN, and 1-OHP) and kidney biomarkers (uKIM-1, uTIMP-1, uCyst-C and uNGAL) were significantly higher among kitchen workers with MAU compared to non-kitchen workers with MAU. Urinary kidney biomarkers viz., uKIM-1, uTIMP-1, uCyst-C, uNGAL, and uOPN showed higher median concentration among the kitchen workers with MAU compared to kitchen workers without MAU. Significant positive correlation was observed for 9-HF with uKIM-1 and uTIMP-1 and 1-OHP with uKIM-1. ACR was also well correlated with urinary kidney biomarkers. ROC analysis showed higher sensitivity and specificity for uKIM-1, uCyst-C, and uNGAL as biomarkers for early prediction of acute kidney injury among kitchen workers., Conclusions: The PAHs exposure among kitchen workers can lead to kidney injury. This was evident from the association of OH-PAHs and kidney injury biomarkers in kitchen workers with microalbuminuria., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Nanosize structures activated by near-infrared (NIR) photoexcitation can provide an optical platform for the image-guided removal of small tumor nodules. We have engineered nanoparticles derived from erythrocytes that can be doped with NIR fluorophore indocyanine green (ICG). We refer to these constructs as NIR erythrocyte-derived transducers (NETs). The objective of this study was to determine if ICG-bound albumin (IbA), as the doping material, could enhance the fluorescence emission of NETs, and evaluate the capability of these nanoprobes in imaging cancer cells. Erythrocytes were isolated from bovine whole blood and depleted of hemoglobin to form erythrocyte ghosts (EGs). EGs were then extruded through nanosize porous membranes in the presence of 10-100 μm ICG or Iba (1:1 molar ratio) to form ICG- or IbA-doped NETs. The resulting nanosize constructs were characterized for their diameters, zeta-potentials, absorption, and fluorescence emission spectra. We used fluorescence microscopic imaging to evaluate the capability of the constructs in imaging SKOV3 ovarian cancer cells. Based on dynamic light-scattering measurements, ICG- and IbA-doped NETs had similar diameter distributions ( Z -average diameter of 236 and 238 nm, respectively) in phosphate-buffered saline supplemented with 10% fetal bovine serum, which remained nearly constant over the course of 2 h at 37 °C. Despite a much-lower loading efficiency of IbA (∼0.7-8%) as compared to ICG (10-45%), the integrated normalized fluorescence emission of IbA-NETs was 2- to 6-fold higher than ICG-doped NETs. IbA-NETs also demonstrated an enhanced capability in fluorescence imaging of SKOV3 ovarian cancer cells, and can serve as potentially effective nanoprobes for the fluorescence imaging of cancerous cells.

A simple and rapid method for the extraction of organochlorine compounds (OCs) including poly-chlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in fish liver using ultrasound assisted dispersive liquid-liquid microextraction based on the solidification of floating organic droplet (US-DLLME-SFO) was developed. For reducing the complexity of the matrix, the sample was pre-treated prior to microextraction. Factors affecting US-DLLME-SFO were optimized by using statistical design of experiment (DoE). The analysis was carried out by Gas Chromatography (GC) equipped with micro electron capture detector (μ-ECD). The optimized parameters were 4.8 min of ultrasound, 3.0 mL of Milli-Q and 24 μL of 1-undecanol as an extraction solvent as determined by DoE. US-DLLME-SFO was validated in terms of limit of detection, limit of quantification, dynamic linearity range, coefficient of determination (linearity) and extraction recovery in fish liver for OCs, and the respective values were (1.06-3.84 ng g -1 ), (3.50-12.67 ng g -1 ), (1.0-500 ng g -1 ), (R 2  = 0.994-0.999), (88.5-108.4%). Interday and intraday precisions were evaluated as relative standard deviation (% RSD) and the values were ≤10%., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Tannery wastewater (TWW) is of serious environmental concern to pollution control authorities, because it contains highly toxic, recalcitrant organic and inorganic pollutants. The nature and characteristics of recalcitrant organic pollutants (ROPs) are not fully explored to date. Hence, the purpose of this study was to characterize and identify the ROPs present in the treated TWW. Gas chromatography-mass spectrometry data analysis showed the presence of a variety of ROPs in the treated TWW. Results unfolded that benzyl chloride, butyl octyl phthalate, 2,6-dihydroxybenzoic acid 3TMS, dibutyl phthalate, benzyl alcohol, benzyl butyl phthalate, 4-chloro-3-methyl phenol, phthalic acid, 2'6'-dihydroxyacetophenone, diisobutyl phthalate, 4-biphenyltrimethylsiloxane, di-(-2ethy hexyl)phthalate, 1,2-benzenedicarboxylic acid, dibenzyl phthalate, and nonylphenol were present in the treated TWW. Due to endocrine disrupting nature and aquatic toxicity, the U.S. Environmental Protection Agency classified many of these as "priority pollutants" and restricted their use in leather industries. In addition, the physicochemical analysis of the treated TWW also showed very high BOD, COD, and TDS values along with high Cr and Pb content beyond the permissible limits for industrial discharge. Furthermore, phytotoxicity assessment unfolds the inhibitory effects of TWW on the seed germination, seedling growth parameters, and α-amylase activity in Phaseolus aureus L. This indicates that the TWW discharged even after secondary treatment into the environment has very high pollution parameters and may cause a variety of serious health threats in living beings upon exposure. Overall, the results reported in this study will be helpful for the proper treatment and management of TWW to combat the environmental threats.

Flavonoids are a widely distributed group of phytochemicals having benzo-pyrone nucleus, and more than 4,000 different flavonoids have been described and categorized into flavonols, flavones, flavanones, isoflavones, catechins and anthocyanidins. Flavonoids occurs naturally in fruits, vegetables, nuts, and beverages such as coffee, tea, and red wine, as well as in medical herbs. Flavonoids are responsible for the different colors of plant parts and are important constituents of the human diet. Flavanoids have different pharmacological activities, such as antioxidant, anti-allergic, antibacterial, anti-inflammatory, antimutagenic and anticancer activity. Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables. Pharmacologically, it has anticancer, antimutagenic, anti-inflammatory, antioxidant, antiproliferative and antiatherogenic activities. Naringenin is used for the treatments of osteoporosis, cancer and cardiovascular diseases, and showed lipid-lowering and insulin-like properties. In the present review, detailed pharmacological and analytical aspects of naringenin have been presented, which revealed the impressive pharmacological profile and the possible usefulness in the treatment of different types of diseases in the future. The information provided in this communication will act as an important source for development of effective medicines for the treatment of various disorders.

Alpha-synuclein (α-synuclein) aggregation and impairment of the Ubiquitin proteasome system (UPS) are implicated in Parkinson's disease (PD) pathogenesis. While zinc (Zn) induces dopaminergic neurodegeneration resulting in PD phenotype, its effect on protein aggregation and UPS has not yet been deciphered. The current study investigated the role of α-synuclein aggregation and UPS in Zn-induced Parkinsonism. Additionally, levodopa (L-Dopa) response was assessed in Zn-induced Parkinsonian model to establish its closeness with idiopathic PD. Male Wistar rats were treated with zinc sulfate (Zn; 20 mg/kg; i.p.) twice weekly for 12 weeks along with respective controls. In few subsets, animals were subsequently treated with L-Dopa for 21 consecutive days following Zn exposure. A significant increase in total and free Zn content was observed in the substantia nigra of the brain of exposed groups. Zn treatment caused neurobehavioral anomalies, striatal dopamine decline, and dopaminergic neuronal cell loss accompanied with a marked increase in α-synuclein expression/aggregation and Ubiquitin-conjugated protein levels in the exposed groups. Zn exposure substantially reduced UPS-associated trypsin-like, chymotrypsin-like, and caspase-like activities along with the expression of SUG1 and β-5 subunits of UPS in the nigrostriatal tissues of exposed groups. L-Dopa treatment rescued from Zn-induced neurobehavioral deficits and restored dopamine levels towards normalcy; however, Zn-induced dopaminergic neuronal loss, reduction in tyrosine hydroxylase expression, and increase in oxidative stress were unaffected. The results suggest that Zn caused UPS impairment, resulting in α-synuclein aggregation subsequently leading to dopaminergic neurodegeneration, and that Zn-induced Parkinsonism exhibited positive L-Dopa response similar to sporadic PD.

Neurotransmitters are signaling molecules which play a key role in the central nervous system allowing signal transmission in the neuronal synapses. The role of these compounds is very crucial in the biological systems. A rapid, sensitive, economical and derivatisation free method has been developed for the analysis of 15 neurotransmitters in a single run on liquid chromatography tandem mass spectrometry. These 15 neurotransmitters are categorized into 5 groups on the basis of their fragmentation pattern. The proposed method "ionic liquid based ultrasound assisted dispersive liquid-liquid microextraction" hyphenated with tandem mass spectrometry is the first report for the analysis of neurotransmitters in cell samples along with other two matrices (rat brain and plasma). All the parameters that influence the extraction efficiency are optimized with aid of response surface methodology and desirability profile. Under these optimized conditions the developed method has been validated. The limit of detection was in the range of (1) 0.021-0.912 μg L -1 for rat brain samples, (2) 0.028-0.978 μg L -1 for plasma samples and (3) 0.025-0.945 μg L -1 for cell samples with good linearity behavior for all analytes in the concentration range of 0.04-200 μg L -1 in all the three matrices. The coefficient of determination for all the neurotransmitters was found in the range of (1) (R 2 ) ≥ 0.996 to 0.999 for rat brain samples and (2) (R 2 ) ≥ 0.991 to 0.999 for plasma and cell samples. The intra-day and inter-day variations were found less than (1) 1.78% and 8.94% for rat brain samples, (2) 1.83% and 8.37% for plasma samples and (3) 1.64% and 8.04% for cell samples respectively. The method has mean recoveries varied between (1) 81-128% for brain samples, (2) 88-107% for plasma samples and (3) 91-104% for cell samples at different spiking levels. The optimized and validated method was found free from matrix interferences and successfully applied for quantitative determination of 15 neurotransmitters in the rat brain, plasma and cell samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The presence of pesticides in food items and beverages is a big threat to humankind, and their quantitative estimation with high precision and accuracy is always a challenge for analytical chemists. Hence, a simple and rapid method is proposed for the simultaneous determination of 30 pesticides in beverages (alcoholic and non-alcoholic drinks). The proposed method hyphenated with triple quadrupole liquid chromatography mass spectrometry has only 2 min chromatographic runtime for the analysis of all the pesticides. All the factors affecting the extraction yield have been optimized using an experimental design; and under optimized conditions, the developed method has been validated. The detection limits for all the pesticides were in the range of 0.001-0.348 μg/L with good linearity in the concentration range of 0.01-80.0 μg/L. The coefficient of determination was in the range of (R 2 ) ≥ 0.977 to 0.999 for all the pesticides. The method was also checked for the precision of the relative standard deviation, which was below 4.75 (intra-day) and 8.96% (inter-day). The recovery of the method was 92-138%., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk-benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3.0 mg (risk of gallstone disease and mild, acute pancreatitis), whereas the adverse events associated with orlistat, lorcaserin, and naltrexone/bupropion were mostly transient tolerability issues. The difficulties surrounding the objective determination of risk-benefit for anti-obesity medications is discussed. The need for more long-term data, thorough patient assessment, individualization of pharmacological interventions and adherence to stopping rules to maximize risk-benefit are highlighted. Overall, the majority of new generation anti-obesity medications present encouraging tolerability profiles; however, in some cases a lack of long-term clinical trials confounds the accurate determination of risk-benefit.

Inflammation is decisive in zinc (Zn)-induced nigrostriatal dopaminergic neurodegeneration; however, the contribution of cyclooxygenase-2 (COX-2) is not yet known. The present study aimed to explore the role of COX-2 in Zn-induced Parkinsonism and its association with the microglial activation. Male Wistar rats were treated intraperitoneally (i.p.) with Zn as zinc sulphate (20 mg/kg) along with respective controls for 2-12 weeks. In a few sets, animals were also treated with/without celecoxcib (CXB, 20 mg/kg, i.p.), a selective COX-2 inhibitor. Indexes of the nigrostriatal neurodegeneration, oxidative stress, inflammation and apoptosis were measured in the animals/nigrostriatal tissue. Zn induced time-dependent increase in the expression of COX-2 while COX-1 expression was unaltered. Zn reduced the neurobehavioral activities, striatal dopamine content, tyrosine hydroxylase (TH) expression and number of dopaminergic neurons. While oxidative stress; microglial activation; expression of microglial cell surface marker-CD11b; cytochrome c release; caspase-9/3 activation; level of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 and Bcl-2-associated protein x (Bax) translocation from the cytosol to mitochondria were induced in the Zn-treated group, expression of B-cell lymphoma-2 (Bcl-2) was found to be reduced. CXB significantly attenuated Zn-induced increase in COX-2 expression and restored TH-expression, dopamine content, level of inflammatory cytokines and neurobehavioral indexes towards normalcy. Moreover, CXB also attenuated Zn-induced increase in microglial activation, oxidative stress and apoptotic markers towards normal levels. Results of the study thus demonstrate that COX-2 induces microglial activation that provokes the release of inflammatory mediators, which in turn augments oxidative stress and intrinsic apoptosis leading to dopaminergic neurodegeneration in Zn-induced Parkinsonism.

Microgliosis and inflammation are major wrongdoers in cypermethrin-induced Parkinsonism along with oxidative stress, mitochondrial dysfunction and α-synuclein aggregation. Dopamine depletion could alter dendritic morphology, length and spine number in the striatum. Present study investigated the effect of ibuprofen on the dendritic morphology, length and spine density in cypermethrin PD model. Male pups were treated intraperitoneally with cypermethrin during postnatal days followed by adulthood to induce Parkinsonism using standard procedure along with controls. Subsets of animals were pre-treated with ibuprofen 2 h prior to cypermethrin treatment during adulthood. Standard methods were used to confirm Parkinsonism/neuroprotection. Striatal dendritic morphology, length, spine number and expression of synaptophysin and postsynaptic density protein-95 (PSD-95) along with the nigrostriatal pro-inflammatory and apoptotic proteins were measured. Cypermethrin induced Parkinsonian traits and attenuated the dendritic length, spine number and expression of synaptophysin and PSD-95. While cypermethrin increased the expression of interleukin-1β, interleukin-4, interferon-γ, inducible nitric oxide synthase, caspase-3, caspase-9 and B-cell lymphoma (Bcl)-xl proteins, it attenuated Bcl-2 expression. Ibuprofen normalized the changes in dendritic morphology, length, spine number and expression of synaptophysin, PSD-95, and pro-inflammatory and apoptotic proteins. Results demonstrate that cypermethrin induces inflammation and alters dendritic morphology, length and spine number, which are encountered by ibuprofen.

Parkinson's disease (PD) is the second most familiar, progressive and movement-related neurodegenerative disorder after Alzheimer disease. This study aimed to decipher the role of autophagy in cypermethrin-induced Parkinsonism, an animal model of PD. Indicators of autophagy [expression of beclin 1, autophagy-related protein 12 (Atg 12), unc-51 like autophagy activating kinase 1 (Ulk 1), p62 and lysosome-associated membrane protein 2 (LAMP 2) and conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3) I to II], signalling cascade [phosphorylated (p) 5' adenosine monophosphate-activated protein kinase (p-AMPK), sirtuin 1 (Sirt 1), phosphorylated-mammalian target of rapamycin (p-mTOR), tuberous sclerosis complex 2 (TSC 2), p 317 Ulk 1 and p 757 Ulk 1 levels] and lysosome morphology were assessed in control and cypermethrin-treated rat model of PD. Autophagy markers were also measured in cypermethrin-treated neuroblastoma cells in the presence of 3-methyl adenine, a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) class III inhibitor; vinblastine, an autophagosome elongation inhibitor; bafilomycin A1, an autophagolysosome and lysosome fusion/abnormal acidification inhibitor or torin 1, a mechanistic target of rapamycin inhibitor. Cypermethrin reduced LAMP 2 and increased p-AMPK and Sirt 1 without causing any change in other signalling proteins. 3-Methyl adenine did not change LC3 conversion; vinblastine and bafilomycin A1 decreased LAMP 2 expression in controls. While cypermethrin increased LC3 conversion in the presence of 3-methyl adenine, LAMP 2 reduction was more pronounced in vinblastine and bafilomycin A1-treated cells. Torin 1 normalized the expression of LAMP 2 without any change in other autophagy markers. Results demonstrate that albeit cypermethrin activates autophagosome formation, it reduces LAMP 2 expression and lysosome quality leading to autophagy inhibition.

Prunus amygdalus Batsch (almond) is a classical nutritive traditional Indian medicine. Along with nutritive with anti-oxidant properties, it is, clinically, used in the treatment of various diseases with underlying anti-oxidant mechanism. This study is an effort to scrutinise the renal protective effect of P. amygdalus Batsch or green almond (GA) seed coat extract and its underlying mechanism in animal model of Ferric nitrilotriacetate (Fe-NTA) induced renal cell carcinoma (RCC). RCC was induced in Swiss Albino Wistar rats by intraperitoneal injection of Fe-NTA. The rats were then treated with ethanolic extract of GA (25, 50 and 100 mg/kg per oral) for 22 weeks. Efficacy of GA administration was evaluated by change in biochemical, renal, macroscopical and histopathological parameters and alterations. Additionally, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inflammatory mediator including prostaglandin E2 (PGE 2 ), nuclear factor-kappa B (NF-κB) were also observed to explore the possible mechanisms. The oral administration of GA significantly (p < .001) altered the Fe-NTA induced RCC in rats by inhibition of renal nodules, decolourisation of tissues, tumour promoter marker including thymidine 3 [H] incorporation, ornithine decarboxylase, renal parameters and anti-oxidant parameters in serum. Additionally, GA treatment significantly (p < .001) down-regulated the IL-6, IL-1β, TNF-α, inflammatory mediators PGE 2 and NF-κB in a dose-dependent manner. Histopathology observation supported the renal protective effect of GA by alteration in necrosis, size of Bowman capsules and inflammatory cells. Hence, it can be concluded that GA possesses observable chemo-protective action and effect on Fe-NTA induced RCC via dual inhibition mechanism one by inhibiting free radical generation and second by inhibiting inflammation.

Surface functionalization of graphene oxide with sulfonate group and subsequent grafting with polyurethane chains leads to the significant improvement in the properties of polymer and modified graphene as a filler. Modification of graphene oxide is revealed through spectroscopy while grafting of polymer chain over sulfonated graphene is confirmed through 1 H NMR and other techniques. Higher order of self-assembly phenomena is observed in nanohybrids as compared to pure polymer through greater interaction between polymer chain and sulfonated graphene. Significant improvement in corrosion inhibition phenomena is observed using nanohybrids at low concentration as compared to pure polymer indicating its superior efficiency as a corrosion inhibitor. Nanohybrids also exhibit better biocompatible nature in lower concentration of filler with considerable sustained release of drug vis-à-vis pure polymer suggest its potential to use as a biomaterial for tissue engineering applications.

Background: Staphylococcus aureus (SA), is a major human pathogen causing wide range of clinical infections, which has been further complicated by drug resistance like methicillin resistant S. aureus (MRSA), vancomycin intermediate S. aureus (VISA)/vancomycin resistant S. aureus (VRSA), etc. The present study was aimed at determining anti-staphylococcal potential of citral against drug resistant clinical isolates alone and in combination with antibiotics., Purpose: To assess the potential of citral in combination with norfloxacin in treating drug resistant infections of SA., Study Design: In the present study, synergistic interaction of citral and norfloxacin against drug resistant SA strains was evaluated. Further the efficacy and possible mechanism of action of the combination was also evaluated using in vitro and in vivo assays., Method: The anti-staphylococcal activity of each of the monoterpene and the antibiotic was determined in terms of MIC and the effective concentration of both compounds in combination was obtained by checkerboard assay. In vivo efficacy and oral acute toxicity was evaluated in Swiss albino mice model. To understand the mechanism of action, time-kill curve, bacteriolysis, leakage, membrane depolarization, salt tolerance and ethidium bromide efflux assays were performed., Results: Citral was found effective against clinical isolates of SA with MIC values ranging from 75 to 150 µg ml -1 exhibiting bacteriostatic activity. Citral interacted synergistically, reducing MIC of norfloxacin up to 32-folds with FICI ≤ 0.50. Citral did not affect cell wall, but could damage cell membrane, inhibit efflux pump and affect the membrane potential. Citral could reduce the staphylococcal load of spleen and liver tissues in a dose-dependent manner which was further reduced when used in combination with norfloxacin. Citral did not exhibit any mortality or morbidity up to 500 mg kg -1 body weight and found to prolong the post-antibiotic effect of norfloxacin., Conclusion: Based on these observations, citral could be a lead candidate phytomolecule for further developing it into an anti-staphylococcal agent. The observations of combination study will help in reducing the burden of antibiotics leading to delayed resistance development., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

For diabetes mellitus patients who require higher doses of insulin, pen-delivered concentrated insulins offer smaller volumes and potentially a lower risk of dosing errors., Competing Interests: Author disclosures Dhiren K. Patel–Speaker’s Bureau: Astra Zeneca, Boehringer Ingelheim, Mannkind Corporation, Merck, Novo Nordisk, Sanofi; Consultant/Advisory Board: Eli Lilly, The Medicines Company, Regeneron, Sanofi. No other authors report actual or potential conflicts of interest with regard to this article.

Two low density organic solvents based liquid-liquid microextraction methods, namely Vortex assisted liquid-liquid microextraction based on solidification of floating organic droplet (VALLME-SFO) and Dispersive liquid-liquid microextraction based on solidification of floating organic droplet(DLLME-SFO) have been compared for the determination of multiclass analytes (pesticides, plasticizers, pharmaceuticals and personal care products) in river water samples by using liquid chromatography tandem mass spectrometry (LC-MS/MS). The effect of various experimental parameters on the efficiency of the two methods and their optimum values were studied with the aid of Central Composite Design (CCD) and Response Surface Methodology(RSM). Under optimal conditions, VALLME-SFO was validated in terms of limit of detection, limit of quantification, dynamic linearity range, determination of coefficient, enrichment factor and extraction recovery for which the respective values were (0.011-0.219ngmL -1 ), (0.035-0.723ngmL -1 ), (0.050-0.500ngmL -1 ), (R 2 =0.992-0.999), (40-56), (80-106%). However, when the DLLME-SFO method was validated under optimal conditions, the range of values of limit of detection, limit of quantification, dynamic linearity range, determination of coefficient, enrichment factor and extraction recovery were (0.025-0.377ngmL -1 ), (0.083-1.256ngmL -1 ), (0.100-1.000ngmL -1 ), (R 2 =0.990-0.999), (35-49), (69-98%) respectively. Interday and intraday precisions were calculated as percent relative standard deviation (%RSD) and the values were ≤15% for VALLME-SFO and DLLME-SFO methods. Both methods were successfully applied for determining multiclass analytes in river water samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A sensitive, rapid and efficient ionic liquid-based vortex assisted liquid-liquid microextraction (IL-VALLME) with Liquid Chromatography Mass spectrometry (LC-MS/MS) method is proposed for the determination of bisphenols in thermal paper. Extraction factors were systematically optimized by response surface methodology. Experimental factors showing significant effects on the analytical responses were evaluated using design of experiment. The limit of detection for Bisphenol-A (BPA) and Bisphenol-S (BPS) in thermal paper were 1.25 and 0.93μgkg -1 respectively. The dynamic linearity range for BPA was between 4 and 100μgkg -1 and the determination of coefficient (R 2 ) was 0.996. The values of the same parameters were 3-100μgkg -1 and 0.998 for BPS. The extraction recoveries of BPA and BPS in thermal paper were 101% and 99%. Percent relative standard deviation (% RSD) for matrix effect and matrix match effects were not more than 10%, for both bisphenols. The proposed method uses a statistical approach for the analysis of bisphenols in environmental samples, and is easy, rapid, requires minimum organic solvents and efficient., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The failure of postoperative surgical site infection to resolve after appropriate antibiotic therapy should alert the clinician to other diagnoses. Pyoderma gangrenosum (PG) is an inflammatory neutrophilic dermatosis that is typically characterized by necrotizing ulceration. PG can be exacerbated by minor trauma leading to exaggerated skin injury, a condition known as pathergy. We present a case series of PG arising after immediate reconstruction for breast oncological surgery from 1st January 2006 to 1st September 2014. 395 immediate breast reconstructions were performed in 335 patients. Three cases of post-surgical PG were identified (0.9%), all in the setting of mastectomy for breast cancer. Two cases underwent immediate reconstruction with pedicled transverse rectus abdominus myocutaneous flaps, and one underwent submuscular expander insertion. A mean delay of 6.3 days was observed from first presentation of symptoms to diagnosis of PG. Immunosuppressants commonly used included methylprednisolone, prednisone, and ciclosporin, with good success at halting disease progress. Significant scarring affected all three women. Once the disease was deemed quiescent, intravenous immunoglobulin used in the perioperative period for further surgical procedures provided favorable results. A diagnostic algorithm is suggested to guide surgeons in investigations and management when post-surgical PG is suspected., (Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Antibiotics that are used excessively and disposed of improperly are categorized as emerging pollutants. The determination of micropollutants in water with an accurate and precise method is always a big challenge. Hence, a simple, rapid, sensitive, economical and almost eco-friendly method is proposed for the quantitative determination of 19 antibiotics. The proposed method, ultrasound-assisted emulsification microextraction and solidified floating organic droplet coupled with liquid chromatography and triple quadrupole mass spectrometry, has only a 3 min chromatographic run time for the determination of the 19 antibiotics. We report for the first time the use of the developed method for the quantitative determination of the antibiotics in waste water samples with better results in terms of higher sensitivity, cost-effectiveness, better detection limits and a greener approach compared to the earlier reported methods. The limits of detection and quantification were in the range of 0.003-0.236 and 0.013-0.834 μg/L, respectively, with good linearity in the concentration range of 0.01-64.0 μg/L. The correlation coefficient was ≥0.987-0.99 for each analyte. The developed method has been successfully applied for the determination of antibiotics in water samples., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective. To assess the effect of incorporating virtual patient activities in a pharmacy skills lab on student competence and confidence when conducting real-time comprehensive clinic visits with mock patients. Methods. Students were randomly assigned to a control or intervention group. The control group completed the clinic visit prior to completing virtual patient activities. The intervention group completed the virtual patient activities prior to the clinic visit. Student proficiency was evaluated in the mock lab. All students completed additional exercises with the virtual patient and were subsequently assessed. Student impressions were assessed via a pre- and post-experience survey. Results. Student performance conducting clinic visits was higher in the intervention group compared to the control group. Overall student performance continued to improve in the subsequent module. There was no change in student confidence from pre- to post-experience. Student rating of the ease of use and realistic simulation of the virtual patient increased; however, student rating of the helpfulness of the virtual patient decreased. Despite student rating of the helpfulness of the virtual patient program, student performance improved. Conclusion. Virtual patient activities enhanced student performance during mock clinic visits. Students felt the virtual patient realistically simulated a real patient. Virtual patients may provide additional learning opportunities for students.