In-silico study of some natural compounds used as antifungal agents against Candida albicans

Fungal diseases are very common these days, so there is a high need to design and develop new antifungal drugs that can counter these diseases. Candida albicans is one of the opportunistic pathogenic yeasts that can cause serious diseases such as oropharyngeal candidiasis, vulvovaginal (genital) candidiasis, and invasive candidiasis (candidemia). This article focuses on the in-silico evaluation of anti-candidal activity of some natural compounds like ajoene, allicin, curcumin, gingerol, nimbin, nimbolide, nimonol and 6-Shogaol. Binding affinity of these compounds have been determined against the most common targets in C. albicans viz. cytochrome p450, lanosterol synthase, serine/threonine protein kinase, squalene monooxygenase, sterol-14-demethylase and thymidylate synthase. PatchDock and FireDock web servers were used to carry out the docking studies. The proposed targets of ajoene, allicin, curcumin, gingerol, nimbin, nimbolide, nimonol and 6-Shogaol are sterol 14-demethylase, cytochrome p450, cytochrome p450, cytochrome p450, cytochrome p450, squalene monooxygenase, lanosterol synthase and squalene monooxygenase respectively based upon the binding energies obtained by the docking studies. This study opens new avenues in the usage of the natural compounds as potential antifungal agents. DOI: http://dx.doi.org/10.5281/zenodo.391129

Simulation-Based Electronic Health Record Usability Evaluation: A Proof of Concept

Poor usability of Electronic Health Records (EHR) solutions is directly associated with physician burnout. While the survey and observational methods have been utilized widely in the usability evaluation of EHRs, it does not seem to be helping with the continuous improvement of EHR design and user satisfaction. We address this gap by presenting a discrete event simulation-based model that can add objectivity to the extant EHR usability methods. Evaluating EHR usability from the perspective of operations and workflow can help vendors design and develop better systems. This short paper presents a proof-of-concept simulation model with assumed task-time distributions. Our main research question is how we can use simulation techniques to objectively evaluate EHR usability? The simulation model results in terms of resource (clinician) utilization metrics can serve as a proxy to evaluate the efficiency component of the EHR usability at the departmental leve

Spectroscopic, Thermal and Biological Studies on Some Trivalent Ruthenium and Rhodium NS Chelating Thiosemicarbazone Complexes

The synthetic, spectroscopic, and biological studies of sixteen ring-substituted 4-phenylthiosemicarbazones and 4-nitrophenyl-thiosemicarbazones of anisaldehyde, 4-chlorobenzaldehyde, 4-fluorobenzaldehyde, and vanillin with ruthenium(III) and rhodium(III) chlorides are reported here. Their structures were determined on the basis of the elemental analyses, spectroscopic data (IR, electronic, (1)H and (13)C NMR) along with magnetic susceptibility measurements, molar conductivity and thermogravimetric analyses. Electrical conductance measurement revealed a 1 : 3 electrolytic nature of the complexes. The resulting colored products are monomeric in nature. On the basis of the above studies, three ligands were suggested to be coordinated to each metal atom by thione sulphur and azomethine nitrogen to form low-spin octahedral complexes with ruthenium(III) while forming diamagnetic complexes with rhodium(III). Both ligands and their complexes have been screened for their bactericidal activities and the results indicate that they exhibit a significant activity

Investigating economic, design, and usability aspects of electronic health record systems

Following a 3-essay approach, this dissertation explores three aspects of healthcare IT using three different methodologies. In the first essay, we use econometric modeling to quantify the business value of information exchange using spillover mechanisms and discuss its implications in propagating sustained collaboration between ambulatory and tertiary care. Leveraging a nationwide sample of 3,483 US hospitals across 13 years, matched with approximately 30,000 ambulatory care facilities, we find that focal hospitals' inpatient cost per discharge decreases as EMR adoption by neighboring ambulatory facilities increases. Further, these effects are more substantial for urban, densely populated regions with more ambulatory entities that are proximal. This represents the bright side of EHR use. Next, the second essay uses a qualitative approach to understand the unintended consequences or dark side of EHR use. In this study, we interviewed 24 physicians across 11 specialties to understand what specific EHR characteristics cause stress among physicians. Following the standard qualitative coding process, we identify fifty-one design issues and ten stress-inducing EHR design themes that provide a deeper understanding of the technostress phenomenon. In addition, our findings can be used by EHR vendors to design better information systems. The final and third essay contributes to the lack of usability testing models and presents a proof of concept EHR usability evaluation model based on discrete event simulation techniques. Using literature-based workflow sequence and time-motion data assumptions, we show how to use simulation techniques to evaluate whether an EHR system delivers operational value in physician utilization. Usability evaluation is the first step in designing better EHR systems, and thus our proof-of-concept model can be used by EHR vendors and certification authorities to appraise the operational value of EHR applications. Overall, this dissertation investigates- 1) the bright side of EHR use that generates economic value for its users; 2) the dark side of EHR use that provides a deeper understanding of the physician burnout problem; 3) provides a solution that helps in designing better EHR systems while mitigating its unintended consequences

A review on biological and chemical diversity in Berberis (Berberidaceae)

Berberis is an important genus and well known in the Indian as well as European systems of traditional medicine. It is used since ancient times for curing eye disease, fever, jaundice, rheumatism, vomiting during pregnancy, kidney and gall balder stones and various other ailments due to the presence of biologically active alkaloid berberine. Action of the root extracts of few species are believed to be as powerful as quinine in the treatment of malarial fever. A plethora of literature pertaining to the taxonomy, biology, chemistry, traditional and ethnic uses of Berberis in different countries and indigenous cultures was collected by both offline (library, journals, textbooks etc.) and online mode (electronic search of available databases). In addition to this, books on traditional medicine and ethno pharmacological knowledge were also referred to extract ancient uses of Berberis in different traditional medicine systems. Most of the folklore, traditional and ethno botanical claims about Berberis species were validated by broad spectrum in vitro and vivo pharmacological studies. The present article summarizes its usage in eye and liver disorder, fever, kidney and gall stones along with anticancer activity. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations

Effect of aquagenic and lithogenic factors on nephro, uretro and urolithiasis

Our study aims to explore different lithogenic and aquagenic factors which lead to the formation of renal calculi. To interpret this, a standard questionnaire is prepared based on the available review data which includes all the variable dietary information’s and other physiological parameters responsible for renal calculi. A study sample size of individuals (n=500) varies 19-65 years of age belongs to Delhi and NCR region. Of the 500 individuals more than 35 percent of individuals’ shows routine consumption of vegetables items includes eggplant, okra and ginger. 77 percent of the total individuals’ showed routine consumption of seasonal vegetables includes radish, carrot and spinach. 85 percent of the total shows routine uptake of whole wheat, grains, gram, black-pepper, soybean and nuts. 82 percent of the total individuals shows regular seasonal uptake of grapes while 35 percent of total shows routine uptake of strawberry and kiwi. Among beverage consumption 92 percent individuals takes tea, coffee, carbonated drink cola in routine while 46 percent takes Juice- apple, Grape, orange in routine and 75 percent takes whisky, beer, wine and other alcoholic beverages. In order to study the effect of potable water on the formation of renal calculi, water samples were collected from 20 different residential places (RPs) of Delhi- NCR and characterize for pH, calcium, magnesium and sodium

Identification of EhTIF-IA: the putative E. histolytica orthologue of the human ribosomal RNA transcription initiation factor-IA

Initiation of rDNA transcription requires the assembly of a specific multi-protein complex at the rDNA promoter containing the RNA Pol I with auxiliary factors. One of these factors is known as Rrn3P in yeast and Transcription Initiation Factor IA (TIF-IA) in mammals. Rrn3p/TIF-IA serves as a bridge between RNA Pol I and the pre-initiation complex at the promoter. It is phosphorylated at multiple sites and is involved in regulation of rDNA transcription in a growth-dependent manner. In the early branching parasitic protist Entamoeba histolytica, the rRNA genes are present exclusively on circular extra chromosomal plasmids. The protein factors involved in regulation of rDNA transcription in E. histolytica are not known. We have identified the E. histolytica equivalent of TIF-1A (EhTIF-IA) by homology search within the database and was further cloned and expressed. Immuno-localization studies showed that EhTIF-IA co-localized partially with fibrillarin in the peripherally localized nucleolus. EhTIF-IA was shown to interact with the RNA Pol I-specific subunit RPA12 both in vivo and in vitro. Mass spectroscopy data identified RNA Pol I-specific subunits and other nucleolar proteins to be the interacting partners of EhTIF-IA. Our study demonstrates for the first time a conserved putative RNA Pol I transcription factor TIF-IA in E. histolytica

RELEVANCE OF KAKOLI (ONE AMONG ASTAVARGA) IN ANCIENT AYURVEDIC TREATISE ALONG WITH ETYMOLOGY OF ITS VARIOUS SANSKRIT SYNONYMS

The knowledge about medicinally useful plants in the early age is scientifically documented, and systematically organized in Ayurveda Samhitas, Nighantus and other texts. The ancient nomenclature of Ayurvedic herbs was not only useful for their identification but also to know their medicinal values for example, Payasvinī means galactogogue, Kākolī means which contains high moisture value, Madhurā means Madhura in Rasa, etc. Moreover, our Acharyas also suggested different names of the Ayurvedic herbs based on their habits, taxonomy and uses. Though the modern science is successful in classifying the flora taxonomically, but could not reach up to the ground breaking concept of classifying plants according to their medicinal properties. Being aware of taxonomic aspects of nomenclature along with the torch of synonyms coined by ancient seers one may be able to preserve the treasury traditional medicinal knowledge. Kākolī has been mentioned as one of the Aṣṭavarga plants. Kākolī has also been documented in the various Saṁhitā and Nighaṇṭu. Description of Kākolī along with its Sanskrit synonyms, habitat and medicinal properties has also been mentioned in different Nighaṇṭu. However, due to the lack of appropriate taxonomic data, mainly three plant species i.e., Roscoea purpurea Sm., Roscoea capitata Sm. and Roscoea alpina Royle are widely accepted as Kākolī. The main objective of this study was to critically review the Sanskrita name of Kākolī described in classical Ayurvedic literature along with medicinal properties

Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion.

The molecular underpinnings of synaptic vesicle fusion for fast neurotransmitter release are still unclear. Here, we used a single vesicle-vesicle system with reconstituted SNARE and synaptotagmin-1 proteoliposomes to decipher the temporal sequence of membrane states upon Ca(2+)-injection at 250-500 μM on a 100-ms timescale. Furthermore, detailed membrane morphologies were imaged with cryo-electron microscopy before and after Ca(2+)-injection. We discovered a heterogeneous network of immediate and delayed fusion pathways. Remarkably, all instances of Ca(2+)-triggered immediate fusion started from a membrane-membrane point-contact and proceeded to complete fusion without discernible hemifusion intermediates. In contrast, pathways that involved a stable hemifusion diaphragm only resulted in fusion after many seconds, if at all. When complexin was included, the Ca(2+)-triggered fusion network shifted towards the immediate pathway, effectively synchronizing fusion, especially at lower Ca(2+)-concentration. Synaptic proteins may have evolved to select this immediate pathway out of a heterogeneous network of possible membrane fusion pathways.DOI:http://dx.doi.org/10.7554/eLife.00109.001