Nanocarriers: more than tour de force for thymoquinone

Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers

Validacija topokemijskih modela za predviđanje permeabilnosti kroz krvno-moždanu barijeru

Recently published topochemical models for permeability through the blood-brain barrier were validated and cross-validated in the present study. Five models based on three topochemical indices, Wiener’s topochemical index - a distance-based topochemical descriptor, molecular connectivity topochemical index - an adjacency-based topochemical descriptor and eccentric connectivity topochemical index - an adjacency-cum-distance based topochemical descriptor, for permeability of structurally and chemically diverse molecules through blood-brain barrier were used in the present investigation. A data set comprising 62 structurally and chemically diverse compounds was selected. This data set was divided into two sets of 31 compounds each - one to serve as the validation set and other as the cross-validation set. The values of all the three-topochemical indices in the original as well as in the normalized form for each of the 31 compounds of the validation set were computed using an in house computer program. Resultant data was analyzed and each compound was assigned a permeability characteristic using topochemical models, which was then compared with the reported permeability through the blood-brain barrier. Accuracy of prediction of these models was calculated. The same procedure was similarly followed for the cross-validation set. Studies revealed accuracy of prediction of the order of 7080% during validation. Surprisingly, very high predictability of the order of 7791% was observed during cross-validation. High predictability observed during validation as well as cross-validation authenticates topochemical models for prediction of permeability through the blood-brain barrier.U ovom radu su validirani i unakrsno validirani nedavno objavljeni topokemijski modeli za permeabilnost kroz krvno-moždanu barijeru. Predviđanje prolaska kroz krvno-moždanu barijeru strukturno i kemijski različitih molekula provedeno je na pet modela koji se temelje na tri topološka indeksa, Wienerovom topološkom indeksu, topološkom indeksu molekularne povezanosti i topološkom indeksu ekscentrične povezanosti. Ukupno 62 spoja podijeljena su u dva seta koji su sadržavali 31 spoj. Jedan set upotrebljen je za validaciju, a drugi za unakrsnu validaciju. Vrijednosti svih triju topoloških indeksa u početnom setu i u normaliziranom setu su računate pomoću kompjutorskog programa. Rezultati su analizirani i svakom spoju je pridružena teorijska vrijednost permeabilnosti, koja je zatim uspoređivana s objavljenim eksperimentalnim podacima za permeabilnost kroz krvno-moždanu barijeru. Točnost predviđanja bila je između 70 i 80%. Isti postupak je proveden za unakrsno validacijski set, a točnost je bila iznenađujeće velika (7791%), što ukazuje da se upotrebljeni topokemijski modeli mogu upotrijebiti za predviđanje permeabilnsot kroz krvno-moždanu barijeru

Satisfiability Checking for Mission-Time LTL

Mission-time LTL (MLTL) is a bounded variant of MTL over naturals designed to generically specify requirements for mission-based system operation common to aircraft, spacecraft, vehicles, and robots. Despite the utility of MLTL as a specification logic, major gaps remain in analyzing MLTL, e.g., for specification debugging or model checking, centering on the absence of any complete MLTL satisfiability checker. We prove that the MLTL satisfiability checking problem is NEXPTIME-complete and that satisfiability checking MLTL0 , the variant of MLTL where all intervals start at 0, is PSPACE-complete. We introduce translations for MLTL-to-LTL, MLTL-to-LTLf , MLTL-to-SMV, and MLTL-to-SMT, creating four options for MLTL satisfiability checking. Our extensive experimental evaluation shows that the MLTL-to-SMT transition with the Z3 SMT solver offers the most scalable performance

Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations.

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities

Numerical modeling of the thermal contact in metal forming processes

Heat flow across the interface of solid bodies in contact is an important aspect in several engineering applications. This work presents a finite element model for the analysis of thermal contact, which takes into account the effect of contact pressure and gap dimension in the heat flow across the interface between two bodies. Additionally, the frictional heat generation is also addressed, which is dictated by the contact forces predicted by the mechanical problem. The frictional contact problem and thermal problem are formulated in the frame of the finite element method. A new law is proposed to define the interfacial heat transfer coefficient (IHTC) as a function of the contact pressure and gap distance, enabling a smooth transition between two contact status (gap and contact). The staggered scheme used as coupling strategy to solve the thermomechanical problem is briefly presented. Four numerical examples are presented to validate the finite element model and highlight the importance of the proposed law on the predicted temperature.The authors gratefully acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) under the project PTDC/EMS-TEC/1805/2012 and by FEDER funds through the program COMPETE Programa Operacional Factores de Competitividade, under the project CENTRO-07-0224- FEDER-002001 (MT4MOBI). The second author is also grateful to the FCT for the postdoctoral grant SFRH/BPD/101334/2014. The authors would like to thank Prof. A. Andrade-Campos for helpful contributions on the development of the finite element code presented in this work.info:eu-repo/semantics/publishedVersio

Evidence and consensus recommendations for the pharmacological management of pain in India

Gur Prasad Dureja,1 Rajagopalan N Iyer,2 Gautam Das,3 Jaishid Ahdal,4 Prashant Narang4 On behalf of the Pain Working Group 1Delhi Pain Management Centre, New Delhi, Delhi, 2Department of Orthopaedics, Raja Rajeswari Medical College and Hospital, Bengaluru, Karnataka, 3Daradia Pain Clinic, Kolkata, West Bengal, 4Department of Medical Affairs, Janssen India, Johnson & Johnson Pvt Ltd, Mumbai, Maharashtra, India Abstract: Despite enormous progress in the field of pain management over the recent years, pain continues to be a highly prevalent medical condition worldwide. In the developing countries, pain is often an undertreated and neglected aspect of treatment. Awareness issues and several misconceptions associated with the use of analgesics, fear of adverse events – particularly with opioids and surgical methods of analgesia – are major factors contributing to suboptimal treatment of pain. Untreated pain, as a consequence, is associated with disability, loss of income, unemployment and considerable mortality; besides contributing majorly to the economic burden on the society and the health care system in general. Available guidelines suggest that a strategic treatment approach may be helpful for physicians in managing pain in real-world settings. The aim of this manuscript is to propose treatment recommendations for the management of different types of pain, based on the available evidence. Evidence search was performed by using MEDLINE (by PubMed) and Cochrane databases. The types of articles included in this review were based on randomized control studies, case–control or cohort studies, prospective and retrospective studies, systematic reviews, meta-analyses, clinical practice guidelines and evidence-based consensus recommendations. Articles were reviewed by a multidisciplinary expert panel and recommendations were developed. A stepwise treatment algorithm-based approach based on a careful diagnosis and evaluation of the underlying disease, associated comorbidities and type/duration of pain is proposed to assist general practitioners, physicians and pain specialists in clinical decision making. Keywords: clinical practice guidelines, consensus recommendations, expert opinion, pain management, treatment algorith

Investigations for dimensional accuracy of Al alloy/Al-MMC developed by combining stir casting and ABS replica based investment casting

In the present research work dimensional accuracy (Î\u94d) of Al-Al2O3based metal matrix composite (MMC) developed by combining stir casting with ABS replica based investment casting (IC) process has been highlighted. Three controllable factors of the IC process, namely: layer combination (LC), material composition (MC), pouring temperature (PT), were studied at three levels by Taguchi's parametric approach along with fixed parameters of stir casting process and single-response optimization was conducted to identify the main factor controlling Î\u94d. Ceramic shell moulds were made on ABS plastic patterns (prepared by FDM process) using primary slurry and fused-silica sand as stucco. The final MMC prepared by stir casting process has been poured in these moulds. Finally results of study highlights the percentage contribution of different input parameters for Î\u94d of MMC prepared by combined stir casting and IC process

Modification of erucic acid content in Indian mustard (Brassica juncea) by up-regulation and down-regulation of the Brassica juncea FATTY ACID ELONGATION1 (BjFAE1) gene

In Brassicas, the Fatty Acid Elongation1 (FAE1) gene product, a 3-ketoacyl-CoA synthase, is the first in a 4-enzyme complex involved in the synthesis of erucic acid from oleic acid. The FAE1 homologue from Brassica juncea cv. Pusa Bold was cloned in a binary vector both in sense and antisense orientations under the control of the CaMV35S promoter. The recombinant binary vectors were used to transform B. juncea cv. RLM 198 via Agrobacterium tumefaciens. The presence of the transgene was confirmed by polymerase chain reaction and Southern hybridization. Northern and western analyses showed the expression of the gene and protein, respectively, in the transgenic plants. Analyses of the fatty acid profile of the seed oil from homozygous T4 generation seeds revealed that over-expression of the FAE1 gene caused a 36% increase in the percent of erucic acid (37-49% compared to 36% in untransformed control). The down-regulation of FAE1 caused an 86% decrease in the percent of erucic acid to as low as 5% in the seed oil of transgenic plants. Thus, it is clearly possible to alter erucic acid content of mustard by altering the expression level of the FAE 1 gene