Shalini Jain, Mukesh Kumar Sharma, Nidhi Gupta
et al.
Background: Plant formulations with antidiabetic and antioxidant properties have recently gained popularity due to their lower cost and lesser side effects. Guggul gum is one such formulation that is extensively being used to cure various ailments. Objective: The present study was designed to explore the antioxidant and antidiabetic properties of the aqua-ethanolic Guggul gum extract (GE) from Commiphora wightii using in silico studies and in vitro assays. Methods: Gas Chromatography Mass Spectroscopy (GCMS) identified compounds were docked to the Human pancreatic α-amylase (HPA, PDB ID: 1HNY) for in silico studies to predict the inhibition. Molecular dynamics simulations (MDS) were performed using GROMACS for 100 ns. The inhibition of the enzyme was further evaluated at in vitro level to show the compounds' hypoglycemic role. Results: The extract showed a good amount of phenolic (5.14 ± 0.011 mg), flavonoid (0.66 ± 0.023 mg) and terpenoid (1.08 ± 0.018 mg) content along with a promising free radical scavenging activity of 41.96 ± 4.02%. In the in silico studies, 3 out of 6 GCMS-identified bioactive compounds showed permissible values of bioavailability properties suggesting them as a potential candidate for antidiabetic drugs. Similarly, in molecular docking studies, 3 compounds showed more binding energy than the standard drug acarbose indicating better inhibition. MDS studies showed Compound 4 (Diisooctyl phthalate), was the most stable with the lowest root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, a consistent radius of gyration (Rg), and stable solvent accessible surface area (SASA). This was further confirmed by in vitro analysis where the pancreatic α-amylase inhibitory activity of the extract and the standard drug (acarbose) were comparable at an IC50 value of 4.17 ± 1.26 mg/mL and 3.69 ± 0.89 mg/mL respectively. Conclusion: The results demonstrated GE as a potential alternative to commercial antidiabetic drugs. Out of the major 6 GCMS-identified compounds, Compound 4 showed the most stable conformation during MDS studies. However, the isolation of the identified compounds could be done in the future for in vivo studies.
Objective: To observe the effect of Xipayimaizibizi oral liquid (XP) in an overactive bladder (OAB) experimental rat model and to explore its pharmacological mechanisms. Methods: Network pharmacology was used to explore the potential mechanisms of action of XP. The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks. The study observed the body weight, water intake, bladder and kidney indices (to evaluate their general status), urination behavior pattern (to observe frequency and urgency), and urodynamics (to measure bladder parameters). Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure. Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor, brain-derived neurotrophic factor, and acetylcholine in the urine. The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and western blot in vivo/vitro experiments. Result: Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways. XP treatment significantly reduced the bladder index, improved urine behavior and urodynamic parameters, decreased the neurotransmitters in urine, and reduced the thickness of the bladder wall and collagen ratio. These results indicate that XP can alleviate OAB symptoms and improve the bladder structure. In vivo/vitro experiments further demonstrated that XP can inhibit targets, such as muscarinic acetylcholine receptor 2, and participate in cholinergic synapses to further regulate the parasympathetic nervous system. It can also reduce the overexpression of Ca2+ caused by agonists, inhibit targets such as transient receptor potential vanilloid type 1, and participate in calcium signaling pathways to maintain Ca2+ homeostasis. Conclusion: These results suggest that XP inhibited bladder overactivity by maintaining Ca2+ homeostasis and regulating the parasympathetic nervous system.
This paper leverages linear systems theory to propose a principled measure of complexity for network systems. We focus on a network of first-order scalar linear systems interconnected through a directed graph. By locally filtering out the effect of nodal dynamics in the interconnected system, we propose a new quantitative index of network complexity rooted in the notion of McMillan degree of a linear system. First, we show that network systems with the same interconnection structure share the same complexity index for almost all choices of their interconnection weights. Then, we investigate the dependence of the proposed index on the topology of the network and the pattern of heterogeneity of the nodal dynamics. Specifically, we find that the index depends on the matching number of subgraphs identified by nodal dynamics of different nature, highlighting the joint impact of network architecture and component diversity on overall system complexity.
Background: Type 2 diabetes mellitus in obese persons is becoming alarming due to the increasing prevalence of its microvascular and macrovascular complications. Multi-targeted treatment can be considered better than single-targeted treatment because of the multiple pathways involved in the pathogenesis of diabetes and its complications. Objective: The study aimed to evaluate the efficacy of ‘Vidangadi Lauha' (VL) (an Ayurveda formulation) compared with Metformin for obese type II diabetes mellitus. Methodology: This is an open-label randomized controlled clinical study.Participants were divided into two groups. The trial Group received VL 5 gm BID, and the control group received tablet metformin (MT) 500 mg BID for three months. Results: VL showed reduction in HbA1c from 8.048(0.95) to 7.14(0.73), (CI, 0.7810 to 1.035; p < 0.0001) while MT showed reduction in HbA1C from 8.3(0.99) to7.18(0.67), (CI, 0.9220 to 1.305; p < 0.0001). VL showed improvement in the Quality of life instrument for the Indian Diabetes questionnaire(QOLID) score from 113.87(11.36) to 136.47(8.703) (CI, −25.68 to −19.52; p < 0.0001) as compared to MT 128.57(7.9) to 102.32(7.9), (CI, 23.19 to 29.39; p < 0.0001) VL showed reduction in bowel symptom questionnaire 30.275(8.077) to 13.2(1.265), (CI, 14.60–19.51; p < 0.0001) as compared to MT from 23.85(7.530) to 38.25(6.332), (CI, −15.99 to −12.80; p < 0.0001). Conclusion: Both treatments were equally effective in reducing blood sugar fasting (F), post-meal (PM) glycated hemoglobin (HbA1C), and body mass index (BMI). VL is more effective than MT in reducing Ayurvedic symptoms, waist-hip ratio, cholesterol, quality of life, and bowel symptom questionnaire score.
Acute upper limb ischemia (AULI) is a medical and surgical emergency involving sudden decrease in limb perfusion resulting in threat for limb viability. A 52 years old male patient was suffered from AULI. He had the complaints of numbness and pain in left upper limb, headache and pale discoloration of left-hand fingers and acute onset left upper extremity weakness.The Ayurveda diagnosis was considered as Vatarakta. He was advised oral medications - Kaishor guggulu in the dose of 750 mg twice a day with Jwarhar kashaya 40 ml twice a day, Ashwagandha Churna 3 g, Guduchi churna1g, Shatavari churna 2 g, Chopchini churna 1 g with milk twice a day, Shilajatwadi loha 500 mg and Mahavatvidhvansana rasa 250 mg twice a day with honey. All these medications were continued for 12 months. Two courses of Mustadi yapana basti (medicated enema enriched with milk) and Shalishastika pinda swedana (a specific type of sudation with a poultice of rice bolus) and Nasya (nasal therapy) with Shadabindu oil were given. Initial computed tomography (CT) angiogram revealed the abrupt cutoff of the left brachial artery in distal part due to hypodense lesion (thrombus) in the lumen while after 12 months of treatment CT angiogram revealed 70–80 % luminal narrowing in proximal part of left ulnar artery. It suggests the revascularization of left ulnar artery. All the symptoms of AULI were also resolved. We report a unique case of AULI managed with Ayurvedic interventions
seyed Mohammad Hosseindokht, SamanehAlsadat Saeedinia
Global stability of the systems has always been vital of importance; however, this concept has not yet been sufficiently developed for the nonlinear systems. This paper extends the Jacobian matrix so that this method be able to seek the criteria to ensure global stability for a special class of nonlinear systems. In this regard, we propose a new analysis method that utilizes the Jacobian matrix concept, integrating with the characteristics of the negative eigenvalues to analyze the global stability of the nonlinear systems with only one equilibrium point. Also, the positive eigenvalue to analyze the global instability of the nonlinear systems with only one equilibrium point. Some theorems such as Hartman-Grobman and Popov criteria can prove this claim. To this end, several examples and a benchmark systems have been intended to evaluate the efficiency of the proposed method. Results indicate the high potential of the proposed approach in order to develop the global stability analysis. The nonlinear compressor model, categorized in this extensive class, is also investigated as a well-known industrial system besides other several examples. The outcomes demonstrate that extended Jacobian stability analysis can ensure global stability for this class of nonlinear systems under some spatial conditions, discussed in this paper.
Gabriel Luiz Nascimento Fioramonte, Maria Jose Sanches Marin, Adriana Avanzi Marques Pinto
Este estudo teve por objetivo verificar as evidências científicas sobre os avanços e os desafios na formação do técnico de enfermagem. Como metodologia, utilizou a Revisão Integrativa da Literatura. A busca foi realizada nas bases de dados da Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Base de Dados de Enfermagem (BDENF), Scientifc Eletronic Library Online (SciELO), Medical Literature Analysis and Retrieval System Online (MEDLINE), Web of Science (WOS), SCOPUS e Embase. Foram utilizados os descritores controlados pelo Descritores em Ciências da Saúde (DeCS) e Medical Subject Headings Section (MeSH) e seus entry terms, em português e inglês: ‘Técnicos de Enfermagem’, ‘Assistentes de Enfermagem’, ‘Educação Técnica em Enfermagem’,’Enfermagem’, ‘Ensino’, ‘Formação’. A seleção dos artigos foi apresentada de acordo com o fluxograma PRISMA. Dos 1.505 artigos identificados, 10 foram selecionados para análise. A maioria dos artigos analisados (n=9) foi publicado no Brasil nos últimos dez anos, nos idiomas português, inglês e espanhol e apresentou baixo nível de evidência científica (Grau de Evidência VI – estudos descritivos ou qualitativos únicos). Os resultados destacaram avanços e desafios relacionados às categorias de análise: estratégias de ensino inovadoras, busca por uma formação abrangente e gestão institucional. Os estudos demonstraram que esforços vêm sendo realizados visando a adoção de novas estratégias de ensino-aprendizagem, com vistas à formação de um profissional da saúde mais ativo e participativo e com olhar integral e humanizado do cuidado. Para tanto, o apoio institucional mostra-se como uma condição essencial. Desafios precisam ser superados, destacando-se a integração da teoria com a prática, a formação docente, bem como a melhoria nas condições do trabalho docente.
Miscellaneous systems and treatments, Public aspects of medicine
Devi Padmavathi Alagarswamy, Christian Berghoff, Vasilios Danos
et al.
Various mobility applications like advanced driver assistance systems increasingly utilize artificial intelligence (AI) based functionalities. Typically, deep neural networks (DNNs) are used as these provide the best performance on the challenging perception, prediction or planning tasks that occur in real driving environments. However, current regulations like UNECE R 155 or ISO 26262 do not consider AI-related aspects and are only applied to traditional algorithm-based systems. The non-existence of AI-specific standards or norms prevents the practical application and can harm the trust level of users. Hence, it is important to extend existing standardization for security and safety to consider AI-specific challenges and requirements. To take a step towards a suitable regulation we propose 50 technical requirements or best practices that extend existing regulations and address the concrete needs for DNN-based systems. We show the applicability, usefulness and meaningfulness of the proposed requirements by performing an exemplary audit of a DNN-based traffic sign recognition system using three of the proposed requirements.
Several sources of uncertainty have to be taken into account in the analysis and design of CPS. The set of parameters used in the model of the physical plant of a CPS may be uncertain due, for example, to manufacturing processes that are precise up to some bounded tolerance. Physical quantities are sensed by electronic components that add noise to the sensed signals. Abstraction of the physical world, which is often necessary to limit the complexity of the models used in analysis and at run-time in decision-making, leads to non-determinism. The cyber side of a CPS, which includes both hardware and software components, exposes several types of uncertainty such as failures, latency, and implementation errors. Design processes and tools allow engineers to minimize the impact of these types of uncertainty, and to deliver systems which can be operated with an acceptable level of risk. In the past several years, cyber-physical systems have evolved, primarily due to pervasive connectivity, miniaturization, cost-effectiveness of hardware, and advances in the area of Artificial Intelligence. This new class of applications features an environment that is much more complex to model than traditional physical systems due not only to their scale, but also to new sources and types of uncertainty. Consider, for example, the typical case of echo chambers which is attributed to the effect that machine learning algorithms have on the bias of people. Such behavior is not easily predictable because of high uncertainty in the environment (people), which is only approximately represented by machine learning models, but that is inherently due to lack of knowledge. New models and analysis methods are therefore needed to capture different types of uncertainties, and to analyze these new classes of systems.
This manuscript presents an innovative framework for constructing barrier functions to bound reachability probabilities for continuous-time stochastic systems described by stochastic differential equations (SDEs). The reachability probabilities considered in this paper encompass two aspects: the probability of reaching a set of specified states within a predefined finite time horizon, and the probability of reaching a set of specified states at a particular time instant. The barrier functions presented in this manuscript are developed either by relaxing a parabolic partial differential equation that characterizes the exact reachability probability or by applying the Grönwall's inequality. In comparison to the prevailing construction method, which relies on Doob's non-negative supermartingale inequality (or Ville's inequality), the proposed barrier functions provide stronger alternatives, complement existing methods, or fill gaps.
Letícia Maria Rostirolla, Edlamar Katia Adamy, Carine Vendruscolo
Este estudo teve por objetivo conhecer a produção científica nacional e internacional sobre as tecnologias educacionais utilizadas para a Consulta do Enfermeiro na Atenção Primária à Saúde (APS). Como metodologia, utilizou a revisão integrativa nas bases de dados Biblioteca Virtual em Saúde, Catálogo de Teses e Dissertações do Portal de Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, PubMed e SciELO. Incluiu estudos publicados entre 2002 e 2019, em inglês, espanhol e português. Da busca emergiram sete artigos e 19 dissertações que apresentam tecnologias educacionais do tipo: materiais educativos, protocolos, cursos, aplicativos, cartilhas, vídeos e roteiro de consulta de enfermagem. A aplicação das tecnologias, em todos os estudos, se desenvolveu na Estratégia Saúde da Família. Quanto ao público para o qual as tecnologias destinaram-se, foram pacientes com doenças crônicas, recém-nascidos, crianças, jovens, gestantes e puérperas, e um estudo com desenvolvimento de tecnologia destinada aos profissionais da saúde. Os estudos demonstram desafios relacionados ao desenvolvimento de tecnologias educacionais, sobretudo, quanto ao público a que se destinam. As tecnologias se mostraram práticas, eficientes e adaptáveis à Consulta do Enfermeiro. Residem no cotidiano da assistência, auxiliando em todos os momentos do cuidado clínico da enfermagem na APS e apontam para a preocupação dos pesquisadores na adoção de modelos teóricos e conceituais que sustentem a Consulta do Enfermeiro.
Miscellaneous systems and treatments, Public aspects of medicine
This paper focuses on the effective use of smart inverters for Volt/Var control (VVC) on a distribution system. New smart inverters offer Var support capability but for their effective use they need to be coordinated with existing Volt/Var schemes. A new VVC scheme is proposed to facilitate such coordination. The proposed scheme decomposes the problem into two levels. The first level uses Load Tap Changer (LTC) and Voltage Regulators (VRs) and coordinates their control with smart inverters to adjust the voltage level on the circuit to keep the voltages along the circuit within the desired range. The second level determines Var support needed from smart inverters to minimize the overall power loss in the circuit. The results of the supervisory control are sent to the devices which have their local controllers. To avoid frequent dispatch, smart inverters are supervised by shifting their Volt/Var characteristics as needed. This allows for the smart inverters to operate close to their optimal control while meeting the limited communication requirements on a distribution system. A case study using the IEEE 34 bus system shows the effectiveness of this supervisory control scheme compared to traditional volt/var schemes.
Background: Recently, gintonin and gintonin-enriched fraction (GEF) have been isolated from ginseng, a herbal medicine. Gintonin induces [Ca2+]i transition in cultured hippocampal neurons and stimulates acetylcholine release through LPA receptor activation. Oral administration of GEF is linked to hippocampus-dependent cognitive enhancement and other neuroprotective effects; however, effects of its long-term administration on hippocampal gene expression remains unknown. Here, we used next-generation sequence (NGS) analysis to examine changes in hippocampal gene expressions after long-term oral administration of GEF. Methods: C57BL/6 mice were divided into three groups: control group, GEF50 (GEF 50 mg/kg, p.o.), and GEF100 (GEF 100 mg/kg, p.o.). After 22 days, total RNA was extracted from mouse hippocampal tissues. NGS was used for gene expression profiling; quantitative-real-time PCR and western blot were performed to quantify the changes in specific genes and to confirm the protein expression levels in treatment groups. Results: NGS analysis screened a total of 23,282 genes, analyzing 11-related categories. We focused on the neurogenesis category, which includes four genes for candidate markers: choline acetyltransferase (ChAT) gene, β3-adrenergic receptor (Adrb3) gene, and corticotrophin-releasing hormone (Crh) gene, and tryptophan 2,3-dioxygenase (Tdo2) gene. Real-time PCR showed a marked overexpression of ChAT, Adrb3, and Crh genes, while reduced expression of Tdo2. Western blot analysis also confirmed increased ChAT and decreased Tdo2 protein levels. Conclusion: We found that GEF affects mouse hippocampal gene expressions, associated with memory, cognitive, anti-stress and anti-anxiety functions, and neurodegeneration at differential degree, that might explain the genetic bases of GEF-mediated neuroprotective effects.
Sandor Beregi, David A. W. Barton, Djamel Rezgui
et al.
Augmenting mechanistic ordinary differential equation (ODE) models with machine-learnable structures is an novel approach to create highly accurate, low-dimensional models of engineering systems incorporating both expert knowledge and reality through measurement data. Our exploratory study focuses on training universal differential equation (UDE) models for physical nonlinear dynamical systems with limit cycles: an aerofoil undergoing flutter oscillations and an electrodynamic nonlinear oscillator. We consider examples where training data is generated by numerical simulations, whereas we also employ the proposed modelling concept to physical experiments allowing us to investigate problems with a wide range of complexity. To collect the training data, the method of control-based continuation is used as it captures not just the stable but also the unstable limit cycles of the observed system. This feature makes it possible to extract more information about the observed system than the open-loop approach (surveying the steady state response by parameter sweeps without using control) would allow. We use both neural networks and Gaussian processes as universal approximators alongside the mechanistic models to give a critical assessment of the accuracy and robustness of the UDE modelling approach. We also highlight the potential issues one may run into during the training procedure indicating the limits of the current modelling framework.
Johannes N. Hendriks, James R. Z. Holdsworth, Adrian G. Wills
et al.
This paper considers the problem of determining an optimal control action based on observed data. We formulate the problem assuming that the system can be modelled by a nonlinear state-space model, but where the model parameters, state and future disturbances are not known and are treated as random variables. Central to our formulation is that the joint distribution of these unknown objects is conditioned on the observed data. Crucially, as new measurements become available, this joint distribution continues to evolve so that control decisions are made accounting for uncertainty as evidenced in the data. The resulting problem is intractable which we obviate by providing approximations that result in finite dimensional deterministic optimisation problems. The proposed approach is demonstrated in simulation on a nonlinear system.
Objective: Buyinqianzheng Formula (BYQZF) is clinically employed in traditional Chinese medicine to treat Parkinson’s disease (PD) by improving mitochondrial dysfunction. However, the underlying mechanisms by which BYQZF affects mitochondrial morphology remain unknown. Therefore, we observed the effects of BYQZF on mitochondria from the perspective of the PINK1/Parkin pathway. Methods: Cell survival rates were assessed by Cell Counting Kit-8 assay. Expression levels of PINK1 and Parkin mRNA were examined by qRT-PCR. Protein expression levels of PINK1, PINK1-Ser228, Parkin, Parkin-Ser65, Drp1, and Drp1-Ser637 were examined by western blotting. PINK1, Parkin, and MitoTracker® Red CMXRos (MTR) were stained by triple-labeled immunofluorescence, and observed under laser confocal microscopy. Results: Cell survival rate, mitochondrial form factor, mean length and number of mitochondrial network branches, mitochondrial activity, mRNA expression levels of PINK1 and Parkin, and protein expression levels of PINK1, Parkin, and Drp1-Ser637 were reduced after 1-methyl-4-phenylpyridinium (MPP+) intervention. In contrast, Pearson’s correlation coefficients between PINK1 and Parkin, and between Parkin and MTR, as well as protein expression levels of PINK1-Ser228, Parkin-Ser65, and Drp1 increased significantly after MPP+ intervention. Treatment with BYQZF increased cell survival rate, mitochondrial form factor, mean length and number of mitochondrial network branches, mitochondrial activity, mRNA expression levels of PINK1 and Parkin, and expression of PINK1, Parkin, and Drp1-Ser637 proteins. Pearson’s correlation coefficients between PINK1 and Parkin, and between Parkin and MTR, as well as protein expression levels of PINK1-Ser228, Parkin-Ser65, and Drp1 decreased after BYQZF treatment. Conclusion: These results demonstrate that BYQZF has a protective effect on mitochondrial molecular mechanisms in the PD cell model, and the mechanism is related to the PINK1/Parkin pathway.
Jennifer Hunter, Susan Arentz, Joshua Goldenberg
et al.
Background: The global COVID-19 pandemic has prompted an urgent search for effective interventions. SARS-CoV-2 mortality/morbidity risk increases with age and for those chronic disease co-morbidities, both of which are associated with lower zinc status, as is the risk of infection. Methods: Rapid review methods will be applied to a systematic review of zinc for the prevention or treatment of SARS-CoV-2 and viral respiratory tract infections in humans. Included are published studies reporting randomised and quasi-randomised controlled trials that compare zinc intervention to placebo and/or other comparator interventions. English and Chinese language databases will be searched for primary studies of viral respiratory tract infections and clinical trial registries for SARS-CoV-2 infections. Due to concerns about indirectness, studies evaluating non-SARS-CoV-2 coronavirus infections will be rated down by one level, and non-specific or confirmed non-coronavirus viral infections will be rated down by two levels. Review constraints include (1) using Google translate when screening articles published in languages other than English or Chinese and limited translation (2) following calibration, only one reviewer will screen articles, extract data, appraise quality and conduct the analysis, (3) prioritising data extraction and meta-analyses of SARS-CoV-2 studies and critical outcomes of other viral infections, followed by high risk groups and (4) reporting important preliminary findings prior to peer review if necessary. Discussion: The application of these rapid review methods and broadening the inclusion criteria to include other coronavirus-related viral respiratory tract infections aims to enable a timely evidence appraisal of priority research questions and dissemination of results. Study registration: PROSPERO CRD42020182044.