scholarly journals Exploring Possible Mechanisms of Hormesis and Homeopathy in the Light of Nanopharmacology and Ultra-High Dilutions

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110229
Author(s):  
Dana Ullman
Keyword(s):  
Toxic Substance ◽  
Biological Properties ◽  
Patient Specific ◽  
Specific Information ◽  
Exclusion Zone ◽  
Short Period ◽  
Specific Manner ◽  
High Dilutions ◽  
Insight Into ◽  
Primary Phenomenon

Serially diluted succussed solutions of a suitable drug/toxic substance can exhibit physicochemical and biological properties even far beyond Avogadro’s limit defying conventional wisdom. They can show hormesis, and homeopathy uses them as medicines. Many studies confirm that they can have an impact on gene expression different than controls. Water in the exclusion zone phase can have memory but for a short period. However, the nanoparticle as the physical substrate can hold information. Nanoparticle and exclusion zone duo as nanoparticle-exclusion zone shell can provide a prolonged memory. The Nanoparticle-Exclusion Zone Shell Model may be an important step toward explaining the nature and bioactivity of serially diluted succussed solutions used as homeopathic medicines. This model may also provide insight into the workings of hormesis. Hormesis is the primary phenomenon through which homeopathic phenomenon may have evolved exhibiting the principle of similars. Hahnemann exploited it to establish homeopathy. The nanoparticle-exclusion zone shells present in the remedy, selected on the principle of similars, can be patient-specific nanoparticles in a symptom syndrome-specific manner. They can carry the drug-specific information for safer clinical applications in an amplified form for high yielding. It suggests homeopathy is a type of nanopharmacology.

Tailoring Communications for Primary Care Settings

1998 ◽  
Vol 37 (02) ◽  
pp. 171-178 ◽  
Author(s):  
B. Glassman ◽  
B. K. Rimer
Keyword(s):  
Primary Care ◽  
Health Professionals ◽  
Contact Time ◽  
Behavioral Changes ◽  
Patient Specific ◽  
Specific Information ◽  
Medical Settings ◽  
Primary Care Settings ◽  
Professional Contact ◽  
Tailored Communications

AbstractIn more and more medical settings, physicians have less and less time to be effective communicators. To be effective, they need accurate, current information about their patients. Tailored health communications can facilitate positive patient-provider communications and foster behavioral changes conducive to health. Tailored communications (TCs) are produced for an individual based on information about that person. The focus of this report is on tailored print communications (TPCs). TPCs also enhance the process of evaluation, because they require a database and the collection of patient-specific information. We present a Tailoring Model for Primary Care that describes the steps involved in creating TPCs. We also provide examples from three ongoing studies in which TPCs are being used in order to illustrate the kinds of variables used for tailoring the products that are developed and how evaluation is conducted. TPCs offer opportunities to expand the reach of health professionals and to give personalized, individualized massages in an era of shrinking professional contact time.

PubChem and ChEMBL Beyond Lipinski

2019 ◽  
Author(s):  
Jean-Louis Reymond ◽  
Mahendra Awale ◽  
Daniel Probst ◽  
Alice Capecchi
Keyword(s):  
Nearest Neighbor ◽  
Molecular Shape ◽  
Biological Properties ◽  
Web Based ◽  
Large Molecules ◽  
Interactive Tools ◽  
Small Molecule Drugs ◽  
Pubchem Database ◽  
Nearest Neighbor Searches ◽  
Insight Into

<p>Seven million of the currently 94 million entries in the PubChem database break at least one of the four Lipinski constraints for oral bioavailability, 183,185 of which are also found in the ChEMBL database. These non-Lipinski PubChem (NLP) and ChEMBL (NLC) subsets are interesting because they contain new modalities that can display biological properties not accessible to small molecule drugs. Unfortunately, the current search tools in PubChem and ChEMBL are designed for small molecules and are not well suited to explore these subsets, which therefore remain poorly appreciated. Herein we report MXFP (macromolecule extended atom-pair fingerprint), a 217-D fingerprint tailored to analyze large molecules in terms of molecular shape and pharmacophores. We implement MXFP in two web-based applications, the first one to visualize NLP and NLC interactively using Faerun (http://faerun.gdb.tools/), the second one to perform MXFP nearest neighbor searches in NLP (http://similaritysearch.gdb.tools/). We show that these tools provide a meaningful insight into the diversity of large molecules in NLP and NLC. The interactive tools presented here are publicly available at http://gdb.unibe.ch and can be used freely to explore and better understand the diversity of non-Lipinski molecules in PubChem and ChEMBL.</p>

scholarly journals Assessment of patient specific information in the wild on fundus photography and optical coherence tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marion R. Munk ◽  
Thomas Kurmann ◽  
Pablo Márquez-Neila ◽  
Martin S. Zinkernagel ◽  
Sebastian Wolf ◽  
...  
Keyword(s):  
Deep Learning ◽  
Cross Sections ◽  
Underlying Disease ◽  
Geographic Atrophy ◽  
Clinical Population ◽  
Fundus Photography ◽  
Peak Performance ◽  
Patient Specific ◽  
Specific Information ◽  
Fundus Images

AbstractIn this paper we analyse the performance of machine learning methods in predicting patient information such as age or sex solely from retinal imaging modalities in a heterogeneous clinical population. Our dataset consists of N = 135,667 fundus images and N = 85,536 volumetric OCT scans. Deep learning models were trained to predict the patient’s age and sex from fundus images, OCT cross sections and OCT volumes. For sex prediction, a ROC AUC of 0.80 was achieved for fundus images, 0.84 for OCT cross sections and 0.90 for OCT volumes. Age prediction mean absolute errors of 6.328 years for fundus, 5.625 years for OCT cross sections and 4.541 for OCT volumes were observed. We assess the performance of OCT scans containing different biomarkers and note a peak performance of AUC = 0.88 for OCT cross sections and 0.95 for volumes when there is no pathology on scans. Performance drops in case of drusen, fibrovascular pigment epitheliuum detachment and geographic atrophy present. We conclude that deep learning based methods are capable of classifying the patient’s sex and age from color fundus photography and OCT for a broad spectrum of patients irrespective of underlying disease or image quality. Non-random sex prediction using fundus images seems only possible if the eye fovea and optic disc are visible.

scholarly journals Depression patient-derived cortical neurons reveal potential biomarkers for antidepressant response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yishai Avior ◽  
Shiri Ron ◽  
Dana Kroitorou ◽  
Claudia Albeldas ◽  
Vitaly Lerner ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Antidepressant Treatment ◽  
Patient Specific ◽  
Specific Gene ◽  
Specific Information ◽  
Patient Response ◽  
Patient Will ◽  
Gene Expression Alterations ◽  
Treatment Alternatives

AbstractMajor depressive disorder is highly prevalent worldwide and has been affecting an increasing number of people each year. Current first line antidepressants show merely 37% remission, and physicians are forced to use a trial-and-error approach when choosing a single antidepressant out of dozens of available medications. We sought to identify a method of testing that would provide patient-specific information on whether a patient will respond to a medication using in vitro modeling. Patient-derived lymphoblastoid cell lines from the Sequenced Treatment Alternatives to Relieve Depression study were used to rapidly generate cortical neurons and screen them for bupropion effects, for which the donor patients showed remission or non-remission. We provide evidence for biomarkers specific for bupropion response, including synaptic connectivity and morphology changes as well as specific gene expression alterations. These biomarkers support the concept of personalized antidepressant treatment based on in vitro platforms and could be utilized as predictors to patient response in the clinic.

scholarly journals A decellularized human corneal scaffold for anterior corneal surface reconstruction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naresh Polisetti ◽  
Anke Schmid ◽  
Ursula Schlötzer-Schrehardt ◽  
Philip Maier ◽  
Stefan J. Lang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Ex Vivo ◽  
Sodium Deoxycholate ◽  
Nuclear Material ◽  
Biological Properties ◽  
Host Cells ◽  
Human Cornea ◽  
Human Donor ◽  
Short Period

AbstractAllogenic transplants of the cornea are prone to rejection, especially in repetitive transplantation and in scarred or highly vascularized recipient sites. Patients with these ailments would particularly benefit from the possibility to use non-immunogenic decellularized tissue scaffolds for transplantation, which may be repopulated by host cells in situ or in vitro. So, the aim of this study was to develop a fast and efficient decellularization method for creating a human corneal extracellular matrix scaffold suitable for repopulation with human cells from the corneal limbus. To decellularize human donor corneas, sodium deoxycholate, deoxyribonuclease I, and dextran were assessed to remove cells and nuclei and to control tissue swelling, respectively. We evaluated the decellularization effects on the ultrastructure, optical, mechanical, and biological properties of the human cornea. Scaffold recellularization was studied using primary human limbal epithelial cells, stromal cells, and melanocytes in vitro and a lamellar transplantation approach ex vivo. Our data strongly suggest that this approach allowed the effective removal of cellular and nuclear material in a very short period of time while preserving extracellular matrix proteins, glycosaminoglycans, tissue structure, and optical transmission properties. In vitro recellularization demonstrated good biocompatibility of the decellularized human cornea and ex vivo transplantation revealed complete epithelialization and stromal repopulation from the host tissue. Thus, the generated decellularized human corneal scaffold could be a promising biological material for anterior corneal reconstruction in the treatment of corneal defects.

Numerical Simulation of Blood Flow in Patient-Specific Stenotic Carotid Bifurcation Geometries

2009 ◽  
Author(s):  
Megan Cummins ◽  
Jenn S. Rossmann
Keyword(s):  
Vortex Shedding ◽  
Carotid Bifurcation ◽  
Secondary Flows ◽  
Patient Specific ◽  
Mechanical Forces ◽  
Plaque Vulnerability ◽  
Governing Equations ◽  
Unstable Plaque ◽  
Recirculation Zones ◽  
Insight Into

The hemodynamics and fluid mechanical forces in blood vessels have long been implicated in the deposition and growth of atherosclerotic plaque. Detailed information about the hemodynamics in vessels affected by significant plaque deposits can provide insight into the mechanisms and likelihood of plaque weakening and rupture. In the current study, the governing equations are solved in their finite volume formulation in several patient-specific geometries. Recirculation zones, vortex shedding, and secondary flows are captured. The forces on vessel walls are shown to correlate with unstable plaque deposits. The results of these simulations suggest morphological features that may usefully supplement percent stenosis as a predictor of plaque vulnerability.

scholarly journals Control of microtubule dynamics using an optogenetic microtubule plus end–F-actin cross-linker

2017 ◽  
Vol 217 (2) ◽  
pp. 779-793 ◽  
Author(s):  
Rebecca C. Adikes ◽  
Ryan A. Hallett ◽  
Brian F. Saway ◽  
Brian Kuhlman ◽  
Kevin C. Slep
Keyword(s):  
Blue Light ◽  
Actin Binding ◽  
Cross Linking ◽  
Dependent Manner ◽  
Exclusion Zone ◽  
Actin Networks ◽  
Drosophila Melanogaster S2 Cells ◽  
Actin Binding Domain ◽  
Specific Factors ◽  
Insight Into

We developed a novel optogenetic tool, SxIP–improved light-inducible dimer (iLID), to facilitate the reversible recruitment of factors to microtubule (MT) plus ends in an end-binding protein–dependent manner using blue light. We show that SxIP-iLID can track MT plus ends and recruit tgRFP-SspB upon blue light activation. We used this system to investigate the effects of cross-linking MT plus ends and F-actin in Drosophila melanogaster S2 cells to gain insight into spectraplakin function and mechanism. We show that SxIP-iLID can be used to temporally recruit an F-actin binding domain to MT plus ends and cross-link the MT and F-actin networks. Cross-linking decreases MT growth velocities and generates a peripheral MT exclusion zone. SxIP-iLID facilitates the general recruitment of specific factors to MT plus ends with temporal control enabling researchers to systematically regulate MT plus end dynamics and probe MT plus end function in many biological processes.

scholarly journals Insight on Solution Plasma in Aqueous Solution and Their Application in Modification of Chitin and Chitosan

2021 ◽  
Vol 22 (9) ◽  
pp. 4308
Author(s):  
Chayanaphat Chokradjaroen ◽  
Jiangqi Niu ◽  
Gasidit Panomsuwan ◽  
Nagahiro Saito
Keyword(s):  
Aqueous Solutions ◽  
Atmospheric Pressure ◽  
Scientific Progress ◽  
Biological Properties ◽  
Environmental Concerns ◽  
Plasma Process ◽  
Renewable Materials ◽  
Chemical Structures ◽  
Chitin And Chitosan ◽  
Insight Into

Sustainability and environmental concerns have persuaded researchers to explore renewable materials, such as nature-derived polysaccharides, and add value by changing chemical structures with the aim to possess specific properties, like biological properties. Meanwhile, finding methods and strategies that can lower hazardous chemicals, simplify production steps, reduce time consumption, and acquire high-purified products is an important task that requires attention. To break through these issues, electrical discharging in aqueous solutions at atmospheric pressure and room temperature, referred to as the “solution plasma process”, has been introduced as a novel process for modification of nature-derived polysaccharides like chitin and chitosan. This review reveals insight into the electrical discharge in aqueous solutions and scientific progress on their application in a modification of chitin and chitosan, including degradation and deacetylation. The influencing parameters in the plasma process are intensively explained in order to provide a guideline for the modification of not only chitin and chitosan but also other nature-derived polysaccharides, aiming to address economic aspects and environmental concerns.

Patient-Specific Modelling of Intracranial Aneurysm Evolution

2011 ◽  
Author(s):  
Paul N. Watton ◽  
Marc Homer ◽  
Justin Penrose ◽  
Harry Thompson ◽  
Haoyu Chen ◽  
...  
Keyword(s):  
Arterial Wall ◽  
Adult Population ◽  
Computational Simulation ◽  
Clinical Intervention ◽  
Patient Specific ◽  
Computational Framework ◽  
Important Concern ◽  
Risk Of Rupture ◽  
Appropriate Therapy ◽  
Insight Into

Intracranial aneurysms appear as sac-like outpouchings of the cerebral vasculature wall; inflated by the pressure of the blood that fills them. They are relatively common and affect up to 5% of the adult population. Fortunately, most remain asymptomatic. However, there is a small but inherent risk of rupture: 0.1% to 1% of detected aneurysms rupture every year. If rupture does occur there is a 30% to 50% chance of fatality. Consequently, if an aneurysm is detected, clinical intervention may be deemed appropriate. Therapy is currently aimed at pre-rupture detection and preventative treatment. However, interventional procedures are not without risk to the patient. The improvement and optimization of interventional techniques is an important concern for patient welfare and is necessary for rationalisation of healthcare priorities. Hence there is a need to develop methodologies to assist in identifying those ICAs most at risk of rupture. We focus on the mathematical modelling and computational simulation of ICA evolution. Models must take into consideration: (i) the biomechanics of the arterial wall; (ii) the biology of the arterial wall and (iii) the complex interplay between (i) and (ii), i.e. the mechanobiology of the arterial wall. The ultimate ambition of such models is to aid clinical diagnosis on a patient-specific basis. However, due to the significant biological complexity coupled with limited histological information such models are still in their relative infancy. Current research focuses on simulating the evolution of an ICA with an aim to yield insight into the growth and remodelling (G&R) processes that give rise to inception, enlargement, stabilisation and rupture. We present a novel Fluid-Structure-Growth computational framework for modelling aneurysm evolution.

scholarly journals New Sesterterpenes from Marine  Sponges from the Tropical Waters of the  Kingdom of Tonga

2021 ◽  
Author(s):  
◽  
Taitusi Taufa
Keyword(s):  
Biological Activities ◽  
Screening Method ◽  
Biological Properties ◽  
Geometric Isomer ◽  
Marine Sponges ◽  
Ring Closure ◽  
Substitution Pattern ◽  
Methyl Group ◽  
Structure Activity ◽  
Insight Into

<p>Over the course of this study, various species of Tongan marine sponges were investigated using an NMR-based screening method and has resulted in the discovery of three new sesterterpenes and 11 known compounds. Examination of the sponge Fascaplysinopsis sp. resulted in the isolation of two novel sesterterpenes, isoluffariellolide (46) and 1-O-methylisoluffariellolide (47). Compounds 46 and 47 share the same backbone pattern as the known luffariellolide (45) and 25-Omethylluffariellolide (107) respectively, and differ only in the substitution pattern of the butenolide rings. Isoluffariellolide (46) was found to be approximately six times less cytotoxic than 1-O-methylisoluffariellolide (47). Interestingly, these results suggested that the 1-O-methyl group in compound 47 plays an important role in the cytotoxicity of the compound. Secothorectolide (49), a new ring-opened and geometric isomer of the known compound thorectolide (48), was obtained from a sponge of the order Dictyoceratida. This ring closure and opening relationship was also observed between manoalide (109) and secomanoalide (110), as well as luffariellins A (141) and B (142). Despite the different carbon skeleton, the functional groups in 141 and 142 are similar with those in 109 and 110, respectively, and not surprisingly the biological properties are almost identical. The biological activities of compounds 48 and 49 were almost the same, which would give an insight into the structure-activity relationship (SAR) between these types of compounds.</p>

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