Chronobiology of Viscum album L.: a time series of daily metabolomic fingerprints spanning 27 years.

Introduction: European mistletoe (Viscum album L.) has been gaining increasing interest in the field of oncology as a clinically relevant adjunctive treatment in many forms of cancer. In the field of phytopharmacology, harvesting time is pivotal. In the last century, a form of metabolomic fingerprinting based on pattern formation was proposed as a way to determine optimal harvesting times to ensure high quality of mistletoe as raw material for pharmaceutical use. In order to further evaluate the information obtained with this metabolomic fingerprinting method, we analysed a large time series of previously undigitised daily mistletoe chromatograms dating back to the 1950s. Methods: These chromatograms were scanned and evaluated using computerized image analysis, resulting in 12 descriptors for each individual chromatogram. We performed a statistical analysis of the data obtained, investigating statistical distributions, cross-correlations and time self-correlations. Results: The analysed dataset spanning about 27 years, contains 19,037 evaluable chromatograms in daily resolution. Based on the distribution and cross-correlation analyses, the 12 descriptors could be clustered into six independent groups describing different aspects of the chromatograms. One descriptor was found to mirror the annual rhythm being well correlated with temperature and a phase shift of 10 days. The time self-correlation analysis showed that most other descriptors had a characteristic self-correlation of ∼50 days, which points to further infradian rhythms (i.e., more than 24 h). Discussion: To our knowledge, this dataset is the largest of its type. The combination of this form of metabolomic fingerprinting with the proposed computer analysis seems to be a promising tool to characterise biological variations of mistletoe. Additional research is underway to further analyse the different rhythms present in this dataset.

Environmental Homeopathy: Homeopathic Potencies Regulate the Toxicity and Growth of Raphidiopsis raciborskii (cyanobacteria) and can be Tracked Physico-Chemically. Part 1: Biological Results.

INTRODUCTION: Cyanobacteria are microorganisms found in many parts of the world and several genera, such as Raphidiopsis raciborskii, are producers of cyanotoxins. Homeopathic potencies have been found to modulate toxicity in different biological models, and the present study endeavors to discover whether this might also be the case with cyanobacteria. OBJECTIVES: Our objective was to investigate the possible effects of homeopathic potencies on the resilience of Artemia franciscana (brine shrimp) embryos to saxitoxin (STX; cyanotoxin) and on controlling the growth of R. raciborskii in vitro. METHOD: A. franciscana cysts were cultivated in seawater in 96-well plates to evaluate the hatching rate and vitality, plus the gene expression of heat shock proteins (HSPs), after being challenged with R. raciborskii extract containing 2.5 µg/L of STX and treated with different homeopathic potencies. Untreated wells were used as controls ("base-line"). Potencies were chosen from a screening process based on seven selected homeopathic preparations according to the similitude of STX symptoms (Sulphur, Zincum metallicum, Nitric acidum, Plumbum metallicum, Mercurius solubilis, Phosphoric acidum, Isotherapic from R. raciborskii extract; all at 6cH, 30cH and 200cH). Cultures of R. raciborskii maintained in an artificial seawater medium were equally treated with screened homeopathic potencies selected from the same list but specifically for their growth control as a function of time. RESULTS: A 15% lower rate of hatching of A. franciscana cysts was observed after treatment with Nitric acidum 6cH in comparison with baseline (p = 0.05). A complete toxicity reversal was seen after treatment with Isotherapic 200cH, with a 23-fold increase of Hsp 26 gene expression (p = 0.023) and a 24-fold increase of p26 gene expression (p ≤ 0.001) in relation to baseline. Nitric acidum 200cH and Mercurius solubilis 30cH limited the exponential growth of cyanobacteria up to 95% and 85% respectively (p ≤ 0.003) in relation to baseline. Succussed water presented only a transitory 50% inhibition effect. CONCLUSION: Isotherapic 200cH improved A. franciscana bioresilience to STX; Nitric acidum 200cH and Mercurius solubilis 30cH showed the optimal performance on limiting R. raciborskii growth. The results point to the potential of homeopathic potencies to mitigate environmental problems related to water quality.

Environmental Homeopathy: Homeopathic Potencies Regulate the Growth and Toxicity of Raphidiopsis raciborskii (cyanobacteria) and Can be Tracked Physico-Chemically. Part 2: Physico-chemical Results.

INTRODUCTION: The control of cyanobacterial toxicity and growth by homeopathic potencies was described in Part 1 of this two-part report. Here, a parallel approach characterized the physico-chemical features of the potencies used and the liquid media treated with them, correlating these results with their respective biological effects. OBJECTIVES: Our objective was to establish if physico-chemical parameters can track homeopathic potencies in seawater or artificial seawater medium (ASM)-1 and to discover whether these parameters correlate with previously described biological effects. METHOD: Artemia franciscana (brine shrimp) cysts were cultivated in seawater challenged with Raphidiopsis raciborskii extract and treated with different homeopathic potencies chosen from a screening process. Cultures of R. raciborskii maintained in ASM-1 were also treated with previously screened homeopathic potencies, and their growth was monitored as a function of time. The physico-chemical properties of the treated media (seawater or ASM-1) were evaluated by their interaction with solvatochromic dyes and changes in pH, conductivity and temperature. RESULTS: Coumarin 7 was found to be a marker for Nitric acidum 6cH and Isotherapic (R. raciborskii extract) 200cH in seawater (analysis of variance [ANOVA], p = 0.0015). Nile red was found to be a marker for Nitric acidum 200cH and Mercurius solubilis 30cH in ASM-1 (ANOVA, p ≤ 0.001). An increase in pH of ASM-1 and endothermic effects were observed after these treatments (two-way ANOVA, p = 0.0001). Seawater and ASM-1 to which potencies had been added were also subjected to a constant unidirectional 2,400 Gauss static magnetic field and found to have enhanced effects on the solvatochromic dyes tested. CONCLUSION: Homeopathic potencies were specifically traceable in aqueous media using solvatochromic dyes, especially when the samples were subjected to a magnetic field. Results from monitoring other physical parameters, such as pH and temperature, were less specific in relation to potency tracking. However, potency-induced endothermic effects might provide valuable thermodynamic data relating to the nature of potencies.

HRI London 2023: The Homeopathy Research Community Reunites after a 4-Year Hiatus, Sparking Fresh Collaborations between Researchers 'Old and New'.

The Homeopathy Research Institute's (HRI) 5th international research conference took place in the heart of London, from 16th to 18th June 2023. With 230 attendees from 27 countries, HRI's conferences remain truly international. HRI London 2023 will be remembered for its inspiring blend of 'old and new', with a programme notable for the maturity of the evidence presented by experienced names drawing on decades of work, as well as the enthusiasm and skill of up-and-coming researchers who took the floor to present their new findings. In this report, we present scientific highlights from the event.

Systematic review of conceptual criticisms of homeopathy.

Homeopathy is the subject of frequent debates, especially in public media. This systematic review aims to give an overview of conceptual criticisms of homeopathy in the scientific literature. The literature search was conducted in four databases (EMBASE, PubMed, Web of Science, PhilPapers) on August 25, 2020. Included were peer reviewed articles in English or German criticising the basic concepts of homeopathy as main topic; excluded were articles criticising homeopathy primarily based on analysis of empirical clinical and/or preclinical data. The formal structure of publications included was evaluated regarding the recommended structure for scientific publications (IMRaD, acronym for 'Introduction', 'Methods', 'Results' and 'Discussion'). Arguments criticising the concepts of homeopathy were extracted and classified into groups. The literature search revealed 5139 articles, of which 15 articles (published between 1959 and 2020) met the inclusion criteria. These articles complied only partly with the IMRaD structure; just four articles considered with 8 or 9 IMRaD criteria the majority of the defined 11 IMRaD criteria. Extracted arguments against the concepts of homeopathy were classified into five groups: 'Conflict with current scientific principles and the foundations of modern medicine', 'Lack of a scientific basis', 'Arguments based on scientific theories', 'Ethical considerations and social consequences', 'Lack of empirical clinical evidence'. This classification is intended to provide a basis for future in-depth scientific analyses and discussions. Based on the number of articles found in the peer reviewed literature, it can be concluded that the on-going discussion about homeopathy in the public media is not reflected in a corresponding academic debate.

Highly Diluted Glyphosate Mitigates Its Effects on Artemia salina: Physicochemical Implications.

Glyphosate is an herbicide widely used in agriculture but can present chronic toxicity in low concentrations. Artemia salina is a common bio-indicator of ecotoxicity; it was used herein as a model to evaluate the effect of highly diluted-succussed glyphosate (potentized glyphosate) in glyphosate-based herbicide (GBH) exposed living systems. Artemia salina cysts were kept in artificial seawater with 0.02% glyphosate (corresponding to 10% lethal concentration or LC10) under constant oxygenation, luminosity, and controlled temperature, to promote hatching in 48 h. Cysts were treated with 1% (v/v) potentized glyphosate in different dilution levels (Gly 6 cH, 30 cH, 200 cH) prepared the day before according to homeopathic techniques, using GBH from the same batch. Controls were unchallenged cysts, and cysts treated with succussed water or potentized vehicle. After 48 h, the number of born nauplii per 100 µL, nauplii vitality, and morphology were evaluated. The remaining seawater was used for physicochemical analyses using solvatochromic dyes. In a second set of experiments, Gly 6 cH treated cysts were observed under different degrees of salinity (50 to 100% seawater) and GBH concentrations (zero to LC 50); hatching and nauplii activity were recorded and analyzed using the ImageJ 1.52, plug-in Trackmate. The treatments were performed blind, and the codes were revealed after statistical analysis. Gly 6 cH increased nauplii vitality (p = 0.01) and improved the healthy/defective nauplii ratio (p = 0.005) but delayed hatching (p = 0.02). Overall, these results suggest Gly 6cH treatment promotes the emergence of the more GBH-resistant phenotype in the nauplii population. Also, Gly 6cH delays hatching, another useful survival mechanism in the presence of stress. Hatching arrest was most marked in 80% seawater when exposed to glyphosate at LC10. Water samples treated with Gly 6 cH showed specific interactions with solvatochromic dyes, mainly Coumarin 7, such that it appears to be a potential physicochemical marker for Gly 6 cH. In short, Gly 6 cH treatment appears to protect the Artemia salina population exposed to GBH at low concentrations.

HRI Online 2022: Leading International Experts Illustrate the Positive Impact of Increased Collaboration in Homeopathy Research.

The Homeopathy Research Institute (HRI) welcomed more than 450 people from 35 countries to their first online event on June 25, 2022. The one-day programme featured an excellent line-up of international speakers and provided a unique interactive platform in keeping with the theme of the event - Key Collaborations in Homeopathy Research. Scientists from a range of different research fields gave an exceptional insight into the current status of homeopathy research. Here we give an overview of the most significant findings in both clinical and basic research presented during HRI Online 2022.

Searching for the Genus Epidemicus in Chinese Patients: Findings from the Clificol COVID-19 Clinical Case Registry.

BACKGROUND: The Clificol COVID-19 Support Project is an innovative international data collection project aimed at tackling some of the core questions in homeopathy. This paper reports on the further investigation of the genus epidemicus concept during the first wave of the pandemic in the Chinese population. METHODS: The design is an observational clinical case registry study of Chinese patients with confirmed or suspected coronavirus disease 2019 (COVID-19). The symptoms were prospectively collected via a 150-item questionnaire. The concept of genus epidemicus, including the role of treatment individualization, was investigated by analyzing whether presenting symptoms clustered into distinct groups. Two standard statistical analysis techniques were utilized: principal component analysis for extracting the most meaningful symptoms of the dataset; the k-means clustering algorithm for automatically assigning groups based on similarity between presenting symptoms. RESULTS: 20 Chinese practitioners collected 359 cases in the first half of 2020 (766 consultations, 363 prescriptions). The cluster analysis found two to be the optimum number of clusters. These two symptomatic clusters had a high overlap with the two most commonly prescribed remedies in these sub-populations: in cluster 1 there were 297 prescriptions, 95.6% of which were Gelsemium sempervirens; in cluster 2 there were 61 prescriptions, 95.1% of which were Bryonia alba. CONCLUSION: This is the first study to investigate the notion of genus epidemicus by using modern statistical techniques. These analyses identified at least two distinct symptom pictures. The notion of a single COVID-19 genus epidemicus did not apply in the studied population.

A fresh look at the concept of Genus Epidemicus: findings from the Clificol Project

The Clificol® COVID-19 Support Project is an innovative international data collection project aimed at tackling some of the core questions in homeopathy, including the notion of Genus Epidemicus. Aims:To shed some light on the notion of Genus Epidemicus in the context of this infection. Going beyond that, the project aims to use these data to tackle more fundamental questions, such as the role of symptoms and rubrics in treatment individualisation. Methodology:This online multi-national data-collection project is supported by the ECH, ECCH, ICH, HRI, LMHI, and other professional associations. The collected data includes demographic information, severity, conventional diagnosis and treatment, presenting symptoms as well as the remedies prescribed. The outcome of treatment was tracked using the ORIDL scale. The concept of Genus Epidemicus, including the role of treatment individualisation, was investigated by analysing whether presenting symptoms cluster into distinct groups (K-Means clustering approach). The symptom data originating from China was obtained using a questionnaire. Results and discussion: 20 Chinese practioners collected 359 cases, primarily in the first half of 2020 (766 consultations, 363 prescriptions). The cluster analysis found two to be the optimum number of clusters. These two symptomatic clusters had a high overlap with the two most commonly prescribed remedies in that population: In cluster 1 there were 297 prescriptions, 95.6% of which were Gelsemium sempervirens, incluster 2, there were 61 prescriptions, 95.1% of which were Bryonia alba. Under the assumption of a single genus epidemicuswe would expect to see a single cluster of symptoms. The data from the Chinese population were not compatible with this assumption. Conclusion:This was the first study that investigated the notion of Genus Epidemicus by using modern statistical techniques. These analyses identified at least two distinct symptom pictures. The notion of a single COVID-19 Genus Epidemicus did not apply to this population.

Update from the Clificol Project: Omicron in Hong-Kongand worldwide overview of the pandemic

The Clificol® COVID-19 Support Project is an innovative international data collection project aimed at documenting the presenting symptoms, use of homeopathy through the pandemic and tackling some of the core questions in homeopathy. The Covid-19 pandemic raised many questions and mobilised many resources. In order to make good use of resources, sound knowledge of the presenting complaints and demographics are required. In particular, we aimed to characterise the recent Omicron wave in Hong-Kong and to get an overall picture of the global pandemic as experienced by the homeopathic community. This online multi-national data-collection project is supported by the ECH, ECCH, ICH, HRI, LMHI, and other professional associations. The collected data includes demographic information, severity, conventional diagnosis and treatment, presenting symptoms as well as the remedies prescribed. The outcome of treatment was tracked using the ORIDL scale. More recently a 23-items prospective questionnaire was added to the input in order to gather targeted data about the presenting complaints. The recent wave of the Omicron variant in Hong-Kong, was analysed (N=372 cases) in terms of the symptomatology of this variant. The data from the 23-items questionnaire is compared to the longer questionnaire (150 items) used by the Hong-Kong team (21 practitioners). The most frequently reported common Clinical symptoms were extreme tiredness (60%), sore throat (46%), headache during fever (45%), dryness of mouth (37%), poor appetite (37%), runny nose (34%) and unusual muscle pains (31%).Also, the cases collected from around the world over the course of the pandemic (N=1300) were analysed, providing an overall picture of the pandemic and its specificities per country and over time. Clificol has shown and continues to show the value of data collection for the homeopathy community, providing important information for the management of future pandemics and opening new avenues for research in homeopathy.

A picket fence function for adherens junctions in epithelial cell polarity.

Adherens junctions are a defining feature of all epithelial cells, providing cell-cell adhesion and contractile ring formation that is essential for cell and tissue morphology. In Drosophila, adherens junctions are concentrated between the apical and basolateral plasma membrane domains, defined by aPKC-Par6-Baz and Lgl/Dlg/Scrib, respectively. Whether adherens junctions contribute to apical-basal polarization itself has been unclear because neuroblasts exhibit apical-basal polarization of aPKC-Par6-Baz and Lgl in the absence of adherens junctions. Here we show that, upon disruption of adherens junctions in epithelial cells, apical polarity determinants such as aPKC can still segregate from basolateral Lgl, but lose their sharp boundaries and also overlap with Dlg and Scrib - similar to neuroblasts. In addition, control of apical versus basolateral domain size is lost, along with control of cell shape, in the absence of adherens junctions. Manipulating the levels of apical Par3/Baz or basolateral Lgl polarity determinants in experiments and in computer simulations confirms that adherens junctions provide a 'picket fence' diffusion barrier that restricts the spread of polarity determinants along the membrane to enable precise domain size control. Movement of adherens junctions in response to mechanical forces during morphogenetic change thus enables spontaneous adjustment of apical versus basolateral domain size as an emergent property of the polarising system.

Physicochemical Investigations of Homeopathic Preparations: A Systematic Review and Bibliometric Analysis-Part 3.

Objectives: In parts I and II of our review of physicochemical research performed on homeopathic preparations, we identified relevant publications and analyzed the data in terms of individual experiments, looking for the most promising techniques that were used in the past. In this third part, we analyze the results of the experiments seeking to extract information about the possible modes of action underpinning homeopathic preparations. Methods: We summarized the results from the 11 experimental areas previously introduced, extracting the general findings and trends. We also summarized the results in terms of specific research topics: aging, medium used for potentization, sample volume, temperature, material of potentization vessel, and, finally, the use of molecules to probe homeopathic samples. Results: We identified a number of effects that appear consistently throughout the data: Differences to controls seem to increase with: time, moderate temperature, small samples volume, and in ionic medium, whereas high temperatures seem to abolish differences to controls. Based on the present analysis, there is no consistent evidence to date for the nanoparticle hypothesis to explain specific homeopathic treatment effects. However, the quantum coherence domain hypothesis, the dynamic water cluster hypothesis, and the weak quantum theory are still contenders and need to be further assessed experimentally. Conclusions: The field requires further targeted experimentation to validate past findings reporting differences between homeopathic dilutions and controls, and to expand these findings by specifically testing the three main working hypotheses that are currently at hand.

HRI London 2019: 10 Years of Excellence in Homeopathy Research.

The Homeopathy Research Institute's (HRI's) 4th International Research Conference took place in the heart of London from 14 to 16 June 2019. With 352 attendees from 38 countries, this was HRI's largest and most international conference to date. HRI London 2019 will be remembered for the highest quality scientific programme so far, combined with a vibrant, positive atmosphere throughout, making it the perfect way to celebrate HRI's 10th Anniversary. Here we summarise the science presented during the intense 2.5-day programme.

Physicochemical Investigations of Homeopathic Preparations: A Systematic Review and Bibliometric Analysis-Part 2.

Objectives: In Part 1 of the review of physicochemical research performed on homeopathic preparations the authors identified relevant publications of sufficient reporting quality for further in-depth analysis. In this article, the authors analyze these publications to identify any empirical evidence for specific physicochemical properties of homeopathic preparations and to identify most promising experimental techniques for future studies. Methods: After an update of the literature search up to 2018, the authors analyzed all publications in terms of individual experiments. They extracted information regarding methodological criteria such as blinding, randomization, statistics, controls, sample preparation, and replications, as well as regarding experimental design and measurement methods applied. Scores were developed to identify experimental techniques with most reliable outcomes. Results: The publications analyzed described 203 experiments. Less than 25% used blinding and/or randomization, and about one third used adequate controls to identify specific effects of homeopathic preparations. The most promising techniques used so far are nuclear magnetic resonance (NMR) relaxation, optical spectroscopy, and electrical impedance measurements. In these three areas, several sets of replicated high-quality experiments provide evidence for specific physicochemical properties of homeopathic preparations. Conclusions: The authors uncovered a number of promising experimental techniques that warrant replication to assess the reported physicochemical properties of homeopathic preparations compared with controls. They further discuss a range of experimental aspects that highlight the many factors that need to be taken into consideration when performing basic research into homeopathic potentization. For future experiments, the authors generally recommend using succussed (vigorously shaken) controls, or comparing different homeopathic preparations with each other to reliably identify any specific physicochemical properties.

HRI Malta 2017-Cutting Edge Research in Homeopathy: HRI's Third International Research Conference in Malta.

The third international conference on "Cutting Edge Research in Homeopathy" organised by the Homeopathy Research Institute (HRI) was held on the inspiring and historic island of Malta from 9th to 11th of June, 2017. One hundred and two abstracts underwent peer review by the HRI Scientific Advisory Committee and external experts to produce the programme of 36 oral presentations and 37 posters, presented by researchers from 19 countries. The 2.5-day programme covered a diverse range of topics, including quantitative and qualitative clinical research, basic research, veterinary research, and provings. These intensive plenary and parallel sessions were interspersed with multiple opportunities for delegates to discuss and exchange ideas, in particular through interactive panel discussions and a pre-conference workshop. The continuing commitment of the homeopathy research community to generate high-quality studies in this rapidly evolving field was clear. In this conference report, we present highlights from this memorable event.