Use of homeopathic preparations in phytopathological models and in field trails: a critical review

Background: The literature on the applications of homeopathy for controlling plant diseases in both plant pathological models and field trials was first reviewed by Scofield in 1984. No other review on homeopathy in plant pathology has been published since, though much new research has subsequently been carried out using more advanced methods. Objectives: To conduct an up-to-date review of the existing literature on basic research in homeopathy using phytopathological models and experiments in the field. Methods: A literature search was carried out on publications from 1969 to 2009, for papers that reported experiments on homeopathy using phytopathological models (in vitro and in planta) and field trials. The selected papers were summarized and analysed on the basis of a Manuscript Information Score (MIS) to identify those that provided sufficient information for proper interpretation (MIS ≥ 5). These were then evaluated using a Study Methods Evaluation Procedure (SMEP). Results: A total of 44 publications on phytopathological models were identified: 19 papers with statistics, 6 studies with MIS ≥ 5. Publications on field were 9, 6 with MIS ≥ 5. In general, significant and reproducible effects with decimal and centesimal potencies were found, including dilution levels beyond the Avogadro's number. Conclusions: The prospects for homeopathic treatments in agriculture are promising, but much more experimentation is needed, especially at a field level, and on potentisation techniques, effective potency levels and conditions for reproducibility. Phytopathological models may also develop into useful tools to answer pharmaceutical questions.

Microarray-based detection of 90 antibiotic resistance genes of gram-positive bacteria

A disposable microarray was developed for detection of up to 90 antibiotic resistance genes in gram-positive bacteria by hybridization. Each antibiotic resistance gene is represented by two specific oligonucleotides chosen from consensus sequences of gene families, except for nine genes for which only one specific oligonucleotide could be developed. A total of 137 oligonucleotides (26 to 33 nucleotides in length with similar physicochemical parameters) were spotted onto the microarray. The microarrays (ArrayTubes) were hybridized with 36 strains carrying specific antibiotic resistance genes that allowed testing of the sensitivity and specificity of 125 oligonucleotides. Among these were well-characterized multidrug-resistant strains of Enterococcus faecalis, Enterococcus faecium, and Lactococcus lactis and an avirulent strain of Bacillus anthracis harboring the broad-host-range resistance plasmid pRE25. Analysis of two multidrug-resistant field strains allowed the detection of 12 different antibiotic resistance genes in a Staphylococcus haemolyticus strain isolated from mastitis milk and 6 resistance genes in a Clostridium perfringens strain isolated from a calf. In both cases, the microarray genotyping corresponded to the phenotype of the strains. The ArrayTube platform presents the advantage of rapidly screening bacteria for the presence of antibiotic resistance genes known in gram-positive bacteria. This technology has a large potential for applications in basic research, food safety, and surveillance programs for antimicrobial resistance.

Introduction of two novel devices for investigating the influence of non-mechanical components such as therapeutic qi in acupuncture

OBJECTIVE: Acupuncture is a complex intervention consisting of specific and non-specific components. Acupuncture studies more frequently focus on collecting data from the patients’ perspective and response, but the acupuncturist’s role remains relatively unclear. In order to investigate potential non-mechanical active factors originating from the acupuncturist and transmitted to the patient during treatment, two novel devices for basic research in acupuncture were designed. The Acuplicator allows the researcher to insert needles without touching the needles themselves, while the Veliusator locks the needle in its place so that no mechanical movement can be transferred. METHODS: The Acuplicator was used to insert needles at Neiguan (PC6) on the right forearm of 23 volunteers. The insertion depth was measured using a depth gauge. The transfer of mechanical movements from the handle to the tip was detected with a precision length gauge with a motoric-tactile sensor. RESULTS: The mean insertion depth was (12.3 ± 1.5) mm (range 9.5 to 15.0 mm). Even with intense manipulation of the needle handle, no movements within ± 1 μm could be detected at the tip when the needle was locked. CONCLUSION: With these two devices it will be possible to investigate the influence of non-mechanical components such as therapeutic qi in acupuncture.

Reproducibility of effects of homeopathically potentised gibberellic acid on the growth of Lemna gibba L. in a randomised and blinded bioassay

BACKGROUND: Reproducibility of basic research investigations in homeopathy is challenging. This study investigated if formerly observed effects of homeopathically potentised gibberellic acid (GA3) on growth of duckweed (Lemna gibba L.) were reproducible. METHODS: Duckweed was grown in potencies (14x-30x) of GA3 and one time succussed and unsuccussed water controls. Outcome parameter area-related growth rate was determined by a computerised image analysis system. Three series including five independent blinded and randomised potency experiments (PE) each were carried out. System stability was controlled by three series of five systematic negative control (SNC) experiments. Gibbosity (a specific growth state of L. gibba) was investigated as possibly essential factor for reactivity of L. gibba towards potentised GA3 in one series of potency and SNC experiments, respectively. RESULTS: Only in the third series with gibbous L. gibba L. we observed a significant effect (p = 0.009, F-test) of the homeopathic treatment. However, growth rate increased in contrast to the former study, and most biologically active potency levels differed. Variability in PE was lower than in SNC experiments. The stability of the experimental system was verified by the SNC experiments. CONCLUSIONS: Gibbosity seems to be a necessary condition for reactivity of L. gibba to potentised GA3. Further still unknown conditions seem to govern effect direction and the pattern of active and inactive potency levels. When designing new reproducibility studies, the physiological state of the test organism must be considered. Variability might be an interesting parameter to investigate effects of homeopathic remedies in basic research.

Optional course "Homeopathically potentised substances: placebos or effective?" for medical students at the University of Bern, Switzerland

Background Apart from compulsory lectures on classical homeopathy (CH), traditional Chinese medicine/acupuncture, neural therapy and anthroposophically extended medicine (AEM), our institute at the University of Bern offers several optional practical courses for medical students. The aim of this course during autumn 2011 and spring 2012 was to discuss basic research, observational and clinical studies in the fields of CH and AEM, so that students i) learned how to read and appraise scientific publications, ii) learned how complementary medicine can be investigated with scientific methods, and iii) were able to form their own opinion about the possible specific effects and effectiveness of homeopathically potentised substances. Methods Introductory lectures on AEM, CH and study design were given to 12 second year medical students. The students appraised 12 research articles and presented the results in class, followed by discussions with experts in the fields of basic and clinical research from our institute. A company producing homeopathic remedies was visited and students could practise potentization procedures and trituration. At the end of the course, students compiled posters with arguments in favour of and against specific effects and effectiveness as well as their own conclusions. The course was evaluated using a written questionnaire with closed and open questions. Results Previous knowledge about CH and AEM was scarce among the students. It slightly increased during the course, and the course itself fostered their interest on the topic. This course was chosen by most students, because they were genuinely interested in the topic (and not because other courses they had wanted to visit were fully booked). The students especially valued the discussions, the various perspectives presented to them, and experiencing a potentization process. Conclusion Medical students were interested to learn more about homeopathically potentised substances. The contradictory study results made it difficult for them to form their own opinion. Apart from appraising articles, the students would have liked to meet and talk to patients.

Adaptive Algorithms for Personalized Diabetes Treatment

Dynamic systems, especially in real-life applications, are often determined by inter-/intra-variability, uncertainties and time-varying components. Physiological systems are probably the most representative example in which population variability, vital signal measurement noise and uncertain dynamics render their explicit representation and optimization a rather difficult task. Systems characterized by such challenges often require the use of adaptive algorithmic solutions able to perform an iterative structural and/or parametrical update process towards optimized behavior. Adaptive optimization presents the advantages of (i) individualization through learning of basic system characteristics, (ii) ability to follow time-varying dynamics and (iii) low computational cost. In this chapter, the use of online adaptive algorithms is investigated in two basic research areas related to diabetes management: (i) real-time glucose regulation and (ii) real-time prediction of hypo-/hyperglycemia. The applicability of these methods is illustrated through the design and development of an adaptive glucose control algorithm based on reinforcement learning and optimal control and an adaptive, personalized early-warning system for the recognition and alarm generation against hypo- and hyperglycemic events.

A novel universal DNA labeling and amplification system for rapid microarray-based detection of 117 antibiotic resistance genes in Gram-positive bacteria.

A rapid and simple DNA labeling system has been developed for disposable microarrays and has been validated for the detection of 117 antibiotic resistance genes abundant in Gram-positive bacteria. The DNA was fragmented and amplified using phi-29 polymerase and random primers with linkers. Labeling and further amplification were then performed by classic PCR amplification using biotinylated primers specific for the linkers. The microarray developed by Perreten et al. (Perreten, V., Vorlet-Fawer, L., Slickers, P., Ehricht, R., Kuhnert, P., Frey, J., 2005. Microarray-based detection of 90 antibiotic resistance genes of gram-positive bacteria. J.Clin.Microbiol. 43, 2291-2302.) was improved by additional oligonucleotides. A total of 244 oligonucleotides (26 to 37 nucleotide length and with similar melting temperatures) were spotted on the microarray, including genes conferring resistance to clinically important antibiotic classes like β-lactams, macrolides, aminoglycosides, glycopeptides and tetracyclines. Each antibiotic resistance gene is represented by at least 2 oligonucleotides designed from consensus sequences of gene families. The specificity of the oligonucleotides and the quality of the amplification and labeling were verified by analysis of a collection of 65 strains belonging to 24 species. Association between genotype and phenotype was verified for 6 antibiotics using 77 Staphylococcus strains belonging to different species and revealed 95% test specificity and a 93% predictive value of a positive test. The DNA labeling and amplification is independent of the species and of the target genes and could be used for different types of microarrays. This system has also the advantage to detect several genes within one bacterium at once, like in Staphylococcus aureus strain BM3318, in which up to 15 genes were detected. This new microarray-based detection system offers a large potential for applications in clinical diagnostic, basic research, food safety and surveillance programs for antimicrobial resistance.

State of the art: Reproduction and pregnancy in rheumatic diseases

Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.

Motive-oriented therapeutic relationship building for patients diagnosed with schizophrenia

Treatment options for patients with schizophrenia demand further improvement. One way to achieve this improvement is the translation of findings from basic research into new specific interventions. Beyond that, addressing the therapy relationship has the potential to enhance both pharmacological and non-pharmacological treatments. This paper introduces motive-oriented therapeutic relationship (MOTR) building for schizophrenia. MOTR enables therapists to proactively adapt to their patient’s needs and to prevent problematic behaviors. For example, a patient might consider medication as helpful in principle, but the rejection of medication might be one of his few remaining means for his acceptable motive to stay autonomous despite hospitalization. A therapist who is motiveoriented proactively offers many degrees of freedom to this patient in order to satisfy his need for autonomy and to weaken the motivational basis for not taking medication. MOTR makes use of findings from basic and psychotherapy research and is generic in this respect, but at the same time guides therapeutic action precisely and flexibly in a patient oriented way.

OsteoMacs: Key players around bone biomaterials.

Osteal macrophages (OsteoMacs) are a special subtype of macrophage residing in bony tissues. Interesting findings from basic research have pointed to their vast and substantial roles in bone biology by demonstrating their key function in bone formation and remodeling. Despite these essential findings, much less information is available concerning their response to a variety of biomaterials used for bone regeneration with the majority of investigation primarily focused on their role during the foreign body reaction. With respect to biomaterials, it is well known that cells derived from the monocyte/macrophage lineage are one of the first cell types in contact with implanted biomaterials. Here they demonstrate extremely plastic phenotypes with the ability to differentiate towards classical M1 or M2 macrophages, or subsequently fuse into osteoclasts or multinucleated giant cells (MNGCs). These MNGCs have previously been characterized as foreign body giant cells and associated with biomaterial rejection, however more recently their phenotypes have been implicated with wound healing and tissue regeneration by studies demonstrating their expression of key M2 markers around biomaterials. With such contrasting hypotheses, it becomes essential to better understand their roles to improve the development of osteo-compatible and osteo-promotive biomaterials. This review article expresses the necessity to further study OsteoMacs and MNGCs to understand their function in bone biomaterial tissue integration including dental/orthopedic implants and bone grafting materials.

[Lineage tracing of epicardial cells during development and regeneration].

Tracing the history of individual cells during embryonic morphogenesis in a structure as complex as the cardiovascular system is one of the major challenges of developmental biology. It involves determining the relationships between the various lineages of cells forming an organ at different stages, describing the topological rearrangements tissues undergo during morphogenesis, and characterizing the interactions between cells in different structures. However, despite the great expectations raised in the field of regenerative medicine, only limited progress has been made in using regenerative therapy to repair the cardiovascular system. Recent research has highlighted the role of the epicardium during cardiac regeneration, but it is still unclear whether it is important for molecular signaling or acts as a source of progenitor cells during this process. Consequently, increasing knowledge about the origin, diversification and potential of epicardial cells during development and homeostasis and under pathological conditions is of fundamental importance both for basic research and for the development of effective cellular therapies. The aims of this article were to provide a general overview of the classical techniques used for tracing cell lineages, including their potential and limitations, and to describe novel techniques for studying the origin and differentiation of the epicardium and its role in cardiac regeneration.

Zebrafish Caudal Fin Angiogenesis Assay-Advanced Quantitative Assessment Including 3-Way Correlative Microscopy.

BACKGROUND Researchers evaluating angiomodulating compounds as a part of scientific projects or pre-clinical studies are often confronted with limitations of applied animal models. The rough and insufficient early-stage compound assessment without reliable quantification of the vascular response counts, at least partially, to the low transition rate to clinics. OBJECTIVE To establish an advanced, rapid and cost-effective angiogenesis assay for the precise and sensitive assessment of angiomodulating compounds using zebrafish caudal fin regeneration. It should provide information regarding the angiogenic mechanisms involved and should include qualitative and quantitative data of drug effects in a non-biased and time-efficient way. APPROACH & RESULTS Basic vascular parameters (total regenerated area, vascular projection area, contour length, vessel area density) were extracted from in vivo fluorescence microscopy images using a stereological approach. Skeletonization of the vasculature by our custom-made software Skelios provided additional parameters including "graph energy" and "distance to farthest node". The latter gave important insights into the complexity, connectivity and maturation status of the regenerating vascular network. The employment of a reference point (vascular parameters prior amputation) is unique for the model and crucial for a proper assessment. Additionally, the assay provides exceptional possibilities for correlative microscopy by combining in vivo-imaging and morphological investigation of the area of interest. The 3-way correlative microscopy links the dynamic changes in vivo with their structural substrate at the subcellular level. CONCLUSIONS The improved zebrafish fin regeneration model with advanced quantitative analysis and optional 3-way correlative morphology is a promising in vivo angiogenesis assay, well-suitable for basic research and preclinical investigations.