Veterinary homeopathy: systematic review of medical conditions studied by randomised trials controlled by other than placebo.

BACKGROUND: No systematic review has previously been carried out on randomised controlled trials (RCTs) of veterinary homeopathy in which the control group was an intervention other than placebo (OTP). For eligible peer-reviewed RCTs, the objectives of this study were to assess the risk of bias (RoB) and to quantify the effect size of homeopathic intervention compared with an active comparator or with no treatment. METHODS: Our systematic review approach complied fully with the PRISMA 2009 Checklist. Cochrane methods were applied to assess RoB and to derive effect size using standard meta-analysis methods. Based on a thorough and systematic literature search, the following key attributes of the published research were distinguished: individualised homeopathy (n = 1 RCT)/non-individualised homeopathy (n = 19); treatment (n = 14)/prophylaxis (n = 6); active controls (n = 18)/untreated controls (n = 2). The trials were highly diverse, representing 12 different medical conditions in 6 different species. RESULTS: No trial had sufficiently low RoB to be judged as reliable evidence: 16 of the 20 RCTs had high RoB; the remaining four had uncertain RoB in several domains of assessment. For three trials with uncertain RoB and without overt vested interest, it was inconclusive whether homeopathy combined with conventional intervention was more or was less effective than conventional intervention alone for modulation of immune response in calves, or in the prophylaxis of cattle tick or of diarrhoea in piglets. CONCLUSION: Due to the poor reliability of their data, OTP-controlled trials do not currently provide useful insight into the effectiveness of homeopathy in animals.

Veterinary homeopathy: meta-analysis of randomised placebo-controlled trials.

BACKGROUND: Meta-analysis of randomised controlled trials (RCTs) of veterinary homeopathy has not previously been undertaken. For all medical conditions and species collectively, we tested the hypothesis that the outcome of homeopathic intervention (treatment and/or prophylaxis, individualised and/or non-individualised) is distinguishable from corresponding intervention using placebos. METHODS: All facets of the review, including literature search strategy, study eligibility, data extraction and assessment of risk of bias, were described in an earlier paper. A trial was judged to comprise reliable evidence if its risk of bias was low or was unclear in specific domains of assessment. Effect size was reported as odds ratio (OR). A trial was judged free of vested interest if it was not funded by a homeopathic pharmacy. Meta-analysis was conducted using the random-effects model, with hypothesis-driven sensitivity analysis based on risk of bias. RESULTS: Nine of 15 trials with extractable data displayed high risk of bias; low or unclear risk of bias was attributed to each of the remaining six trials, only two of which comprised reliable evidence without overt vested interest. For all N = 15 trials, pooled OR = 1.69 [95% confidence interval (CI), 1.12 to 2.56]; P = 0.01. For the N = 2 trials with suitably reliable evidence, pooled OR = 2.62 [95% CI, 1.13 to 6.05]; P = 0.02). CONCLUSIONS: Meta-analysis provides some very limited evidence that clinical intervention in animals using homeopathic medicines is distinguishable from corresponding intervention using placebos. The low number and quality of the trials hinders a more decisive conclusion.

Membrane-inlet mass spectrometry reveals a high driving force for oxygen production by photosystem II.

Oxygenic photosynthesis is the basis for aerobic life on earth. The catalytic Mn(4)O(x)CaY(Z) center of photosystem II (PSII), after fourfold oxidation, extracts four electrons from two water molecules to yield dioxygen. This reaction cascade has appeared as a single four-electron transfer that occurs in typically 1 ms. Inevitable redox intermediates have so far escaped detection, probably because of very short lifetime. Previous attempts to stabilize intermediates by high O(2)-back pressure have revealed controversial results. Here we monitored by membrane-inlet mass spectrometry (MIMS) the production of from (18)O-labeled water against a high background of in a suspension of PSII-core complexes. We found neither an inhibition nor an altered pattern of O(2) production by up to 50-fold increased concentration of dissolved O(2). Lack of inhibition is in line with results from previous X-ray absorption and visible-fluorescence experiments, but contradictory to the interpretation of previous UV-absorption data. Because we used essentially identical experimental conditions in MIMS as had been used in the UV work, the contradiction was serious, and we found it was not to be resolved by assuming a significant slowdown of the O(2) release kinetics or a subsequent slow conformational relaxation. This calls for reevaluation of the less direct UV experiments. The direct detection of O(2) release by MIMS shows unequivocally that O(2) release in PSII is highly exothermic. Under the likely assumption that one H(+) is released in the S(4) â†’ S(0) transition, the driving force at pH 6.5 and atmospheric O(2) pressure is at least 220 meV, otherwise 160 meV.

Geographical and temporal distribution of basic research experiments in homeopathy.

The database HomBRex (Homeopathy Basic Research experiments) was established in 2002 to provide an overview of the basic research already done on homeopathy (http://www.carstens-stiftung.de/hombrex). By this means, it facilitates the exploration of the Similia Principle and the working mechanism of homeopathy. Since 2002, the total number of experiments listed has almost doubled. The current review reports the history of basic research in homeopathy as evidenced by publication dates and origin of publications. In July 2013, the database held 1868 entries. Most publications were reported from France (n = 267), followed by Germany (n = 246) and India (n = 237). In the last ten years, the number of publications from Brazil dramatically increased from n = 13 (before 2004) to n = 164 (compared to n = 251 published in France before 2004, and n = 16 between 2004 and 2013). The oldest database entry was from Germany (1832).

CORE-Hom: a powerful and exhaustive database of clinical trials in homeopathy.

The CORE-Hom database was created to answer the need for a reliable and publicly available source of information in the field of clinical research in homeopathy. As of May 2014 it held 1048 entries of clinical trials, observational studies and surveys in the field of homeopathy, including second publications and re-analyses. 352 of the trials referenced in the database were published in peer reviewed journals, 198 of which were randomised controlled trials. The most often used remedies were Arnica montana (n = 103) and Traumeel(®) (n = 40). The most studied medical conditions were respiratory tract infections (n = 126) and traumatic injuries (n = 110). The aim of this article is to introduce the database to the public, describing and explaining the interface, features and content of the CORE-Hom database.

Randomised controlled trials of homeopathy in humans: characterising the research journal literature for systematic review.

INTRODUCTION: A new programme of systematic reviews of randomised controlled trials (RCTs) in homeopathy will distinguish important attributes of RCT records, including: placebo controlled versus other-than-placebo (OTP) controlled; individualised versus non-individualised homeopathy; peer-reviewed (PR) versus non peer-reviewed (NPR) sources. AIMS: (a) To outline the methods used to search and categorise the RCT literature; (b) to report details of the records retrieved; (c) to compare our retrieved records with those reported in two previous systematic reviews (Linde et al., 1997; Shang et al., 2005). METHODS: Ten major electronic databases were searched for records published up to the end of 2011. A record was accepted for subsequent systematic review if it was a substantive report of a clinical trial of homeopathic treatment or prophylaxis in humans, randomised and controlled, and published in a PR or NPR journal. RESULTS: 489 records were potentially eligible: 226 were rejected as non-journal, minor or repeat publications, or lacking randomisation and/or controls and/or a 'homeopathic' intervention; 263 (164 PR, 99 NPR) were acceptable for systematic review. The 263 accepted records comprised 217 (137 PR, 80 NPR) placebo-controlled RCTs, of which 121 were included by, 66 were published after, and 30 were potentially eligible for, but not listed by, Linde or Shang. The 137 PR records of placebo-controlled RCTs comprise 41 on individualised homeopathy and 96 on non-individualised homeopathy. CONCLUSION: Our findings clarify the RCT literature in homeopathy. The 263 accepted journal papers will be the basis for our forthcoming programme of systematic reviews.

The effect of aquatic exercise on bone mineral density in older adults. A systematic review and meta-analysis.

Introduction: Aquatic or water-based exercise is a very popular type of exercise in particular for people with physical limitations, joint problems and fear of falling. The present systematic review and meta-analysis aimed to provide evidence for the effect of aquatic exercise on Bone Mineral Density (BMD) in adults. Methods: A systematic literature search of five electronic databases (PubMed/MEDLINE, Cochrane Library, Scopus, Web of Science and CINAHL) according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was conducted until 2022/01/30, with an update to 2022/10/07. We included controlled trials with a duration of more than 6 months and at least two study groups, aquatic exercise (EG) versus non-training controls (CG) with no language restrictions. Outcome measures were standardized mean differences (SMD) with 95%-confidence intervals (95%-CI) for BMD changes at the lumbar spine (LS) and femoral neck (FN). We applied a random-effects meta-analysis and used the inverse heterogeneity (IVhet) model to analyze the data. Results: Excluding an outlier study with an exceptionally high effect size for LS-BMD, we observed a statistically significant (p = .002) effect (EG vs. CG) of aquatic exercise for the LS-BMD (n = 10; SMD: 0.30; 95%-CI: 0.11-0.49). In parallel, the effect of aquatic exercise on FN-BMD was statistically significant (p = .034) compared to the CG (n = 10; SMD: 0.76, 95%-CI: 0.06-1.46). Of importance, heterogeneity between the trial results was negligible for LS (I2: 7%) but substantial for FN-BMD (I2: 87%). Evidence for risks of small study/publication bias was low for LS-BMD and considerable for FN-BMD. Discussion: In summary, the present systematic review and meta-analysis provides further evidence for the favorable effect of exercise on bone health in adults. Due to its safety and attractiveness, we particularly recommend water-based exercise for people unable, afraid or unmotivated to conduct intense land-based exercise programs.

Randomised controlled trials of veterinary homeopathy: characterising the peer-reviewed research literature for systematic review.

INTRODUCTION: Systematic review of the research evidence in veterinary homeopathy has never previously been carried out. This paper presents the search methods, together with categorised lists of retrieved records, that enable us to identify the literature that is acceptable for future systematic review of randomised controlled trials (RCTs) in veterinary homeopathy. METHODS: All randomised and controlled trials of homeopathic intervention (prophylaxis and/or treatment of disease, in any species except man) were appraised according to pre-specified criteria. The following databases were systematically searched from their inception up to and including March 2011: AMED; Carstens-Stiftung Homeopathic Veterinary Clinical Research (HomVetCR) database; CINAHL; Cochrane Central Register of Controlled Trials; Embase; Hom-Inform; LILACS; PubMed; Science Citation Index; Scopus. RESULTS: One hundred and fifty records were retrieved; 38 satisfied the acceptance criteria (substantive report of a clinical treatment or prophylaxis trial in veterinary homeopathic medicine randomised and controlled and published in a peer-reviewed journal), and were thus eligible for future planned systematic review. Approximately half of the rejected records were theses. Seven species and 27 different species-specific medical conditions were represented in the 38 papers. Similar numbers of papers reported trials of treatment and prophylaxis (n=21 and n=17 respectively) and were controlled against placebo or other than placebo (n=18, n=20 respectively). Most research focused on non-individualised homeopathy (n=35 papers) compared with individualised homeopathy (n=3). CONCLUSION: The results provide a complete and clarified view of the RCT literature in veterinary homeopathy. We will systematically review the 38 substantive peer-reviewed journal articles under the main headings: treatment trials; prophylaxis trials.

Exercise Reduces the Number of Overall and Major Osteoporotic Fractures in Adults. Does Supervision Make a Difference? Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis (PROSPERO ID: CRD42021250467) was to evaluate the effects of exercise on low-trauma overall and major osteoporotic fractures (hip, spine, forearm, or humerus fractures) and to determine the corresponding effect of supervision of the exercise program. Our systematic search of six literature databases according to the PRISMA guideline was conducted from January 1, 2013 (ie, date of our last search) to May 22, 2021, and included controlled clinical exercise trials with (i) individuals aged ≥45 years, (ii) cohorts without therapies/diseases related to fractures, (iii) observation periods of ≥3 months, and (iv) the number of low-trauma fractures listed separately for the exercise (EG) and control (CG) groups. We included 20 intervention studies with 21 EGs and 20 CGs comprising a pooled number of participant-years of n = 11.836 in the EG and n = 11.275 in the CG. The mixed-effects conditional Poisson regression revealed significant effects of exercise on low-trauma overall incidence (rate) ratio (IR 0.67, 95% confidence interval [95% CI] 0.51-0.87) and major osteoporotic fractures IR (0.69, 95% CI 0.52-0.92). Heterogeneity between the trials was moderate for low-trauma overall (I2 = 40%) and negligible (I2 < 1%) for major osteoporotic fractures. Supervision of the exercise program plays a significant role in the reductions of overall and major osteoporotic fractures with IR about twice as favorable in the predominately supervised (IR 0.44; 95% CI 0.27-0.73 and 0.38; 0.19-0.76) versus the predominately non-supervised exercise trials (IR 0.83; 95% CI 0.60-1.14 and 0.82; 0.64-1.05). In summary, the present study provides evidence for the positive effect of exercise on low-trauma overall and major osteoporotic fractures in middle aged to older adults. Supervision of the exercise program is a crucial aspect in exercise programs on fracture reduction. Thus, home-based exercise protocols should increasingly implement online classes to ensure widely consistent supervision and monitoring of the exercise program. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Review of the use of high potencies in basic research on homeopathy.

The HomBRex database includes details of about 1500 basic research experiments in homeopathy. A general overview on the experiments listed in the HomBRex database is presented, focusing on high dilutions and the different settings in which those were used. Though often criticised, many experiments with remedies diluted beyond Avogadro's number demonstrate specific effects. A total of 830 experiments employing high potencies was found; in 745 experiments of these (90%), at least one positive result was reported. Animals represent the most often used model system (n=371), followed by plants (n=201), human material (n=92), bacteria and viruses (n=37) and fungi (n=32). Arsenicum album (Ars.) is the substance most often applied (n=101), followed by Sulphur (Sulph.) and Thuja (Thuj.) (n=65 and 48, respectively). Proving, prophylactic and therapeutic study designs have all been used and appear appropriate for homeopathy basic research using high dilutions. The basic research data set to support specific effects unique to high dilutions and opposite to those observed with low dilutions is, to date, insufficient.

Database on veterinary clinical research in homeopathy.

OBJECTIVE: The aim of the present report is to provide an overview of the first database on clinical research in veterinary homeopathy. PROCEDURES: Detailed searches in the database 'Veterinary Clinical Research-Database in Homeopathy' (http://www.carstens-stiftung.de/clinresvet/index.php). RESULTS: The database contains about 200 entries of randomised clinical trials, non-randomised clinical trials, observational studies, drug provings, case reports and case series. Twenty-two clinical fields are covered and eight different groups of species are included. The database is free of charge and open to all interested veterinarians and researchers. CONCLUSION: The database enables researchers and veterinarians, sceptics and supporters to get a quick overview of the status of veterinary clinical research in homeopathy and alleviates the preparation of systematical reviews or may stimulate reproductions or even new studies.

Infection models in basic research on homeopathy.

INTRODUCTION: The objective of this study was to search for effective agents for the treatment of infections in animals or infected cell lines. METHODS: The Homeopathic Basic Research experiments (HomBRex) database (http://www.carstens-stiftung.de/hombrex) on model biological systems in homeopathic research was searched. Eligible experiments were reviewed and analysed. RESULTS: The database contains 48 eligible experiments published from 1832 to 2009. Causative pathogens were bacteria, fungi, viruses, proto- and metazoa. In the experiments, various parameters were observed and a large set of medicines was investigated. In eight of the 48 experiments, at least one of the investigated medicines was selected according to the similia principle. Nosodes and homeopathic complexes were investigated in 8 and 14 experiments respectively. Mice were the most often used host organisms (13 experiments). In 31 experiments at least one homeopathic medicine was found effective for treatment. CONCLUSION: The results of basic research experiments may invigorate new clinical trials that investigate complementary treatments for infectious diseases. However, all experiments reviewed here await replication and no clear-cut conclusion can be drawn regarding the transferability of in vitro results to in vivo outcomes.

[Participatory research in the German Rheumatism League. Content implementation and practical realisation of participatory research in a patient organisation]. / Partizipative Forschung in der Deutschen Rheuma-Liga ­ Inhaltliche und praktische Umsetzung der partizipativen Forschung in einer Patientenorganisation.

The German Rheumatism League ("Deutsche Rheuma-Liga") is the largest patient organisation in Germany, with about 300,000 members. In the sense of participatory research, the Deutsche Rheuma-Liga involves trained patient representatives in research projects funded by either the Deutsche Rheuma-Liga or other organisations. In order to invigorate the principle of participatory research in the field of rheumatology in Germany various measures have been undertaken: the principle of participatory research has been implemented as obligatory in the funding guidelines of the German Rheumatism League. A training course for German-speaking patients was created, and reference cards and an explanatory brochure were provided. In a letter campaign, about 70 universities and hospitals with rheumatology departments were contacted and informed about the benefits of participatory research. Since 2014, three training courses with 21 participants have been conducted. The trained patient representatives have participated in more than 30 projects up to the end of 2019. The overall experience of the patient representatives actively involved in research projects was mainly positive, and participatory research was perceived as being interesting and enriching. The implementation of participatory research in the German Rheumatism League can be described as successful. The article describes the measures taken to implement the principle of participatory research into the structures of the German Rheumatism League and summarises the experiences of patients and the patient organisation during five years of active participation in research projects.

Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis.

BACKGROUND: A rigorous systematic review and meta-analysis focused on randomised controlled trials (RCTs) of non-individualised homeopathic treatment has not previously been reported. We tested the null hypothesis that the main outcome of treatment using a non-individualised (standardised) homeopathic medicine is indistinguishable from that of placebo. An additional aim was to quantify any condition-specific effects of non-individualised homeopathic treatment. METHODS: Literature search strategy, data extraction and statistical analysis all followed the methods described in a pre-published protocol. A trial comprised 'reliable evidence' if its risk of bias was low or it was unclear in one specified domain of assessment. 'Effect size' was reported as standardised mean difference (SMD), with arithmetic transformation for dichotomous data carried out as required; a negative SMD indicated an effect favouring homeopathy. RESULTS: Forty-eight different clinical conditions were represented in 75 eligible RCTs. Forty-nine trials were classed as 'high risk of bias' and 23 as 'uncertain risk of bias'; the remaining three, clinically heterogeneous, trials displayed sufficiently low risk of bias to be designated reliable evidence. Fifty-four trials had extractable data: pooled SMD was -0.33 (95% confidence interval (CI) -0.44, -0.21), which was attenuated to -0.16 (95% CI -0.31, -0.02) after adjustment for publication bias. The three trials with reliable evidence yielded a non-significant pooled SMD: -0.18 (95% CI -0.46, 0.09). There was no single clinical condition for which meta-analysis included reliable evidence. CONCLUSIONS: The quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions. Better designed and more rigorous RCTs are needed in order to develop an evidence base that can decisively provide reliable effect estimates of non-individualised homeopathic treatment.

Model validity and risk of bias in randomised placebo-controlled trials of individualised homeopathic treatment.

BACKGROUND: To date, our programme of systematic reviews has assessed randomised controlled trials (RCTs) of individualised homeopathy separately for risk of bias (RoB) and for model validity of homeopathic treatment (MVHT). OBJECTIVES: The purpose of the present paper was to bring together our published RoB and MVHT findings and, using an approach based on GRADE methods, to merge the quality appraisals of these same RCTs, examining the impact on meta-analysis results. DESIGN: Systematic review with meta-analysis. METHODS: As previously, 31 papers (reporting a total of 32 RCTs) were eligible for systematic review and were the subject of study. MAIN OUTCOME MEASURES: For each trial, the separate ratings for RoB and MVHT were merged to obtain a single overall quality designation ('high', 'moderate, "low", 'very low'), based on the GRADE principle of 'downgrading'. RESULTS: Merging the assessment of MVHT and RoB identified three trials of 'high quality', eight of 'moderate quality', 18 of 'low quality' and three of 'very low quality'. There was no association between a trial's MVHT and its RoB or its direction of treatment effect (P>0.05). The three 'high quality' trials were those already labelled 'reliable evidence' based on RoB, and so no change was found in meta-analysis based on best-quality evidence: a small, statistically significant, effect favouring homeopathy. CONCLUSION: Accommodating MVHT in overall quality designation of RCTs has not modified our pre-existing conclusion that the medicines prescribed in individualised homeopathy may have small, specific, treatment effects.

Time-resolved oxygen production by PSII: chasing chemical intermediates.

Photosystem II (PSII) produces dioxygen from water in a four-stepped process, which is driven by four quanta of light and catalysed by a Mn-cluster and tyrosine Z. Oxygen is liberated during one step, coined S(3)=>S(0). Chemical intermediates on the way from reversibly bound water to dioxygen have not yet been tracked, however, a break in the Arrhenius plot of the oxygen-evolving step has been taken as evidence for its existence. We scrutinised the temperature dependence of (i) UV-absorption transients attributable to the reduction of the Mn-cluster and tyrosine Z by water, and (ii) polarographic transients attributable to the release of dioxygen. Using a centrifugatable and kinetically competent Pt-electrode, we observed no deviation from a linear Arrhenius plot of oxygen release in the temperature range from -2 to 32 degrees C, and hence no evidence, by this approach, for a sufficiently long-lived chemical intermediate. The half-rise times of oxygen release differed between Synechocystis WT* (at 20 degrees C: 1.35 ms) and a point mutant (D1-D61N: 13.1 ms), and the activation energies differed between species (Spinacia oleracea, 30 kJ/mol versus Synechocystis, 41 kJ/mol) and preparations (PSII membranes, 41 kJ/mol versus core complexes, 33 kJ/mol, Synechocystis). Correction for polarographic artefacts revealed, for the first time, a temperature-dependent lag-phase of the polarographic transient (duration at 20 degrees C: 0.45 ms, activation energy: 31 kJ/mol), which was indicative of a short-lived intermediate. It was, however, not apparent in the UV-transients. Thus the "intermediate" was probably newly formed and transiently bound oxygen.

Veterinary homeopathy: systematic review of medical conditions studied by randomised placebo-controlled trials.

A systematic review of randomised controlled trials (RCTs) of veterinary homeopathy has not previously been undertaken. Using Cochrane methods, this review aims to assess risk of bias and to quantify the effect size of homeopathic intervention compared with placebo for each eligible peer-reviewed trial. Judgement in seven assessment domains enabled a trial's risk of bias to be designated as low, unclear or high. A trial was judged to comprise reliable evidence if its risk of bias was low or was unclear in specified domains. A trial was considered to be free of vested interest if it was not funded by a homeopathic pharmacy. The 18 eligible RCTs were disparate in nature, representing four species and 11 different medical conditions. Reliable evidence, free from vested interest, was identified in two trials: homeopathic Coli had a prophylactic effect on porcine diarrhoea (odds ratio 3.89, 95 per cent confidence interval [CI], 1.19 to 12.68, P=0.02); and individualised homeopathic treatment did not have a more beneficial effect on bovine mastitis than placebo intervention (standardised mean difference -0.31, 95 per cent CI, -0.97 to 0.34, P=0.35). Mixed findings from the only two placebo-controlled RCTs that had suitably reliable evidence precluded generalisable conclusions about the efficacy of any particular homeopathic medicine or the impact of individualised homeopathic intervention on any given medical condition in animals.

Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis.

BACKGROUND: A rigorous and focused systematic review and meta-analysis of randomised controlled trials (RCTs) of individualised homeopathic treatment has not previously been undertaken. We tested the hypothesis that the outcome of an individualised homeopathic treatment approach using homeopathic medicines is distinguishable from that of placebos. METHODS: The review's methods, including literature search strategy, data extraction, assessment of risk of bias and statistical analysis, were strictly protocol-based. Judgment in seven assessment domains enabled a trial's risk of bias to be designated as low, unclear or high. A trial was judged to comprise 'reliable evidence' if its risk of bias was low or was unclear in one specified domain. 'Effect size' was reported as odds ratio (OR), with arithmetic transformation for continuous data carried out as required; OR > 1 signified an effect favouring homeopathy. RESULTS: Thirty-two eligible RCTs studied 24 different medical conditions in total. Twelve trials were classed 'uncertain risk of bias', three of which displayed relatively minor uncertainty and were designated reliable evidence; 20 trials were classed 'high risk of bias'. Twenty-two trials had extractable data and were subjected to meta-analysis; OR = 1.53 (95% confidence interval (CI) 1.22 to 1.91). For the three trials with reliable evidence, sensitivity analysis revealed OR = 1.98 (95% CI 1.16 to 3.38). CONCLUSIONS: Medicines prescribed in individualised homeopathy may have small, specific treatment effects. Findings are consistent with sub-group data available in a previous 'global' systematic review. The low or unclear overall quality of the evidence prompts caution in interpreting the findings. New high-quality RCT research is necessary to enable more decisive interpretation.

Photosynthetic water oxidation at high O2 backpressure monitored by delayed chlorophyll fluorescence.

The atmospheric dioxygen is produced by photosynthetic organisms. This light-driven process culminates in what appears as one step: a four-electron abstraction from two water molecules bound to the Mn4Ca complex of photosystem II. Recently, an intermediate of the O2-producing reaction sequence was stabilized by elevated oxygen backpressure and detected by UV flash photometry [Clausen, J., and Junge, W. (2004) Nature 430, 480]. We scrutinized its properties by delayed chlorophyll fluorescence measurements. Half-suppression of oxygen evolution was observed at a similar O2 pressure of 2.3 bar, as previously, now with photosystem II membrane particles from spinach, without artificial electron acceptors, and at a high signal-to-noise ratio. The data are tentatively interpreted as the stabilization of a 2-fold oxidized state of the catalytic center (S2*) with bound peroxide and its slow conversion into the normal S2 state by the release of peroxide.

CaiT of Escherichia coli, a new transporter catalyzing L-carnitine/gamma -butyrobetaine exchange.

l-Carnitine is essential for beta-oxidation of fatty acids in mitochondria. Bacterial metabolic pathways are used for the production of this medically important compound. Here, we report the first detailed functional characterization of the caiT gene product, a putative transport protein whose function is required for l-carnitine conversion in Escherichia coli. The caiT gene was overexpressed in E. coli, and the gene product was purified by affinity chromatography and reconstituted into proteoliposomes. Functional analyses with intact cells and proteoliposomes demonstrated that CaiT is able to catalyze the exchange of l-carnitine for gamma-butyrobetaine, the excreted end product of l-carnitine conversion in E. coli, and related betaines. Electrochemical ion gradients did not significantly stimulate l-carnitine uptake. Analysis of l-carnitine counterflow yielded an apparent external K(m) of 105 microm and a turnover number of 5.5 s(-1). Contrary to related proteins, CaiT activity was not modulated by osmotic stress. l-Carnitine binding to CaiT increased the protein fluorescence and caused a red shift in the emission maximum, an observation explained by ligand-induced conformational alterations. The fluorescence effect was specific for betaine structures, for which the distance between trimethylammonium and carboxyl groups proved to be crucial for affinity. Taken together, the results suggest that CaiT functions as an exchanger (antiporter) for l-carnitine and gamma-butyrobetaine according to the substrate/product antiport principle.