Syzygium cumini (L.) skeels mitigate diabetic nephropathy by regulating Nrf2 pathway and mitocyhondrial dysfunction: In vitro and in vivo studies.

ETHNOPHARMACOLOGICAL PREVALENCE: Hyperglycemia in diabetes increases the generation of advanced glycation end products (AGEs) through non-enzymatic reactions. The interaction between AGEs and their receptors (RAGE) leads to oxidative and inflammatory stress, which plays a pivotal role in developing diabetic nephropathy. Syzygium cumini (SC) L. (DC.) homeopathic preparations viz. 200C, 30C, and mother tincture [MT] are used to treat diabetes. This study aimed to elucidate the regulatory effects of SC preparations (200C, 30C, and MT) on the nuclear factor erythroid 2-related factor 2 (Nrf2) - nuclear factor-κB (NF-κB) pathways and mitochondrial dysfunction in mitigating diabetic nephropathy (DN). MATERIALS AND METHODS: Streptozotocin-induced diabetic rats were treated with SC preparations (200C, 30C, MT; 1:20 dilution in distilled water; 600 µL/kg body weight) and metformin (45 mg/kg body weight) twice daily for 40 days. DN was evaluated through biochemical parameters and histological examination. Renal tissue lysates were analyzed for glycation markers. Protein and gene levels of Nrf2, NF-κB, and mitochondrial dysfunctional signaling were determined via western blotting and RT-qPCR. An immunohistochemical analysis of the kidneys was performed. In vitro, human serum albumin (HSA - 10 mg/ml) was glycated with methylglyoxal (MGO - 55 mM) in the presence of SC preparations (200C, 30C, MT) for eight days. Glycated samples (400 µg/mL) were incubated with renal cells (HEK-293) for 24 h. Further reactive oxygen species production, Nrf2 nuclear translocation, and protein or gene expression of Nrf2 and apoptosis markers were analyzed by western blotting, RT-qPCR, and flow cytometry. Molecular docking of gallic and ellagic acid with the HSA-MGO complex was performed. RESULT: In vivo experiments using streptozotocin-induced diabetic rats treated with SC preparations exhibited improved biochemical parameters, preserved kidney function, and reduced glycation adduct formation in a dose-dependent manner. Furthermore, SC preparations downregulated inflammatory mediators such as RAGE, NF-κB, vascular endothelial growth factor (VEGF), and Tumor necrosis factor α (TNF-α) while upregulating the Nrf2-dependent antioxidant and detoxification pathways. They downregulated B-cell lymphoma 2 (Bcl-2) associated X-protein (BAX), C/EBP homologous protein (CHOP), Dynamin-related protein 1 (DRP1), and upregulated BCL 2 gene expression. Notably, SC preparations facilitated nuclear translocation of Nrf2, leading to the upregulation of antioxidant enzymes and the downregulation of oxidative stress markers. Molecular docking studies revealed favorable interactions between gallic (-5.26 kcal/mol) and ellagic acid (-4.71 kcal/mol) with the HSA-MGO complex. CONCLUSION: SC preparations mitigate renal cell apoptosis and mitochondrial dysfunction through Nrf2-dependent mechanisms.

From the Gorgon's blood to Behring's Blutserumtherapie: A long path towards serum therapy.

At the end of the 19th century medicine was turned upside down by the development of serum therapy, a great therapeutic revolution as was vaccination a few years earlier. Many serums were developed, the most famous being the German doctor Emil von Behring's diphtheria serum, which saved countless children's lives from this dreadful disease. The discovery of the serum therapy principle, allowed by the progressive understanding of humoral immunity, occurred both in Germany and France, almost at the same time. Interestingly, this principle arose from two different intellectual paths, reviving the age-old opposition between mechanism and vitalism: while Behring came to this discovery reasoning as a chemist, French researchers Charles Richet and Jules Héricourt behaved as physiologists, focusing on the role of the host in the host-pathogen interaction. However, we should maybe consider that serum therapy history begins much earlier. Great forerunners must not be forgotten, especially researchers who investigated the field of immunity as soon as in the very beginning of the microbiological revolution; but also many people throughout centuries who tried to cure diseases with blood: as a transfer of blood serum, serum therapy also lies in the tradition of blood transfusion.

Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomised trials: a systematic review and network meta-analysis.

OBJECTIVE: To quantify the effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis through a systematic review and Bayesian random-effects network meta-analysis. DESIGN: We searched CENTRAL and regulatory agency websites (inception-2023) for large, English-language, randomised controlled trials (RCTs) (≥100 patients/group) examining any intra-articular intervention. PRIMARY OUTCOME: pain intensity. SECONDARY OUTCOMES: physical function and safety outcomes. Pain and function outcomes were analyzed at 2,6,12,24, and 52 weeks post-randomization, and presented as standardized mean differences (SMDs) (95% credible intervals, 95%CrI). The prespecified minimal clinically important between-group difference (MID) was -0.37 SMD. Safety outcomes were presented as odds ratios (OR) (95%CrI). FINDINGS: Among 57 RCTs (22,795 participants) examining 18 intra-articular interventions, usual care or placebo, treatment effects were larger in high-risk-of-bias trials (n=35) than low/unclear-risk-of-bias trials (n=22). In the main analysis (excluding high-risk-of-bias trials), triamcinolone had the highest probabilities of reaching the MID at weeks 2-6 (75.3% and 90%, respectively) with corresponding SMDs of -0.48 (95%CrI,-0.85 to -0.10) and -0.53 (95%CrI,-0.79 to -0.27) compared to placebo. Tr14/Ze14 homeopathic product showed therapeutic potential at week 6 compared to placebo (SMD:-0.42, 95%CrI,-0.71 to -0.11, 63.5% probability of reaching the MID). Hyaluronic acid had higher risk of dropouts due to adverse events (OR:2.01, 95%CrI,1.08 to 3.77) and serious adverse events (OR:1.86, 95%CrI,1.16 to 3.03) than placebo. CONCLUSION: Triamcinolone had the highest probabilities to have a treatment effect beyond the MID at weeks 2-6. Large RCTs with lower risk of bias do not support the notion that 16 other intra-articular interventions assessed improve pain or function beyond placebo effects in knee or hip OA. Lack of evidence of long-term effectiveness underscores the need for further research beyond 24-52 weeks.

Environmentally Sustainable Detection of Arsenic using Convolutional Neural Networks and Imidazole-Based Organic Probes: Application in Food Samples and Arsenic Album.

Arsenic contamination poses a significant health risk, particularly when it infiltrates water supplies. While current detection methods offer precise analysis, they often involve complex instrumentation not suitable for field use. This study presents a novel approach by developing two probes, A1 and A2, based on 4-diethylaminosalicyladehyde, 2-hydroxy-1-naphthaldehyde, and 1,2-diaminoanthraquinone. These probes are highly sensitive and selective for detecting arsenite (As(III)) and arsenate (As(V)) in water, food samples, and homeopathic medicine with limits of detection in the nanomolar range. To elaborate our contribution to on-site arsenic detection, we introduce a convolutional neural network-based image recognition system. This system interprets images of the probes' colorimetric response, effectively categorizing different ranges of arsenic concentrations in parts per million (ppm). Our approach offers a real-time, cost-effective, and user-friendly solution for arsenic detection, extending its applicability from scientific laboratories to in-field conditions and even household monitoring. The findings fill critical research gaps in real-time detection methods, potentially revolutionizing the way we monitor environmental contaminants like arsenic.

Low Concentrations of Wyethia Helenioides-derived Flavonoids as Anti-Inflammatory Against Allergic Rhinitis.

Context: Allergic rhinitis (AR) is a common immune disease of the nasal mucosa, and anti-allergenic medications provide only momentary relief. Multiple factors, such as rising pollution, especially in urban areas; dust particles, such as from air conditioners; house mites; and the use of chemicals and aromatic products can stimulate AR. Objective: The literature review intended to examine the effectiveness of homoeopathic remedies in immune- and inflammatory-model systems based on the basic homoeopathic principle-the law of similarity of pharmacological action at the cellular level-and to evaluate the effects of dilution or dynamization on the drug activity of Wyethia tested under controlled settings, interpreting data based on similarity. Design: The research team performeda narrative review by searching Google scholar & Pubmed databases. The search usedthe keywords "Wyethia Helenioides", "Allergic Rhinitis", "Homoeopathy", "Homeopathy", "Anti-inflammatory", "Invitro", "Invivo", "Clinical Trial", "Case report" & "Flavanoids". Setting: The study took place at Department of Homoeopathic Materia Medica, Dr. D Y Patil Homoeopathic Medical College and Research Institute, Pimpri, Pune, Maharashtra, India. Results: Clinical observations indicated that the homoeopathic preparations of Wyethia in low concentrations, even beyond Avogadro's number, may have antimicrobial, antioxidant, and anti-inflammatory properties. The hormesis concept-a biphasic dose response with a low-dose stimulation or beneficial effect and a high dose inhibitory or toxic effect-may explain the effects against human mast cells(HMC-1s). Conclusions: Clinical observations indicate that the homoeopathic preparations of Wyethia in low concentrations, even beyond Avogadro's number, might show anti-inflammatory properties that the hormesis concept against HMC-1 can explain. The current research team thus anticipates that the analysis of this little-known material will provide a novel and insightful look at the state-of-the-art of homoeopathy without drawing any firm judgments for or against this treatment. Although it could be challenging to accept, it's currently the most receptive stance.

Solvatochromic Dyes Track a Homeopathic Preparation through Water-Stream Systems in a Program to Control Tick Infestation at a Wild Animal Rehabilitation Center in Brazil.

INTRODUCTION: In 2021, the area of CRAS (Centro de Reabilitação de Animais Selvagens - Wild Animal Rehabilitation Center), located in a state park in Campo Grande City, Mato Grosso do Sul, Brazil, was suffering from a tick infestation affecting wild animals that inhabit the area and humans that visited its trails. Following a formal technical-scientific cooperation agreement between IMASUL, an institute for the environment in Mato Grosso do Sul state, and SIGO Homeopatia, a formulated homeopathic complex (Formula Parques Urbanos, FPU) was designed and prepared specifically to treat the animals. This environmental intervention used specially designed slow-release water biodegradable devices. Tracking the FPU signal in water was necessary to monitor and manage the intervention. AIMS: Our aims were (1) to evaluate, among six previously standardized solvatochromic dyes, which would serve as a marker for the homeopathic complex under study; and (2) to evaluate whether the chosen solvatochromic dye could map the propagation of the homeopathic complex activity throughout the stream system from water samples harvested at different locations over time. METHOD: Water samples were harvested from each point at different times, filtered, frozen, and sent to the laboratory, where they were prepared at 1cH potency for analysis using 30% ethanol as the vehicle. Solvatochromic dyes were used to analyze the samples since they alter their absorbance when in contact with homeopathic potencies. Of the six dyes tested, Coumarin 7 was found to be the most suitable for tracking the FPU complex. A static and average unidirectional magnetic field of 2,400 Gauss (240 mT), generated by a neodymium magnet, was applied to the samples immediately before reading. RESULTS: There were significant differences in the delta absorbance of dyes when adding treated/potentized water samples, making it possible to map the propagation of the FPU signal throughout the park over time. The signals were identifiable at the same point 1 minute and 32 days after the insertion of the device into the water. These signals were also identifiable after 75 minutes and 8 days at a point far from the insertion place. CONCLUSION: Coumarin 7 was the best marker for the homeopathic complex (FPU) used to treat the wild animals living in the park. The microplates/enzyme-linked immunosorbent assay reader method and the application of a magnetic field to samples were shown to be effective in tracing homeopathic signals by changes in dye absorbance (p ≤ 0.02) in a real-life situation, with large volumes of water, involving many environmental variables, and over large distances.

Pharmacoeconomic evaluation of treatments for Poly Cystic Ovarian Syndrome (PCOS).

BACKGROUND: Treatment cost and high prevalence of Poly Cystic Ovarian Syndrome (PCOS) is a very challenging issue globally. Due to this reason; current study was conducted to determine pharmaco-economy of conventional and non-conventional treatments for the management of PCOS. METHODS: Prospective Cross-Sectional study was conducted in the metropolitan city of Karachi from January - December 2019. Primary data of 200 PCOS patients were collected from different hospitals and clinics. An instrument was used to collect data pertaining to the direct and indirect cost associated with the disease management. Collected data was analyzed by the tools for cost analysis and software called Statistical Package of Social Sciences (SPSS) - 22. RESULTS: In Cost Minimization Analysis (CMA); Allopathic treatment [Mean cost/month: PKR:4479.32 ± 350.95 (USD:27.46 ± 2.15)], Herbal treatment [Mean cost/month: PKR:1527.78 ± 78.15 (USD:9.37 ± 0.48)], Combination treatment [Mean cost/month: PKR:2803.09 ± 654.22 (USD:17.18 ± 4.01)], and Homoeopathic treatment [Mean cost/month: PKR:976.95 ± 46.19 (USD:5.99 ± 0.28)]. Incremental cost/month for Allopathic treatment is 358%, Herbal treatment is 56%, Combination treatment is 187%. In Cost Effectiveness Analysis (CEA); Allopathic treatment (Incremental cost-effectiveness ratio/month: 1334.24), Herbal treatment (Incremental cost-effectiveness ratio/month: 936.41), Combination treatment (Incremental cost-effectiveness ratio/month: 1017.09). Due to lowest cost of Homeopathic treatment, cost of Homeopathic treatment was considered as a threshold value. In-direct cost/month of Allopathic treatment is PKR:593.33 ± 24.00 (USD:3.64 ± 0.15), Herbal treatment is PKR:307.84 ± 26.69 (USD:1.89 ± 0.16), Combination treatment is PKR:409.09 ± 45.63 (USD:2.51 ± 0.28) and Homoeopathic treatment is PKR:300.00 ± 26.39 (USD:1.84 ± 0.16). CONCLUSION: The most cost-effective is treatment is Homeopathic; Herbal treatment is second most cost-effective option for the treatment of PCOS. Lowest direct and indirect costs and short treatment duration collaboratively lessen the %incremental cost per year and incremental cost effectiveness ratio per year.

Update on the pathogenesis of atopic dermatitis.

Atopic dermatitis is a chronic, recurrent, and multifactorial skin-mucosal manifestation resulting from the interaction between elements mainly associated with the skin barrier deficit, the homeostasis of the immune response, neurological aspects, and patterns of reactivity to environmental antigens, which are established in genetically predisposed individuals. In addition to the skin, atopic diathesis involves other organs such as the airways (upper and lower), eyes, digestive tract, and neuropsychiatric aspects, which inflict additional morbidity on the dermatological patient. The different phenotypes of the disease fundamentally depend on the participation of each of these factors, in different life circumstances, such as age groups, occupational exposure patterns, physical activity, pollution, genetic load, and climatic factors. A better understanding of the complexity of its pathogenesis allows not only the understanding of therapeutic targets but also how to identify preponderant elements that mediate disease activity in each circumstance, for selecting the best treatment strategies and mitigation of triggering factors. This narrative review presents an update on the pathogenesis of atopic dermatitis, especially aimed at understanding the clinical manifestations, the main disease phenotypes and the context of available therapeutic strategies.

Exploring the Role of Homeopathic Intervention in Post-COVID Functional Gastrointestinal Disorders: A Case Series of 12 Patient Profiles.

BACKGROUND: In the last 2 years of the pandemic, a wide range of cases of post-COVID functional gastrointestinal disorders (PC-FGIDs) has been reported. AIM: This case series aimed to investigate the role of homeopathic intervention in the treatment of PC-FGIDs. METHODS: This is a retrospective analysis of the clinical data of individuals who had suffered from PC-FGIDs that were diagnosed based on clinical symptoms using the Gastrointestinal Symptoms Rating Scale (GSRS) and treated exclusively with individualized homeopathic medicines. Cases that had undergone regular monthly assessment using the GSRS and had a Post-COVID-19 Functional Status (PCFS) score for up to 3 months were considered. RESULTS: Thirty cases were screened and twelve were included according to the study criteria. The mean age of seven women and five men was 36 years. GSRS and PCFS scores showed marked improvement in each of 10 cases within the 3-month treatment period. CONCLUSION: Homeopathic intervention proved beneficial in 10 of 12 patients with PC-FGIDs. The findings may help researchers plan future controlled clinical studies in this field.

Esoteric beliefs and CAM impact SARS-CoV-2 immunization drivers, uptake and pediatric immunization views in Germany.

Recent studies demonstrate that sociopolitical attitudes partially explain variance in (SARS-CoV-2) vaccine hesitancy and uptake. Other attitudes, such as those towards esoteric beliefs, complementary and alternative medicine (CAM), and religion, have also been proposed. However, pertinent studies provide limited direction for public health efforts, as the impact of such attitudes has been tested in isolation or on different outcomes. Moreover, related associations between SARS-CoV-2 immunization drivers as well as views towards other modes of immunization (e.g., routine pediatric immunization), remain unclear. Based on a sample of ~7400 survey participants (Germany), where esoteric belief systems and CAM (Waldorf, homeopathy) are rather prevalent, and controlling for other sociological factors, we found that (i) individuals with positive attitudes towards Waldorf education and homeopathy are significantly less likely to have received a (further) dose of SARS-CoV-2 vaccine compared to those with positive views of mainstream medicine; (ii) for the former, immunization decisions are primarily driven by external pressures, and for the latter overwhelmingly by voluntary considerations; (iii) attitudes influencing adult SARS-CoV-2 vaccine uptake similarly influence views towards routine pediatric immunization. Our findings provide significant evidence informing a more nuanced design of public health and communication campaigns, and pertinent policies.

Physicians' knowledge, attitudes, and practices regarding fibromyalgia: A systematic review and meta-analysis of cross-sectional studies.

BACKGROUND: The diagnosis, etiology, and optimal management of fibromyalgia remains contentious. This uncertainty may result in variability in clinical management. We conducted a systematic review and meta-analysis of cross-sectional studies examining physicians' knowledge, attitudes, and practices regarding fibromyalgia. METHODS: We searched MEDLINE, Embase, and PubMed from inception to February 2023 for cross-sectional surveys evaluating physicians' attitudes toward, and management of, fibromyalgia. Pairs of independent reviewers conducted article screening, data extraction, and risk of bias assessment in duplicate. We used random-effects meta-analysis to pool proportions for items reported by more than one study and the Grading of Recommendations Assessment, Development, and Evaluation approach to summarize the certainty of evidence. RESULTS: Of 864 citations, 21 studies (8904 participants) were eligible for review. Most physicians endorsed fibromyalgia as a distinct clinical entity (84%; 95% confidence interval [CI], 74-92), and half (51%; 95% CI, 40-62) considered fibromyalgia a psychosocial condition. Knowledge of formal diagnostic criteria for fibromyalgia was more likely among rheumatologists (69%, 95% CI, 45-89) versus general practitioners (38%, 95% CI, 24-54) (P = .04). Symptom relief was endorsed as the primary management goal by most physicians (73%, 95% CI, 52-90). Exercise, physiotherapy, antidepressants, nonsteroidal anti-inflammatory drugs, and non-opioid analgesics were most endorsed for management of fibromyalgia, but with wide variability between surveys. Opioids and most complementary and alternative interventions (e.g., homeopathy, chiropractic, and massage) received limited endorsement. CONCLUSION: There is moderate certainty evidence to suggest that physicians are divided regarding whether fibromyalgia is a biomedical or psychosocial disorder. Physicians typically prioritize symptom relief as the primary goal of management, and often endorse management with exercise, non-opioid analgesics, nonsteroidal anti-inflammatory drugs, antidepressants, and physiotherapy (moderate to high certainty evidence); however, important practice variation exists.

What do Brazilian paediatric dentists know about bruxism in children? Cross-sectional study.

PURPOSE: Little is known about the knowledge of paediatric dentists on bruxism in children. The aim of this cross-sectional study was to assess the knowledge of paediatric dentists on the concept, associated factors of bruxism and management of sleep bruxism (SB) in children'. METHODS: An electronic questionnaire was sent to paediatric dentists in the state of Goiás, Brazil. Information was collected on (1) characteristics of the participants; (2) the concept of bruxism; (3) diagnosis; (4) associated factors; (5) strategies for the management of SB; and (6) updated knowledge on bruxism in children. The data were analysed descriptively. RESULTS: Fifty-seven paediatric dentists participated (10.7% of the total number of professionals). A high level of agreement was found with statements on the concepts of SB (94.7%) and awake bruxism (96.5%). The main strategy for the diagnosis was the combination of a parental report and a clinical examination (79.0%). Most participants indicated that bruxism is associated with anxiety/stress (96.5%), screen use (93%), airway obstruction (91.2%), and sleep apnoea (91.2%). In suspected cases of bruxism, the dentists would send the child for assessment by other health care providers (87.7%). The management options frequently indicated were the use of an occlusal splint, aromatherapy, and homeopathy. More than 70% of them considered themselves to be updated on the issue and sought information through scientific articles and discussions with colleagues. CONCLUSION: Paediatric dentists have knowledge on the concept of bruxism and associated factors. However, further information is needed on the management of this condition in children.

Characterisation of Aqueous Ultra-high Homeopathic Potencies: Nanoparticle Tracking Analysis.

BACKGROUND AND OBJECTIVES: Over the past decade, research using various methods has claimed the material nature, including nanoparticles (NPs), of high homeopathic potencies. The current study aims to verify these findings using NP tracking analysis (NTA). METHODS: Six independent serial dilutions of commonly used homeopathic medicines-either soluble (Gelsemium, Pyrogenium, Kalium mur) or insoluble (Cuprum, Argentum, Silicea)-were prepared according to European Pharmacopoeia standards. We compared the homeopathic dynamisations (DYNs) in pure water with their potentised controls and with simple dilutions (DIL) up to 30cH/10-60. We also tested the influence of the container (glass or PET) on the solvent controls. RESULTS: We observed the presence of particles from 20 to 300-400 nm in all DYNs, DILs and controls, except in pure unstirred water. The sizes and size distributions of NPs in high homeopathic potencies were smaller than those in controls for soluble sources and larger for insoluble sources, even above 11cH. The opposite behaviour was observed in the number of NPs. When comparing DYN and DIL, the number, size, presence of aggregates or chains and brightness of NPs increased with DYNs, which was also observed above 11cH. Many NPs scattered light of low intensity, indicating the presence of material particles. The container had a significant effect on the number and size of NPs, indicating the involvement of the atmosphere and leaching processes. CONCLUSION: Homeopathic medicines contain NPs with specific properties, even when diluted beyond Avogadro's number. Homeopathic potentisation is not a simple dilution. The starting material, the solvent used, the type of container and the manufacturing method influence the characteristics of these NPs. The nature of these NPs is not known, but most likely they are a mixture of nanobubbles and elements from the atmosphere and container, including insoluble ones.

Anti-Biofilm Action of Cineole and Hypericum perforatum to Combat Pneumonia-Causing Drug-Resistant P. aeruginosa.

Hospital-acquired antibiotic-resistant pneumonia is one of the major causes of mortality around the world that pose a catastrophic threat. Pseudomonas aeruginosa is one of the most significant opportunistic pathogens responsible for hospital-acquired pneumonia and gained resistance to the majority of conventional antibiotics. There is an urgent need for antibiotic alternatives to control drug-resistant pneumonia and other related respiratory infections. In the present study, we explored the antibacterial potential of cineole in combination with homeopathic medicines against biofilm-forming drug-resistant P. aeruginosa. Out of 26 selected and screened homeopathic medicines, Hypericum Perforatum (HyPer) was found to eradicate biofilm-forming drug-resistant P. aeruginosa most effectively when used in combination with cineole. Interestingly, the synergistic action of HyPer and cineole was also found to be similarly effective against planktonic cells of P. aeruginosa. Further, the potential synergistic killing mechanisms of cineole and HyPer were determined by analyzing zeta membrane potential, outer membrane permeability, and DNA release from P. aeruginosa cells upon treatment with cineole and HyPer. Additionally, molecular docking analysis revealed strong binding affinities of hypericin (an active ingredient of HyPer) with the PqsA (a quorum sensing protein) of P. aeruginosa. Overall, our findings revealed the potential synergistic action of cineole and HyPer against biofilm-forming drug-resistant P. aeruginosa. Cineole and HyPer could be used in combination with other bronchodilators as inhalers to control the biofilm-forming drug-resistant P. aeruginosa.

The effect of prior hysterosalpingo-foam sonography or hysterosalpingography on tubal patency: a secondary analysis of a randomized controlled trial.

STUDY QUESTION: Does hysterosalpingo-foam sonography (HyFoSy) prior to hysterosalpingography (HSG) or HSG prior to HyFoSy affect visible tubal patency when compared HSG or HyFoSy alone? SUMMARY ANSWER: Undergoing either HyFoSy or HSG prior to tubal patency testing by the alternative method does not demonstrate a significant difference in visible tubal patency when compared to HyFoSy or HSG alone. WHAT IS KNOWN ALREADY: HyFoSy and HSG are two commonly used visual tubal patency tests with a high and comparable diagnostic accuracy for evaluating tubal patency. These tests may also improve fertility, although the underlying mechanism is still not fully understood. One of the hypotheses points to a dislodgment of mucus plugs that may have disrupted the patency of the Fallopian tubes. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of the randomized controlled FOAM study, in which women underwent tubal patency testing by HyFoSy and HSG, randomized for order of the procedure. Participants either had HyFoSy first and then HSG, or vice versa. Here, we evaluate the relative effectiveness of tubal patency testing by HyFoSy or HSG prior to the alternative tubal patency testing method on visible tubal patency, compared to each method alone. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women aged between 18 and 41 years scheduled for tubal patency testing were eligible for participating in the FOAM study. Women with anovulatory cycles, endometriosis, or with a partner with male infertility were excluded. To evaluate the effect HyFoSy on tubal patency, we relied on HSG results by comparing the proportion of women with bilateral tubal patency visible on HSG in those who underwent and who did not undergo HyFoSy prior to their HSG (HyFoSy prior to HSG versus HSG alone). To evaluate the effect of HSG on tubal patency, we relied on HyFoSy results by comparing the proportion of women with bilateral tubal patency visible on HyFoSy in those who underwent and who did not undergo HSG prior to their HyFoSy (HSG prior to HyFoSy versus HyFoSy alone). MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, we randomized 1160 women (576 underwent HyFoSy first followed by HSG, and 584 underwent HSG first followed by HyFoSy). Among the women randomized to HyFoSy prior to HSG, bilateral tubal patency was visible on HSG in 467/537 (87%) women, compared with 472/544 (87%) women who underwent HSG alone (risk difference 0.2%; 95% CI: -3.8% to 4.2%). Among the women randomized to HSG prior to HyFoSy, bilateral tubal patency was visible on HyFoSy in 394/471 (84%) women, compared with 428/486 (88%) women who underwent HyFoSy alone (risk difference -4.4%; 95% CI: -8.8% to 0.0%). LIMITATIONS, REASONS FOR CAUTION: The results of this secondary analysis should be interpreted as exploratory and cannot be regarded as definitive evidence. Furthermore, it has to be noted that pregnancy outcomes were not considered in this analysis. WIDER IMPLICATIONS OF THE FINDINGS: Tubal patency testing by either HyFoSy or HSG, prior to the alternative tubal patency testing method does not significantly affect visible tubal patency, when compared to alternative method alone. This suggests that both methods may have comparable abilities to dislodge mucus plugs in the Fallopian tubes. STUDY FUNDING/COMPETING INTEREST(S): The FOAM study was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, or interpretation of the data. H.R.V. reports consultancy fees from Ferring. M.v.W. received a travel grant from Oxford University Press in the role of Deputy Editor for Human Reproduction and participates in a Data Safety and Monitoring Board as an independent methodologist in obstetrics studies in which she has no other role. M.v.W. is coordinating editor of Cochrane Fertility and Gynaecology. B.W.J.M. received an investigator grant from NHMRC (GNT1176437) and research funding from Merck KGaA. B.W.J.M. reports consultancy for Organon and Merck KGaA, and travel support from Merck KGaA. B.W.J.M. reports holding stocks of ObsEva. V.M. received research grants from Guerbet, Merck and Ferring and travel and speaker fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

In India, most principal investigators have run very few trials over the years.

Background: In the past, clinical trials run in India have been the subject of criticism. Among other steps to improve the trial ecosystem, for some time the government limited the number of trials that a Principal Investigator (PI) could run to three at a time. We were interested to know how many trials PIs in India tend to run at a time. Methods: We accessed the 52,149 trial records hosted by the Clinical Trials Registry-India in April 2023. Of these, we shortlisted trials that had run in India, were interventional, and involved certain interventions such as drug, biological etc. We used multiple parameters, such as email ID, phone number etc. to determine whether one name always represented the same PI and whether two names corresponded to the same PI. We then determined how many trials each PI had run. Results: We found that 3,916 unique PI names were associated with 6,665 trials. Of these, 2,963 (75.7%) PIs had run a single study. Only 251 (6.4%) had run more than three trials. A mere 14 PIs had run 20 or more trials. The 14 PIs were affiliated with local pharma companies (6), local or global contract research organizations (4), multinational pharma companies (3) and the Central Council for Research in Homeopathy (1). The maximum number of trials run by a single PI was 108. Of these, the largest number run in a single year, 2022, was 53. Conclusion: Each PI name needs to be connected to a unique ID that does not change with time, so that it is easier to track the number of trials that a given PI has run. The number of studies run by a given PI at a given time must not be excessive and needs to be monitored more actively. The government needs to consider whether a cap on the number of trials that a PI runs at a time is required and what infrastructure needs to be in place to facilitate higher numbers of trials. Trial registry records need to be updated more regularly. Other countries may wish to do likewise.

Integrative therapeutics for ocular surface disorders.

PURPOSE OF REVIEW: Integrative medicine techniques are increasingly accepted into the treatment paradigm for many chronic disorders including eye disease. Over 71% of patients, including 67% of those with eye disorders, use some form of Integrative therapy. Physicians should be well versed in evidence-based therapies to know how to refer patients for the best complimentary care. We highlight the most effective integrative therapeutics from different complementary treatment paradigms to offer a framework for approaching therapy in patients with ocular surface disorders (OSDs). RECENT FINDINGS: Lifestyle and behavioral modifications help a proportion of people with OSDs like dry eye disease and allergic conjunctivitis, which are interrelated disorders. Nutrition and supplementation can also play a role in addressing underlying inflammation and improving OSD symptoms. Acupuncture and traditional herbal medicine may also benefit some patients. New technologies offer innovative treatment pathways in the treatment of OSD but require referral to Ocular Surface Treatment Centers. SUMMARY: Integrative treatment approach for OSD incorporates allopathic medicine, traditional remedies and lifestyle behavioral interventions, Ayurveda and herbal medicine, Nutritional Supplements, Homeopathy, Acupuncture and Chinese Medicine. New cutting-edge technologies offer breakthroughs in difficult to treat ocular surface cases. Collaboration between allergy or otolaryngology offices, complementary practitioners, as well as optometrists and ophthalmologists in Ocular Surface Treatment Centers can offer patients new avenues of treatment.

Unveiling the Immunostimulatory Potential of Rhus Toxicodendron in Immunocompromised Balb/C Mice Induced with Cyclophosphamide.

This study investigated how Rhus toxicodendron (RT) (6C, 30C, and 200C) can boost the immune system of BALB/c mice that were given cyclophosphamide (CPM), which is an anticancer drug that weakens the immune system. RT, known for its historical use in traditional homeopathic remedies, has demonstrated immunomodulatory and anti-inflammatory effects in various experimental models. To test the immune-boosting effects of RT, CPM (80 mg/kg) was given intraperitoneally to mice on days 4, 8, and 12 of the study but not to the normal control group. CPM-induced immunosuppression led to significant decreases in red blood cell (RBC), white blood cell (WBC), and hemoglobin (Hb) levels, and reduced spleen and thymus indices. Phagocytic activity, cytokine concentrations, and spleen architecture were also adversely affected. RT treatment, particularly at 200C, significantly ameliorated these effects, improving RBC, WBC, and Hb levels. Furthermore, RT partially prevented CPM-induced atrophy of immune organs. Treatment positively influenced cytokine production at both the protein and mRNA levels, restoring immune balance. Histopathological results confirmed that RT stimulated the immune system. The cells were more stable, and the white pulp in the spleen was arranged in a regular pattern. These findings suggest that RT may serve as an adjunctive immunostimulant therapy for conditions characterized by immunosuppression. However, further investigations in other immunocompromised states must validate these results before considering human clinical trials.

Homoeopathic Treatment Of Psoriasis Using Fifty-Millesimal (LM) Potency: A Case Report.

Context: Psoriasis is a chronic, proliferative, and inflammatory skin disease related to the systemic manifestation of numerous organs. The typical lesion comprises red, scaly, sharply demarcated, indurated plaques, especially over the extensor surfaces and scalp. The degree and severity vary after some time and between people. Morphological variations are normal; both hereditary and environmental factors play important roles in etiology and pathogenesis.Psoriasis is very difficult to treat due to its chronicity. As a medical system, Homoeopathy treats both patients' physical ailments and overall wellness. The use of highly potentized homoeopathic anti-miasmatic intercurrent medicines will be very beneficial in dealing with this. Fifty-millesimal (LM) potency was a great discovery by Dr. Samuel Hahnemann. While treating numerous chronic illnesses, he was able to quickly relieve symptoms without any aggravation by using fifty-millesimal (LM) potency. Case Report: The present case report is of 24-year-old male patient having psoriasis for one year. This case report describes the homoeopathic management of psoriasis using fifty-millesimal (LM) potency. On the basis of presenting sign and symptoms, Arsenic Album 30C was prescribed with frequent repetitions after repertorisation. During follow-ups, Arsenic Album 1LM was prescribed in to accelerate the cure. Psoriasis is a chronic condition that tends to recur. To prevent the recurrence, Psorinum 1000C was prescribed as an intercurrent anti-miasmatic medicine in a single dose during the course of treatment. Psorinum is a nosode that was chosen for therapy since it is recommended when symptoms reappear and the best selected homoeopathic medicine is not very effective. Psorinum was prescribed in this case to clear the miasmatic obstruction because the Arsenic Album was only temporarily easing the complaints. Result: The patient has exhibited improvement in their mental state and quick alleviation from physical issues after receiving multiple doses of Arsenic Album 1LM and a single dose of Psorinum 1000C, all without their symptoms getting worse. The patient's condition was followed up on at every appointment for a considerable amount of time, and no new concerns had surfaced as of yet. Conclusion: This case report shows favourable results of homoeopathic medicine in fifty-millesimal (LM) potency. Therefore, it can be concluded that using fifty-millesimal (LM) potency of accurately selected homoeopathic medicine will shorten the cure process without the aggravation of symptoms. Further research studies are required to explore the efficacy of fifty-millesimal (LM) potency of homoeopathic medicine in treatment of chronic illnesses.