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.

What over the counter (OTC) products have been evaluated for anxiety in adults aged 18-60? A scoping review.

BACKGROUND: Anxiety symptoms and disorders are common in the UK. Whilst waiting for, or alongside, treatments such as anxiolytics or psychological therapies, people often self-manage anxiety symptoms with products purchased over-the-counter (OTC), such as herbal medicines or dietary supplements. However, the evidence for these products is often presented across different reviews and is not easy for patients or healthcare professionals to compare and understand. AIMS: To determine the nature and size of the evidence base available for these products. METHODS: A scoping review. CENTRAL, MEDLINE, EMBASE, PsycInfo, and AMED (inception-Dec 2022) were searched for RCTs assessing OTC products in people aged 18-60 with symptoms or a diagnosis of anxiety. RESULTS: In total 69 papers assessing a range of products were found, which mostly focussed on kava, lavender, saffron, probiotics, Galphimia glauca and valerian. Studies used varying dosages. Compared to herbal medicine studies, there were much fewer dietary supplement studies and homeopathic remedy studies, despite some of use of these by the general public. CONCLUSION: Future research needs to investigate commonly used but less evaluated products (e.g. chamomile, St John's Wort) and to evaluate products against or alongside conventional treatments to better reflect patient decision making.

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.

Homeopathy, Acupuncture and Phytotherapy in the Veterinary Treatment or Prophylaxis of Diseases in Animals: An Overview of Systematic Reviews.

INTRODUCTION: Complementary and alternative veterinary medicine (CAVM) has been intensively used, and there is currently an increasing demand for a more rigorous approach regarding its clinical effectiveness. AIMS: The objectives of this overview were: first, to identify systematic reviews on homeopathy, acupuncture and phytotherapy in veterinary medicine and assess their methodological quality; and second, to map interventions and findings in the treatment or prophylaxis of any medical conditions in any animal species for which high-quality systematic reviews had identified reliable evidence of efficacy or effectiveness in randomized controlled trials (RCTs) or controlled clinical trials (CCTs). METHOD: The study was an overview of systematic reviews published in the years 2000 to 2022 inclusive. The following databases were used: CAB Abstracts, PubMed and Vet Index, from which the abstracts of 173 articles were extracted, 22 of which were initially included for complete analysis. After excluding 15 studies according to the exclusion/inclusion criteria, 7 review papers were comprehensively analyzed. The review quality was assessed by the Measurement Tool to Assess Systematic Reviews (AMSTAR 2) method. The reported RCTs/CCTs in these reviews were analyzed for their reliability, and the results were classified according to statistical significance and risk of bias. RESULTS: Seven eligible systematic reviews reported studies on dogs, horses, cats, cattle, sheep, goats, swine, rabbits and poultry. The number of primary RCTs/CCTs was 38 for homeopathy, 35 for acupuncture, and 171 for phytotherapy. The AMSTAR 2 evaluation ranked two reviews of veterinary homeopathy as high-quality, in which two placebo-controlled RCTs comprised reliable evidence, one of which reported efficacy of homeopathy as prophylaxis for diarrhea in pigs. The systematic reviews of acupuncture and phytotherapy were all of low quality, preventing formal assessment of their reviewed RCTs/CCTs. CONCLUSION: Only the systematic reviews of homeopathy were rated of sufficient quality to enable the assessment of reliable evidence within their reviewed RCTs. Contemporary high-quality systematic reviews of clinical trials in each of the three areas of CAVM are required.

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.

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.

Use of complementary and alternative medicine in patients with chronic liver diseases in Germany- a multicentric observational study.

BACKGROUND: The use of Complementary and alternative medicine (CAM) in chronic liver disease (CLD) patients in Germany is unknown. This study investigated the frequency of CAM use and associated sociodemographic, clinical and personality factors in CLD patients in Germany. METHODS: This is a cross-sectional multicenter study of CLD patients attending liver outpatient clinics of university hospitals in Halle(-Saale) and Homburg between 2015 and 2017. Dedicated questionnaires recorded CAM use, sociodemographic and personality factors (evaluated with the "Big five" model, "Hospital Anxiety and Depression"-, "Multidimensional Health Locus of Control"- score). Uni- and multivariate analyses assessed factors associated to CAM use. RESULTS: Overall 378 patients were recruited, 92 (24.3%) reported to CAM use. On univariate analysis, female CAM users were older (p = 0.001) and more physically active (p = 0.002), male CAM users more often used homeopathy (p = 0.000), actively promoted their health (p = 0.010) or had UDC in their medication (p = 0.004). Logistic regression analysis adjusted for personality factors showed significant association of age, physical exercise (females) and satisfaction with alternative medicine (females, males) to CAM use. CONCLUSIONS: CAM use is prevalent among CLD patients in Germany and is significantly associated to satisfaction with alternative medicine (females, males), physical exercise and older age (females). Doctors should actively inquire CLD patients about CAM use, as hepatotoxicity or interaction with medication can occur.

Individualized Homeopathic Treatment for Persistent Insomnia and Generalized Anxiety Disorder: A Case Report.

Insomnia is a widespread disease that tends to be associated with other problems, like anxiety. The most frequent anxiety disorder is generalized anxiety disorder (GAD), which is characterized by excessive worrying about everyday situations. Medications for insomnia and anxiety can have adverse reactions and the latter may be ineffective in up to 30% of patients. Here we present a case report of a 27-year-old male patient who suffered from persistent insomnia with comorbid GAD and schizophreniform disorder. Initially, he was taking alprazolam, paroxetine, and risperidone, which had a less-than-satisfactory effect. He was treated with individualized homeopathy, which produced a remarkable improvement within four months. This was evidenced by a decrease in difficulty falling asleep and daytime sleepiness; in addition, anxiety and its accompanying symptoms, such as irritability and diaphoresis, were reduced. This improvement persists for up to one year after the commencement of treatment and despite discontinuation of all medications. This clinical report provides preliminary evidence that persistent insomnia and comorbid GAD can be treated successfully with individualized homeopathy. However, further randomized controlled studies are needed to evaluate its efficacy, effectiveness, and safety more conclusively.

COVID 19: Prevention and treatment through the Indian perspective.

The most destructive period the world has experienced seems to be behind us. Not a single nation was spared by this disease, and many continue to struggle today. Even after recovering from COVID, patient may continue to experience some post-COVID effects, such as heart irregularities or a decline in lung vitality. In the past three years (2019-2022), the world has witnessed the power of a small entity, a single peculiar virus. Science initially appeared to be helpless in this regard, but due to the emergence of disease, pharmaceutics (the development of anti-covid drugs), immunology (the rapid antigen test), microbiology (the isolation of viruses from infected people), biotechnology (the development of recombinant vaccines), biochemistry (the blood profile, the D-dimer test), and biochemistry (blood profile, D-dimer test), biophysics (PCR, RT-PCR, CT Scan, MRI) had worked together to fight the disease. The results of these efforts are the development of new diagnostic techniques, possible treatment and finally the availability of vaccines against COVID-19. However, it is not proven that the treatment through the traditional medical system is directly active on SARS-CoV-2 but is instead indirectly acting on SARS-CoV-2 effects by improving symptoms derived from the viral disease. In India, the traditional system of medicine and tradition knowledge together worked in the pandemic and proved effective strategies in prevention and treatment of SARS-CoV-2. The use of effective masks, PPE kits, plasma therapy, yoga, lockdowns and social seclusion, use of modern antiviral drugs, monoclonal antibodies, herbal remedies, homoeopathy, hygienic practice, as well as the willpower of people, are all contributing to the fight against COVID. Which methods or practices will be effective against COVID nobody is aware since medical professionals who wear PPE kits do not live longer, and some people in India who remained unprotected and roamed freely were not susceptible to infection. The focus of this review is on the mode of transmission, diagnosis, preventive measures, vaccines currently under development, modern medicine developed against SARS-CoV-2, ayurvedic medicine used during pandemic, homoeopathic medicine used during pandemic, and specific yoga poses that can be used to lessen COVID-related symptoms.

Individualized Homeopathic Medicinal Products in the Treatment of Post-COVID-19 Conditions: A Double-Blind, Randomized, Placebo-Controlled, Feasibility Trial.

Objectives: Evidence suggests that post-coronavirus disease 2019 (COVID-19) is associated with reduced health-related quality of life, and up to 80% of those infected with COVID-19 may experience these symptoms. The objective of the present study was to identify the effects of individualized homeopathic medicinal products (IHMPs) against placebos in postCOVID-19 conditions. Design: Double-blind, randomized (1:1), two parallel arms, placebo-controlled, feasibility trial. Setting: D. N. De Homoeopathic Medical College & Hospital, Kolkata, West Bengal, India. Subjects: Sixty participants with post-COVID-19 conditions. Interventions: Group verum (n = 30; IHMPs plus concomitant care) versus group control (n = 30; placebos plus concomitant care). Outcome Measures: Feasibility issues; primary-post-COVID-19 symptoms checklist; secondary-Measure Yourself Medical Outcomes Profile version 2 (MYMOP-2); all of them were measured at baseline, and monthly intervals, up to 3 months. The intention-to-treat sample was analyzed; group differences were reported using descriptive statistics: means, 95% confidence intervals (CIs), and between group effect sizes (Cohen's d). Results: Feasibility concerns showed promise; recruitment, retention, and attrition rates were 34.2%, 95%, and 5%, respectively. Group differences in both primary and secondary outcomes favored IHMPs against placebos: symptoms checklist score mean difference after 3 months: -4.2, 95% CI -4.9 to -3.4, d = 2.854 and MYMOP-2 mean difference after 3 months: -2.2, 95% CI -2.8 to -1.7, d = 2.082, respectively. Natrum muriaticum (11.7%), Pulsatilla nigricans (10%), Rhus toxicodendron (8.3%), and Calcarea carbonica (8.3%) were the most frequently prescribed remedies. Conclusions: IHMPs produced better results than placebos in reducing symptoms checklist scores and MYMOP-2 scores in the treatment of post-COVID-19 conditions. Definitive trials are warranted to confirm the findings.

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

OBJECTIVE: To quantify the effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis (OA) 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, randomized 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 35 high-risk-of-bias trials than in 22 low/unclear-risk-of-bias trials. In the main analysis (excluding high-risk-of-bias trials), triamcinolone had the highest probabilities of reaching the MID at weeks 2 and 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 (1 trial). The complex homeopathic products Tr14/Ze14 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, 1 trial). Hyaluronic acid had no effect on pain (SMD:-0.04, 95% CrI,-0.19 to 0.11, 11 trials) but a 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 indicate that the effects of 16 intra-articular interventions in knee or hip OA were smaller than the MID, and that most were consistent with placebo effects. Lack of evidence of long-term effectiveness underscores the need for further research beyond 24 weeks.

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.

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.

Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

STUDY QUESTION: Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? SUMMARY ANSWER: Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. WHAT IS KNOWN ALREADY: HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. STUDY DESIGN, SIZE, DURATION: This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. MAIN RESULTS AND THE ROLE OF CHANCE: School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. LIMITATIONS, REASONS FOR CAUTION: The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. STUDY FUNDING/COMPETING INTEREST(S): The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER: NCT05168228.