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.

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.

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.

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.

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 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.

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.

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.

Plants and their uses in dermatological recipes of the Receptarium of Burkhard III von Hallwyl from 16th century Switzerland - Data mining a historical text and preliminary in vitro screening.

ETHNOPHARMACOLOGICAL RELEVANCE: Historical texts on materia medica can be an attractive source of ethnopharmacological information. Various research groups have investigated corresponding resources from Europe and the Mediterranean region, pursuing different objectives. Regardless of the method used, the indexing of textual information and its conversion into data sets useful for further investigations represents a significant challenge. AIM OF THE STUDY: First, this study aims to systematically catalogue pharmaco-botanical information in the Receptarium of Burkhard von Hallwyl (RBH) in order to identify candidate plants in a targeted manner. Secondly, the potential of RBH as a resource for pharmacological investigations will be assessed by means of a preliminary in vitro screening. MATERIALS AND METHODS: We developed a relational database for the systematic recording of parameters composing the medical recipes contained in the historical text. Focusing on dermatological recipes, we explored the mentioned plants and their uses by drawing on specific literature. The botanical identities (candidate species) suggested in the literature for the historical plant names were rated based on their plausibility of being the correct attribution. The historical uses were interpreted by consulting medical-historical and modern clinical literature. For the subsequent in vitro screening, we selected candidate species used in recipes directed at the treatment of inflammatory or infectious skin disorders and wounds. Plants were collected in Switzerland and their hydroethanolic crude extracts tested for possible cytotoxic effects and for their potential to modulate the release of IL-6 and TNF in PS-stimulated whole blood and PBMCs. RESULTS: The historical text analysis points up the challenges associated with the assessment of historical plant names. Often two or more plant species are available as candidates for each of the 161 historical plant names counted in the 200 dermatological recipes in RBH. On the other hand, our method enabled to draw conclusions about the diseases underlying the 56 medical applications mentioned in the text. On this basis, 11 candidate species were selected for in vitro screening, four of which were used in RBH in herbal simple recipes and seven in a herbal compound formulation. None of the extracts tested showed a noteworthy effect on cell viability except for the sample of Sanicula europaea L. Extracts were tested at 50 µg/mL in the whole blood assay, where especially Vincetoxicum hirundinaria Medik. or Solanum nigrum L. showed inhibitory or stimulatory activities. In the PBMC assay, the root of Vincetoxicum hirundinaria revealed a distinct inhibitory effect on IL-6 release (IC50 of 3.6 µg/mL). CONCLUSIONS: Using the example of RBH, this study illustrates a possible ethnopharmacological path from unlocking the historical text and its subsequent analysis, through the selection and collection of plant candidates to their in vitro investigation. Fully documenting our approach to the analysis of historical texts, we hope to contribute to the discussion on solutions for the digital indexing of premodern information on the use of plants or other natural products.

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.

A life dedicated to research and ideal: Johannes Müller between empirical universality and idealistic vitalism mirrored in lecture notes from 1851.

Until the mid-nineteenth century, "physiology" was a comprehensive theory of life, expounded and shaped by Johannes P. Müller (1801-1858). Biologists and medical doctors still refer to him today. In the summer term of 1851, Müller gave a lecture on the Comparative Anatomy of animals. This lecture was attended and recorded by Ernst Zeller (1830-1902), a future physician and zoologist, and has recently been published together with a German transcript. In this paper, we situate Johannes Müller within the intellectual history of his time. Through his "empirical idealism," we show how he opposed the speculative tendencies of the romantic understanding of nature, the emerging evolutionism, and the growing splits in the natural sciences. Müller focused on recognizing living nature as a whole and realizing ideal "phenomena" through his empirical research. He considered the notion of the soul of the world. Müller's lecture transcript serves as a poignant testament to German scientific culture in the mid-nineteenth century, a few years before the publication of Darwin's Origin of Species. It also provides valuable insights into the self-contained epistemological foundations of morphology.

Population-level trends in self-reported healthcare utilization among older adults in Mexico with and without cognitive impairment.

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico. METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and being screened for cholesterol, diabetes, and hypertension in the past two years. Cognitive impairment was defined using a modified version of the Cross Cultural Cognitive Examination that assessed verbal memory, visuospatial and visual scanning. Total sample included 5,673 participants with cognitive impairment and 34,497 without cognitive impairment interviewed between 2001 and 2018. Generalized Estimating Equation models that adjusted for time-varying demographic and health characteristics and included an interaction term between time and cognitive status were used. RESULTS: For all participants, the risk for one or more overnight hospital stays, doctor visits, and dental visits in the past year, and being screened for diabetes, hypertension, and high cholesterol increased from 2001 to 2012 and leveled off or decreased in 2015 and 2018. Conversely, seeing a homeopathic doctor decreased. Cognitive impairment was associated with higher risk of hospitalization (RR = 1.13, 1.03-1.23) but lower risk of outpatient services (RR = 0.95, 0.93-0.97), cholesterol screening (RR = 0.93, 0.91-0.96), and diabetes screening (RR = 0.95, 0.92-0.97). No significant difference was observed in the use of pharmacists, homeopathic doctors, or folk healers based on cognitive status. Interaction effects indicated participants with cognitive impairment had lower risk for dental visits and hypertension screening but that these trajectories differed over time compared to participants without cognitive impairment. CONCLUSIONS: We identified distinct population-level trends in self-reported healthcare utilization and differences according to cognitive status, particularly for elective and screening services. These findings highlight the necessity for policy interventions to ensure older adults with cognitive impairment have their healthcare needs met.

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.

Ultra-diluted/dynamized doxorubicin reduces the toxicity caused by doxorubicin during the in vitro culture of pig preantral follicles enclosed in ovarian tissue.

The present study investigated the effect of adding allopathic doxorubicin (DOX 0.3 µg/mL), the vehicle of ultradiluted/dynamized doxorubicin (0.2 % ethanol), different dynamizations of ultradiluted/dynamized doxorubicin (DOX 6CH, DOX 12CH and DOX 30CH), both in the absence or presence of chemical stress induced by doxorubicin at 0.3 µg/mL on follicular survival and activation, antioxidant capacity of the medium, Catalase activity (CAT), production of reactive protein thiol, maintenance of type I and III collagen fibers and accumulation of lipofuscin in porcine ovarian tissue cultured in vitro for 48 hours. To do this, part of the ovarian tissue fragments was fixed for the uncultured control and the rest were cultured in: MEM (cultured control), DOX 0.3 µg/mL, Ethanol, DOX 6CH, DOX 12CH, DOX 30CH, DOX (0.3 µg/mL) + DOX 6CH, DOX (0.3 µg/mL) + DOX 12CH, DOX (0.3 µg/mL) + DOX 30CH treatments. The results showed that, in general, ultradiluted/dynamized doxorubicin (DOX 6CH, DOX 12CH and DOX 30CH) mitigated the toxic effect of allopathic doxorubicin (0.3 µg/mL) on the morphology of preantral follicles, the content of type I and III collagen fibers, and the production of lipofuscin in the tissue. However, only DOX (0.3 µg/mL) + DOX 6CH attenuated the oxidative stress induced by DOX (0.3 µg/mL), maintaining adequate CAT activity that was similar to the uncultured control. Additionally, when the three isolated ultradiluted/dynamized doxorubicin were considered, only DOX 12CH increased the reduced thiol levels compared to the uncultured control and MEM. In conclusion, supplementing the culture medium with ultradiluted/dynamized DOX (DOX 6CH, DOX 12CH and DOX 30CH) attenuated the toxicity induced by allopathic doxorubicin during the in vitro culture of pig preantral follicles enclosed in ovarian tissue.

Improving the food safety of bakery products by simultaneously monitoring the occurrence of pyrrolizidine, tropane and opium alkaloids.

The exponential number of food alerts about concerning levels of some plant-alkaloids, such as pyrrolizidine, tropane and opium alkaloids, have stressed the need to monitor their occurrence in foods to avoid toxic health effects derived from their intake. Therefore, analytical strategies to simultaneously monitor the occurrence of these alkaloids should be developed to ensure food safety an comply with regulations. Accordingly, this work proposes an efficient multicomponent analytical strategy for the simultaneous extraction of these alkaloids from commercial bakery products. The analytical method was validated and applied to the analysis of 15 samples, revealing that 100% of them contained at least one of the target alkaloids, in some cases exceeding the maximum limits legislated. Moreover, in two samples the 3 different alkaloid families were detected. These results confirm the importance of simultaneously monitoring these alkaloids in food and highlight also considering some opium alkaloids in current legislation.