Optimizing Behavioral Interventions to Regulate Gestational Weight Gain With Sequential Decision Policies Using Hybrid Model Predictive Control.

Excessive gestational weight gain is a significant public health concern that has been the recent focus of control systems-based interventions. Healthy Mom Zone (HMZ) is an intervention study that aims to develop and validate an individually-tailored and "intensively adaptive" intervention to manage weight gain for pregnant women with overweight or obesity using control engineering approaches. This paper presents how Hybrid Model Predictive Control (HMPC) can be used to assign intervention dosages and consequently generate a prescribed intervention with dosages unique to each individuals needs. A Mixed Logical Dynamical (MLD) model enforces the requirements for categorical (discrete-level) doses of intervention components and their sequential assignment into mixed-integer linear constraints. A comprehensive system model that integrates energy balance and behavior change theory, using data from one HMZ participant, is used to illustrate the workings of the HMPC-based control system for the HMZ intervention. Simulations demonstrate the utility of HMPC as a means for enabling optimized complex interventions in behavioral medicine, and the benefits of a HMPC framework in contrast to conventional interventions relying on "IF-THEN" decision rules.

Treatment of Gastrointestinal Disorders-Plants and Potential Mechanisms of Action of Their Constituents.

The worldwide prevalence of gastrointestinal diseases is about 40%, with standard pharmacotherapy being long-lasting and economically challenging. Of the dozens of diseases listed by the Rome IV Foundation criteria, for five of them (heartburn, dyspepsia, nausea and vomiting disorder, constipation, and diarrhoea), treatment with herbals is an official alternative, legislatively supported by the European Medicines Agency (EMA). However, for most plants, the Directive does not require a description of the mechanisms of action, which should be related to the therapeutic effect of the European plant in question. This review article, therefore, summarizes the basic pharmacological knowledge of synthetic drugs used in selected functional gastrointestinal disorders (FGIDs) and correlates them with the constituents of medicinal plants. Therefore, the information presented here is intended as a starting point to support the claim that both empirical folk medicine and current and decades-old treatments with official herbal remedies have a rational basis in modern pharmacology.

Antibacterial Activity of Medicinal Plants and Their Constituents in the Context of Skin and Wound Infections, Considering European Legislation and Folk Medicine-A Review.

Bacterial infections of skin and wounds may seriously decrease the quality of life and even cause death in some patients. One of the largest concerns in their treatment is the growing antimicrobial resistance of bacterial infectious agents and the spread of resistant strains not only in the hospitals but also in the community. This trend encourages researchers to seek for new effective and safe therapeutical agents. The pharmaceutical industry, focusing mainly on libraries of synthetic compounds as a drug discovery source, is often failing in the battle with bacteria. In contrast, many of the natural compounds, and/or the whole and complex plants extracts, are effective in this field, inactivating the resistant bacterial strains or decreasing their virulence. Natural products act comprehensively; many of them have not only antibacterial, but also anti-inflammatory effects and may support tissue regeneration and wound healing. The European legislative is in the field of natural products medicinal use formed by European Medicines Agency (EMA), based on the scientific work of its Committee on Herbal Medicinal Products (HMPC). HMPC establishes EU monographs covering the therapeutic uses and safe conditions for herbal substances and preparations, mostly based on folk medicine, but including data from scientific research. In this review, the medicinal plants and their active constituents recommended by EMA for skin disorders are discussed in terms of their antibacterial effect. The source of information about these plant products in the review is represented by research articles listed in scientific databases (Science Direct, PubMed, Scopus, Web of Science, etc.) published in recent years.

Adherence to Cervical Cancer Screening Programs in Migrant Populations: A Systematic Review and Meta-Analysis.

Organized cervical cancer screening programs to promote the early identification of precancerous lesions have proven to be effective in decreasing the burden associated with cervical cancer, but knowledge regarding screening adherence among migrant women compared to that of native women has not been summarized. A systematic search of the literature on PubMed, Scopus and Embase led to the identification of 772 papers that were published up to July 2022 and reported population-based data regarding adherence to cervical screening. The screening participation rates among migrant women, compared to native women, were pooled using a random-effects meta-analysis. A total of 18 papers were included in the review, with most of them being conducted in Europe (83.3%). Overall, migrants showed a significantly lower participation rate compared to native women (OR for screening adherence: 0.54, 95% CI = 0.42-0.70). This discrepancy was especially evident for migrant women from North Africa and Sub-Saharan Africa (OR = 0.47, 95% CI = 0.35-0.63, and OR = 0.35, 95% CI = 0.24-0.49, respectively). The results of this systematic review emphasize the importance of increasing cervical cancer screening adherence among migrant women. A significant heterogeneity in screening adherence was observed based on the country of origin. Interventions aimed at reducing the disparities in screening participation should specifically consider how to improve the recruitment of migrant women.

The role of gut microbiota for the activity of medicinal plants traditionally used in the European Union for gastrointestinal disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Many medicinal plants have been traditionally used for the treatment of gastrointestinal disorders. According to the monographs published by the Committee on Herbal Medicinal Products (HMPC) at the European Medicines Agency, currently 44 medicinal plants are recommended in the European Union for the treatment of gastrointestinal disorders based on traditional use. The main indications are functional and chronic gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome (IBS), and typical effects of these plants are stimulation of gastric secretion, spasmolytic and carminative effects, soothing effects on the gastrointestinal mucosa, laxative effects, adstringent or antidiarrheal activities, and anti-inflammatory effects. A possible interaction with human gut microbiota has hardly been considered so far, although it is quite likely. AIM OF THE STUDY: In this review, we aimed to identify and evaluate published studies which have investigated interactions of these plants with the gut microbiome. RESULTS: According to this survey, only a minor portion of the 44 medicinal plants considered in EMA monographs for the treatment of gastrointestinal diseases has been studied so far with regard to potential interactions with gut microbiota. We could identify eight relevant in vitro studies that have been performed with six of these medicinal plants, 17 in vivo studies performed in experimental animals involving seven of the medicinal plants, and three trials in humans performed with two of the plants. The most robust evidence exists for the use of inulin as a prebiotic, and in this context also the prebiotic activity of chicory root has been investigated quite intensively. Flaxseed dietary fibers are also known to be fermented by gut microbiota to short chain fatty acids, leading to prebiotic effects. This could cause a health-beneficial modulation of gut microbiota by flaxseed supplementation. In flaxseed, also other compound classes like lignans and polyunsaturated fatty acids are present, that also have been shown to interact with gut microbiota. Drugs rich in tannins and anthocyanins also interact intensively with gut microbiota, since these compounds reach the colon at high levels in unchanged form. Tannins and anthocyanins are intensively metabolized by certain gut bacteria, leading to the generation of small, bioavailable and potentially bioactive metabolites. Moreover, interaction with these compounds may exert a prebiotic-like effect on gut microbiota. Gut microbial metabolization has also been shown for certain licorice constituents, but their potential effects on gut microbiota still need to be investigated in detail. Only a limited amount of studies investigated the interactions of essential oil- and secoiridoid-containing drugs with human gut microbiota. However, other constituents present in some of these drugs, like curcumin (curcuma), shogaol (ginger), and rosmarinic acid have been shown to be metabolized by human gut microbiota, and preliminary data also indicate potential gut microbiome modulatory effects. To conclude, the interaction with gut microbiota is still not fully investigated for many herbal drugs traditionally used for gastrointestinal disorders, which offers a vast field for future research.

Herbal medicinal products in pregnancy - which data are available?

This review aims to highlight recent approaches concerning usage of (traditional) herbal medicinal products in pregnancy and to discuss appropriate strategies to handle limited information. Therefore, published monographs of the Committee on Herbal Medicinal products (HMPC) and selected publicly funded webpages, medicinal handbooks, publications and industry and health care organisations webpages were evaluated. While within the monographs of the HMPC a rather conservative approach could be found (mainly because of lacking nonclinical and/or clinical studies), all other sources display a wide variety of information or assessments, thereby often giving contradictory recommendations. However, some experience with the usage of herbal substances/preparations exists in daily clinical practise without clinical trials or observational studies and some herbal substances/preparations are also used as food/food supplements/cosmetics/medical devices. Discussions should be started how to use that knowledge and experience to adjust regulatory decisions on a case-by-case basis, if possible.

Assessment of genotoxicity of herbal medicinal products: application of the "bracketing and matrixing" concept using the example of Valerianae radix (valerian root).

An assessment of genotoxicity is a precondition for marketing authorization respectively registration of herbal medicinal products (HMPs), as well as for inclusion into the 'Community list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products' established by the European Commission in accordance with Directive 2001/83/EC as amended, and based on proposals from the Committee on Herbal Medicinal Products (HMPC). In the 'Guideline on the assessment of genotoxicity of herbal substances/preparations' (EMEA/HMPC/107079/2007) HMPC has described a stepwise approach for genotoxicity testing, according to which the Ames test is a sufficient base for the assessment of genotoxicity in case of an unequivocally negative result. For reducing efforts for testing of individual herbal substances/preparations, HMPC has also developed the 'guideline on selection of test materials for genotoxicity testing for traditional herbal medicinal products/herbal medicinal products' (EMEA/HMPC/67644/2009) with the aim to allow testing of a standard range of test materials which could be considered representative of the commonly used preparations from a specific herbal drug according to a 'bracketing/matrixing' approach. The purpose of this paper is to provide data on the practical application of this bracketing and matrixing concept using the example of Valerianae radix, with the intention of facilitating its inclusion in the "Community list". Five extraction solvents, representing the extremes of the polarity range and including also mid-range extraction solvents, were used, covering the entire spectrum of phytochemical constituents of Valerianae radix, thereby including polar and non-polar constituents. Extracts were tested in the Ames test according to all relevant guidelines. Results were unequivocally negative for all extracts. A review of the literature showed that this result is in accordance with the available data, thus demonstrating the lack of a genotoxic potential. In conclusion the two guidelines on genotoxicity provide a practically applicable concept. Valerianae radix has no genotoxic potential, supporting its use in HMPs and its inclusion in the Community list.

Challenges of safety evaluation.

Each application for authorisation of a medicinal product must be accompanied by the particulars and documents referred to in Directive 2001/83/EC on the Community code relating to medicinal products for human use. Details on the documentation needed for traditional herbal medicinal products (THMP) are given in article 16c of the above mentioned Directive. It is pointed out that a bibliographic review of safety data together with an expert report and additional data, if necessary, are required. The Committee on Herbal Medicinal Products (HMPC) provides in its "Guideline on the use of the CTD format in the preparation of a registration application for traditional herbal medicinal products" (EMA/HMPC/71049/2007 Rev. 1) guidance on how to present the information and the dossier needed for an application. There, in agreement with the Directive 2001/83/EC, a bibliographical review of safety data is required within the "Non-clinical Overview". However, it is assumable that for such products, with a long tradition of usage bibliographical information relating to non-clinical safety are available, even if incomplete or not in accordance with today׳s state of the art. In the "Guideline on non-clinical documentation for herbal medicinal products in applications for marketing authorisation (bibliographical and mixed applications) and in applications for simplified registration" (EMEA/HMPC/32116/2005) it is reflected how to deal with such an incomplete set of data for traditional herbal medicinal products and crucial information are highlighted. This article will focus on the explanation of the requirements needed for the non-clinical safety evaluation of THMPs and some detailed explanations of the performance and interpretation of the mutagenicity studies.