Tracing the origin and authenticity of Spanish PDO honey using metagenomics and machine learning.

The Protected Designation of Origin (PDO) indication for foods intends to guarantee the conditions of production and the geographical origin of regional products within the European Union. Honey products are widely consumed due to their health-promoting properties and there is a general interest in tracing their authenticity. In this regard, metagenomics sequencing and machine learning (ML) have been proposed as complementary technologies to improve the traceability methods of foods. Therefore, the aim of this study was to analyze the metagenomic profiles of Spanish honeys from three different PDOs (Granada, Tenerife and Villuercas-Ibores), and compare them with non-PDO honeys using ML models (PLS, RF, LOGITBOOST, and NNET). According to the results obtained, non-PDO honeys and Granada PDO showed higher beta diversity values than Tenerife and Villuercas-Ibores PDOs. ML classification of honey products allowed the identification of different microbial biomarkers of the geographical origin of honeys: Lactobacillus kunkeei, Parasaccharibacter apium and Lactobacillus helsingborgensis for PDO honeys and Paenibacillus larvae, Lactobacillus apinorum and Klebsiella pneumoniae for non-PDO honeys. In addition, potential microbial biomarkers of some honey varieties including L. kunkeei for Albaida and Retama del Teide varieties, and P. apium for Tajinaste variety, were identified. ML models were validated on an independent set of samples leading to high accuracy rates (above 90 %). This work demonstrates the potential of ML to differentiate different types of honey using metagenome-based methods, leading to high performance metrics. In addition, ML models discriminate both the geographical origin and variety of products corresponding to different PDOs and non-PDO products. Results here presented may contribute to develop enhanced traceability and authenticity methods that could be applied to a wide range of foods.

Effects of ground transport on the presence of heavy metals in selected honeybee products.

Honeybees are insects very sensitive to environmental pollution and at the same time very good indicators of the pollution levels for certain types of pollutants. The morphology and ethology of these insects make them perfect vectors for dust and substances, including heavy metals produced by anthropic activities or naturally generated and deposited on foraged flora. When bees are raised to produce foods such as honey and pollen, they can easily transfer pollutants collected from contaminated flower affecting the quality of these products. However, depending on geographical location of the apiaries and their distance from pollution sources, the risk to contaminate bee products can be higher or lower requiring deep investigations. In this study, two apiaries were built near ground transport infrastructures and used as monitoring stations for investigating heavy metal presence in beehive products such as bee wax, pollen, and honey. Another apiary was placed between these two locations at a distance of 500 m from each one and used as central node to asses possible diffusion trends. Parallel, air quality was monitored in the proximity of each apiary to verify the air pollution of the environments close to these sites. The results of the study suggest that the presence of the highway and the train station affected the levels of heavy metal presence in the apiary products. Air quality near apiaries was also negatively affected by ground transport, especially in proximity of the highway. Wax resulted significantly more polluted in the apiary close to train station with elements such as Al, Zn, and Ni, while honey and pollen were significantly more polluted in the proximity of the highway with elements such as Al, Fe, Cu, and Zn. Honey was the product suffering less the contamination by heavy metals while pollen was the worse. In conclusion, the presence of transportation nodes determined a higher accumulation of heavy metals in beehive products respect the apiary placed in between, suggesting to pay particular attention in the site selection for the placement of apiaries to protect both bees and human health.

A fluorescent NBD "turn-on" probe for the rapid and on-site analysis of fructose in food.

High fructose intake is an important cause of metabolic disease. Due to the increasing prevalence of metabolic diseases worldwide, the development of an accurate and efficient tool for monitoring fructose in food is urgently needed to control the intake of fructose. Herein, a new fluorescent probe NBD-PQ-B with 7-nitrobenz-2-oxa-1, 3-diazole (NBD) as the fluorophore, piperazine (PQ) as the bridging group and phenylboronic acid (B) as the recognition receptor, was synthesized to detect fructose. The fluorescence of NBD-PQ-B increased linearly at 550 nm at an excitation wavelength of 497 nm with increasing fructose concentration from 0.1 to 20 mM. The limit of detection (LOD) of fructose was 40 µM. The pKa values of NBD-PQ-B and its fructose complexes were 4.1 and 10.0, respectively. In addition, NBD-PQ-B bound to fructose in a few seconds. The present technique was applied to determine the fructose content in beverages, honey, and watermelon with satisfactory results. Finally, the system could not only be applied in an aqueous solution with a spectrophotometer, but also be fabricated as a NBD-PQ-B/polyvinyl oxide (PEO) film by electrospinning for on-site food analysis simply with the assistance of a smartphone.

Manuka honey as a non-antibiotic alternative against Staphylococcus spp. and their small colony variant (SCVs) phenotypes.

The antibiotic resistance (ABR) crisis is an urgent global health priority. Staphylococci are among the problematic bacteria contributing to this emergency owing to their recalcitrance to many clinically important antibiotics. Staphylococcal pathogenesis is further complicated by the presence of small colony variants (SCVs), a bacterial subpopulation displaying atypical characteristics including retarded growth, prolific biofilm formation, heightened antibiotic tolerance, and enhanced intracellular persistence. These capabilities severely impede current chemotherapeutics, resulting in chronic infections, poor patient outcomes, and significant economic burden. Tackling ABR requires alternative measures beyond the conventional options that have dominated treatment regimens over the past 8 decades. Non-antibiotic therapies are gaining interest in this arena, including the use of honey, which despite having ancient therapeutic roots has now been reimagined as an alternative treatment beyond just traditional topical use, to include the treatment of an array of difficult-to-treat staphylococcal infections. This literature review focused on Manuka honey (MH) and its efficacy as an anti-staphylococcal treatment. We summarized the studies that have used this product and the technologies employed to study the antibacterial mechanisms that render MH a suitable agent for the management of problematic staphylococcal infections, including those involving staphylococcal SCVs. We also discussed the status of staphylococcal resistance development to MH and other factors that may impact its efficacy as an alternative therapy to help combat ABR.

The use of antimicrobial dressings for the management of diabetic foot ulcers: A survey of podiatrists in Aotearoa New Zealand.

INTRODUCTION: Diabetic foot ulcers (DFUs) are commonly contaminated with pathogenic organisms and precede most diabetes-related amputations. Antimicrobial dressings are used in the treatment of DFUs; however, recent guidelines do not support their use. There are no data describing the experience of antimicrobial dressing use among podiatrists in Aotearoa New Zealand (AoNZ). This study aimed to (i) determine which antimicrobial dressings podiatrists in AoNZ use for the management of diabetic foot ulcers; and (ii) determine what factors influence AoNZ podiatrists' use of antimicrobial dressing when managing DFUs. METHODS: An anonymous cross-sectional web-based survey was undertaken. Participants were AoNZ registered podiatrists who managed DFUs in their practice. The survey included questions relating to personal and professional demographic characteristics and DFU management and dressing practices. Descriptive statistics were computed to address the research aims. RESULTS: Responses from 43 AoNZ podiatrists were included. Participants reported both cadexomer iodine and silver dressings were the most common antimicrobial dressings used, with honey dressings being the least frequently used. The most influential factors in choosing antimicrobial dressings when managing DFUs were the presence of current infection, ulcer exudate and ability to prevent future infection. The least influential factors in choosing antimicrobial dressings when managing DFUs were patient preferences, cost of dressings and comfort of dressing/pain on removal. CONCLUSIONS: AoNZ podiatrists managing DFUs primarily use antimicrobial dressings containing cadexomer iodine or silver as active ingredients, while lower-cost options, such as honey and povidone iodine are less often used. Current recommendations highlight the lack of evidence to support positive outcomes from any particular antimicrobial dressing over another and advocate that exudate control, comfort and cost be prioritised in decision-making. As cost has been an increasing burden to our healthcare funding, clinicians and organisations may consider this before purchasing and stocking expensive dressings.

Effects of Ziziphus Honey on Bone Healing of the Extracted Tooth Socket by Evaluating Osteopontin Levels.

OBJECTIVE: To evaluate the effect of Ziziphus honey on the healing of post-extraction alveolar sockets by estimating the levels of osteopontin (OPN) in humans. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Dental section of the Lahore General Hospital, Lahore, Pakistan, from March 2020 to February 2021. METHODOLOGY: A total of 30 patients were included in the study. The mean age was 35 ± 0.28 years. The participants were adults undergoing permanent molar extraction, randomly divided into two groups, a control group and an experimental group. After tooth extractions in both groups, 1ml of Ziziphus honey was administered into the extracted tooth socket of the experimental group while no intervention was done to the control group. Saliva samples were collected on day 0 before tooth extraction and on days 3 and 7 after tooth extractions. Enzyme-linked immunosorbent assay (ELISA) technique was used to measure the levels of OPN in the saliva sample. Radiographic evaluation was also done with the help of periapical radiographs using Image J® software. To find out the significance of the outcome in experimental and control groups, an unpaired t-test was applied. A p-value <0.05 was considered statistically significant. RESULTS: A total of 30 participants were selected for the study, of which 16 were females and 14 were males. The OPN levels between the control vs. experimental groups were (22.55 ± 2.45 vs. 23.31 ± 2.38; p = 0.4) on day 0, (30.95 ± 2.96 vs. 53.29 ± 4.69; p = 0.001) on day 3, and (55.33 ± 4.52 vs. 81.90 ± 4.49; p = 0.001) on day 7. CONCLUSION: Increased salivary levels of the OPN in the experimental group with the use of Ziziphus honey suggests better bone healing as compared to the control group. KEY WORDS: Extraction tooth, Honey, Osteopontin, Ziziphus, Bone healing.

The first ITS1 profiling of honey samples from the Southeast Asian region Lombok, Bali and Banggi Island.

Southern Asian flowers offer honeybees a diversity of nectar. Based on its geographical origin, honey quality varies. Traditional methods are less authentic than DNA-based identification. The origin of honey is determined by pollen, polyphenolic, and macro-microorganisms. In this study, amplicon sequencing targets macro-microorganisms in eDNA using the ITS1 region to explore honey's geographical location and authentication. The variety of honey samples was investigated using ITS1 with Illumina sequencing. For all four honey samples, raw sequence reads showed 979,380 raw ITS1 amplicon reads and 375 ASVs up to the phylum level. The highest total number of 202 ASVs up to phylum level identified Bali honey with 211,189 reads, followed by Banggi honey with 309,207 a total number of 111 ASVs, and Lombok represents only 63 ASVs up to phylum level with several read 458,984. Based on Shannon and Chao1, honey samples from Bali (B2) and (B3) exhibited higher diversity than honey from Lombok (B1) and green honey from Sabah (B4), while the Simpson index showed that Banggi honey (B4) had higher diversity. Honey samples had significant variance in mycobiome taxonomic composition and abundance. Zygosaccharomyces and Aspergillus were the main genera found in Lombok honey, with percentages of 68.81% and 29.76% respectively. Bali honey samples (B2 and B3) were identified as having a significant amount of the genus Aureobasidium, accounting for 40.81% and 25% of the readings, respectively. The microbiome composition of Banggi honey (B4) showed a high presence of Zygosaccharomyces 45.17% and Aureobasidium 35.24%. The ITS1 analysis effectively distinguishes between honey samples of different origins and its potential as a discriminatory tool for honey origin and authentication purposes.

Synthesis and characterization of honey based hybrid dental implants with enhanced antibacterial activity.

Dental implants are commonly used for tooth replacement tools due to their good oral rehabilitation and reconstruction capacities. Dental implants treatment for natural teeth is desired to achieve successful implants treatment with improved osseointegration through promotion of mammalian cell activity and prevention of bacterial activity. Honey is potentially known for its antimicrobial and antibacterial potential, specifically for burns and wound healing. In this study, honey based silver nanoparticles were synthesized using various concentrations of honey. The synthesized HNY-AgNPs, MSN and HNY-AgMSN were characterized for their surface Plasmon resonance using UV spectroscopy, Hydrodynamic diameter using Zetasizer. Morphology using AFM. Furthermore, surface functional groups were characterized using FTIR spectroscopy at 4cm-1 resolutions. The developed hybrid nanoparticles were tested for their anti-bacterial activity at concentration of 3000µg/mL. It was found HNY-AgNPs was active against both bacterial strains i.e, Streptococcus mutans and streptococcus aureus. HNY-AgNPs-MSN hybrid implant demonstrated potential new type of dental implants, which can offer an effective design for the fabrication of advanced dental implants.

Pollen analysis of honey and pollen stored by Melipona (Melikerria) fasciculata Smith, 1854 (Apidae Meliponini), in an Amazon and Cerrado transition area, Maranhão, Brazil.

The identification of meliponicultural flora is fundamental for the preservation of bees, as well as enabling the development of pollinator management and reforestation programs. In this context, this study aimed to investigate the types of pollen found in the honey and pollen pots of the Melipona fasciculata bee in Arari, State of Maranhão, between August 2022 and July 2023. 40 types of pollen were identified, distributed among 18 botanical families, with Fabaceae standing out (46.15% in pollen pots and 37.86% in honey pots), Myrtaceae (11.53% in pollen and 13.51% in honey) and Rubiaceae (7.69% in pollen and 5.40% in honey). Sapindaceae, in the honey pots, accounted for 5.40%. The other families showed lower percentages, 3.84% in the pollen pots and 2.70% in the honey pots. In terms of similarity, two distinct groups were observed in both the pollen and honey pots. In the pollen pots, group A (May-June ~ 97%) and group B (Feb-Mar ~ 99%) stood out, while in the honey pots, group A (Mar-Apr ~ 98%) and group B (Jun-Jul-Sept ~ 98%) showed the highest percentages. These findings highlight the wide range of resources used by the M. fasciculata species, as well asits preference for Fabaceae and Myrtaceae, due to the diversity and availability of trophic resources. An understanding of the meliponicultural flora is essential to support effective conservation strategies, which aim not only to guarantee the survival of the bees, but also to ensure the continued production of honey, a resource of great importance to local communities.

Evaluating the Therapeutic Properties of Natural Products in Orthodontic and Surgical Treatment of Dentofacial Deformities: A Systematic Review of Clinical Trials.

The use of natural products as alternatives to traditional pharmacological treatments in orthodontics is gaining interest due to their anti-inflammatory, antibacterial, and antioxidant properties. This systematic review synthesizes evidence from clinical trials to evaluate the efficacy of natural products in reducing inflammation and bacterial presence in orthodontic and orthognathic treatment settings. The database search was conducted across PubMed, Scopus, and Embase up to January 2024. The review focused on randomized controlled trials only. The selected studies centered on the anti-inflammatory, antibacterial, and antioxidant effects of natural products, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for data extraction. Nine studies, totaling 358 participants, were included. Significant findings demonstrated a reduction in gingival inflammation by over 40% with the use of Aloe vera compared to chlorhexidine. Another study noted a decrease in bleeding on probing by 13.6 points in the treatment group over placebo. Additionally, honey showed a rapid modulation of plaque pH and significantly reduced bacterial counts of Streptococcus mutans. Furthermore, the use of resveratrol emulgel was linked to substantial improvements in gingival health, with a reduction in the gingival index and probing pocket depth. The results indicate that natural products can significantly enhance orthodontic treatment outcomes by reducing inflammation and bacterial levels. These products offer effective alternatives to traditional treatments and show potential for integration into routine orthodontic care protocols. Further research is encouraged to standardize application methods and dosages to maximize clinical benefits and patient satisfaction.

Antibacterial Effect of Spanish Honeys of Different Botanical Origins against Staphylococcus epidermidis.

Honey is traditionally used for its medicinal properties attributed to its antibacterial and antioxidant effects. It is considered a natural alternative to conventional antibiotics. This effect has been attributed to their physico-chemical properties, as various chemical parameters can synergistically influence this effect. The aim of this study is to assess Spanish honeys of diverse botanical origins for their antibacterial efficacy against Staphylococcus epidermidis, correlating their physico-chemical attributes, (poly)phenol content, and antioxidant activity. The methods included colour determination via two methodologies, acidity, pH, moisture content, and sugar concentration. (Poly)phenol content was quantified using the Folin-Ciocalteau method, while antioxidant activity was evaluated via the FRAP method. Subsequently, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against S. epidermidis were investigated with different concentrations of honeys. The results revealed a direct relationship between honey darkness, (poly)phenol concentration, antioxidant activity, and antibacterial efficacy. Darker honeys exhibited higher (poly)phenol levels, greater antioxidant activity, and consequently, lower MIC and MBC values, showing enhanced antibacterial properties. These findings underscore the potential of honey as a therapeutic agent against S. epidermidis, particularly in wound healing applications to avoid infection. Further research into honey's multifaceted properties is warranted to unveil novel therapeutic avenues in healthcare.

An extra honey polyphenols-rich diet ameliorates the high-fat diet induced chronic kidney disease via modulating gut microbiota in C57BL/6 mice.

Honey is not equivalent to sugar and possess a worldwide health promoting effects such as antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. Nevertheless, the potential impacts of honey on high-fat diet induced chronic kidney disease (CKD) and gut microbiota remain to be explored. Herein a high-fat diet was used to induce a mouse CKD model, and analysis was conducted on liver, kidney, spleen indices, tissue morphology, biochemical parameters, CKD related genes, and gut microbial diversity. The results indicated that significant inhibitory effects on renal damage caused by a high-fat diet in mice and improvement in disease symptoms were observed upon honey treatment. Significant changes were also found in serum TC, TG, UA, and BUN as well as the inflammation-related protein TNF-α and IL-6 levels in renal tissues. Gene expression analysis revealed that honey intake closely relates to gut microbiota diversity, which can regulate the composition of gut microbiota, increase microbial diversity, especially Bifidobacteriales and S24_7 and promote the synthesis of short chain fatty acids (SCFAs). In summary, this study suggests that honey has both preventive and therapeutic effects on CKD, which may be associated with its ability to improve microbial composition, increase microbial diversity, and regulate SCFAs levels.

Influence of Novel Microcapsulates of Bee Products on Gut Microbiota Modulation and Their Prebiotic and Pro-Adhesive Properties.

With the aim to obtain controlled-release systems and to preserve the antioxidant, immunomodulatory, and prebiotic activity of the bioactive compounds, microencapsulation of both honeydew honey and royal jelly into biopolymeric microparticles based on rye bran heteropolysaccharides (HPS) was successfully performed. Honeydew honey and royal jelly microcapsules were prepared by spray-drying method and were characterized in terms of morphology and biological properties. Due to the resistance of the obtained encapsulates to the acidic pH in the stomach and digestive enzymes, the microcapsules showed prebiotic properties positively influencing both the growth, retardation of the dying phase, and the pro-adhesive properties of probiotic bacteria, i.e., Bifidobacterium spp. and lactic acid bacteria. Moreover, as a result of fermentation of the microcapsules of bee products in the lumen of the large intestine, an increased synthesis of short-chain fatty acids, i.e., butyric acid, was found on average by 39.2% in relation to the SCFA concentrations obtained as a result of fermentation of native bee products, thus opening new perspectives for the exploitation of honeydew honey and royal jelly loaded microcapsules for nutraceutical applications.

Long-Term Fasting-Induced Ketosis in 1610 Subjects: Metabolic Regulation and Safety.

BACKGROUND: There is a growing consensus that fasting-induced ketosis has beneficial effects on human physiology. Despite these compelling benefits, fasting-induced ketosis raises concerns in some clinicians because it is often inappropriately compared with the pathologic uncontrolled ketone production in diabetic ketoacidosis. The determinants of the inter-individual differences in the intensity of ketosis during long-term fasting is unknown. METHODS: We monitored daily variations in fasting ketonemia, as well as ketonuria, which is less invasive, in a large cohort of 1610 subjects, fasting between 4 and 21 days with the Buchinger Wilhelmi program, minimally supplemented with ~75-250 kcal (daily fruit juice, vegetable soup, and honey). RESULTS: Ketonuria was detected in more than 95% of fasting subjects from day 4 onwards. Subjects consuming only soups, without fruit juice or honey, exhibited reduced caloric intake (72 kcal instead of 236 kcal) and carbohydrate intake (15.6 g instead of 56.5 g), leading to more intense ketonuria. Participants with high ketonuria were, in the majority, males, young, had a higher body weight, and had lower HDL-C and urea values. They had a larger decrease in blood glucose, glycated haemoglobin levels, body weight, and waist circumference. Furthermore, in the high-ketonuria group, a larger increase in blood uric acid concentration was observed. CONCLUSION: Our study showed that long-term fasting triggered ketosis, never reaching pathological levels, and that ketosis is influenced by age, gender, health, and the level of physical activity. Furthermore, it is modulated but not suppressed by minimal carbohydrate intake. Our study paves the way for better understanding how supplementation can modulate the therapeutic effects and tolerability of long-term fasting.

Improved stability and specificity of baits for oral administration of substances to wild boar.

Oral vaccination is one of the most effective interventions for disease control in wildlife. As a result of the recent global reemergence of African swine fever and ongoing classical swine fever and animal tuberculosis, oral vaccination of Eurasian wild boar (Sus scrofa) receives increased interest. Several baits for wild boar and feral pigs have been described, but developing more stable and personalized formulations is important. This paper proposes a new bait formulation primarily composed of corn flour, piglet feed, sugar, and honey as a binder to obtain improved elasticity. The bait consists of a matrix with no protective coats, has a hemispherical shape (ø 3.4 ×1.6 cm), and displays an anise aroma and blue color. The color and aroma did not affect bait choice by wild boar, while bait coloring contributed to avoid consumption by non-target species (corvids). Baits with the new formulation were significantly more resistant to humidity and high temperatures than previous versions. Simulations suggest that baits with the new formulation are elastic enough to resist impacts from a maximum altitude of 750 m. Thus, the new bait prototype solves several problems of previous bait formulations while keeping a format that can be selectively consumed by piglets and adult wild boar.

Manuka honey's anti-metastatic impact on colon cancer stem-like cells: unveiling its effects on epithelial-mesenchymal transition, angiogenesis and telomere length.

Colorectal cancer often leads to metastasis, with cancer stem cells (CSCs) playing a pivotal role in this process. Two closely linked mechanisms, epithelial-mesenchymal transition and angiogenesis, contribute to metastasis and recent research has also highlighted the impact of telomere replication on this harmful tumor progression. Standard chemotherapy alone can inadvertently promote drug-resistant CSCs, posing a challenge. Combining chemotherapy with other compounds, including natural ones, shows promise in enhancing effectiveness while minimizing side effects. This study investigated the anti-metastatic potential of Manuka honey, both alone and in combination with 5-fluorouracil, using a 3D model of colonospheres enriched with CSC-like cells. In summary, it was observed that the treatment reduced migration ability by downregulating the transcription factors Slug, Snail, and Twist, which are key players in epithelial-mesenchymal transition. Additionally, Manuka honey downregulated pro-angiogenic factors and shortened CSC telomeres by downregulating c-Myc - demonstrating an effective anti-metastatic potential. This study suggests new research opportunities for studying the impact of natural compounds when combined with pharmaceuticals, with the potential to enhance effectiveness and reduce side effects.

Following Regulation, Imidacloprid Persists and Flupyradifurone Increases in Nontarget Wildlife.

After regulation of pesticides, determination of their persistence in the environment is an important indicator of effectiveness of these measures. We quantified concentrations of two types of systemic insecticides, neonicotinoids (imidacloprid, acetamiprid, clothianidin, thiacloprid, and thiamethoxam) and butenolides (flupyradifurone), in off-crop nontarget media of hummingbird cloacal fluid, honey bee (Apis mellifera) nectar and honey, and wildflowers before and after regulation of imidacloprid on highbush blueberries in Canada in April 2021. We found that mean total pesticide load increased in hummingbird cloacal fluid, nectar, and flower samples following imidacloprid regulation. On average, we did not find evidence of a decrease in imidacloprid concentrations after regulation. However, there were some decreases, some increases, and other cases with no changes in imidacloprid levels depending on the specific media, time point of sampling, and site type. At the same time, we found an overall increase in flupyradifurone, acetamiprid, thiamethoxam, and thiacloprid but no change in clothianidin concentrations. In particular, flupyradifurone concentrations observed in biota sampled near agricultural areas increased twofold in honey bee nectar, sevenfold in hummingbird cloacal fluid, and eightfold in flowers after the 2021 imidacloprid regulation. The highest residue detected was flupyradifurone at 665 ng/mL (parts per billion [ppb]) in honey bee nectar. Mean total pesticide loads were highest in honey samples (84 ± 10 ppb), followed by nectar (56 ± 7 ppb), then hummingbird cloacal fluid (1.8 ± 0.5 ppb), and least, flowers (0.51 ± 0.06 ppb). Our results highlight that limited regulation of imidacloprid does not immediately reduce residue concentrations, while other systemic insecticides, possibly replacement compounds, concurrently increase in wildlife. Environ Toxicol Chem 2024;43:1497-1508. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

The Effects of a Dietary Supplement (PediaFlù) Plus Standard of Care in Children With Acute Tonsillopharyngitis/Rhinopharyngitis: Protocol for a Randomized Controlled Trial.

BACKGROUND: A dietary supplement containing Pelargonium sidoides extract, propolis, zinc, and honey has been recently developed and proven to be an effective adjuvant in clinical practice for seasonal diseases and the treatment of respiratory tract disorders. OBJECTIVE: This trial aims to verify the efficacy of the tested dietary supplement in a pediatric population with acute tonsillopharyngitis/rhinopharyngitis (ATR). METHODS: The trial includes children aged between 3 and 10 years with ATR ≤48 h, a negative rapid test for beta-hemolytic streptococcus or culture identification of nasal and/or pharyngeal exudates, and SARS-CoV-2 infection. The dietary supplement tested is an oral solution already on the market based on Pelagon P-70 (equivalent to Pelargonium sidoides d.e. 133.3 mg/100 ml), propolis, zinc, and honey. The product is administered at 5 ml 3 times a day for 6 days for children younger than 6 years and 10 ml 3 times a day for 6 days for children older than 6 years. The study design is open label, randomized, and controlled, with the tested dietary supplement plus standard of care (SoC) versus SoC alone. Patients are enrolled from 3 sites in Romania. The change in Tonsillitis Severity Score and number of treatment failures (using ibuprofen or high-dose paracetamol as rescue medication) are the primary end points. Based on the Tonsillitis Severity Score and the 2-sample comparison of the means formula with a 5% significance level, 80% power, and a minimally clinically important difference of 2 (SD 3.85) points, 120 patients are required. To account for potential screening failures and dropouts, we need to screen a population of approximately 150 children. RESULTS: Patient enrollment began on June 3, 2021 (first patient's first visit), and ended on August 12, 2021 (last patient's last visit). The data collection period was from June 3, 2021, to September 16, 2021. The study was funded in February 2023. Data analysis is currently ongoing (April 2024). We expect the results to be published in a peer-reviewed clinical journal in the third quarter of 2024 and presented at scientific meetings in the last quarter of 2024. CONCLUSIONS: The data from this trial may help identify new adjuvant treatments for children with ATR when streptococcal infection is excluded by a negative rapid test, thereby avoiding unnecessary antibiotic administration. TRIAL REGISTRATION: ClinicalTrials.gov NCT04899401 https://clinicaltrials.gov/study/NCT04899401. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53703.