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Context: The population's use of halophyte plants in traditional medicine is a fundamental component of the exploration of natural remedies. Aims: To analyze a list of halophyte plants and their ethnobotanical characteristics, with a focus on those most commonly used in traditional medicine in the southeast of Algeria (Biskra). Methods: The ethnobotanical surveys were conducted between 2017 and 2019 by interviewing 120 informants using a questionnaire and applying a semi-structured interview methodology. The data was analyzed using ethnobotanical statistical tools, including the informant consensus factor (ICF), citation frequency (CF), use value (UV), family importance value (FIV), relative frequency of citation (RFC), plant part value (PPV), and relative importance (RI), as well as statistics analysis (ANOVA) to compare the use of medicinal plants according to age, gender, and education level. Results: The results of the survey enabled us to identify 12 species distributed across eight different families. The most common family was that of the Amaranthaceae (four species), while the most frequently utilized parts of plants were leaves (PPV = 0.4). Furthermore, decoctions were the most commonly prepared form (33.39%). The highest ICF values were observed for the endocrinological and digestive disease groups (ICF = 0.97). The statistical analysis (ANOVA) revealed a significant difference in the knowledge of the use of halophyte plants in traditional medicine according to age and level of education. Conclusions: The findings of this research suggest that the halophyte flora in our arid study area may offer a promising source for the discovery of new drugs, a prospect that requires further investigation and exploration.

Context: Acrylic resin is used in dentistry as a removable denture base. It can cause various pathologies when not properly cleaned. One of the pathologies is denture stomatitis caused by Candida albicans and Streptococcus mutans accumulation on the acrylic resin surface. Therefore, microbial agents such as denture cleansers are needed. Aims: To evaluate the characteristics of lemongrass (Cymbopogon citratus) nanoparticles as a better antibacterial and antifungal herbal ingredient and their relationship with acrylic hardness. Methods: C. citratus oil nanoparticles (LON) were synthesized and analyzed by transmission electron microscopy (TEM). Electrospray ionization tandem mass spectrometry (ESI-MS) analysis was used to analyze the characteristics of LON bioactive components. Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) against C. albicans and S. mutans and mechanical hardness test of acrylic were performed. Results: The LON concentration of MIC and MBC against C. albicans and S. mutans was 25 and 100%, respectively. One-way ANOVA showed no significant difference between groups of LON with different concentrations (p=0.687). A paired t-test showed significant differences in acrylic resin hardness before and after treatment of LON with 100% (p=0.022) and 50% (p=0.021) concentration. There was no significant difference in hardness before and after treatment of other concentrations of LON and chlorhexidine as positive control. Conclusions: LON treatment on acrylic resin decreased the growth of C. albicans and S. mutans without altering the mechanical properties (hardness).

Context: The Javanese culture includes the consumption of traditional herbal medicine known as jamu. One commonly consumed type of jamu to enhance physical fitness and alleviate fatigue is Beras Kencur, which contains the kencur (Kaempferia galanga) rhizome. Although it has been used for generations, scientific testing on the effects of K. galanga as an anti-fatigue agent remains rare. Aims: To assess the anti-fatigue effects of K. galanga rhizome extract (KGE) through an endurance swimming test conducted on male Wistar rats. Methods: This study involved 30 Wistar rats randomly allocated into 5 groups: a negative control group administered with syrup vehicle, a positive control group receiving 9 mg/kg body weight (BW) of caffeine syrup, and three treatment groups receiving KGE syrup at different doses - dose 1 (37 mg/kg BW), dose 2 (73.5 mg/kg BW), and dose 3 (147 mg/kg BW). The anti-fatigue effect was evaluated based on the duration of struggling in the water in the endurance swimming test. Results: The results demonstrated that the treatment groups exhibited a significant anti-fatigue effect compared to the negative control group. The administration of a syrup formulation containing KGE at doses 1 (37 mg/kg BW), 2 (73.5 mg/kg BW), and 3 (147 mg/kg BW) revealed an anti-fatigue effect on male Wistar rats. Conclusions: The administration of K. galanga demonstrated dose-dependent anti-fatigue activity in rats. The most effective dose was found to be 147 mg/kg body weight in rats.

Context: Doxorubicin is an anticancer drug that can adversely affect the liver. Therefore, seeking medical attention to manage pain and minimize side effects is crucial. Aims: To evaluate the hepatoprotective potential of Vitis gracilis Wall. nanoherbs against doxorubicin-induced hepatotoxicity. Methods: The study included five treatment groups: T0 (negative control), T+ (positive control with doxorubicin alone), TC (doxorubicin + vitamin C at 0.2 mg/kg body weight/day), T125 (doxorubicin + V. gracilis at 125 mg/kg body weight/day), and T150 (doxorubicin + V. gracilis at 150 mg/kg body weight/day). Doxorubicin, administered intraperitoneally at 0.0019 mg/kg body weight once a week for three weeks, induced hepatotoxicity in the T+ group. Results: Serum transaminases were significantly reduced in the T125 and T150 groups, indicative of the hepatoprotective effects of V. gracilis. Immunohistochemical analysis demonstrated the modulation of key markers, with decreased levels of pro-inflammatory tumor necrosis factor-α and increased levels of anti-inflammatory interleukin 10 in the T125 and T150 groups. The activities of oxidative stress markers, including superoxide dismutase and caspase 3, were favorably influenced by V. gracilis nanoherb treatment. Conclusions: These findings suggest that V. gracilis nanoherbs may effectively attenuate doxorubicin-induced hepatotoxicity, evidenced by biochemical and immunohistochemical changes. This study provides a foundation for further exploration of V. gracilis nanoherbs as a potential adjunctive therapy in preventing chemotherapy-associated liver damage.

Context: Polycystic ovary syndrome (PCOS) and thyroid are the most common endocrine disorders affecting women of childbearing age, causing anovulation and infertility. There is an increased prevalence of thyroid dysfunction reported among PCOS women. Aims: To evaluate the benefits of acarbose plus myo-inositol therapy on the thyroid profile of PCOS. Methods: An open-labelled, parallel randomised clinical trial on 80 PCOS women based on inclusion and exclusion criteria was performed at the Department of Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur. Institutional ethics committee approval and prior informed consent were obtained. The trial was registered in CTRI (No: CTRI/2022/04/041877). Group A (n = 38) received metformin 500 mg TID, and group B (n = 39) received acarbose 50 mg TID along with myoinositol 1000 mg BID. Assessment of metabolic and hormonal profile was done at baseline and at the end of six months. Results: Both groups showed significant reductions in luteinising hormone (p

Context: Honey has been employed for its therapeutic attributes since ancient eras, with a history of medicinal utilization, and recent studies have highlighted its diverse clinical applications. The medicinal benefits of honey can be ascribed to various mechanisms, encompassing its osmotic and acidic characteristics, hydrogen peroxide generation, and particular bioactive compounds. While honey generally has a good safety profile, rare risks exist, particularly in infants under one year of age. More rigorous clinical trials and standardized protocols are needed to establish its optimal dosage, application methods, and specific indications. Economic considerations and regional variations in honey composition and quality should also be considered. Aims: To provide an overview of the clinical uses of honey in the medical field, emphasizing its effectiveness and potential therapeutic benefits. Methods: A comprehensive literature search was conducted to gather relevant studies on the clinical applications of honey. The search encompassed various databases and included studies published with the range from May 2001 to May 2023. The selected studies were critically reviewed to extract pertinent information for this critical review. Results: Natural honey comes from two types of honey-producing bees: honeybees and stingless bees. Honey constitutes a multifaceted amalgamation of sugars, enzymes, minerals, vitamins, and bioactive compounds, all contributing to its therapeutic attributes. It exhibits antibacterial, anti-inflammatory, wound healing, and antioxidant effects. In wound management, honey promotes healing, reduces infection rates, and minimizes scarring. It also shows promise in treating bacterial and fungal infections. Furthermore, honey has effectively alleviated symptoms associated with respiratory tract infections, gastrointestinal disorders, and dermatological conditions. Conclusions: Honey possesses multifaceted clinical applications in the medical field. Its diverse therapeutic properties and minimal adverse effects make it an attractive option for various conditions. However, further research is necessary to solidify its role in evidence-based clinical practice, including conducting more rigorous clinical trials, establishing standardized protocols, and considering economic and regional factors.

Context: Mentha species are well known for their health benefits. Products extracted from aromatic plants of this genus (Mentha) are increasingly being studied for their active constituents in order to replace synthetic products that are harmful to health. Aims: To determine the chemical composition, physicochemical parameters, and antioxidant properties of essential oils of M. spicata, M. piperita, and M. pulegium. These plants were collected from three different geographical areas in the Rabat-Sale-Kenitra region of Morocco, with an additional focus on analyzing the fluctuation of their chemical composition based on their locations. Methods: Essential oils obtained through hydrodistillation of the fresh aerial parts of the plants were analyzed via gas chromatography and gas chromatography-mass spectrometry. The antioxidant capacity was measured by several chemical tests: DPPH, ABTS, and FRAP. Results: Multiple major components were identified, showcasing variations in composition between species as well as between plants of the same species. M. spicata was characterized by carvone, piperitone, 1,3,8-p-menthatriene; while M. piperita features linalool, D-carvone, 1,3,8-p-menthatriene; and M. pulegium had a single major component which is pulegone. To the best of our knowledge, it is assumed that a new set of chemotypes may be defined based on the geographical regions studied. The examined essential oils demonstrated notable antioxidant efficacy. Conclusions: These findings suggest the potential use of extracts from these plants as an alternative to synthetic chemical products. Therefore, they could find applications in complementary medicine as well as in the pharmaceutical and food industries.

Context: Perilla frutescens and its dried extract have been employed in food and pharmaceutical manufacturing due to the plant's biological activities, which include antibacterial, anti-allergic, anticancer, antiviral, antioxidant, and antidepressant properties. Despite numerous studies on preparing dry extracts from various medicinal herbs, no research has been conducted to optimize spray-drying conditions specifically for P. frutescens. Aims: To optimize the spray-drying parameters using BCPharSoft software and evaluate the quality of P. frutescens dry extract. Methods: D-optimal design based on four independent variables carrier type (Glucidex, Glucidex: Arabic gum 9:1, Glucidex: Arabic gum 8:2), carrier mass (10, 15, and 20 g), inlet air temperature (160, and 180℃) and flow rate (12, and 14 rpm/min) was applied to investigate the cause-effect relations and optimized preparation process. The drying performance, moisture content, total phenol, and total flavonoid content were investigated as four dependent variables. Results: All independent variables had significant effects on the dependent variables. The optimal parameters of the preparation process included using carrier Glucidex: Arabic gum at a ratio of 9:1, carrier mass of 19 g, inlet air temperature of 161°C, and flow rate of 12 rpm/min. The drying performance, moisture content, total phenol, and flavonoid content of the optimized P. frutescens dry extract were found to be 10.42%, 4.80%, and 90.57 mg GA/g, and 53.55 mg QE/g, respectively. Conclusions: Dried P. frutescens extract has been efficiently produced using the spray-drying technique, establishing a foundation for future manufacturing of pharmaceuticals and functional foods derived from P. frutescens.

Context: Hyperuricemia is the cause of gout in the inflammatory joint condition. The xanthine oxidase enzyme is a therapeutic target for gout treatment because it plays a role in the generation of uric acid. Allopurinol is used to treat gout. It prevents the xanthine oxidase enzyme from producing as much uric acid. When selecting a medication, one must consider the various adverse effects of allopurinol. Phyllanthus emblica plants are among the medicinal plants that can be used as an alternative treatment for gout. Aims: To evaluate isolated compounds from the Phyllanthus emblica as antihyperuricemia candidates. Methods: The isolated compounds were characterized using High-Performance Liquid Chromatography Analysis and Thin Layer Chromatography-Densitometry. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and cupric ion (CUPRAC) antioxidant capacity procedures were used to develop the antioxidant activity index. The ability to inhibit xanthine oxidase was determined using a spectrophotometer. Results: Compound 1 was indicated as rutin having antioxidant capacity with an antioxidant activity index (AAI) DPPH value of 7.89 ± 0.03 and AAI CUPRAC value of 15.83 ± 0.04 stronger than compound 2 (quercitrin) with an AAI DPPH value of 3.72 ± 0.01 and AAI CUPRAC 3.24 ± 0.03. The IC50 for quercitrin's inhibition of xanthine oxidase is 23.85 ± 2.04, which was higher than rutin’s IC50 value of 32.77 ± 4.49 µg/mL. Conclusions: Flavonol glycosides present in the ethanol extract of Phyllanthus emblica leaves gave potent xanthine oxidase inhibitory activity stronger than the extract. Quercitrin gave stronger xanthine oxidase inhibitory activity, but this compound has weaker antioxidant capacity compared to rutin.

Context: Simvastatin can be modified by the formation of multicomponent crystals to increase its solubility. Aims: To compare the solubility of multicomponent simvastatin crystals to pure simvastatin. Methods: The in silico study of simvastatin and the coformers arginine and glycine revealed non-covalent interactions, so multicomponent preparations of simvastatin crystals were prepared by solvent evaporation using a mole ratio of 1:1; 1:2 and 2:1. Results: Each simvastatin-arginine and simvastatin-glycine ratio increased the solubility, with the highest increase observed for the 1:2 ratio compared to pure simvastatin. Conclusions: Simvastatin-arginine multicomponent crystals (1:2) showed the best dissolution profile in phosphate buffer medium pH 7.0 with 67.69% dissolution, while simvastatin-glycine multicomponent crystals (1:2) exhibited the best dissolution profile in buffer media pH 1.2 with 16.19% dissolution. Characterization of the multicomponent crystals revealed a shift in the peaks, a decreased melting point, and enthalpy, indicating decreased % crystallinity and the formation of a new solid phase.

Context: Obesity represents a significant global health challenge. The limited efficacy and possible side effects of available anti-obesity agents highlight the need to find new, effective, and safe agents. Lemongrass (Cymbopogon citratus) is an aromatic herbal plant traditionally used as an anti-obesity agent, but previous review studies did not explain the mechanism in detail. Aims: To evaluate the anti-obesity activity of C. citratus in vitro, in vivo, and in humans. Methods: Full-text relevant articles published between 2003 and 2023 were searched through Google Scholar, PubMed, and Scopus. The American Dietetic Association (ADA) quality criteria checklist was used to assess the risk of bias. Data were systematically analysed and presented in tables and flowcharts. Results: Eighteen articles met the inclusion criteria. The anti-obesity activity of C. citratus could come from various parts of the plant (leaves, stalks, roots, or whole plant). Its hydroalcoholic-based extract was rich in polyphenols, which had anti-obesity activity through inhibiting digestive enzymes, appetite suppression, modulation of lipid metabolism, and adipogenesis inhibition. Its essential oil and citral had anti-obesity activity through energy expenditure stimulation, lipid metabolism modulation, and adipogenesis inhibition. Dietary fibre from C. citratus had anti-obesity activity by inhibiting digestive enzymes and modulating lipid metabolism. Conclusions: The anti-obesity activity of C. citratus could come from its polyphenol content, essential oil, or fibre through the same or different mechanisms, namely inhibition of digestive enzymes, suppression of appetite, modulation of lipid metabolism, inhibition of adipogenesis, and stimulation of energy expenditure.

Context: High-fat diets contribute to oxidative stress and trigger cellular senescence through an imbalance in reactive oxygen species. The potential of coriander (Coriandrum sativum) seed, known for its therapeutic properties against oxidative stress and senescence in obese hearts, has been relatively unexplored. Aims: To evaluate the impact of ethanol-based C. sativum seed extract on oxidative stress, antioxidant levels, and senescence parameters in the hearts of obese rats induced by a high-fat diet. Methods: Twenty-nine male Wistar rats were divided into five groups, fed different diets for 24 weeks, and received C. sativum extract treatment for 12 weeks. This experiment assessed malondialdehyde (MDA) as an oxidative stress marker, antioxidant level by measuring catalase and glutathione (GSH), cellular senescence state by measuring senescence-associated β-galactosidase (SA-β-Gal) activity, and p21 levels in heart tissue. Results: C. sativum seed extract demonstrated a significant reduction in MDA levels in the hearts of obese rats when compared to the control groups. Furthermore, the extract led to a significant increase in catalase and GSH levels in the hearts of non-obese rats, whether on a normal or high-fat diet. Although the C. sativum-treated groups exhibited a downward trend in senescence markers (SA-β-Gal and p21), the observed differences did not reach statistical significance. Conclusions: Ethanol-based C. sativum seed extract exhibited promising potential in mitigating oxidative stress in the hearts of obese rats and enhancing antioxidant levels in the hearts of non-obese rats subjected to both normal and high-fat diets. This underscores the preventive role of C. sativum seed extract in alleviating oxidative stress, particularly in the context of a high-fat diet. However, there was insufficient evidence to conclusively demonstrate a significant improvement in cellular senescence with the use of ethanol-based C. sativum seed extract.

Context: The prevalence of obesity was 8% in 2002 and increased to 11.5% in 2011 in Indonesia. The results of the 2018 Basic Health Research stated that 13.6% of people over the age of 18 were overweight, and 21.8% were obese. Aims: To analyze the effect of intermittent restriction diet and continuous exercise with moderate intensity on individuals exposed to a high-calorie diet. Methods: A randomized posttest control group design was used as the research design, with 6 mice in each group as the study subjects. The groups in this study were the control group with a high-calorie diet (CON+), the intermittent restriction diet group (IRD), the moderate-intensity continuous exercise group (MEX), the combined intermittent restriction diet group and the moderate-intensity continuous exercise (HYB) group. The measured variables were cardiomyocyte diameter and brain natriuretic peptide (BNP) expression. Results: The results of this study were cardiomyocyte diameter CON+ (27.94 ± 5.65 µm), IRD (20.99 ± 11.80 µm), MEX (25.08 ± 9.14 µm), HYB (24.52 ± 5.90 µm) with p=0.578. Expression scores of BNP CON+ (6.00 ± 1.50), IRD (4.67 ± 1.00), MEX (5.42±2.09), HYB (6.27 ± 1.54) with p=0.335. These results showed no significant difference, but the intermittent restriction diet showed the most optimal mean with the lowest mean cardiomyocyte diameter and BNP expression. Conclusions: There was no effect between the combination of an intermittent restriction diet and moderate-intensity continuous exercise on cardiomyocyte diameter and BNP expression. However, there is a potential that an intermittent restriction diet has the optimal effect in preventing changes in the cardiac structure.

Context: Colorectal cancer (CRC) is a major global health concern as innovative therapeutic strategies to enhance treatment outcomes. This study investigates the therapeutic potential of the ethanol extract derived from Volvariella volvacea in combination with cetuximab for CRC. Aims: To evaluate the inhibition of topoisomerase II alpha (TOP2A) and include the peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of cell growth and differentiation. Methods: The method used computational modeling and molecular docking to assess the binding affinities and interactions between the bioactive components, cetuximab, TOP2A, and PPARγ. In vitro experiments were conducted using CRC cell lines. Cells were treated with cetuximab alone or in combination with V. volvacea extract. Cell viability and immunofluorescence were conducted to evaluate the effect of combination therapy on TOP2A and PPARγ. Results: The results unveiled compelling binding interactions, suggesting the potential for dual targeting of TOP2A and PPARγ. The results demonstrated a reduction in cell viability, downregulation of TOP2A, and modulation of PPARγ. These findings indicate the potential of V. volvacea extract as an adjuvant therapy to cetuximab in CRC. Targeting both TOP2A and PPARγ enhances the efficacy of CRC treatment. Conclusions: Moreover, it highlights the importance of harnessing natural compounds and molecular insights to develop innovative combinatorial therapies for complex diseases like CRC.

The present study investigated the anion composition of drinking water from various cities and villages in Armenia, including spring water and tap water samples. The simultaneous separation was achieved for fluoride, chloride, bromide, nitrite, nitrate, sulfate, and phosphate anions with the correlation coefficients >0.998. Validation of the method was carried out in accordance with the requirements of guidelines in terms of selectivity, specificity, system suitability, linearity, accuracy, precision, lower limits of detection and quantitation, robustness, and stability. The method was suitable for routine drinking water quality assessment in line with the national or World Health Organization (WHO) regulations. The validated method was further used to analyze drinking water samples from different regions of Armenia. The observed concentrations for the anions in drinking water complied with the WHO limits for drinking water with some exceptions. The test method can be submitted to quality control laboratories as a convenient and practical tool for routine analysis and monitoring studies.

Canagliflozin was assessed for its anti-inflammatory and antioxidant effects as an anti-aging drug in animal models. 50 Swiss albino male mice were divided into five groups; all groups received their intervention using gastric gavage; group 1 received normal saline for 14 weeks; group 2 received induction by D-galactose 200 mg/kg/day for seven weeks; and group 3 to 5 received the same induction for seven weeks, followed by another seven weeks of investigated drugs; group 3 received Vitamin C (100 mg/kg/day); group 4 received canagliflozin (3 mg/kg/day); and group 5 received canagliflozin (1 mg/kg/day). At the end of 14 weeks, all animals were euthanasiad, and heart and skin tissue were harvested for further analysis. Canagliflozin at both 1 and 3 mg/kg was successful in reducing the levels of inflammatory mediators (TNF-alpha and IL6), reducing levels of MDA, increasing the levels of SOD, and increasing the levels of collagen-1 and elastin in skin tissue. Additionally, 3 mg/kg Canagliflozin showed a better effect compared to 1 mg/kg regarding its effect on IL6, SOD, and elastin. Histopathologically, treatment with both doses of Canagliflozin attenuates abnormalities induced by D-galactose (bizarre, irregular, and hyperchromatic nuclei). Canagliflozin exhibits potent antioxidant and anti-inflammatory effects in living organisms, effectively prevents cardiac and skin damage generated by D-galactose, and possibly reduces aging.

Introduction: Improper protection of an active substance may lead to a loss of its original properties. Many methods can be used to assess the photoprotective properties of drug packaging, including the hemispherical directional reflectance method. The aim of the study is to assess the reflectance value for both the outer and direct packaging containing cefuroxime. Material and methods: Two formulations (Ceroxim and Zinnat) of both expired and unexpired packages were tested with a 410-Solar reflectometer. Three types of measurement areas were analyzed: “white” (white areas of the outer cardboard box), “coloured” (coloured areas of the outer cardboard box) and “blister” (the direct packaging made of aluminium/PVC). Results: The highest reflectance value was found in the 700–1100 nm range for both the unexpired and expired preparations. In the 335–380 nm band, the amount of reflected radiation for the unexpired Ceroxim vs Zinnat packages was as follows: 30% vs 12% from the coloured areas, 39% vs 24% from the white areas and 74% vs 70% from the blisters, respectively. For the expired coloured areas of Ceroxim, the reflectance was significantly higher compared to the unexpired (p < 0.001) in all the spectral bands, except 1700–2500 nm. In contrast, the reflectance of the expired white areas of Ceroxim was higher than the unexpired (p < 0.001) for 480–600 nm, 590–720 nm, 700–1100 nm, and 1700–2500 nm. The blisters of the unexpired Zinnat preparation exhibited greater photoprotective properties than the expired in the 335–380 nm range while the unexpired and expired blisters of Ceroxim did not differ. Conclusions: Based on the reflectance value, blisters and white cardboard packages protect cefuroxime against radiation to a greater extent than coloured packages.

Introduction: Tick-borne encephalitis (TBE) is an infection caused by the tick-borne encephalitis virus transmitted to humans by tick bites. The prevalence of TBE is between 10,000 and 15,000 cases annually and is comparable in Europe and Asia. About 10–20% of all infected persons are children. The vast majority of TBE cases, even up to 70–98% of them, are asymptomatic or undiagnosed. The main clinical symptoms are meningitis (present in 69%), meningoencephalitis (30%), and meningoencephalomyelitis (1%). About 2.1% of patients develop long-term neurological sequelae. Methods: The articles for our work were selected from three open-access databases. The databases were searched using keywords such as: “infection/epidemiology” + “tick bites/tick-borne encephalitis” + “clinical manifestation/pathogenesis/treatment” and “aseptic/viral/bacterial” + “encephalitis/meningitis”. Ultimately, 71 scientific articles and 8 websites, published between 1995 to 2023 were used. State of knowledge: TBE can be differentiated from diseases such as babesiosis, Lyme disease, southern tick-associated rash illness (STARI), chlamydiosis, ehrlichiosis, Colorado tick fever (CTF), Heartland virus (HRTV), Powassan virus (POWV), granulocytic anaplasmosis, tick-borne relapsing fever (TBRF), toxoplasmosis, tularemia, rickettsioses; or similar symptomatology: stroke, brucellosis, infectious mononucleosis (IM), yellow fever (YF), Japanese encephalitis (JE), other viral meningitis, encephalitis, spinal cord inflammation and aseptic meningitis. Conclusions: The differential diagnosis of TBE is extensive and should include a wide range of central nervous system infections caused by both other infectious agents and non-infectious diseases.

The Bruns-Garland syndrome (diabetic amyotrophy) is a rare disorder that affects fewer than 1% of patients with diabetes. It is manifested by unilateral or bilateral pain, weakness and muscle wasting in the proximal part of the lower limbs (proximal motor neuropathy). We present a 72-year-old patient with long-term type 2 diabetes mellitus and with the Bruns-Garland syndrome. All the symptoms, including neurological manifestations, were reversible and resolved after the implementation of intensive treatment. Optimizing diabetes treatment, rehabilitation, pain management and the use of benfotiamine and alpha-lipoic acid preparations were crucial to accelerate the treatment effects of diabetic amyotrophy.

Introduction: In recent times, there has been an increased number of published materials related to artificial intelligence (AI) in both the medical field, and specifically, in the domain of neurosurgery. Studies integrating AI into neurosurgical practice suggest an ongoing shift towards a greater dependence on AI-assisted tools for diagnostics, image analysis, and decision-making. Material and methods: The study evaluated the performance of ChatGPT-3.5 and ChatGPT-4 on a neurosurgery exam from Autumn 2017, which was the latest exam with officially provided answers on the Medical Examinations Center in Łódź, Poland (Centrum Egzaminów Medycznych – CEM) website. The passing score for the National Specialization Exam (Państwowy Egzamin Specjalizacyjny – PES) in Poland, as administered by CEM, is 56% of the valid questions. This exam, chosen from CEM, comprised 116 single-choice questions after eliminating four outdated questions. These questions were categorized into ten thematic groups based on the subjects they address. For data collection, both ChatGPT versions were briefed on the exam rules and asked to rate their confidence in each answer on a scale from 1 (definitely not sure) to 5 (definitely sure). All the interactions were conducted in Polish and were recorded. Results: ChatGPT-4 significantly outperformed ChatGPT-3.5, showing a notable improvement with a 29.4% margin (p < 0.001). Unlike ChatGPT-3.5, ChatGPT-4 successfully reached the passing threshold for the PES. ChatGPT-3.5 and ChatGPT-4 had the same answers in 61 questions (52.58%), both were correct in 28 questions (24.14%), and were incorrect in 33 questions (28.45%). Conclusions: ChatGPT-4 shows improved accuracy over ChatGPT-3.5, likely due to advanced algorithms and a broader training dataset, highlighting its better grasp of complex neurosurgical concepts.

Odontogenic foci are bacterial inflammatory changes, whose primary center is located in the area of the causal tooth. Various mechanisms result in the formation of secondary foci or systemic infections. Reliable diagnostics and elimination of the aforementioned foci are essential in the process of preparing patients qualified for ophthalmic surgery, organ transplants, dialysis, and anti-cancer therapy. Particular vigilance should also be exercised in the cases of patients with cardiovascular disease, especially those at high risk of infective endocarditis due to cyanotic congenital heart disease or an implanted valve prosthesis. The review paper presents the justification for conducting in-depth diagnostic and therapeutic procedures in the aforementioned groups of patients, citing methods for identifying the foci as well as methods for their elimination. The basic and overarching goal of the presented actions is to avoid complications in the form of severe infection and death.

Introduction: Traditional Eastern medicine (TEM) is becoming increasingly more popular in highly developed Western countries as an alternative form of supporting health and body care. Many herbs used in this medical practice possess antioxidant, anti-inflammatory and immunomodulatory effects. The skin aging process may progress with age, when collagen and elastin fibers gradually decrease. Excessive exposure to UV radiation, resulting in an increase in the production of free radicals, leads to damage at the molecular level to numerous structures in the body including the acceleration of skin aging. Material and methods: The content of polyphenolic compounds (among others: phenolic acids and flavonoids), antioxidant potential (ABTS, DPPH and FRAP assays) as well as the influence on the activity of enzymes, collagenase and elastase, were determined in infusions obtained from Gynostemma pentaphyllum, Tinospora cordifolia, Astragalus membranaceus, Codonopsis pilosula, Asparagus racemosus and Ocimum sanctum. Results: The highest content of polyphenolic compounds and the strongest antioxidant properties were observed in the infusions obtained from the O. sanctum herb, while the greatest ability to inhibit collagenase and elastase was observed in the infusions obtained from the T. cordifolia leaves. Conclusions: Infusions from the O. sanctum herb and T. cordifolia leaves may have a potentially beneficial effect on the skin and may be used in anti-aging formulations.

This study explores the successful implementation of activities aimed at scaling traceability for COVID-19 and routine immunization (RI) vaccines to the local government area and selected healthcare facilities in Nigeria, funded by the Bill and Melinda Gates Foundation. The study was executed by the National Agency for Food and Drug Administration and Control (NAFDAC) and sought to enhance supply chain systems by deploying advanced traceability mechanisms and ensuring real-time stock visibility. The article discusses the accomplishments, challenges, and regulatory framework of NAFDAC, emphasizing GS1 technology-driven traceability, and presents the results of the field scanning activities conducted in July 2023. The approach involved a phased public sector pilot, showcasing the feasibility and challenges of tracking vaccine movement through the supply chain. The result shows the detection of 43 unique products across 1022 facilities from a total of 110,113 scans, offering valuable insights into vaccine distributions. The strategic goals of the project aligned with developing safety surveillance systems in low- and middle-income countries (LMICs) to facilitate patient access to global health products. Similarly, significant improvement in traceability through automated data capture (barcode scanning) and expanded coverage for COVID-19 and selected RI vaccines in Nigeria was found. Against this background, the information derived from this report will build confidence in patients regarding vaccine authenticity, establish a transparent and robust supply chain, and foster pharmacovigilance capability through integration with the track-and-trace systems. Thus, the study provides invaluable insights and opportunities for global health practitioners, policymakers, and researchers to incorporate track-and-trace into regulatory systems by other national regulatory authorities.

Liver cirrhosis and its complications constitute one of the most important causes of hospitalization in internal medicine departments. Liver cirrhosis is not a homogeneous disease entity, but is the final stage of many different liver diseases, and the most important causes leading to the development of liver cirrhosis are alcoholic liver disease and viral hepatitis. One of the typical complications of liver cirrhosis are symptoms of bleeding diathesis. The most common bleeding complication in patients with liver cirrhosis is bleeding from the upper gastrointestinal tract. The aim of this publication is to present a case report of a 32-year-old man in the terminal stage, hospitalized due to decompensated alcoholic cirrhosis of the liver, who during hospitalization developed a spontaneous large hematoma in the rectus abdominis muscle on the left side. The presented case report shows that in the care of patients with decompensated liver cirrhosis, vigilance must be maintained to recognize bleeding complications, including those with an atypical clinical course.

Introduction: The abrupt transition to remote learning caused by the COVID-19 pandemic clearly indicated the need to implement radical technological and institutional changes to the current approach to teaching. Virtual reality (VR) and artificial intelligence (AI) assisted programs have emerged as the new and effective methods utilized in education and medical training. Material and methods: The Virtual Clinic (VC) is a new online application developed by Polish medical universities which implement AI algorithms to teach students the medical interview including obtaining patients medical history, performing a physical examination as well as diagnostics and treatment planning. Our study enrolled 164 medical students who tested the VC and completed an online questionnaire. Results: The results of the survey showed that 93.9% of the respondents believe that the VC will prove effective as an educational tool supporting teaching at faculties of medicine and health sciences. Conclusions: Our preliminary experiences suggest that the use of AI assisted programs such as the VC seems highly anticipated and justified in medical higher education.

Tiina Liipo,1,2 Tuire Prami,2 Ilona Iso-Mustajärvi,2 Mari Pölkki,2 Anne Juppo1 1University of Helsinki, Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, Helsinki, Finland; 2Oriola, Espoo, FinlandCorrespondence: Anne Juppo, University of Helsinki, Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, Viikinkaari 5 E, 00014 University of Helsinki, Helsinki, Finland, Tel +358505306147, Email anne.juppo@helsinki.fiBackground: Finnish authorities have published specific instructions for prescribing, handling, and dispensing unlicensed medicines and for the associated communication with patients. However, there is a clear research gap concerning the quality of medication counselling given by doctors and especially pharmacists to patients who are prescribed unlicensed medicines. The success of such counselling was studied with a survey for both pharmacy staff and patients.Methods: The survey was conducted in 2022 with two electronic semi-structured questionnaires, one for patients (or caregivers of underaged patients) purchasing medicines with special or fixed-term special permits from community pharmacies in Finland and one for the pharmacy staff dispensing such medication.Results: In all, 49% of the 389 pharmacists did not know if the prescribing doctor had given any counselling to the patient, and 52% of the pharmacists had not given any counselling to the patient themselves. Still, 51% of the pharmacists considered that the patient had received sufficient medication counselling. Almost every one of the 36 patients expressed that they had received medication counselling, 61% of them from the prescribing doctor and 53% from a pharmacist.Conclusion: Medication counselling on unlicensed medicines should be improved to ensure their safe and effective use. This survey revealed that many patients did not receive any such medication counselling as required by the Finnish Medicines Decree.Plain Language Summary: If patients need medicines that are not available in their own country, they can be treated with unlicensed medicines imported from abroad.Community pharmacies deliver tens of thousands of packages of unlicensed medicines yearly in Finland, and we wanted to find out whether patients receive appropriate information about their use.We contacted pharmacy staff and patients using unlicensed medicines and conducted an electronic survey to ask about their experiences on whether patients receive sufficient information on these medicines.Almost every patient participating the survey felt that they had received counselling on their unlicensed medication, more often from a doctor than a pharmacist, despite most of the pharmacist responding to this survey had a lot of work experience and dispensed these medicines regularly.Patients have the right to receive supporting information to ensure the effectiveness and safety of their medication, and pharmacists have a crucial role in ensuring this.Based on this study, we suggest that pharmaceutical companies and authorities should provide reliable supporting material on the use of unlicensed medicines for doctors, pharmacists, and patients, bearing in mind the respective information needs of these groups.Keywords: unlicensed medicines, medicines with special permit, medication counselling, survey

Abstract Background Cancer and diabetes mellitus are quite common diseases found together worldwide. A considerable amount of evidence is available for the rapid development and presentation of various types of cancer in the type 2 diabetes mellitus (DM2) population as compared with the population without diabetes. The objective of the study is to formulate and evaluate 5-fluorouracil (5-FU) and metformin (MET) nanoparticles (NPs) and to establish the characteristic features of the biodegradable NPs. 5-FU and MET NPs with chitosan as a biodegradable polymer were formulated by the ionotropic cross-linking method. 0.25 gm of MET and 0.25 gm of 5-FU were dissolved in 100 ml of distilled water, and stock solution was prepared. 5 ml of stock solution was slowly mixed into the chitosan solution to obtain the mixture of drugs and chitosan. The tripolyphosphate reserve liquid was dripped slowly into the chitosan solution with constant stirring until the opaline appearance was noticed in the mixture, then filtered, and dried. The NPs were evaluated for their physical properties and drug release kinetics. Cell proliferation assay was done using human colorectal carcinoma cell line (HCT 116). Results The formulation composed of 1.5 w/v of chitosan, 0.25 w/v of MET, and 5-FU had an average particle diameter of 198.7 nm. The polydispersity index was 0.757. Thermal and infrared spectroscopy results indicated the drugs and polymers selected for the formulation were unique without any identifiable interaction. The NPs were spherical in appearance, with numerous pours on the surface, which was evident when microscopically examined. Uniformity in drug release was observed, and the formulation demonstrated excellent release kinetics. HTC 116 cell line confirmed that the maximum percentage of cell death and minimum viability of cells were observed while using the combination of MET and 5-FU-NPs as compared to the pure MET or 5-FU alone. Conclusion MET and 5-FU-loaded chitosan NPs were found to have excellent physiochemical properties, particle size, and drug release from the polymer in a controlled manner. Half-maximal inhibitory concentration value (IC50) of MET and 5-FU-NPs was found to be significantly less as compared to MET and 5-FU alone or the combination.

Abstract Background Infections caused by biofilm-forming bacteria have significantly linked to dental plaque and caries. The aim of this study is to assess efficacy of some natural compounds in inhibition and eradication of biofilm formed by bacterial isolates from dental infections. Results Bacterial isolates were recovered from dental plaque/caries and identified using standard microbiological tests and 16S rDNA sequencing. The isolated bacterial strains include Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Klebsiella pneumoniae, and Escherichia coli. The antibiotic susceptibility was determined by disk diffusion method and revealed that the majority of isolates showed high antibiotic resistance, and 61% of isolates were found to be multidrug resistant. The biofilm formation capacity of isolates was investigated using microtiter plate assay. Among the 77 bacterial isolates, seventeen showed moderate biofilm formation capacity, twenty-two showed near-moderate, thirty-four had weak biofilm-forming capacity, and four were non-biofilm producers. The antibiofilm activity of tested compounds (rose and jasmine oils, propolis, vanillin, and vinegar) was evaluated against isolates with highest biofilm-forming capacity. The in vitro antibiofilm ability of tested substances were investigated alone or in combination with each other to evaluate their ability to prevent biofilm formation or destroy preformed single-/multispecies biofilms. Finally, antibiofilm ability of tested combination was evaluated ex vivo on natural teeth. Our results showed that vanillin in combination with rose or jasmine oils showed promising biofilm inhibition and biofilm eradication activities in both the in vitro and ex vivo models. Conclusions Dental plaque and caries can be successfully prevented using combination of vanillin with rose or jasmine oils, and these compounds can be incorporated in new anticaries dental formulations.

Abstract Background The main aim of the current study is to develop, synthesize, in silico, in vitro and in vivo potentials of N-[5-(1,3,4,5-tetrahydroxycyclohexyl)-1,3,4-thiadiazole-2-yl] benzamide derivatives for a possible anticancer drug to improve their efficiency and selectivity against cancer cells, computational approaches aided in the rational design of these chemicals. Spectroscopic methods verified the chemical structures of the target compounds. The structures of the synthesized analogs were determined by elemental analysis, IR, 1H NMR, 13C NMR and MS. Structure shows the presence of 1,3,4, thiadiazole also responsible for anticancer activity. The 10 analogs were synthesized and showed encouraging anticancer efficacy in preliminary biological evaluation, suggesting they might be suitable lead candidates for more optimization and preclinical exploration. Result N-[5-(1,3,4,5-tetrahydroxycyclohexyl)-1,3,4-thiadiazole-2-yl] benzamide derivatives were synthesized (5a-5j) showed an optimum IC50 value in in vitro activity by SRB assay using MCF-7 as a strain, and the few selected analogs 5b,5 g & 5 h were subjected for in vivo anticancer activity by DMBA induction of tumors in mice. Conclusion Through a computational and experimental approach, this study results a way for newer derivatives for the class of anticancer drugs.

Abstract Background The prevalence of cognitive diseases, including Alzheimer’s disease and other forms of dementia, poses a significant global health challenge due to the limited availability of effective therapeutic options. Recent years have witnessed a growing emphasis in research on the exploration of natural compounds and their derivatives as prospective therapeutic agents for cognitive impairments. Main body Xanthotoxin, a furanocoumarin compound derived from botanical sources, exhibits promising therapeutic promise in several neurological conditions such as depression, neuronal inflammation, Alzheimer’s disease, vascular cognitive impairment, epilepsy, and Parkinson’s disease. This potential stems from its notable neuroprotective, antioxidant, and anti-inflammatory characteristics. The present study offers a comprehensive examination of the acquisition of XAT from both natural sources and synthetic means. It delves into the significance of XAT in the treatment of cognitive disorders and delineates potential avenues for future research in the domain of XAT and cognitive disorders. Conclusion Ongoing research and advancements in the field of XAT have the potential to enhance its use as a potent therapeutic intervention for cognitive impairments, consequently enhancing the holistic welfare of those afflicted by these incapacitating disorders.

Abstract Background Denosumab and alendronate had a positive impact on bone mineral density (BMD) preservation after kidney transplantation. However, the cost-effectiveness of these agents in the context of kidney transplantation remains largely unexplored. We have conducted a cost-effectiveness analysis to compare the cost and the clinical outcomes of adding subcutaneous (SC) 60 mg denosumab every 6 months vs. oral weekly 70 mg Alendronate, to the standard care therapy (vitamin D and calcium) in renal transplant recipients (RTRs). The impact of both drugs on BMD t-score improvement and fracture prevention was investigated. A decision-analysis model from a health care payer perspective was applied. Results The cost-effectiveness analysis has shown that alendronate add-on to the standard therapy was the most cost-effective regimen, in terms of BMD improvement and fracture prevention with an incremental cost-effectiveness ratio (ICER) of $154/patient/year. The one-way sensitivity analyses have delineated the change in cost-effectiveness when alendronate retail unit price was increased by 25% and 50%, or when denosumab retail unit price was decreased by 25% and 50%. The model was sensitive to the uncertainties (95% confidence interval) in the probabilities of fracture prevention and the probabilities of attaining the desired outcome. Conclusion The model suggests that oral once weekly alendronate add-on regimen to standard therapy seems to be substantially more cost effective than twice yearly SC denosumab in terms of BMD improvement and fracture prevention in RTRs. Longer time horizon models with longer follow-up periods for fracture risks and adverse events are warranted to validate these data.

Objectives: The research sought to examine the antibacterial properties of the conditioned media derived from dental pulp mesenchymal stem cells (DPSC) that were treated with curcumin. Methods: An investigation of the physicochemical characteristics of curcumin nanoparticles was conducted utilizing scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and mapping techniques. The optimal dose of curcumin for treating DPSC cells was determined using the MTT test. The study investigated the antioxidant properties of curcumin on DPSC cells by measuring ROS. Two groups were isolated, one without treatment (control) and the other treated with curcumin. The antibacterial and antifungal properties of the supernatant culture medium of DPSC cells were then investigated. Results: The present study results indicate that curcumin possesses suitable physicochemical properties, including morphology and purity. Additionally, it exhibits no toxicity at doses ranging from 0 to 1.25 (μg/ml) and displays antioxidant properties at the IC50 concentration. Furthermore, it increases DPSCs. The antimicrobial results demonstrate that CM-CUR, at various concentrations, reduces the viability of Streptococcus mutans (S. mutans) and inhibits the growth of Candida albicans (C. albicans) by 85%. Conclusion: The research results indicate that the combination of CM-CUR is suitable for antibacterial and antifungal applications in dentistry to enhance human health.

Multiple myeloma is a hematological malignancy characterized by the clonal proliferation of plasma cells. Recent advancements in treatment strategies have led to a significant shift in the management of this malignancy. Venetoclax, an apoptosis inducer, has emerged as a promising therapeutic option for multiple myeloma. Fatty acid oxidation (FAO) is one of the metabolic reprogramming events that occurs because of mutations in certain genes and thus plays a crucial role in cancer progression. Teglicar, a reversible inhibitor of FAO, targets carnitine palmitoyl transferase 1 (CPT1) and has shown potential in cancer treatment due to its interaction with apoptotic regulators such as Bcl-2. In this study we investigated the in vitro anti-cancer activity of teglicar, in myeloma cell lines (RPMI 8226 and U266B1). Our findings revealed a significant inhibition of RPMI 8226 cell viability with an IC50 = 50 µM, but at a higher concentration for U266B1 cells. Notably, the combination of teglicar with venetoclax showed a synergistic effect. Although both cell lines were known to be resistant to venetoclax, teglicar significantly reduced IC50 of venetoclax by 5.33 and 1.7 folds in RPMI 8226 and U266B1 respectively. In addition, single agent and combination treatment were associated with a significant increase in apoptosis in both cell lines. However, the combination therapy had no significant effect on reactive oxygen species (ROS) levels in either cell lines. Our results suggest that the combination of teglicar and venetoclax holds promise in multiple myeloma through induction of apoptosis. This study sheds light on the potential therapeutic implications of targeting FAO, specifically through CPT1 inhibition, in conjunction with apoptosis inducers for enhanced anticancer effects in multiple myeloma.

Objetivo: revisar y validar un cuestionario de conocimientos sobre manejo de insulinas inyectables (JH-SEFAC) por pacientes con diabetes para utilización en las farmacias comunitarias (FC). Métodos: diseño del estudio: observacional transversal en FC españolas durante el primer semestre de 2023. Criterios de inclusión: pacientes con diabetes, mayores de edad, en tratamiento con insulina. Diseño del cuestionario: un grupo nominal de FC revisó y pilotó el cuestionario inicial para determinar su viabilidad. Fue aprobado por el CEIC de Aragón (PI22/375). Validación de contenido: por un grupo multidisciplinar de expertos en diabetes, mediante un cuestionario de evaluación ad hoc de 10 preguntas (escala Likert de 1-5). Fiabilidad: mediante el índice de consistencia interna (alfa de Cronbach) y el coeficiente de correlación intraclase (CCI). Reproducibilidad (test/retest): se compararon los resultados del cuestionario administrado dos veces separadas 2-3 semanas al grupo de pacientes. Colaboraron farmacéuticos miembros del Grupo de Trabajo de Diabetes de SEFAC. Muestra: se calculó en 127 sujetos (IC del 95 % y precisión del 10 %). Resultados: 20 FC de 13 CCAA incorporaron 131 pacientes. La valoración de los expertos fue de 4,52 sobre 5 (90,4 %). El test Keiser-Meyer-Olkin fue de 0,626 y la prueba de Bartlett resultó significativa (p

Introducción: la revisión de medicamentos en el servicio de seguimiento farmacoterapéutico (SFT) parece ser un método efectivo para estudiar la seguridad del medicamento a largo plazo en el paciente ambulatorio. Las reacciones adversas a medicamentos (RAM) que no son inmediatamente evidentes son difíciles de identificar y en ocasiones se pueden confundir con algún cuadro más común. El diagnóstico erróneo por no asociar los síntomas de RAM a su causa farmacológica origina su enmascaramiento y dificulta su detección. Objetivos: detectar en el servicio de SFT errores diagnósticos relacionados con la no detección de reacciones adversas a estatinas Material y Método: los datos obtenidos de la revisión de medicamentos en el SFT se agruparon para su análisis. Los pacientes que recibieron el servicio se seleccionaron con la herramienta rápida de “cribado DLGM”, siglas de “Diagnóstico lastre generado por medicamentos”, que nos permite describir RAM cuando sus síntomas son atribuidos a una patología concomitante o no, sin considerar a la medicación como causa subyacente. Se muestran solo los resultados de pacientes mayores de 60 años que, tras un período prolongado de uso de estatinas, presentaron gradualmente trastornos musculoesqueléticos (TME) y otros síntomas descritos teóricamente como posibles RAM. Resultados: en el 66 % de los casos, correspondiente a 14 pacientes de un total de 21 estudiados, el médico modificó el tratamiento y en el 92 % de estos casos se observó mejoría y disminución del consumo de fármacos analgésicos, antiinflamatorios y otros empleados para tratar síntomas de RAM. Conclusiones: el cribado DLGM identificó RAM ocultas en el 62 % de pacientes.

El envejecimiento es una realidad global que va acompañada del incremento de la polifarmacia. En esta etapa vital surgen como actores relevantes los cuidadores, pues su intervención impacta en la seguridad del proceso de uso de los medicamentos y en la calidad de vida del paciente al que asisten. Cómo el conocimiento sobre los tratamientos que los cuidadores supervisan para el paciente a su cargo condiciona los resultados en salud de los medicamentos, este estudio tiene como objetivo principal la caracterización de los cuidadores de pacientes usuarios de analgésicos opioides y la identificación de factores que incrementen el riesgo de aparición de Problemas Relacionados con la Medicación (PRM). Los resultados revelan que el perfil del cuidador afecta en resultados en salud de este grupo terapéutico, tanto en la prevalencia como en tipo de PRM. De los 63 pacientes usuarios de analgésicos opiáceos en seguimiento farmacoterapéutico durante este estudio, 17 (27 %) contaban con cuidadores. La figura del cuidador de este estudio se erige como predominantemente femenina (61,1 %). Atendiendo a PRM y parentesco, se observa mayor prevalencia de PRM cuando son hijos o personal externo. Analizando la farmacoterapia de estos cuidadores se detecta que un 4,8 % ha iniciado un tratamiento antidepresivo y 3,2 % tratamiento hipnótico tras convertirse en cuidador de estos pacientes. El Test Zarit revela que 29,4 % de los cuidadores de estos pacientes manifiestan sobrecarga. Concluimos que la Atención Farmacéutica debe considerar la oportunidad y pertinencia de diseñar e implementar protocolos de intervención y educación enfocados en los cuidadores.

Introducción: los Centros de Información de Medicamentos (CIM) actúan como fuente de información técnica y científica de los medicamentos y productos sanitarios, promoviendo así su uso racional. Objetivos: analizar y categorizar, de acuerdo con criterios estandarizados, las consultas farmacoterapéuticas, grupos terapéuticos y principios activos que se consultan de forma más frecuente en el CIM del Muy Ilustre Colegio Oficial de Farmacéuticos de Valencia (MICOF). Metodología: se realizó un estudio observacional ambispectivo y transversal desde el 1 de junio de 2021 hasta el 1 de junio de 2022. Se registraron y analizaron un total de 445 consultas realizadas por farmacéuticos de la provincia de Valencia, recogiéndose los siguientes datos: principio activo (PA), grupo terapéutico ATC-4 y categoría farmacoterapéutica de la consulta. Resultados: las categorías más consultadas fueron comercialización y seguridad, siendo los Inhibidores de la Bomba de Protones (IBPs, A02BC) y Antagonistas de la Vitamina K (AVKs, B01AA) los grupos farmacológicos más consultados, 2,7 % y 2,3 % del total de consultas, respectivamente. Respecto a la categorización, el 90,0 % de las consultas sobre acenocumarol fueron por interacciones; mientras que el 33,3 % de las consultas sobre IBPs fueron referentes a la comercialización. Conclusiones: el análisis de las consultas recibidas ha permitido identificar los grupos terapéuticos, principios activos y categorías farmacoterapéuticas que generan un mayor número de consultas. Esta información es valiosa para mejorar la eficiencia de las respuestas en el CIM, aportando uniformidad y reduciendo errores. Además, proporciona una base de datos amplia que facilita la integración normalizada de la información.

Los organismos reguladores, como la Food and Drug Administration (FDA) y la European Medicines Agency (EMA), reconocen la farmacogenética como una herramienta clave en sus guías farmacológicas para el asesoramiento farmacéutico. En este contexto, la farmacia comunitaria tiene un papel esencial al responder a esta necesidad asistencial, lo que podría traducirse en una mejora significativa en la calidad de vida de los pacientes al evitar tratamientos ineficaces o potencialmente contraindicados. En este trabajo, hemos llevado a cabo una revisión sistemática de la evidencia científica disponible sobre las interacciones entre fármacos y genes de interés para la farmacia comunitaria. Se han identificado los principales genes y polimorfismos relacionados con la respuesta y los efectos adversos a tratamientos comunes en atención primaria. Finalmente, proponemos un modelo para la implementación de servicios de farmacogenética en la farmacia comunitaria.

Descripción del caso: paciente (29 años) con eritema palmoplantar, acude a la farmacia comunitaria (FC) solicitando una crema para atopia. Evaluación: la paciente accedió al Servicio Profesional de Indicación Farmacéutica (SPIF), evidenciando que las manifestaciones aparecieron a las 24 h del comienzo de tratamiento odontológico con amoxicilina 1 g/12 h e ibuprofeno 600 mg/8 h sin más medicación concomitante. Intervención: tras explicar a la paciente que las manifestaciones cutáneas podrían ser debidas a una reacción adversa a la medicación, se cumplimentó el informe de derivación al médico mediante SEFAC-expert. Resultados: La paciente acudió a urgencias donde fue tratada con corticoide intravenoso y prescripción de cetirizina 10 mg. El odontólogo cambió el betalactámico por un macrólido (azitromicina) y el ibuprofeno por paracetamol. Desde la FC se hizo seguimiento de la evolución de los síntomas, que tardaron 72 horas en desaparecer. Las pruebas de alergia sugirieron evitar betalactámicos, cefalosporinas y arilpropiónicos sin ser concluyentes. Meses después, la paciente sufrió síntomas similares tras inhalar un espray desinfectante y se confirmó el diagnóstico de alergia. Conclusiones: la FC identificó y derivó de manera inmediata mediante SPIF un caso de hipersensibilidad en una paciente susceptible a RNM. La cercanía del farmacéutico comunitario facilita la detección temprana de RNM y el SPIF ayuda a registrar la intervención y el seguimiento, aumentando la seguridad de los pacientes.

Presentación del caso: mujer de 73 años, independiente, con antecedentes médicos de psicopatología en tratamiento y no adherente. Tras una caída, sufre fractura de antebrazo y, en dicho contexto, se sospechó de un abuso de psicofármacos y de antiinflamatorios no esteroideos. Estudio y evaluación del caso: el estado de situación de la paciente se observó un abuso del tratamiento hipnótico-ansiolítico que puede estar relacionado con su reciente caída y fractura de antebrazo. Su mala adherencia terapéutica conllevó a un mal control de sus problemas de salud y a la aparición de posibles Resultados Negativos Asociados a la Medicación (RNM) que empeorarían su estado de salud. Intervención: se derivó a su médico de atención primaria con un informe de interconsulta farmacéutico, indicando los posibles RNM y alternativas terapéuticas en el tratamiento antihipertensivo y antidepresivo. Resultados: el médico de Atención Primaria relacionó la caída y subsecuente fractura del antebrazo, así como la descompensación de su patología basal, con el mal cumplimiento terapéutico. Se aceptó la propuesta de intervención farmacéutica, monitorizando la presión arterial para su correspondiente reajuste posológico. Se retiró el bupropión, se comenzó una desprescripción gradual de las dosis de benzodiazepinas y se sustituyó el antiinflamatorio por analgésicos opioides. Consecuentemente, la paciente mejoró significativamente su salud cardiovascular y aumentó su autonomía personal y autocuidado. Conclusiones: la comunicación multidisciplinar entre los profesionales sanitarios permite un mejor control de la enfermedad cardiovascular y una optimización de la farmacoterapia, lo que contribuye a mejorar su estado de salud.

Abstract Objective Darunavir (DRV) is a P-glycoprotein (P-gp) inhibitor. Dabigatran etexilate, prodrug of the anticoagulant dabigatran, is a P-gp probe substrate. This study evaluated the effect of single and multiple doses of DRV, coadministered with cobicistat (COBI) or ritonavir (rtv), on the pharmacokinetics (PK) of single-dose dabigatran etexilate. Methods This was an open-label, fixed-sequence, single-center, 2-panel, phase 1 study in which healthy adult participants were equally divided over 2 panels. In panel 1, participants received single and multiple doses of DRV/COBI 800/150 mg coadministered with single-dose dabigatran etexilate 150 mg. In panel 2, participants received single and multiple doses of DRV 800 mg + rtv 100 mg coadministered with single-dose dabigatran etexilate 150 mg. Key PK parameters evaluated were maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinity (AUCinf) for free and total dabigatran. Results Overall, 28 participants were enrolled and treated (n = 14 per panel). Dabigatran Cmax and AUCinf increased 2.64-fold after a single dose of DRV/COBI and 1.99- and 1.88-fold, respectively, after multiple doses of DRV/COBI. Dabigatran Cmax and AUCinf increased 1.64- and 1.72-fold, respectively, after a single dose of DRV + rtv and 1.22- and 1.18-fold, respectively, after multiple doses of DRV + rtv. In both panels, the most commonly reported adverse events were diarrhea and headache. Conclusion Findings of increased dabigatran exposure with DRV/COBI or DRV + rtv coadministration indicate an inhibitory effect of single-dose boosted DRV on P-gp, and a mixed inhibitory/inductive effect of multiple doses of boosted DRV on P-gp. Trial registration ClinicalTrials.gov, NCT04208061 . Registered December 19, 2019

Abstract Background The therapeutic landscape for ulcerative colitis (UC) has recently broadened to include anti-TNFα, anti-integrin, and anti-IL-12/23p40 antibody agents. These biological agents are tailored to individual patient profiles. However, some patients cease biological treatment. This study investigates factors influencing the discontinuation of biological treatment in UC patients. Methods This retrospective single-cohort study encompasses UC patients who commenced treatment with biological agents like infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab from April 2019 to March 2022. Patients were categorized into continuation and discontinuation groups based on their one-year treatment status. Baseline characteristics were compared between the groups. Results Of the 116 UC patients, 102 were included in the study. Among these, 74 (72.5%) continued and 28 (27.5%) discontinued biological therapy. Discontinuation rates for infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab were 33.3%, 25.0%, 50.0%, 30.2%, and 15.6%, respectively. The primary discontinuation reason was lack of efficacy (85.7%), followed by adverse events (7.1%), pregnancy (3.6%), and death (3.6%). The discontinuation group had a significantly lower rate of concomitant thiopurine compared to the continuation group (28.6% vs. 56.8%, p = 0.0132). Multivariable analysis revealed that concomitant thiopurine was independently associated with therapy continuation (p = 0.0075). Conclusion The study indicates that concomitant thiopurine significantly correlates with the continuation of biological therapies in UC patients, underscoring the importance of concomitant thiopurine in sustaining biological therapy. Further studies are warranted to assess the efficacy of combination therapy.

Abstract Background The support system for research activities has not been sufficiently established in clinical settings. A survey should be conducted to identify the causes of low research activity among pharmacists and the characteristics of pharmacists who could serve as mentors to build a support system at the regional level. Methods A retrospective cross-sectional survey was conducted with 156 pharmacists, including hospital and community pharmacists, who attended a webinar on research ethics held once a year in Mie Prefecture. Decision tree (DT) analysis was performed to extract the low research activities and pharmacists who could serve as mentors in research activities using independent factors identified by multivariate logistic regression analysis. Results The questionnaire response rate was 72.4% (113/156), and most respondents were community pharmacists (81.4%). In the DT model, pharmacists who did not belong to academic societies (78%, 46/59) or those who belonged to one or two academic societies but had no certifications (100%, 5/5) had low research activities. Pharmacists who read papers more than once a month and had a nearby mentor (73%, 11/15) were more likely to become mentors in research activities. Conclusions The combination of the number of academic societies and the presence of certifications determines the efforts in research activities. In addition to reading at least one paper monthly, the presence of a mentor for writing research papers may also be a crucial factor in becoming a mentor. The proposed DT model may be helpful in building a support system for research activities at the regional level.

A retrospective, cost-of-illness study aimed at identifying direct healthcare costs of vulvar, vaginal, anal, penile, and H&N cancers in Bulgaria from the payer perspective and calculating indirect costs and the associated years of life lost was carried out. Costs’ data were obtained from the National Health Insurance Fund from January 2018 to December 2020. Years of life lost were calculated based on the country and gender-specific life expectancy. The human capital approach was used to evaluate the indirect costs. The total treatment costs for 3623 patients were EUR 10,875,771 (2018), EUR 11,922,521 (2019) and EUR 12,329,463 (2020). The costs associated with radiotherapy and drug acquisition and administration accounted for the majority (75–78%) of total healthcare costs. A cumulative loss of approximately 33,299 life years occurred between 2018 and 2020. The costs of productivity losses were estimated at EUR 14,113,265.

The genus Cecropia (Urticaceae) comprises 61 tree species primarily found in tropical rainforests from Mexico to South America, including Argentina, Brazil, Paraguay, and Panama. These species are under-researched, with most studies focusing on phenolic derivatives from leaf extracts. Traditionally, Cecropia species are used to treat ailments such as asthma, bronchitis, and diabetes. This study focuses on the underexplored species C. longipes from Panama, aiming to analyze triterpene derivatives in its leaves. Through a series of chromatographic separations and purifications, three pentacyclic triterpenoids were isolated. Using 1D and 2D NMR experiments and HRESI-MS analysis, the following compounds were identified: 19α hydroxyasiatic acid, 1α,3β,23-trihydroxyolean-12-en-28-oic acid, and rosamultic acid. These compounds were isolated for the first time from C. longipes and the genus Cecropia. Genotoxicity tests using S. cerevisiae revealed that two compounds exhibited genotoxic activity at all concentrations. For 19α hydroxyasiatic acid, genotoxic potential was observed at higher concentrations, unrelated to oxidative stress, suggesting other mechanisms.

Methyl jasmonate (MeJA) treatment is known to increase the levels of plant secondary metabolites. The significant medicinal benefits of cycloartane type saponins, including immune modulation, antiviral properties, and antitumor activity, drive high global demand, making sustainable production methods economically, medically, and ecologically important. In this study the effect of MeJA as an elicitor for promoting higher accumulation of cycloartane saponins – astragaloside I, II and IV was evaluated. The experiment was conducted using biotechnological approaches for sustainable production using in vitro root cultures of the endemic plant species Astragalus aitosensis, which is known to produce rare cycloartane saponins. LC-HRESI-MS analysis was used to identify and quantify compounds. The content of astragaloside I increased significantly by 68% (118 ng/mg DW) compared to control group (70 ng/mg DW). Astragaloside II was found with 1.5 points increased amount (473 ng/mg DW), compared to control (331 ng/mg DW) and astragaloside IV production was also improved. The highest cost-efficacy concentration of the elicitor for all tested astragalosides was observed at 50 µL MeJA.

This study compares the treatment effects after six months of therapy with nintedanib and pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) by comprehensively analyzing key parameters and establishing the diagnostic performance of two biomarkers, Krebs von den Lungen-6(KL-6) and CC chemokine Ligand-18 (CCL-18), to predict treatment outcomes. In a hospital-based retrospective cohort study, 75 patients diagnosed with IPF were divided into three groups based on their treatment: the newly diagnosed group, which included newly diagnosed IPF patients without receiving any antifibrotic treatment (25 patients), IPF patients on pirfenidone treatment (26 patients), and IPF patients on nintedanib treatment (24 patients). After adjustment for age, sex, body mass index, and baseline values of predicted forced vital capacity (FVCp), there was no significant difference in the rate of changes after 24 weeks of follow-up for FVCp (-0.2 ± 0.6, 0.0 ± 2.3, and 0.8 ± 3.5 ml change after 4, 12, and 24 weeks for pirfenidone) and (-1.7 ± 5.9, 1.0 ± 8.9, and 1.4 ± 9.5 ml change after 4, 12, and 24 weeks for nintedanib). CCL-18 offers a better ability to predict radiological findings than KL-6. Most side effects were minor and included diarrhea, stomach pain, skin rash, and hyperpigmentation. In conclusion, both drugs have demonstrated the capacity to postpone the beginning stages of FVCp decrease and lung function decline. There was little difference between the efficacy of nintedanib and pirfenidone. Both drugs were safe and well tolerated for the treatment of IPF.

The pathogenesis of many diseases, such as obesity, depression, cancer, cataract, and neurodegenerative diseases, is related to the generation of reactive oxygen species (ROS). Structures possessing radical-scavenging properties act as antioxidants and they could prevent the progression of the aforementioned diseases. Therefore, the current work was focused on the resynthesis and the antioxidant evaluation of 13 hydrazide-hydrazones. Two in vitro tests - DPPH and ABTS, were applied for the determination of the antioxidant capacities. The free-radical scavenging assays displayed that the hydrazide-hydrazone synthesized after condensation with a salicylaldehyde (5b) is the most potent antioxidant. The in vitro evaluation through the ABTS test showed that the former structure has greater antioxidant properties compared with the used standard - Trolox (6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). In concentrations of 31 µM, the pyrrole-based structure showed 35.77% radical-scavenging effects. A possible binding conformation of the most active hydrazide-hydrazone in the active site of NADPH oxidase was visualised through docking simulations. The active amino acids involved in the stabilisation of the complexes were discussed. DFT studies demonstrated that 5b is a stable structure with good hydrogen and electron donating properties. Overall, the pyrrole-based hydrazide-hydrazone possesses promising antioxidant properties, however further in vitro/in vivo biological evaluations are required.

Introduction: The study of the competitive environment in the pharmaceutical market is an element of the analysis of the drug supply system. The purpose of the study is to analyze the dynamics of concentration levels in the wholesale segment of the regional pharmaceutical market. Materials and methods: Data on market shares of key players were collected and summarized based on the executed contracts (461 contracts in total) for the supply of pharmaceutical products in the model region. For the competitive analysis of pharmaceutical distributors, the Herfindahl-Hirschman Index (HHIn) calculation method was used. We also used the method of constructing the SV matrix, which has the form of a graph consisting of four quadrants divided on the abscissa scale by the obtained values of market concentration ratios (CRSV) and on the ordinate scale by the values of Hall-Teidman indices (HTSV). Results: Market concentration indicators in the wholesale segment of the regional pharmaceutical market indicate the formation of oligopoly. The constructed SV matrix demonstrated the dynamics of market concentration levels corresponding to the changing economic situation. Based on the results of the analysis, proposals to improve the competitiveness of regional pharmaceutical distributors were formed. Conclusion: The study of the dynamics of market concentration indicators allowed to analyze their state, establish the vectors of their drift, and propose measures to optimize the wholesale supply of pharmaceutical goods.

Tadalafil (TDA) is a class II drug of the biopharmaceuticals classification system (BCS), with limited aqueous solubility and high permeability. This study aims to improve the bioavailability of poorly soluble tadalafil by developing intranasal nanocrystals (NCs) of TDA. TDA NCs that were stabilised by polyvinyl alcohol (PVA) had the lowest size and the best solubility. F11 had a 196 nm in size with PDI and zeta potential of 0.21 and -11.20, respectively, which shows 5.5 and 1.6-fold higher in solubility (9.37 ± 0.36 μg/mL) and dissolution (50.11 ± 1.69%) than pure tadalafil, respectively. An in vivo animal study demonstrated that the maximum plasma concentration (Cmax) and total area under the curve (AUC0∞) achieved in the TDA NCs group were 352.77 ± 35.17 ng/mL and 3377 ± 558 ng.h/mL, respectively, and were significantly higher than the pure TDA group after intranasal administration. In conclusion, TDA NCs were successfully prepared by the sonoprecipitation technique, with significant enhancement in in vitro and in vivo properties. Therefore, intranasal administration of TDA nanocrystals was a good model for the treatment of erectile dysfunction.