Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Surface treatment of implants facilitates osseointegration, with nanostructured surfaces exhibiting accelerated peri-implant bone regeneration. This study compared bone-to-implant contact (BIC) in implants with hydroxyapatite (HA), sand-blasted and acid-etched (SLA), and SLA with calcium (Ca)-coated (XPEED®) surfaces. Seventy-five disk-shaped grade 4 Ti specimens divided into three groups were prepared, with 16 implants per group tested in New Zealand white rabbits. Surface characterization was performed using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), digital microscopy, and a contact angle analyzer. Cell viability, proliferation, and adhesion were assessed using MC3T3-E1 cells. Apatite formation was evaluated using modified simulated body fluid (m-SBF) incubation. After 4 weeks of healing, the outcomes reviewed were BIC, bone area (BA), removal torque tests, and histomorphometric evaluation. Microstructure analysis revealed irregular pores across all groups, with the XPEED group exhibiting a nanostructured Ca-coated surface. Surface characterization showed a crystalline CaTiO3 layer on XPEED surfaces, with evenly distributed Ca penetrating the implants. All surfaces provided excellent environments for cell growth. The XPEED and SLA groups showed significantly higher cell density and viability with superior osseointegration than HA (p < 0.05); XPEED exhibited the highest absorbance values. Thus, XPEED surface treatment improved implant performance, biocompatibility, stability, and osseointegration.

Purpose: The evaluation of the efficacy of topical hypotensive treatment and/or systemic corticosteroids therapy in patients with elevated intraocular pressure and Graves’ orbitopathy (GO). Methods: 172 eyes in 86 individuals with duration of GO ≥ 3 months, intraocular pressure in either eye ≥ 25.0 mmHg and GO ranked ≥ 3 at least in one eye in modified CAS form, were included. The study subjects were divided into three treatment subgroups: subgroup I was administered latanoprost QD; subgroup II was administered a combined preparation of brimonidine and timolol BID; subgroup III was the control group, not receiving any topical hypotensive treatment. All the study participants received systemic treatment – intravenous corticosteroid therapy at the same dose, according to the EUGOGO guideline Results: On the final visit, the mean IOP value was significantly lower in all treatment subgroups comparing to the initial values. In both subgroups receiving topical treatment the IOP reduction was higher than in the control group receiving systemic corticosteroids only. However, the latanoprost eye drops decreased intraocular pressure more effectively than drops containing brimonidine and timolol. Conclusion: Topical ocular hypotensive treatment is effective in reducing intraocular pressure in GO and decreases intraocular pressure more effectively than systemic corticosteroid therapy alone.

Peritoneal dialysis (PD) is a home-based efficacious modality for replacement of renal function in end-stage kidney failure patients but is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of long-term morpho-functional peritoneal changes eventually resulting in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile proves quite difficult. New approaches targeting the composition of the PD solution include replacement of glucose with other osmotic agents and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include infusion of mesenchymal cells or the administration of orally active agents. In the present article we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Biocompatibility of ceramic materials in CaO-P2O5 system was investigated using different methods, including in vitro and in vivo tests. Ceramics based on calcium pyrophosphate Ca2P2O7 were obtained by annealing cement-salt stone from highly concentrated hardening suspensions (HCHS). Cement-salt stone was prepared using powder mixtures of calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate (MCPM) Ca(H2PO4)2·H2O. These salts were mixed with each other in such a way that calcium pyrophosphate and calcium polyphosphate were present in the final ceramic product in the following weight ratios: Ca(PO3)2/Ca2P2O7 = 0/100; 5/95; 10/90 and 20/80. Distilled water was added to a homogenized powder mixtures of Ca3(C6H5O7)2·4H2O and Ca(H2PO4)2·H2O by a water/solid ratio of 0,5 by weight. The obtained suspensions were shaped using silicon molds and left to dry in air for a week. The phase composition of the obtained samples of cement-salt stone was represented by brushite CaHPO4·2H2O, monetite CaHPO4, calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate Ca(H2PO4)2·H2O. According to the XRD data, the phase composition of ceramic materials after annealing in the temperature range of 800-1000 0C was mainly represented by the β-Ca2P2O7 phase. In vivo tests shown that obtained ceramic materials can be recommended for regenerative treatments for bone defects.

Clostridial infections in cattle are a significant concern for Brazilian livestock. These diseases are caused by various species of Clostridium, which are known for their ability to produce potent toxins. Botulism in cattle is a serious and often fatal condition caused by the ingestion of neurotoxins produced by C. botulinum. This bacterium thrives in decomposing organic matter, such as spoiled feed, carcasses, and contaminated water. Tetanus while less common, tetanus is a serious disease following contamination of wounds with Clostridium tetani spores. It results in muscle stiffness, spasms, and often death due to respiratory failure. Blackleg (C. chauvoei) is this disease primarily affects young cattle, leading to acute lameness, swelling, and high fever. Malignant edema (C. septicum and others) is characterized by rapid onset of swelling at wound sites, malignant edema can occur after injuries or surgical procedures. Enterotoxemia is triggered by the rapid growth of C. perfringens in the gut following excessive carbohydrate intake. This leads to toxin production that causing sudden death. In conclusion, clostridial bovine infections remain a persistent challenge for Brazilian cattle farmers. With continued focus on vaccination, good management practices, and research, the impact of these diseases can be minimized, safeguarding the livestock industry's economic viability.

Acne vulgaris is a prevalent skin condition that affects people of all ages and can have significant physical and psychological impacts. Hydroxy acids, such as alpha-hydroxy acids (AHA) and beta-hydroxy acids (BHA), have demonstrated potential as effective ingredients for topical acne treatments due to their exfoliating and skin-rejuvenating properties. This study assessed the effectiveness of encapsulating AHA and BHA in pullulan-collagen nanofibers as a novel approach to acne treatment. The study involved preparing Pullulan and polyvinyl alcohol (PVA) solutions combined with sodium chloride (NaCl) to create a stable mixture. Collagen and Pullulan were then dissolved in deionized water and mixed to form a collagen-pullulan solution. Various weight ratios of Collagen to Pullulan were tested to optimize nanofiber formation. This research achieved electrospinning of nanofibers, confirmed by scanning electron microscopy (SEM) analysis, which revealed well-formed and continuous nanofiber structures in acidic solutions. Fourier transform infrared spectroscopy (FTIR) analysis provided insights into the chemical composition of the nanofibers, indicating the presence of ester, carboxylic acid, hydroxyl, and phenolic groups. Contact angle measurements demonstrated that the pullulan-collagen nanocomposite exhibited hydrophilic properties, albeit less hydrophilic than pure Collagen. Biocompatibility assays using mesenchymal stem cells (MSCs) and human skin fibroblasts (HSFs) revealed that the pullulan-collagen nanocomposite promoted higher cell viability compared to pure Collagen, suggesting its potential as a supportive matrix for cell growth and tissue regeneration. AHA-BHA-infused nanofiber skin masks hold promise as effective topical treatments for acne vulgaris. The successful encapsulation of hydroxy acids within pullulan-collagen nanofibers, in conjunction with their favourable chemical composition, hydrophilicity, and biocompatibility, positions them as promising candidates for delivering active ingredients and enhancing skin health. Further nanofiber formulation optimisation is necessary to exploit their therapeutic potential in skincare applications.

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, like diabetic foot ulcers, have increased significantly in the last years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: Methicillin-Resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had not proteolytic effects. MRSA infections increased cytokines expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography-mass spectrometry (LC-MS/MS) identified 50 main compounds of CF, then the targets of them were obtained from TCMSP, ETCM, ITCM and Swiss TargetPrediction databases. RA disease related targets were obtained from DisGenet, OMIM and GeneCards databases. 99 overlapped targets were obtained using Venn diagram. The protein-protein interaction network (PPI)、the compound-target network (CT) and the compound-potential target genes-signaling pathways network (CPS) were built and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. And the core therapeutic targets were identified as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, RELA by network pharmacology analysis, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in mice model of xylene-induced ear edema and strong analgesic effect on acetic acid-induced withing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF could alleviate toe swelling and ameliorate joint damage. The elevation of serum content of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may exert regulation on the ERK and NF-κB pathway. The results provided a new perspective for the topical application of CF on RA.

Low temperature cofired ceramics (LTCC) have conquered a niche segment in biological microelectromechanical systems (BioMEMS) during the last two decades. Since 3-dimensional assembly and rapid prototyping capability are outstanding features of the technology, bioreactors with complex geometry can easily be produced. Particularly needed functions are working electrodes, e.g. for impedance measurements and reference electrodes consisting in platinum or silver-silver chloride. Although the distinct grainy surface of thick film materials influences the double layer properties, data describing the bioelectronic interface and biocompatibility of common thick film materials are rarely published up to now. This works aims to fill this gap by studying the surface properties, composition, electrochemical properties and biocompatibility of commercially available thick film materials. It was found that thick film gold is suitable as electrode material in direct cell contact since an appropriate proliferation of the cell culture was observed. Poly(3,4-ethylenedioxythiophene) coating decreases the absolute value of the zeta potential of thick film gold from 16.55 V to 11.78 mV without any change in vitality of the cells. Thick film platinum layers have a porous structure entailing an enlargement of the effective surface by a factor of 21.6 and can be used as reference instead of silver/silver chloride, which was identified to be incompatible with cell culture. The investigations show that some commercially available cost-effective thick film materials are compatible with cell culture and the here presented data give an orientation for the use of the same in LTCC bioreactors.

The capacity of 3D printing (3DP) technologies to initiate speedy polymerization of solvent free resins accounts for their utility in the manufacturing of medical devices. Nonetheless, independent biological evaluation of 3D printed materials is recommended due to the unique parameters of the manufacturing process, which can influence their physical, chemical, and biological properties. In this study, E-Shell 450 material indicated for 3DP of hearing aid shells and inner ear devices was examined for biological safety using zebrafish bioassays adapted to OECD fish embryo test. In addition, the proprietary material was characterized for composition using headspace gas-chromatography mass spectrometry (GC-MS). To initiate test, newly fertilized zebrafish eggs were cultured on non-treated and ethanol-treated materials in glass petri dishes with ultrapure water, incubated at 28.5°C and assessed for developmental endpoints of toxicity at 24h interval until 96h. Data confirmed non-treated material was extremely toxic in bioassays within 24h whereas ethanol-treated material showed a relative lower toxicity possibly due to ethanoic-aqueous interactions as observed by GC-MS. With the current influx of 3D printing materials, users are urged to exercise caution. Operators must also take cognizance of the potential toxicity of the chemicals used in 3DP and implement safety measures to limit their exposure.

Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic antiinflamatory and antioxidant activity. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with a potential anti-inflammatory and antioxidant action for topical treatment of inflammatory skin disorders. The micro-emulsion system was obtained from a 20% CBD oil as hydrophobic phase, Labrasol/Plurol Oleique (1:1) as surfactant and cosurfactant (S/CoS) respectively and an aqueous vegetal extract obtained from S. ebulus L. ripe fruits, with a potential anti-oxidant and anti-inflammatory activity, as water phase. A pseudo-ternary phase diagram was elaborated, selecting an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after testing its reproducibility, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size by laser scattering, compatibility of components by differential scanning calorimetry and rheological properties using a rotational rheometer. The designed microemulsion showed good stability and a slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the water phase of the microemulsion were studied by in vitro diffusion experiments using flow-through diffusion cells in comparison to a CBD oil and a microemulsion only with CBD as active substance. It was evidenced that the inclusion of the original oil in microemulsions did not provoke a significant modification of the release of CBD, incorporating the possibility of including hydrophilic active compounds in the formulation, stablishing an interesting strategy for the development of future formulations.

Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague-Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p < 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8-mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days, and procured at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, i.e. the percentage wound area changes, did not show an increase with NPY (p = 0.938) but did with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism is elusive but likely involves NPY receptor subtypes other than Y2R.

The active form of fingolimod (FTY720; FT) is a sphingosine-1-phosphate receptor agonist with potential ocular applications. The goal of the present study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. FT-NE formulations were prepared with homogenization followed by probe sonication method. The lead FT-NE formulation (0.15% and 0.3% w/v loading), comprising soybean oil as lipid and Tween® 80 and Poloxamer 188 as surfactants, was further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature post-filtration through polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release, compared with the control FT solution (FT-S), over 24 h. The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.

Nanostructured carriers have been widely used in pharmaceutical formulations for dermatological treatment. They offer targeted drug delivery, sustained release, improved biostability, and low toxicity, usually presenting advantages over conventional formulations. Due to its large surface area, small size and photothermal properties, graphene oxide (GO) has the potential to be used for such applications. Nanographene oxide (GOn) presented average sizes of 197.6 ± 11.8 nm, and a surface charge of -39.4 ± 1.8 mV, being stable in water for over 6 months. 55.5 % of the mass of GOn dispersion (at a concentration of 1 mg mL-1) permeated the skin after 6 h of exposure. GOn dispersions have been shown to absorb near-infrared radiation, reaching temperatures up to 45.7 °C, within mild photothermal therapy temperature range. Furthermore, GOn in amounts superior to those which could permeate the skin were shown not to affect human skin fibroblasts (HFF-1) morphology or viability, after 24 h of incubation. Due to its large size, no skin permeation was observed for graphite particles in aqueous dispersions stabilized with Pluronic P-123 (Gt-P-123). Altogether, for the first time, GOn potential as a topic administration agent and for delivery of photothermal therapy has been demonstrated.

Microbicides, topical antiseptic agents, and a revolutionary advance in HIV prevention aim to prevent the entry of infectious agents into the human body, thus stopping the sexual transmission of HIV and other sexually transmitted diseases. Microbicides represent the promise of a new age in preventive measures against one of the world's most pressing health challenges. In addition to their direct antiviral effects during HIV transmission, microbicides also influence vaginal mucosal immunity. This article reviews microbicides by presenting different drug classifications and highlighting significant representatives from each group. It also explains their mechanisms of action and presents information about vaginal mucosal immune responses, emphasizing the critical role they play in responding to HIV during sexual transmission. For each chemical compound, the article provides a brief overview of relevant preclinical and clinical research, emphasizing their potential as microbicides.The article offers insights into the multifaceted impact of microbicides, which signify a pivotal step forward in the pursuit of effective and accessible pre-exposure prophylaxis (PrEP).

Research has shown a protective association between social support and depression, depression among stroke patients, and health impacts of depression. Yet not much is known on the effect of social support on depression among stroke patients. This review aims to summarize the current research examining the association between social support and depression among stroke patients. A literature search was performed in PubMed to find original peer-reviewed journal articles from 2016 to Mar. 12, 2023 that examined the association between social support and depression among stroke patients. The search terms were depression and "social support" and stroke, which lead to 172 articles. After abstract review, seven observational studies that studied the target association among stroke patients were selected. One additional study was found using PsycINFO as a complementary source with the same search strategy and criteria. Overall, a negative association was found between social support and depression among stroke patients in seven studies, with more social support leading to lower rates of depression post-stroke. One study found that social support was positively related with depression, but the result was nonsignificant. Overall, the results of recent studies suggest that social support is negatively associated with depression among stroke patients. In most studies, this association was statistically significant. The findings suggest the importance of improving social support perceived by stroke patients in the prevention of depression after the occurrence of stroke.

Due to their well-defined plasmonic properties, gold nanorods (GNRs) can be fabricated with optimal light absorption in the near-infrared region of the electromagnetic spectrum, which make them suitable for cancer-related theranostic applications. However, their controversial safety profile, as a result of surfactant stabilization during synthesis, limits their clinical translation. We report a facile method to improve GNR biocompatibility through the presence of sodium dodecyl sulfate (SDS). GNRs (120 x 40 nm) were synthesized through a seed-mediated approach, using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant to direct the growth of nanorods and stabilize the particles. Post-synthesis, SDS was used as an exchange ligand to modify the net surface charge of the particles from positive to negative while maintaining rod stability in an aqueous environment. GNR cytotoxic effects, as well as the mechanisms of their cellular uptake, were examined in two different cancer cell lines, Lewis lung carcinoma (LLC) and HeLa cells. We not only found a significant dose-dependent effect of GNR treatment on cell viability but also a time-dependent effect of GNR surfactant charge on cytotoxicity over the two cell lines. Our results promote a better understanding of how we can mediate the undesired consequences of GNR synthesis byproducts when exposed to a living organism, which so far has limited GNR use in cancer theranostics.

Degnala is one of the main mycotoxicoses that affects buffaloes, and the fungus Fusarium spp. is the main causative agent. This disease is strongly related to the supply of rice straw to buffaloes and is considered endemic to regions where this crop is cultivated. Cases of the disease are concentrated in the winter, when conditions favour fungal growth in inadequately stored rice straw. Degnala is characterized by necrosis and gangrene of the extremities, including the tail, lower limbs, ears, tongue, muzzle and teats. The pelvic limbs are more affected than the thoracic limbs. A tortuous appearance of the tail is very common, and cracks or corneal loss of the hooves may occur, with exposure of the blades and even the bones. There is no diagnostic method for identifying the disease in animals other than the clinical and epidemiological criteria associated with fungal culture of rice straw samples. There is no treatment that neutralizes the effects of the toxins, and the treatment currently used is a palliative and supportive method consisting of pentasulfate solution, anti-Degnala liquid, 2% nitroglycerin ointment and broad-spectrum antibiotics for secondary infections. In addition, the management of drying straw and proper storage are essential for controlling this disease.

Molecular engineering research is the fundamental way and the only way for the development of biomaterials. Based on molecular engineering, the biocompatibility of natural conformation and polymer biomaterials was studied. In this paper, we discuss that natural conformation is the basis of protein biological function, and that the synergistic action of peptide chain and side group is the motive force for protein to construct natural conformation and complete biological function. On the basis of the influence of the adsorption of polymer biomaterials on the natural conformation of proteins, the relationship between biocompatibility of biomaterials and protein conformation is further explained. Studies have shown that bismuth molecular materials can only be applied in the market and have their functionality if they have good biocompatibility. Therefore, the biocompatibility evaluation of new materials has important practical significance.

Candidiasis is a significant fungal infection caused by various species of the genus Candida, posing health challenges to a wide range of animals, including Choloepus species (two-toed sloths). This review article aims to provide a comprehensive understanding of candidiasis in Choloepus sp., highlighting the etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention strategies.The article begins by examining the causative agents, primarily focusing on Candida albicans, which is the most commonly implicated species in candidiasis. The epidemiological aspects are discussed, emphasizing the prevalence of candidiasis in wild and captive Choloepus populations and identifying predisposing factors such as immunosuppression, stress, poor nutrition, and environmental conditions. Pathogenesis is explored, detailing the mechanisms through which Candida species invade host tissues and evade immune responses. Clinical manifestations in Choloepus sp. are described, including oral thrush, cutaneous lesions, and gastrointestinal infections, and their impact on the health and behavior of affected individuals. Diagnostic methods, including culture techniques, histopathology, and molecular assays, are reviewed to highlight their roles in accurately identifying Candida infections. The article also covers treatment options, focusing on antifungal therapies and supportive care tailored to the unique physiology of Choloepus sp. Finally, prevention and management strategies are discussed, emphasizing the importance of maintaining optimal husbandry practices, regular health monitoring, and early intervention to reduce the incidence and impact of candidiasis in Choloepus populations. This review underscores the need for further research to enhance our understanding of candidiasis and improve health outcomes for these unique and vulnerable animals.

Additive manufacturing or 3D printing applying polycaprolactone-(PCL)-based medical devices represents an important branch of tissue engineering, where the sterilization method is a key process for further safe application in vitro and in vivo. In this study, the authors intend to access the most suitable gamma radiation conditions to sterilize PCL-based scaffolds in a preliminary biocompatibility assessment, envisioning future studies for airway obstruction conditions. Three radiation levels were considered, 25 kGy, 35 kGy and 45 kGy and evaluated as to their cyto- and biocompatibility. All three groups presented biocompatible properties, indicating an adequate sterility condition. As for the cytocompatibility analysis, devices sterilized by 35 kGy and 45 kGy showed better results, with the 45 kGy showing overall improved outcomes. This study allowed to select the most suitable sterilization condition for PCL-based scaffolds, aiming at immediate future assays, by applying 3D-customized printing techniques to specific airway obstruction lesions of the trachea.

The introduction of biologic therapies has led to dramatic improvements in the management of moderate-to-severe psoriasis. Even though the efficacy and safety of the newer biologic agents are difficult to match, oral administration is considered an important advantage by many patients. Current research is focused on development of oral therapies with improved efficacy and safety compared to available alternatives, as exemplified by deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for the treatment of moderate-to-severe psoriasis in adults. Recent advances in our knowledge of psoriasis pathogenesis have also led to the development of targeted topical molecules, mostly focused on intracellular signaling pathways, such as AhR, PDE-4 and Jak-STAT. Topical tapinarof, an AhR modulator, and roflumilast, a PDE-4 inhibitor, have exhibited favorable efficacy and safety outcomes have been approved by the FDA for the topical treatment of plaque psoriasis. This revision focuses on the most recent oral and topical therapies available for psoriasis and specially on those that are currently under evaluation and development for the treatment of psoriasis.

In this experimental report the biocompatibility of elastomeric scaffold structures made via stereolithography employing table-top 3D printer (Ember, Autodesk) and commercial resin FormLabs Flexible (FormLabs) was studied. The samples were manufactured using standard printing and development protocol, which is known to inherit cytotoxicity due to remaining non-polymerized remaining monomers, despite the polymerized material being fully biocompatible. Additional steps were taken to remedy this problem: the fabricated structures were soaked in isopropanol and methanol for different conditions (temperature, duration) in order to leach out the non-polymerized monomers. Also printed structures were UV exposed to assure maximum polymerization degree of the material. Post-processed structures were seeded with myogenic stem cells and the number of live cells was evaluated as an indicator for the material biocompatibility. The straightforward post-processing protocol enhances the biocompatibility by 7 times after 7 days soaking in isopropanol and methanol and is comparable to control (glass and polystyrene) samples. This proposes the approach as a novel and simple method to be widely applicable for dramatic cytotoxicity reduction of optically 3D printed micro-/nano-scaffolds for biomedical applications.

Worldwide, oral lesions and cancers are still being significant public health conditions. Thus, an introduction of new oral healthcare protocols is becoming essential. Oral diseases are related to many causative factors, manly dental plaque/biofilm due to poor hygiene. New anti-biofilm therapies are needed to develop. The strategies of anti-biofilm therapies should help to control biofilm formation and microbial attachment to dental surfaces. The present review aimed to provide a comprehensive over-view on evidence related to the potential utility of topical oxygen therapy (BlueM formula) as novel oral care therapies in clinical practice.

The injectable hydrated calcium phosphate bone-like paste (hCPP) have been developed with suitable nanoscale characteristics and unindered injection through 23G standard needles. In vitro assays showed the cytocompatibility of hCPP with mesenchymal embryonic C3H10T1/2 cell cultures. The hCPPs were identified to be composed of aggregated nano-sized particles with sphere-like shapes with low crystallinity. The ability of serum proteins (FBS) to adsorb on hCPP particles was also studied. The hCPP demonstrated high protein adsorption capacity, thereby indicating its potential in various biomedical applications. The results of the in vivo assay upon subcutaneous injection in Wistar rats indicated the nontoxicity and biocompatibility of experimental hCPP, as well as the gradual resorption of hCPP, comparable to the period of bone regeneration. The data obtained are of great interest for the development of commercial highly effective osteoplastic materials for bone tissue regeneration and augmentation.

(1) Background: The evaluation of ventricular assist devices requires the usage of biocompatible and chemically stable materials. The commonly used polyurethanes are characterized by versatile properties making them well suited for heart prostheses applications but simultaneously they show low stability in biological environment. (2) Methods: An innovative material - copolymer of poly(ethylene-terephthalate) and dimer linoleic acid - with controlled and reproducible physico-mechanical and biological properties was developed for medical applications. Biocompatibility (cytotoxicity, surface thrombogenicity, hemolysis and biodegradation) were evaluated. All results were compared to medical grade polyurethane currently used in the extracorporeal heart prostheses. (3) Results: No cytotoxicity was observed and no significant decrease of cells density as well as no cells growth reduction was noticed. Thrombogenicity analysis showed that the investigated copolymers have the thrombogenicity potential similar to medical grade polyurethane. No hemolysis was observed (the hemolytic index was under 2% according to ASTM 756-00 standard). These new materials revealed excellent chemical stability in simulated body fluid during 180 days ageing. (4) Conclusions: The biodegradation analysis showed no changes in chemical structure, molecular weight distribution, good thermal stability and no changes in surface morphology. Investigated copolymers revealed excellent biocompatibility and great potential as materials for blood contacting devices.

The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.

Purpose: The aim of this research was to prepare adhesive nanoparticles for the topical application of Minoxidil (MXD). Methods: Thiolated β-CDs were prepared via conjugation of cysteamine with oxidized CDs. MXD was encapsulated within thiolated and unmodified β-CDs. Nanoparticles (Thio-NP and blank NP) were prepared by ionic gelation of CDs with chitosan. Particle size and zeta potential were measured. FTIR analyses were performed for characterization of inclusion complex. Drug dissolution studies were carried out. An in vitro adhesion study over human hair was performed. An in vivo skin irritation study was performed. Ex vivo drug uptake was evaluated by using a Franz diffusion cell. Results: Thiolated β-CDs presented 1804.68 ± 25 μmol/g thiol groups and 902.34 ± 25 μmol/g disulfide bonds. Nanoparticles displayed particle sizes within a range of 231 nm to 319 nm. The zeta potential was in the range of ̶ 8.1 to + 12.0. FTIR analyses confirmed no interaction between the excipients and drug. Delayed drug release was observed from Thio-NP. Thio-NP retained over hair surfaces for a significantly longer time. Similarly, drug retention was significantly improved. Thio-NP displayed no irritation over rabbit skin. Conclusion: Owing to the above results, nanoparticles developed with MXD-loaded thiolated β-CDs might be a potential drug delivery system for topical scalp diseases.

Mechanical robustness, biocompatibility, and antibacterial performances are key features for materials suitable to be used in tissue engineering applications. In this work, we investigated the link existing between structural and functional properties of TiCu(Ag) thin films deposited by physical vapor deposition magnetron sputtering on Si substrates. The thin films were characterized by X-ray diffraction (XRD), nanoindentation, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). The TiCu(Ag) thin films showed complete amorphous structure and improved mechanical properties in comparison with pure Ti films. However, for contents in excess of 20% Ag, we observed the appearance of nanometric Ag crystallite. The TiCu(Ag) thin films displayed excellent biocompatibility properties, allowing adhesion and proliferation of the human fibroblasts MRC-5 cell line. Moreover, all the investigated TiCu(Ag) alloy display bactericidal properties, preventing the growth of both Pseudomonas aeruginosa and Staphylococcus aureus. Results obtained from biological tests have been correlated to the surface structure and microstructure of films. The excellent biocompatibility and bactericidal properties of these multifunctional thin films opens to their use in tissue engineering applications.

This study used Dutch potatoes at the end of dormancy as the material to explore the impact of menthol (0.2 and 0.5 g/kg based on potato mass) treatment on sprouting inhibition and potato quality. The findings revealed that a menthol concentration of 0.5 g/kg effectively inhibited potato tuber sprouting and significantly reduced glucoside alkaloids production. After a storage period of 15 days, the sprouting percentage and glucoside alkaloids content of potatoes treated with 0.5 g/kg menthol were observed to be significantly lower at 4.17% and 68.63 mg/kg, respectively, compared to the control group which exhibited values of 100% and 282.01 mg/kg, respectively (P < 0.05). Throughout the storage period, 0.5 g/kg of menthol promoted respiration, reduced malondialdehyde production in potatoes, inhibited polyphenol oxidase activity, and slowed down tissue browning. Additionally, it mitigated the decline in starch and soluble protein content, inhibiting the accumulation of reducing sugars.

The aim of this study was to analyse the biocompatibility of a material based on lactic acid (PLA)/polyhydroxybutyrate(PHB)/thermoplastic starch (TPS) in combination with additives (plasticizers: acetyltributyl citrate (ATBC) and oligomeric lactic acid ( OLA)). Three types of materials were tested: I: PLA/PHB/TPS + 25% OLA, II: PLA/PHB/TPS + 30% ATBC, III: PLA/PHB/TPS + 30% OLA. The 3D printing itself was preceded by the creation of filaments from granulate and the design of samples. A filament production machine – Composer 450 (3devo; The Netherlands) was used to produce the filaments. Experimental samples were produced by FDM technology on a 3D printer DeltiQ2 (Trilab, Czech Republic). The evaluation of the biocompatibility of the materials included cytotoxicity tests such as the monitoring of viability, proliferation, morphology of cells, and their settlement on the surface of the materials. The cell line 7F2 osteoblasts (Mus musculus) was used in the experiments. Based on the tests, results confirmed the significant influence of plasticizers and their proportions in the mixtures. PLA/PHB/ATBC + 25% OLA was evaluated as the optimal material for biocompatibility with 7F2 osteoblasts. The tested biomaterials have the potential for further investigation, with a possible change in the proportion of the plasticizer, which has a fundamental impact on their biological properties.

This study aimed to evaluate the physico-chemical properties, biocompatibility and bioabsorption of 3 different new membranes for bone guided regeneration (PLGA associated with hydroxyapatite and beta-TCP) with three thicknesses (200, 500 and 700 µm) implanted in mice subcutaneously. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the quantification of Carbon, Hidrogen and Nitrogen were used to characterize the physico-chemical properties. One hundred Balb-C mice were divided into 5 experimental groups: Group 1 - Sham (without implantation); Group 2 - 200 μm; Group 3 - 500 μm; Group 4 - 700 μm; and Group 5 - Pratix®. Each group was subdivided into four experimental periods (7, 30, 60 and 90 days). Samples were collected and processed for histological and histomorphometrical evaluation. The membranes showed no moderate or severe tissue reactions in the experimental periods studied. The 500 μm membrane did not show tissue reaction for any experimental periods studied. The 200 μm membrane membranes began to exhibit fragmentation after 30- day, while the 500 and 700 µm membranes started the fragmentation at 90-day. All membranes studied were biocompatible, and the 500µm membrane showed the best results being a promissory membrane for bone guided regeneration.

Tellurium exhibits exceptional intrinsic electronic properties. However, investigations into the modulation of tellurium's electronic properties through physical modification are notably scarce. Here, we present a comprehensive study focused on the evolution of the electronic properties of tellurium crystal flakes under plasma irradiation treatment by employing conductive atomic force microscopy and Raman spectroscopy. The plasma-treated tellurium experienced a process of defect generation through lattice broken. Prior to the degradation of electronic transport performance due to plasma irradiation treatment, a remarkable observation emerged: in the low-energy region of hydrogen plasma-treated tellurium, a notable enhancement in conductivity was unexpectedly detected. The mechanism underlying this enhancement in electronic transport performance was thoroughly elucidated by comparing it with the electronic structure induced by argon plasma irradiation. This study not only fundamentally uncovers the effects of plasma irradiation on tellurium crystal flakes, but also unearths an unprecedented trend of enhanced electronic transport performance at low irradiation energies when utilizing hydrogen plasma. This abnormal trend bears significant implications for guiding the prospective application of tellurium-based 2D materials in the realm of electronic devices.

Nitric oxide (NO) is involved in physiological processes, including vasodilatation, wound healing and antibacterial activities. As NO is a free radical, designing drugs to generate therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL) - chitosan (CS) hydrogel, with an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL^-1 of hydrogel, which corresponds to 1 mmol·L^-1 of GSNO). Interestingly, the concentration range in which the NO-releasing hydrogel demonstrated an antibacterial effect was not found to be toxic to the Vero mammalian cell. Thus, the GSNO-PL/CS hydrogel is a suitable biomaterial for topical NO delivery applications.

Macrophages are cells involved in the primary response to debris derived from wear of implanted CoCr alloys. The biocompatibility of wear particles from a high carbon CoCr alloy produced under polarization in physiological hyaluronic acid (HA) solution was evaluated in J774A.1 mouse macrophages cultures. Polarization was applied to mimic the electrical interactions observed in living tissues. Wear tests were performed in a pin-on-disk tribometer integrating an electrochemical cell in phosphate buffer solution (PBS) and in PBS supplemented with 0.3% HA, physiological synovial fluid concentration, used as lubricant solution. Wear particles produced in 0.3% HA solution showed a higher biocompatibility in J774A.1 macrophages in comparison to those elicited by PBS. A considerable improvement in macrophages biocompatibility in the presence of 0.3 % of HA was further observed by the application of polarization at potentials having current densities typical of injured tissues suggesting that polarization produces an effect on the surface of the metallic material that leads to the production of wear particles that are macrophages biocompatible and less cytotoxic. The results showed the convenience to consider electric interactions together with other particles parameters, as are size and composition, to get a better understanding of the biological effects of the wear products.

Background: Micrococcus luteus is a commensal bacterial member on the human skin and is essential in keeping the balance among the various microbial flora of the skin. M. luteus strain Q24 or BLIS Q24^TM was isolated from the skin of a healthy human adult and has been identified to produce a unique antimicrobial spectrum that is inhibitory towards pathogenic bacteria associated with many skin diseases such as acne. It has been developed as a probiotic with potential applications in improving overall skin health.Aim: This study aimed to evaluate the perceived changes in skin quality following topical application of a formulation containing skin commensal probiotic BLIS Q24^TM. Materials and methods: A 28-day study involving 100 adult participants with self-reported normal skin with occasional blemishes or breakouts, topically applied a serum formulation containing BLIS Q24^TM to the face. Participants quantitatively evaluated the probiotic serum effect on their skin at baseline Day 0 and then again on Day 10, 20 and 28 of the application. In addition, participants maintained a photo diary to record the perceived changes to their skin.Results: A total of 96 participants completed this research. In comparison to the baseline (Day 0), within 10 days, a significant reduction in blackheads (48%), oiliness (48%), blemishes (57%), dry areas (23%), redness/rosacea (45%) and flaky and rough skin (38%) were reported. The probiotic serum was also effective in a significant reduction in fine lines and wrinkles (38%), whiteheads (41%), pimples (55%), age spots (29%), and acne (21%) by the end of 28 days of probiotic application. Overall, there’s agreement that probiotic serum delivers or exceeds consumer expectations from the concept and performs just as well, or better, than their regular moisturiser.Conclusions: An approach of delivering a live probiotic packaged in an innovative formula to improve several skin conditions in otherwise healthy individuals was found to be successful. This study highlights that a serum formulation containing BLIS Q24^TM has a positive impact on skin health with it being effective topically in reducing the appearance of skin blemishes, oiliness, wrinkles, redness, and dryness. BLIS Q24^TM offers the potential for the prevention of skin health-related issues and routine maintenance of skin microbiome for healthy skin.

The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 hour, patients took 50 mg lasmiditan within 2 hours of migraine onset. Patients recorded headache intensity and adverse events(AEs) caused by lasmiditan at 1, 2, and 4 hours after intake of additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p &lt; 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 hour after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 hour after lasmiditan intake. Our study revealed the significant headache reliefs provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short term. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied alone or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning / positive control (CONP); (2) castration and dehorning / negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and behaviour following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (P < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (P < 0.001). All dehorned and castrated calves spent more time walking (P = 0.024) and less time eating (P < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (P = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (P = 0.098) and tail flicks to be highest in CONN and BM calves (P = 0.061). The findings of this study suggest that TA and MEL can improve welfare and production of calves following surgical castration and amputation dehorning.

Background: Gender differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, gender-specific analysis remains underexplored. This retrospective study aimed to evaluate the gender-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). Methods: Data were collected from 47 patients (31 women, 16 men), with age > 18 years, BMI ≥ 30 kg/m^2, absence of T2D, and with exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. Results: Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, % WL, WL >5% and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant gender differences were observed in glucose metabolism or renal function. Conclusion: This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.

Adenomyosis, a benign gynecological condition characterized by the infiltration of endometrial tissue into the myometrium, poses significant challenges to women's reproductive health. Recently, the landscape of adenomyosis diagnosis transformed significantly, thanks to advancements in imaging technologies such as transvaginal ultrasound and magnetic resonance imaging. This lead to a noticeable shift in the demographic profile of patients diagnosed with adenomyosis, including younger women of reproductive age who frequently present with a diverse array of symptoms. Approximately 20% of women are affected by adenomyosis. Adenomyosis manifests with various subtypes, distinct epidemiological profiles, symptomatology, and treatment responses, necessitating tailored approaches for optimal management. Despite its clinical significance, adenomyosis remains understudied, resulting in a significant disparity in research and literature compared to other gynecological conditions. The severity of adenomyosis is compounded when coexisting with endometriosis, particularly deep infiltrating endometriosis (DIE), leading to exacerbated fertility issues and severe symptomatology. The wide range of symptoms, including adverse pregnancy outcomes such as pre-eclampsia, highlights its wider impact and emphasizes the need for increased awareness of the condition. Furthermore, Adenomyosis is frequently associated with treatment failure in endometriosis, contributing to dienogest resistance, elevated discontinuation rates, and persistent pain post endometriosis surgery. Additionally, the lack of specific treatments tailored to adenomyosis poses a considerable challenge in clinical management.

To assess the clinical efficacy of a novel organic olive oil-based denture adhesive and its effect on Candida Albicans growth in maxillary edentulous individuals wearing complete dentures. Individuals were selected from two Dental Schools in Portugal and Spain. Twenty-eight complete dentures were relined, following a standardized protocol. The novel product (Test) was compared with a commercialized adhesive (Control) and Vaseline (Placebo) randomly assigned in a cross-study design. The retention resistance was measured with a Gnathometer and a dynamometer, the patient related outcome evaluations with a 5-points questionnaire and the Candida albicans growth in a Sabouraud dextrose agar (SDA) medium in order to evaluate differences between the placebo and experimental product. Twenty-three participants were included. Dynamometer evaluation showed significant differences between not using a denture adhesive and using either (experimental, p = .03; control, p = .04), no significant differences between the two adhesives (p &gt; .05). In the subjective analysis, the experimental adhesive showed a significantly longer effectiveness (p = .001); the control reported better results at taste (p = .03) in chewing (p = .001). The test adhesive showed better (p &lt; .001) Candida albicans growth inhibition. The experimental adhesive showed longer effectiveness than the control and placebo with a better inhibition capacity for the growth of Candida albicans, patients reported better abilities for speech, chewing, taste and retirement in the control adhesive.

This article describes a novel topical composition constituted by gamma-amino butyric acid (GABA) and microbial chondroitin sulfate. This composition, formulated by the author and manufactured in a certified facility in the United States of America, exhibits potential for non-invasive intervention in anxiety management, sleep quality enhancement, and promotion of brain-related functions like meditation and nonlocal consciousness. The core component comprises GABA, a key inhibitory neurotransmitter within the central nervous system, complexed with a suitable carrier molecule, microbial chondroitin sulfate. This complexation aims to enhance transdermal absorption and optimize delivery of GABA to target tissues. The proposed mechanism of action involves modulation of GABAergic signal transduction pathways. Application of the topical composition allows GABA penetration into the skin and potentially deeper tissues, where it interacts with GABA receptors. This interaction leads to mental calmness and relaxation as assessed by electroencephalography. The influence of GABAergic signaling on brain circuits demonstrated in this article, when associated with meditation and nonlocal consciousness, suggests potential for the composition to support these practices. The advantage of such an approach consists in avoiding the potential systemic side effects associated with oral or injectable administration of GABA, anxiolytics or hypnotics. Furthermore, the combination of GABA and microbial chondroitin sulfate may offer synergistic benefits, potentially enhancing the overall biological effects. In conclusion, this article presents a novel topical approach for managing anxiety, enhancing sleep quality, and potentially facilitating meditation and nonlocal consciousness through modulation of GABAergic signaling pathways. While further research is necessary, the potential for a non-invasive and potentially side-effect-free intervention in these areas is promising.

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

Recent years have been abundant in research concerning human microbiome and its impact on the host’s health. Studies have shown, that not only the commensal bacteria itself, but also postbiotics, understood as unalived microorganisms, possibly with the presence of their components, may have themselves effect on various elements of human physiology. In this article we take a closer look on the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today’s world being a serious subject of concern. Through altering patients’ immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given greatly promising findings in the field of their immunomodulating potential.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

The Internet of Things (IoT) is still a relatively new field of research, and its potential for use in the healthcare and medical sectors is enormous. In the last five years, IoT has been a go-to option for various applications such as using sensors for different features, machine-to-machine communication, etc., but precisely, in the medical sector, it is still lagging far behind compared to other sectors. Hence, this study emphasizes the IoT applications in medical fields, Medical IoT sensors and devices, IoT platforms for data visualization, and artificial intelligence in medical applica-tions. A systematic review considering PRISMA guidelines on research articles as well as the websites on IoMT sensors and devices have been carried out. A total of 986 articles after the year 2001 have been initially selected, and by applying the inclusion-exclusion criterion, a total of 597 articles have been identified. From these, 23 studies have been finally selected for this systematic review. This review analyzes different sensor monitoring circuits in detail, considering an Inten-sive Care Unit (ICU) scenario, device applications, and the data management system, including IoT platforms for the patients. Lastly, detailed discussion and challenges have been outlined, and possible prospects have been presented.

The development of computational acoustics allows simulation of sound generation and propagation in complex environment. In particular, meshfree methods are widely used to solve acoustics problems through arbitrarily distributed field points and approximation smoothness flexibility. As a Lagrangian meshfree method, smoothed particle hydrodynamics (SPH) method reduce the difficulty in solving problems with deformable boundaries, complex topologies, or multiphase medium. The traditional SPH method has been applied in acoustic simulation. This study presents the corrective smoothed particle method (CSPM), which is a combination of SPH kernel estimate and Taylor series expansion. The CSPM is introduced as a Lagrangian approach to improve accuracy in solving acoustic wave equations in the time domain. Moreover, a boundary treatment technique based on the hybrid meshfree and finite difference time domain (FDTD) method is proposed to represent different acoustic boundaries with particles. To model sound propagation in pipes with different boundaries, soft, rigid, and absorbing boundary conditions are built with this technique. Numerical results show that the CSPM algorithm is consistent and demonstrates convergence with exact solutions. Main computational parameters are discussed, and different boundary conditions are validated to be effective for benchmark problems in computational acoustics.

Probiotics in cosmetics is a new and burgeoning area of research attracting attention from cosmetic manufacturers and customers looking for natural or additional alternatives in their skincare regimens. Probiotics not only promote beneficial microbiomes to improve skin health but can also modulate the visual, topographical, and mechanical attributes to improve skin quality. This study was conducted in healthy adults to determine the effect of a topical serum formulation containing the live probiotic Micrococcus luteus Q24 on several key cosmetic skin quality parameters and its beneficial impact on the modulation of the skin microbiome. Quantitative changes in various skin parameters were measured using a skin analyzer device and skin swabs were analysed using whole genome sequencing to monitor microbial diversity and levels of probiotic colonisation. Compared to the baseline, a significant reduction in the pore, spots, wrinkles, and impurities scores; and an increase of 101% in the hydration scores were observed. Additionally, 45-80% of participants showed a decrease in pores, spots, wrinkles, and impurities and 90% of participants showed an increase in hydration after 25 days of probiotic serum application. The WGS analysis of the skin swab samples showed a significant increase in the relative abundance of M. luteus Q24. The results from this study indicated that topical application of serum-containing probiotic M. luteus Q24 offers the benefit of improving skin health quality.

Atopic dermatitis (AD) is a chronic eczematous inflammatory disease that may arise from environmental, genetic and immunological factors. Despite the efficacy of current treatment options like corticosteroids, such approaches are mainly focused on symptoms relief, and may present certain undesirable side effects. In recent years, investigation regarding isolated natural compounds, oils, mixtures and/or extracts, have gained scientific attention because of their high efficiency and moderate to low toxicity. Despite their promising therapeutic effects, the applicability of such natural health care solutions is somehow limited by their instability, poor solubility, and low bioavailability. Therefore, novel nanoformulation-based systems have been designed to overpass these limitations, thus enhancing the therapeutic potential, by promoting the capacity of these natural drugs to properly exert their action in AD-like skin lesions. For the best of our knowledge, this is the first literature review that focused on summarizing the last nanoformulation-based solutions loaded with natural ingredients, and specifically for the management of AD. We suggest that future studies should focus on robust clinical trials that may confirm the security and effectiveness of such natural-based nanosystems, thus paving the way for more reliable AD treatments.

Electrochemical methods are used for the treatment of both municipal and industrial wastewater, either independently or in conjunction with biological methods. This conjunction is used for pretreatment or posttreatment of biologically treated wastewater. In our work, we focused on the combination of these processes, where pre-electrolysis was used to produce dissolved iron before the activation process. Electrolysis was also directly introduced into the activation using either iron or carbon electrodes. The surface of one iron electrode was 32.2 cm2, the applied voltage was 21 V, and the supplied current was 270 mA. The surface of one carbon electrode was 7.54 cm2, the supplied current was 82.5 mA, and the applied voltage was 21 V. From laboratory research on the treatment of synthetic municipal wastewater using a combination of electrolysis and activation processes, it resulted that the use of iron electrodes increased the efficiency of phosphorus removal compared to its precipitation with iron salts. The electrolysis had a positive effect on the sedimentation properties of sludge and the destruction of filamentous microorganisms. Electrolysis negatively affected the respiration rates of activated sludge and the efficiency of denitrification. However, it did not have a negative impact on the nitrification activity of the sludge.

An analysis of the physical and chemical phenomena accompanying the electrical discharges was carried out, principal factors inactivating microorganisms is studied. Characteristic factors of an electric discharge in cavitation mode providing a synergistic effect when disinfecting water with a discharge and chemical reagents are identified in order of importance. As a result of the integral action of cavitation, the inactivation of bacteria is intensified both due to the emergence of chem-ically active particles and due to local shock waves, acoustic currents and ultraviolet radiation in the area of cavitating bubbles. The similarity of cavitation processes in water systems implemented by underwater electric discharges and with the ultrasound has been experimentally proved. The main advantage of electric discharge cavitation in comparison with ultrasonic one is the wide band of ultrasonic frequencies of radiation inherent in electric discharge, high intensity and power of cav-itation processes, and, accordingly, the possibility of a significant increase in the volume of the disinfected liquid. The study enable better understanding and prediction of the effects that occur during a high-voltage underwater electrical discharge and have a bactericidal effect.

Introduction: Psoriasis is an inflammatory skin disease. The objective was to elaborate a cream with natural products and salicylic acid. Hypothesis: ¿Will the topical cream made from natural products reduce the characteristic clinical signs of psoriasis? Methodology: Quasi-experimental clinical trial, in 100 healthy volunteer subjects, five formulations of the new product were prepared and applied to each 20 healthy subjects. The universe was 270 patients with different type of dermatology disease, 120 volunteer patients were selected with Psoriasis, of which he creams was applied to 60 volunteer patients with mild and moderate psoriasis were no randomly administered the full formulation of the new product at TMC Hospital. The database for this study is in the Figshare and Dryad repository. Outcome: In healthy subjects showed that 99% had no side effects. In psoriasis patient mild and moderate psoriasis at TMC Hospital was evaluated the results before and after treatment with the new formulation, Using T Student for paired tests, in the clinical variables, as well as the PASI index and the SBA, the alternative hypothesis was proved, the new formula is effective in the control post treatment of psoriasis (p=0.000). Discussion: The new formulation showed greater efficacy after 10 days treatment. This cream is recommended as an alternative and complementary therapy for psoriasis, since it did not show secondary reactions in healthy subjects, so its effectiveness was demonstrated in this study. A new population study is recommended by regions in Ecuador: coast, highlands, Amazon and Galapagos Island, to evaluate the response to treatment.

LCK, a member of the Scr kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibition of Lck has been mainly to treat hematologic malignancies with a high rate of success. They may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown inter-esting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs host disease. Drug repurposing and bioinformatics can aid in solving several unsolved is-sues on the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

Background: this interventional pilot study aimed to evaluate the short-term (3 years) efficacy of focal laser ablation (FLA) in treating the index lesion of low-intermediate risk prostate cancer, along with assessing the safety of the procedure (ClinicalTrials.gov ID NCT04045756). Methods: forty patients aged between 46 and 86 with histologically proven organ-confined prostate cancer and low to intermediate progression risk were included. FLA was performed under percutaneous fusion magnetic resonance/ultrasound guidance in a Day Hospital setting under local anesthesia. Patients underwent regular clinical assessments, PSA measurements, post-procedure MRI scans, and biopsies at 36 months or if positive findings were detected earlier. Statistical analyses were conducted to assess trends in PSA levels and cavity dimensions over time. Results: forty patients were initially included, with 15 lost to follow-up. At 36 months, a mean PSA reduction of 60% was observed, and 80% of MRI scans showed no signs of in-field clinically significant residual/recurrent cancer. Biopsies at 36 months revealed no malignant findings in 20 patients. No deterioration in sexual function or urinary symptoms was recorded. Conclusions: FLA appears to be safe, feasible and effective in the index lesion treatment of low-intermediate risk prostate cancer, with a high rate of tumor eradication and preservation of quality of life.

The magnesium ion is an essential cation in the human body and participates in numerous physiological activities. A deficiency in magnesium ions is closely associated with tumor development, and supplementation with magnesium ions has been shown to partially inhibit tumor growth. However, the specific mechanisms by which magnesium ions suppress tumor proliferation remain unclear. Currently, studies have revealed that mitochondria may serve as a crucial intermediate link in the regulation of tumors by magnesium ions. Mitochondria might intervene in the proliferation and invasion of tumor cells by modulating energy metabolism and oxidative stress levels. Therefore, this article provides a comprehensive review of the relationship between magnesium ions and tumors, the mechanisms by which magnesium ions regulate mitochondrial function, and the theoretical basis and prospects of magnesium ion regulation of mitochondrial function for tumor treatment. This review aims to offer insights for clinical tumor treatment strategies involving magnesium ion intervention.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

Mitochondria play a significant role in the functioning of the cell, acting both as an intracellular energy source and a signaling organelle. In the heart, mitochondria produce more than 95% of the ATP in addition to regulating the redox state, calcium homeostasis, apoptosis, and lipid synthesis. However, there is also evidence that mitochondria exist outside of cells where they have been observed to mediate cell-to-cell communication, repair, and participate in the immune response. Cardiometabolic disease (CMD) has a complex pathogenesis closely associated with mitochondrial dysregulation, inflammation, and metabolic abnormalities. Because of this metabolic interdependence between the myocardium and the intracellular mitochondria, circulating extracellular mitochondria (CEMI) are being identified as possible regulators of CMD. Outside of the cell, mitochondrial functions are determined by the mitochondrial form, either as whole functional structures (e.g., small extracellular mitochondria) or as mitochondrial components with or without membrane encapsulation. Here, we explore the different forms of CEMI, their role in CMD pathogenesis, their potential therapeutic utility in treating diseases, and their role as biomarkers.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

Abstract. Daily vitamin D supplementation using higher than normal dosing (up to the upper limit, UL) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database an adequate search for published randomized control trials and other studies was done and results were analyzed. This review provides overview of use of 7000 IU daily, 30,000 IU per week or twice weekly and 50,000 IU weekly of vitamin D on rapid restore of 25(OH)D concentrations to at least 30 ng/mL in different groups of patients at high risk of vitamin D deficiency. The above mention dosing should be considered in adults with obesity or multi-diseased patients on requiring multi-treatment with the use of several drugs, including drugs affecting vitamin D metabolism. The simple schedule for 7000 IU/day, 30,000 IU/week or twice weekly or 50,000 IU/week, all for 6-8 weeks of use by patients representing the increased risk of vitamin D deficiency were provided for consideration. It appeared that higher daily doses or intermittent doses suggested above are effective, safe and responsive for patient’s preferences.

Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases.

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

The per capita availability of freshwater resources on a global scale is gradually decreasing due to population growth, rapid urbanization, industrialization, and modern lifestyles. In this situation, wastewater management becomes a major concern. Conventional treatment processes used to treat wastewater discharges are not adequate for the advanced removal of pollutants, especially refractory organic pollutants, which are mainly organic compounds that are not easily biodegradable in the environment. The use of photocatalytic membrane reactors (PMRs) for tertiary wastewater treatment has attracted much interest in recent periods, and various configurations have been investigated. The performance of a PMR using an iron doped titanium photo catalyst and Polysulfone-based polymeric membrane for municipal wastewater treatment was evaluated under natural and simulated solar light. Obtained results proved that solar driven PMRs can remove organic loading (COD) with high efficiencies and may represent a suitable alternative for the tertiary treatment step of municipal wastewater.

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via selective laser melting (SLM), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 ℃ for 1 hour. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also the influence of the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 hour and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving SLM and heat treatment.

Background Endometrial cancer is the fourth most common type of cancer in the world. Due to the prevalence and high morbidity, it is of key importance to make a quick and accurate diagnosis and effective therapy. The use of photodynamic therapy (PDT) in the treatment of endometrial cancer is a significant challenge in conducting clinical trials. PDT is non-invasive, with few side effects, damaging only neoplastic tissue, leaving healthy adjacent structures intact. Thanks to numerous experiments (also in vitro), PDT is gaining more and more recognition as a potential tool in endometrium cancer treatment. Objective The aim of the study was to analyze the effectiveness of photodynamic therapy on endometrial cancer tissue samples Methods In the in vitro experiment of PDT, sections of endometrial cancer tissue taken from female patients were subjected to. Rose Bengal was used as a photosensitizer in order to assess the usefulness of the applied PDT and to introduce these solutions into the in vivo test procedure. Results Changes on the cellular substrate, such as: chromatin condensation, disturbed structure and shape of cell nuclei were observed in all tissues subjected to PDT. Conclusions The PDT experiment in vitro offers opportunities and hopes for using the chosen procedure also in vivo. Keywords endometrial cancer; photodynamic therapy; in vitro; treatment; rose bengal

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

The supply chain has incorporated products by putting them into hair scarfs. This study introduces the use of mini chips in health and beauty products and can reduce fatigue through enhanced sleep patterns. The mini chip could be placed in the scarf and used as a prototype. RFID technology provides the supply chain with specific information that is used to identify products and make communication easier. (Muhammad, et. al. 2013) This paper presents a new tool herein referred to as a scarf prototype which is developed to analyse EMG (electromyogram), ECG (electrocardiography), EEG (electroencephalogram), and EOG (electro-oculogram) signals that focuses in the area of sleep disorders. The mini chips used can be used to determine a solution for sleep disruption by using automated analytics. This could lead to improvement in our understanding of sleep disruption and overall sleep physiology. Automated technology allows repeated measurements, evaluation of sleep patterns, and provide suggestions to improve a person’s quality of sleep. This analysis compares the use of polysomnography and the scarf prototype. The analytics provide models and shows correlation between variables, such as EMG, ECG, EEG, and EOG. This study shows that the results from the scarf prototype is just as reliable as the original method, polysomnography.

Abstract: Ovarian cancer (OC) ranks as the fifth most common cancer among women in the United States and globally, posing a significant health threat. Reactive oxygen species (ROS) have emerged as critical factors in the pathophysiology of this malignancy. ROS, characterized by their instability due to an unpaired electron, are involved in essential cellular functions and play a crucial role in the immune response under normal physiological conditions. However, an imbalance in ROS homeostasis, leading to excessive ROS production, results in oxidative stress (OS), which can cause indiscriminate damage to cellular structures and contribute to the pathogenesis of specific diseases, including OC. OC is primarily classified based on the originating cell type into epithelial, stromal, and germinal tumors, with epithelial tumors being the most prevalent. Despite advancements in medical technology, early detection of OC remains challenging, often leading to delayed treatment initiation. Current therapeutic approaches include surgical excision of tumor tissue, radiotherapy and chemotherapy. While these treatments are effective in early-stage OC, high mortality rates and frequent relapse underscore the urgent need for novel diagnostic and therapeutic strategies. This review aims to elucidate the role of ROS in OC, emphasizing the potential for developing innovative diagnostic tools and treatments that target ROS-mediated pathways. Given the critical impact of early detection and effective treatment, advancing our understanding of ROS in the context of OC could significantly enhance patient outcomes.

Histone changes that are adjustable and transmitted without altering the DNA sequence are part of epigenetic control. In many disorders, most famously malignancy, abnormal genetic information is seen as a result of mismanagement of typical epigenetic mechanisms. A paradigm change in the diagnosis and treatment of cancer has been brought about by recent discoveries about the processes of epigenetic modifications, chromatin remodeling, and noncoding RNAs implicated in the changed expression patterns of tumor cells. There is a significant increase in the search for drugs that could alter the epigenetic environment altered by tumor cells and benefit from their therapeutic potential. Phytochemicals with a high concentration of naturally produced phenol molecules known as flavonoids can regulate genomic processes. Understanding the precise epigenetic alterations brought on by flavonoid-mediated mechanisms is necessary to develop combination therapy techniques and genomic therapies for cancer. This article aims to thoroughly examine the epigenetic modifications of flavonoids, including their anticancer properties.

We set up this preliminary study to evaluate one main question: could strengthening the microbiome have potential benefits for patients suffering with adverse effects after stopping long term topical steroid use? We aim to turn it into a much larger study if the results show promise. After commonly being prescribed for eczema, cessation of topical steroid use, especially after long periods of inappropriate use, can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). Furthermore, the subsequent withdrawal the body experiences when coming off the drug can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). This preliminary study involved seven human participants suffering with skin problems associated with TSW who approached Dr. Anja Gijsberts-Veens of their own volition because they were interested in more natural recovery methods. Five completed the study in full. Progress in skin condition was tracked by self-assessed symptom severity questionnaires filled out at the beginning and end of the study. The skin microbiome was addressed by using a 100% natural product shown in previous work to significantly increase skin microbiome biodiversity. Three participants implemented dietary changes and supplementation in response to guidance after fecal sample analysis to improve their gut health and biodiversity. The average improvement in skin symptoms for all participants was 40% and average symptom improvement ranged from 14% for Patient 5 to 92% for Patient 1. On average, the participants saw an improvement in 85% of their symptoms and a stagnation or regression in 11% and 4% respectively. We believe these results show enough promise to warrant expansion of this research to use a larger sample size, preferably 50+ participants, in future work. We also aim to swab the skin of participants to assess the effect on the skin microbiome from skin and gut treatments, as well as including more in-depth analysis of skin and gut microbiomes.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement, but for its use adapted to the peculiarities of the disease manifestation and of the patients. A “broad” comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation and platelet-rich plasma therapies. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation, in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using the latest algorithms for meta-analysis and meta-regression implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, HA-based products, currently under circumspection, are still clinically useful.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

Lyme disease is a highly prevalent tick-borne infection caused by Borrelia burgdorferi spirochetes in North America and Eurasia. Diagnosis of the early disease remains difficult with the currently approved serological tests in the absence of noticeable tick bite or erythema migrans due to presentation of non-specific symptoms and the absence of antibodies early in infection. Furthermore, it is difficult to distinguish persistence of disease and reinfection in the endemic regions. If not treated early, infection spreads throughout the body and affects most organs with disease manifestations including arthritis, musculoskeletal pain, neuroborreliosis and acrodermatitis chronicum atrophicans. Although most patients recover after antibiotic treatment, ~10-12% of show recurrence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). Various causes of PTLDS are not well-defined; however, the spirochete persisters, antigenic debris, dysregulation of immunological response in individuals or a combination of these factors are proposed to result in continuation of Lyme disease manifestations. Based on these considerations, this review highlights currently employed treatment approaches with antimicrobials and vaccines being tried for prevention of B. burgdorferi infection. We also summarize combinatorial approaches that could be employed to alleviate symptoms to improve the quality of life of the individuals suffering from long Lyme disease.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

Childhood obesity is a public health problem and most of the interventions are focused on healthy habits as reducing energy intake, avoiding a sedentary lifestyle and increasing physical activity. However, usually they are based in individual programs, with few structured interventions in health systems without satisfactory results. PinPo aims to carry out an integral intervention in children with obesity, as well as in their parents and caregivers, to get motivation to change towards healthy lifestyle habits. The program contains 9 educational grupal sessions directed by a multidisciplinary expert team. 10 boys and girls, and another group with 10 family members and/or caregivers participate in sessions during 90 min biweekly. Moreover, there is an individual adaptation depending on the severity and comorbidities. At the beginning and at the end of the program, an integral evaluation for health status is developed including anthropometric, nutritional, physical activity, and psychologist and analytical measurements. Finally, a satisfaction survey is carried out on the participants.In conclusion, the implementation of PinPo could offer to paediatric patients with obesity and their families, an integral intervention to treat obesity and its complications. So, there are expectations of achieving favorable results that also allow to optimize its effectiveness.

Global crop yields are estimated to be reduced by 30–40% per year on account of plant pests and pathogens. Agricultural insect pests raise concerns about constraining global food security and climate changes contributing to the rise of infestation. The current management relies on plant breeding, associated or not with transgenes and chemical pesticides. Both approaches face serious technology obsolescence on the field due to resistance breakdown or development of insecticide resistance. The need for new Modes of Action (MoA) approaches in managing crop health grows each year, driven by market demands to reduce economic losses and phytosanitary requirements to meet the consumer perception. Disabling pest genes by sequence-specific expression silencing is considered a promising tool in the development of environment and health respectful biopesticides. The specificity conferred by long dsRNA-base solutions give support to minimizing effects on off-targeted genes in the insect pest genome and the target gene in non-target organisms (NTOs). In this review, we summarize the current status of gene silencing by RNA interference (RNAi) for agricultural control. More specifically, we focus on the engineering, development and application of gene silencing to control Lepidoptera by the employment of non-transforming dsRNA technologies. Despite some delivery and stability drawbacks of topical applications, we reviewed works showing convincing proof-of-concept results that point to imminent innovative solutions. Considerations about the regulamentation of the ongoing research on dsRNA-based pesticides to produce commercialized products for exogenous application are discussed. Academic and industry initiatives reveal a worthy effort to accomplish controlling Lepidoptera pests with this new mode of action to provide more sustainable and reliable technologies to field management. New data on genomics of this taxon encourage the increment of a customized target genes portfolio. As a case of study, we illustrate how dsRNA and associated methodologies could be applied to control an important Lepidopteran coffee pest.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p&lt;0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

The main purpose of this work was to tests of form and size of fatigue wear of the top layer of oil gear pump wheel (3PW-BPF-24). The object of tests was operated during a determined number of hours at strictly controlled operational and environmental parameters. A microscope of focal differentiation by Alicona InfiniteFocus G4 (with Focus-Variation optical measuring technology) was used for an identification, measurement and description of noticed superficial defects, which resulted from the fatigue process of the top layer and an earlier thermochemical treatment. The work was finished with an analysis of obtained results (based on the analysis of 3D scans) and conclusions concerning about optimization of the thermal treatment. Taking into consideration the presented results (suggestions) in the technology of improving strength properties of gear wheels (of this type oil pumps) may render it possible to obtain an appropriate fatigue endurance of the top layer, i.e. a minimization of observed superficial defects.

We present a case report of a 26-years-old female suffering from Coffin Siris Syndrome, who underwent orthodontic treatment and surgery to solve her malocclusion and improve her aes-thetics and functional occlusion. Methods: The presurgical phase involved multibracket self-ligating attachments, Damon prescription. The patient underwent maxillofacial surgery to correct the severe skeletal malocclusion and relocate the bone bases in the right relationship. The post-surgical orthodontic treatment was performed to complete the alignment. Results: The pa-tient improved her aesthetics and functional abilities. Conclusions: Syndromic patients can un-dergo orthodontictreatment if comorbidities and collaboration allow it. Support and collaboration of families and psychotherapists must be considered, but clinical cases of syndromic patients can be faced and solved. Obviously, each syndromic patient is considered unique, and the risk-benefit ratio must be correctly assessed for each one.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This, has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized to have important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial. Its seems that the role of NtproBNP in the diagnosis of HFpEF, is mainly driven by the pathophysiological characteristics of the patients.

Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dys-function. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, throm-boembolism, kidney, and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta–blockers, calcium inhibitors, ACE inhibitors, and anti–platelet drugs remain a second–line treatment after dietary intervention and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be quite effective and free from side effects, either taken together or before the standard pharmacological intervention. Such herbal–originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea–buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (mother-wort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and po-tential therapeutic option in the management of cardiovascular disorders.

In the process of sewage coagulation treatment, quartz sand is often used as a heavy medium to accelerate the settling rate of flocs, but it will adversely affect the removal efficiency of pollutants. The factors that affect the coagulation effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc, their reasonable setting is critical to. This paper was to study the optimal conditions of quartz sand enhanced coagulation(QSEC), first, single-factor tests were conducted to preliminarily explore the optimal range of influencing factors, and then response surface methodology（RSM）tests were performed to accurately determine the optimums of significant factors. The results showed that the addition of quartz sand can’t improve the water quality of coagulation treatment, but it can significantly accelerate the coagulation settlement process, the quartz sand dosage, the coagulant dosage and sewage pH all impacted significantly on its coagulation effect, and existed inflection points. A model that could guide QSEC was obtained by RSM tests. The model optimization and experimental validation showed that the optimal QSEC conditions for treating domestic sewage were as follows: the polyaluminum chloride(PAC) dosage, cationic polyacrylamide(CPAM) dosage, the sewage pH, quartz sand dosage, stirring time and settling time were 0.97 g·L-1, 2.25 mg·L-1, 7.22, 2 g·L-1, 5 minutes and 30 minutes, respectively, and the turbidity of treated sewage was reduced to 1.15 NTU.

CoCrFeNiMn high-entropy alloy coatings were prepared on compacted graphite iron（CGI） through plasma cladding to strength the CGI substrate. The effects of heat treatment temperatures and times on the microstructure and mechanical properties of the CoCrFeNiMn coatings were investigated. After heat treatment, a single FCC phase was remained in the coating as compared to the deposited one, with smaller dendrites, larger dendritic spacing and more Cr-rich compounds precipitated between dendrites. The coatings’ microhardness was increased after heat treatment. After heat treated at 660°C for 90 minutes, the coating had the highest microhardness of 563±6.9 HV0.2, the lowest frictional coefficient of 0.71 and the smallest wear mass loss of 1.12 mg, and it had the best wear resistance.

Anastomotic insufficiencies are severe complications of abdominal surgery, often leading to pro-longed hospitalization, serious tissue inflammation, even sepsis and the need for recurrent sur-gery. Current non-surgical treatments such as self-expanding metal stents (SEMS) and endoscopic vacuum therapy (EVT) have limitations, including stent migration or perforation. This review evaluates the effectiveness of the VacStent GITM, a novel medical device combining SEMS and negative-pressure wound therapy in treating gastrointestinal leaks. Data were gathered from four prospective studies and compared with existing treatments. Studies on the VacStent GITM applica-tion demonstrate technical success and competitive closure rates in upper gastrointestinal leaks, with minimal complications reported. Comparative analyses with SEMS and EVT reveal prom-ising and most importantly equally good outcomes while maintaining the possibility for sus-tained enteral nutrition and reducing stent migration risk. The VacStent GITM presents a promis-ing alternative to current non-surgical treatments. Ongoing research aims to validate its efficacy in lower gastrointestinal leaks and establish its role in leak management comprehensively. Fur-ther investigation is necessary to confirm these findings and optimize treatment protocols. Future usages of the VacStent GITM in colonic anastomotic insufficiencies promise an effective approach and might be able to lower the rates of necessary implementations of a stoma.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The patho-genesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counteract disease progression and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the cy-tokines in the pathogenesis and treatment of ALD.

Introduction: Parkinson’s disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (9 homozygous or compound heterozygous PRKN carriers, 4 Heterozygous PRKN carriers and 3 biallelic PINK1 carriers) were evaluated. Results: The average Levodopa Equivalent daily dose (LEDD) was 806.8±453.5 (range 152-1810) in PRKN carriers and 765±96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of Levodopa. The response to Dopamine Agonists (DA) was often favorable both as initial and longitudinal therapy. 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate Levodopa or DA. Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any Levodopa treatment decades after disease initiation. DA or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments will be further discussed.

The introduction on Zinc oxide nanoparticles (ZnOn) in sunscreens solved the issue of poor spreadability of these formulations, which often left a white film on the skin. However, safety concerns have arisen regarding the topical application of ZnOn. Some studies employed commercial sunscreens to address the safety issues of the topical application of ZnOn; however, commercial formulations are often complex and contain a wide range of ingredients that could attenuate the potential damage caused by the ZnOn. Therefore, in this study we aimed to develop a simple stable formulation containing 20% of coated and uncoated ZnOn, characterize the formulations and the nanoparticles, and assess the skin penetration in Franz diffusion cell. The Feret's diameter for the uncoated and coated ZnOn was 137 nm and 134 nm, respectively. For the uncoated ZnOn the hydrodynamic size in water was 368 nm and for the coated ZnOn, the average hydrodynamic size in ethyl acetate was 135 nm. The incorporation of ZnOn led to formulations more consistent and easier to spread, as suggested by the lower work of shear and higher values of firmness, cohesiveness, consistency and index of viscosity compared with the vehicle. The stability assessment at 45ºC suggested that the formulations containing the ZnOn were stable for 30 days and the vehicle was stable for 90 days. The assessment off the skin penetration by reflectance confocal laser microscopy indicated that the formulations did not permeate into the deepest layers of the skin, but accumulated on the skin furrows, hair and hair follicle.

BACKGROUND: diabetic foot ulcers (DFU) represent the main cause of major amputations and hospitalizations in diabetic patients. Aim of this study was to assess safety and cost-efficacy of intramuscular injection of peripheral blood mononuclear cells (PBMNCs), in diabetic patients with no-option chronic limb-threatening ischemia (CLTI) and small artery disease (SAD). METHODS: a retrospective study was carried out on a series of types 2 diabetic patients with DFU grade Texas 3 and no-option CLTI and SAD. All patients had undergone at least a previous revascularization and were allocated in a surgery waiting-list for major amputation. The principal endpoint evaluated at 90 days was a composite of TcPO2 values at the first toe ≥30 mmHg and/or TcPO2 increase of at least 50% from baseline and/or ulcer healing. Secondary endpoint were individual components of the primary endpoint, any serious and non-serious adverse events, direct costs at one year. RESULTS: the composite endpoint was achieved in 9 patients (60.0 %); one patient (6.7%) healed within 90 days and 26.7% and 46.7% showed TcPO2 ≥30 mmHg and a TcPO2 increase of at least 50% at 90 days, respectively. At 1-year, three (20.0%) patients underwent a major amputation (all diagnosed SAD grade III). One patient died after seven months, and seven patients (46.7%) healed. The overall median and mean cost per patient were 8,238±7,798€ and 4,426[3,798;8,262]€, respectively. CONCLUSIONS: the use of PBMNCs implants in no-option CLTI diabetic patients with SAD seems to be of help in reducing the risk of major amputation.

Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled in the ocular surface. To evaluate the safety, tolerability, and biologic activity of TALF, an animal study and a phase I clinical assay was performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biologic activity of the formulation. No inflammation, lens opacity, swelling or intraocular pressure rising were recorded after the instillation of TALF in any of the animal or clinical study. Mainly, mild and transient adverse events such as dry eye (30%) and burning (30%) were reported. TALF improves significantly visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biologic activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroids IVTs and its associated hazards.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with GWAS studies showing that many psoriasis risk genes lie along the IL23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. The pathogenesis of psoriasis is complex and focusing on the IL23/Th17 axis can provide insight into key cell types, cytokines and intracellular signaling pathways involved. Examination of currently available biological treatments, time to relapse post drug withdrawal and rates of drug primary/secondary drug failure show the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely reduce dis-ease burden for the longest period possible.