Systemic Absorption Research Articles

Effect of postprandial gastric conditions on in vitro drug release from modified release mesalamine formulations

The effect of gastric prandial conditions on in vitro drug release from oral, locally acting, colon-targeted, mesalamine formulations has not been previously evaluated. In vitro dissolution of four mesalamine formulations were investigated using a USP II paddle apparatus. Fed gastric conditions were simulated under three consecutive phases of milk/buffer at different ratios to simulate changes in physicochemical, gastric composition during food digestion. Drug release was not observed from enteric coated preparations in the fasted state. Under simulative postprandial gastric conditions, however, drug release from Apriso® extended release (ER) capsules was 19 ± 4.7 %. As for Lialda® delayed release (DR) tablets, following two hours of exposure to simulative ileo-colonic media comprising bicarbonate buffer, drug release in the fed and fasted states was 55.7 ± 22.4 % and 12.4 ± 6.4 %, respectively. Significant differences in in vitro dissolution profiles were not observed between fasted and fed conditions for Pentasa® ER capsules and Asacol® HD DR tablets. Published pharmacokinetic data for Apriso and Lialda show higher systemic absorption of mesalamine in fed compared to fasted individuals. Our in vitro data is consistent with these pharmacokinetic findings since fed conditions may give rise to a higher extent of proximal drug release and therefore greater systemic absorption. Furthermore, extent of systemic exposure to mesalamine from Pentasa and Asacol was found not to be affected by food intake. In vitro dissolution studies simulating the gastric prandial state can possibly predict the impact of food on drug release from delayed and sustained release, locally acting formulations.

Antioxidants had No Effects on the In-Vitro Permeability of BCS III Model Drug Substances

Reformulation with addition of antioxidants is one potential mitigation strategy to prevent or reduce nitrosamine drug substance-related impurities (NDSRIs) in drug products. To explore whether there could be other approaches to demonstrate bioequivalence for a reformulated oral product, which typically needs in vivo bioequivalence studies to support the changes after approval, the effects of antioxidant on the in vitro permeability of BCS III model drug substances were investigated to see whether there could be any potential impact on drug absorption. Six antioxidants were screened and four (ascorbic acid, cysteine, α-tocopherol and propyl gallate) were selected based on their nitrosamine inhibition efficiencies. The study demonstrated that these four antioxidants, at the tested amounts, did not have observable impact on the in vitro permeability of the BCS III model drug substances across Caco-2 cell monolayers in the In Vitro Dissolution Absorption System (IDAS). An in vitro permeability study could be considered as part of one potential bioequivalence bridging approach for reformulated low-risk immediate release solid oral products and oral suspension products. Other factors such as the influence of antioxidants on intestinal transporter activities should be considered where appropriate.

Ingestion of Fluids of the Ocular Surface Containing Eye Drops of Imidazole Derivatives-Alpha Adrenergic Receptor Agonists as Paragons.

Accidental poisonings by ingesting conjunctival fluid mixed with eye drops commonly involve alpha-2 adrenergic receptor agonists and tetrahydrozoline. These substances are recognized in commonly reported ingestions. Victims of all ages, otherwise in good health, often present as pale and lethargic to the emergency department (ED) after unintentionally ingesting topical eye medication. While eye drop poisoning cases in childhood include accidents during the play and poisonings in adults mean either suicide attempts or side effects caused by the systemic absorption of the substance, fluid of the ocular surface is a risk to all age groups. With this in mind, this study aimed to summarize data in the literature on tetrahydrozoline and alpha-2 adrenergic receptor agonists as dangerous medications, even when administered in low-bioavailability forms, such as eye drops. With this aim, a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review of relevant studies was conducted. A search of PubMed, Scopus, Web of Science, and EBSCOhost yielded nine studies that met the rigorous inclusion criteria. The primary studies were subject to a meta-analysis once a quality appraisal of the studies and a narrative synthesis of the extracted data had been conducted. The author hopes that this information will provide observations that will lead to better designs for over-the-counter eye drops, off-label drug usage policies, and parental attention.

Qualification of In Vitro Dissolution Absorption System 2 (IDAS2) with Caco-2 and MDCK Cell Monolayers: Dose Sensitivity Study Using BCS Class I and III Drugs.

This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell monolayer through dose sensitivity studies. Metoprolol and propranolol were selected as Biopharmaceutics Classification System (BCS) Class I model drugs, and atenolol as a Class III model drug. The IDAS2 is comprised of a dissolution vessel (500 mL) and two permeation chambers (2 × 8.0 mL) mounted with Caco-2 or MDCK cell monolayer. One or two immediate-release tablet(s) of the model drug were added to the dissolution vessel, and the time profiles of dissolution and permeation were observed. Greater than 85% of metoprolol and propranolol (tested at two dosing concentrations) were dissolved by 15 min, and all drugs were fully dissolved by 30 min. All three drugs were more permeable across Caco-2 cells than MDCK cells with a linear increase in permeation across both cells at both dose concentrations. Thus, the dose sensitivity of the IDAS2 was demonstrated using both cell barriers. These results indicate a successful qualification of IDAS2 for the development/optimization of oral formulations and that MDCK cells can be utilized as a surrogate for Caco-2 cells.

Effect of Celery (Apium graveolens L.) Extract Administration on Kidney Function of White Rats (Rattus norvegicus) Wistar Strains Exposed to Lead

Lead significantly affects health because of its sensitivity to the central nervous system and rapid absorption rate. The phytochemicals included in celery, such as flavonoids, may mitigate lead-induced kidney damage. This research aimed to determine how administering celery extract affected the expression of the Caspase-3 gene and the kidney TNF-α gene in Rattus Norvegicus Wistar white rats exposed to lead. The research method true experiment examined the effects of 80 mg/day celery extract on Caspase-3 gene expression and renal TNF-α gene expression in rats exposed to lead. Each of the three groups will include six rats; there will be eighteen male Wistar rats in the study. The study used SPSS 26.0 and the Saphiro Wills test to analyze data on TNF-α and Caspase 3 expression in rats exposed to lead acetate (Pb). The results showed a normal distribution for the negative control group (K-) and the positive control group (K+) and a normal distribution for the treatment group (P). However, the paired t-test showed significant differences in all treatment groups (p <0.05), indicating a normal distribution in the data. The study concludes the impact of celery extract on kidney function in lead-exposed Wistar rats, revealing various active compounds like flavonoids. Despite insignificant caspase 3 reduction, flavonoids showed potential in mitigating lead-induced kidney damage.

A Comprehensive Review of the Use of Nanoparticles in Cosmeceutical Science

Nanotechnology is significantly impacting the cosmeceutical sector, revolutionizing how skincare products are formulated and delivered. Innovative nanoparticle delivery systems such as liposomes, niosomes, nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), gold nanoparticles, and nano-emulsions are at the forefront of this transformation. These systems enhance the bioavailability, stability, and efficacy of active ingredients, offering controlled release and targeted delivery features that are crucial for optimizing cosmetic results. Nanotechnology facilitates improved penetration of actives into the skin, protects ingredients from degradation, and ensures sustained release, thereby enhancing the therapeutic effectiveness of cosmeceuticals. Additionally, the integration of nanoparticles into cosmetic products allows for reduced dosages and minimized side effects, which contributes to better skin tolerance and safety. However, the use of nanotechnology in cosmeceuticals is not without challenges. It raises significant safety and environmental concerns due to the potential systemic absorption of nanoparticles. Regulatory bodies globally are striving to address these issues, with guidelines and regulations continuously evolving to ensure consumer safety while fostering innovation. The current review highlights the dual aspects of opportunity and oversight that nanotechnology brings to the beauty and skincare industry, emphasizing the need for ongoing research and regulatory vigilance to harness its full potential responsibly

A phase 1, open-label, dose escalation study on the safety and tolerability of ANK-101 in advanced solid tumors.

TPS2689 Background: IL-12 is a cytokine that can stimulate both innate and adaptive tumor immunity. Clinical trials of intravenous IL-12 demonstrated anti-tumor activity limited by significant systemic toxicity, including patient deaths. ANK-101 is an anchored immunotherapy that links IL-12 to aluminum hydroxide through an alum-binding protein (ABP). The ANK-101 complex anchors IL-12 in the tumor microenvironment (TME), resulting in prolonged local retention and low levels of systemic absorption. Preclinical studies in murine tumor models showed that ANK-101 is retained at the injection site for up to 28 days, recruits and activates T and NK cells, promotes M1 myeloid cell differentiation, induces regression of both injected and un-injected tumors, and induces immunologic memory. Methods: This is a first-in-human, open-label dose escalation study of ANK-101 in advanced solid tumors with a planned sample size of 12-36 participants. The first three dose escalation cohorts include a single participant, and then study enrollment follows a standard 3+3 dose escalation design. If no dose limiting toxicity (DLT) is observed, the dose level will be escalated until ≥1/3 or ≥2/6 patients experience a DLT. An additional ten patients will be enrolled at the recommended dose for expansion (RDE). Participants will be treated with intratumoral ANK-101 every 3 weeks for 4 cycles. Imaging or clinical assessments will be performed at week 12. If there is no significant clinical deterioration or unacceptable toxicity at this visit, participants may receive four more cycles. Eligible patients must have an advanced solid malignancy refractory to standard treatment and be accessible for injection and biopsy, measurable disease by RECIST v1.1, and ECOG PS of 0-1. Key exclusion criteria include tumors close to vital structures, uncontrolled bleeding disorders, and active autoimmune disease. Primary objectives of the study are to determine the safety and tolerability of ANK-101 and identify the RDE. Secondary objectives include pharmacokinetics (PK) and immunogenicity (ADA) of ANK-101 and clinical activity as measured by ORR, DCR, DOR and PFS by RECIST v1.1. Exploratory objectives include assessment of QOL using FACT-G and profiling immune-based pharmacodynamic (PD) changes. PD assessments will include serum cytokines and circulating immune cells, and local levels of PD-L1, CD8+ T cells, and CD68+ macrophages, and changes in gene expression within the TME. This clinical trial is in progress. Clinical trial information: NCT06171750 .

Life cycle cost assessment of geothermal energy assisted hydrogen liquefaction for sustainable and renewable energy applications: Case study and adaptation for Afyon geothermal power plant

This study presents a comprehensive Life Cycle Cost Assessment (LCCA) of geothermal-assisted hydrogen liquefaction, explicitly focusing on the Afyon Geothermal Power Plant (AGPP) as a case study. The study evaluates the economic viability and sustainability of integrating geothermal energy into hydrogen liquefaction. The results of the LCCA contribute to the ongoing discourse on sustainable energy solutions, offering a nuanced understanding of the economic considerations associated with geothermal-assisted hydrogen liquefaction. The study serves as a model for assessing the economic feasibility of similar systems, fostering informed decision-making in the pursuit of cleaner and more economically sustainable energy pathways. This study has conducted a technical and economic investigation of liquid hydrogen production using geothermal heat and electricity effects. Geothermal water pre-cools the hydrogen by providing heat to the absorption system. Then, the electricity generated in the geothermal plant is used to work in the liquefaction cycle. The generated electricity is used to liquefy hydrogen in the liquefaction cycle. The capacity of the electricity generated from the AGPP produced here is 2621 kW. The proposed system can be achieved by pre-cooling unit H2 up to −30 °C at 120 °C and 150 kg/s geothermal source. In the liquefaction cycle, 0.84 kg/s H2 can be liquefied. As a result, the total energy efficiency of the proposed system can be calculated as 32.4% and exergy efficiency as 15.4%. The system's net present value (NPV) was calculated as 65,320,000 $. When life cycle cost analysis was performed using the levelized annual cost (LAC) method, the project's levelized cost was calculated as 7,673,000 $/yr. The unit cost of the liquid hydrogen produced is 1.252 $/kg. This system's discounted payback period (Ndpp) is calculated as 3.48.

Nutrition Requirements and Nutrition Intervention for People Living with HIV/AIDS (Adults)

AbstractNutrition plays a crucial role in the overall health and well-being of people living with human immunodeficiency virus (HIV). This review aims to provide a current summary of the macronutrient and micronutrient requirements for HIV-positive individuals. The author emphasizes the fundamentals of nutrition treatment as a guide for medical professionals to adopt the right strategy based on risk-adapted nutrition therapy. The majority of nutrition guidelines were published over 10 years ago and have failed to address the protein requirements for people with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Proper nutrition can reduce the risk of malnutrition, infections, and other complications, while also assisting with symptom management, maintaining a healthy weight, and improving immune function. In this review, the author has identified the latest reliable and validated nutrition screening tool specifically designed for people with HIV/AIDS, along with a risk-stratified nutrition therapy based on the screening tool to facilitate the nutrition care process. People living with HIV/AIDS have unique nutritional needs due to the virus's impact on the body's immune system, metabolism, and nutrient absorption. It is important for them to work with a healthcare professional, namely a dietitian, to assess nutrition risk and develop an individualized dietary intervention for a healthy lifestyle.

Oleanolic Acid Promotes the Formation of Probiotic Escherichia coli Nissle 1917 (EcN) Biofilm by Inhibiting Bacterial Motility.

Probiotic biofilms have been beneficial in the fight against infections, restoring the equilibrium of the host's gut microbiota, and enhancing host health. They are considered a novel strategy for probiotic gut colonization. In this case, we evaluated the effects of various active substances from traditional Chinese medicine on Escherichia coli Nissle 1917 (EcN) to determine if they promote biofilm formation. It was shown that 8-64 μg/mL of oleanolic acid increased the development of EcN biofilm. Additionally, we observed that oleanolic acid can effectively suppress biofilm formation in pathogenic bacteria such as Salmonella and Staphylococcus aureus. Next, we assessed the amount of EcN extracellular polysaccharides, the number of live bacteria, their metabolic activity, the hydrophobicity of their surface, and the shape of their biofilms using laser confocal microscopy. Through transcriptome analysis, a total of 349 differentially expressed genes were identified, comprising 134 upregulated and 215 downregulated genes. GO functional enrichment analysis and KEGG pathway enrichment analysis revealed that oleanolic acid functions are through the regulation of bacterial motility, the iron absorption system, the two-component system, and adhesion pathways. These findings suggest that the main effects of oleanolic acid are to prevent bacterial motility, increase initial adhesion, and encourage the development of EcN biofilms. In addition, oleanolic acid interacts with iron absorption to cooperatively control the production of EcN biofilms within an optimal concentration range. Taking these results together, this study suggests that oleanolic acid may enhance probiotic biofilm formation in the intestines, presenting new avenues for probiotic product development.

Utilization of Geothermal Fluid as a Heat Source for Absorption Refrigeration System for Food Preservation – A Case of Bwanda and Gwisho Hotsprings

Zambia has significant geothermal resources with over 86 hotsprings identified. Installation of a 250kW off-grid pilot binary-cycle power plant is currently underway at the Bwanda and Gwisho goethermal site. It is estimated that there is 90,000 herd of cattle in the villages around the pilot power plant. Little milk from these herds of cattle reaches the market due to scarce collection points with cooling facilities. This study assesses the applicability of utilizing exhaust geothermal fluid from a binary-cycle geothermal power plant for powering an absorption refrigeration system (ARS) for storing food, specifically milk. Two absorption systems; Lithium Bromide-water and the ammonia-water ARS are compared. The COPs, energy input and mass flowrates required to produce various cooling loads (40kW – 160kW) are compared. The results show that the exhaust geothermal fluid energy (504kW) is sufficient for powering both ARSs for storing milk to its suitable storage temperature of 4oC. The results also show that the Lithium Bromide-water system is more suitable for this application, because it produces a higher maximum COP (0.76) compared to the ammonia-water system’s maximum COP (0.64), it produces a higher maximum cooling capacity (380kW) compared to the ammonia-water systems maximum capacity (216kW). It requires lower input mass flowrate and pump work at all cooling capacities (40kW – 160kW). Therefore, a Lithium Bromide-water absorption chiller for storing the amounts of milk currently collected in the study area is designed. Optimized design specifications are provided.

Effect of phospholipid curcumin Meriva on liver histology and kidney disease in nonalcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial.

NASH confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed the safety and efficacy of Meriva in NASH. In this double-blind trial, 52 patients with biopsy-proven NASH (71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a chronic kidney disease) were randomized 1:1 to receive Meriva 2g/d or placebo for 72 weeks. The primary endpoint was NASH resolution with no worsening of fibrosis. The secondary endpoints included a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant (ie, stage ≥F2) fibrosis and CKD; and improvement in renal, glucose, lipid, and inflammatory parameters. We also explored the treatment effect on hepatic activation of NF-kB, a key proinflammatory transcription factor and a major target of curcumin. Fifty-one patients (26 on Meriva and 25 on placebo) completed the trial. Sixteen (62%) patients on Meriva versus 3 (12%) patients on placebo had NASH resolution (RR = 5.33 [95% CI = 1.76-12.13]; p = 0.003). Thirteen (50%) patients on Meriva versus 2 (8%) patients on placebo had ≥1 stage fibrosis improvement (RR = 6.50 [1.63-21.20]; p = 0.008). Eleven (42%) patients on Meriva versus 0 (0%) on placebo had regression of significant liver fibrosis (RR = 18.01 [1.43-36.07]; p = 0.02). Hepatic NF-kB inhibition predicted NASH resolution (AUC = 0.90, 95% CI = 0.84-0.95) and fibrosis improvement (AUC = 0.89, 95% CI = 0.82-0.96). Thirteen (50%) patients on Meriva versus 0 (0%) on placebo had chronic kidney disease regression (RR = 10.71 [1.94-17.99)]; p = 0.004). Compared with placebo, Meriva improved eGFR (difference in adjusted eGFR change: +3.59 [2.96-4.11] mL/min/1.73m 2 /y, p = 0.009), fasting glucose(-17mg/dL; 95% CI = -22, -12), HbA1c (-0.62%; 95% CI = -0.87%, -0.37%), LDL-C (-39mg/dL; 95% CI = -45, -33), triglycerides (-36mg/dL, 95% CI = -46, -26), HDL-C (+10mg/dL; 95% CI = +8, +11), and inflammatory markers. Adverse events were rare, mild, and evenly distributed. In patients with NASH, Meriva administration for 72 weeks was safe, well-tolerated, and improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile.

Development and Evaluation of Mucoadhesive Buccal Patch of Losartan Potassium

The buccal mucosa is regarded as an ideal location for administering medications for both local and systemic absorption. Mucin and polymers interact chemically during the mucoadhesion process. Much emphasis has been paid to the use of mucoadhesive polymers in buccal medication delivery. There are now many mucoadhesive dosage forms available, including pills, patches, disks, wafers, ointments, and gels. Buccal patches stand out among them for their higher comfort and flexibility. With their effective carrier capacity, smart materials like stimuli-responsive hydrogels, liposome-based patches, polymeric micelles, etc. play a crucial role in the development of these drug delivery systems by extending the drug's residence time at the site of absorption, improving drug bioavailability, reducing the frequency of dosing, and increasing patient compliance. Different designs and production techniques, including as electrospinning, electrospraying, and 3D printing, are thought to be novel and effective ways to manufacture buccal patches with certain distinctive qualities in comparison to conventional procedures like solvent casting. Aiming to develop buccal mucoadhesive patches as a novel controlled drug delivery system, this review aims to examine and introduce the most promising smart polymeric materials, new designs, and production techniques.

Energy and exergy analysis of an experimental NH3-LiNO3 air-conditioning absorption system

An energy and exergy analysis of an experimental air-conditioning absorption system operating with the ammonia-lithium nitrate mixture has been performed. The system was operated under controlled and steady-state conditions. The main operating parameters, such as flow ratio, coefficient of performance, exergy coefficient of performance, and exergy destruction in each one of the main components, were determined at different heat sources and condensing temperatures. The coefficients of performance varied between 0.5 and 0.65, while the exergy coefficients of performance varied between 0.1 and 0.2. Clear trends were found for the coefficient of performance and flow ratio as a function of the generator and condenser temperatures; however, no trends were found in the exergy coefficients of performance due to the high variability of the ambient temperature. The highest values of the exergy destruction occurred in the generator, followed by the condenser and the evaporator, while the lowest values were obtained in the absorber and the economizer.

Correlation between Vascularity and Advancing Histological Grades of Oral Submucous Fibrosis with a Plausible Role in Malignisation: Systematic review of a persisting matter of conflict.

This study aimed to quantify the vascularity in histological grades of oral submucous fibrosis (OSMF) and to determine if there is any connection between vasculogenesis and malignisation. Recent studies show no significant change in vascularity as the stage advances as opposed to the conventional concept. A comprehensive database search until December 2022 was conducted for published articles on vascularity in OSMF following preferred reporting items for systematic reviews and meta-analyses guidelines. A total of 98 articles were screened of which 13 were included for systematic evaluation. The study included 607 cases, with a definite predilection for the male gender. Of the 13 studies, 11 evaluated mean vascular density. In more than half of the studies, the vascularity decreased as the stage advanced. Similar results were obtained for endothelial cells/μm2, mean vascular area percentage and mean vascular area. The present review supports the prevailing concept that vascularity decreases with the advancement of the OSMF stage. This denies the systemic absorption of carcinogens into the circulation with resultant longer exposure of compromised epithelium and malignisation.

Mitigating phase changes in the gas-phase that disrupt CO2 capture in membrane contactors: CO2-NH3-H2O as a model ternary system

Solid and liquid products can form in the gas phase of membrane contactors applied to reactive ternary systems for CO2 absorption, which poses a critical barrier for carbon capture applications. The mechanism initiating these unwanted phase changes in the gas phase is unclear. This study therefore systematically characterises CO2 absorption in distinct regions of the vapour-liquid equilibrium (VLE) within an illustrative ternary system (CO2-NH3-H2O), to provide an explanation for the formation and mitigation of these solid and liquid products in the gas-phase. Unstable CO2 absorption and increased pressure drop indicated product formation within the gas-phase, which occurred at high CO2 capture ratios. Temporal analysis of gas-phase composition enabled gas-phase products to be related to the relative ternary composition. This was subsequently correlated to distinct regions of the VLE. Consequently, mitigation strategies can be developed with recognition for where products are least likely to form. Pressurisation was proposed to modify the relative gas-phase ammonia composition to reposition conditions within the VLE. The commensurate increase of CO2 into the solvent shifts the ammonia-ammonium equilibrium towards ammonium to indirectly reduce vapour pressure. This synergistic strategy allows sustained operation of membrane contactors for CO2 separation within reactive ternary systems which are critical to delivering carbon capture economically at scale.

In-situ monitoring of in vitro drug release processes in tablets using optical coherence tomography

Film-coated modified-release tablets are an important dosage form amenable to targeted, controlled, or delayed drug release in the specific region of the gastrointestinal (GI) tract. Depending on the film composition and interaction with the GI fluid, such coated products can modulate the local bioavailability, systemic absorption, protection as an enteric barrier, etc. Although the interaction of a dosage form with the surrounding dissolution medium is vital for the resulting release behavior, the underlying physicochemical phenomena at the film and core levels occurring during the drug release process have not yet been well described. In this work, we attempted to tackle this limitation by introducing a novel in vitro test based on optical coherence tomography (OCT) that allows an in-situ investigation of the sub-surface processes occurring during the drug release. Using a commercially available tablet based on osmotic-controlled release oral delivery systems (OROS), we demonstrated the performance of the presented prototype in terms of monitoring the membrane thickness and thickness variability, the surface roughness, the core swelling behavior, and the porosity of the core matrix throughout the in vitro drug release process from OROS. The superior spatial (micron scale) and temporal (less than 10 ms between the subsequent tomograms) resolution achieved in the proposed setup provides an improved understanding of the dynamics inside the microstructure at any given time during the dissolution procedure with the previously unattainable resolution, offering new opportunities for the design and testing of patient-centric dosage forms.

Tailoring 3D Star-Shaped Auxetic Structures for Enhanced Mechanical Performance

Auxetic lattice structures are three-dimensionally designed intricately repeating units with multifunctionality in three-dimensional space, especially with the emergence of additive manufacturing (AM) technologies. In aerospace applications, these structures have potential for use in high-performance lightweight components, contributing to enhanced efficiency. This paper investigates the design, numerical simulation, manufacturing, and testing of three-dimensional (3D) star-shaped lattice structures with tailored mechanical properties. Finite element analysis (FEA) was employed to examine the effect of a lattice unit’s vertex angle and strut diameter on the lattice structure’s Poisson’s ratio and effective elastic modulus. The strut diameter was altered from 0.2 to 1 mm, while the star-shaped vertex angle was adjusted from 15 to 90 degrees. Laser powder bed fusion (LPBF), an AM technique, was employed to experimentally fabricate 3D star-shaped honeycomb structures made of Ti6Al4V alloy, which were then subjected to compression testing to verify the modelling results. The effective elastic modulus was shown to decrease when increasing the vertex angle or decreasing the strut diameter, while the Poisson’s ratio had a complex behaviour depending on the geometrical characteristics of the structure. By tailoring the unit vertex angle and strut diameter, the printed structures exhibited negative, zero, and positive Poisson’s ratios, making them applicable across a wide range of aerospace components such as impact absorption systems, aircraft wings, fuselage sections, landing gear, and engine mounts. This optimization will support the growing demand for lightweight structures across the aerospace sector.

An open-label feasibility trial of transdermal cannabidiol for hand osteoarthritis

Hand osteoarthritis (OA) is an irreversible degenerative condition causing chronic pain and impaired functionality. Existing treatment options are often inadequate. Cannabidiol (CBD) has demonstrated analgesic and anti-inflammatory effects in preclinical models of arthritis. In this open-label feasibility trial, participants with symptomatically active hand OA applied a novel transdermal CBD gel (4% w/w) three times a day for four weeks to their most painful hand. Changes in daily self-reported pain scores were measured on a 0–10 Numeric Pain Rating Scale (NPRS). Hand functionality was determined via daily grip strength measures using a Bluetooth equipped squeeze ball and self-report questionnaire. Quality of life (QoL) ratings around sleep, anxiety, stiffness and fatigue were also measured. All self-report measures and grip strength data were gathered via smartphone application. Urinalysis was conducted at trial end to determine systemic absorption of CBD. Eighteen participants were consented and 15 completed the trial. Pain ratings were significantly reduced over time from pre-treatment baseline including current pain (− 1.91 ± 0.35, p < 0.0001), average pain (− 1.92 ± 0.35, p < 0.0001) and maximum pain (− 1.97 ± 0.34, p < 0.0001) (data represent mean reduction on a 0–10 NPRS scale ± standard error of the mean (SEM)). A significant increase in grip strength in the treated hand (p < 0.0001) was observed although self-reported functionality did not improve. There were significant (p < 0.005) improvements in three QoL measures: fatigue, stiffness and anxiety. CBD and its metabolites were detected at low concentrations in all urine samples. Measured reductions in pain and increases in grip strength seen during treatment reverted back towards baseline during the washout phase. In summary, pain, grip strength and QoL measures, using smartphone technology, was shown to improve over time following transdermal CBD application suggesting feasibility of this intervention in relieving osteoarthritic hand pain. Proof of efficacy, however, requires further confirmation in a placebo-controlled randomised trial.Trial registration: ANZCTR public trials registry (ACTRN12621001512819, 05/11/2021).

Systematic-Narrative Hybrid Literature Review: Crosstalk between Gastrointestinal Renin-Angiotensin and Dopaminergic Systems in the Regulation of Intestinal Permeability by Tight Junctions.

In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin-angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin-angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both renin-angiotensin and dopaminergic systems influence intestinal Na+/K+-ATPase activity, thus maintaining electrolyte and nutritional homeostasis. The colocalization of B0AT1 and ACE2 indicates the direct role of the renin-angiotensin system in amino acid absorption. Yet, more studies are needed to thoroughly define the structural and functional interaction between TJ-associated proteins and GI renin-angiotensin and dopaminergic systems.