Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization.

The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.

Simultaneous Formation of Polyhydroxyurethanes and Multicomponent Semi-IPN Hydrogels.

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU), grew within a colloidal solution of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers A and E, respectively). This method, applied for the first time in Semi-Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a 20-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. Monomer E-based PHU exhibited higher Mw¯ than monomer A-based PHU (34.1 kDa and 16.4 kDa, respectively). Applying the enhanced methodology to prepare 10 multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating monomer E enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when monomer A was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

Do social media interventions increase vaccine uptake?

Introduction: The Italian mass COVID-19 vaccination campaign has included children aged 5-11 years as part of the target population since December 2021. One of the biggest challenges to vaccine uptake was vaccine hesitancy among parents and children's caregivers. Primary care pediatricians (PCPs), as the first point of contact between the National Health Service (NHS) and parents/caretakers, initiated various communication strategies to tackle this hesitancy. This study aims to evaluate the impact of a PCP-led social media intervention and a digital reminder service (DRS) on parental hesitancy regarding vaccinating their 5-11-year-old children against COVID-19. Methods: A prospective cohort study was designed, and the chosen target populations were parents and caretakers of children aged 5-11 years. Two PCP cohorts were recruited. The first group received a social media intervention and a DRS; while the second group did not. Both cohorts had access to traditional face-to-face and telephone-based counseling. The vaccination coverage rate in the two groups was evaluated. Results: A total of 600 children were enrolled. The exposed cohort (277 patients) received social media intervention, DRS, and counseling options (face-to-face and telephone-based), whereas the non-exposed cohort (323 patients) received only counseling options. In total, 89 patients from the exposed cohort did not receive any dose of the COVID-19 vaccine (32.5%), 165 were fully immunized (59.5%), and 23 received only one dose (8.5%). A total of 150 non-exposed patients did not receive any dose of the COVID-19 vaccine (47%), 147 were fully immunized (45.5%), and 24 only received one dose (7.4%). The difference between the two groups was statistically significant (chi square = 11.5016; p = 0.0006). Conclusion: Social media and DRS interventions had a positive impact on vaccine uptake and may be helpful in tackling vaccine hesitancy. Better-designed studies are needed to corroborate these findings.

Biodegradable Guar-Gum-Based Super-Porous Matrices for Gastroretentive Controlled Drug Release in the Treatment of Helicobacter pylori: A Proof of Concept.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Scope and Limitations of Current Antibiotic Therapies against Helicobacter pylori: Reviewing Amoxicillin Gastroretentive Formulations.

Even though general improvement of quality of life has happened around the globe, statistics show that gastric cancer is still a very serious medical concern in some regions of the world. A big portion of malignant neoplasms that develop inside the stomach are linked to an infection of Helicobacter pylori; in fact, this pathogen has already been categorized as a group 1 carcinogen by the World Health Organization (WHO). Still, the efficacy of current anti-H. pylori therapeutic approaches is insufficient and follows a worrying decreasing trend, mainly due to an exponential increase in resistance to key antibiotics. This work analyzes the clinical and biological characteristics of this pathogen, especially its link to gastric cancer, and provides a comprehensive review of current formulation trends for H. pylori eradication. Research effort has focused both on the discovery of new combinations of chemicals that function as optimized antibiotic regimens, and on the preparation of gastroretentive drug delivery systems (GRDDSs) to improve overall pharmacokinetics. Regarding the last topic, this review aims to summarize the latest trend in amoxicillin-loaded GRDDS, since this is the antibiotic that has shown the least bacterial resistance worldwide. It is expected that the current work could provide some insight into the importance of innovative options to combat this microorganism. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of this infection and the consequent prevention of gastric cancer.

Thiolated-Polymer-Based Nanoparticles as an Avant-Garde Approach for Anticancer Therapies-Reviewing Thiomers from Chitosan and Hyaluronic Acid.

Thiomers (or thiolated polymers) have broken through as avant-garde approaches in anticancer therapy. Their distinguished reactivity and properties, closely linked to their final applications, justify the extensive research conducted on their preparation and use as smart drug-delivery systems (DDSs). Multiple studies have demonstrated that thiomer-rich nanoformulations can overcome major drawbacks found when administering diverse active pharmaceutical ingredients (APIs), especially in cancer therapy. This work focuses on providing a complete and concise review of the synthetic tools available to thiolate cationic and anionic polymers, in particular chitosan (CTS) and hyaluronic acid (HA), respectively, drawing attention to the most successful procedures. Their chemical reactivity and most relevant properties regarding their use in anticancer formulations are also discussed. In addition, a variety of NP formation procedures are outlined, as well as their use in cancer therapy, particularly for taxanes and siRNA. It is expected that the current work could clarify the main synthetic strategies available, with their scope and drawbacks, as well as provide some insight into thiomer chemistry. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of cancer.

Reproducibility of Kidney Perfusion Measurements With Arterial Spin Labeling at 1.5 Tesla MRI Combined With Semiautomatic Segmentation for Differential Cortical and Medullary Assessment.

Magnetic resonance imaging with arterial spin labeling (ASL) is a noninvasive approach to measure organ perfusion. The purpose of this study was to evaluate the reproducibility of ASL kidney perfusion measurements with semiautomatic segmentation, which allows separate quantification of cortical and medullary perfusion. The right kidneys of 14 healthy volunteers were examined 6 times on 2 occasions (3 times at each occasion). There was a 10-minute pause between each examination and a 14-day interval between the 2 occasions. Cortical, medullary, and whole kidney parenchymal perfusion was determined with customized semiautomatic segmentation software. Coefficient of variances (CVs) and intraclass correlations (ICCs) were calculated. Mean whole, cortical, and medullary kidney perfusion was 307.26 ±â€Š25.65, 337.10 ±â€Š34.83, and 279.61 ±â€Š26.73 mL/min/100 g, respectively. On session 1, mean perfusion for the whole kidney, cortex, and medulla was 307.08 ±â€Š26.91, 336.79 ±â€Š36.54, and 279.60 ±â€Š27.81 mL/min/100 g, respectively, and on session 2, 307.45 ±â€Š24.65, 337.41 ±â€Š33.48, and 279.61 ±â€Š25.94 mL/min/100 g, respectively (P > 0.05; R²â€Š= 0.60/0.59/0.54). For whole, cortical, and medullary kidney perfusion, the total ICC/CV were 0.97/3.43 ±â€Š0.86%, 0.97/4.19 ±â€Š1.33%, and 0.96/4.12 ±â€Š1.36%, respectively. Measurements did not differ significantly and showed a very good correlation (P > 0.05; R²â€Š= 0.75/0.76/0.65). ASL kidney measurements combined with operator-independent semiautomatic segmentation revealed high correlation and low variance of cortical, medullary, and whole kidney perfusion.

Fecal calprotectin (FC) in newborns: is it a predictive marker of gastrointestinal and/or allergic disease?

Fecal calprotectin seems to provide a safe and non-invasive means of helping differentiate between patients with organic and non-organic intestinal disease. Aim of our study was to evaluate if FC levels at birth and at first month of age can be a predictive biomarker of organic or functional gastrointestinal disease (FGIDs) and/or allergic disease diagnosed in 2 years old children. Between December 2007 and January 2008 a telephonic interview has been proposed to the parents of 109 consecutive healthy children, in which FC was measured at birth two years before. For our study, a modified version of the original paediatric questionnaire on paediatric functional gastrointestinal disorders (QPGS) was used for the interview. Specific questions were added to detect allergic diseases. We did’nt find any statistically significant result between FC measured at birth and during first month of life in children with allergy or not. The interference of familiarity does not lead to a statistically significant change in the fecal calprotectin values during the first month of life.

Bowel habit in preterm newborns: effect of new formulas.

Preterm infants may pass meconium only after the first 48 hours of life, even in absence of any gastrointestinal disease. The role of various factors in determining the time of meconium elimination has been recently assessed. Gestational age and start of feeding had been demonstrated to influence first meconium timing. The aim of our study was to evaluate time of first meconium passage and the time to achieve regular bowel movements (RBM), correlating these two events to different factors such as gestational age (GA), sex, type of delivery [caesarean section (CS) vs spontaneous delivery (SD)], 1' and 5' Apgar score (1'AS, 5'AS), time and type of feeding, oxygen requirement and any mode of respiratory support.

Lactobacillus GG improves recovery in infants with blood in the stools and presumptive allergic colitis compared with extensively hydrolyzed formula alone.

OBJECTIVES: To determine the benefits of Lactobacillus rhamnosus GG (LGG) in an extensively hydrolyzed casein formula (EHCF) in improving hematochezia and fecal calprotectin over EHCF alone. STUDY DESIGN: Fecal calprotectin was compared in 30 infants with hematochezia and 4 weeks after milk elimination with that of a healthy group. We also compared fecal calprotectin and hematochezia on 26 formula-fed infants randomly assigned to EHCF with LGG (Nutramigen LGG) (EHCF + LGG) or without (Nutramigen) (EHCF - LGG) and on 4 breastfed infants whose mothers eliminated dairy. RESULTS: Fecal calprotectin in those with hematochezia was significantly higher than in comparisons (mean +/- SD 325.89 +/- 152.31 vs 131.97 +/- 37.98 microg/g stool, t = 6.79, P < .0001). At 4 weeks, fecal calprotectin decreased to 50% of baseline but was still significantly higher than in comparisons (157.5 +/- 149.13 vs 93.72 +/- 36.65 microg/g, P = .03). Fecal calprotectin mean decrease was significantly larger among EHCF + LGG compared with EHCF - LGG (-214.5 +/- 107.93 vs -112.7 +/- 105.27 microg/g, t = 2.43, P = .02). At 4 weeks, none of the EHCF + LGG had blood in stools, and 5/14 on EHCF - LGG did (P = .002). CONCLUSION: Fecal calprotectin is elevated in infants with hematochezia and possible allergic colitis. EHCF + LGG resulted in significant improvement of hematochezia and fecal calprotectin compared with the EHCF alone.

Celiac disease: pathogenesis and novel therapeutic strategies.

Celiac disease is a digestive disease, considered as an autoimmune disorder, that damages the small intestine and interferes with absorption of nutrients. Individuals affected by celiac disease cannot tolerate a protein called gluten, present in wheat, rye, and barley, but also in other common products such as stamp and envelope adhesive, medicines, and vitamins. Celiac disease is a genetic condition that is triggered--or becomes active for the first time--after surgery, pregnancy, childbirth, viral infection, or severe emotional stress. Symptoms may occur in the digestive system, or in other parts of the body. Diagnosis involves blood tests and a biopsy of the small intestine. Recent findings estimate that about 2 million people in the United States have celiac disease, or about 1 in 133 people, as in Europe. Recent studies have shown that it may be more common in Africa, South America, and Asia than previously believed. The only treatment for celiac disease is to follow a gluten-free diet. Various other approaches are being studied that would reduce the need of dieting. One of those promising new approaches involves treating celiac patients with AT-1001, a paracellular permeability inhibitor, and with R-spondin1, a recombinant, secreted protein that early animal studies have shown to act as a highly specific stimulator of the gastrointestinal (GI) epithelial cells.

Fast and adaptive finite element approach for modeling brain shift.

OBJECTIVE: In this paper we introduce a finite element-based strategy for simulation of brain deformation occurring during neurosurgery. The phenomenon, known as brain shift, causes a decrease in the accuracy of neuronavigation systems that rely on preoperatively acquired data. This can be compensated for with a computational model of the brain deformation process. By applying model calculations to preoperative images, an update within the operating room can be performed. METHODS: One of the crucial concerns in the context of developing a physical-based model is the choice of governing equations describing the physics of the phenomenon. In this work, deformation of brain tissue is expressed in terms of a 3D consolidation model for a linearly elastic and porous fluid. The next crucial issue is ensuring stable calculations within the chosen model. For this purpose, we developed a special technique for generating the underlying geometry for the simulation. With this technique an unstructured grid consisting of regular tetrahedra is created, whereupon time-dependent finite element simulation is performed in an adaptive manner. RESULTS: We applied our algorithm to preoperative MR scans and investigated the value of the method. Due to the adaptivity of the method, only 5-10% of the computing time was needed as compared to traditional finite element approaches based on a uniformly subdivided grid. The results of the experiments were compared to the corresponding intraoperative MR scans. A close match between the computed deformation of the brain and the displacement resulting from the intraoperative data was observed. CONCLUSION: A model-based approach for the simulation of brain shift is presented. In this computational model the brain tissue is described as an elastic and porous material using Biot consolidation theory. Validating experiments conducted with MR data provided promising results.