Small polystyrene microplastics interfere with the breakdown of milk proteins during static in vitro simulated human gastric digestion.

Human ingestion of microplastics (MPs) is common and inevitable due to the widespread contamination of food items, but implications on the gastric digestion of food proteins are still unknown. In this study, the interactions between pepsin and polystyrene (PS) MPs were evaluated by investigating enzyme activity and conformation in a simulated human gastric environment in the presence or absence of PS MPs. The impact on food digestion was also assessed by monitoring the kinetics of protein hydrolysis through static in vitro gastric digestion of cow's milk contaminated with PS. The binding of pepsin to PS showed that the surface chemistry of MPs dictates binding affinity. The key contributor to pepsin adsorption seems to be π-π interactions between the aromatic residues and the PS phenyl rings. During quick exposure (10 min) of pepsin to increasing concentrations (222, 2219, 22188 particles/mL) of 10 µm PS (PS10) and 100 µm PS (PS100), total enzymatic activities were not affected remarkably. However, upon prolonged exposure at 1 and 2 h, preferential binding of pepsin to the small, low zeta-potential PS caused structural changes in the protein which led to a significant reduction of its activity. Digestion of cow's milk mixed with PS10 resulted in transient accumulation of larger peptides (10-35 kDa) and reduced bioavailability of short peptides (2-9 kDa) in the gastric phase. This, however, was only observed at extremely high PS10 concentration (0.3 mg/mL or 5.46E+05 particles/mL). The digestion of milk peptides, bound preferentially over pepsin within the hard corona on the PS10 surface, was delayed up to 15 min in comparison to bulk protein digestion. Intact caseins, otherwise rapidly digested, remained bound to PS10 in the hard corona for up to 15 min. This work presents valuable insights regarding the interaction of MPs, food proteins, and pepsin, and their dynamics during gastric digestion.

LogP of N-acyl-gemcitabine and lectin-corona emerge as key parameters in nanoparticulate intravesical cancer therapy.

After surgical removal of the tumour tissue, bladder cancer is treated by intravesical instillation of cytotoxic drugs such as gemcitabine. Gemcitabine, however, is highly hydrophilic and possesses a short half-life due to fast enzymatic deamination. Additionally, continuous dilution by urine, a hardly permeable urothelial barrier and rapid excretion by urination make therapy difficult. To modify lipophilicity of the drug, N-acyl-gemcitabine derivatives with quite different solubility and logP were synthesized, purified and characterized. The loading of PLGA nanoparticles with the N-acyl-gemcitabine derivatives followed by release in artificial urine, revealed that the drug content increases but the subsequent release decreases with lipophilicity. Additionally, acylation increased cytotoxicity and opened passive diffusion as an additional pathway into cancer cells. To address physiological constraints, the surface of the monodisperse nanoparticles was grafted with bioadhesive wheat germ agglutinin. Cytoadhesion to artificial bladder cancer tissue and even uptake into the cells as indicated by microscopic imaging are expected to prolong the retention time in the bladder cavity as well as to promote uptake into the cells. By using N-caprylic-gemcitabine as most appropriate gemcitabine-derivative for drug loading and making use of the bioadhesive characteristics of wheat germ agglutinin for grafting the corona of PLGA-nanoparticles, an innovative strategy towards smart drug delivery for instillative therapy of bladder cancer is proposed.

Impact of Parental Education and Physical Activity on the Long-Term Development of the Physical Fitness of Primary School Children: An Observational Study.

Low physical fitness (PF) has been associated with higher risk of suffering from different diseases. The importance of PF is evident already in early ages, as children's PF appears to be a key factor of their future PF and physical activity level. Among the variables that may have an influence on children's PF, the importance of parent's socioeconomic status and active/inactive behaviors has been stressed in several previous studies. However, previous literature has mostly reported this association through cross-sectional studies. The purpose of this study was to examine the impact of parental education and self-reported parental physical activity (PA) on their children's development of PF during the 4-year duration of primary education. Using German Motor Test 6-18, the major components of PF (sprint velocity, coordination, flexibility, strength endurance, power, and endurance) were measured on a total of 371 children (46.9% girls, 30.6% migration background, 19.6% overweight/obese at the fourth test time point, compliance 70.1%) from 20 primary schools in Tyrol, Austria. Results showed that children with at least one parent with upper secondary education or above obtained significantly higher PF scores at all time points compared to children with both parents with lower secondary education and below. However, PF in both groups developed over time in a comparable manner irrespective of parental education. From the age of 9 years old, children with regularly physically active parents showed a stronger development of PF over the time compared to their peers with parents reporting irregular/no PA. Our results suggest that low-educated parents' children might be considered a special target group for interventions aiming at increasing PF. More research is needed in order to delve into the potential underdevelopment of PF in 9-year-old children whose parents have low PA levels.

Implant-prosthetic rehabilitation of patients with severe horizontal bone deficit on mini-implants with two-piece design-retrospective analysis after a mean follow-up of 5 years.

BACKGROUND: As a consequence of tooth loss due to trauma or extraction, a reduced alveolar crest volume limits the deployment of standard implants in certain patient cases. For this reason, minimal-invasive treatment with mini-dental implants (MDI) might be an option to allow implant treatment even in cases with severe horizontal bone loss without augmentation measures. The aim of this retrospective cohort study was to investigate clinical and radiological implant, as well as patient-related parameters after treatment with MDI. RESULTS: Clinical and radiological records of 19 female (82.6%) and 4 male patients (17.4%) (N = 23), who received 52 mini-dental implants with a two-piece design in a single surgical center between November 2011 and October 2018, were retrospectively analyzed. Implants were submitted to conventional loading on different types of screwed superstructures. Crestal bone loss was measured on standardized periapical radiographs. Patient-related outcome parameters (PROMs) were recorded during follow-up period. Mean clinical and radiological follow-up was 69.6 months (5.8 years) and 51.6 months (4.3 years), respectively. Three implants were lost in two patients, leading to an implant survival rate of 94.2%. Mean radiological crestal bone loss was 1.6 mm. Both amount of peri-implant recession and crestal bone loss were significantly correlated (r = 0.65; p < 0.001). Likewise, a significant correlation was observed between deeper probing depths and increased peri-implant bone loss (r = 0.41; p = 0.012). Alveolar ridges with a reduced alveolar crest width were significantly correlated with higher peri-implant bone loss as well (r = - 0.33; p = 0.011). No prosthetic complications were reported during follow-up. Extent of midfacial recession and papilla height loss had a significant negative impact on most of the PROMs. CONCLUSIONS: Treatment with MDI seems to be a successful alternative treatment option, especially for elderly patients with reduced crest width at implant sites. Due to the good clinical results and high survival and success rates, this treatment option was associated with high patient satisfaction. Despite the promising results, particular consideration should be given to appropriate treatment planning in these patients due to the strong correlation between peri-implant soft-tissue parameters, crestal bone loss, and reduced alveolar crest width.