Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Association between dental diseases and oral hygiene care and the risk of vertebral fracture: a nationwide cohort study.

Periodontal disease and increased missing teeth were associated with incident vertebral fractures. In contrast, professional dental cleaning and frequent tooth brushing, was associated with a lower risk of vertebral fracture. Better oral hygiene care attenuated the risk associated with dental diseases. PURPOSE: To investigate the association between oral health and the risk of vertebral fractures. METHODS: We included 2,532,253 individuals aged ≥40 years who underwent the Korean National Health Insurance Service health examinations in 2008 and followed up until December 31, 2017. We performed multivariable Cox proportional hazard regression analyses to evaluate the association between dental diseases and oral hygiene care and the risk of vertebral fractures. RESULTS: Over the 9.3-year median follow-up, 1.46% (n = 36,857) experienced vertebral fractures. Individuals with dental diseases had a higher risk of vertebral fracture than those without (hazard ratio [HR] 1.04, 95% confidence interval [CI]: 1.02-1.07 for periodontal diseases; 1.02, 1.00-1.05 for dental caries; 1.12, 1.05-1.20 for ≥15 missing teeth). Good oral hygiene care was associated with a lower vertebral fracture risk (HR 0.89, 95% CI: 0.86-0.91 for ≥1 time/year [vs. <1 time/year] of professional dental cleaning; 0.90, 0.87-0.93 for ≥2 times/day [vs. 0-1 time/day] of toothbrushing). The combined dental diseases was significantly associated with an increased vertebral fracture risk, whereas combined oral hygiene care was associated with further risk reduction. Better oral hygiene care reduced vertebral fracture risk associated with dental diseases (all P <0.001). CONCLUSION: Periodontal disease, dental caries, and an increased number of missing teeth were independently associated with higher risks for vertebral fractures. Conversely, improved oral hygiene care, such as personal dental cleaning and frequent tooth brushing, may modify vertebral fracture risks associated with dental disease.

Maturation of pathogenic biofilms induces enhanced resistance against gaseous chlorine dioxide.

Biofilms are surface-associated microbial clusters embedded in extracellular polymeric substances. Biofilms formed on food-contact surfaces create challenges for the food industry due to their increased tolerance to antimicrobial agents and disinfectants. This study aimed to evaluate the effect of the biofilm maturation period on their resistance to gaseous ClO2. Listeria monocytogenes, Salmonellaserotype Typhimurium, and Escherichia coli O157:H7 biofilms formed on stainless steel (SS) and high-density polyethylene (HDPE) surfaces were investigated. The total cell mass and protein content significantly increased (P < .05) between the second and the fifth day of maturation, and the biofilms' resistance to gaseous ClO2 increased as they matured. Generally, the cell counts of 0-day-old L. monocytogenes, Salm. Typhimurium, and E. coli O157:H7 biofilms on SS and HDPE reduced below the detection limit (0.48 log CFU/cm2) within 5 min. The cell counts of 2-day-old biofilms of the three pathogens were reduced by 6.22 to over 7.52 log, while those of 5-day-old biofilms were reduced by 3.64 to over 6.34 log after 20 min of treatment with 30 ppmv of gaseous ClO2. Therefore, as resistance increases with biofilm maturation, daily gaseous ClO2 treatment would maximize the antimicrobial efficacy of the cleaning strategy against biofilms.

Damage patterns in polyethylene fixed bearings of retrieved total ankle replacements.

INTRODUCTION: Poor long-term outcomes continue to hinder the universal adoption of total ankle replacements (TAR) for end stage arthritis. In the present study, polyethylene inserts of TARs retrieved at revision surgery were analyzed for burnishing, scratching, mechanical damage, pitting, and embedded particles. METHODS: Fourteen retrieved polyethylene inserts from a fixed bearing total ankle replacement design currently in clinical use were analyzed. Duration of time in vivo was between 11.5 months and 120.1 months. Three investigators independently graded each articular surface in quadrants for five features of damage: burnishing, scratching, mechanical damage, pitting, and embedded particles. RESULTS: No correlation was found for burnishing between the anterior and posterior aspects (p = 0.47); however, scratching and pitting were significantly higher on the posterior aspect compared to the anterior aspect (p < 0.03). There was a high correlation between burnishing and in vivo duration of the implant (anterior: R = 0.67, p = 0.01, posterior: R = 0.68, p = 0.01). CONCLUSION: The higher concentration of posterior damage on these polyethylene inserts suggested that prosthesis-related (design) or surgeon-related (technique) factors might restrict the articulation of the implant. The resulting higher stresses in the posterior articular surfaces may have contributed to the failure of retrieved implants Keywords: Retrieval, Polyethylene Damage, Total Ankle Replacement.

Evaluation of Swine Protection with Three Commercial Foot-and-Mouth Disease Vaccines against Heterologous Challenge with Type A ASIA/G-VII Lineage Viruses.

Outbreaks caused by foot-and-mouth disease (FMD) A/ASIA/G-VII lineage viruses have often occurred in Middle Eastern and Southeast Asian countries since 2015. Because A/ASIA/G-VII lineage viruses are reported to have distinct antigenic relatedness with available commercial FMD vaccine strains, it is necessary to investigate whether inoculation with vaccines used in Korea could confer cross-protection against A/ASIA/G-VII lineage viruses. In the present study, we conducted two vaccination challenge trials to evaluate the efficacy of three commercial FMD vaccines (O/Manisa + O/3039 + A/Iraq, O/Campos + A/Cruzeiro + A/2001, and O/Primorsky + A/Zabaikalsky) against heterologous challenge with ASIA/G-VII lineage viruses (A/TUR/13/2017 or A/BHU/3/2017 strains) in pigs. In each trial, clinical signs, viremia, and salivary shedding of virus were measured for 7 days after challenge. In summary, the O/Campos + A/Cruzeiro + A/2001 vaccine provided full protection against two A/ASIA/G-VII lineage viruses in vaccinated pigs, where significant protection was observed. Although unprotected animals were observed in groups vaccinated with O/Manisa + O/3039 + A/Iraq or O/Primorsky + A/Zabaikalsky vaccines, the clinical scores and viral RNA levels in the sera and oral swabs of vaccinated animals were significantly lower than those of unvaccinated controls.

An Alternative Serological Measure for Assessing Foot-and-Mouth Disease Vaccine Efficacy against Homologous and Heterologous Viral Challenges in Pigs.

To analyze the relationship between homologous and heterologous serological titers of immunized pigs and their protection statuses against FMD virus challenges, in the present study, the correlation between the virus neutralization titers at 21 and 28 dpv and the protection statuses at 28 dpv against challenge with FMD virus was analyzed using data sets comprising five different combinations of homologous or heterologous challenge experiments in pigs vaccinated with type O (n = 96), A (n = 69), and Asia 1 (n = 74). As a result, the experiments were divided into three groups (21D-1, 21D-2, and 21D-3) in the 21-dpv model and two groups (28D-1 and 28D-2) in the 28-dpv model. Each response curve of groups 21D-1 and 21D-2 in the 21-dpv model was very similar to each curve of groups 28D-1 and 28D-2 in the 28-dpv model, respectively, even though there was an exceptional extra group (21D-3) in the 21-dpv model. The average titers estimating 0.75 probability of protection ranged from 1.06 to 1.62 log10 in the 21-dpv model and from 1.26 to 1.64 log10 in the 28-dpv model. In summary, we demonstrated that the serological method is useful for predicting the homologous and heterologous protection statuses of vaccinated pigs.

Association of Dental Diseases and Oral Hygiene Care With the Risk of Heart Failure in Patients With Type 2 Diabetes: A Nationwide Cohort Study.

Background To evaluate the association of dental diseases and oral hygiene care with incidence of heart failure (HF) among patients with type 2 diabetes. Methods and Results This study included 173 927 patients with type 2 diabetes aged ≥40 years, who underwent Korean National Health Insurance Service health examinations in 2008 and were followed up until the end of 2017. Hazard ratios (HRs) and 95% CIs for HF were estimated using multivariable Cox proportional hazards regression analysis. During a median follow-up of 9.3 years, 1.94% of participants developed HF. An increased number of missing teeth was associated with a higher risk of HF (P<0.001). HRs of HF increased among individuals with ≥15 missing teeth (HR, 1.37 [95% CI, 1.14-1.64]) compared with those without missing teeth. Decreased risk of HF was observed in individuals with ≥1 time/year of professional dental cleaning (HR, 0.93 [95% CI, 0.87-0.99]) and in those with ≥2 times/d of toothbrushing (HR, 0.90 [95% CI, 0.82-0.98]) compared with those without these practices. While combined presence of missing teeth and periodontal disease (P=0.004) or dental caries (P=0.007) increased HF risk, combined oral hygiene care was associated with further HF risk reduction (P=0.024). Better oral hygiene care was associated with decreased HF risk, even as the number of missing teeth increased (P<0.001). Conclusions Among patients with type 2 diabetes, dental diseases and oral hygiene care are important determinants of HF development. Dental disease management and good oral care may prevent HF in patients with type 2 diabetes.

Association between Dental Diseases and Oral Hygiene Care and the Risk of Dementia: A Retrospective Cohort Study.

OBJECTIVES: To investigate the associations of dental diseases and oral hygiene care with the risk of dementia. DESIGN: Retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: We conducted a population-based study of individuals in the Korean National Health Insurance System. A total of 2,555,618 participants who underwent cardiovascular and dental screenings in 2008 were included. METHODS: Dental diseases including periodontal diseases, dental caries, and tooth loss were assessed by dentists. Information on oral hygiene care, including professional dental cleaning and the frequency of tooth brushing, was collected using a self-administered questionnaire. Study outcomes were all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: Periodontal diseases [adjusted hazard ratio (aHR) 1.07, 95% CI 1.04-1.09], dental caries (aHR 1.03, 95% CI 1.00-1.05), and 8-14 missing teeth (aHR 1.07, 95% CI 1.02-1.12) were associated with an increased risk of all-cause dementia. In contrast, either professional dental cleaning or frequent tooth brushing were associated with decreased risks of all-cause dementia (aHR 0.91, 95% CI 0.89-0.93 each; aHR 0.83, 95% CI 0.80-0.86 for both). The increased risks by dental diseases were reduced by oral hygiene care: periodontal diseases with professional dental cleaning (aHR 0.94, 95% CI 0.91-0.98) or tooth brushing ≥2 times/day (aHR 0.97, 95% CI 0.94-1.00) and 1 to 7 missing teeth with professional dental cleaning (aHR 0.94, 95% CI 0.89-0.98) or tooth brushing ≥2 times/day (aHR 0.92, 95% CI 0.89-0.95). Consistent results were noted for AD and VaD and in various subgroup analyses. CONCLUSION AND IMPLICATIONS: Periodontal disease, dental caries, and a high number of missing teeth were independently associated with a higher risk of dementia. Conversely, improved oral hygiene care, such as professional dental cleaning and frequent tooth brushing, may modify the risk of dementia associated with dental diseases.

Actively Triggerable Metals via Liquid Metal Embrittlement for Biomedical Applications.

Actively triggerable materials, which break down upon introduction of an exogenous stimulus, enable precise control over the lifetime of biomedical technologies, as well as adaptation to unforeseen circumstances, such as changes to an established treatment plan. Yet, most actively triggerable materials are low-strength polymers and hydrogels with limited long-term durability. By contrast, metals possess advantageous functional properties, including high mechanical strength and conductivity, that are desirable across several applications within biomedicine. To realize actively triggerable metals, a mechanism called liquid metal embrittlement is leveraged, in which certain liquid metals penetrate the grain boundaries of certain solid metals and cause them to dramatically weaken or disintegrate. In this work, it is demonstrated that eutectic gallium indium (EGaIn), a biocompatible alloy of gallium, can be formulated to reproducibly trigger the breakdown of aluminum within different physiologically relevant environments. The breakdown behavior of aluminum after triggering can further be readily controlled by manipulating its grain structure. Finally, three possible use cases of biomedical devices constructed from actively triggerable metals are demonstrated.

Probing the role of methyl methacrylate release from spacer materials in induced membrane bone healing.

In the induced membrane (IM) technique for bone reconstruction, a poly(methyl methacrylate) (PMMA) spacer is implanted to induce formation of a foreign body membrane around the defect site. Membrane development is essential for later bone grafting success, yet the mechanism by which the IM promotes bone regeneration remains unknown, as are the ways that spacer composition plays a role in the membrane's healing potential. This study investigated the impact of leached methyl methacrylate (MMA)-the major monomeric component of PMMA-on IM development. In vitro cell culture found that MMA elution did not impact endothelial cell or mesenchymal stem cell proliferation. For in vivo analysis, we advanced a streamlined rat femoral model to efficiently study the influence of spacer properties on IM characteristics. Comparison of membrane formation around polycaprolactone (PCL), MMA-eluting PCL (high-dose PCL-MMA and low-dose PCL-MMA), and surgical PMMA revealed robust membranes enveloped all groups after 4 weeks in vivo, with elevated expression of osteogenic bone morphogenetic protein-2 and angiogenic vascular endothelial growth factor compared with the surrounding muscle and bone tissues. Growth factor quantitation in IM tissue found no statistically significant difference between groups. New bone growth, vascularization, and CD163+ macrophage populations surrounding the polymer implants were also quantified; and blood vessel formation around high-dose PCL-MMA was found to be significantly decreased compared with PCL alone. To the best of our knowledge, these findings represent the first time that results have been obtained about the characteristics of membranes formed around PCL in the IM setting.