Proof of concept design for a toothbrush with on-board vacuum to reduce oral aspirates.

BACKGROUND: Over the course of brushing, aerosolised particles develop in the mouth. In individuals who do not have the ability to expel these oral aspirates, they can be inhaled and cause aspiration pneumonia. This article showcases a novel vacuum toothbrush, termed "ToothVac," and provides findings from its first human trial. METHODS: The ToothVac device suctions saliva and aspirates during brushing, storing them in a removable reservoir at the bottom of the brush, to minimise the risk of inhalation and subsequent infection. Further descriptions of the various components of the ToothVac are included. This trial involved 18 participants who brushed using the ToothVac with the vacuum suction turned on and then off. RESULTS: The volume of saliva produced was measured and compared. The ToothVac significantly reduced the amount of saliva that was produced by these participants when brushing. CONCLUSION: The device has potential clinical potential in that it may reduce the risk of aspiration pneumonia and related lung infections. Potential future research may include clinical trials for specific indications or marketing for oral aspirate removal, as well as optimisation of brush design using injection moulding for scalable manufacturing.

Biomaterials and tissue engineering approaches using glycosaminoglycans for tissue repair: Lessons learned from the native extracellular matrix.

Glycosaminoglycans (GAGs) are an important component of the extracellular matrix as they influence cell behavior and have been sought for tissue regeneration, biomaterials, and drug delivery applications. GAGs are known to interact with growth factors and other bioactive molecules and impact tissue mechanics. This review provides an overview of native GAGs, their structure, and properties, specifically their interaction with proteins, their effect on cell behavior, and their mechanical role in the ECM. GAGs' function in the extracellular environment is still being understood however, promising studies have led to the development of medical devices and therapies. Native GAGs, including hyaluronic acid, chondroitin sulfate, and heparin, have been widely explored in tissue engineering and biomaterial approaches for tissue repair or replacement. This review focuses on orthopaedic and wound healing applications. The use of GAGs in these applications have had significant advances leading to clinical use. Promising studies using GAG mimetics and future directions are also discussed. STATEMENT OF SIGNIFICANCE: Glycosaminoglycans (GAGs) are an important component of the native extracellular matrix and have shown promise in medical devices and therapies. This review emphasizes the structure and properties of native GAGs, their role in the ECM providing biochemical and mechanical cues that influence cell behavior, and their use in tissue regeneration and biomaterial approaches for orthopaedic and wound healing applications.

Comparison of SGLT1, SGLT2, and Dual Inhibitor biological activity in treating Type 2 Diabetes Mellitus.

Diabetes Mellitus Type 2 (T2D) is an emerging health burden in the USand worldwide, impacting approximately 15% of Americans. Current front-line therapeutics for T2D patients include sulfonylureas that act to reduce A1C and/or fasting blood glucose levels, or Metformin that antagonizes the action of glucagon to reduce hepatic glucose production. Next generation glucomodulatory therapeutics target members of the high-affinity glucose transporter Sodium-Glucose-Linked-Transporter (SGLT) family. SGLT1 is primarily expressed in intestinal epithelium, whose inhibition reduces dietary glucose uptake, whilst SGLT2 is highly expressed in kidney - regulating glucose reabsorption. A number of SGLT2 inhibitors are FDA approved whilst SGLT1 and dual SGLT1 & 2 inhibitor are currently in clinical trials. Here, we discuss and compare SGLT2, SGLT1, and dual inhibitors' biochemical mechanism and physiological effects.

Sustained Release of Antibody-Conjugated DNA Nanocarriers from a Novel Injectable Hydrogel for Targeted Cell Depletion to Treat Cataract Posterior Capsule Opacification.

Purpose: To compare a novel, sustained release formulation and a bolus injection of a targeted nanocarrier for the ability to specifically deplete cells responsible for the development of posterior capsule opacification (PCO) in week-long, dynamic cell cultures. Methods: A novel, injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer hydrogel was engineered for the sustained release of targeted, nucleic acid nanocarriers loaded with cytotoxic doxorubicin (G8:3DNA:Dox). Human rhabdomyosarcoma (RD) cells were used due to their expression of brain-specific angiogenesis inhibitor 1 (BAI1), a specific marker for the myofibroblasts responsible for PCO. Under constant media flow, nanocarriers were injected into cell cultures as either a bolus or within the hydrogel. Cells were fixed and stained every other day for 7 days to compare targeted depletion of BAI1+ cells. Results: The formulation transitions to a gel at physiological temperatures, is optically clear, noncytotoxic, and can release G8:3DNA:Dox nanocarriers for up to 4 weeks. In RD cell cultures, G8:3DNA:Dox nanocarriers specifically eliminated BAI1+ cells. The bolus nanocarrier dose showed significantly reduced cell depletion overtime, while the sustained release of nanocarriers showed increased cell depletion over time. By day 7, <2% of BAI1+ cells were depleted by the bolus injection and 74.2% BAI1+ cells were targeted by the sustained release of nanocarriers. Conclusions: The sustained release of nanocarriers from the hydrogel allows for improved therapeutic delivery in a dynamic system. This method can offer a more effective and efficient method of prophylactically treating PCO after cataract surgery.

Evaluating the effect of a water exercise routine on the postural stability of the elderly / Evaluación del efecto de una rutina de ejercicios acuáticos sobre la estabilidad postural de adultos mayores

Abstract Background: Postural stability enables humans to maintain the center of mass of their body within their base of support. Nevertheless, over time, such stability is affected by different factors such as age, repetitive strain, and accidents. Although studies in this field have investigated the effectiveness of hydrotherapy, only a few of them have explored its influence on postural stability, which is reflected in a lack of research that estimates its impact on rehabilitation. Aim: To determine the immediate and final effects of an aquatic routine protocol on the postural stability of elderly subjects. Methods: The postural stability of 20 adults over 60 years of age was analyzed using electromyographic and baropodometric methods. Electromyographic signals were obtained from the tibialis anterior, soleus, both gastrocnemius, vastus medialis, and biceps femoris to calculate the coactivation percentage of the muscles in charge of postural stability. The baropodometric data were collected to analyze the area of the stabilometric ellipse, mean plantar pressure, and weight distribution percentage. Results: The outcome of both methods revealed improvements in the elderly patients after the aquatic routine protocol was applied, which indicates that the type of water exercises implemented in this study has positive effects on their postural stability. Conclusion: The postural stability of the elderly participants was improved after each session because their stability index decreased along with the electrical activity of some muscle pairs, their body weight was better distributed, and the area of body oscillation was reduced. However, this effect was immediate and not final.

Resumen Antecedentes: La estabilidad postural permite a los humanos mantener el centro de masa de su cuerpo dentro de su base de apoyo. Sin embargo, con el tiempo, dicha estabilidad se ve afectada por diferentes factores como la edad, el esfuerzo repetitivo y los accidentes. Si bien los estudios en este campo han investigado la efectividad de la hidroterapia, solo algunos de ellos han explorado su influencia en la estabilidad postural, lo que se refleja en la falta de investigaciones que estimen su impacto en la rehabilitación. Objetivo: Determinar los efectos inmediatos y finales de un protocolo de rutina acuática sobre la estabilidad postural de adultos mayores. Métodos: Se analizó la estabilidad postural de 20 adultos mayores de 60 años mediante métodos electromiográficos y baropodométricos. Se obtuvieron señales electromiográficas del tibial anterior, sóleo, gastrocnemio, vasto interno y bíceps femoral para calcular el porcentaje de coactivación de los músculos encargados de la estabilidad postural. Los datos baropodométricos se recolectaron para analizar el área de la elipse estabilométrica, la presión plantar media y el porcentaje de distribución del peso corporal. Resultados: Ambos métodos mostraron mejoras en los pacientes luego de la aplicación del protocolo de rutina acuática, lo que indica que el tipo de ejercicios acuáticos implementados en este estudio tiene efectos positivos en su estabilidad postural. Conclusión: La estabilidad postural de los participantes mejoró después de cada sesión porque su índice de estabilidad disminuyó junto con la actividad eléctrica de algunos pares de músculos, su peso corporal se distribuyó mejor y se redujo el área de oscilación corporal. Sin embargo, este efecto fue inmediato y no definitivo.

Review of Contemporary Self-Assembled Systems for the Controlled Delivery of Therapeutics in Medicine.

The novel and unique design of self-assembled micro and nanostructures can be tailored and controlled through the deep understanding of the self-assembly behavior of amphiphilic molecules. The most commonly known amphiphilic molecules are surfactants, phospholipids, and block copolymers. These molecules present a dual attraction in aqueous solutions that lead to the formation of structures like micelles, hydrogels, and liposomes. These structures can respond to external stimuli and can be further modified making them ideal for specific, targeted medical needs and localized drug delivery treatments. Biodegradability, biocompatibility, drug protection, drug bioavailability, and improved patient compliance are among the most important benefits of these self-assembled structures for drug delivery purposes. Furthermore, there are numerous FDA-approved biomaterials with self-assembling properties that can help shorten the approval pathway of efficient platforms, allowing them to reach the therapeutic market faster. This review focuses on providing a thorough description of the current use of self-assembled micelles, hydrogels, and vesicles (polymersomes/liposomes) for the extended and controlled release of therapeutics, with relevant medical applications. FDA-approved polymers, as well as clinically and commercially available nanoplatforms, are described throughout the paper.

Evaluating the effect of a water exercise routine on the postural stability of the elderly.

Background: Postural stability enables humans to maintain the center of mass of their body within their base of support. Nevertheless, over time, such stability is affected by different factors such as age, repetitive strain, and accidents. Although studies in this field have investigated the effectiveness of hydrotherapy, only a few of them have explored its influence on postural stability, which is reflected in a lack of research that estimates its impact on rehabilitation. Aim: To determine the immediate and final effects of an aquatic routine protocol on the postural stability of elderly subjects. Methods: The postural stability of 20 adults over 60 years of age was analyzed using electromyographic and baropodometric methods. Electromyographic signals were obtained from the tibialis anterior, soleus, both gastrocnemius, vastus medialis, and biceps femoris to calculate the coactivation percentage of the muscles in charge of postural stability. The baropodometric data were collected to analyze the area of the stabilometric ellipse, mean plantar pressure, and weight distribution percentage. Results: The outcome of both methods revealed improvements in the elderly patients after the aquatic routine protocol was applied, which indicates that the type of water exercises implemented in this study has positive effects on their postural stability. Conclusion: The postural stability of the elderly participants was improved after each session because their stability index decreased along with the electrical activity of some muscle pairs, their body weight was better distributed, and the area of body oscillation was reduced. However, this effect was immediate and not final.

Antecedentes: La estabilidad postural permite a los humanos mantener el centro de masa de su cuerpo dentro de su base de apoyo. Sin embargo, con el tiempo, dicha estabilidad se ve afectada por diferentes factores como la edad, el esfuerzo repetitivo y los accidentes. Si bien los estudios en este campo han investigado la efectividad de la hidroterapia, solo algunos de ellos han explorado su influencia en la estabilidad postural, lo que se refleja en la falta de investigaciones que estimen su impacto en la rehabilitación. Objetivo: Determinar los efectos inmediatos y finales de un protocolo de rutina acuática sobre la estabilidad postural de adultos mayores. Métodos: Se analizó la estabilidad postural de 20 adultos mayores de 60 años mediante métodos electromiográficos y baropodométricos. Se obtuvieron señales electromiográficas del tibial anterior, sóleo, gastrocnemio, vasto interno y bíceps femoral para calcular el porcentaje de coactivación de los músculos encargados de la estabilidad postural. Los datos baropodométricos se recolectaron para analizar el área de la elipse estabilométrica, la presión plantar media y el porcentaje de distribución del peso corporal. Resultados: Ambos métodos mostraron mejoras en los pacientes luego de la aplicación del protocolo de rutina acuática, lo que indica que el tipo de ejercicios acuáticos implementados en este estudio tiene efectos positivos en su estabilidad postural. Conclusión: La estabilidad postural de los participantes mejoró después de cada sesión porque su índice de estabilidad disminuyó junto con la actividad eléctrica de algunos pares de músculos, su peso corporal se distribuyó mejor y se redujo el área de oscilación corporal. Sin embargo, este efecto fue inmediato y no definitivo.

Extended Release of Doxorubicin-Loaded 3DNA Nanocarriers from In-Situ Forming, Self-Assembled Hydrogels.

Purpose: Cataracts are the leading cause of blindness worldwide, resulting in over 30 million surgeries each year. These cases are expected to double within the next 10 years. About 25% of all patients develop secondary cataracts or posterior capsule opacification (PCO) postsurgery. PCO is a vision impairment disorder that develops from myofibroblasts migration and contraction that deforms the capsule surrounding the lens. Currently, Nd:YAG laser therapy is used to treat PCO; however, laser is not available worldwide and adverse side effects may arise. Thus, there is a considerable unmet need for more efficacious and convenient preventive treatments for PCO. Our work focuses on engineering an innovative, prophylactic sustained release platform for DNA-based nanocarriers to further reduce the incidence of PCO. Methods: Novel, optically clear, self-assembled poly(d,l-lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) triblock copolymer hydrogels were used for the sustained release of the DNA-based nanocarriers (3DNA®) loaded with cytotoxic doxorubicin (DOX) and targeted with a monoclonal antibody called G8 (3DNA:DOX:G8), which is specific to cells responsible for PCO. Results: The 29 (w/v)% polymer hydrogels with the 3DNA nanocarriers presented over 80% of light transmittance, soft mechanical properties (<350 Pa), and sustained release for 1 month. Conclusions: In this work, we show for the first time that the hydrophobic PLGA-PEG-PLGA hydrogels can be used as platforms for sustained delivery of nucleic acid-based nanocarriers. This work demonstrates that polymeric formulations can be used for the extended delivery of ocular therapeutics and other macromolecules to treat a variety of ocular conditions.

Cleavable ester linked magnetic nanoparticles for labeling of solvent exposed primary amine groups of peptides/proteins.

Covalent labeling of solvent exposed amino acid residues using chemical reagents/crosslinkers followed by mass spectrometric analysis can be used to determine the solvent accessible amino acids of a protein. A variety of chemical reagents containing cleavable bonds were developed to label abundantly found lysine residues on the surface of protein. To achieve efficient separation of labeled peptides prior to mass spectrometric analysis, magnetic nanoparticles can be decorated with amino acid reactive functional groups and utilized for quick recovery of labeled peptides. [1] In this work, iron oxide magnetic nanoparticles (Fe3O4 MNPs) were synthesized by thermal decomposition method and coated with silica (SiO2@Fe3O4 MNPs) by reverse micro emulsion approach. The Fe3O4 MNPs and SiO2@Fe3O4 MNPs were characterized by TEM and XRD. The SiO2@Fe3O4 MNPs were further coated with amine groups and conjugated to N-hydroxysuccinimidyl (NHS) ester groups via a cleavable ester bond. Fluorescence based qualitative analysis of ester linked NHS ester modified SiO2@Fe3O4 MNPs was performed to confirm the presence of NHS ester group. The active NHS ester sites on the surface of SiO2@Fe3O4 MNPs were determined by depletion approach and found to be 694 active sites per 1 mg of SiO2@Fe3O4 MNPs. Free amine groups of a small peptide, ACTH (4-11) were labeled by ester linked, NHS ester modified SiO2@Fe3O4 MNPs under physiological conditions. Superparamagnetic nature of SiO2@Fe3O4 MNPs allowed quick and efficient magnetic separation of labeled peptides from the solution. The ester bond was further cleaved to separate labeled peptides followed by mass spectrometric analysis. The ester linked, NHS ester modified SiO2@Fe3O4 MNPs introduced a mass shift of 115.09 Da on amine groups of ACTH (4-11), which was confirmed by mass spectrometry.

Cleavable ester-linked magnetic nanoparticles for labeling of solvent-exposed primary amine groups of peptides/proteins.

To study the solvent-exposed lysine residues of peptides/proteins, we previously reported disulfide-linked N-hydroxysuccinimide ester-modified silica-coated iron oxide magnetic nanoparticles (NHS-SS-SiO2@Fe3O4 MNPs). The presence of a disulfide bond in the linker limits the use of disulfide reducing agent during protein digestion and allows unwanted disulfide formation between the MNPs and protein. In the current work, the disulfide bond was replaced with a cleavable ester group to synthesize NHS ester-modified SiO2@Fe3O4 MNPs. Use of the cleavable ester group provides an improved method for protein labeling and allows the use of disulfide reducing agents during protein digestion.