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A method of overcoming barriers associated with implementing lifestyle interventions in CKD may be through the use of eHealth technologies. The aim of this review was to provide an up-to-date overview of the literature on this topic. Four bibliographical databases, two trial registers, and one database for conference proceedings were searched from inception to August 2023. Studies were eligible if they reported a lifestyle intervention using eHealth technologies. A narrative synthesis of the findings from the included studies structured around the type of eHealth intervention was presented. Where a sufficient number of studies overlapped in terms of the type of intervention and outcome measure these were brought together in a direction of effect plot. There were 54 included articles, of which 23 were randomised controlled trials (RCTs). The main component of the intervention for the included studies was mobile applications (n = 23), with the majority being in the dialysis population (n = 22). The majority of eHealth interventions were reported to be feasible and acceptable to participants. However, there was limited evidence that they were efficacious in improving clinical outcomes with the exception of blood pressure, intradialytic weight gain, potassium, and sodium. Although eHealth interventions appear acceptable and feasible to participants, there is insufficient evidence to make recommendations for specific interventions to be implemented into clinical care. Properly powered RCTs which not only demonstrate efficacy, but also address barriers to implementation are needed to enhance widespread adoption., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Curtis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Bonded retainers are widely used to maintain the positions of anterior teeth after orthodontic treatment. Various types of bonded retainer exist however, there is a lack of evidence to indicate which type is superior., Aim: To compare upper and lower CAD/CAM nitinol bonded retainers (Memotain ® ) with upper and lower chairside rectangular-chain bonded retainers (Ortho-FlexTech™), in terms of stability, retainer failures and patient satisfaction., Trial Design: Multi-centre, two-arm, parallel-group, randomised controlled clinical trial with 1:1 allocation., Setting: Three trial centres: University Teaching Hospital; District General Hospital; and Specialist Orthodontic Practice. All treatment was provided free as part of a state-funded healthcare system., Materials and Methods: A total of 68 patients were randomly allocated to receive either upper and lower Memotain ® bonded retainers or upper and lower Ortho-FlexTech™ bonded retainers. Ten trained operators placed and reviewed the bonded retainers. Measurements were carried out on study models taken at debond and after six months. Patient satisfaction questionnaires were completed at six months following debond., Results: The trial was terminated due to the high number of failures (50%) of the upper Memotain® retainers within six months. Memotain ® retainers were three times more likely to fail (unadjusted hazard ratio = 2.82, 95% confidence interval = 1.00-7.99) than Ortho-FlexTech™ retainers at six months in the upper arch. Patients were satisfied with both types of retainer., Limitations: Early termination of the trial means that the a priori sample size was not reached, so outcomes should be interpreted with caution., Conclusion: The trial was terminated early due to the high failure rate of upper Memotain ® bonded retainers. They had a higher risk of failure in the maxillary arch when compared to upper Ortho-FlexTech™ bonded retainers after six months.

Epidermal growth factor (EGF) is required for various regulations of skin tissue including wound healing; however, it has limited stability due to the physicochemical conditions of the wound milieu. The lack of functional EGF within the wound can cause permanent tissue defects and therefore, current wound patch designs involve EGF-releasing components. Consequently, the focus of such systems is to improve the wound healing mechanism, with minimal attention on melanogenesis of the scar tissue. The present study investigates in vitro / in vivo wound healing and melanogenesis potential of the EGF-doped films comprised of arrays of chitosan:gelatin nanopillars (nano C:G films) prepared by using nanoporous anodic alumina molds. The potential of EGF-doped films in wound healing was examined with individual and coculture systems of fibroblasts and melanocytes to mimic the wound conditions. The outcomes demonstrated that compared to the control groups, the combination of EGF doping and nanotopography consistently provided the highest levels of melanogenic activity-related genes, melanin contents as well as EGFR expressions for both melanocyte-only and coculture setups. Proteomic, genomic and histological analysis of the excisional wound model further demonstrated that if EGF was present within the nanostructured films, the performance of these substrates in terms of wound closure, collagen thickness as well as melanin deposition was considerably improved. Furthermore, when compared with the control saline treatment and healthy mice groups, significant differences for such parameters were obtained for the nano C:G films, irrespective of their EGF contents. Overall, the results indicate that EGF-doped nano C:G films are good candidates as wound patches that not only provide desirable healing characteristics but also cause improved melanogenic outputs.

Salmonella contamination of low-water activity (a w ) foods poses a serious concern worldwide. The present study was conducted to assess the effects of drying conditions, food composition, and water activity on the desiccation tolerance and thermal resistance of S. Enteritidis FUA1946, S. Senftenberg ATCC43845 and S. Typhimurium ATCC13311 in pet food, binder formulation, and skim milk powder. The samples were wet inoculated with the individual Salmonella strains and were equilibrated to a w 0.33 and 0.75, followed by an isothermal treatment at 70 °C. The thermal inactivation data was fitted to the Weibull model. Irrespective of the a w , food composition and physical structure of the selected foods, strain S. Enteritidis FUA1946 displayed the highest desiccation and thermal resistance, followed by S. Senftenberg ATCC43845 and S. Typhimurium ATCC13311. The food matrix and strain type significantly (p < 0.05) influenced the thermal resistance of microorganisms in foods along with a w change during thermal treatments. To further study the effect of food composition, an additional set of experiments using dry inoculation of the resistant Salmonella strain in the low-a w foods was designed. Significant (p < 0.05) matrix-dependent interaction on Salmonella reduction was observed. The water adsorption isotherms of selected low-a w foods were measured at 20 and 70 °C to relate the thermal inactivation kinetics with the change in the a w . The characterization of thermal resistance of the Salmonella serovars in low-a w products with different compositions and a w in this study may be used for the validation of thermal challenge studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nucleic acid-based therapeutics, including the use of messenger RNA (mRNA) as a drug molecule, has tremendous potential in the treatment of chronic diseases, such as age-related neurodegenerative diseases. In this study, we have developed a cationic liposomal formulation of mRNA and evaluated the potential of intranasal delivery to the brain in murine model. Preliminary in vitro studies in J774A.1 murine macrophages showed GFP expression up to 24 h and stably expressed GFP protein in the cytosol. Upon intranasal administration of GFP-mRNA/cationic liposomes (3 mg/kg dose) in mice, there was significantly higher GFP-mRNA expression in the brain post 24 h as compared to either naked mRNA or the vehicle-treated group. Luciferase mRNA encapsulated in cationic liposomes was used for quantification of mRNA expression distribution in the brain. The results showed increased luciferase activity in the whole brain in a dose-dependent manner. Specifically, the luciferase-mRNA/cationic liposome group (3 mg/kg dose) showed significantly higher luciferase activity in the cortex, striatum, and midbrain regions as compared with the control groups, with minimal systemic exposure. Overall, the results of this study demonstrate the feasibility of brain-specific, nonviral mRNA delivery for the treatment of various neurological disorders.

Iron is a nutrient metal, but excess iron promotes tissue damage. Since iron chelation therapies exhibit multiple off-target toxicities, there is a substantial demand for more specific approaches to decrease iron burden in iron overload. While the divalent metal transporter 1 (DMT1) plays a well-established role in the absorption of dietary iron, up-regulation of intestinal DMT1 is associated with iron overload in both humans and rodents. Hence, we developed a novel pH-sensitive multi-compartmental particulate (MCP) oral delivery system that encapsulates DMT1 siRNA and validated its efficacy in mice. Using the gelatin NPs coated with Eudragit® L100-55, we demonstrated that DMT1 siRNA-loaded MCPs down-regulated DMT1 mRNA levels in the duodenum, which was consistent with decreased intestinal absorption of orally-administered 59 Fe. Together, the Eudragit® L100-55-based oral siRNA delivery system could provide an effective strategy to specifically down-regulate duodenal DMT1 and mitigate iron absorption., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Glioblastoma multiforme (GBM) is one of the most aggressive cancers, where the aggressiveness of tumor has been associated to its high vascularization rate. Bevacizumab (Avastin®), an anti-angiogenic monoclonal antibody, has been used to decrease the angiogenic profile. To circumvent the blood-brain barrier (BBB) and decrease off-target organ toxicity, bevacizumab-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) were developed and intranasally administrated in CD-1 mice to study their pharmacokinetic and pharmacodynamic profile. After 7 days of administration, PLGA NP showed a higher brain bioavailability of bevacizumab when compared to intranasally administrated free bevacizumab. On the other hand, bevacizumab-loaded PLGA NP were able to increase the penetration (higher Cmáx) and the residence time of bevacizumab into the brain (higher Clast). Furthermore, PLGA NP formulation totally prevented bevacizumab systemic exposure. The efficacy of this nanosystem was next evaluated in a validated orthotopic GBM nude mice model, studying the tumor growth over time by bioluminescence and the anti-angiogenic effects. After 14 days, bevacizumab-loaded PLGA NP demonstrated a reduction in the tumor growth accompanied by a higher anti-angiogenic effect compared to the free bevacizumab. These results can be explained by the fact that bevacizumab was found in the brain just for bevacizumab-loaded PLGA NP group, after 14 days of formulation administration. Therefore, we believe that our strategy would be an efficient alternative to improve GBM treatment with high impact for patient life quality and survival., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Biomimicry strategies, inspired from natural organization of living organisms, are being widely used in the design of nanobiomaterials. Particularly, nonlithographic techniques have shown immense potential in the facile fabrication of nanostructured surfaces at large-scale production. Orthopedic biomaterials or coatings possessing extracellular matrix-like nanoscale features induce desirable interactions between the bone tissue and implant surface, also known as osseointegration. In this study, nanopillared chitosan/gelatin (C/G) films were fabricated using nanoporous anodic alumina molds, and their antibacterial properties as well as osteogenesis potential were analyzed by comparing to the flat C/G films and tissue culture polystyrene as controls. In vitro analysis of the expression of RUNX2, osteopontion, and osteocalcin genes for mesenchymal stem cells as well as osteoblast-like Saos-2 cells was found to be increased for the cells grown on nano C/G films, indicating early-stage osteogenic differentiation. Moreover, the mineralization tests (quantitative calcium analysis and alizarin red staining) showed that nanotopography significantly enhanced the mineralization capacity of both cell lines. This work may provide a new perspective of biomimetic surface topography fabrication for orthopedic implant coatings with superior osteogenic differentiation capacity and fast bone regeneration potential.

Chronic wounds are characterized by impaired healing and uncontrolled inflammation, which compromise the protective role of the immune system and may lead to bacterial infection. Upregulation of miR-223 microRNAs (miRNAs) shows driving of the polarization of macrophages toward the anti-inflammatory (M2) phenotype, which could aid in the acceleration of wound healing. However, local-targeted delivery of microRNAs is still challenging, due to their low stability. Here, adhesive hydrogels containing miR-223 5p mimic (miR-223*) loaded hyaluronic acid nanoparticles are developed to control tissue macrophages polarization during wound healing processes. In vitro upregulation of miR-223* in J774A.1 macrophages demonstrates increased expression of the anti-inflammatory gene Arg-1 and a decrease in proinflammatory markers, including TNF-α, IL-1β, and IL-6. The therapeutic potential of miR-223* loaded adhesive hydrogels is also evaluated in vivo. The adhesive hydrogels could adhere to and cover the wounds during the healing process in an acute excisional wound model. Histological evaluation and quantitative polymerase chain reaction (qPCR) analysis show that local delivery of miR-223* efficiently promotes the formation of uniform vascularized skin at the wound site, which is mainly due to the polarization of macrophages to the M2 phenotype. Overall, this study demonstrates the potential of nanoparticle-laden hydrogels conveying miRNA-223* to accelerate wound healing., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polymeric systems have been extensively studied as polyelectrolyte complexes to enhance the cellular delivery and transfection efficiency of genetic materials, such as plasmid DNA (pDNA). Here, self-assembled nanoparticles were formulated by complexation of hyaluronic acid (HA)-conjugated poly(ethylene glycol) (HA-PEG) and poly(ethylenimine) (HA-PEI), respectively, with pDNA creating relatively small, stable, and multifunctional nanoparticle complex formulations with high transfection efficiency. This formulation strategy offers high gene expression efficiency and negligible cytotoxicity in HeLa and A549 human lung cancer cell lines. To develop the ideal formulation, in vitro transfection efficiency was studied for three different nanoparticle formulations (HA-PEI/HA-PEG, HA-PEI, and HA-PEG) with different concentrations. The combination of the three polymers (HA, PEG, and PEI) was significant for the formulation to achieve the maximum gene expression results. The nanoparticles were found to be stable for up to a week at 4 °C conditions. Overall, these HA-based nanoparticles showed promising aspects that can be utilized in the designing of gene delivery vectors for cancer therapy.

Acrylate allergies have been reported in dental professionals as a result of repeat exposure to various acrylate monomers and in dental patients with removable prostheses or longstanding composite restorations. To date, there is only one report of an allergic reaction in a young patient from small volumes of resin-based orthodontic adhesive. This case report demonstrates a recent case of gingival inflammation and lip oedema attributed to an acrylate allergy arising from the composite adhesive used with fixed appliances. The impact on orthodontic treatment is reported and the wider implications for dentistry are discussed.

Botulinum neurotoxins (BoNTs) are the most toxic proteins known to cause flaccid muscle paralysis as a result of inhibition of neurotransmitter release from peripheral cholinergic synapses. BoNT type A (BoNT/A) is a 150 kDa protein consisting of two major subunits: light chain (LC) and heavy chain (HC). The LC is required for the catalytic activity of neurotoxin, whereas the C and N terminal domains of the HC are required for cell binding, and translocation of LC across the endosome membranes, respectively. To better understand the structural and functional aspects of BoNT/A intoxication we report here the development of high yield Escherichia coli expression system (2-20-fold higher yield than the value reported in the literature) for the production of recombinant light chain-translocation domain (rLC-TD/A) module of BoNT/A which is catalytically active and translocation competent. The open reading frame of rLC-TD/A was PCR amplified from deactivated recombinant BoNT/A gene (a non-select agent reagent), and was cloned using pET45b (+) vector to express in E. coli cells. The purification procedure included a sequential order of affinity chromatography, trypsinization, and anion exchange column chromatography. We were able to purify > 95% pure, catalytically active and structurally well-folded protein. Comparison of enzyme kinetics of purified LC-TD/A to full-length toxin and recombinant light chain A suggest that the affinity for the substrate is in between endopeptidase domain and botulinum toxin. The potential application of the purified protein has been discussed in toxicity and translocation assays.

Objectives: Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment., Methods: We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin)., Results: Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2-8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84-111.6; P=0.07)., Conclusions: Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.

Objective: New methods of teaching and learning are constantly being sought in the adult learning environment. Audience Response Systems (ARS) have been used in many different learning environments, especially in the field of medical education. The objective of this investigation was to ascertain the effect of ARS use in undergraduate teaching in a UK dental school., Design: A cross-over clustered randomized educational trial., Setting: Leeds Dental Institute., Participants: Year 4 undergraduate dental students in orthodontics., Methods: Students at Leeds Dental Institute were taught two different topics within the curriculum to test the use of ARS in a cross-over trial. A questionnaire was delivered to the test (ARS) and control (non-ARS) groups., Results: The response rate to the questionnaires was 89·5% (test group) and 82·9% (control group). The ARS enabled students to perform better as shown by knowledge retention (P = 0·013). Students found the seminar more interesting (P = 0·013), easier to concentrate (P = 0·025) and easier to participate in (P = 0·020) when ARS was used. When ARS was used, students were more able to answer questions (P<0·0001), were more likely to prepare for the seminar (P<0·0001) and significantly preferred using ARS (P<0·0001)., Conclusions: ARS was found to significantly improve student concentration and participation in small group seminar teaching and significantly improved knowledge retention. ARS may be useful in facilitating orthodontic teaching in the future.

Intrusion injuries to the permanent dentition are amoung the most severe types of dental injuries, occurring in 0.3-1.9% of all dental trauma cases. The current clinical guidelines in the management of intrusion injuries are based on level B evidence due to the infrequent nature of this type of injury, coupled with a lack of high quality evidence-based studies. This paper presents four cases of severe intrusion injuries that were successfully managed using an interdisciplinary approach. The cases described here highlight the benefits of orthodontic repositioning of severely intruded teeth in the short and medium terms. Although orthodontic repositioning was unsuccessful in the final case, this did not preclude subsequent surgical repositioning. Interdisciplinary collaboration allowed two of the cases described to be effectively managed with premolar autotransplantation alongside orthodontic treatment. The cases demonstrated here indicate the difficulties in providing the current recommended treatment modalities at non-specialist clinics. They accentuate the importance of an immediate referral of such complex cases to a specialist centre where interdisciplinary management is readily available.

Unlabelled: Azathioprine (AZA) is used to maintain remission in autoimmune hepatitis (AIH), but up to 18% of patients are unresponsive. AZA is a prodrug, and the formation of active thioguanine nucleotide (TGN) metabolites varies widely. We aimed to assess the relationship between AZA metabolite concentrations (i.e., TGNs and methylmercaptopurine nucleotides [MeMPNs]), thiopurine methyltransferase (TPMT) activity, therapeutic response, and toxicity in adult patients with AIH prescribed a stable dose of AZA for the maintenance of remission. Red blood cell (RBC) TGNs and MeMPNs were measured in serial blood samples over a 2-year period. The average TGNs (avTGNs) and MeMPNs (avMeMPNs) concentrations for each patient were used for analysis. Therapeutic response was defined as the ability to maintain remission, defined as a normal serum alanine aminotransferase (ALT) level (ALT <33 IU/mL). Patients who maintained remission (n = 53), compared to those who did not (n = 17), tended to be on lower doses of AZA (1.7 versus 2.0 mg/kg/day; P = 0.08), but had significantly higher concentrations of avTGN (237 versus 177 pmol/8 × 10(8) RBCs; P = 0.025). There was no difference in MeMPN concentrations or TPMT activities between the two groups. There was a negative correlation between ALT and avTGN (r(s) = -0.32; P = 0.007). An avTGN concentration of >220 pmol/8 × 10(8) RBCs best predicted remission, with an odds ratio of 7.7 (P = 0.003). There was no association between TGN, MeMPN, or TPMT activity and the development of leucopenia. Two patients developed AZA-induced cholestasis and the avMeMPN concentration was higher in those patients, compared to those who did not (14,277 versus 1,416 pmol/8 × 10(8) RBCs)., Conclusion: TGN concentrations of >220 pmol/8 × 10(8) RBCs are associated with remission. TGN measurement may help identify inadequate immunosupression. AZA-induced cholestasis was associated with increased MeMPN concentrations., (Copyright © 2012 American Association for the Study of Liver Diseases.)