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3D bioprinting is a promising technique for creating artificial tissues and organs. One of the main challenges of bioprinting is cell damage, due to high pressures and tensions. During the biofabrication process, extrusion bioprinting usually results in low cell viability, typically ranging from 40% to 80%, although better printing performance with higher cell viability can be achieved by optimising the experimental design and operating conditions, with nozzle geometry being a key factor. This article presents a review of studies that have used computational fluid dynamics (CFD) to optimise nozzle geometry. They show that the optimal ranges for diameter and length are 0.2 mm to 1 mm and 8 mm to 10 mm, respectively. In addition, it is recommended that the nozzle should have an internal angle of 20 to 30 degrees, an internal coating of ethylenediaminetetraacetic acid (EDTA), and a shear stress of less than 10 kPa. In addition, a design of experiments technique to obtain an optimal 3D bioprinting configuration for a bioink is also presented. This experimental design would identify bioprinting conditions that minimise cell damage and improve the viability of the printed cells.
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OBJECTIVES: The aim of this study was to evaluate the systemic effect of non-surgical peri-implantitis treatment (NSPIT) with or without the administration of systemic metronidazole. METHODS: In this secondary analysis from a previously published clinical trial (NCT03564301), peri-implantitis patients were randomized into two groups: test, receiving NSPIT plus 500 mg of oral systemic metronidazole three times a day for 7 days (n = 10); and control group, receiving NSPIT plus placebo (n = 11). Serum samples were obtained at baseline, 3 and 6 months after therapy to determine levels of inflammatory biomarkers, lipid fractions and complete blood counts. RESULTS: Both treatment modalities produced improvements in clinical and radiographic parameters. After 6 months from NSPIT, a substantial reduction in C-reactive protein (6.9 mg/dL; 95% CI: 3.7 to 9.9, p < .001) and low-density lipoprotein cholesterol (21.8 mg/dL; 95% CI: -6.9 to 50.5, p = .013) as well as a modest increase in neutrophils counts (0.4 × 103/µL; 95% CI: -0.4 to 1.1, p = .010) was observed in the control group while the test group showed a significant reduction of TNF-α (110.1; 95% CI: 38.9 to 181.4, p = .004). CONCLUSIONS: NSPIT showed a short-term beneficial systemic effect regardless of adjunctive use of systemic metronidazole.
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BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries in children is on the rise. Despite this trend, the optimal management of these injuries remains a matter of ongoing debate. In this light, our study seeks to assess the clinical, radiological, and functional outcomes of transphyseal ACL reconstruction in preadolescent patients in the medium-term. METHODS: This prospective study included preadolescent patients aged up to 12 years who underwent ACL transphyseal reconstruction between 2010 and 2020 and had a minimum follow-up of 2 years. Clinical assessments encompassed joint stability and range of motion. Furthermore, leg length discrepancy (LLD) and femorotibial alignment were evaluated both clinically and radiologically using full-length lower limb standing radiographs. Pre- and postoperative functional outcomes were assessed using the International Knee Documentation Committee (IKDC) and Lysholm scales, and the return to normal sports activity was evaluated using the ACL-Return to Sport after Injury (ACL-RSI) scale. Complications and relevant follow-up data were also recorded. Statistical analyses were conducted to evaluate these outcomes. RESULTS: A total of 35 preadolescent patients, consisting of 24 males and 11 females, with a mean age at surgery of 11.2 ± 0.7 years (8.7-12), were included in the study. The mean follow-up was 52.3 ± 20.7 months (24.1-95.9). No significant growth disturbances or clinically relevant LLD were evidenced. All patients demonstrated clinically stable knees with full range of motion at the 2-year follow-up. There were statistically significant improvements in pre- and postoperative IKDC (39.3 ± 13.5 vs. 99.7 ± 0.8, p < 0.005) and Lysholm scores (48.2 ± 15.1 vs. 99.6 ± 1.4, p < 0.005). All but two patients were able to return to their pre-injury level of sports activity, with a mean ACL-RSI score of 93.5 ± 1.3. The analysis revealed an 8.6% rerupture rate and an 11.4% rate of contralateral ACL injuries, with 5-year survival rates of 92.3% and 88.8%, respectively. Subgroup analyses based on age, gender, surgical delay, or associated meniscal lesions did not reveal any significant differences in functional outcomes. Additionally, there was no discernible relationship between age or timing of ACL reconstruction and the risk of meniscal injuries. CONCLUSIONS: Our study reinforces the value of ACL reconstruction in skeletally immature preadolescent patients, with transphyseal technique proven to be a safe, effective, and technically simpler option, even for children under the age of 12. The findings indicate excellent functional outcomes, a high rate of successful return to sporting activities, and minimal to no incidence of growth-related complications in the medium-term. LEVEL OF EVIDENCE: Level II, prospective comparative cohort study, before and after intervention.
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ABSTRACT: A 58-year-old man with dysphagia and trismus symptoms presented a lobulated tumor in the right tonsil and ipsilateral laterocervical stony adenopathies in the physical examination. He had prostate carcinoma as clinical precedent. The tonsilar lesion showed focal FDG uptake (SUVmax, 10.89) on PET/CT and increased glycemic metabolism in the left sacral wing (SUVmax, 10.90) without clear morphological lesion in CT. There was also uptake of the tracer in sacrum in the bone scan. Metastatic involvement was suspected, requiring radioguided biopsy to determine the etiology. Due to radioguided biopsy, histological analysis of the metastasis was performed, with epidermoid carcinoma metastasis diagnosis.
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The interaction between multi-component rare earth element (REE) aqueous solutions and carbonate grains (dolomite, aragonite, and calcite) are studied at hydrothermal conditions (21-210 °C). The effect of ionic radii of five REEs (La, Ce, Pr, Nd, Dy) on solid formation are analyzed using two solution types: equal REE concentrations and concentrations normalized to Post Archean Australian Shale Standard (PAAS). The interaction replaces the host Ca-Mg carbonate grains with a series of REE minerals (lanthanite â kozoite â bastnäsite â cerianite). At 165 °C, equal concentration solutions promote kozoite crystallization, maintaining similar REE ratios in solids and solution. PAAS solutions result in zoned REE-bearing crystals with heterogeneous elemental distributions and discreet REE phases (e.g., cerianite). Chemical signatures indicate metastable REE-bearing phases transforming into more stable polymorphs, along with symplectite textures formed by adjacent phase reactions. Overall, experiments highlight the dependence of polymorph selection, crystallization pathway, mineral formation kinetics, and chemical texture on REE concentrations, ionic radii, temperature, time, and host grain solubility.
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The aim of this present clinical trial is to evaluate the effectiveness of a multicomponent prehabilitation programme administered through educational videos versus another programme based on written exercise recommendations, in patients scheduled for lumbar radiculopathy surgery. This study will be a multicentre, controlled, randomised, parallel clinical trial. One hundred participants undergoing lumbar radiculopathy surgery who meet the established inclusion criteria will be recruited at different Spanish hospitals. The experimental group will follow a 4-week prehabilitation programme combining therapeutic exercise, back care education, and pain neuroscience education delivered through videos designed for consumption at home. The control group will be provided with written instructions to perform therapeutic exercises during the same prehabilitation time period. The primary outcome of the study will be disability, assessed using the Spanish version of the Oswestry Disability Index. The secondary outcomes will be pain perception, health-related quality of life, fear avoidance, kinesiophobia, catastrophising, anxiety, depression, physical activity, and the treatment satisfaction of the patients. This study will provide evidence for the effectiveness of a home-based multicomponent prehabilitation programme that addresses some already identified barriers to patient attendance in face-to-face programmes. Understanding the medium and long-term effects of pre-surgery lumbar muscle training and pain neuroscience education administered via instructional videos watched by patients at home, will help improve the design of prehabilitation programmes in this population while also improving the cost-effectiveness of such interventions.
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Educação de Pacientes como Assunto , Radiculopatia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Dor Lombar/terapia , Dor Lombar/cirurgia , Neurociências , Manejo da Dor/métodos , Educação de Pacientes como Assunto/métodos , Exercício Pré-Operatório , Qualidade de Vida , Radiculopatia/cirurgia , Radiculopatia/terapia , Radiculopatia/reabilitação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Estudos Multicêntricos como AssuntoRESUMO
Fluocerite is a rare earth element (REE) fluoride found as an accessory mineral in magmatic-hydrothermal REE ore deposits, including alkaline complexes and carbonatites, where it is often associated with REE-fluorocarbonates. This study investigates the crystallisation kinetics, mechanisms and energetics of fluocerite (REEF3) and its role as a precursor phase of bastnäsite, one of the key minerals used for the extraction of REE. Fluocerite was synthesized by reacting pure fluorite (CaF2) with La-, Ce- and Nd-bearing solutions at temperatures ranging from ambient to low hydrothermal (30-90 °C). The synthetic fluocerites were then placed in contact with Na2CO3 solutions at temperatures up to 200 °C. A combined approach using powder X-ray diffraction and scanning electron microscopy with energy dispersive spectroscopy was used to determine the nature and quantify the crystallising solids. Our findings reveal a temperature-dependent fluorite-fluocerite transformation, with completion observed within 1 hour at 90 °C and extending to around 30 days at 30 °C. The rate of crystallisation decreases proportionally with the atomic number of the rare earth elements. On the other hand, the carbonation reaction of fluocerite exhibits a significantly slower rate, by â¼3 orders of magnitude, in comparison to the fluorite-fluocerite transformation, regardless of temperature conditions. The synthetic La, Ce and Nd fluocerites transformed into bastnäsite at all temperatures, also forming cerianite (CeO2) in the Ce-bearing experiments and metastable kozoite, NdCO3OH(orth), in the Nd-bearing experiments. Activation energies of fluocerite nucleation increase proportionally with the ionic radii of the REE (81 ± 6 (La); 84 ± 5 (Ce), 96 ± 10 (Nd) kJ mol-1), while the activation energies associated with fluocerite crystallisation are slightly higher for La (90 ± 12 kJ mol-1) and similar for Ce and Nd (76 ± 12 and 72 ± 8 kJ mol-1, respectively).
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The survival of an organism relies on its ability to repair the damage caused by trauma, toxic agents, and inflammation. This process involving cell proliferation and differentiation is driven by several growth factors and is critically dependent on the organization of the extracellular matrix. Since autologous platelet concentrates (APCs) are fibrin matrices in which cells, growth factors, and cytokines are trapped and delivered over time, they are able to influence that response at different levels. The present review thoroughly describes the molecular components present in one of these APCs, leukocyte- and platelet-rich fibrin (L-PRF), and summarizes the level of evidence regarding the influence of L-PRF on anti-inflammatory reactions, analgesia, hemostasis, antimicrobial capacity, and its biological mechanisms on bone/soft tissue regeneration.
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The green energy transition requires rare earth elements (REE) for the permanent magnets used in electric cars and wind turbines. REE extraction and beneficiation are chemically intensive and highly damaging to the environment. We investigated the use of eggshell waste as a sustainable alternative sorbent for the capture and separation of REE from aqueous solutions. Hen eggshell calcite was placed in multi-REE (La, Nd, Dy) solutions at 25 to 205 °C for up to 3 months. A pervasive diffusion of the REE inside the eggshell calcite was observed along pathways formed by the intracrystalline organic matrix and calcite crystal boundaries. At 90 °C, kozoite (REECO3OH, orthorhombic) spherulites precipitate on the surface of the dissolving calcite. At 165 and 205 °C, an interface-coupled dissolution-precipitation mechanism is observed, resulting in the complete dissolution of the calcite shell and its pseudomorphic replacement by polycrystalline kozoite. At 205 °C, kozoite is slowly replaced by hydroxylbastnäsite (REECO3OH, hexagonal), the stable form of the rare earth hydroxycarbonate polymorphs. Our results demonstrate two potential applications of eggshell waste for the uptake of rare earth elements in solution: at low temperatures, as a mixed organic-inorganic adsorbent and absorbent, given sufficient sorption time; and at higher temperatures, as an efficient sacrificial template for the precipitation of rare earth hydroxycarbonates.
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BACKGROUND: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. METHODS: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. RESULTS: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. CONCLUSIONS: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.
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Bacteriemia , Enterobacter aerogenes , Enterobacter cloacae , Infecções por Enterobacteriaceae , Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Enterobacter cloacae/isolamento & purificação , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Feminino , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Idoso , Pessoa de Meia-Idade , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Enterobacter aerogenes/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Estudos de Coortes , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Recidiva , Resultado do TratamentoRESUMO
AIM: This retrospective cohort study aimed to volumetrically investigate the bone stability rate of prefabricated allogeneic bone blocks (PBB) and computer-aided design (CAD)/computer-aided manufacturing (CAM) custom-milled allogeneic bone blocks (CCBB) for ridge augmentation. MATERIALS AND METHODS: Nineteen patients were treated with 20 allografts: 11 CCBB, 9 PBB; 10 in the maxilla and 10 in the mandible. Clinical treatment history and cone beam computed tomography scans before surgery (t0), directly after graft surgery (t1) and after 6 months of healing prior to implant insertion (t2) were evaluated using a three-dimensional evaluation software for absolute bone volume, stability as well as vertical and horizontal bone gain. Furthermore, the inserted implants were analysed for survival, marginal bone loss (MBL) and complications for a mean follow-up period of 43.75 (±33.94) months. RESULTS: A mean absolute volume of 2228.1 mm3 (±1205) was grafted at t1. The bone stability rate was 87.6% (±9.9) for CCBB and 83.0% (±14.5) for PBB. The stability was higher in the maxilla (91.6%) than in the mandible (79.53%). Surgery time of PBB was longer than for CCBB (mean Δ = 52 min). The survival rate of the inserted implants was 100% with a mean MBL of 0.41 mm (±0.37). CONCLUSION: The clinical performance of both allograft block designs was equally satisfactory for vertical and horizontal bone grafting prior to implant placement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT06027710.
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Transplante Ósseo , Desenho Assistido por Computador , Tomografia Computadorizada de Feixe Cônico , Implantes Dentários , Imageamento Tridimensional , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perda do Osso Alveolar/diagnóstico por imagem , Aumento do Rebordo Alveolar/métodos , Transplante Ósseo/métodos , Estudos de Coortes , Implantação Dentária Endóssea/métodos , Seguimentos , Imageamento Tridimensional/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: When using biological variation (BV) data, BV estimates need to be robust and representative. High-endurance athletes represent a population under special physiological conditions, which could influence BV estimates. Our study aimed to estimate BV in athletes for metabolism and growth-related biomarkers involved in the Athlete Biological Passport (ABP), by 2 different statistical models. METHODS: Thirty triathletes were sampled monthly for 11 months. The samples were analyzed for human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), insulin, and N-terminal propeptide of type III procollagen (P-III-NP) by immunoassay. Bayesian and ANOVA methods were applied to estimate within-subject (CVI) and between-subject BV. RESULTS: CVI estimates ranged from 7.8% for IGFBP-3 to 27.0% for insulin, when derived by the Bayesian method. The 2 models gave similar results, except for P-III-NP. Data were heterogeneously distributed for P-III-NP for the overall population and in females for IGF-1 and IGFBP-3. BV components were not estimated for hGH due to lack of steady state. The index of individuality was below 0.6 for all measurands, except for insulin. CONCLUSIONS: In an athlete population, to apply a common CVI for insulin would be appropriate, but for IGF-1 and IGFBP-3 gender-specific estimates should be applied. P-III-NP data were heterogeneously distributed and using a mean CVI may not be representative for the population. The high degree of individuality for IGF-1, IGFBP-3, and P-III-NP makes them good candidates to be interpreted through reference change values and the ABP.
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Atletas , Biomarcadores , Hormônio do Crescimento Humano , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I , Insulina , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Biomarcadores/sangue , Masculino , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Feminino , Adulto , Insulina/sangue , Hormônio do Crescimento Humano/sangue , Teorema de Bayes , Pró-Colágeno/sangue , Fragmentos de Peptídeos/sangueRESUMO
Paralytic shellfish poisoning is an important concern for mollusk fisheries, aquaculture, and public health. In Galicia, NW Iberian Peninsula, such toxicity has been monitored for a long time using mouse bioassay. Therefore, little information exists about the precise toxin analogues and their possible transformations in diverse mollusk species and environments. After the change in the European PSP reference method, a refinement of the Lawrence method was developed, achieving a 75% reduction in chromatogram run time. Since the beginning of 2021, when this refinement Lawrence method was accredited under the norm UNE-EN ISO/IEC 17025, it has been used in the area to determine the toxin profiles and to estimate PSP toxicity in more than 4500 samples. In this study, we have summarized three years of monitoring results, including interspecific, seasonal, and geographical variability of PSP toxicity and toxin profile. PSP was detected in more than half of the samples analyzed (55%), but only 4.4% of the determinations were above the EU regulatory limit. GTX1,4 was the pair of STX analogs that produced the highest toxicities, but GTX2,3 was found in most samples, mainly due to the reduction of GTX1,4 but also by the higher sensitivity of the method for this pair of analogs. STX seems to be mainly a product of biotransformation from GTX2,3. The studied species (twelve bivalves and one gastropod) accumulated and transformed PSP toxins to a different extent, with most of them showing similar profiles except for Spisula solida and Haliotis tuberculata. Two seasonal peaks of toxicity were found: one in spring-early summer and another in autumn, with slightly different toxin profiles during outbreaks in relation to the toxicity during valleys. In general, both the total toxicity and toxin profiles of the southernmost locations were different from those in the northern part of the Atlantic coast and the Cantabrian Sea, but this general pattern is modified by the PSP history of some specific locations.
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Toxinas Marinhas , Moluscos , Estações do Ano , Intoxicação por Frutos do Mar , Animais , Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Moluscos/química , Espanha , Saxitoxina/análise , Saxitoxina/análogos & derivados , Saxitoxina/toxicidadeRESUMO
OBJECTIVE: The objective of this study is to evaluate the changes at marginal bone level at implants restored with screw-retained prosthesis connected directly to the implants or with an intermediate abutment, after 3-year follow-up. MATERIAL AND METHODS: Thirty-six partially edentulous patients received 72 implants. Each patient received 2 implants and a 2-4-unit screw-retained implant-prosthesis. The test group implants received a screw-retained prosthesis connected directly to the implant shoulder, the control group prosthesis were connected through a 3-mm standardised intermediate abutment. Clinical and radiological data were recorded at baseline and at 6-, 12-, and 36-month follow-up. RESULTS: At 36 months, the mean marginal bone loss was 0.13 ± 0.18 mm for the control group and 0.20 ± 0.24 for the test group, with no significant differences between groups (p > .05). Clinical variables (Probing Pocket Depth, Bleeding on Probing and Plaque Index) at 36 months also showed no significant difference between groups. Minor complications frequency was 6.7% in the control group and 5.3% in test group. None of the groups suffered from mayor complications. Patient Reported Outcomes (PROs) showed a General Satisfaction mean score in the control group of 9.40 (SD 0.82) and 9.37 (SD 1.06) in the test group with no significant differences between groups. CONCLUSIONS: Bone-level implants restored with screw-retained partial prostheses with or without intermediate abutments showed similar radiographic and clinical outcomes after 3 years.
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Brain drug delivery is severely hindered by the presence of the blood-brain barrier (BBB). Its functionality relies on the interactions of the brain endothelial cells with additional cellular constituents, including pericytes, astrocytes, neurons, or microglia. To boost brain drug delivery, nanomedicines have been designed to exploit distinct delivery strategies, including magnetically driven nanocarriers as a form of external physical targeting to the BBB. Herein, a lipid-based magnetic nanocarrier prepared by a low-energy method is first described. Magnetic nanocapsules with a hydrodynamic diameter of 256.7 ± 8.5 nm (polydispersity index: 0.089 ± 0.034) and a ξ-potential of -30.4 ± 0.3 mV were obtained. Transmission electron microscopy-energy dispersive X-ray spectroscopy analysis revealed efficient encapsulation of iron oxide nanoparticles within the oily core of the nanocapsules. Both thermogravimetric analysis and phenanthroline-based colorimetric assay showed that the iron oxide percentage in the final formulation was 12 wt.%, in agreement with vibrating sample magnetometry analysis, as the specific saturation magnetization of the magnetic nanocapsules was 12% that of the bare iron oxide nanoparticles. Magnetic nanocapsules were non-toxic in the range of 50-300 µg/mL over 72 h against both the human cerebral endothelial hCMEC/D3 and Human Brain Vascular Pericytes cell lines. Interestingly, higher uptake of magnetic nanocapsules in both cell types was evidenced in the presence of an external magnetic field than in the absence of it after 24 h. This increase in nanocapsules uptake was also evidenced in pericytes after only 3 h. Altogether, these results highlight the potential for magnetic targeting to the BBB of our formulation.
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Several drugs can be used for treating inflammatory skin pathologies like dermatitis and psoriasis. However, for the management of chronic and long-term cases, topical administration is preferred over oral delivery since it prevents certain issues due to systemic side effects from occurring. Cyclosporin A (CsA) has been used for this purpose; however, its high molecular weight (1202 Da) restricts the diffusion through the skin structure. Here, we developed a nano-in-micro device combining lipid vesicles (LVs) and dissolving microneedle array patches (DMAPs) for targeted skin delivery. CsA-LVs allowed the effective incorporation of CsA in the hydrophilic DMAP matrix despite the hydrophobicity of the drug. Polymeric matrix composed of poly (vinyl alcohol) (5% w/v), poly (vinyl pyrrolidine) (15% w/v) and CsA-LV dispersion (10% v/v) led to the formation of CsA-LVs@DMAPs with adequate mechanical properties to penetrate the stratum corneum barrier. The safety and biocompatibility were ensured in an in vitro viability test using HaCaT keratinocytes and L929 fibroblast cell lines. Ex vivo permeability studies in a Franz-diffusion cell setup showed effective drug retention in the skin structure. Finally, CsA-LVs@DMAPs were challenged in an in vivo murine model of delayed-type hypersensitivity to corroborate their potential to ameliorate skin inflammatory conditions. Different findings like photon emission reduction in bioluminescence study, normalisation of histological damage and decrease of inflammatory cytokines point out the effectivity of CsA-LVs@DMAPs to treat these conditions. Overall, our study demonstrates that CsA-LVs@DMAPs can downregulate the skin inflammatory environment which paves the way for their clinical translation and their use as an alternative to corticosteroid-based therapies.
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The development of a self-regulated minimally invasive system for insulin delivery can be considered as the holy grail in the field of diabetes mellitus. A delivery system capable of releasing insulin in response to blood glucose levels would significantly improve the quality of life of diabetic patients, eliminating the need for frequent finger-prick tests and providing better glycaemic control with lower risk of hypoglycaemia. In this context, the latest advances in glucose-responsive microneedle-based transdermal insulin delivery are here compiled with a thorough analysis of the delivery mechanisms and challenges lying ahead in their clinical translation. Two main groups of microneedle-based systems have been developed so far: glucose oxidase-containing and phenylboronic acid-containing systems. Both strategies in combination have also been tested and two other novel strategies are under development, namely electronic closed-loop and glucose transporter-based systems. Results from preclinical studies conducted using these different types of glucose-triggered release systems are comprehensively discussed. Altogether, this analysis from both a mechanistic and translational perspective will provide rationale and/or guidance for future trends in the research hotspot of glucose-responsive microneedle-based insulin delivery systems.
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Diabetes Mellitus Tipo 1 , Insulina , Humanos , Insulina/uso terapêutico , Glucose , Qualidade de Vida , Sistemas de Liberação de Medicamentos/métodos , Administração Cutânea , Glicemia/análiseRESUMO
An approach was proposed to control the displacement of domain walls in magnetic microwires, which are employed in magnetic sensors. The velocity of the domain wall can be altered by the interaction of two magnetic microwires of distinct types. Thorough investigations were conducted utilizing fluxmetric, Sixtus-Tonks, and magneto-optical techniques. The magneto-optical examinations revealed transformation in the surface structure of the domain wall and facilitated the determination of the mechanism of external influence on the movement of domain walls in magnetic microwires.
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Antimicrobial resistance and tolerance (AMR&T) are urgent global health concerns, with alarmingly increasing numbers of antimicrobial drugs failing and a corresponding rise in related deaths. Several reasons for this situation can be cited, such as the misuse of traditional antibiotics, the massive use of sanitizing measures, and the overuse of antibiotics in agriculture, fisheries, and cattle. AMR&T management requires a multifaceted approach involving various strategies at different levels, such as increasing the patient's awareness of the situation and measures to reduce new resistances, reduction of current misuse or abuse, and improvement of selectivity of treatments. Also, the identification of new antibiotics, including small molecules and more complex approaches, is a key factor. Among these, novel DNA- or RNA-based approaches, the use of phages, or CRISPR technologies are some potent strategies under development. In this perspective article, emerging and experienced leaders in drug delivery discuss the most important biological barriers for drugs to reach infectious bacteria (bacterial bioavailability). They explore how overcoming these barriers is crucial for producing the desired effects and discuss the ways in which drug delivery systems can facilitate this process.
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Antibacterianos , Sistemas de Liberação de Medicamentos , Humanos , Antibacterianos/administração & dosagem , Antibacterianos/química , Animais , Resistência Microbiana a Medicamentos , Farmacorresistência Bacteriana , Bactérias/efeitos dos fármacos , Tolerância a MedicamentosRESUMO
BACKGROUND: Current recommendations support guiding fluid resuscitation through the assessment of fluid responsiveness. Recently, the concept of fluid tolerance and the prevention of venous congestion (VC) have emerged as relevant aspects to be considered to avoid potentially deleterious side effects of fluid resuscitation. However, there is paucity of data on the relationship of fluid responsiveness and VC. This study aims to compare the prevalence of venous congestion in fluid responsive and fluid unresponsive critically ill patients after intensive care (ICU) admission. METHODS: Multicenter, prospective cross-sectional observational study conducted in three medical-surgical ICUs in Chile. Consecutive mechanically ventilated patients that required vasopressors and admitted < 24 h to ICU were included between November 2022 and June 2023. Patients were assessed simultaneously for fluid responsiveness and VC at a single timepoint. Fluid responsiveness status, VC signals such as central venous pressure, estimation of left ventricular filling pressures, lung, and abdominal ultrasound congestion indexes and relevant clinical data were collected. RESULTS: Ninety patients were included. Median age was 63 [45-71] years old, and median SOFA score was 9 [7-11]. Thirty-eight percent of the patients were fluid responsive (FR+), while 62% were fluid unresponsive (FR-). The most prevalent diagnosis was sepsis (41%) followed by respiratory failure (22%). The prevalence of at least one VC signal was not significantly different between FR+ and FR- groups (53% vs. 57%, p = 0.69), as well as the proportion of patients with 2 or 3 VC signals (15% vs. 21%, p = 0.4). We found no association between fluid balance, CRT status, or diagnostic group and the presence of VC signals. CONCLUSIONS: Venous congestion signals were prevalent in both fluid responsive and unresponsive critically ill patients. The presence of venous congestion was not associated with fluid balance or diagnostic group. Further studies should assess the clinical relevance of these results and their potential impact on resuscitation and monitoring practices.