Peptides that comprise the functional subunits of proteins have been conjugated to versatile materials (biomolecules, polymers, surfaces and nanoparticles) in an effort to modulate cell responses, ...specific binding affinity and/or self-assembly behavior. However, the efficient and convenient synthesis of peptide-conjugates, especially the constructs with multiple types of peptide functionality remains challenging. In this critical review, we focus on "click" reactions that have been used to synthesis peptide-functionalized conjugates, introducing their reaction conditions, specifically elucidating parameters that influence reaction kinetics and total conversion, and highlighting examples that have been completed recently. Moreover, orthogonal "click" reactions that synthesize multi-functional biomaterials in a one-pot or sequential manner are noted. Through this review, a comprehensive understanding of "click" reactions aims to provide insight on how one might choose suitable "click" reactions to constitute peptide-functionalized molecules/surfaces/matrices for the development of advanced biomaterials.
Objectives
To review the scientific literature pertaining to the use of hand‐carried and hand‐held ultrasound devices in low‐ and middle‐income countries (LMIC), with a focus on clinical ...applications, geographical areas of use, the impact on patient management and technical features of the devices used.
Methods
The electronic databases PubMed and Google Scholar were searched. No language or date restrictions were applied. Case reports and original research describing the use of hand‐carried ultrasound devices in LMIC were included if agreed upon as relevant by two‐reviewer consensus based on our predefined research questions.
Results
A total of 644 articles were found and screened, and 36 manuscripts were included for final review. Twenty‐seven studies were original research articles, and nine were case reports. Several reports describe the successful diagnosis and management of difficult, often life‐threatening conditions, using hand‐carried and hand‐held ultrasound. These portable ultrasound devices have also been studied for cardiac screening exams, as well as a rapid triage tool in rural areas and after natural disaster. Most applications focus on obstetrical and abdominal complaints. Portable ultrasound may have an impact on clinical management in up to 70% of all cases. However, no randomised controlled trials have evaluated the impact of ultrasound‐guided diagnosis and treatment in resource‐constrained settings. The exclusion of articles published in journals not listed in the large databases may have biased our results. Our findings are limited by the lack of higher quality evidence (e.g. controlled trials).
Conclusions
Hand‐carried and hand‐held ultrasound is successfully being used to triage, diagnose and treat patients with a variety of complaints in LMIC. However, the quality of the current evidence is low. There is an urgent need to perform larger clinical trials assessing the impact of hand‐carried ultrasound in LMIC.
Objectifs
Passer en revue la littérature scientifique portant sur l'utilisation d'appareils d’échographie portatifs dans les pays à faible revenu et à revenu intermédiaire (PFR‐PRI) en mettant l'accent sur les applications cliniques, les zones géographiques d'utilisation, l'impact sur la prise en charge des patients et les caractéristiques techniques des appareils utilisés.
Méthodes
Recherche effectuée dans les bases de données électroniques PubMed et Google Scholar. Aucune restriction linguistique ou de période n'a été appliquée. Les rapports de cas et les recherches originales décrivant l'utilisation d'appareils d’échographie portatifs dans les PFR‐PRI ont été inclus, si trouvés pertinents par le consensus de deux reviewers, basé sur nos questions de recherche prédéfinies.
Résultats
644 articles ont été trouvés et analysés, 36 manuscrits ont été inclus pour analyse finale. 27 études faisaient l'objet d'articles de recherche originale et 9 étaient des rapports de cas. Plusieurs rapports décrivent le diagnostic et la prise en charge avec succès de conditions difficiles, souvent mortelles, en utilisant des appareils d’échographie portatifs. Ces dispositifs d’échographie portatifs ont également été étudiés pour les examens de dépistage cardiaques, ainsi que comme outil de triage rapide dans les zones rurales et à la suite de catastrophes naturelles. La plupart des applications se concentrent sur les plaintes obstétricales et abdominales. L’échographie portative peut avoir un impact sur la prise en charge clinique dans 70% de tous les cas. Cependant, aucun essai contrôlé randomisé n'a évalué l'impact sur le diagnostic et le traitement guidé par l’échographie dans les milieux à ressources limitées. L'exclusion des articles publiés dans des revues ne figurant pas dans les grandes bases de données peut avoir biaisé nos résultats. Nos résultats sont limités par le manque de donnée de meilleure qualité (par ex., les essais contrôlés).
Conclusions
L’échographie portative et réalisée à la main est utilisée avec succès au triage, au diagnostic et pour le traitement des patients avec diverses plaintes dans PFR‐PRI. Cependant, la qualité des données actuelles est faible. Il est urgent de procéder à des essais cliniques de grande envergure évaluant l'impact de l’échographie réalisée à la main dans les PFR‐PRI.
Objetivos
Revisar la literatura científica existente sobre el uso de aparatos portátiles de ultrasonido en países con ingresos bajos y medios (PIBM), con especial atención en las aplicaciones clínicas, las áreas geográficas de uso, el impacto sobre el manejo del paciente y las características técnicas de los aparatos utilizados.
Métodos
Se realizó una búsqueda en las bases de datos electrónicas PubMed y Google Scholar. No se aplicaron restricciones de idioma o fecha. Se incluyeron los informes de casos y artículos originales que describían el uso de aparatos de ultrasonido portátiles en PIBM, si dos revisores estaban de acuerdo sobre su relevancia basándose en las preguntas predefinidas de búsqueda.
Resultados
Se encontraron y revisaron 644 artículos, y se incluyeron 36 manuscritos en la revisión final. 27 estudios eran artículos de investigaciones originales y 9 eran informes de casos. Varios informes describan el diagnóstico exitoso y el manejo de condiciones difíciles, a menudo letales, utilizando equipos portátiles de ultrasonido. Estos equipos también han sido estudiados en pruebas de riesgo cardiaco, al igual que como herramientas de triaje rápido en áreas rurales y después de un desastre natural. La mayoría de las aplicaciones se centran en problemas obstétricos y abdominales. El ultrasonido portátil podría tener un impacto sobre el manejo clínico en hasta un 70% de todos los casos. Sin embargo, ningún ensayo aleatorizado y controlado ha evaluado el impacto del diagnóstico y el tratamiento guiado por ultrasonido en lugares con recursos limitados. Excluir aquellos artículos publicados en revistas que no figuran en las grandes bases de datos podría haber sesgado nuestros resultados. Nuestros hallazgos están limitados por la falta de evidencia de mayor calidad (ej. ensayos controlados).
Conclusiones
El uso de equipos de ultrasonido portátiles es exitoso para realizar el triaje, diagnóstico y tratamiento de pacientes con una variedad de problemas en PIBM. Sin embargo, la calidad de la evidencia actualmente disponible es baja. Existe una necesidad urgente de realizar ensayos clínicos grandes para evaluar el impacto de equipos de ultrasonido portátiles en PIBM.
Hospital-acquired infections arising from implanted polymeric medical devices continue to pose a significant challenge for medical professionals and patients. Often times, these infections arise from ...biofilm accumulation on the device, which is difficult to eradicate and usually requires antibiotic treatment and device removal. In response, significant efforts have been made to design functional polymeric devices or coatings that possess antimicrobial or antifouling properties that limit biofilm formation and subsequent infection by inhibiting or eliminating bacteria near the device surface or by limiting the initial attachment of proteins and bacteria. In this Viewpoint, we highlight the magnitude of device-associated infections, the role of biofilm formation in human pathogenesis, and recent advances in antimicrobial and antifouling polymers, as well as current strategies employed in commercial devices for preventing infection.
Sufficient molecular diagnostic capacity is important for public health interventions such as case detection and isolation, including for health-care professionals.1 Protocols for RNA RT-PCR testing ...of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became available early in the pandemic, yet the infrastructure of testing laboratories is stretched and in some areas it is overwhelmed.2 We propose a testing strategy that is easy to implement and can expand the capacity of the available laboratory infrastructure and test kits when large numbers of asymptomatic people need to be screened. Viral load during symptomatic infection with SARS-CoV-2 was investigated by Zou and colleagues.3 To analyse the effect of pooling samples on the sensitivity of RT-PCR, we compared cycle threshold (Ct) values of pools that tested positive with Ct values of individual samples that tested positive. The Ct values for both E-gene and S-gene assays in pools and individual positive samples were below 30 and easily categorised as positive.
The first two oral antivirals, molnupiravir and nirmatrelvir–ritonavir, are now becoming available in many countries. These medicines will be indicated to treat mild-to-moderate COVID-19 in ...non-hospitalised patients who are at high risk of progressing to severe COVID-19. These antivirals should be prescribed within 5 days of symptom onset, and after SARS-CoV-2 infection has been confirmed. However, the availability of these antivirals will be scarce for some time due to manufacturing constraints. Each country should establish a policy on the conditions under which these antivirals can be prescribed. Such a policy should be based on the fulfilment of five ethical elements: transparency, relevance, appeals, enforcement, and fairness. Following the principles of distributive justice, molnupiravir and nirmatrelvir–ritonavir should be prescribed according to a hierarchy of predicted efficacy, ideally on the basis of an evidence-based scoring system. The placebo-controlled randomised trials that supported the temporary authorisation of these two antivirals were conducted in unvaccinated patients with COVID-19, so an evidence-based prescription practice would only use these drugs for unvaccinated patients until further data become available. However, in the countries that authorised these antivirals in 2021 (the UK and the USA), both vaccinated and unvaccinated patients meeting particular requirements have access to these antivirals. Due to the complexity of prioritisation, national health authorities should start issuing their draft policies as soon as possible and these policies should be regularly updated. The effectiveness of these antivirals against the omicron variant of SARS-CoV-2 must be urgently assessed. Once implemented, molnupiravir and nirmatrelvir–ritonavir must show their effectiveness and safety in the real world, and health systems must be adequately adapted for the correct use of these antivirals.
...without a strategic transition plan in place, communities that used to benefit from lymphatic filariasis control activities run the risk of undermining the gains already made for soil-transmitted ...helminthiasis control once GPELF is discontinued. ...the Committee welcomes the recent approval of a new, rapidly disintegrating chewable formulation of mebendazole. ...as for other chronic infections (e.g., tuberculosis, human immune deficiency virus HIV, and malaria), combination therapy against soil-transmitted helminthiasis might decrease this risk and could enhance efficacy 25. ...the need for combination therapy is further supported by coendemicity of multiple helminth infections. ...there is a need to develop a new survey design that (1) is sufficiently powered to assess if the prevalence of moderate- or heavy-intensity infections falls below 1% and (2) is feasible and affordable, considering the limited resources and capacity of national soil-transmitted helminthiasis control programs.
Abstract
Background
Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to ...account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO.
Methods
Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints.
Results
The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem.
Conclusions
ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.
Complex three-dimensional (3D) pore geometries, useful for tissue engineering scaffolds, can be fabricated via photo-crosslinking of resorbable poly(propylene fumarate) (PPF) resins using ...stereolithography (SLA) and/or continuous digital light processing (cDLP) methods. Physico-chemical parameters inherent to 3D printable resin design, include viscosity, polymer concentration, degree of polymerization, and resin printing temperature. We report here on our study of these parameters and their influence the cDLP 3D printing process and the resulting mechanical properties. A series of PPF oligomers were synthesized by the ring-opening copolymerization (ROCOP) of maleic anhydride and propylene oxide followed by a base-catalyzed isomerization. The resin viscosities were measured as a function of number-average molecular mass ( M n ̅ ) of the PPF oligomers (1.1, 1.7 and 2.0 kDa), concentrations of PPF in the reactive diluent diethyl fumarate (DEF) (50 and 75 wt %) and resin temperature (25 to 55 °C). The zero-shear viscosity (η0) of the resins was found to be temperature-dependent and follow a linear Arrhenius relationship. Tensile tests demonstrated mechanical properties within the range of trabecular bone, with the ultimate strength at break above 15 MPa and elastic moduli between 178 and 199 MPa.
Degradable polymers are used widely in tissue engineering and regenerative medicine. Maturing capabilities in additive manufacturing coupled with advances in orthogonal chemical functionalization ...methodologies have enabled a rapid evolution of defect-specific form factors and strategies for designing and creating bioactive scaffolds. However, these defect-specific scaffolds, especially when utilizing degradable polymers as the base material, present processing challenges that are distinct and unique from other classes of materials. The goal of this review is to provide a guide for the fabrication of biodegradable polymer-based scaffolds that includes the complete pathway starting from selecting materials, choosing the correct fabrication method, and considering the requirements for tissue specific applications of the scaffold.
PDF
