Water-Enhancing Gels Exhibiting Heat-Activated Formation of Silica Aerogels for Protection of Critical Infrastructure During Catastrophic Wildfire.

A promising strategy to address the pressing challenges with wildfire, particularly in the wildland-urban interface (WUI), involves developing new approaches for preventing and controlling wildfire within wildlands. Among sprayable fire-retardant materials, water-enhancing gels have emerged as exceptionally effective for protecting civil infrastructure. They possess favorable wetting and viscoelastic properties that reduce the likelihood of ignition, maintaining strong adherence to a wide array of surfaces after application. Although current water-enhancing hydrogels effectively maintain surface wetness by creating a barricade, they rapidly desiccate and lose efficacy under high heat and wind typical of wildfire conditions. To address this limitation, unique biomimetic hydrogel materials from sustainable cellulosic polymers crosslinked by colloidal silica particles are developed that exhibit ideal viscoelastic properties and facile manufacturing. Under heat activation, the hydrogel transitions into a highly porous and thermally insulative silica aerogel coating in situ, providing a robust protective layer against ignition of substrates, even when the hydrogel fire suppressant becomes completely desiccated. By confirming the mechanical properties, substrate adherence, and enhanced substrate protection against fire, these heat-activatable biomimetic hydrogels emerge as promising candidates for next-generation water-enhancing fire suppressants. These advancements have the potential to dramatically improve the ability to protect homes and critical infrastructure during wildfire.

Biomimetic Non-ergodic Aging by Dynamic-to-covalent Transitions in Physical Hydrogels.

Hydrogels are soft materials engineered to suit a multitude of applications that exploit their tunable mechanochemical properties. Dynamic hydrogels employing noncovalent, physically cross-linked networks dominated by either enthalpic or entropic interactions enable unique rheological and stimuli-responsive characteristics. In contrast to enthalpy-driven interactions that soften with increasing temperature, entropic interactions result in largely temperature-independent mechanical properties. By engineering interfacial polymer-particle interactions, we can induce a dynamic-to-covalent transition in entropic hydrogels that leads to biomimetic non-ergodic aging in the microstructure without altering the network mesh size. This transition is tuned by varying temperature and formulation conditions such as pH, which allows for multivalent tunability in properties. These hydrogels can thus be designed to exhibit either temperature-independent metastable dynamic cross-linking or time-dependent stiffening based on formulation and storage conditions, all while maintaining structural features critical for controlling mass transport, akin to many biological tissues. Such robust materials with versatile and adaptable properties can be utilized in applications such as wildfire suppression, surgical adhesives, and depot-forming injectable drug delivery systems.

Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management.

Polyacrylamide-based hydrogel coatings improve biocompatibility of implanted pump devices.

The introduction of transcutaneous and subcutaneous implants and devices into the human body instigates fouling and foreign body responses (FBRs) that limit their functional lifetimes. Polymer coatings are a promising solution to improve the biocompatibility of such implants, with potential to enhance in vivo device performance and prolong device lifetime. Here we sought to develop novel materials for use as coatings on subcutaneously implanted devices to reduce the FBR and local tissue inflammation in comparison to gold standard materials such as poly(ethylene glycol) and polyzwitterions. We prepared a library of polyacrylamide-based copolymer hydrogels, which were selected from materials previously shown to exhibit remarkable antifouling properties with blood and plasma, and implanted them into the subcutaneous space of mice to evaluate their biocompatibility over the course of 1 month. The top performing polyacrylamide-based copolymer hydrogel material, comprising a 50:50 mixture of N-(2-hydroxyethyl)acrylamide (HEAm) and N-(3-methoxypropyl)acrylamide (MPAm), exhibited significantly better biocompatibility and lower tissue inflammation than gold standard materials. Moreover, when applied to polydimethylsiloxane disks or silicon catheters as a thin coating (45 ± 1 µm), this leading copolymer hydrogel coating significantly improved implant biocompatibility. Using a rat model of insulin-deficient diabetes, we showed that insulin pumps fitted with HEAm-co-MPAm hydrogel-coated insulin infusion catheters exhibited improved biocompatibility and extended functional lifetime over pumps fitted with industry standard catheters. These polyacrylamide-based copolymer hydrogel coatings have the potential to improve device function and lifetime, thereby reducing the burden of disease management for people regularly using implanted devices.

Sustained Delivery of GLP-1 Receptor Agonists from Injectable Biomimetic Hydrogels Improves Treatment of Diabetes.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L-cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. GLP-1 in itself is rapidly degraded, but long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central in the treatment of T2D because of the beneficial effects extending also beyond glucose control. Currently, these therapeutics must be injected either daily or weekly or taken daily orally, leaving room for technological innovations that enable less frequent administrations, which will reduce patient burden and increase patient compliance. An ideal GLP-1 RA drug product would provide continuous therapy for upwards of four months from a single administration to match the cadence with which T2D patients typically visit their physician. In this work, we leveraged an injectable hydrogel depot technology to develop a long-acting GLP-1 RA drug product. By modulating the hydrogel properties to tune GLP-1 RA retention within the hydrogel depot, we engineered formulations capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirmed that a single injection of hydrogel-based therapies exhibits sustained exposure of GLP-1 RA over 42 days, corresponding to a once-every four month therapy in humans. Moreover, these hydrogel therapies maintained optimal management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug molecule. The pharmacokinetics and pharmacodynamics of these hydrogel-based long-acting GLP-1 RA treatments are promising for development of novel therapies reducing treatment burden for more effective management of T2D. Progress and Potential: While insufficient access to quality healthcare is problematic for consistent management of Type II diabetes (T2D), poor adherence to burdensome treatment regimens is one of the greatest challenges for disease management. Glucagon-like peptide 1 (GLP1) drugs have become central to the treatment of T2D due to their many beneficial effects beyond improving glucose control. Unfortunately, while optimization of GLP1 drugs has reduced treatment frequency from daily to weekly, significant patient burden still leads to poor patience compliance. In this work we developed an injectable hydrogel technology to enable GLP1 drugs only requiring administration once every four months. We showed in a rat model of T2D that one injection of a hydrogel-based therapy improves management of blood glucose and weight when compared with daily injections of the leading drug used clinically. These hydrogel-based GLP1 treatments are promising for reducing treatment burden and more effectively managing T2D. Future Impact: A GLP-1-based drug product providing four months of continuous therapy per administration could be transformational for the management of Type II diabetes (T2D). One of the most challenging aspects of diabetes management with GLP-1 mimics is maintenance of consistent levels of the drugs in the body, which is complicated by poor patient compliance on account of the high frequency of dosing required for current treatments. By leveraging a unique sustained release hydrogel depot technology we develop a months-long GLP-1 drug product candidate that has the potential to reduce patient burden and improving diabetes management. Overall, the hydrogel technology we describe here can dramatically reduce the frequency of therapeutic interventions, significantly increasing patient quality of life and reducing complications of diabetes management.Our next steps will focus on optimization of the drug formulations in a swine model of T2D, which is the most advanced and translationally-relevant animal model for these types of therapeutics. The long-term vision for this work is to translate lead candidate drug products towards clinical evaluation, which will also require comprehensive safety evaluation in multiple species and manufacturing our these materials according to Good Manufacturing Practices. The months-long-acting GLP-1 drug product that will come from this work has the potential to afford thus far unrealized therapeutic impact for the hundreds of millions of people with diabetes worldwide.

Stable High-Concentration Monoclonal Antibody Formulations Enabled by an Amphiphilic Copolymer Excipient.

Monoclonal antibodies are a staple in modern pharmacotherapy. Unfortunately, these biopharmaceuticals are limited by their tendency to aggregate in formulation, resulting in poor stability and often requiring low concentration drug formulations. Moreover, existing excipients designed to stabilize these formulations are often limited by their toxicity and tendency to form particles such as micelles. Here, we demonstrate the ability of a simple "drop-in", amphiphilic copolymer excipient to enhance the stability of high concentration formulations of clinically-relevant monoclonal antibodies without altering their pharmacokinetics or injectability. Through interfacial rheology and surface tension measurements, we demonstrate that the copolymer excipient competitively adsorbs to formulation interfaces. Further, through determination of monomeric composition and retained bioactivity through stressed aging, we show that this excipient confers a significant stability benefit to high concentration antibody formulations. Finally, we demonstrate that the excipient behaves as an inactive ingredient, having no significant impact on the pharmacokinetic profile of a clinically relevant antibody in mice. This amphiphilic copolymer excipient demonstrates promise as a simple formulation additive to create stable, high concentration antibody formulations, thereby enabling improved treatment options such as a route-of-administration switch from low concentration intravenous (IV) to high concentration subcutaneous (SC) delivery while reducing dependence on the cold chain.

Cosmogenic radionuclides in the Cavezzo meteorite: Gamma-ray measurement and detection efficiency simulations.

The Cavezzo meteorite was recovered on January 4th, 2020, just three days after the fall observed over Northern Italy by the all-sky cameras of the Italian PRISMA fireball network. Two specimens, weighing 3.1 g (F1) and 52.2 g (F2), were collected in the predicted strewn-field and the meteorite has been classified as an L5 anomalous chondrite. The gamma-activity of the F2 sample was measured at the Monte dei Cappuccini underground Research Station (Torino, Italy) with a large-volume HPGe-NaI(Tl) spectrometer. Thanks to the high efficiency, selectivity, and low background of the spectrometer, we were able to detect fifteen cosmogenic radioisotopes. The presence of nuclides with half-lives down to a few days (47Ca, 52Mn, and 48V) undoubtedly confirmed the recent fall of the sample. The very low activity of 44Ti and 60Co was revealed with a particular coincidence between the HPGe and NaI(Tl) detectors. To obtain the detection efficiency, we have simulated the response of the detector with the GEANT4 toolkit, once the spectrometer's dead layer thickness was estimated using standards of known activity. Moreover, the simulation of the Dhajala meteorite (H3/4 chondrite) measurement allowed us to verify that the self-absorption of the sample is correctly taken into account and validate our simulations. In this contribution, we focus on the coincidence optimization techniques and the detection efficiency computation.

Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors.

Adoptive cell therapy (ACT) has proven to be highly effective in treating blood cancers, but traditional approaches to ACT are poorly effective in treating solid tumors observed clinically. Novel delivery methods for therapeutic cells have shown promise for treatment of solid tumors when compared with standard intravenous administration methods, but the few reported approaches leverage biomaterials that are complex to manufacture and have primarily demonstrated applicability following tumor resection or in immune-privileged tissues. Here, we engineer simple-to-implement injectable hydrogels for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improve treatment of solid tumors. The unique architecture of this material simultaneously inhibits passive diffusion of entrapped cytokines and permits active motility of entrapped cells to enable long-term retention, viability, and activation of CAR-T cells. The generation of a transient inflammatory niche following administration affords sustained exposure of CAR-T cells, induces a tumor-reactive CAR-T phenotype, and improves efficacy of treatment.

Hydrogel-Based Slow Release of a Receptor-Binding Domain Subunit Vaccine Elicits Neutralizing Antibody Responses Against SARS-CoV-2.

The development of effective vaccines that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID-19. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is efficient to manufacture, highly stable, and a target for neutralizing antibodies. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, clinically-relevant adjuvants Alum, AddaVax, and CpG/Alum are found unable to elicit neutralizing responses following a prime-boost immunization. Here, it has been shown that sustained delivery of an RBD subunit vaccine comprising CpG/Alum adjuvant in an injectable polymer-nanoparticle (PNP) hydrogel elicited potent anti-RBD and anti-spike antibody titers, providing broader protection against SARS-CoV-2 variants of concern compared to bolus administration of the same vaccine and vaccines comprising other clinically-relevant adjuvant systems. Notably, a SARS-CoV-2 spike-pseudotyped lentivirus neutralization assay revealed that hydrogel-based vaccines elicited potent neutralizing responses when bolus vaccines did not. Together, these results suggest that slow delivery of RBD subunit vaccines with PNP hydrogels can significantly enhance the immunogenicity of RBD and induce neutralizing humoral immunity.

Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats.

Dual-hormone replacement therapy with insulin and amylin in patients with type 1 diabetes has the potential to improve glucose management. Unfortunately, currently available formulations require burdensome separate injections at mealtimes and have disparate pharmacokinetics that do not mimic endogenous co-secretion. Here, amphiphilic acrylamide copolymers are used to create a stable co-formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra-rapid action. The co-formulation is stable for over 16 h under stressed aging conditions, whereas commercial insulin lispro (Humalog) aggregates in 8 h. The faster pharmacokinetics of monomeric insulin in this co-formulation result in increased insulin-pramlintide overlap of 75 ± 6% compared to only 47 ± 7% for separate injections. The co-formulation results in similar delay in gastric emptying compared to pramlintide delivered separately. In a glucose challenge, in rats, the co-formulation reduces deviation from baseline glucose compared to insulin only, or separate insulin and pramlintide administrations. Further, comparison of interspecies pharmacokinetics of monomeric pramlintide suggests that pharmacokinetics observed for the co-formulation will be well preserved in future translation to humans. Together these results suggest that the co-formulation has the potential to improve mealtime glucose management and reduce patient burden in the treatment of diabetes.

Affinity-Directed Dynamics of Host-Guest Motifs for Pharmacokinetic Modulation via Supramolecular PEGylation.

Proteins are an impactful class of therapeutics but can exhibit suboptimal therapeutic performance, arising from poor control over the timescale of clearance. Covalent PEGylation is one established strategy to extend circulation time but often at the cost of reduced activity and increased immunogenicity. Supramolecular PEGylation may afford similar benefits without necessitating that the protein be permanently modified with a polymer. Here, we show that insulin pharmacokinetics can be modulated by tuning the affinity-directed dynamics of a host-guest motif used to non-covalently endow insulin with a poly(ethylene glycol) (PEG) chain. When administered subcutaneously, supramolecular PEGylation with higher binding affinities extends the time of total insulin exposure systemically. Pharmacokinetic modeling reveals that the extension in the duration of exposure arises specifically from decreased absorption from the subcutaneous depot governed directly by the affinity and dynamics of host-guest exchange. The lifetime of the supramolecular interaction thus dictates the rate of absorption, with negligible impact attributed to association of the PEG upon rapid dilution of the supramolecular complex in circulation. This modular approach to supramolecular PEGylation offers a powerful tool to tune protein pharmacokinetics in response to the needs of different disease applications.

Hydrogel-based slow release of a receptor-binding domain subunit vaccine elicits neutralizing antibody responses against SARS-CoV-2.

The development of effective vaccines that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID-19. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is efficient to manufacture, highly stable, and a target for neutralizing antibodies. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, we found that clinically-relevant adjuvants Alum, AddaVax, and CpG/Alum were unable to elicit neutralizing responses following a prime-boost immunization. Here we show that sustained delivery of an RBD subunit vaccine comprising CpG/Alum adjuvant in an injectable polymer-nanoparticle (PNP) hydrogel elicited potent anti-RBD and anti-spike antibody titers, providing broader protection against SARS-CoV-2 variants of concern compared to bolus administration of the same vaccine and vaccines comprising other clinically-relevant adjuvant systems. Notably, a SARS-CoV-2 spike-pseudotyped lentivirus neutralization assay revealed that hydrogel-based vaccines elicited potent neutralizing responses when bolus vaccines did not. Together, these results suggest that slow delivery of RBD subunit vaccines with PNP hydrogels can significantly enhance the immunogenicity of RBD and induce neutralizing humoral immunity.

Multi-State Dynamic Coordination Complexes Interconverted through Counterion-Controlled Phase Transfer.

We studied a series of dynamic weak-link approach (WLA) complexes that can be shuttled between two immiscible solvents and switched between two structural states via ion exchange. Here, we established that hydrophobic anions transfer cationic, amphiphilic complexes from the aqueous phase to the organic phase, while a chloride source reverses the process. As a result of the dynamic metal coordination properties of WLA complexes, the denticity of these complexes (mono- to bi-) can be modulated as they partition into different phases. In addition, we discovered that heteroligated complexes bearing ligands of different donor strengths preferentially rearrange into two homoligated complexes that are phase-partitioned to maximize the number of stronger coordination bonds. This behavior is not observed in systems with one solvent, highlighting the dynamic and stimuli-responsive nature of hemilabile ligands in a multiphasic solvent environment. Taken together, this work shows that the highly reconfigurable WLA modality can enable the design of biphasic reaction networks or chemical separations driven by straightforward salt metathesis reactions.

Engineering biopharmaceutical formulations to improve diabetes management.

Insulin was first isolated almost a century ago, yet commercial formulations of insulin and its analogs for hormone replacement therapy still fall short of appropriately mimicking endogenous glycemic control. Moreover, the controlled delivery of complementary hormones (such as amylin or glucagon) is complicated by instability of the pharmacologic agents and complexity of maintaining multiple infusions. In this review, we highlight the advantages and limitations of recent advances in drug formulation that improve protein stability and pharmacokinetics, prolong drug delivery, or enable alternative dosage forms for the management of diabetes. With controlled delivery, these formulations could improve closed-loop glycemic control.

COVID-19 with and without pneumonia: clinical outcomes in the internal medicine ward / COVID-19 con y sin neumonía: resultados en la sala de medicina interna

Abstract The clinical features of COVID-19 differ substantially upon the presence (or absence) of viral pneumonia. The aim of this article was to describe the clinical characteristics of COVID-19 patients admitted to the Internal Medicine ward, as divided into those with and without pneumonia. This single-center prospective cohort study was conducted in a tertiary teaching public hospital in Buenos Aires City named Hospital General de Agudos Carlos G. Durand. Baseline data collection was performed within 48 hours of admission and patients were followed until discharge or in-hospital death. Epidemiological, clinical, laboratory, and radiological characteristics together with treatment data were obtained from the medical records. Of the 417 included, 243 (58.3%) had pneumonia. Median age was 43 years (IQR:32-57) and 222 (53.2%) were female. The overall crude case-fatality rate was 3.8%. None of the COVID-19 patients without pneumonia developed critical disease, required invasive mechanical ventilation nor died during hospitalization. However, 7 (4%) developed severe disease during follow-up. Among patients with COVID-19 pneumonia, in-hospital mortality rate was 6.6%, severe disease developed in 81 (33.3%), critical disease in 23 (9.5%), and 22 (9.1%) were admitted to the intensive care unit. A largely good prognosis was observed among COVID-19 patients without pneumonia, still, even among this group, unfavorable clinical progression can develop and should be properly monitored. Critical illness among patients with COVID-19 pneumonia was frequent and observed rates from this cohort provide a sound characterization of COVID-19 clinical features in a major city from South America.

Resumen Las características clínicas del COVID-19 difieren sustancialmente según la presencia (o ausencia) de neumonía viral. El objetivo de este artículo fue describir las características clínicas de los pacientes con COVID-19 internados en el servicio de Clínica Médica, divididos en pacientes con y sin neumonía. Fue un estudio de cohorte prospectivo, con base en un único centro, realizado en un hospital público de la ciudad de Buenos Aires: Hospital General de Agudos Carlos G. Durand. La recolección basal de datos se realizó dentro de las 48 horas del ingreso y los pacientes fueron seguidos hasta el alta o la muerte hospitalaria. Las características epidemiológicas, clínicas, de laboratorio y radiológicas junto con los datos del tratamiento se obtuvieron de la historia clínica. De los 417 incluidos, 243 (58.3%) tenían neumonía. La mediana de edad fue de 43 años (RIC: 32-57) y 222 (53.2%) eran mujeres. La tasa global de letalidad fue del 3.8%. Ninguno de los pacientes con COVID-19 sin neumonía desarrolló enfermedad crítica, requirió ventilación mecánica invasiva ni falleció durante la hospitalización. Sin embargo, 7 (4%) desarrollaron enfermedad grave durante el seguimiento. Entre aquellos con neumonía COVID-19, la tasa de mortalidad hospitalaria fue del 6.6%, se desarrolló enfermedad grave en 81 (33.3%), enfermedad crítica en 23 (9.5%) y 22 (9.1%) fueron trasladados a la unidad de cuidados intensivos. Los pacientes con COVID-19 sin neumonía presentaron buen pronóstico; sin embargo, incluso en este grupo, se observaron algunos con progresión clínica desfavorable, por lo que se requirió seguimiento adecuado. En los pacientes con neumonía por COVID-19, el desarrollo de enfermedad crítica fue frecuente y las tasas observadas en esta cohorte proporcionan una caracterización sólida de las características clínicas de los pacientes con COVID-19 en una importante ciudad de América del Sur.

Estudio de cohorte prospectivo de pacientes con COVID-19 hospitalizados en servicio de clínica médica del Hospital Durand Protocolo de estudio / Prospective cohort study of patients with COVID-19 hospitalized in the Internal Medicine ward of Hospital Durand: study protocol

INTRODUCCIÓN: Conocer los predictores de mala evolución en pacientes con Enfermedad por Coronavirus 2019 (COVID-19) permite identificar de forma temprana a los pacientes con peor pronóstico, aportando mejores herramientas a la hora de tomar decisiones clínicas. Se presenta el protocolo de un estudio de cohorte cuyo objetivo principal es identificar factores de riesgo de infección severa, critica y mortalidad en pacientes con COVID-19 internados en el Servicio de Clínica Médica del Hospital Durand (Buenos Aires, Argentina). MÉTODOS: Estudio de cohorte prospectivo con base en un único centro. Se incluirá a todos los pacientes que ingresen al servicio de Clínica Médica con diagnóstico de COVID-19 durante el periodo de estudio. Se recolectarán las características epidemiológicas, clínicas, de laboratorio, radiológicas y los datos de tratamiento, al ingreso y al momento del alta o muerte hospitalaria. El evento final primario es la muerte en la internación; los eventos secundarios son el desarrollo de enfermedad grave y enfermedad crítica, la internación en unidad cerrada y el requerimiento de asistencia respiratoria mecánica.

COVID-19 with and without pneumonia: clinical outcomes in the internal medicine ward.

The clinical features of COVID-19 differ substantially upon the presence (or absence) of viral pneumonia. The aim of this article was to describe the clinical characteristics of COVID-19 patients admitted to the Internal Medicine ward, as divided into those with and without pneumonia. This single-center prospective cohort study was conducted in a tertiary teaching public hospital in Buenos Aires City named Hospital General de Agudos Carlos G. Durand. Baseline data collection was performed within 48 hours of admission and patients were followed until discharge or in-hospital death. Epidemiological, clinical, laboratory, and radiological characteristics together with treatment data were obtained from the medical records. Of the 417 included, 243 (58.3%) had pneumonia. Median age was 43 years (IQR:32-57) and 222 (53.2%) were female. The overall crude case-fatality rate was 3.8%. None of the COVID-19 patients without pneumonia developed critical disease, required invasive mechanical ventilation nor died during hospitalization. However, 7 (4%) developed severe disease during follow-up. Among patients with COVID-19 pneumonia, in-hospital mortality rate was 6.6%, severe disease developed in 81 (33.3%), critical disease in 23 (9.5%), and 22 (9.1%) were admitted to the intensive care unit. A largely good prognosis was observed among COVID-19 patients without pneumonia, still, even among this group, unfavorable clinical progression can develop and should be properly monitored. Critical illness among patients with COVID-19 pneumonia was frequent and observed rates from this cohort provide a sound characterization of COVID-19 clinical features in a major city from South America.

Las características clínicas del COVID-19 difieren sustancialmente según la presencia (o ausencia) de neumonía viral. El objetivo de este artículo fue describir las características clínicas de los pacientes con COVID-19 internados en el servicio de Clínica Médica, divididos en pacientes con y sin neumonía. Fue un estudio de cohorte prospectivo, con base en un único centro, realizado en un hospital público de la ciudad de Buenos Aires: Hospital General de Agudos Carlos G. Durand. La recolección basal de datos se realizó dentro de las 48 horas del ingreso y los pacientes fueron seguidos hasta el alta o la muerte hospitalaria. Las características epidemiológicas, clínicas, de laboratorio y radiológicas junto con los datos del tratamiento se obtuvieron de la historia clínica. De los 417 incluidos, 243 (58.3%) tenían neumonía. La mediana de edad fue de 43 años (RIC: 32-57) y 222 (53.2%) eran mujeres. La tasa global de letalidad fue del 3.8%. Ninguno de los pacientes con COVID-19 sin neumonía desarrolló enfermedad crítica, requirió ventilación mecánica invasiva ni falleció durante la hospitalización. Sin embargo, 7 (4%) desarrollaron enfermedad grave durante el seguimiento. Entre aquellos con neumonía COVID-19, la tasa de mortalidad hospitalaria fue del 6.6%, se desarrolló enfermedad grave en 81 (33.3%), enfermedad crítica en 23 (9.5%) y 22 (9.1%) fueron trasladados a la unidad de cuidados intensivos. Los pacientes con COVID-19 sin neumonía presentaron buen pronóstico; sin embargo, incluso en este grupo, se observaron algunos con progresión clínica desfavorable, por lo que se requirió seguimiento adecuado. En los pacientes con neumonía por COVID-19, el desarrollo de enfermedad crítica fue frecuente y las tasas observadas en esta cohorte proporcionan una caracterización sólida de las características clínicas de los pacientes con COVID-19 en una importante ciudad de América del Sur.

A Redox-Switchable, Allosteric Coordination Complex.

A redox-regulated molecular tweezer complex was synthesized via the weak-link approach. The PtII complex features a redox-switchable hemilabile ligand (RHL) functionalized with a ferrocenyl moiety, whose oxidation state modulates the opening of a specific coordination site. Allosteric regulation by redox agents gives reversible access to two distinct structural states-a fully closed state and a semi-open state-whose interconversion was studied via multinuclear NMR spectroscopy, cyclic voltammetry, and UV-vis-NIR spectroscopy. Two structures in this four-state system were further characterized via SCXRD, while the others were modeled through DFT calculations. This fully reversible, RHL-based system defines an unusual level of electrochemical control over the occupancy of a specific coordination site, thereby providing access to four distinct coordination states within a single system, each defined and differentiated by structure and oxidation state.

Metal-Organic Framework Nanoparticles.

Due to their well-defined 3D architectures, permanent porosity, and diverse chemical functionalities, metal-organic framework nanoparticles (MOF NPs) are an emerging class of modular nanomaterials. Herein, recent developments in the synthesis and postsynthetic surface functionalization of MOF NPs that strengthen the fundamental understanding of how such structures form and grow are highlighted; the internal structure and external surface properties of these novel nanomaterials are highlighted as well. These fundamental advances have resulted in MOF NPs being used as components in chemical sensors, biological probes, and membrane separation materials, as well as building blocks for colloidal crystal engineering.

An Allosterically Regulated, Four-State Macrocycle.

Macrocycles capable of host-guest chemistry are an important class of structures that have attracted considerable attention because of their utility in chemical separations, analyte sensing, signal amplification, and drug delivery. The deliberate design and synthesis of such structures are rate-limiting steps in utilizing them for such applications, and coordination-driven supramolecular chemistry has emerged as a promising tool for rapidly making large classes of such systems with attractive molecular recognition capabilities and, in certain cases, catalytic properties. A particularly promising subset of such systems are stimuli-responsive constructs made from hemilabile ligands via the weak-link approach (WLA) to supramolecular coordination chemistry. Such structures can be reversibly toggled between different shapes, sizes, and charges based upon small-molecule and elemental-anion chemical effectors. In doing so, one can deliberately change their recognition properties and both stoichiometric and catalytic chemistries, thereby providing mimics of allosteric enzymes. The vast majority of structures made to date involve two-state systems, with a select few being able to access three different states. Herein, we describe the synthesis of a new allosterically regulated four-state macrocycle assembled via the WLA. The target structure was made via the stepwise assembly of ditopic bidentate hemilabile N-heterocyclic carbene thioether (NHC,S) and phosphino thioether (P,S) ligands at PtII metal nodes. The relatively simple macrocycle displays complex dynamic behavior when addressed with small-molecule effectors, and structural switching can be achieved with several distinct molecular cues. Importantly, each state was fully characterized by multinuclear NMR spectroscopy and, in some cases, single-crystal X-ray diffraction studies and density functional theory computational models. This new structure opens the door to complex multicue switching reminiscent of multistate chemoswitches that could be important in controlling stoichiometric and catalytic transformations as well as generating molecular logic systems.