Synthesis of Antiprotozoal 2-(4-Alkyloxyphenyl)-Imidazolines and Imidazoles and Their Evaluation on Leishmania mexicana and Trypanosoma cruzi.

Twenty 2-(4-alkyloxyphenyl)-imidazolines and 2-(4-alkyloxyphenyl)-imidazoles were synthesized, with the former being synthesized in two steps by using MW and ultrasonication energy, resulting in good to excellent yields. Imidazoles were obtained in moderate yields by oxidizing imidazolines with MnO2 and MW energy. In response to the urgent need to treat neglected tropical diseases, a set of 2-(4-alkyloxyphenyl)- imidazolines and imidazoles was tested in vitro on Leishmania mexicana and Trypanosoma cruzi. The leishmanicidal activity of ten compounds was evaluated, showing an IC50 < 10 µg/mL. Among these compounds, 27-31 were the most active, with IC50 values < 1 µg/mL (similar to the reference drugs). In the evaluation on epimastigotes of T. cruzi, only 30 and 36 reached an IC50 < 1 µg/mL, showing better inhibition than both reference drugs. However, compounds 29, 33, and 35 also demonstrated attractive trypanocidal activities, with IC50 values < 10 µg/mL, similar to the values for benznidazole and nifurtimox.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

BACKGROUND: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018 - 2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n= 10), mucormycosis (n= 8), histoplasmosis (n= 2), cryptococcosis (n= 2), and others (n= 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSIONS: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Characterization of Polylactic Acid Biocomposites Filled with Native Starch Granules from Dioscorea remotiflora Tubers.

Biocomposites were fabricated utilizing polylactic acid (PLA) combined with native starch sourced from mountain's yam (Dioscorea remotiflora Knuth), an underexplored tuber variety. Different starch compositions (7.5, 15.0, 22.5, and 30.0 wt.%) were blended with PLA in a batch mixer at 160 °C to produce PLA/starch biocomposites. The biocomposites were characterized by analyzing their morphology, particle size distribution, thermal, X-ray diffraction (XDR), mechanical, and dynamic mechanical (DMA) properties, water absorption behavior, and color. The results showed that the amylose content of Dioscorea remotiflora starch was 48.43 ± 1.4%, which corresponds to a high-amylose starch (>30% of amylose). Particle size analysis showed large z-average particle diameters (Dz0) of the starch granules (30.59 ± 3.44 µm). Scanning electron microscopy (SEM) images showed oval-shaped granules evenly distributed throughout the structure of the biocomposite, without observable agglomeration or damage to its structure. XDR and DMA analyses revealed an increase in the crystallinity of the biocomposites as the proportion of the starch increased. The tensile modulus (E) underwent a reduction, whereas the flexural modulus (Eflex) increased with the amount of starch incorporated. The biocomposites with the highest Eflex were those with a starch content of 22.5 wt.%, which increased by 8.7% compared to the neat PLA. The water absorption of the biocomposites demonstrated a higher uptake capacity as the starch content increased. The rate of water absorption in the biocomposites followed the principles of Fick's Law. The novelty of this work lies in its offering an alternative for the use of high-amylose mountain's yam starch to produce low-cost bioplastics for different applications.

Effect of surface modification of graphene oxide with a reactive silane coupling agent on the mechanical properties and biocompatibility of acrylic bone cements.

Carbon allotrope materials (i.e. carbon nanotubes (CNTs), graphene, graphene oxide (GO)), have been used to reinforce acrylic bone cement. Nevertheless, the intrinsic incompatibility among the above materials produces a deficient interphase. Thus, in this work, the effect of the content of functionalized graphene oxide with a reactive silane on the mechanical properties and cell adhesion of acrylic bone cement was studied. GO was obtained by an oxidative process on natural graphite; subsequently, GO was functionalized with 3-methacryloxypropyltrimethoxysilane (MPS) to enhance the interphase between the graphenic material and acrylic polymeric matrix. Pristine GO and functionalized graphene oxide (GO-MPS) were characterized physicochemically (XPS, XRD, FTIR, and Raman) and morphologically (SEM and TEM). Silanized GO was added into the acrylic bone cement at different concentrations; the resulting materials were characterized mechanically, and their biocompatibility was also evaluated. The physicochemical characterization results showed that graphite was successfully oxidized, and the obtained GO was successfully functionalized with the silane coupling agent (MPS). SEM and TEM images showed that the GO is composed of few stacked layers. Compression testing results indicated a tendency of increasing stiffness and toughness of the acrylic bone cements at low concentration of functionalized GO. Additionally, the bending testing results showed a slightly increase in bone cement strain with the incorporation of GO-MPS. Finally, all samples exhibited cell viability higher than 70%, which means that materials are considered non-cytotoxic, according to the ISO 10993-5 standard.

Oxidation mechanism of pyrite in a thiosulfate solution: electrochemical impedance (EIS) and in situ Raman spectroscopy.

Ammoniacal thiosulfate has been used lately as an alternative lixiviant for leaching gold from sulfides ores which are not amenable for cyanidation. However, the oxidation of the sulfide minerals generates products that inhibit the dissolution of gold and can promote the degradation of the leaching solution. The complexity of the ammoniacal thiosulfate leaching system has prevented the unification and clarification of the mechanisms of oxidation of sulfide ores used for gold extraction. In this study, a method combining polarization curves, Electrochemical impedance spectroscopy (EIS), and in situ Raman spectroscopy was implemented to investigate the oxidation process of high-purity pyrite. Pyrite samples were dispersed in carbon paste electrode (CPE-Py). The polarization curves of CPE-Py exhibited an increase in current values for overpotentials greater than 0.1 V, indicating the initiation of mineral oxidation processes. Subsequently, a maximum current was observed initially, followed by subsequent decrease, indicating the occurrence of passivation processes on the electrode surface. Hydrodynamic polarization curves demonstrated that the overpotential at which the passivation process occurs is independent of mass transport, suggesting that the passivation products were formed through solid-state transformation. Impedance spectra revealed that at overpotentials below 0.1 V, a partially resolved capacitive semicircle was observed, which was associated with the resistance encountered when charge was transferred between the solution and the surface layer interface. This resistance decreased as the polarization overpotential increased, implying a decrease in charge transfer kinetics. At higher overpotentials (0.3 V-0.4 V), a second capacitive semicircle appeared, linked to the oxidation of one or several species present in the mineral. In situ Raman spectroscopy was utilized to identify the oxidation species of pyrite in ammonia-thiosulfate ((NH4)2S2O3) leaching solution at a pH = 10.2. The composition of the species varied depending on the applied anodic potential. At low anodic potentials (0.1 V), Fe(OH)2 and thiosulfate (S2O32-) were formed, while at high anodic potentials (0.4 V), iron products such as Fe3O4 and γ-FeOOH, as well as sulfide species including thiosulfate, tetrathionates and sulfates (S2O32-, S4O6-2 and SO42-) were formed.

Ignored and distressed: a cross-sectional study of the impact of COVID-19 on last responders.

BACKGROUND: Last responders constitute an occupational category that includes all those that are involved in the postmortem care of deceased persons and their families. Last responders are exposed to several categories of work-related stressors that affect their health and well-being. COVID-19 exacerbated these stressors. Research to understand the consequences of COVID-19 on the health and wellbeing of last responders is nascent. This study aimed to assess COVID-19 related stress, coping and wellbeing among last responders in the United States. METHODS: We conducted a national cross-sectional survey of last responders in July through September of 2020. The survey measured wellbeing, stress, coping, and stigma; COVID-19 experiences, and socio-demographics. A ridge regression model was fit for the outcome variables. RESULTS: Analysis was conducted on 366 respondents from 43 states. Respondents were male (55.4%), age 50 + (57.4%), and White non-Hispanic (90.3%); 54% reported moderate-high stress and 41% endorsed mild-severe anxiety. Seventy-seven percent had experienced at least one form of stigma related to their occupation. Variables associated with higher perceived stress and anxiety included gender (female), shorter length of employment, perceiving a higher impact from COVID-19 on everyday life, and increased perceived stigma. CONCLUSIONS: Last responders are a critical part of the health care system. Throughout this pandemic, last responders have been frequently ignored and not prioritized for protection and support. Interventions to support last responders cope with stress, and to decrease anxiety are urgently needed. There is also a critical need to challenge community stigma towards last responders.

Use of Digital Images as a Low-Cost System to Estimate Surface Optical Parameters in the Ocean.

Ocean color is the result of absorption and scattering, as light interacts with the water and the optically active constituents. The measurement of ocean color changes enables monitoring of these constituents (dissolved or particulate materials). The main objective of this research is to use digital images to estimate the light attenuation coefficient (Kd), the Secchi disk depth (ZSD), and the chlorophyll a (Chla) concentration and to optically classify plots of seawater using the criteria proposed by Jerlov and Forel using digital images captured at the ocean surface. The database used in this study was obtained from seven oceanographic cruises performed in oceanic and coastal areas. Three approaches were developed for each parameter: a general approach that can be applied under any optical condition, one for oceanic conditions, and another for coastal conditions. The results of the coastal approach showed higher correlations between the modeled and validation data, with rp values of 0.80 for Kd, 0.90 for ZSD, 0.85 for Chla, 0.73 for Jerlov, and 0.95 for Forel-Ule. The oceanic approach failed to detect significant changes in a digital photograph. The most precise results were obtained when images were captured at 45° (n = 22; Fr cal=11.02>Fr crit=5.99). Therefore, to ensure precise results, the angle of photography is key. This methodology can be used in citizen science programs to estimate ZSD, Kd, and the Jerlov scale.

Chitosan Nanoparticles as Oral Drug Carriers.

The use of nanoparticles as drug delivery systems has increased in importance in the last decades. Despite the disadvantages of difficulty swallowing, gastric irritation, low solubility, and poor bioavailability, oral administration stands out as the most widely used route for therapeutic treatments, though it may not always be the most effective route. The effect of the first hepatic pass is one of the primary challenges that drugs must overcome to carry out their therapeutic effect. For these reasons, controlled-release systems based on nanoparticles synthesized from biodegradable natural polymers have been reported to be very efficient in enhancing oral delivery in multiple studies. Chitosan has been shown to have an extensive variability of properties and roles in the pharmaceutical and health fields; of its most important properties are the ability to encapsulate and transport drugs within the body and enhance the drug interaction with the target cells, which improves the efficacy of the encapsulated drugs. The physicochemical properties of chitosan give it the ability to form nanoparticles through multiple mechanisms, which will be addressed in this article. The present review article focuses on highlighting the applications of chitosan nanoparticles for oral drug delivery.

Exchange bias coupling and bipolar resistive switching at room temperature on GaSb/Mn multilayers for resistive memories applications.

This work present structural, morphological, magnetic, and electrical properties of GaSb/Mn multilayer deposited via DC magnetron sputtering at room temperature and at 423 K. The samples are characterized by forming layers of 3, 6 and 12 periods of the GaSb/Mn structure. Through XRD patterns, it was possible to stablish the formation of GaSb, Mn3Ga, and Mn2Sb2 phases. FTIR measurements present an optical interference associated with periodicity and the homogenous thickness of the layers. HR-SEM shows the multilayer architecture with columnar microstructure in the formation of layers with grain nucleation on the surface. A ferromagnetic-like behavior was observed in the multilayers at room temperature related to the domains and interlayers interaction. Additionally, the hysteresis curves present shifts attributed to the effect of exchange bias coupling. I-V curves show RESET-SET states of the multilayer system with bipolar resistive behavior, which can be modified by external magnetic fields. The resistive switching evidenced corresponds to the conductive mechanism based on the capacitive conductance and the formation of conductive filaments in multilayer structure.

Influence of Molecular Weight and Grafting Density of PEG on the Surface Properties of Polyurethanes and Their Effect on the Viability and Morphology of Fibroblasts and Osteoblasts.

Grafting polyethylene glycol (PEG) onto a polymer's surface is widely used to improve biocompatibility by reducing protein and cell adhesion. Although PEG is considered to be bioinert, its incorporation onto biomaterials has shown to improve cell viability depending on the amount and molecular weight (MW) used. This phenomenon was studied here by grafting PEG of three MW onto polyurethane (PU) substrata at three molar concentrations to assess their effect on PU surface properties and on the viability of osteoblasts and fibroblasts. PEG formed a covering on the substrata which increased the hydrophilicity and surface energy of PUs. Among the results, it was observed that osteoblast viability increased for all MW and grafting densities of PEG employed compared with unmodified PU. However, fibroblast viability only increased at certain combinations of MW and grafting densities of PEG, suggesting an optimal level of these parameters. PEG grafting also promoted a more spread cell morphology than that exhibited by unmodified PU; nevertheless, cells became apoptotic-like as PEG MW and grafting density were increased. These effects on cells could be due to PEG affecting culture medium pH, which became more alkaline at higher MW and concentrations of PEG. Results support the hypothesis that surface energy of PU substrates can be tuned by controlling the MW and grafting density of PEG, but these parameters should be optimized to promote cell viability without inducing apoptotic-like behavior.

[Implementation of a protocol for neuropsychiatric disease surveillance in a general hospital]. / Implementación de un sistema protocolizado de pesquisa temprana de patología psiquiátrica en un hospital general. Protocolo de Vigilancia Neuropsiquiátrica (VNP): avanzando hacia un modelo de psiquiatría de enlace proactivo.

BACKGROUND: The COVID-19 pandemic increased the incidence of neuropsychiatric diseases. Proactive models of consultation-liaison psychiatry (CLP-p) could play a key role in the prevention and management of these diseases in a general hospital. AIM: To develop a protocol for implementing screening tools for neuropsychiatric symptoms in routine clinical practice. MATERIAL AND METHODS: Elements of the Plan-Do-Study-Act (PDSA) model were used to modify the Neuropsychiatric Surveillance protocol implemented at a clinical hospital during the COVID-19 pandemic by members of the hospital's CLP team. RESULTS: A flowchart for active follow-up of neuropsychiatric symptoms during hospitalization is presented, with sequential management and referral flows, accompanied by suggestions for pre-discharge evaluation to define continuity of care actions. The COSMOS tool is also presented, designed for the detection of risk factors and actions for the prevention of neuropsychiatric diseases in general hospitals. CONCLUSIONS: The neuropsychiatric surveillance protocol facilitates early and timely interventions and establishes criteria for the continuity of post-discharge care. These changes could improve the quality of care in general hospitals and reduce the gap between mental and physical health.

[Delirium, catatonia and substance withdrawal syndrome manifested as psychomotor agitation in COVID-19: a pharmacological management approach for the general hospital setting]. / Delirium, catatonía y síndrome de abstinencia manifestados como agitación psicomotora en COVID-19: una propuesta de manejo farmacológico en el hospital general.

BACKGROUND: Neuropsychiatric symptoms can be part of the clinical spectrum of COVID-19 infections. AIM: To devise an evidence based clinical algorithm as a guide for clinicians, to identify and treat underlying clinical syndromes of psychomotor agitation, such as delirium, catatonia or substance withdrawal in patients who are hospitalized and infected with SARS-CoV-2. MATERIAL AND METHODS: A review of the literature about the pharmacological management of neuropsychiatric manifestations of COVID-19 at the general hospital, to develop a clinical protocol based on a consensus from an interdisciplinary expert panel at a Clinical Hospital. RESULTS: A consensual clinical algorithm for the management of delirium, catatonia, and substance withdrawal, manifested as psychomotor agitation in patients hospitalized with COVID-19, was developed as a clinical proposal for physicians at different levels of complexity in health services. CONCLUSIONS: Cooperation among different clinical units in the general hospital facilitated the implementation of a clinical algorithm for clinicians for the management of psychomotor agitation in COVID-19 patients.

Perihematomal Edema and Clinical Outcome After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

BACKGROUND: Perihematomal edema (PHE) has been proposed as a radiological marker of secondary injury and therapeutic target in intracerebral hemorrhage (ICH). We conducted a systematic review and meta-analysis to assess the prognostic impact of PHE on functional outcome and mortality in patients with ICH. METHODS: We searched major databases through December 2020 using predefined keywords. Any study using logistic regression to examine the association between PHE or its growth and functional outcome was included. We examined the overall pooled effect and conducted secondary analyses to explore the impact of individual PHE measures on various outcomes separately. Study quality was assessed by three independent raters using the Newcastle-Ottawa Scale. Odds ratios (per 1-unit increase in PHE) and their confidence intervals (CIs) were log transformed and entered into a DerSimonian-Laird random-effects meta-analysis to obtain pooled estimates of the effect. RESULTS: Twenty studies (n = 6633 patients) were included in the analysis. The pooled effect size for overall outcome was 1.05 (95% CI 1.02-1.08; p < 0.00). For the following secondary analyses, the effect size was weak: mortality (1.01; 95% CI 0.90-1.14), functional outcome (1.04; 95% CI 1.02-1.07), both 90-day (1.06; 95% CI 1.02-1.11), and in-hospital assessments (1.04; 95% CI 1.00-1.08). The effect sizes for PHE volume and PHE growth were 1.04 (95% CI 1.01-1.07) and 1.14 (95% CI 1.04-1.25), respectively. Heterogeneity across studies was substantial except for PHE growth. CONCLUSIONS: This meta-analysis demonstrates that PHE volume within the first 72 h after ictus has a weak effect on functional outcome and mortality after ICH, whereas PHE growth might have a slightly larger impact during this time frame. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.

Microneedles as an Alternative Strategy for Drug Delivery.

The transdermal route has been widely studied in the last decade due to its multiple advantages, where one of the most promising transdermal systems are microneedles, these allow the delivery of drugs in a painless way and with easy application, being very attractive for patients with chronic treatments. This review highlights the new research that develops this approach to transdermal therapies, including examples of materials and methods used for their manufacture and presenting an overview of the clinical trials currently available in Cochrane in a demonstrative way to understand the growing popularity of this strategy.

Physicochemical, Mechanical, and Structural Properties of Bio-Active Films Based on Biological-Chemical Chitosan, a Novel Ramon (Brosimum alicastrum) Starch, and Quercetin.

The properties of biological-chemical chitosan (BCh) films from marine-industrial waste and a non-conventional Ramon starch (RS) (Brosimum alicastrum) were investigated. Blended films of BCh/RS were prepared to a volume ratio of 4:1 and 1:4, named (BChRS-80+q, biological-chemical chitosan 80% v/v and Ramon starch, BChRS-20+q, biological-chemical chitosan 20% v/v and Ramon starch, both with quercetin), Films from commercial chitosan (CCh) and corn starch (CS), alone or blended (CChCS-80+q, commercial chitosan 80% v/v and corn starch, CChCS-20+q commercial chitosan 20% v/v and corn starch, both with quercetin) were also prepared for comparison purposes. Films were investigated for their physicochemical characteristics such as thickness, moisture, swelling, water-vapor permeability, and water solubility. In addition, their mechanical and structural properties were studied using Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA) and Scanning Electron Microscopy (SEM) techniques. Antioxidant activity was evaluated as radical scavenging, and antimicrobial effect was also determined. The BCh and RS films presented similar tensile strength values compared with commercial biopolymers. Only films with chitosan presented antioxidant and antimicrobial activity. The FTIR spectra confirmed the interactions between functional groups of the biopolymers. Although, BChRS-80+q and BChRS-20+q films exhibited poor mechanical performance compared to their commercial counterparts, they showed good thermal stability, and improved antioxidant and antimicrobial activity in the presence of quercetin. BChRS-80+q and BChRS-20+q films have promising applications due to their biological activity and mechanical properties, based on a novel material that has been underutilized (Ramon starch) that does not compete with materials for human feeding and may be used as a coating for food products.

Implementación de un sistema protocolizado de pesquisa temprana de patología psiquiátrica en un hospital general. Protocolo de Vigilancia Neuropsiquiátrica (VNP): avanzando hacia un modelo de psiquiatría de enlace proactivo / Implementation of a protocol for neuropsychiatric disease surveillance in a general hospital

BACKGROUND: The COVID-19 pandemic increased the incidence of neuropsychiatric diseases. Proactive models of consultation-liaison psychiatry (CLP-p) could play a key role in the prevention and management of these diseases in a general hospital. AIM: To develop a protocol for implementing screening tools for neuropsychiatric symptoms in routine clinical practice. MATERIAL AND METHODS: Elements of the Plan-Do-Study-Act (PDSA) model were used to modify the Neuropsychiatric Surveillance protocol implemented at a clinical hospital during the COVID-19 pandemic by members of the hospital's CLP team. RESULTS: A flowchart for active follow-up of neuropsychiatric symptoms during hospitalization is presented, with sequential management and referral flows, accompanied by suggestions for pre-discharge evaluation to define continuity of care actions. The COSMOS tool is also presented, designed for the detection of risk factors and actions for the prevention of neuropsychiatric diseases in general hospitals. CONCLUSIONS: The neuropsychiatric surveillance protocol facilitates early and timely interventions and establishes criteria for the continuity of post-discharge care. These changes could improve the quality of care in general hospitals and reduce the gap between mental and physical health.

Caracterización fisicoquímica y evaluación in vitro de sistemas autoemulsionables de liberación de indometacina

Objetivo: incorporar la indometacina en sistemas autoemulsionables de liberación con la finalidad de aumentar su solubilidad en medio acuoso, la velocidad de disolución y permeación in vitro. Metodología: se llevaron a cabo ensayos de solubilidad al equilibrio para preparar formulaciones con los excipientes, en los cuales la indome-tacina presentó mayor incremento de solubilidad; los sistemas fueron caracterizados por medio del tiempo de autoemulsificación, estabilidad física, tamaño de partícula, potencial zeta, perfiles de disolución y permeación a través de membrana sintética. Resultados: el diseño experimental de los sistemas autoemulsionables de liberación permitió crear formulaciones que aumentaron la solubilidad de la indometacina en un orden de 105 veces con respecto a la solubilidad acuosa. Las formulaciones que resultaron viables presentaron tiempos de autoemulsificación menores que 60 segundos, además, las distribuciones de tamaño de partícula de las dispersiones fueron inferiores a los 300 nm, presentó índices de polidispersión inferiores a 0,3 y valores de potencial zeta menores de -25 mV. Los perfiles de disolución mostraron que las formulaciones cumplen con un valor de factor de similitud mayor que 50, además, la permeabilidad a través de membrana sintética es mayor para las formulaciones autoemulsionables que el producto de referencia. Conclusiones: la formulación de indometacina en sistemas autoemulsionables de liberación incrementa la solubilidad en medio acuoso, aumenta la disolución y liberación. Estos resultados sugieren que la administración oral de indometacina incorporada en sistemas autoe-mulsionables puede acelerar el inicio del efecto farmacológico.

SUMMARY Aim: To load indomethacin into self-emulsifying delivery systems in order to increase, water-solubility, rate dissolution and in vitro permeation. Methodology: Equilibrium solubility tests were carried out to prepare formulations with the excipients, in which indomethacin presented a greater increase in solubility; the systems were characterized by self-emulsification time, physical stability, particle size, zeta potential, dissolution profiles and permeation through synthetic membrane. Results: The experimental design of self-emulsifying delivery systems allowed to create formulations that increase the solubility of indomethacin in an order of 105 times with respect to the aqueous solubility. The feasible formulations presented autoemulsification times less than 60 seconds, in addition, the particle size distributions of the dispersions were less than 300 nm, with polydispersity index smaller than 0.3, and zeta potential values lower than -25 mV. The dissolution profiles showed that the formulations comply with a similarity factor value greater than 50, in addition, the permeability through a synthetic membrane is higher for the self-emulsifying formulations than the reference product. Conclusion: The formulation of indomethacin into self-emulsifying delivery systems enhances the solubility in aqueous medium, increases dissolution and accelerate release. These results suggest that the oral administration of indomethacin incorporated into self-emulsifying delivery systems can accelerate the onset of the pharmacological effect.

Objetivo: incorporar a indometacina em sistemas de liberação autoemulsificantes a fim de aumentar sua solubilidade em meio aquoso, a taxa de dissolução e permeação in vitro. Metodologia: foram realizados testes de solubilidade de equilíbrio para preparar formulações com os excipientes, nas quais a indometacina apresentou maior aumento na solubilidade; os sistemas foram caracterizados quanto ao tempo de autoemulsificação, estabilidade física, tamanho de partícula, potencial zeta, perfis de dissolução e permeação através de membrana sintética. Resultados: o desenho experimental dos sistemas de liberação autoemulsificantes permitiu a criação de formulações que aumentaram a solubilidade da indometacina na ordem de 105 vezes em relação à solubilidade aquosa. As formulações que se mostraram viáveis apresentaram tempos de autoemulsificação inferiores a 60 segundos, além disso, as distribuições granulométricas das dispersões foram inferiores a 300 nm, apresentaram índices de polidispersidade inferiores a 0,3 e valores de potencial zeta inferiores a -25 mV. Os perfis de dissolução mostraram que as formulações atendem a um valor de fator de similaridade maior que 50, além disso, a permeabilidade através da membrana sintética é maior para as formulações autoemulsionantes do que para o produto de referência. Conclusões: a formulação de indometacina em sistemas de liberação autoemulsificantes aumenta a solubilidade em meio aquoso, aumenta a dissolução e a liberação. Esses resultados sugerem que a administração oral de indometacina incorporada em sistemas autoemulsificantes pode acelerar o início do efeito farmacológico.

Delirium, catatonía y síndrome de abstinencia manifestados como agitación psicomotora en COVID-19: una propuesta de manejo farmacológico en el hospital general

Background: Neuropsychiatric symptoms can be part of the clinical spectrum of COVID-19 infections. Aim: To devise an evidence based clinical algorithm as a guide for clinicians, to identify and treat underlying clinical syndromes of psychomotor agitation, such as delirium, catatonia or substance withdrawal in patients who are hospitalized and infected with SARS-CoV-2. Material and Methods: A review of the literature about the pharmacological management of neuropsychiatric manifestations of COVID-19 at the general hospital, to develop a clinical protocol based on a consensus from an interdisciplinary expert panel at a Clinical Hospital. Results: A consensual clinical algorithm for the management of delirium, catatonia, and substance withdrawal, manifested as psychomotor agitation in patients hospitalized with COVID-19, was developed as a clinical proposal for physicians at different levels of complexity in health services. Conclusions: Cooperation among different clinical units in the general hospital facilitated the implementation of a clinical algorithm for clinicians for the management of psychomotor agitation in COVID-19 patients.

Anaplastic thyroid carcinoma with unusual long-term survival: a case report.

BACKGROUND: Anaplastic thyroid carcinoma is a rare, rapidly progressive, and highly aggressive tumor. It has a global annual incidence of 1-2 per million people. It mostly affects older adults and women. The median survival duration after diagnosis does not exceed 6-8 months. CASE PRESENTATION: A 60-year-old female patient of mixed race (Honduran) presented to the local medical service with dysphonia that had started approximately 2 months earlier, accompanied by orthopnea that had started 1 month earlier. On physical examination, a soft mass was palpated within the anterior neck region; it was approximately 4 cm in diameter, painless, and mobile on swallowing, and had irregular margins. Ultrasound and computed tomography of the neck were performed. Subsequently, fine needle aspiration biopsy was performed. The histological diagnosis was anaplastic thyroid carcinoma (stage IVB). She underwent total thyroidectomy and chemotherapy. She is currently in her fifth year of remission after diagnosis and remains under oncologic surveillance. DISCUSSION: Anaplastic thyroid carcinoma demonstrates a lethal behavior. Approximately 18% survive for more than a year after diagnosis, and 0-10% survive for 5 years. Different pretherapeutic prognostic factors may affect survival, including age < 70 years, the absence of distant metastases, and complete local resection. CONCLUSION: Conventional treatment improves the quality of life of the patient, but the results are not encouraging for the medium and long term. Only a few patients manage to exceed the average life expectancy of 3-6 months, despite undergoing the currently available therapeutic regimen.

Antiviral capacity of polypropylene/(1-Hexadecyl) trimethyl-ammonium bromide composites against COVID-19.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, scientists from different areas are looking for alternatives to fight it. SARS-CoV-2, the cause of the infectious respiratory disease COVID-19, is mainly transmitted through direct or indirect contact with infected respiratory droplets. The integrity of the virus structure is crucial for its viability to attack human cells. Quaternary ammonium salts are characterized by having antiviral capabilities which alter or destroy the structure of the viral capsid. In this work, polypropylene (PP)/(1-Hexadecyl) trimethyl-ammonium bromide (CTAB) composites have been prepared in order to create an antiviral material. The composites were melt processed and blown to produce thin films. The CTAB content on the antiviral effect was evaluated using antibodies and serum from infected patients with the SARS-CoV-2 virus. In addition, the mechanical and thermal properties of blown films were investigated, and CTAB release kinetics from the films was followed by UV-Vis. The results indicate that the virus tends to remain less on the polymer surface by increasing the amount of CTAB in the PP matrix.