Potentially inappropriate prescriptions and potential prescription omissions in older people living with HIV.

OBJECTIVES: This study aimed to determine the prevalence of potentially inappropriate prescriptions (PIPs) and potential prescription omissions (PPOs) in a Spanish cohort of people living with HIV (PLWH) aged ≥65 years and to identify risk factors for the presence of PIPs and PPOs. METHODS: This retrospective cross-sectional study was conducted across 10 public hospitals in the Autonomous Community of Madrid, Spain. Clinical and demographic data were cross-checked against hospital and community pharmacy dispensation registries. PIPs and PPOs were assessed using the American Geriatrics Society (AGS)/Beers and Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert Doctors to Right Treatment (START) criteria. Risk factors for PIPs and PPOs and agreement between AGS/Beers and STOPP/START criteria were statistically analysed. RESULTS: This study included 313 PLWH (median age 72 years), of whom 80.5% were men. PIP prevalence rates were 29.4% and 44.4% based on the AGS/Beers and STOPP criteria, respectively. The concordance between AGS/Beers and STOPP criteria was moderate. Benzodiazepines and proton pump inhibitors were the chronic comedications most commonly involved in PIPs. PPOs were observed in 61.4% of the patients. The leading omissions were insufficient influenza and pneumococcal vaccine coverage and inadequate bone health-related treatments. The number of chronic comedications, female sex, neuropsychiatric disorders, and cancer diagnosis were risk factors for PIPs, whereas osteopenia and osteoporosis were risk factors for PPOs. CONCLUSIONS: A high prevalence of PIPs and PPOs was observed in our cohort of older PLWH. These findings emphasize the importance of comprehensive medication reviews in this population to reduce inappropriate medication use and address their specific and underserved therapeutic needs.

Risk of dementia among antidepressant elderly users: A population-based cohort analysis in Spain.

The use of antidepressants with anticholinergic effects has been associated with an increased risk of dementia. However, the results published are contradictory. The aim of the study is to compare the risk of developing dementia in elderly who were prescribed tricyclic antidepressants (TCA) versus those who were prescribed selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OA). A prospective population-based cohort study was performed using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) data (from 2005 to 2018). The cohort study included 62,928 patients age ≥ 60 without dementia and with antidepressant long-term monotherapy. Patients were divided into exposure antidepressant groups based on ATC system [TCA, SSRIs users and OAs users]. The risk of dementia was calculated by Cox regression models, providing hazard ratios (HR) and 95 % confidence intervals. The Kaplan-Meier model was used for survival analysis. Chi2 test was used as association test. The results showed SSRI users had higher dementia risk than TCA users (HR = 1.864; 95%CI = 1.624-2.140). Moreover, OA users had also significant risk of dementia (HR = 2.103; 95%CI = 1.818-2.431). Several limitations are the variation of the trend in the prescription of antidepressants, the small number of patients that use some antidepressants, the lack of information related to the dose, or socioeconomic characteristics, the use of antidepressant drugs for other indications, or the therapeutic compliance. Our findings showed that older users of SSRI and OA have more risk of developing dementia than TCA elderly users. However, additional studies would be needed.

Engineering 3D-Printed Advanced Healthcare Materials for Periprosthetic Joint Infections.

The use of additive manufacturing or 3D printing in biomedicine has experienced fast growth in the last few years, becoming a promising tool in pharmaceutical development and manufacturing, especially in parenteral formulations and implantable drug delivery systems (IDDSs). Periprosthetic joint infections (PJIs) are a common complication in arthroplasties, with a prevalence of over 4%. There is still no treatment that fully covers the need for preventing and treating biofilm formation. However, 3D printing plays a major role in the development of novel therapies for PJIs. This review will provide a deep understanding of the different approaches based on 3D-printing techniques for the current management and prophylaxis of PJIs. The two main strategies are focused on IDDSs that are loaded or coated with antimicrobials, commonly in combination with bone regeneration agents and 3D-printed orthopedic implants with modified surfaces and antimicrobial properties. The wide variety of printing methods and materials have allowed for the manufacture of IDDSs that are perfectly adjusted to patients' physiognomy, with different drug release profiles, geometries, and inner and outer architectures, and are fully individualized, targeting specific pathogens. Although these novel treatments are demonstrating promising results, in vivo studies and clinical trials are required for their translation from the bench to the market.

The cytotoxicity effect of 7-hydroxy-3,4-dihydrocadalene from Heterotheca inuloides and semisynthetic cadalenes derivates towards breast cancer cells: involvement of oxidative stress-mediated apoptosis.

Background: Heterotheca inuloides, traditionally employed in Mexico, has demonstrated anticancer activities. Although it has been proven that the cytotoxic effect is attributed to cadinane-type sesquiterpenes such as 7-hydroxy-3,4-dihydrocadalene, the mechanism of action by which these agents act in tumor lines and their regulation remain unknown. This study was undertaken to investigate for first time the cytotoxic activity and mechanism of action of 7-hydroxy-3,4-dihydrocadalene and two semi-synthetic cadinanes derivatives towards breast cancer cells. Methods: Cell viability and proliferation were assayed by thiazolyl blue tetrazolium bromide (MTT) assay and Trypan blue dye exclusion assay. Cell migration measure was tested by wound-healing assay. Moreover, the reactive oxygen species (ROS) and lipid peroxidation generation were measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay and thiobarbituric acid reactive substance (TBARS) assay, respectively. Furthermore, expression of caspase-3, Bcl-2 and GAPDH were analyzed by western blot. Results: The results showed that 7-hydroxy-3,4-dihydrocadalene inhibited MCF7 cell viability in a concentration and time dependent manner. The cytotoxic potency of semisynthetic derivatives 7-(phenylcarbamate)-3,4-dihydrocadalene and 7-(phenylcarbamate)-cadalene was remarkably lower. Moreover, in silico studies showed that 7-hydroxy-3,4-dihydrocadalene, and not so the semi-synthetic derivatives, has optimal physical-chemical properties to lead a promising cytotoxic agent. Further examination on the action mechanism of 7-hydroxy-3,4-dihydrocadalene suggested that this natural product exerted cytotoxicity via oxidative stress as evidenced in a significantly increase of intracellular ROS levels and in an induction of lipid peroxidation. Furthermore, the compound increased caspase-3 and caspase-9 activities and slightly inhibited Bcl-2 levels. Interestingly, it also reduced mitochondrial ATP synthesis and induced mitochondrial uncoupling. Conclusion: Taken together, 7-hydroxy-3,4-dihydrocadalene is a promising cytotoxic compound against breast cancer via oxidative stress-induction.

Mental health and drug use in college students: Should we take action?

BACKGROUND: College students are vulnerable to suffering from anxiety and depression. Moreover, mental disorders can contribute to drug consumption or inappropriate use of prescribed drugs. Studies on this topic in Spanish college students are limited. This work analyses anxiety and depression and psychoactive drug intake pattern in the post-COVID era in college students. METHODS: An online survey was conducted among college students from UCM (Spain). The survey collected data including demographic, academic student perception, GAD-7 and PHQ-9 scales, and psychoactive substances consumption. RESULTS: A total of 6798 students were included; 44.1 % (CI95%: 42.9 to 45.3) showed symptoms of severe anxiety and 46.5 % (CI95%: 45.4 to 47.8) symptoms of severe or moderately severe depression. The perception of these symptoms did not change after returning to face-to-face university classes in the post-COVID19 era. Despite the high percentage of cases with clear symptoms of anxiety and depression, most students never had a diagnosis of mental illnesses [anxiety 69.2 % (CI95%: 68.1 to 70.3) and depression 78.1 % (CI95%: 77.1 to 79.1)]. Regarding psychoactive substances, valerian, melatonin, diazepam, and lorazepam were the most consumed. The most worrying issue was the consumption of diazepam, 10.8 % (CI95%: 9.8 to 11.8), and lorazepam, 7.7 % (CI95%: 6.9 to 8.6) without medical prescription. Among illicit drugs, cannabis is the most consumed. LIMITATIONS: The study was based on an online survey. CONCLUSIONS: The high prevalence of anxiety and depression aligned with poor medical diagnosis and high intake of psychoactive drugs should not be underestimated. University policies should be implemented to improve the well-being of students.

Lichen Depsides and Tridepsides: Progress in Pharmacological Approaches.

Depsides and tridepsides are secondary metabolites found in lichens. In the last 10 years, there has been a growing interest in the pharmacological activity of these compounds. This review aims to discuss the research findings related to the biological effects and mechanisms of action of lichen depsides and tridepsides. The most studied compound is atranorin, followed by gyrophoric acid, diffractaic acid, and lecanoric acid. Antioxidant, cytotoxic, and antimicrobial activities are among the most investigated activities, mainly in in vitro studies, with occasional in silico and in vivo studies. Clinical trials have not been conducted using depsides and tridepsides. Therefore, future research should focus on conducting more in vivo work and clinical trials, as well as on evaluating the other activities. Moreover, despite the significant increase in research work on the pharmacology of depsides and tridepsides, there are many of these compounds which have yet to be investigated (e.g., hiascic acid, lassalic acid, ovoic acid, crustinic acid, and hypothamnolic acid).

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis.

BACKGROUND: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. METHODS: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. RESULTS AND CONCLUSION: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events.

Remdesivir in kidney transplant patients with SARS-CoV-2 pneumonia.

BACKGROUND: Remdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in Kidney transplant (KT) patients are limited to some published cases. METHODS: We performed a retrospective observational study that included all KT patients admitted between August 01, 2020 and December 31, 2020 with SARS-CoV-2 pneumonia who received remdesivir. The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir. DISCUSSION: A total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30 mL/min or they did not present clinical criteria. In addition to remdesivir, all pacients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53-71) years. Median time from transplantation was 43 (16-82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low oxygen flow therapy upon admission, requiring high flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9-27) days. CONCLUSIONS: Our study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection.

Lichen Extracts from Cetrarioid Clade Provide Neuroprotection against Hydrogen Peroxide-Induced Oxidative Stress.

Oxidative stress is involved in the pathophysiology of many neurodegenerative diseases. Lichens have antioxidant properties attributed to their own secondary metabolites with phenol groups. Very few studies delve into the protective capacity of lichens based on their antioxidant properties and their action mechanism. The present study evaluates the neuroprotective role of Dactylina arctica, Nephromopsis stracheyi, Tuckermannopsis americana and Vulpicida pinastri methanol extracts in a hydrogen peroxide (H2O2) oxidative stress model in neuroblastoma cell line "SH-SY5Y cells". Cells were pretreated with different concentrations of lichen extracts (24 h) before H2O2 (250 µM, 1 h). Our results showed that D. arctica (10 µg/mL), N. stracheyi (25 µg/mL), T. americana (50 µg/mL) and V. pinastri (5 µg/mL) prevented cell death and morphological changes. Moreover, these lichens significantly inhibited reactive oxygen species (ROS) production and lipid peroxidation and increased superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) levels. Furthermore, they attenuated mitochondrial membrane potential decline and calcium homeostasis disruption. Finally, high-performance liquid chromatography (HPLC) analysis revealed that the secondary metabolites were gyrophoric acid and lecanoric acid in D. artica, usnic acid, pinastric acid and vulpinic acid in V. pinastri, and alectoronic acid in T. americana. In conclusion, D. arctica and V. pinastri are the most promising lichens to prevent and to treat oxidative stress-related neurodegenerative diseases.

Evolving Concepts on Inflammatory Biomarkers and Malnutrition in Chronic Kidney Disease.

While patient care, kidney replacement therapy, and transplantation techniques for chronic kidney disease (CKD) have continued to progress, the incidence of malnutrition disorders in CKD appears to have remained unchanged over time. However, there is now a better understanding of the underlying pathophysiology according to the disease background, disease stage, and the treatment received. In CKD patients, the increased production of proinflammatory cytokines and oxidative stress lead to a proinflammatory milieu that is at least partially responsible for the increased morbidity and mortality in this patient population. New insights into the pathogenic role of innate immunity and the proinflammatory cytokine profile, characterized, for instance, by higher levels of IL-6 and TNF-α, explain some of the clinical and laboratory abnormalities observed in these patients. In this article, we will explore currently available nutritional-inflammatory biomarkers in distinct CKD populations (hemodialysis, peritoneal dialysis, transplantation) with a view to evaluating their efficacy as predictors of malnutrition and their involvement in the common proinflammatory process. Although there is a direct relationship between inflammatory-nutritional status, signs and symptoms [e.g., protein-energy wasting (PEW), anorexia], and comorbidities (e.g., atheromatosis, atherosclerosis), we are in need of clearly standardized markers for nutritional-inflammatory assessment to improve their performance and design appropriate bidirectional interventions.

The Genus Cetraria s. str.-A Review of Its Botany, Phytochemistry, Traditional Uses and Pharmacology.

The genus Cetraria s. str. (Parmeliaceae family, Cetrarioid clade) consists of 15 species of mostly erect brown or greenish yellow fruticose or subfoliose thallus. These Cetraria species have a cosmopolitan distribution, being primarily located in the Northern Hemisphere, in North America and in the Eurasia area. Phytochemical analysis has demonstrated the presence of dibenzofuran derivatives (usnic acid), depsidones (fumarprotocetraric and protocetraric acids) and fatty acids (lichesterinic and protolichesterinic acids). The species of Cetraria, and more particularly Cetraria islandica, has been widely employed in folk medicine for the treatment of digestive and respiratory diseases as decoctions, tinctures, aqueous extract, and infusions. Moreover, Cetraria islandica has had an important nutritional and cosmetic value. These traditional uses have been validated in in vitro and in vivo pharmacological studies. Additionally, new therapeutic activities are being investigated, such as antioxidant, immunomodulatory, cytotoxic, genotoxic and antigenotoxic. Among all Cetraria species, the most investigated by far has been Cetraria islandica, followed by Cetraria pinastri and Cetraria aculeata. The aim of the current review is to update all the knowledge about the genus Cetraria covering aspects that include taxonomy and phylogeny, morphology and distribution, ecological and environmental interest, phytochemistry, traditional uses and pharmacological properties.

A New Cryptic Lineage in Parmeliaceae (Ascomycota) with Pharmacological Properties.

We used molecular data to address species delimitation in a species complex of the parmelioid genus Canoparmelia and compare the pharmacological properties of the two clades identified. We used HPLC_DAD_MS chromatography to identify and quantify the secondary substances and used a concatenated data set of three ribosomal markers to infer phylogenetic relationships. Some historical herbarium specimens were also examined. We found two groups that showed distinct pharmacological properties. The phylogenetic study supported the separation of these two groups as distinct lineages, which are here accepted as distinct species: Canoparmelia caroliniana occurring in temperate to tropical ecosystems of a variety of worldwide localities, including America, Macaronesia, south-west Europe and potentially East Africa, whereas the Kenyan populations represent the second group, for which we propose the new species C. kakamegaensis Garrido-Huéscar, Divakar & Kirika. This study highlights the importance of recognizing cryptic species using molecular data, since it can result in detecting lineages with pharmacological properties previously overlooked.

Phytochemical Characterization and Pharmacological Properties of Lichen Extracts from Cetrarioid Clade by Multivariate Analysis and Molecular Docking.

Introduction: Lichens, due to the presence of own secondary metabolites such as depsidones and depsides, became a promising source of health-promoting organisms with pharmacological activities. However, lichens and their active compounds have been much less studied. Therefore, the present study aims to evaluate for the first time the antioxidant capacity and enzyme inhibitory activities of 14 lichen extracts belonging to cetrarioid clade in order to identify new natural products with potential pharmacological activity. Materials and Methods: In this study, an integrated strategy was applied combining multivariate statistical analysis (principal component analysis and hierarchical cluster analysis), phytochemical identification, activity evaluation (in vitro battery of antioxidant assays FRAP, DPPH, and ORAC), and enzyme inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) and molecular profiling with in silico docking studies of the most promising secondary metabolites. Results. Among fourteen lichen samples, Dactylina arctica stands out for its higher antioxidant capacities, followed by Nephromopsis stracheyi, Tuckermannopsis americana, Vulpicida pinastri, and Asahinea scholanderi. Moreover, Asahinea scholanderi and Cetraria cucullata extracts were the best inhibitors of AChE and BuChE. The major secondary metabolites identified by HPLC were alectoronic acid and α-collatolic acid for Asahinea scholanderi and usnic acid and protolichesterinic acid for Cetraria cucullata. Molecular docking studies revealed that alectoronic acid exhibited the strongest binding affinity with both AChE and BuChE with and without water molecules. Conclusions: Our results concluded that these species could be effective in the treatment of neurodegenerative diseases, being mandatory further investigation in cell culture and in vivo models.

Remdesivir en pacientes trasplantados renales con neumonía por SARS-CoV-2 / Remdesivir in kidney transplant patients with SARS-CoV-2 pneumonia

Introducción: El remdesivir es el único tratamiento antiviral que ha demostrado ser útil frente al SARS-CoV-2 acortando el tiempo de hospitalización frente a placebo. Su efecto en pacientes trasplantados renales (TR) se limita a algunos casos publicados.Material y métodosEstudio retrospectivo observacional de los pacientes TR que ingresaron entre el 1 de agosto de 2020 hasta el 31 de diciembre de 2020 con neumonía por SARS-CoV-2 y recibieron remdesivir.El objetivo es describir la experiencia de una cohorte de pacientes TR con neumonía por SARS-CoV-2 tratados con remdesivir.Resultados37 pacientes TR ingresaron por infección secundaria a SARS-CoV-2, 7 de ellos recibieron tratamiento con remdesivir. El resto de pacientes fueron excluidos por CKD-EPI menor a 30mL/min o por no presentar criterios clínicos. Además de remdesivir, todos recibieron dexametasona y anticoagulación. Cuatro eran hombres, siendo la mediana de edad de 59 (53-71) años. La mediana de tiempo post-trasplante fue de 43 (16-82) meses. Todos los pacientes presentaban neumonía y requirieron oxigenoterapia de bajo flujo al ingreso, precisando en tres de ellos oxigenoterapia de alto flujo durante el ingreso. Dos presentaron deterioro de la función del injerto al diagnóstico, no precisando en ningún caso hemodiálisis, y recuperándose al alta. Dos pacientes elevaron 1,5 veces el valor normal de las transaminasas. Ningún paciente falleció ni precisó ingreso en unidad de críticos. La mediana de días de ingreso fue de 12 (9-27) días.ConclusionesNuestro estudio sugiere que el uso de remdesivir podría ser útil en los pacientes TR con neumonía por SARS-CoV-2 sin presentar efectos secundarios. Son necesarios más estudios con un mayor número de pacientes para ampliar el conocimiento de este fármaco en la infección por SARS-CoV-2. (AU)

Background: Remdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in kidney transplant (KT) patients are limited to some published cases.MethodsWe performed a retrospective observational study that included all KT patients admitted between August 1st, 2020 and December 31st, 2020 with SARS-CoV-2 pneumonia who received remdesivir.The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir.DiscussionA total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30mL/min or they did not present clinical criteria. In addition to remdesivir, all patients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53–71) years. Median time from transplantation was 43 (16–82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low-oxygen flow therapy upon admission, requiring high-flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9–27) days.ConclusionsOur study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection. (AU)

Lichen Depsidones with Biological Interest.

Depsidones are some of the most abundant secondary metabolites produced by lichens. These compounds have aroused great pharmacological interest due to their activities as antioxidants, antimicrobial, and cytotoxic agents. Hence, this paper aims to provide up-to-date knowledge including an overview of the potential biological interest of lichen depsidones. So far, the most studied depsidones are fumarprotocetraric acid, lobaric acid, norstictic acid, physodic acid, salazinic acid, and stictic acid. Their pharmacological activities have been mainly investigated in in vitro studies and, to a lesser extent, in in vivo studies. No clinical trials have been performed yet. Depsidones are promising cytotoxic agents that act against different cell lines of animal and human origin. Moreover, these compounds have shown antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungi, mainly Candida spp. Furthermore, depsidones have antioxidant properties as revealed in oxidative stress in vitro and in vivo models. Future research should be focused on further investigating the mechanism of action of depsidones and in evaluating new potential actions as well as other depsidones that have not been studied yet from a pharmacological perspective. Likewise, more in vivo studies are prerequisite, and clinical trials for the most promising depsidones are encouraged.

[Remdesivir in kidney transplant patients with SARS-CoV-2 pneumonia]. / Remdesivir en pacientes trasplantados renales con neumonía por SARS-CoV-2.

Background: Remdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in kidney transplant (KT) patients are limited to some published cases. Methods: We performed a retrospective observational study that included all KT patients admitted between August 1st, 2020 and December 31st, 2020 with SARS-CoV-2 pneumonia who received remdesivir.The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir. Discussion: A total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30 mL/min or they did not present clinical criteria. In addition to remdesivir, all patients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53-71) years. Median time from transplantation was 43 (16-82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low-oxygen flow therapy upon admission, requiring high-flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9-27) days. Conclusions: Our study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection.

Self-assembling, supramolecular chemistry and pharmacology of amphotericin B: Poly-aggregates, oligomers and monomers.

Antifungal drugs such as amphotericin B (AmB) interact with lipids and phospholipids located on fungal cell membranes to disrupt them and create pores, leading to cell apoptosis and therefore efficacy. At the same time, the interaction can also take place with cell components from mammalian cells, leading to toxicity. AmB was selected as a model antifungal drug due to the complexity of its supramolecular chemical structure which can self-assemble in three different aggregation states in aqueous media: monomer, oligomer (also known as dimer) and poly-aggregate. The interplay between AmB self-assembly and its efficacy or toxicity against fungal or mammalian cells is not yet fully understood. To the best of our knowledge, this is the first report that investigates the role of excipients in the supramolecular chemistry of AmB and the impact on its biological activity and toxicity. The monomeric state was obtained by complexation with cyclodextrins resulting in the most toxic state, which was attributed to the greater production of highly reactive oxygen species upon disruption of mammalian cell membranes, a less specific mechanism of action compared to the binding to the ergosterol located in fungal cell membranes. The interaction between AmB and sodium deoxycholate resulted in the oligomeric and poly-aggregated forms which bound more selectively to the ergosterol of fungal cell membranes. NMR combined with XRD studies elucidated the interaction between drug and excipient to achieve the AmB aggregation states, and ultimately, their diffusivity across membranes. A linear correlation between particle size and the efficacy/toxicity ratio was established allowing to modulate the biological effect of the drug and hence, to improve pharmacological regimens. However, particle size is not the only factor modulating the biological response but also the equilibrium of each state which dictates the fraction of free monomeric form available. Tuning the aggregation state of AmB formulations is a promising strategy to trigger a more selective response against fungal cells and to reduce the toxicity in mammalian cells.

Effect of Phenolic Compounds on Human Health.

This book, based on a Special Issue of Nutrients, contains a total of 12 papers (8 original research and 4 reviews) on the effect of phenolic compounds on human health [...].

Routine Biomarkers for the Severity of COVID-19 Pneumonia May Present Differently in Kidney Transplant Recipients.

BACKGROUND: The treatment of coronavirus disease 2019 (COVID-19) is based on the patient's clinical status and levels of inflammatory biomarkers. The comparative activity of these biomarkers in kidney transplant (KT) patients with COVID-19 pneumonia from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and non-SARS-CoV-2 etiologies is unknown. The aim of this study was to compare the clinical presentation and inflammatory parameters at admission of KT patients with COVID-19 pneumonia and those with non-COVID-19 pneumonia over the same period. METHODS: Biomarkers were measured and compared between KT patients with COVID-19 pneumonia (n = 57) and non-COVID-19 pneumonia (n = 20) from March 2020 to March 2021. RESULTS: Both groups showed comparable demographics. The KT patients with COVID-19 had fewer neutrophils (6824 ± 5000 vs 8969 ± 4206; P = .09) than the non-COVID group, although there was no significant difference in the lymphocyte count. Non-COVID-19 pneumonia was associated with higher d-dimer (median, 921 [interquartile range (IQR), 495-1680] vs median, 2215 [IQR, 879-3934]; P = 0.09) and interleukin-6 (median, 35 [IQR, 20-128] vs median, 222 [IQR, 38-500]; P = 0.006) levels. The ferritin level was higher in the COVID-19 group (median, 809 [IQR, 442-1,330] vs median, 377 [IQR, 276-885]; P = 0.008). In multivariable analysis, only d-dimer (hazard ratio [HR], 1; 95% confidence interval [CI],1-1.002; P = .02) and ferritin (HR, 1; 95% CI, 0.9-0.9; P = .02) increase the statistic signification. CONCLUSION: COVID-19 pneumonia in KT patients shows a different presentation of inflammatory biomarkers than other non-COVID pneumonias. It could be useful to identify KT patients with COVID-19. More detailed studies are necessary to understand the presentation of biomarkers in KT with COVID-19.

Nutritional Value of Moringa oleifera Lam. Leaf Powder Extracts and Their Neuroprotective Effects via Antioxidative and Mitochondrial Regulation.

Age-related neurodegenerative disorders are an increasing public health problem. Oxidative stress is one of the major causes. Medicinal plant-based functional foods can be effective for these diseases. The aim of this work is to investigate the neuroprotective role of methanol extracts of Moringa oleifera leaf powder on antioxidant/oxidant imbalance and mitochondrial regulation in a H2O2-induced oxidative stress model in human neuroblastoma cells. On nutritional analysis, results showed that moringa contained 28.50% carbohydrates, 25.02% proteins, 10.42% fat, 11.83% dietary fiber, 1.108 mg ß-carotene, 326.4 µg/100 g vitamin B1 and 15.2 mg/100 g vitamin C. In-vitro assays revealed that moringa methanol extracts had more phenolic content and higher antioxidant activity than acetone extracts. Moreover, pretreatments with methanol extracts showed a protective effect against H2O2-induced oxidative damage through increasing cell viability and reducing free radicals. Furthermore, the extract decreased lipid peroxidation and enhanced glutathione levels and antioxidant enzyme activity. Finally, moringa also prevented mitochondrial dysfunction by regulating calcium levels and increasing mitochondrial membrane potential. The most active concentration was 25 µg/mL. In summary, the nutritional and functional properties of Moringa oleifera as a neuroprotective agent could be beneficial to protect against oxidative stress and provide necessary nutrients for a healthy diet.