Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients to prevent hospitalization or death during the Omicron era: a propensity score-matched study.

Background: Even though worldwide death rates from coronavirus disease 2019 (COVID-19) have decreased, the threat of disease progression and death for high-risk groups continues. Few direct comparisons between the available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals have been made. Objective: We aimed to compare two SARS-CoV-2 antivirals (nirmatrelvir/ritonavir and remdesivir) against all-cause hospitalization or death. Design: This is a propensity score-matched cohort study. Methods: We included all high-risk outpatients with COVID-19 in a tertiary referral center in Mexico City from 1 January 2022 to 31 July 2023. The primary outcome was all-cause hospitalization or death 28 days after symptom onset. The secondary outcome was COVID-19-associated hospitalization or death 28 days after symptom onset. Logistic regression analysis for characteristics associated with the primary outcome and a multi-group comparison with Kaplan-Meier survival estimates were performed. Results: Of 1566 patients analyzed, 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. The median age was 60 years (interquartile range: 46-72), 62.5% were female and 97.8% had at least one comorbidity. The use of nirmatrelvir/ritonavir was associated with an absolute risk reduction of 8.8% and a relative risk reduction of 90% for all-cause hospitalization or death. The use of remdesivir was associated with an absolute risk reduction of 6.4% and a relative risk reduction of 66% for all-cause hospitalization or death. In multivariable analysis, both antivirals reduced the odds of 28-day all-cause hospitalization or death [nirmatrelvir/ritonavir odds ratio (OR) 0.08 - 95% confidence interval (CI): 0.03-0.19, remdesivir OR 0.29 - 95% CI: 0.18-0.45]. Conclusion: In high-risk COVID-19 outpatients, early antiviral treatment with nirmatrelvir/ritonavir or remdesivir was associated with lower 28-day all-cause hospitalization or death.

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients In this study, we included high-risk non-hospitalized patients with confirmed mild COVID-19. We compared those who received antiviral treatment (nirmatrelvir/ritonavir or remdesivir) against those who only received symptomatic treatment. The aim was to detect differences in hospitalization or death 28 days after symptom onset. We analyzed 1566 patients: 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. Most patients were female and over 60 years old. The most common comorbidities were chronic hypertension (44%), diabetes mellitus (26%), and autoimmune diseases (25%); systemic immunosuppression was registered in 35% of patients. Hospitalization or death 28 days after symptom onset occurred in 168 patients (136 in the symptomatic treatment group, 27 in the remdesivir group, and 5 in the nirmatrelvir/ritonavir group). Considering multiple variables like age, sex, comorbidities, and previous vaccination, both antivirals significantly reduced the odds of hospitalization or death (nirmatrelvir/ritonavir odds ratio 0.08, 95% confidence interval 0.03-0.19; remdesivir odds ratio 0.29, 95% confidence interval 0.18-0.45).

Clinical, molecular, and histological characteristics of severely necrotic and fatal mpox in HIV-infected patients.

BACKGROUND: This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites. CASE PRESENTATIONS: Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out. CONCLUSIONS: Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes.

RNA-Binding Proteins: A Role in Neurotoxicity?

Despite sustained efforts to treat neurodegenerative diseases, little is known at the molecular level to understand and generate novel therapeutic approaches for these malignancies. Therefore, it is not surprising that neurogenerative diseases are among the leading causes of death in the aged population. Neurons require sophisticated cellular mechanisms to maintain proper protein homeostasis. These cells are generally sensitive to loss of gene expression control at the post-transcriptional level. Post-translational control responds to signals that can arise from intracellular processes or environmental factors that can be regulated through RNA-binding proteins. These proteins recognize RNA through one or more RNA-binding domains and form ribonucleoproteins that are critically involved in the regulation of post-transcriptional processes from splicing to the regulation of association of the translation machinery allowing a relatively rapid and precise modulation of the transcriptome. Neurotoxicity is the result of the biological, chemical, or physical interaction of agents with an adverse effect on the structure and function of the central nervous system. The disruption of the proper levels or function of RBPs in neurons and glial cells triggers neurotoxic events that are linked to neurodegenerative diseases such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), fragile X syndrome (FXS), and frontotemporal dementia (FTD) among many others. The connection between RBPs and neurodegenerative diseases opens a new landscape for potentially novel therapeutic targets for the intervention of these neurodegenerative pathologies. In this contribution, a summary of the recent findings of the molecular mechanisms involved in the plausible role of RBPs in RNA processing in neurodegenerative disease is discussed.

Psychosocial factors associated with the intention to get a COVID-19 booster vaccine: evidence from a low-income country.

Aim: To identify psychosocial predictors of the intention to get a booster COVID-19 vaccine in a low-income country, given that increasing booster vaccination rates against COVID-19 remains a global challenge, especially among low- and middle-income countries (LMIC). Subject and methods: We used an online survey to collect responses from a non-probabilistic sample of 720 Bolivians regarding vaccine uptake, motives, perceived confidence, information sources, attitudes favouring COVID-19 vaccines, biosafety behaviour, and sociodemographic characteristics. Descriptive, bivariate, and multivariate analyses were performed to identify significant associations and predictors. Results: We found that having already received the third dose, obtaining recommendations from family or friends, recommendation from the government, perceived confidence in the previously received dose, and higher attitudes in favour of COVID-19 vaccines significantly predicted the intention to get a booster dose. The associations were significant even when adjusting the model for sociodemographic variables. Conclusion: Including certain psychosocial factors could enhance the promotion of voluntary booster doses among residents of low- and middle-income countries such as Bolivia, where cultural, social, political, and contextual variables may influence health behaviour and increase health-associated risk factors. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01937-x.

New Insights into the Toxin Diversity and Antimicrobial Activity of the "Fire Coral" Millepora complanata.

To date, few studies have been carried out aimed at characterizing the toxins synthesized by hydrocorals of the genus Millepora. The purpose of this study was to explore the toxin diversity and antibacterial activity of the "fire coral" M. complanata using a transcriptomic data mining approach. In addition, the cytolytic and antibacterial activities of the M. complanata nematocyst proteome were experimentally confirmed. Cytolysins were predicted from the transcriptome by comparing against the Animal Toxin Annotation Project database, resulting in 190 putative toxins, including metalloproteases, hemostasis-impairing toxins, phospholipases, among others. The M. complanata nematocyst proteome was analyzed by 1D and 2D electrophoresis and zymography. The zymograms showed different zones of cytolytic activity: two zones of hemolysis at ~25 and ~205 kDa, two regions corresponding to phospholipase A2 (PLA2) activity around 6 and 25 kDa, and a proteolytic zone was observed between 50 and 205 kDa. The hemolytic activity of the proteome was inhibited in the presence of PLA2 and proteases inhibitors, suggesting that PLA2s, trypsin, chymotrypsin, serine-proteases, and matrix metalloproteases are responsible for the hemolysis. On the other hand, antimicrobial peptide sequences were retrieved from their transcripts with the amPEPpy software. This analysis revealed the presence of homologs to SK84, cgUbiquitin, Ubiquicidin, TroTbeta4, SPINK9-v1, and Histone-related antimicrobials in the transcriptome of this cnidarian. Finally, by employing disk diffusion and microdilution assays, we found that the nematocyst peptidome of M. complanata showed inhibitory activity against both Gram-positive and Gram-negative bacteria including S. enteritidis, P. perfectomarina, E. coli, and C. xerosis, among others. This is the first transcriptomic data mining analysis to explore the diversity of the toxins synthesized by an organism of the genus Millepora. Undoubtedly, this work provides information that will broaden our general understanding of the structural richness of cnidarian toxins.

Exceptional T CD4+ Recovery Post-antiretroviral Is Linked to a Lower HIV Reservoir with a Specific Immune Differentiation Pattern.

We present a cohort of individuals who reached CD4+ T cell counts of greater than 1,000 cells/mm3 (Hypers) after starting antiretroviral treatment (ART) and compared them with those who reached between 350 and 999 CD4+ T cells/mm3 (Concordants). Demographic data, immune recovery kinetics, T CD4+ subset phenotypes, and integrated HIV DNA were analyzed. Data from individuals living with HIV on their first ART regimen and after 48 months of follow-up were obtained. Immune phenotype by Flow Cytometry analysis on whole blood was performed, cytokines were measured, and integrated HIV-1 DNA was measured by polymerase chain reaction. From a total of 424 individuals, 26 Hypers (6.1%), 314 Concordants (74.1%), and 84 (19.8%) discordants were identified. Hypers had a higher proportion of CD4+-naive (Nv) T cells (37.6 vs. 24.8, p < .05), and a low proportion of CD4+ effector memory T cells (27.9 vs. 39.4, p < .05), with similar results found in CD8+ T cells. Hypers demonstrated a higher percentage of CD4+CD45RA+CD31neg cells with a lower response to interleukin-2 stimulation and a lower integrated HIV-1 DNA/CD4 ratio (1.2 vs. 2.89, p < .05). In Hypers, T cell recovery occurs very early after initiation of ART. Following this initial recovery state, their CD4+ T cell level homeostasis seems to be driven by nonthymic-central-Nv cells. This exceptional recovery is associated with a lower HIV reservoir, which may be related to an increase in noninfected CD4+ T cells. These patients could then be eligible candidates for cure trials.

Spontaneous mediastinal emphysema in a non-intubated patient with COVID-19 related pneumonia: a case report.

Spontaneous mediastinal emphysema (ME) is a rare clinical entity often associated with sudden changes in intrathoracic pressures. The presumed pathophysiological mechanism is diffuse alveolar injury leading to alveolar rupture and air leak. Inflammatory alterations installed over the airway following SARS-CoV-2 infection may reduce its distensibility and compliance conferring an increased risk of developing the complication, even in the absence of mechanical ventilation. However, the exact mechanism by which ME occurs in SARS-CoV-2 pneumonia is unknown. We report a case of a 58-year-old man that presented to the emergency department with dyspnea, subcutaneous emphysema of the neck and high clinical suspicion of COVID-19 infection. There was no smoking history and no lung comorbidities. The patient was admitted into a monitored unit and received management accordingly (having never required mechanical intubation). During chest radiological evaluation ME was found and ultimately resolved with noninvasive maneuvers. We want to emphasize the importance of this adverse event despite their non-smoking history and the exclusion of positive pressure ventilation. Given the recent increase in the number of patients with COVID-19 related pneumonia, the presence of pneumomediastinum in patients with COVID-19 infection should alert the clinician to monitor the patients carefully for possible worsening of disease, especially when lung lesions are severe.

Comparative Analysis of the Soluble Proteome and the Cytolytic Activity of Unbleached and Bleached Millepora complanata ("Fire Coral") from the Mexican Caribbean.

Coral bleaching caused by global warming has resulted in massive damage to coral reefs worldwide. Studies addressing the consequences of elevated temperature have focused on organisms of the class Anthozoa, and up to now, there is little information regarding the mechanisms by which reef forming Hydrozoans face thermal stress. In this study, we carried out a comparative analysis of the soluble proteome and the cytolytic activity of unbleached and bleached Millepora complanata ("fire coral") that inhabited reef colonies exposed to the 2015-2016 El Niño-Southern Oscillation in the Mexican Caribbean. A differential proteomic response involving proteins implicated in key cellular processes, such as glycolysis, DNA repair, stress response, calcium homeostasis, exocytosis, and cytoskeleton organization was found in bleached hydrocorals. Four of the proteins, whose levels increased in bleached specimens, displayed sequence similarity to a phospholipase A2, an astacin-like metalloprotease, and two pore forming toxins. However, a protein, which displayed sequence similarity to a calcium-independent phospholipase A2, showed lower levels in bleached cnidarians. Accordingly, the hemolytic effect of the soluble proteome of bleached hydrocorals was significantly higher, whereas the phospholipase A2 activity was significantly reduced. Our results suggest that bleached M. complanata is capable of increasing its toxins production in order to balance the lack of nutrients supplied by its symbionts.

Encapsulation and immobilization of ficin extract in electrospun polymeric nanofibers.

In this work, ficin extract (3.4.22.3, >1.0 u/mg) was immobilized for the first time in poly (vinyl alcohol) (PVA) electrospun nanofibers in order to preserve its tridimensional molecular structure. The analysis of the morphology of the electrospun nanofibers was carried out using scanning electron microscopy (SEM) showing a diameter in the range of 124-194 nm. The interaction of the ficin extract with the nanofibers structure was analyzed by infrared spectroscopy (FTIR) analysis. The immobilization step was achieved through crosslinking involving the exposure to glutaraldehyde (GA) vapor. The enzyme catalytic behavior was followed by ultraviolet spectroscopy (UV) using the Earlanger method using Nα-benzoyl-l-arginine-4-nitroanilide hydrochloride (BAPA) as substrate. The maximum catalytic activity was reached with 1 h of crosslinking, 20% of enzyme loading and pH 8. The immobilized ficin extract showed 92% of the enzyme activity of the crude ficin extract. The enzymatic activity of the immobilized ficin extract was conserved after a total of nine reuse cycles and maintained after being stored for 25 days. Finally, both the glass transition (Tg) and heat of fusion (Hf) were affected by number of enzyme molecules inside the polymeric nanofibers matrix according to the study of the thermal properties by differential scanning calorimetry (DSC).

Trastornos de angustia y ansiedad en momentos críticos del nacimiento: estudio comparativo de dos modelos de entrevistas / Anxiety disorders in critical moment at birth: development of an interview model and intervention style in the perinatal field

El objetivo del trabajo es presentar los resultados de la tarea de investigación y asistencia que realizó un equipo de psicología perinatal entre 1996 y 1999 ante la angustia y ansiedad que desencadena en la madre la internación prolongada de su bebé o la propia despues del nacimiento. Se detectaron: sucesos significativos,problemas físicos y/o psicológicos y conflictos infantiles que emergen detrás de los trastornos de angustia y ansiedad. Se administró un modelo de entrevista psicológica con diseño óptico y se realizó el estudio comparativo con un modelo de entrevista "clasica". El trabajo permitió analizar y sistematizar 1264 entrevistas psicológicas administradas a madres e incorporar a las historias clínicas neonatales un protocolo que detecte factores psicológicos. La investigación coomprobó que los sucesos significativos para la madre se centran principalmente en: muertes,problemas de pareja, problemas actuales y problemas sociales. Ello implica el reconocimiento de la dimensión psicológica en ámbitos tan influídos por el "saber" médico ,y el desarrollo de la Psicología perinatal.

La palabra en las maternidades: detección de sucesos significativos durante el embarazo y el puerperio / The word in maternity: detection of significant events during pregnancy and the postpartum period

El objetivo de la investigación fue la construcción de una entrevista que tomara en cuenta los sucesos significativos de vida ("life event") que pudieron influír durante el embarazo y parto a los efectos de introducir la dimensión psicosocial de la madre en las maternidades.Con el propósito de incorporarla a la historia clínica obstétrica y neonatal la entrevista fue transformada en un instrumento de diseño óptico de fácil interpretación para el equipo médico.La aplicación en ambos Servicios permitió clasificar la problemática materna en seis categorías generales: pareja, muerte, problemas sociales, preocupacion por otros hijos , problemas asociados al embarazo fisicos o psicologicos y conclictos en la infancia.Se administró desde 1996 a 1999 en el servicio de Neonatología a un total de 1.264 madres en las primeras 96 horas de vida del bebé y en Obstetricia ( salas de internación embarazo de riesgo) se aplicó a 212 pacientes desde el mes de Marzo de 1998 hasta el mes de Julio de 2000. Incorporar a las historias clínicas un protocolo que detecte factores psicológicos implica el reconocimiento de la dimensión psicológica en ámbitos tan influidos por el "saber" médico y el desarrollo de la psicología perinatal...

La palabra en las maternidades: detección de sucesos significativos durante el embarazo y el puerperio / The word in maternity hospitals: detection of significant events during female pregnancy and puerperium: risk reduction and health promotion

El objetivo de la investigación fue la construcción de una entrevista que tomara en cuenta los sucesos significativos de vida ("life event") que pudieron influír durante el embarazo y parto a los efectos de introducir la dimensión psicosocial de la madre en las maternidades. Con el propósito de incorporarla a la historia clínica obstétrica y neonatal la entrevista fue transformada en un instrumento de diseño óptico de fácil interpretación para el equipo médico. La aplicación en ambos Servicios permitió clasificar la problemática materna en seis categorías generales: pareja, muerte, problemas sociales, preocupacion por otros hijos , problemas asociados al embarazo fisicos o psicologicos y conclictos en la infancia. Se administró desde 1996 a 1999 en el servicio de Neonatología a un total de 1.264 madres en las primeras 96 horas de vida del bebé y en Obstetricia ( salas de internación embarazo de riesgo) se aplicó a 212 pacientes desde el mes de Marzo de 1998 hasta el mes de Julio de 2000. Incorporar a las historias clínicas un protocolo que detecte factores psicológicos implica el reconocimiento de la dimensión psicológica en ámbitos tan influidos por el "saber" médico y el desarrollo de la psicología perinatal

As a research goal we created a schedule interview to consider the significant "life events" that could appear during the pregnancy and childbirth, giving us mother's psychosocial dimension into the maternity hospital. Incorporated to the obstetric an neonatal clinical history, it's an easy "optical designed" tool to every medical team. There are six items classified: couples, death, social problems, worry about other children, psychological or physical problems associated with pregnancy, childhood conflicts. This interview was used since 1996 up to 1999: in Neonatology with 1264 mother in the first 96 hours baby life; in Obstetrics it was applied to 212 patients since March 1998 till July 2000. Incorporing to clinical histories a protocol which detects psychological events, denotes recognition psychological dimension in medical knowledge and perinatal psychology develop

Un nuevo instrumento diagnóstico en situaciones perinatales: la entrevista psicológica de diseño óptico / A new diagnostic tool in perinatal situations: optical design of psychologist interview

Se presenta un modelo de entrevista psicológica con diseño óptico para ser aplicado en el posparto inmediato.El equipo esta formado por un grupo de profesionales que realizan el acompañamiento psicológico de la madre y su bebé durante las primeras interacciones, cuando los acontecimientos se desarrollan normalmente, pero también cuando sobreviven incidentes, amenazas de partos prematuros, muerte fetal , nacimiento prematuro y descompensación postnatal.Se elaboró una lista de temas preocupantes que surgen del discurso materno a partir de la aplicación del instrumento.

Detección de factores de riesgo psicosocial en el postparto inmediato / Detection of psychosocial risk factors in the immediate postpartum

El presente trabajo tuvo por objetivo detectar los factores psicosociales que intervienen en las amenazas de partos prematuros, bebés de bajo peso al nacer, muertes fetales y descompensaciones posnatales.Numerosas investigaciones dieron cuenta de la incidencia de los factores biológicos, genéticos y médicos en los nacimientos prematuros, de bajo peso u otras complicaciones al nacer.Sin embargo, quedan aún por investigar los factores psicosociales, e identificar cuales son los sucesos significativos de la vida (life event) que impiden el normal desarrollo del embarazo, parto y puerperio. Para ello hemos elaborado y aplicado una entrevista psicológica semidirigida, que interrogaba sobre sucesos significativos de vida (lige event) durante el último año a 80 madres con bebés internados en Unidad de terapia neonatológica (grupo experimental) con otro grupo de madres (grupo control) cuyos bebés no habían tenido problemas al nacer. Se compararon ambos grupos en cuanto a la edad, educación, pareja y sucesos significativos de vida. Se encontró diferencias significativas (p< o.o1) en relación a los sucesos significativos que habían sufrido ese año. Las madres del grupo experimental habían padecido problemas en 55 casos (80 en total). Y las madres del grupo control manifestaron problemas en 25 casos (80 casos)...