Next-generation treatments: Immunotherapy and advanced therapies for COVID-19.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 following prior outbreaks of coronaviruses like SARS and MERS in recent decades, underscoring their high potential of infectivity in humans. Insights from previous outbreaks of SARS and MERS have played a significant role in developing effective strategies to mitigate the global impact of SARS-CoV-2. As of January 7, 2024, there have been 774,075,242 confirmed cases of COVID-19 worldwide. To date, 13.59 billion vaccine doses have been administered, and there have been 7,012,986 documented fatalities (https://www.who.int/) Despite significant progress in addressing the COVID-19 pandemic, the rapid evolution of SARS-CoV-2 challenges human defenses, presenting ongoing global challenges. The emergence of new SARS-CoV-2 lineages, shaped by mutation and recombination processes, has led to successive waves of infections. This scenario reveals the need for next-generation vaccines as a crucial requirement for ensuring ongoing protection against SARS-CoV-2. This demand calls for formulations that trigger a robust adaptive immune response without leading the acute inflammation linked with the infection. Key mutations detected in the Spike protein, a critical target for neutralizing antibodies and vaccine design -specifically within the Receptor Binding Domain region of Omicron variant lineages (B.1.1.529), currently dominant worldwide, have intensified concerns due to their association with immunity evasion from prior vaccinations and infections. As the world deals with this evolving threat, the narrative extends to the realm of emerging variants, each displaying new mutations with implications that remain largely misunderstood. Notably, the JN.1 Omicron lineage is gaining global prevalence, and early findings suggest it stands among the immune-evading variants, a characteristic attributed to its mutation L455S. Moreover, the detrimental consequences of the novel emergence of SARS-CoV-2 lineages bear a particularly critical impact on immunocompromised individuals and older adults. Immunocompromised individuals face challenges such as suboptimal responses to COVID-19 vaccines, rendering them more susceptible to severe disease. Similarly, older adults have an increased risk of severe disease and the presence of comorbid conditions, find themselves at a heightened vulnerability to develop COVID-19 disease. Thus, recognizing these intricate factors is crucial for effectively tailoring public health strategies to protect these vulnerable populations. In this context, this review aims to describe, analyze, and discuss the current progress of the next-generation treatments encompassing immunotherapeutic approaches and advanced therapies emerging as complements that will offer solutions to counter the disadvantages of the existing options. Preliminary outcomes show that these strategies target the virus and address the immunomodulatory responses associated with COVID-19. Furthermore, the capacity to promote tissue repair has been demonstrated, which can be particularly noteworthy for immunocompromised individuals who stand as vulnerable actors in the global landscape of coronavirus infections. The emerging next-generation treatments possess broader potential, offering protection against a wide range of variants and enhancing the ability to counter the impact of the constant evolution of the virus. Furthermore, advanced therapies are projected as potential treatment alternatives for managing Chronic Post-COVID-19 syndromeand addressing its associated long-term complications.

Analysis of drug of abuse compounds using passive sampling and ultrahigh-liquid chromatography coupled to mass spectrometry.

The present study proposes the monitoring of compounds of drugs of abuse through the use of passive samplers in water systems. Initially, four positive ion compounds of interest were determined according to national surveys, and then composite sampling and passive sampling were implemented using continuous-flow passive samplers containing two types of sorbents, the Empore disk and Gerstel Twister. Two study sites were established at the beginning and at the end of the middle Bogotá River basin. After 4 days, the sorbents were removed so that they could be desorbed and analyzed using UHPLC-MS in the laboratory. For the composite samples, the results were below the first calibration curve point (FCCP) of the chromatographic method, and for passive sampling, peaks of benzoylecgonine (BE) (21427.3 pg mL-1), methamphetamine (MET) (67101.5 pg mL-1), MDMA (ecstasy) (225844.8 pg mL-1) and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) (15908.4 pg mL-1) were found. Therefore, passive sampling could be suggested as an alternative to composite sampling for the monitoring of compounds.

Research Trends on Pillared Interlayered Clays (PILCs) Used as Catalysts in Environmental and Chemical Processes: Bibliometric Analysis.

Over the last four decades, a large number of studies have been published on pillared interlayered clays (PILCs) used as adsorbent materials and catalysts or supports for transition metals in heterogeneous catalysis. Particularly, PILCs have been used for water treatment through advanced oxidation processes (AOPs) to remove organic pollutants. They have also been studied in various chemical and environmental processes. Because of the growing interest in PILCs, this article is focused on analyzing scientific publications such as research/review articles and book chapters from the last four decades (from 1980 to 2019) through a bibliometric analysis (BA) to visualize and describe research trends on PILCs. By narrowing the bibliographic search to titles, keywords, and abstracts of publications related to PILCs, using Scopus and Web of Science (WoS) (the two scientific databases), a total of 3425 documents have been retrieved. The bibliometric dataset was analyzed by VantagePoint®. The main research trends identified in the last four decades were the use of PILCs in environmental processes (34.4% of total publications) along with chemical processes (petrochemical reactions 17.5%, SCR NOx 10.8%, and decomposition 8.2%). In environmental processes, PILCs have been used in photo-oxidation (32%), CWPO (21.1%), and heterogeneous catalysis (19.4%). Phenols, dyes, and VOCs have been the main pollutants studied using PILCs as catalysts. Fe, Ti, Zr, Cu, and Co are the most supported active phases in PILCs. Other research trends grouped by characterization techniques, countries, research areas, institutes, scientific journals that have published the most on this topic, number of publications per 5-year period, and most frequently used keywords through the last four decades have been identified. It was determined that the number of publications on PILCs has increased since 1980 and the countries with the highest number of publications are China, Spain, and The United States of America.

Decision Making and Interventions During Interfacility Transport of High-Acuity Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

OBJECTIVE: There are limited data regarding the typical characteristics of coronavirus disease 2019 (COVID-19) patients requiring interfacility transport or the clinical capabilities of the out-of-hospital transport clinicians required to provide safe transport. The objective of this study is to provide epidemiologic data and highlight the clinical skill set and decision making needed to transport critically ill COVID-19 patients. METHODS: A retrospective chart review of persons under investigation for COVID-19 transported during the first 6 months of the pandemic by Johns Hopkins Lifeline was performed. Patients who required interfacility transport and tested positive for severe acute respiratory syndrome coronavirus 2 by polymerase chain reaction assay were included in the analysis. RESULTS: Sixty-eight patients (25.4%) required vasopressor support, 35 patients (13.1%) were pharmacologically paralyzed, 15 (5.60%) were prone, and 1 (0.75%) received an inhaled pulmonary vasodilator. At least 1 ventilator setting change occurred for 59 patients (22.0%), and ventilation mode was changed for 11 patients (4.10%) during transport. CONCLUSION: The safe transport of critically ill patients with COVID-19 requires experience with vasopressors, paralytic medications, inhaled vasodilators, prone positioning, and ventilator management. The frequency of initiated critical interventions and ventilator adjustments underscores the tenuous nature of these patients and highlights the importance of transport clinician reassessment, critical thinking, and decision making.

Bibliometric analysis of advanced oxidation processes (AOPs) in wastewater treatment: global and Ibero-American research trends.

Advanced oxidation processes (AOPs) constitute a developing area of particular interest for researchers in different fields due to their broad range of applications. However, there are few studies dedicated to the bibliometric analysis of AOPs. Hence, a systematic literature review of research publications (research articles, review articles, and book chapters) from 1980 to 2018 was carried out to visualize and evaluate research trends on AOPs around the world and, especially in Ibero-America (IA), on the field of wastewater treatment. Using the most extensive databases in literature search, Scopus and Web of Science (WoS), which encompass 95% of the publications in the world, a total of 18,751 records were retrieved by limiting the search results to words associated with AOPs in the titles, keyword, and abstracts. Raw data were manually organized and filtered, standardizing authors and institution names, publication titles, and keywords for the purpose of eliminating double-counted entries. Similarly, homonymous authors and institutions were identified for all records retrieved. The bibliometric dataset was processed using the VantagePoint software. The research trends visualized about AOPs were as follows: number of publications per triennium, publications by country, participation by continent, most important journals and authors, most referenced institutions, global network of co-authors, and keywords network visualization, highlighting the Ibero-American contribution to global research.

Comparación del tiempo de rotura de la película lagrimal entre el topógrafo corneal y la técnica con fluoresceína, y su correlación con el cuestionario OSDI / Comparison of the tear break time between the corneal topography and the technique with fluoresceine, and its correlation with the OSDI questionnaire

Introducción: El síndrome de ojo seco es una enfermedad subdiagnosticada. El método diagnóstico más utilizado es la medición del tiempo de rotura de la lágrima con fluoresceína (TRLf). Sin embargo, no hay una prueba de referencia.­ Objetivo: Estimar la correlación del TRLf y el tiempo de rotura lagrimal no invasivo (TRLNI) con el puntaje del cuestionario OSDI (Ocular Surface Disease Index). Método: Estudio transversal. Se incluyeron 60 ojos de 30 pacientes mayores de edad que asistían a consulta de oftalmología en una clínica especializada de Cali, Colombia. Se recolectó por medio del cuestionario OSDI la sintomatología asociada y se tomó el TRLNI con el topógrafo corneal por personal calificado. El TRLf se tomó de la historia clínica. Se realizaron correlaciones con método de Kendall, Kappa y Spearman. Resultados: La mediana del TRLf para el ojo derecho (OD) fue de 15.2 s (6.4-22.4) y para el ojo izquierdo (OI) de 15.3 s (6.2-22.6). La mediana del TRLNI para el OD fue de 7.5 s (2.6-17.7) y para el OI de 6.7 s (1.4-17.1). El 36.6% de los pacientes presentaron TRLf < 10 s y el 70.0% por TRLNI. El coeficiente de correlación de Kendall mostró OD tau-b 0,2966 y OI tau-b 0,3065. La correlación del puntaje OSDI y el tiempo de rotura de la lágrima fue negativa, pero no significativa. Conclusiones: El TRLNI fue más corto que el TRLf. La correlación del puntaje del cuestionario OSDI fue moderada para ambos métodos.

Introduction: Dry eye syndrome is a sub diagnose disease. The diagnostic method most commonly used is the fluorescein tear break up time (fBUT). However, there is no gold test. Objective: To estimate the correlation of fBUT, non-invasive tear break up time (NIBUT) and with the score of the Ocular Surface Disease Index (OSDI). Method: Cross-sectional study. 60 eyes of 30 adult patients attending an ophthalmology clinic in Cali, Colombia were included. The associated symptomatology was collected through the OSDI questionnaire and the NIBUT was taken with the corneal topograph by qualified personnel. The fBUT was taken from the medical records. Correlations were made with the method of Kendall, Kappa and Spearman. Results: The median fBUT for the right eye (OD): 15.2 (6.4-22.4 s) and left eye (OS): 15.3 (6.2-22.6). The median of the TRLNI of the OD:7.5 (2.6-17.7 s) and OS 6.7 (1.4-17.1 s). 36.6% of the patients presented fBUT < 10 s and 70.0% due to NIBUT. The Kendall correlation coefficient showed OD: tau-b: 0.2966 and OS: tau-b: 0.3065. The correlation of the OSDI score and tear break time was negative but not significant. Conclusions: NIBUT had shorter tear film rupture time compared to the fluorescein method. The correlation of OSDI questionnaire score was moderate for both methods.

Características de pacientes con desgarros de retina que requirieron fotocoagulación láser en la Clínica de Oftalmología de Cali (2015-2016) / Characteristics of patients with retina trears that required laser photocoagulation in Clínica de Oftalmología de Cali (2015-2016)

Introducción: Entre las causas más frecuentes de disminución de la agudeza visual no reversible está el desprendimiento de retina regmatógeno causado por un desgarro previo. Objetivo: Caracterizar la población con desprendimiento de vítreo posterior (DVP) y desgarros de retina tratados con lasér, y describir sus caracteristicas clínicas y los resultados en el contexto local en una clínica de Cali, Colombia. Método: Historias clínicas de pacientes adultos con DVP no traumático y desgarros de retina sometidos a fotocoagulación láser entre enero de 2015 y julio de 2018. Se recolectaron las características clínicas, los antecedentes patológicos y los resultados. Se hizo un análisis descriptivo de la información. Resultados: Un total de 194 ojos de 184 pacientes, el 52% de sexo masculino, con una mediana de edad de 60 años. Los sintomas se presentaron en el 21% de la población y los desgarros fueron herradura, de ubicacion superotemporal y con hemorragia vítrea en su mayoria. Requirieron retratamiento el 8.7% de los pacientes, los cuales fueron en su mayoría hombres (81.2%), mayores de 60 años, con mayor frecuencia de miopía y hemorragia vítrea en un 62.5%. Conclusiones: La descripción de las características clínicas de la población adulta con DVP y desgarros de retina, sometida a fotocoagulación láser en Cali, Colombia, fue similar a la reportada en la literatura.

Introduction: Among the most frequent causes of non-reversible decreased visual acuity is regmatogenous retinal detachment caused by a previous tear. Objective: To characterize the population with posterior vitreous derangement (PVD) and retinal tears treated with which to describe the clinical characteristics and the results in the local context in a clinic in Cali, Colombia. Method: Clinical records of adult patients with nontraumatic PVD and retinal tears undergoing laser photocoagulation between January 2015 and July 2018. Clinical characteristics, pathological antecedents and results were collected. A descriptive analysis of the information was made. Results: A total of 184 patients and 194 eyes with a median age of 60 years male sex in 52%. Symptoms occurred in 21% of the population and the tears were horseshoe, with a super-temporal location and mostly vitreous hemorrhage. Retention withdrawal 8.7% of patients, who were men 81.2%, older than 60 years, with more frequency of myopia and vitreous hemorrhage in 62.5%. Conclusions: Description of the clinical characteristics of the adult population with PVD and retinal tears, subjected to laser photocoagulation in Cali, Colombia, was similar to the one reported in the literature

Pediatric Hospitalizations: Are We Missing an Opportunity to Immunize?

OBJECTIVES: Fewer than half of children receive all recommended immunizations on time. Hospitalizations may be opportunities to address delayed immunizations. Our objectives were to assess (1) prevalence of delayed immunizations among hospitalized patients, (2) missed opportunities to administer delayed immunizations, and (3) time to catch up after discharge. METHODS: We conducted a retrospective cohort study investigating immunization status of patients 0 to 21 years of age admitted to an academic children's center from 2012 to 2013 at the time of admission, at discharge, and 18 months postdischarge. Immunization catch-up at 18 months postdischarge was defined as having received immunizations due on discharge per Centers for Disease Control and Prevention recommendations. χ2 and t test analyses compared characteristics among patients caught up and not caught up at 18 months postdischarge. Analysis of variance and logistic regression analyses compared mean number of immunizations needed and odds of immunization catch-up among age groups. Kaplan-Meier and Cox proportional hazards analyses compared catch-up time by age, race, sex, and insurance. RESULTS: Among 166 hospitalized patients, 80 were not up to date on immunizations at admission, and only 1 received catch-up immunizations before discharge. Ninety-nine percent (79 of 80) were not up to date on discharge per Centers for Disease Control and Prevention recommendations. Thirty percent (24 of 79), mostly adolescents, were not caught up at 18 months postdischarge. Median postdischarge catch-up time was 3.5 months (range: 0.03-18.0 months). Patients 0 to 35 months of age were more likely to catch up compared with those of other ages (hazard ratio = 2.73; P = .001), with no differences seen when comparing race, sex, or insurance. CONCLUSIONS: Pediatric hospitalizations provide important opportunities to screen and immunize children.

Nuclear Receptor Corepressor 1 Expression and Output Declines with Prostate Cancer Progression.

PURPOSE: Castration therapy in advanced prostate cancer eventually fails and leads to the development of castration-resistant prostate cancer (CRPC), which has no cure. Characteristic features of CRPC can be increased androgen receptor (AR) expression and altered transcriptional output. We investigated the expression of nuclear receptor corepressor 1 (NCOR1) in human prostate and prostate cancer and the role of NCOR1 in response to antiandrogens. EXPERIMENTAL DESIGN: NCOR1 protein levels were compared between matched normal prostate and prostate cancer in 409 patient samples. NCOR1 knockdown was used to investigate its effect on bicalutamide response in androgen-dependent prostate cancer cell lines and transcriptional changes associated with the loss of NCOR1. NCOR1 transcriptional signature was also examined in prostate cancer gene expression datasets. RESULTS: NCOR1 protein was detected in cytoplasm and nuclei of secretory epithelial cells in normal prostate. Both cytoplasmic and nuclear NCOR1 protein levels were lower in prostate cancer than in normal prostate. Prostate cancer metastases show significant decrease in NCOR1 transcriptional output. Inhibition of LNCaP cellular proliferation by bicalutamide requires NCOR1. NCOR1-regulated genes suppress cellular proliferation and mediate bicalutamide resistance. In the mouse, NCOR1 is required for bicalutamide-dependent regulation of a subset of the AR target genes. CONCLUSIONS: In summary, we demonstrated that NCOR1 function declines with prostate cancer progression. Reduction in NCOR1 levels causes bicalutamide resistance in LNCaP cells and compromises response to bicalutamide in mouse prostate in vivo Clin Cancer Res; 22(15); 3937-49. ©2016 AACR.

INPP4B suppresses prostate cancer cell invasion.

BACKGROUND: INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer. RESULTS: We demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine IL-8 and induced PAK6. These genes were regulated in a reciprocal manner following downregulation of INPP4B in the independently derived INPP4B-positive LNCaP prostate cancer cell line. Inhibition of PI3K/Akt pathway, which is highly active in both PC-3 and LNCaP cells, did not reproduce INPP4B mediated suppression of IL-8 mRNA expression in either cell type. In contrast, inhibition of PKC signaling phenocopied INPP4B-mediated inhibitory effect on IL-8 in either prostate cancer cell line. In PC-3 cells, INPP4B overexpression caused a decline in the level of metastases associated BIRC5 protein, phosphorylation of PKC, and expression of the common PKC and IL-8 downstream target, COX-2. Reciprocally, COX-2 expression was increased in LNCaP cells following depletion of endogenous INPP4B. CONCLUSION: Taken together, we discovered that INPP4B is a novel suppressor of oncogenic PKC signaling, further emphasizing the role of INPP4B in maintaining normal physiology of the prostate epithelium and suppressing metastatic potential of prostate tumors.

Determinants of the tumor suppressor INPP4B protein and lipid phosphatase activities.

The tumor suppressor INPP4B is an important regulator of phosphatidyl-inositol signaling in the cell. Reduced INPP4B expression is associated with poor outcomes for breast, prostate, and ovarian cancer patients. INPP4B contains a CX5R catalytic motif characteristic of dual-specificity phosphatases, such as PTEN. Lipid phosphatase activity of INPP4B has previously been described. In this report we show that INPP4B can dephosphorylate para-nitrophenyl phosphate (pNPP) and 6,8-difluoro-4-methylumbelliferyl (DiFMUP), synthetic phosphotyrosine analogs, suggesting that INPP4B has protein tyrosine phosphatase (PTP) activity. Using mutagenesis, we examined the functional role of specific amino acids within the INPP4B C842KSAKDR catalytic site. The K843M mutant displayed increased pNPP hydrolysis, the K846M mutant lost lipid phosphatase activity with no effect on PTP activity, and the D847E substitution ablated PTP activity and significantly reduced lipid phosphatase activity. Further, we show that INPP4B but not PTEN is able to reduce tyrosine phosphorylation of Akt1 and both the lipid and PTP activity of INPP4B likely contribute to the reduction of Akt1 phosphorylation. Taken together our data identified key residues in the INPP4B catalytic domain associated with lipid and protein phosphatase activities and found a robust downstream target regulated by INPP4B but not PTEN.

[Impact of the intra-aortic balloon pump in the mortality due to cardiogenic shock secondary to acute myocardial infarction]. / Impacto del balón intra-aórtico de contrapulsación en la mortalidad por choque cardiogénico secundario a infarto agudo del miocardio.

OBJECTIVE: To determine the impact of the intra-aortic balloon pump in the mortality due to cardiogenic shock post-acute myocardial infarction. METHODS: In a two-year period, 292 patients with acute myocardial infarction were admitted to the coronary intensive care unit, 40 were included in the study. Afterwards, patients were divided in two groups: early cardiogenic and late cardiogenic shock, and they were assigned randomly and blind to treatment with inotropics and inotropics plus intra-aortic balloon pump. RESULTS: There were significant differences in the measurements of pulmonary wedge pressure (20.4 +/- 1.6 vs 24.4 +/- 1.50, p = 0.0004) and the cardiac index (2.06 +/- 0.7 vs 1.65 +/- 0.18, p = 0.0002) between the two groups. The late cardiogenic shock group showed an increased mortality (25.9% vs 61.5%, p < 0.05). Patients treated with inotropics + balloon, in both early and late shock groups, showed a reduction in mortality of 66% and 69%, respectively. CONCLUSIONS: The use of the intra-aortic balloon pump in the treatment of cardiogenic shock post acute myocardial infarction reduces the mortality when associated with the use of inotropics and reperfusion.