Favorable Radiographic Response in a Patient With an Oligodendroglioma Treated With Azacitidine and Venetoclax for Acute Myeloid Leukemia.

The standard chemotherapy for treating oligodendrogliomas consists of a combination of procarbazine, lomustine, and vincristine (PCV). The combination of hypomethylating agents like azacitidine and BCL2 inhibitors like venetoclax has not been formally studied in the treatment of glial tumors. The combination of these two drugs is commonly used to treat acute myeloid leukemia (AML), with IDH-mutant disease being a particularly sensitive subtype. The use of azacitidine for the treatment of IDH-mutant gliomas has been reported in the literature, with mixed results that might suggest at least some benefits in a subtype of patients. It is also reported in the literature that the BCL2 gene is associated with treatment resistance and tumor recurrence in gliomas. Here, we present a patient with an oligodendroglioma who was treated with a conventional chemotherapy regimen for AML and, at the same time, had a favorable radiographic response to his brain tumor.

Critical Care Nurses' Perceptions of Abuse and Its Impact on Healthy Work Environments in Five European Countries: A Cross-Sectional Study.

Objective: Workplace violence is a prevalent phenomenon in hospital settings which critical care nurses are particularly exposed to. The aim of this study was to research abuse against Critical Care Nurses in five European countries, and its association with and impact on Healthy Work Environments. Methods: This was a multinational cross-sectional study. The 1,183 participants were nurses working in intensive care units from five European countries: Croatia, Cyprus, Poland, Spain, and Romania. The participants were selected by the convenience sampling method from 1 January 2021 to April 2022. Results: Of 1,033 critical care nurses who answered questions about abuse, 646 reported at least one incident in the previous year. The highest number of incidents came from patients (2,050), followed by another nurse (1,453) and physicians (1,039). Conclusion: Although nurses in ICUs are aware that a healthy working environment benefits them in their daily work, most of them still face some form of abuse. Organizations must take a realistic approach to prevent abuse and to educate nurses and nurse managers by implementing standards for healthy work environments.

A new role for erythropoietin in the homeostasis of red blood cells.

The regulation of red blood cell (RBC) homeostasis is widely assumed to rely on the control of cell production by erythropoietin (EPO) and the destruction of cells at a fixed, species-specific age. In this work, we show that such a regulatory mechanism would be a poor homeostatic solution to satisfy the changing needs of the body. Effective homeostatic control would require RBC lifespan to be variable and tightly regulated. We suggest that EPO may control RBC lifespan by determining CD47 expression in newly formed RBCs and SIRP-α expression in sinusoidal macrophages. EPO could also regulate the initiation and intensity of anti-RBC autoimmune responses that curtail RBC lifespan in some circumstances. These mechanisms would continuously modulate the rate of RBC destruction depending on oxygen availability. The control of RBC lifespan by EPO and autoimmunity emerges as a key mechanism in the homeostasis of RBCs.

Evaluation of a blended training solution for critical care nurses' work environment: Lessons learned from focus groups in four European countries.

AIM: The aim of this study was to evaluate a blended pilot training course on Healthy Work Environments (HWEs) for critical care nurses as follows: 1) to explore the experience of trainees and trainers who took part in the training; and 2) to identify the strengths and weaknesses of the training program in its potential transferability to nursing practice in Intensive Care Units (ICUs). BACKGROUND: Despite the evidence supporting the association between HWEs and job satisfaction, nursing retention, and patient outcomes, nurses still have high rates of burnout, mental health problems and intent to leave. To address this challenge, a blended training was created and piloted with the aim to highlight the relevance and impact of HWEs, enhancing its transferability to daily practice. The training was based on the six standards of HWEs as proposed by the American Association of Critical Care Nurses and created within an Erasmus + project. The pilot was delivered by trainers (critical care nursing educators) to critical care nurses and included six workshops of eight hours each (48 h in total) in each country. DESIGN: After the pilot testing, a qualitative approach, with focus group discussions was used. METHODS: All the trainees (n=82), who had attended at least one workshop were invited to participate in the focus groups. Overall, eight focus groups were held with critical care nurses who participated as trainees (n=39) from four testing countries: Cyprus, Croatia, Spain and Poland. One international focus group was held with trainers who conducted the training (n=4). Four more trainers completed the questionnaire online. All focus group were video recorded, and transcribed verbatim. Then, the national transcripts were translated into English. An inductive thematic analysis was carried out. FINDINGS: Three themes were identified: 1) Valuing the relevance of the training program and a positive learning experience; 2) A powerful insight leading to increased awareness and empowerment in personal and professional life; 3) Challenges identified in terms of training, follow up and management of change. Both trainees and trainers expressed a positive opinion with regard to the content of the training and the didactic methods used. They emphasized the strong influence of the training on their understanding of a HWEs, its impact in an ICU context and the need for action, mainly related to communication issues. CONCLUSION: The proposed blended training program may be used by trainers, who can enable nurses develop the competencies required to influence their work environment, in a context of shared responsibility.

The coordination of anti-phage immunity mechanisms in bacterial cells.

Bacterial cells are equipped with a variety of immune strategies to fight bacteriophage infections. Such strategies include unspecific mechanisms directed against any phage infecting the cell, ranging from the identification and cleavage of the viral DNA by restriction nucleases (restriction-modification systems) to the suicidal death of infected host cells (abortive infection, Abi). In addition, CRISPR-Cas systems generate an immune memory that targets specific phages in case of reinfection. However, the timing and coordination of different antiviral systems in bacterial cells are poorly understood. Here, we use simple mathematical models of immune responses in individual bacterial cells to propose that the intracellular dynamics of phage infections are key to addressing these questions. Our models suggest that the rates of viral DNA replication and cleavage inside host cells define functional categories of phages that differ in their susceptibility to bacterial anti-phage mechanisms, which could give raise to alternative phage strategies to escape bacterial immunity. From this viewpoint, the combined action of diverse bacterial defenses would be necessary to reduce the chances of phage immune evasion. The decision of individual infected cells to undergo suicidal cell death or to incorporate new phage sequences into their immune memory would be determined by dynamic interactions between the host's immune mechanisms and the phage DNA. Our work highlights the importance of within-cell dynamics to understand bacterial immunity, and formulates hypotheses that may inspire future research in this area.

Cancer Biomarkers in Liquid Biopsy for Early Detection of Breast Cancer: A Systematic Review.

Background: Breast cancer (BC) is the most common neoplasm in women worldwide. Liquid biopsy (LB) is a non-invasive diagnostic technique that allows the analysis of biomarkers in different body fluids, particularly in peripheral blood and also in urine, saliva, nipple discharge, volatile respiratory fluids, nasal secretions, breast milk, and tears. The objective was to analyze the available evidence related to the use of biomarkers obtained by LB for the early diagnosis of BC. Methods: Articles related to the use of biomarkers for the early diagnosis of BC due to LB, published between 2010 and 2022, from the databases (WoS, EMBASE, PubMed, and SCOPUS) were included. The MInCir diagnostic scale was applied in the articles to determine their methodological quality (MQ). Descriptive statistics were used, as well as determination of weighted averages of each variable, to analyze the extracted data. Sensitivity, specificity, and area under the curve values for specific biomarkers (individual or in panels) are described. Results: In this systematic review (SR), 136 articles met the selection criteria, representing 17 709 patients with BC. However, 95.6% were case-control studies. In 96.3% of cases, LB was performed in peripheral blood samples. Most of the articles were based on microRNA (miRNA) analysis. The mean MQ score was 25/45 points. Sensitivity, specificity, and area under the curve values for specific biomarkers (individual or in panels) have been found. Conclusions: The determination of biomarkers through LB is a useful mechanism for the diagnosis of BC. The analysis of miRNA in peripheral blood is the most studied methodology. Our results indicate that LB has a high sensitivity and specificity for the diagnosis of BC, especially in early stages.

In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study.

Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis. Objective: The aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida. Methods: Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated. Results: Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC50s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis. Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida.

Assessing Nursing Students' Self-Perceptions about Safe Medication Management: Design and Validation of a Tool, the NURSPeM.

OBJECTIVE: The objective was to design and validate a tool for assessing nursing students' self-perceptions about safe medication management. METHODS: A descriptive instrumental study was conducted involving construct definition, development of the tool, analysis of the content validity, and psychometric evaluation. Consensus regarding the content was obtained through a two-round Delphi process, and the resulting tool (the NURSPeM) was administered to nursing students to examine its internal consistency, temporal stability, and construct validity, the latter through exploratory factor analysis. RESULTS: Thirteen experts participated in the Delphi process, which yielded a tool comprising two questionnaires: (1) Self-perceptions about safe medication management (27 items) and (2) the frequency and learning of drug-dose calculation (13 items). The tool's psychometric properties were then examined based on responses from 559 nursing students. This analysis led to the elimination of three items from questionnaire 1, leaving a total of 24 items distributed across seven dimensions. All 13 items in questionnaire 2 were retained. Both questionnaires showed good internal consistency (Cronbach's alpha = 0.894 and 0.893, respectively) and temporal stability (ICC = 0.894 and 0.846, respectively). CONCLUSIONS: The NURSPeM is a valid and reliable tool for assessing nursing students' self-perceptions about safe medication management. It may be used to identify areas in which their training needs to be enhanced, and to evaluate the subsequent impact of new teaching initiatives.

In vitro and in vivo anti-Candida activity of citral in combination with fluconazole.

BACKGROUND: The ability of Candida to develop biofilms on inert surfaces or living tissues favors recalcitrant and chronic candidiasis associated, in many instances, with resistance to current antifungal therapy. AIM: The aim of this study was to evaluate the antifungal activity of citral, a phytocompound present in lemongrass essential oil, in monotherapy and combined with fluconazole against azole-resistant Candida planktonic cells and biofilms. The effect of citral combined with fluconazole was also analysed with regard to the expression of fluconazole resistance-associated genes in Candida albicans and the effectiveness of the combination therapy in a Caenorhabditis elegans model of candidiasis. RESULTS: Citral reduced biofilm formation at initial stages and the metabolic activity of the mature biofilm. The combination of citral with fluconazole was synergistic, with a significant increase in the survival of C. elegans infected with Candida. RNA analysis revealed a reduction of the expression of the efflux pump encoded by MDR1, leading to a greater effect of fluconazole. CONCLUSION: Citral in monotherapy and in combination with fluconazole could represent an interesting therapy to treat recalcitrant Candida infections associated to biofilms.

Killing the competition: a theoretical framework for liver-stage malaria.

The first stage of malaria infections takes place inside the host's hepatocytes. Remarkably, Plasmodium parasites do not infect hepatocytes immediately after reaching the liver. Instead, they migrate through several hepatocytes before infecting their definitive host cells, thus increasing their chances of immune destruction. Considering that malaria can proceed normally without cell traversal, this is indeed a puzzling behaviour. In fact, the role of hepatocyte traversal remains unknown to date, implying that the current understanding of malaria is incomplete. In this work, we hypothesize that the parasites traverse hepatocytes to actively trigger an immune response in the host. This behaviour would be part of a strategy of superinfection exclusion aimed to reduce intraspecific competition during the blood stage of the infection. Based on this hypothesis, we formulate a comprehensive theory of liver-stage malaria that integrates all the available knowledge about the infection. The interest of this new paradigm is not merely theoretical. It highlights major issues in the current empirical approach to the study of Plasmodium and suggests new strategies to fight malaria.

Clinical utility of liquid biopsy in breast cancer: A systematic review.

Advancements in genetic sequencing techniques along with the identification of specific mutations and structural changes in multiple cancer genes, make it possible to identify circulating tumor cells and cell free nucleic acids as blood-based biomarkers, serving as a liquid biopsy (LB) with great utility for the diagnosis, treatment and follow-up of patients with neoplasms. This systematic review focuses on the clinical utility of LB in patients with breast cancer (BC). Articles published between 1990 and 2021 were included. Databases searched: Trip Database, WoS, EMBASE, PubMed, SCOPUS, and Clinical Keys. Variables studied: Publication year, country, number of cases, primary study design, LB detection methods, genes found, overall survival, disease-free survival, stage, response to treatment, clinical utility, BC molecular type, systemic treatment and methodological quality of primary studies. Of 2619 articles, 74 were retained representing 12 658 patients, mainly cohort studies (66.2%), the majority were from China (15%) and Japan (12.2%). All primary studies described clinical stage and type of systemic treatment used. Most used biomarker detection method: DNA (52.7%) and type of analysis: quantification of total cfDNA (35.1%). PIK3CA mutation was most frequent (62.9%). Evidence suggests clinically useful applications of BC. Though heterogeneous, publications suggest that LB will constitute part of the standard diagnostic-therapeutic process of BC.

Retinal Protection from LED-Backlit Screen Lights by Short Wavelength Absorption Filters.

(1) Background: Ocular exposure to intense light or long-time exposure to low-intensity short-wavelength lights may cause eye injury. Excessive levels of blue light induce photochemical damage to the retinal pigment and degeneration of photoreceptors of the outer segments. Currently, people spend a lot of time watching LED screens that emit high proportions of blue light. This study aims to assess the effects of light emitted by LED tablet screens on pigmented rat retinas with and without optical filters. (2) Methods: Commercially available tablets were used for exposure experiments on three groups of rats. One was exposed to tablet screens, the other was exposed to the tablet screens with a selective filter and the other was a control group. Structure, gene expression (including life/death, extracellular matrix degradation, growth factors, and oxidative stress related genes), and immunohistochemistry in the retina were compared among groups. (3) Results: There was a reduction of the thickness of the external nuclear layer and changes in the genes involved in cell survival and death, extracellular matrix turnover, growth factors, inflammation, and oxidative stress, leading decrease in cell density and retinal damage in the first group. Modulation of gene changes was observed when the LED light of screens was modified with an optical filter. (4) Conclusions: The use of short-wavelength selective filters on the screens contribute to reduce LED light-induced damage in the rat retina.

In vitro activities of carvacrol, cinnamaldehyde and thymol against Candida biofilms.

Oral candidiasis is frequently associated with Candida biofilms. Biofilms are microbial communities related to persistent, recalcitrant and difficult to-treat infections. Conventional treatments are not sufficient to overcome biofilm-associated candidiasis; thus, the search of new antifungal compounds is necessary. In the current study, we have evaluated the effect of three phytocompounds, carvacrol, cinnamaldehyde and thymol, against Candida planktonic and sessile cells. Reduction in biofilm biomass and metabolic activity was assessed during adhesion and mature biofilm phases. Candida albicans was the most biofilm-producing Candida species. All phytocompounds tested were fungicidal against Candida planktonic cells. Cinnamaldehyde was the most active in inhibiting biofilm adhesion, but carvacrol and thymol significantly reduced both mature biofilm biomass and metabolic activity. These results highlight the role of cinnamaldehyde, carvacrol and thymol as promising alternatives for the treatment of candidiasis due to their antibiofilm capacities, and stress the necessity to continue studies on their safety, toxicity and pharmacodynamics and pharmacokinetics.

Isquemia mesentérica no oclusiva tras revascularización escalonada de troncos viscerales y miembros inferiores / Non-occlusive mesenteric ischemia after staged revascularization of visceral trunks and lower extremities

Introducción:la isquemia mesentérica crónica (IMC) es una patología con alta morbimortalidad. La revascularización puede plantearse de forma escalonada con el fin de mejorar el estado nutricional del paciente. La isquemia no oclusiva es un tipo de isquemia mesentérica aguda que con frecuencia se manifiesta en el posoperatorio de una cirugía mayor o como complicación en un paciente crítico.Caso clínico:presentamos el caso de una paciente con IMC e isquemia crítica de miembros inferiores por enfermedad obstructiva aortoiliaca en el que se planteó una revascularización en dos tiempos. La paciente tuvo un posoperatorio tórpido como consecuencia de una isquemia mesentérica no oclusiva con desenlace fatal.Discusión:la isquemia mesentérica no oclusiva es un tipo de isquemia mesentérica aguda que puede manifestarse con dos tipos de patrones: bien en el contexto de una hipoperfusión sistémica, o bien en el de una hipoperfusión intestinal tras un evento precipitante como una intervención quirúrgica. El diagnóstico y tratamiento precoces son imprescindibles para intentar reducir unas tasas de mortalidad que alcanza el 70-90 % de los casos. El tratamiento endovascular es con frecuencia la primera elección aunque la cirugía abierta todavía juega un rol importante en casos de enfermedad extensa.(AU)

Introduction:chronic mesenteric ischemia (CMI) is a pathology with high morbidity and mortality rates since it’s usually associated with severe systemic arteriosclerosis. Revascularization of visceral trunks can be staggered in order to improve the nutritional status of the patient. Non-occlusive mesenteric ischemia is a type of acute mesenteric ischemia that frequently occurs in the postoperative period of major surgery or as a complication in critical patients.Case report:we present the case of a female patient with chronic mesenteric ischemia and critical ischemia of the lower limbs due to aortoiliac disease in which two-staged revascularization was performed. The patient had a torpid postoperative period as a result of a non-occlusive mesenteric ischemia which led to a fatal outcome.Discussion:non-occlusive mesenteric ischemia is a type of acute mesenteric ischemia that can occur in two contexts: either in a systemic hypoperfusion, or in the context of intestinal hypoperfusion after a precipitating event such as a surgical intervention. Diagnosis and early treatment are essential to trying to reduce mortality rates that reach 70-90 % of the cases. Endovascular treatment is often the first choice although bypass surgery still plays an important role in cases of extensive disease.(AU)

Acute arterial ischemia in COVID-19.

Since the coronavirus pandemic set in in Spain in March 2020, a noteworthy increase in the incidence of acute limb ischemia (ALI) has been observed. It has been recently discovered that SARS-CoV 2 may lead to ALI secondary to arterial thrombosis. Elevation of D-dimer (DD) in patients with coronavirus infection (COVID-19) indicates that a hypercoagulable state causes acute arterial thrombosis. A remarkably high DD elevation has been reported to be a poor prognosis factor in COVID-19. The ways in which SARS-CoV 2 results in arterial thrombosis may be multiple. On the other hand, surgical revascularization for ALI is associated with poor outcomes in COVID-19 patients, probably in relation to hypercoagulability. Here, we describe two ALI cases in patients who required urgent surgical treatment for limb salvage and were positive for the novel coronavirus infection (COVID 19).

Desde que a pandemia pelo novo coronavírus se estabeleceu na Espanha, em março de 2020, um aumento notável da incidência de isquemia aguda de membros foi observado. Recentemente, descobriu-se que o coronavírus 2 causador da síndrome respiratória aguda grave (SARS-CoV-2) pode ocasionar isquemia aguda de membros secundária à trombose arterial. A elevação do D-dímero em pacientes acometidos pela doença do novo coronavírus (COVID-19) indica o estado de hipercoagulabilidade como causa da trombose arterial aguda. Vale destacar que a alta elevação do D-dímero foi relatada como um fator de prognóstico reservado na COVID-19. Há diversas maneiras pelas quais o SARS-CoV-2 pode resultar em trombose arterial. Em pacientes com COVID-19, a revascularização cirúrgica para isquemia aguda de membros está associada a desfechos desfavoráveis, provavelmente relacionados a hipercoagulabilidade. Descrevemos dois casos de isquemia aguda de membros de pacientes que necessitaram de tratamento cirúrgico de urgência para salvamento de membro e que haviam testado positivo para COVID-19.

Nursing students on the frontline: Impact and personal and professional gains of joining the health care workforce during the COVID-19 pandemic in Spain.

BACKGROUND: Final-year nursing students in Spain augmented the health care workforce during the COVID-19 pandemic. PURPOSE: To understand the lived experience of nursing students who joined the health care workforce during the first wave of the COVID-19 outbreak (March-May 2020). METHOD: Qualitative content analysis of the reflective journals of 40 nursing students in Spain. FINDINGS: The analysis identified four main themes: 1) Willingness to help; 2) Safety and protective measures: Impact and challenges; 3) Overwhelming experience: Becoming aware of the magnitude of the epidemic; and 4) Learning and growth. DISCUSSION: The wish to help, the sense of moral duty, and the opportunity to learn buffered the impact of the students' lived experience. Despite the challenges they faced, they saw their experiences as a source of personal and professional growth, and they felt reaffirmed in their choice of career. Promoting opportunities for reflection and implementing adequate support and training strategies is crucial for building a nursing workforce that is capable of responding to future health crises.

Development of a Method to Potentially Substitute Direct Evaluation of Mesopic Visual Acuity in Drivers.

(1) Background: In mesopic lighting conditions, or under adverse environmental circumstances, visual information is reduced, which increases the risk of traffic accidents. This effect could be reduced with a precise evaluation of the visual function under mesopic conditions, but it is difficult to replicate in clinics. This study aims to develop an easy-to-adopt method to evaluate mesopic visual acuity (VA) in drivers. (2) Methods: Prospective and observational study in drivers. logMAR mesopic VA was compared with photopic VA measured under different combinations of contrast charts and filters to find the combination that responds best to mesopic conditions. (3) Results: Fifty-six drivers were examined. The best correlation was found with an 80% density filter and a Weber contrast chart of 20%. The logMAR VA for this combination was 0.01 ± 0.11, which was close to the mesopic VA values (0.01 ± 0.12). The difference between both logMAR VA was 0.00 ± 0.06 (R = 0.86; p ≤ 0.001; ICC = 0.86). (4) Conclusions: The use of 20% contrast optotypes and the interposition of an 80% filter under photopic conditions provide VA values similar to those measured under mesopic lighting conditions, making this simple system a good predictor of mesopic VA values.