Challenges for palliative care in times of COVID-19: a scoping review.

Introduction: Many of the essential practices in palliative care (PC) had to be adapted to the COVID-19 pandemic. This global spread of the infectious respiratory disease, caused by SARS-CoV-2, created unprecedented obstacles. The aim of this research was to comprehensively assess the experiences and perceptions of healthcare professionals, individuals, and families in palliative and end-of-life situations during the COVID-19 pandemic. Methods: A scoping review was conducted using the databases CINAHL Complete, MEDLINE, Scopus, SciELO, Cochrane Central Register of Controlled Trials, Psychology and Behavioral Sciences, MEDIClatina, and Portugal's Open Access Scientific Repository. The review followed the JBI® methodological approach for scoping reviews. Results: Out of the initially identified 999 articles, 22 studies were included for analysis. The deprivation of relationships due to the safety protocols required to control the spread of COVID-19 was a universally perceived experience by healthcare professionals, individuals in PC, and their families. Social isolation, with significant psychological impact, including depersonalization and despair, was among the most frequently reported experiences by individuals in palliative situation. Despite healthcare professionals' efforts to mitigate the lack of relationships, the families of these individuals emphasized the irreplaceability of in-person bedside contact. Systematic review registration: https://osf.io/xmpf2/.

Prioritization of genes for translation: a computational approach.

INTRODUCTION: Gene identification for genetic diseases is critical for the development of new diagnostic approaches and personalized treatment options. Prioritization of gene translation is an important consideration in the molecular biology field, allowing researchers to focus on the most promising candidates for further investigation. AREAS COVERED: In this paper, we discussed different approaches to prioritize genes for translation, including the use of computational tools and machine learning algorithms, as well as experimental techniques such as knockdown and overexpression studies. We also explored the potential biases and limitations of these approaches and proposed strategies to improve the accuracy and reliability of gene prioritization methods. Although numerous computational methods have been developed for this purpose, there is a need for computational methods that incorporate tissue-specific information to enable more accurate prioritization of candidate genes. Such methods should provide tissue-specific predictions, insights into underlying disease mechanisms, and more accurate prioritization of genes. EXPERT OPINION: Using advanced computational tools and machine learning algorithms to prioritize genes, we can identify potential targets for therapeutic intervention of complex diseases. This represents an up-and-coming method for drug development and personalized medicine.

Evaluation of Mitochondrial Phagy (Mitophagy) in Human Non-small Adenocarcinoma Tumor Cells.

Non-small cell lung cancer (NSCLC) is a predominant form of lung cancer characterized by its aggressive nature and high mortality rate, primarily due to late-stage diagnosis and metastatic spread. Recent studies underscore the pivotal role of mitophagy, a selective form of autophagy targeting damaged or superfluous mitochondria, in cancer biology, including NSCLC. Mitophagy regulation may influence cancer cell survival, proliferation, and metastasis by modulating mitochondrial quality and cellular energy homeostasis. Herein, we present a comprehensive methodology developed in our laboratory for the evaluation of mitophagy in NSCLC tumor cells. Utilizing a combination of immunoblotting, immunocytochemistry, and fluorescent microscopy, we detail the steps to quantify early and late mitophagy markers and mitochondrial dynamics. Our findings highlight the potential of targeting mitophagy pathways as a novel therapeutic strategy in NSCLC, offering insights into the complex interplay between mitochondrial dysfunction and tumor progression. This study not only sheds light on the significance of mitophagy in NSCLC but also establishes a foundational approach for its investigation, paving way for future research in this critical area of cancer biology.

The NDV-MLS as an Immunotherapeutic Strategy for Breast Cancer: Proof of Concept in Female Companion Dogs with Spontaneous Mammary Cancer.

The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease virus (NDV) shows oncolytic activity, as well as immune modulating potential, in the treatment of breast cancer in vitro and in vivo; however, its potential to enhance tumor-infiltrating immune cells in breast cancer has yet to be evaluated. Since spontaneous canine mammary tumors represent a translational model of human breast cancer, we conducted this proof-of-concept study, which could provide a rationale for further investigating NDV-MLS as immunotherapy for mammary cancer. Six female companion dogs with spontaneous mammary cancer received a single intravenous and intratumoral injection of oncolytic NDV-MLS. Immune cell infiltrates were evaluated by histology and immunohistochemistry in the stromal, intratumoral, and peritumoral compartments on day 6 after viral administration. Increasing numbers of immune cells were documented post-viral treatment, mainly in the peritumoral compartment, where plasma cells and CD3+ and CD3-/CD79- lymphocytes predominated. Viral administration was well tolerated, with no significant adverse events. These findings support additional research on the use of NDV-MLS immunotherapy for mammary cancer.

Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed.

PURPOSE: The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. METHODS: The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). RESULTS: 1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27-85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1-17.9), median OS was 16.1 months (95% CI, 14.4-18.8) and PFS was 9.9 months (95% CI, 8.8-11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6-17.1). ORR was 43.4% (95% CI, 40.4-46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). CONCLUSIONS: First-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study.

A Lipidomics Approach to Determine the Role of Lipids and Its Crosstalk with Autophagy in Lung Cancer Metastasis.

Non-small cell lung cancer (NSCLC) is among the most malignant tumors with high propensity for metastasis and is the leading cause of cancer-related death globally. Most patients present with regional and distant metastasis, associated with poor prognosis. Lipids may play an essential role in either activating or inhibiting detachment-induced apoptosis (anoikis), where the latter is a crucial mechanism to prevent metastasis, and it may have a cross-talk with autophagy. Autophagy has been shown to be induced in various human cancer metastasis, modulating tumor cell motility and invasion, cancer cell differentiation, resistance to anoikis, and epithelial to mesenchymal transition. Hence, it may play a crucial role in the transition of benign to malignant phenotypes, the core of metastasis initiation. Here, we provide a method we have established in our laboratory for detecting lipids in attached and detached non-small lung cancer cells and show how to analyze lipidomics data to find its correlation with autophagy-related pathways.

Corpus luteum presence in the bovine ovary increase intrafollicular progesterone concentration: consequences in follicular cells gene expression and follicular fluid small extracellular vesicles miRNA contents.

BACKGROUND: It is well described that circulating progesterone (P4) plays a key role in several reproductive events such as oocyte maturation. However, during diestrus, when circulating P4 is at the highest concentrations, little is known about its local impact on the follicular cells such as intrafollicular P4 concentration due to corpus luteum (CL) presence within the same ovary. Based on that, our hypothesis is that the CL presence in the ovary during diestrus alters intrafollicular P4 concentrations, oocyte competence acquisition, follicular cells gene expression, and small extracellular vesicles (sEVs) miRNAs contents. RESULTS: P4 hormonal analysis revealed that ipsilateral to the CL follicular fluid (iFF) presented higher P4 concentration compared to contralateral follicular fluid (cFF). Furthermore, oocyte maturation and miRNA biogenesis pathways transcripts (ADAMTS-1 and AGO2, respectively) were increased in cumulus and granulosa cells of iFF, respectively. Nevertheless, a RT-PCR screening of 382 miRNAs showed that three miRNAs were upregulated and two exclusively expressed in sEVs from iFF and are predicted to regulate cell communication pathways. Similarly, seven miRNAs were higher and two exclusively expressed from cFF sEVs and are predicted to modulate proliferation signaling pathways. CONCLUSION: In conclusion, intrafollicular P4 concentration is influenced by the presence of the CL and modulates biological processes related to follicular cell development and oocyte competence, which may influence the oocyte quality. Altogether, these results are crucial to improve our knowledge about the follicular microenvironment involved in oocyte competence acquisition.

Posttraumatic growth in women after a childbirth experience: The influence of individual characteristics and intrusive and deliberate rumination.

OBJECTIVE: This study targets women who had a self-defined traumatic childbirth experience to (a) explore the differences between sociodemographic-, obstetric-, and trauma-related variables in relation to the rumination style; (b) determine differences between intrusive and deliberate rumination in relation to posttraumatic growth (PTG) dimensions, and (c) test whether intrusive rumination is associated with deliberate rumination, which in turn is associated with PTG dimensions. METHOD: A cross-sectional study design was employed using a web-based survey method for data collection. In total, 202 women who identified their childbirth experience as traumatic participated in this study. RESULTS: Intrusive rumination and deliberate rumination were positively associated with all dimensions of PTG in women following the traumatic childbirth event. Deliberate rumination fully explained the relationship between intrusive rumination and PTG aspects of relating to others, new opportunities, and personal strength, and partially explained the relationship between intrusive rumination and PTG aspects of spiritual changes and appreciation of life. CONCLUSIONS: The results suggest that deliberate rumination can contribute to explain the occurrence of PTG. These findings could help develop psychosocial interventions to maximize opportunities for deliberate rumination for women with traumatic childbirth experiences. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response.

Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes, PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine transforming growth factor beta (TGF-ß). This overexpression of TGF-ß1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes epithelial to mesenchymal transition (EMT). Overexpression of TGF-ß also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-ß in this tumor type. We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-ß1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.

Effects of calcium supplementation on changes in the IL2, IL4, IL6, IL10 axes and oxidative stress in pregnant women at risk for pre-eclampsia.

BACKGROUND: Pregnant women with hypertensive disorders are at increased risk for inflammatory diseases and oxidative stress. The dilemma raised by the best dosage of calcium supplementation on these factors is evident. The aim of the current study was to examine the effects of calcium on biomarkers of the purinergic system, inflammation and oxidative stress, which are factors contributing to vascular damage in pregnant women at high risk of pre-eclampsia. METHODS: A prospective, double-blind and placebo-controlled study conducted with 101 women at risk of pre-eclampsia were randomized to take 500 mg calcium/day or 1,500 mg calcium/day or placebo for 6 weeks from the 20th gestational week until delivery. Fasting blood samples were collected at the beginning of the study and 6 weeks after the intervention. RESULTS: Taking calcium supplements (500 mg calcium/day) led to a significant increase in ATP hydrolysis (p < 0.05), NTPDase activity with increased hydrolysis of ADP and AMP nucleotides in platelets and lymphocytes. In the intragroup analysis IL-2, IL-6, IL-4 and interferon-É£ presented lower values in the calcium 1,500 mg/day group (p < 0.005). Oxidative stress was assessed by TBARS pro-oxidant marker, with an increase for the calcium groups when compared to the placebo group. The Vitamin C antioxidant marker presented a significant increase (p < 0.005) for the group that received high calcium doses. CONCLUSIONS: Calcium administration for 6 weeks had antioxidant action and positively modulated the purinergic system and inflammatory markers in pregnant women at risk of pre-eclampsia.

Spatial-temporal risk clusters, social vulnerability, and identification of priority areas for surveillance and control of cutaneous leishmaniasis in Maranhão, Brazil: an ecological study.

Cutaneous leishmaniasis (CL) is a neglected disease widely distributed in Maranhão, Brazil and presents a significant public health problem. However, its transmission dynamics and determining factors are not clearly understood. In this context, geospatial technologies help interpret the process. This study, then, characterized the space-time dynamics and the influence of social vulnerability on CL in an endemic area in Northeast Brazil. This is an ecological study about new cases of CL in Maranhão, from 2007 to 2020, obtained directly from the Notifiable Diseases Information System. The incidence rate was smoothed using a spatial empirical Bayesian method. Subsequently, global and local Moran statistics and their association with social vulnerability indicators were determined. Disease distribution was not random but grouped in space and time. All Social Vulnerability Index domains were positively correlated with the CL incidence. A likely cluster was detected in western Maranhão (P < 0.001), which encompassed 18 municipalities, from January 2007 to December 2013, with a high relative risk (5.06). The research findings suggest that planning public health actions and allocating resources should be prioritized in these areas to help effectively reduce the incidence of the disease.

Atividades de extensão em enfermagem: Medidas excecionais em tempos de pandemia por COVID-19 / Extension activities in nursing: Exceptional measures during the COVID-19 pandemic / Actividades de extensión en enfermería: medidas excepcionales en tiempos de pandemia por COVID-19

Resumo Enquadramento: A Escola Superior de Enfermagem de Coimbra, ciente do valor das unidades de extensão na articulação do tripé Ensino-Investigação-Extensão tem na sua estrutura a Unidade de Prestação de Serviços à Comunidade e Coordenação das Atividades de Extensão na Comunidade (UPSCCAEC). Objetivo: Descrever o trabalho desenvolvido pela UPSCCAEC em 2019 e 2020, destacando a sua capacidade adaptativa mediante a pandemia pela COVID-19. Principais tópicos em análise: Utilizaram-se como fonte de dados os relatórios de atividades realizadas no contexto da UPSCCAEC nos anos civis de 2019 e 2020, e realizou-se a comparação com achados nos dois anos, os quais foram discutidos à luz do referencial teórico disponível, considerando a pandemia COVID-19 e o impacte a nível das Instituições do Ensino Superior (IES) em seus processos formativos, de investigação e extensão. Conclusão: A atividade da UPSCCAEC nos referidos anos contribuiu para a afirmação da instituição, do desenvolvimento académico, e constituiu recurso de excelência na resposta aos atuais desafios da sociedade, particularmente num período caracterizado por enorme turbulência resultante da pandemia COVID-19.

Abstract Background: The Nursing School of Coimbra knows the importance of extension units in the articulation between teaching, research, and extension. For this reason, the School has a Service Provision and Community Extension Activities Coordination Unit (UPSCCAEC). Objective: To describe the work developed by the UPSCCAEC in 2019 and 2020, highlighting its adaptive capacity in the face of the COVID-19 pandemic. Main topics under analysis: The reports of activities carried out within the scope of the UPSCCAEC in 2019 and 2020 were used as a data source. A comparison was made with findings in the two years, discussed based on the available theoretical framework and considering the COVID-19 pandemic and its impact on Higher Education Institutions' training, research, and extension processes. Conclusion: The UPSCCAEC's activity in those years contributed to the institution's excellence and academic development and successful response to the current societal challenges in a time of great instability due to the COVID-19 pandemic.

Resumen Marco contextual: La Escuela Superior de Enfermería de Coímbra, consciente del valor de las unidades de extensión en la articulación del trípode Enseñanza-Investigación-Extensión, cuenta en su estructura con la Unidad de Prestación de Servicios a la Comunidad y Coordinación de Actividades de Extensión Comunitaria (UPSCCAEC). Objetivo: Describir el trabajo desarrollado por la UPSCCAEC en 2019 y 2020, y destacar su capacidad de adaptación frente a la pandemia por COVID-19. Principales temas en análisis: La fuente de datos utilizada fueron los informes de las actividades realizadas en el marco de la UPSCCAEC en los años civiles de 2019 y 2020, y se realizó una comparación con los hallazgos en ambos años, los cuales se discutieron considerando el marco teórico disponible, la pandemia del COVID-19 y el impacto en las Instituciones de Educación Superior (IES), en sus procesos de formación, investigación y extensión. Conclusión: La actividad de la UPSCCAEC en estos años contribuyó a la afirmación de la institución, al desarrollo académico y constituyó un recurso de excelencia para responder a los desafíos actuales de la sociedad, particularmente en un período caracterizado por enormes turbulencias derivadas de la pandemia del COVID-19.

The role of BCL2L13 in glioblastoma: turning a need into a target.

Glioblastoma (GBM) is the most common aggressive central nervous system cancer. GBM has a high mortality rate, with a median survival time of 12-15 months after diagnosis. A poor prognosis and a shorter life expectancy may result from resistance to standard treatments such as radiation and chemotherapy. Temozolomide has been the mainstay treatment for GBM, but unfortunately, there are high rates of resistance with GBM bypassing apoptosis. A proposed mechanism for bypassing apoptosis is decreased ceramide levels, and previous research has shown that within GBM cells, B cell lymphoma 2-like 13 (BCL2L13) can inhibit ceramide synthase. This review aims to discuss the causes of resistance in GBM cells, followed by a brief description of BCL2L13 and an explanation of its mechanism of action. Further, lipids, specifically ceramide, will be discussed concerning cancer and GBM cells, focusing on ceramide synthase and its role in developing GBM. By gathering all current information on BCL2L13 and ceramide synthase, this review seeks to enable an understanding of these pieces of GBM in the hope of finding an effective treatment for this disease.

Association between persistent organic pollutants in human milk and the infant growth and development throughout the first year postpartum in a cohort from Rio de Janeiro, Brazil.

Persistent organic pollutants (POPs) are compounds that are recalcitrant and ubiquitous that bioaccumulate in human milk (HM) and can impact infant growth and development. We explore the association between POP concentration in HM at 2-50 days postpartum and infant growth and development trajectory throughout the first year of life. A cohort of 68 healthy adult Brazilian women and their infants were followed from 28 to 35 gestational weeks to 12 months postpartum. HM samples were collected between 2 and 50 days postpartum, and POP concentrations were analyzed using gas chromatography with mass spectrometry. Concentrations of POPs >limit of quantification (LOQ) were defined as presence, and concentrations ≤LOQ as an absence. Growth z-scores were analyzed according to WHO growth charts and infant development scores according to Age & Stages Questionnaires at 1 (n = 66), 6 (n = 50), and 12 months (n = 45). Linear mixed effects (LME) models were used to investigate the association of POPs in HM with infant growth and development. Benjamini-Hochberg (BH) correction for multiple testing was performed to reduce the false discovery ratio. P < 0.1 was considered for models with the interaction between POPs and time/sex. After BH correction, adjusted LME models with time interaction showed (1) a positive association between the presence of ß hexachlorocyclohexane and an increase in head circumference-for-age z-score (ß = 0.003, P = 0.095); (2) negative associations between total POPs (ß = -0.000002, P = 0.10), total organochlorine pesticides (ß = -0.000002, P = 0.10), and dichlorodiphenyldichloroethylene concentrations in HM (ß = -0.000002, P = 0.10) and fine motor scores. No statistical difference between the sexes was observed. Postnatal exposure to organochlorine pesticides in HM shows a positive association with the trajectory of head circumference-for-age z-score and a negative association with the trajectories of fine motor skills scores. Future studies on POP variation in HM at different postpartum times and their effect on infant growth and development should be encouraged.

Genomic features of an extensively drug-resistant and NDM-1-positive Klebsiella pneumoniae ST340 isolated from river water.

The environmental contamination plays a significant role in the emergence of antimicrobial resistance. In this study, we report a genomic analysis of an extensively drug-resistant and blaNDM-1-producing Klebsiella pneumoniae (EW807) strain recovered from a surface water sample. Strain EW807 belonged to sequence type (ST) 340 and serotype O4:KL15, a high-risk clone of the clonal group 258. This strain carried a broad resistome, including blaNDM-1 and blaCTX-M-15. The core genome multilocus sequence typing phylogenetic analysis revealed that the EW807 strain was most related to strains from Brazil and the USA. An IncX3 plasmid was identified harboring the blaNDM-1 gene, while an IncFIB(K) plasmid was detected carrying the blaCTX-M-15 in addition to multidrug resistance and multimetal tolerance regions. IncX3 and IncFIB(K) plasmids shared high similarity with plasmids from a human in China and a dog in Brazil, respectively. The regions harboring the blaNDM-1 and blaCTX-M-15 genes contained sequences from the Tn3 family. These findings suggest that IncX3 plasmid could play a role in the spread of NDM-1 in a post-pandemic scenario. To the best of our knowledge, this is the first report of blaNDM-1-producing K. pneumoniae ST340 O4:KL15 strain in the environment. Therefore, the presence of high-risk clones of K. pneumoniae carrying carbapenemases in the environment requires strict surveillance.

Experienced barriers in the use of ICT for social interaction in older adults ageing in place: a qualitative systematic review protocol (SYSR-D-22-00848).

BACKGROUND: Several information and communication technologies (ICT) have been developed to enhance social connectedness of older adults aging in place, although they are not accessible for all. Barriers in using ICT might for example relate to health issues, sensory loss, lack of technical skills, or reluctance to use technologies. Though knowledge on these barriers is crucial for the development and implementation of ICT for older adults, no systematic review was found on this subject. The proposed qualitative systematic review aims to explore barriers experienced by older adults aging in place in using ICT for social interaction. METHODS: The review will be conducted in accordance with the JBI methodology. Databases for search will include MEDLINE (via PubMed), CINAHL (via EBSCO), and Web of Science (ISI), among others. Included studies focus on older adults ageing in place 60 years or older. Pairs of authors will independently, by following agreed guidelines, assess the eligibility of studies, and extract data. The testing of eligibility criteria and screening of titles, abstracts, and full texts will be performed. The findings will describe for example populations, context, culture, and the phenomena of interest. Qualitative research findings will, where possible, be pooled by using JBI SUMARI for the meta-aggregation approach. DISCUSSION: The mapping of published studies has the potential to identify research gaps in the existing literature, which again may inform developers and stakeholders in designing more user-friendly and adaptive ICT solutions for older people ageing in place. SYSTEMATIC REVIEW REGISTRATION: CRD42022370044.

Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms.

Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.

Experiences with remote communication in adult intensive care units during the COVID-19 pandemic: a systematic review protocol.

OBJECTIVE: The objective of this review is to explore the lived experiences of critically ill adults, their families, or health care professionals with remote communication in intensive care units (ICUs) during the COVID-19 pandemic. INTRODUCTION: Family visiting restrictions in ICUs during the COVID-19 pandemic imposed significant challenges to communication between critically ill adults, their families, and the health care team. Evidence shows that several communication strategies were developed and implemented in ICUs during the COVID-19 pandemic to promote family engagement; however, the experiences of critically ill adults, their families, and health care professionals with these strategies are scattered across primary qualitative studies. INCLUSION CRITERIA: This review will consider qualitative studies that include critically ill adults, their families, or health care professionals, focusing on their experiences with remote communication strategies in ICUs during the COVID-19 pandemic. METHODS: This review will be conducted in accordance with JBI methodology. The search strategy will aim to locate both published and unpublished qualitative studies in English, Spanish, and Portuguese. Studies published after January 2020 will be included. Study selection, critical appraisal, and data extraction will be performed independently by 2 reviewers. Data will be presented in narrative format and synthesized using the JBI meta-aggregation process. A ConQual Summary of Findings will be presented. REVIEW REGISTRATION: PROSPERO CRD42022383603.

Ceramides and ceramide synthases in cancer: Focus on apoptosis and autophagy.

Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis and autophagy in the context of cancer. These mechanisms of regulation, however, appear to be context dependent in terms of ceramides' fatty acid chain length, subcellular localization, and the presence or absence of their downstream targets. Our current understanding of the role of ceramide synthases and ceramides in regulation of apoptosis and autophagy could be harnessed to pioneer the development of new treatments to activate or inhibit a single type of ceramide synthase, thereby regulating the apoptosis induction or cross talk of apoptosis and autophagy in cancer cells. Moreover, the apoptotic function of ceramide suggests that ceramide analogues can pave the way for the development of novel cancer treatments. Therefore, in the current review paper we discuss the impact of ceramide synthases and ceramides in regulation of apoptosis and autophagy in context of different types of cancers. We also briefly introduce the latest information on ceramide synthase inhibitors, their application in diseases including cancer therapy, and discuss approaches for drug discovery in the field of ceramide synthase inhibitors. We finally discussed strategies for developing strategies to use lipids and ceramides analysis in biological fluids for developing early biomarkers for cancer.

NLRP3 Inflammasome Involved with Viral Replication in Cytopathic NADL BVDV Infection and IFI16 Inflammasome Connected with IL-1ß Release in Non-Cytopathic NY-1 BVDV Infection in Bovine Macrophages.

Inflammasomes are multiprotein complexes that play a role in the processing of proinflammatory cytokines such as interleukin 1 beta (IL-1ß). The secretion of IL-1ß in bovine macrophages infected with the bovine viral diarrhea virus (BVDV) cytopathic strain NADL (NADLcp-BVDV) is caspase 1-dependent. In the present study, we found that in macrophages infected with NADL, the NLRP3 inflammasome participated in the maturation of IL-1ß as the level decreased from 4629.3 pg/mL to 897.0 pg/mL after treatment with cytokine release inhibitory drug 3 (CRID3). Furthermore, NLRP3 activation has implications regarding viral replication, as there was a decrease in the viral titer until 1 log of a supernatant of macrophages that were inhibited with CRID3 remained. In the case of the non-cytopathic BVDV strain NY-1 (NY-1 ncpBVDV), IL-1ß secretion is not affected by NLRP3, but could be related to the IFI16 inflammasome; we found a colocalization of IFI16 with ASC using confocal microscopy in infected macrophages with the NY-1 ncp-BVDV biotype. To relate IFI16 activation to IL-1ß release, we used ODN TTAGGG (A151), a competitive inhibitor of IFI16; the results show a decrease in its level from 248 pg/mL to 128.3 pg/mL. Additionally, we evaluated the caspase 1 activation downstream of IFI16 and found a decrease in the IL-1ß from 252.9 pg/mL to 63.5 pg/mL when caspase 1 was inhibited with Y-VAD. Our results provide an improved understanding of the mechanisms involved in the viral replication, inflammation and pathogenesis of bovine viral diarrhea.