Flower isoforms promote competitive growth in cancer.

In humans, the adaptive immune system uses the exchange of information between cells to detect and eliminate foreign or damaged cells; however, the removal of unwanted cells does not always require an adaptive immune system1,2. For example, cell selection in Drosophila uses a cell selection mechanism based on 'fitness fingerprints', which allow it to delay ageing3, prevent developmental malformations3,4 and replace old tissues during regeneration5. At the molecular level, these fitness fingerprints consist of combinations of Flower membrane proteins3,4,6. Proteins that indicate reduced fitness are called Flower-Lose, because they are expressed in cells marked to be eliminated6. However, the presence of Flower-Lose isoforms at a cell's membrane does not always lead to elimination, because if neighbouring cells have similar levels of Lose proteins, the cell will not be killed4,6,7. Humans could benefit from the capability to recognize unfit cells, because accumulation of damaged but viable cells during development and ageing causes organ dysfunction and disease8-17. However, in Drosophila this mechanism is hijacked by premalignant cells to gain a competitive growth advantage18. This would be undesirable for humans because it might make tumours more aggressive19-21. It is unknown whether a similar mechanism of cell-fitness comparison is present in humans. Here we show that two human Flower isoforms (hFWE1 and hFWE3) behave as Flower-Lose proteins, whereas the other two isoforms (hFWE2 and hFWE4) behave as Flower-Win proteins. The latter give cells a competitive advantage over cells expressing Lose isoforms, but Lose-expressing cells are not eliminated if their neighbours express similar levels of Lose isoforms; these proteins therefore act as fitness fingerprints. Moreover, human cancer cells show increased Win isoform expression and proliferate in the presence of Lose-expressing stroma, which confers a competitive growth advantage on the cancer cells. Inhibition of the expression of Flower proteins reduces tumour growth and metastasis, and induces sensitivity to chemotherapy. Our results show that ancient mechanisms of cell recognition and selection are active in humans and affect oncogenic growth.

Grass xylan structural variation suggests functional specialization and distinctive interaction with cellulose and lignin.

Xylan is the most abundant non-cellulosic polysaccharide in grass cell walls, and it has important structural roles. The name glucuronoarabinoxylan (GAX) is used to describe this variable hemicellulose. It has a linear backbone of ß-1,4-xylose (Xyl) residues that may be substituted with α-1,2-linked (4-O-methyl)-glucuronic acid (GlcA), α-1,3-linked arabinofuranose (Araf), and sometimes acetylation at the O-2 and/or O-3 positions. The role of these substitutions remains unclear, although there is increasing evidence that they affect the way xylan interacts with other cell wall components, particularly cellulose and lignin. Here, we used substitution-dependent endo-xylanase enzymes to investigate the variability of xylan substitution in grass culm cell walls. We show that there are at least three different types of xylan: (i) an arabinoxylan with evenly distributed Araf substitutions without GlcA (AXe); (ii) a glucuronoarabinoxylan with clustered GlcA modifications (GAXc); and (iii) a highly substituted glucuronoarabinoxylan (hsGAX). Immunolocalization of AXe and GAXc in Brachypodium distachyon culms revealed that these xylan types are not restricted to a few cell types but are instead widely detected in Brachypodium cell walls. We hypothesize that there are functionally specialized xylan types within the grass cell wall. The even substitutions of AXe may permit folding and binding on the surface of cellulose fibrils, whereas the more complex substitutions of the other xylans may support a role in the matrix and interaction with other cell wall components.

Strategies for nursing care of critically ill multicultural patients: A scoping review.

BACKGROUND: In society, people live in a social reality where multiculturalism is an increasingly relevant and prevalent topic in their contexts. Facing this, caring for multicultural patients in an emergency service or intensive care unit setting requires a high level of cultural competence due to the complexity, vulnerability of the patient, rapid changes in hemodynamic status, involvement of the family, their informational needs. OBJECTIVE: To map the strategies for nursing care of critically ill multicultural patients. METHOD: A Scoping Review was conducted following the Joanna Briggs Institute's recommendations, with the research question: What are the strategies for nursing care of critically ill multicultural patients? The study was guided by PRISMA. The research was conducted through the EBSCOHost platform, SciELO, Portugal's Open Access Scientific Repository, the Virtual Health Library and a search in grey literature. This was achieved by combining the descriptors DECS/MESH: cultural competence; critical care; emergency room; intensive care; and natural words: cultural care; nurs* interventions; nurs* strategies; within the time frame from 2012 to 2024. The study screening was performed by three independent reviewers through the reading of titles, abstracts and full texts, applying exclusion criteria. The study results were then subjected to content analysis, from which categories emerged. RESULTS: The selected articles highlight various strategies that contribute to the improvement of nursing care for critically ill multicultural patients, focusing on care practice and cultural diversity training for both nurses and nursing students. CONCLUSION: Nurses with cultural competence possess more knowledge and strategies to provide tailored care for multicultural critically ill patients, thereby enhancing the quality of care delivered and contributing to the humanization of healthcare. RELEVANCE TO CLINICAL PRACTICE: Nurses need to have knowledge of existing strategies for caring for multicultural critically ill patients. PATIENT OR PUBLIC CONTRIBUTION: No direct patient or public contribution to the review.

Exploring Bioactivities and Peptide Content of Body Mucus from the Lusitanian Toadfish Halobatrachus didactylus.

Identifying bioactive molecules from marine organisms is still vastly understudied. Fish remain an untapped source of bioactive molecules, even when considering species whose toxicity to other fish species has been noticed before. We assessed potential applications of crude body mucus of the Lusitanian toadfish (Halobratachus didactylus) and characterized its peptide fraction composition. Mucus samples from three individuals (two wild and one captive) revealed potential antioxidant, antihypertensive, and antimicrobial activities. For antioxidant activity, the best results of 2371 ± 97 µmol Trolox Equivalent/g protein for ORAC and 154 ± 6 µmol Trolox Equivalent/g protein for ABTS were obtained. For antihypertensive activity, the relevant inhibitory activity of ACE resulted in IC50 of 60 ± 7 µg protein/mL. Antimicrobial activity was also identified against the pathogenic bacteria Escherichia coli and Listeria monocytogenes. The peptide profile of the crude body mucus was obtained through size exclusion chromatography, with a conspicuous peak at ca. 800 Da. LC-MS/MS allowed the detection of the most probable peptide sequences of this dominant peptide. This is the first study where the bioactive potential of mucus from the Lusitanian toadfish is demonstrated. Peptides with such properties can be applied in the food and pharmaceutical industries.

Motor neuron translatome reveals deregulation of SYNGR4 and PLEKHB1 in mutant TDP-43 amyotrophic lateral sclerosis models.

Amyotrophic lateral sclerosis (ALS) is an incurable neurological disease with progressive loss of motor neuron (MN) function in the brain and spinal cord. Mutations in TARDBP, encoding the RNA-binding protein TDP-43, are one cause of ALS, and TDP-43 mislocalization in MNs is a key pathological feature of >95% of ALS cases. While numerous studies support altered RNA regulation by TDP-43 as a major cause of disease, specific changes within MNs that trigger disease onset remain unclear. Here, we combined translating ribosome affinity purification (TRAP) with RNA sequencing to identify molecular changes in spinal MNs of TDP-43-driven ALS at motor symptom onset. By comparing the MN translatome of hTDP-43A315T mice to littermate controls and to mice expressing wild type hTDP-43, we identified hundreds of mRNAs that were selectively up- or downregulated in MNs. We validated the deregulated candidates Tex26, Syngr4, and Plekhb1 mRNAs in an independent TRAP experiment. Moreover, by quantitative immunostaining of spinal cord MNs, we found corresponding protein level changes for SYNGR4 and PLEKHB1. We also observed these changes in spinal MNs of an independent ALS mouse model caused by a different patient mutant allele of TDP-43, suggesting that they are general features of TDP-43-driven ALS. Thus, we identified SYNGR4 and PLEKHB1 to be deregulated in MNs at motor symptom onset in TDP-43-driven ALS models. This spatial and temporal pattern suggests that these proteins could be functionally important for driving the transition to the symptomatic phase of the disease.

TDP-43 enhances translation of specific mRNAs linked to neurodegenerative disease.

The RNA-binding protein TDP-43 is heavily implicated in neurodegenerative disease. Numerous patient mutations in TARDBP, the gene encoding TDP-43, combined with data from animal and cell-based models, imply that altered RNA regulation by TDP-43 causes Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. However, underlying mechanisms remain unresolved. Increased cytoplasmic TDP-43 levels in diseased neurons suggest a possible role in this cellular compartment. Here, we examined the impact on translation of overexpressing human TDP-43 and the TDP-43A315T patient mutant protein in motor neuron-like cells and primary cultures of cortical neurons. In motor-neuron like cells, TDP-43 associates with ribosomes without significantly affecting global translation. However, ribosome profiling and additional assays revealed enhanced translation and direct binding of Camta1, Mig12, and Dennd4a mRNAs. Overexpressing either wild-type TDP-43 or TDP-43A315T stimulated translation of Camta1 and Mig12 mRNAs via their 5'UTRs and increased CAMTA1 and MIG12 protein levels. In contrast, translational enhancement of Dennd4a mRNA required a specific 3'UTR region and was specifically observed with the TDP-43A315T patient mutant allele. Our data reveal that TDP-43 can function as an mRNA-specific translational enhancer. Moreover, since CAMTA1 and DENND4A are linked to neurodegeneration, they suggest that this function could contribute to disease.

HIF-transcribed p53 chaperones HIF-1α.

Chronic hypoxia is associated with a variety of physiological conditions such as rheumatoid arthritis, ischemia/reperfusion injury, stroke, diabetic vasculopathy, epilepsy and cancer. At the molecular level, hypoxia manifests its effects via activation of HIF-dependent transcription. On the other hand, an important transcription factor p53, which controls a myriad of biological functions, is rendered transcriptionally inactive under hypoxic conditions. p53 and HIF-1α are known to share a mysterious relationship and play an ambiguous role in the regulation of hypoxia-induced cellular changes. Here we demonstrate a novel pathway where HIF-1α transcriptionally upregulates both WT and MT p53 by binding to five response elements in p53 promoter. In hypoxic cells, this HIF-1α-induced p53 is transcriptionally inefficient but is abundantly available for protein-protein interactions. Further, both WT and MT p53 proteins bind and chaperone HIF-1α to stabilize its binding at its downstream DNA response elements. This p53-induced chaperoning of HIF-1α increases synthesis of HIF-regulated genes and thus the efficiency of hypoxia-induced molecular changes. This basic biology finding has important implications not only in the design of anti-cancer strategies but also for other physiological conditions where hypoxia results in disease manifestation.

AVP dynamically increases paracellular Na+ permeability and transcellular NaCl transport in the medullary thick ascending limb of Henle's loop.

The medullary thick ascending limb of Henle's loop (mTAL) is crucial for urine-concentrating ability of the kidney. It is water tight and able to dilute the luminal fluid by active transcellular NaCl transport, fueling the counter current mechanism by increasing interstitial osmolality. While chloride is exclusively transported transcellularly, approx. 50% of sodium transport occurs via the paracellular route, driven by the lumen-positive transepithelial potential. Antidiuretic hormone (AVP) is known to increase active NaCl transport to support collecting duct water reabsorption. Here, we investigated the concomitant effects of AVP on the paracellular properties of mTAL. Freshly isolated mouse mTALs were perfused and electrophysiological transcellular and paracelluar properties were assessed in a paired fashion before and after AVP stimulation. In addition, the same parameters were measured in mice on a water-restricted (WR) or water-loaded (WL) diet for 5 days. Acute ex vivo stimulation as well as long-term in vivo water restriction increased equivalent short circuit current as a measure of active transcellular NaCl transport. Intriguingly, in both experimental approaches, this was accompanied by markedly increased paracellular Na+ selectivity. Thus, AVP is able to acutely regulate paracellular cation selectivity in parallel to transcellular NaCl transport, allowing balanced paracellular Na+ absorption under an increased transepithelial driving force.

How can information systems provide support to nurses' hand hygiene performance? Using gamification and indoor location to improve hand hygiene awareness and reduce hospital infections.

BACKGROUND: Hospital-acquired infections are still amongst the major problems health systems are facing. Their occurrence can lead to higher morbidity and mortality rates, increased length of hospital stay, and higher costs for both hospital and patients. Performing hand hygiene is a simple and inexpensive prevention measure, but healthcare workers' compliance with it is often far from ideal. To raise awareness regarding hand hygiene compliance, individual behaviour change and performance optimization, we aimed to develop a gamification solution that collects data and provides real-time feedback accurately in a fun and engaging way. METHODS: A Design Science Research Methodology (DSRM) was used to conduct this work. DSRM is useful to study the link between research and professional practices by designing, implementing and evaluating artifacts that address a specific need. It follows a development cycle (or iteration) composed by six activities. Two work iterations were performed applying gamification components, each using a different indoor location technology. Preliminary experiments, simulations and field studies were performed in an Intensive Care Unit (ICU) of a Portuguese tertiary hospital. Nurses working on this ICU were in a focus group during the research, participating in several sessions across the implementation process. RESULTS: Nurses enjoyed the concept and considered that it allows for a unique opportunity to receive feedback regarding their performance. Tests performed on the indoor location technology applied in the first iteration regarding distances estimation presented an unacceptable lack of accuracy. Using a proximity-based technique, it was possible to identify the sequence of positions, but beacons presented an unstable behaviour. In the second work iteration, a different indoor location technology was explored but it did not work properly, so there was no chance of testing the solution as a whole (gamification application included). CONCLUSIONS: Combining automated monitoring systems with gamification seems to be an innovative and promising approach, based on the already achieved results. Involving nurses in the project since the beginning allowed to align the solution with their needs. Despite strong evolution through recent years, indoor location technologies are still not ready to be applied in the healthcare field with nursing wards.

E-cadherin immunohistochemistry in breast pathology: uses and pitfalls.

E-cadherin immunohistochemistry is used commonly in surgical pathology practice to help distinguish lobular carcinoma in situ from ductal carcinoma in situ and invasive lobular carcinoma from invasive ductal carcinoma in histologically problematic or indeterminate cases. However, the interpretation of E-cadherin immunostains is not always straightforward. Failure to recognize the pitfalls and limitations of E-cadherin immunostains can lead to an erroneous diagnosis which may result in inappropriate patient management, particularly for patients with in-situ lesions. In this paper we review the uses and, particularly, the pitfalls in the interpretation of E-cadherin immunostains in distinguishing lobular from ductal lesions of the breast.

ISBAR: A Handover Nursing Strategy in Emergency Departments, Scoping Review.

The present work aims to map the available scientific evidence on the benefits of using the ISBAR tool in the nursing care of acutely ill adult patients' handover in an emergency department context. To this end, a scoping review was conducted, according to the guidelines proposed by the Joanna Briggs Institute (JBI), to answer the following research question: "What are the benefits of using the ISBAR tool in the nursing care of acutely ill adult patients' handover in an emergency department context?" The bibliographic search was carried out during August and September 2023 in the following electronic databases: CINAHL Complete; MEDLINE Complete; Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; and Cochrane Methodology Register. Only works published between 2013 and 2023 were deemed fit for inclusion. All the included studies (9) show that ISBAR methodology, as a standardized tool for transferring nursing care in the emergency service, allows for a safe, clear, and concise transition of nursing care. The benefits relate to patient and professional safety, continuity, and quality of care, as well as patient and professional comfort, with health gains.

Synchronous Gastric and Rectal Adenocarcinoma With Complete Response After Total Neoadjuvant Therapy: A Case Report.

Synchronous gastric cancer with another neoplasm is a rare condition, with colorectal cancer being the most frequently associated neoplasm. This article presents a case of a 76-year-old male diagnosed with synchronous gastric and rectal cancer with complete remission of gastric and rectal neoplasms after adjuvant therapy. The patient exhibited symptoms prompting upper and lower endoscopies, revealing gastric and rectal adenocarcinomas, respectively. Staging was performed, and due to the locally advanced nature of both malignancies, the patient underwent total neoadjuvant therapy (TNT) for rectal cancer. The treatment consisted of external radiotherapy and neoadjuvant chemotherapy with oxaliplatin, leucovorin, folinic acid, and fluorouracil (FOLFOX). Remarkably, after seven cycles, a complete clinical response of the rectal neoplasm was achieved. Subsequent surgical resection included simultaneous subtotal gastrectomy and rectal anterior resection, resulting in a complete pathological response for both tumors. To the best of our knowledge, it is among the first cases to report a full pathological response in gastric cancer following TNT intended for rectal cancer.

Kaplan-Meier Survival Analysis: Practical Insights for Clinicians.

This article aims to provide a guide that will help healthcare professionals and clinical researchers from all fields that deal with Kaplan-Meier curves. Survival analysis methods are among the most frequently used in the medical sciences and in clinical research. Overall survival, progression free survival, time to recurrence, or any other clinically relevant parameter represented by a Kaplan-Meier curve will be discussed. We will present a practical and straightforward interpretation of these curves, setting aside intricate mathematical considerations. Our focus will be on essential concepts that interface with biological sciences and medicine in order to guarantee proficiency in one of the most popular yet frequently misunderstood methods in clinical research. Being familiar with these concepts is not only essential for designing new clinical studies but also for critically assessing and interpreting published data.

Appendiceal Neoplasm: It's Never What It Seems.

Appendiceal neoplasms are a rare and heterogeneous condition with a non-specific clinical presentation, often concealing intricate predicaments; hence they require complex and diverse management. The present case report aims not only to describe a less usual form of presentation and its orientation but also to provide a modest literature review in a rather demanding pathology.

Photochemical and photocatalytic degradation of trans-resveratrol.

Photochemical and photocatalytic degradation of the emerging pollutant trans-resveratrol has been studied under different irradiation wavelengths and using different TiO2 catalysts. trans-Resveratrol was more easily degraded when irradiated using the whole spectral range (UV-Vis) rather than with UV and near-UV to visible irradiation. The main intermediate of trans-resveratrol phototransformation was identified as its isomer cis-resveratrol. Different TiO2 catalysts were used to carry out the photocatalytic degradation of trans-resveratrol. Catalysts properties such as crystallite dimensions, surface area and presence of hydroxy surface groups are shown to be crucial to the photocatalytic efficiency of the materials tested. From the point of view of trans-resveratrol abatement, the photocatalytic process was more efficient than the pure photochemical one resulting in higher degradation rates and higher organic content removal. Six photoproducts of trans-resveratrol phototransformation were identified mainly resulting from the attack of the hydroxyl radical to the organic molecule.

Production of Bi-Compartmental Tablets by FDM 3D Printing for the Withdrawal of Diazepam.

Diazepam (DZP) is a long-acting benzodiazepine to treat anxiety or acute alcohol withdrawal. Although this class of drugs should be taken for a short period of time, many patients take them for longer than recommended, which has been linked to an increased risk of dementia and dependence. The present work aimed at using the dual-nozzle system of fused deposition modeling (FDM) 3D printers to prepare tablets with gradual doses of DZP with constant mass and size. Placebo and DZP-loaded filaments were prepared by hot-melt extrusion and used to print the bi-compartmental tablets. Thermal processing allowed the conversion of crystalline DZP to its amorphous counterpart. Tablets with different DZP contents were effectively printed with a mass, thickness and diameter average of 111.6 mg, 3.1 mm, and 6.4 mm, respectively. Microscopic data showed good adhesion between the different layers in the printed tablets. The desired drug contents were successfully achieved and were within the acceptance criteria (European Pharmacopeia). The combination of a placebo and drug-loaded extrudates proved to be beneficial in the production of tablets by FDM for patients in need of drug withdrawal.

Fournier Gangrene Management: Is a Stoma Mandatory?

Fournier gangrene is a rare life-threatening surgical emergency mainly due to a polymicrobial infection of the perineal, genital, or perianal region. It is characterized by rapid tissue destruction and systemic signs of toxicity. It is more frequent in males and immunocompromised patients, such as patients with poorly controlled diabetes, alcoholism, or human immunodeficiency virus (HIV) infection. Treatment often involves surgical intervention, broad-spectrum antibiotic therapy, fecal diversion surgery, and negative pressure wound therapy (NPWT). Delays in diagnosis are associated with high mortality due to rapid progression to septic shock.

Buerger's Disease - A Clinical Case.

Buerger's disease is a distal segmental nonatherosclerotic vasculopathy that involves the inferior and superior limbs of smoker males younger than 45 years old. This article aims to describe a clinical case and revise the literature about Buerger's disease. A 45-year-old smoker male repeatedly visited the emergency department for refractory pain and inflammatory signs in the right hallux. After developing ulcers in the right foot, Doppler ultrasonography revealed segmental occlusion of distal arteries of that limb. It was also observed in arteriography "corkscrew" collaterals. Autoimmune, thrombophilic and cardiovascular diseases were excluded. Analgesia, antibiotics and alprostadil were implemented. As a result, the patient stopped smoking and was submitted to minor amputation with complete healing, after which he remained asymptomatic. Buerger's disease is a diagnosis of exclusion. Therefore, smoking cessation is the most effective treatment and is crucial to prevent disease progression.

Prostate-specific antigen response after Abiraterone treatment in mCRPC: PSA as a predictor of overall survival.

OBJECTIVES: Abiraterone Acetate (AA) is an important agent in the treatment of advanced prostate cancer. It was primarily approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) after failure of androgen deprivation therapy. There is still no available strong data regarding the impact of early decline of prostate-specific antigen (PSA) in the overall survival. The aim of this study was to evaluate the clinical efficacy of an early prostate-specific antigen response as a predictor of overall survival (OS) in metastatic castration-resistant prostate cancer when treated with Abiraterone Acetate. MATERIALS AND METHODS: A dual center, retrospective, cohort study on patients diagnosed with mCRPC treated with abiraterone between 2013 and 2020 was performed. Primary end-point was to demonstrate the efficacy of AA, with the analysis of PSA decline, and the correlation with overall survival. RESULTS: The cohort analysis consisted of 84 patients with a median age of 71 ± 9 years. A PSA response of > 30% and > 50% at 60 and 90 days was associated with improved OS. Multivariate analysis revealed that a 60 day PSA decline of > 30% was predictive of overall survival. Median OS of diag-nosed mCRPC patients was 28 months. Docetaxel pre-treatment was not associated with longer OS. The median duration of drug exposure for patients submitted to AA was found to be 14 months. CONCLUSIONS: Early PSA response rate can offer clinically meaningful information and can be considered a surrogate of longer OS. A > 30% or > 50% prostate-specific antigen decline at 60 and 90 days provided an important low-cost clinical tool to predict subsequent events in mCRPC patients treated with abiraterone.