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Mammalian professional phagocytic cells ingest and kill invading microorganisms and prevent the development of bacterial infections. Our understanding of the sequence of events that results in bacterial killing and permeabilization in phagosomes is still largely incomplete. In this study, we used the Dictyostelium discoideum amoeba as a model phagocyte to study the fate of the bacteria Klebsiella pneumoniae inside phagosomes. Our analysis distinguishes three consecutive phases: bacteria first lose their ability to divide (killing), then their cytosolic content is altered (permeabilization), and finally their DNA is degraded (digestion). Phagosomal acidification and production of free radicals are necessary for rapid killing, membrane-permeabilizing proteins BpiC and AlyL are required for efficient permeabilization. These results illustrate how a combination of genetic and microscopical tools can be used to finely dissect the molecular events leading to bacterial killing and permeabilization in a maturing phagosome.

Anxiety and depressive symptoms adversely affect surgical outcomes in patients with rotator cuff tear (RCT) undergoing surgical repair. Patients without a diagnosis of mood disorders, such as anxiety and depression, before rotator cuff repair (RCR) can be considered an optimal candidate for surgery. The objective of this prospective observational study was to evaluate the relationship between anxiety and depressive symptoms, using the Hospital Anxiety and Depression Scale (HADS) as an assessment tool, and patient-reported outcome measures in RCT after repair surgery. This study included patients with RCT undergoing arthroscopic rotator cuff repair (RCR). Forty-three patients were included who had completed the HADS, Constant Murley Score (CMS), and Short Form Health Survey 36 (SF-36) questionnaires before surgery and in the postoperative follow-up, at 1 month, 3 months, and 6 months. The Friedman test showed that there were statistically significant changes in the different times point for HADS (p < 0.001), anxiety subscale of HADS, i.e., HADS-A (p < 0.001), depression subscale of HADS, i.e., HADS-D (p < 0.001), CMS (p < 0.001), and SF-36 (p < 0.001). The average scores of HADS, HADS-A, and HADS-D improved at each follow-up, showing improvement in discomfort. From the third month after surgery, there was an improvement in anxiety and depression disorders related to improved quality of life, functionality, and pain perception. The trend remained stable until the sixth month of follow up. This study shows that anxiety and depressive symptoms in RCT patients are significantly reduced after RCR with subsequent important improvements in terms of functionality, ability to carry out activities of daily living, perceived pain, and quality of life.

Background Cisd1 and Cisd2 proteins share very similar structures with an N-terminal membrane-anchoring domain and a C-terminal cytosolic domain containing an iron-cluster binding domain and ending with a C-terminal KKxx sequence. Despite sharing a similar structure, Cisd1 and Cisd2 are anchored to different compartments: mitochondria for Cisd1 and endoplasmic reticulum for Cisd2. The aim of this study was to identify the protein motifs targeting Cisd2 to the ER and ensuring its retention in this compartment. Results We used new recombinant antibodies to localize Cisd1 and Cisd2 proteins, as well as various protein chimeras. Cisd2 is targeted to the ER by its N-terminal sequence. It is then retained in the ER by the combined action of a C-terminal COPI-binding KKxx ER retrieval motif, and of an ER-targeting transmembrane domain. As previously reported for Cisd1, Cisd2 can alter the morphology of the compartment in which it accumulates. Conclusion Although they share a very similar structure, Cisd1 and Cisd2 use largely different intracellular targeting motifs to reach their target compartment (mitochondria and endoplasmic reticulum, respectively).

Aim To explore the experiences of being discharged from hospital of older patients with chronic diseases at time of discharge. Design Multi-centre descriptive qualitative study. Methods Semi-structured interviews were conducted with older patients with chronic diseases discharged from two Italian university hospitals, between March 2017 and October 2019. The interviews were audio-recorded, transcribed verbatim and analysed using inductive content analysis. Several strategies were used to ensure the credibility, dependability, confirmability, authenticity and transferability of the findings. The study was reported in accordance with Standards for Reporting Qualitative Research and Consolidated criteria for reporting qualitative research. Results Sixty-five patients participated in the study. Six main categories emerged: feelings, need for information, time of fragility, need for support, need for trusting relationships, and home as a caring place. Conclusion Older patients with chronic diseases are patients who require quality discharge planning with a patient-centred care vision. Healthcare professionals should intervene more extensively and deeply in the discharge process, balancing the patients' perception of their needs against organizational priorities and the wish to return home with that of not being abandoned. Impact Discharge from hospital remains an area of concern as older people have varying degrees of met and unmet needs during and following hospital discharge. Discharge is characterized by conflicting feelings of patients, who need information and support of healthcare professionals through trusting and continuous relationships. Understanding the experience of discharge is essential to support older patients with chronic diseases, considering that discharge from hospital is not an end point of care but a stage of the process involving care transition. The reframing of discharge as another transition point is crucial for healthcare professionals, who will be responsible for making their patients fit for discharge by preparing them to manage their chronic condition at home.

Osteoarthritis negatively impacts the patient’s quality of life. Qualitative research is an effective tool in detecting the various emotions experienced by patients with osteoarthritis. Such studies play a crucial role in promoting comprehension of the patient’s experiences of health and illness among healthcare professionals, including nurses. The purpose of this study is to examine patients’ perceptions during the pre-admission process for total hip replacement (THR). The study utilized a qualitative descriptive methodology with a phenomenological approach. A sample of patients awaiting THR consented to participate in the study and were interviewed until data saturation was achieved. The results of the phenomenological analysis resulted in the identification of three themes: 1—Surgery generates mixed feelings; 2—Pain negatively impacts daily life activities; 3—Pain requires personal strategies to be alleviated. Patients awaiting THR demonstrate frustration and anxiety. They experience intense pain during daily activities, which persists even during night rest.

Objectives This study aimed to describe patients’ perspectives on their experience in osteopathic treatment, to contribute toward developing interpretative models on effectiveness. Methods A descriptive phenomenological approach was used. The data were collected through a semistructured interview. To capture the variability of the phenomenon, a purposive sample of 12 participants with previous experience of osteopathic care was selected. The data analysis was carried out in an inductive way, and it was parallel to the recruitment to continuously monitor the data saturation. Results Data saturation was reached with 12 participants (female = 9; male = 3). Participants’ age ranged from 27 to 82 years old (mean: 55.25 ± 17.15; median: 59; kurtosis: -0.82). Participants had different reasons for consultation. The analysis showed 1 overarching theme, “Osteopathy is a path of awareness,” 3 themes, and 12 categories. Themes were: (1) “The experience of pain produces awareness of the need for care,” (2) “Osteopathy is a journey to be shared over time,” and (3) “The effectiveness of the osteopathic treatment is the discovery of the person's unity by experience.” Conclusion Participants affirm that osteopathy is a path of awareness that starts from an experience of pain; leads them to contact an osteopath; and ends with their experience of the unity of body, mind, and spirit.

BackgroundIn recent years, the licensure exam in nursing has focused on the range of curricula and teaching methods used in international universities. ‘Tuning’ was the first document that sought to harmonise training purposes in terms of competences and learning outcomes in Europe. Nursing has 47 specific competences divided into 5 domains.MethodsA multicentric observational perspective study was conducted in four universities in the Lazio region for to describe which of 47 Tuning competences are evaluated during the licensure exam in Italian nursing degree courses, at what level of performance, in which clinical area and setting are contextualised, and what types of tests are used for their evaluation. The commissioners of the Professional Order of Rome – OPI – collected data via tests in the licensure exams for the academic years 2017–2019 using 2 grids, one for cognitive and one for psychomotor assessments.ResultsThe Tuning competences were requested 7522 times, 5130 for the cognitive trials and 2392 for the psychomotor trials. The most frequently requested competences were those associated with domain 2, and the level of performance most required in cognitive tests was autonomy of judgement (52.30%). In both tests, the most-investigated competences concerned the area of non-communicable diseases and the hospitalised adult patient. ConclusionsThe competences assessed most often were associated with nursing practice and clinical decision-making. These areas coincided with those deemed essential for the first cycle of studies and are contextualised for the priority health problems of hospitalised adult patients. This indicates that nursing education still focuses on the preparation of nursing students for hospital settings. Moreover, there is still a high degree of discrepancy in the types of tests used in different schools. Their choices are influenced by the number of students and the structural resources available.

Background One of the most common bacteria responsible for most Periprosthetic joint infection (PJI) is Propionibacterium acnes. Even though the rate of infections in patients undergoing total shoulder arthroplasty is increasing, effective diagnostic tests and the precautions taken during the surgery are not yet adequate. This systematic review aims to evaluate the effectiveness of antimicrobial prophylaxis in PJI in shoulder replacement and to provide health workers with the best approach to the use of antimicrobial agents based on currently available clinical evidence. Methods a systematic review of the literature was carried out in accordance with the PRISMA Statement. Studies concerning the effectiveness of antimicrobial prophylaxis in the prevention of PJI in patients undergoing shoulder replacement were included. Results Seven studies were included in the final analysis because they were considered valid. A total of 3272 patients underwent a surgical procedure, most of which were males. The male population has a greater presence of hair, therefore a greater risk of P. acnes. in surface cultures. Patients were assessed at an average follow-up period of 20 months ranging from 9 weeks to 53 months. Conclusion The optimal perioperative antimicrobial regimen is controversial. The clinical guidelines recommend the use of only one antibiotic as prophylaxis but considering the increase in the rates of antibiotic-resistant infections, the question arises whether antibiotic prophylaxis should be extended for adequate coverage. Shoulder arthroplasty performed on the male population must be carefully checked after surgery for the possible presence of P. Acnes.

Background and purpose Stakeholder engagement is the basis of an emerging and innovative educational model called competency-based education. However, although several studies have analysed the stakeholders' perspective in nursing, few studies have analysed the stakeholders' perspective in competence-based curriculum design. Thus, the aim of this study was to analyse the opinions and perspectives of stakeholders about the development of a competency-based baccalaureate nursing curriculum with stakeholder engagement. Methods A phenomenological study was conducted. This method combines descriptive features (Husserlian) and interpretive phenomenology (Gadamerian). The interviews were ended when data saturation was achieved, specifically the redundancy of themes. Results The content analysis identified three main categories: (1) a “bridge” that merges education and the work context, (2) stakeholder engagement – a contentious issue; and (3) stakeholder engagement – structuring a methodology. Conclusions Through the stakeholder engagement, university could have a constant interaction between the didactics and professional practice and could improve professional identity and job satisfaction among nurses.

This review aimed to summarize existing nursing literature to provide an overview of the extent, range, and nature of nurses' involvement in artificial nutrition and hydration (ANH) at the end of life and to map the key concepts underpinning nurses' involvement in ANH. A scoping review was designed following the methodological framework guidelines of Arksey and O'Malley and the recommendations for advancing the methodology by Levac et al. An inductive qualitative content analysis was conducted according to the guidelines by Elo and Kyngäs. Thirty-nine articles were identified. Content analysis revealed 1 main category: "nurses' role in the decision-making process," with the 2 subcategories of "mediator" and "activator." The category and subcategories are influenced by the following generic categories: "being," "feeling," and "knowing," each of them constituted by 2 subcategories in their turn. Nurses perform the roles of activator and mediator. Their ability to establish good relationships and their attitudes enable the creation of teamwork and closeness to patients and family: relationships and attitudes are the subcategories of the "being" category. The category "feeling" represents the ways nurses experience the decision-making process, which can raise ethical and moral dilemmas and cause emotional responses. For these reasons, nurses have to create the right balance between personal-self and professional-self. The category "knowing" includes nurses' clinical and ethical knowledge about ANH. It emerges that deep clinical and ethical knowledge of ANH is necessary to provide consistent, adequate care at end of life.

Work-related musculoskeletal disorders (WMSDs) are among the main causes of injury and pain in healthcare professionals. Previous reviews provided a fragmented view of the interventions available for WMSDs. This review aims to provide a comprehensive description of interventions for preventing and reducing work-related musculoskeletal injuries and/or pain among healthcare professionals, and to assess the methodological quality of studies.A systematic literature review was performed, based on the Effective Public Health Practice Project process. A comprehensive search was conducted on six peer-reviewed databases and manually. The methodological quality of the studies included was rated as weak, moderate, or strong. The studies were organized based on the 2019 classification of the interventions by Oakman and colleagues.Twenty-seven articles were included reporting individual (n = 4), task-specific (n = 4), work organization and job design (n = 2), work environment (n = 1), and multifactorial (n = 16) interventions. Overall quality rating was strong for 6 studies, moderate for 16, and weak for 5. Individual interventions such as neuromuscular and physical exercise were effective in reducing pain. Task-specific and work organization interventions could prevent certain injuries. Significant reduction of both injuries and pain resulted from multifactorial interventions, which were reported by the majority of strong (n = 5) and moderate (n = 10) quality articles.This review provides healthcare professionals with evidence-based information to plan interventions targeted towards reducing WMSDs. In particular, more efforts are needed to implement and extend effective multifactorial interventions. Moreover, studies about each professional healthcare target group are needed.Our results can guide policy-makers, healthcare managers and professionals to choose the best strategies to prevent and reduce WMSDs and to shape continuous education programs. This study prompts clinicians to develop inter-professional collaborations and to practice physical activities in order to reduce WMSDs.

Bone marrow (BM) microenvironment contributes to the regulation of normal hematopoiesis through a finely tuned balance of self-renewal and differentiation processes, cell-cell interaction and secretion of cytokines that during leukemogenesis are altered and favor tumor cell growth. In pediatric acute myeloid leukemia (AML), chemotherapy is the standard of care, but still >30% of patients relapse. The need to accelerate the evaluation of innovative medicines prompted us to investigate the mesenchymal stromal cells (MSCs) role in the leukemic niche to define its contribution to the mechanisms of leukemia escape. We generated humanized three-dimensional (3D) niche with AML cells and MSCs derived from either patients (AML-MSCs) or healthy donors. We observed that AML cells establish physical connections with MSCs, mediating a reprogrammed transcriptome inducing aberrant cell proliferation and differentiation, and severely compromising their immunomodulatory capability. We confirmed that AML cells modulate h-MSCs transcriptional profile promoting functions similar to the AML-MSCs when co-cultured in vitro, thus facilitating leukemia progression. Conversely, MSCs derived from BM of patients at time of disease remission showed recovered healthy features, at transcriptional and functional levels, including the secretome. We proved that AML blasts alter MSCs activities in the BM niche, favoring disease development and progression. We discovered that a novel AML-MSCs selective CaV1.2 channel blocker drug, Lercanidipine, is able to impair leukemia progression in 3D niche both in vitro and when implanted in vivo, if used in combination with chemotherapy, supporting the hypothesis that synergistic effects can be obtained by dual targeting approaches.

Aim and objective To test the psychometric properties of the nursing students' version of the 24-item Caring Behaviours Inventory. Background Caring is at the heart of nursing and should also be a core value in nursing education. Caring can be manifested through measurable behaviours. The Caring Behaviors Inventory is a valid and reliable measure of nurses' caring behaviours in clinical settings. It has already been used among nursing students, but it needs more psychometric testing. Design Cross-sectional validation study. Method The questionnaire was filled in by 300 undergraduate nursing students at two Italian universities in May 2016. Exploratory factor analysis was conducted using Mplus maximum likelihood with GEOMIN oblique rotation. A multifaceted approach was used to evaluate the model fit. The STROBE checklist for cross-sectional studies was followed. Results Four dimensions were identified: "being with," "doing with competence," "responding to individual needs" and "providing effective care." Adequate fit indices and high reliability of the factors were found. Correlations between factors were positive and significant. Conclusion This study makes it possible to use the same tool to compare the caring practices perceived by students, nurses and patients. Further studies with bigger samples could be stratified to investigate the associations between caring levels and student characteristics. The Caring Behaviors Inventory can be used to call attention to caring in nursing education, helping to make this concept less elusive. Relevance to clinical practice The effective self-assessment of nursing students' caring behaviours offers opportunities for reflection on their caring practice. This could improve the caring level of their behaviours in clinical practice and help them to become caring nurses in the future.

Aims and objectives To summarise the evidence about patient-related risk factors for difficult intravenous access in adults, and at identifying nurses' beliefs and their consistency with evidence. Background Peripheral intravenous cannulation is a common procedure for nurses, but rates of failure at first attempt of peripheral intravenous cannulation range 10%-40%. Nurses' beliefs about difficult intravenous access factors might influence their clinical practice more than current evidence. Design The study included a literature review of the evidence on patient-related risk factors for difficult intravenous access, the development of an instrument to investigate nurses' beliefs about this topic and a cross-sectional multicentre survey on clinical nurses. Methods The quality of the studies included was evaluated through the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A synthesis of evidence for each risk factor was produced. A survey instrument was developed including 26 risk factors, which were then rated by nurses as perceived predictors of difficult intravenous access. The STROBE guidelines for study reporting were followed. Results Four hundred and fifty clinical nurses working in four hospitals in Italy were surveyed. Nurses' beliefs were in line with evidence in considering body mass index, drug abuse, lymphadenectomy and chemotherapy as difficult intravenous access factors. Beliefs about difficult intravenous access factors were influenced by nurses' work experience and frequency of peripheral intravenous cannulation. Nurses also identified as risk factors for difficult intravenous access oedema, thrombophlebitis, hypovolaemia, skin lesions and irritant therapies, which have been minimally investigated by research. Conclusions An overall congruence between nurses' beliefs and evidence about risk factors for difficult intravenous access was found. With their expertise, nurses may fill the knowledge gap of clinical evidence and open new paths for clinically meaningful research. Relevance to clinical practice Nurses' beliefs about difficult intravenous access factors can be influenced by their work experience and clinical setting. Integrating nurses' beliefs with scientific evidence can increase the quality of care.

Background Dependence is a common life experience and innate condition for human beings due to their bodily and relational essence, but in contemporary society, it has become a stressful condition. Care dependence is central to nursing, and patients with advanced cancer are often dependent on care. Understanding nurses' perceptions of care dependence can contribute to awareness of the impact it has on nurses. Objective The aim of this study was to explore palliative care nurses' experiences and perceptions regarding patient dependence. Methods Sixteen nurses taking care of dependent patients in a palliative care center in Rome were interviewed. Giorgi's descriptive phenomenological method was used. Results Nurses caring for dependent patients transcend the boundaries of dependence. Care dependence is an experience of powerlessness and regression. A patient's life in dependence is precarious, as they have to overcome the daily limits of life. Taking care of dependent patients requires nurses to manage the unmanageable and to know and to embrace change from within in order to build positive relations of personal closeness and reciprocal self-giving. Conclusions Nurses should be aware that self-transcendence and the consequent positive relations could make the difference in the experience of care dependence and promote personal growth for both patient and nurse. Positive and transcending relationships can transform care dependence into the opportunity to find meaning and purpose in life. Implications for practice The study highlights what nurses feel in caring for dependent patients. Understanding nurses' perceptions is important to delineate a proper caring for dependent patients.

Aims and objectives To describe which nursing activities are observed during the discharge of older patients with chronic diseases and to investigate the consistency between the nursing activities actually observed and those documented. Background The discharge from hospital of older patients with chronic diseases is a critical transition that can lead to dissatisfaction, delays in discharge, re-admission, adverse events and increased mortality. Although nurses' interventions during discharge are important for patient outcomes, little is known about the nursing activities actually performed as compared with those documented. Design An observational study of the nursing activities performed during patients' discharge and a retrospective audit of the nursing records of the same patients and nurses. Methods Structured nonparticipant observations were conducted of the activities performed by nurses at discharge. A retrospective audit of the nursing records relating to patient discharge, including the nursing diary and the assessment of critical issues at hospital discharge, was also conducted. The STROBE guidelines were followed (See Supporting Information Appendix S2). Results During hospital discharge of 102 patients, 1,224 nursing activities were observed. The number of activities was not related to patients' age, gender and educational level, nor to nurses' postgraduate education. Statistically significant correlations emerged between the number of activities observed and the nurses' work experience. Conclusions A predefined discharge plan guiding nurses' activities during discharge would enable them to respond better to the care needs of elderly patients. Relevance to clinical practice Results from the study could help clinical nurses to address care priorities of patients at discharge, by using appropriate plans and checklists and improving recording rates. Novice nurses should be supported when caring for elderly patients with chronic disease at discharge.

The AW288 and AX067 antibodies recognize human actin in paraformaldehyde-fixed HEK cells by immunofluorescence.

The AK423 antibody, raised against Dictyostelium actin, recognizes both Dictyostelium and human actin by western blot. However, it recognizes Dictyostelium actin with higher affinity than human actin.

AF397, AK652, AN193 and AV442 antibodies against the GFP protein recognize a GFP-tagged human B4GT1 protein by immunofluorescence in paraformaldehyde-fixed HEK cells.

AF397, AK652, AN193 and AV442 antibodies against the GFP protein recognize a GFP-tagged human TAC protein by western blot.

The AE765, AK692, AO233 and AO234 antibodies recognize human actin in PAF-fixed HEK cells by immunofluorescence. Phalloidin, which recognizes polymerized actin, is more adequate to label actin filamentous structures. The AK423 antibody recognizes human actin in methanol-fixed HEK cells, but in these conditions the actin network is poorly preserved.

The AK423 antibody, raised against Dictyostelium actin, recognizes human actin by western blot; AE765, AK692, AO233 and AO234 do not.

Background and Objectives: Unicompartmental knee arthroplasty (UKA) is a valid alternative to total knee arthroplasties (TKAs) in selected cases. After surgery, patients’ experience and satisfaction were traditionally evaluated by pre- and postsurgical scores and Patient-Reported Outcome Measures (PROMs). Otherwise, a statistically significant change does not necessarily correlate to a clinically meaningful improvement when measured using PROMs. To evaluate the real effect of a specific treatment and understand the difference between groups in a clinical trial, it is necessary to use a meaningful quantum of change on the score assessed. The minimal clinically important difference (MCID) and the Patient Acceptable Symptom State (PASS) can provide this meaningful change. This paper aimed to calculate the MCID and the PASS of the Forgotten Joint Score (FJS-12) after UKA. Materials and Methods: A total of 40 patients with a mean age 72.5 ± 6.4 years undergoing UKA were assessed preoperatively and six months postsurgery using the FJS-12 and the Oxford Knee Score (OKS). The baseline and 6-month postoperative scores were compared using the Wilcoxon signed ranks test. The correlation was calculated with Spearman’s rho. Both distribution-based approaches and anchor approaches were used to estimate MCID for the FJS-12. The 75th percentile and the Receiver operating characteristic (ROC) curve methods were used to calculate the PASS of FJS-12. Results: MCID estimates for normalized FJS-12 for UKA ranged from 5.68 to 19.82. The threshold of the FJS-12 with ROC method was 72.92 (AUC = 0.76). The cut-off value computed with the 75th percentile approach was 92.71. Conclusions: The MCID and PASS represent valid tools to assess the real perception of clinical improvement in patients who underwent UKA. The MCID value of FJS-12 was 12.5 for patients who underwent UKA. The value of the PASS for the FJS-12 in patients who underwent UKA was 72.92.

LrrkA is a Dictyostelium discoideum kinase with leucine-rich repeats. LrrkA stimulates Kil2 and intra-phagosomal killing of ingested bacteria in response to folate. In this study, we show that genetic inactivation of lrrkA also causes a previously unnoticed phenotype: lrrkA KO cells exhibit enhanced phagocytosis and cell motility compared to parental cells. This phenotype is cell autonomous, is reversible upon re-expression of LrrkA, and is not due to an abnormal response to inhibitory quorum-sensing factors secreted by D. discoideum in its medium. In addition, folate increases motility in parental D. discoideum cells, but not in lrrkA KO cells, suggesting that LrrkA plays a pivotal role in the cellular response to folate. On the contrary, lrrkA KO cells regulate gene transcription in response to folate in a manner indistinguishable from parental cells. Overall, based on analysis of mutant phenotypes, we identify gene products that participate in the control of intracellular killing, cell motility, and gene transcription in response to folate. These observations reveal a mechanism by which D. discoideum encountering bacterially-secreted folate can migrate, engulf, and kill bacteria more efficiently.

Ingestion and killing of bacteria by phagocytic cells protect the human body against infections. While many mechanisms have been proposed to account for bacterial killing in phagosomes, their relative importance, redundancy, and specificity remain unclear. In this study, we used the Dictyostelium discoideum amoeba as a model phagocyte and quantified the requirement of 11 individual gene products, including nine putative effectors, for the killing of bacteria. This analysis revealed that radically different mechanisms are required to kill Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis AlyL, a lysozyme-like protein equipped with a distinct bacteriolytic region, plays a specific role in the intracellular killing of K. pneumoniae, with assistance from BpiC and Aoah, two lipopolysaccharide (LPS)-binding proteins. Rapid killing of E. coli and P. aeruginosa requires the presence of BpiC and of the NoxA NADPH oxidase. No single effector tested is essential for rapid killing of S. aureus or B. subtilis Overall, our observations reveal an unsuspected degree of specificity in the elimination of bacteria in phagosomes.IMPORTANCE Phagocytic cells ingest and kill bacteria, a process essential for the defense of the human body against infections. Many potential killing mechanisms have been identified in phagocytic cells, including free radicals, toxic ions, enzymes, and permeabilizing peptides. Yet fundamental questions remain unanswered: what is the relative importance of these mechanisms, how redundant are they, and are different mechanisms used to kill different species of bacteria? We addressed these questions using Dictyostelium discoideum, a model phagocytic cell amenable to genetic manipulations and quantitative analysis. Our results reveal that vastly different mechanisms are required to kill different species of bacteria. This very high degree of specificity was unexpected and indicates that a lot remains to be discovered about how phagocytic cells eliminate bacteria.

A prospective comparative study was conducted in 487 pediatric patients (69% male, mean age = 6.4 ± 4.0) to evaluate (a) the incidence, intensity, and characteristics of pain in pediatric patients at home during the first 24 hours and 5 days after surgery and (b) the factors associated with higher pain intensity, including the impact of an application (App) compared to the paper-and-pencil approach. Postoperative pain was assessed by patients or their parents at home using the ‘Bambino Gesù’ Children’s Hospital (Ospedale Pediatrico Bambino Gesù, OPBG) tool for participants aged 4–17 years or the Faces, Legs, Arms, Cry, and Consolability scale for participants less than four years old. Participants were assigned to two groups: those who used the paper-and-pencil version of the pain scale and those who used the App. Overall, 209 of the 472 (44%) participants reported pain during the first 24 hours, and 92 of the 420 (22%) reported pain between one and five days after surgery. Higher pain intensity scores were associated with being in the App group, directly assessing own pain, and using the OPBG tool. The App was effective in facilitating pain assessment. Health professionals could empower pediatric patients and their parents in assessing pain at home through a dedicated App.

Simple Summary Nucleophosmin (NPM1) protein regulates several cellular processes and is predominantly located in the nucleolus, owing to the localization signal provided by two tryptophan residues. In acute myeloid leukemia (AML), NPM1 gene is frequently mutated, leading to the aberrant translocation of the protein into cytoplasm. In the present work, we classified NPM1 mutations according to the loss of either one or both tryptophan residues as non-A-like and A-like mutations, respectively, and evaluated their biological features. We found that non-A-like mutations partially delocalize NPM1 protein into the cytoplasm, with a proportion of remaining nucleolar protein preserving p53 protein expression and downstream activity. Different HOXA and HOXB gene expression and cell death pathway activation between A-like and non-A-like NPM1-mutated cells were shown, with an enhanced sensitivity to chemotherapy for AML cells with non-A-like mutations. This study suggests the need for a sub-classification of NPM1-mutated AML, with subsequent implications in the therapeutic management. Abstract Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling protein, predominantly located in the nucleolus, that regulates a multiplicity of different biological processes. NPM1 localization in the cell is finely tuned by specific signal motifs, with two tryptophan residues (Trp) being essential for the nucleolar localization. In acute myeloid leukemia (AML), several NPM1 mutations have been reported, all resulting in cytoplasmic delocalization, but the putative biological and clinical significance of different variants are still debated. We explored HOXA and HOXB gene expression profile in AML patients and found a differential expression between NPM1 mutations inducing the loss of two (A-like) Trp residues and those determining the loss of one Trp residue (non-A-like). We thus expressed NPM1 A-like- or non-A-like-mutated vectors in AML cell lines finding that NPM1 partially remained in the nucleolus in the non-A-like NPM1-mutated cells. As a result, only in A-like-mutated cells we detected HOXA5, HOXA10, and HOXB5 hyper-expression and p14ARF/p21/p53 pathway deregulation, leading to reduced sensitivity to the treatment with either chemotherapy or Venetoclax, as compared to non-A-like cells. Overall, we identified that the NPM1 mutational status mediates crucial biological characteristics of AML cells, providing the basis for further sub-classification and, potentially, management of this subgroup of patients.

The AF300 and AW922 antibodies detect by immunofluorescence human cytokeratin in methanol-fixed HeLa cells.

The AN703 antibody, derived from the 221-42-1 hybridoma, detects PDI-containing endoplasmic reticulum of Dictyostelium discoideum by immunofluorescence.

Background Nutrition is a basic patients' need and an important component of nursing. End-of-life cancer patients can experience difficulties in eating and drinking, sometimes requiring artificial nutrition and hydration (ANH). Nurses' knowledge and attitudes greatly influence nursing care. Nurses may lack knowledge of ANH. To date, no study has explored the knowledge and attitudes of oncology and palliative care nurses toward end-of-life ANH. Objective To describe oncology and palliative care nurses' knowledge of and attitudes toward ANH. Methods A multicenter cross-sectional study was conducted in 7 regions of Italy using the Italian version of the Questionnaire on Knowledge and Attitudes in Providing ANH for Terminal Cancer Patients. Attitudes were divided into benefits and burdens of providing ANH. Data were analyzed by descriptive statistics. Results High percentages of oncology and palliative care nurses showed reasonable knowledge about ANH. More disagreement was evidenced about benefits and burdens of ANH, and lower importance was given to them. Conclusions Some misconceptions and a low level of awareness exist among some nurses about ANH. More nursing studies should be conducted and extended to different care settings. Moreover, guidelines should be reinforced with a nursing perspective to better define nurses' role in the decision-making process on ANH. Implications for practice This exploration of nurses' knowledge of and attitudes toward ANH in end-of-life cancer patients can contribute to an understanding of how nurses can be involved in better meeting cancer patients' nutritional needs at the end of life.