Role of CDKL1-SOX11 signaling axis in Acute Kidney Injury.

The biology of CDKL (Cyclin-Dependent Kinase-Like) kinase family remains enigmatic. Contrary to their nomenclature, CDKLs do not rely on cyclins for activation and are not involved in cell cycle regulation. Instead, they share structural similarities with MAPKs (Mitogen-Activated Protein Kinases) and GSK3 (glycogen synthase kinase 3), though their specific functions and associated signaling pathways are still unknown. Previous studies have shown that the activation of CDKL5 kinase contributes to the development of acute kidney injury (AKI) by suppressing the protective SOX9-dependent transcriptional program in tubular epithelial cells. In the current study, we measured the functional activity of all the five CDKL kinases and discovered that, in addition to CDKL5, CDKL1 is also activated in tubular epithelial cells during AKI. To explore the role of CDKL1, we generated a germline knockout mouse which exhibited no abnormalities under normal conditions. Notably, when these mice were challenged with bilateral ischemia reperfusion and rhabdomyolysis, they were found to be protected from AKI. Further mechanistic investigations revealed that CDKL1 phosphorylates and destabilizes SOX11, contributing to tubular dysfunction. In summary, these studies have unveiled a previously unknown CDKL1-SOX11 axis that drives tubular dysfunction during AKI.

Brain 3T magnetic resonance imaging in neonates: features and incidental findings from a research cohort enriched for preterm birth.

BACKGROUND AND OBJECTIVES: The survival rate and patterns of brain injury after very preterm birth are evolving with changes in clinical practices. Additionally, incidental findings can present legal, ethical and practical considerations. Here, we report MRI features and incidental findings from a large, contemporary research cohort of very preterm infants and term controls. METHODS: 288 infants had 3T MRI at term-equivalent age: 187 infants born <32 weeks without major parenchymal lesions, and 101 term-born controls. T1-weighted, T2-weighted and susceptibility-weighted imaging were used to classify white and grey matter injury according to a structured system, and incidental findings described. RESULTS: Preterm infants: 34 (18%) had white matter injury and 4 (2%) had grey matter injury. 51 (27%) infants had evidence of intracranial haemorrhage and 34 (18%) had punctate white matter lesions (PWMLs). Incidental findings were detected in 12 (6%) preterm infants. Term infants: no term infants had white or grey matter injury. Incidental findings were detected in 35 (35%); these included intracranial haemorrhage in 22 (22%), periventricular pseudocysts in 5 (5%) and PWMLs in 4 (4%) infants. From the whole cohort, 10 (3%) infants required referral to specialist services. CONCLUSIONS: One-fifth of very preterm infants without major parenchymal lesions have white or grey matter abnormalities at term-equivalent age. Incidental findings are seen in 6% of preterm and 35% of term infants. Overall, 3% of infants undergoing MRI for research require follow-up due to incidental findings. These data should help inform consent procedures for research and assist service planning for centres using 3T neonatal brain MRI for clinical purposes.

Atf4 protects islet ß-cell identity and function under acute glucose-induced stress but promotes ß-cell failure in the presence of free fatty acid.

Glucolipotoxicity, caused by combined hyperglycemia and hyperlipidemia, results in ß-cell failure and type 2 diabetes (T2D) via cellular stress-related mechanisms. Activating transcription factor 4 (Atf4) is an essential effector of stress response. We show here that Atf4 expression in ß-cells is dispensable for glucose homeostasis in young mice, but it is required for ß-cell function during aging and under obesity-related metabolic stress. Henceforth, aged Atf4- deficient ß-cells display compromised secretory function under acute hyperglycemia. In contrast, they are resistant to acute free fatty acid-induced loss-of identity and dysfunction. At molecular level, Atf4 -deficient ß-cells down-regulate genes involved in protein translation, reducing ß-cell identity gene products under high glucose. They also upregulate several genes involved in lipid metabolism or signaling, likely contributing to their resistance to free fatty acid-induced dysfunction. These results suggest that Atf4 activation is required for ß-cell identity and function under high glucose, but this paradoxically induces ß-cell failure in the presence of high levels of free fatty acids. Different branches of Atf4 activity could be manipulated for protecting ß-cells from metabolic stress-induced failure. Highlights: Atf4 is dispensable in ß-cells in young miceAtf4 protects ß-cells under high glucoseAtf4 exacerbate fatty acid-induced ß-cell defectsAtf4 activates translation but depresses lipid-metabolism.

Femoral Neck Fractures With Associated Ipsilateral Femoral Shaft Fractures in Young Adults <50 Years Old: A Multicenter Comparison of 80 Cases Versus Isolated Femoral Neck Fractures.

OBJECTIVES: To analyze patients, injury patterns, and treatment of femoral neck fractures (FNFs) in young patients with FNFs associated with shaft fractures (assocFNFs) to improve clinical outcomes. The secondary goal was to compare this injury pattern to that of young patients with isolated FNFs (isolFNFs). DESIGN: Retrospective multicenter cohort series. SETTING: Twenty-six North American level-1 trauma centers. PATIENT SELECTION CRITERIA: Skeletally mature patients, <50 years old, treated with operative fixation of an FNF with or without an associated femoral shaft fracture. OUTCOME MEASURES AND COMPARISONS: The main outcome measurement was treatment failure defined as nonunion, malunion, avascular necrosis, or subsequent major revision surgery. Odds ratios for these modes of treatment were also calculated. RESULTS: Eighty assocFNFs and 412 isolFNFs evaluated in this study were different in terms of patients, injury patterns, and treatment strategy. Patients with assocFNFs were younger (33.3 ± 8.6 vs. 37.5 ± 8.7 years old, P < 0.001), greater in mean body mass index [BMI] (29.7 vs. 26.6, P < 0.001), and more frequently displaced (95% vs. 73%, P < 0.001), "vertically oriented" Pauwels type 3, P < 0.001 (84% vs. 43%) than for isolFNFs, with all P values < 0.001. AssocFNFs were more commonly repaired with an open reduction (74% vs. 46%, P < 0.001) and fixed-angle implants (59% vs. 39%) (P < 0.001). Importantly, treatment failures were less common for assocFNFs compared with isolFNFs (20% vs. 49%, P < 0.001) with lower rates of failed fixation/nonunion and malunion (P < 0.001 and P = 0.002, respectively). Odds of treatment failure [odds ratio (OR) = 0.270, 95% confidence interval (CI), 0.15-0.48, P < 0.001], nonunion (OR = 0.240, 95% CI, 0.10-0.57, P < 0.001), and malunion (OR = 0.920, 95% CI, 0.01-0.68, P = 0.002) were also lower for assocFNFs. Excellent or good reduction was achieved in 84.2% of assocFNFs reductions and 77.1% in isolFNFs (P = 0.052). AssocFNFs treated with fixed-angle devices performed very well, with only 13.0% failing treatment compared with 51.9% in isolFNFs treated with fixed-angle constructs (P = <0.001) and 33.3% in assocFNFs treated with multiple cannulated screws (P = 0.034). This study also identified the so-called "shelf sign," a transverse ≥6-mm medial-caudal segment of the neck fracture (forming an acute angle with the vertical fracture line) in 54% of assocFNFs and only 9% of isolFNFs (P < 0.001). AssocFNFs with a shelf sign failed in only 5 of 41 (12%) cases. CONCLUSIONS: AssocFNFs in young patients are characterized by different patient factors, injury patterns, and treatments, than for isolFNFs, and have a relatively better prognosis despite the need for confounding treatment for the associated femoral shaft injury. Treatment failures among assocFNFs repaired with a fixed-angle device occurred at a lower rate compared with isolFNFs treated with any construct type and assocFNFs treated with multiple cannulated screws. The radiographic "shelf sign" was found as a positive prognostic sign in more than half of assocFNFs and predicted a high rate of successful treatment. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Evidence of Lactobacillus strains shared between the female urinary and vaginal microbiota.

Lactobacillus species are common inhabitants of the 'healthy' female urinary and vaginal communities, often associated with a lack of symptoms in both anatomical sites. Given identification by prior studies of similar bacterial species in both communities, it has been hypothesized that the two microbiotas are in fact connected. Here, we carried out whole-genome sequencing of 49 Lactobacillus strains, including 16 paired urogenital samples from the same participant. These strains represent five different Lactobacillus species: L. crispatus, L. gasseri, L. iners, L. jensenii, and L. paragasseri. Average nucleotide identity (ANI), alignment, single-nucleotide polymorphism (SNP), and CRISPR comparisons between strains from the same participant were performed. We conducted simulations of genome assemblies and ANI comparisons and present a statistical method to distinguish between unrelated, related, and identical strains. We found that 50 % of the paired samples have identical strains, evidence that the urinary and vaginal communities are connected. Additionally, we found evidence of strains sharing a common ancestor. These results establish that microbial sharing between the urinary tract and vagina is not limited to uropathogens. Knowledge that these two anatomical sites can share lactobacilli in females can inform future clinical approaches.

VAMP2 regulates phase separation of α-synuclein.

α-Synuclein (αSYN), a pivotal synaptic protein implicated in synucleinopathies such as Parkinson's disease and Lewy body dementia, undergoes protein phase separation. We reveal that vesicle-associated membrane protein 2 (VAMP2) orchestrates αSYN phase separation both in vitro and in cells. Electrostatic interactions, specifically mediated by VAMP2 via its juxtamembrane domain and the αSYN C-terminal region, drive phase separation. Condensate formation is specific for R-SNARE VAMP2 and dependent on αSYN lipid membrane binding. Our results delineate a regulatory mechanism for αSYN phase separation in cells. Furthermore, we show that αSYN condensates sequester vesicles and attract complexin-1 and -2, thus supporting a role in synaptic physiology and pathophysiology.

A prospective evaluation of the prostate microbiome in malignant and benign tissue using transperineal biopsy.

BACKGROUND: The link between the prostate microbiome and prostate cancer remains unclear. Few studies have analyzed the microbiota of prostate tissue, and these have been limited by potential contamination by transrectal biopsy. Transperineal prostate biopsy offers an alternative and avoids fecal cross-contamination. We aim to characterize the prostate microbiome using transperineal biopsy. METHODS: Patients with clinical suspicion for prostate cancer who were to undergo transperineal prostate biopsy with magnetic resonance imaging (MRI) fusion guidance were prospectively enrolled from 2022 to 2023. Patients were excluded if they had Prostate Imaging Reporting and Data System lesions with scores ≤ 3, a history of prostate biopsy within 1 year, a history of prostate cancer, or antibiotic use within 30 days of biopsy. Tissue was collected from the MRI target lesions and nonneoplastic transitional zone. Bacteria were identified using 16S ribosomal RNA gene sequencing. RESULTS: Across the 42 patients, 76% were found to have prostate cancer. Beta diversity indices differed significantly between the perineum, voided urine, and prostate tissue. There were no beta diversity differences between cancerous or benign tissue, or between pre- and postbiopsy urines. There appear to be unique genera more abundant in cancerous versus benign tissue. There were no differences in alpha diversity indices relative to clinical findings including cancer status, grade, and risk group. CONCLUSIONS: We demonstrate a rigorous method to better characterize the prostate microbiome using transperineal biopsy and to limit contamination. These findings provide a framework for future large-scale studies of the microbiome of prostate cancer.

Deuterium MRI of serine metabolism in mouse models of glioblastoma.

PURPOSE: Serine is a major source of one-carbon units needed for the synthesis of nucleotides and the production of intramitochondrial nicotinamide adenine dinucleotide phosphate (NADPH), and it plays an important role in cancer cell proliferation. The aim of this study was to develop a deuterium (2H) MRS imaging method for imaging tumor serine metabolism. METHODS: Sequential (2H) spectra and spectroscopic images were used to monitor the metabolism of [2,3,3-2H3]serine in patient-derived glioblastoma cells in vitro and in tumors obtained by their orthotopic implantation in mouse brain. RESULTS: [14,14-2H2] 5,10-methylene-tetrahydrofolate, [2H]glycine, [2H]formate, and labeled water were detected in cell suspensions and water labeling in spectroscopic images of tumors. Studies in cells and tumors with variable mitochondrial content and inhibitor studies in cells demonstrated that most of the labeled serine was metabolized in the mitochondria. Water labeling in the cell suspensions was correlated with formate labeling; therefore, water labeling observed in tumors could be used to provide a surrogate measure of flux in the pathway of one-carbon metabolism in vivo. CONCLUSION: The method has the potential to be used clinically to select patients for treatment with inhibitors of one-carbon metabolism and subsequently to detect their early responses to such treatment.

Visual perspective taking neural processing in forensic cases with high density EEG.

This EEG study aims at dissecting the differences in the activation of neural generators between borderline personality disorder patients with court-ordered measures (BDL-COM) and healthy controls in visual perspective taking. We focused on the distinction between mentalizing (Avatar) and non-mentalizing (Arrow) stimuli as well as self versus other-perspective in the dot perspective task (dPT) in a sample of 15 BDL-COM cases and 54 controls, all of male gender. BDL-COM patients showed a late and diffuse right hemisphere involvement of neural generators contrasting with the occipitofrontal topography observed in controls. For Avatars only and compared to controls, the adoption of Self perspective involved a lower EEG activity in the left inferior frontal, right middle temporal cortex and insula in BDL-COM patients prior to 80 ms post-stimulus. When taking the Other-perspective, BDL-COM patients also showed a lower activation of superior frontal, right inferior temporal and fusiform cortex within the same time frame. The beta oscillation power was significantly lower in BDL-COM patients than controls between 400 and 1300 ms post stimulus in the Avatar-Other condition. These results indicate that BDL-COM patients display both altered topography of EEG activation patterns and reduced abilities to mobilize beta oscillations during the treatment of mentalistic stimuli in dPT.

Nourishing Physical Productivity and Performance On a Warming Planet - Challenges and Nutritional Strategies to Mitigate Exertional Heat Stress.

PURPOSE OF REVIEW: Climate change is predicted to increase the frequency and severity of exposure to hot environments. This can impair health, physical performance, and productivity for active individuals in occupational and athletic settings. This review summarizes current knowledge and recent advancements in nutritional strategies to minimize the impact of exertional-heat stress (EHS). RECENT FINDINGS: Hydration strategies limiting body mass loss to < 3% during EHS are performance-beneficial in weight-supported activities, although evidence regarding smaller fluid deficits (< 2% body mass loss) and weight-dependent activities is less clear due to a lack of well-designed studies with adequate blinding. Sodium replacement requirements during EHS depends on both sweat losses and the extent of fluid replacement, with quantified sodium replacement only necessary once fluid replacement > 60-80% of losses. Ice ingestion lowers core temperature and may improve thermal comfort and performance outcomes when consumed before, but less so during activity. Prevention and management of gastrointestinal disturbances during EHS should focus on high carbohydrate but low FODMAP availability before and during exercise, frequent provision of carbohydrate and/or protein during exercise, adequate hydration, and body temperature regulation. Evidence for these approaches is lacking in occupational settings. Acute kidney injury is a potential concern resulting from inadequate fluid replacement during and post-EHS, and emerging evidence suggests that repeated exposures may increase the risk of developing chronic kidney disease. Nutritional strategies can help regulate hydration, body temperature, and gastrointestinal status during EHS. Doing so minimizes the impact of EHS on health and safety and optimizes productivity and performance outcomes on a warming planet.

Glutamine metabolism improves left ventricular function but not macrophage-mediated inflammation following myocardial infarction.

Glutamine is a critical amino acid that serves as an energy source, building block, and signaling molecule for the heart tissue and the immune system. However, the role of glutamine metabolism in regulating cardiac remodeling following myocardial infarction (MI) is unknown. In this study, we show in adult male mice that glutamine metabolism is altered both in the remote (contractile) area and in infiltrating macrophages in the infarct area after permanent left anterior descending artery occlusion. We found that metabolites related to glutamine metabolism were differentially altered in macrophages at days 1, 3, and 7 after MI using untargeted metabolomics. Glutamine metabolism in live cells was increased after MI relative to no MI controls. Gene expression in the remote area of the heart indicated a loss of glutamine metabolism. Glutamine administration improved LV function at days 1, 3, and 7 after MI, which was associated with improved contractile and metabolic gene expression. Conversely, administration of BPTES, a pharmacological inhibitor of glutaminase-1, worsened LV function after MI. Neither glutamine nor BPTES administration impacted gene expression or bioenergetics of macrophages isolated from the infarct area. Our results indicate that glutamine metabolism plays a critical role in maintaining LV contractile function following MI, and that glutamine administration improves LV function. Glutamine metabolism may also play a role in regulating macrophage function, but macrophages are not responsive to exogenous pharmacological manipulation of glutamine metabolism.

Draft genome assemblies of three Klebsiella grimontii strains isolated from catheterized urine samples from the same male participant over the course of 6 months.

Klebsiella grimontii is a newly identified species within the Klebsiella oxytoca complex. Here, we present the draft genome sequence of three K. grimontii strains that were isolated from catheterized urine samples collected from a participant in a longitudinal study over ~6 months.

Emerging genetic technologies informing personalized medicine in SDS and other inherited bone marrow failure disorders.

The ribosomopathy Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive inherited bone marrow failure syndrome (IBMFS) caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, that is associated with an increased risk of myeloid malignancy. Tracking how hematopoietic stem cell (HSC) clonal dynamics change over time, assessing whether somatic genetic rescue mechanisms affect these dynamics, and mapping out when leukemic driver mutations are acquired is important to understand which individuals with SDS may go on to develop leukemia. In this review, we will discuss how new technologies that allow researchers to map mutations at the level of single HSC clones are generating important insights into genetic rescue mechanisms and their relative risk for driving evolution to leukemia, and how these data can inform the future development of personalized medicine approaches in SDS and other IBMFSs.

Comprehensive Micro-SPE-Based Bottom-Up Proteomic Workflow for Sensitive Analysis of Limited Samples.

Clinical and biological samples are often scarce and precious (e.g., rare cell isolates, microneedle tissue biopsies, small-volume liquid biopsies, and even single cells or organelles). Typical large-scale proteomic methods, where significantly higher protein amounts are analyzed, are not directly transferable to the analysis of limited samples due to their incompatibility with pg-, ng-, and low-µg-level protein sample amounts. Here, we report the on-microsolid-phase extraction tip (OmSET)-based sample preparation workflow for sensitive analysis of limited biological samples to address this challenge. The developed platform was successfully tested for the analysis of 100-10,000 typical mammalian cells and is scalable to allow for lower and larger protein amounts and more samples to be analyzed (i.e., higher throughput of analysis).

Outcomes of Patients With Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease at 3 and 5 Years After Diagnosis.

BACKGROUND AND OBJECTIVES: Retrospective studies indicate that dementia with Lewy bodies (DLB) may be preceded by a mild cognitive impairment (MCI) prodrome. Research criteria for the prospective identification of MCI with Lewy bodies (MCI-LB) have been developed. We aimed to assess the prognosis of a prospectively identified MCI-LB cohort at 2 key milestones, 3- and 5 years after diagnosis, to examine classification stability over time and rates of adverse outcomes (dementia or death). METHODS: This was a retrospective examination of data from 2 longitudinal observational cohort studies where participants with MCI were prospectively recruited from North East England and differentially classified as MCI due to Alzheimer disease (MCI-AD), possible MCI-LB, or probable MCI-LB. Adverse outcomes (DLB/other dementia or death) and stability of disease-specific classifications were examined in each group. RESULTS: Of 152 participants with baseline MCI (54 MCI-AD, 29 possible MCI-LB, and 69 probable MCI-LB), 126 were followed for up to 3 years (mean age 75.3 years; 40% female). We found that prospective probable MCI-LB classifications were both sensitive (91%) and specific (94%) to classifications either remaining as probable MCI-LB or progressing to DLB (in some cases autopsy confirmed) for 3 or more years after. Classifications were at least as stable as those in MCI-AD. In this cohort with disease-specific MCI classifications, rates of progression to dementia were high: 55% of MCI-LB had developed DLB within 3 years. Dementia occurred in 47% of MCI-AD over the same duration (odds ratio 1.68, 95% CI 0.66-4.26, p = 0.278). Premature death was a common competing risk, occurring in 9% of MCI-AD and 11% of MCI-LB within 3 years. DISCUSSION: These findings support that prospectively identified probable MCI-LB is a prodromal presentation of DLB and that disease-specific classifications of MCI may reliably identify different prodromal dementias.

Transferring Learned Behaviors between Similar and Different Radios.

Transfer learning (TL) techniques have proven useful in a wide variety of applications traditionally dominated by machine learning (ML), such as natural language processing, computer vision, and computer-aided design. Recent extrapolations of TL to the radio frequency (RF) domain are being used to increase the potential applicability of RFML algorithms, seeking to improve the portability of models for spectrum situational awareness and transmission source identification. Unlike most of the computer vision and natural language processing applications of TL, applications within the RF modality must contend with inherent hardware distortions and channel condition variations. This paper seeks to evaluate the feasibility and performance trade-offs when transferring learned behaviors from functional RFML classification algorithms, specifically those designed for automatic modulation classification (AMC) and specific emitter identification (SEI), between homogeneous radios of similar construction and quality and heterogeneous radios of different construction and quality. Results derived from both synthetic data and over-the-air experimental collection show promising performance benefits from the application of TL to the RFML algorithms of SEI and AMC.

It Is in Our DNA: Bringing Electronic Health Records and Genomic Data Together for Precision Medicine.

Health care is at a turning point. We are shifting from protocolized medicine to precision medicine, and digital health systems are facilitating this shift. By providing clinicians with detailed information for each patient and analytic support for decision-making at the point of care, digital health technologies are enabling a new era of precision medicine. Genomic data also provide clinicians with information that can improve the accuracy and timeliness of diagnosis, optimize prescribing, and target risk reduction strategies, all of which are key elements for precision medicine. However, genomic data are predominantly seen as diagnostic information and are not routinely integrated into the clinical workflows of electronic medical records. The use of genomic data holds significant potential for precision medicine; however, as genomic data are fundamentally different from the information collected during routine practice, special considerations are needed to use this information in a digital health setting. This paper outlines the potential of genomic data integration with electronic records, and how these data can enable precision medicine.

Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils.

Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.

Development of a survey to support assessment of safety learning systems.

BACKGROUND: Patient safety learning systems play a critical role in supporting safety culture in healthcare organisations. A lack of explicit standards leads to inconsistent implementation across organisations, causing uncertainty about their roles and impact. Organisations can address inconsistent implementation by using a self-assessment tool based on agreed-on best practices. Therefore, we aimed to create a survey instrument to assess an organisation's approach to learning from safety events. METHODS: The foundation for this work was a recent systematic review that defined features associated with the performance of a safety learning system. We organised features into themes and rephrased them into questions (items). Face validity was checked, which included independent pre-testing to ensure comprehensibility and parsimony. It also included clinical sensibility testing in which a representative sample of leaders in quality at a large teaching hospital (The Ottawa Hospital) answered two questions to judge each item for clarity and necessity. If more than 20% of respondents judged a question unclear or unnecessary, we modified or removed that question accordingly. Finally, we checked the internal consistency of the questionnaire using Cronbach's alpha. RESULTS: We initially developed a 47-item questionnaire based on a prior systematic review. Pre-testing resulted in the modification of 15 of the questions, 2 were removed and 2 questions were added to ensure comprehensiveness and relevance. Face validity was assessed through yes/no responses, with over 80% of respondents confirming the clarity and 85% the necessity of each question, leading to the retention of all 47 questions. Data collected from the five-point responses (strongly disagree to strongly agree) for each question were used to assess the questionnaire's internal consistency. The Cronbach's alpha was 0.94, indicating a high internal consistency. CONCLUSION: This self-assessment questionnaire is evidence-based and on preliminary testing is deemed valid, comprehensible and reliable. Future work should assess the range of survey responses in a large sample of respondents from different hospitals.