Development and validation of assessment instruments for cervical collar and spinal board placement in simulated environments for nursing students in the care of polytrauma patients.

BACKGROUND: Multiple trauma injuries are the leading cause of death and disability in people under the age of 45 and require prompt and specialised care. However, medical and nursing education programmes do not always include specific training in emergency pre-hospital care, resulting in a lack of basic practical skills in trauma management. OBJECTIVE: To develop and validate two instruments for assessing nursing students' competence in cervical collar and spinal board application in simulated pre-hospital emergency scenarios. METHOD: This is an instrumental study that involves the development of two assessment instruments and the evaluation of their psychometric properties in a sample of 392 nursing students. Content validity was assessed using expert judgement, by calculating the content validity ratio (CVR) for each item and the scale level content validity index average (S-CVI/Ave) for the instruments. Exploratory factor analysis using the MINRES extraction method and Promax rotation was performed to analyse the performance of the items and structure of the rubrics. Internal consistency was analysed using the Omega coefficient and inter-rater agreement was assessed using Cohen's Kappa coefficient. RESULTS: Initially, two rubrics were obtained: one with six items for cervical collar placement (S-CVI/Ave = 0.86) and one with nine items for spinal board placement (S-CVI/Ave = 0.81). Both had a single-factor structure, with all items having factor loadings greater than 0.34 for the cervical collar rubric and 0.56 for the spinal board rubric, except for item 2 of the cervical collar rubric (λ = 0.24), which was subsequently removed. The final cervical collar rubric (five items) had an overall internal consistency of 0.84 and the spinal board rubric had an overall internal consistency of 0.90, calculated using the Omega statistic. The weighted Kappa coefficient for each item ranged from acceptable (0.32) to substantial (0.79). These results show that we have successfully developed two sufficiently valid instruments to assess the immobilisation competencies proposed in the objective of the study. CONCLUSION: Whilst further research is needed to fully establish their psychometric properties, these instruments offer a valuable starting point for evaluating nursing students' competence in cervical collar and spinal board application in simulated pre-hospital scenarios.

Cross-cultural adaptation of the eHealth Literacy Scale for Brazilian adolescents.

The aim of this study was to undertake a cross-cultural adaptation of the eHealth Literacy Scale (eHEALS) instrument to measure digital health literacy of Brazilian adolescents. eHEALS is a scale consisting of 8 items that measure self-perception related to the consumption of electronic health information. This is a methodological study of cross-cultural adaptation, conducted out from February 2022 to June 2022. The following steps were carried out: a) assessment and adequacy of cultural equivalence by a committee of experts; b) back-translation; c) synthesis of back-translations; d) cognitive testing with 42 Brazilian adolescents, using cognitive interviews with probing questions. All items that were difficult to understand were adapted to the (language) context of Brazilian adolescents. Cronbach's alpha coefficient for eHEALS-BrA was 0.81 and, if one of the items were excluded from the instrument, it ranged from 0.75-0.81. This version of the eHEALS proved to be culturally well-adapted to the context of Brazilian adolescents, and has the potential to measure digital health literacy in this population after having its validation confirmed through psychometric analyses.

Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease.

OBJECTIVE: Mitochondrial DNA (mtDNA) depletion/deletions syndrome (MDDS) comprises a group of diseases caused by primary autosomal defects of mtDNA maintenance. Our objective was to study the etiology of MDDS in 4 patients who lack pathogenic variants in known genetic causes. METHODS: Whole exome sequencing of the probands was performed to identify pathogenic variants. We validated the mitochondrial defect by analyzing mtDNA, mitochondrial dNTP pools, respiratory chain activities, and GUK1 activity. To confirm pathogenicity of GUK1 deficiency, we expressed 2 GUK1 isoforms in patient cells. RESULTS: We identified biallelic GUK1 pathogenic variants in all 4 probands who presented with ptosis, ophthalmoparesis, and myopathic proximal limb weakness, as well as variable hepatopathy and altered T-lymphocyte profiles. Muscle biopsies from all probands showed mtDNA depletion, deletions, or both, as well as reduced activities of mitochondrial respiratory chain enzymes. GUK1 encodes guanylate kinase, originally identified as a cytosolic enzyme. Long and short isoforms of GUK1 exist. We observed that the long isoform is intramitochondrial and the short is cytosolic. In probands' fibroblasts, we noted decreased GUK1 activity causing unbalanced mitochondrial dNTP pools and mtDNA depletion in both replicating and quiescent fibroblasts indicating that GUK1 deficiency impairs de novo and salvage nucleotide pathways. Proband fibroblasts treated with deoxyguanosine and/or forodesine, a purine phosphatase inhibitor, ameliorated mtDNA depletion, indicating potential pharmacological therapies. INTERPRETATION: Primary GUK1 deficiency is a new and potentially treatable cause of MDDS. The cytosolic isoform of GUK1 may contribute to the T-lymphocyte abnormality, which has not been observed in other MDDS disorders. ANN NEUROL 2024.

Role of rectal colonization by third-generation cephalosporin-resistant Enterobacterales on the risk of surgical site infection after hepato-pancreato-biliary surgery.

The impact of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) rectal colonization in the development of subsequent infection after surgery is controversial. In particular, there is a lack of data in the context of hepato-pancreato-biliary (HPB) surgery. The objective of this study was to assess the prevalence of 3GCR-E intestinal carriage among patients undergoing elective HPB resection surgery and its impact on the incidence and etiology of surgical site infections (SSIs). This retrospective cohort study (January 2016-December 2022) was performed at Valme University Hospital (Seville, Spain). The inclusion criteria included (i) 18 years of age or older, (ii) undergoing elective HPB resection surgery, and (iii) availability of a periprocedural surveillance rectal swab culture to detect 3GCR-E. The prevalence of 3GCR-E intestinal carriage at elective HPB resection surgery was assessed, as well as SSI incidence at 30 days and possible associated factors. Two hundred nine patients were included. Eleven (5.3%) patients were colonized by 3GCR-E at baseline. According to 3GCR-E carriage status, 6 (55%) of the carriers developed SSI, whereas this occurred in 50 (25%) of non-carriers (P = 0.033). Likewise, the rates of SSI caused specifically by 3GCR-E were 83% (5 of 6) in 3GCR-E carriers and 6% (3 of 50) in non-carriers (P < 0.001). After multivariate analyses, 3GCR-E colonization at the time of surgery was identified as an independent predictor for developing SSI (adjusted odds ratio 4.63, 95% confidence interval: 1.177-18.232, P = 0.028). Despite a low prevalence of 3GCR-E intestinal carriage at surgery, 3GCR-E rectal colonization is associated with a higher risk of SSI among patients undergoing elective HPB resection surgery, with most SSIs being caused by the colonizing bacteria. IMPORTANCE: In this Spanish retrospective cohort study, previous 3GCR-E rectal colonization was associated with a higher risk of SSI after hepato-pancreato-biliary resection surgeries. Most of SSIs were caused by the colonizing bacteria, suggesting a rationale for adapted perioperative antibiotic prophylaxis in known 3GCR-E colonized patients.

A landscape of liver cirrhosis and transplantation in Mexico: Changing leading causes and transplant as response.

Liver cirrhosis causes include alcoholism, viral infections (hepatitis B virus (HBV) and hepatitis C virus (HCV)), alcohol-associated liver disease (ALD), and metabolic dysfunction associated with steatotic liver disease (MASLD), among others. Cirrhosis frequency has increased in recent years, with a prevalence of 1395 cases per 100,000 and a mortality rate of 18 per 100,000, which corresponded to 1,472,000 deaths during 2017. In Mexico, liver disease is a public health problem since it was associated to 41,890 deaths in 2022, including liver cirrhosis (>25,000) and ALD (14,927). This represents 114 individuals daily due to these causes, and correspond to the 4th to 5th place of all causes. The global prevalence of MASLD is estimated to 25 % of the world's population, while in pediatric population could be higher. In Mexican population is more prevalent since estimations are up to 41.3 % in 2023. Alcohol consumption, a global health issue due to its high prevalence and associated morbidities, is associated to ALD in 32.9 %, with a mortality rate of 23.9 %, primarily due to liver-related causes. In Mexico, ALD is present in 23 % of all cirrhosis cases. already surpassed by hepatitis B cases in 2009. HCV and HBV frequencies changed due programs implementing screening detection, vaccines and direct-acting antivirals during the last years. A switch of causes has occurred, increasing MASLD and diminishing viral causes. Efficient performed liver transplantation has grown as response to increasing cirrhosis cases, including recent authorized centers. These efforts are necessary, whereas preventive strategies should be implemented according to leading causes.

Development of a FUT8 Inhibitor with Cellular Inhibitory Properties.

Core fucosylation is catalyzed by α-1,6-fucosyltransferase (FUT8), which fucosylates the innermost GlcNAc of N-glycans. Given the association of FUT8 with various diseases including cancer, selective FUT8 inhibitors applicable to in vivo or cell-based systems are highly sought-after. Here, we report the discovery of a compound that selectively inhibits FUT8 in cell-based assays. High-throughput screening revealed a FUT8-inhibiting pharmacophore, and further structural optimization yielded an inhibitor with a KD of 49 nM. Notably, this binding occurs only in the presence of GDP (a product of the enzymatic reaction catalyzed by FUT8). Mechanistic studies suggested that this inhibitor generates a highly reactive naphthoquinone methide derivative at the binding site in FUT8, which subsequently reacts with FUT8. Furthermore, prodrug derivatization of this inhibitor improved its stability, enabling suppression of core fucose expression and subsequent EGFR and T-cell signaling in cell-based assays, paving the way for the development of drugs targeting core fucosylation.

IA-Body Composition CT at T12 in Idiopathic Pulmonary Fibrosis: Diagnosing Sarcopenia and Correlating with Other Morphofunctional Assessment Techniques.

BACKGROUND: Body composition (BC) techniques, including bioelectrical impedance analysis (BIVA), nutritional ultrasound® (NU), and computed tomography (CT), can detect nutritional diagnoses such as sarcopenia (Sc). Sc in idiopathic pulmonary fibrosis (IPF) is associated with greater severity and lower survival. Our aim was to explore the correlation of BIVA, NU and functional parameters with BC at T12 level CT scans in patients with IPF but also its relationship with degree of Sc, malnutrition and mortality. METHODS: This bicentric cross-sectional study included 60 IPF patients (85.2% male, 70.9 ± 7.8 years). Morphofunctional assessment (MFA) techniques included BIVA, NU, CT at T12 level (T12-CT), handgrip strength, and timed up and go. CT data were obtained using FocusedON®. Statistical analysis was conducted using JAMOVI version 2.3.22 to determine the cutoff points for Sc in T12-CT and to analyze correlations with other MFA techniques. RESULTS: the cutoff for muscle area in T12-CT was ≤77.44 cm2 (area under the curve (AUC) = 0.734, sensitivity = 41.7%, specificity = 100%). The skeletal muscle index (SMI_T12CT) cutoff was ≤24.5 cm2/m2 (AUC = 0.689, sensitivity = 66.7%, specificity = 66.7%). Low SMI_T12CT exhibited significantly reduced median survival and higher risk of mortality compared to those with normal muscle mass (SMI cut off ≥ 28.8 cm/m2). SMI_T12CT was highly correlated with body cell mass from BIVA (r = 0.681) and rectus femoris cross-sectional area (RF-CSA) from NU (r = 0.599). Cronbach's α for muscle parameters across different MFA techniques and CT was 0.735, confirming their validity for evaluating muscle composition. CONCLUSIONS: T12-CT scan is a reliable technique for measuring low muscle mass in patients with IPF, specifically when the L3 vertebrae are not captured. An SMI value of <28.8 is a good predictor of low lean mass and 12-month mortality in IPF patients.

The role of the Arabidopsis tandem zinc-finger C3H15 protein in metal homeostasis.

Living organisms have developed finely regulated homeostatic networks to mitigate the effects of environmental fluctuations in transition metal micronutrients, including iron, zinc, and copper. In Saccharomyces cerevisiae, the tandem zinc-finger protein Cth2 post-transcriptionally regulates gene expression under conditions of iron deficiency by controlling the levels of mRNAs that code for non-essential ferroproteins. The molecular mechanism involves Cth2 binding to AU-rich elements present in the 3' untranslated region of target mRNAs, negatively affecting their stability and translation. Arabidopsis thaliana has two TZF proteins homologous to yeast Cth2, C3H14 and C3H15, which participate in cell wall remodelling. The present work examines the expression of representative metal homeostasis genes with putative AREs in plants with altered levels of C3H14 and C3H15 grown under varying metal availabilities. The results suggest that C3H15 may act as a post-transcriptional plant modulator of metal adequacy, as evidenced by the expression of SPL7, the main transcriptional regulator under copper deficiency, and PETE2, which encodes plastocyanin. In contrast to S. cerevisiae, the plant C3H15 affects copper and zinc homeostasis rather than iron. When grown under copper-deficient conditions, adult C3H15OE plants exhibit lower chlorophyll content and photosynthetic efficiency compared to control plants, suggesting accelerated senescence. Likewise, metal content in C3H15OE plants under copper deficiency shows altered mobilization of copper and zinc to seeds. These data suggest that the C3H15 protein plays a role in modulating both cell wall remodelling and metal homeostasis. The interaction between these processes may be the cause of altered metal translocation.

Individual and contextual determinants associated with bullying in schoolchildren eight to ten years of age.

Investigate individual and contextual determinants associated with bullying in schoolchildren eight to ten years of age. A cross-sectional study was conducted with 739 schoolchildren, who answered a question about episodes of bullying related to oral health and questionnaires addressing childhood anxiety and orofacial dysfunction. The guardians provided information on sociodemographic characteristics, sleep disorders, and oral health literacy. Trained examiners assessed the children for the diagnosis of dental caries using the International Caries Detection and Assessment System, malocclusion using the Dental Aesthetic Index, orofacial dysfunction using the Nordic Orofacial Test-Screening and traumatic dental injury (Andreasen criteria) (Kappa> 0.80). The contextual variables were the type of school and the monthly income of the school neighborhood. Descriptive statistics was performed to characterize the sample and unadjusted and adjusted (p <0.05) multilevel Poisson regression models were run. The prevalence of bullying was 13.3%. After the adjusted analysis, malocclusion (PR=1.59; 95%CI:1.03-2.44) and anxiety (PR=1.79; 95%CI:1.10-2.93) remained associated with bullying. In terms of context, the monthly income of the neighborhood of the school was associated with bullying (PR=1.75; 95%CI:1.12-2.72). Malocclusion and anxiety influenced the occurrence of bullying. A lower average income in the school neighborhood was an important contextual determinant for the increase in the prevalence of bullying.

Inter-institutional laboratory standardization for SARS-CoV-2 surveillance through wastewater-based epidemiology applied to Mexico City.

Objectives: Wastewater-based surveillance applied to SARS-CoV-2 viral load quantification for COVID-19 has become one of the most relevant complementary tools in epidemiologic prevention programs worldwide. However, this valuable decision-making tool still requires fine-tuning to produce comparable results between laboratories, especially when applied to the surveillance of megacities. Methods: Six laboratories across Mexico and one from the United States executed an interlaboratory study to set up a singular standardized protocol considering method cost, installed infrastructure, materials available, and supply availability for SARS-CoV-2 quantification from five Mexico City sampling sites across this megacity. Results: Comparable data from processing outcomes in the Mexican laboratories and in the external international laboratory serve as a validating data source. The Bland-Altman comparison showed consistency, with cycle threshold values within ±1.96 SD of SARS-CoV-2 genetic copies for the standard curve quantification, with a mismatch of two laboratories. In addition, MS2 bacteriophage recovery rates varied between 35% and 67% among all participating laboratories. Finally, the efficiency of viral genetic material recovered from all participating laboratories varied between 65% and 93% for the participating laboratories. Conclusion: This work lays the foundation for extensive and continuous wastewater-based surveillance application across independent Mexican laboratories in a time- and resource-effective manner.

A WO3-CuCrO2 Tandem Photoelectrochemical Cell for Green Hydrogen Production under Simulated Sunlight.

The development of photoelectrochemical tandem cells for water splitting with electrodes entirely based on metal oxides is hindered by the scarcity of stable p-type oxides and the poor stability of oxides in strongly alkaline and, particularly, strongly acidic electrolytes. As a novelty in the context of transition metal oxide photoelectrochemistry, a bias-free tandem cell driven by simulated sunlight and based on a CuCrO2 photocathode and a WO3 photoanode, both unprotected and free of co-catalysts, is demonstrated to split water while working with strongly acidic electrolytes. Importantly, the Faradaic efficiency for H2 evolution for the CuCrO2 electrode is found to be about 90%, among the highest for oxide photoelectrodes in the absence of co-catalysts. The tandem cell shows no apparent degradation in short-to-medium-term experiments. The prospects of using a practical cell based on this configuration are discussed, with an emphasis on the importance of modifying the materials for enhancing light absorption.

Update of the Consensus Statement of the Spanish Society of Rheumatology on the use of biological and synthetic targeted therapies in rheumatoid arthritis.

OBJECTIVE: To update the consensus document of the Spanish Society of Rheumatology (SER) regarding the use of targeted biological and synthetic therapies in rheumatoid arthritis (RA) with the aim of assisting clinicians in their therapeutic decisions. METHODS: A panel of 13 experts was assembled through an open call by SER. We employed a mixed adaptation-elaboration-update methodology starting from the 2015 Consensus Document of the Spanish Society of Rheumatology on the use of biological therapies in RA. Starting with systematic reviews (SR) of recommendations from EULAR 2019, American College of Rheumatology 2021, and GUIPCAR 2017, we updated the search strategies for the PICO questions of GUIPCAR. An additional SR was conducted on demyelinating disease in relation to targeted biological and synthetic therapies. Following the analysis of evidence by different panelists, consensus on the wording and level of agreement for each recommendation was reached in a face-to-face meeting. RESULTS: The panel established 5 general principles and 15 recommendations on the management of RA. These encompassed crucial aspects such as the importance of early treatment, therapeutic goals in RA, monitoring frequency, the use of glucocorticoids, the application of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs. Additionally, recommendations on dose reduction of these drugs in stable patients were included. This update also features recommendations on the use of bDMARDs and Janus Kinase inhibitors in some specific clinical situations, such as patients with lung disease, a history of cancer, heart failure, or demyelinating disease. CONCLUSIONS: This update provides recommendations on key aspects in the management of RA using targeted biological and synthetic therapies.

Cytokines and Pancreatic Ductal Adenocarcinoma: Exploring Their Relationship with Molecular Subtypes and Prognosis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis. The current challenge remains the absence of predictive biomarkers. Cytokines are crucial factors in the pathogenesis and prognosis of PDAC. Furthermore, there is growing interest in differentiating between molecular subtypes of PDAC. The aim of our study is to evaluate the association between the analyzed cytokines and the molecular subtypes of PDAC and to determine their prognostic value. Cytokine levels were measured in 73 patients, and molecular subtypes were analyzed in 34 of these patients. Transforming Growth Factor Beta 2 (TGF-ß2) levels were independently associated with the basal-like and null subtypes. In patients with locally advanced and metastatic PDAC, elevated levels of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, IL-9, and IL-15 were associated with a higher risk of progression during first-line treatment, and increased levels of IL-1ß, IL-6, IL-8, IL-9, and IL-15 were related to increased mortality. Furthermore, a significant association was observed between higher percentiles of IL-6 and IL-8 and shorter progression-free survival (PFS) during first-line treatment, and between higher percentiles of IL-8 and shorter overall survival (OS). In the multivariate analysis, only elevated levels of IL-8 were independently associated with a higher risk of progression during first-line treatment and mortality. In conclusion, the results of our study suggest that cytokine expression varies according to the molecular subtype of PDAC and that cytokines also play a relevant role in patient prognosis.

Validation of a Clinical Scale for Early Detection of Infections at the Exit Site of Central Venous Catheters for Hemodialysis.

Introduction: Exit-site infections (ESI) of central venous catheters for hemodialysis (CVC-HD) has been associated with early catheter removal and an increased risk of CVC-HD related bacteremia. No specific clinical scales to predict ESI have previously been validated. Methods: A multicenter prospective cohort study was performed to validate the proposed scale, which is based on the following 5 signs and symptoms: (i) pain at exit site during interdialytic period; (ii) hyperemia or erythema ≥2 cm from exit site; (iii) inflammation, induration, or swelling at exit site; (iv) fever ≥38 °C not attributable to other causes, and (v) obvious abscess or purulent exudate at the exit site. Adult patients with a tunneled CVC-HD for at least 1 month after insertion has been included. During each hemodialysis session, the exit site was assessed with the proposed scale by nurses. If any item was present, a pericatheter skin swab culture was collected: positive results were gold standard. The scale was validated using receiver operating characteristic (ROC) curves and logistic regression analysis. For this purpose, the logit function was applied, and the ESI probability calculated, as elogit ESI/1 + elogit ESI. Results: Three hundred thirty-seven CVC-HDs from 310 patients were analyzed, producing 515 cultures (117 infected and 398 healthy). The final version of the scale includes the following 3 signs and symptoms, which present the greatest predictive capacity: (i) pain at exit site during interdialytic period, (ii) hyperemia or erythema ≥2 cm from exit site, and (iii) abscess or purulent exudate at the exit site. The final version generated an area under the ROC curve (AUC) of 88.3% (95% confidence interval [CI]: 85.2%-91%; P < 0.001), Youden index 0.7557 ≈ 1, sensitivity 80.34% (95% CI: 71.36%-87.71%) and specificity 95.23% (95% CI: 92.73%-97%). Conclusions: The validation shows that the scale has good predictive properties, detecting approximately 90% of ESI with very acceptable validity parameters.

Combination of locoregional radiotherapy with a TIM-3 aptamer improves survival in diffuse midline glioma models.

Pediatric diffuse midline gliomas (DMG) with altered H3-K27M are aggressive brain tumors that arise during childhood. Despite advances in genomic knowledge and the significant number of clinical trials testing new targeted therapies, patient outcomes are still poor. Immune checkpoint blockades with small molecules, such as aptamers, are opening new therapeutic options that represent hope for this orphan disease. Here, we demonstrated that a TIM-3 aptamer (TIM-3 Apt) as monotherapy increased the immune infiltration and elicited a strong specific immune response with a tendency to improve the overall survival of treated DMG-bearing mice. Importantly, combining TIM-3 Apt with radiotherapy increased the overall median survival and led to long-term survivor mice in 2 pediatric DMG orthotopic murine models. Interestingly, TIM-3 Apt administration increased the number of myeloid populations and the proinflammatory CD8-to-Tregs ratios in the tumor microenvironment as compared with nontreated groups after radiotherapy. Importantly, the depletion of T cells led to a major loss of the therapeutic effect achieved by the combination. This work uncovers TIM-3 targeting as an immunotherapy approach to improve the radiotherapy outcome in DMGs and offers a strong foundation for propelling a phase I clinical trial using radiotherapy and TIM-3 blockade combination as a treatment for these tumors.

It's good to know what to BACE the specificity of your inhibitors on.

Production, aggregation, and clearance of the amyloid ß peptide (Aß) are important processes governing the initial pathogenesis of Alzheimer's disease (AD). Inhibition of ß-site amyloid precursor protein (APP) cleaving enzyme (BACE1) (one of two key proteases responsible for Aß production) as an AD-therapeutic approach so far has failed to yield a successful drug. BACE1 and its homologue BACE2 are frequently inhibited by the same inhibitors. Several genetic and cerebral organoid modeling studies suggest that BACE2 has dose-dependent AD-suppressing activity, which makes its unwanted inhibition potentially counterproductive for AD treatment. The in vivo effects of an unwanted cross inhibition of BACE2 have so far been impossible to monitor because of the lack of an easily accessible pharmacodynamic marker specific for BACE2 cleavage. In this issue of the JCI, work led by Stefan F. Lichtenthaler identifies soluble VEGFR3 (sVEGFR3) as a pharmacodynamic plasma marker for BACE2 activity not shared with BACE1.