Calorie restriction modulates mitochondrial dynamics and autophagy in leukocytes of patients with obesity.

BACKGROUND: Although it is established that caloric restriction offers metabolic and clinical benefits, the molecular mechanisms underlying these effects remain unclear. Thus, this study aimed to investigate whether caloric restriction can modulate mitochondrial function and remodelling and stimulate autophagic flux in the PBMCs of patients with obesity. METHODS: This was an interventional study of 38 obese subjects (BMI > 35 kg/m2) who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical variables, mitochondrial function parameters (by fluorescence imaging of mitochondrial ROS and membrane potential), and protein expression of markers of mitochondrial dynamics (MNF1, MFN2, OPA, DRP1 and FIS1) and autophagy (LC3, Beclin, BCL2 and NBR1) by western blot. RESULTS: Caloric restriction induced an improvement in metabolic outcomes that was accompanied by an increase in AMPK expression, a decrease of mitochondrial ROS and mitochondrial membrane potential, which was associated with increased markers of mitochondrial dynamics (MFN2, DRP1 and FIS1) and activation of autophagy as evidenced by augmented LC3 II/I, Beclin1 and NBR1, and a decrease in BCL2. CONCLUSION: These findings shed light on the specific molecular mechanisms by which caloric restriction facilitates metabolic improvements, highlighting the relevance of pathways involving energy homeostasis and cell recovery, including mitochondrial function and dynamics and autophagy.

Analysis of household waste production in Ecuador: Limitations for sustainable management in local communities.

Municipal solid waste management is one of the greatest challenges for environmental sustainability and well-being in developing countries, where the infrastructure and financial resources required to carry out such services are often lacking. The design of solutions that adequately respond to local needs must be based on quality information about the quantity and composition of the generated waste and current management practices. This study evaluated domestic waste generation and its management in 81 communities in Ecuador based on sampling at the source and population surveys. An average household waste generation value of 0.613 kg/cap/d was obtained, of which biowaste accounted for 68 % of the total generation, followed by 23 % recyclable material and 9 % other non recyclable waste. Even though some councils have set up differentiated collection systems for inorganic material in urban areas, these systems are still absent in many rural areas, which explains why waste is not separated in 70 % of the studied communities. Furthermore, only 70 % of the rural population in the country has a waste collection service, and waste in some communities is still thrown into water bodies or burned. Rural populations often use biowaste at home by composting it or as animal feed, which are good practices that should be considered in the diagnosis reports and incorporated into waste management planning.

Study of Mechanical and Thermal Properties of Environmentally Friendly Composites from Beer Bagasse.

The influence of bagasse fibres from beer manufacturing in mechanical, thermal, and rheological properties of three polymers (BioPE, PLA, and PP) has been studied in order to develop new environmentally friendly biocomposites for injection moulding applications. Totals of 10 wt%, 20 wt%, and 30 wt% of bagasse fibre (BSG) were added to the polymers by extrusion compounding, adding specific compatibilising additives, and injected samples were mechanically characterised by tensile, Charpy impact, and hardness tests. In addition, the fractures obtained after the impact test were observed using scanning electron microscopy (SEM) to assess the compatibility matrix filler. Characterisation of the thermal properties is also carried out by using differential scanning calorimetry (DSC) and thermogravimetry (TGA). Additionally, melt flow index of the biocomposites is also studied. An increase in the rigidity of the BioPE and PP composites was produced with the increase in BSG content, dealing with a decrease in maximum strain and impact resistance; whereas, in the filled BGS PLA biocomposites, Young's modulus was lower than that of the PLA material, improving the ductility of the PLA-BGS formulations. Compatibilisation effect was, therefore, different in the nine developed formulations, and the BGS content also influenced their thermal, mechanical, and rheological behaviours.

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.

Hazard assessment of fenozan, a released non-intentionally added substance from polyester-based can coating.

Since the safety of new-generation polyester-based internal coatings regarding the migration of non-intentionally added substances (NIAS) is poorly documented, studies are needed to identify NIAS originating from these food-contact materials (FCM). The aim of this study was to identify volatile and semi-volatile NIAS from polyester-based coatings in order to assess their hazard and ensure consumers' safety with regard to exposure from canned food. Extraction and migration tests were carried out on a single polyester-coated tin plate (5 batches) using two solvents: acetonitrile and ethanol 95%, then FCM's extracts and migrates were analysed by GC-MS. An antioxidant degradation (hydrolysis) product, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid or fenozan (CAS RN: 20170-32-5), was identified and confirmed by reference standard in all migrates. To assess fenozan's toxicity, several in vitro bioassays, such as the Ames test (to assess point mutation), the micronucleus assay (to detect chromosomal aberrations), and the iodide uptake assay (to study one mode of action for thyroid disruption) were conducted. Fenozan was negative in the Ames test on three strains of S. typhimurium (TA98, TA100, and TA1535) and on one strain of E.coli (WP2), with and without metabolic activation system (S9 mix) using direct incorporation and pre-incubation methods. The in vitro micronucleus assay conducted on HepG2 cells also exhibited a negative response following a 4-hour treatment with the S9 mix, and a 48-hour treatment without the S9 mix. A weak inhibitory effect was obtained when testing fenozan in the iodide uptake assay using rat thyroid FRTL-5 cells. Significant inhibition started from 800 µM of fenozan, with a maximal inhibition of almost 47% at 1000 µM. The findings indicate that fenozan exhibits an anti-thyroid activity in vitro.

Bictegravir alters glucose tolerance in vivo and causes hepatic mitochondrial dysfunction.

Growing evidence associates antiretroviral therapies containing integrase strand transfer inhibitors or tenofovir alafenamide (TAF) with increased weight gain and metabolic diseases, but the underlying mechanisms remain unclear. This study evaluated the impact of lamivudine, dolutegravir (DTG), bictegravir (BIC), tenofovir disoproxil fumarate, and TAF on metabolic alterations, and explored glucose homeostasis and mitochondrial stress as potential mechanisms. These pathways were analyzed both in vivo (C57BL/6J mice treated with the abovementioned drugs or vehicle for 16 weeks) and in vitro (in Hep3B cells). Mice treated with BIC exhibited higher glucose levels and a slower decrease during a glucose tolerance test. Functional enrichment analyses of livers from antiretroviral-treated mice revealed that only BIC altered the cellular response to insulin and induced a gluconeogenic-favoring profile, with Fgf21 playing a significant role. In vitro, BIC significantly reduced hepatocyte glucose uptake in a concentration-dependent manner, both under basal conditions and post-insulin stimulation, while the other drugs produced no significant changes. Hep3B cells treated with clinically relevant concentrations of BIC exhibited significant alterations in the mRNA expression of enzymes related to glucose metabolism. Both DTG and BIC reduced mitochondrial dehydrogenase activity, but only BIC increased reactive oxygen species, mitochondrial membrane potential, and cellular granularity, thereby indicating mitochondrial stress. BIC promoted mitochondrial dysfunction, modified carbohydrate metabolism and glucose consumption in hepatocytes, and altered glucose tolerance and gluconeogenesis regulation in mice. These findings suggest that BIC contributes to insulin resistance and diabetes in people living with HIV, warranting clinical studies to clarify its association with carbohydrate metabolism disorders.

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.

Evaluation of a risk-sharing agreement for atezolizumab treatment in patients with non-small cell lung cancer: a strategy to improve access in low-income countries.

BACKGROUND: Using immune checkpoint inhibitors (IO) is a promising approach to maximize clinical benefits for patients with non-small cell lung cancer (NSCLC). PD-L1 expression serves as a predictive factor for treatment outcomes with IO. However, the high cost of this treatment creates significant barriers to access. Substantial evidence demonstrates the sustained clinical benefits experienced by patients who respond to immunotherapy. While IOs show promise in NSCLC treatment, their high cost poses access barriers. AIM: This study focused on a prospective cost analysis conducted at a high-specialty health facility to assess the economic implications of implementing a risk-sharing agreement (RSA) for atezolizumab in NSCLC. METHODS: The study included 30 patients with advanced NSCLC, with the pharmaceutical company funding the initial cycles. If patients responded, a government program covered costs until disease progression. RESULTS: A median progression-free survival of 4.67 months across populations, rising to 9.4 months for responders. The 2-year overall survival rate for the response group was 64%, significantly higher than for non-response. Without an RSA, a total treatment cost of $881 859.36 ($29 395.31/patient) was reported, compared to $530 467.12 ($17 682.24/patient) with an RSA, representing a 40% cost reduction. In responders, the average cost per year of life per patient dropped by 22%. Risk-sharing, assessed through non-parametric tests, showed a statistically significant difference in pharmacological costs (P < .001). CONCLUSION: Implementing RSAs can optimize resource allocation, making IO treatment more accessible, especially in low-income countries.

Body transformations: An opportunity to work on the ethical perspective through photovoice and bodymapping.

BACKGROUND: Body transformations are alterations of the body due to symbolic, aesthetic, religious or cultural reasons. The increase in frequency, especially among young people, raises ethical questions. Future nurses must understand the ethical implications of social phenomena. AIM: The aim was to find out how nursing students perceive bodily transformations from the perspective of Foulcauldian self-care and to determine the ethical value and health consequences of these transformations. RESEARCH DESIGN: A qualitative study based on the socio-critical paradigm and based on the theory's principles of the Technologies of the self (Foucault). Photovoice and bodymapping were used for the reflection process. The participants were 267 first-year nursing students from two Spanish universities. A content analysis was conducted. ETHICAL CONSIDERATIONS: The Research Ethics Committee of both universities approved this study. FINDINGS: The body transformations most photographed by the students were piercing, tattoos and surgical interventions. Two main categories emerged: 1. Body modifications as constructions of the self with two subcategories, the pursuit of bodily aesthetics and the pursuit of spiritual aesthetics. 2. Health consequences. The need to build an identity of their own, as well as to be integrated into their environment by helping to improve not only their external appearance but also their inner side were the main inputs. The major ethical dilemmas are evident when body modifications are influenced by social and cultural values. The debate and reflection of the students through photovoice and its symbolic representation in bodymapping highlighted its health consequences. For the students, nursing should accompany them throughout the entire process, highlighting the importance of ethical values. CONCLUSION: The ethical value attributed to the different body modifications has been shown, revealing how they have a common origin, the improvement of their corporal and spiritual aesthetics. Nursing has a role as an active carer of the health of these people and must act in accordance with the ethical principles of this profession.

Terrestrial Animal Source Foods and Health Outcomes for Those with Special Nutrient Needs in the Life Course.

Background. Animal source foods are under scrutiny for their role in human health, yet some nutritionally vulnerable populations are largely absent from consideration. Methods. Applying a Population Intervention/Exposure Comparator Outcome (PICO/PECO) framework and prioritizing systematic review and meta-analyses, we reviewed the literature on terrestrial animal source foods (TASFs) and human health, by life course phase. Results. There were consistent findings for milk and dairy products on positive health outcomes during pregnancy and lactation, childhood, and among older adults. Eggs were found to promote early childhood growth, depending on context. Unprocessed meat consumption was associated with a reduced risk for anemia during pregnancy, improved cognition among school-age children, and muscle health in older adults. Milk and eggs represent a risk for food sensitivities/allergies, though prevalence is low, and individuals tend to outgrow the allergies. TASFs affect the human microbiome and associated metabolites with both positive and negative health repercussions, varying by type and quantity. Conclusions. There were substantial gaps in the evidence base for studies limiting our review, specifically for studies in populations outside high-income countries and for several TASF types (pig, poultry, less common livestock species, wild animals, and insects). Nonetheless, sufficient evidence supports an important role for TASFs in health during certain periods of the life course.

Unveiling the Nutritional Quality of Terrestrial Animal Source Foods by Species and Characteristics of Livestock Systems.

Background. It is well-established that a range of macronutrients, micronutrients and bioactive compounds found in animal-source foods play unique and important roles in human health as part of a healthy diet. Methods. This narrative review focuses on terrestrial animal source foods (TASFs). It particularly analyzes five groups: poultry eggs, milk, unprocessed meat, foods from hunting and wildlife farming, and insects. The objectives were as follows: (1) examine the nutrient composition of TASFs within and across livestock species, drawing on the country and regional food composition databases; (2) analyze the influence of intrinsic animal characteristics and production practices on TASF nutritional quality. Results. TASFs are rich in high-quality proteins and fats, as well as micronutrients such as vitamin B12, iron or zinc. This study found differences in the nutritional quality of TASFs by livestock species and animal products, as well as by characteristics of livestock production systems. Our findings suggest that there may be public health opportunities by diversifying TASF consumption across species and improving certain aspects of the production systems to provide products that are both more sustainable and of higher quality. Conclusions. Future research should adopt a more holistic approach to examining the food matrix and the dietary patterns that influence TASF digestibility. It is necessary to include meat from hunting and wildlife farming and insects in global food composition databases, as limited literature was found. In addition, scarce research focuses on low- and middle-income countries, highlighting the need for further exploration of TASF food composition analysis and how intrinsic animal characteristics and livestock production system characteristics impact their nutritional value.

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.

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.

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.

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.

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.

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.