Validation of an in vivo transit dosimetry algorithm using Monte Carlo simulations and ionization chamber measurements.

PURPOSE: Transit dosimetry is a safety tool based on the transit images acquired during treatment. Forward-projection transit dosimetry software, as PerFRACTION, compares the transit images acquired with an expected image calculated from the DICOM plan, the CT, and the structure set. This work aims to validate PerFRACTION expected transit dose using PRIMO Monte Carlo simulations and ionization chamber measurements, and propose a methodology based on MPPG5a report. METHODS: The validation process was divided into three groups of tests according to MPPG5a: basic dose validation, IMRT dose validation, and heterogeneity correction validation. For the basic dose validation, the fields used were the nine fields needed to calibrate PerFRACTION and three jaws-defined. For the IMRT dose validation, seven sweeping gaps fields, the MLC transmission and 29 IMRT fields from 10 breast treatment plans were measured. For the heterogeneity validation, the transit dose of these fields was studied using three phantoms: 10 , 30 , and a 3 cm cork slab placed between 10 cm of solid water. The PerFRACTION expected doses were compared with PRIMO Monte Carlo simulation results and ionization chamber measurements. RESULTS: Using the 10 cm solid water phantom, for the basic validation fields, the root mean square (RMS) of the difference between PerFRACTION and PRIMO simulations was 0.6%. In the IMRT fields, the RMS of the difference was 1.2%. When comparing respect ionization chamber measurements, the RMS of the difference was 1.0% both for the basic and the IMRT validation. The average passing rate with a γ(2%/2 mm, TH = 20%) criterion between PRIMO dose distribution and PerFRACTION expected dose was 96.0% ± 5.8%. CONCLUSION: We validated PerFRACTION calculated transit dose with PRIMO Monte Carlo and ionization chamber measurements adapting the methodology of the MMPG5a report. The methodology presented can be applied to validate other forward-projection transit dosimetry software.

Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6.

The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, from end resection to Holliday junction (HJ) dissolution. Sgs1 has both pro- and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment and activation of Sgs1 at damaged sites are unknown. Here we show a two-step role for Smc5/6 in recruiting and activating Sgs1 through SUMOylation. First, auto-SUMOylation of Smc5/6 subunits leads to recruitment of Sgs1 as part of the STR (Sgs1-Top3-Rmi1) complex, mediated by two SUMO-interacting motifs (SIMs) on Sgs1 that specifically recognize SUMOylated Smc5/6. Second, Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for the efficient function of STR. Sgs1 mutants impaired in recognition of SUMOylated Smc5/6 (sgs1-SIMΔ) or SUMO-dead alleles (sgs1-KR) exhibit unprocessed HJs at damaged replication forks, increased crossover frequencies during double-strand break repair, and severe impairment in DNA end resection. Smc5/6 is a key regulator of Sgs1's recombination functions.

Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Gamma passing rates of daily EPID transit images correlate to PTV coverage for breast cancer IMRT treatment plans.

PURPOSE: The use of the transit image obtained with the electronic portal-imaging device (EPID) is becoming an extended method to perform in-vivo dosimetry. The transit images acquired during each fraction can be compared with a predicted image, if available, or with a baseline image, usually the obtained in the first fraction. This work aims to study the dosimetric impact of the failing fractions and to evaluate the appropriateness of using a baseline image in breast plans. MATERIAL AND METHODS: Twenty breast patients treated in a Halcyon were retrospectively selected. For each patient and fraction, the treatment plan was calculated over the daily CBCT image. For each fraction, the differences respect to the treatment plan values of OARs and PTV dosimetric parameters were analyzed: ΔDmean , ΔD95%, ΔD98%, ΔD2%, ΔV36Gy, ΔV38.5Gy, and ΔV43.5Gy. Daily fractions were ranked according to the differences found in the dosimetric parameters between the treatment plan and the daily CBCT to establish the best fraction. The daily transit images acquired in every fraction were compared to the first fraction using the global gamma index with the Portal Dosimetry tool. The comparison was repeated using the best fraction image as a baseline. We assessed the correlation of the dosimetric differences obtained from the CBCT images-based treatment plans with the gamma index passing rates obtained using first fraction and best fraction as baseline. RESULTS: Average values of -11.6% [-21.4%, -3.3%] and -3.2% [-1.0%, -10.3%] for the ∆PTVD98% and ∆PTVD95% per every 10% decrease in the passing rate were found, respectively. When using the best fraction as baseline patients were detected with failing fractions that were not detected with the first fraction as baseline. CONCLUSION: The gamma passing rates of daily transit images correlate with the coverage loss parameters in breast IMRT plans. Using first fraction image as baseline can lead to the non-detectability of failing fractions.

PRIMO Monte Carlo software as a tool for commissioning of an external beam radiotherapy treatment planning system.

Background: The purpose was to validate the PRIMO Monte Carlo software to be used during the commissioning of a treatment planning system (TPS). Materials and methods: The Acuros XB v. 16.1 algorithm of the Eclipse was configured for 6 MV and 6 MV flattening-filter-free (FFF) photon beams, from a TrueBeam linac equipped with a high-definition 120-leaf multileaf collimator (MLC). PRIMO v. 0.3.64.1814 software was used with the phase space files provided by Varian and benchmarked against the reference dosimetry dataset published by the Imaging and Radiation Oncology Core-Houston (IROC-H). Thirty Eclipse clinical intensity-modulated radiation therapy (IMRT)/volumetric modulated arc therapy (VMAT) plans were verified in three ways: 1) using the PTW Octavius 4D (O4D) system; 2) the Varian Portal Dosimetry system and 3) the PRIMO software. Clinical validation of PRIMO was completed by comparing the simulated dose distributions on the O4D phantom against dose measurements for these 30 clinical plans. Agreement evaluations were performed using a 3% global/2 mm gamma index analysis. Results: PRIMO simulations agreed with the benchmark IROC-H data within 2.0% for both energies. Gamma passing rates (GPRs) from the 30 clinical plan verifications were (6 MV/6MV FFF): 99.4% ± 0.5%/99.9% ± 0.1%, 99.8% ± 0.4%/98.9% ± 1.4%, 99.7% ± 0.4%/99.7% ± 0.4%, for the 1), 2) and 3) verification methods, respectively. Agreement between PRIMO simulations on the O4D phantom and 3D dose measurements resulted in GPRs of 97.9% ± 2.4%/99.7% ± 0.4%. Conclusion: The PRIMO software is a valuable tool for dosimetric verification of clinical plans during the commissioning of the primary TPS.

Independent effects of secondary hyperparathyroidism and hyperphosphataemia on chronic kidney disease progression and cardiovascular events: an analysis from the NEFRONA cohort.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers. METHODS: The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE. RESULTS: The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia. CONCLUSIONS: We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients.

Validation of virtual water phantom software for pre-treatment verification of single-isocenter multiple-target stereotactic radiosurgery.

The aim of this study was to benchmark the accuracy of the VIrtual Phantom Epid dose Reconstruction (VIPER) software for pre-treatment dosimetric verification of multiple-target stereotactic radiosurgery (SRS). VIPER is an EPID-based method to reconstruct a 3D dose distribution in a virtual phantom from in-air portal images. Validation of the VIPER dose calculation was assessed using several MLC-defined fields for a 6 MV photon beam. Central axis percent depth doses (PDDs) and output factors were measured with an ionization chamber in a water tank, while dose planes at a depth of 10 cm in a solid flat phantom were acquired with radiochromic films. The accuracy of VIPER for multiple-target SRS plan verification was benchmarked against Monte Carlo simulations. Eighteen multiple-target SRS plans designed with the Eclipse treatment planning system were mapped to a cylindrical water phantom. For each plan, the 3D dose distribution reconstructed by VIPER within the phantom was compared with the Monte Carlo simulation, using a 3D gamma analysis. Dose differences (VIPER vs. measurements) generally within 2% were found for the MLC-defined fields, while film dosimetry revealed gamma passing rates (GPRs) ≥95% for a 3%/1 mm criteria. For the 18 multiple-target SRS plans, average 3D GPRs greater than 93% and 98% for the 3%/2 mm and 5%/2 mm criteria, respectively. Our results validate the use of VIPER as a dosimetric verification tool for pre-treatment QA of single-isocenter multiple-target SRS plans. The method requires no setup time on the linac and results in an accurate 3D characterization of the delivered dose.

Atherosclerosis in Chronic Kidney Disease: More, Less, or Just Different?

Patients with chronic kidney disease (CKD) are at an increased risk of premature mortality, mainly from cardiovascular causes. The association between CKD on hemodialysis and accelerated atherosclerosis was described >40 years ago. However, more recently, it has been suggested that the increase in atherosclerosis risk is actually observed in early CKD stages, remaining stable thereafter. In this regard, interventions targeting the pathogenesis of atherosclerosis, such as statins, successful in the general population, have failed to benefit patients with very advanced CKD. This raises the issue of the relative contribution of atherosclerosis versus other forms of cardiovascular injury such as arteriosclerosis or myocardial injury to the increased cardiovascular risk in CKD. In this review, the pathophysiogical contributors to atherosclerosis in CKD that are shared with the general population, or specific to CKD, are discussed. The NEFRONA study (Observatorio Nacional de Atherosclerosis en NEFrologia) prospectively assessed the prevalence and progression of subclinical atherosclerosis (plaque in vascular ultrasound), confirming an increased prevalence of atherosclerosis in patients with moderate CKD. However, the adjusted odds ratio for subclinical atherosclerosis increased with CKD stage, suggesting a contribution of CKD itself to subclinical atherosclerosis. Progression of atherosclerosis was closely related to CKD progression as well as to the baseline presence of atheroma plaque, and to higher phosphate, uric acid, and ferritin and lower 25(OH) vitamin D levels. These insights may help design future clinical trials of stratified personalized medicine targeting atherosclerosis in patients with CKD. Future primary prevention trials should enroll patients with evidence of subclinical atherosclerosis and should provide a comprehensive control of all known risk factors in addition to testing any additional intervention or placebo.

How service users and carers understand, perceive, rephrase, and communicate about "depressive episode" and "schizophrenia" diagnoses: an international participatory research.

BACKGROUND: For ICD-11, the WHO emphasized the clinical utility of communication and the need to involve service users and carers in the revision process. AIMS: The objective was to assess whether medical vocabulary was accessible, which kinds of feelings it activated, whether and how users and carers would like to rephrase terms, and whether they used diagnosis to talk about mental health experiences. METHOD: An innovative protocol focused on two diagnoses (depressive episode and schizophrenia) was implemented in 15 different countries. The same issues were discussed with users and carers: understanding, feelings, rephrasing, and communication. RESULTS: Most participants reported understanding the diagnoses, but associated them with negative feelings. While the negativity of "depressive episode" mostly came from the concept itself, that of "schizophrenia" was largely based on its social impact and stigmatization associated with "mental illness". When rephrasing "depressive episode", a majority kept the root "depress*", and suppressed the temporal dimension or renamed it. Almost no one suggested a reformulation based on "schizophrenia". Finally, when communicating, no one used the phrase "depressive episode". Some participants used words based on "depress", but no one mentioned "episode". Very few used "schizophrenia". CONCLUSION: Data revealed a gap between concepts and emotional and cognitive experiences. Both professional and experiential language and knowledge have to be considered as complementary. Consequently, the ICD should be co-constructed by professionals, service users, and carers. It should take the emotional component of language, and the diversity of linguistic and cultural contexts, into account.

Subclinical atherosclerosis burden predicts cardiovascular events in individuals with diabetes and chronic kidney disease.

BACKGROUND: Individuals with diabetes have remarkably high rates of cardiovascular morbidity and mortality. However, the incremental cardiovascular risk in diabetes is heterogeneous and has often been related to renal involvement. The purpose of this study was to analyse the prognostic value of subclinical atherosclerosis in determining the incidence of first cardiovascular events (CVEs) in individuals with diabetes and chronic kidney disease (CKD) compared to CKD individuals without diabetes. METHODS: We included data from individuals with CKD with and without diabetes, free from pre-existing cardiovascular disease, from the NEFRONA cohort. Participants underwent baseline carotid and femoral ultrasound and were followed up for 4 years. All CVEs during follow-up were registered. Bivariate analysis and Fine-Gray competing risk models were used to perform the statistical analysis. RESULTS: During the mean follow-up time of 48 months, a total of 203 CVE was registered. 107 CVE occurred among participants without diabetes (19.58 per 1000 person-years) and 96 CVE occurred among participants with diabetes (44.44 per 1000 person-years). Following the competing risk analysis, the variables predicting CVEs in CKD individuals without diabetes were the number of territories with plaque at baseline (HR 1.862, 95% CI [1.432;2.240]), age (HR 1.026, 95% CI [1.003;1.049]) and serum concentrations of 25-OH vitamin D (HR 0.963, 95% CI [0.933;0.094]). The only variable predicting CVEs among CKD participants with diabetes was the number of territories with plaque at baseline (HR 1.782, 95% CI [1.393, 2.278]). For both models, concordance (C) index yielded was over 0.7. CONCLUSIONS: The burden of subclinical atherosclerosis is the strongest predictor of future CVEs in diabetic individuals with CKD. Early detection of subclinical atherosclerotic burden by multiterritorial vascular ultrasound could improve CVE prediction in this population.

Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project.

BACKGROUND: Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage. METHODS: Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines. RESULTS: Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects. CONCLUSIONS: The prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner. Trial registration NCT03228459 (clinicaltrials.gov).

Association of the rs495392 Klotho polymorphism with atheromatosis progression in patients with chronic kidney disease.

BACKGROUND: Prevalence of atherosclerotic cardiovascular disease and its rate of progression are higher in patients with chronic kidney disease (CKD) compared with the general population. Mineral metabolism parameters have been shown to be involved in the increased velocity of atheromatosis progression. The aim of this study is to determine the role of 11 single-nucleotide polymorphisms (SNPs) of the Klotho gene on the rate of atherosclerosis progression in CKD. METHODS: This was a multicentre, prospective, observational study of 1439 CKD patients from the NEFRONA cohort. Carotid and femoral ultrasounds were performed at baseline and after 24 months in 10 arterial territories. Progression of atheromatosis was defined as an increase in the number of territories with plaque. Genotyping of 11 SNPs of the Klotho gene was performed and its association with atheromatosis progression was determined by multivariate logistic regression. RESULTS: Bivariate analysis showed that none of the 11 SNPs was associated with atheroma plaque prevalence, but 3 of them (rs495392, rs562020 and rs567170) showed association with atheromatosis progression. The multivariate analysis revealed that only rs495392 showed a statistically significant association with atheromatosis progression, after adjustment for several parameters known to affect it in CKD patients. Thus, the presence of one allele T was associated with a reduction of 30% of the odds of progression, whereas the presence of the two T alleles was associated with a decrease close to 50%. CONCLUSIONS: The presence of the allele T of the SNP rs495392 of the Klotho gene is associated with a decrease in the odds of progression of atheromatosis in CKD patients.

ATPase-dependent control of the Mms21 SUMO ligase during DNA repair.

Modification of proteins by SUMO is essential for the maintenance of genome integrity. During DNA replication, the Mms21-branch of the SUMO pathway counteracts recombination intermediates at damaged replication forks, thus facilitating sister chromatid disjunction. The Mms21 SUMO ligase docks to the arm region of the Smc5 protein in the Smc5/6 complex; together, they cooperate during recombinational DNA repair. Yet how the activity of the SUMO ligase is controlled remains unknown. Here we show that the SUMO ligase and the chromosome disjunction functions of Mms21 depend on its docking to an intact and active Smc5/6 complex, indicating that the Smc5/6-Mms21 complex operates as a large SUMO ligase in vivo. In spite of the physical distance separating the E3 and the nucleotide-binding domains in Smc5/6, Mms21-dependent sumoylation requires binding of ATP to Smc5, a step that is part of the ligase mechanism that assists Ubc9 function. The communication is enabled by the presence of a conserved disruption in the coiled coil domain of Smc5, pointing to potential conformational changes for SUMO ligase activation. In accordance, scanning force microscopy of the Smc5-Mms21 heterodimer shows that the molecule is physically remodeled in an ATP-dependent manner. Our results demonstrate that the ATP-binding activity of the Smc5/6 complex is coordinated with its SUMO ligase, through the coiled coil domain of Smc5 and the physical remodeling of the molecule, to promote sumoylation and chromosome disjunction during DNA repair.

Assessment of the Monitor Unit Objective tool for VMAT in the Eclipse treatment planning system.

AIM: This work aims to achieve the highest possible monitor units (MU) reduction using the MU Objective tool included in the Eclipse treatment planning system, while preserving the plan quality. BACKGROUND: The treatment planning system Eclipse (Varian Medical Systems, Palo Alto, CA) includes a control mechanism for the number of monitor units of volumetric modulated arc therapy (VMAT) plans, named the MU Objective tool. MATERIAL AND METHODS: Forty prostate plans, 20 gynecological plans and 20 head and neck plans designed with VMAT were retrospectively studied. Each plan (base plan) was optimized without using the MU Objective tool, and it was re-optimized with different values of the Maximum MU (MaxMU) parameter of the MU Objective tool. MU differences were analyzed with a paired samples t-test and changes in plan quality were assessed with a set of parameters for OARs and PTVs. RESULTS: The average relative MU difference [Formula: see text] considering all treatment sites, was the highest when MaxMU = 400 (-4.2%, p < 0.001). For prostate plans, the lowest [Formula: see text] was obtained (-3.7%, p < 0.001). For head and neck plans [Formula: see text] was -7.3% (p < 0.001) and for gynecological plans [Formula: see text] was 7.0% (p = 0.002). Although similar MU reductions were observed for both sites, for some gynecological plans maximum differences were greater than 10%. All the assessed parameters for PTVs and OARs sparing showed average differences below 2%. CONCLUSION: For the three studied clinical sites, establishing MaxMU = 400 led to the optimum MU reduction, maintaining the original dose distribution and dosimetric parameters practically unaltered.

Smc5/6 complex regulates Sgs1 recombination functions.

The family of RecQ helicases is evolutionary conserved from bacteria to humans and play key roles in genome stability. The budding yeast RecQ helicase Sgs1 has been implicated in several key processes during the repair of DNA damage by homologous recombination as part of the STR complex (Sgs1-Top3-Rmi1). Limited information on how is Sgs1 recruited and regulated at sites of damage is available. Recently, we and others have uncover a direct link between the Smc5/6 complex and Sgs1. Most roles of Sgs1 during recombination, including DNA end resection, Holiday junction dissolution, and crossover suppression, are regulated through Mms21-dependent SUMOylation. Smc5/6 first acts as a recruiting platform for STR and then SUMOylates STR components to regulate their function. Importantly, the assembly of STR is totally independent of Smc5/6. Here, we provide a brief overview of STR regulation by Smc5/6.

Does Employment Promote Recovery? Meanings from Work Experience in People Diagnosed with Serious Mental Illness.

Employment has been highlighted as a determinant of health and as an essential milestone in the recovery process of people with serious mental illness. Different types of programs and public services have been designed to improve the employability of this population. However, there has not been much interest in the meanings attributed to these experiences and the negative aspects of work experience. In this research, we explored the meanings that participants attributed to their work experience and the impact of work on their recovery process. Research participants lived in Andalusia (Spain), a region in southern Europe with a high unemployment rate. Two versions of a semi-structured interview were designed: one for people who were working, and one for unemployed people. Participants' narratives were categorized according to grounded theory and the analyses were validated in group sessions. Apart from several positive effects for recovery, the analysis of the narratives about work experience outlined certain obstacles to recovery. For example, participants mentioned personal conflicts and stress, job insecurity and meaningless jobs. While valid, the idea that employment is beneficial for recovery must be qualified by the personal meanings attributed to these experiences, and the specific cultural and economic factors of each context.

Cognitive and Social Functioning Correlates of Employment Among People with Severe Mental Illness.

We assess how social and cognitive functioning is associated to gaining employment for 213 people diagnosed with severe mental illness taking part in employment programs in Andalusia (Spain). We used the Repeatable Battery for the Assessment of Neuropsychological Status and the Social Functioning Scale and conducted two binary logistical regression analyses. Response variables were: having a job or not, in ordinary companies (OCs) and social enterprises, and working in an OC or not. There were two variables with significant adjusted odds ratios for having a job: "attention" and "Educational level". There were five variables with significant odds ratios for having a job in an OC: "Sex", "Educational level", "Attention", "Communication", and "Independence-competence". The study looks at the possible benefits of combining employment with support and social enterprises in employment programs for these people and underlines how both social and cognitive functioning are central to developing employment models.

Matrix Gla protein polymorphism rs1800802 is associated with atheroma plaque progression and with cardiovascular events in a chronic kidney disease cohort.

Background: Chronic kidney disease (CKD) is associated with increased atherosclerotic burden and higher risk for cardiovascular events (CVE). Atherosclerosis has a significant genetic component and, in CKD, it is influenced by mineral metabolism alterations. Therefore, genetic modifications of mineral metabolism-related proteins could affect atherosclerosis in CKD patients. In the present study we investigated the role of single nucleotide polymorphisms (SNPs) of the matrix gamma-carboxy glutamic acid protein (MGP) on atherosclerosis progression and CVE in a CKD cohort. Methods: A total of 2187 CKD patients from the Observatorio Nacional de Aterosclerosis en Nefrologia (NEFRONA) study were genotyped for SNPs present in the matrix gamma-carboxy glutamic acid (Gla) protein (MGP) gene. Atheromatosis was detected by vascular ultrasound. Progression of atheromatosis, defined as an increase in territories with plaque, was assessed after 24 months. Patients were followed for 48 months for CVE. Association of SNPs with plaque progression was assessed by logistic regression and their capacity to predict CVE by Cox regression. Results: Three SNPs of the MGP gene were analyzed. No association of the rs4236 or the rs1800801 SNPs was detected with any of the outcomes. However, patients homozygotes for the minor allele of the rs1800802 SNP showed higher adjusted risk for plaque progression [odds ratio 2.3 (95% confidence interval 1.06-4.9)] and higher risk of suffering a CVE [hazard ratio 2.16 (95% confidence interval 1.13-4.12)] compared with the rest of genotypes. No association of the SNP with total or dp-ucMGP levels was found in a subsample. Conclusions: The rs1800802 polymorphism of MGP is associated with plaque progression and CVE in CKD patients.

Gender-specific risk factors and outcomes of hyperkalemia in CKD patients: smoking as a driver of hyperkalemia in men.

Background: Hyperkalemia is common among patients with chronic kidney disease (CKD) but there is scarce information on differential risk factors and outcomes for men and women. For instance, smoking has been suggested to be a risk factor for hyperkalemia, but specific analysis of the sex-specific impact of smoking on hyperkalemia in CKD is lacking. Methods: We studied serum potassium levels in 2891 participants from the NEFRONA cohort: 483 controls (47% women) and 2408 CKD patients (38% women) without prior cardiovascular disease (CVD), assessing whether smoking is a risk factor for hyperkalemia, and if hyperkalemia is associated with outcomes separately for men and women. Results: Median potassium levels and prevalence of hypo and hyperkalemia were higher in CKD participants than in controls. Serum potassium levels were higher and hyperkalemia and severe hyperkalemia more prevalent in men than in women with non-dialysis CKD (G3-G5). The highest prevalence of hyperkalemia for each gender was found in CKD G4-G5 and hemodialysis patients for men (46%) and in hemodialysis (54%) for women. Gender-specific etiological multivariate analysis identified current smoking as a risk factor for hyperkalemia only in men. Hyperkalemia was independently associated with stopping RAASi, an outcome which was more common in women. Hyperkalemia was also associated to higher risk of cardiovascular events within 4 years in men. In conclusion, hyperkalemia is common among men and women with CKD, but the prevalence, risk factors and outcomes may differ by gender. Specifically, current smoking is a driver of hyperkalemia in men.

Influence of nonalcoholic fatty liver disease severity on carotid adventitial vasa vasorum.

Introduction: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the world's population and encompasses a spectrum of liver conditions, from non-alcoholic steatohepatitis (NASH) to inflammation and fibrosis. In addition, NAFLD also links to extrahepatic conditions like diabetes or obesity. However, it remains unclear if NAFLD independently correlates with the onset and progression of atherosclerosis. Material and methods: This cross-sectional study aimed to explore the relationship between NAFLD severity, assessed via liver biopsy, and early atherosclerosis using adventitial vasa vasorum (VV) density. It included 44 patients with obesity (33 with steatosis, 11 with NASH) undergoing bariatric surgery. Results: Results revealed no significant differences in adventitial VV density between steatosis and NASH groups, neither in the mean values [0.759 ± 0.104 vs. 0.780 ± 0.043, P=0.702] nor left-right sides. Similarly, carotid intima-media thickness (cIMT) did not vary between these groups. Additionally, no linear correlation existed between VV density and cIMT. Only gender showed an association with VV density. Conclusion: These findings suggest that NASH severity doesn't independently drive early atherosclerosis or affects cIMT. Gender might play a role in early atherosclerotic disease in NAFLD, impacting VV density and cIMT. This highlights the need to consider other risk factors when evaluating cardiovascular risk in NAFLD patients.