The expanding clinical and genetic spectrum of DYNC1H1-related disorders.

Intracellular trafficking involves an intricate machinery of motor complexes including the dynein complex to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains as well as cytoplasmic light and intermediate chains have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons. Dominant pathogenic variants in DYNC1H1 have been previously implicated in peripheral neuromuscular disorders (NMD) and neurodevelopmental disorders (NDD). As heavy-chain dynein is ubiquitously expressed, the apparent selectivity of heavy-chain dyneinopathy for motor neuronal phenotypes remains currently unaccounted for. Here, we aimed to evaluate the full DYNC1H1-related clinical, molecular and imaging spectrum, including multisystem features and novel phenotypes presenting throughout life. We identified 47 cases from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years) and collected phenotypic data via a comprehensive standardized survey and clinical follow-up appointments. Most patients presented with divergent and previously unrecognized neurological and multisystem features, leading to significant delays in genetic testing and establishing the correct diagnosis. Neurological phenotypes include novel autonomic features, previously rarely described behavioral disorders, movement disorders, and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies, and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. We also identified an age-dependent biphasic disease course with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, we observed several cases in whom neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross-River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of NDD manifestations, indicating a role of dynein in anti-viral immunity and neuronal health. In summary, our findings expand the clinical, imaging, and molecular spectrum of pathogenic DYNC1H1 variants beyond motor neuropathy disorders and suggest a life-long continuum and age-related progression due to deficient intracellular trafficking. This study will facilitate early diagnosis and improve counselling and health surveillance of affected patients.

Concurrence of anemia and stunting and associated factors among children aged 6 to 59 months in Peru.

Anemia and stunting are two health problems in the child population; therefore, their concurrence needs to be quantified. We estimated the prevalence of concurrent anemia and stunting (CAS) in children aged 6-59 months and identified the factors associated with this condition. The data came from the Demographic and Health Survey of Peru (DHS), 2022. The study design was cross-sectional and included 19,191 children. Height and hemoglobin measurement followed the specifications of National Health Institute of Peru. To reduce error in measures, the anthropometry personnel was training, the quality of measuring equipment was ensuring, and protocolized techniques and procedures was applying. Hemoglobin concentration was measured in capillary blood using the Hemocue model Hb 201+. Stunting was defined as a height-for-age Z-score less than minus two standard deviations (SD) from the median, following the 2006 WHO child growth standard. Anemia was classified into mild (10.0 to 10.9 g/dL), moderate (7.0 to 9.9 g/dL), severe (< 7.0 g/dL), and no anemia (11.0 to 14.0 g/dL). We performed a bivariate analysis to evaluate factors associated with CAS. To include variables in the multivariate analysis, we applied a statistical criterion (p < 0.10 in the crude analysis) and an epidemiological criterion. We used a binary logistic hierarchical regression model. The prevalence of CAS was 5.6% (95%CI: 5.2 to 5.9). The modifiable factors associated with higher odds of CAS were: "poorest" (aOR: 3.87, 95%CI: 1.99 to 7.5) and "poorer" (aOR: 2.07, 95%CI: 1.08 to 3.98) wealth quintiles, mother with no formal education or primary (aOR: 2.03, 95%CI: 1.46 to 2. 81), father with no formal education or primary (aOR: 1.55, 95%CI: 1.16 to 2.07), no improved water source (aOR: 1.36, 95%CI: 1.10 to 1.68), no roof with improved material (aOR: 1.49, 95%CI: 1.12 to 1.98) and low birth weight (aOR: 7.31, 95%CI: 4.26 to 12.54). In Peru, five out of every 100 children suffer from anemia and stunting simultaneously; there are modifiable factors that, if addressed, could reduce their prevalence.

Caffeic Acid Phenethyl Ester (CAPE): Biosynthesis, Derivatives and Formulations with Neuroprotective Activities.

Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity; and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-κB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023), addressing their neuroprotective activity in vitro and in vivo.

The Potential Role of Epigallocatechin-3-Gallate (EGCG) in Breast Cancer Treatment.

Breast cancer is one of the most diagnosed cancers worldwide, with an incidence of 47.8%. Its treatment includes surgery, radiotherapy, chemotherapy, and antibodies giving a mortality of 13.6%. Breast tumor development is driven by a variety of signaling pathways with high heterogeneity of surface receptors, which makes treatment difficult. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol isolated as the main component in green tea; it has shown multiple beneficial effects in breast cancer, controlling proliferation, invasion, apoptosis, inflammation, and demethylation of DNA. These properties were proved in vitro and in vivo together with synergistic effects in combination with traditional chemotherapy, increasing the effectiveness of the treatment. This review focuses on the effects of EGCG on the functional capabilities acquired by breast tumor cells during its multistep development, the molecular and signal pathways involved, the synergistic effects in combination with current drugs, and how nanomaterials can improve its bioavailability on breast cancer treatment.

The potential role of Epigallocatechin-3-Gallate (EGCG) in breast cancer treatment

Breast cancer is one of the most diagnosed cancers worldwide, with an incidence of 47.8%. Its treatment includes surgery, radiotherapy, chemotherapy, and antibodies giving a mortality of 13.6%. Breast tumor development is driven by a variety of signaling pathways with high heterogeneity of surface receptors, which makes treatment difficult. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol isolated as the main component in green tea; it has shown multiple beneficial effects in breast cancer, controlling proliferation, invasion, apoptosis, inflammation, and demethylation of DNA. These properties were proved in vitro and in vivo together with synergistic effects in combination with traditional chemotherapy, increasing the effectiveness of the treatment. This review focuses on the effects of EGCG on the functional capabilities acquired by breast tumor cells during its multistep development, the molecular and signal pathways involved, the synergistic effects in combination with current drugs, and how nanomaterials can improve its bioavailability on breast cancer treatment.

Drimane Sesquiterpene Alcohols with Activity against Candida Yeast Obtained by Biotransformation with Cladosporium antarcticum.

Fungal biotransformation is an attractive synthetic strategy to produce highly specific compounds with chemical functionality in regions of the carbon skeleton that are not easily activated by conventional organic chemistry methods. In this work, Cladosporium antarcticum isolated from sediments of Glacier Collins in Antarctica was used to obtain novel drimane sesquiterpenoids alcohols with activity against Candida yeast from drimendiol and epidrimendiol. These compounds were produced by the high-yield reduction of polygodial and isotadeonal with NaBH4 in methanol. Cladosporium antarcticum produced two major products from drimendiol, identified as 9α-hydroxydrimendiol (1, 41.4 mg, 19.4% yield) and 3ß-hydroxydrimendiol (2, 74.8 mg, 35% yield), whereas the biotransformation of epidrimendiol yielded only one product, 9ß-hydroxyepidrimendiol (3, 86.6 mg, 41.6% yield). The products were purified by column chromatography and their structure elucidated by NMR and MS. The antifungal activity of compounds 1-3 was analyzed against Candida albicans, C. krusei and C. parapsilosis, showing that compound 2 has a MIC lower than 15 µg/mL against the three-pathogenic yeast. In silico studies suggest that a possible mechanism of action for the novel compounds is the inhibition of the enzyme lanosterol 14α-demethylase, affecting the ergosterol synthesis.

Drimane Sesquiterpene Aldehydes Control Candida Yeast Isolated from Candidemia in Chilean Patients.

Drimys winteri J.R. (Winteraceae) produce drimane sesquiterpenoids with activity against Candida yeast. In this work, drimenol, polygodial (1), isotadeonal (2), and a new drimane α,ß-unsaturated 1,4-dialdehyde, named winterdial (4), were purified from barks of D. winteri. The oxidation of drimenol produced the monoaldehyde drimenal (3). These four aldehyde sesquiterpenoids were evaluated against six Candida species isolated from candidemia patients in Chilean hospitals. Results showed that 1 displays fungistatic activity against all yeasts (3.75 to 15.0 µg/mL), but irritant effects on eyes and skin, whereas its non-pungent epimer 2 has fungistatic and fungicide activities at 1.9 and 15.0 µg/mL, respectively. On the other hand, compounds 3 and 4 were less active. Molecular dynamics simulations suggested that compounds 1-4 are capable of binding to the catalytic pocket of lanosterol 14-alpha demethylase with similar binding free energies, thus suggesting a potential mechanism of action through the inhibition of ergosterol synthesis. According to our findings, compound 2 appears as a valuable molecular scaffold to pursue the future development of more potent drugs against candidiasis with fewer side effects than polygodial. These outcomes are significant to broaden the alternatives to treat fungal infections with increasing prevalence worldwide using natural compounds as a primary source for active compounds.

Analysis of illicit pills and drugs of abuse in urine samples using a 3D-printed open port probe hyphenated with differential mobility spectrometry-mass spectrometry.

The present work describes the application of an in-house developed 3D-printed open port probe (3DP-OPP) with differential ion mobility spectrometry (DMS) mass spectrometry. Targeted quantitative analysis in urine was performed with a triple quadrupole mass spectrometer in the selected reaction monitoring mode (OPP-DMS-SRM/MS) and illicit pill screening using data independent acquisition (OPP-DMS-SWATH/MS). The combination of compensation voltage (CoV) scanning in DMS using modifiers with SWATH/MS acquisition for MS/MS spectrum generation enabled the differentiation of isobaric signals with a large dynamic range and enhance the information contained in the screening of illicit ecstasy pills. As for any direct MS introduction technique where no chromatographic separation is applied DMS with acetonitrile as a modifier allows the separation of cocaine and tramadol, and their isomeric metabolites in urine samples. Quantitative application using OPP-DMS-SRM/MS is presented without the need for sample preparation with a lower limit of quantification at 10-25 ng mL-1 for the analytes and less than 40 seconds for sample to sample analysis.

A systematic review of social participation in ecosystem services studies in Latin America from a transdisciplinary perspective, 1996-2020.

In this article, we propose that ecosystem services (ES) should be studied integrating social participation and the narrative of social actors. We analyzed the ES literature (1996-2020) in Latin America (LA), basing our review on the concept that the study of this topic should be transdisciplinary and post-normal (i.e., extended peer communities). We prepared the review using the Scopus® and Web of Science™ (WoS) databases. We found 1069 articles related to social participation in ES studies in 20 LA countries, identifying 310 articles for further analysis using screening and eligibility protocols. We also used a random sample (n = 50) of the 310 articles for a detailed analysis of social participation and extended peer communities. Results showed that articles increased from seven in 2010 to 39 per year from 2015 to 2019. English is the primary language used (91% of the articles), with only one journal accepting publications in Spanish. The most common collaboration combination has been one LA author and one or more non-LA authors (41% of the articles). The semantic network analysis showed 35 thematic clusters, with the most common corresponding to ES protection and provision issues. Direct social participation was included in 62% of the articles, mainly through interviews; however, consultancy processes have dominated the participatory perspective of the authors without transformative involvement. We discuss article language and low inter-countries collaboration, both influencing the lack of social participation required for the transdisciplinary analysis of ES.

Reproducibility of global LV function and dyssynchrony parameters derived from phase analysis of gated myocardial perfusion SPECT: A multicenter comparison with core laboratory setting.

BACKGROUND: Gated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population. METHODS: This is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab. RESULTS: 276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland-Altman plots demonstrated good agreement. CONCLUSIONS: The presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.

Clinical and gated SPECT MPI parameters associated with super-response to cardiac resynchronization therapy.

PURPOSE: We sought to evaluate the behavior of cardiac mechanical synchrony as measured by phase SD (PSD) derived from gated MPI SPECT (gSPECT) in patients with super-response after CRT and to evaluate the clinical and imaging characteristics associated with super-response. METHODS: 158 subjects were evaluated with gSPECT before and 6 months after CRT. Patients with an improvement of LVEF > 15% and NYHA class I/II or reduction in LV end-systolic volume > 30% and NYHA class I/II were labeled as super-responders (SR). RESULTS: 34 patients were classified as super-responders (22%) and had lower PSD (32° ± 17°) at 6 months after CRT compared to responders (45° ± 24°) and non-responders 46° ± 28° (P = .02 for both comparisons). Regression analysis identified predictors independently associated with super-response to CRT: absence of previous history of CAD (odds ratio 18.7; P = .002), absence of diabetes mellitus (odds ratio 13; P = .03), and history of hypertension (odds ratio .2; P = .01). CONCLUSION: LV dyssynchrony after CRT implantation, but not at baseline, was significantly better among super-responders compared to non-super-responders. The absence of diabetes, absence of CAD, and history of hypertension were independently associated with super-response after CRT.

Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles.

Stem-cell-derived extracellular vesicles (EVs) have demonstrated multiple beneficial effects in preclinical models of cardiac diseases. However, poor retention at the target site may limit their therapeutic efficacy. Cardiac extracellular matrix hydrogels (cECMH) seem promising as drug-delivery materials and could improve the retention of EVs, but may be limited by their long gelation time and soft mechanical properties. Our objective was to develop and characterize an optimized product combining cECMH, polyethylene glycol (PEG), and EVs (EVs-PEG-cECMH) in an attempt to overcome their individual limitations: long gelation time of the cECMH and poor retention of the EVs. The new combined product presented improved physicochemical properties (60% reduction in half gelation time, p < 0.001, and threefold increase in storage modulus, p < 0.01, vs. cECMH alone), while preserving injectability and biodegradability. It also maintained in vitro bioactivity of its individual components (55% reduction in cellular senescence vs. serum-free medium, p < 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, p < 0.05). In conclusion, the combination of EVs-PEG-cECMH is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.

Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia.

Gut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.

Phenotypic and genotypic detection of antibiotic-resistant bacteria in fresh fruit juices from a public hospital in Rio de Janeiro.

Gram-negative bacteria are worrisome because they are becoming resistant to many antibiotic available options, mainly in hospital environment. Several studies have noted the presence of bacteria producing extended-spectrum beta-lactamase, with the presence of antibiotic-resistance genes in fresh vegetables and fruits. This study aimed to detect the presence of phenotypic and genotypic resistance in eight samples of fresh fruit juices served to patients admitted to a hospital in Rio de Janeiro. The growth of microorganisms on MacConkey and XLD agar was carried out to obtain a "pool" of Gram-negative bacteria. The disk diffusion test and the polymerase chain reaction were performed to detect the phenotypic and genotypic resistance of Gram-negative bacteria to the tested antibiotics. The multidrug resistance was detected in all samples and the shv, tem, ctx, tetA, tetB and oxa- 48 genes were found in the samples, including the presence of class 2 and 3 integrons. We can conclude that the selection methodology allows the detection of a greater number of genes and this found warns about the risk of making these foods available to patients in hospitals.

Toward social-ecological coastal zone governance of Chiloé Island (Chile) based on the DPSIR framework.

Coastal zones are complex systems where sustainability needs local participative governance, whose absence may result in conflicts between social actors. In its absence, the first step should be a diagnosis of the current situation based on integrative conceptual frameworks such as the DPSIR. However, in conflicting situations, the generated model needs validation from social actors. Chiloé Island is a critical Chilean coastal fishery and aquaculture area, coexisting with subsistence and cultural uses of marine resources. This article analyzes the current ecological state of the Chiloé coastal zone and its main social-ecological impact using a DPSIR model. We validated its results through a household survey and interviews with local experts and social actors. Results show that increased coastal fisheries and aquaculture generate a critical decrease of coastal species, eutrophication, and pollution that, along with harmful algal blooms, generate conflicts. Social validation showed that experts and local social actors have different perceptions of conflicting parties and conflict solutions. Following a post-normal approach, we propose three ideas to start social-ecological governance of Chiloé coastal marine ecosystems.

High Serum Levels of Caspase-3 and Early Mortality in Patients with Severe Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Apoptotic cell death leads to secondary brain injury after spontaneous intracerebral hemorrhage (SIH). There is an association between serum caspase-3 levels and late mortality (at 6 months) in patients with SIH in basal ganglia. The new objective of this study was to determine whether there exists an association between serum caspase-3 levels and early mortality (at 30 days) in patients with SIH at different sites and not only in basal ganglia. METHODS: Patients with severe supratentorial SIH (defined as Glasgow Coma Scale < 9) admitted in 6 Spanish hospitals were included in this observational and prospective study. Patients with SIH due to aneurysm, arteriovenous malformation, and anticoagulant or fibrinolytic treatment were excluded. Serum caspase-3 levels at days 1, 4, and 8 of SIH were determined. Thirty-day mortality was the end-point study. RESULTS: Non-surviving (n = 53) showed higher serum caspase-3 levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001) than survivor patients (n = 64). Multiple logistic regression analysis showed an association of serum caspase-3 levels > 0.167 ng/mL with 30-day mortality (Odds Ratio = 47.007; 95% CI = 4.838-456.727; p = 0.001). CONCLUSIONS: The new findings of our study are that serum caspase-3 levels are associated with early mortality in patients with severe supratentorial SIH at different sites and that those levels during the first week of SIH are higher in non-survivors than in survivors.

Value of intraventricular dyssynchrony assessment by gated-SPECT myocardial perfusion imaging in the management of heart failure patients undergoing cardiac resynchronization therapy (VISION-CRT).

BACKGROUND: Placing the left ventricular (LV) lead in a viable segment with the latest mechanical activation (vSOLA) may be associated with optimal cardiac resynchronization therapy (CRT) response. We assessed the role of gated SPECT myocardial perfusion imaging (gSPECT MPI) in predicting clinical outcomes at 6 months in patients submitted to CRT. METHODS: Ten centers from 8 countries enrolled 195 consecutive patients. All underwent gSPECT MPI before and 6 months after CRT. The procedure was performed as per current guidelines, the operators being unaware of gSPECT MPI results. Regional LV dyssynchrony (Phase SD) and vSOLA were automatically determined using a 17 segment model. The lead was considered on-target if placed in vSOLA. The primary outcome was improvement in ≥1 of the following: ≥1 NYHA class, left ventricular ejection fraction (LVEF) by ≥5%, reduction in end-systolic volume by ≥15%, and ≥5 points in Minnesota Living With Heart Failure Questionnaire (MLHFQ). RESULTS: Sixteen patients died before the follow-up gSPECT MPI. The primary outcome occurred in 152 out of 179 (84.9%) cases. Mean change in LV phase standard deviation (PSD) at 6 months was 10.5°. Baseline dyssynchrony was not associated with the primary outcome. However, change in LV PSD from baseline was associated with the primary outcome (OR 1.04, 95% CI 1.01-1.07, P = .007). Change in LV PSD had an AUC of 0.78 (0.66-0.90) for the primary outcome. Improvement in LV PSD of 4° resulted in the highest positive likelihood ratio of 7.4 for a favorable outcome. In 23% of the patients, the CRT lead was placed in the vSOLA, and in 42% in either this segment or in a segment within 10° of it. On-target lead placement was not significantly associated with the primary outcome (OR 1.53, 95% CI 0.71-3.28). CONCLUSION: LV dyssynchrony improvement by gSPECT MPI, but not on-target lead placement, predicts clinical outcomes in patients undergoing CRT.

Diastolic dyssynchrony assessment by gated myocardial perfusion-SPECT in subjects who underwent cardiac resynchronization therapy.

BACKGROUND: Left ventricular diastolic dyssynchrony (LVDD) can be assessed by gated myocardial perfusion single-photon emission computed tomography (GMP-SPECT). LVDD is an area of interest in subjects who underwent cardiac resynchronization therapy (CRT). The aim of this post hoc analysis was to assess the role of LVDD in subjects with CRT who were followed up at 6-month period. MATERIAL & METHODS: Left ventricular diastolic dyssynchrony was assessed by GMP-SPECT at baseline and after CRT procedure in 160 subjects from 10 different cardiological centers. CRT procedure was performed as per current guidelines. Outcomes were defined as improvement in ≥1 New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF) by 5%, and reduction in end-systolic volume (ESV) by 15% and 5% points in Minnesota Living with Heart Failure Questionnaire. LVDD was defined as diastolic phase standard deviation ≥40 ± 14°. RESULTS: Improvement in NYHA functional class occurred in 105 (65.6%), LVEF in 74 (46.3%), decrease in ESV in 86 (53.8%), and Minnesota score in 85 (53.1%) cases. Baseline LV diastolic standard deviation was 53.53° ± 20.85 and at follow-up 40.44° ± 26.1283; (P < 0.001). LVDD was not associated with improvement in clinical outcomes at follow-up. CONCLUSION: CRT improves both systolic and diastolic dyssynchrony values at 6-month follow-up. LVDD at baseline is correlated with cardiac functionality at follow-up, but not with overall favorable clinical outcomes.

High serum levels of TAC and early mortality in patients with spontaneous intracerebral haemorrhage.

OBJECTIVE: Oxidation contributes to secondary brain injury after spontaneous intracerebral haemorrhage (SIH). One study found lower levels of total antioxidant capacity (TAC) in the blood in patients with SIH than in healthy subjects. However, there are no data on blood TAC levels and survival in patients with SIH. Therefore, the objective of our study was to determine if an association exists between serum TAC levels and mortality in patients with SIH. METHODS: We included patients with severe supratentorial SIH. We considered severe when Glasgow Coma Scale (GCS) < 9. Patients from 6 Spanish hospitals were included in this observational and prospective study. Serum TAC levels at days 1, 4 and 8 of SIH were determined. Thirty-day mortality was our end-point study. RESULTS: Non-surviving patients compared with surviving patients showed higher serum TAC levels at day 1 (p < 0.001), 4 (p < 0.001) and 8 (p = 0.001). An area under the curve was found for the prediction of 30-day mortality by serum TAC levels of 0.92 (95% CI = 0.85-96%; p < 0.001). Multiple logistic regression analysis showed an association of serum TAC levels with 30-day mortality (odds ratio = 16.513; 95% CI = 2.548-107.015; p = 0.003) controlling for midline shift, glycemia, early evacuation of SIH, intracerebral haemorrhage (ICH) score, age and volume of SIH. CONCLUSIONS: The new findings of this study are that serum TAC levels are higher in non-surviving than in surviving patients, and that they are associated with mortality and could be used to predict mortality.