Oxidized High-Density Lipoprotein Induces Endothelial Fibrosis Promoting Hyperpermeability, Hypotension, and Increased Mortality.

During systemic inflammation, reactive oxygen species (ROS) are generated in the bloodstream, producing large amounts of oxidized HDL (oxHDL). OxHDL loses the vascular protective features of native HDL, acquiring detrimental actions. Systemic inflammation promotes endothelial fibrosis, characterized by adhesion protein downregulation and fibrotic-specific gene upregulation, disrupting endothelial monolayer integrity. Severe systemic inflammatory conditions, as found in critically ill patients in the intensive care unit (ICU), exhibit endothelial hyperpermeability, hypotension, and organ hypoperfusion, promoting organ dysfunction and increased mortality. Because endothelial fibrosis disturbs the endothelium, it is proposed that it is the cellular and molecular origin of endothelial hyperpermeability and the subsequent deleterious consequences. However, whether oxHDL is involved in this process is unknown. The aim of this study was to investigate the fibrotic effect of oxHDL on the endothelium, to elucidate the underlying molecular and cellular mechanism, and to determine its effects on vascular permeability, blood pressure, and mortality. The results showed that oxHDL induces endothelial fibrosis through the LOX-1/NOX-2/ROS/NF-κB pathway, TGF-ß secretion, and ALK-5/Smad activation. OxHDL-treated rats showed endothelial hyperpermeability, hypotension, and an enhanced risk of death and mortality, which was prevented using an ALK-5 inhibitor and antioxidant diet consumption. Additionally, the ICU patients showed fibrotic endothelial cells, and the resuscitation fluid volume administered correlated with the plasma oxHDL levels associated with an elevated risk of death and mortality. We conclude that oxHDL generates endothelial fibrosis, impacting blood pressure regulation and survival.

Evaluación del canino maxilar permanente en niños entre 8 y 11 años en radiografía panorámica

RESUMEN: El canino maxilar permanente (CMP) es el segundo diente con mayor frecuencia de impactación debido a su largo descenso intraóseo y cronología de erupción. El objetivo de este estudio fue evaluar el grado de desarrollo dentario y posición del CMP entre los 8 años y los 11 años 11 meses con el fin de sugerir una edad cronológica óptima para su evaluación temprana en radiografía panorámica. Se realizó un estudio retrospectivo, en donde se analizaron 239 radiografías panorámicas de niños de 8 a 11 años. Éstas se agruparon según edad, género y área apical; luego se analizó el grado de desarrollo dentario y posición del vértice CMP izquierdo. En los resultados se observó que no existen diferencias significativas de la posición del CMP respecto a la edad cronológica. Además, entre los ocho años seis meses y nueve años seis meses un 61% de los caninos tuvieron más de la mitad de formación radicular. En conclusión, la evaluación temprana con radiografía panorámica del CMP se sugiere desde los ocho años seis meses a los nueve años seis meses, para alertar al clínico en casos donde el trayecto eruptivo se encuentre desviado.

ABSTRACT: The permanent maxillary canine (PMC) is the second most frequently impacted tooth due to its long intraosseous descent and eruption chronology. The objective of this study was to evaluate the degree of dental development and position of the PMC between the ages of 8 and 11 years 11 months in order to suggest an optimal chronological age for their early evaluation in panoramic radiography. A retrospective study was carried out, where 239 panoramic radiographs of children aged 8 to 11 years were analyzed. They were grouped according to age, gender and apical area; Then, the degree of dental development and position of the left PMC apex were analyzed. The results show that there are no significant differences in the position of the PMC with respect to chronological age. Furthermore, between eight years six months and nine years six months, 61% of the canines had more than half of the root formed. In conclusion, the early evaluation with panoramic radiography of the PMC is suggested from eight years six months to nine years six months, to alert the clinician in cases where the eruptive path is deviated.

Linguistic profiles of variants of primary progressive aphasia.

BACKGROUND: Several subtypes of primary progressive aphasia (PPA) have been proposed. Most reports use small samples, and few have included Spanish-speaking participants. AIM: To analyze the language profile and nonlinguistic deficits in a large sample of PPA Spanish monolingual participants. METHOD: 177 individuals were diagnosed with PPA in a sample consisting of 69 men and 108 women (Mage = 66.40 years, SD = 9.30). The participants were assessed using the Spanish versions of the Western Aphasia Battery Revised (SWAB-R) and the Boston Diagnostic Aphasia Examination (SBDAE). Non-verbal reasoning was evaluated with the Raven's Colored Progressive Matrices. RESULTS: 41.8% of the sample met the criteria for the logopenic variant (lvPPA), while 28.2% met the criteria for semantic (svPPA), 15.3% for lexical (lxvPPA), and 14.7% for nonfluent/agrammatic (nfvPPA) variants. Language difficulties were similar in all variants except for lxvPPA. Scores on Spontaneous Language, Auditory Comprehension, Repetition, and Naming were significantly higher for the lxvPPA group. Raven's Colored Progressive Matrices scores were significantly lower in lvPPA. Years of education correlated with all test scores, while age was negatively associated with naming. When the PPA variants were classified according to the traditional aphasia classification, discrepancies were evident. Furthermore, the most frequent type of aphasia was Amnesic, while the least frequent was Wernicke's aphasia. CONCLUSION: The SWAB-R is useful in describing the clinical characteristics of aphasia for each variant of PPA, but quantitative scores from this battery are not capable of distinguishing between variants of PPA, with the exception of lxvPPA.

Autophagy modulates growth and development in the moss Physcomitrium patens.

Physcomitrium patens apical growing protonemal cells have the singularity that they continue to undergo cell divisions as the plant develops. This feature provides a valuable tool to study autophagy in the context of a multicellular apical growing tissue coupled to development. Herein, we showed that the core autophagy machinery is present in the moss P. patens, and characterized the 2D and 3D growth and development of atg5 and atg7 loss-of-function mutants under optimal and nutrient-deprived conditions. Our results showed that 2D growth of the different morphological and functional protonemata apical growing cells, chloronema and caulonema, is differentially modulated by this process. These differences depend on the protonema cell type and position along the protonemal filament, and growth condition. As a global plant response, the absence of autophagy favors the spread of the colony through protonemata growth at the expense of a reduction of the 3D growth, such as the buds and gametophore development, and thus the adult gametophytic and reproductive phases. Altogether this study provides valuable information suggesting that autophagy has roles during apical growth with differential responses within the cell types of the same tissue and contributes to life cycle progression and thus the growth and development of the 2D and 3D tissues of P. patens.

Acalculia in Aphasia.

BACKGROUND: Patients with aphasia can present a type of acalculia referred to as aphasic acalculia. AIMS: To investigate the correlation and to test regression models for one- and two-digit calculation skills using verbal and nonverbal predictors. METHODS AND PROCEDURES: We selected an aphasia sample of 119 men and 81 women with a mean age of 57.37 years (SD = 15.56) and an average level of education of 13.52 years (SD = 4.08). Spanish versions of the Western Aphasia Battery and Boston Diagnostic Aphasia Examination, plus a Written Calculation test, were individually administered. The calculation section of the Western Aphasia Battery and the Written Calculation tests were used to pinpoint calculation difficulties. OUTCOMES AND RESULTS: Calculation difficulties were more severe in Global and Mixed non-fluent aphasia; they were very similar in Broca, Conduction, and Amnesic Aphasia. All correlations between the two calculation subtests and the other subtests of the Western Aphasia Battery were statistically significant. Calculation subtests correlated negatively with age and positively with schooling. Sex and time post-onset did not show any correlation with the calculation scores. Education, Reading, Block Design, and Raven's Colored Progressive Matrices were significant predictors of Western Aphasia Battery Calculation. Writing was the only significant predictor of the Written Calculation scores. CONCLUSIONS: Nonverbal abilities were predictors of calculation tests, whereas agraphia defects were predictors of the Written Calculation test. Therefore, calculation abilities can be regarded both as written language-dependent and verbal language-independent.

Alexia and agraphia in Spanish.

BACKGROUND: Every language has certain specific idiosyncrasies in its writing system. Cross-linguistic analyses of alexias and agraphias are fundamental to understand commonalities and differences in the brain organization of written language. Few reports of alexias and agraphias in the Spanish language are currently available. AIMS: To analyse the clinical manifestations of alexias and agraphias in Spanish, and the effect of demographic variables. METHODS & PROCEDURES: Spanish versions of the Western Aphasia Battery (WAB) and Boston Diagnostic Aphasia Examination (BDAE) were used for language assessment. Lesion localization was obtained by using computed axial tomography and magnetic resonance imaging. The final sample included 200 patients: 195 (97.5%) right-handed and five (2.5%) left-handed; 119 men and 81 women with a mean age of 57.37 years (SD = 15.56), education of 13.52 years (SD = 4.08), and mean time post-onset of 6.58 months (SD = 12.94). Using the WAB, four quotients were calculated: aphasia quotient (AQ), reading-writing quotient (RWQ), language quotient (LQ) and cortical quotient (CQ). OUTCOMES & RESULTS: The types of aphasia were: global = 11 patients (5.5%), Broca = 31 (15.5%), Wernicke = 30 (15.0%), conduction = 22 (11.0%), transcortical sensory = 17 (8.5%), transcortical motor = 3 (1.5%), amnesic or anomic = 54 (27.0%) and mixed non-fluent = 32 (16.0%). The degree of oral and written language impairment differed across the various aphasia types. Most severe reading and writing difficulties were found in global, mixed non-fluent and transcortical motor aphasia; fewer difficulties were observed in amnesic, Broca and conduction aphasia. The severity of the written language impairments paralleled the severity of the oral language disturbances. Age negatively, while schooling positively, correlated with the scores in reading and writing tests. No effect of sex and time since onset was found. CONCLUSIONS & IMPLICATIONS: In Spanish-speaking aphasia patients, difficulties in reading and writing are similar to oral language difficulties. This similarity of performance is mostly based on severity rather than the participants' patterns of errors. What this paper adds What is already known on the subject There is limited information about alexia and agraphia in Spanish. What this paper adds to existing knowledge An extensive study with a large sample of patients. What are the potential or actual clinical implications of this work? The study contributes to the clinical management of patients with reading and writing disturbances.

Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury.

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI.

Myeloid CD11c+ Antigen-Presenting Cells Ablation Prevents Hypertension in Response to Angiotensin II Plus High-Salt Diet.

Increasing evidence shows that antigen-presenting cells (APCs) are involved in the development of inflammation associated to hypertension. However, the potential role of APCs in the modulation of renal sodium transport has not been addressed. We hypothesized that APCs participate in renal sodium transport and, thus, development of high blood pressure in response to angiotensin II plus a high-salt diet. Using transgenic mice that allow the ablation of CD11chigh APCs, we studied renal sodium transport, the intrarenal renin-angiotensin system components, blood pressure, and cardiac/renal tissue damage in response to angiotensin II plus a high-salt diet. Strikingly, we found that APCs are required for the development of hypertension and that the ablation/restitution of APCs produces rapid changes in the blood pressure in mice with angiotensin II plus a high-salt diet. Moreover, APCs were necessary for the induction of intrarenal renin-angiotensin system components and affected the modulation of natriuresis and tubular sodium transporters. Consistent with the prevention of hypertension, the ablation of APCs also prevented cardiac hypertrophy and the induction of several indicators of renal and cardiac damage. Thus, our findings indicate a prominent role of APCs as modulators of blood pressure by mechanisms including renal sodium handling, with kinetics that suggest the involvement of tubular cell functions in addition to the modulation of inflammation and adaptive immune response.

The needs of the relatives in the adult intensive care unit: Cultural adaptation and psychometric properties of the Chilean-Spanish version of the Critical Care Family Needs Inventory.

INTRODUCTION: The admission of a patient to an intensive care unit is an extraordinary event for their family. Although the Critical Care Family Needs Inventory is the most commonly used questionnaire for understanding the needs of relatives of critically ill patients, no Spanish-language version is available. The aim of this study was to culturally adapt and validate theCritical Care Family Needs Inventory in a sample of Chilean relatives of intensive care patients. METHODS: The back-translated version of the inventory was culturally adapted following input from 12 intensive care and family experts. Then, it was evaluated by 10 relatives of recently transferred ICU patients and pre-tested in 10 relatives of patients that were in the intensive care unit. Psychometric properties were assessed through exploratory factor analysis and Cronbach's α in a sample of 251 relatives of critically ill patients. RESULTS: The Chilean-Spanish version of the Critical Care Family Needs Inventoryhad minimal semantic modifications and no items were deleted. A two factor solution explained the 31% of the total instrument variance. Reliability of the scale was good (α=0.93), as were both factors (α=0.87; α=0.93). CONCLUSION: The Chilean-Spanish version of theCritical Care Family Needs Inventory was found valid and reliable for understanding the needs of relatives of patients in acute care settings.

Endothelial fibrosis induced by suppressed STAT3 expression mediated by signaling involving the TGF-ß1/ALK5/Smad pathway.

During systemic inflammatory pathologies, mediators of inflammation circulate in the bloodstream and interact with endothelial cells (ECs), resulting in endothelial dysfunction that maintains and enhances the pathological condition. Inflammatory mediators change the protein expression profile of ECs, which become activated fibroblasts via endothelial-to-mesenchymal transition. This process is characterized by downregulated endothelial proteins and strongly upregulated fibrotic-specific genes and extracellular matrix-forming proteins. The main inductor of endothelial fibrosis is transforming growth factor-ß1 (TGF-ß1), which acts through the TGF-ß1/activin receptor-like kinase 5 (ALK5)/Smads intracellular signaling pathway. The signal transducer and activator of transcription 3 (STAT3) is also involved in fibrosis in several tissues (e.g. heart and vascular system), where STAT3 signaling decreases TGF-ß1-induced responses by directly interacting with Smad proteins, suggesting that decreased STAT3 could induce TGF-ß1-mediated fibrosis. However, it is unknown if suppressed STAT3 expression induces EC fibrosis through a mechanism involving the TGF-ß signaling pathway. The present study evaluated the fibrotic actions of STAT3 suppression in ECs and investigated TGF-ß1/ALK5/Smad4 signaling pathway participation. Suppressed STAT3 expression stimulated fibrotic conversion in ECs, as mediated by protein expression reprograming that decreased endothelial marker expression and increased fibrotic and extracellular matrix protein levels. The potential mechanism underlying these changes was dependent on TGF-ß1 secretion, the ALK5 activation pathway, and Smad4 translocation into the nucleus. We conclude that suppressed STAT3 expression converts ECs into activated fibroblasts via TGF-ß1/ALK5/Smad4 signaling pathway involvement.

Mineralocorticoids modulate the expression of the ß-3 subunit of the Na+, K+-ATPase in the renal collecting duct.

Renal sodium reabsorption depends on the activity of the Na+,K+-ATPase α/ß heterodimer. Four α (α1-4) and 3 ß (ß1-3) subunit isoforms have been described. It is accepted that renal tubule cells express α1/ß1 dimers. Aldosterone stimulates Na+,K+-ATPase activity and may modulate α1/ß1 expression. However, some studies suggest the presence of ß3 in the kidney. We hypothesized that the ß3 isoform of the Na+,K+-ATPase is expressed in tubular cells of the distal nephron, and modulated by mineralocorticoids. We found that ß3 is highly expressed in collecting duct of rodents, and that mineralocorticoids decreased the expression of ß3. Thus, we describe a novel molecular mechanism of sodium pump modulation that may contribute to the effects of mineralocorticoids on sodium reabsorption.

Active aging promotion: results from the vital aging program.

Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative) are reported. Formative evaluation reflected participants' satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished.

Chemical analysis of the resinous exudate isolated from Heliotropium taltalense and evaluation of the antioxidant activity of the phenolics components and the resin in homogeneous and heterogeneous systems.

H. taltalense (Phil.) Johnst. (Heliotropiaceae) is an endemic species of the northern coast of Chile that produces a resinous exudate that covers its foliar surface and stems. Its chemical composition was analyzed for the first time, and two aromatic geranyl derivatives: filifolinol and filifolinyl senecionate and three flavonoids - naringenin, 3-O-methylgalangin and 7-O-methyleriodictiol - were isolated. The antioxidant activity of the flavonoids and the resinous exudates was carried out by measuring the 1,1-diphenyl-2-picrylhydrazyl (DPPH) bleaching effect in ethanolic solution and in sodium dodecyl sulfate (SDS) micelles. The influence of the reaction medium was analyzed. The initial velocity reactions for the pure compounds and for the extract were higher in SDS media than in ethanolic solution. The velocity of reaction observed was interpreted in terms of the reaction medium environment in the micelle.

Antioxidant activity of a new aromatic geranyl derivative of the resinous exudates from Heliotropium glutinosum Phil.

Heliotropium glutinosum Phil. (Heliotropiceae) is a resinous bush that grows at a height of 2000 m in Chañaral, Chile. From the resinous exudates of Heliotropium glutinosum Phil. a new aromatic geranyl derivative: 4-methoxy-3-[(2)-7'-methyl-3'-hydroxymethyl-2',6'-octadienyl] phenol (1) and three flavonoids: 5,3'-dihydroxy-7,4'-dimethoxyflavanone (2), 5,4'-dihydroxy-7-methoxyflavanone (3) and 4'-acetyl-5-hydroxy-7-methoxyflavanone (4) were isolated and their structures were determined. Their antioxidant activity were evaluated using the bleaching of ABTS and DPPH derived cation radical methods and expressed in terms of FRE (fast reacting equivalents) and TRE (total reacting equivalents), where FRE is a good measure of the quick protection of a given compound against oxidants and TRE measures the degree of long-term protection of the antioxidant, or how effective it is against a strong oxidative stress.