Asymptomatic parenchymal haemorrhage following endovascular treatment: Impact on functional outcome in patients with acute ischaemic stroke.

BACKGROUND AND PURPOSE: In patients with acute ischaemic stroke (AIS), haemorrhagic transformation (HT) following endovascular treatment (EVT) is associated with poor functional outcome. However, the impact of asymptomatic HT, not linked to neurological deterioration in the acute phase, is unknown. We aimed to investigate the impact of asymptomatic PH1 (aPH1) and PH2 (aPH2) subtypes of HT on the functional outcome of patients treated with EVT. METHODS: We conducted a retrospective study of patients with AIS who were consecutively admitted to our comprehensive stroke centre between January 2019 and December 2022, and who underwent EVT. We collected clinical, radiological, and procedural data. HTs were categorized according to the Heidelberg classification. The primary outcome was the shift on the modified Rankin Scale (mRS) at 3 months of follow-up. We performed bivariate and multivariable ordinal regression analyses to test the association between aPH1/aPH2 and the primary outcome. RESULTS: We included 314 patients (mean age = 72.5 years [SD = 13.6], 171 [54.5%] women). We detected 54 (17.2%) patients with HT; 23 (7.3%) were classified as PH2 (11 asymptomatic) and 17 (5.4%) as PH1 (16 asymptomatic). The adjusted common odds ratio for aPH2 of worsening 1 point on the 3-month mRS was 3.32 (95% confidence interval = 1.16-9.57, p = 0.026). No association was observed for aPH1. aPH2 was also independently associated with lower odds of achieving a favourable outcome (mRS = 0-2). Neither aPH1 nor aPH2 was associated with mortality. CONCLUSIONS: In patients with AIS treated with EVT, aPH2 is independently associated with unfavourable functional outcome.

Assessment of Changes in the Outcome of Autogenous Tooth Grafts Over Time: A Clinical Study Evaluating Periodontal Healing in Bone Defects After Lower Third Molar Removal.

BACKGROUND: The removal of impacted lower third molars (ILTMs) is associated with bone defects in the distal area of second molars. Different methods have been described to minimize these defects. PURPOSE: The primary objective was to assess changes in probing depth (PD) over time (up to 36 months) between test (grafted) and control (ungrafted) groups; the graft was obtained from the extracted ILTM. STUDY DESIGN, SETTING, SAMPLE: This split-mouth randomized clinical trial was conducted at the Postgraduate Course in Oral Surgery of the Faculty of Dentistry of the Complutense University of Madrid. Adult patients requiring bilateral ILTM extraction with adjacent second molars were recruited, excluding pregnant/lactating women, patients in treatment with nonsteroidal anti-inflammatory drugs and patients with periodontal diseases. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The predictor variable was the graft technique. The bone defect after ILTM removal was treated with autogenous tooth graft (ATG) in the test group, leaving the control group ungrafted. MAIN OUTCOME VARIABLE: PD on the distobuccal, distomedial, and distolingual surfaces was recorded in both groups and averaged at baseline (T0), 3 (T1), 6 (T2), and 36 months (T3) postoperatively. COVARIATES: Sex, age, surgical time, ILTM situation and position between groups were assessed. ANALYSES: ANOVA repeated measures for comparisons between groups and the Friedman test for comparisons within the groups over time were applied. Statistical significance was established with a confidence interval of 95% (P < .05). RESULTS: The sample comprised 22 patients (6 males, 16 females) with a mean age of 21.68 ± 2.19 years; 44 ILTM extractions were performed. Statistically significant differences in PD average were found between groups (P < .001, 95% confidence interval) at 3 (1.63 ± 0.29), 6 (1.76 ± 0.3), and 36 months (1.74 ± 0.36). Reductions from T0 to T3 of 2.74 ± 0.28 (P < .001) and 0.54 ± 0.3 (P = .43) were observed in test and control groups, respectively. CONCLUSION AND RELEVANCE: ATG placed on the distal surface of lower second molars and almost completely filling the extraction socket improved PD 3, 6 and 36 months after ILTM. Furthermore, no significant changes in PD were observed over time; no major complications occurred. ATG appears to be a viable alternative graft material for this procedure.

Novel pharmacological approaches in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a severe vascular disease and a major public health issue with an unmet medical need for therapy. This disease is featured by a progressive dilation of the abdominal aorta, boosted by atherosclerosis, ageing, and smoking as major risk factors. Aneurysm growth increases the risk of aortic rupture, a life-threatening emergency with high mortality rates. Despite the increasing progress in our knowledge about the etiopathology of AAA, an effective pharmacological treatment against this disorder remains elusive and surgical repair is still the unique available therapeutic approach for high-risk patients. Meanwhile, there is no medical alternative for patients with small aneurysms but close surveillance. Clinical trials assessing the efficacy of antihypertensive agents, statins, doxycycline, or anti-platelet drugs, among others, failed to demonstrate a clear benefit limiting AAA growth, while data from ongoing clinical trials addressing the benefit of metformin on aneurysm progression are eagerly awaited. Recent preclinical studies have postulated new therapeutic targets and pharmacological strategies paving the way for the implementation of future clinical studies exploring these novel therapeutic strategies. This review summarises some of the most relevant clinical and preclinical studies in search of new therapeutic approaches for AAA.

Phase transitions and topological defects in discotic liquid crystal droplets with planar anchoring: a Monte Carlo simulation study.

In this work we present the results of Monte Carlo (MC) simulations at the isothermal-isobaric ensemble for a discotic liquid crystal (DLC) droplet whose surface promotes edge-on (planar) anchoring. For a given pressure, we simulate an annealing process that enables observation of phase transitions within the spherical droplet. In particular, we report a first order isotropic-nematic transition as well as a nematic-columnar transition at the center of the droplet. We found the appearance of topological defects consisting of two disclination lines with ends at the surface of the sphere. We also observed that both transitions, isotropic-nematic and nematic-columnar, occur at lower temperatures as compared to the unconfined system.

A General Path-Integral Monte Carlo Method for Exact Simulations of Chemical Reaction Networks.

Chemical Reaction Networks (CRNs) are stochastic many-body systems used to model real-world chemical systems through a differential Master Equation (ME); analytical solutions to these equations are only known for the simplest systems. In this paper, we construct a path-integral inspirited framework for studying CRNs. Under this scheme, the time-evolution of a reaction network can be encoded in a Hamiltonian-like operator. This operator yields a probability distribution which can be sampled, using Monte Carlo Methods, to generate exact numerical simulations of a reaction network. We recover the grand probability function used in the Gillespie Algorithm as an approximation to our probability distribution, which motivates the addition of a leapfrog correction step. To assess the utility of our method in forecasting real-world phenomena, and to contrast it with the Gillespie Algorithm, we simulated a COVID-19 epidemiological model using parameters from the United States for the Original Strain and the Alpha, Delta and Omicron Variants. By comparing the results of these simulations with official data, we found that our model closely agrees with the measured population dynamics, and given the generality of this framework it can also be applied to study the spread dynamics of other contagious diseases.

Collective dynamics and self-motions in the van der Waals liquid tetrahydrofuran from meso- to inter-molecular scales disentangled by neutron spectroscopy with polarization analysis.

By using time-of-flight neutron spectroscopy with polarization analysis, we have separated coherent and incoherent contributions to the scattering of deuterated tetrahydrofuran in a wide scattering vector (Q)-range from meso- to inter-molecular length scales. The results are compared with those recently reported for water to address the influence of the nature of inter-molecular interactions (van der Waals vs hydrogen bond) on the dynamics. The phenomenology found is qualitatively similar in both systems. Both collective and self-scattering functions are satisfactorily described in terms of a convolution model that considers vibrations, diffusion, and a Q-independent mode. We observe a crossover in the structural relaxation from being dominated by the Q-independent mode at the mesoscale to being dominated by diffusion at inter-molecular length scales. The characteristic time of the Q-independent mode is the same for collective and self-motions and, contrary to water, faster and with a lower activation energy (≈1.4 Kcal/mol) than the structural relaxation time at inter-molecular length scales. This follows the macroscopic viscosity behavior. The collective diffusive time is well described by the de Gennes narrowing relation proposed for simple monoatomic liquids in a wide Q-range entering the intermediate length scales, in contraposition to the case of water.

CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes.

The mechanisms that control the inflammatory-immune response play a key role in tissue remodelling in cardiovascular diseases. T cell activation receptor CD69 binds to oxidized low-density lipoprotein (oxLDL), inducing the expression of anti-inflammatory NR4A nuclear receptors and modulating inflammation in atherosclerosis. To understand the downstream T cell responses triggered by the CD69-oxLDL binding, we incubated CD69-expressing Jurkat T cells with oxLDL. RNA sequencing revealed a differential gene expression profile dependent on the presence of CD69 and the degree of LDL oxidation. CD69-oxLDL binding induced the expression of NR4A receptors (NR4A1 and NR4A3), but also of PD-1. These results were confirmed using oxLDL and a monoclonal antibody against CD69 in CD69-expressing Jurkat and primary CD4 + lymphocytes. CD69-mediated induction of PD-1 and NR4A3 was dependent on NFAT activation. Silencing NR4A3 slightly increased PD-1 levels, suggesting a potential regulation of PD-1 by this receptor. Moreover, expression of PD-1, CD69 and NR4A3 was increased in human arteries with chronic inflammation compared to healthy controls, with a strong correlation between PD-1 and CD69 mRNA expression (r = 0.655 P < 0.0001). Moreover, PD-1 was expressed in areas enriched in CD3 infiltrating T cells. Our results underscore a novel mechanism of PD-1 induction independent of TCR signalling that might contribute to the role of CD69 in the modulation of inflammation and vascular remodelling in cardiovascular diseases.

PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets.

3',5'-cyclic adenosine monophosphate (cAMP) is a second messenger critically involved in the control of a myriad of processes with significant implications for vascular and cardiac cell function. The temporal and spatial compartmentalization of cAMP is governed by the activity of phosphodiesterases (PDEs), a superfamily of enzymes responsible for the hydrolysis of cyclic nucleotides. Through the fine-tuning of cAMP signaling, PDE4 enzymes could play an important role in cardiac hypertrophy and arrhythmogenesis, while it decisively influences vascular homeostasis through the control of vascular smooth muscle cell proliferation, migration, differentiation and contraction, as well as regulating endothelial permeability, angiogenesis, monocyte/macrophage activation and cardiomyocyte function. This review summarizes the current knowledge and recent advances in understanding the contribution of the PDE4 subfamily to cardiovascular function and underscores the intricate challenges associated with targeting PDE4 enzymes as a therapeutic strategy for the management of cardiovascular diseases.

Director Distortion and Phase Modulation in Deformable Nematic and Smectic Liquid Crystal Spheroids.

The growing interest in integrating liquid crystals (LCs) into flexible and miniaturized technologies brings about the need to understand the interplay between spatially curved geometry, surface anchoring, and the order associated with these materials. Here, we integrate experimental methods and computational simulations to explore the competition between surface-induced orientation and the effects of deformable curved boundaries in uniaxially and biaxially stretched nematic and smectic microdroplets. We find that the director field of the nematic LCs upon uniaxial strain reorients and forms a larger twisted defect ring to adjust to the new deformed geometry of the stretched droplet. Upon biaxial extension, the director field initially twists in the now oblate geometry and subsequently transitions into a uniform vertical orientation at high strains. In smectic microdroplets, on the other hand, LC alignment transforms from a radial smectic layering to a quasi-flat layering in a compromise between interfacial and dilatation forces. Upon removing the mechanical strain, the smectic LC recovers its initial radial configuration; however, the oblate geometry traps the nematic LC in the metastable vertical state. These findings offer a basis for the rational design of LC-based flexible devices, including wearable sensors, flexible displays, and smart windows.

Evaluating the effect of curcumin on the metacestode of Taenia crassiceps.

Curcumin, a curcuminoid present in the rhizome of the plant Curcuma longa has multiple pharmacological effects including anticarcinogenic and anti-inflammatory properties. This work evaluates the anthelmintic effect of the curcumin molecule (98% pure) on Taenia crassiceps cysticerci viability in vitro. Cysticerci incubated in the presence of increasing concentrations of curcumin showed a dose-dependent mortality correlated with a significant increase in the production of reactive oxygen species and a partial inhibition of thioredoxin-glutathione reductase, the only disulfide reductase present in these parasites. At 500 µM curcumin, a 100% of cysticerci lethality was obtained after 2 h of treatment. These results suggest the curcumin-induced oxidative stress could be in the origin of the anthelminthic effect of curcumin. Mice with cysticerci were injected intraperitoneally with 20, 40, or 60 mM curcumin daily for 30 days. A decrease in the burden of cysticerci (46%) was observed with a 60 mM dose of curcumin, supporting this compound as a potential anthelmintic drug.

Xerostomia, the perception of general and oral health and health risk behaviours in people over 65 years of age.

BACKGROUND: This study investigated the association between xerostomia and health risk behaviours, general and oral health and quality of life. METHODS: A cross-sectional study involving 800 adults over 65 years of age residing in Spain using a computer-assisted telephone questionnaire. The severity of xerostomia was assessed through the Xerostomia Inventory (XI). Both univariate and adjusted multinomial logistic regression were used to determine the risk (OR) of xerostomia. RESULTS: The sample comprised of 492 females (61.5%) and 308 males, with a mean age of 73.7 ± 5.8 years. Some, 30.7% had xerostomia: 25.6% mild, 4.8% moderate and 0.3% severe, the majority being female (34.8% vs 24%; p = 0.003). The mean XI was 24.6 ± 6.3 (95% CI 19.2-24.8) for those with poor health, whereas it was 17.4 ± 6.3 (95%CI 16.1-18.6) in those reporting very good health (p < 0.001). This difference was also observed in terms of oral health, with the XI mean recorded as 14.7 ± 10.7 for very poor oral health and 6.4 ± 5.4 for those with very good health (p = 0.002). Logistic regression showed that the highest OR for xerostomia was observed among adults with poor general health (2.81; 95%CI 1.8-4.3; p < 0.001) and for adjusted model the OR was still significant (2.18; 95%CI 1.4-3.4; p = 0.001). Those who needed help with household chores had 2.16 higher OR (95%CI 1.4-3.4; p = 0.001) and 1.69 (95%CI 1.1-2.7; p = 0.03) in the adjusted model. Females had a higher risk of suffering from xerostomia than males. CONCLUSION: The strong association between xerostomia and the general and oral health status of older adults justifies the need for early assessment and regular follow-up.

Vibrational Analysis of Hydration-Layer Water around Ubiquitin, Unpeeled Layer by Layer: Molecular-Dynamics Perceptions.

Classical molecular-dynamics simulations have been performed to examine the interplay between ubiquitin and its hydration-water sub-layers, chiefly from a vibrational-mode and IR viewpoint-where we analyse individual sub-layers characteristics. The vibrational Density of States (VDOS) revealed that the first solvation sub-shell indicates a confined character therein. For layers of increasing distance from the surface, the adoption of greater bulk-like spectral behaviour was evident, suggesting that vibrational harmonisation to bulk occurs within 6-7 Å of the surface.

NR4A3: A Key Nuclear Receptor in Vascular Biology, Cardiovascular Remodeling, and Beyond.

The mechanisms committed in the activation and response of vascular and inflammatory immune cells play a major role in tissue remodeling in cardiovascular diseases (CVDs) such as atherosclerosis, pulmonary arterial hypertension, and abdominal aortic aneurysm. Cardiovascular remodeling entails interrelated cellular processes (proliferation, survival/apoptosis, inflammation, extracellular matrix (ECM) synthesis/degradation, redox homeostasis, etc.) coordinately regulated by a reduced number of transcription factors. Nuclear receptors of the subfamily 4 group A (NR4A) have recently emerged as key master genes in multiple cellular processes and vital functions of different organs, and have been involved in a variety of high-incidence human pathologies including atherosclerosis and other CVDs. This paper reviews the major findings involving NR4A3 (Neuron-derived Orphan Receptor 1, NOR-1) in the cardiovascular remodeling operating in these diseases.

Oxidized Low-Density Lipoprotein Receptor in Lymphocytes Prevents Atherosclerosis and Predicts Subclinical Disease.

BACKGROUND: Although the role of Th17 and regulatory T cells in the progression of atherosclerosis has been highlighted in recent years, their molecular mediators remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/regulatory T cell immunity, and atherosclerosis development in animal models and in patients with subclinical disease. METHODS: Low-density lipoprotein receptor-deficient chimeric mice expressing or not expressing CD69 on either myeloid or lymphoid cells were subjected to a high fat diet. In vitro functional assays with human T cells were performed to decipher the mechanism of the observed phenotypes. Expression of CD69 and NR4A nuclear receptors was evaluated by reverse transcription-polymerase chain reaction in 305 male participants of the PESA study (Progression of Early Subclinical Atherosclerosis) with extensive (n=128) or focal (n=55) subclinical atherosclerosis and without disease (n=122). RESULTS: After a high fat diet, mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/regulatory T cell ratio in blood. Oxidized low-density lipoprotein was shown to bind specifically and functionally to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% CI, 0.40-0.94; P=0.006) after adjustment for traditional risk factors, the expression of NR4A1, the level of oxidized low-density lipoprotein, and the counts of different leucocyte subsets. CONCLUSIONS: CD69 depletion from the lymphoid compartment promotes a Th17/regulatory T cell imbalance and exacerbates the development of atherosclerosis. CD69 binding to oxidized low-density lipoprotein on T cells induces the expression of anti-inflammatory transcription factors. Data from a cohort of the PESA study with subclinical atherosclerosis indicate that CD69 expression in PBLs inversely correlates with the presence of disease. The expression of CD69 remained an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors.

Neuron-derived orphan receptor-1 modulates cardiac gene expression and exacerbates angiotensin II-induced cardiac hypertrophy.

Hypertensive cardiac hypertrophy (HCH) is a common cause of heart failure (HF), a major public health problem worldwide. However, the molecular bases of HCH have not been completely elucidated. Neuron-derived orphan receptor-1 (NOR-1) is a nuclear receptor whose role in cardiac remodelling is poorly understood. The aim of the present study was to generate a transgenic mouse over-expressing NOR-1 in the heart (TgNOR-1) and assess the impact of this gain-of-function on HCH. The CAG promoter-driven transgenesis led to viable animals that over-expressed NOR-1 in the heart, mainly in cardiomyocytes and also in cardiofibroblasts. Cardiomyocytes from TgNOR-1 exhibited an enhanced cell surface area and myosin heavy chain 7 (Myh7)/Myh6 expression ratio, and increased cell shortening elicited by electric field stimulation. TgNOR-1 cardiofibroblasts expressed higher levels of myofibroblast markers than wild-type (WT) cells (α 1 skeletal muscle actin (Acta1), transgelin (Sm22α)) and were more prone to synthesise collagen and migrate. TgNOR-1 mice experienced an age-associated remodelling of the left ventricle (LV). Angiotensin II (AngII) induced the cardiac expression of NOR-1, and NOR-1 transgenesis exacerbated AngII-induced cardiac hypertrophy and fibrosis. This effect was associated with the up-regulation of hypertrophic (brain natriuretic peptide (Bnp), Acta1 and Myh7) and fibrotic markers (collagen type I α 1 chain (Col1a1), Pai-1 and lysyl oxidase-like 2 (Loxl2)). NOR-1 transgenesis up-regulated two key genes involved in cardiac hypertrophy (Myh7, encoding for ß-myosin heavy chain (ß-MHC)) and fibrosis (Loxl2, encoding for the extracellular matrix (ECM) modifying enzyme, Loxl2). Interestigly, in transient transfection assays, NOR-1 drove the transcription of Myh7 and Loxl2 promoters. Our findings suggest that NOR-1 is involved in the transcriptional programme leading to HCH.

The role of mitochondrial oxidative stress in the metabolic alterations in diet-induced obesity in rats.

The impact of the mitochondria-targeted antioxidant MitoQ was evaluated in the metabolic alterations and the adipose tissue remodeling associated with obesity. Male Wistar rats were fed either a high-fat diet (HFD; 35% fat) or a standard diet (3.5% fat) for 7 wk and treated with MitoQ (200 µM). A proteomic analysis of visceral adipose tissue from patients with obesity and patients without obesity was performed. MitoQ partially prevented the increase in body weight, adiposity, homeostasis model assessment index, and adipose tissue remodeling in HFD rats. It also ameliorated protein level changes of factors involved in insulin signaling observed in adipose tissue of obese rats: reductions in adiponectin and glucose transporter 4 (GLUT 4) and increases in dipeptidylpeptidase 4, suppressor of cytokine signaling 3 (SOCS3), and insulin receptor substrate 1 phosphorylation. MitoQ prevented down-regulation of adiponectin and GLUT 4 and increases in SOCS3 levels in a TNF-α-induced insulin-resistant 3T3-L1 adipocyte model. MitoQ also ameliorated alterations in mitochondrial proteins observed in obese rats: increases in cyclophylin F and carnitine palmitoyl transferase 1A and reductions in mitofusin1, peroxiredoxin 4, and fumarate hydratase. The proteomic analysis of the visceral adipose tissue from patients with obesity show alterations in mitochondrial proteins similar to those observed in obese rats. Therefore, the data show the beneficial effect of MitoQ in the metabolic dysfunction induced by obesity.-Marín-Royo, G., Rodríguez, C., Le Pape, A., Jurado-López, R., Luaces, M., Antequera, A., Martínez-González, J., Souza-Neto, F. V., Nieto, M. L., Martínez-Martínez, E., Cachofeiro, V. The role of mitochondrial oxidative stress in the metabolic alterations in diet-induced obesity in rats.

Endothelial NOD1 directs myeloid cell recruitment in atherosclerosis through VCAM-1.

Atherosclerosis is a chronic disease characterized by vascular lipid retention and inflammation, and pattern recognition receptors (PRRs) are important contributors in early stages of the disease. Given the implication of the intracellular PRR nucleotide-binding oligomerization domain 1 (NOD1) in cardiovascular diseases, we investigated its contribution to early atherosclerosis. We evidenced NOD1 induction in atherosclerotic human and mouse tissues, predominantly in vascular endothelial cells. Accordingly, NOD1 genetic inactivation in Apoe-/- mice reduced not only atherosclerosis burden, but also monocyte and neutrophil accumulation in atheromata. Of note, in the presence of either peptidoglycan or oxidized LDLs, endothelial NOD1 triggered VCAM-1 up-regulation through the RIP2-NF-κB axis in an autocrine manner, enhancing firm adhesion of both sets of myeloid cells to the inflamed micro- and macrovasculature in vivo. Our data define a major proatherogenic role for endothelial NOD1 in early leukocyte recruitment to the athero-prone vasculature, thus introducing NOD1 as an innovative therapeutic target and potential prognostic molecule.-González-Ramos, S., Paz-García, M., Rius, C., del Monte-Monge, A., Rodríguez, C., Fernández-García, V., Andrés, V., Martínez-González, J., Lasunción, M. A., Martín-Sanz, P., Soehnlein, O., Boscá, L. Endothelial NOD1 directs myeloid cell recruitment in atherosclerosis through VCAM-1.

Mesoscale martensitic transformation in single crystals of topological defects.

Liquid-crystal blue phases (BPs) are highly ordered at two levels. Molecules exhibit orientational order at nanometer length scales, while chirality leads to ordered arrays of double-twisted cylinders over micrometer scales. Past studies of polycrystalline BPs were challenged by the existence of grain boundaries between randomly oriented crystalline nanodomains. Here, the nucleation of BPs is controlled with precision by relying on chemically nanopatterned surfaces, leading to macroscopic single-crystal BP specimens where the dynamics of mesocrystal formation can be directly observed. Theory and experiments show that transitions between two BPs having a different network structure proceed through local reorganization of the crystalline array, without diffusion of the double-twisted cylinders. In solid crystals, martensitic transformations between crystal structures involve the concerted motion of a few atoms, without diffusion. The transformation between BPs, where crystal features arise in the submicron regime, is found to be martensitic in nature when one considers the collective behavior of the double-twist cylinders. Single-crystal BPs are shown to offer fertile grounds for the study of directed crystal nucleation and the controlled growth of soft matter.

Evaluation of the maxillary midline, curve of the upper lip, smile line and tooth shape: a prospective study of 140 Caucasian patients.

BACKGROUND: A number of reference patterns such as the interincisal line, curve of the upper lip, width of the smile or shape of the teeth have been studied in different populations. Determining the frequency of different smile aesthetic parameters in a European Caucasian population and exploring possible gender differences is important in order to obtain predictable treatment outcomes. METHODS: Photographs were obtained under resting and forced smiling conditions in 140 individuals (70 males and 70 females) with a mean age of 20.1 ± 4.3 years. Different variables were recorded, including the position of the maxillary interincisal midline in relation to the facial midline, the arc and width of the smile, and the shape of the teeth. The data were processed using the SPSS version 15.0 statistical package, with application of the chi-squared test and a confidence level of 95%. The statistical power was 80%, and the level of significance 5% (α = 0.05). RESULTS: A total of 94.3% of the sample presented a maxillary interincisal midline coinciding with the facial midline, and 80% had a consonant smile line. The curve of the upper lip was upwards in 47.1% of the cases, followed by a straight curve in 41.4%. Most of the subjects (84.3%) presented a medium smile line with tooth exposure to the second premolar (61.4%). There were no significant differences between males and females. CONCLUSIONS: The integration of aesthetic criteria is needed in order to guarantee satisfactory and predictable dental treatment outcomes. There were no statistically significant differences between males and females. The maxillary interincisal midline coincided with the facial midline, with a consonant smile arc and a medium smile line, upward lip curve and oval tooth shape.

Enhanced endoplasmic reticulum and mitochondrial stress in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a degenerative vascular disease with a complex aetiology that remains to be fully elucidated. Clinical management of AAA is limited to surgical repair, while an effective pharmacotherapy is still awaited. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction have been involved in the pathogenesis of cardiovascular diseases (CVDs), although their contribution to AAA development is uncertain. Therefore, we aimed to determine their implication in AAA and investigated the profile of oxysterols in plasma, specifically 7-ketocholesterol (7-KC), as an ER stress inducer.In the present study, we determined aortic ER stress activation in a large cohort of AAA patients compared with healthy donors. Higher gene expression of activating transcription factor (ATF) 6 (ATF6), IRE-1, X-binding protein 1 (XBP-1), C/EBP-homologous protein (CHOP), CRELD2 and suppressor/enhancer of Lin-12-like (SEL1L) and greater protein levels of active ATF6, active XBP1 and of the pro-apoptotic protein CHOP were detected in human aneurysmatic samples. This was accompanied by an exacerbated apoptosis, higher reactive oxygen species (ROS) production and by a reduction in mitochondrial biogenesis in the vascular wall of AAA. The quantification of oxysterols, performed by liquid chromatography-(atmospheric pressure chemical ionization (APCI))-mass spectrometry, showed that levels of 7-KC were significantly higher while those of 7α-hydroxycholesterol (HC), 24-HC and 27-HC were lower in AAA patients compared with healthy donors. Interestingly, the levels of 7-KC correlate with the expression of ER stress markers.Our results evidence an induction of ER stress in the vascular wall of AAA patients associated with an increase in circulating 7-KC levels and a reduction in mitochondrial biogenesis suggesting their implication in the pathophysiology of this disease.