Early automated cerebral edema assessment following endovascular therapy: impact on stroke outcome.

BACKGROUND: Cerebral edema (CED) is associated with poorer outcome in patients with acute ischemic stroke (AIS). The aim of the study was to investigate the factors contributing to greater early CED formation in patients with AIS who underwent endovascular therapy (EVT) and its association with functional outcome. METHODS: We conducted a multicenter cohort study of patients with an anterior circulation AIS undergoing EVT. The volume of cerebrospinal fluid (CSF) was extracted from baseline and 24-hour follow-up CT using an automated algorithm. The severity of CED was quantified by the percentage reduction in CSF volume between CT scans (∆CSF). The primary endpoint was a shift towards an unfavorable outcome, assessed by modified Rankin Scale (mRS) score at 3 months. Multivariable ordinal logistic regression analyses were performed. The ∆CSF threshold that predicted unfavorable outcome was selected using receiver operating characteristic curve analysis. RESULTS: We analyzed 201 patients (mean age 72.7 years, 47.8% women) in whom CED was assessable for 85.6%. Higher systolic blood pressure during EVT and failure to achieve modified Thrombolysis In Cerebral Infarction (mTICI) 3 were found to be independent predictors of greater CED. ∆CSF was independently associated with the probability of a one-point worsening in the mRS score (common odds ratio (cOR) 1.05, 95% CI 1.03 to 1.08) after adjusting for age, baseline mRS, National Institutes of Health Stroke Scale (NIHSS), and number of passes. Displacement of more than 25% of CSF was associated with an unfavorable outcome (OR 6.09, 95% CI 3.01 to 12.33) and mortality (OR 6.72, 95% CI 2.94 to 15.32). CONCLUSIONS: Early CED formation in patients undergoing EVT was affected by higher blood pressure and incomplete reperfusion. The extent of early CED, measured by automated ∆CSF, was associated with worse outcomes.

Comportamiento clínico, radiográfico e histomorfométrico del diente autólogo como biomaterial en elevación de seno maxilar de acceso lateral. Caso clínico con seis mese de seguimiento post-carga protésica / Clinical, radiographic and histomorphometric behaviour of the autologous tooth as a biomaterial in lateral access maxillary sinus elevation. Case report with six months of post-prosthetic loading follow-up

Introducción: la pérdida ósea tras las extracciones puede requerir en el maxilar posterior la realización de una elevación de seno para la correcta colocación de implantes. El hueso autólogo se considera el gold estándar, pero tiene una alta tasa de reabsorción y morbilidad, haciendo que haya otras alternativas como el diente autólogo, con buenos resultados en procedimientos regenerativos. Este caso clínico evalúa a nivel clínico, radiográfico e histomorfométrico el empleo del diente autólogo en elevación de seno maxilar y el comportamiento de dos implantes colocados de manera diferida. Caso clínico: se presenta el caso de una mujer de 48 años, que acudió a consulta para reponer el sector posterior derecho. Se realizó la exodoncia del 4.8 como diente donante para utilizarlo como biomaterial en una elevación de seno de acceso lateral, colocando dos implantes seis meses tras la intervención, y evaluándolos seis meses tras su carga protésica. Discusión: el diente autólogo en el presente caso clínico presentó un 30,56% de hueso neoformado tras seis meses de espera, con mejores resultados que al emplear aloinjertos y xenoinjertos. Además, diferentes aspectos culturales y étnicos respaldan la aceptación del diente autólogo por parte de los pacientes, aunque se necesitan más estudios a largo plazo para evaluar la estabilidad de este tipo de injerto en elevación de seno maxilar. Conclusiones: el diente autólogo en la elevación de seno ofrece biocompatibilidad, baja incidencia de complicaciones y buena aceptación por parte del paciente, con un buen comportamiento clínico y radiográfico de los implantes, a pesar del poco tiempo transcurrido en este caso tras la carga. (AU)

Introduction: Bone loss after extractions may require a sinus elevation to be performed in the posterior maxilla for the correct placement of implants. Autologous bone is considered the gold standard, but has a high rate of resorption and morbidity, leading to other alternatives such as autologous tooth, with good results in regenerative procedures. This case report evaluates at the clinical, radiographic and histomorphometric level the use of the autologous tooth in maxillary sinus elevation and the behaviour of two implants placed in a delayed manner. Case report: The case is presented of a 48-year-old woman who came for consultation to replace the right posterior sector. The extraction of 4.8 as a donor tooth was performed to use it as a biomaterial in a lateral access sinus elevation, placing two implants six months after the intervention, and evaluating them six months after their prosthetic loading. Discussion: The autologous tooth in this case report showed 30.56% of newly formed bone following a six-month wait, with better results than when allografts and xenografts were used. In addition, different cultural and ethnic aspects support the acceptance of the autologous tooth by patients. However, more longterm studies are needed to evaluate the stability of this type of graft in maxillary sinus elevation. Conclusions: The autologous tooth in the sinus elevation offers biocompatibility, low incidence of complications and good patient acceptance, with good clinical and radiographic behaviour of the implants, despite the short time elapsed in this case after loading.(AU)

Lysyl oxidase expression in smooth muscle cells determines the level of intima calcification in hypercholesterolemia-induced atherosclerosis. / La expresión de la lisil oxidasa en las células musculares lisas determina el nivel de calcificación de la íntima en la aterosclerosis inducida por hipercolesterolemia.

INTRODUCTION: Cardiovascular calcification is an important public health issue with an unmeet therapeutic need. We had previously shown that lysyl oxidase (LOX) activity critically influences vascular wall smooth muscle cells (VSMCs) and valvular interstitial cells (VICs) calcification by affecting extracellular matrix remodeling. We have delved into the participation of LOX in atherosclerosis and vascular calcification, as well as in the mineralization of the aortic valve. METHODS: Immunohistochemical and expression studies were carried out in human atherosclerotic lesions and experimental models, valves from patients with aortic stenosis, VICs, and in a genetically modified mouse model that overexpresses LOX in CMLV (TgLOXCMLV). Hyperlipemia and atherosclerosis was induced in mice through the administration of adeno-associated viruses encoding a PCSK9 mutated form (AAV-PCSK9D374Y) combined with an atherogenic diet. RESULTS: LOX expression is increased in the neointimal layer of atherosclerotic lesions from human coronary arteries and in VSMC-rich regions of atheromas developed both in the brachiocephalic artery of control (C57BL/6J) animals transduced with PCSK9D374Y and in the aortic root of ApoE-/- mice. In TgLOXCMLV mice, PCSK9D374Y transduction did not significantly alter the enhanced aortic expression of genes involved in matrix remodeling, inflammation, oxidative stress and osteoblastic differentiation. Likewise, LOX transgenesis did not alter the size or lipid content of atherosclerotic lesions in the aortic arch, brachiocephalic artery and aortic root, but exacerbated calcification. Among lysyl oxidase isoenzymes, LOX is the most expressed member of this family in highly calcified human valves, colocalizing with RUNX2 in VICs. The lower calcium deposition and decreased RUNX2 levels triggered by the overexpression of the nuclear receptor NOR-1 in VICs was associated with a reduction in LOX. CONCLUSIONS: Our results show that LOX expression is increased in atherosclerotic lesions, and that overexpression of this enzyme in VSMC does not affect the size of the atheroma or its lipid content, but it does affect its degree of calcification. Further, these data suggest that the decrease in calcification driven by NOR-1 in VICs would involve a reduction in LOX. These evidences support the interest of LOX as a therapeutic target in cardiovascular calcification.

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.

Upregulation of NOR-1 in calcified human vascular tissues: impact on osteogenic differentiation and calcification.

Cardiovascular calcification is a significant public health issue whose pathophysiology is not fully understood. NOR-1 regulates critical processes in cardiovascular remodeling, but its contribution to ectopic calcification is unknown. NOR-1 was overexpressed in human calcific aortic valves and calcified atherosclerotic lesions colocalizing with RUNX2, a factor essential for osteochondrogenic differentiation and calcification. NOR-1 and osteogenic markers were upregulated in calcifying human valvular interstitial cells (VICs) and human vascular smooth muscle cells (VSMCs). Gain- and loss-of-function approaches demonstrated that NOR-1 negatively modulates the expression of osteogenic genes relevant for the osteogenic transdifferentiation (RUNX2, IL-6, BMP2, and ALPL) and calcification of VICs. VSMCs from transgenic mice overexpressing NOR-1 in these cells (TgNOR-1VSMC) expressed lower basal levels of osteogenic genes (IL-6, BMP2, ALPL, OPN) than cells from WT littermates, and their upregulation by a high-phosphate osteogenic medium (OM) was completely prevented by NOR-1 transgenesis. Consistently, this was associated with a dramatic reduction in the calcification of both transgenic VSMCs and aortic rings from TgNOR-1VSMC mice exposed to OM. Atherosclerosis and calcification were induce in mice by the administration of AAV-PCSK9D374Y and a high-fat/high-cholesterol diet. Challenged-TgNOR-1VSMC mice exhibited decreased vascular expression of osteogenic markers, and both less atherosclerotic burden (assessed in whole aorta and lesion size in aortic arch and brachiocephalic artery) and less vascular calcification (assessed either by near-infrared fluorescence imaging or histological analysis) than WT mice. Our data indicate that NOR-1 negatively modulates the expression of genes critically involved in the osteogenic differentiation of VICs and VSMCs, thereby restraining ectopic cardiovascular calcification.

Rolipram impacts on redox homeostasis and cellular signaling in an experimental model of abdominal aortic aneurysm. / Impacto del tratamiento con rolipram sobre la homeostasis rédox y la señalización celular en un modelo experimental de aneurisma de aorta abdominal.

INTRODUCTION: Cyclic nucleotide phosphodiesterases (PDEs) of the PDE4 subfamily are responsible for the hydrolysis and subcellular compartmentalization of cAMP, a second messenger that modulates vascular functionality. We had shown that PDE4B is induced in abdominal aortic aneurysms (AAA) and that PDE4 inhibition by rolipram limits experimental aneurysms. In this study we have delved into the mechanisms underlying the beneficial effect of rolipram on AAA. METHODS: AAA were induced in ApoE-/- mice by angiotensin II (Ang II) infusion. Aneurysm formation was evaluated by ultrasonography. The expression of enzymes involved in rédox homeostasis was analyzed by real-time RT-PCR and the activation of signaling pathways by Western blot. RESULTS: Induction of PDE4B in human AAA has been confirmed in a second cohort of patients. In Ang II-infused ApoE-/- mice, rolipram increased the percentage of animals free of aneurysms without affecting the percentage of aortic ruptures. Quantitative analyses determined that this drug significantly attenuated aortic collagen deposition. Additionally, rolipram reduced the increased Nox2 expression triggered by Ang II, exacerbated Sod1 induction, and normalized Sod3 expression. Likewise, PDE4 inhibition decreased the activation of both ERK1/2 and the canonical Wnt pathway, while AKT activity was not altered. CONCLUSIONS: The inhibition of PDE4 activity modulates the expression of enzymes involved in rédox homeostasis and affects cell signaling pathways involved in the development of AAA.

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.

Retratamiento multidisciplinar de una agenesia de un incisivo lateral superior con un implante cerámico monobloque. A propósito de un caso clínico / Multidisciplinary re-treatment of an agenesis of an upper lateral incisor with an one-piece ceramic implant. A clinical report

Introducción: Los implantes dentales de circona son una buena opción terapéutica que surge como alternativa a los implantes dentales convencionales de titanio, dadas sus excelentes propiedades de biocompatibilidad, baja acumulación de placa bacteriana y escaso infiltrado inflamatorio. El objetivo del presente caso clínico es describir la colocación de un implante monobloque de circona para reponer un incisivo lateral superior izquierdo en un paciente de 34 años de edad, para la posterior realización de una corona implantosoportada monolítica de circona. Descripción del caso: Se presenta un paciente varón de 34 años de edad, no fumador y sin antecedentes médico-quirúrgicos de interés (ASA I), que acudió a la consulta demandando una mejora en la estética de su sonrisa. El paciente presentaba una agenesia congénita en el incisivo lateral superior izquierdo que había sido tratada previamente con ortodoncia para cerrar dicho espacio. Tras el examen intraoral del paciente y el estudio radiográfico, se plantea la opción de tratamiento de abrir nuevamente el espacio mediante ortodoncia para rehabilitar la ausencia con un implante de circona, asegurando la estética que demandaba el paciente. Conclusiones: La rehabilitación mediante implantes de circona para el tratamiento de agenesias congénitas en incisivos laterales superiores, es una opción válida y efectiva, obteniendo resultados óptimos a nivel estético y funcional. Sin embargo, se necesitan más estudios clínicos con tamaños muestrales suficientes que comparen implantes de titanio y cerámicos con el fin de tener datos más concluyentes. (AU)

Introduction: Zirconia dental implants are a good therapeutic option emerging as an alternative to conventional titanium dental implants, given their excellent properties of biocompatibility, low bacterial plaque accumulation and low inflammatory infiltrate. The aim of the present clinical case is to describe the placement of a zirconia implant to replace an upper left lateral incisor in a 34-year-old patient, for the subsequent restoration of a monolithic implant-supported zirconia crown. Case description: A clinical case of a 34-year-old man is presented, nonsmoker and with no previous registered medical records (ASA I) who came to the dental clinic demanding an improvement in the aesthetics of his smile. The patient had a congenital agenesis of the left lateral incisor that had previously been treated with orthodontics to close the space. After the radiographic study and intraoral examination of the patient, the treatment option of reopening the space with a new phase of corrective orthodontics to rehabilitate the absence with a zirconia implant was proposed, ensuring the aesthetics demanded by the patient. Conclusions: Restoration using zirconia implants for the treatment of congenital agenesis in upper lateral incisors is a valid and effective option, obtaining optimal aesthetic and functional results. However, more clinical studies with sufficient sample sizes comparing titanium and ceramic implants are needed in order to have more conclusive data. (AU)

Sinusitis originada por patologías o tratamientos dentales: revisión de la literatura / Sinusitis caused by dental treatment or pathology: a literature review

Introducción: la sinusitis odontogénica (SO) es una condición infradiagnosticada de la esfera otorrinolaringológica a pesar de su frecuencia que se estima entre 10 y el 40% de la rinosinusitis crónica. La SO representa hasta 75% de los casos de sinusitis maxilar unilateral y sigue pasando desapercibida en las guías más actuales de rinosinusitis, ocasionando una falta de consenso sobre los criterios diagnósticos y las pautas terapéuticas a observar. La dificultad en identificar el foco odontogénico en otorrinolaringología (ORL), y la de estimar la magnitud de la sinusitis en consultas de odontología, conduce frecuentemente a la persistencia de los síntomas y al fracaso de las terapias conducidas, impactando considerablemente en la calidad de vida de los pacientes. Por lo tanto, se elaboró esta revisión de la literatura para entender los desafíos que esta condición supone, a la luz de los estudios recientes en el tema. Métodos: se ha realizado una búsqueda exhaustiva de la literatura en Pubmed, Scopus y Google Scholar con términos relativos a las secciones y subsecciones de esta revisión. Resultados y conclusiones: el diagnóstico y el manejo de la SO plantean, por tanto, un desafío importante debido a la falta de protocolos estandarizados de diagnóstico y de procedimientos terapéuticos multidisciplinares consensuados. Se recomienda un enfoque interdisciplinar personalizado para lograr la resolución de la sintomatología y se precisan estudios bien diseñados, con estratificación según los causantes dentales y iatrogénicos, para generar una evidencia que respalde los futuros protocolos. (AU)

Introduction: Despite it being responsible for 10-40% of chronic rhinosinusitis cases, odontogenic sinusitis (OS) is an underdiagnosed otorhinolaryngological condition. OS represents up to 75% of cases of unilateral maxillary sinusitis and is still overlooked in most current rhinosinusitis guidelines. This leads to a lack of consensus on the diagnostic criteria and therapeutic guidelines to be observed. The difficulty in identifying the odontogenic focus in ENT consultations as well as estimating the magnitude of sinusitis in dental consultations frequently leads to the persistence of symptoms and the failure of the therapies undertaken, considerably impacting the quality of life of patients. This literature review was implemented to understand the challenges that this condition poses, in the light of recent studies on the subject. Methods: An exhaustive search of the literature in PubMed, Scopus and Google Scholar with terms related to the sections and subsections of this review. Results and conclusions: The diagnosis and management of OS therefore poses a significant challenge due to the lack of standardised diagnostic protocols and consensual multidisciplinary therapeutic procedures. A personalised interdisciplinary approach is recommended to achieve resolution of symptoms along with well-designed studies, stratified according to dental and iatrogenic causes, to provide evidence to support future protocols. (AU)

Retratamiento multidisciplinar de una agenesia de un incisivo lateral superior con un implante cerámico monobloque. A propósito de un caso clínico / Multidisciplinary re-treatment of an agenesis of an upper lateral incisor with an one-piece ceramic implant. A clinical report

Introducción: Los implantes dentales de circona son una buena opción terapéutica que surge como alternativa a los implantes dentales convencionales de titanio, dadas sus excelentes propiedades de biocompatibilidad, baja acumulación de placa bacteriana y escaso infiltrado inflamatorio. El objetivo del presente caso clínico es describir la colocación de un implante monobloque de circona para reponer un incisivo lateral superior izquierdo en un paciente de 34 años de edad, para la posterior realización de una corona implantosoportada monolítica de circona. Descripción del caso: Se presenta un paciente varón de 34 años de edad, no fumador y sin antecedentes médico-quirúrgicos de interés (ASA I), que acudió a la consulta demandando una mejora en la estética de su sonrisa. El paciente presentaba una agenesia congénita en el incisivo lateral superior izquierdo que había sido tratada previamente con ortodoncia para cerrar dicho espacio. Tras el examen intraoral del paciente y el estudio radiográfico, se plantea la opción de tratamiento de abrir nuevamente el espacio mediante ortodoncia para rehabilitar la ausencia con un implante de circona, asegurando la estética que demandaba el paciente. Conclusiones: La rehabilitación mediante implantes de circona para el tratamiento de agenesias congénitas en incisivos laterales superiores, es una opción válida y efectiva, obteniendo resultados óptimos a nivel estético y funcional. Sin embargo, se necesitan más estudios clínicos con tamaños muestrales suficientes que comparen implantes de titanio y cerámicos con el fin de tener datos más concluyentes. (AU)

Introduction: Zirconia dental implants are a good therapeutic option emerging as an alternative to conventional titanium dental implants, given their excellent properties of biocompatibility, low bacterial plaque accumulation and low inflammatory infiltrate. The aim of the present clinical case is to describe the placement of a zirconia implant to replace an upper left lateral incisor in a 34-year-old patient, for the subsequent restoration of a monolithic implant-supported zirconia crown. Case description: A clinical case of a 34-year-old man is presented, nonsmoker and with no previous registered medical records (ASA I) who came to the dental clinic demanding an improvement in the aesthetics of his smile. The patient had a congenital agenesis of the left lateral incisor that had previously been treated with orthodontics to close the space. After the radiographic study and intraoral examination of the patient, the treatment option of reopening the space with a new phase of corrective orthodontics to rehabilitate the absence with a zirconia implant was proposed, ensuring the aesthetics demanded by the patient. Conclusions: Restoration using zirconia implants for the treatment of congenital agenesis in upper lateral incisors is a valid and effective option, obtaining optimal aesthetic and functional results. However, more clinical studies with sufficient sample sizes comparing titanium and ceramic implants are needed in order to have more conclusive data. (AU)

Sinusitis originada por patologías o tratamientos dentales: revisión de la literatura / Sinusitis caused by dental treatment or pathology: a literature review

Introducción: la sinusitis odontogénica (SO) es una condición infradiagnosticada de la esfera otorrinolaringológica a pesar de su frecuencia que se estima entre 10 y el 40% de la rinosinusitis crónica. La SO representa hasta 75% de los casos de sinusitis maxilar unilateral y sigue pasando desapercibida en las guías más actuales de rinosinusitis, ocasionando una falta de consenso sobre los criterios diagnósticos y las pautas terapéuticas a observar. La dificultad en identificar el foco odontogénico en otorrinolaringología (ORL), y la de estimar la magnitud de la sinusitis en consultas de odontología, conduce frecuentemente a la persistencia de los síntomas y al fracaso de las terapias conducidas, impactando considerablemente en la calidad de vida de los pacientes. Por lo tanto, se elaboró esta revisión de la literatura para entender los desafíos que esta condición supone, a la luz de los estudios recientes en el tema. Métodos: se ha realizado una búsqueda exhaustiva de la literatura en Pubmed, Scopus y Google Scholar con términos relativos a las secciones y subsecciones de esta revisión. Resultados y conclusiones: el diagnóstico y el manejo de la SO plantean, por tanto, un desafío importante debido a la falta de protocolos estandarizados de diagnóstico y de procedimientos terapéuticos multidisciplinares consensuados. Se recomienda un enfoque interdisciplinar personalizado para lograr la resolución de la sintomatología y se precisan estudios bien diseñados, con estratificación según los causantes dentales y iatrogénicos, para generar una evidencia que respalde los futuros protocolos. (AU)

Introduction: Despite it being responsible for 10-40% of chronic rhinosinusitis cases, odontogenic sinusitis (OS) is an underdiagnosed otorhinolaryngological condition. OS represents up to 75% of cases of unilateral maxillary sinusitis and is still overlooked in most current rhinosinusitis guidelines. This leads to a lack of consensus on the diagnostic criteria and therapeutic guidelines to be observed. The difficulty in identifying the odontogenic focus in ENT consultations as well as estimating the magnitude of sinusitis in dental consultations frequently leads to the persistence of symptoms and the failure of the therapies undertaken, considerably impacting the quality of life of patients. This literature review was implemented to understand the challenges that this condition poses, in the light of recent studies on the subject. Methods: An exhaustive search of the literature in PubMed, Scopus and Google Scholar with terms related to the sections and subsections of this review. Results and conclusions: The diagnosis and management of OS therefore poses a significant challenge due to the lack of standardised diagnostic protocols and consensual multidisciplinary therapeutic procedures. A personalised interdisciplinary approach is recommended to achieve resolution of symptoms along with well-designed studies, stratified according to dental and iatrogenic causes, to provide evidence to support future protocols. (AU)

Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease.

Extracellular matrix (ECM) is an active player in cardiovascular calcification (CVC), a major public health issue with an unmet need for effective therapies. Lysyl oxidase (LOX) conditions ECM biomechanical properties; thus, we hypothesized that LOX might impact on mineral deposition in calcific aortic valve disease (CAVD) and atherosclerosis. LOX was upregulated in calcified valves from two cohorts of CAVD patients. Strong LOX immunostaining was detected surrounding calcified foci in calcified human valves and atherosclerotic lesions colocalizing with RUNX2 on valvular interstitial cells (VICs) or vascular smooth muscle cells (VSMCs). Both LOX secretion and organized collagen deposition were enhanced in calcifying VICs exposed to osteogenic media. ß-aminopropionitrile (BAPN), an inhibitor of LOX, attenuated collagen deposition and calcification. VICs seeded onto decellularized matrices from BAPN-treated VICs calcified less than cells cultured onto control scaffolds; instead, VICs exposed to conditioned media from cells over-expressing LOX or cultured onto LOX-crosslinked matrices calcified more. Atherosclerosis was induced in WT and transgenic mice that overexpress LOX in VSMC (TgLOXVSMC) by AAV-PCSK9D374Y injection and high-fat feeding. In atherosclerosis-challenged TgLOXVSMC mice both atherosclerosis burden and calcification assessed by near-infrared fluorescence (NIRF) imaging were higher than in WT mice. These animals also exhibited larger calcified areas in atherosclerotic lesions from aortic arches and brachiocephalic arteries. Moreover, LOX transgenesis exacerbated plaque inflammation, and increased VSMC cellularity, the rate of RUNX2-positive cells and both connective tissue content and collagen cross-linking. Our findings highlight the relevance of LOX in CVC and postulate this enzyme as a potential therapeutic target for CVC.

Photonic features of blue phase liquid crystals under curved confinement.

Blue phase (BP) liquid crystals represent a fascinating state of soft matter that showcases unique optical and electro-optical properties. Existing between chiral nematic and isotropic phases, BPs are characterized by a three-dimensional cubic lattice structure resulting in selective Bragg reflections of light and consequent vivid structural colors. However, the practical realization of these material systems is hampered by their narrow thermal stability and multi-domain crystalline nature. This feature article provides an overview of the efforts devoted to stabilizing these phases and creating monodomain structures. In particular, it delves into the complex relationship between geometrical confinement, induced curvature, and the structural stability and photonic features of BPs. Understanding the interaction of curved confinement and structural stability of BPs proves crucially important for the integration of these materials into flexible and miniaturized devices. By shedding light on these critical aspects, this feature review aims to highlight the significance of understanding the coupling effects of physical and mechanical forces on the structural stability of these systems, which can pave the way for the development of efficient and practical devices based on BP liquid crystals.

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.

Comportamiento del injerto autólogo de diente en preservación alveolar: evaluación clínica, radiográfica e histomorfométrica de un caso clínico tras un año de seguimiento / Behavior of the autologous tooth graft in alveolar preservation: clinical, radiographic and histomorphometric evaluation of a clinical case after one year of follow-up

Introducción: tras las extracciones, se producen una serie de cambios dimensio nales en sentido horizontal y vertical de la cresta alveolar, los cuales pueden ser minimizados mediante algunas técnicas quirúrgicas, como la preservación alveo lar, que utiliza diferentes sustitutos óseos, entre los que se encuentra actualmente el injerto autólogo de diente. Caso clínico: se presenta el caso clínico de una mujer de 61 años, que acudió a consulta presentando dolor intenso en la zona del segundo premolar superior de recho (1.5). Se realizó la exodoncia del 1.5, usándose como diente donante para realizar una preservación del alveolo tras la extracción. Cuatro meses tras el proce dimiento, se colocó un implante y se tomó una biopsia para realizar un análisis histo morfométrico. Un año tras la carga del im plante se observaron buenos resultados clínicos y radiográficos. Discusión: el diente y el tejido óseo tie nen similitudes en su composición quími ca, tanto en sus componentes inorgáni cos y orgánicos como en la cantidad de agua. En cuanto al contenido orgánico destacan los factores de crecimiento, la proteína morfogenética ósea 2 (BMP-2) y el colágeno tipo 1, dotando al diente como biomaterial de la propiedad de os teoinducción. El empleo del diente como sustituto en preservación alveolar consi gue porcentajes altos de hueso neofor mado, variando entre 37,55% cuando se usa el diente completo, al 48,40% usando dentina desmineralizada. Además de los buenos resultados histomorfométricos, goza de una buena aceptación por parte de los pacientes, fundamentalmente en determinadas ra zas o culturas, y consigue una reducción de las dimensio nes óseas evaluadas mediante escáner de haz cónico. Sin embargo, requiere un tiempo de preparación, que aumenta si el diente tiene restauraciones o tratamientos de conduc tos asociados (AU)

Introduction: following tooth extraction, horizontal and vertical resorption of bone volume occurs, but they can be reduced by many surgical procedures, such as alveolar ridge preservation, which uses different bone substitutes, being one of them autogenous tooth-graft. Clinical case: a 61-year-old woman is presented, who came to private dental clinic presenting intense pain in the area of an upper bicuspid of the first quadrant (1.5). Exodontia of the 1.5 was performed, using it as a donor tooth to obtain the biomaterial to preserve its alveolus. After 4 months re-entry was performed and an implant was placed, harvesting a bone biopsy for histomorphometric analysis. One year post-loading, good clinical and radiographic results were shown. Discussion: human bone and tooth have similarities in their chemical composition, both in their inorganic and organic components and in the amount of water. The organic content, growth factors, bone morphogenetic protein 2 (BMP-2) and type 1 collagen stand out, give the tooth the property of osteoinduction. The use of the tooth as a substitute in alveolar preservation achieves high percentages of neoformed bone, varying between 37.55% when the whole tooth is used, to 48.40% using demineralized dentin. In addition, it is well accepted by patients, especially in certain races or cultures, and achieves a reduction in bone dimensions evaluated by cone beam computed tomography. However, it has a drawback, requiring a long preparation time, which increases if the tooth has associated restorations or root canals. Conclusions: Autologous tooth-graft has a high biocompatibility, a low rate of intraoperative complications and good patient acceptance. It requires 25 minutes for preparation, which increases if there are restorations, root canals and caries. The percentage of vital bone obtained in the present clinical case shows new bone formation of 20% 4 months after alveolar ridge preservation (AU)

Targeting lysyl-oxidase (LOX) may facilitate intramural periarterial drainage for the treatment of Alzheimer's disease.

Alzheimer's disease is the commonest form of dementia. It is likely that a lack of clearance of amyloid beta (Aß) results in its accumulation in the parenchyma as Aß oligomers and insoluble plaques, and within the walls of blood vessels as cerebral amyloid angiopathy (CAA). The drainage of Aß along the basement membranes of blood vessels as intramural periarterial drainage (IPAD), could be improved if the driving force behind IPAD could be augmented, therefore reducing Aß accumulation. There are alterations in the composition of the vascular basement membrane in Alzheimer's disease. Lysyl oxidase (LOX) is an enzyme involved in the remodelling of the extracellular matrix and its expression and function is altered in various disease states. The expression of LOX is increased in Alzheimer's disease, but it is unclear whether this is a contributory factor in the impairment of IPAD in Alzheimer's disease. The pharmacological inhibition of LOX may be a strategy to improve IPAD and reduce the accumulation of Aß in the parenchyma and within the walls of blood vessels.

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.

Functional soft materials from blue phase liquid crystals.

Blue phase (BP) liquid crystals are chiral fluids wherein millions of molecules self-assemble into cubic lattices that are on the order of hundred nanometers. As the unit cell sizes of BPs are comparable to the wavelength of light, they exhibit selective Bragg reflections in the visible. The exploitation of the photonic properties of BPs for technological applications is made possible through photopolymerization, a process that renders mechanical robustness and thermal stability. We review here the preparation and characterization of stimuli-responsive, polymeric photonic crystals based on BPs. We highlight recent studies that demonstrate the promise that polymerized BP photonic crystals hold for colorimetric sensing and dynamic light control. We review using Landau-de Gennes simulations for predicting the self-assembly of BPs and the potential for using theory to guide experimental design. Finally, opportunities for using BPs to synthesize new soft materials, such as highly structured polymer meshes, are discussed.

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.