Stereotactic Body Radiotherapy: is less fractionation more effective in adrenal and renal malignant lesions?

PURPOSE: Stereotactic body radiotherapy (SBRT) has become an excellent non-invasive alternative for many patients with primary renal cell carcinoma (RCC) and adrenal malignancies (AM). The aims of this study were to analyse how tumor-, patient- and treatment-related factors may influence the outcomes and side effects of SBRT and to assess its benefits as an alternative to surgery. METHODS: This retrospective, multicenter study included 25 lesions in 23 patients treated with SBRT using different devices (LINAC, CyberKnife® and Tomotherapy®). A multivariate linear regression was used for the statistical study. RESULTS: Local control time was higher than six months in more than 87% of patients and treatment response was complete for 73.68%. There was an overall 2-year survival of 40% and none of the deaths were secondary to renal or adrenal local progression. Patients treated with lower total radiation dose (mean [m] = 55 Gy) but less fractions with more dose per fraction (> 8.5 Gy) showed better outcome. Patients with previous chemotherapy and surgery treatments also showed higher complete response and disease-free survival (> 6 months). CONCLUSIONS: This study highlights the importance of ultra-hypofractionated regimens with higher doses per session. Thus, the referral of patients with RCC and AM to Radiotherapy and Oncology departments should be encouraged supporting the role of SBRT as a minimally invasive and outpatient treatment.

Feasibility and Acute Toxicity of Hypo-Fractionated Radiotherapy on 0.35T MR-LINAC: The First Prospective Study in Spain.

This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies.

Harmonic radiation contribution and X-ray transmission at the Small Quantum Systems instrument of European XFEL.

Transmission measurements of the soft X-ray beamline to the Small Quantum Systems (SQS) scientific instrument at the SASE3 undulator of European XFEL are presented. Measurements are reported for a wide range of photon energies (650 eV to 2400 eV), using X-ray gas monitors as well as a bolometric radiometer. The results are in good agreement with simulations for the beam transport and show a transmission of up to 80% over the whole photon energy range. The contribution of second- and third-harmonic radiation of the soft X-ray undulator is determined at selected photon energies by performing transmission measurements using a gas absorber to provide variable attenuation of the incoming photon flux. A comparison of the results with semi-analytic calculations for the generation of free-electron laser pulses in the SASE3 undulator reveals an influence of apertures along the beam transport on the exact harmonic content to be accounted for at the experiment. The second-harmonic content is measured to be in the range of 0.1% to 0.3%, while the third-harmonic contributed a few percent to the SASE3 emission. For experiments at the SQS instrument, these numbers can be reduced through specific selections of the mirror reflection angles.

Adenylate cyclase type 9 antagonizes cAMP accumulation and regulates endothelial signalling involved in atheroprotection.

AIMS: The adenylate cyclase type 9 (ADCY9) gene appears to determine atherosclerotic outcomes in patients treated with dalcetrapib. In mice, we recently demonstrated that Adcy9 inactivation potentiates endothelial function and inhibits atherogenesis. The objective of this study was to characterize the contribution of ADCY9 to the regulation of endothelial signalling pathways involved in atherosclerosis. METHODS AND RESULTS: We show that ADCY9 is expressed in the endothelium of mouse aorta and femoral arteries. We demonstrate that ADCY9 inactivation in cultured endothelial cells paradoxically increases cAMP accumulation in response to the adenylate cyclase activators forskolin and vasoactive intestinal peptide (VIP). Reciprocally, ADCY9 overexpression decreases cAMP production. Using mouse femoral artery arteriography, we show that Adcy9 inactivation potentiates VIP-induced endothelial-dependent vasodilation. Moreover, Adcy9 inactivation reduces mouse atheroma endothelial permeability in different vascular beds. ADCY9 overexpression reduces forskolin-induced phosphorylation of Ser157-vasodilator-stimulated phosphoprotein (VASP) and worsens thrombin-induced fall of RAP1 activity, both leading to increased endothelial permeability. ADCY9 inactivation in thrombin-stimulated human coronary artery endothelial cells results in cAMP accumulation, increases p-Ser157-VASP, and inhibits endothelial permeability. MLC2 phosphorylation and actin stress fibre increases in response to thrombin were reduced by ADCY9 inactivation, suggesting actin cytoskeleton regulation. Finally, using the Miles assay, we demonstrate that Adcy9 regulates thrombin-induced endothelial permeability in vivo in normal and atherosclerotic animals. CONCLUSION: Adcy9 is expressed in endothelial cells and regulates local cAMP and endothelial functions including permeability relevant to atherogenesis.

Long-Term Outcomes of Dose-Escalated Hypofractionated Radiotherapy in Localized Prostate Cancer.

This retrospective study aimed to provide some clinical outcomes regarding effectiveness, toxicity, and quality of life in PCa patients treated with dose-escalated moderately hypofractionated radiation therapy (HFRT). Patients received HFRT to a total dose of 66 Gy in 22 fractions (3 Gy/fraction) delivered via volume modulated arc therapy (VMAT) in 2011-2016. Treatment effectiveness was measured by the biochemical failure-free survival rate. Toxicity was assessed according to the criteria of the Radiation Therapy Oncology Group (RTOG) and quality of life according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC). In this regard, quality of life (QoL) was measured longitudinally, at a median of 2 and 5 years after RT. Enrolled patients had low-risk (40.2%), intermediate-risk (47.5%), and high-risk (12.3%) PCa. Median follow-up was 75 months. The biochemical failure-free survival rate was 94.2%. The incidence of acute grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicity was 9.84% and 28.69%, respectively. The incidence rate of late grade 2 or higher GI and GU toxicity was 1.64% and 4.10%, respectively. Expanded Prostate Cancer Index Composite (EPIC) scores showed that the majority of patients maintained their QoL. HFRT to 66 Gy with VMAT was associated with adequate biochemical control, low toxicity and good reported GU and GI quality of life.

Hábitos alimentarios y rendimiento académico en escolares chilenos de quinto a octavo año básico

RESUMEN Introducción: Los hábitos alimentarios en escolares se han relacionado con las habilidades cognitivas y el rendimiento académico. Objetivo: Determinar la relación entre hábitos alimentarios y rendimiento académico en escolares chilenos. Métodos: Estudio transversal en 733 escolares de quinto al octavo básico. Se evaluaron hábitos alimentarios mediante frecuencia de consumo de grupos de alimentos, tiempos de comida, habilidades culinarias y gusto por preparar alimentos. Estas variables se relacionaron con calificaciones de las asignaturas de matemática y lenguaje. Resultados: Los escolares presentaron baja proporción de frecuencia de consumo saludable (FCS). Las niñas presentaron mayor FCS de pan (p<0,001), los niños presentaron mayor FCS de lácteos (p= 0,016). Por sexo, se observó diferencia en el rendimiento académico en lenguaje (p= 0,013). La FCS de lácteos se asoció con diferencias del rendimiento académico en lenguaje (p= 0,017) y matemática (p= 0,035). Desayunar se asoció a diferencias en el rendimiento académico en matemática (p= 0,028) y lenguaje (p= 0,001). No consumir pasteles y masas dulces (p= 0,016), y papas fritas, completos y masas fritas (p= 0,025) se asoció al rendimiento académico en matemática. Un 29,1% tiene habilidades culinarias, siendo 54% niñas (p= 0,006). La presencia de habilidades culinarias se relacionó significativamente con 7 de los 12 grupos de alimentos analizados. Conclusión: Los hábitos alimentarios se asociaron con el rendimiento académico de escolares.

ABSTRACT Introduction: Eating habits in school-age children have been associated with cognitive skills and academic performance. Aim: To determine the relationship between eating habits and academic performance in Chilean school-age children. Methods: Cross-sectional study with 733 school-age children. Eating habits were assessed by the frequency of consumption of food groups, mealtimes, cooking skills and if they liked to cook. Grades of math and language subjects were reported. Results: There was a low proportion of healthy consumption frequency (HCF). Girls had a higher HCF of bread (p<0.001), boys had a higher HCF of dairy (p= 0.016). By sex, academic performance in language was different in girls (p= 0.013). HCF of dairy was associated with academic performance in language (p= 0.017) and mathematics (p= 0.035). Eating breakfast was associated with academic performance in mathematics (p= 0.028) and language (p= 0.001). Not consuming cakes and sweet doughs (p= 0.016), French fries, hot dogs and sopaipillas (p= 0.025) was associated with academic performance in mathematics. 29.1% of children had cooking skills, 54.0% being girls (p= 0.006). Having cooking skills was significantly associated with 7 of the 12 food groups analyzed. Conclusion: Eating habits are associated to the academic performance of Chilean school-age children.

COVID-19 pneumonia treated with ultra-low doses of radiotherapy (ULTRA-COVID study): a single institution report of two cases.

INTRODUCTION: Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, healthcare systems have focused their efforts into finding a treatment to avoid the fatal outcomes of severe acute respiratory syndrome due to coronavirus­2 (SARS-CoV-2). Benefits and risks of systemic treatments remain unclear, with multiple clinical trials still ongoing. Radiotherapy could play a role in reducing the inflammatory response in the lungs and relieve life-threatening symptoms. METHODS: We designed a prospective study of Ultra-Low Doses of Therapy with Radiation Applied to COVID-19 (ULTRA-COVID) for patients who suffer pneumonia, are not candidates for invasive mechanical ventilation and show no improvement with medical therapy. RESULTS: We present the preliminary results of two patients diagnosed with COVID-19 pneumonia treated with ULTRA-COVID. After one radiotherapy session, significant clinical response and a good radiological response was observed in both cases, resulting in both patients being discharged from hospital in less than 2 weeks after radiation treatment. CONCLUSION: Preliminary clinical and radiological results suggest a potential benefit of treating COVID-19 pneumonia with ULTRA-COVID. ClinicalTrials.gov Identifier: NCT04394182.

Spanish risk management framework across 17 radiation oncology centers during COVID-19 pandemic.

The COVID-19 pandemic has impacted our healthcare systems and the rapid introduction of new protocols that have been required to keep patients and workforce safe. In order to maintain activity with radiotherapy clinical assistance, we have implemented different measures in our centers from a patient and staff safety perspective.

Differential Effects of Long-Term Caloric Restriction and Dietary Protein Source on Bone and Marrow Fat of the Aging Rat.

Long-term caloric restriction (CR) has been shown to be beneficial to various tissues and organs. In contrast, CR exerts differential effects on bone, which could be due in part to the nature of the protein regime utilized. Male Sprague Dawley rats (8-month-old) were subjected for 12 months to 40% CR in macronutrients and compared with rats fed ad libitum for the same period. Casein- and soy-fed groups were compared. There was a significant decrease in bone quality in both CR groups, which was independent of the source of protein in the diet. In contrast, the group fed soy protein ad libitum showed better bone quality and higher levels of bone formation compared with casein-fed animals. Notably, bone marrow adipocytes were not mobilized upon CR as demonstrated by an absence of change in adipocyte number and tissue expression of leptin. This study demonstrates that the negative effect of CR on bone quality could not be prevented by the most common protein regimes.

Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer.

Colorectal cancer is one of the main causes of cancer death worldwide, and novel biomarkers are urgently needed for its early diagnosis and treatment. The utilization of metabolomics to identify and quantify metabolites in body fluids may allow the detection of changes in their concentrations that could serve as diagnostic markers for colorectal cancer and may also represent new therapeutic targets. Metabolomics generates a pathophysiological 'fingerprint' that is unique to each individual. The purpose of our study was to identify a differential metabolomic signature for metastatic colorectal cancer. Serum samples from 60 healthy controls and 65 patients with metastatic colorectal cancer were studied by liquid chromatography coupled to high-resolution mass spectrometry in an untargeted metabolomic approach. Multivariate analysis revealed a separation between patients with metastatic colorectal cancer and healthy controls, who significantly differed in serum concentrations of one endocannabinoid, two glycerophospholipids, and two sphingolipids. These findings demonstrate that metabolomics using liquid-chromatography coupled to high-resolution mass spectrometry offers a potent diagnostic tool for metastatic colorectal cancer.

Challenging the heterogeneity of disease presentation in malignant melanoma-impact on patient treatment.

There is an increasing global interest to support research areas that can assist in understanding disease and improving patient care. The National Cancer Institute (NIH) has identified precision medicine-based approaches as key research strategies to expedite advances in cancer research. The Cancer Moonshot program ( https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative ) is the largest cancer program of all time, and has been launched to accelerate cancer research that aims to increase the availability of therapies to more patients and, ultimately, to eradicate cancer. Mass spectrometry-based proteomics has been extensively used to study the molecular mechanisms of cancer, to define molecular subtypes of tumors, to map cancer-associated protein interaction networks and post-translational modifications, and to aid in the development of new therapeutics and new diagnostic and prognostic tests. To establish the basis for our melanoma studies, we have established the Southern Sweden Malignant Melanoma Biobank. Tissues collected over many years have been accurately characterized with respect to the tumor and patient information. The extreme variability displayed in the protein profiles and the detection of missense mutations has confirmed the complexity and heterogeneity of the disease. It is envisaged that the combined analysis of clinical, histological, and proteomic data will provide patients with a more personalized medical treatment. With respect to disease presentation, targeted treatment and medical mass spectrometry analysis and imaging, this overview report will outline and summarize the current achievements and status within malignant melanoma. We present data generated by our cancer research center in Lund, Sweden, where we have built extensive capabilities in biobanking, proteogenomics, and patient treatments over an extensive time period.

Endogenous expression mapping of malignant melanoma by mass spectrometry imaging.

BACKGROUND: Currently, only a limited number of molecular biomarkers for malignant melanoma exist. This is the case for both diagnosing the disease, staging, and efficiently measuring the response to therapy by tracing the progression of disease development and drug impact. There is a great need to identify novel landmarks of disease progression and alterations. METHODS: Matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI) has been developed within our group to study drug localisation within micro-environmental tissue compartments. Here, we expand further on this technology development and introduce for the first time melanoma tumour tissues to map metabolite localisation utilising high resolution mass spectrometry. MALDI-MSI can measure and localise the distribution pattern of a number of small molecule metabolites within tissue compartments of tumours isolated from melanoma patients. Data on direct measurements of metabolite identities attained at the local sites in tissue compartments has not been readily available as a measure of a clinical index for most cancer diseases. The current development on the mapping of endogenous molecular expression melanoma tumours by mass spectrometry imaging focuses on the establishment of a cancer tissue preparation process whereby a matrix crystal formation is homogenously built on the tissue surface, providing uniform molecular mapping. We apply this micro-preparation technology to disease presentation by mapping the molecular signatures from patient tumour sections. RESULTS: We have automated the process with a micro-technological dispensing platform. This provides the basis for thin film generation of the cancer patient tissues prior to imaging screening. Compartmentalisation of the tumour regions are displayed within the image analysis interfaced with histopathological grading and characterisation. CONCLUSIONS: This enables site localisation within the tumour with image mapping to disease target areas such as melanoma cells, macrophages, and lymphocytes.

ADCY9 (Adenylate Cyclase Type 9) Inactivation Protects From Atherosclerosis Only in the Absence of CETP (Cholesteryl Ester Transfer Protein).

BACKGROUND: Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the CETP (cholesteryl ester transfer protein) inhibitor dalcetrapib on cardiovascular events and atherosclerosis imaging. The underlying mechanisms responsible for the interactions between ADCY9 and CETP activity have not yet been determined. METHODS: Adcy9-inactivated ( Adcy9Gt/Gt) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETPtg Adcy9Gt/Gt and CETPtg Adcy9WT), were submitted to an atherogenic protocol (injection of an AAV8 [adeno-associated virus serotype 8] expressing a PCSK9 [proprotein convertase subtilisin/kexin type 9] gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, vasorelaxation, telemetry, and adipose tissue magnetic resonance imaging were evaluated. RESULTS: Adcy9Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P<0.01). CD68 (cluster of differentiation 68)-positive macrophage accumulation and proliferation in plaques were reduced in Adcy9Gt/Gt mice compared to WT animals ( P<0.05 for both). Femoral artery endothelial-dependent vasorelaxation was improved in Adcy9Gt/Gt mice (versus WT, P<0.01). Selective pharmacological blockade showed that the nitric oxide, cyclooxygenase, and endothelial-dependent hyperpolarization pathways were all responsible for the improvement of vasodilatation in Adcy9Gt/Gt ( P<0.01 for all). Aortic endothelium from Adcy9Gt/Gt mice allowed significantly less adhesion of splenocytes compared to WT ( P<0.05). Adcy9Gt/Gt mice gained more weight than WT with the atherogenic diet; this was associated with an increase in whole body adipose tissue volume ( P<0.01 for both). Feed efficiency was increased in Adcy9Gt/Gt compared to WT mice ( P<0.01), which was accompanied by prolonged cardiac RR interval ( P<0.05) and improved nocturnal heart rate variability ( P=0.0572). Adcy9 inactivation-induced effects on atherosclerosis, endothelial function, weight gain, adipose tissue volume, and feed efficiency were lost in CETPtg Adcy9Gt/Gt mice ( P>0.05 versus CETPtg Adcy9WT). CONCLUSIONS: Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, and improved endothelial function and autonomic tone.

Anomalous Origin of Right Coronary Artery From Left Coronary Sinus-13 Cases Treated With the Reimplantation Technique.

OBJECTIVES: Anomalous aortic origin of a coronary artery is uncommon but potentially clinically significant. Manifestations vary from asymptomatic patients to those who present with angina pectoris, myocardial infarction, heart failure, syncope, arrhythmias, and sudden death. We describe our experience with surgical reimplantation and results at midterm follow-up. METHODS: Between February 2003 and July 2016, a total of 13 patients with anomalous origin of the right coronary artery (RCA) from the left sinus underwent surgical reimplantation. RESULTS: Mean age was 39 years (range, 11-72 years). Eight patients presented with dyspnea and angina, two with acute myocardial infarction, and the remaining three were studied for atypical chest pain and ventricular premature contractions. Definitive diagnosis was achieved with coronary angiography in eight cases and with computed tomography scan in five. In all cases, the anomalous origin of the RCA from the left sinus had an intramural course except one case with interarterial (but not intramural) course. At operation, the RCA was dissected at the takeoff from the intramural course and reimplanted into the right sinus of Valsalva. There was no mortality. One patient had associated atherosclerotic coronary artery disease that required stent placement postoperatively. After a mean follow-up of 65 months (maximum 12 years), all patients are asymptomatic and have returned to exercise without limitations. CONCLUSIONS: The reimplantation technique provides a good physiological and anatomical repair, eliminates a slit-like ostium, avoids compression of the coronary artery between the aorta and the pulmonary artery, and gives similar results to the unroofing technique.

Myocardial Infarction-Associated SNP at 6p24 Interferes With MEF2 Binding and Associates With PHACTR1 Expression Levels in Human Coronary Arteries.

OBJECTIVE: Coronary artery disease (CAD), including myocardial infarction (MI), is the main cause of death in the world. Genome-wide association studies have identified dozens of single nucleotide polymorphisms (SNPs) associated with CAD/MI. One of the most robust CAD/MI genetic associations is with intronic SNPs in the gene PHACTR1 on chromosome 6p24. How these PHACTR1 SNPs influence CAD/MI risk, and whether PHACTR1 itself is the causal gene at the locus, is currently unknown. APPROACH AND RESULTS: Using genetic fine-mapping and DNA resequencing experiments, we prioritized an intronic SNP (rs9349379) in PHACTR1 as causal variant. We showed that this variant is an expression quantitative trait locus for PHACTR1 expression in human coronary arteries. Experiments in endothelial cell extracts confirmed that alleles at rs9349379 are differentially bound by the transcription factors myocyte enhancer factor-2. We engineered a deletion of this myocyte enhancer factor-2-binding site using CRISPR/Cas9 genome-editing methodology. Heterozygous endothelial cells carrying this deletion express 35% less PHACTR1. Finally, we found no evidence that PHACTR1 expression levels are induced when stimulating human endothelial cells with vascular endothelial growth factor, tumor necrosis factor-α, or shear stress. CONCLUSIONS: Our results establish a link between intronic SNPs in PHACTR1, myocyte enhancer factor-2 binding, and transcriptional functions at the locus, PHACTR1 expression levels in coronary arteries and CAD/MI risk. Because PHACTR1 SNPs are not associated with the traditional risk factors for CAD/MI (eg, blood lipids or pressure, diabetes mellitus), our results suggest that PHACTR1 may influence CAD/MI risk through as yet unknown mechanisms in the vascular endothelium.

Miocarditis aguda y meningoencefalitis por Trypanosoma cruzi en un paciente seropositivo al VIH / Acute miocarditis and meningoencephalitis caused by Trypanosoma cruzi in an HIV-seropositive patient

La enfermedad de Chagas, endémica en Argentina, transcurre en dos fases: aguda y crónica. En los pacientes seropositivos al VIH, el Trypanosoma cruzi afecta a aquellos con inmunodeficiencia severa, se localiza principalmente en el sistema nervioso central y menos frecuentemente en el miocardio. La distinción entre miocarditis aguda y reactivación de la infección crónica, no es sencilla. El bajo recuento de linfocitos T CD4+ es un factor predictivo positivo de reactivación. En los enfermos con inmunodeficiencia avanzada, los resultados negativos de las pruebas serológicas no excluyen el diagnóstico de enfermedad de Chagas, que se confirma por la aplicación de métodos directos en sangre o líquido cefalorraquídeo. Se presenta el caso de un paciente infectado por el VIH, adquirido por transmisión vertical, con inmunodeficiencia severa, miocarditis aguda y compromiso del SNC. La parasitemia y parasitorraquia positivas para T. cruzi, establecieron la asociación de estos síntomas con la enfermedad de Chagas(AU)

Chagas disease, endemic in Argentina, goes through two stages: acute and chronic. In VIH seropositive patients, Trypanosomacruzi affects those with severe immunodeficiency; it is mainly located in the central nervous system and less frequently in the myocardium. Distinction between acute myocarditis and chronic infection reactivation is not simple. Low T CD4+ lymphocyte count is a positive predictive factor of reactivation. In patients with advanced immunodeficiency, negative results of serological tests do not exclude diagnosis of Chagas disease which may bre confirmed through the application of direct methods in blood and cerebrospinal fluid. The case of a VIH infected patient who got the disease through vertical transmission with severe immunodeficiency, acute myocarditis and central nervous system damage. Positive parasitemia and parasitorrachya for T. cruzi established the association between these symptoms and Chagas disease(AU)

Calidad de Vida en Pacientes con Diagnóstico de Psoriasis: Servicio de Dermatología, Ciudad Hospitalaria "Enrique Tejera". Valencia, Venezuela 2011 / Life quality in patients with psoriasis diagnosis who attend to dermatology service ciudad hospitalaria "Enrique Tejera" february-april 2011

Las psoriasis es una enfermedad inflamatoria crónica de piel, caracterizada por placas eritemato-descamativas, únicas o múltiples, en ocasiones generan rechazo y segregación social. con el objetivo de conocer la calidad de vida en pacientes con reciente diagnóstico de psoriasis que acuden al Servicio de Dermatología, se realizó un estudio descriptivo de corte transversal dentro del paradigma cuantitativo. El muestreo probabilístico, tuvo tamaño de 104 pacientes. La recolecciónde datos se realizó mediante los cuestionarios: Índice dermatológico de calidad de vida, Graffar Méndez Castellanos. En los resultados predomino el sexo masculino 50,96% (53/ 104 casos) la edad promedio fue 35,70 años, estrato socioeconómico IV (42,17%), 37,5% (39 casos) .sostuvo que en Poco grado ha representado el tratamiento de su dermopatía un problema, seguido de aquellos pacientes que afirmaron en Nada tal tratamiento representa un problema y 36,54% demuestra la preocupación de los pacientes por su condición. Se sugiere estudiar la calidad de vida en estos pacientes en forma periódica a fin de objetivar el impacto de las terapias en la vida del paciente.

Psoriasis is a chronic and relapsing disease affecting patients in many ways especially their quality of life, using triggers, be affected in a health, social, labor, without leaving aside the psychological health of the patient the objetive was. To describe the life quality in patients presenting to Dermatology Service, CHET diagnosed with psoriasis. We performed a descriptive crosssectional non-experimental, with a sample consist of 104 patients diagnosed with psoriasis attending the consultation of psoriasis of the Dermatology Service, CHET Data collection is performed by the test Dermatology Life Quality Index, Graffar Mendez Castellanos. The main results observed the mean age of 35.70 years, largely male 50.96% (53/104 cases), prevailing socioeconomic stratum Graffar IV (42.17%), 37.5% (39 cases) held that in lesser degree has represented dermopathy treatment of a problem, followed by those patients whom reported such treatment in Nothing is a problem.

Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro.

Although increased bone marrow fat in age-related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two-chamber system to co-culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell-cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS-formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte-conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age-related changes in bone mass and can be prevented by the inhibition of FA synthase.

Shear stress regulates angiotensin type 1 receptor expression in endothelial cells.

RATIONALE: Shear stress (SS) has an established role in atherosclerotic plaque localization, but how it exerts its protective effect is not fully understood. OBJECTIVE: To test the hypothesis that SS may downregulate angiotensin type 1 receptors (AT(1)Rs). Angiotensin II has been shown to be proinflammatory and to promote atherosclerosis. METHODS AND RESULTS: Using immunohistochemistry, we found a pronounced expression of AT(1)R in the inner, atheroprone regions of the aortic arch of C57BL/6 and endothelial NO synthase-deficient (eNOS(-/-)) mice but not eNOS-overexpressing mice. In human umbilical vein endothelial cells (HUVECs), laminar SS (15 dyn/cm(2)) induced a biphasic decrease in AT(1)R protein expression characterized by a first reduction at 1 hour (31+/-4% of static control, P<0.01), partial recovery at 3 hours (65+/-9%), and a second more prolonged decline at 6, 12, and 24 hours (48+/-9%, 36+/-9%, 33+/-5%, respectively, P<0.05). One and 24 hours of SS significantly reduced fluorescent angiotensin binding compared to static HUVECs. Shear-induced downregulation of AT(1)R was abolished by treatment with protein kinase A and G inhibitors or N(G)-nitro-l-arginine methyl ester (L-NAME). Fittingly, stimulating static HUVECs with an NO donor decreased AT(1)R protein levels. RT-PCR revealed a significant (P<0.05) decrease of AT(1)R mRNA in HUVECs exposed to SS during 3 (6+/-2% of static control), 6 (4+/-1%), 12 (4+/-1%), and 24 hours (15+/-4%), suggesting a transcriptional downregulation of AT(1)R at length. Finally, angiotensin-induced vascular cell adhesion molecule was abated in HUVECs exposed to SS and in the outer aortic arch of mice. CONCLUSIONS: Our results demonstrate that SS may convey some of its atheroprotective effects through downregulation of AT(1)R in endothelial cells.

Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.

Age-related bone loss is associated with changes in bone cellularity, which include marrow fat infiltration and decreasing levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although nuclear lamina alterations occur in premature aging syndromes that include changes in body fat and severe osteoporosis, the role of proteins of the nuclear lamina in age-related bone loss remains unknown. Using the Zmpste24-null progeroid mice (Zmpste24(-/-)), which exhibit nuclear lamina defects and accumulate unprocessed prelamin A, we identified several alterations in bone cellularity in vivo. We found that defective prelamin A processing induced accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis. In summary, processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis.