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1.
Nat Commun ; 10(1): 4955, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672989

RESUMO

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

2.
PLoS Negl Trop Dis ; 13(11): e0007859, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31751351

RESUMO

Host genetic factors have been suggested to play an important role in the susceptibility to Chagas disease. Given the influence of interleukin 18 (IL-18) in the development of the disease, in the present study, we analyzed three IL18 genetic variants (rs2043055, rs1946518, rs360719) regarding the predisposition to Trypanosoma cruzi infection and the development of chronic Chagas cardiomyopathy (CCC), in different Latin America populations. Genetic data of 3,608 patients from Colombia, Bolivia, Argentina, and Brazil were meta-analyzed to validate previous findings with increased statistical power. Seropositive and seronegative individuals were compared for T. cruzi infection susceptibility. In the Colombian cohort, the allelic frequencies of the three variants showed a significant association, with adjustment for sex and age, and also after applying multiple testing adjustments. Among the Colombian and Argentinean cohorts, rs360719 showed a significant genetic effect in a fixed-effects meta-analysis after a Bonferroni correction (OR: 0.76, CI: 0.66-0.89, P = 0.001). For CCC, the rs2043055 showed an association with protection from cardiomyopathy in the Colombian cohort (OR: 0.79, CI: 0.64-0.99, P = 0.037), with adjustment for sex and age, and after applying multiple testing adjustments. The meta-analysis of the CCC vs. asymptomatic patients from the four cohorts showed no evidence of association. In conclusion, our results validated the association found previously in the Colombian cohort suggesting that IL18 rs360719 plays an important role in the susceptibility to T. cruzi infection and no evidence of association was found between the IL18 genetic variants and CCC in the Latin American population studied.

3.
Hip Int ; : 1120700019884557, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746228

RESUMO

INTRODUCTION: The management of massive femoral bone defects following prosthetic infection remains a surgical challenge, particularly when the entire femur is affected. METHODS: We present the first results of a new biarticular cement spacer with antibiotic technique using a cephalomedullary nail for the treatment of infected hip arthroplasty involving complete femoral bone loss. RESULTS: 5 patients with a minimum follow-up of 1 year were included. In all cases 2-stage replacement due to hip periprosthetic infection was carried out, with the need for a biarticular complete femoral spacer in view of the magnitude of the bone defect. The infection was resolved in all patients, with no complications (spacer fracture or dislocation) associated to spacer use, and the patients were all able to maintain the sitting position with active knee movements between the 2 surgical stages. Improvement with respect to preoperative functional status was observed in all cases, as evidenced by the Harris Hip Score (HHS) (from 24.2 to 73; p < 0.001) and 12-Item Short-Form Health Survey (SF-12) (from 16.8 to 33.2; p = 0.001), with a lessened need for walking aids. DISCUSSION: The described technique offers a possible solution to a number of complications observed with the use of spacers in massive defects, affording greater patient comfort and autonomy while waiting to receive total femoral replacement.

5.
Food Res Int ; 126: 108721, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31732031

RESUMO

This study aimed to assess how packaging imagery used to convey that a natural yogurt is sweetened influences consumer expectations and willingness to buy. Four packages of sweetened natural yogurt were designed, in which the message that they were sweetened was conveyed through three different images (sugar cubes, a sack of sugar and a spoon of sugar) and through only text. The results of a pretest consisting of a word association task and a main experiment consisting of an online survey show that packages in which the message that the yogurt is sweetened is conveyed by using an image together with a textual claim instead of just a textual claim are expected to be sweeter. However, some differences can be appreciated depending on the specific image that is depicted (with the package showing an image of sugar cubes raising the higher sweetness expectations). Moreover, results show that Willingness to buy is positively associated with the attributes Natural Ingredients, Healthy and Quality, and in a slightly negative way with the attribute Sweet. Overall, these results suggest that although using packaging imagery to convey a message may enhance consumer expectations and willingness to buy, its effect on consumers' attitude towards the product may ultimately depend on the subject of the image that is depicted and in the valence of the message to be conveyed. These findings are discussed in the context of packaging design and consumer research, and directions for further research are provided. This study may help packaging designers and dairy companies to better communicate the desired message to consumers and to improve the marketing performance of their products.

6.
Ecotoxicol Environ Saf ; : 109917, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31776030

RESUMO

Pollinator populations are in decline worldwide. Multiple factors have been cited as potential causes to these declines. In honey bees, a combination of stressors is known to cause colony losses. Adequate nutrition is a key factor for honey bee growth and colony development. Several studies show that the nutritional quality of the diet is directly proportional to the ability of the bee to face challenges or stressors. We explored the effect of p-coumaric (600 µM) and indole-3-acetic acid (2, 20 or 200 µM) supplementation on the survival and activity of key detoxification enzymes of honey bees exposed to tau-fluvalinate. The dietary supplementation with p-coumaric and indole-3-acetic acids (20 µM) enhanced the survival of bees exposed to tau-fluvalinate (approximately 20%). We also showed that dietary p-coumaric acid increased the levels of cytochrome P450 and glutathione reductase activity in bees treated with tau-fluvalinate, as well as in the untreated controls, while glutathione-S-transferase activity was lower in treated bees than in untreated. In bees fed with indole-3-acetic acid, cytochrome P450 showed increased levels, however, glutathione-S-transferase showed the lowest activity. Moreover, the results showed that supplementation with p-coumaric and indole-3-acetic acids did not alter acetyl cholinesterase activity, nor did treatment with tau-fluvalinate. Altogether, the enzymatic changes related to the detoxification mechanisms observed in bees that were fed with p-coumaric and indole-3-acetic acids could be responsible for the increased survival of bees treated with tau-fluvalinate compared to those that received a control diet. The results presented in this study, together with previous studies, provide evidence of the importance of dietary phytochemicals in the response of honey bees to pesticide exposure. Moreover, these results are the first report of the beneficial effect of the phytohormone indole-3-acetic acid on the survival of honey bees treated with tau-fluvalinate.

7.
BMC Geriatr ; 19(1): 270, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615446

RESUMO

BACKGROUND: Physical activity and sedentary behaviour have been suggested to independently affect a number of health outcomes. To what extent different combinations of physical activity and sedentary behaviour may influence physical function and frailty outcomes in older adults is unknown. The aim of this study was to examine the combination of mutually exclusive categories of accelerometer-measured physical activity and sedentary time on physical function and frailty in older adults. METHODS: 771 older adults (54% women; 76.8 ± 4.9 years) from the Toledo Study for Healthy Aging participated in this cross-sectional study. Physical activity and sedentary time were measured by accelerometry. Physically active was defined as meeting current aerobic guidelines for older adults proposed by the World Health Organization. Low sedentary was defined as residing in the lowest quartile of the light physical activity-to-sedentary time ratio. Participants were then classified into one of four mutually exclusive movement patterns: (1) 'physically active & low sedentary', (2) 'physically active & high sedentary', (3) 'physically inactive & low sedentary', and (4) 'physically inactive & high sedentary'. The Short Physical Performance Battery was used to measure physical function and frailty was assessed using the Frailty Trait Scale. RESULTS: 'Physically active & low sedentary' and 'physically active & high sedentary' individuals had significantly higher levels of physical function (ß = 1.73 and ß = 1.30 respectively; all p < 0.001) and lower frailty (ß = - 13.96 and ß = - 8.71 respectively; all p < 0.001) compared to 'physically inactive & high sedentary' participants. Likewise, 'physically inactive & low sedentary' group had significantly lower frailty (ß = - 2.50; p = 0.05), but significance was not reached for physical function. CONCLUSIONS: We found a dose-response association of the different movement patterns analysed in this study with physical function and frailty. Meeting the physical activity guidelines was associated with the most beneficial physical function and frailty profiles in our sample. Among inactive people, more light intensity relative to sedentary time was associated with better frailty status. These results point out to the possibility of stepwise interventions (i.e. targeting less strenuous activities) to promote successful aging, particularly in inactive older adults.

8.
Korean J Intern Med ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31640337

RESUMO

Background/Aims: Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS. Methods: Eighty-eight genetic mutations associated with myeloid malignancy were sequenced in 73 MDS patients. The association between these mutations and AID was then analyzed. Results: The median age of the 73 MDS patients was 70 years (interquartile range, 56 to 75), and 49 (67.1%) were male. AID was observed in 16 of 73 patients (21.9%). Mutations were detected in 57 (78.1%) patients. The percentage (68.8% vs. 80.7%, p = 0.32) and the mean number of mutations (1.8 ± 1.6 vs. 2.2 ± 1.8, p = 0.34) in MDS patients with or without AID were similar. However, the ten-eleven translocation- 2 (TET2) mutation rate was significantly higher in patients with AID than in those without (31.3% vs. 5.3%, respectively; p = 0.001). All TET2 mutations were variants of strong clinical significance. Conclusions: Mutation of TET2 in patients with MDS may be associated with increased risk of developing AID.

9.
Br J Pharmacol ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31652355

RESUMO

BACKGROUND AND PURPOSE: Excessive GABAergic inhibition contributes to cognitive dysfunctions in Down syndrome (DS). Selective negative allosteric modulators (NAMs) of α5-containing GABAA receptors such as α5IA restore learning and memory deficits in Ts65Dn mice modelling DS. This study aimed at testing long-lasting effects of α5IA on in vivo long-term potentiation (LTP) and behavior in Ts65Dn mice. EXPERIMENTAL APPROACH: We performed in vivo long-term potentiation (LTP) recordings for six consecutive days in freely moving Ts65Dn mice and their wild-type littermates, treated with vehicle or α5IA. In parallel, Ts65Dn mice were subjected to various learning and memory tests (Y-maze, Morris water maze or the novel object recognition) up to seven days following one single injection of α5IA or vehicle. KEY RESULTS: We found that LTP could not be evoked in vivo in Ts65Dn mice at the hippocampal CA3-CA1 synapse. However, this deficit was sustainably reversed for at least six consecutive days following a single injection of α5IA. This long-lasting effect of α5IA was also unveiled when assessing working and long-term memory deficits in Ts65Dn mice. CONCLUSION AND IMPLICATIONS: We show for the first time in vivo LTP deficits in Ts65Dn mice. These deficits are restored for at least six days following acute treatment with α5IA and might be the substrate for the long-lasting pharmacological effects of α5IA demonstrated here on spatial working and long-term recognition and spatial memory tasks. Altogether, these results highlight the interest of NAMs of α5-containing GABAA receptors for treating cognitive deficits associated with DS.

10.
Acta Reumatol Port ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31575843

RESUMO

OBJECTIVE: The purpose of this study was to evaluate serum Endothelin-1(ET-1) levels in women Rheumatoid Arthritis (RA) patients compared with healthy controls, examine possible associations between ET-1 with different characteristic of the disease and investigate possible associations between ET-1 with surrogate markers of cardiovascular disease (CVD). METHODS: This cross-sectional study was performed in Vega-Baja Hospital, Orihuela (Spain) from November 2016 to May 2018. Sixty-three women with RA and sixty-five age and sex healthy controls were included in this study. Serum ET-1 was analyzed using ELISA. RESULTS: Serum levels of ET-1 in RA women patients were higher than those in healthy controls (p ˂0.001). Serum levels of ET-1 were positively associated with N-terminal pro-brain natriuretic peptide (NT-proBNP) (r = 0.27, p < 0.05) and with C-reactive protein (CRP) (r = 0.36, p < 0.05). ET-1 levels in women with RA were higher in smokers. Prednisone use was associated with lower ET-1 levels. No association with carotid intima media thickness was found. CONCLUSIONS: we observed the presence of higher levels of serum ET-1 in RA women patients compared with healthy controls. These increased levels of ET-1 are associated with inflammation and smoking and reduced by prednisone intake.

11.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(7): 443-458, ago.-sept. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182864

RESUMO

Objetivo: El tratamiento de la diabetes tipo 2 (DM2) es complejo y su propósito es reducir la morbimortalidad, por lo que su manejo tiene que incluir: un control glucémico individualizado precoz (mediante una adecuada educación diabetológica, modificaciones del estilo de vida y tratamiento farmacológico), el control de los factores de riesgo cardiovascular (CV), la detección y tratamiento precoz de las complicaciones y la evaluación de las comorbilidades asociadas. El objetivo fue elaborar un documento para unificar los aspectos necesarios para el abordaje integral de las personas con DM2. Participantes: Miembros del Grupo de trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición. Métodos: Se realizó una revisión de la evidencia disponible relativa a cada aspecto del manejo de la diabetes: objetivos de control glucémico, dieta y ejercicio, tratamiento farmacológico, tratamiento y control de factores de riesgo, detección de complicaciones y manejo del paciente frágil con DM2. Las recomendaciones se formularon según los grados de evidencia recogidos en los Standards of Medical Care in Diabetes 2018. Tras la formulación de las recomendaciones el documento fue consensuado por los miembros del Grupo de trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición. Conclusiones: El objetivo de este documento es proporcionar, desde el punto de vista del endocrinólogo clínico, unas recomendaciones prácticas basadas en la evidencia acerca de todos los aspectos necesarios para el abordaje integral de la DM2


Objective: Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. Participants: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology. Methods: The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. Conclusions: This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists


Assuntos
Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco , Sociedades Médicas/normas , Documentos , Índice Glicêmico , Estilo de Vida , Sociedades Médicas/organização & administração , Estratégias de eSaúde , Exercício/fisiologia
12.
Artigo em Espanhol | LILACS-Express | ID: biblio-1020666

RESUMO

RESUMEN: Objetivo: el objetivo de este estudio epidemiológico, fue determinar la prevalencia y severidad de caries dental, expresados en el índice de dientes definitivos con caries, obturados y perdidos (COPD), índice de dientes primarios con caries, extraídos y obturados (ceod) e Índice Significante de Caries (ISC) además establecer la necesidad de tratamiento restaurador y recursos humanos necesarios para ello, en una población escolar de 6 a 12 años de la Provincia de Santiago, Región Metropolitana. Metodología: Este estudio de corte transversal se realizó en 7 colegios entre públicos y privados que se encontraban debidamente registrados en la base de datos de la Secretaría Regional Ministerial de Educación pertenecientes a Provincia de Santiago, Región Metropolitana. Se seleccionó mediante un muestreo aleatorio estratificado por nivel socioeconómico, sexo y edad, una muestra de 1333 escolares de entre 6 a 12 años los cuales fueron evaluados previo asentimiento y con el consentimiento de sus tutores legales, por dos dentistas calibrados (Kappa 0.94). Para el diagnóstico de caries se utilizaron los criterios OMS. Los datos fueron recolectados en una ficha diseñada especialmente para ello y analizados utilizando el programa estadístico SPSS realizando pruebas no paramétricas de Kruskal-Wallis y U Mann-Whitney con un valor de significancia estadística del 95% (p<0,05). Resultados La prevalencia de caries encontrada en esta población, en dentición permanente fue de 24,5%, mientras que para dentición primaria 47,8%, los valores obtenidos del Índice COPD 0,48; ceod 1,67; ISC para COPD 1,45 y ISC para ceod 4,52. Las horas profesionales de odontólogos/as con sus respectivos/as asistentes, necesarias destinadas sólo a tratamiento restaurador para dar solución al daño encontrado en la muestra de estudio al momento del examen, corresponden a 167 horas para dentición permanente y 689 horas para dentición primaria. Conclusiones: La prevalencia y distribución de caries dental en escolares de 6 a 12 años de la Provincia de Santiago correspondió a cifras menores a las consignadas en el Diagnóstico de Salud Oral del Ministerio de Salud del año 2007, y menores a los índices propuestos por las organizaciones internacionales. Para resolver la necesidad de tratamiento restaurador en esta muestra se necesitarán 856 horas odontológicas.


ABSTRACT: Objective: The aim of the study was to determine prevalence and severity of dental caries, treatment needs and human resources required, in a school population aged 6 to 12 years in province of Santiago. Methodology: This cross-sectional study was conducted in seven schools. A stratified random sample was selected by socioeconomic level, sex and age. 1333 school children were evaluated by two calibrated dentists (Kappa 0.94). WHO criteria were used for caries diagnosis. Data were statistically analyzed by nonparametric tests of Kruskal-Wallis and U Mann-Whitney, statistical significance value of 95% (p <0.05). Results: 1333 patients fit the inclusion criteria. Caries prevalence was 24.5% for permanent teeth and 47.8% for primary teeth. DMFT index was 0.48, dmft index was 1.67. SiC was 1.45 for DMFT and 4.52 for dmft. A total of 167 and 689 hours of restorative treatment were required for permanent dentition and primary dentition, respectively. Conclusions: The prevalence and severity distribution of dental caries in school children aged 6 to 12 years in the Province of Santiago were lower than those recorded in the past, and lower than the rates proposed by the international organizations. To restore damaged founded in this sample 856 hours will be needed.

13.
Front Immunol ; 10: 1796, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428096

RESUMO

Vasculitides are a heterogeneous group of low frequent disorders, mainly characterized by the inflammation of blood vessels that narrows or occlude the lumen and limits the blood flow, leading eventually to significant tissue and organ damage. These disorders are classified depending on the size of the affected blood vessels in large, medium, and small vessel vasculitis. Currently, it is known that these syndromes show a complex etiology in which both environmental and genetic factors play a major role in their development. So far, these conditions are not curable and the therapeutic approaches are mainly symptomatic. Moreover, a percentage of the patients do not adequately respond to standard treatments. Over the last years, numerous genetic studies have been carried out to identify susceptibility loci and biological pathways involved in vasculitis pathogenesis as well as potential genetic predictors of treatment response. The ultimate goal of these studies is to identify new therapeutic targets and to improve the use of existing drugs to achieve more effective treatments. This review will focus on the main advances made in the field of genetics and pharmacogenetics of vasculitis and their potential application for ameliorating long-term outcomes in patient management and in the development of precision medicine.

14.
Ann Rheum Dis ; 78(11): 1505-1516, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31371305

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly targets joints. Monocytes and macrophages are critical in RA pathogenesis and contribute to inflammatory lesions. These extremely plastic cells respond to extracellular signals which cause epigenomic changes that define their pathogenic phenotype. Here, we interrogated how DNA methylation alterations in RA monocytes are determined by extracellular signals. METHODS: High-throughput DNA methylation analyses of patients with RA and controls and in vitro cytokine stimulation were used to investigate the underlying mechanisms behind DNA methylation alterations in RA as well as their relationship with clinical parameters, including RA disease activity. RESULTS: The DNA methylomes of peripheral blood monocytes displayed significant changes and increased variability in patients with RA with respect to healthy controls. Changes in the monocyte methylome correlate with DAS28, in which high-activity patients are divergent from healthy controls in contrast to remission patients whose methylome is virtually identical to healthy controls. Indeed, the notion of a changing monocyte methylome is supported after comparing the profiles of same individuals at different stages of activity. We show how these changes are mediated by an increase in disease activity-associated cytokines, such as tumour necrosis factor alpha and interferons, as they recapitulate the DNA methylation changes observed in patients in vitro. CONCLUSION: We demonstrate a direct link between RA disease activity and the monocyte methylome through the action of inflammation-associated cytokines. Finally, we have obtained a DNA methylation-based mathematical formula that predicts inflammation-mediated disease activity for RA and other chronic immune-mediated inflammatory diseases.

15.
J Bone Miner Res ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369697

RESUMO

In adults with X-linked hypophosphatemia (XLH), excess FGF23 impairs renal phosphate reabsorption and suppresses production of 1,25-dihydroxyvitamin D, resulting in chronic hypophosphatemia and persistent osteomalacia. Osteomalacia is associated with poor bone quality causing atraumatic fractures, pseudofractures, delayed fracture healing, and bone pain. Burosumab is a fully human monoclonal antibody against FGF23. UX023-CL304 is an ongoing, open-label, single-arm, phase 3 study investigating the efficacy of subcutaneous burosumab, 1.0 mg/kg administered every 4 weeks, in improving osteomalacia in adults with XLH who have not been treated for at least 2 years before enrollment. The primary endpoint was improvement in osteoid volume/bone volume assessed by transiliac bone biopsies obtained at baseline and week 48. Additional assessments included serum phosphorus, markers of bone turnover, fracture/pseudofracture healing, and safety. Fourteen subjects enrolled, 13 completed 48 weeks, and 11 completed paired biopsies. All osteomalacia-related histomorphometric measures improved significantly at week 48 (mean percent change: osteoid volume/bone volume, -54%, osteoid thickness, -32%, osteoid surface/bone surface, -26%, [median] mineralization lag time, -83%). Mean serum phosphorus concentration averaged across the mid-point of the dose cycle between weeks 0 and 24 was 3.3 mg/dL, a 50% increase from 2.2 mg/dL at baseline. Markers of bone formation and resorption increased at week 48 (least squares [LS] mean increase: P1NP, +77%; CTx, +36%; both p < 0.0001). All subjects had one or more treatment-emergent adverse event (AE). Most AEs were mild to moderate in severity. Two subjects experienced serious AEs (migraine; paresthesia) that were unrelated to treatment and resolved. Eleven subjects had 18 biopsy procedure-related AEs: 14 for pain, two for itch, and one each for headache and bandage irritation. No deaths or incidents of hyperphosphatemia occurred. In conclusion, by normalizing phosphate homeostasis, burosumab significantly improved osteomalacia in adults with XLH, which likely explains the improved fracture healing and amelioration of skeletal complications. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

16.
Inorg Chem ; 58(18): 12199-12208, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31469550

RESUMO

Two new heteroleptic complexes [Fe(1bppCOOH)(3bpp-bph)](ClO4)2·solv (1·solv, solv = various solvents; 1bppCOOH = 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid; 3bpp-bph = 2,6-bis(5-([1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)pyridine) and [Fe(1bppCOOH)(1bppCOOEt)](ClO4)2·0.5Me2CO (2·0.5Me2CO, 1bppCOOEt = ethyl 2,6-bis(1H-pyrazol-1-yl)isonicotinate) were designed and prepared. The heteroleptic compound 1·solv was obtained by the combination of stoichiometric amounts of Fe(ClO4)2, 1bppCOOH, and 3bpp-bph, and it was designed to fine-tune the spin crossover (SCO) properties with respect to the previously reported homoleptic compound [Fe(1bppCOOH)2](ClO4)2. Indeed, the introduction of a new substituted 3bpp ligand induces a weaker ligand field in addition to promoting the formation of π···π and C-H···π intermolecular interactions through the biphenyl groups. For the desolvated counterpart 1, this results in a shift of the SCO curve toward room temperature and the observation of a 13 K hysteresis width. Besides, compound 2·0.5Me2CO, which represents the first example of a heteroleptic complex containing two 1bpp tridentate ligands, stabilizes the LS state at room temperature confirming the same trend observed for the corresponding homoleptic compounds. Interestingly, both 1 and 2·0.5Me2CO heteroleptic complexes exhibit photoswitchable properties when irradiating with a 523 nm laser at 10 K. Preliminary characterization of the deposited complexes on native SiO2 by X-ray absorption measurements suggests oxidation and decomposition of the complexes.

17.
Surg Endosc ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399943

RESUMO

INTRODUCTION: There are few studies that investigate the usefulness of the preoperative intragastric balloon (IGB). This study will evaluate if pre-surgical weight loss with IGB reduces morbidity and mortality after surgery. METHOD: Prospective randomised study of patients with morbid obesity treated with gastric bypass or vertical gastrectomy, with two arms: the balloon arm (B-arm), where an IGB was inserted within the 6 months before surgery, and the control arm (C-arm). RESULTS: The study included 66 patients: 65.6% women, 69.6% with bypass. Age: 43 years (SD 10.2) B-arm and 42.6 years (SD 9.2) in the C-arm. We found 34.4% therapeutic failures in IGB. The mean body weight loss, %EWL and BMI reduction before surgery was 16.2 kg (SD 9.84) B-arm versus 4.7 (SD 8.70) in the C-arm, 23.6% versus 4.7% (p < 0.001) and 6.04 versus 1 (p < 0.001), respectively. The hospital stay was 7 days (p25-75: 5-8) B-arm and 7 days (p25-75: 5-9) in the C-arm (p = 0.937). Post-surgical morbidity with IGB was 25% versus 29.5% in the C-arm, p = 0.689. The number needed to treat (NNT) to prevent of post-surgical morbidity was 23 patients. The B-arm presented 54.5% moderate-severe post-surgical adverse events (12.5%) versus 82.6% in the C-arm (23.5%), p = 0.111. The cost of placing a balloon was more than 4000 Euros each. CONCLUSIONS: The preoperative balloon does not achieve a reduction in the post-surgical morbidity, nor does it reduce the hospital stay or rate of re-operations. The balloon achieves a higher weight loss result when compared to a diet programme, its added cost must also be given due consideration. TRAIL REGISTRY: This study has been registered on ClinicalTrials.gov with the Identifier: NCT01998243 (November 28, 2013).

18.
Curr Rheumatol Rep ; 21(9): 50, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414306

RESUMO

The original version of this article unfortunately contained a mistake. The legend of Fig. 1 was incorrect.

19.
Front Immunol ; 10: 1880, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440254

RESUMO

Mixed Connective Tissue Disease (MCTD) is a rare complex systemic autoimmune disease (SAD) characterized by the presence of increased levels of anti-U1 ribonucleoprotein autoantibodies and signs and symptoms that resemble other SADs such as systemic sclerosis (SSc), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Due to its low prevalence, this disease has been very poorly studied at the molecular level. We performed for the first time an epigenome-wide association study interrogating DNA methylation data obtained with the Infinium MethylationEPIC array from whole blood samples in 31 patients diagnosed with MCTD and 255 healthy subjects. We observed a pervasive hypomethylation involving 170 genes enriched for immune-related function such as those involved in type I interferon signaling pathways or in negative regulation of viral genome replication. We mostly identified epigenetic signals at genes previously implicated in other SADs, for example MX1, PARP9, DDX60, or IFI44L, for which we also observed that MCTD patients exhibit higher DNA methylation variability compared with controls, suggesting that these sites might be involved in plastic immune responses that are relevant to the disease. Through methylation quantitative trait locus (meQTL) analysis we identified widespread local genetic effects influencing DNA methylation variability at MCTD-associated sites. Interestingly, for IRF7, IFI44 genes, and the HLA region we have evidence that they could be exerting a genetic risk on MCTD mediated through DNA methylation changes. Comparison of MCTD-associated epigenome with patients diagnosed with SLE, or Sjögren's Syndrome, reveals a common interferon-related epigenetic signature, however we find substantial epigenetic differences when compared with patients diagnosed with rheumatoid arthritis and systemic sclerosis. Furthermore, we show that MCTD-associated CpGs are potential epigenetic biomarkers with high diagnostic value. Our study serves to reveal new genes and pathways involved in MCTD, to illustrate the important role of epigenetic modifications in MCTD pathology, in mediating the interaction between different genetic and environmental MCTD risk factors, and as potential biomarkers of SADs.

20.
Curr Rheumatol Rep ; 21(9): 44, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31304568

RESUMO

PURPOSE OF THE REVIEW: Nowadays, important advances have occurred in our understanding of the pathogenesis of systemic sclerosis (SSc), which is a rare immune-mediated inflammatory disease (IMID) characterized by vascular damage, immune imbalance, and fibrosis. Its etiology remains unknown; nevertheless, both environmental and genetic factors play a major role in the disease. This review will focus on the main advances made in the field of genetics of SSc. RECENT FINDINGS: The assessment of how interindividual genetic variability affects disease onset and progression has enhanced our knowledge of disease biology, and this will eventually translate in the development of new diagnostic and therapeutic tools, which is the final goal of personalized medicine. We will provide an overview of the most relevant achievements in the genetics of SSc, its shared genetics among IMIDs with special attention on drug repurposing, current challenges for the functional characterization of risk variants, and future directions.

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