Redox reactions of an Mo (V) tetrasulfophthalocyanine

The preparation of an Mo(V) tetrasulfophthalocyanine and some of its thermal and photochemical reactions have been investigated in this work. Electrochemical processes have been followed by means of the UVVis spectral changes and compared with those observed in flash photolysis. Mo(IV) and Mo(V)-ligand-radical species are common intermediates of the electrochemical and photochemical reactions. In 254 nm irradiations of the Mo(V) tetrasulfophthalocyanine in aqueous solutions of 2-propanol, the macrocycle can be photohydrogenated and the product of the photolysis can be reoxidized with O2 back to the parent complex

Policondritis recurrente. Estudio de 19 casos en Colombia

Resumen Objetivo: Describir el comportamiento clínico y paraclínico de la PR en la población colombiana y comparar nuestros resultados con otras series publicadas. Materiales y métodos: Estudio descriptivo observacional de 19 casos de PR presentados en 4 centros de reumatología del país durante los últimos 10 años. Los pacientes cumplieron con el diagnóstico de PR de acuerdo al parámetro establecido. Se obtuvo la frecuencia de todas las manifestaciones de la enfermedad y se compararon los hallazgos con 9 series de pacientes con PR publicadas en la literatura entre 1966 y 2007. Resultados: La edad promedio fue 46 años. Se observó una relación por género de 4:1 a favor del sexo femenino. El seguimiento se realizó por 4 años en promedio. La primera manifestación de la enfermedad fue condritis auricular en el 89%, y fue la manifestación más frecuente al presentarse en la totalidad de los casos. Respecto otras series publicadas, se encontró una menor frecuencia de artritis (21%), compromiso ocular (10%) y dermatológico (10%). El compromiso renal (10%), neurológico (5%) y la asociación con otras enfermedades autoinmunes (50%) tuvieron la frecuencia esperada. No se observó compromiso cardiovascular en esta serie. El 100% de los pacientes recibieron corticoides. Adicionalmente el 57% recibieron terapia inmunosupresora asociada. La mortalidad fue del 10% por complicaciones asociadas a la PR. Conclusiones: En este estudio, a diferencia de otras series de origen caucásico y oriental, observamos una clara predominancia del género femenino, el compromiso extracartilaginoso es menos frecuente y la condritis auricular es nuestra manifestación inicial más importante. Estos hallazgos podrían ser el reflejo de diferencias genéticas, inmunológicas o ambientales. Palabras claves: Policondritis recurrente, condritis, vasculitis, corticoides. Abstract Objective: To describe clinical and paraclinical involvement in RP in a Colombian population and compare it with another series previously published. Methods and materials: Retrospective review of 19 cases of RP presented in 4 rheumatology centers in our country in the last 10 years. All patients met diagnostic criteria previously established. In every case, each clinical feature was analized and then compared with another 9 series of RP previously published between 1966 y 2007. Results: Mean age at diagnosis was 46 years. A female predominance was observed in a relation 4:1. Mean follow-up was 4 years. Auricular condritis was the initial clinical feature in 89% of patients and finally was observed in the 100% of our report. Compared with other series, we found less frequently arthritis (21%), ocular (10%) and dermatologic involvement (10%). Renal and neurologic involvement and the association between RP and another autoimmune disorder were found in the expected frequency. We not observed any cardiovascular involvement in our serie. All of the patients received corticosteroids and 57% had had another immunosuppressive medication. Observed mortality was 10% by complications associated to RP. Conclusions: In contrast with another series from Caucasian and Oriental population, we observed a marked predominance of female sex, a minor frequency of systemic involvement and auricular condritis is our most frequent initial clinical feature. Probably, these findings are the result of a different genetic, immunological and environmental background. Key words: Relapsing polychondritis, chondritis, vasculitis, corticosteroids

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Identification of candidate Parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets

Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objective To investigate what genes and genomic processes underlie the risk of sporadic PD. Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance. Conclusions and Relevance Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies

Photochemical and Photophysical Reactions of f ac -Rhenium(I) Tricarbonyl Complexes. Effects from Binucleating Spectator Ligands on Excited and Ground State Processes

Ground and excited state properties of the newly prepared complexes Re(CO)3(2,2¢-biquinoline) LS3(2,2¢-biquinoline) LSS +, LS ) pyrazine or 4,4¢-bipyridine, and Re(CO)3(2,2¢-bipy)(2-pyrazinecarboxylate) were investigated by steady state and time-resolved spectroscopy. The X-ray structure of the latter compound showed that the spectator ligand 2-pyrazinecarboxylate is coordinated through the carboxylate group to Re(I). A component of the complexes’ luminescence was associated with long-lived Re to ligand, 2,2¢-biquinoline or 2,2¢-bipy, charge transfer, while a fast component of the emission was associated with intraligand excited states. Quenching of the luminescence by CuCl2 involved energy transfer via dynamic and static mechanisms. The complexes in their excited states were reduced by 2,2¢,2¢¢-nitrilotriethanol with the formation of Re(I) ligand-radical species. Similar products were generated by the pulse radiolytic reduction of the complexes. The photochemical properties of the 2,2¢-biquinoline complexes and Re(CO)3(1,10-phen)4-nitrobenzoate are compared, and the mechanisms of their photochemical reactions are discussed., LS ) pyrazine or 4,4¢-bipyridine, and Re(CO)3(2,2¢-bipy)(2-pyrazinecarboxylate) were investigated by steady state and time-resolved spectroscopy. The X-ray structure of the latter compound showed that the spectator ligand 2-pyrazinecarboxylate is coordinated through the carboxylate group to Re(I). A component of the complexes’ luminescence was associated with long-lived Re to ligand, 2,2¢-biquinoline or 2,2¢-bipy, charge transfer, while a fast component of the emission was associated with intraligand excited states. Quenching of the luminescence by CuCl2 involved energy transfer via dynamic and static mechanisms. The complexes in their excited states were reduced by 2,2¢,2¢¢-nitrilotriethanol with the formation of Re(I) ligand-radical species. Similar products were generated by the pulse radiolytic reduction of the complexes. The photochemical properties of the 2,2¢-biquinoline complexes and Re(CO)3(1,10-phen)4-nitrobenzoate are compared, and the mechanisms of their photochemical reactions are discussed.¢-biquinoline or 2,2¢-bipy, charge transfer, while a fast component of the emission was associated with intraligand excited states. Quenching of the luminescence by CuCl2 involved energy transfer via dynamic and static mechanisms. The complexes in their excited states were reduced by 2,2¢,2¢¢-nitrilotriethanol with the formation of Re(I) ligand-radical species. Similar products were generated by the pulse radiolytic reduction of the complexes. The photochemical properties of the 2,2¢-biquinoline complexes and Re(CO)3(1,10-phen)4-nitrobenzoate are compared, and the mechanisms of their photochemical reactions are discussed.2 involved energy transfer via dynamic and static mechanisms. The complexes in their excited states were reduced by 2,2¢,2¢¢-nitrilotriethanol with the formation of Re(I) ligand-radical species. Similar products were generated by the pulse radiolytic reduction of the complexes. The photochemical properties of the 2,2¢-biquinoline complexes and Re(CO)3(1,10-phen)4-nitrobenzoate are compared, and the mechanisms of their photochemical reactions are discussed.¢,2¢¢-nitrilotriethanol with the formation of Re(I) ligand-radical species. Similar products were generated by the pulse radiolytic reduction of the complexes. The photochemical properties of the 2,2¢-biquinoline complexes and Re(CO)3(1,10-phen)4-nitrobenzoate are compared, and the mechanisms of their photochemical reactions are discussed.¢-biquinoline complexes and Re(CO)3(1,10-phen)4-nitrobenzoate are compared, and the mechanisms of their photochemical reactions are discussed.3(1,10-phen)4-nitrobenzoate are compared, and the mechanisms of their photochemical reactions are discussed.Fil: Guerrero, J.. Universidad de Santiago de Chile; ChileFil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Wolcan, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Feliz, Mario Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Ferraudi, G.. University of Notre Dame; Estados UnidosFil: Moya, S. A.. Universidad de Santiago de Chile; Chil

On the homogeneous catalysis of the photochemical and thermal O 2-degrading of lignin in aqueous solution. Mechanistic observations on the processes catalyzed by Al III(phthalocyaninetetrasulfonate) 3- and Co III dimethylglyoximate complexes

We have explored in this work the photo- and thermally-induced degradations of water soluble lignin in aqueous homogeneous media. Coordination complexes, Al(III) phthalocyaninetetrasulfonate ([Al III(tspc)] 3- and tspc 6- = phthalocyaninetetrasulfonate) and Co III/II dimethylglyoximate (dimethylglyoximate = DMG -) were used as catalysts of degrading processes with different mechanisms. The photodegradation was induced with visible light, λ exc ≥ 470 nm, and [Al III(tspc)] 3- as the photosensitizer of the ( 3Σ g -)O 2 to ( 1Δ g)O 2 conversion. ( 1Δ g)O 2 was the primary active species of the degrading process. [Co(DMG) 2(SO 3) 2] 3- and [Co(DMG) 2Cl 2] - in the presence and absence of SO 3 2- were used as catalysts of the thermal lignin degrading process. Differences in the mechanisms of the photo and thermally induced processes lead to some diversity of products. Adducts formed in solutions containing [Al III(tspc)] 3- and lignin have the absorption spectrum of phthalocyanine oligomers and could be located in pockets of the lignin. Under a steady state irradiation, the attack of lignin by ( 1Δ g)O 2 was followed by changes in the spectrum of the solution and by the formation of various products. The participation of O 2 ·- radicals in the mechanism photodegrading process was investigated with the pulse radiolysis technique. Different lignin radicals were produced when pulse radiolytically generated O 2 ·- and N 3 · radicals reacted with lignin. The Co III/II dimethylglyoximate catalyzed lignin degrading process was investigated in the presence and absence of SO 3 2-. Although the presence SO 3 2- in the medium is not essential, it accelerates the degrading process. This observation shows the participation of inorganic S(V) radicals, e.g., SO 3 ·-, as active species in the mechanism when SO 3 2- is present. Moreover, the pulse radiolysis experiments demonstrate that O 2 ·- can be an active species when SO 3 2- is absent.Fil: Ruiz, Gustavo Teodosio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Juliarena, María Paula. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Fisica Arroyo Seco; ArgentinaFil: Ferraudi, G. J.. University of Notre Dame; Estados UnidosFil: Lappin, A. G.. University of Notre Dame; Estados UnidosFil: Bogges,W.. University of Notre Dame; Estados UnidosFil: Feliz, Mario R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentin

Comportamiento de los factores de riesgo del cáncer de mama en mujeres adultas mayores

Se realizó un estudio retrospectivo, descriptivo y longitudinal en pacientes con carcinoma de mama, para caracterizar los factores de riesgo en pacientes femeninas mayores de 60 años diagnosticadas con cáncer de mama, en el policlínico Aquiles Espinosa del municipio de Las Tunas, Cuba; en el período de enero a diciembre de 2012. El universo fue de 149 pacientes y la muestra que se tomó fue de 83 pacientes adultas mayores. El grupo de edad más afectado fue el de 60 a 64 años para un 37,3%, la raza blanca fue la más representativa con un 36,2%, el antecedente familiar de cáncer de mama fue relevante en más de la mitad de las pacientes. El 62,7% de las pacientes no ofreció lactancia materna a sus hijos y el 61,4% de las adultas mayores tenía historia anterior de uno o dos partos. El consumo de café predominó con un 92,8%. La mayoría de las mujeres tienen conocimiento del autoexamen mamario, pero sólo el 35.9% lo practica