Fluorescence studies on new potential antitumoral benzothienopyran-1-ones in solution and in liposomes

Fluorescence properties of four new potential antitumoral compounds, 3-arylbenzothieno[2,3-c]pyran-1-ones, were studied in solution and in lipid membranes of dipalmitoyl phosphatidylcholine (DPPC), egg yolk phosphatidylcholine (Egg-PC) and dioctadecyldimethylammonium bromide (DODAB). The 3-(4-methoxyphenyl)benzothieno[2,3-c]pyran-1-one (1c) exhibits the higher fluorescence quantum yields in all solvents studied. All compounds present a solvent sensitive emission, with significant red shifts in polar solvents for the methoxylated compounds. The results point to an ICT character of the excited state, more pronounced for compound 1c. Fluorescence (steady-state) anisotropy measurements of the compounds incorporated in liposomes of DPPC, DODAB and Egg-PC indicate that all compounds have two different locations, one due to a deep penetration in the lipid membrane and another corresponding to a more hydrated environment. In general, the methoxylated compounds prefer hydrated environments inside the liposomes. The 3-(4- fluorophenyl)benzothieno[2,3-c]pyran-1-one (1a) clearly prefers a hydrated environment, with some molecules located at the outer part of the liposome interface. On the contrary, the preferential location of 3-(2-fluorophenyl)benzothieno[2,3-c]pyran-1-one (1b) is in the region of lipid hydrophobic tails. Compounds with a planar geometry (1a and 1c) have higher mobility in the lipid membranes when phase transition occurs.Portugal and FEDER (Fundo Europeu de Desenvolvimento Regional), for financial support through Centro de Física (CFUM) and Centro de Química (CQ-UM) of University of Minho and through the Project PTDC/QUI/81238/2006. M.S.D. Carvalho and R.C. Calhelha acknowledge FCT for their PhD grants SFRH/BD/47052/2008 and SFRH/BD/29274/2006, respectively.Fundação para a Ciência e a Tecnologia (FCT

New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and nanosized liposomes

Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide). Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05). The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, Ki = (8.7 ± 0.9) × 103 M-1 for compound 1 and Ki = (5.9 ± 0.6) × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%), while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Taller de Fotografía Periodística - PE66 - 202101

Description: Taking our present day as context, where images have become the most effective medium of communication, this course has been designed to introduce the student to photojournalism through a hands on approach. This course will give them a general vision of the work as a photojournalist and the options he/she has on the job market. Finalizing the course, the student will be able to work as an independent photojournalist or with different written media such as magazines, newspapers and news agencies. Purpose: This is a specialized course from the career path of Communications and Journalism. It is a theoretical course as well as a hands on course, geared to the students of the sixth semester who wish to develop the general Competences in the Management of Information and innovative thinking. NT: The Photojournalism Workshop has been designed so that the student, through constant hands on practice, will produce portraits, action shots and photo stories which will help her/him develop their capacity to inform and communicate through images an event of public interest in a media of mass communication. This workshops goal is to develop the General Competences of Information Management (level 2)and Innovative Thinking (level 2); and the faculty competence Policy Language (nivel3)

Taller de Fotografía Periodística - PE66 - 202102

Description: Taking our present day as context, where images have become the most effective medium of communication, this course has been designed to introduce the student to photojournalism through a hands on approach. This course will give them a general vision of the work as a photojournalist and the options he/she has on the job market. Finalizing the course, the student will be able to work as an independent photojournalist or with different written media such as magazines, newspapers and news agencies. Purpose: This is a specialized course from the career path of Communications and Journalism. It is a theoretical course as well as a hands on course, geared to the students of the sixth semester who wish to develop the general Competences in the Management of Information and innovative thinking. NT: The Photojournalism Workshop has been designed so that the student, through constant hands on practice, will produce portraits, action shots and photo stories which will help her/him develop their capacity to inform and communicate through images an event of public interest in a media of mass communication. This workshops goal is to develop the General Competences of Information Management (level 2)and Innovative Thinking (level 2); and the faculty competence Policy Language (nivel3)

Valor nutritivo de Nassella longiglumis y N. tenuissima bajo pastoreo bovino en un pastizal de planicie de La Pampa = Nutritive value of Nassella longiglumis and N. tenuissima under cattle grazing in a plain grassland of La Pampa

39° Congreso Argentino de Producción Animal, Tandil, 19 al 21 de Octubre de 2016El inadecuado manejo del pastoreo en el pastizal natural ha conducido muchas veces a su sobrepastoreo y posterior degradación. La magnitud de los cambios producidos en el valor nutritivo de las especies vegetales del pastizal a lo largo del año y la respuesta a altas presiones de pastoreo, podrían explicar ciertos cambios estructurales en los pastizales de planicie de la provincia de La Pampa. El objetivo de este trabajo fue evaluar el efecto del momento de ciclo de crecimiento y de la distancia a la aguada, sobre el valor nutritivo de dos gramíneas nativas presentes en el pastizal.EEA AnguilFil: Lentz, Betiana Celeste. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. INTA-AUDEAS-CONADEV; ArgentinaFil: Gambarte, M. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Rabotnikof, Celia Mónica. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Zapata, Ricardo Raul. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. INTA-AUDEAS-CONADEV; ArgentinaFil: Petruzzi, Horacio Javier. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Anguil; ArgentinaFil: Morici, Ernesto. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Gallace, Maria Eugenia. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. INTA-AUDEAS-CONADEV; ArgentinaFil: Sawczuk, Natalia. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Stritzler, Nestor Pedro. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Anguil; Argentin

Hybrid Treatment with Complete Transposition of Supra-Aortic Trunks versus Conventional Surgery for the Treatment of Aortic Arch Aneurysm

Abstract Objective: The disease of the aortic arch is traditionally approached by open surgical repair requiring cardiopulmonary bypass and circulatory arrest. This study performed a retrospective analysis comparing outcomes through primary hybrid patients submitted to aortic arch surgery without cardiopulmonary bypass with patients submitted to conventional open surgery. Methods: 25 patients submitted to the aortic arch surgery were selected in the period 2003-2012 at the Madre Teresa Hospital in the city of Belo Horizonte, Brazil; 13 of these underwent hybrid technique without cardiopulmonary bypass and 12 underwent conventional open surgery. Results: The mortality rate for the hybrid group was 23% and for the conventional surgery group was 17% (P=0.248). The postoperative complication rate was also similar in both groups, with no significant difference. Conclusion: Both techniques proved to be similar in mortality and morbidity. However, due to the small sample, more analytical studies with larger samples and long-term follow-up are needed to clarify this issue