Blood Pressure and Cognitive Decline Over 8 Years in Middle-Aged and Older Black and White Americans

Although the association between high blood pressure (BP), particularly in midlife, and late-life dementia is known, less is known about variations by race and sex. In a prospective national study of 22 164 blacks and whites ≥45 years without baseline cognitive impairment or stroke from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), enrolled 2003 to 2007 and followed through September 2015, we measured changes in cognition associated with baseline systolic and diastolic BP (SBP and DBP), as well as pulse pressure (PP) and mean arterial pressure, and we tested whether age, race, and sex modified the effects. Outcomes were global cognition (Six-Item Screener; primary outcome), new learning (Word List Learning), verbal memory (Word List Delayed Recall), and executive function (Animal Fluency Test). Median follow-up was 8.1 years. Significantly faster declines in global cognition were associated with higher SBP, lower DBP, and higher PP with increasing age ( P<0.001 for age×SBP×follow-up-time, age×DBP×follow-up-time, and age×PP×follow-up-time interaction). Declines in global cognition were not associated with mean arterial pressure after adjusting for PP. Blacks, compared with whites, had faster declines in global cognition associated with SBP ( P=0.02) and mean arterial pressure ( P=0.04). Men, compared with women, had faster declines in new learning associated with SBP ( P=0.04). BP was not associated with decline of verbal memory and executive function, after controlling for the effect of age on cognitive trajectories. Significantly faster declines in global cognition over 8 years were associated with higher SBP, lower DBP, and higher PP with increasing age. SBP-related cognitive declines were greater in blacks and men

Green fluorescent diamidines as diagnostic probes for trypanosomes

LED fluorescence microscopy offers potential benefits to the diagnosis of human African trypanosomiasis, as well as to other aspects of diseases management, such as detection of drug resistant strains. To advance such approaches reliable and specific fluorescent markers to stain parasites in human fluids are needed. Here we report a series of novel green fluorescent diamidines and their suitability as probes to stain trypanosomes

Zonisamide (CI-912) and Cognition: Results from Preliminary Study

Nine patients with refractory partial seizures were evaluated in a pilot study of a new anticonvulsant compound, zonisamide (l,2-benzisoxazole-3-methane-sulfonamide; CI-912). Cognitive functioning was evaluated prior to treatment with zonisamide and repeated after 12 and 24 weeks of treatment with zonisamide. At minimum steady-state plasma concentrations >30 jjug/ml, zonisamide appeared to affect specific cognitive functions such as acquisition and consolidation of new information. Previously learned material, such as vocabulary, and psychomotor performance were not affected. Verbal learning was affected, while visual-perceptual learning was unimpaired. These cognitive effects were observed in the absence of the usual clinical signs and symptoms of toxicity. A linear relationship was found between impairment of cognitive abilities and the minimum plasma concentration (r = -0.73; p < 0.05). Findings also suggest the development of tolerance to the adverse cognitive effects. RESUMEN En un estudio piloto realizado para valorar la eficacia de la zonisamida (1,2-Bencisoxazol-melanosulfonamida [CI-912]), un nuevo compuesto anticonvulsive se han evaluado unos 9 pa-cientes con ataques parciales refractarios al tratamiento. Se de-terminÓ la capacidad cognitiva anterior al tratamiento y se re-pitio 12 y 24 semanas despuÉs del tratamiento con zonisamida. Con concentraciones plasmÁticas mÍnimas estables per encima de 30 mcg/ml, la zonisamida afectÓ las funciones cognitives especÍficas tales como la adquisiciÓn y consolidaciÓn de nueva informaciÓn. El material aprendido previamente, tal como el vo-cabulario, y las funciones psicomotoras no se afectaron. El aprendizaje verbal se modificÓ mientras que el aprendizaje visuo-perfectivo no se modificÓ. Estos efectos cognitivos se ob-servaron en ausencia de los habituales signos y sÍntomas clÍnicos de toxicidad. Se encontrÓ una relaciÓn lineal entre la alteraciÓn de las posibilidades cognitivas y la concentraciÓn plasmÁtica mÍnima (r = -0.73, p < 0.05). Estos hallazgos tambiÉn sugieren el desarrollo de una tolerancia a los efectos cognitivos adversos. ZUSAMMENFASSUNG 9 Patienten mit rezidivierenden Partial-AnfÄllen wurden in einer Pilotstudie mit einer neuen antiepileptischen Substanz: Zonisamide untersucht. Die kognitiven Funktionen wurden vor der Behandlung mit Zonisamide geprtÜft und nach 12 und 24 Therapiewochen mit Zonisamide wiederholt. Bei einem Min-destplasmaspiegel von 30 mcg/ml schien Zonisamide spezifische kognitive FÄhigkeiten wie Aufnahme und Speicherung neuer In-formationen zu beeintrÄchtigen. Vorher gelernte Inhalte wie sprachliche und psychomotorische Fertigkeiten wurden nicht beeinflußt. Verbales Lernen war ebenfalls betroffen, wÄhrend visuell, perzeptives Lernen nicht verschlechtert war. Diese BeeintrÄchtigung kognitiver Funktionen wurde bei fehlenden klinischen Intoxikationszeichen beobachtet. Eine lineare Bezie-hung zwischen Verschlechterung kognitiver FÄhigkeiten und Mindest-Plasmaspiegel konnte hergestellt werden (r = -0,73; p < 0,05). Allerdings lassen die Ergebnisse auch auf eine GewÖhnung an diese unerwÜnschten Nebenwirkungen schließen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65995/1/j.1528-1157.1987.tb03624.x.pd

Effect of the solvent on the conformation of monocrotaline as determined by isotropic and anisotropic NMR parameters.

The conformation in solution of monocrotaline, a pyrrolizidine alkaloid presenting an eleven-membered macrocyclic diester ring, has been investigated using a combination of isotropic and anisotropic NMR parameters measured in four solvents of different polarity (D2 O, DMSO-d6 , CDCl3 , and C6 D6 ). Anisotropic NMR parameters were measured in different alignment media, based on their compatibility with the solvent of interest: cromoglycate liquid crystal solution was used for D2 O, while a PMMA polymer gel was chosen for CDCl3 and C6 D6 , and a poly-HEMA gel for DMSO-d6 . Whereas the pyrrolizidine ring shows an E6 exo-puckered conformation in all of the solvents, the macrocyclic eleven-membered ring adopts different populations of syn-parallel and anti-parallel relative orientation of the carbonyl groups according to the polarity of the solvent

Structural analysis and corrosion studies on an ISO 5832-9 biomedical alloy with TiO2 sol–gel layers

The aim of this study was to demonstrate the relationship between the structural and corrosion properties of an ISO 5832-9 biomedical alloy modified with titanium dioxide (TiO2) layers. These layers were obtained via the sol–gel method by acid-catalyzed hydrolysis of titanium isopropoxide in isopropanol solution. To obtain TiO2 layers with different structural properties, the coated samples were annealed at temperatures of 200, 300, 400, 450, 500, 600 and 800 C for 2 h. For all the prepared samples, accelerated corrosion measurements were performed in Tyrode’s physiological solution using electrochemical methods. The most important corrosion parameters were determined: corrosion potential, polarization resistance, corrosion rate, breakdown and repassivation potentials. Corrosion damage was analyzed using scanning electron microscopy. Structural analysis was carried out for selected TiO2 coatings annealed at 200, 400, 600 and 800 C. In addition, the morphology, chemical composition, crystallinity, thickness and density of the deposited TiO2 layers were determined using suitable electron and X-ray measurement methods. It was shown that the structure and character of interactions between substrate and deposited TiO2 layers depended on annealing temperature. All the obtained TiO2 coatings exhibit anticorrosion properties, but these properties are related to the crystalline structure and character of substrate–layer interaction. From the point of view of corrosion, the best TiO2 sol–gel coatings for stainless steel intended for biomedical applications seem to be those obtained at 400 C.This study was supported by Grant No. N N507 501339 of the National Science Centre. The authors wish to express their thanks to J. Borowski (MEDGAL, Poland) for the Rex 734 alloy

The Quantity Theory of Money is Valid. The New Keynesians are Wrong!

We test the quantity theory of money (QTM) using a novel approach and a large new sample. We do not follow the usual approach of first differentiating the logarithm of the Cambridge equation to obtain an equation relating the growth rate of real GDP, the growth rate of money and inflation. These variables must then again be ‘integrated’ by averaging in order to obtain stable relationships. Instead we suggest a much simpler procedure for testing directly the stability of the coefficient of the Cambridge equation. For 125 countries and post-war data we find the coefficient to be surprisingly stable. We do not select for high inflation episodes as was done in most empirical studies; inflation rates do not even appear in our data set. Much work supporting the QTM has been done by economic historians and at the University of Chicago by Milton Friedman and his associates. The QTM was a foundation stone of the monetarist revolution. Subsequently belief in it waned. The currently dominant New Keynesian School, implicitly or explicitly denies the validity of the QTM. We survey this history and argue that the QTM is valid and New Keynesians are wrong

Cupuassu byproduct in supplements for buffalo cows: milk yield and calf performance.

The aim of this study was to evaluate milk yield and calf performances of Murrah buffalo cows supplemented with rations containing cupuassu byproduct in substitution of ground corn

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development