Dyslipidemia in a Cohort of HIV-infected Latin American Children Receiving Highly Active Antiretroviral Therapy*

In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART.

Oral lesions in 166 patients with cutaneous psoriasis: A controlled study

Objectives. This study was aimed to test if the frequency of oral lesions bears statistical correlation or not with the condition of cutaneous psoriasis. Study design. Two groups were examined, one made up of 166 patients with skin psoriasis and the other with the same number of individuals with a negative history of skin diseases (control group), matched by age, race, and sex. Patients with psoriasis were grouped according to their having localized or generalized forms of the disease. The oral mucosa was thoroughly examined in both groups. Data were analyzed using chi-square test, Fisher`s test, the odds ratio (OR) with a 95% confidence interval (CI), and the Ryan-Holm step-down Bonferroni procedure. The overall significance was set at P <= 0.05. Results. The oral lesions significantly associated with psoriasis were fissured tongue (FT, OR=2.7; 95% CI: 1.3-5.6), and geographic tongue (GT, OR=5.0; 95% CI: 1.5-16.8). Other factors analyzed, such as topical and/or systemic medication for treatment of psoriasis versus nontreated patients, and localized versus generalized forms of psoriasis presented no statistical association with the frequency of FT or GT lesions (P > 0.05). Conclusions. Patients with psoriasis presented no specific oral lesion different from those seen in the control group. Although further investigation is warranted to establish whether or not either FT or GT can be characterized as an oral expression of psoriasis, the present investigation did find for both these types of lesions that the frequency of each bore a statistically significant relation with the presence of cutaneous psoriasis.

Thue's theorem and the diophantine equation x2 - Dy2 = ±N

A constructive version of a theorem of Thue is used to provide representations of certain integers as x(2) - Dy-2, where D = 2, 3, 5, 6, 7.

Carbene and nitrene rearrangements: A theoretical study of cyclic allenes and carbenes, carbodiimides, and azirines

B3LYP/6-31G(d) calculations of structures, energies, and infrared spectra of several rearrangement products of (hetero)aromatic nitrenes and carbenes are reported. 3-Isoquinolylnitrene 36 ring closes to the azirine 37 prior to ring expansion to the potentially stable but unobserved seven-membered-ring carbodiimide 38 and diazacycloheptatrienylidene C-s-39S. A new, stable cycloheptatrienylidene, C-s-19S, is located on the naphthylcarbene energy surface. 4-Quinolylnitrene undergoes reaction via the azirine 50 in solution, but ring expansion to the stable seven-membered-ring ketenimine 47 under Ar matrix photolysis conditions. There is excellent agreement between calculated infrared spectra of 1,5-diazacyclohepta-1,2,4,6-tetraene 54 (obtained by photolysis of 4-pyridyl azide), 1-azacyclohepta-1,2,4,6-tetraene 5, 1-azacyclohepta-1,3,5,6-tetraene 55, and 1-azacyclohepta-1,3,4,6-tetraene 56 and the available experimental data.

Development of a fully quantitative approach to the interpretation of stress echocardiography using radial and longitudinal myocardial velocities

Background: Tissue Doppler may be used to quantify regional left ventricular function but is limited by segmental variation of longitudinal velocity from base to apex and free to septal walls. We sought to overcome this by developing a composite of longitudinal and radial velocities. Methods and Results. We examined 82 unselected patients undergoing a standard dobutamine echocardiogram. Longitudinal velocity was obtained in the basal and mid segments of each wall using tissue Doppler in the apical views. Radial velocities were derived in the same segments using an automated border detection system and centerline method with regional chords grouped according to segment location and temporally averaged. In 25 patients at low probability of coronary disease, the pattern of regional variation in longitudinal velocity (higher in the septum) was the opposite of radial velocity (higher in the free wall) and the combination was homogenous. In 57 patients undergoing angiography, velocity in abnormal segments was less than normal segments using longitudinal (6.0 +/- 3.6 vs 9.0 +/- 2.2 cm/s, P = .01) and radial velocity (6.0 +/- 4.0 vs 8.0 +/- 3.9 cm/s, P = .02). However, the composite velocity permitted better separation of abnormal and normal segments (13.3 +/- 5.6 vs 17.5 +/- 4.2 cm/s, P = .001). There was no significant difference between the accuracy of this quantitative approach and expert visual wall motion analysis (81% vs 84%, P = .56). Conclusion: Regional variation of uni-dimensional myocardial velocities necessitates site-specific normal ranges, probably because of different fiber directions. Combined analysis of longitudinal and radial velocities allows the derivation of a composite velocity, which is homogenous in all segments and may allow better separation of normal and abnormal myocardium.

Efeito de sistemas de manejo do solo e velocidade de semeadura no desenvolvimento do sorgo forrageiro

O sorgo forrageiro é uma gramínea indicada para cultivo em ambientes secos e quentes, nos quais a produtividade de outras forrageiras pode ser antieconômica. Objetivou-se, com este trabalho, estudar diferentes sistemas de manejo e diferentes velocidades de semeadura, no desenvolvimento do sorgo forrageiro cv. BRS 610. O solo da área experimental foi um Nitossolo Vermelho distroférrico. O experimento foi instalado em condições de campo, na FCA/UNESP, Campus de Botucatu-SP, utilizando-se o delineamento em blocos ao acaso, em esquema de parcela subdividida, com dezesseis tratamentos (quatro sistemas de manejo e quatro velocidades de semeadura). Os sistemas de manejo utilizados foram: semeadura direta; gradagem pesada; gradagem pesada + duas gradagens leves e escarificação. As velocidades na operação de semeadura utilizadas foram: 3, 5, 6 e 9 km h-1. Foram analisadas as seguintes variáveis: população de plantas, altura de plantas, diâmetro do colmo, massa de mil grãos e produtividades de massa verde e de massa seca. O sistema de semeadura direta foi o que proporcionou maior população de plantas, maior diâmetro do colmo e maior produção de massas verde e seca. Com o aumento da velocidade na operação de semeadura, houve redução da população de plantas e aumento do diâmetro do colmo. A velocidade de 5 km h-1 foi a que proporcionou maior produção de massas verde e seca (kg ha-1), seguida da velocidade de 3 km h-1.

Serotyping and evaluation of the virulence in mice of Streptococcus suis strains isolated from diseased pigs

A total of 110 strains of Streptococcus suis, isolated from diseased pigs in Brazil were serotyped and analyzed for virulence. Serotyping of the strains resulted in the following classification: 42 strains of serotype 2 (38.2%), 10 strains of serotype 14 (9.1%), seven strains of serotype 9 (6.4%), three strains each of serotype 7 and 11 (2.7%), two strains each of serotype 1 and 8 (1.8%) and one strain each of serotypes ½, 3, 5, 6 and 10 (0.9%). Cross reactions among serotypes 1, 14 and 7 were observed in 21 strains (19.1%). Only 41.9% of the strains were lethal for mice using the pathogenicity test.

Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a marked decline in cognition and memory function. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, including those produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (Aß) pathology in AD. Therefore, understanding the response at the brain barriers may unravel novel pathways of relevance for the pathophysiology of AD. Herein, we focused on the study of the choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, in aging and in AD. Specifically, we used the PDGFB-APPSwInd (J20) transgenic mouse model of AD, which presents early memory decline and progressive Aß accumulation, and littermate age-matched wild-type (WT) mice, to characterize the CP transcriptome at 3, 5-6 and 11-12months of age. The most striking observation was that the CP of J20 mice displayed an overall overexpression of type I interferon (IFN) response genes at all ages. Moreover, J20 mice presented a high expression of type II IFN genes in the CP at 3months, which became lower than WT at 5-6 and 11-12months. Importantly, along with a marked memory impairment and increased glial activation, J20 mice also presented a similar overexpression of type I IFN genes in the dorsal hippocampus at 3months. Altogether, these findings provide new insights on a possible interplay between type I and II IFN responses in AD and point to IFNs as targets for modulation in cognitive decline.

Фотоснимки и рукописи по языковедению

ეს არის ურარტულ სახელმძღვანელოში შესატანი ურარტული ტექსტები: 1.ურარტუს მეფე სარდურის წარწერის ლურსმული ტექსტი; 2.იშფუინის (სარდურის ვაჟის) წარწერის ლურსმული ტექსტი; 3-5. იშფუინი და მენუა (იშფუინის ვაჟი) ურარტული ლურსმული ტექსტი (კელიშინის სტელის წარწერიდან); 6-8. ურარტული ტექსტის ასურული ვერსია

Continuous monitoring of liver oxygenation with near infrared spectroscopy during naso-gastric tube feeding in neonates.

Near infrared spectroscopy (NIRS) is a non-invasive method of estimating the haemoglobin concentration changes in certain tissues. It is frequently used to monitor oxygenation of the brain in neonates. At present it is not clear whether near infrared spectroscopy of other organs (e.g. the liver as a corresponding site in the splanchnic region, which reacts very sensitively to haemodynamic instability) provides reliable values on their tissue oxygenation. The aim of the study was to test near infrared spectroscopy by measuring known physiologic changes in tissue oxygenation of the liver in newborn infants during and after feeding via a naso-gastric tube. The test-retest variability of such measurements was also determined. On 28 occasions in 25 infants we measured the tissue oxygenation index (TOI) of the liver and the brain continuously before, during and 30 minutes after feeding via a gastric tube. Simultaneously we measured arterial oxygen saturation (SaO2), heart rate (HR) and mean arterial blood pressure (MAP). In 10 other newborn infants we performed a test-retest analysis of the liver tissue oxygenation index to estimate the variability in repeated intra-individual measurements. The tissue oxygenation index of the liver increased significantly from 56.7 +/- 7.5% before to 60.3 +/- 5.6% after feeding (p < 0.005), and remained unchanged for the next 30 minutes. The tissue oxygenation index of the brain (62.1 +/- 9.7%), SaO2 (94.4 +/- 7.1%), heart rate (145 +/- 17.3 min-1) and mean arterial blood pressure (52.8 +/- 10.2 mm Hg) did not change significantly. The test-retest variability for intra-individual measurements was 2.7 +/- 2.1%. After bolus feeding the tissue oxygenation index of the liver increased as expected. This indicates that near infrared spectroscopy is suitable for monitoring changes in tissue oxygenation of the liver in newborn infants.

Antibacterial xanthones from Kielmeyera variabilis mart. (Clusiaceae)

The bioassay-guided fractionation of stems from Kielmeyera variabilis, traditionally used in Brazilian folk medicine, yielded assiguxanthone-B (1), kielcorin (4), 2,5-dihydroxybenzoic acid (3), and a mixture of xanthones containing assiguxanthone-B (1) and 1,3,5,6-tetrahydroxy-2-prenylxanthone (2) (1:1 w/w). The xanthone mixture inhibited Staphylococcus aureus and Bacillus subtilis at a concentration of 6.25 µg/ml. When tested alone, the minimal inhibitory concentration of assiguxanthone-B was 25 µg/ml against B. subtilis. Kielcorin and 2,5-dihydroxybenzoic acid were inactive against both strains. None of the fractions was active against Escherichia coli or Pseudomonas aeruginosa. Viable cells of S. aureus were reduced by a 1-3 log CFU/ml within 12 h after exposure of one to eight times the MIC of the xanthone mixture. It is not known whether the tetrahydroxy-2-prenylxanthone or other components of the xanthone mixture are responsible for the main antibacterial activity or whether additive or synergistic action is involved

Blood pressure changes after renal denervation at 10 European expert centers.

We did a subject-level meta-analysis of the changes ([6;) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P&#58106;0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P&#58102;0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of &#58102;10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20- 56;mol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.

Rapid Improvement in Health-Related Quality of Life in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by interleukin (IL)-1b. Canakinumab inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 wk double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150mg divided in doses every 4 wks (50þ50þ25þ25mg [q4wk]) or colchicine 0.5mg p.o. daily for 16 wks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to number of flares occurring during first 16 wks. Secondary outcomes included number of patients with flares and C-reactive protein (CRP) levels during the first 16 wks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine couldn't be determined. Based on a negative binomialmodel, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25mg 0.60, 50mg 0.34, 100mg 0.28, 200mg 0.37, 300mg 0.29, q4wk 0.38; p_0.05). Percentage of patients with flares was lower for all canakinumab groups (25mg 27.3%, 50mg 16.7%, 100mg 14.8%, 200mg 18.5%, 300mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p_0.05 for all). Median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN¼3 mg/L) throughout the 16 wk period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg), 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. 1 fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusions: In this randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine and was well tolerated.Disclosure statement: U.A., A.B., G.K., D.R. and P.S. are employees of and have stock options or bold holdings with Novartis Pharma AG. E.M. is a principal investigator for Novartis Pharmaceuticals Corporation. E.N. has received consulting fees from Roche. N.S. has received research grants from Novartis Pharmaceuticals Corporation. A.S. has received consultancy fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interest.

Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX.METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed.RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (+/-s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (+/-s.e.) was 61.3 +/- 5.3% at 3 months and 41.3 +/- 5.6% at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy.CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.