Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients.

BACKGROUND: Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. METHODS: To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥ 1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. RESULTS: We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥ 4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥ 1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0-1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5-1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. CONCLUSIONS: The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.

[3 lettres autographes signées de Jules Barbier à Henri Heugel, 1886]

26 mars 1886. Accepte son invitation à dîner : "Ce ne sera pas un dîner socialiste... (pardon) ! je voulais écrire : ce ne sera pas un dîner sot s'il y a Liszt". - 20 juillet. Lui adresse ses félicitations. - 30 juillet : Au sujet de l'argent que Heugel doit à Barbier et des reçus conservés entre ses mains

[3 lettres autographes signées de Jules Barbier à Henri Heugel, 1898]

12 novembre 1898. Le remercie de la bonne grâce qu'il a mise à lui rendre service. - 1er décembre 1898. Lui demande 500 francs. - 3 décembre 1898. Au sujet de l'argent qu'il doit à Heugel. - Papier bordé de noir

[3 lettres autographes signées de Jules Barbier à Henri Heugel, 1899]

2 juin 1899. Epuisé et fatigué, il sollicite Heugel en lui demandant une avance de1000 francs. - 7 juin 1899. Regrette que les relations avec Heugel s'enveniment : "Non, il ne fallait pas la caisse d'un Rotschild pour me les donner, il fallait simplement vous souvenir des centaines de mille francs que j'ai fait gagner au "Menestrel" ; mais vous avez la mémoire plus courte que votre cher père. Le spectacle de ma misère manquerait apparemment aux joies de votre fortune!..." Elude la question des dettes de son fils Pierre : "Quant à la dette de Pierre, permettez-moi de vous répéter une fois de plus qu'elle ne me regarde pas. Comment ne lui avez-vous pas donné un travail qui vous eut amplement remboursé?". - 14 juillet 1899. "Le relevé des comptes définitifs que me donne Chevalier prouve que je ne me trompais pas". - Papier bordé de noir

Subclinical coronary and aortic atherosclerosis detected by magnetic resonance imaging in type 1 diabetes with and without diabetic nephropathy.

BACKGROUND: Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic nephropathy using cardiovascular magnetic resonance imaging. METHODS AND RESULTS: In a cross-sectional study, 136 subjects with long-standing type 1 diabetes without symptoms or history of cardiovascular disease, including 63 patients (46%) with nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden, expressed as right coronary artery mean wall thickness (1.7+/-0.3 versus 1.3+/-0.2 mm; P<0.001) and maximum right coronary artery wall thickness (2.2+/-0.5 versus 1.6+/-0.3 mm; P<0.001), was greater in subjects with nephropathy. The prevalence of thoracic (3% versus 0%; P=0.28) and abdominal aortic plaque (22% versus 16%; P=0.7) was similar in both groups. Subjects with and without abdominal aortic plaques had similar coronary plaque burden. CONCLUSIONS: In asymptomatic type 1 diabetes, cardiovascular magnetic resonance imaging reveals greater coronary plaque burden in subjects with nephropathy compared with those with normoalbuminuria.

Indução de alterações morfológicas e anatômicas em folhas de abacaxizeiro 'Pérola' pelo ácido 2-(3-clorofenoxi) propiônico

Em estudo que visou controlar a floração natural do abacaxizeiro 'Pérola' com fitorreguladores, nas plantas pulverizadas com 50 e 100 mg L-1 (3 aplicações) do ácido 2-(3-clorofenoxi) propiônico (ACP), foram observadas alterações internas e externas nas folhas. O limbo foliar apresentou ligeiro estrangulamento na porção mediana das folhas 'E' e 'F' e próximo ao ponto de inserção no caule nas C' e 'D'. A cerca de 5-10 cm desse ponto surgiram estruturas similares a calos, que originaram raízes adventícias. A roseta central das plantas apresentou-se torcida, com as folhas mais curtas e largas. Cortes anatômicos permitiram observar, sob microscópio óptico (40X), que as raízes adventícias foram formadas a partir de meristemas nos feixes vasculares (xilema e floema), e que a estrutura anatômica foliar nos pontos de estrangulamento do limbo não foi alterada. Parênquima assimilador formou-se no córtex dessas raízes adventícias, indicando a realização de fotossíntese nesse tecido. A localização das raízes adventícias nas folhas correspondeu às áreas de provável acúmulo do produto pulverizado sobre as plantas. Os efeitos causados pelo ACP neste trabalho sugerem o seu uso em estudos relacionados à indução de enraizamento na propagação vegetativa (convencional e micropropagação) e na formação de calos "in vitro". E servem, também, para orientar novos estudos sobre a inibição da floração natural e seu uso prático, a fim de se evitar danos às plantas.