Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aß) and Tau) and exacerbates AD pathology. Neuroinflammation can also be induced by systemic influences (factors from outside the central nervous system). However, the role of systemic inflammation in AD pathophysiology is much less understood. Thus, our main objective in this study was to verify whether the presence of serum cytokines (IL-1ß, IL-6, IL-10, IL-12, and TNF-α) affects different AD biomarkers: Aß1-42 and Tau protein levels, hippocampal volumes (HV), and default mode network functional connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this, we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the groups, we found that the mild AD patients presented smaller HV, disrupted DMN FC, and proportionally less IL-1ß than the controls. The aMCI patients only differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD with detectable levels of cytokines (TNF-α, IL-1ß, IL-10, and IL-12) had decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF Aß1-42, and less p-Tau), indicating a possible protective role of these ILs. Our findings indicate a possible relationship between systemic inflammation with DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects with mild AD and aMCI.

Parâmetros e ganhos genéticos em características de crescimento de bovinos Tabapuã da Bahia / Parameters and gains in genetic characteristics of Bahia Tabapuã bovine Growth

Compararam-se dois modelos (com ou sem o efeito materno) na estimativa de parâmetros genéticos por meio do fator de Bayes (FB) e do critério de informação da deviance (DIC). Adicionalmente, avaliaram-se as tendências genéticas, maternas e fenotípicas em características de crescimento de bovinos da raça Tabapuã do estado da Bahia. O modelo que incluiu o efeito materno proporcionou menores valores de FB (167629,2; 117341,2 e 124804,8) e DIC (174550,0; 120242,7 e 128037,2) para pesos aos 205 (P205), 365 (P365) e 550 (P550) dias de idade, respectivamente. As estimativas médias, a posteriori, das herdabilidades diretas e maternas foram 0,33; 0,43 e 0,44 e 0,15; 0,14 e 0,16 para as três características, respectivamente. As tendências genéticas para o efeito direto foram de 0,4415 e 0,3613kg/ano para P205 e P365 e representam incrementos de apenas 0,25 e 0,15% nas médias das características ao ano. As tendências genéticas maternas para as três características demonstraram perdas e indicam ausência de seleção de matrizes para boa habilidade materna. Apesar de existir variabilidade genética suficiente para justificar ganhos genéticos via seleção, estes e os ganhos fenotípicos foram pequenos, sugerindo necessidade de melhorias genéticas e ambientais.(AU)

We compared two models (with or without maternal effect) in the estimation of genetic parameters through Bayes Factor (BF) and the Deviance Information Criterion (DIC). Additionally, we evaluated the genetic, maternal and phenotypic trends in Tabapuã bovine growth characteristics in the state of Bahia. The model that included the maternal effect provided smaller BF values (167,629.2; 117,341.2 and 124,804.8) and DIC (174,550.0; 120,242.7 and 128,037.2) for weights at 205 (W205), 365 (W365) and 550 (W550) days of age, respectively. The average estimates, a posteriori, the direct and maternal heritability (0.33, 0.43 and 0.44) and (0.15, 0.14 and 0.16) for the three characteristics, respectively. Genetic trends for direct effect were 0.4415 and 0.3613kg/year for W205 and W365 and presented increases of 0.25 and 0.15% in the average characteristics of the year. The phenotypic trend for W205 was 0.7039kg/year. Maternal genetic trends for the three characteristics showed losses and indicate absence of selection matrices for good maternal ability. Despite the magnitude of the estimated direct and maternal heritability, they indicate genetic gain opportunities, genetic and phenotypic trends indicated few direct gains and no gains for maternal ability.(AU)

3T MRI quantification of hippocampal volume and signal in mesial temporal lobe epilepsy improves detection of hippocampal sclerosis.

BACKGROUND AND PURPOSE: In mesial temporal lobe epilepsy, MR imaging quantification of hippocampal volume and T2 signal can improve the sensitivity for detecting hippocampal sclerosis. However, the current contributions of these analyses for the diagnosis of hippocampal sclerosis in 3T MRI are not clear. Our aim was to compare visual analysis, volumetry, and signal quantification of the hippocampus for detecting hippocampal sclerosis in 3T MRI. MATERIALS AND METHODS: Two hundred three patients with mesial temporal lobe epilepsy defined by clinical and electroencephalogram criteria had 3T MRI visually analyzed by imaging epilepsy experts. As a second step, we performed automatic quantification of hippocampal volumes with FreeSurfer and T2 relaxometry with an in-house software. MRI of 79 healthy controls was used for comparison. RESULTS: Visual analysis classified 125 patients (62%) as having signs of hippocampal sclerosis and 78 (38%) as having normal MRI findings. Automatic volumetry detected atrophy in 119 (95%) patients with visually detected hippocampal sclerosis and in 10 (13%) with visually normal MR imaging findings. Relaxometry analysis detected hyperintense T2 signal in 103 (82%) patients with visually detected hippocampal sclerosis and in 15 (19%) with visually normal MR imaging findings. Considered together, volumetry plus relaxometry detected signs of hippocampal sclerosis in all except 1 (99%) patient with visually detected hippocampal sclerosis and in 22 (28%) with visually normal MR imaging findings. CONCLUSIONS: In 3T MRI visually inspected by experts, quantification of hippocampal volume and signal can increase the detection of hippocampal sclerosis in 28% of patients with mesial temporal lobe epilepsy.

Tigeciclina versus vancomycin más aztreonam en el tratamiento de infecciones complicadas de piel y tejidos blandos: Experiencia en Latinoamérica / Tigecycline as effective as vancomycin plus aztreonam in the treatment of complicated skin and skin structure infections: Experience in Latin America

BACKGROUND: Treating complicated skin and skin structure infections (cSSSIs) can be challenging. Tigecycline was compared to vancomycin/aztreonam in patients with cSSSIs in a multinational trial; this article reports on the Latin American (LA) population. METHODS: Patients were randomly assigned to receive tigecycline or vancomycin/ aztreonam. Primary endpoint was clinical cure rate at test-of-cure (TOC). Several secondary endpoints and safety were also assessed. RESULTS: A subtotal of 167 LA patients from the multinational trial (N = 573) received ≥ 1 dose of study drug. At TOC, cure rates were similar between tigecycline and vancomycin/aztreonam in the clinically evaluable population.) Noninferiority of tigecycline could not be demonstrated (insufficient sample sizes). Tigecycline-treated patients had higher incidences of nausea, vomiting, anorexia; vancomycin/aztreonam-treated patients had higher incidences of pruritus and rash. CONCLUSIONS: Efficacy results in the LA population were consistent with the multinational study suggesting that tigecycline is noninferior to vancomycin/aztreonam in treating patients with cSSSI.

INTRODUCCIÓN: El tratamiento de infecciones complicadas de piel y tejidos blandos (ICPTB) puede representar un desafío. Se comparó la eficacia de tigeciclina versus vancomicina/aztreonam en pacientes con ICPTB en un estudio multicéntrico; este artículo se refiere a la experiencia en Latinoamérica (LA). MÉTODO: Se asignaron, en forma randomizada, los pacientes a dos grupos de tratamiento: tigeciclina o vancomicina/aztreonam. La meta a evaluar (outcome) primaria fue la curación clínica, denominada test de curación (TC). Se establecieron, además, metas secundarias y la evaluación de seguridad del fármaco. RESULTADOS: Un subtotal de 167 pacientes procedentes de LA, de un estudio multinacional que incluyó 573 pacientes, recibieron ≥ 1 dosis del fármaco en estudio. Al TC, los porcentajes de curación fueron similares entre tigeciclina y vanco-micina/aztreonam en los pacientes clínicamente evaluables). La no inferioridad de tigeciclina no pudo ser demostrada (tamaño de muestra insuficiente). Los pacientes tratados con tigeciclina tuvieron mayor incidencia de náuseas, vómitos y anorexia; los pacientes que recibieron vancomicina/aztreonam tuvieron mayor incidencia de prurito y rash. CONCLUSIONES: Los resultados de eficacia en LA fueron consistentes con el estudio multinacional sugiriendo que tigeciclina no es inferior a vancomicina/aztreonam en el tratamiento de pacientes con ICPTB.