Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos

Fundamento:Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose.Objetivos:Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV.Métodos:Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA.Resultados:Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas.Conclusões:Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.     

Upregulation of Shiga Toxin Receptor CD77/Gb3 and Interleukin‐1β Expression in the Brain of EHEC Patients with Hemolytic Uremic Syndrome and Neurologic Symptoms

In 2011, a large outbreak of Shiga toxin‐producing enterohemorrhagic Escherichia coli (EHEC) infections occurred in northern Germany, which mainly affected adults. Out of 3842 patients, 104 experienced a complicated course comprising hemolytic uremic syndrome and neurological complications, including cognitive impairment, aphasia, seizures and coma. T2 hyperintensities on magnet resonance imaging (MRI) bilateral in the thalami and in the dorsal pons were found suggestive of a metabolic toxic effect. Five of the 104 patients died because of toxic heart failure. In the present study, the post‐mortem neuropathological findings of the five EHEC patients are described. Histological investigation of 13 brain regions (frontal, temporal, occipital cortex, corpora mammillaria, thalamus, frontal operculum, corona radiata, gyrus angularis, pons, medulla oblongata, cerebellar vermis and cerebellar hemisphere) showed no thrombosis, ischemic changes or fresh infarctions. Further, no changes were found in electron microscopy. In comparison with five age‐matched controls, slightly increased activation of microglia and a higher neuronal expression of interleukin‐1β and of Shiga toxin receptor CD77/globotriaosylceramide 3 was observed. The findings were confirmed by Western blot analyses. It is suggested that CD77/globotriaosylceramide upregulation may be a consequence to Shiga toxin exposure, whereas increased interleukin‐1β expression may point to activation of inflammatory cascades.     

Spectral karyotyping and interphase FISH reveal abnormalities not detected by conventional G-banding. Implications for treatment stratification of childhood acute lymphoblastic leukaemia: detailed analysis of 70 cases

Seventy uniformly treated children with acute lymphoblastic leukemia were analysed for chromosomal abnormalities with conventional G-banding, spectral karyotyping (SKY) and interphase fluorescent in situ hybridisation (FISH) using probes to detect MLL, BCR/ABL, TEL/AML1 rearrangements and INK4 locus deletions. Numerical and/or structural changes could be identified in 80% of the patients by the use of molecular cytogenetic techniques, whereas abnormalities could be detected in 60% of the patients using G-banding alone. Altogether, 106 structural aberrations were defined by FISH compared to 34 using G-banding. Seventy-four percent of the patients had numerical aberrations, 54% structural aberrations and 20% had no identified aberrations. Twelve cases had prognostically unfavourable chromosomal aberrations that had not been detected in the G-banded analysis. We identified three novel TEL partner breakpoints on 1q41, 8q24 and 21p12, and a recurrent translocation t(1;12)(p32;p13) was found. In addition, two cases displayed amplification (7-15 copies) of AML1. Our results demonstrate the usefulness of SKY and interphase FISH for the identification of novel chromosome aberrations and cytogenetic abnormalities that provide prognostically important information in childhood ALL.     

Is small bowel biopsy necessary in adults with suspected celiac disease and IgA anti-endomysium antibodies?

The comparative diagnostic value of IgA anti-endomysium and IgA antigliadin antibodies in adults with histologically confirmed celiac disease is reported. Sera from 144 adult patients (without concurrent dermatitis herpetiformis or IgA deficiency) who underwent small bowel biopsy were analyzed for both IgA anti-endomysium and IgA anti-gliadin antibodies. Nineteen patients (13%) had celiac disease. The presence of IgA antiendomysium antibodies had a sensitivity of 74% and a specificity of 100%. The positive and negative predictive values were 100% and 96%, respectively, and the diagnostic accuracy was 97%. In contrast, IgA anti-gliadin antibodies had positive and negative predictive values of 28% and 96%, respectively, with a diagnostic accuracy of 71%. Based on these data, we suggest that small bowel biopsy is not necessary to diagnose celiac disease in symptomatic adults with IgA antiendomysium antibodies. Due to a negative predictive value of 96%, some symptomatic adults lacking anti-endomysium antibodies will not be correctly diagnosed without small bowel biopsy.     

Intraoperative liver steatosis characterization using diffuse reflectance spectroscopy

Background

Liver steatosis is associated with poor outcome after liver transplantation and liver resection. There is a need for an accurate and reliable intraoperative tool to identify and quantify steatosis. This study aimed to investigate whether surface diffuse reflectance spectroscopy (DRS) measurements could detect liver steatosis on humans during liver surgery.

Clinical significance of serum cytokine patterns during start of fever in patients with neutropenia

Summary. Serum concentrations of tumour necrosis factor alpha (TNF-α), interleukin-1 receptor antagonist (IL-1ra), interferon gamma (IFN-γ), interleukin-6 (IL-6) and interleukin-10 (IL-10) were studied in 31 patients with haematological malignancies during febrile neutropenia. Samples were obtained when blood cultures were performed (time 0) and, when possible, after 2, 4, 6, 12 and 24 h. Increased levels of all cytokines were detected after start of fever with peak values in gram-negative (Gr⁻) bacteraemias after 2 h (TNF-α, IL-lra and IFN-γ), 4h (IL-6) and 6 h (IL-10), respectively. At time 0 the median TNF-α value was higher in the Gr⁻ group (80 pg/ml; range 54-516 pg/ml) as compared to both gram-positive bacteraemias (Gr⁺, 14pg/ ml; range 7-60 pg/ml; P < 0 05) and blood culture negative episodes (BCN, 8pg/ml; range 0-87pg/ml; P<0 05).
Furthermore, the peak values of TNF-α, IL-lra, IL-6 and IL-10 during the 24 h study period were significantly and/or numerically higher in the ^Gr- group in comparison to the Gr⁺ and BCN groups, respectively. It may be concluded that neutropenic patients have increased levels of both pro- and anti-inflammatory cytokines at start of fever, with the highest values recorded during the first hours in ^Gr- bacteraemias. Prospective studies will show whether monitoring of serum cytokines may be used as an early diagnostic tool before results of blood cultures are available, which may have important therapeutic implications.     

Reported normal values and weighted means for commonly used echocardiography pulsed Doppler and tissue Doppler measurements

Pulsed Doppler (PW) and tissue Doppler imaging (TDI) measurements are part of every echocardiography examination for evaluation of left ventricular (LV) diastolic function and filling pressure. The purpose of this study was to summarize published data on normal values for PW and TDI measurements. A PubMed search was performed on the 10th of October 2016 to identify relevant articles. Studies were considered relevant if they included more than 200 healthy individuals. A total of 13 studies were identified. Of these, 13 studies with 7777 subjects reported PW measurement over the mitral valve, six studies with 4082 subjects reported PW measurement in the pulmonary vein and 10 studies with 5988 subjects reported TDI. We also report weighted mean values for 14 different variables. As expected, measurements varied with age. There were no major differences between men and women. In contrast, there was a large difference in reported values between studies, in corresponding age groups. This review therefore raises caution about relying on normal values from just one study.     

MgH2–CoO: a conversion-type composite electrode for LiBH4-based all-solid-state lithium ion batteries

Several studies have demonstrated that MgH₂ is a promising conversion-type anode toward Li. A major obstacle is the reversible capacity during cycling. Electrochemical co-existence of a mixed metal hydride-oxide conversion type anode is demonstrated for lithium ion batteries using a solid-state electrolyte. 75MgH₂·25CoO anodes are obtained from optimized mixing conditions avoiding reactions occurring during high-energy ball-milling. Electrochemical tests are carried out to investigate the cycling capability and reversibility of the on-going conversion reactions. The cycling led to formation of a single-plateau nanocomposite electrode with higher reversibility yield, lowered discharge–charge hysteresis and mitigated kinetic effect at high C-rate compared to MgH₂ anodes. It is believed that reduced diffusion pathways and less polarized electrodes are the origin of the improved properties. The designed composite-electrode shows good preservation and suitability with LiBH₄ solid electrolyte as revealed from electron microscopy analyses and X-ray photoelectron spectroscopy.

The findings point to a means of guided formation of MgH₂–CoO conversion-type nanocomposite electrode for all-solid-state Li-ion batteries.     

An evaluation of a high‐pressure 11CO carbonylation apparatus

[¹¹C]Carbon monoxide (¹¹CO) is a versatile building block for the synthesis of Positron Emission Tomography (PET) radioligands. However, the difficulty of trapping ¹¹CO in a small solvent volume has limited its utility. We here report an evaluation of a simple, fully automated high‐pressure synthesizer prototype for the use in ¹¹C‐carbonylation reactions. [¹¹C]Carbon monoxide was easily prepared by online reduction of [¹¹C]carbon dioxide using either Mo(s) or Zn(s) as the reducing agent. The conversion yield of ¹¹CO was >99% when zinc was used as the reducing agent, and the corresponding value for Mo was approximately 71%. When the Zn or Mo column was constantly kept under inert atmosphere, no significant decrease in reducing properties was observed for more than 100 ¹¹CO productions. However, in our hands, Mo reductant was much easier to service. A total of nine functional groups were successfully radiolabeled using the ¹¹CO synthesizer prototype. All measured radiochemical yields exceeded 37%, and the ¹¹CO trapping efficiency was generally above 90%, except for the Suzuki coupling where the trapping efficiency was 80%. This high‐pressure synthesizer using [¹¹C]carbon monoxide as the labeling precursor is easy to operate allowing for ¹¹C‐carbonylation reactions to be performed in a high yield and in a routinely fashion.