Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

<p>Abstract</p> <p>Background</p> <p>Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE) of newborns with bacterial sepsis during the acute and the recovery phases.</p> <p>Methods</p> <p>We studied nineteen neonates (27.3 ± 17.2 days old) with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO₂and VCO₂measured by gas chromatography.</p> <p>Results</p> <p>REE significantly increased from 49.4 ± 13.1 kcal/kg/day during the acute to 68.3 ± 10.9 kcal/kg/day during recovery phase of sepsis (P < 0.01). Similarly, VO₂(7.4 ± 1.9 <it>vs </it>10 ± 1.5 ml/kg/min) and VCO₂(5.1 ± 1.7 <it>vs </it>7.4 ± 1.5 ml/kg/min) were also increased during the course of the disease (P < 0.01).</p> <p>Conclusion</p> <p>REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities.</p

Karyology of the Atlantic forest rodent Juliomys (Cricetidae): A new karyotype from southern Brazil

Juliomys is a small rodent from the family Cricetidae which inhabits the Atlantic forest and forests from Argentina to eastern Brazil. The three species recognized so far have different karyotypes. In this paper, we describe a new karyotype with 2n = 32, FN = 48 found in Juliomys specimens from a high-altitude area in the Atlantic forest of southern Brazil. The karyotype was analyzed after G- and C-banding and silver staining of the nucleolus organizer regions (Ag-NOR) and its G-banding patterns were compared with those of the newly described species Juliomys ossitenuis (2n = 20, FN = 36). The 2n = 32 karyomorph presented peculiar features and was very different from those of the other species of the genus: J. pictipes (2n = 36, FN = 34), J. rimofrons (2n = 20, FN = 34) and J. ossitenuis (2n = 20, FN = 36). Differences were mostly due to centric and tandem fusions, pericentric inversion and loss of heterochromatin. The karyotype represents a powerful tool to differentiate Juliomys species and our data suggest that the karyotype described herein belongs to a new species

Multiple inflammatory markers and 15-year incident ADL disability in admixed older adults: The Bambui-Epigen Study

BACKGROUND: The ability of inflammatory markers to predict disability in later life has received growing attention. However, the current evidence came predominantly from Caucasians and the role of genomic ancestry has not been investigated. OBJECTIVE: We investigated the prognostic value of multiple citokynes and chemokines for incident disability in admixed older Brazilians and whether genomic African and Native American ancestry affects the association. DESIGN: Population-based longitudinal study. SETTING: The Bambui-Epigen (Brazil) Cohort Study of Aging. SUBJECTS: 1171 males and females aged ≥60 years over 15-year of follow-up. METHODS: Outcome examined was incident activity of daily living (ADL) disability assessed annually (10,039 measures were performed). Serum levels of citokynes (IL6, IL12, TNF, IL10, and IL1β) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) were measured at baseline. We used 370,539 Single Nucleotide Polymorphisms (SNPs) to estimate each individual genomic ancestry proportions. Potential confounding variables included a wide range of socio-demographic variables and health indicators. Statistical analyses were based on competing risk framework. RESULTS: The incidence rate of disability was 57.9 per 1000 person-years. IL6 level at the highest quartile showed an independent association with ADL disability (SRH = 1.32; 95% CI: 1.03, 1.70). Other inflammatory markers showed no statistically significant associations with the outcome. Neither genomic African nor Native American ancestry had an effect modifier on the associations (P for interaction >0.05 for all). CONCLUSION: Among multi-inflammatory markers, only IL6 had the potential to identify people at increased risk of ADL disability, independently of ethno-racial background

Predictive value of multiple cytokines and chemokines for mortality in an admixed population: 15-year follow-up of the Bambui-Epigen (Brazil) cohort study of aging

Inflammation, particularly elevated IL-6 serum levels, has been associated with increased mortality risk, mostly in Caucasians. The influence of genetic ethno-racial background on this association is unknown. We examined associations between baseline serum levels of Interleukin-6 (IL-6) and other cytokines (IL1-2, TNF, IL-10, and IL1β) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) with 15-year mortality in 1,191 admixed Brazilians aged 60 years and over. Elevated IL6 level (but not other biomarkers) was associated with increased risk of deaths with fully adjusted hazard ratios of 1.51 (95% CI = 1.15, 1.97), 1.54 (95% CI = 1.20, 1.96) and 1.79 (95% CI = 1.40, 2.29) for the 2nd, 3rd and the highest quartiles, respectively. Genomic African and Native American proportions did not modify the association (p > 0.05). The discriminatory ability to predict death of a model based on IL-6 alone was similar as that of a comprehensive morbidity score (C statistics = 0.59 and 0.60, respectively). The abilities of IL-6 and the morbidity score models to predict death remained stable for very long term after the baseline measurement. Our results indicate that genome-based African and Native American ancestries have no impact on the prognostic value of IL-6 for mortality

Immunohistochemistry profiles of breast ductal carcinoma: factor analysis of digital image analysis data

<p>Abstract</p> <p>Background</p> <p>Molecular studies of breast cancer revealed biological heterogeneity of the disease and opened new perspectives for personalized therapy. While multiple gene expression-based systems have been developed, current clinical practice is largely based upon conventional clinical and pathologic criteria. This gap may be filled by development of combined multi-IHC indices to characterize biological and clinical behaviour of the tumours. Digital image analysis (DA) with multivariate statistics of the data opens new opportunities in this field.</p> <p>Methods</p> <p>Tissue microarrays of 109 patients with breast ductal carcinoma were stained for a set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16). Aperio imaging platform with the Genie, Nuclear and Membrane algorithms were used for the DA. Factor analysis of the DA data was performed in the whole group and hormone receptor (HR) positive subgroup of the patients (n = 85).</p> <p>Results</p> <p>Major factor potentially reflecting aggressive disease behaviour (i-Grade) was extracted, characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α. The i-Grade factor scores revealed bimodal distribution and were strongly associated with higher Nottingham histological grade (G) and more aggressive intrinsic subtypes. In HR-positive tumours, the aggressiveness of the tumour was best defined by positive Ki67 and negative ER loadings. High Ki67/ER factor scores were strongly associated with the higher G and Luminal B types, but also were detected in a set of G1 and Luminal A cases, potentially indicating high risk patients in these categories. Inverse relation between HER2 and PR expression was found in the HR-positive tumours pointing at differential information conveyed by the ER and PR expression. SATB1 along with HIF-1α reflected the second major factor of variation in our patients; in the HR-positive group they were inversely associated with the HR and BCL2 expression and represented the major factor of variation. Finally, we confirmed high expression levels of p16 in Triple-negative tumours.</p> <p>Conclusion</p> <p>Factor analysis of multiple IHC biomarkers measured by automated DA is an efficient exploratory tool clarifying complex interdependencies in the breast ductal carcinoma IHC profiles and informative value of single IHC markers. Integrated IHC indices may provide additional risk stratifications for the currently used grading systems and prove to be useful in clinical outcome studies.</p> <p>Virtual Slides</p> <p>The virtual slide(s) for this article can be found here: <url>http://www.diagnosticpathology.diagnomx.eu/vs/1512077125668949</url></p

Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

<p>Abstract</p> <p>Background</p> <p>Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether <it>NOTCH1 </it>mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.</p> <p>Methods</p> <p>T-ALL subtypes, status of <it>SIL-TAL1 </it>fusion, ectopic expression of <it>TLX3</it>, and mutations in <it>FBXW7</it>, <it>KRAS</it>, <it>PTEN </it>and <it>NOTCH1 </it>were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test.</p> <p>Results</p> <p>The frequencies of mutations were 43.5% for <it>NOTCH1</it>, while <it>FBXW7</it>, <it>KRAS </it>and <it>PTEN </it>exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of <it>NOTCH1 </it>mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between <it>NOTCH1 </it>mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. <it>SIL-TAL1 </it>was identified as an adverse prognostic factor. <it>NOTCH1 </it>mutation status was not associated with outcome, while the presence of <it>NOTCH1 </it>complex mutations (indels) were associated with a longer overall survival (<it>p </it>= 0.031) than point mutations.</p> <p>Conclusion</p> <p><it>NOTCH1 </it>mutations alone or in combination with <it>FBXW7 </it>did not impact T-ALL prognosis. Nevertheless, complex <it>NOTCH1 </it>mutations appear to have a positive impact on OS and the <it>SIL-TAL1 </it>fusion was validated as a negative prognostic marker in our series of T-ALL.</p