Effect of nutritional support in patients with lower respiratory tract infection: Secondary analysis of a randomized clinical trial.

BACKGROUND In polymorbid patients with bronchopulmonary infection, malnutrition is an independent risk factor for mortality. There is a lack of interventional data investigating whether providing nutritional support during the hospital stay in patients at risk for malnutrition presenting with lower respiratory tract infection lowers mortality. METHODS For this secondary analysis of a randomized clinical trial (EFFORT), we analyzed data of a subgroup of patients with confirmed lower respiratory tract infection from an initial cohort of 2028 patients. Patients at nutritional risk (Nutritional Risk Screening [NRS] score ≥3 points) were randomized to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). The primary endpoint of this analysis was all-cause 30-day mortality. RESULTS We included 378 of 2028 EFFORT patients (mean age 74.4 years, 24% with COPD) into this analysis. Compared to usual care hospital nutrition, individualized nutritional support to reach caloric and protein goals showed a similar beneficial effect of on the risk of mortality in the subgroup of respiratory tract infection patients as compared to the main EFFORT trial (odds ratio 0.47 [95%CI 0.17 to 1.27, p = 0.136] vs 0.65 [95%CI 0.47 to 0.91, p = 0.011]) with no evidence of a subgroup effect (p for interaction 0.859). Effects were also similar among different subgroups based on etiology and type of respiratory tract infection and for other secondary endpoints. CONCLUSION This subgroup analysis from a large nutrition support trial suggests that patients at nutritional risk as assessed by NRS 2002 presenting with bronchopulmonary infection to the hospital likely have a mortality benefit from individualized inhospital nutritional support. The small sample size and limited statistical power calls for larger nutritional studies focusing on this highly vulnerable patient population. CLINICAL TRIAL REGISTRATION Registered under ClinicalTrials.gov Identifier no. NCT02517476

Bayesian inference of signaling network topology in a cancer cell line

Motivation: Protein signaling networks play a key role in cellular function, and their dysregulation is central to many diseases, including cancer. To shed light on signaling network topology in specific contexts, such as cancer, requires interrogation of multiple proteins through time and statistical approaches to make inferences regarding network structure. Results: In this study, we use dynamic Bayesian networks to make inferences regarding network structure and thereby generate testable hypotheses. We incorporate existing biology using informative network priors, weighted objectively by an empirical Bayes approach, and exploit a connection between variable selection and network inference to enable exact calculation of posterior probabilities of interest. The approach is computationally efficient and essentially free of user-set tuning parameters. Results on data where the true, underlying network is known place the approach favorably relative to existing approaches. We apply these methods to reverse-phase protein array time-course data from a breast cancer cell line (MDA-MB-468) to predict signaling links that we independently validate using targeted inhibition. The methods proposed offer a general approach by which to elucidate molecular networks specific to biological context, including, but not limited to, human cancers. © 2012 The Author

Visual influences on ferret auditory cortex

Multisensory neurons are now known to be widespread in low-level regions of the cortex usually thought of as being responsible for modality-specific processing. The auditory cortex provides a particularly striking example of this, exhibiting responses to both visual and somatosensory stimulation. Single-neuron recording studies in ferrets have shown that each of auditory fields that have been characterized using physiological and anatomical criteria also receives visual inputs, with the incidence of visually-sensitive neurons ranging from 15% to 20% in the primary areas to around 50% or more in higher-level areas. Although some neurons exhibit spiking responses to visual stimulation, these inputs often have subthreshold influences that modulate the responses of the cortical neurons to sound. Insights into the possible role played by the visual inputs can be obtained by examining their sources of origin and the way in which they alter the processing capabilities of neurons in the auditory cortex. These studies suggest that one of the functions of the visual input to auditory cortex is to sharpen the relatively imprecise spatial coding typically found there. Because the extent to which this happens varies between cortical fields, the investigation of multisensory interactions can also help in understanding their relative contributions to auditory perception

Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society

Cystic Fibrosis (CF) occurs most frequently in caucasian populations. Although less common, this disorder have been reported in all the ethnicities. Currently, there are more than 2000 described sequence variations in CFTR gene, uniformly distributed and including variants pathogenic and benign (CFTR1:www.genet.sickkids.on.ca/). To date,only a subset have been firmily established as variants annotated as disease-causing (CFTR2: www.cftr2.org). The spectrum and the frequency of individual CFTR variants, however, vary among specific ethnic groups and geographic areas. Genetic screening for CF with standard panels of CFTR mutations is widely used for the diagnosis of CF in newborns and symptomatic patients, and to diagnose CF carrier status. These screening panels have an high diagnostic sensitivity (around 85%) for CFTR mutations in caucasians populations but very low for non caucasians. Developed in the last decade, Next-Generation Sequencing (NGS) has been the last breakthrough technology in genetic studies with a substantial reduction in cost per sequenced base and a considerable enhancement of the sequence generation capabilities. Extended CFTR gene sequencing in NGS includes all the coding regions, the splicing sites and their flankig intronic regions, deep intronic regions where are localized known mutations,the promoter and the 5'-3' UTR regions. NGS allows the analysis of many samples concurrently in a shorter period of time compared to Sanger method . Moreover, NGS platforms are able to identify CFTR copy number variation (CNVs), not detected by Sanger sequencing. This technology has provided new and reliable approaches to molecular diagnosis of CF and CFTR-Related Disorders. It also allows to improve the diagnostic sensitivity of newborn and carrier screeningmolecular tests. In fact, bioinformatics tools suitable for all the NGS platforms can filter data generated from the gene sequencing, and analyze only mutations with well-established disease liability. This approach allows the development of targeted mutations panels with a higher number of frequent CF mutations for the target populationcompared to the standard panels and a consequent enhancement of the diagnostic sensitivity. Moreover, in the emerging challenge of diagnosing CF in non caucasians patients, the possibility of customize a NGS targeted mutations panel should increase the diagnostic sensitivity when the target population has different ethnicities