Bridging the gap between Natural and Medical Images through Deep Colorization

Deep learning has thrived by training on large-scale datasets. However, in many applications, as for medical image diagnosis, getting massive amount of data is still prohibitive due to privacy, lack of acquisition homogeneity and annotation cost. In this scenario, transfer learning from natural image collections is a standard practice that attempts to tackle shape, texture and color discrepancies all at once through pretrained model fine-tuning. In this work, we propose to disentangle those challenges and design a dedicated network module that focuses on color adaptation. We combine learning from scratch of the color module with transfer learning of different classification backbones, obtaining an end-to-end, easy-to-train architecture for diagnostic image recognition on X-ray images. Extensive experiments showed how our approach is particularly efficient in case of data scarcity and provides a new path for further transferring the learned color information across multiple medical datasets

Bridging the gap between Natural and Medical Images through Deep Colorization

Deep learning has thrived by training on large-scale datasets. However, in many applications, as for medical image diagnosis, getting massive amount of data is still prohibitive due to privacy, lack of acquisition homogeneity and annotation cost. In this scenario, transfer learning from natural image collections is a standard practice that attempts to tackle shape, texture and color discrepancies all at once through pretrained model fine-tuning. In this work, we propose to disentangle those challenges and design a dedicated network module that focuses on color adaptation. We combine learning from scratch of the color module with transfer learning of different classification backbones, obtaining an end-to-end, easy-to-train architecture for diagnostic image recognition on X-ray images. Extensive experiments showed how our approach is particularly efficient in case of data scarcity and provides a new path for further transferring the learned color information across multiple medical datasets

Involvement of Autophagic Pathway in the Progression of Retinal Degeneration in a Mouse Model of Diabetes

The notion that diabetic retinopathy (DR) is essentially a micro-vascular disease has been recently challenged by studies reporting that vascular changes are preceded by signs of damage and loss of retinal neurons. As to the mode by which neuronal death occurs, the evidence that apoptosis is the main cause of neuronal loss is far from compelling. The objective of this study was to investigate these controversies in a mouse model of streptozotocin (STZ) induced diabetes. Starting from 8 weeks after diabetes induction there was loss of rod but not of cone photoreceptors, together with reduced thickness of the outer and inner synaptic layers. Correspondingly, rhodopsin expression was downregulated and the scotopic electroretinogram (ERG) is suppressed. In contrast, cone opsin expression and photopic ERG response were not affected. Suppression of the scotopic ERG preceded morphological changes as well as any detectable sign of vascular alteration. Only sparse apoptotic figures were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and glia was not activated. The physiological autophagy flow was altered instead, as seen by increased LC3 immunostaining at the level of outer plexiform layer (OPL) and upregulation of the autophagic proteins Beclin-1 and Atg5. Collectively, our results show that the streptozotocin induced DR in mouse initiates with a functional loss of the rod visual pathway. The pathogenic pathways leading to cell death develop with the initial dysregulation of autophagy well before the appearance of signs of vascular damage and without strong involvement of apoptosis

Correlation between Specific Bacterial Groups in the Oral Cavity and the Severity of Halitosis: Any Possible Beneficial Role for Selected Lactobacilli?

Objective: Halitosis is a widespread problem, normally attributable to specific volatile sulphur compounds (VSC) in the breath. The aim of this study was to first relate halitosis with possible gastric infection by Helicobacter pylori and secondly to quantify specific bacterial groups in the oral cavity flora, thus correlating them with VSC concentrations and Proton Pump Inhibitors (PPIs) intake. Four selected lactobacilli were then assessed in the possible reduction of halitosis in subjects with a total salivary bacterial concentration higher than 105 CFU/ml. Methods: Specific bacterial groups, namely total bacteria, total coliforms, sulphite-reducing bacteria (SRB) and lactobacilli, were quantified in samples of saliva from 29 subjects taking PPIs compared with 36 control subjects. The amount of the three VSC hydrogen sulfide (H2S), methyl mercaptan (CH3SH) and dimethyl sulfide (CH3)2S in the breath and the presence of H. pylori were determined. Results: No significant correlation was found between H. pylori and halitosis as well as with PPIs intake. The baseline bacterial groups quantification (log10 CFU/ml of saliva, PPI group vs. control) showed: total bacteria 8.44 vs. 4.47 (p=0.001); total coliforms 4.95 vs. 2.82 (p=0.001); sulfite-reducing bacteria 5.47 vs. 2.58 (p=0.052); total lactobacilli 4.00 vs. 2.36 (p=0.016). After 15 days of lactobacilli supplementation, the same parameters (d15 vs baseline) gave: total bacteria 7.92 vs. 8.44 (p=0.019); total coliforms 3.13 vs. 4.95 (p=0.001); sulfite-reducing bacteria 4.69 vs. 5.47 (p=0.047); total lactobacilli 7.86 vs. 4.00 (p=0.048). No statistically significant differences were noted in VSC concentrations at any time. Conclusions: The intake of PPIs directly correlated with the overgrowth of specific bacterial groups in the oral cavity, but there was no correlation with H. pylori or with VSC concentration. The significant reduction in all the bacterial groups analysed after two weeks suggested the improvement of the overall oral flora in subjects chronically treated with PPIs

Attività biologica e studi di docking di derivati bis-ammidici dell'acido 5,6- diidrossiindolo-2-carbossilico come inibitori dell'enzima HIV-1 integrasi

In un precedente studio, nel tentativo di identificare nuovi inibitori dell'HIV-1 integrasi, è stata da noi considerata la modifica strutturale dell'estere feniletilico dell'acido caffeico I (CAPE), il primo prodotto naturale inibitore dell'IN identificato, incorporando il legame vinilico del CAPE all'interno di una struttura rigida costituita dall'anello pirrolico. In questa comunicazione, a completamento dello studio svolto, noi presentiamo i dati relativi all'attività  inibitoria enzimatica per i derivati IIIe-i, lo studio SAR per tutti i derivati ed uno studio di docking nel sito attivo dell'HIV-1 IN eseguito al fine di investigare le possibili interazioni tra i ligandi e gli a.a. del sito catalitico

TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit

Photoreceptors rely upon highly specialized synapses to efficiently transmit signals to multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release, but also gates calcium-activated chloride channels (TMEM), which in turn regulate VGCC activity. In order to investigate the relationship between VGCC and TMEM channels, we analyzed the retina of wild type (WT) and Cacna2d4 mutant mice, in which the VGCC auxiliary a2d4 subunit carries a nonsense mutation, disrupting the normal channel function. Synaptic terminals of mutant photoreceptors are disarranged and synaptic proteins as well as TMEM16A channels lose their characteristic localization. In parallel, calcium-activated chloride currents are impaired in rods, despite unaltered TMEM16A protein levels. Co-immunoprecipitation revealed the interaction between VGCC and TMEM16A channels in the retina. Heterologous expression of these channels in tsA-201 cells showed that TMEM16A associates with the CaV1.4 subunit, and the association persists upon expression of the mutant a2d4 subunit. Collectively, our experiments show association between TMEM16A and the a1 subunit of VGCC. Close proximity of these channels allows optimal function of the photoreceptor synaptic terminal under physiological conditions, but also makes TMEM16A channels susceptible to changes occurring to calcium channels

Probiotics-addicted low-protein diet for microbiota modulation in patients with advanced chronic kidney disease (ProLowCKD): A protocol of placebo-controlled randomized trial

Abstract Microbiota is a term coined to describe the population of bacteria, viruses and fungi that inhabit in symbiosis within a living host. A connection between unbalanced microbiota and chronic kidney disease has been established. In these patients, high levels of urea reach the intestine promoting the overgrowth of bacterial species that are prone to generate uremic toxins. Due to the high morbidity and mortality of this condition, a large number of therapeutic approaches to reduce inflammation and microbial uremic toxins have been proposed, with controversial results. A low protein diet, with a protein intake of 0.6–0.8 g/kg of body weight, is a useful and historically pursued option with this regard. The aim of our study is to evaluate, among patients with advanced renal failure not on dialysis, the synergic beneficial effects of this diet and the selected probiotics Bifidobacterium longum (mix DLBL) and Lactobacillus reuteri LRE02 (DSM 23878)

One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage

Introduction: Down syndrome (DS) is the most common chromosomal disorder and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS show a large heterogeneity of phenotypes and the most constant clinical features present are typical facies and intellectual disability (ID). Several studies demonstrated that trisomy 21 causes an alteration in the metabolic profile, involving among all the one-carbon cycle. Methods: We performed enzyme-linked immunosorbent assays (ELISAs) to identify the concentration of 5 different intermediates of the one-carbon cycle in plasma samples obtained from a total of 164 subjects with DS compared to 54 euploid subjects. We investigated: tetrahydrofolate (THF; DS n = 108, control n = 41), 5-methyltetrahydrofolate (5-methyl-THF; DS n = 140, control n = 34), 5-formyltetrahydrofolate (5-formyl-THF; DS n = 80, control n = 21), S-adenosyl-homocysteine (SAH; DS n = 94, control n = 20) and S-adenosyl-methionine (SAM; DS n = 24, control n = 15). Results: Results highlight specific alterations of THF with a median concentration ratio DS/control of 2:3, a decrease of a necessary molecule perfectly consistent with a chromosomal dosage effect. Moreover, SAM and SAH show a ratio DS/control of 1.82:1 and 3.6:1, respectively. Discussion: The relevance of these results for the biology of intelligence and its impairment in trisomy 21 is discussed, leading to the final proposal of 5-methyl-THF as the best candidate for a clinical trial aimed at restoring the dysregulation of one-carbon cycle in trisomy 21, possibly improving cognitive skills of subjects with DS

Engineering hemoglobin to enable homogenous PEGylation without modifying protein functionality

In order to infuse hemoglobin into the vasculature as an oxygen therapeutic or blood substitute, it is necessary to increase the size of the molecule to enhance vascular retention. This aim can be achieved by PEGylation. However, using non-specific conjugation methods creates heterogenous mixtures and alters protein function. Site-specific PEGylation at the naturally reactive thiol on human hemoglobin (βCys93) alters hemoglobin oxygen binding affinity and increases its autooxidation rate. In order to avoid this issue, new reactive thiol residues were therefore engineered at sites distant to the heme group and the α/β dimer/dimer interface. The two mutants were βCys93Ala/αAla19Cys and βCys93Ala/βAla13Cys. Gel electrophoresis, size exclusion chromatography and mass spectrometry revealed efficient PEGylation at both αAla19Cys and βAla13Cys, with over 80% of the thiols PEGylated in the case of αAla19Cys. For both mutants there was no significant effect on the oxygen affinity or the cooperativity of oxygen binding. PEGylation at αAla19Cys had the additional benefit of decreasing the rates of autoxidation and heme release, properties that have been considered contributory factors to the adverse clinical side effects exhibited by previous hemoglobin based oxygen carriers. PEGylation at αAla19Cys may therefore be a useful component of future clinical products

Prenatal tobacco smoke exposure increases hospitalizations for bronchiolitis in infants

BACKGROUND: Tobacco smoke exposure (TSE) is a worldwide health problem and it is considered a risk factor for pregnant women's and children's health, particularly for respiratory morbidity during the first year of life. Few significant birth cohort studies on the effect of prenatal TSE via passive and active maternal smoking on the development of severe bronchiolitis in early childhood have been carried out worldwide. METHODS: From November 2009 to December 2012, newborns born at ≥ 33 weeks of gestational age (wGA) were recruited in a longitudinal multi-center cohort study in Italy to investigate the effects of prenatal and postnatal TSE, among other risk factors, on bronchiolitis hospitalization and/or death during the first year of life. RESULTS: Two thousand two hundred ten newborns enrolled at birth were followed-up during their first year of life. Of these, 120 (5.4%) were hospitalized for bronchiolitis. No enrolled infants died during the study period. Prenatal passive TSE and maternal active smoking of more than 15 cigarettes/daily are associated to a significant increase of the risk of offspring children hospitalization for bronchiolitis, with an adjHR of 3.5 (CI 1.5-8.1) and of 1.7 (CI 1.1-2.6) respectively. CONCLUSIONS: These results confirm the detrimental effects of passive TSE and active heavy smoke during pregnancy for infants' respiratory health, since the exposure significantly increases the risk of hospitalization for bronchiolitis in the first year of lif