Paratransgenesis to control malaria vectors: a semi-field pilot study

BACKGROUND: Malaria still remains a serious health burden in developing countries, causing more than 1 million deaths annually. Given the lack of an effective vaccine against its major etiological agent, Plasmodium falciparum, and the growing resistance of this parasite to the currently available drugs repertoire and of Anopheles mosquitoes to insecticides, the development of innovative control measures is an imperative to reduce malaria transmission. Paratransgenesis, the modification of symbiotic organisms to deliver anti-pathogen effector molecules, represents a novel strategy against Plasmodium development in mosquito vectors, showing the potential to reduce parasite development. However, the field application of laboratory-based evidence of paratransgenesis imposes the use of more realistic confined semi-field environments. METHODS: Large cages were used to evaluate the ability of bacteria of the genus Asaia expressing green fluorescent protein (Asaia (gfp)), to diffuse in Anopheles stephensi and Anopheles gambiae target mosquito populations. Asaia (gfp) was introduced in large cages through the release of paratransgenic males or by sugar feeding stations. Recombinant bacteria transmission was directly detected by fluorescent microscopy, and further assessed by molecular analysis. RESULTS: Here we show the first known trial in semi-field condition on paratransgenic anophelines. Modified bacteria were able to spread at high rate in different populations of An. stephensi and An. gambiae, dominant malaria vectors, exploring horizontal ways and successfully colonising mosquito midguts. Moreover, in An. gambiae, vertical and trans-stadial diffusion mechanisms were demonstrated. CONCLUSIONS: Our results demonstrate the considerable ability of modified Asaia to colonise different populations of malaria vectors, including pecies where its association is not primary, in large environments. The data support the potential to employ transgenic Asaia as a tool for malaria control, disclosing promising perspective for its field application with suitable effector molecules

Salmonella enterica serovar typhimurium exploits inflammation to modify swine intestinal microbiota

Salmonella enterica serovar Typhimurium is an important zoonotic gastrointestinal pathogen responsible for foodborne disease worldwide. It is a successful enteric pathogen because it has developed virulence strategies allowing it to survive in a highly inflamed intestinal environment exploiting inflammation to overcome colonization resistance provided by intestinal microbiota. In this study, we used piglets featuring an intact microbiota, which naturally develop gastroenteritis, as model for salmonellosis. We compared the effects on the intestinal microbiota induced by a wild type and an attenuated S. Typhimurium in order to evaluate whether the modifications are correlated with the virulence of the strain. This study showed that Salmonella alters microbiota in a virulence-dependent manner. We found that the wild type S. Typhimurium induced inflammation and a reduction of specific protecting microbiota species (SCFA-producing bacteria) normally involved in providing a barrier against pathogens. Both these effects could contribute to impair colonization resistance, increasing the host susceptibility to wild type S. Typhimurium colonization. In contrast, the attenuated S. Typhimurium, which is characterized by a reduced ability to colonize the intestine, and by a very mild inflammatory response, was unable to successfully sustain competition with the microbiota

Seven years cognitive functioning and early assessment in extremely low birth weight children

Infants born preterm are at high risk for the onset of cognitive dysfunctions at school age. The aim of this study was to investigate the association between early neurodevelopmental assessment and the risk of adverse cognitive outcome in extremely low birth weight children. We enrolled all newborns (January 2002 - April 2007) consecutively admitted to our Institution, with a birthweight < 1000 g. Exclusion criteria were genetic abnormalities, severe neurofunctional impairment, and/or neurosensory disabilities. Ninety-nine children were assessed at 1 year of corrected age using the Griffiths Mental Development Scales Revised. The same children were re-assessed at school age through the Wechsler Intelligence Scale for Children. Children with impaired Griffiths General Quotient (i.e., < 1 SD) at 1 year of corrected age showed a significantly lower Full Scale Intelligence Quotient at 7 years of chronological age when compared to children who scored in the normal range at 1 year (p < 0.01). Considering the Griffiths Sub-quotients separately, a poor score in the Performance or in the Personal-Social Sub-quotients at 1 year was associated with significantly worse cognitive outcomes both in the Verbal and in the Performance Intelligence Quotients at 7 years (p < 0.01 and p < 0.05, respectively). A score < 1 SD in the Locomotor or in the Eye and Hand Coordination Sub-quotients were specifically associated with poorer Performance or Verbal Intelligence Quotients, respectively (p < 0.05). Our findings suggest that a poor score on the Griffiths Scales at 1 year is associated with a higher risk of cognitive impairment at school age. Larger confirmation studies are needed

Impact of a probiotic diet on well-being of healthy senior: THE PROBIOSENIOR PROJECT

Aims: The aim of this work was to assess the effects of a probiotic diet on well-being of healthy seniors living in boarding and private homes in Marche Region, Italy. In particular, we focused on the modulation of high-sensitivity C-reactive protein (HsCRP), intestinal microbiota and short-chain fatty acids (SCFAs). Methods and Results: Ninety-seven healthy seniors took part in a double-blind, placebo-controlled feeding study (59 fed probiotics, 38 fed placebo) for 6&nbsp;months. Each volunteer ingested daily one food product or a dietary supplement enriched with Synbio® blend (Synbiotec Srl, Camerino, Italy) or the placebo (control group). Blood and faecal samples were collected before and at the end of the intervention period to perform biochemical and microbiological analyses. The serum HsCRP difference value after 6&nbsp;months of treatment was significantly higher in the probiotic group than placebo (p &lt; 0.05). After the intervention, a significant increase in faecal lactobacilli and a bifidobacteria increase in more participants were observed in the probiotic group. The 16S NGS analysis on the probiotic group showed a decreasing trend of Proteobacteria at the end of the treatment and conversely, an increasing trend of Actinobacteria and Verrucomicrobia phyla, to which the increase of Akkermansiaceae and Bifidobacteriaceae contributes at the family level. Finally, total short-chain fatty acids (SCFAs) and butyric acid were significantly higher in the probiotic group at the end of the treatment respect to the beginning. Conclusions: Overall, this study emphasizes the beneficial anti-inflammageing effect of a prolonged diet based on functional foods enriched with Synbio® through the modulation of the intestinal microbiota and the consequent increase in the SCFA production. Significance and Impact of the Study: Synbio® integration in elderly daily diet may be a preventive strategy to support healthy ageing

Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed. Here, we propose a machine learning-based approach to detect the key metabolites and proteins involved in MCI progression to AD using data from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Study. Proteins and metabolites were evaluated separately in multiclass models (controls, MCI and AD) and together in MCI conversion models (MCI stable vs converter). Only features selected as relevant by 3/4 algorithms proposed were kept for downstream analysis. Multiclass models of metabolites highlighted nine features further validated in an independent cohort (0.726 mean balanced accuracy). Among these features, one metabolite, oleamide, was selected by all the algorithms. Further in-vitro experiments in rodents showed that disease-associated microglia excreted oleamide in vesicles. Multiclass models of proteins stood out with nine features, validated in an independent cohort (0.720 mean balanced accuracy). However, none of the proteins was selected by all the algorithms. Besides, to distinguish between MCI stable and converters, 14 key features were selected (0.872 AUC), including tTau, alpha-synuclein (SNCA), junctophilin-3 (JPH3), properdin (CFP) and peptidase inhibitor 15 (PI15) among others. This omics integration approach highlighted a set of molecules associated with MCI conversion important in neuronal and glia inflammation pathways

Analysis and Design of a Yolo like DNN for Smoke/Fire Detection for Low-cost Embedded Systems

This paper proposes a video-based fire and smoke detection technique to be implemented as antifire surveillance system into low cost and low power single board computer (SBC). Such algorithm is inspired by YOLO (You Only Look once), a real-time state of the art object detector system able to classify and localize several objects into a single camera frame. Our architecture is based in three main segments: Bounding Box Generator, Support Classifier and Alarm Generator. The custom Yolo network was trained using already available dataset from literature and tested with respect to Classical and DL (Deep Learning) algorithms achieving best performance in terms of accuracy, F1, Recall and precision. The proposed technique has been implemented on four low cost embedded platform and compared respect the frame per second that they can achieve in real-time

Usefulness of an early neurofunctional assessment in predicting neurodevelopmental outcome in very low birthweight infants

OBJECTIVE: To evaluate whether early neurofunctional assessment may be useful in predicting neurodevelopmental outcome in children of very low birth weight (VLBW). DESIGN: Observational longitudinal study. SETTINGS: Northern Italy. PATIENTS: A total of 250 VLBW children (129 boys, 121 girls) born consecutively 1996-1999. MAIN OUTCOME MEASURES: Neurodevelopment at 36 months of chronological age, classified in accordance with the classification of Tardieu and the International classification of functioning. RESULTS: Of the infants exhibiting normal neurodevelopment (n = 183) or major dysfunction (n = 17) at 3 months of corrected age, 72% and 94% respectively did not change their score during the study. Minor dysfunctions at 3 months of corrected age were transient in 17 (34%) children. After adjustment for neonatal variables, neurodevelopment at 3 months of corrected age remained predictive of dysfunction at 36 months (odds ratio = 4.33, 95% confidence interval 2.05 to 9.12). If the results for the normal and minor dysfunction groups were pooled, the predictive qualities of the 3 month neurofunctional assessment were: sensitivity 0.5, specificity 0.99, positive predictive value 0.94, negative predictive value 0.93. CONCLUSION: Early neurofunctional evaluation may be useful in predicting later neurodevelopmental outcome in VLBW children