probiotics and vaccination in children

Immunisation is one of the most beneficial and cost-effective disease prevention measures. However several immunisations are associated with suboptimal seroconversion rates and so the protective effect is not optimal. In the last two decades the concept about the use of probiotic bacteria as novel mucosal adjuvants has engendered a lot of interest due to our increased immunological understanding and the availability of various techniques to enhance existing vaccine specific-immune responses. Mostly in developing countries, many people still die every year from vaccine-preventable diseases such as pneumonia and diarrhea. To date, emphasis has been placed on identifying novel vaccine antigens and adjuvants that induce stronger protective immune responses, as well as developing mucosally-administered vaccines. We would have enormous benefits in allowing safe administration of vaccines in remote areas and we may overcome the necessity for multiple doses. The precise mechanism of action of probiotics is not fully understood, but several animal and human studies have proven immunomodulatory effects involving both the humoral and cellular components of the host's immune system. This review discusses whether dietary supplementation with oral probiotics enhances the immune response of infants after routine vaccinations and also evaluates clinical effects of probiotics in adults. Further well designed, randomized, placebo-controlled studies are needed to understand fully the immunomodulatory properties of probiotics, whether the effects exerted are strain and age-dependent, and their clinical relevance in enhancing protection following vaccination

Neumonía por COVID-19 en niños: De su etiología a su manejo

El COVID-19 es menos serio en niños que en adultos. Sin embargo, las afecciones respiratorias dominan el cuadro clínico de pacientes hospitalizados por COVID-19, aun en niños. En algunas series de casos, el deterioro del estado clínico, donde la disnea, la cianosis y el inicio del síndrome de dificultad respiratoria aguda (SDRA) emergieron ∼8–10 días después del inicio de la infección por SARS-CoV-2, pudo progresar rápidamente hasta la falla multiorgánica y la muerte. Esta revisión tiene como objetivo evaluar las características de la neumonía por COVID-19 en poblaciones pediátricas, comenzando con su etiología y sus mecanismos patológicos, para cerrar con su manejo clínico

K-string tensions at finite temperature and integrable models

It has recently been pointed out that simple scaling properties of Polyakov correlation functions of gauge systems in the confining phase suggest that the ratios of k-string tensions in the low temperature region is constant up to terms of order T^3. Here we argue that, at least in a three-dimensional Z_4 gauge model, the above ratios are constant in the whole confining phase. This result is obtained by combining numerical experiments with known exact results on the mass spectrum of an integrable two-dimensional spin model describing the infrared behaviour of the gauge system near the deconfining transition.Comment: 22 pages, 7 figures, 1 tabl

TinderMIX : Time-dose integrated modelling of toxicogenomics data

Background: Omics technologies have been widely applied in toxicology studies to investigate the effects of different substances on exposed biological systems. A classical toxicogenomic study consists in testing the effects of a compound at different dose levels and different time points. The main challenge consists in identifying the gene alteration patterns that are correlated to doses and time points. The majority of existing methods for toxicogenomics data analysis allow the study of the molecular alteration after the exposure (or treatment) at each time point individually. However, this kind of analysis cannot identify dynamic (time-dependent) events of dose responsiveness. Results: We propose TinderMIX, an approach that simultaneously models the effects of time and dose on the transcriptome to investigate the course of molecular alterations exerted in response to the exposure. Starting from gene log fold-change, TinderMIX fits different integrated time and dose models to each gene, selects the optimal one, and computes its time and dose effect map; then a user-selected threshold is applied to identify the responsive area on each map and verify whether the gene shows a dynamic (time-dependent) and dose-dependent response; eventually, responsive genes are labelled according to the integrated time and dose point of departure. Conclusions: To showcase the TinderMIX method, we analysed 2 drugs from the Open TG-GATEs dataset, namely, cyclosporin A and thioacetamide. We first identified the dynamic dose-dependent mechanism of action of each drug and compared them. Our analysis highlights that different time- and dose-integrated point of departure recapitulates the toxicity potential of the compounds as well as their dynamic dose-dependent mechanism of action.Peer reviewe

Multiparametric MRI of the bladder: inter-observer agreement and accuracy with the Vesical Imaging-Reporting and Data System (VI-RADS) at a single reference center

Objectives: To evaluate accuracy and inter-observer variability using Vesical Imaging-Reporting and Data System (VI-RADS) for discrimination between non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Methods: Between September 2017 and July 2018, 78 patients referred for suspected bladder cancer underwent multiparametric MRI of the bladder (mpMRI) prior to transurethral resection of bladder tumor (TURBT). All mpMRI were reviewed by two radiologists, who scored each lesion according to VI-RADS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each VI-RADS cutoff. Receiver operating characteristics curves were used to evaluate the performance of mpMRI. The Ƙ statistics was used to estimate inter-reader agreement. Results: Seventy-five patients were included in the final analysis, 53 with NMIBC and 22 with MIBC. Sensitivity and specificity were 91% and 89% for reader 1 and 82% and 85% for reader 2 respectively when the cutoff VI-RADS > 2 was used to define MIBC. At the same cutoff, PPV and NPV were 77% and 96% for reader 1 and 69% and 92% for reader 2. When the cutoff VI-RADS > 3 was used, sensitivity and specificity were 82% and 94% for reader 1 and 77% and 89% for reader 2. Corresponding PPV and NPV were 86% and 93% for reader 1 and 74% and 91% for reader 2. Area under curve was 0.926 and 0.873 for reader 1 and 2 respectively. Inter-reader agreement was good for the overall score (Ƙ = 0.731). Conclusions: VI-RADS is accurate in differentiating MIBC from NMIBC. Inter-reader agreement is overall good. Key Points: • Traditionally, the local staging of bladder cancer relies on transurethral resection of bladder tumor. • However, transurethral resection of bladder tumor carries a significant risk of understaging a cancer; therefore, more accurate, faster, and non-invasive staging techniques are needed to improve outcomes. • Multiparametric MRI has proved to be the best imaging modality for local staging; therefore, its use in suitable patients has the potential to expedite radical treatment when necessary and non-invasive diagnosis in patients with poor fitness

Hepatitis B vaccination failure in children with Diabetes Mellitus? The debate continues

The aim of our study was to evaluate the presence of specific antibodies against HBsAg in diabetic children (IDDM) previously vaccinated against hepatitis B virus.110 diabetic children were retrospectively studied and 100 healthy controls were recruited. In all patients surface antigen, HBV core IgG, antibodies against HBV "e" antigen and quantitative HBV surface antibodies were detected. In 45 patients molecular typing of HLA alleles was performed. Metabolic control was evaluated as mean glycated hemoglobin (HbA1c) and all patients were compliant to insulin therapy.46 of 110 diabetic children (41.8%) and 16 of 100 healthy controls (16%) were found to have not anti-HBs antibodies (p0.0001). The mean antibody titer was found significantly-lower (p0.0001) in IDDM children than healthy controls. No correlation was found between antibody titer, age, duration of disease and HbA1c. We did not find any difference of gender, age, years of onset of the disease and metabolic control, between diabetics with anti-HBs antibodies and those without.Our data confirm the reduced seroprotection rate for HBV vaccination in diabetics. However it remains poorly clarify the real clinical significance of this result. In our study no diabetic children showed markers of HBV infection

Acoustic pharyngometry: clinical and instrumental correlations in sleep disorders

Summary Matteo Gelardi 1 , Alessandro Maselli del Giudice 2 , Francesco Cariti 3 , Michele Cassano 4 , Aline Castelante Farras 5 , Maria Luisa Fiorella 6 , Pasquale Cassano 7 1 ENT specialist (Physician of the Bari University Otorhinolaryngology Department - Italy) 2 Physician (ENT Resident - Bari University - Italy) 3 Physician (ENT Resident - Bari University - Italy) 4 ENT specialist (Researcher of the Foggia University Otorhinolaryngology Department - Italy) 5 ENT specialist (Fellow of the Foggia University Otorhinolaryngology Department - Italy) 6 ENT specialist (Researcher of the Bari University Otorhinolaryngology Department - Italy) 7 ENT and Audiology specialist (Head of the Foggia University Otorhinolaryngology Department and Full Professor of Otorhinolaryngology at Foggia University - Italy)Bari University - Italy; Foggia University - ItalyDr. Michele Cassano Via: Crispi 34/C CEP: 70123 Bari - Italy. Telephone: 00xx39-080-5235508/ 00xx39-3388105268 Fax: 00xx39-080-5211318. Dra. Aline Castelante Farras Rua Sete de Setembro, 676 Centro Vila Velha - ES Telefone: 27-32393661 E-mail: [email protected] [email protected] Paper submitted to the ABORL-CCF SGP (Management Publications System) on July 29th, 2005 and accepted for publication on November 3th, 2006. cod. 567

Integrated Network Pharmacology Approach for Drug Combination Discovery : A Multi-Cancer Case Study

Simple Summary Current treatments for complex diseases, including cancer, are generally characterized by high toxicity due to their low selectivity for target cells. Moreover, patients often develop drug resistance, hence becoming less sensitive to the therapy. For this reason, novel, improved, and more specific pharmacological therapies are needed. The high cost and the time required to develop new drugs poses the attention on the development of computational methods for drug repositioning and combination therapy prediction. In this study, we developed an integrated network pharmacology framework that combines mechanistic and chemocentric approaches in order to predict potential drug combinations for cancer therapy. We applied our paradigm in five cancer types, which we used as case studies. Our strategy can be applied to the study of any complex disease by guiding the prioritization of drug combinations. Despite remarkable efforts of computational and predictive pharmacology to improve therapeutic strategies for complex diseases, only in a few cases have the predictions been eventually employed in the clinics. One of the reasons behind this drawback is that current predictive approaches are based only on the integration of molecular perturbation of a certain disease with drug sensitivity signatures, neglecting intrinsic properties of the drugs. Here we integrate mechanistic and chemocentric approaches to drug repositioning by developing an innovative network pharmacology strategy. We developed a multilayer network-based computational framework integrating perturbational signatures of the disease as well as intrinsic characteristics of the drugs, such as their mechanism of action and chemical structure. We present five case studies carried out on public data from The Cancer Genome Atlas, including invasive breast cancer, colon adenocarcinoma, lung squamous cell carcinoma, hepatocellular carcinoma and prostate adenocarcinoma. Our results highlight paclitaxel as a suitable drug for combination therapy for many of the considered cancer types. In addition, several non-cancer-related genes representing unusual drug targets were identified as potential candidates for pharmacological treatment of cancer.Peer reviewe