Epidermal growth factor receptor (EGFR) downstream signalling pathway in primary colorectal tumours and related metastatic sites: optimising EGFR-targeted treatment options

We analysed the expression of activated (phosphorylated) Akt and MAPK in 98 cases of paired primary colorectal tumours and metastases with the aim to define better the epidermal growth factor receptor (EGFR)-related molecular profile of colorectal cancer as a tool for treatment selection. Among 47 (48%) EGFR-negative primary tumours, 35 cases (74%) were positive for phosphorylated Akt and MAPK. Among 51 (52%) EGFR-positive primary colorectal cancers, 13 (25%) cases were negative for phosphorylated Akt and 15 (29%) were negative for phosphorylated MAPK. In EGFR-negative metastases (56 cases, 55%), phosphorylated Akt was expressed in 41 (73%) and phosphorylated MAPK was expressed in 36 (64%) samples, whereas in EGFR-positive metastases, phosphorylated Akt and MAPK were negative in 14 (31%) and in 10 (22%) cases, respectively. Phosphorylated Akt expression in primary colorectal tumours changed from positive to negative in 16 (16%) paired metastases and from negative to positive in 13 (13%) related metastatic sites. Phosphorylated MAPK expression in primary tumours changed from positive to negative in 13 (13%) paired metastases and from negative to positive in 12 (12%) related metastatic sites. Our findings suggest that phosphorylated Akt and MAPK status in primary tumours does not correlate with Akt and MAPK status in corresponding metastases. EGFR downstream signalling pathway can be overactivated even in the absence of EGFR expression in a considerable proportion of patients

Passive immunoprophylaxis against respiratory syncytial virus in children: Where are we now?

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab’s usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio

Single strain high-depth ngs reveals high rdna (Its-lsu) variability in the four prevalent pathogenic species of the genus candida

Ribosomal RNA in fungi is encoded by a series of genes and spacers included in a large operon present in 100 tandem repeats, normally in a single locus. The multigene nature of this locus was somehow masked by Sanger sequencing, which produces a single sequence reporting the prevalent nucleotide of each site. The introduction of next generation sequencing led to deeper knowledge of the individual sequences (reads) and therefore of the variants between the same DNA sequences located in different tandem repeats. In this framework, NGS sequencing of the rDNA region was used to elucidate the extent of intra-and inter-genomic variation at both the strain and species level. Specifically, the use of an innovative NGS technique allowed the high-throughput highdepth sequencing of the ITS1-LSU D1/D2 amplicons of 252 strains belonging to four opportunistic yeast species of the genus Candida. Results showed the presence of a large extent of variability among strains and species. These variants were differently distributed throughout the analyzed regions with a higher concentration within the Internally Transcribed Spacer (ITS) region, suggesting that concerted evolution was not able to totally homogenize these sequences. Both the internal variability and the SNPs between strain can be used for a deep typing of the strains and to study their ecology

Sub-Domain Solution of the Boltzmann Equation in MOS Means of Spherical Harmonics Expansion

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Thermal structure of the northern outer Albanides and adjacent Adriatic crustal sector, and implications for geothermal energy systems

none8sìopenSantini, S.; Basilici, M.; Invernizzi, C.; Mazzoli, S.; Megna, A.; Pierantoni, P.P.; Spina, V.; Teloni, S.Santini, S.; Basilici, M.; Invernizzi, C.; Mazzoli, S.; Megna, A.; Pierantoni, P. P.; Spina, V.; Teloni, S

Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics

Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens’ reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide

Exposure to outdoor air pollution and risk of hospitalization for bronchiolitis in an urban environment: A 9-year observational study

Background: Outdoor air pollution is supposed to influence the course of bronchiolitis, but the evidence is limited. The present study aimed at evaluating the role of outdoor air pollutants on hospitalization for bronchiolitis. Methods: Infants aged ≤12 months referred for bronchiolitis to our Pediatric Emergency Department in Bologna, Italy, from 1 October 2011 to 16 March 2020 (nine epidemic seasons) were retrospectively included. Daily concentrations of benzene (C6H6), nitrogen dioxide (NO2), particulate matter ≤2.5 μm (PM2.5), and ≤10 μm (PM10), and the mean values of individual patient exposure in the week and the 4 weeks before hospital access were calculated. The association between air pollutants exposure and hospitalization was evaluated through logistic regression analysis. Results: A total of 2902 patients were enrolled (59.9% males; 38.7% hospitalized). Exposure to PM2.5 in the 4 weeks preceding bronchiolitis was identified as the main parameter significantly driving the risk of hospitalization (odds ratio [95% confidence interval]: 1.055 [1.010–1.102]). After stratifying by season, higher values of other outdoor air pollutants were found to significantly affect hospitalization: 4-week exposure to C6H6 (Season 2011–2012, 4.090 [1.184–14.130]) and PM2.5 (Season 2017–2018, 1.282 [1.032–1.593]), and 1-week exposure to C6H6 (Season 2012–2013, 6.193 [1.552–24.710]), NO2 (Season 2013–2014, 1.064 [1.009–1.122]), PM2.5 (Season 2013–2014, 1.080 [1.023–1.141]), and PM10 (Season 2018–2019, 1.102 [0.991–1.225]). Conclusion: High levels of PM2.5, C6H6, NO2, and PM10 may increase the risk of hospitalization in children affected by bronchiolitis. Open-air exposure of infants during rush hours and in the most polluted areas should be avoided