Diagnostic accuracy of cell-free DNA in maternal blood in detecting chromosomal anomalies in twin pregnancies: systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of cell-free DNA (cfDNA) in maternal blood in detecting chromosomal anomalies in twin pregnancies. METHODS: Medline, Embase and Cochrane databases were searched. The inclusion criteria were twin pregnancies undergoing cfDNA screening for Trisomies 13, 18, 21, monosomy X0 and other sex chromosomal anomalies (SCA). The index test was represented by a positive results of cfDNA test. The reference standard was represented by the karyotype results (obtained either pre or postnatally) or, in case of negative cfDNA result, by a normal neonatal phenotype. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR), with the corresponding 95% Confidence Intervals (95% CI), were computed using the bivariate random-effects model. RESULTS: Thirty-five studies were included. cfDNA had an overall high accuracy in detecting Trisomy 21 in twin pregnancies with a sensitivity of 98.8% (95% CI 96.5-100), a specificity of 100% (95% CI 99.9-100). Sensitivity and specificity were of 94.9% (95% CI 75.6-99.1) and 100 (95% CI 99.9-100) for Trisomy 18, and 84.6% (95% C% 54.6-98.1) and 100% (95% CI 99.9-100) for Trisomy 13 . We could not compute the diagnostic accuracy of cfDNA in detecting monosomy X0 in twins, while cfDNA had a sensitivity of 100% (95% CI 71.5-100) and a specificity of 99.8% (95% CI 99.7-99.9) in detecting other SCA (11 cases). The accuracy of cfDNA in detecting Trisomy 21, 18 and 13 was similar in dichorionic and monochorionic twin pregnancies. CONCLUSION: cfDNA has a high diagnostic accuracy in detecting Trisomy 18 and 21 in twin pregnancies, irrespective of chorionicity. Accuracy in the detection of Trisomy 13 and SCA was limited by the small number of affected cases and the difficulties in the confirmation of false negative cases in case of SCA and requires confirmation in larger studies. This article is protected by copyright. All rights reserved.

Outcome measures for chronic rhinosinusitis with nasal polyps.

BACKGROUND: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus. METHODS: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses. RESULTS: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each. CONCLUSIONS: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Developing an improved optical biosensing system based on gold nanoparticles acting as interferometric enhancers in Lactoferrin detection.

We report for the first time the whole development of a biosensing system based on the Interferometric Optical Detection Method (IODM) enriched with gold nanoparticles (AuNPs), acting as interferometric enhancers for improving the performance of immunoassays. For this purpose, the Lactoferrin sandwich immunoassay model was employed. We describe in detail the entire value chain from the AuNPs production, its functionalization, and characterization with anti-Lactoferrin (anti-LF), the biosensing response of these conjugates as well as their corresponding calculation of the kinetic constants, performance comparison of the readout interferometric signals versus Scanning Electron Microscopy (SEM) and the percentage of the sensing surface covered. Finally, a Lactoferrin sandwich immunoassay was carried out and correlated with Enzyme-Linked ImmunoSorbent Assay (ELISA), and the Limit of Detection and sensitivity figures were obtained. As a result, we demonstrate how the AuNPs act as interferometric amplifiers of the IODM for improving the biosensing response, opening the possibility of being applied in multiple biological detection applications.

Developing an Optical Interferometric Detection Method based biosensor for detecting specific SARS-CoV-2 immunoglobulins in Serum and Saliva, and their corresponding ELISA correlation.

The standard rapid approach for the diagnosis of coronavirus disease 2019 (COVID-19) is the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. The detection of specific anti-SARS-CoV-2 immunoglobulins is crucial for screening people who have been exposed to the virus, whether or not they presented symptoms. Recent publications report different methods for the detection of specific IgGs, IgMs, and IgAs against SARS-CoV-2; these methods mainly detect immunoglobulins in the serum using conventional techniques such as rapid lateral flow tests or enzyme-linked immunosorbent assay (ELISA). In this article, we report the production of recombinant SARS-CoV-2 spike protein and the development of a rapid, reliable, cost-effective test, capable of detecting immunoglobulins in serum and saliva samples. This method is based on interferometric optical detection. The results obtained using this method and those obtained using ELISA were compared. Owing to its low cost and simplicity, this test can be used periodically for the early detection, surveillance, detection of immunity, and control of the spread of COVID-19.

Allergooncology: an expanding research area.

The relationship between allergic diseases and cancer is a very controversial topic, widely discussed in the last decades. Many studies have demonstrated inverse association between allergy and cancer, but others have reached neutral conclusions or have indicated a positive role of allergy in the development of cancer. However, either inhibiting or favoring, many cells and molecules relevant in the allergic process play a role in tumorigenesis. On the one hand, activated immune cells, like classically activated macrophages "M1", activated dendritic cells, IL-33 and amphiregulin stimulated Innate Lymphoid Cells (ILC2), Th1, IFN-γ producing T CD8+ and B lymphocytes have inhibitory effects on tumorigenesis and tumor progression. On the other hand, tolerogenic immune cells, like alternatively activated macrophages "M2" (M2a, M2b and M2c), tolerogenic dendritic cells, ILC3, T regulatory and B regulatory lymphocytes, while inhibiting allergic sensitization and response, appear to favour carcinogenesis. Furthermore, M2 subtypes macrophages (M2a, M2b), IL-25 stimulated ILC2 and Th2 lymphocytes have a role both in inducing allergic reactions and in favouring cancer progression. In addition, mast cells, pivotal cells in allergy, have a different effect of tumorigenesis based on their location - they can promote cancer progression or inhibit it. Finally, eosinophils have shown a prevalent tumoricidal function mediated by α-defensins, TNF-α, granzymes A and IL-18. Better understanding the role of various cells on carcinogenesis can help in developing new strategies (diagnostic, therapeutic and of follow up) against tumor.

Fuelling the mechanisms of asthma: Increased fatty acid oxidation in inflammatory immune cells may represent a novel therapeutic target.

BACKGROUND: Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up-regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid-derived suppressor cells. Asthma is a chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology. OBJECTIVE: We tested whether FAO might play a role in the development of asthma-like traits and whether the inhibition of this metabolic pathway could represent a novel therapeutic approach. METHODS: OVA- and house dust mite (HDM)-induced murine asthma models were used in this study. RESULTS: Key FAO enzymes were significantly increased in the bronchial epithelium and inflammatory immune cells infiltrating the respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of FAO significantly decreased allergen-induced airway hyperresponsiveness, decreased the number of inflammatory cells, and reduced the production of cytokines and chemokines associated with asthma. CONCLUSIONS AND CLINICAL RELEVANCE: These novel observations suggest that allergic airway inflammation increases FAO in inflammatory cells to support the production of cytokines, chemokines, and other factors important in the development of asthma. Inhibition of FAO by re-purposing existing drugs approved for the treatment of heart disease may provide a novel therapeutic approach for the treatment of asthma.

A survey for gregarines (Protozoa: Apicomplexa) in arthropods in Spain.

Gregarines thrive in the digestive tract of arthropods and may be deleterious to their hosts, especially when present in high densities. The impact of parasites on these invertebrates may affect both the ecosystem equilibrium and human economic activities. However, information available on gregarines in Spain is limited. Therefore, a microscopic study on prevalence of gregarine infection in 560 insects and crustaceans was undertaken in Madrid and Tarragona.Gregarina ormierei (78 % prevalence), Stylocephalus gigas (56 %), Oocephalus hispanus (13 %) and Actinocephalus permagnus (only one infected out of six beetles examined) were found in coleopteran hosts. Gregarina ovata and G. chelidurellae showed moderate frequency of infection (35 %) in dermapterans. An undescribed Gregarina sp. (76 % prevalence) was observed for the first time in freshwater decapod crustaceans. Interestingly, G. ormierei showed a noticeable phenotypic dimorphism, which justifies its redescription based on modern taxonomic criteria. Sequences of the 18S rRNA gene could be obtained only in the presence of highly prevalent gregarines. G. ormierei and Gregarina sp. were related (85 and 94 % identity by BLASTN, respectively) to G. basiconstrictonea and G. cloptoni, respectively, whereas S. gigas was closely related to both Xiphocephalus ellisi and S. giganteus (>97 % identity). Phylogenetic trees based on ribosomal sequences unequivocally grouped these new isolates either with the Gregarinidae (G. ormierei and Gregarina sp.) or the Stylocephalidae (S. gigas).

Do knowledge of uterine artery resistance in the second trimester and targeted surveillance improve maternal and perinatal outcome? UTOPIA study: a randomized controlled trial.

OBJECTIVES: To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population. METHODS: This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor < 37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications. RESULTS: In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early-onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index > 90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)). CONCLUSIONS: Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Temporal and geographic clustering of polyomavirus-associated olfactory tumors in 10 free-ranging raccoons (Procyon lotor).

Reports of primary nervous system tumors in wild raccoons are extremely rare. Olfactory tumors were diagnosed postmortem in 9 free-ranging raccoons from 4 contiguous counties in California and 1 raccoon from Oregon within a 26-month period between 2010 and 2012. We describe the geographic and temporal features of these 10 cases, including the laboratory diagnostic investigations and the neuropathologic, immunohistochemical, and ultrastructural characteristics of these tumors in the affected animals. All 9 raccoons from California were found within a localized geographic region of the San Francisco Bay Area (within a 44.13-km radius). The tight temporal and geographic clustering and consistent anatomic location in the olfactory system of tumor types not previously described in raccoons (malignant peripheral nerve sheath tumors and undifferentiated sarcomas) strongly suggest either a common cause or a precipitating factor leading to induction or potentiation of neuro-oncogenesis and so prompted an extensive diagnostic investigation to explore possible oncogenic infectious and/or toxic causes. By a consensus polymerase chain reaction strategy, a novel, recently reported polyomavirus called raccoon polyomavirus was identified in all 10 tumors but not in the normal brain tissue from the affected animals, suggesting that the virus might play a role in neuro-oncogenesis. In addition, expression of the viral protein T antigen was detected in all tumors containing the viral sequences. We discuss the potential role of raccoon polyomavirus as an oncogenic virus.

Biomolecular identification of beta-defensin-like peptides from the skin of the soft-shelled turtle Apalone spinifera.

Numerous bacteria are frequently observed in the superficial corneocytes forming the corneous layer of the soft-shelled turtle Apalona spinifera. The resistance to bacterial penetration through the living epidermis in this turtle suggests the presence of an antimicrobial barrier, possibly derived from the presence of anti-microbial peptides in the epidermis. Four beta-defensin-like peptides, named As-BD-1 to 4, have been characterized from skin tissues using molecular and bioinformatics methods. The precursor peptides contain the beta-defensin motif with the typical cysteine localization pattern. The analysis of the expression for the four different beta-defensin-like proteins show that these molecules are expressed in the skin (epidermis and dermis) of the carapace, neck, digit, and tail but are apparently not expressed in the liver or intestine under normal conditions. These data suggest that in the skin of the soft-shelled turtle there are potential effective anti-microbial peptides against epidermal bacteria.

Molecular characterization of alpha-keratins in comparison to associated beta-proteins in soft-shelled and hard-shelled turtles produced during the process of epidermal differentiation.

The tough corneous layer in the carapace and plastron of hard-shelled turtles derives from the accumulation of keratin-associated beta-proteins (KAbetaPs, formerly called beta-keratins) while these proteins are believed to be absent in soft-shelled turtles. Our bioinformatics and molecular study has instead shown that the epidermis of the soft-shelled turtle Apalone spinifera expresses beta-proteins like or even in higher amount than in the hard-shelled turtle Pseudemys nelsoni. The analysis of a carapace cDNAs library has allowed the identification and characterization of three alpha-keratins of type I and of ten beta-proteins (beta-keratins). The acidic alpha-keratins probably combine with the basic beta-proteins but the high production of beta-proteins in A. spinifera is not prevalent over that of alpha-keratin so that their combination does not determine the formation of hard corneous material. Furthermore the presence of a proline and cisteine in the beta-sheet region of beta-proteins in A. spinifera may be unsuited to form hard masses of corneous material. The higher amount of beta-proteins over alpha-keratins instead occurs in keratinocytes of the hard and inflexible epidermis of P. nelsoni determining the deposition of hard corneous material. The study suggests that the hardness of the corneous layer derives not exclusively from the interactions between alpha-keratins with KAbetaPs but also from the different dynamic of accumulation and loss of corneocytes in the corneous layer of the hard shelled turtles where a prevalent accumulation and piling of corneocytes takes place versus the soft shelled turtle where a rapid turnover of the stratum corneum occurs.

Which factors are important for crossmodal attentional effect?

Some results in the literature suggest that crossmodal attention is very sensitive to the features of the experimental protocol. The current work examined the possible contribution of the asynchrony between the onset of the cue and the target (SOA) and the kind of task performed by the observer to the manifestation of crossmodal attentional effect. In a first experiment, a target (Gabor patch), whose spatial frequency had to be discriminated, was presented 133 or 159 ms after an auditory cue, in a close location on the same side or in a distant location on the opposite side. The crossmodal attentional effect was observed only for the 159 ms SOA. In a second experiment, the SOA was again 133 ms, but the location of the target had to be discriminated, instead of its spatial frequency. A crossmodal attentional effect was observed. The results of these two experiments indicate that crossmodal attentional effect depends on the SOA and the task. It takes longer to develop when the task requires the discrimination of the spatial frequency of the target than the discrimination of its location.

Distribution of specific keratin-associated beta-proteins (beta-keratins) in the epidermis of the lizard Anolis carolinensis helps to clarify the process of cornification in lepidosaurians.

The epidermis of different scales in the lizard Anolis carolinensis expresses specific keratin-associated beta-proteins (beta-keratins). In order to localize the sites of accumulation of different beta-proteins, we have utilized antibodies directed against representative members of the main families of beta-proteins, the glycine-rich (HgG5), glycine-cysteine rich (HgGC3), glycine-cysteine medium-rich (HgGC10), and cysteine-rich (HgC1) beta-proteins. Immunoblotting and immunocytochemical controls confirm the specificity of the antibodies made against these proteins. Light and ultrastructural immunocytochemistry shows that the glycine-rich protein HgG5 is present in beta-layers of different body scales but is scarce in the oberhautchen and claws, and is absent in alpha-layers and adhesive setae. The cysteine-glycine-rich protein HgGC3 is low to absent in the oberhautchen, beta-layer, and mesos-layer but increases in alpha-layers. This beta-protein is low in claws where it is likely associated with the hard alpha-keratins previously studied in this lizard. The glycine-cysteine medium-rich HgGC10 protein is low in the beta-layer, higher in alpha-layers, and in the oberhautchen. This protein forms a major component of setal proteins including those of the adhesive spatula that allow this lizard to stick on vertical surfaces. HgC1 is poorly localized in most epidermis analyzed including adhesive setae and claws and appears as a minor component of the alpha-layers. In conclusion, the present study suggests that beta- and alpha-layers of lizard epidermis represent regions with different accumulation of glycine-rich proteins (mainly for mechanical resistance and hydrophobicity in the beta-layer) or cysteine-glycine-rich proteins (for both resistance and elasticity in both alpha- and beta-layers).

The knockdown of maternal glucocorticoid receptor mRNA alters embryo development in zebrafish.

In zebrafish, ovulated oocytes contain both maternal cortisol and the mRNA for the glucocorticoid receptor (gr), which is spread as granular structures throughout the ooplasm. At 0.2 hpf, this transcript is relocated in the blastodisc area and partitioned among blastomeres. At 6-8 hpf, it is replaced by zygotic transcript. We used morpholinos to block translation of both maternal and zygotic gr transcripts, and a missplicing morpholino to block post-transcriptionally the zygotic transcript alone. Only knockdown of translation produced an increase of apoptosis and subsequent craniofacial and caudal deformities with severe malformations of neural, vascular, and visceral organs in embryos and 5-dpf larvae. Such defects were rescued with trout gr2 mRNA. Microarray analysis revealed that 114 and 37 highly expressed transcripts were up- and down-regulated, respectively, by maternal Gr protein deficiency in 5-hpf embryos. These results indicate that the maternal gr transcript and protein participate in the maternal programming of zebrafish development.

Cervical length vs VOCAL cervical volume for predicting pre-term delivery in asymptomatic women at 20-22 weeks' pregnancy.

We conducted a prospective observational study of 306 asymptomatic women at 20-22 weeks of pregnancy to compare 3-dimensional ultrasound measurements of cervical volume with 2-dimensional ultrasound measurements of cervical length to evaluate the performance of cervical volume as a predictor of pre-term delivery, compared with the current standard, cervical length. Participants underwent transvaginal ultrasound measurements of cervical length (mm) and cervical volume (cm(3)). Cervical volume as measured by 3-dimensional ultrasound was found to be a useful tool for predicting pre-term delivery; however, due to the high correlation between cervical length and cervical volume and the lack of differences in the sensitivity, specificity, positive predictive value, negative predictive value and relative risk between the two methods, replacing cervical length measurements with cervical volume calculations does not seem to be justified for this purpose, because of increased difficulty in volume acquisition.

No association between germline allele-specific expression of TGFBR1 and colorectal cancer risk in Caucasian and Ashkenazi populations.

BACKGROUND: Germline allele-specific expression (ASE) of the TGFBR1 gene has been reported as a strong risk factor for colorectal cancer (CRC) with an odds ratio close to 9. Considering the potential implications of the finding, we undertook the task of validating the initial results in this study. METHODS: Allele-specific expression was measured using the highly quantitative and robust technique of pyrosequencing. Individuals from two different populations were studied, one Caucasian-dominated and the other of Ashkenazi Jewish descent, with different sources of non-tumoral genetic material in each. RESULTS: Our results showed no statistically significant differences in the degree of ASE between CRC patients and controls, considering ASE as either a quantitative or a binary trait. Using defined cutoff values to categorise ASE, 1.0% of blood lymphocytes from informative Israeli cases (total n=96) were ASE positive (median 1.00; range 0.76-1.31) and 2.2% of informative matched controls (total n=90) were ASE positive (median 1.00; range 0.76-1.87). Likewise, normal mucosae from Spanish patients (median 1.03; range: 0.68-1.43; n=75) did not show significant differences in the degree of ASE when compared with the Israeli patients or controls. CONCLUSIONS: Taken together, these results suggest that ASE of TGFBR1 does not confer an increased risk of CRC.

Automatic attention lateral asymmetry in visual discrimination tasks.

There is evidence that automatic visual attention favors the right side. This study investigated whether this lateral asymmetry interacts with the right hemisphere dominance for visual location processing and left hemisphere dominance for visual shape processing. Volunteers were tested in a location discrimination task and a shape discrimination task. The target stimuli (S2) could occur in the left or right hemifield. They were preceded by an ipsilateral, contralateral or bilateral prime stimulus (S1). The attentional effect produced by the right S1 was larger than that produced by the left S1. This lateral asymmetry was similar between the two tasks suggesting that the hemispheric asymmetries of visual mechanisms do not contribute to it. The finding that it was basically due to a longer reaction time to the left S2 than to the right S2 for the contralateral S1 condition suggests that the inhibitory component of attention is laterally asymmetric.

Impact of influenza during the post-pandemic season: epidemiological picture from syndromic and virological surveillance.

INTRODUCTION: Following the observation that 1 or 2 pandemic peak due to the circulation ofAHINlv had occurred in most countries and in most World Health Organization (WHO) Regions, WHO declared on August 10"h, 2010 that the world was moving into the post-pandemic period, whose surveillance presents considerable interest both from epidemiological and clinical point of view. We described the epidemiological picture emerged from syndromic and virological surveillance during the post-pandemic season in Liguria, Italy. MATERIALS AND METHODS: An Emergency Department Syndrome surveillance system, based on data collected at "San Martino" and IRCCS "G. Gaslini" Liguria Regional Reference University Hospitals for adults and children is active since July 2007. Monitored syndromes include "Influenza-Like Illness" (ILl) and "Low Respiratory Tract Infections" (LRTI). The Ligurian Regional Reference laboratory for Influenza virological surveillance and diagnosis offers rapid detection of influenza viruses by real-time and block RT-PCR, viral culture and genetic characterization by entire sequence analysis of haemagglutinin- and neuraminidase-coding regions in accordance with the international standards established by the global laboratory network. RESULTS AND DISCUSSION: The integration of syndromic surveillance system and laboratory surveillance for rapid detection and characterization of the disease responsible agent represented a specific and sensitive tool for influenza surveillance. The post-pandemic season was characterized by early onset and by the heaviest impacts for ILI and LRTI among the recent epidemic seasons. In contrast to the picture observed during the pandemic season, the 2010/11 winter was characterized by the intensive circulation of pandemic AH1N1v coupled with sustained activity due to influenza B and Respiratory Syncytial Virus (RSV). Antigenic and molecular characterization of influenza strains confirmed the good matching between circulating and 2010/11 vaccine viruses.

Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer.

Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight.