Detection of Malawi polyomavirus sequences in secondary lymphoid tissues from Italian healthy children: a transient site of infection

BACKGROUND: The novel Malawi polyomavirus (MWPyV) was initially detected in stool specimens from healthy children and children with gastrointestinal symptoms, mostly diarrhea, indicating that MWPyV might play a role in human gastroenteric diseases. Recently, MWPyV sequences were additionally identified in respiratory secretions from both healthy and acutely ill children suggesting that MWPyV may have a tropism for different human tissues. This study was designed to investigate the possible sites of latency/persistence for MWPyV in a cohort of healthy Italian children. METHODS: Specimens (n\ub0 500) of tonsils, adenoids, blood, urines and feces, from 200 healthy and immunocompetent children (age range: 1-15 years) were tested for the amplification of the MWPyV LT antigen sequence by quantitative real-time PCR. Samples (n\ub0 80) of blood and urines from 40 age-matched children with autoimmune diseases, were screened for comparison. Polyomaviruses JC/BK and Epstein-Barr Virus (EBV) were also tested as markers of infection in all samples using the same molecular technique. RESULTS: In our series of healthy children, MWPyV was detected only in the lymphoid tissues showing a prevalence of 6 % in tonsils and 1 % in adenoids, although with a low viral load. No JCPyV or BKPyV co-infection was found in MWPyV positive samples, while EBV showed a similar percentage of both in tonsils and adenoids (38 and 37 %). Conversely, no MWPyV DNA was detected in stool from babies with gastroenteric syndrome. With regards to autoimmune children, neither MWPyV nor BKPyV were detected in blood, while JCPyV viremia was observed in 15 % (6/40) of children treated with Infliximab. Urinary BKPyV shedding was observed in 12.5 % (5/40) while JCPyV in 100 % of the samples. CONCLUSIONS: The detection of MWPyV sequences in tonsils and adenoids of healthy children suggests that secondary lymphoid tissues can harbour MWPyV probably as transient sites of persistence rather than actual sites of latency

The Vaginal Community State Types Microbiome-Immune Network as Key Factor for Bacterial Vaginosis and Aerobic Vaginitis

Regarding bacterial vaginosis (BV), the relevance of the vaginal microbiota to the women's health fulfills a key role, but knowledge gaps regarding aerobic vaginitis (AV) exist. This study aims to characterize vaginal microbiome and its relationship with the local immune mediators, providing an opportunity to define the link between vaginal commensal microorganisms and opportunistic pathogens in the relation of a given vaginal community state type (CST). A total of 90 vaginal samples from Caucasian asymptomatic women of reproductive age (18-40 years) attending the yearly examination and not reporting any vaginal complaints were retrospectively evaluated for microbiome assessment and immune factor dosage. The samples were tested by the Ion Torrent PGM and the Luminex Bio-Plex technologies for the analysis of microbiome and immune factors, respectively. In our study, the CST classification together with the local immune response profiling represented a good predictive indicator of the vaginal health, suggesting that the predominance of a specific Lactobacillus and its relative abundance are pivotal elements to maintain a physiologic status. A vaginal colonization from Bifidobacterium may absolve a protective role similar to that of Lactobacillus, corresponding to a newly identified CST, although studies are needed to better clarify its clinical significance. Moreover, within each CST, a different pattern of inflammation is activated and orchestrated both by the dominant Lactobacillus spp. and by specific non-Lactobacillus bacteria and can give insights into the pathogenic mechanisms. In conclusion, this study contributes to the characterization of vaginal dysbiosis, reshaping this concept by taking into consideration the CST profiling, local immune marker, and immune-microbial network

Measles: An overview of a re-emerging disease in children and immunocompromised patients

Despite the availability of a safe and effective vaccine, in 2018, around 350,000 measles cases were reported worldwide, which resulted in an estimate of 142,300 deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death of 110,000 people, mostly children under the age of 5 years and immunocompromised adults. The increase in measles incidence is caused by the ongoing reduction of vaccination coverage. This event has triggered public and scientific interest. For this reason, we reviewed the pathophysiology of measles infection, focusing on mechanisms by which the virus spreads systemically through the host organism. By reaching the lymphocytes from the airways through a \u201ctrojan horse\u201d strategy, measles induces an immunosuppression status. H and F glycoproteins, both expressed in the envelope, ensure attachment of the virus to host cells and spreading from one cell to another by binding to several receptors, as described in detail. The severity of the disease depends both on the age and underlying conditions of patients as well as the social and health context in which epidemics spread, and is often burdened by sequelae and complications that may occur several years after infection. Particular attention was paid to special groups that are more susceptible to severe or atypical measles. An overview of microbiology, symptoms, diagnosis, prevention, and treatment completes and enriches the review

Oncogenic Virome Benefits from the Different Vaginal Microbiome-Immune Axes.

The picture of dynamic interaction between oncogenic viruses and the vaginal bacteria-immune host milieu is incomplete. We evaluated the impact of Polyomaviridae, Papillomaviridae, and Herpesviridae oncoviruses on the vaginal Community State Types (CSTs) and host immune response in reproductive-age women. In our cohort, only Polyomaviridae and Papillomaviridae were detected and were associated with changes in the resident bacteria of CST I and IV (p < 0.05). Lactobacillus crispatus increased in CST I while Prevotella timonensis and Sneathia sanguinegens increased in CST IV. Conversely, CST II and III showed an alteration of the immune response, with the decrease of Eotaxin, MCP-1, IL-7, IL-9, and IL-15 (p < 0.05), leading to reduced antiviral efficacy. An efficient viral clearance was observed only in women from CST I, dominated by Lactobacillus crispatus. Our in vivo study begins to address the knowledge gap with respect to the role of vaginal bacteria and immune response in susceptibility to oncoviral infections

Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects

The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO2 laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects

Late Post-traumatic Epilepsy in Children and Young Adults : Impropriety of Long-Term Antiepileptic Prophylaxis and Risks in Tapering

Background: After traumatic brain injury, epilepsy affects up to 20\uc2 % of children. It is a risk factor, for both clinical recovery and cognitive performance; therefore pharmacological therapy is advisable. Current guidelines recommend prophylaxis to be initiated as soon as possible and tapered 1\uc2 week after trauma. However, no guideline exists for paediatric patients and the clinical practice is heterogeneous. Objective: In our institute, prophylaxis was routinely tapered 6\uc2 months after trauma. Therefore we investigated whether this prophylaxis or its tapering influenced the development of post-traumatic epilepsy, together with several clinical-demographic factors. Methods: The study population comprised all patients with post-traumatic brain injury referred to this institute between 2002 and 2009 who consented to participate. Clinical, epileptological and pharmacological data were collected. The role of prophylaxis and several other predictors on occurrence of post-traumatic epilepsy was analysed through logistic regressions. Results: Two hundred and three patients (145 paediatric) were followed for 57\uc2 months on average. Risk factors for epilepsy were past neurosurgery [odds ratio (OR)\uc2 =\uc2 2.61, 95\uc2 % confidence interval (CI) 1.15\u20135.96], presence of epileptiform anomalies (OR\uc2 =\uc2 6.92, 95\uc2 % CI 3.02\u201315.86) and the presence of prophylaxis (OR\uc2 =\uc2 2.49, 95\uc2 % CI 1.12\u20135.52), while higher intelligence quotient (IQ) was protective (OR\uc2 =\uc2 0.96, 95\uc2 % CI 0.95\u20130.98). While evaluating possible different effects within and after 6\uc2 months (tapering, for those under prophylaxis), we found that epileptiform anomalies (OR\uc2 =\uc2 7.61, 95\uc2 % CI 2.33\u201324.93, and OR\uc2 =\uc2 8.21, 95\uc2 % CI 3.00\u201322.44) and IQ (OR\uc2 =\uc2 0.96, 95\uc2 % CI 0.94\u20130.98, and OR\uc2 =\uc2 0.97, 95\uc2 % CI 0.95\u20130.98) were always significant predictors of epilepsy, while neurosurgery (OR\uc2 =\uc2 4.38, 95\uc2 % CI 1.10\u201317.45) was significant only within 6\uc2 months from trauma, and prophylaxis (OR\uc2 =\uc2 3.98, 95\uc2 % CI 1.62\u20139.75) only afterwards. Conclusions: These results suggest that prophylaxis was irrelevant when present; furthermore its tapering increased the risk of epilepsy. Since the presence of epileptiform anomalies was the main predictor of post-traumatic epilepsy, such anomalies may be useful to better direct the choice of prophylaxis

Cryptogenic Epileptic Syndromes Related to SCN1A Twelve Novel Mutations Identified

Background: Sodium channel alpha 1 subunit gene, SCN1A, is the gene encoding the neuronal voltage-gated sodium channel alpha 1 subunit (Na(v)1.1) and is mutated in different forms of epilepsy. Mutations in this gene were observed in more than 70% of patients with severe myoclonic epilepsy of infancy (SMEI) and were also found in different types of infantile epileptic encephalopathy. Objective: To search for disease-causing mutations in SCN1A in patients with cryptogenic epileptic syndromes (ie, syndromes with an unknown cause). Design: Clinical characterization and molecular genetic analysis of a cohort of patients. Setting: University hospitals, rehabilitation centers, and molecular biology laboratories. Patients: Sixty unrelated patients with cryptogenic epileptic syndromes. Main Outcome Measures: Samples of DNA were analyzed for mutations and for large heterozygous deletions encompassing the SCN1A gene. A search for microdeletions in the SCN1A gene was also performed in the subset of patients with SMEI/SMEI-borderland who had negative results at the point mutation screening. Results: No large deletions at the SCN1A locus were found in any of the patients analyzed. In contrast, 13 different point mutations were identified in 12 patients: 10 with SMEI, 1 with generalized epilepsy with febrile seizures plus, and 1 with cryptogenic focal epilepsy. An additional search for SCN1A intragenic microdeletions in the remaining patients with SMEI/SMEI-borderland and no point mutations was also negative. Conclusions: These results confirm the role of the SCN1A gene in different types of epilepsy, including cryptogenic epileptic syndromes. However, large deletions encompassing SCN1A were not common disease-causing rearrangements in this group of epilepsies

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221