Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity

Assessing the reliability of retrospective reports of adverse childhood experiences among adolescents with documented childhood maltreatment

The literature suggests that childhood maltreatment is related to a higher probability of developing psychopathology and disease in adulthood. However, some authors have questioned the reliability of self-reports of maltreatment, suggesting that psychopathology at the time of evaluation affects self-reports. We evaluated the reliability of the self-reports of 79 young adults who were identified in childhood by Child Protective Services by comparing two moments of evaluation. Psychological and physical symptoms were tested to evaluate their interference with the reports. We found good to excellent agreement, with no significant correlation between the changes in self-reported experiences and the changes in physical and psychological symptoms, suggesting that the reliability of reports is not related to the health state at the time of the report

The Clinical Psychology Training Program at the University of Nebraska–Lincoln

The Clinical Psychology Training Program (CPTP) at the University of Nebraska–Lincoln (UNL) has been continuously accredited by the American Psychological Association (APA) since 1948, the first year any programs were accredited. The CPTP’s history and approach to training through the years have been described in numerous articles (DiLillo & McChargue, 2007; Hargrove, 1991; Hargrove & Howe, 1981; Hargrove & Spaulding, 1988; Hope, Hansen, & Cole, 1994; Howe, 1974; Howe & Neimeyer, 1979; Jones & Levine, 1963; Rivers & Cole, 1976). Our program was historically described as a “Community-Clinical” psychology training program, and this focus on understanding and enhancing well-being at the individual, family, and community levels continues to be valued in our program today across a variety of clinical and research activities. The CPTP has followed the scientistpractitioner, Boulder-model of clinical training since its inception. Our Director of Clinical Training in 1949, Marshall Jones, was a participant in the Boulder Conference on Graduate Education in Clinical Psychology. Both clinical and research training are continuous, integrated processes in the CPTP, continuously supervised and monitored by the clinical faculty. The CPTP subscribes to the APA evidence- based practice model (APA, 2006) across all of our clinical training. Integration of EBP into our scientist-practitioner curriculum was highlighted in a special issue of Journal of Clinical Psychology that focused on EBP training (DiLillo & McChargue, 2007). Students in the CPTP are trained to be both consumers and producers of research, applying best research evidence in clinical practice and generating new knowledge to improve treatment. Within this EBP framework our emphasis is on behavioral and cognitive behavioral therapies. The department made an active decision, beginning in 1990, to hire scientist- practitioner faculty members with a behavioral or cognitive-behavioral orientation. The core clinical faculty provide clinical and research training in behavioral and cognitive-behavioral therapies, third-generation cognitive-behavioral approaches (e.g., mindfulness and acceptance-based), motivational enhancement approaches, and, to a lesser degree, family systems. The CPTP was honored to receive the 2013 ABCT Outstanding Training Program Award. The award is given for “significant contribution to training behavior therapists and/or promoting behavior therapy.

Serotonin reuptake inhibitors in pregnancy : can genes help us in predicting neonatal adverse outcome?

Lots has been written on use of SSRI during pregnancy and possible short and long term negative outcomes on neonates. the literature so far has described a various field of peripartum illness related to SSRI exposure during foetal life, such as increased incidence of low birth weight, respiratory distress, persistent pulmonary hypertension, poor feeding, and neurobehavioural disease. We know that different degrees of outcomes are possible, and not all the newborns exposed to SSRIs during pregnancy definitely will develop a negative outcome. So far, still little is known about the possible etiologic mechanism that could not only explain the adverse neonatal effects but also the degree of clinical involvement and presentation in the early period after birth. Pharmacogenetics and moreover pharmacogenomics, the study of specific genetic variations and their effect on drug response, are not widespread. This review describes possible relationship between SSRIs pharmacogenetics and different neonatal outcomes and summarizes the current pharmacogenetic inquiries in relation to maternal-foetal environment

Relevance of sonographic parameters for inflammatory bowel disease in children

Purpose: Intestinal ultrasound (IUS) is widely used as the first exam in patients with suspected inflammatory bowel disease (IBD). This study investigated the accuracy of several IUS parameters, including increased bowel wall thickening (BWT), in detecting IBD in a paediatric population. Methods: The study included an unselected series of 113 patients aged 2–18 years (mean age 10.8 years, 65 male), referred for recurrent abdominal pain or altered bowel habits, without known organic diseases, to perform an IUS as first investigation of a diagnostic workup. Patients with full systematic IUS examination, clinical and biochemical exams, and ileocolonoscopy or an uneventful follow-up at least one year follow up were eligible. Results: 23 IBD patients (20.4%; 8 ulcerative colitis, 12 Crohn’s disease and 3 indeterminate colitis) were diagnosed. We found that increased BWT > 3 mm (OR 5.4), altered IUS bowel pattern (IUS-BP, OR 9.8) and mesenteric hypertrophy (MH, OR 5.2) accurately identified IBD at the multivariate analysis. IUS-BP, MH and BWT > 3 mm had a sensitivity of 78.3%, 65.2% and 69.6% and a specificity of 93.3%, 92.2% and 96.7%, respectively. The combination of these three alterations increased the specificity up to 100%, whilst decreased sensitivity to 56.5%. Conclusion: Among several US parameters suggestive of IBD, the increased BWT, MH and altered echopattern are independent predictors of IBD. The ultrasonographic diagnosis of IBD could be more accurate if relied on combination of different sonographic parameters, than on the sole BWT evaluation

Determining oncogenic patterns and cancer predisposition through the transcriptomic profile in Mitchell–Riley syndrome with heterotopic gastric mucosa and duodenal atresia : a case report

Background: Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell–Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia. Results: We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including “Evading apoptosis” (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), “Proliferation” (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), “Sustained angiogenesis” (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), “Genomic instability” (BAD, BBC3) and “Insensitivity to anti-growth signals” (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as “PI3K signaling”, “ERK signaling”, “JAK-STAT signaling”, “Calcium signaling”, “Other RAS signaling”, “WNT signaling”. Conclusions: In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed

Dietary Intakes and Nutritional Issues in Neurologically Impaired Children

Neurologically impaired (NI) children are at increased risk of malnutrition due to several nutritional and non-nutritional factors. Among the nutritional factors, insufficient dietary intake as a consequence of feeding difficulties is one of the main issues. Feeding problems are frequently secondary to oropharyngeal dysphagia, which usually correlates with the severity of motor impairment and presents in around 90% of preschool children with cerebral palsy (CP) during the first year of life. Other nutritional factors are represented by excessive nutrient losses, often subsequent to gastroesophageal reflux and altered energy metabolism. Among the non-nutritional factors, the type and severity of neurological impairment, ambulatory status, the degree of cognitive impairment, and use of entiepileptic medication altogether concur to determination of nutritional status. With the present review, the current literature is discussed and a practical approach for nutritional assessment in NI children is proposed. Early identification and intervention of nutritional issues of NI children with a multidisciplinary approach is crucial to improve the overall health and quality of life of these complex children

The role of carrageenan in inflammatory bowel diseases and allergic reactions: Where do we stand?

Carrageenan (CGN) is a high molecular weight polysaccharide extracted from red sea-weeds, composed of D-galactose residues linked in β-1,4 and α-1,3 galactose-galactose bond, widely used as a food additive in processed foods for its properties as a thickener, gelling agent, emulsifier, and stabilizer. In recent years, with the spread of the Western diet (WD), its consumption has in-creased. Nonetheless, there is a debate on its safety. CGN is extensively used as an inflammatory and adjuvant agent in vitro and in animal experimental models for the investigation of immune processes or to assess the activity of anti-inflammatory drugs. CGN can activate the innate immune pathways of inflammation, alter the gut microbiota composition and the thickness of the mucus barrier. Clinical evidence suggests that CGN is involved in the pathogenesis and clinical manage-ment of inflammatory bowel diseases (IBD), indeed food-exclusion diets can be an effective therapy for disease remission. Moreover, specific IgE to the oligosaccharide α-Gal has been associated with allergic reactions commonly referred to as the “α-Gal syndrome”. This review aims to discuss the role of carrageenan in inflammatory bowel diseases and allergic reactions following the current ev-idence. Furthermore, as no definitive data are available on the safety and the effects of CGN, we suggest gaps to be filled and advise to limit the human exposure to CGN by reducing the consumption of ultra-processed foods

Acute encephalitis in pediatric multisystem inflammatory syndrome associated with COVID-19

Objective: To characterize neurological involvement in multisystem inflammatory syndrome in children (MIS-C) related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: Retrospective analysis of the clinical, electroencephalographic, CSF and neuroradiological parameters recorded in seven children (3 males, aged 3–10 years) affected by MIS-C with acute neurological involvement. Results: All cases presented acute encephalopathy with drowsiness, irritability, mood deflection and diffuse EEG slowing with periodic posterior complexes. Focal neurological signs, normal brain MRI and CSF, were present in four patients; these patients received intravenous methylprednisolone at 30 mg/kg/day for 3 days. In all cases, the clinical picture rapidly improved in the first three days, and all neurological symptoms and EEG abnormalities disappeared within 10 and 30 days respectively. The severity and duration of the EEG abnormalities was proportional to the extent of the neurological involvement. Conclusions: Patients with MIS-C may present acute encephalitis characterized by rapid-onset encephalopathy and EEG abnormalities (slow wave activity and/or epileptic abnormalities), in some cases associated with focal neurological signs that disappear with immunomodulatory therapy. The detection through neurological evaluation of sentinel neurological signs and distinctive EEG patterns documentable at disease onset will allow timely diagnosis and treatment of these cases