922 research outputs found
Vaccines for mucosal immunity to combat emerging infectious diseases.
The mucosal immune system consists of molecules, cells, and organized lymphoid structures intended to provide immunity to pathogens that impinge upon mucosal surfaces. Mucosal infection by intracellular pathogens results in the induction of cell- mediated immunity, as manifested by CD4-positive (CD4 + ) T helper-type 1 cells, as well as CD8 + cytotoxic T-lymphocytes. These responses are normally accompanied by the synthesis of secretory immunoglobulin A (S-IgA) antibodies, which provide an important first line of defense against invasion of deeper tissues by these pathogens. New-generation live, attenuated viral vaccines, such as the cold-adapted, recombinant nasal influenza and oral rotavirus vaccines, optimize this form of mucosal immune protection. Despite these advances, new and reemerging infectious diseases are tipping the balance in favor of the parasite; continued mucosal vaccine development will be needed to effectively combat these new threats
Substrate specificity of a long-chain alkylamine-degrading Pseudomonas sp isolated from activated sludge
A bacterium strain BERT, which utilizes primary long-chain alkylamines as nitrogen, carbon and energy source, was isolated from activated sludge. This rod-shaped motile, Gram-negative strain was identified as a Pseudomonas sp. The substrate spectrum of this Pseudomonas strain BERT includes primary alkylamines with alkyl chains ranging from C3 to C18, and dodecyl-1,3-diaminopropane. Amines with alkyl chains ranging from 8 to 14 carbons were the preferred substrates. Growth on dodecanal, dodecanoic acid and acetic acid and simultaneous adaptation studies indicated that this bacterium initiates degradation through a Calkyl–N cleavage. The cleavage of alkylamines to the respective alkanals in Pseudomonas strain BERT is mediated by a PMS-dependent alkylamine dehydrogenase. This alkylamine dehydrogenase produces stoichiometric amounts of ammonium from octylamine. The PMS-dependent alkylamine was found to oxidize a broad range of long-chain alkylamines. PMS-dependent long-chain aldehyde dehydrogenase activity was also detected in cell-free extract of Pseudomonas strain BERT grown on octylamine. The proposed pathway for the oxidation of alkylamine in strain BERT proceeds from alkylamine to alkanal, and then to the fatty acid
Do internationally adopted children in the Netherlands use more medication than their non-adopted peers?
Young offenders caught in the act:A population-based cohort study comparing internationally adopted and non-adopted adolescents
Empirical research has shown an elevated risk for externalizing behavior problems in international adoptees. To address the extent to which this risk exists for more serious externalizing problems we compared the rates of registered criminal offending of internationally adopted adolescents with those of non-adopted adolescents in the Netherlands. In a large population-based cohort study (N = 3,758,506 including n = 10,563 international adoptees) on Dutch youth with ages up to 19 years we examined registrations in the program on juvenile crime and in the national police system from 2005 to 2013. Controlling for time lapse and background variables we found that international adoptees had been in contact with the criminal justice system more frequently than non-adoptees. However, the findings differed across region of adoption: Adoptees from South America and from Africa had been in contact with the criminal justice system most frequently (and more often than non-adoptees), whereas adoptees from China (total n = 4569) had the least contacts (and less often than non-adoptees). The percentages of criminal offending of adoptees ranged between 1.16% and 15.83% across regions of adoption (versus 10.86% in non-adoptees). The large majority of adoptees – including those from South America and Africa – were not involved in criminal acts. We hypothesize that the higher and lower risks of criminal offending found for adoptees from certain countries are associated with the varying levels of pre-adoption adversity (e.g., neglect and abuse) that the adoptees have experienced
RETURNEES: WHO ARE THEY, WHY ARE THEY (NOT) COMING BACK AND HOW SHOULD WE DEAL WITH THEM? Assessing Policies on Returning Foreign Terrorist Fighters in Belgium, Germany and the Netherlands. Egmont Paper 101, February 2018
Some 5000 men, women and children have travelled from Europe to Syria and Iraq since 2012. An estimated 1500 of these foreign terrorist fighters (FTF) have returned so far. Belgium, Germany and the Netherlands represent a third of European FTF and returnees. This report looks into the evolution of policies on returning foreign fighters in these three countries, comparing responses with regard to fighters that are still in the conflict zone, policies to deal with returnees in prison and attitudes towards the children of foreign fighters. It is the very first systematic and in-depth study into national approaches and policies vis-Ă -vis returnees. Its added value lies in the wealth of data, including data that has not been published before, and in the comparative angle
Exploring the Psychosocial Needs of Adolescents Whose Parent Is Diagnosed With Breast Cancer
Purpose: Cancer has a major impact on the individual patient and their family, especially children. However, little is known about the needs of adolescents (10–19 years) whose parent is diagnosed with cancer, especially breast cancer. Insights into psychosocial needs are important to develop appropriate guidance and support for these adolescents. The aim of this study is to explore the psychosocial needs of adolescents whose parent is diagnosed with breast cancer to improve the support for these adolescents. Data sources: This is an exploratory, qualitative study. In-depth interviews were conducted, and an interview guide was designed with the following topics: experiences, needs, and support. Participants were selected purposively and approached via the parent(s) after consultation. Interviews were audiotaped, transcribed, and thematically analyzed by using the software program NVivo. Conclusion: Fourteen adolescents (12–19 years) were interviewed, which resulted in five themes: distraction, support, being able to talk about it, information, and continuing a normal life. Adolescents whose parent is diagnosed with breast cancer need the best possible preservation of their normal lives. It is important for them to be able to share their story and find support from someone close to them. Implication for Nursing Practice: The route to the adolescent is always through the parent. Healthcare professionals can discuss the well-being of the adolescent during regular consultation with the parent. If there are concerns, healthcare professionals can advise the parent about the possible needs of the adolescent and could coach the parent in supporting the adolescent to discuss their needs.</p
IL-1RL1a serum levels and IL1RL1 SNPs in the prediction of food allergy
Food allergy is a common disorder in the Western world, with increasing prevalence and substantial healthcare costs(1). Food allergy is often accompanied by the presence of specific IgE against harmless proteins in food, but not all sensitized children show clinical reactions upon exposure. Therefore, double-blind placebo-controlled food challenges (DBPCFC) remain the gold standard to diagnose food allergy, yet this test is demanding. Biomarkers that can predict clinical response to food are urgently needed
Orca-010, a Novel Potency-enhanced Oncolytic Adenovirus, Exerts Strong Antitumor Activity in Preclinical Models
Improving the antitumor potency of current oncolytic adenoviruses represents one of the major challenges in development of these viruses for clinical use. We have generated an oncolytic adenovirus carrying the safety-enhancing E1A Delta 24 deletion, the potency-enhancing T1 mutation, and the infectivity-enhancing fiber RGD modification. The results of in vitro cytotoxicity assays on 15 human cancer cell lines derived from different tumor types demonstrated that ORCA-010 is more potent than Ad5-Delta 24RGD or ONYX-015. As ORCA-010 will initially be developed for the treatment of prostate cancer, selectivity experiments were performed using primary human prostate cells. ORCA-010 killed cancer cells more effectively than these primary human cells. In both primary prostate fibroblasts and epithelial cells, ORCA-010 was as safe as Ad5-Delta 24RGD. Evaluation of ORCA-010 in in vivo xenograft tumor models in nude mice showed that ORCA-010 significantly inhibited growth of prostate, lung, and ovarian tumors and conferred prolonged survival of tumor-bearing animals. Furthermore, we observed a substantial increase in infectious viral particles in tumors injected with ORCA-010. The number of infectious viral particles increased after treatment and infectious particles remained present up to at least 4 weeks posttreatment. Intratumoral virus replication was associated with substantial necrosis and fibrosis. In conclusion, ORCA-010 is more potent than earlier generation oncolytic adenoviruses, without demonstrating increased toxicity. ORCA-010 exerted strong in vivo antitumor activity and is therefore a suitable candidate for clinical evaluation
Systematic Review of Factors Affecting Quality of Life After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy
Background: Previous studies have shown that, overall, quality of life (QoL) decreases within the first 3–6 months after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC), returning to baseline levels by 6–12 months. This systematic review aims to evaluate the factors affecting QoL after CRS + HIPEC within 12 months of surgery. Methods: Electronic databases were investigated searching for articles reporting QoL with validated questionnaires up to September 2019. Risk of bias was assessed with the methodological index for non-randomized studies tool. The primary outcomes were short-term (< 6 months after surgery) and medium-term (6–12 months after surgery) determinants of QoL after CRS + HIPEC. Secondary outcomes were QoL and reported symptoms over time. Results: We included 14 studies that used 12 different questionnaires. The reported data were collected prospectively or retrospectively for 1556 patients (dropout < 50% in four studies). Overall, studies showed diminished QoL within 3 months after surgery and a recovery to baseline or greater by 12 months. QoL was negatively influenced by higher age, female sex, prolonged operation time, extensive disease, residual disease, adjuvant chemotherapy, complications, stoma placement, and recurrent disease. QoL results were comparable between studies, with dropout rates above and below 50%. Conclusions: QoL returns to baseline levels within 12 months after CRS + HIPEC provided the disease does not recur, and this recovery process is influenced by several factors
Adding diagnostic laparoscopy to computed tomography for the evaluation of peritoneal metastases in patients with colorectal cancer:A retrospective cohort study
Background: Despite its widespread use, computed tomography (CT) is not perfect for evaluating peritoneal metastases of colorectal origin before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). We therefore evaluated the value of adding diagnostic lapamscopy to CT when assessing patient eligibility for CRS + HIPEC. Methods: This was a retrospective study of a consecutive series of 112 patients evaluated systematically by diagnostic laparoscopy and CT between January 2012 and January 2018. Patient eligibility for CRS + HIPEC was assessed by the peritoneal cancer index (PCI) both at the time of initial diagnostic lapamscopy and during the retrospective review of CT images. Two experienced radiologists who were blinded to the PCI result at laparoscopy then independently estimated the PCI based on CT imaging. The primary outcome was the number of patients eligible for CRS + HIPEC by each method. Results: We identified 112 patients, of whom 95 (85%) were eligible for CRS + HIPEC based on diagnostic laparoscopy and 84 underwent CRS + HIPEC. Overall, 14 patients (17%) experienced an "open-and-close" procedure. In contrast to diagnostic lapamscopy, 100 patients (89%) were identified as being eligible for CRS + HIPEC by CT (p = 0.13), which would have resulted in an additional five open-and-close procedures. Conclusions: Adding diagnostic laparoscopy to CT produced a clinically relevant, but statistically non-significant, reduction in the number of patients eligible for CRS + HIPEC. We conclude that diagnostic lapamscopy may be of use in preoperative assessments when systematic analysis by CT scores the PCI as greater than ten. Future research should focus on the cost-effectiveness of this approach
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