Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review

BACKGROUND: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. OBJECTIVE: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. METHODS: Electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. RESULTS: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitisation; 9, wheezing/asthma; 6, food allergy; 3, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. CONCLUSION AND CLINICAL RELEVANCE: In contrast with previous findings we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardised methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required

Super-Resolution Dissection of Coordinated Events during Malaria Parasite Invasion of the Human Erythrocyte

Erythrocyte invasion by the merozoite is an obligatory stage in Plasmodium parasite infection and essential to malaria disease progression. Attempts to study this process have been hindered by the poor invasion synchrony of merozoites from the only in vitro culture-adapted human malaria parasite, Plasmodium falciparum. Using fluorescence, three-dimensional structured illumination, and immunoelectron microscopy of filtered merozoites, we analyze cellular and molecular events underlying each discrete step of invasion. Monitoring the dynamics of these events revealed that commitment to the process is mediated through merozoite attachment to the erythrocyte, triggering all subsequent invasion events, which then proceed without obvious checkpoints. Instead, coordination of the invasion process involves formation of the merozoite-erythrocyte tight junction, which acts as a nexus for rhoptry secretion, surface-protein shedding, and actomyosin motor activation. The ability to break down each molecular step allows us to propose a comprehensive model for the molecular basis of parasite invasion. © 2011 Elsevier Inc

Development and Evaluation of Two Simple, Rapid Immunochromatographic Tests for the Detection of Yersinia pestis Antibodies in Humans and Reservoirs

Plague is due to the bacterium Yersinia pestis. It is accidentally transmitted to humans by the bite of infected fleas. Currently, approximately 20 developing countries with very limited infrastructure are still affected. A plague case was defined according to clinical, epidemiological and biological features. Rapid diagnosis and surveillance of the disease are essential for its control. Indeed, the delay of treatment is often rapidly fatal for patients and outbreaks may occur. Bubo aspirate is the most appropriate specimen in case of bubonic plague, but its collection is not always feasible. The main current biological approaches for the diagnosis of human plague are F1 antigen detection, serology for antibody detection by ELISA and Y. pestis isolation. The biological diagnosis of plague remains a challenge because the clinical signs are not specific. In this study, we developed some simple, rapid and affordable tests able to detect specific plague antibodies. These tests can be used as alternative methods for plague diagnosis in the field and for plague surveillance

Diagnosis and management of adhesive capsulitis

Adhesive capsulitis is a musculoskeletal condition that has a disabling capability. This review discusses the diagnosis and both operative and nonoperative management of this shoulder condition that causes significant morbidity. Issues related to medications, rehabilitation, and post surgical considerations are discussed

"I am becoming more and more like my eldest brother!": the relationship between older siblings, adolescent gambling severity, and the attenuating role of parents in a large-scale nationally representative survey study

The present study examined the association between having older siblings who gamble and adolescent at-risk/problem gambling and how parents (i.e., parental knowledge of their whereabouts) and peers might moderate such effects. Data were drawn from the ESPAD®Italia2012 survey (European School Survey Project on Alcohol and Other Drugs) comprising a nationally representative Italian sample of adolescents. The analysis was carried out on a subsample of 10,063 Italian students aged 15–19 years (average age = 17.10; 55 % girls) who had at least one older sibling and who had gambled at some point in their lives. Respondents’ problem gambling severity, older gambler sibling, gambler peers, parental knowledge, and socio-demographic characteristics were individually assessed. Multinomial logistic regression analyses including two- and three-way interactions were conducted. The odds of being an at-risk/problem gambler were higher among high school students with older siblings that gambled and those with peers who gambled. Higher parental knowledge (of who the adolescent was with and where they were in their leisure time) was associated with lower rates of at-risk/problem gambling. There was also an interaction between gamblers with older siblings and parental knowledge. The combination of having siblings who gambled and a greater level of parental knowledge was associated with lower levels of problem gambling. The present study confirmed the occurrence of social risk processes (older siblings and peers who gambled) and demonstrated that gambling among older siblings and peers represents an important contextual factor for increased at-risk/problem gambling. However, parental knowledge appears to be sufficient to counterbalance the influence of older siblings

Long-term consequences of an intensive care unit stay in older critically ill patients: design of a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Modern methods in intensive care medicine often enable the survival of older critically ill patients. The short-term outcomes for patients treated in intensive care units (ICUs), such as survival to hospital discharge, are well documented. However, relatively little is known about subsequent long-term outcomes. Pain, anxiety and agitation are important stress factors for many critically ill patients. There are very few studies concerned with pain, anxiety and agitation and the consequences in older critically ill patients. The overall aim of this study is to identify how an ICU stay influences an older person's experiences later in life. More specific, this study has the following objectives: (1) to explore the relationship between pain, anxiety and agitation during ICU stays and experiences of the same symptoms in later life; and (2) to explore the associations between pain, anxiety and agitation experienced during ICU stays and their effect on subsequent health-related quality of life, use of the health care system (readmissions, doctor visits, rehabilitation, medication use), living situation, and survival after discharge and at 6 and 12 months of follow-up.</p> <p>Methods/Design</p> <p>A prospective, longitudinal study will be used for this study. A total of 150 older critically ill patients in the ICU will participate (ICU group). Pain, anxiety, agitation, morbidity, mortality, use of the health care system, and health-related quality of life will be measured at 3 intervals after a baseline assessment. Baseline measurements will be taken 48 hours after ICU admission and one week thereafter. Follow-up measurements will take place 6 months and 12 months after discharge from the ICU. To be able to interpret trends in scores on outcome variables in the ICU group, a comparison group of 150 participants, matched by age and gender, recruited from the Swiss population, will be interviewed at the same intervals as the ICU group.</p> <p>Discussion</p> <p>Little research has focused on long term consequences after ICU admission in older critically ill patients. The present study is specifically focussing on long term consequences of stress factors experienced during ICU admission.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN52754370">ISRCTN52754370</a></p

A Multitrait–Multimethod Analysis of the Construct Validity of Child Anxiety Disorders in a Clinical Sample

The present study examines the construct validity of separation anxiety disorder (SAD), social phobia (SoP), panic disorder (PD), and generalized anxiety disorder (GAD) in a clinical sample of children. Participants were 174 children, 6 to 17 years old (94 boys) who had undergone a diagnostic evaluation at a university hospital based clinic. Parent and child ratings of symptom severity were assessed using the Multidimensional Anxiety Scale for Children (MASC). Diagnostician ratings were obtained from the Anxiety Disorders Interview Schedule for Children and Parents (ADIS: C/P). Discriminant and convergent validity were assessed using confirmatory factor analytic techniques to test a multitrait–multimethod model. Confirmatory factor analyses supported the current classification of these child anxiety disorders. The disorders demonstrated statistical independence from each other (discriminant validity of traits), the model fit better when the anxiety syndromes were specified than when no specific syndromes were specified (convergent validity), and the methods of assessment yielded distinguishable, unique types of information about child anxiety (discriminant validity of methods). Using a multi-informant approach, these findings support the distinctions between childhood anxiety disorders as delineated in the current classification system, suggesting that disagreement between informants in psychometric studies of child anxiety measures is not due to poor construct validity of these anxiety syndromes

Fluorescence in situ hybridization with high-complexity repeat-free oligonucleotide probes generated by massively parallel synthesis

The ability to visualize specific DNA sequences, on chromosomes and in nuclei, by fluorescence in situ hybridization (FISH) is fundamental to many aspects of genetics, genomics and cell biology. Probe selection is currently limited by the availability of DNA clones or the appropriate pool of DNA sequences for PCR amplification. Here, we show that liquid-phase probe pools from sequence capture technology can be adapted to generate fluorescently labelled pools of oligonucleotides that are very effective as repeat-free FISH probes in mammalian cells. As well as detection of small (15 kb) and larger (100 kb) specific loci in both cultured cells and tissue sections, we show that complex oligonucleotide pools can be used as probes to visualize features of nuclear organization. Using this approach, we dramatically reveal the disposition of exons around the outside of a chromosome territory core and away from the nuclear periphery

Assessment of Virally Vectored Autoimmunity as a Biocontrol Strategy for Cane Toads

BACKGROUND: The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner. METHODOLOGY/PRINCIPAL FINDINGS: The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads. A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival. In B. marinus we established for the first time that the switch from tadpole to adult globin exists. The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures. However, we were unable to detect any differences between treated and control animals. Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs. CONCLUSIONS/SIGNIFICANCE: While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis. The short development time of B. marinus tadpoles may preclude this approach

What You Find Depends on How You Measure It: Reactivity of Response Scales Measuring Predecisional Information Distortion in Medical Diagnosis

“Predecisional information distortion” occurs when decision makers evaluate new information in a way that is biased towards their leading option. The phenomenon is well established, as is the method typically used to measure it, termed “stepwise evolution of preference” (SEP). An inadequacy of this method has recently come to the fore: it measures distortion as the total advantage afforded a leading option over its competitor, and therefore it cannot differentiate between distortion to strengthen a leading option (“proleader” distortion) and distortion to weaken a trailing option (“antitrailer” distortion). To address this, recent research introduced new response scales to SEP. We explore whether and how these new response scales might influence the very proleader and antitrailer processes that they were designed to capture (“reactivity”). We used the SEP method with concurrent verbal reporting: fifty family physicians verbalized their thoughts as they evaluated patient symptoms and signs (“cues”) in relation to two competing diagnostic hypotheses. Twenty-five physicians evaluated each cue using the response scale traditional to SEP (a single response scale, returning a single measure of distortion); the other twenty-five did so using the response scales introduced in recent studies (two separate response scales, returning two separate measures of distortion: proleader and antitrailer). We measured proleader and antitrailer processes in verbalizations, and compared verbalizations in the single-scale and separate-scales groups. Response scales did not appear to affect proleader processes: the two groups of physicians were equally likely to bolster their leading diagnosis verbally. Response scales did, however, appear to affect antitrailer processes: the two groups denigrated their trailing diagnosis verbally to differing degrees. Our findings suggest that the response scales used to measure information distortion might influence its constituent processes, limiting their generalizability across and beyond experimental studies