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Summary Background Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema. Objective We investigated whether dietary supplementation of infants with eczema at age 3-6 months with L actobacillus paracasei CNCM I-2116 or B ifidobacterium lactis CNCM I-3446 had a treatment effect or altered allergic disease progression. Methods Primary outcome included eczema severity ( SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life ( IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen-sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 ( SCORAD≥10, consuming ≥200 mL standard formula/day) were randomized to daily supplements containing L . paracasei or B . lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed ( n = 22) and the other, standard formula-fed ( n = 49). Trial number: ISRCTN41490500. Results Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period ( SCORAD-score pre-/post-intervention: B . lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.4-16.6]; L . paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4-30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups. Conclusion and Clinical Relevance We found no benefit from supplementation with B . lactis or L . paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years. [ABSTRACT FROM AUTHOR]

Reflex sympathetic dystrophy (RSD), an unusual diagnosis in general paediatrics, is well recognised by paediatric rheumatologists. This study reports the presentation and the clinical course of 46 patients (35 female, age range 8-15.2) with RSD. The patients saw professionals from an average of 2.3 specialties (range 1-5). Twenty five (54%) had a history of trauma. Median time to diagnosis was 12 weeks (range 1-130). Many children had multiple investigations and treatments. Once diagnosis was made, treatment followed with physiotherapy and analgesics. Median time to recovery was seven weeks (range 1-140), with 27.5% relapsing. Nine children required assessment by the child and adolescent psychiatry team. This disease, though rare, has significant morbidity and it is therefore important to raise clinicians' awareness of RSD in childhood. Children with the condition may then be recognised and referred for appropriate management earlier, and spared unnecessary investigations and treatments which may exacerbate the condition. [ABSTRACT FROM AUTHOR]

This article cites a study on a 59-year-old man presented with a 4-week history of an eruption on his upper limbs and trunk, without a history of sun exposure. He had rheumatoid arthritis and had been commenced on leflunomide 6 weeks before the rash appeared. Subacute cutaneous lupus erythematosus (SCLE) has been associated with the use of a number of structurally disparate drugs, including thiazides, terbinafine and calcium blockers. Leflunomide, as an inhibitor of pyrimidine synthesis, has a different mechanism of action to other disease-modifying antirheumatic drugs. It is currently licensed for the treatment of moderate to severe active rheumatoid arthritis.

Background Tuberculosis cases in Greater Manchester (GM) have increased annually since 2004. The Paediatric TB clinic at Royal Manchester Children's Hospital has grown since its inception in 2004, but it is unclear as to whether this is due to a true increase in cases or a change in referral patterns. At the same time the uptake of BCG vaccine is sub-optimal. Objectives To investigate the incidence, epidemiology and BCG vaccination eligibility and status of childhood tuberculosis cases in GM between 2006 and 2010. Methods All children (≤16 years) notified through the Enhanced Tuberculosis Surveillance System between 1 January 2006 and 31 December 2010 were identified. Vaccination records were obtained from Primary Care Child Health Systems. Missing data were supplemented with examination of case-notes. Eligibility for BCG vaccine was determined by place of birth and ethnicity. Results 215 children (89 male; mean age 8.8 years) were notified over the 5 years. A rise of 64.5% in overall number of cases was reported from 2006 to 2010. Pakistanis comprised 39.1% of TB cases, Black Africans 28.8% and white British 14.9%. The majority of children were UK-born (60.5%). Of non-UK born cases 67.1% entered the UK within 2 years of their diagnosis. Of 130 UK-born children, 111 were deemed eligible for BCG vaccination. Of these 85 (75.6%) received the vaccine. Of 85 children born outside the UK, vaccination status could not be determined in 8, and one child was ineligible for vaccination. Vaccination was confirmed in 53% of non-UK born children (BCG record or BCG scar). In children who had not received BCG, although the number of cases was very small, a threefold higher risk of more severe forms of infection (military, CNS involvement) was identified. Conclusion There has been a significant rise in incidence of Paediatric TB in GM over the last 5 years. The reason for this remains unclear. However, BCG vaccination uptake rates were poor (75% of UK born individuals and 67% overall). Systems for identifying eligible children and immunising them need to be reviewed and strengthened both for high risk neonates and children entering the country. [ABSTRACT FROM AUTHOR]

Background Results of studies investigating the association between obesity and asthma, atopy and lung function have been inconsistent, in part due to the limitation of BMI in evaluating body adiposity. Objectives To investigate the association between obesity and asthma, wheeze, atopy, lung function and bronchial hyper-responsiveness in children at age 11 years using bioelectrical impedance (BIA) and BMI. Methods Children from the unselected birth cohort study attending follow-up at age 11 years had percent body fat (PBF) and truncal fat (PTF) assessed using BIA (Tanita BC-418). Weight and height were also measured. Current asthma and wheeze were derived from a validated respiratory questionnaire. Atopy was ascertained using skin prick testing. Lung function was assessed using spirometry and bronchial hyper-responsiveness by 5-step methacholine challenge according to ATS guidelines. Results 646 children (339 male) completed anthropometric measurements. BMI z-score, PBF and PTF were associated with current wheeze (OR [95% CI]: 1.27 [1.03 to 1.57], p=0.03; 1.04 [1.00, 1.08], p=0.04; 1.04 [1.00, 1.08], p=0.04 respectively). BMI z-score, PBF and PTF were also associated with current asthma (1.30 [1.04 to 1.63], p=0.02; 1.04 [1.00 to 1.08], p=0.06; 1.04 [1.00 to 1.08], p=0.04). However, the effect of PBF and PTF appeared strongest in girls (PBF: 1.12 [1.04 to 1.20], p=0.004; PFT: 1.11[1.04 to 1.20], p=0.003; p=0.05 and p=0.04 for interactions respectively). Children were defined as normal or overweight according to BMI (23% overweight) and PBF (29.8% overweight) cut-offs; overweight children had an increased risk of asthma (BMI: 1.73 [0.99 to 3.02], p=0.05; PBF: 2.09 [1.23 to 3.32] p=0.006). Thiswas highly significant in girls (BMI: 3.34 [1.43 to 7.83], p=0.005; PBF: 4.74 [1.98 to 11.35], p<0.001; p=0.05 and p=0.02 for interactions respectively). Increasing BMI was associated with increases in both FEV1 and FVC but reductions in FEV1: FVC ratios. This associationwas again stronger in girls than boys.No associations between adiposity and atopy or bronchial hyper-responsiveness were found. Conclusion Higher BMI z-score, PBF and PTF were associated with increased risks of wheeze and asthma. This effect was stronger in girls. BIA measurements appeared to have stronger associations in girls with outcomes than BMI. This may reflect the ability of BIA to measure adiposity more accurately than BMI. [ABSTRACT FROM AUTHOR]

Background: In a population-based birth cohort, we aimed to identify longitudinal trajectories of atopic dermatitis (AD) during childhood using data from different sources (validated questionnaires and healthcare records). We investigated the impact of different AD definitions on such trajectories and their relationships with various risk factors., Methods: Of the 1184 children born into the study, 1083 had information on current AD for at least three follow-ups from birth to age 11 years and were included in the analysis for parentally reported AD (PRAD). Data were transcribed from healthcare records for 916 of 1184 children for the analysis of doctor-diagnosed AD (DDAD). We also derived a composite definition of AD (CDAD) (at least two of the following: PRAD, DDAD, current use of AD treatment). Using latent class analysis (LCA), we determined longitudinal profiles of AD using the three definitions. Filaggrin (FLG) genotype data were available for 803 white participants., Results: For PRAD, LCA identified four AD classes ('no AD', 'persistent', 'early-onset remitting' and 'late-onset'). For DDAD and CDAD, the optimal number of phenotypes was three ('no AD', 'persistent' and 'early-onset remitting'). Although AD classes at population level appeared similar in different models, a considerable proportion of children (n = 485, 45%) moved between classes. The association with FLG genotype, atopic diseases and early-life risk factors was inconsistent across different definitions, but the association with oral food challenge-confirmed peanut allergy was similar, with a nine- to 11-fold increase among children in the persistent AD class. In a CDAD model, compared with the early-onset remitting class, those with persistent AD were significantly more likely to have (at age 3 years) moderate/severe AD, polysensitization and current wheeze, and were less likely to have been breastfed., Conclusions: Standardized composite definitions of AD may help to define AD cases with more precision and identify more consistent long-term trajectories., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Ocean acidification is occurring in conjunction with warming and deoxygenation as a result of anthropogenic greenhouse gas emissions. Multistressor experiments are critically needed to better understand the sensitivity of marine organisms to these concurrent changes. Growth and survival responses to acidification have been documented for many marine species, but studies that explore underlying physiological mechanisms of carbon dioxide (CO 2 ) sensitivity are less common. We investigated oxygen consumption rates as proxies for metabolic responses in embryos and newly hatched larvae of an estuarine forage fish (Atlantic silverside, Menidia menidia ) to factorial combinations of CO 2 ×temperature or CO 2 ×oxygen. Metabolic rates of embryos and larvae significantly increased with temperature, but partial pressure of CO 2 ( P CO 2 ) alone did not affect metabolic rates in any experiment. However, there was a significant interaction between P CO 2  and partial pressure of oxygen ( P O 2 ) in embryos, because metabolic rates were unaffected by P O 2  level at ambient P CO 2 , but decreased with declining P O 2  under elevated P CO 2 For larvae, however, P CO 2  and P O 2  had no significant effect on metabolic rates. Our findings suggest high individual variability in metabolic responses to high P CO 2 , perhaps owing to parental effects and time of spawning. We conclude that early life metabolism is largely resilient to elevated P CO 2  in this species, but that acidification likely influences energetic responses and thus vulnerability to hypoxia., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Background: There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD), and no uniform clinical definition., Objectives: To investigate to what extent operational definitions of AD cause fluctuation in the prevalence estimates and the associated risk factors., Methods: We first reviewed the operational definitions of AD used in the literature. We then tested the impact of the choice of the most common definitions of 'cases' and 'controls' on AD prevalence estimates and associated risk factors (including filaggrin mutations) among children aged 5 years in two population-based birth cohorts: the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford. Model performance was measured by the percentage of children within an area of clinical indecision (defined as having a posterior probability of AD between 25% and 60%)., Results: We identified 59 different definitions of AD across 45 reviewed studies. Of those, we chose four common 'case' definitions and two definitions of 'controls'. The prevalence estimates using different case definitions ranged between 22% and 33% in MAAS, and between 12% and 22% in Ashford. The area of clinical indecision ranged from 32% to 44% in MAAS and from 9% to 29% in Ashford. Depending on the case definition used, the associations with filaggrin mutations varied, with odds ratios (95% confidence intervals) ranging from 1·8 (1·1-2·9) to 2·2 (1·3-3·7) in MAAS and 1·7 (0·8-3·7) to 2·3 (1·2-4·5) in Ashford. Associations with filaggrin mutations also differed when using the same 'case' definition but different definitions of 'controls'., Conclusions: Use of different definitions of AD results in substantial differences in prevalence estimates, the performance of prediction models and association with risk factors. What's already known about this topic? There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD) and no uniform clinical definition. This results in different definitions utilized in AD studies, raising concerns on the generalizability of the results and comparability across different studies. What does this study add? This study has shown that different definitions of 'cases' and 'controls' have major impacts upon prevalence estimates and associations with risk factors, including genetics, in two population-based birth cohorts. These findings suggest the importance of developing a consensus on AD definitions of both 'controls' and 'cases' to minimize biases in studies., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

We propose a novel method for defining patterns of contacts present in protein-protein complexes. A new use of the traditional contact maps (more frequently used for representation of the intra-chain contacts) is presented for analysis of inter-chain contacts. Using an algorithm based on image processing techniques, we can compare protein-protein interaction maps and also obtain a dissimilarity score between them. The same algorithm used to compare the maps can align the contacts of all the complexes and be helpful in the determination of a pattern of conserved interactions at the interfaces. We present an example for the application of this method by analyzing the pattern of interaction of bovine pancreatic trypsin inhibitors and trypsins, chymotrypsins, a thrombin, a matriptase, and a kallikrein - all classified as serine proteases. We found 20 contacts conserved in trypsins and chymotrypsins and 3 specific ones are present in all the serine protease complexes studied. The method was able to identify important contacts for the protein family studied and the results are in agreement with the literature.

The nucleotide sequence for a surface-associated protein (A. Joe, A. Yamamoto, and B. C. McBride, Infect. Immun. 61:3294-3303, 1993) of Porphyromonas gingivalis was determined. The structural gene comprises 1,338 bp and codes for a protein of 445 amino acids. The deduced molecular weight of the protein is 49,243. A data base search for homologous proteins revealed significant sequence similarity to the subunit protein of glutamate dehydrogenases (GDHs) isolated from various sources. This protein, which was previously labelled PgAg1, will now be called GDH. Recombinant GDH was purified to homogeneity, and native GDH was partially purified from P. gingivalis. Both preparations exhibited NAD-dependent GDH activity. Intact P. gingivalis and an extract of cell surface components also demonstrated NAD-dependent GDH activity. To help elucidate the role of this protein, an isogenic mutant of P. gingivalis lacking the GDH protein was generated by deletion disruption. Biological characterization of the mutant strain, P. gingivalis E51, demonstrated complete loss of GDH activity. Immunogold bead labelling of intact cells showed that GDH was no longer present on the surface of the bacterial cell. The GDH-negative mutant displayed impaired cell growth, as demonstrated by an increased generation time and an inability to grow to the same cell density as the parent.