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Inflammatory bowel disease (IBD) chronicity results from memory T helper cell (Tmem) reactivation. Identifying patient-specific immunotypes is crucial for tailored treatment. We conducted a comprehensive study integrating circulating immune proteins and circulating Tmem, with intestinal tissue histology and mRNA analysis, in therapy-naïve pediatric IBD (Crohn's disease, CD: n = 62; ulcerative colitis, UC: n = 20; age-matched controls n = 43), and after 10-12 weeks' induction therapy. At diagnosis, plasma protein profiles unveiled two UC and three CD clusters with distinct disease courses. UC patients displayed unchanged circulating Tmem, while CD exhibited increased frequencies of gut-homing ex-Th17, known for high IFN-γ production. UC#2 had elevated Th17/neutrophil-pathway-related proteins and severe disease, with higher endoscopic and histological damage and Th17/neutrophil infiltration. Although both UC#1 and UC#2 responded to therapy, UC#2 required earlier immunomodulation. CD#3 had lower plasma protein concentrations, especially IFN-γ pathway proteins, fewer gut-homing ex-Th17 and clinically milder disease, confirmed by intestinal gene expression. CD#1 and CD#2 had comparably high Th1-related immune profiles, but CD#1 exhibited higher concentrations of proteins previously associated with poorer prognosis. Both CD clusters responded to induction therapy, with similar one-year outcomes. This study highlights feasibility of discriminating patient-specific immunotypes in IBD, advancing our understanding of immune pathogenesis, needed for tailored treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Determination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND)., Methods: Fifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex., Results: Subjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners., Conclusions: A consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.

This review focusses on impact of a better knowledge of pathogenic mechanisms of Marfan and related disorders on their treatment strategies. It was long believed that a structural impairment formed the basis of Marfan syndrome as deficiency in the structural extracellular matrix component, fibrillin-1 is the cause of Marfan syndrome. However, the study of Marfan mouse models has revealed the strong involvement of the transforming growth factor-β signalling pathway in the pathogenesis of Marfan. Similarly, this pathway was demonstrated to be key in the pathogenesis of Loeys-Dietz and Shprintzen-Goldberg syndrome. The elucidation of the underlying pathogenic mechanisms has led to new treatment strategies, targeting the overactive TGF-β pathway. Various clinical trials are currently investigating the potential new treatment options. A meta-analysis will contribute to a better understanding of the various trial results., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Effects of conventional (4°C, air velocity 0·5 m/s) and forced chilling at -5°C (120 min) or -30°C (30 min) with air velocities of 1, 2 or 4 m/s, followed by conventional chilling till 24 h post mortem on temperatures, meat quality and weight losses, were studied. Experiments were carried out in six batches of six slaughter pigs each (crossbred gilts, weighing 105-110 kg. The subcutaneous temperature decreased very rapidly to values below 0°C when 'ultra' rapid chilling (-30°C) at high air velocities (4 m/s was used. Immediately after rapid chilling, when the carcasses were railed into a conventional chiller, the subcutaneous temperature increased above the air temperature, after which the decline in temperature was continued. Temperature inside the biceps femoris muscle decreased from the start of chilling rather slowly according to an asymptotic curve until ultimate values of 4°C were reached. Theoretically calculated temperatures during slaughter and chilling were comparable with the measured values; indicating that a finite-element calculation method in combination with a cylindrical model for heat transport can be used to predict muscle temperatures for various chilling regimes. Losses in carcass weight, 24 h after conventional and forced chilling at -5°C, were about 2%. After 'ultra' rapid chilling (-30°C) the losses were reduced to 1·3% when air velocity was increased to 4 m/s. Meat quality of the longissimus lumborum muscle was not significantly affected by the various chilling regimes except for the variables related to tenderness. The Warner-Bratzler shear forces were higher (P < 0·05) together with shorter sarcomere lengths (P < 0·10) after 'ultra' rapid chilling at a high (4 m/s) air velocity, indicating an increased risk of cold shortening.

Scalding of pig carcasses (n = 34) at 60°C for a period of at least 5·5 to 7·5 min gave satisfactory dehairing results, with the exception of autumn hair for which a longer period (9 mins) was required. Temperature curves were recorded for a subcutaneous position in the ham (n = 26) between the rind and the underlying fat layer. These showed a curve starting at about 30·8°C and increasing to an asymptotic value of 53°C during scalding. Results of calculations with a finite element model of a flat layer of muscle covered with a layer of 1·0 cm fat broadly showed the same temperature increase at about 0·5 cm below the surface as the actual values measured. Immediately after dehairing, about 1·5 mins after finishing scalding, the subcutaneous temperature had already dropped to 46·1 ± 3·0°C, which was considerably higher than the muscle temperature at the same position at a depth of 5 cm under the skin (40·6°C). The heat removal and temperatures during the cooling period after scalding were also calculated. It can be concluded that the increase in temperature due to scalding has only a minor influence on muscle temperature and that meat quality (pH, FOP) is not affected., (Copyright © 1993. Published by Elsevier Ltd.)