11 research outputs found

    Using observational facial descriptors to infer pain in persons with and without dementia

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    Abstract Background For patients with advanced dementia, pain diagnosis and assessment requires observations of pain-indicative behavior by others. One type of behavior that has been shown to be a promising candidate is the facial response to pain. To further test how pain-indicative facial responses are, we investigated the predictive power of observational facial descriptors to (i) predict the self-report of pain and (ii) to differentiate between non-painful and painful conditions. In addition, the expertise of the observers (nurses vs. healthy controls) and the cognitive status of the observed (dementia vs. cognitively healthy) were considered. Methods Overall 62 participants (32 nurses and 30 control subjects) watched 40 video-clips, showing facial expressions of older individuals with and without dementia during non-painful and painful pressure stimulation. After each clip, participants were asked to rate the videos using commonly used facial descriptors of pain and also to provide global pain estimate ratings of how much pain the observed individual might have experienced. Results Out of the 12 facial descriptors used, only 7 were able to differentiate between non-painful and painful conditions. Moreover, participants were better in predicting the pain self-report of the observed individuals when using facial descriptors than when using global pain estimates. Especially, the anatomically-orienting descriptors (e.g. opened mouth, narrowing eyes) showed greatest predictive power. Results were not affected by pain-expertise of the observers (nurses vs. control subjects) or diagnostic status of the observed (patients with dementia vs. cognitively unimpaired subjects). Conclusions The fine-grained and specific observation of facial responses to acute pain appeared to provide valid indication of pain that is not compromised when patients with dementia are observed. The regular professional training does not put nurses at advantage to detect pain via facial responses

    Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency

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    Inherited CARMIL2 deficiency underlies infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation. CARMIL2 deficiency impairs CD28 signaling only partially in T cells. The comparison of CARMIL2 and CD28 deficiency in humans suggests that CARMIL2 governs immunological pathways beyond CD28. Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-kappa B but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4(+) and CD8(+) memory T cells and CD4(+) T(REG)s. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4(+) T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28

    Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors

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    Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct reprogramming towards renal cells remains an unmet challenge. Here, we identify renal cell fate-inducing factors on the basis of their tissue specificity and evolutionarily conserved expression, and demonstrate that combined expression of Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells (iRECs). iRECs exhibit epithelial features, a global gene expression profile resembling their native counterparts, functional properties of differentiated renal tubule cells and sensitivity to nephrotoxic substances. Furthermore, iRECs integrate into kidney organoids and form tubules in decellularized kidneys. Our approach demonstrates that reprogramming factors can be identified by targeted in silico analysis. Renal tubular epithelial cells generated ex vivo by forced expression of transcription factors may facilitate disease modelling, drug and nephrotoxicity testing, and regenerative approaches