Deficiency of the human cysteine protease inhibitor cystatin M/E causes hypotrichosis and dry skin

Purpose: We aimed to assess the biological and clinical significance of the human cysteine protease inhibitor cystatin M/E, encoded by the CTS6 gene, in diseases of human hair and skin. Methods: Exome and Sanger sequencing was performed to reveal the genetic cause in two related patients with hypotrichosis. Immunohistochemical, biophysical, and biochemical measurements were performed on patient skin and 3D-reconstructed skin from patient-derived keratinocytes. Results: We identified a homozygous variant c.361C>T (p.Gln121*), resulting in a premature stop codon in exon 2 of CST6 associated with hypotrichosis, eczema, blepharitis, photophobia and impaired sweating. Enzyme assays using recombinant mutant cystatin M/E protein, generated by site-directed mutagenesis, revealed that this p.Gln121* variant was unable to inhibit any of its three target proteases (legumain and cathepsins L and V). Three-dimensional protein structure prediction confirmed the disturbance of the protease/inhibitor binding sites of legumain and cathepsins L and V in the p.Gln121* variant. Conclusion: The herein characterized autosomal recessive hypotrichosis syndrome indicates an important role of human cystatin M/E in epidermal homeostasis and hair follicle morphogenesis

Care-resistant behaviour during oral examination in Dutch nursing home residents with dementia

Objective: To assess the occurrence and associations of verbal and non-verbal care-resistant behaviour (CRB) during oral examination by a dental hygienist in nursing home residents with dementia. Background: CRB is a barrier to providing professional oral care and daily oral hygiene care. Understanding the predictors of CRB might help care professionals in learning to anticipate this behaviour. Methods: In this multicentre cross-sectional study signs of verbal and non-verbal CRB were reported during the oral examination. Data collection occurred in the psychogeriatrics wards of 14 different nursing homes in the Netherlands (N = 367). Results: A total of 367 residents were included. CRB was evident in 82 residents (22.3%), of whom 45 (55%) showed verbal and 37 (45%) non-verbal CRB. Associated with CRB were age >85 years, duration of residential stay longer than 2 years, and having Korsakov dementia. Other factors associated with CRB were duration of residential stay (categories “>2 and ≤4 years” or “>4 years”) and having a natural dentition (P =.043-.005, OR = 1.20-1.33, 95% CI = 1.00-8.48). Significant associations for verbal and non-verbal CRB were age between 76 and 85 years, vascular dementia and Korsakov dementia (P =.031-.006, OR =.020-1.49, 95% CI = 0.43-2.15). Conclusion: The occurrence of CRB was 22.3% and was associated with older age and longer duration of residential stay, Vascular and Korsakov dementia and natural dentition