Selenoproteins Are Essential for Proper Keratinocyte Function and Skin Development

Dietary selenium is known to protect skin against UV-induced damage and cancer and its topical application improves skin surface parameters in humans, while selenium deficiency compromises protective antioxidant enzymes in skin. Furthermore, skin and hair abnormalities in humans and rodents may be caused by selenium deficiency, which are overcome by dietary selenium supplementation. Most important biological functions of selenium are attributed to selenoproteins, proteins containing selenium in the form of the amino acid, selenocysteine (Sec). Sec insertion into proteins depends on Sec tRNA; thus, knocking out the Sec tRNA gene (Trsp) ablates selenoprotein expression. We generated mice with targeted removal of selenoproteins in keratin 14 (K14) expressing cells and their differentiated descendents. The knockout progeny had a runt phenotype, developed skin abnormalities and experienced premature death. Lack of selenoproteins in epidermal cells led to the development of hyperplastic epidermis and aberrant hair follicle morphogenesis, accompanied by progressive alopecia after birth. Further analyses revealed that selenoproteins are essential antioxidants in skin and unveiled their role in keratinocyte growth and viability. This study links severe selenoprotein deficiency to abnormalities in skin and hair and provides genetic evidence for the role of these proteins in keratinocyte function and cutaneous development

Proteoglycan-4 Regulates Fibroblast to Myofibroblast Transition and Expression of Fibrotic Genes in the Synovium

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo. Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or isotype control antibodies and cellular uptake of rhPRG4 was determined following a 30-min incubation and α-SMA expression following a 24-h incubation. HEK-TGF-β cells were treated with TGF-β ± rhPRG4 and Smad3 phosphorylation was determined using immunofluorescence and TGF-β/Smad pathway activation was determined colorimetrically. We probed for stress fibers and focal adhesions (FAs) in TGF-β-treated murine fibroblasts and fibroblast migration was quantified ± rhPRG4. Synovial expression of fibrotic markers: α-SMA, collagen type-I, and PLOD2 in Prg4 gene-trap (Prg4GT) and recombined Prg4GTR animals were studied at 2 and 9 months of age. Synovial expression of α-SMA and PLOD2 was determined in 2-month-old Prg4GT/GT&Cd44−/− and Prg4GTR/GTR&Cd44−/− animals. Results: PRG4 reduced α-SMA content in OA synoviocytes (p \u3c 0.001). rhPRG4 was internalized by OA synoviocytes via CD44 and CD44 neutralization attenuated rhPRG4’s antifibrotic effect (p \u3c 0.05). rhPRG4 reduced pSmad3 signal in HEKTGF- β cells (p \u3c 0.001) and TGF-β/Smad pathway activation (p \u3c 0.001). rhPRG4 reduced the number of stress fiberpositive myofibroblasts, FAs mean size, and cell migration in TGF-β-treated NIH3T3 fibroblasts (p \u3c 0.05). rhPRG4 inhibited fibroblast migration in a macrophage and fibroblast co-culture model without altering active or total TGF-β levels. Synovial tissues of 9-month-old Prg4GT/GT animals had higher α-SMA, collagen type-I, and PLOD2 (p \u3c 0.001) content and Prg4 re-expression reduced these markers (p \u3c 0.01). Prg4 re-expression also reduced α-SMA and PLOD2 staining in CD44-deficient mice. Conclusion: PRG4 is an endogenous antifibrotic modulator in the joint and its effect on myofibroblast formation is partially mediated by CD44, but CD44 is not required to demonstrate an antifibrotic effect in vivo

Starting point for benchmarking outcomes and reporting of pituitary adenoma surgery within the European Reference Network on Rare Endocrine Conditions (Endo-ERN): results from a meta-analysis and survey study

Objective: The European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, inc luding care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pi tuitary adenoma within Endo-ERN. Design and Methods: Systematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by refere nce centers on their current surgical practice. Results: A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6- represented countries published 48 articles. Remission rates we re 50% (95% CI: 42–59) for patients with acromegaly, 68% (95% CI: 60–75) for Cushing’s disease, and 53% (95% CI: 39–66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37–61%) of patients and visual improvement in 78% (95% CI: 68–87). Mort ality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11–23), transient diabetes insipidus in 12% (95 % CI: 6–21), permanent diabetes insipidus in 4% (95% CI: 3–6), syndrome of inappropria te secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5–14), severe epist axis in 2% (95% CI: 0–4), and cerebrospinal fluid leak in 4% (95% CI: 2–6). Thirty-five (81 %) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon. Conclusion: The results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the hete rogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries

Ultrasound-guided placement of central venous catheters: A comprehensive guide for the clinician

Background: Using ultrasound as a guidance tool during central venous catheter placement has repeatedly been shown to improve procedural safety. More recent evidence has shown its potential as a diagnostic modality to detect placement-associated complications. A protocol combining these modalities is lacking. This article uses the Indication, Acquisition, Interpretation and Medical decision-making (I-AIM) model, common to other ultrasound protocols, to provide a systematic ultrasound approach to guide central venous catheter placement and assess potential related complications. It is part of a larger series published in this journal. Methods: Relevant articles were found in a thorough search in PubMed using the MeSH terms: “diagnostic imaging” or “ultrasonography” or “sonography” and “central venous catheter” or “central venous cannulation” and “complications” or “placement procedure”. Studies conducted on patients younger than 18 years and studies conducted in animals were excluded. Two independent researchers evaluated the articles for relevance and quality. The results of the various studies were used to create the following structured ultrasound approach. Recommended approach: Following the I-AIM model, acquiring the most valuable images is subdivided into patient, probe, picture and protocol considerations. Ultrasound guidance during central venous catheter placement should be conducted in four steps: pre-cannulation, confirming patency, dynamic guidance during insertion, and confirmation of intravenous central venous catheter position. After these steps, ultrasound should be used in the diagnostic evaluation of malposition and iatrogenic pneumothorax. Conclusions: This model provides a comprehensive and ready to use ultrasound approach to guide central venous catheter placement and assess potential placement associated complications

Reversibele tandverkleuring tijdens oraal gebruik van antibiotica

From January 1991 until June 1995. 25 cases were reported to the Netherlands Pharmacovigilance Foundation LAREB of yellow to brown tooth discoloration following the oral use of medication; 21 cases (84%) involved antibiotics, of which 14 were amoxicillin. 17/21 patients were children, with ages ranging from 1 to 10 years. All children used liquid formulations (suspension or solutabs). Discoloration was reversible in all cases, but had a protracted course in some. Presumably a pigment precipitated on (and not in) the teeth, but the nature of the pigment was uncertain

Reversible tooth discoloration during oral use of antibiotics

From January 1991 until June 1995. 25 cases were reported to the Netherlands Pharmacovigilance Foundation LAREB of yellow to brown tooth discoloration following the oral use of medication; 21 cases (84%) involved antibiotics, of which 14 were amoxicillin. 17/21 patients were children, with ages ranging from 1 to 10 years. All children used liquid formulations (suspension or solutabs). Discoloration was reversible in all cases, but had a protracted course in some. Presumably a pigment precipitated on (and not in) the teeth, but the nature of the pigment was uncertain.</p

Ultrasound to Detect Central Venous Catheter Placement Associated Complications: A Multicenter Diagnostic Accuracy Study

BACKGROUND: Mechanical complications arising after central venous catheter placement are mostly malposition or pneumothorax. To date, to confirm correct position and detect pneumothorax, chest x-ray film has been the reference standard, while ultrasound might be an accurate alternative. The aim of this study was to evaluate diagnostic accuracy of ultrasound to detect central venous catheter malposition and pneumothorax. METHODS: This was a prospective, multicenter, diagnostic accuracy study conducted at the intensive care unit and postanesthesia care unit. Adult patients who underwent central venous catheterization of the internal jugular vein or subclavian vein were included. Index test consisted of venous, cardiac, and lung ultrasound. Standard reference test was chest x-ray film. Primary outcome was diagnostic accuracy of ultrasound to detect malposition and pneumothorax; for malposition, sensitivity, specificity, and other accuracy parameters were estimated. For pneumothorax, because chest x-ray film is an inaccurate reference standard to diagnose it, agreement and Cohen's κ-coefficient were determined. Secondary outcomes were accuracy of ultrasound to detect clinically relevant complications and feasibility of ultrasound. RESULTS: In total, 758 central venous catheterizations were included. Malposition occurred in 23 (3.3%) out of 688 cases included in the analysis. Ultrasound sensitivity was 0.70 (95% CI, 0.49 to 0.86) and specificity 0.99 (95% CI, 0.98 to 1.00). Pneumothorax occurred in 5 (0.7%) to 11 (1.5%) out of 756 cases according to chest x-ray film and ultrasound, respectively. In 748 out of 756 cases (98.9%), there was agreement between ultrasound and chest x-ray film with a Cohen's κ-coefficient of 0.50 (95% CI, 0.19 to 0.80). CONCLUSIONS: This multicenter study shows that the complication rate of central venous catheterization is low and that ultrasound produces a moderate sensitivity and high specificity to detect malposition. There is moderate agreement with chest x-ray film for pneumothorax. In conclusion, ultrasound is an accurate diagnostic modality to detect malposition and pneumothorax

Ultrasound to detect central venous catheter placement associated complications: A multicenter diagnostic accuracy study

Background: Mechanical complications arising after central venous catheter placement are mostly malposition or pneumothorax. To date, to confirm correct position and detect pneumothorax, chest x-ray film has been the reference standard, while ultrasound might be an accurate alternative. The aim of this study was to evaluate diagnostic accuracy of ultrasound to detect central venous catheter malposition and pneumothorax. Methods: This was a prospective, multicenter, diagnostic accuracy study conducted at the intensive care unit and postanesthesia care unit. Adult patients who underwent central venous catheterization of the internal jugular vein or subclavian vein were included. Index test consisted of venous, cardiac, and lung ultrasound. Standard reference test was chest x-ray film. Primary outcome was diagnostic accuracy of ultrasound to detect malposition and pneumothorax; for malposition, sensitivity, specificity, and other accuracy parameters were estimated. For pneumothorax, because chest x-ray film is an inaccurate reference standard to diagnose it, agreement and Cohen's κ-coefficient were determined. Secondary outcomes were accuracy of ultrasound to detect clinically relevant complications and feasibility of ultrasound. Results: In total, 758 central venous catheterizations were included. Malposition occurred in 23 (3.3%) out of 688 cases included in the analysis. Ultrasound sensitivity was 0.70 (95% CI, 0.49 to 0.86) and specificity 0.99 (95% CI, 0.98 to 1.00). Pneumothorax occurred in 5 (0.7%) to 11 (1.5%) out of 756 cases according to chest x-ray film and ultrasound, respectively. In 748 out of 756 cases (98.9%), there was agreement between ultrasound and chest x-ray film with a Cohen's κ-coefficient of 0.50 (95% CI, 0.19 to 0.80). Conclusions: This multicenter study shows that the complication rate of central venous catheterization is low and that ultrasound produces a moderate sensitivity and high specificity to detect malposition. There is moderate agreement with chest x-ray film for pneumothorax. In conclusion, ultrasound is an accurate diagnostic modality to detect malposition and pneumothorax