CASZ1 Is Essential for Skin Epidermal Terminal Differentiation.

The barrier function of skin epidermis is crucial for our bodies to interface with the environment. Because epidermis continuously turns over throughout the lifetime, this barrier must be actively maintained by regeneration. Although several transcription factors have been established as essential activators in epidermal differentiation, it is unclear whether additional factors remain to be identified. In this study, we show that CASZ1, a multi zinc-finger transcription factor previously characterized in nonepithelial cell types, shows highest expression in skin epidermis. CASZ1 expression is upregulated during epidermal terminal differentiation. In addition, CASZ1 expression is impaired in several skin disorders with impaired barrier function, such as atopic dermatitis, psoriasis, and squamous cell carcinoma. Using transcriptome profiling coupled with RNA interference, we identified 674 differentially expressed genes with CASZ1 knockdown. Downregulated genes account for 91.2% of these differentially expressed genes and were enriched for barrier function. In organotypic epidermal regeneration, CASZ1 knockdown promoted proliferation and strongly impaired multiple terminal differentiation markers. Mechanistically, we found that CASZ1 upregulation in differentiation requires the action of both the master transcription factor, p63, and the histone acetyltransferase, p300. Taken together, our findings identify CASZ1 as an essential activator of epidermal differentiation, paving the way for future studies understanding of CASZ1 roles in skin disease.

Defining key pharmacist and technician roles in response to a hospital downtime or cyberattack.

The occurrence of ransomware, or "cyberattacks," on hospital institutions has steadily increased in recent years. Pharmacy departments that rely on automation and software applications are greatly affected when those systems are offline. Pharmacy workflow without automation can be manually intensive and unsafe for patients. More challenges may be present if the hospital pharmacy is not prepared for a cyberattack or does not have standardized downtime procedures for such an event. This article describes a specific event that took place at a 350-bed acute care hospital located in the United States during the summer of 2021. The hospital lost access to the electronic health record, admitting and registration system, financial systems, pharmacy information systems, barcode medication administration systems, server for the automated dispensing cabinets or inventory management applications, diversion software, compliance applications, and all clinical decision support tools. The goal is to describe a standardized downtime procedure for medication management by identifying specific pharmacist and technician roles when automated processes are offline.

Use of iPhone technology in improving acetabular component position in total hip arthroplasty.

Improper acetabular cup positioning is associated with high risk of complications after total hip arthroplasty. The aim of our study is to objectively compare 3 methods, namely (1) free hand, (2) alignment jig (Sputnik), and (3) iPhone application to identify an easy, reproducible, and accurate method in improving acetabular cup placement. We designed a simple setup and carried out a simple experiment (see Method section). Using statistical analysis, the difference in inclination angles using iPhone application compared with the freehand method was found to be statistically significant (F[2,51] = 4.17, P = .02) in the "untrained group". There is no statistical significance detected for the other groups. This suggests a potential role for iPhone applications in junior surgeons in overcoming the steep learning curve.

Periprosthetic Bone Remodeling After Novel Short-Stem Neck-Sparing Total Hip Arthroplasty.

BACKGROUND: Short femoral stems have been designed with the aims of reducing proximal bone loss, improving load transfer, and increasing compressive loads at the medial proximal femoral calcar. This study examines bone mineral density (BMD) changes associated with a novel neck sparing short femoral stem design. METHODS: The study was a prospective, single-center, multi-investigator consecutive series, which assessed bone-remodeling changes after insertion of the MSA Stem (Global Orthopaedic Technology). Dual-energy X-ray absorptiometry scans were performed preoperatively and postoperatively at 6, 12, and 24 months assessing the BMD at the 7 Gruen zones. The secondary objectives assessed were the Harris Hip Score, 12-Item Short Form Health Survey preoperatively, and perioperative complications. RESULTS: Thirty-nine total hip arthroplasties were performed on 37 patients, with 27 patients completing the 24-month dual-energy X-ray absorptiometry scan. The overall preoperative baseline BMD was 0.2. At 6 months, the Gruen zone BMD had increased significantly in all zones in comparison to the preoperative mean BMD. Between 6 months and 24 months, there were only slight changes in the Gruen zones, with small gains in zones 1-2 and zones 4-6, with no zone showing a significant decrease. The Harris Hip Score improved from a preoperative mean of 39.7-75.3, whereas the 12-Item Short Form Health Survey score also improved from 32.6 to 49 at 24 months. However, 5 patients had aseptic loosening requiring revision surgery (4 femoral and 1 acetabular component). CONCLUSION: Short-stem neck-sparing femoral stem prosthesis has the capacity to address the stress-shielding problem identified in femoral stems. However, the high early revision rate is a significant issue.

Review of para-articular soft tissue osteochondromas of the knee.

Para-articular osteochondromas (PAOCs) are a rare benign subtype of chondroma that occur in the soft tissues around the joints. Initially hypothesized to be derived from cartilaginous metaplasia, its aetiology and pathogenesis are still not fully understood. This tumour often causes a diagnostic and management dilemma due to similar clinical and histopathological features compared with other pathology. We report the fourth case of PAOC arising from the suprapatella region of the knee joint and review the literature to update our understanding of this tumour. From the data analysed, a distinctive pattern of tumour formation within or adjacent to a fat pad structure was evident, while trauma appears to play a role in its pathogenesis. Histologically, the tumour consists of a cartilage cap, with varying degrees of trabecular bone and endochondral ossification. Importantly, there are no features of nuclear pleomorphism or increased mitotic activity suggestive of a malignant process. All tumours were surgically removed and behaved in a benign fashion without evidence of recurrence. PAOC may often be suspected for more malignant processes; thus, recognition of this entity is important as simple excision is curative.

Loss of cell-surface receptor EphB2 is important for the growth, migration, and invasiveness of a colon cancer cell line.

PURPOSE: In normal colonic epithelium, the receptor tyrosine kinase, EphB2 interacts with ephrinB1 ligand to maintain the integrity and architecture of the colonic crypt. Loss of EphB2 is seen in most colorectal cancers and correlates with poor prognosis. In this study, we investigated the effects of two levels of EphB2 expression on cell migration and invasion in a colon cancer cell line and on the growth of tumour xenografts. METHODS: An EphB2-negative colon cancer cell line (LIM2405) was transfected with a full-length EphB2 cDNA in a vector designed to respond to the drug tetracycline. The effect of two levels of EphB2 expression on the ability of cells to migrate through a porous barrier in response to a chemo-attractant and to invade through artificial basement membranes was tested in vitro. Finally, the effects of two expression levels of EphB2 on tumour growth using an in vivo model of colonic tumour xenograft in a mouse model were assessed. RESULTS: Expression of moderate levels of EphB2 significantly reduced the migration of tumour cells compared to control (p < 0.05, Kruskal-Wallis test). Expression of high levels of EphB2 further reduced migration of tumour cells (p < 0.05, Kruskal-Wallis test). Similarly, expression of EphB2 markedly reduces the invasive ability of tumour cells. The in vivo model of tumour growth showed that tumours with the highest level of EphB2 expression had a reduced risk of reaching a 10-mm size (defined event) compared with the control group (Cox regression, hazard ratio (HR) = 0.052, 95% CI 0.005-0.550; p = 0.014). Tumours derived from EphB2 expressing cells had a significantly reduced number of mitotic figures (p < 0.05) and an increased number of apoptotic cells (p < 0.05) compared to tumours from control cells. CONCLUSION: Even a moderate level of EphB2 expression has effects on tumour cells which results in reduced migration and invasiveness and slows the growth of colonic tumour implants in an in vivo model.