The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes.

Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.

Local antibiotic treatment with calcium sulfate as carrier material improves the outcome of debridement, antibiotics, and implant retention procedures for periprosthetic joint infections after hip arthroplasty - a retrospective study.

Purpose: Debridement, antibiotics, and implant retention (DAIR) is an established treatment modality in periprosthetic joint infections (PJIs), but success rates vary. This study compared the success of DAIR for PJIs after a total hip arthroplasty (THA), with or without local antibiotic delivery with CaSO 4 as the carrier material. Methods: A retrospective review of DAIR for PJIs after THA performed between 2010 and 2018, including 41 patients is conducted. A total of 27 patients were treated by DAIR with local antibiotics with CaSO 4 as the carrier material, and 14 patients were treated by a standard DAIR. The endpoints were treatment failure, defined as the need for a reoperation, either a second DAIR or a prosthesis removal or exchange due to persistent or recurrent infection, the initiation of a long-term suppressive antibiotic treatment, or death related to infection. Results: Considering any reoperation as an outcome, 11 of 14 cases treated without AB-CaSO 4 (79 %) and 4 of the 27 cases treated with AB-CaSO 4 failed (15 %). Considering revision as an outcome, 9 out of 14 cases treated without AB-CaSO 4 (64 %) and 4 of the 27 cases treated with AB-CaSO 4 (15 %) failed. A Kaplan-Meier survival analysis showed that local antibiotic delivery with CaSO 4 as the carrier material led to a significantly longer infection-free survival, considering any surgical revision ( p < 0.0001 ; hazard ratio 8.9 (95 % CI 2.8-28.2)) or revision with component exchange ( p = 0.0015 ; hazard ratio 5.6 (95 % CI 1.7-18.2)) as the endpoint. Conclusion: The addition of local antibiotics with CaSO 4 as the carrier material to DAIR for PJIs after THA significantly increases success rates, such as infection-free survival, any reoperation, and revision with component exchange in particular.

Autologous lipotransfer for bone defects secondary to osteomyelitis: A report of a novel method and systematic review of the literature.

Autologous bone grafting is the gold standard in patients with bone defects but is associated with significant pain and donor site morbidity. Autologous lipotransfer (fat grafting or lipofilling) has become very popular in the therapy of chronic wounds. Mesenchymal stem cells from adipose tissue are known for their regenerative, reparative, and immunomodulatory effects. This case study and review evaluates the use of autologous lipotransfer for chronic osteomyelitis in a 26-year-old patient. A 26-year-old female suffering from chronic tibial osteomyelitis was initially treated with surgical debridement and antibiotics followed by lipoharvest and autologous lipofilling. MRI and computed tomography scans were performed at 2 and 6 weeks and 6 months postoperatively. A formal systematic review of clinical trials investigating autologous lipotransfer for osteomyelitis was conducted. The patient remained asymptomatic without recurrence, and the bone defect cavity showed vascularised adipose tissue after 6 weeks, with early signs of osteogenesis. The highest foot and ankle disability index was 100. The systematic review identified 266 studies after duplicates were removed. After screening for eligibility, seven manuscripts were further assessed, with none meeting the inclusion criteria. This is the first study to report the successful use of autologous lipotransfer with early signs of osteogenesis in a patient suffering from chronic osteomyelitis. Autologous lipotransfer is relatively simple, safe, and minimally invasive, making it a potential alternative to current treatments. Further research is required to assess the safety, feasibility, and efficacy of autologous fat grafting and the mechanism of osteogenesis.

Agreeableness as Predictor of Induced Scratching in Patients with Atopic Dermatitis: A Replication Study.

In patients with atopic dermatitis agreeableness and public self-consciousness have previously been shown to be significant predictors of induced scratching, while depression was significantly related to induced itch. This study aimed to replicate these findings. Itch and scratching were induced by videos of crawling insects or skin diseases. Induced itch was measured using a visual analogue scale. Scratching behavior was evaluated by two raters. Psychological variables were assessed using validated questionnaires. Induced scratching could be predicted significantly by agreeableness (corrected R2 = 15.5% or 38 % after exclusion of one outlier): Patients scoring low on agreeableness showed a higher increase in scratch movements than patients scoring high on this scale. No associations between induced scratching/itch and public self-consciousness/depression were found. One clinical implication that arises from this study could be to offer patients scoring low on agreeableness certain psychological interventions.

Dupuytren Disease: Is There Enough Comprehensive Patient Information on the Internet?

BACKGROUND: Dupuytren disease is a chronic nonmalign fibroproliferative disorder that causes finger contractures via proliferation of new tissue under the glabrous skin of the hand, resulting in multiple functional limitations for the patient. As many surgical therapy options exist, patients suffering from this condition actively search for information in their environment before consulting a health professional. OBJECTIVE: As little is known about the quality of Web-based patient information, the aim of this study was to conduct its systematic evaluation using a validated tool. METHODS: A total of 118 websites were included, and qualitative and quantitative assessment was performed using the modified Ensuring Quality Information for Patients (EQIP) tool. This standardized and reproducible tool consists of 36 items to assess available information in three categories: contents, identification, and structure data. Scientific data with restricted access, duplicates, and irrelevant websites were not included. RESULTS: Only 32 websites addressed more than 19 items, and the scores did not significantly differ among the website developers. The median number of items from the EQIP tool was 16, with the top websites addressing 28 out of 36 items. The quality of the newly developed websites did not increase with passing time. CONCLUSIONS: This study revealed several shortcomings in the quality of Web-based information available for patients suffering from Dupuytren disease. In the world of continuously growing and instantly available Web-based information, it is the health providers' negligence of the last two decades that there are very few good quality, informative, and educative websites that could be recommended to patients.