The psychological impact on an orthopaedic outpatient setting in the early phase of the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: World Health Organization declared coronavirus disease-19 (COVID-19) a global pandemic on 11 March 2020, after the coronavirus claimed 4628 lives worldwide. Mental health challenges such as making impossible decisions and working under extreme pressures are expected to be faced by frontline healthcare workers who are directly involved in the care of COVID-19 patients. However, we question if significant stress levels might also be observed in a subspecialty musculoskeletal outpatient department, where staff are not first-line care providers of COVID-19 patients. We hypothesize that these healthcare workers also face significant psychological strain, and we aim to objectively determine the prevalence using a validated caregiver strain index. METHODS: A cross-sectional study was conducted in outpatient musculoskeletal clinics in a tertiary hospital in Singapore. We collected basic demographic data and used a 13-question tool adapted from the validated Caregiver Strain Index (CSI) to measure psychological strain in these healthcare workers. Participants were divided into 2 groups depending on the level of strain experienced. RESULTS: A total of 62 healthcare workers volunteered for this study. There were 32 participants (51.6%) who had 7 or more positive responses (group 1) and the remaining 30 participants (48.4%) were allocated to group 2. There were no significant differences between the two groups in terms of demographic data. "Work adjustments" (74.2%), "changes in personal plans" (72.6%), and finding it "confining" (72.6%) garnered the most positive responses in the questionnaire. On the other hand, "financial concerns" garnered the least positive responses (21.0%). CONCLUSION: The protracted duration of the COVID-19 outbreak and its resultant prolonged adjustments can have unintended consequences of wearing down healthcare resources otherwise allocated to chronic and elective conditions. Countries should ensure that measures are put in place to safeguard the mental well-being of our healthcare workers to avoid needing another reactive strategy in this battle against COVID-19.

A distinct class of plant and animal viral proteins that disrupt mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1.

Many animal viral proteins, e.g., Vpr of HIV-1, disrupt host mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1. However, it is unknown whether plant viruses may use this mechanism in their pathogenesis. Here, we report that the 17K protein, encoded by barley yellow dwarf viruses and related poleroviruses, delays G2/M transition and disrupts mitosis in both host (barley) and nonhost (fission yeast, Arabidopsis thaliana, and tobacco) cells through interrupting the function of Wee1-Cdc25-CDKA/Cdc2 via direct protein-protein interactions and alteration of CDKA/Cdc2 phosphorylation. When ectopically expressed, 17K disrupts the mitosis of cultured human cells, and HIV-1 Vpr inhibits plant cell growth. Furthermore, 17K and Vpr share similar secondary structural feature and common amino acid residues required for interacting with plant CDKA. Thus, our work reveals a distinct class of mitosis regulators that are conserved between plant and animal viruses and play active roles in viral pathogenesis.

The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF-κB and CD9/gp130/STAT3 signalling pathway.

The balance between bone formation and bone resorption is closely related to bone homeostasis. Osteoclasts, originating from the monocyte/macrophage lineage, are the only cell type possessing bone resorption ability. Osteoclast overactivity is thought to be the major reason underlying osteoclast-related osteolytic problems, such as Paget's disease, aseptic loosening of prostheses and inflammatory osteolysis; therefore, disruption of osteoclastogenesis is considered a crucial treatment option for these issues. WKYMVm, a synthetic peptide, which is a potent FPR2 agonist, exerts an immunoregulatory effect. This peptide inhibits the production of inflammatory cytokines, such as (IL)-1ß and TNF-α, thus regulating inflammation. However, there are only few reports on the role of WKYMVm and FPR2 in osteoclast cytology. In the current study, we found that WKYMVm negatively regulates RANKL- and lipopolysaccharide (LPS)-induced osteoclast differentiation and maturation in vitro and alleviates LPS-induced osteolysis in animal models. WKYMVm down-regulated the expression of osteoclast marker genes and resorption activity. Furthermore, WKYMVm inhibited osteoclastogenesis directly through reducing the phosphorylation of STAT3 and NF-kB and indirectly through the CD9/gp130/STAT3 pathway. In conclusion, our findings demonstrated the potential medicinal value of WKYMVm for the treatment of inflammatory osteolysis.

Dual-Peptide-Functionalized Nanofibrous Scaffolds Recruit Host Endothelial Progenitor Cells for Vasculogenesis to Repair Calvarial Defects.

Vasculogenesis (de novo formation of vessels) induced by endothelial progenitor cells (EPCs) is requisite for vascularized bone regeneration. However, there exist few available options for promoting vasculogenesis within artificial bone grafts except for exogenous EPC transplantation, which suffers from the source of EPC, safety, cost, and time concerns in clinical applications. This study aimed at endogenous EPC recruitment for vascularized bone regeneration by using a bioinspired EPC-induced graft. The EPC-induced graft was created by immobilizing two bioactive peptides, WKYMVm and YIGSR, on the surface of poly(ε-caprolactone) (PCL)/poliglecaprone (PGC) nanofibrous scaffolds via a polyglycolic acid (PGA)-binding peptide sequence. Remarkable immobilization efficacy of WKYMVm and YIGSR peptides and their sustained release (over 14 days) from scaffolds were observed. In vivo and in vitro studies showed robust recruitment of EPCs, which subsequently contributed to early vasculogenesis and ultimate bone regeneration. The dual-peptide-functionalized nanofibrous scaffolds proposed in this study provide a promising therapeutic strategy for vasculogenesis in bone defect repair.

The TuMYB46L-TuACO3 module regulates ethylene biosynthesis in einkorn wheat defense to powdery mildew.

Powdery mildew disease, elicited by the obligate fungal pathogen Blumeria graminis f.sp. tritici (Bgt), causes widespread yield losses in global wheat crop. However, the molecular mechanisms governing wheat defense to Bgt are still not well understood. Here we found that TuACO3, encoding the 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase functioning in ethylene (ET) biosynthesis, was induced by Bgt infection of the einkorn wheat Triticum urartu, which was accompanied by increased ET content. Silencing TuACO3 decreased ET production and compromised wheat defense to Bgt, whereas both processes were enhanced in the transgenic wheat overexpressing TuACO3. TuMYB46L, phylogenetically related to Arabidopsis MYB transcription factor AtMYB46, was found to bind to the TuACO3 promoter region in yeast-one-hybrid and EMSA experiments. TuMYB46L expression decreased rapidly following Bgt infection. Silencing TuMYB46L promoted ET content and Bgt defense, but the reverse was observed when TuMYB46L was overexpressed. Hence, decreased expression of TuMYB46L permits elevated function of TuACO3 in ET biosynthesis in Bgt-infected wheat. The TuMYB46L-TuACO3 module regulates ET biosynthesis to promote einkorn wheat defense against Bgt. Furthermore, we found four chitinase genes acting downstream of the TuMYB46L-TuACO3 module. Collectively, our data shed a new light on the molecular mechanisms underlying wheat defense to Bgt.

Total knee arthroplasty in Asian subjects: preoperative range of motion determines postoperative range of motion?

OBJECTIVE: To evaluate whether preoperative range of motion is a key determinant of postoperative range of motion in Asian patients undergoing conventional total knee arthroplasty. METHODS: A retrospective review of 302 patients who underwent primary total knee arthroplasty performed by a single surgeon was conducted. Patients who had a fixed flexion deformity of ≥15° were excluded. Postoperative range of motion (ROM) was measured prospectively. Patients were stratified into two groups: preoperative ROM < 110° and preoperative ROM ≥ 110°. Postoperative ROM and mean change in ROM at 6 months and 2 years of follow-up were then compared using Student's t-test. RESULTS: Group of ROM < 110° had a poorer postoperative range of motion at both 6-months and 2-years of follow-up than Group of ROM ≥ 110° (P < 0.001). Postoperatively, Group of ROM < 110° had gained range of motion whereas Group of ROM ≥ 110° had lost range of motion (P < 0.001). CONCLUSIONS: Similar to the Western population, preoperative range of motion is a key determinant of postoperative range of motion in Asian patients. This should be taken into consideration by surgeons during preoperative planning and in managing patients' expectations.

The truth behind subchondral cysts in osteoarthritis of the knee.

BACKGROUND: Subchondral cysts have always been taught to be one of the cardinal radiological features of knee osteoarthritis but are not well understood. We aimed to evaluate the radiological prevalence and epidemiology of subchondral cysts in patients with knee osteoarthritis to determine if they are truly a cardinal radiological feature. METHODS: All patients of a single surgeon with symptoms of knee osteoarthritis were selected for this study. All patients had failed a trial of conservative therapy and were planned for total knee arthroplasty. Patients with symptoms of and documentary evidence of inflammatory arthritis, other neurological and orthopaedic problems causing functional deficits were excluded from this study. A total of 806 plain radiographs were analyzed with the aid of an atlas for the presence of narrowed joint space, osteophytes, subchondral sclerosis and subchondral cysts. The radiological prevalence of each feature was then calculated. Demographics and pre-operative measurements were compared between patients with and without radiological evidence of subchondral cysts. RESULTS: Subchondral cysts were only present in 30.6% of the study population. Narrowed joint space was present in 99.5%, osteophytes in 98.1% and subchondral sclerosis in 88.3% of all radiographs. The differences in prevalence were statistically significant. There was a higher proportion of females in patients with radiological evidence of subchondral cysts. These patients also had a greater varus deformity preoperatively. CONCLUSION: With a radiological prevalence of 30.6%, subchondral cysts should not be considered a cardinal radiological feature of osteoarthritis. Subchondral cysts may be associated with the female gender and genu varum.