Target Deletion of the Cytoskeleton-Associated Protein Palladin Does Not Impair Neurite Outgrowth in Mice

Palladin is an actin cytoskeleton–associated protein which is crucial for cell morphogenesis and motility. Previous studies have shown that palladin is localized to the axonal growth cone in neurons and may play an important role in axonal extension. Previously, we have generated palladin knockout mice which display cranial neural tube closure defect and embryonic lethality before embryonic day 15.5 (E15.5). To further study the role of palladin in the developing nervous system, we examined the innervation of palladin-deficient mouse embryos since the 200 kd, 140 kd, 90–92 kd and 50 kd palladin isoforms were undetectable in the mutant mouse embryo brain. Contrary to the results of previous studies, we found no inhibition of the axonal extension in palladin-deficient mouse embryos. The cortical neurons derived from palladin-deficient mice also showed no significant difference in neurite outgrowth as compared with those from wild-type mice. Moreover, no difference was found in neurite outgrowth of neural stem cell derived-neurons between palladin-deficient mice and wild-type mice. In conclusion, these results suggest that palladin is dispensable for normal neurite outgrowth in mice

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Effect of hTERT Gene Expression on Proliferation and Apoptosis of Cervical Cancer Caski Cells by Lentivirus-Mediated Small Interfering RNA

Objective: To explore the feasibility of lentivirus-mediated small interfering RNA (siRNA) silencing the human telomerase reverse transcriptase (hTERT) and its influence on the proliferation and apoptosis of cervical cancer Caski cells.Methods: The cervical cancer Caski cells were transfected by lentivirus expression vectors anti-hTERT-TV and NC-LV which had been constructed in advance. There were three groups in the experiment, namely blank group (NC group), negative control group (NC-LV group) and interference group (anti-hTERT-LV group). The expression level of hTERT mRNA was determined by real-time fluorescent quantitative polymerase chain reaction (PCR), while the cell cycle and apoptosis were detected by flow cytometry.Results: The relative expression level of hTERT mRNA in anti-hTERT-LV group was significantly lower than those in NC group and NC-LV group (P<0.001). The proportion of cells in G1 phase in anti-hTERT-LV group was significantly higher than those in NC group and NC-LV group (P<0.001), while that in S phase was significantly lower than those in NC group and NC-LV group (P<0.001). The number of cell clones in anti-hTERT-LV group was significantly lower than those in NC group and NC-LV group (P<0.001), but there was no statistical significance between NC-LV group and NC group (P>0.05).Conclusion: The lentivirus-mediated siRNA can induce silencing hTERT gene, effectively suppress its expression, promote the cell apoptosis and inhibit the proliferation of cervical cancer Caski cells

An Updated Systematic Review and Meta-analysis of the Short- and Long-term Outcomes of Percutaneous Coronary Intervention for Patients with Severe Left Ventricular Systolic Dysfunction

Background: Coronary artery disease (CAD) is the most common cause of left ventricular dysfunction(LVD). Confl icting evidence exists with regards to available treatments and patient prognosis.Revascularization may improve ventricular function while coronary artery bypass surgery (CABG) hassignifi cantly improved survival. The effectiveness of percutaneous coronary intervention (PCI) has alsonot been thoroughly investigated to date.Objectives: To ascertain the in-hospital and long-term (≥1 year) outcomes of CAD patients with LVsystolic dysfunction (ejection fraction ≤40%) after PCI according to a meta-analysis.Methods: A systematic literature search and a series of random-effect meta-analyses were conducted to evaluate the short- and long-term outcomes of PCI of the selected studies. Single-center studies andthose that did not report evidence on long-term mortality were excluded in the analysis. All statistical tests were performed with 95% confi dence intervals. A p-value of less than 0.05 was considered statistically significant.</p

Quality appraisal of clinical guidelines for venous thromboembolism prophylaxis in patients undergoing hip and knee arthroplasty: a systematic review

Introduction Venous thromboembolism (VTE) occurs in up to 40%–80% of patients after hip and knee arthroplasty. Clinical decision-making aided by guidelines is the most effective strategy to reduce the burden of VTE. However, the quality of guidelines is dependent on the strength of their evidence base. The objective of this article is to critically evaluate the quality of VTE prevention guidelines and the strength of their recommendations in VTE prophylaxis in patients undergoing hip and knee arthroplasty.Methods Relevant literature up to 16 March 2020 was systematically searched. We searched databases such as Web of Science, PubMed, EMBASE, Cumulative Index of Nursing and Allied Health Literature, China National Knowledge Infrastructure and WanFang and nine guidelines repositories. The identified guidelines were appraised by two reviewers using the Appraisal of Guidelines for Research and Evaluation II and appraised the strength of their recommendations independently. Following quality assessment, a predesigned data collection form was used to extract the characteristics of the included guideline.Results We finally included 15 guidelines. Ten of the included guidelines were rated as ‘recommended’ or ‘recommended with modifications’. The standardised scores were relatively high in the domains of Clarity of Presentation, and Scope and Purpose. The lowest average standardised scores were observed in the domains of Applicability and Stakeholder Involvement. In reference to the domains of Rigour of Development and Editorial Independence, the standardised scores varied greatly between the guidelines. The agreement between the two appraisers is almost perfect (intraclass correlation coefficients higher than 0.80). A considerable proportion of the recommendations is based on low-quality or very-low-quality evidence or is even based on working group expert opinion.Conclusions In summary, the majority of the recommendations are based on low-quality evidence, and further confirmation is needed. Furthermore, guideline developers should pay more attention to methodological quality, especially in the Stakeholder Involvement domain and the Applicability domain

Deficiency of adiponectin protects against ovariectomy-induced osteoporosis in mice.

Adipokine adiponectin (APN) has been recently reported to play a role in regulating bone mineral density (BMD). To explore the mechanism by which APN affects BMD, we investigated BMD and biomechanical strength properties of the femur and vertebra in sham-operated (Sham) and ovariectomized (OVX) APN knockout (KO) mice as compared to their operated wild-type (WT) littermates. The results show that APN deficiency has no effect on BMD but induces increased ALP activity and osteoclast cell number. While OVX indeed leads to significant bone loss in both femora and vertebras of WT mice with comparable osteogenic activity and a significant increase in osteoclast cell number when compared to that of sham control. However, no differences in BMD, ALP activity and osteoclast cell number were found between Sham and OVX mice deficient for APN. Further studies using bone marrow derived mesenchymal stem cells (MSCs) demonstrate an enhanced osteogenic differentiation and extracellular matrix calcification in APN KO mice. The possible mechanism for APN deletion induced acceleration of osteogenesis could involve increased proliferation of MSCs and higher expression of Runx2 and Osterix genes. These findings indicate that APN deficiency can protect against OVX-induced osteoporosis in mice, suggesting a potential role of APN in regulating the balance of bone formation and bone resorption, especially in the development of post-menopausal osteoporosis

Increased osteogenic differentiation and extracellular matrix calcification in MSCs from <i>APN</i> KO mice.

<p>(A) RT-PCR shows that mRNA expression of the indicated genes (left). The respective ratio of band density (KO/WT, %) normalized with <i>β-actin</i> represents relative mRNA levels (right). A representative result of three independent experiments is shown. (B) Increased ALP activity in MSC lysate from <i>APN</i> KO mice. (C) Alizarin red S staining shows enhanced calcification ability of MSCs from <i>APN</i> KO mice (n = 3 for each). (D) Ca²⁺ content in cell lysate from <i>APN</i> KO mice is higher than that from WT mice (n = 3 for each). **indicates <i>p</i><0.01.</p