Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering.

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.

Emerging Point-of-care Technologies for Food Safety Analysis.

Food safety issues have recently attracted public concern. The deleterious effects of compromised food safety on health have rendered food safety analysis an approach of paramount importance. While conventional techniques such as high-performance liquid chromatography and mass spectrometry have traditionally been utilized for the detection of food contaminants, they are relatively expensive, time-consuming and labor intensive, impeding their use for point-of-care (POC) applications. In addition, accessibility of these tests is limited in developing countries where food-related illnesses are prevalent. There is, therefore, an urgent need to develop simple and robust diagnostic POC devices. POC devices, including paper- and chip-based devices, are typically rapid, cost-effective and user-friendly, offering a tremendous potential for rapid food safety analysis at POC settings. Herein, we discuss the most recent advances in the development of emerging POC devices for food safety analysis. We first provide an overview of common food safety issues and the existing techniques for detecting food contaminants such as foodborne pathogens, chemicals, allergens, and toxins. The importance of rapid food safety analysis along with the beneficial use of miniaturized POC devices are subsequently reviewed. Finally, the existing challenges and future perspectives of developing the miniaturized POC devices for food safety monitoring are briefly discussed.

Implementation and impact of rapid SARS-CoV-2 point of care test on patient flow in the frailty pathway; A quality improvement approach.

To maintain patient flow during the COVID-19 pandemic, rapid and accurate decisions for the safe triage of geriatrics patients was essential as turnaround times for laboratory testing was ineffective at supporting rapid clinical decision-making for transfer of care. Thus, to mitigate and inform these clinical decisions, a quality improvement collaborative project with the geriatrics and virology department was conducted at the Frailty Assessment Unit (FAU) at Aberdeen Royal Infirmary. The goal was to facilitate patient triage during transfer of care with the introduction of Point of Care testing (POCT). The interventions which resulted in significant improvements were based on the fishbone problem solving approach and the driver diagram with change ideas informing the five Plan, Do, Study and Act (PDSA) cycles. The QI intervention was crucial in supporting clinical staff decision making during transfers for 95% of patients who had been clinically judged as asymptomatic for COVID-19 infection. High staff engagement was observed with 83% of staff suggesting the process map was easy to follow and 92% of clinical staff agreed it contained sufficient information to support the testing process. With POCT introduction, the proportion of patients who were transferred with an early POCT result increased by 20% in the Rosewell House group and by 65% in the community Hospitals group, once governance arrangements were in place. Finally, the considerable uptake of POCT by the ward consequently led to a decrease of up to 86% in the number of samples sent to the laboratory for rapid SARS-CoV-2 testing. The quality improvement project provided a rapid and reliable SARS-CoV-2 triage tool and was effectively integrated into the geriatrics triage algorithm to facilitate patient placement and flow.

Accuracy of injection pressure measurement at peripheral nerves using high-resolution 40 MHz ultrasound in an anesthetized porcine model.

BACKGROUND: Fluid injection pressure measurement is promoted as a marker of needle tip position that discriminates between tissue layers. However, clinical ultrasound has insufficient resolution to identify the exact position of the needle tip. Our primary objective was to use 40 MHz ultrasound in anesthetized pigs in order to precisely locate the tip of the needle and measure opening injection pressure in muscle, at epineurium and in subepineurium. METHODS: We surgically exposed the axillae of four anesthetized pigs. Two operators placed a 40 MHz ultrasound transducer over the pectoral muscle and imaged axillary, median and radial nerves. Injections (0.5 mL) were randomized to in-plane and out-of-plane needle trajectories and flow rates of 1, 6 and 12 mL/min. RESULTS: We identified 541 fascicles in 23 nerves. The ratio of fascicle area to nerve area remained constant at ~0.30 for all nerves. Axillary nerves were smaller than median and radial nerves, difference in diameter (95% CI) 1.61 (0.87 to 2.36) mm, p<0.001 and 1.59 (0.82 to 2.36) mm, p=0.001, respectively. Axillary nerves had less fascicles per nerve than median nerves, difference 7.63 (2.43 to 12.83) and radial nerves, difference 9.02 (3.64 to 14.40). We visualized the circumneurium and injection within the subcircumneural compartment. Intraneural injection increased nerve area (SD) from 5.7 (2.2) mm2 to 13.7 (5.5) mm2, difference 8.0 (5.4-10.6) mm2, p<0.001. Mean injection pressure was greater in subepineurium compared with muscle, geometric ratio 2.29 (1.30 to 4.10), p<0.001; and greater on epineurium compared with muscle, geometric ratio 1.73 (1.03 to 3.00), p=0.01. Twenty-two out of 23 injections in muscle, 14 out of 23 injections at epineurium and 11 out of 22 injections in subepineurium were <138 kPa (20 psi). CONCLUSION: Needle tip position was not discernible using pressure monitoring. The circumneurium and subcircumneural injection compartment were observed but not intrafascicular injection.

Effects of renal volume and single-kidney glomerular filtration rate on renal functional outcome in atherosclerotic renal artery stenosis.

BACKGROUND: Renal functional outcome is unpredictable after revascularization of high-grade atherosclerotic renal artery stenosis (RAS). 'Hibernating' parenchyma describes acute parenchymal injury where renal dysfunction is potentially reversible with treatment of the stenosis. We analysed renal parenchymal volume (PV) and single-kidney glomerular filtration rate (SK-GFR) characteristics to identify kidneys with hibernating parenchyma and hence determine renal functional outcome after revascularization. METHODS: Fifty patients with > or =50% RAS underwent baseline analyses: (i) PV using magnetic resonance imaging; (ii) radioisotopic SK-GFR. Twenty-one patients (27 kidneys) underwent renal revascularization and 29 medical therapy alone. RESULTS: Patients with revascularized kidneys manifesting high PV:SK-GFR showed improvement in global estimated GFR compared to conservatively managed counterparts at 6 months and 1 year (6 months: 6.2 +/- 2.9 versus -3.7 +/- 6.8, P = 0.038; 1 year: 3.5 +/- 3.0 versus -5.1 +/- 5.1 ml/min/1.73 m(2), P = 0.021). Twelve revascularized patients (16 kidneys) underwent repeat SK-GFR 4 months post-revascularization. Six of 16 revascularized kidneys had high baseline PV:SK-GFR and showed improved SK-GFR compared to kidneys with low or normal PV:SK-GFR (6.3 +/- 2.0 versus -0.9 +/- 4.2 ml/min, P = 0.002). CONCLUSIONS: Our data suggest that, after revascularization, GFR improvement is likely if there is a disproportionately higher baseline PV:SK-GFR in the RAS kidney. Analysing these parameters can potentially identify these 'hibernating' kidneys and aid determination of renal functional outcome in RAS.

Single-Cell RNA Sequencing and Its Combination with Protein and DNA Analyses.

Heterogeneity in cell populations poses a significant challenge for understanding complex cell biological processes. The analysis of cells at the single-cell level, especially single-cell RNA sequencing (scRNA-seq), has made it possible to comprehensively dissect cellular heterogeneity and access unobtainable biological information from bulk analysis. Recent efforts have combined scRNA-seq profiles with genomic or proteomic data, and show added value in describing complex cellular heterogeneity than transcriptome measurements alone. With the rising demand for scRNA-seq for biomedical and clinical applications, there is a strong need for a timely and comprehensive review on the scRNA-seq technologies and their potential biomedical applications. In this review, we first discuss the latest state of development by detailing each scRNA-seq technology, including both conventional and microfluidic technologies. We then summarize their advantages and limitations along with their biomedical applications. The efforts of integrating the transcriptome profile with highly multiplexed proteomic and genomic data are thoroughly reviewed with results showing the integrated data being more informative than transcriptome data alone. Lastly, the latest progress toward commercialization, the remaining challenges, and future perspectives on the development of scRNA-seq technologies are briefly discussed.

Challenges in diagnosing acute pancreatitis in renal transplant patients.

Acute pancreatitis is a recognized occurrence in patients with end-stage renal disease, those on dialysis and those who have undergone renal transplantation. The incidence is significantly increased in comparison to the general population and carries significant mortality. We report two cases of acute pancreatitis that occurred in stable renal transplant recipients, and in which there was diagnostic difficulty. The etiology of the acute pancreatitis is not always identifiable in these patients. Classical symptoms and laboratory findings are often absent, which may cause diagnostic difficulty. Our experience suggests that in immunosuppressed patients with unexplained abdominal pain or abnormal liver function tests, acute pancreatitis should be considered at an early stage in order to initiate appropriate treatment and therefore minimize mortality and morbidity.

Progress in Molecularly Imprinted Polymers for Biomedical Applications.

BACKGROUND: Molecularly Imprinted Polymers (MIPs), a type of biomimetic materials have attracted considerable interest owing to their cost-effectiveness, good physiochemical stability, favorable specificity and selectivity for target analytes, and long shelf life. These materials are able to mimic natural recognition entities, including biological receptors and antibodies, providing a versatile platform to achieve the desirable functionality for various biomedical applications. OBJECTIVE: In this review article, we introduce the most recent development of MIPs to date. We first highlight the advantages of using MIPs for a broad range of biomedical applications. We then review their various methods of synthesis along with their latest progress in biomedical applications, including biosensing, drug delivery, cell imaging and drug discovery. Lastly, the existing challenges and future perspectives of MIPs for biomedical applications are briefly discussed. CONCLUSION: We envision that MIPs may be used as potential materials for diverse biomedical applications in the near future.

Recent advances in photo-crosslinkable hydrogels for biomedical applications.

Photo-crosslinkable hydrogels have recently attracted significant scientific interest. Their properties can be manipulated in a spatiotemporal manner through exposure to light to achieve the desirable functionality for various biomedical applications. This review article discusses the recent advances of the most common photo-crosslinkable hydrogels, including poly(ethylene glycol) diacrylate, gelatin methacryloyl and methacrylated hyaluronic acid, for various biomedical applications. We first highlight the advantages of photopolymerization and discuss diverse photosensitive systems used for the synthesis of photo-crosslinkable hydrogels. We then introduce their synthesis methods and review their latest state of development in biomedical applications, including tissue engineering and regenerative medicine, drug delivery, cancer therapies and biosensing. Lastly, the existing challenges and future perspectives of engineering photo-crosslinkable hydrogels for biomedical applications are briefly discussed.

The effects of statins on the progression of atherosclerotic renovascular disease.

BACKGROUND/AIMS: The aim was to examine the influence of statin therapy on the natural history of atherosclerotic renal artery stenosis (RAS). METHODS: Our hospital atherosclerotic renovascular disease (ARVD) database was analysed for patients who underwent repeat renal angiography during clinical follow-up. Patients with >or=1 RAS lesion and >or=4 months between baseline and repeat renal angiography were analysed. 79 patients were included. Baseline renal arterial anatomy was classified as normal, 50% RAS or renal artery occlusion. RESULTS: Mean follow-up time between angiograms was 27.8 +/- 22.3 (4.0-101.9) months. Progression of RAS occurred in 28 (23%) vessels, regression in 14 (12%) and no significant change in 79 (65%). Multivariate regression analysis showed that baseline proteinuria >0.6 g/day increased the risk of progressive disease (relative risk, RR, 3.8; 95% confidence interval, CI, 1.2-12.1), treatment with statin reduced the risk of progression (RR 0.28; 95% CI 0.10-0.77). 14 renal arteries from 12 patients showed RAS regression with a greater proportion on statin [statin treatment 10 (83%) versus no statin treatment 2 (17%), p = 0.001]. Change in estimated glomerular filtration rate (eGFR) per year was not different between statin- and no-statin-treated groups. CONCLUSIONS: Progression or development of RAS was significantly less likely to occur with statin therapy. Delta eGFR did not correlate with progression of RAS, reflecting the importance of intrarenal injury in the aetiology of renal dysfunction. Our results suggest statin therapy can alter the natural history of ARVD.

Major spontaneous renal haemorrhage as an unusual complication of systemic amyloidosis.

We report the case of a patient with systemic amyloidosis who developed a life-threatening spontaneous haemorrhage from an amyloid kidney. A review of the literature suggests that this is a rare complication of renal amyloidosis. However, the grossly abnormal renal angiography observed in our patient has previously been described in the literature. Therefore, spontaneous renal haemorrhage should be considered a risk in any systemic amyloid patient, especially in the differential diagnosis for those patients with the condition who present with an acute abdomen.

Gadolinium-enhanced magnetic resonance imaging for renovascular disease and nephrogenic systemic fibrosis: critical review of the literature and UK experience.

PURPOSE: To examine the positive reporting bias regarding the link with gadolinium (Gd) exposure and nephrogenic systemic fibrosis (NSF) in patients with renal impairment. This link has impacted strongly the international radiology safety guidelines. We believe that positive reporting bias has prevailed in the literature and that very few patients with a glomerular filtration rate (GFR) 15-29 mL/min (stage 4 chronic kidney disease [CKD]) should be regarded as high risk. MATERIALS AND METHODS: To examine this, we conducted the following steps: 1. A critical literature search on NSF. 2. An analysis of our centers magnetic resonance angiography (MRA) experience since 1999. 3. A survey of participating centers of the multicenter ASTRAL trial to assess whether any patients screened or enrolled into ASTRAL had developed NSF. RESULTS: The vast majority (90%) of NSF cases reported in the literature have occurred in patients with endstage renal disease treated with dialysis; very have had stable stage 4 or 5 (nondialysis) CKD. In all, 562 patients were followed up at our center: 30.4% were CKD4, 14.4% CKD5, 5.3% on dialysis, and 0.2% had renal transplants when imaged. No patients developed any symptoms or signs of NSF. In all, 347 patients were enrolled into ASTRAL on the basis of MRA (32% CKD4/5). One patient out of 45 centers (CKD5, received two Gd scans) developed NSF. Approximately 5 times as many patients were screened as were entered into ASTRAL. CONCLUSION: No cases of NSF were observed at our center. By extrapolation, 1/1735 patients screened for the ASTRAL trial developed NSF, giving a crude incidence rate of 0.06%. We would argue that patients with CKD4 can safely undergo Gd-MRA, albeit using a minimal dose of a macrocyclic agent and avoiding repeat doses.

Small bowel angiodysplasia in a patient on haemodialysis: difficulties in diagnosis and management.

Angiodysplasia is a common cause of gastrointestinal blood loss in patients with end stage renal disease. Diagnosis is especially difficult when the angiodysplastic lesions are concentrated in the small bowel. This report describes a case of a patient on haemodialysis who had transfusion-dependent anaemia from small bowel angiodysplasia. Endoscopic treatment was unsuccessful, tranexamic acid caused complications with thrombosis, and thalidomide showed no benefit. This case report highlights the problems in the diagnosis and management of this condition in patients on haemodialysis. Early diagnosis and optimisation of the patient for treatment is key to the successful outcomes of such patients.

Renal imaging in patients requiring renal replacement therapy.

Recent advances in imaging technology and interventional radiologic procedures have resulted in an increased variety of radiological techniques that can be used to assess patients who present with renal failure and require renal replacement therapy. This chapter provides an overview of the relative strengths and weaknesses of the available imaging methods. In particular, it covers the expanding role of the cross-sectional, noninvasive, multiplanar imaging techniques such as gray-scale and Doppler ultrasound, magnetic resonance imaging (MRI) and angiography (MRA), and nonenhanced helical or multislice computed tomography (CT). These imaging methods are increasingly replacing those used in the past, such as the conventional radiographic urogram, which requires a high dose of intravenous contrast media, and digital subtraction arteriography. The chapter also covers the radiologic investigation of complications of acquired renal cystic disease, including renal cell carcinoma, hemorrhage, cyst infection and rupture, and nephrolithiasis.

Endovascular aneurysm repair with the Talent stent-graft.

PURPOSE: Evaluation of the Talent endovascular aortic stent graft in the management of abdominal aortic aneurysms. MATERIALS AND METHODS: Thirty-eight patients with suitable abdominal aortic aneurysms were treated over an 18-month period using the modular Talent stent graft. The suprarenal Talent device was deployed in 31 cases. Clinical follow-up of all patients has been performed by clinical examination, contrast-enhanced CT, and Duplex ultrasound for a mean period of 12.5 months. RESULTS: Graft placement was successful in all 38 patients. The immediate exclusion rate was 84%, the 1-month primary exclusion rate was 92.1%, and the 3-month exclusion rate was 97%. There were no deaths in the first 30 days, one death at 3 months due to a presumed rupture, and one other death at 1 year due to carcinomatosis. There have been no migrations or renal complications in the suprarenal group. CONCLUSIONS: Our short- and medium-term results are comparable with other published Talent stent-graft series. Suprarenal graft fixation is a safe procedure that may aid in preventing graft migration. Long-term follow-up is required to assess the durability of the suprarenal Talent device.