4D Printing of origami structures for minimally invasive surgeries using functional scaffold

Origami structures have attracted attention in biomedical applications due to their ability to develop surgical tools that can be expanded from a minimal volume to a larger and functional device. On the other hand, four-dimensional (4D) printing is an emerging technology, which involves 3D printing of smart materials that can respond to external stimuli such as heat. This short communication introduces the proof of concept of merging origami and 4D printing technologies to develop minimally invasive delivery of functional biomedical scaffolds with high shape recovery. The shape-memory effect (SME) of the PLA filament and the origami designs were also assessed in terms of deformability and recovery rate. The results showed that herringbone tessellation origami structure combined with internal natural cancellous bone core satisfies the design requirement of foldable scaffolds. The substantial and consistent SME of the 4D printed herringbone tessellation origami, which exhibited 96% recovery compared to 61% for PLA filament, was the most significant discovery of this paper. The experiments demonstrated how the use of 4D printing in situ with origami structures could achieve reliable and repeatable results, therefore conclusively proving how 4D printing of origami structures can be applied to biomedical scaffolds

Fabrication and characterization of oxygen-generating polylactic acid/calcium peroxide composite filaments for bone scaffolds

The latest advancements in bone scaffold technology have introduced novel biomaterials that have the ability to generate oxygen when implanted, improving cell viability and tissue maturation. In this paper, we present a new oxygen-generating polylactic acid (PLA)/calcium peroxide (CPO) composite filament that can be used in 3D printing scaffolds. The composite material was prepared using a wet solution mixing method, followed by drying and hot melting extrusion. The concentration of calcium peroxide in the composite varied from 0% to 9%. The prepared filaments were characterized in terms of the presence of calcium peroxide, the generated oxygen release, porosity, and antibacterial activities. Data obtained from scanning electron microscopy and X-ray diffraction showed that the calcium peroxide remained stable in the composite. The maximum calcium and oxygen release was observed in filaments with a 6% calcium peroxide content. In addition, bacterial inhibition was achieved in samples with a calcium peroxide content of 6% or higher. These results indicate that an optimized PLA filament with a 6% calcium peroxide content holds great promise for improving bone generation through bone cell oxygenation and resistance to bacterial infections

Early Versus Late Tracheostomy for Patients with High and Low Cervical Spinal Cord Injuries

Objectives: This study aimed to evaluate the effects of early versus late tracheostomies among patients with cervical spinal cord injuries (CSCIs). Methods: This retrospective study included 69 adult CSCI patients who underwent bedside percutaneous tracheostomies at the Intensive Care Unit of Khoula Hospital, Muscat, Oman, between January 2011 and October 2015. The tracheostomy was considered early if the procedure took place within one week of the CSCI. The impact of an early tracheostomy on patient outcomes was analysed in terms of duration of mechanical ventilation and intensive care unit (ICU) stay among patients with high (C1–C2 vertebrae) and low (C3–C7 vertebrae) CSCIs. Ventilator dependence, bradycardia episodes and surgical intervention outcomes were also examined. Results: Patients with a high CSCI who underwent an early tracheostomy spent significantly fewer days on mechanical ventilation compared to those who underwent a late tracheostomy (9.3 ± 7.2 days versus 13.7 ± 3.2 days; P = 0.041). Low CSCI patients who received an early tracheostomy also experienced significantly fewer days on mechanical ventilation compared to those undergoing a late tracheostomy (12.1 ± 10.4 days versus 25.2 ± 17.7 days; P = 0.035). Moreover, ICU mortality was significantly lower for high CSCI patients who underwent an early tracheostomy (P = 0.015). However, there was no association between length of ICU stay and either type of CSCI or timing of the tracheostomy procedure. Conclusion: An early tracheostomy is beneficial in reducing the duration of mechanical ventilation among patients with CSCIs, irrespective of the level of injury

EFFECT OF ROSEMARY EXTRACTS ON DIABETIC AND LIVER MALFUNCTIONAL RATS

rosemary and its oil were used to investigate their effects on diabetic and liver malfunctional rats by administrating them with STZ or CCl4 for three weeks. The therapeutic effects of rosemary extracts (alcoholic and aqueous) and its oil against acute hyperglycemia induced by STZ in rats showed a decrease in the levels of fasting and postprandial blood glucose of rats treated with alcoholic extract of rosemary. In addition, results showed a restoration of these levels of the rats treated with aqueous extract or oil to their normal ranges after 3 weeks. There is a significant difference in lipid profile between rats treated with alcoholic or aqueous extracts and the negative control, where, the HDL in group administrated rosemary oil is significantly higher than both positive and negative control.                  The protective effects of rosemary extracts (alcoholic and aqueous) and its oil against liver toxicity induced by CCl4 in rats showed a significant difference between both (negative and positive control) and the activity of AST and ALT in the rats treated by alcoholic and aqueous extracts of rosemary. The protective effects of the plant extracts against liver toxicant occurred by decreasing the activities of these enzymes. Oil rosemary had restored effect more than both ethanolic and aqueous extracts, but not significant. This protective effect occurred by decreasing the activities of AST, ALT and Alp enzymes. No significant (p≤0.05) differences were noticed among the levels of serum total protein for all treatments compared to the negative and positive controls. The levels of total cholesterol and triglycerides recorded high values for the positive controls compared to the negative control. The protective effects of rosemary extracts against liver toxicant occurred by restoring the levels of these parameters to their normal values

An extremely rare complete bilateral duplication of Inferior vena cava in a male cadaver: anatomy, embryology and clinical relevance

The study presented an extremely rare case of real complete bilateral duplication of inferior vena cava (IVC) in a male cadaver which has never been reported before. Both IVC had approximately the same diameter. The right IVC drained into the right atrium; the left IVC continued as hemiazygos vein and drained into the superior vena cava. Three anastomotic venous channels, a cranial preaortic, a middle and a caudal retroaortic, joined both vessels. Multiple variations in the way of drainage of posterior intercostal veins, on both sides, were also present. The present report invalidates an old classification defining the two vessels when joined at the level of the renal veins as complete bilateral duplication of IVC. Although the presence of combination of venous variations is extremely rare, awareness of such variations is essential for clinical and surgical procedures to avoid misdiagnosis and surgical complications

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Evaluation of anti-biofilm activity of acidic amino acids and synergy with ciprofloxacin on Staphylococcus aureus biofilms

Acidic amino acids, aspartic acid (Asp) and glutamic acid (Glu) can enhance the solubility of many poorly soluble drugs including ciprofloxacin (Cip). One of the mechanisms of resistance within a biofilm is retardation of drug diffusion due to poor penetration across the matrix. To overcome this challenge, this work set to investigate novel counter ion approach with acidic amino acids, which we hypothesised will disrupt the biofilm matrix as well as simultaneously improve drug effectiveness. The anti-biofilm activity of D-Asp and D-Glu was studied on Staphylococcus aureus biofilms. Synergistic effect of combining D-amino acids with Cip was also investigated as a strategy to overcome anti-microbial resistance in these biofilms. Interestingly at equimolar combinations, D-Asp and D-Glu were able to significantly disperse (at 20 mM and 40 mM) established biofilms and inhibit (at 10 mM, 20 mM and 40 mM) new biofilm formation in the absence of an antibiotic. Moreover, our study confirmed L-amino acids also exhibit anti-biofilm activity. The synergistic effect of acidic amino acids with Cip was observed at lower concentration ranges (<40 mM amino acids and <90.54 µM, respectively), which resulted in 96.89% (inhibition) and 97.60% (dispersal) reduction in CFU with exposure to 40 mM amino acids. Confocal imaging indicated that the amino acids disrupt the honeycomb-like extracellular DNA (eDNA) meshwork whilst also preventing its formation

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

A phase Ib/IIa trial of 9 repurposed drugs combined with temozolomide for the treatment of recurrent glioblastoma: CUSP9v3

BACKGROUND: The dismal prognosis of glioblastoma (GBM) may be related to the ability of GBM cells to develop mechanisms of treatment resistance. We designed a protocol called Coordinated Undermining of Survival Paths combining 9 repurposed non-oncological drugs with metronomic temozolomide - version 3 - (CUSP9v3) to address this issue. The aim of this phase Ib/IIa trial was to assess the safety of CUSP9v3. METHODS: Ten adults with histologically confirmed GBM and recurrent or progressive disease were included. Treatment consisted of aprepitant, auranofin, celecoxib, captopril, disulfiram, itraconazole, minocycline, ritonavir, and sertraline added to metronomic low-dose temozolomide. Treatment was continued until toxicity or progression. Primary endpoint was dose-limiting toxicity defined as either any unmanageable grade 3–4 toxicity or inability to receive at least 7 of the 10 drugs at ≥ 50% of the per-protocol doses at the end of the second treatment cycle. RESULTS: One patient was not evaluable for the primary endpoint (safety). All 9 evaluable patients met the primary endpoint. Ritonavir, temozolomide, captopril, and itraconazole were the drugs most frequently requiring dose modification or pausing. The most common adverse events were nausea, headache, fatigue, diarrhea, and ataxia. Progression-free survival at 12 months was 50%. CONCLUSIONS: CUSP9v3 can be safely administered in patients with recurrent GBM under careful monitoring. A randomized phase II trial is in preparation to assess the efficacy of the CUSP9v3 regimen in GBM