Medical therapy vs early revascularization in diabetics with chronic total occlusions: A meta-analysis and systematic review

BACKGROUND: Management of chronic total occlusions (CTO) in diabetics is challenging, with a recent trend towards early revascularization [ER: Percutaneous coronary intervention (PCI) and bypass grafting] instead of optimal medical therapy (OMT). We hypothesize that ER improves morbidity and mortality outcomes in diabetic patients with CTOs as compared to OMT. AIM: To determine the long term clinical outcomes and to compare morbidity and mortality between OMT and ER in diabetic patients with CTOs. METHODS: Potentially relevant published clinical trials were identified in Medline, Embase, chemical abstracts and Biosis (from start of the databases till date) and pooled hazard ratios (HR) computed using a random effects model, with significant P value \u3c 0.05. Primary outcome of interest was all-cause death. Secondary outcomes included cardiac death, prompt revascularization (ER) or repeat myocardial infarction (MI). Due to scarcity of data, both Randomized control trials and observational studies were included. 4 eligible articles, containing 2248 patients were identified (1252 in OMT and 1196 in ER). Mean follow-up was 45-60 mo. RESULTS: OMT was associated with a higher all-cause mortality [HR: 1.70, 95% confidence interval (CI): 0.80-3.26,P = 0.11] and cardiac mortality (HR: 1.68, 95%CI: 0.96-2.96, P = 0.07). Results were close to significance. The risk of repeat MI was almost the same in both groups (HR: 0.97, 95%CI: 0.61-1.54,P = 0.90). Similarly, patients assigned to OMT had a higher risk of repeat revascularization (HR: 1.62, 95%CI: 1.36-1.94,P \u3c 0.00001). Sub-group analysis of OMT vs PCI demonstrated higher all-cause (HR: 1.98, 95%CI: 1.36-2.87,P = 0.0003) and cardiac mortality (HR: 1.87, 95%CI: 0.96-3.62,P = 0.06) in the OMT group. The risk of repeat MI was low in the OMT groupvs PCI (HR: 0.53, 95%CI: 0.31-0.91,P = 0.02). Data on repeat revascularization revealed no difference between the two (HR: 1.00, 95%CI: 0.52-1.93, P = 1.00). CONCLUSION: In diabetic patients with CTO, there was a trend for improved outcomes with ER regarding all-cause and cardiac death as compared to OMT. These findings were reinforced with statistical significance on subgroup analysis of OMT vs PCI

Embedded-grid silver transparent electrodes fabricated by selective metal condensation

We report a new materials system for the fabrication of embedded silver grid electrodes with micron-sized linewidth >10 times narrower than can be achieved using the conventional printing techniques of screen, inject and flexographic printing. Using micro-contact printed thin films of the highly fluorinated polymer poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl methacrylate) together with low temperature heating of the substrate during metal deposition by thermal evaporation, we have fabricated embedded silver transparent grid electrodes on flexible plastic substrates without the need for a metal etching step or a separate grid-embedding step. This simplified approach to grid electrode fabrication is made possible by the very low condensation coefficient of Ag on areas of the substrate covered with the printed organofluorine layer, removing the need for harmful chemical etchants and slow chemical intensive electrochemical deposition steps

von Willebrand disease: proposing definitions for future research

Thrombosis and Hemostasi

Development of eco-friendly wall insulation layer utilising the wastes of the packing industry

Efficient thermal insulation materials considerably lower power consumption for heating and cooling of buildings, which in turn minimises CO2 emissions and improves indoor comfort conditions. However, the selection of suitable insulation materials is governed by several factors, such as the environmental impact, health impact, cost and durability. Additionally, the disposal of used insulation materials is a major factor that affects the selection of materials because some materials could be very toxic for humans and the environment, such as asbestos-containing materials. Therefore, there is a continuous research effort, in both industry and academia, to develop sustainable and affordable insulation materials. In this context, this work aims at utilising the packing industry wastes (cardboard) to develop an eco-friendly insulation layer, which is a biodegradable material that can be disposed of safely after use. Experimentally, wasted cardboard was collected, cleaned, and soaked in water for 24 h. Then, the wet cardboard was minced and converted into past papers, then cast in square moulds and left in a ventilated oven at 75 °C to dry before de-moulding them. The produced layers were subjected to a wide range of tests, including thermal conductivity, acoustic insulation, infrared imaging and bending resistance. The obtained results showed the developed material has a good thermal and acoustic insulation performance. Thermally, the developed material had the lowest thermal conductivity (λ) (0.039 W/m.K) compared to the studied traditional materials. Additionally, it successfully decreased the noise level from 80 to about 58 dB, which was better than the efficiency of the commercial polyisocyanurate layer. However, the bending strength of the developed material was a major drawback because the material did not resist more than 0.6 MPa compared to 2.0 MPa for the commercial polyisocyanurate and 70.0 MPa for the wood boards. Therefore, it is recommended to investigate the possibility of strengthening the new material by adding fibres or cementitious materials

Multilayered graphene/ZnFe2O4 hybrid composite: Rational preparation, characterization and superior adsorption of Congo red

Multilayered porous hierarchical structure of graphene/ZnFe2O4 hybrids was prepared via in situ hydrothermal growth of ZnFe2O4 nanocrystals within interlayer space of reduced graphene oxide, which demonstrated a high specific area of 117 m2∙g−1 and rational porous structures. Batch adsorption studies showed that the product possesses superior adsorption capacity of dyes such as Congo red from aqueous solution. Adsorption equilibrium and kinetic analysis indicated that the adsorption isotherm was well fitted by Langmuir isothermal model with the maximum adsorption capacity of 404.12 mg∙g−1, and the adsorption kinetics followed the pseudo-second-order kinetic equation. Furthermore, this new product can be magnetically separated and regenerated easily, presenting an effective adsorbent for wastewater purification

Modulation of Cytochrome P450 Metabolism and Transport across Intestinal Epithelial Barrier by Ginger Biophenolics

Natural and complementary therapies in conjunction with mainstream cancer care are steadily gaining popularity. Ginger extract (GE) confers significant health-promoting benefits owing to complex additive and/or synergistic interactions between its bioactive constituents. Recently, we showed that preservation of natural ‘‘milieu’’ confers superior anticancer activity on GE over its constituent phytochemicals, 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S), through enterohepatic recirculation. Here we further evaluate and compare the effects of GE and its major bioactive constituents on cytochrome P450 (CYP) enzyme activity in human liver microsomes by monitoring metabolites of CYPspecific substrates using LC/MS/MS detection methods. Our data demonstrate that individual gingerols are potent inhibitors of CYP isozymes, whereas GE exhibits a much higher half-maximal inhibition value, indicating no possible herb-drug interactions. However, GE’s inhibition of CYP1A2 and CYP2C8 reflects additive interactions among the constituents. In addition, studies performed to evaluate transporter-mediated intestinal efflux using Caco-2 cells revealed that GE and its phenolics are not substrates of P-glycoprotein (Pgp). Intriguingly, however, 10G and 6S were not detected in the receiver compartment, indicating possible biotransformation across the Caco-2 monolayer. These data strengthen the notion that an interplay of complex interactions among ginger phytochemicals when fed as whole extract dictates its bioactivity highlighting the importance of consuming whole foods over single agents. Our study substantiates the need for an indepth analysis of hepatic biotransformation events and distribution profiles of GE and its active phenolics for the design of safe regimens

The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients

Genomics and proteomics will improve outcome prediction in cancer and have great potential to help in the discovery of unknown mechanisms of metastasis, ripe for therapeutic exploitation. Current methods of prognosis estimation rely on clinical data, anatomical staging and histopathological features. It is hoped that translational genomic and proteomic research will discriminate more accurately than is possible at present between patients with a good prognosis and those who carry a high risk of recurrence. Rational treatments, targeted to the specific molecular pathways of an individual’s high-risk tumor, are at the core of tailored therapy. The aim of targeted oncology is to select the right patient for the right drug at precisely the right point in their cancer journey. Optical proteomics uses advanced optical imaging technologies to quantify the activity states of and associations between signaling proteins by measuring energy transfer between fluorophores attached to specific proteins. Förster resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) assays are suitable for use in cell line models of cancer, fresh human tissues and formalin-fixed paraffin-embedded tissue (FFPE). In animal models, dynamic deep tissue FLIM/FRET imaging of cancer cells in vivo is now also feasible. Analysis of protein expression and post-translational modifications such as phosphorylation and ubiquitination can be performed in cell lines and are remarkably efficiently in cancer tissue samples using tissue microarrays (TMAs). FRET assays can be performed to quantify protein-protein interactions within FFPE tissue, far beyond the spatial resolution conventionally associated with light or confocal laser microscopy. Multivariate optical parameters can be correlated with disease relapse for individual patients. FRET-FLIM assays allow rapid screening of target modifiers using high content drug screens. Specific protein-protein interactions conferring a poor prognosis identified by high content tissue screening will be perturbed with targeted therapeutics. Future targeted drugs will be identified using high content/throughput drug screens that are based on multivariate proteomic assays. Response to therapy at a molecular level can be monitored using these assays while the patient receives treatment: utilizing re-biopsy tumor tissue samples in the neoadjuvant setting or by examining surrogate tissues. These technologies will prove to be both prognostic of risk for individuals when applied to tumor tissue at first diagnosis and predictive of response to specifically selected targeted anticancer drugs. Advanced optical assays have great potential to be translated into real-life benefit for cancer patients

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction