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Objective: FFA is a well-established investigation for the diagnosis of optic nerve abnormalities, requiring an intravenous cannula and extended imaging acquisition time. Cannulation can present a challenge in paediatric patients and whilst oral FFA has been used for decades, it has been limited by imaging technology and unconfirmed image acquisition timings. For years, we have used a modern ultra-widefield retinal camera, and established imaging time-points to demonstrate dynamic optic nerve head changes upon ingestion of fluorescein and collected a database of oFFA images for various presentations. Methods: Using an established protocol, optic nerve colour images were obtained, followed by oral administration of fluorescein dye. The optic nerves are then imaged at established intervals. An interpretation of oFFA tutorial was delivered to consultant ophthalmologists and trainees. Subsequently, these groups were assessed using a series of fifteen cases with the sensitivity and specificity of the test determined. Results: Our study presents a series of images and descriptions for common optic nerve abnormalities in paediatric populations. In the interpretation part of the study, overall sensitivity of 76.8% in the consultant group vs 63.3% in the combined consultant + trainees and specificity of 87.5% vs 68.4% in the combined group. Conclusions: This is the first study that describes characteristic features of several common, and serious, optic nerve abnormalities specifically for oFFA interpretation in a paediatric population. It also highlights the rapid accumulation of oFFA interpretation skills in non-specialist consultant and trainee ophthalmologists such as to obtain a high diagnostic accuracy with high sensitivity and specificity.

A reliable hemicellulose extraction method from oil palm empty fruit bunches (OPEFB) is required for subsequent investigations into its composition and participation in pyrolysis and anaerobic digestion processes. Previous hemicellulose OPEFB research only looked at yield, purity and functional characteristics. In this study, OPEFB extractives were removed followed by hemicellulose A (HA) and B (HB) isolation and characterisation using Fourier-transform infrared, thermogravimetric and ultimate analysis. Energy dispersive X-ray spectroscopy (EDS) was deployed on the extractive-free OPEFB ash. Ethanol-toluene removed 8.2 ± 0.1 wt% extractives from OPEFB, with ethanol only removing another 1.6 ± 0.1 wt% while water extracted a further 5.4 ± 1.1 wt%. Alkaline extraction of OPEFB with 3 M KOH at 40 °C and subsequent centrifugation yielded 28.6 wt% HA, while 8.0 wt% HB was obtained as a precipitate from the supernatant of HA using 95% ethanol. The empirical formula of commercial xylan, a hemicellulose surrogate, and HA and HB were C5H9.5O4.4, C5H9.4O4.1and C5H9.8O2.9, respectively. FTIR analysis suggests that xylose and arabinose were the main constituents of xylan, HA and HB. The ash content (AC) of HA and HB was ten times greater than xylan (2.7 wt%). EDS analysis suggests that the high AC of HA and HB is attributed to Ca, Mg and Si which could not be effectively removed during extractives removal. Thermogravimetry identified a common decomposition peak at 219 °C confirming the presence of hemicellulose in the isolated HA and HB. Further research is required to refine the extraction protocol to obtain purer OPEFB hemicellulose.

Spinal pial arteriovenous fistulas (spAVFs) are rare, high-flow vascular malformations consisting of a single dilated pial artery connecting directly to an enlarged draining vein. This article describes the anatomic, clinical, and diagnostic features of spAVFs, to help clinicians to select the best treatment option. Both surgical and endovascular treatments are effective; microsurgery has a higher success rate. To maximize the exclusion rate, a multidisciplinary approach and adequate preoperative study are mandatory.

Solvent extraction is commonly used to extract oil from most seeds, including Moringa oleifera (MO). Oil extraction is a critical step in the production of cosmetics, pharmaceuticals, and other products that require the maximum amount of oil from the seed. On the other hand, MO as a coagulant need to be oil-free for coagulation performance. Therefore, optimization of oil yield is kept up to date. The extraction time, seed to solvent ratio, and particle size are the most optimised parameters reported on MO. Most Soxhlet extraction methodologies reported in the past mention a time range for extracting oil from the seed. Following the same extraction time, however, frequently results in variation in the yield of MO obtained. Because of this lack of reproducibility in oil yield, it has been demonstrated that using extraction time as a basis for monitoring the point at which maximum oil yield is achieved is not completely reliable. The range of ratios, solvent type, moisture content of the seed and the heating mantle vary from one to another. This study is focusing on oil extraction based on the number of siphons(8,16,24,32 siphons) using 2 different solvents (ethanol with a boiling point of and n-henaxe with a boiling point of) and shows that the optimum oil yield is at 16 siphons. It is also important to see when the extraction should stop for industrial scale to be cost effective. This method is then validated with two batches of MO seed for reproducibility. In addition, the use of polar solvents such as ethanol may also remove more protein and minerals from the seed, which can affect the quality and performance of the defatted MO seed in coagulation assays. Hence, EDS tests are included for preparing the suitable solvent used based on mineral removal.

Aureobasidin A (abA) is a natural depsipeptide that inhibits inositol phosphorylceramide (IPC) synthases with significant broad-spectrum antifungal activity. abA is known to have two distinct conformations in solution corresponding to trans-and cis-proline (Pro) amide bond rotamers. While the trans-Pro conformation has been studied extensively, cis-Pro conformers have remained elusive. Conformational properties of cyclic peptides are known to strongly affect both potency and cell permeability, making a comprehensive characterization of abA conformation highly desirable. Here, we report a high-resolution 3D structure of the cis-Pro conformer of aureobasidin A elucidated for the first time using a recently developed NMR-driven computational approach. This approach utilizes ForceGen’s advanced conformational sampling of cyclic peptides augmented by sparse distance and torsion angle constraints derived from NMR data. The obtained 3D conformational structure of cis-Pro abA has been validated using anisotropic residual dipolar coupling measurements. Support for the biological relevance of both the cis-Pro and trans-Pro abA configurations was obtained through molecular similarity experiments, which showed a significant 3D similarity between NMR-restrained abA conformational ensembles and another IPC synthase inhibitor, pleofungin A. Such ligand-based comparisons can further our understanding of the important steric and electrostatic characteristics of abA and can be utilized in the design of future therapeutics.

•The vertebral artery is in adults the main source of supply of the posterior fossa;•Its embryological development depends mostly on the longitudinal neural arteries;•Most of the adult’s variants can be explained through an embryological event.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX.

Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P < .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease.

Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P< .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease.

Current prognostic tools in aneurysmal subarachnoid hemorrhage (aSAH) are constrained by being primarily based on patient and disease characteristics on admission.

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Graphical Abstract

Background:Previous studies of nurses' critical thinking skills that included demographic characteristics as determinants have been inconclusive. This study explored demographic determinants of critical thinking skills among nurses from public hospitals in Peninsular Malaysia.Method:This cross-sectional study included 549 nurses recruited via multistage cluster sampling. Nurses completed the demographic questionnaire and Health Sciences Reasoning Test (HSRT).Results:The majority of respondents failed to demonstrate critical thinking skills with a mean overall HSRT score of 13.8 (The majority of respondents failed to demonstrate critical thinking skills with a mean overall HSRT score of 13.8 (SD= 3.4). Educational qualifications (p= .003) and clinical specialties (p= .022) were significantly related to nurses' critical thinking skills. Years of clinical experience, age, and job ranking were not significantConclusion:The findings indicate a need to address the present curriculum in nursing education and to reinforce critical thinking skills in the nursing workforce. Future research on how nurses in Malaysia acquire critical thinking skills is needed. The findings indicate a need to address the present curriculum in nursing education and to reinforce critical thinking skills in the nursing workforce. Future research on how nurses in Malaysia acquire critical thinking skills is needed. [[J Contin Educ Nurs. 2020;51(3):109–117.]

Mankind’s quest to reduce its dependency on fossil fuel involves biomass as a promising alternative. However, direct application of raw biomass faces problems such as high moisture content, low heating value, and poor grindability. Pyrolysis is one of the pre-treatment methods to improve biomass properties particularly its energy density. This study is aimed at investigating the pyrolysis of oil palm trunk (OPT) into biocoal and its suitability for solid fuel applications in terms of slagging and fouling tendencies, bulk density, proximate and ultimate analysis, higher heating value, energy densification ratio, and mass and energy yield. The biocoal was produced using a top-lit, updraft reactor with a peak temperature of 550 °C and fixed air flowrate of 4.63 L/min. The bulk density of OPT biocoal was 87.7 kg/m3which is 4.63% lower than that of original OPT due to the increased porosity. The elemental composition of our biocoal resembles lignite. The volatile matter content decreased by a factor of 1.87 while the fixed carbon content and higher heating value (HHV) increased from 4.29 to 30.9% and from 14.5 to 19.6 MJ/kg, respectively. The HHV of biocoal increased by a factor of 1.36 relative to that of raw OPT; however, the resulting energy yield was low (37.6 ± 1.9%) due to a low biocoal yield of 27.8 ± 1.4%. The ash content increased by a factor of 1.5, resulting in an ash content of 27.8 wt% for biocoal. This increment may exacerbate the slagging and fouling propensity in furnaces and boilers as indicated by the slagging and bed agglomeration index which increased from 2.0 to 5.2 and from 0.4 to 0.7, respectively. Demineralization, a lower pyrolysis temperature and subsequent briquetting of OPT biocoal are suggested to improve its fuel properties for co-combustion in coal-firing power plants.

Device‐encapsulated human stem cell‐derived pancreatic endoderm (PE) can generate functional β‐cell implants in the subcutis of mice, which has led to the start of clinical studies in type 1 diabetes. Assessment of the formed functional β‐cell mass (FBM) and its correlation with in vivo metabolic markers can guide clinical translation. We recently reported ex vivo characteristics of device‐encapsulated human embryonic stem cell‐derived (hES)‐PE implants in mice that had established a metabolically adequate FBM during 50‐week follow‐up. Cell suspensions from retrieved implants indicated a correlation with the number of formed β cells and their maturation to a functional state comparable to human pancreatic β cells. Variability in metabolic outcome was attributed to differences in number of PE‐generated β cells. This variability hinders studies on processes involved in FBM‐formation. This study reports modifications that reduce variability. It is undertaken with device‐encapsulated human induced pluripotent stem cell‐derived‐PE subcutaneously implanted in mice. Cell mass of each cell type was determined on intact tissue inside the device to obtain more precise data than following isolation and dispersion. Implants in a preformed pouch generated a glucose‐controlling β‐cell mass within 20 weeks in over 60% of recipients versus less than 20% in the absence of a pouch, whether the same or threefold higher cell dose had been inserted. In situ analysis of implants indicated a role for pancreatic progenitor cell expansion and endocrine differentiation in achieving the size of β‐ and α‐cell mass that correlated with in vivo markers of metabolic control. Stem Cells Translational Medicine2019;8:1296&1305 Device‐encapsulated human induced pluripotent stem cell‐derived pancreatic endoderm can generate a glucose‐controlling β‐cell mass in immune‐compromised mice. For a dose of 5 × 106cells, this involves pancreatic progenitor cell differentiation as well as a cell mass increase following an initial cell loss. Measurement of these processes inside the device allows selection of conditions that help achieve metabolic control.

We recently reported the case of a patient who experienced three consecutive episodes of acute kidney injury, all of them following a “Brazilian” hair-straightening treatment. The cream used for the straightening procedure contained glyoxylic acid. To examine possible underlying mechanisms causing kidney injury, four groups of mice were exposed to topical application of (i) the straightening product, (ii) a cream containing 10% glyoxylic acid, (iii) a cream containing 10% glycolic acid or (iv) a control cream. Application of glycolic acid slightly increased urine oxalate excretion, while glyoxylic acid and the straightening product dramatically increased urine oxalate excretion and caused calcium oxalate nephropathy after transcutaneous absorption. Thus, glyoxylic acid was presumptively absorbed through the skin, metabolized to oxalate and promoted crystallization of calcium oxalate in urine. Hence, cosmetic products containing glyoxylic acid may induce acute kidney injury and should be discontinued. Further studies are needed to investigate the metabolism of glycolic acid and glyoxylic acid following topical application.

The aim of this study is to provide a comprehensive review of the current literature on test techniques that imitate the contact phase between the shoe and the ground to study shoe wear over time. Scoping review. Peer-reviewed studies were identified from electronic databases using a structured keyword search and a screening process. Relevant characteristics have been classified into three fields: the control of the test machines, the characteristics of the foot-ankle complex machine control and the outputs of the mechanical tests. Eight peer-reviewed studies were retrieved after screening and further analyzed. They described seven different machines and testing arrangements presenting different mechanical designs and controls. The most advanced machines not only controlled the kinematic of shod passive prosthesis, but also included a form of control of the vertical ground reaction forces and the use of an active foot system with two joints. Still, the resulting foot kinematics and ground reaction forces remained far from those of a real human when the machines simulate walking or running at a realistic speed. Moreover, none of the reviewed studies presented results of wear tests for a long period of time. This review summarizes the different mechanical approaches described in existing shoe wear study literature. Although none of the reviewed studies proposed a fully satisfying mechanical solution, they presented encouraging results. The most promising concepts and the remaining research tracks have been identified.

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R2D(51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy.

Graphical abstract Abstract Conventional coagulants, like aluminium sulphate and ferric chloride, are used in potable water treatment and involve non-sustainable mining and transformation of raw materials for their production with costly sludge disposal. Natural coagulants are mostly obtained from bacteria, fungi, animals and plants and are classified as polysaccharide, amino-polysaccharide, poly-phenols and proteins-based substances. Plant-based coagulants extracted from Moringa oleifera , Strychnos potatorum Linn , Plantago ovate , Trigonella foenum graecum and Opuntia ficus indica are potential substitutes to chemicals mostly based on bench-scale testing. These are organic polymers and polyelectrolytes that are classified as cationic, anionic and non-ionic coagulants. This paper provides a historical and contemporary review of plant-based coagulants, their notable milestones achieved, chemistry involved, as well as bench, pilot and full scale trials, highlighting the effects of plant-based coagulants on physico-bio-chemical properties of raw water. Commercialisation constrains are also included and discussed. [ABSTRACT FROM AUTHOR]

The benefit of belatacept on antibody‐mediated rejection (ABMR) incidence after kidney transplant with preformed donor‐specific antibodies (DSAs)has never been assessed. Between 2014 and 2016, we conducted a multicenter prospective clinical trial with 49 patients to determine kidney allograft outcome in recipients with preformed DSAs(maximal mean fluorescence intensity 500 to 3000) treated with belatacept (BELACORtrial). Immunosuppressive strategy included antithymocyte globulin, belatacept, mycophenolate mofetil, and steroids. An ancillary control group was designed retrospectively, including patients fulfilling the same inclusion criteria treated with calcineurin inhibitors. In BELACORgroup, no patient exhibited acute ABMR, patient and allograft survival at 1 year was 100% and 95.4%, respectively, and the estimated glomerular filtration rate was 53.2 mL/min/1.73 m2. However, the 12‐month incidence of acute T cell–mediated rejection was 25.4% (14.5% to 42.4%). Comparison with the control group showed significantly higher T cell–mediated rejectionincidence only in the BELACORgroup (P = .003). Considering the DSAs, the outcome was similar in the 2 groups except a significantly higher number of patients displayed a complete disappearance of class II DSAsin the BELACORgroup (P= .001). Belatacept was not associated with an acute ABMRincreased risk and may be considered as immunosuppressive strategy in transplant recipients with preformed DSAs(maximal mean fluorescence intensity500 to 3000). Prospective randomized trials are needed to confirm these results. The BELACOR prospective clinical trial finds no increased risk of antibody‐mediated rejection when kidney transplant recipients with mild immunological risks are treated with belatacept.

The benefit of belatacept on antibody-mediated rejection (ABMR) incidence after kidney transplant with preformed donor-specific antibodies (DSAs) has never been assessed. Between 2014 and 2016, we conducted a multicenter prospective clinical trial with 49 patients to determine kidney allograft outcome in recipients with preformed DSAs (maximal mean fluorescence intensity 500 to 3000) treated with belatacept (BELACOR trial). Immunosuppressive strategy included antithymocyte globulin, belatacept, mycophenolate mofetil, and steroids. An ancillary control group was designed retrospectively, including patients fulfilling the same inclusion criteria treated with calcineurin inhibitors. In BELACOR group, no patient exhibited acute ABMR, patient and allograft survival at 1 year was 100% and 95.4%, respectively, and the estimated glomerular filtration rate was 53.2 mL/min/1.73 m2. However, the 12-month incidence of acute T cell–mediated rejection was 25.4% (14.5% to 42.4%). Comparison with the control group showed significantly higher T cell–mediated rejection incidence only in the BELACOR group (P= .003). Considering the DSAs, the outcome was similar in the 2 groups except a significantly higher number of patients displayed a complete disappearance of class II DSAs in the BELACOR group (P= .001). Belatacept was not associated with an acute ABMR increased risk and may be considered as immunosuppressive strategy in transplant recipients with preformed DSAs (maximal mean fluorescence intensity 500 to 3000). Prospective randomized trials are needed to confirm these results.

PurposeSelf-expandable stents have broadened the spectrum of endovascular treatment of intracranial aneurysms. However, procedures involving double stenting in Y/X configurations carry a relatively high risk of procedural complications. The Neuroform ATLAS, the evolution of Neuroform EZ, is a nitinol self-expanding hybrid/open cell stent which can be delivered through a low profile 0.017 inch catheter. We present our experience in the treatment of intracranial aneurysms with this stent in Y and X configurations.Materials and methodsWe prospectively maintained a database from consecutive patients who underwent double stent assisted coiling with the Neuroform ATLAS, from July 2015 to February 2019. Clinical and angiographic results were analyzed.Results55 patients harboring 55 bifurcation aneurysms were treated with double stenting: 52 ‘Y’ configurations, 3 ‘X’ configurations. Deployment was successful in all cases. Post-treatment control angiography showed complete occlusion in 33 cases (60%), neck remnant in 8 cases (14.5%), and incomplete occlusion in 14 cases (25.4%). The overall symptomatic periprocedural complication rate was 12.7%. 38 aneurysms underwent follow-up (69%, mean duration 16 months): 33 aneurysms (87%) were completely occluded, 3 aneurysms (8%) had a neck remnant, and 2 aneurysms (5%) were incompletely occluded.ConclusionThe Neuroform ATLAS is an effective device for treatment of bifurcation aneurysms, allowing good conformability, a high level of navigability, and easy mesh crossing to perform Y/X stenting procedures. The rate of procedural complications remains non-negligible, and an indication for a double stenting procedure should be carefully discussed in a multidisciplinary meeting.

Increasing numbers of cancer patients are using Chinese herbs (CHs). However, differences among prior studies make it difficult to draw firm conclusions about the clinical usefulness of any specific CH formula. The primary objective of this study was to establish the acceptability of taking a standardized CH formula for patients with advanced lung cancer. The secondary objective was to identify any toxicities attributable to this CH formula and to measure changes in quality of life.