Revolution in acute ischaemic stroke care: a practical guide to mechanical thrombectomy

Rapid, safe and effective arterial recanalisation to restore blood flow and improve functional outcome remains the primary goal of hyperacute ischaemic stroke management. The benefit of intravenous thrombolysis with recombinant tissue-type plasminogen activator for patients with severe stroke due to large artery occlusion is limited; early recanalisation is generally less than 30% for carotid, proximal middle cerebral artery or basilar artery occlusion. Since November 2014, nine positive randomised controlled trials of mechanical thrombectomy for large vessel occlusion in the anterior circulation have led to a revolution in the care of patients with acute ischaemic stroke. Its efficacy is unmatched by any previous therapy in stroke medicine, with a number needed to treat of less than 3 for improved functional outcome. With effectiveness shown beyond any reasonable doubt, the key challenge now is how to implement accessible, safe and effective mechanical thrombectomy services. This review aims to provide neurologists and other stroke physicians with a summary of the evidence base, a discussion of practical aspects of delivering the treatment and future challenges. We aim to give guidance on some of the areas not clearly described in the clinical trials (based on evidence where available, but if not, on our own experience and practice) and highlight areas of uncertainty requiring further research

Investigating GAP45 localisation and phosphorylation during plasmodium falciparum schizont development

The invasion of erythrocytes by merozoites is driven by an actomyosin motor assembled below the parasite’s plasma membrane, with the myosin anchored on the inner membrane complex (IMC). The myosin (MyoA) is within a protein complex that is comprised of several proteins including myosin tail domain interacting protein (MTIP) and glideosome associated proteins (GAP) 45 and 50. A ternary complex of MyoA, MTIP and GAP45 is formed and later associates with GAP50. GAP45 is acylated by both myristoyl- and palmitoyl-fatty acids and is phosphorylated. This study has highlighted the GAP45 phosphorylation by calcium dependent protein kinase 1 (CDPK1) in vitro and its possible roles in schizogony. By site directed mutagenesis, substitution of S31, S89, S103 and S156 to alanine decreased the level of GAP45 phosphorylation, with S103A exhibiting a major decrease in 32P incorporation. Phosphorylation on S89 and S103 was studied further in parasites as both residues were among the phospho-sites in phosphopeptides identified in vivo. This study also showed that full length GAP45 labelled internally with GFP (FL-GAP45) is assembled into the motor complex, phosphorylated and transported to the developing IMC in early schizogony, where it accumulates during intracellular development until merozoite release. The C-terminal truncated GFP-GAP45 (N-GAP45; residues 1-29) localised at the plasma membrane instead of the IMC and was not assembled into the motor complex. The N-terminal truncated GFP-GAP45 (C-GAP45; residues 30-205) behaved like FL-GAP45. Modifying serine residues, S89 and S103, in GAP45 with alanine or aspartate had no apparent effect on its assembly into the protein complex or its intracellular location during schizont development and merozoite maturation. A second highly phosphorylated component of the complex (GAP40) was also identified. The early assembly of the motor complex suggests that it has functions in addition to its role in erythrocyte invasion

Green consumerism, green perceived value, and restaurant revisit intention: Millennials' sustainable consumption with moderating effect of green perceived quality

Adopting green practices does not always guarantee customer retention and loyalty. Employing the theoretical lens of cue utilization theory, we conceptualize green perceived quality as sending internal and external cues which help consumers form judgments about product quality and perceived value. Based on a survey of 280 restaurant customers, we hypothesize and report a positive and significant influence of both green consumerism and green perceived value on customer revisit intention. Further, the results confirm the moderating role of green perceived quality. From a practical point of view, managers interested in benefiting from the green practices of their restaurants should focus on increasing their customers' evaluation and overall judgment of the environmental quality of both their food and services

The cyclic interaction between daytime behavior and the sleep behavior of laboratory dogs

Sleep deprivation has been found to negatively affect an individual´s physical and psychological health. Sleep loss affects activity patterns, increases anxiety-like behaviors, decreases cognitive performance and is associated with depressive states. The activity/rest cycle of dogs has been investigated before, but little is known about the effects of sleep loss on the behavior of the species. Dogs are polyphasic sleepers, meaning the behavior is most observed at night, but bouts are also present during the day. However, sleep can vary with ecological and biological factors, such as age, sex, fitness, and even human presence. In this study, kennelled laboratory adult dogs’ sleep and diurnal behavior were recorded during 24-h, five-day assessment periods to investigate sleep quality and its effect on daily behavior. In total, 1560 h of data were analyzed, and sleep metrics and diurnal behavior were quantified. The relationship between sleeping patterns and behavior and the effect of age and sex were evaluated using non-parametric statistical tests and GLMM modelling. Dogs in our study slept substantially less than previously reported and presented a modified sleep architecture with fewer awakenings during the night and almost no sleep during the day. Sleep loss increased inactivity, decreased play and alert behaviors, while increased time spent eating during the day. Males appeared to be more affected by sleep fragmentation than females. Different age groups also experienced different effects of sleep loss. Overall, dogs appear to compensate for the lack of sleep during the night by remaining inactive during the day. With further investigations, the relationship between sleep loss and behavior has the potential to be used as a measure of animal welfare

[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography

Purpose 111In (typically as [111In]oxinate3) is a gold standard radiolabel for cell tracking in humans by scintigraphy. A long half-life positron-emitting radiolabel to serve the same purpose using positron emission tomography (PET) has long been sought. We aimed to develop an 89Zr PET tracer for cell labelling and compare it with [111In]oxinate3 single photon emission computed tomography (SPECT). Methods [89Zr]Oxinate4 was synthesised and its uptake and efflux were measured in vitro in three cell lines and in human leukocytes. The in vivo biodistribution of eGFP-5T33 murine myeloma cells labelled using [89Zr]oxinate4 or [111In]oxinate3 was monitored for up to 14 days. 89Zr retention by living radiolabelled eGFP-positive cells in vivo was monitored by FACS sorting of liver, spleen and bone marrow cells followed by gamma counting. Results Zr labelling was effective in all cell types with yields comparable with 111In labelling. Retention of 89Zr in cells in vitro after 24 h was significantly better (range 71 to >90 %) than 111In (43–52 %). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with 111In or 89Zr (initial pulmonary accumulation followed by migration to liver, spleen and bone marrow), but later translocation of radioactivity to kidneys was much greater for 111In. In liver, spleen and bone marrow at least 92 % of 89Zr remained associated with eGFP-positive cells after 7 days in vivo. Conclusion [89Zr]Oxinate4 offers a potential solution to the emerging need for a long half-life PET tracer for cell tracking in vivo and deserves further evaluation of its effects on survival and behaviour of different cell types

Impact of phosphorus application on drought resistant responses of Eucalyptus grandis seedlings

Eucalyptus grandis is the most widely planted tree species worldwide and can face severe drought during the initial months after planting because the root system is developing. A complete randomized design was used to study the effects of two water regimes (well-watered and water-stressed) and phosphorus (P) applications (with and without P) on the morphological and physio-biochemical responses of E. grandis. Drought had negative effects on the growth and metabolism of E. grandis, as indicated by changes in morphological traits, decreased net photosynthetic rates (Pn), pigment concentrations, leaf relative water contents (LRWCs), nitrogenous compounds, over-production of reactive oxygen species (ROS) and higher lipid peroxidation. However, E. grandis showed effective drought tolerance strategies, such as reduced leaf area and transpiration rate (E), higher accumulation of soluble sugars and proline and a strong antioxidative enzyme system. P fertilization had positive effects on well-watered seedlings due to improved growth and photosynthesis, which indicated the high P requirements during the initial E. grandis growth stage. In drought-stressed seedlings, P application had no effects on the morphological traits, but it significantly improved the LRWC, Pn, quantum efficiency of photosystem II (Fv/Fm), chlorophyll pigments, nitrogenous compounds and reduced lipid peroxidation. P fertilization improved E. grandis seedling growth under well-watered conditions but also ameliorated some leaf physiological traits under drought conditions. The effects of P fertilization are mainly due to the enhancement of plant N nutrition. Therefore, P can be used as a fertilizer to improve growth and production in the face of future climate change.Fil: Tariq, Akash. Chinese Academy of Sciences; República de China. University of Chinese Academy of Sciences; ChinaFil: Pan, Kaiwen. Chinese Academy of Sciences; República de ChinaFil: Olatunji, Olusanya A. Chinese Academy of Sciences; República de China. University of Chinese Academy of Sciences; ChinaFil: Graciano, Corina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; ArgentinaFil: Li, Zilong. Chinese Academy of Sciences; República de China. University of Chinese Academy of Sciences; ChinaFil: Li, Ningning. Southwest University; ChinaFil: Song, Dagang. Chinese Academy of Sciences; República de China. University of Chinese Academy of Sciences; ChinaFil: Sun, Feng. Chinese Academy of Sciences; República de China. University of Chinese Academy of Sciences; ChinaFil: Wu, Xiaogang. Chinese Academy of Sciences; República de ChinaFil: Dakhil, Mohammed A.. Chinese Academy of Sciences; República de China. University of Chinese Academy of Sciences; China. Helwan University; EgiptoFil: Sun, Xiaoming. Chinese Academy of Sciences; República de ChinaFil: Zhang, Lin. Chinese Academy of Sciences; República de Chin

Molecular characteristics and chromatin texture features in acute promyelocytic leukemia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background: Acute promyelocytic leukemia is a cytogenetically well defined entity. Nevertheless, some features observed at diagnosis are related to a worse outcome of the patients. Methods: In a prospective study, we analyzed peripheral (PB) leukocyte count, immunophenotype, methylation status of CDKN2B, CDKN2A and TP73; FLT3 and NPM1 mutations besides nuclear chromatin texture characteristics of the leukemic cells. We also examined the relation of these features with patient's outcome. Results: Among 19 cases, 4 had a microgranular morphology, 7 presented PB leukocytes >10x10(9)/l, 2 had FLT3-ITD and 3 had FLT3-TKD (all three presenting a methylated CDKN2B). NPM1 mutation was not observed. PB leukocyte count showed an inverse relation with standard deviation of gray levels, contrast, cluster prominence, and chromatin fractal dimension (FD). Cases with FLT3-ITD presented a microgranular morphology, PB leukocytosis and expression of HLA-DR, CD34 and CD11b. Concerning nuclear chromatin texture variables, these cases had a lower entropy, contrast, cluster prominence and FD, but higher local homogeneity, and R(2)45, in keeping with more homogeneously distributed chromatin. In the univariate Cox analysis, a higher leukocyte count, FLT3-ITD mutation, microgranular morphology, methylation of CDKN2B, besides a higher local homogeneity of nuclear chromatin, a lower chromatin entropy and FD were associated to a worse outcome. All these features lost significance when the cases were stratified for FLT3-ITD mutation. Methylation status of CDNK2A and TP73 showed no relation to patient's survival. Conclusion: in APL, patients with FLT3-ITD mutation show different clinical characteristics and have blasts with a more homogeneous chromatin texture. Texture analysis demonstrated that FLTD-ITD was accompanied not only by different cytoplasmic features, but also by a change in chromatin structure in routine cytologic preparations. Yet we were not able to detect chromatin changes by nuclear texture analysis of patients with the FTLD-TKD or methylation of specific genes.7Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2007/54686-0]CNPq [302277/2009-9, 307270/2010-6, 402022/2010-6

A one-stop perineal clinic: our eleven-year experience.

INTRODUCTION AND HYPOTHESIS: The perineal clinic is a dedicated setting offering assessment for various childbirth-related presentations including obstetric anal sphincter injuries (OASIs), perineal wound complications, pelvic floor dysfunction and other conditions such as female genital mutilation(FGM). We describe the clinical presentation and outcomes of women from a tertiary perineal clinic based on data collected over an 11-year period. METHODS: This is a retrospective observational study. A one-stop outpatient service was offered to all women who sustained OASIs (postnatally and antenatally in a subsequent pregnancy), perineal complications (within 16 weeks postpartum), FGM and/or peripartum symptoms of urinary/anal incontinence or prolapse. Assessment included history with validated questionnaires, examination and anal manometry and endoanal ultrasound when appropriate. Outcomes were compared among different grades of OASIs. Management of each type of presentation was reported with outcomes. RESULTS: There were 3254 first attendance episodes between 2006 and 2016. The majority (58.1%) were for OASIs, followed by perineal wound complications. Compared to the lower grades, the higher grades of OASI were associated with poorer outcomes in terms of symptoms, investigations and complications. Women with OASIs had unrelated symptoms such as urinary incontinence, perineal pain and wound infections that needed further intervention. A high proportion(42%) of wound complications required further specialist management. CONCLUSION: We describe a dedicated, one-stop perineal clinic model for antenatal and postnatal women for management of perineal and pelvic floor disorders. This comprehensive and novel data will enable clinicians to better counsel women regarding of outcomes after OASI and focus training to minimize risks of morbidities

Successful Surgical Treatment of a Spontaneous Rupture of the Esophagus Diagnosed Two Days after Onset

Esophageal perforation is a relatively uncommon disease with a high rate of mortality and morbidity. Delay in the diagnosis and treatment occurs in more than 50% of cases, leading to a mortality rate of 40–60%. Primary repair is generally considered the gold standard for patients who present within the first 24 h following perforation of the esophagus. In this paper, we present a case of successful surgical treatment of spontaneous rupture of the esophagus that was diagnosed 2 days after onset. The patient was a 42-year-old man admitted to internal medicine with a diagnosis of pleuritis and complaining of chest and back pain. The next day, computed tomography revealed left-sided pleural effusion and mediastinal emphysema. An esophagogram revealed extravasation of the contrast medium from the lower left esophagus to the mediastinal cavity. These results confirmed a rupture of the esophagus, and an emergency left thoracotomy was performed. The perforation was repaired with a single-layered closure and was covered with elevated great omentum obtained by laparotomy. The patient was discharged 23 days after the first surgery. In conclusion, primary repair surgery must be selected as the best treatment beyond 24 h if the patient's general state was stable and there was no evidence of clinical sepsis

Validation of MRC Centre MRI calf muscle fat fraction protocol as an outcome measure in CMT1A

OBJECTIVE: To translate the quantitative MRC Centre MRI protocol in Charcot-Marie-Tooth disease type 1A (CMT1A) to a second site; validate its responsiveness in an independent cohort; and test the benefit of participant stratification to increase outcome measure responsiveness. METHODS: Three healthy volunteers were scanned for intersite standardization. For the longitudinal patient study, 11 patients with CMT1A were recruited with 10 patients rescanned at a 12-month interval. Three-point Dixon MRI of leg muscles was performed to generate fat fraction (FF) maps, transferred to a central site for quality control and analysis. Clinical data collected included CMT Neuropathy Score. RESULTS: Test-retest reliability of FF within individual healthy calf muscles at the remote site was excellent: intraclass correlation coefficient 0.79, limits of agreement -0.67 to +0.85 %FF. In patients, mean calf muscle FF was 21.0% and correlated strongly with disease severity and age. Calf muscle FF significantly increased over 12 months (+1.8 ± 1.7 %FF, p = 0.009). Patients with baseline FF >10% showed a 12-month FF increase of 2.9% ± 1.3% (standardized response mean = 2.19). CONCLUSIONS: We have validated calf muscle FF as an outcome measure in an independent cohort of patients with CMT1A. Responsiveness is significantly improved by enrolling a stratified patient cohort with baseline calf FF >10%