Assessment of health literacy in a French emergency department.

BACKGROUND: Health literacy (HL) has become a subject of major interest in public health worldwide. It is known to be linked to self-efficacy in care use and to global health status, and a non-negligible frequency of problematic or inadequate levels of HL in populations worldwide is reported. As this has yet to be evaluated in France, the present study aimed to evaluate the HL level of patients in a French emergency department (ED). METHODS: We conducted a descriptive, cross-sectional observational, single center study in the ED of the Lyon Sud hospital (Hospices civils de Lyon, Lyon, France). The primary endpoint was the HL level of the patients determined according to the score obtained using the 16-item European Health Literacy Survey Questionnaire. The secondary endpoint was the identification of sociodemographic factors associated with the HL level. RESULTS: A total of 189 patients were included for analysis. 10% (95% CI [3%; 17%]) of the patients had an inadequate HL, 38% (95% CI [31%; 45%]) had a problematic HL, and 53% (95% CI [46%; 61%] had an adequate HL. In multivariate analysis, age and perceived health status were independent predictors of the HL level; OR =0.82 (95% CI [0.69; 0.97]; p=0.026) for a 10-year increase in age, and OR =1.84 (95% CI [1.22; 2.82]; p=0.004]). CONCLUSIONS: The HL level of the patients in the ED studied herein was similar to that found in the population of France and other European countries and was influenced by age and perceived health status, which are both associated with care needs. It may be therefore interesting to explore in future studies how taking into consideration HL in the general population may lead to a better self-efficacy in care and optimize the use of the healthcare system.

The Janus face of endogenous neuronal tPA: promoting self-protection and worsening the death of neighboring neurons.

Recombinant tissue-type plasminogen activator (r-tPA/Actilyse) stands as the prevailing pharmacological solution for treating ischemic stroke patients, of whom because their endogenous circulating tPA alone is not sufficient to rescue reperfusion and to promote favorable outcome. Beyond the tPA contributed by circulating endothelial cells and hepatocytes, neurons also express tPA, sparking debates regarding its impact on neuronal fate ranging from pro-survival to neurotoxic properties. In order to investigate the role of neuronal tPA during brain injuries, we developed models leading to its conditional deletion in neurons, employing AAV9-pPlat-GFP and AAV9-pPlat-Cre-GFP along with tPA floxed mice. These models were subjected to N-methyl-D-aspartate (NMDA)-induced excitotoxicity or thromboembolic ischemic stroke in mice. Initially, we established that our AAV9 constructs selectively transduce neurons, bypassing other brain cell types. Subsequently, we demonstrated that tPA-expressing neurons exhibit greater resistance against NMDA-induced excitotoxicity compared to tPA negative neurons. The targeted removal of tPA in neurons heightened the susceptibility of these neurons to cell death and prevented a paracrine neurotoxic effect on tPA non-expressing neurons. Under ischemic conditions, the self-neuroprotective influence of tPA encompassed both excitatory (GFP+/Tbr1+) and inhibitory (GFP+/GABA+) neurons. Our data indicate that endogenous neuronal tPA is a protective or deleterious factor against neuronal death in an excitotoxic/ischemic context, depending on whether it acts as an autocrine or a paracrine mediator.

Anatomical classification of feline congenital extrahepatic portosystemic shunts based on CT angiography: A SVSTS and VIRIES multi-institutional study in 231 cats.

The prevalence of anatomical-based subtypes of feline congenital extrahepatic portosystemic shunts (EHPSS) has not been completely elucidated. The goal of this study was to use CT angiography to create an anatomical-based nomenclature system for feline congenital EHPSS. Additionally, subjective portal perfusion scores were generated to determine if intrinsic portal vein development was associated with different shunt conformations or patient age at the time of CT. The SVSTS and VIRIES list services were used to recruit cases. Data collected included patient DOB, gender, breed, weight, CT date, and reported diagnosis. Shunts were classified based upon (1) the shunt portal vessel(s) of origin, (2) the shunt systemic vessel(s) of insertion, and (3) any substantial portal vessels contributing to the shunt. Additionally, hepatic portal perfusion was subjectively scored between 1 (poor/none) and 5 (good/normal) based on the caliber of the intrahepatic PVs. A total of 264 CT scans were submitted from 29 institutions. Due to exclusion criteria, 33 (13%) were removed, leaving 231 CT scans to be included. Twenty-five different EHPSS anatomies were identified with five classifications accounting for 78% of all shunts (LGP [53%], LGC-post [11%], LCG [7%], LGC-pre [4%], and PC [4%]). Shunt origin involved the left gastric vein in 75% of the described classifications. Significant differences were identified among the five most common shunt types with respect to age at the time of CT scan (P = .002), breed (P < .001), and subjective portal perfusion score (P < .001). This refined anatomical classification system for feline EHPSS may enable improved understanding, treatment comparisons, and outcome prediction for cats with these anomalies.

Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.

Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single bolus administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities of rtPA and TNK were evaluated in endothelial cells, astrocytes, and neuronal cells. In addition, their in vivo efficacy was independently assessed at two research centers using an ischemic thromboembolic mouse model. Both therapies were tested via early (20 and 30 min) and late administration (4 and 4.5 h) after stroke. rtPA, but not TNK, caused cell death only in neuronal cultures. Mice were less sensitive to thrombolytic therapies than humans, requiring doses 10-fold higher than the established clinical dose. A single bolus dose of 2.5 mg/kg TNK led to an infarct reduction similar to perfusion with 10 mg/kg of rtPA. Early administration of TNK decreased the hemorrhagic transformations compared to that by the early administration of rtPA; however, this result was not obtained following late administration. These two independent preclinical studies support the use of TNK as a promising reperfusion alternative to rtPA.

Continuous low-level dietary exposure to glyphosate elicits dose and sex-dependent synaptic and microglial adaptations in the rodent brain.

Prolonged exposure to low levels of dietary contaminants is a context in modern life that could alter organ physiology gradually. Here, we aimed to investigate the impact of continuous exposure to acceptable daily intake (ADI) and non-observable adverse effect level (NOAEL) of glyphosate from gestation to adulthood using C57BL/6J mice and incorporating these levels into their food pellets. From adulthood, we analyzed neurophysiological and neuro-glia cellular adaptations in male and female animals. Using ex-vivo hippocampal slice electrophysiology, we found a reduced efficacy of Schaffer collateral-to-CA1 excitatory synapses in glyphosate-exposed dietary conditions, with ADI and NOAEL dose-dependent effects. Short-term facilitation of excitatory synaptic transmission was specifically increased in NOAEL conditions, with a predominant influence in males, suggesting a reduced probability of neurotransmitter release. Long-term synaptic potentiation (LTP) was decreased in NOAEL-exposed mice. Next, we explore whether these neurophysiological modifications are associated with neuro-glia changes in the somatosensory cortex and hippocampus. High-resolution confocal microscopy analyses unveil a dose-dependent increased density of excitatory Vglut1+ Homer1+ synapses. Microglial Iba1+ cells displayed a shortening of their ramifications, a sign of cellular reactivity that was more pronounced in males at NOAEL levels. The morphology of GFAP+ astrocytes was generally not modified. Finally, we asked whether mouse-specific cross-correlations exist among all data sets generated. This examination included the novel object recognition (NOR) test performed before ex vivo functional and immunohistochemical examinations. We report a negative linear regression between the number of synapses and NOR or LTP maintenance when plotting ADI and NOAEL datasets. These results outline synaptic and microglial cell adaptations resulting from prenatal and continuous dietary low levels of glyphosate, discernible in, but not limited to, adult males exposed to the NOAEL. We discuss the potential significance of these findings to real-world consumer situations and long-term brain resilience.

Improving stroke outcomes in hyperglycemic mice by modulating tPA/NMDAR signaling to reduce inflammation and hemorrhages.

ABSTRACT: The pharmacological intervention for ischemic stroke hinges on intravenous administration of the recombinant tissue-type plasminogen activator (rtPA, Alteplase/Actilyse) either as a standalone treatment or in conjunction with thrombectomy. However, despite its clinical significance, broader use of rtPA is constrained because of the risk of hemorrhagic transformations (HTs). Furthermore, the presence of diabetes or chronic hyperglycemia is associated with an elevated risk of HT subsequent to thrombolysis. This detrimental impact of tPA on the neurovascular unit in patients with hyperglycemia has been ascribed to its capacity to induce endothelial N-methyl-D-aspartate receptor (NMDAR) signaling, contributing to compromised blood-brain barrier integrity and neuroinflammatory processes. In a mouse model of thromboembolic stroke with chronic hyperglycemia, we assessed the effectiveness of rtPA and N-acetylcysteine (NAC) as thrombolytic agents. We also tested the effect of blocking tPA/NMDAR signaling using a monoclonal antibody, Glunomab. Magnetic resonance imaging, speckle contrast imaging, flow cytometry, and behavioral tasks were used to evaluate stroke outcomes. In hyperglycemic animals, treatment with rtPA resulted in lower recanalization rates and increased HTs. Conversely, NAC treatment reduced lesion sizes while mitigating HTs. After a single administration, either in standalone or combined with rtPA-induced thrombolysis, Glunomab reduced brain lesion volumes, HTs, and neuroinflammation after stroke, translating into improved neurological outcomes. Additionally, we demonstrated the therapeutic efficacy of Glunomab in combination with NAC or as a standalone strategy in chronic hyperglycemic animals. Counteracting tPA-dependent endothelial NMDAR signaling limits ischemic damages induced by both endogenous and exogenous tPA, including HTs and inflammatory processes after ischemic stroke in hyperglycemic animals.

Parabiosis Discriminates the Circulating, Endothelial, and Parenchymal Contributions of Endogenous Tissue-Type Plasminogen Activator to Stroke.

BACKGROUND: Intravenous injection of alteplase, a recombinant tPA (tissue-type plasminogen activator) as a thrombolytic agent has revolutionized ischemic stroke management. However, tPA is a more complex enzyme than expected, being for instance able to promote thrombolysis, but at the same time, also able to influence neuronal survival and to affect the integrity of the blood-brain barrier. Accordingly, the respective impact of endogenous tPA expressed/present in the brain parenchyma versus in the circulation during stroke remains debated. METHODS: To address this issue, we used mice with constitutive deletion of tPA (tPANull [tPA-deficient mice]) or conditional deletion of endothelial tPA (VECad [vascular endothelial-Cadherin-Cre-recombinase]-Cre∆tPA). We also developed parabioses between tPANull and wild-type mice (tPAWT), anticipating that a tPAWT donor would restore levels of tPA to normal ones, in the circulation but not in the brain parenchyma of a tPANull recipient. Stroke outcomes were investigated by magnetic resonance imaging in a thrombo-embolic or a thrombotic stroke model, induced by local thrombin injection or FeCl3 application on the endothelium, respectively. RESULTS: First, our data show that endothelial tPA, released into the circulation after stroke onset, plays an overall beneficial role following thrombo-embolic stroke. Accordingly, after 24 hours, tPANull/tPANull parabionts displayed less spontaneous recanalization and reperfusion and larger infarcts compared with tPAWT/tPAWT littermates. However, when associated to tPAWT littermates, tPANull mice had similar perfusion deficits, but less severe brain infarcts. In the thrombotic stroke model, homo- and hetero-typic parabionts did not differ in the extent of brain damages and did not differentially recanalize and reperfuse. CONCLUSIONS: Together, our data reveal that during thromboembolic stroke, endogenous circulating tPA from endothelial cells sustains a spontaneous recanalization and reperfusion of the tissue, thus, limiting the extension of ischemic lesions. In this context, the impact of endogenous parenchymal tPA is limited.

Thrombolytic therapy based on lyophilized platelet-derived nanocarriers for ischemic stroke.

BACKGROUND: Intravenous administration of fibrinolytic drugs, such as recombinant tissue plasminogen activator (rtPA) is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and risk of hemorrhagic transformations. Platelet membrane-based nanocarriers have received increasing attention for ischemic stroke therapies, as they have natural thrombus-targeting activity, can prolong half-life of the fibrinolytic therapy, and reduce side effects. In this study we have gone further in developing platelet-derived nanocarriers (defined as cellsomes) to encapsulate and protect rtPA from degradation. Following lyophilization and characterization, their formulation properties, biocompatibility, therapeutic effect, and risk of hemorrhages were later investigated in a thromboembolic model of stroke in mice. RESULTS: Cellsomes of 200 nm size and loaded with rtPA were generated from membrane fragments of human platelets. The lyophilization process did not influence the nanocarrier size distribution, morphology, and colloidal stability conferring particle preservation and long-term storage. Encapsulated rtPA in cellsomes and administered as a single bolus showed to be as effective as a continuous clinical perfusion of free rtPA at equal concentration, without increasing the risk of hemorrhagic transformations or provoking an inflammatory response. CONCLUSIONS: This study provides evidence for the safe and effective use of lyophilized biomimetic platelet-derived nanomedicine for precise thrombolytic treatment of acute ischemic stroke. In addition, this new nanoformulation could simplify the clinical use of rtPA as a single bolus, being easier and less time-consuming in an emergency setting than a treatment perfusion, particularly in stroke patients. We have successfully addressed one of the main barriers to drug application and commercialization, the long-term storage of nanomedicines, overcoming the potential chemical and physical instabilities of nanomedicines when stored in an aqueous buffer.

FGF19 and its analog Aldafermin cooperate with MYC to induce aggressive hepatocarcinogenesis.

FGF19 hormone has pleiotropic metabolic functions, including the modulation of insulin sensitivity, glucose/lipid metabolism and energy homeostasis. On top of its physiological metabolic role, FGF19 has been identified as a potentially targetable oncogenic driver, notably in hepatocellular carcinoma (HCC). Nevertheless, FGF19 remained an attractive candidate for treatment of metabolic disease, prompting the development of analogs uncoupling its metabolic and tumor-promoting activities. Using pre-clinical mice models of somatic mutation driven HCC, we assessed the oncogenicity of FGF19 in combination with frequent HCC tumorigenic alterations: p53 inactivation, CTNNB1 mutation, CCND1 or MYC overexpression. Our data revealed a strong oncogenic cooperation between FGF19 and MYC. Most importantly, we show that this oncogenic synergy is conserved with a FGF19-analog Aldafermin (NGM282), designed to solely mimic the hormone's metabolic functions. In particular, even a short systemic treatment with recombinant proteins triggered rapid appearance of proliferative foci of MYC-expressing hepatocytes. The fact that FGF19 analog Aldafermin is not fully devoid of the hormone's oncogenic properties raises concerns in the context of its potential use for patients with damaged, mutation-prone liver.

Dietary Amino Acid Source Elicits Sex-Specific Metabolic Response to Diet-Induced NAFLD in Mice.

SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a sexually dimorphic disease influenced by dietary factors. Here, the metabolic and hepatic effects of dietary amino acid (AA) source is assessed in Western diet (WD)-induced NAFLD in male and female mice. METHODS AND RESULTS: The AA source is either casein or a free AA mixture mimicking the composition of casein. As expected, males fed a casein-based WD display glucose intolerance, fasting hyperglycemia, and insulin-resistance and develop NAFLD associated with changes in hepatic gene expression and microbiota dysbiosis. In contrast, males fed the AA-based WD show no steatosis, a similar gene expression profile as males fed a control diet, and a distinct microbiota composition compared to males fed a casein-based WD. Females are protected against WD-induced liver damage, hepatic gene expression, and gut microbiota changes regardless of the AA source. CONCLUSIONS: Free dietary AA intake prevents the unhealthy metabolic outcomes of a WD preferentially in male mice.

Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism.

Background & Aims: The constitutive androstane receptor (CAR) is a nuclear receptor that binds diverse xenobiotics and whose activation leads to the modulation of the expression of target genes involved in xenobiotic detoxification and energy metabolism. Although CAR hepatic activity is considered to be higher in women than in men, its sex-dependent response to an acute pharmacological activation has seldom been investigated. Methods: The hepatic transcriptome, plasma markers, and hepatic metabolome, were analysed in Car+/+ and Car-/- male and female mice treated either with the CAR-specific agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or with vehicle. Results: Although 90% of TCPOBOP-sensitive genes were modulated in a sex-independent manner, the remaining 10% showed almost exclusive female liver specificity. These female-specific CAR-sensitive genes were mainly involved in xenobiotic metabolism, inflammation, and extracellular matrix organisation. CAR activation also induced higher hepatic oxidative stress and hepatocyte cytolysis in females than in males. Hepatic expression of flavin monooxygenase 3 (Fmo3) was almost abolished and was associated with a decrease in hepatic trimethylamine-N-oxide (TMAO) concentration in TCPOBOP-treated females. In line with a potential role in the control of TMAO homeostasis, CAR activation decreased platelet hyper-responsiveness in female mice supplemented with dietary choline. Conclusions: More than 10% of CAR-sensitive genes are sex-specific and influence hepatic and systemic responses such as platelet aggregation. CAR activation may be an important mechanism of sexually-dimorphic drug-induced liver injury. Impact and implications: CAR is activated by many drugs and pollutants. Its pharmacological activation had a stronger impact on hepatic gene expression and metabolism in females than in males, and had a specific impact on liver toxicity and trimethylamine metabolism. Sexual dimorphism should be considered when testing and/or prescribing xenobiotics known to activate CAR.

[Prehospital triage of undifferentiated syndromes in the ambulance]. / Prehospitale triage op basis van onduidelijke symptomen.

Increasing complexity due to an ageing population, a shortage of healthcare professionals and the rising costs are major concerns for the acute care in the coming years. Innovative triage methods in the ambulance could improve appropriate care for patients with subacute undifferentiated syndromes. A proportion of these patients should not be transferred to an emergency department. We conducted a systematic literature search on prehospital triage in the ambulance and evaluated the results relevant to the Dutch acute care system. Consultation of primary care or hospital physicians by paramedics to decide on the optimal strategy for the individual patient seems promising. Adding a video connection could increase the potential benefits. Point-of-care testing in well-defined syndromes does improve prehospital triage and may therefore be of benefit in undifferentiated syndromes. Both techniques may keep ambulances away from presenting specific patients on emergency departments, enabling appropriate use of scarce acute care facilities.

Emergency medicine research in the Philippines: A scoping review.

Objectives: In this review, we aim to synthesize the current emergency medicine literature in the Philippines in order to determine the depth of research available in the country while delineating the gaps, helping to provide focus to future research in the field. Methods: A literature review was done using 4 databases to identify emergency medicine studies in the Philippines. To explore the research trends among eligible studies, data on study type, countries, and institutions involved as well as study themes were collected and described. Results: A total of 845 studies were screened, and 43 were included in this review. Results show that only 25% of emergency medicine studies were published before 2015. Most studies were observational (37.2%) or descriptive (37.2%) in nature with the University of the Philippines/Philippine General Hospital being the most common contributing institution (17.4%). Metro Manila was the most common study site with more than half of studies conducted in the area. Lastly, among the variety of study disciplines, disaster medicine was the most frequent topic comprising 30.2% of studies reviewed. Conclusions: Compared to the global scene, Philippine emergency medicine research still has a long way to go. This study was able to provide a landscape of the current literature and highlight the study trends. Further, the findings here emphasize the need to expand the scope of emergency medicine studies in the country as it is still a young and growing field with studies tending to cluster around just a small number of institutions and regions.

The histone demethylase Kdm3 prevents auto-immune piRNAs production in Drosophila.

Genome integrity of the animal germline is protected from transposable element activity by PIWI-interacting RNAs (piRNAs). While piRNA biogenesis is intensively explored, little is known about the genetical determination of piRNA clusters, the genomic sources of piRNAs. Using a bimodal epigenetic state piRNA cluster (BX2), we identified the histone demethylase Kdm3 as being able to prevent a cryptic piRNA production. In the absence of Kdm3, dozens of coding gene-containing regions become genuine germline dual-strand piRNA clusters. Eggs laid by Kdm3 mutant females show developmental defects phenocopying loss of function of genes embedded into the additional piRNA clusters, suggesting an inheritance of functional ovarian "auto-immune" piRNAs. Antagonizing piRNA cluster determination through chromatin modifications appears crucial to prevent auto-immune genic piRNAs production.

Qualification and impact of a video-assisted control system in a chemotherapy compounding unit.

OBJECTIVES: Anticancer drug preparation control is essential to ensure quality and patient safety. Drugcam (Eurekam Company) is a digital video-assisted control system based on artificial intelligence methods to identify vials used and volumes withdrawn. As for any control system, qualification is required before use in a chemotherapy compounding unit (CCU). METHODS: We conducted an operational qualification (sensitivity, specificity and accuracy assessment of vials and volumes recognition and quantitative analysis of measured volumes) and a performance qualification (comparison with visual control) of Drugcam in our CCU, as well as an impact study on compounding time and compound supply time. RESULTS: Sensitivity, specificity and accuracy of vials (94%, 98% and 96%, respectively) and volumes (86%, 96% and 91%, respectively) recognition are satisfactory. It depends on both the object presented and the camera tested. False positives, which could lead to release of non-compliant preparation, were detected. Volume reading errors may exceed the tolerance threshold of ±5% for small volumes. Drugcam did not significantly lengthen compounding time and compound supply time. CONCLUSIONS: No recommendations for a qualification method of this new type of control equipment exist. However, a qualification process is essential to understand tool limitations and integrate them into the CCU risk management system. Drugcam enables anticancer drug preparation to be secure and is also useful for initial and continuous staff training.

Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens.

Background: Chemotherapy options in patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of standard chemotherapies are limited. Objectives: We aimed to report the efficacy and safety of the leucovorin and 5-fluorouracil (LV5FU2) and carboplatin combination in this setting. Design: We performed a retrospective study including consecutive patients with advanced PDAC who received LV5FU2-carboplatin between 2009 and 2021 in an expert center. Methods: We measured overall survival (OS) and progression-free survival (PFS), and explored associated factors using Cox proportional hazard models. Results: In all, 91 patients were included (55% male, median age 62), with a performance status of 0/1 in 74% of cases. LV5FU2-carboplatin was mainly used in third (59.3%) or fourth line (23.1%), with three (interquartile range: 2.0-6.0) cycles administered on average. The clinical benefit rate was 25.2%. Median PFS was 2.7 months (95% CI: 2.4-3.0). At multivariable analysis, no extrahepatic metastases (p = 0.083), no ascites or opioid-requiring pain (p = 0.023), <2 prior treatment lines (p < 0.001), full dose of carboplatin (p = 0.004), and treatment initiation >18 months after initial diagnosis (p < 0.001) were associated with longer PFS. Median OS was 4.2 months (95% CI: 3.48-4.92) and was influenced by the presence of extrahepatic metastases (p = 0.058), opioid-requiring pain or ascites (p = 0.039), and number of prior treatment lines (0.065). Prior tumor response under oxaliplatin did not impact either PFS or OS. Worsening of preexisting residual neurotoxicity was infrequent (13.2%). The most common grade 3-4 adverse events were neutropenia (24.7%) and thrombocytopenia (11.8%). Conclusion: Although the efficacy of LV5FU2-carboplatin appears limited in patients with pretreated advanced PDAC, it may be beneficial in selected patients.

Accessory ESCRT-III proteins are conserved and selective regulators of Rab11a-exosome formation.

Exosomes are secreted nanovesicles with potent signalling activity that are initially formed as intraluminal vesicles (ILVs) in late Rab7-positive multivesicular endosomes, and also in recycling Rab11a-positive endosomes, particularly under some forms of nutrient stress. The core proteins of the Endosomal Sorting Complex Required for Transport (ESCRT) participate in exosome biogenesis and ILV-mediated destruction of ubiquitinylated cargos. Accessory ESCRT-III components have reported roles in ESCRT-III-mediated vesicle scission, but their precise functions are poorly defined. They frequently only appear essential under stress. Comparative proteomics analysis of human small extracellular vesicles revealed that accessory ESCRT-III proteins, CHMP1A, CHMP1B, CHMP5 and IST1, are increased in Rab11a-enriched exosome preparations. We show that these proteins are required to form ILVs in Drosophila secondary cell recycling endosomes, but unlike core ESCRTs, they are not involved in degradation of ubiquitinylated proteins in late endosomes. Furthermore, CHMP5 knockdown in human HCT116 colorectal cancer cells selectively inhibits Rab11a-exosome production. Accessory ESCRT-III knockdown suppresses seminal fluid-mediated reproductive signalling by secondary cells and the growth-promoting activity of Rab11a-exosome-containing EVs from HCT116 cells. We conclude that accessory ESCRT-III components have a specific, ubiquitin-independent role in Rab11a-exosome generation, a mechanism that might be targeted to selectively block pro-tumorigenic activities of these vesicles in cancer.

Diagnosis and Differential Diagnosis of Poikiloderma of Civatte: A Dermoscopy Cohort Study.

INTRODUCTION: Poikiloderma of Civatte (PC) is a common, acquired, chronic, benign poikiloderma of the neck and face, most commonly affecting peri-menopausal females. At the time of writing, few studies have been published regarding the dermoscopy of PC. OBJECTIVE: To describe the dermoscopic picture of PC, so as to provide a clinico dermoscopic diagnosis and differential diagnosis for PC. METHODS: Twenty-eight patients with PC, aged 26-73 years, of whom 19 females (67.86%) were evaluated by detailed history, clinical examination, and dermoscopic examination with hand-held dermoscope. RESULTS: The reticular pattern was observed in 15 cases (53.6%); the white dot in 10 (35.7%); the non-specific in 9 (32.1%); and the combination of linear and dotted vessels in 8 (28.6%). Regarding local dermoscopic features, converging curved vessels were observed in 18 cases (64.3%); linear irregular vessels in 17 (60.7%); rhomboidal/polygonal vessels in 15 (53.6%); dotted/globular vessels in 10 (35.7%); white macules in 23 (82.1%); brown macules in 11 (39.3%); and whitish follicular plugs in 6 (21.4%). CONCLUSIONS: The dermoscopic picture of PC is highly characteristic and corresponds well to both clinical and histological findings. Dermoscopy may assist clinical diagnosis, as well as the differentiation from other dermatoses of the neck and face, especially poikilodermas with guarded prognosis.

Relevance of a Simulation Model to Microvascular Surgery for Military Surgical Residents.

Introduction: Microsurgical training is an asset for deployed military orthopaedic surgeons who frequently treat hand or nerve injuries in the field. The objective of this study was to evaluate a microvascular surgery simulation model intended to prepare residents prior to their enrolment in conventional microsurgery degree training. Methods: An experimental study was conducted to evaluate technical progress and satisfaction of military surgical residents using a model based on Japanese noodles with four tests of increasing difficulty. Objective endpoints included instruments handling, distribution, and quality of stitches, as well as anastomoses duration. Responses to the Structured Assessment of Microsurgery Skill self-assessment questionnaire were also analyzed. Results: Nine residents from different specialties participated in the study. Their anastomoses quality and average satisfaction significantly increased between the first and the last session (p < 0.05). Conversely, the average operating time decreased significantly over the sessions (p < 0.001). Conclusion: This simulation model seems to constitute a satisfactory initiation to microsurgery and could limit the use of animal models. It could also be included in the continuing education of military surgeons who have an occasional microsurgical practice during deployments.