Experts outperform novices on many cognitive and perceptual tasks. Extensive training has tuned experts to the most relevant information in their specific domain, allowing them to make decisions quickly and accurately. We compared a group of fingerprint examiners to a group of novices on their ability to search for information in fingerprints across two experiments—one where participants searched for target features within a single fingerprint and another where they searched for points of difference between two fingerprints. In both experiments, we also varied how useful the target feature was and whether participants searched for these targets in a typical fingerprint or one that had been scrambled. Experts more efficiently located targets when searching for them in intact but not scrambled fingerprints. In Experiment 1, we also found that experts more efficiently located target features classified as more useful compared to novices, but this expert-novice difference was not present when the target feature was classified as less useful. The usefulness of the target may therefore have influenced the search strategies that participants used, and the visual search advantages that experts display appear to depend on their vast experience with visual regularity in fingerprints. These results align with a domain-specific account of expertise and suggest that perceptual training ought to involve learning to attend to task-critical features. In the forensic sciences, decisions about the source of a handwriting sample, cartridge case, shoe print or fingerprint rest on the perceptual judgments of human examiners. These decisions are often highly consequential, yet we lack a comprehensive scientific understanding of the nature and acquisition of perceptual expertise in these domains. Criticisms about the reliability and validity of the forensic sciences have prompted efforts to understand the nature of forensic pattern matching expertise, including in fingerprint examination. Fingerprint examiners can accurately distinguish fingerprints originating from the same source and those originating from different sources, but what cognitive mechanisms underlie this ability? In this study, we use fingerprint examination as a case domain to investigate how well perceptual experts can search for features in domain-relevant tasks and how experts differ from novices. We found that examiners search efficiently for useful fingerprint features, but not less useful features, nor features in scrambled fingerprint images. It may follow that judgments made by perceptual experts are valid only in the domain with which they have had considerable practice. Effective training may also rely on developing a sensitivity to the most useful features in one’s particular domain.Many experts possess extraordinary perceptual and cognitive abilities for stimuli specific to their domain of practice. Medical diagnosticians, for example, can rapidly detect whether a chest radiograph contains an anomaly , and the second assesses the ability to spot differences (Experiment 2). Like other experts, fingerprint examiners appear sensitive to the more useful features within fingerprints; examiners and novices often consider different kinds of features to be useful  among a jumble of other shapes and colors  to detect a medium effect size for all planned analyses, but we intended to collect data from as many experts as possible. Every participant completed this experiment as well as Experiment 2 along with a suite of other tasks presented in a randomized order during the same testing session. These other tasks address different research questions beyond the scope of this paper.Novices We collected data from 44 novice participants that were age (± 2 years), gender and education matched to each of the expert participants  × 2  × 2  mixed design ‘yoked’ to expertise. Participants in each of the 48 trials saw a small fragment of fingerprint detail presented on the left of the screen and a larger fingerprint image (the array) on the right. They were instructed to click where they thought the smaller fragment was located in the larger array see Fig. . Half ofIntact array images We used 72 of the 100 fingerprint images used in Robson et al.’s , the delta , we presented novices with a version of the Find-the-Fragment task where the target fragment gradually increased in size every five seconds. Participants were 50% correct when locating fragments that were 1.45% of the area of the larger fingerprint. We used this fragment size in the present study because 50% performance was equidistant from floor and ceiling, and therefore seemed appropriately difficult. We randomly sampled eight ‘more useful’ fragments and eight ‘less useful’ fragments of this size from each of the 72 fingerprints in this experiment, a total of 1152 possible combinations.Scrambled images The purpose of the scramble was to remove the fingerprint-like structure of the images while retaining low-level visual properties and the location and appearance of the fragments. We generated 16 different scrambled versions of the 72 intact fingerprints (one for each of the randomly sampled fragments). We deselected the area where the fragment was located, deleted and replaced one quadrant of the print with alternative information using Photoshop’s Content Aware Fill tool.We measured performance on the Find-the-Fragment task using a speed–accuracy measure known as the Balanced Integration Score  and their Rate Correct Score (RCS), which measures speed–accuracy as the proportion of correct responses per second .Participants first read information about the project and watched an instructional video about the task with examples. They were then presented with their 48 randomly sequenced Find-the-Fragment trials. After clicking the array, immediate feedback was provided. If participants made an incorrect click (they did not click where the fragment was located) they were presented with a red cross, a blue semitransparent circle highlighting the correct location  = 0.53, p < 0.001. This correlation was similar for within experts, r(42) = 0.57, p < 0.001, and within novices, r(42) = 0.59, p < 0.001. We present the speed–accuracy correlations for each condition in Fig. In this experiment, accuracy data were not homogenous nor normally distributed in every cell. Because the target fragment was present on every trial and participants could inspect the images for as long as they desired, there was a ceiling effect in accuracy. Overall, the time spent making a decision was moderately correlated with accuracy, perts, r4 = 0.57, The speed–accuracy data are presented in Fig. F = 0.94, p = 0.334. However, the Expertise × Target interaction was significant, F = 21.61, p < 0.001, η2G = 0.055. Experts  were better than novices  at locating the more useful fragments, F = 32.49, p < 0.001, η2G = 0.157, but there was no difference between the experts  and novices  for the less useful target fragments, F = 0.82, p = 0.367.The 2 (Expertise) × 2 (Target) × 2 (Structure) mixed methods ANOVA did not reveal a significant three-way interaction, F = 8.06, p = 0.006, η2G = 0.016. Experts  were better at locating fragments in intact prints than novices were , F = 9.47, p = 0.002, η2G = 0.052. However, the novices  performed as well as the experts  at locating target fragments in scrambled prints, F = 0.23, p = 0.633.We also found a significant Expertise × Structure interaction, , F = 9.34, p = 0.003, η2G = 0.018. Participants were better at locating the more useful target fragments  than the less useful fragments  during the intact trials, F = 95.95, p < 0.001, η2G = 0.285. Experts were also better at spotting the more useful target fragments  than the less useful fragments  during the scrambled trials, F = 30.96, p < 0.001, but the effect size was smaller in comparison (η2G = 0.147).The Target × Structure interaction was also significantSimple interactions We predicted that experts would perform better than novices solely when finding useful fragments within intact fingerprints, but we did not find the expected three-way interaction that follows from this. We explored the results further by observing the simple interaction effects. As expected, there was an Expertise × Target interaction when observing solely the intact trials, F = 8.65, p = 0.004, η2G = 0.036. Experts  were better than novices  at locating more useful target fragments in the intact prints, F = 27.23, p < 0.001, η2G = 0.240. However, experts  performed similarly to novices  when locating less useful fragments in the intact prints, F = 0.57, p = 0.454. Unexpectedly, there was an Expertise × Target interaction for the scrambled trials as well, F = 16.95, p < 0.001. Counter to our predictions, experts  were better than novices  at locating the more useful fragments in scrambled prints, F = 10.05, p = 0.002, η2G = 0.105. Moreover, the novices  outperformed the experts  at locating less useful target fragments in scrambled prints, F = 5.33, p = 0.023, η2G = 0.058.Correlating performance and experience When correlating years of experience with performance on the Find-the-Fragment task, we found no significant associations. Among experts, there was no correlation between their years of experience in fingerprint examination and their overall accuracy, r(42) = 0.05, p = 0.739, nor between years of experience and speed–accuracy, r(42) = − 0.19, p = 0.223. There was also no correlation between years of experience and accuracy when observing solely the useful-intact data, r(42) = − 0.14, p = 0.370, nor between years of experience and speed–accuracy for this cell, r(42) = 0.05, p = 0.755.In Experiment 1, we compared the performance of professional fingerprint examiners to novices on a fingerprint-like visual search task. Our aim was to investigate whether any expert-novice differences in visual search depend on the usefulness of the target and the structure of the array image. We expected experts to outperform novices solely when locating useful target fragments in intact fingerprints. We did not find the expected three-way interaction, but the findings nonetheless partially support our hypothesis. Overall, experts were better than novices at locating the more useful target fragments, but they performed like novices when locating the less useful fragments. The examiners therefore appear highly sensitive to useful features, as has been demonstrated in many other domains of expertise , but not less meaningful changes  or changes to scenes unrelated to football  were the same as in Experiment 1 because each participant completed both tasks in the same testing session. Novices were compensated in the same manner as in Experiment 1.https://osf.io/my28c.The design, procedure and software used in Experiment 2 were identical to Experiment 1 except for the nature of the task see Fig. . On eachIntact images The 72 intact fingerprint images (750 × 750 pixels) in this task were identical to the intact fingerprints from Experiment 1. However, we also created altered versions of each print where we made a change to some feature. We used the more useful and less useful points gathered by Robson et al. (https://osf.io/3g4e7), we gave 48 novices a Spot-the-Difference task where the size of the change gradually increased every five seconds. These novices could spot the change about 50% of the time when it was 3.71% the size of the image that it was located in. We used changes of this size as it was equidistant from floor and ceiling. For each of the 72 fingerprints, we created a pool of 16 altered images; eight had a change made to a more useful feature and eight had a change made to a less useful feature.n et al.  as centeScrambled images We generated a scrambled image for each of the 16 variants of every intact fingerprint. We scrambled them in the same way as we did in Experiment 1, except the area we kept unchanged was larger this time (3.71% the size of the image). In total, we generated 1152 scrambled prints (750 × 750 pixels). For each of the scrambled images, we also created an altered variant just as we did for each intact print.r(86) = 0.50, p < 0.001. Among novices, accuracy and response time were positively correlated, r(42) = 0.68, p < 0.001, as well as among experts, r(42) = 0.36, p = 0.015. The speed–accuracy correlations for each condition are presented in Fig. We found that participants who took more time to make a decision in the Spot-the-Difference task tended to be more accurate, F = 0.912, p = 0.342. The Expertise × Target interaction was nonsignificant, F = 0.07, p = 0.790, and the Target × Structure interaction was also nonsignificant, F = 1.41, p = 0.239. However, there was a significant Expertise × Structure interaction, F = 10.04, p = 0.002, η2G = 0.025. Experts  were better than novices  at spotting differences between intact fingerprints F = 49.98, p < 0.001, η2G = 0.213, whereas experts  and novices  performed similarly at spotting differences between scrambled prints, F = 0.59, p = 0.445.We performed a parametric test (three-way mixed methods ANOVA) and a nonparametric test  on the BIS data. The pattern of effects was identical in both models, so we only report the parametric ANOVA here see Fig. . CounterSimple interactions We explored why we did not find the expected three-way interaction by observing simple interactions. We expected experts to outperform novices only when spotting changes to useful features in intact prints, but we found no significant Expertise × Target interaction for the intact trials, F = 0.35, p = 0.559. Experts  were indeed better than novices  at locating changes to more useful features in intact prints, F = 19.16, p < 0.001, and the effect was large (η2G = 0.182). However, experts  were surprisingly better than novices  at locating changes to less useful features in intact fingerprints as well, F = 30.43, p < 0.001, and the effect was larger still (η2G = 0.261). As expected, we found no significant Expertise × Target interaction when observing only the scrambled trials, F = 0.45, p = 0.506, Experts  and novices  did not differ at spotting changes to more useful features in scrambled prints, F = 1.36, p = 0.247, nor did experts  and novices  differ at locating changes to less useful features in scrambled prints, F = 0.12, p = 0.912.Correlating performance and experience We found no significant correlations between performance on the Spot-the-Difference task and years of experience as an examiner. Years of experience did not correlate with accuracy in the task, r(42) = − 0.25, p = 0.103, nor did years of experience and speed–accuracy, r(42) = − 0.27, p = 0.080. There was also no correlation between years of experience and accuracy in the useful-intact condition, r(42) = − 0.19, p = 0.205, nor years of experience and speed–accuracy for this condition, r(42) = − 0.28, p = 0.062.In Experiment 2, we set out to compare fingerprint examiners and novices on a fingerprint comparative visual search task. We also sought to understand how the usefulness of the target and the structure of the array affect performance. We expected that experts would outperform novices only at spotting useful changes to intact fingerprints, but not in any other condition. We did not find the expected three-way interaction, but our results partially support our hypothesis. Experts were indeed better than novices at locating differences between intact fingerprints, but not scrambled prints. Their visual search abilities therefore do not appear to generalize beyond the stimuli that they have been exposed to in their formal training and everyday workflow. This finding lends support to a domain-specific account of perceptual expertise  = 0.50, p < 0.001. The correlations were similar among novices, r(42) = 0.48, p = 0.001, and among experts, r(42) = 0.44, p = 0.003. Overall, the relationship was weaker but still positive in the useful-intact condition, r(86) = 0.30, p = 0.005. However, the relationship between speed–accuracy on each task for this condition was nonsignificant among experts, r(42) = − 0.07, p = 0.640, and nonsignificant among novices, r(42) = 0.20, p = 0.19.We found a moderate positive correlation between speed–accuracy in the Find-the-Fragment task and speed–accuracy in the Spot-the-Difference task, 2  = 36.72, p < 0.001, together explaining 30.1% of the variance. In fact, performance on both tasks contributed to the model. Every increase of one in BIS on the Find-the-Fragment task translated to 3.15  times greater odds of being an expert, and every increase of one in the BIS on the Spot-the-Difference task translated to 3.32  times greater odds of being an expert. A dominance analysis revealed that Find-the-Fragment performance was the most important predictor, contributing an average of 17.5% of the variance, whereas Spot-the-Difference performance contributed an average of 12.6%.We also conducted a binomial logistic regression to establish whether performance in the useful-intact variations of each task could correctly classify participants as either an expert or a novice. Speed–accuracy on the useful-intact versions of each task predicted expertise, χAcross two experiments—one where participants searched for points of correspondence and one where they searched for differences—we tested whether domain experts have superior visual search skills than novices. We also examined whether any visual search advantages are constrained to useful target features and to images containing intact domain structure. In both experiments, we hypothesized that fingerprint examiners would be better than novices at spotting useful features and changes (but not less useful features and changes) in intact fingerprints (but not scrambled prints). We did not find the expected three-way interaction in either experiment, but our findings nonetheless supported our hypotheses to a large extent. Across both experiments, experts were generally more efficient at searching for targets compared to novices when these targets were located in the intact fingerprints, but not when they were located in the scrambled prints. Just as a chess expert’s recall for chess pieces is disrupted when the pieces are randomly arranged (Chase & Simon, In Experiment 1, the fingerprint examiners also appeared to be highly sensitive to useful domain features, but not to less useful features. They were far more efficient than novices at locating useful features, but equal to novices at locating less useful features. Perceptual experts across a range of domains demonstrate a similar sensitivity to the most useful features and regions for the task at hand (e.g., Krupinski, In sum, our results suggest that professional fingerprint examiners possess superior visual search skills compared to novices. However, their skills are limited to domain-specific stimuli and to features that are most relevant to their routine decisions. Our results say little about the proficiency of these examiners, nor how often they might make mistakes, but they do speak to the nature of their expertise. The fact that an examiner’s visual search ability is highly constrained by the stimuli used in the task is a finding that we would expect from a group that possesses genuine expertise. Nevertheless, our results deviated somewhat from our expectations. Below we discuss why this might be, along with the broader implications of our findings.Experts in the Find-the-Fragment task outperformed novices at finding useful fragments in both intact and scrambled fingerprints. Therefore, an expert’s sensitivity to useful features may aid their visual search even when a target is situated in an unfamiliar context. Experts possess a rich visual working memory for useful features, which means they need to switch between target and array far less than a novice would (e.g., Maturi & Sheridan, Despite the differences between the two tasks, performance on one task correlated with performance on the other. This association suggests that the tasks tap into a similar underlying ability, presumably visual search efficiency. However, in the only condition where we expected an expert-novice difference—the useful intact condition—the relationship between the two tasks was weaker. We also found that speed–accuracy performance for the useful-intact variants of both tasks uniquely contributed to predicting expertise, together explaining almost one-third of the variance. Efficiently locating corresponding features and locating differences may be two unique and necessary skills to reach expert levels of performance in a domain. However, many other perceptual abilities underlie feature comparison expertise, including working memory and statistical learning (see Growns & Martire, Our results also revealed that neither the Find-the-Fragment task nor the Spot-the-Difference task could distinguish between examiners with more experience from those with less. Perhaps the tasks were not sufficiently sensitive to parse the varied levels of skill within our sample of experts. Alternatively, self-reported years of experience is a poor measure of actual domain expertise because it can vary considerably from one person to the next and does not capture the quality of one’s training (Carrigan et al., In any case, our findings have implications for recruitment and training. Some police agencies in the past have recruited forensic pattern matchers, such as fingerprint examiners, using tasks that supposedly measure general visual comparison abilities. It may be that general skills before training predict who flourishes later on, but there is no evidence that this is true for fingerprint identification. Moreover, if an ability to search for features only in domain-specific stimuli is what separates experts from novices, as we demonstrate here, then time and resources may be wasted by recruiting individuals with tasks that are unrelated to the domain.Learning to efficiently locate features and spot differences between prints may also help one develop the ability to match fingerprints. Training programs of this kind, such as attentional highlighting, are already being tested (Roads et al., This is the first study to investigate how fingerprint examiners and novices differ in their visual search ability, and how the target feature and structure of the stimuli affect performance. Across both tasks, examiners demonstrated more efficient search than novices, but only for images specific to their domain of expertise. Although these experts performed exceptionally well at locating features in typical fingerprints, scrambling the structure of these prints reduced expert search performance to novice levels. In our first experiment, examiners also efficiently located ‘useful’ features that they typically encounter in their routine decisions. However, their performance fell to novice levels when locating less useful features. Visual search ability in the domain of fingerprint identification clearly hinges on domain-specific experience and on the attentional fine-tuning that results from extensive training.


Curcuma longa (turmeric), has been studied in several experimental and clinical trial studies. Curcumin has some useful clinical effects such as antiviral, antinociceptive, anti‐inflammatory, antipyretic, and antifatigue effects that could be effective to manage the symptoms of the infected patient with COVID‐19. It has several molecular mechanisms including antioxidant, antiapoptotic, and antifibrotic properties with inhibitory effects on Toll‐like receptors, NF‐κB, inflammatory cytokines and chemokines, and bradykinin. Scientific evidence suggests that curcumin could have a potential role to treat COVID‐19. Thus, the use of curcumin in the clinical trial, as a new treatment option, should be considered.In late December 2019, the outbreak of respiratory illness emerged in Wuhan, China, and spreads worldwide. World Health Organization (WHO) named this disease severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) caused by a new member of beta coronaviruses. Several medications are prescribed to patients, and some clinical trials are underway. Scientists are trying to find a specific drug against this virus. In this review, we summarize the pathogenesis, clinical features, and current treatments of coronavirus disease 2019 (COVID‐19). Then, we describe the possible therapeutic effects of curcumin and its molecular mechanism against coronavirus‐19. Curcumin, as an active constituent of  Curcumin has antinociceptive, antipyretic, antifatigue, and antiemetic effects. Curcumin could alleviate symptoms of the infected patient with COVID‐19. Curcumin could reduce inflammatory cytokines via inhibiting TLR/MAPK/NF‐κB signaling. Curcumin might attenuate ARDS and pulmonary fibrosis due to anti‐inflammatory properties. After a while, the cause of this unknown pneumonia was recognized as a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by World Health Organization (WHO)  are enveloped positive‐stranded RNA viruses that cause respiratory, enteric, hepatic, and neurological diseases in humans and animals , curcumin and tumor necrosis factor‐alpha (TNF‐α), curcumin and NF‐κB, curcumin and Toll‐like receptors (TLRs), curcumin and antiapoptotic.The most important articles about COVID‐19 (from starting disease up to now) and curcumin were selected. We considered all articles of curcumin—human and animal studies—that could be effective to treat or rescue COVID‐19‐infected patients. PubMed and Web of Science were used as databases. As the importance of the subject, some selected papers were in the press. The keywords used for the search were as follows: coronavirus‐19, COVID‐19, SARS‐CoV‐2, curcumin, 3The SARS‐CoV‐2 is an enveloped nonsegmented positive‐sense RNA virus. Two‐thirds of viral RNA is located in the first open reading frames that encode 16 nonstructural proteins, whereas the remaining part of the genome encodes four essential structural proteins including spike (S) glycoprotein, envelope (E) protein, matrix (M) protein, and nucleocapsid (N) protein , and the entrance of the virus into the host cell , chronic obstructive pulmonary disease (COPD), pulmonary hypertension, ALI, and asthma Jia, . It has 3.1The patients mainly were 30–79 years old , erythrocyte sedimentation rate (ESR), and lactate dehydrogenase (LDH) were the most prevalent results in the patients , procalcitonin, IL‐6, and serum ferritin, and multiple organ involvement, such as liver , kidney (increased blood urea nitrogen and creatinine levels), and heart and muscle (increased creatinine kinase levels) compared with patients with mild symptoms. Also, there was higher neutrophil‐to‐lymphocyte ratio (NLR) and lower percentages of monocytes, eosinophils, and basophils in complete blood count , IL‐7, IL‐8, IL‐9, IL‐10, basic fibroblast growth factors (FGF), granulocyte colony‐stimulating factor (GCSF), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interferon‐gamma (IFNγ), interferon γ‐induced protein 10 kDa (IP‐10), monocyte chemoattractant protein‐1 (MCP1), macrophage inflammatory protein‐1 alpha (MIP1‐α), macrophage inflammatory protein‐1β (MIP‐1β), platelet‐derived growth factor (PDGF), tumor necrosis factor‐alpha (TNF‐α), and vascular endothelial growth factor (VEGF) were observed in serum sample of patients. Plasma levels of IL‐5, IL‐12p70, IL‐15, eotaxin, and RANTES (chemokine (C‐C motif) ligand 5, CCL5) were similar between healthy adults and patients infected with SARS‐COV‐19. Moreover, plasma concentrations of IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNF‐α were higher in the intensive care unit (ICU) patients compared with non‐ICU patients. These data suggest that the initial response of the immune system may lead to the production of cytokines and chemokines, which damage normal host organs such as lung and heart. Also, hypersensitive troponin I (hs‐cTnI) was increased in patients with virus‐related cardiac injury , is a hydrophobic polyphenol , chemokines such as macrophage inhibitory factor (MIF), and macrophage chemoattractant protein, metabolites of arachidonic acid (prostanoids and leukotrienes), and oxyradicals. Until yet, mechanical ventilation is only a proven strategy for treatment to improve the survival of patients  that were stimulated with S. aureus. It has been suggested that some part of the anti‐inflammatory effects of curcumin are due to regulating NF‐κB activity  in influenza A virus‐infected human macrophages and BAL fluid of infected mice. Similar to other noted studies, curcumin downregulated the expression of NF‐κB and increased the cytosolic IκBα and inhibited its phosphorylation in the cytoplasm in human macrophages  in human macrophages. Curcumin also reduced the expression of TLR2/JNK that may be involved in the apoptosis of macrophages  with strong inhibition activity  compared with BK2 receptor   metabolites; then, these metabolites activate transient receptor potential (TRP) channel subfamily vanilloid member 1 (TRPV1) and subfamily A member 1 (TRPA1) channels result in an increase in both cough response and airway obstruction  significantly inhibits ovalbumin (OVA)‐induced airway constriction and airway hyperreactivity to histamine in sensitized guinea pigs  reduced tracheal contractile response to OVA and maximum response to methacholine in rats. It also decreased interstitial fibrosis  decreased the protein level of the AT1 receptor and enhanced the expression of the AT2 receptor/ACE2 and results in the attenuation of myocardial fibrosis in a rat model of angiotensin II infusion (Pang et al., Dietary administration of curcumin (150 mg kg6Advantage of curcumin over other important natural agents with reported anti‐inflammatory activities such as zerumbone (Prasannan et al., 7To date, over 100 clinical trials have been completed with curcumin and safety, tolerability, and outcome have been reported in all of them (Kunnumakkara et al., 8COVID‐19 is spreading worldwide, leading a pandemic. There is no definitive treatment yet for this disease. In this review, we summarized clinical and molecular mechanisms that curcumin might be effective to treat COVID‐19. Research evidence suggests that curcumin will be useful to treat patients especially in ARDS cases with high mortality risk. Curcumin has several therapeutic effects including antiviral, antinociceptive, anti‐inflammatory, antipyretic, and antifatigue effects with several molecular mechanisms such as antioxidant, antiapoptotic, antifibrotic effects, and inhibitory effects on NF‐κB, inflammatory cytokines and chemokines, Toll‐like receptors, and bradykinin. The importance of this review is due to the fact that curcumin is a nutraceutical that could be a new treatment option to combat the COVID‐19 pandemic. Designing the best formulation with high efficacy and good bioavailability is necessary. Further clinical studies should focus on curcumin against COVID‐19 infection.The authors have no conflict of interest to declare.The study did not involve any human or animal testing.


Aromatic L‐amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive inherited disorder which is characterized by neurological and vegetative symptoms. To date, only 130 patients with AADCD have been reported worldwide.We demonstrated 14 previously undescribed patients together with three reportedly patients in Mainland China. Full clinical information was collected, and disease‐causing variants in the DDC gene were detected.The common clinical manifestation of patients, including intermittent oculogyric crises, retarded movement development, and autonomic symptoms. Notably, a patient showed bone‐density loss which have not been reported and two mildly phenotype patients improved psychomotor function after being prescribed medication. The most common genotype of Mainland Chinese AADCD is the splice‐site variant , which accounts for 58.8%, followed by c.1234C>T variant. Three novel compound heterozygous variants, c. 565G>T, c.170T>C, and c.1021+1G>A, were firstly reported. It is important to recognize the milder phenotypes of the disease as these patients might respond well to therapy. Besides, we discovered that patients may presented with milder if found to be compound heterozygote or homozygote for one of the following variants c.478C>G, c.853C>T, c.1123C>T, c.387G>A, and c.665T>C.The clinical data of the cohort of 17 patients in Mainland China broaden the clinical, molecular, and treatment spectrum of aromatic L‐amino acid decarboxylase deficiency. DDC genotype with mild or moderate clinical phenotype correlation. In short, our study expanded the clinical spectrum of AADCD and contributes to the knowledge of the genotype and phenotype correlation for the DDC gene.The most intriguing aspects of our study is that we present clinical details on a cohort of 17 patients in Mainland China with broad clinical variability, three novel variants in DDC gene, and different responses to treatment. In addition, we explored  Aromatic L‐amino acid decarboxylase, encoded by the DDC gene, catalyzes the decarboxylation step of the monoamine neurotransmitter biosynthetic pathway, using pyridoxal‐5′‐phosphate as a cofactor, in which 5‐hydroxytryptophan and levodopa (L‐dopa) are irreversibly converted to serotonin and dopamine, respectively  and informed parental consent was obtained before including the patients in the study. From 2017 to 2019, we recruited 14 previously unreported patients who were diagnosed with AADCD based on characteristic clinical manifestations suggestive of AADCD and identification of DDC gene mutations in Mainland China from the China League of AADC Rare Disease. Three previously reportedly patients, two siblings and a boy from Mainland China, were also discussed in our study , degenerative changes in the white matter (one case), hypomyelination (one case), and reduced brain volume or enlargement of the subarachnoid spaces (one case). EEG results were normal in seven cases (50%), nonspecific in five cases (35.7%), and abnormal in two cases (14.28%), with generalized slow background, spike waves, sharp waves, and spike (or sharp) slow wave complexes. The organic acid profiles in urine and blood were normal in all tested patients. Four index patients screened in Taiwan presented with elevated 3‐O‐methyldopa (3‐OMD) levels in dried blood spots screen. A complete list of clinical phenotype and auxiliary examination results are given in Table As soon as AADCD was confirmed, all index patients were treated with drug. All index patients were treated with pyridoxine which function as an enzyme cofactor and can bolster the catalytic activity of the remaining enzyme. Dopamine agonists which mimic the dopamine function under physiological condition by directly activating postsynaptic dopamine receptors were used as well, including bromocriptine (one case), pergolide (five cases), and the rotigotine patch (four cases). Besides, eight patients were treated with MAO inhibitors blocking the breakdown of dopamine and serotonin, thus increasing monoamine level in brain. The responses are not satisfactory particularly in patients having severe symptoms even when drugs were administered in combination. It is worth to mentioning that two patients improved psychomotor function after being medication. Patient 12 improved significantly after selegiline and L‐dopa treatment. She started to babble at 1 year and 5 months, and her episodes of oculogyric crisis became primarily restricted to periods of fatigue. Another patient, patient13, responded dramatically to bromocriptine, and she can able to eat food with her fingers when she turned 2 years old.3.2https://sift.bii.a-star.edu.sg/), PolyPhen‐2 (http://genetics.bwh.harvard.edu/pph2/), and MutationTaster2 (http://www.mutationtaster.org/) were used. All identified DDC variants were predicted as possibly damaging, probably damaging, or deleterious , which shares 88% sequence identity with the human enzyme , 2 (C100S), and 3 (R347Q), affected the proper apo‒holo transition, thus decreasing the catalytic efficiency. Moreover, R347Q is not only located at a central position in loop 3 at the entrance to the active site cavity, but it is also close to the decarboxylase catalytic element (residues 328–339). With respect to the other detected mutations, G36R, I57T, D59N, and V60A are located at the dimer interface; R412W and I433N are located in peripheral regions, and R160W and D189Y are located in the large domain near the active site.The crystal structure of human AADC in the holo form is not available; however, the protein from DDC  genotype with mild or moderate clinical phenotype correlation. As shown in the DDC gene exon structure schematic diagram, an interesting phenomenon that identified DDC variants in literature associated with milder phenotype obviously aggregated in exon5‐exon6 (436‐714) residues can be found , monoamine oxidase inhibitors, and dopamine agonists as first‐line treatments. Gene therapy which has become an emerging approach for treating disease, was performed in a small group of AADCD patient with modest but promising results (Zwagerman and Richardson, DDC variants includes 58 missenses, 6 frame‐shift, 9 splice‐site,1 in‐frame, 3 complex, and 2 nonsense variants (Himmelreich et al., Tay et al reported the cases of two Chinese AADCD siblings with compound heterozygous mutations IVS 6+4 A>T and 853 C>T presented with unusual mild phenotype (Tay et al., Patient 12 harbored the compound heterozygous missense mutation p.R160W and p.D189Y, and presented with moderate clinical phenotype. Interestingly, the patient described by Barth et al. harbored the compound heterozygous mutations pR160W and pR347Q and also showed moderate clinical features (Barth, Serre, & Hubert, 5DDC genotype with mild or moderate clinical phenotype correlation. In short, our research expands the clinical spectrum of AADCD and contributes to the knowledge of the genotype and phenotype correlation for the DDC gene.The most intriguing aspects of our study are that we presented clinical details on a cohort of 17 patients in Mainland China with broad clinical variability, molecular spectrum, and different responses to medications. In addition, we explored The author has no conflict of interest to declare.


The majority of patients with myasthenia gravis (MG) initially present with ocular symptoms, but it is difficult to predict which cases will remain as ocular MG (OMG) or will progress to generalized MG. Herein we evaluated the serologic profile of Japanese OMG and its relationship with clinical features.Seventy‐three patients with OMG from five Japanese myasthenia gravis (MG) centers were enrolled. Live cell‐based assays (CBAs) were used to determine the presence of autoantibodies (Abs) to clustered adult  and fetal  acetylcholine receptor (AChR) isoforms, muscle‐specific receptor tyrosine kinase (MuSK), and lipoprotein receptor–related protein‐4 (LRP4).Thirty‐four of 73 (46.5%) serum samples were positive for Abs against both the adult‐type and fetal‐type AChR, as expected, but 7 (9.6%) and 2 (2.7%) were positive only for fetal or adult AChR‐Abs, respectively. Four (5.4%) samples were positive for MuSK‐Abs, but two of these also contained antibodies to fetal AChR or LRP4. Twenty‐six (35.6%) samples were seronegative.Abs against fetal‐specific AChR, MuSK, and LRP4 are found in some patients with OMG. Future studies attempting to predict conversion from ocular symptoms to generalized MG may benefit from measurement of these antibodies. AbantibodyAChRacetylcholine receptorCBAcell‐based assaycDNAcomplementary DNADMEMDulbecco’s modified Eagle’s mediumEGFPenhanced green fluorescent proteinGMGgeneralized myathenia gravisIgGimmunoglobulin GITimmunotherapyLRP4lipoprotein receptor–related protein‐4MGFAMyasthenia Gravis Foundation of AmericaMuSKmuscle‐specific receptor tyrosine kinaseOMGocular myathenia gravisRIAradioimmunoassayRTroom temperature1Patients with myasthenia gravis (MG) have varied clinical courses, but the majority initially present with ocular symptoms, and it is difficult to predict which of these cases will remain ocular MG (OMG) or progress to generalized MG (GMG). Acetylcholine receptor antibodies (AChR‐Abs) are found in 80% to 90% of GMG and usually around 50% of OMG casesIn human muscle, the AChR subunits largely switch from the fetal type  to the adult type  by birth. However, γ‐subunit expression persists into adulthood in the extraocular musclesRecently, live cell‐based assays (CBAs) have been established to detect autoantibody binding to native clustered AChR, MuSK, and lipoprotein receptor–related protein‐4 (LRP4). These live CBAs offer better sensitivity than fixed CBAs or radioimmunoassays (RIAs),2We obtained approval from the ethics committee of Nagasaki Kawatana Medical Center  and permission from the ethics committee of each institution that participated in this study. All subjects provided informed consent.2.1Consecutive MG patients at five member institutes for MG research in the Intractable/Rare Disease Control Division of the Japanese Ministry of Health, Labor and Welfare were enrolled in this study during January to December 2015. Diagnoses of OMG were based on patients' symptoms and results of an electrophysiologic exam of repetitive nerve stimulation and/or jitter measurements and an edrophonium test. Only patients with a diagnosis of OMG  for 1 hour at room temperature (RT). After washing, the cells were fixed with 4% paraformaldehyde for 10 minutes at RT, rinsed twice, and incubated with a secondary goat anti‐human IgG Fc(γ) antibody , diluted 1:750, for 45 minutes at RT. Next, a third antibody layer was applied , diluted 1:750, for 45 minutes at RT. After the final washes, coverslips were mounted using fluorescence mounting medium  containing 1% 4′,6′‐diamidino‐2‐phenylindole dichloride (nuclear stain) and examined using a fluorescent microscope.13: 0 = no labeling; 1 = weak labeling of some transfected cells; 2 = moderate labeling of approximately 20% to 50% of transfected cells; 3 = moderate/strong labeling of approximately 50% to 80% of transfected cells; and 4 = strong labeling of almost all transfected cells.The CBAs were scored as described by Leite et al2.3U test was used for analyses according to the age of onset. The significance of statistical differences between subgroups was evaluated using Fisher’s exact test. Differences were considered significant at P < .05.Statistical analysis was performed using GraphPad Prism 8 version 8.2.1 . The Mann‐Whitney 3P = .0297), but there was no gender difference.Serum samples from 73 OMG patients were tested. Forty‐seven patients were seropositive for CBA antibodies to both adult and fetal AChR (n = 34), fetal AChR only (n = 7), adult AChR only (n = 2), or MuSK (n = 4) Table . Two of The CBA results, symptoms, and immunotherapy histories of each patient are shown in Figure Finally, we compared results of these assays with those at diagnosis and at sampling using RIA for AChR‐ and MuSK‐Abs. All patients positive for AChR‐Abs on CBA had been positive for AChR‐Abs on RIA at onset, but three were no longer positive by RIA at time of CBA testing. In addition, two of the patients positive for MuSK‐Abs on CBA and 12 who had been designated positive for AChR‐Abs on RIA had had very low RIA titers (≤1.0 nmol/L) at onset and were negative at sampling.4We used CBAs to evaluate the serologic profiles of Japanese OMG patients, 61.6% of whom had undergone a variety of immunotherapies. As expected, 46.6% of the patients were positive for both clustered adult and fetal AChR‐Abs, but another 17.8% had antibodies only binding to fetal AChR, adult AChR, or MuSK .Most patients with MG have antibodies that bind effectively to solubilized mixtures of adult and fetal AChRs by RIA, but, increasingly, cell‐based assays are used to measure antibodies for increased sensitivity and specificity.It was surprising to find seven patients with only fetal AChR antibodies, although, in one previous study,MuSK‐Abs were first described in patients with severe generalized symptoms who often presented with bulbar and respiratory failure,This study has some limitations. Further examination of human ocular muscles and the relationships between specific antibodies and OMG is needed. In addition, we used sera collected years after the onset of disease, and many patients had already been given immunotherapies. Some patients may have undergone a change in the serologic profile after treatment or over the natural disease course. Twelve of the cohort had been positive previously for AChR antibodies on RIA, but had low titers (<1.0 nmol/L); such patients could have become antibody‐negative after immunotherapies, but caution is necessary with such low titers.In conclusion, we have observed Abs against MuSK, LRP4, and fetal‐ and adult‐specific AChR‐Abs in OMG patients. Further studies attempting to predict conversion from ocular symptoms to generalized MG may benefit from the measurement of these antibodies.University of Oxford and A.V. hold a patent (2001) for MuSK antibody assays, licensed to Athena Diagnostics USA; A.V. has received a proportion of royalties for antibody tests.We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.


Lectures with slide presentations are widely used to teach evidence-based medicine to large groups. Take-home messages (THMs) are poorly identified and recollected by students. We investigated whether an instruction to list THMs in written form on slides would improve the retention thereof by residents, and the residents’ level of knowledge, 1 month after lectures.Prospective blinded randomized controlled study was conducted. Twelve lectures (6 control and 6 intervention lectures) were delivered to 73 residents. For the intervention lectures, the lecturers were instructed to incorporate clear written THMs into their slide presentations. The outcomes were ability of resident to recollect THMs delivered during a lecture (as assessed by accordance rate between the lecturers’ and residents’ THMs) and knowledge (as assessed by multiple choice questions (MCQs)).n = 20/26), 95% CI 56–91 vs 64% (n = 18/28), 95% CI 44–81, p = 0.31) nor THMs retention (13% (n = 238/1791), 95% CI 12–15 vs 17% (n = 326/1947), 95% 15–18, p = 0.40) nor knowledge . In multivariable analyses performed with all THMs written on slides from the two groups, a superior knowledge was associated with notetaking during lectures  and THMs retention ; and THMs retention was associated with written THMs .Data for 3738 residents’ THMs and 3410 MCQs were analyzed. The intervention did not significantly increase the number of THMs written on slides . Medical education is fundamental to improve the quality of health care but also poses great challenges . Severalclinicaltrials.gov) NCT01795651.We conducted a prospective randomized controlled blinded study at the University of Clermont-Ferrand, France, in February 2013 during the delivery of an ICU educational module (part of a postgraduate Intensive Care Unit (ICU) diploma program) attended by 25% of the national residents enrolled on the ICU training course. We enrolled all residents and lecturers who took part in the module into this study, except those who refused to participate. Written informed consent was obtained retrospectively from lecturers and prospectively from residents. The study protocol was approved by the Ethics Committee of the French Intensive Care Society  and the local Institutional Review Board  in accordance with French law. The study was registered on the Clinical Trials Registry , the duration (30 min followed by 15 min for questions) and the learners’ characteristics (postgraduate resident doctors enrolled on an ICU training programme). At 1 month and at 1 week before the beginning of the module, a reminder e-mail was sent to each lecturer. The intervention element of the study was an explicit instruction to lecturers to include at least one slide entitled “Message” or “Take-home Message” into their slide presentations containing the written THM, for each THM delivered. A THM was defined as a short message of key relevant to medical practice. The number of THMs was limited to five per lecture. The choice and the wording of the THMs were decided on the lecturer. Each written THM was limited to 15 words. The instruction to the lecturers was clearly stated in a separate paragraph within the e-mail, which also included an article reporting the failure of residents to identify THMs in ICU postgraduate lectures , according to statistical distribution. The normality of the data was assessed using the Shapiro-Wilk’s test. To take into account variability between and within lecturers and residents, random-effect models were generated (lecturers and residents as crossed random effects). These models  were used to determine factors associated with THMs retention and residents’ knowledge. Multivariable analyses were then performed, with covariates (fixed effects) determined according to their significance in univariate analysis  with an age of 31 ± 3 years and 2 ± 1 years of ICU experience. The two lecturer groups were similar at baseline in terms of general characteristics and lecture characteristics , 95% CI 56–91 vs 64% (n = 18/28), 95% CI 44–81, P = 0.31). The rate of THMs retention was not different between the intervention and control groups (13% (n = 238/1791), 95% CI 12–15 vs 17% (n = 326/1947), 95% CI 15–18, P = 0.40) .Residents’ knowledge was assessed by 22 MCQs related to the THMs in the intervention lectures, and by 26 MCQs in the control lectures. The level of knowledge in the intervention lectures did not have higher than that in the control lecture , 95% CI 17–20 vs 8% (n = 91/1108), 95% CI 7–10, P < 0.001)  and notetaking by resident during the lecture .Of the 54 THMs delivered during the 12 lectures, 38 (70%) appeared in written form on a slide. The THMs retention was higher for written THMs compared to THMs delivered only orally (18% (P < 0.001): the THMs retention was 10.9 ± 16.1%, 13.0 ± 18.5% and 22.3 ± 25.2% in the low-, medium-, and high-performance groups, respectively. Univariate analyses comparing knowledge, gender, notetaking (yes/no) and THMs retention (≤ or > 25%) between the control and intervention lectures groups are shown in Table p < 0.001) and a higher rate of THMs retention . Sensitivity analysis with THMs retention as continuous variable , and then with THMs retention thresholds of 20%  and 30% , was conducted to verify that this choice of THMs retention threshold did not affect the relationship between THMs retention and knowledge.The relationship between THMs retention and residents’ knowledge was significant . Legend: THM, take-home message; MCQ: multiple choice question.


Childhood disruptive behaviour has been linked to later antisocial and criminal behaviour. Emotion recognition and empathy impairments, thought to be caused by inattention to the eye region, are hypothesised to contribute to antisocial and criminal behaviour. This is the first study to simultaneously examine emotion recognition and empathy impairments, their relationship, and the mechanism behind these impairments, in children with disruptive behaviour. We hypothesised that children with disruptive behaviour would exhibit negative emotion recognition and cognitive and affective empathy impairments, but that these impairments would not be due to reduced attention to the eye region. We expected these emotion impairments to be driven by disruptive behaviour. We also expected a relationship between emotion recognition and cognitive empathy only. Ninety-two children with disruptive behaviour, who were participating in a police crime prevention programme and rated by their schoolteacher using the Strengths and Difficulties Questionnaire , took part. There was a comparison group of 58 typically developing children . All children completed emotion recognition and empathy tasks, both with concurrent eye tracking to assess social attention. Not only were DB children significantly impaired in negative emotion and neutral emotion recognition, and in cognitive and affective empathy compared to the TD children, but severity of disruptive behaviour also predicted intensity of emotion impairments. There were no differences in social attention to the eye region. Negative emotion recognition and empathy impairments are already present in an identifiable group of children displaying disruptive behaviour. These findings provide evidence to encourage the use of targeted interventions. Antisocial behaviour (ASB) describes a persistent pattern of negative behaviours , which hAntisocial individuals are typically impaired in recognising expressions of fear and sadness . HoweverEmpathy is the ability to understand and share another’s emotional state. Cognitive empathy is the cognitive awareness of another’s emotional state and affective empathy is the vicarious experience of another’s emotions . Some stEmotion recognition impairments are thought to underlie impaired empathy , 14. ModAttention to the eyes is a mechanism thought to be responsible for both emotion recognition and empathy abilities. Dadds and colleagues showed that boys with ASB plus callous-unemotional (CU) traits showed normal patterns of fear recognition when directing their attention to the eye region . ResearcBoth emotion recognition and empathy are important mechanisms in the development and continuation of ASB. Distress cues, such as facial expressions of fear and sadness, are thought to possess perceptual cues that elicit empathy . The abiOne of the strongest predictors of later criminal and antisocial behaviour is disruptive behaviour in childhood , 26. HowThis study investigated emotion recognition and empathy impairments in children showing disruptive behaviour, as described by their schoolteacher. Their performance on emotion recognition and empathy tasks was compared to a sample of typically developing children. Concurrent eye tracking was conducted during both emotion recognition and empathy tasks to gain a better understanding of the mechanism behind these impairments, namely social attention to the eyes.This study had the following hypotheses. First, we predicted that children with disruptive behaviour would show negative emotion recognition impairments and cognitive and affective empathy impairments. However, we predicted that affective empathy impairments would be limited to negative emotions only in comparison to the typically developing children. Second, we expected that emotion recognition impairments would be related to cognitive, but not affective, empathy impairments. Third, based on recent research findings, we predicted that emotion recognition and empathy impairments would not be related to impaired social attention to the eyes. Finally, we predicted that the more severe the disruptive behaviour, the more intense the emotion recognition and empathy impairments.The 164 participants  aged 7–11 years who took part in this study were categorised into two groups according to the behaviours which they displayed. One participant group showed disruptive behaviour (DB group). The other group formed a typically developing comparison group (TD group).The 106 children assigned to the DB group were showing disruptive behaviour and participating in a police crime prevention programme, called the Early Intervention Hub, developed by Northamptonshire Police Force. The Hub was set up to address the high number of children displaying problematic behaviour in the county  and aimsChildren in the DB group were referred to participate in this study from the Hub PCSO working at the child’s school. After referral, the children’s teachers completed the Strengths and Difficulties Questionnaire (SDQ)  to confiThe hyperactivity subscale of the SDQ was not chosen as a recruitment criterion, because recent studies have shown that emotion recognition impairments in ADHD are specific to those with comorbid CD . SimilarA comparison group of 58 typically developing children participated. Parent-completed SDQ scores confirmed TD group status . Inclusion criteria were a referral from school teachers for not showing disruptive behaviour and meeting the SDQ criteria previously described.Exclusion criterion for both groups was an estimated IQ (intelligence quotient) less than 70 and not completing the tasks within the study. Based on these criteria, 14 children were excluded from the DB group, leaving a final sample of 92 DB children and 58 TD children.The Wechsler Abbreviated Scale of Intelligence  providedThe SDQ is a 25-item widely used, valid, and reliable questionnaire assessing problematic and prosocial behaviour .The Facial Emotion Recognition (FER)  test conParticipants viewed three clips from Harry Potter films, which evoked empathic reactions. Each clip represented happiness, sadness, or fear as agreed upon by 96% of 31 6-to-11-year old children in a preliminary study. The previous experience with each clip revealed no effect of film familiarity. Participants were asked questions about the main character’s emotions in the clip (cognitive empathy) and their own emotions while viewing the clip (affective empathy). They were asked how strongly they and the main character felt eight emotions and to explain the reason for the emotion. Responses were coded by two individuals using the Cardiff Empathy Scoring System , 36. Cogn = 96; TD: n = 43; DB: n = 53) or empathy  tasks.During both emotion recognition and empathy tasks, social attention was examined using concurrent eye tracking. A portable Tobii X2-60 compact eye-tracker sampling at 60 Hz with a screen resolution of 1920 × 1080 was used. Participants were positioned 60 cm away from a 15″ laptop screen. Calibration quality was checked and repeated if necessary. An I-VT fixation filter with a minimum fixation criterion of 60 ms sampled average raw data of both eyes to produce information on eye position and duration. Eye-gaze validity was checked for all recordings using a percentage score of successfully recorded data. Validity ranged from 60 to 99% . Not all children were able to complete eye tracking during the emotion recognition  and Bonferroni corrections were applied.Tobii Studio analysed eye gaze; areas of interest (AOIs) were created around the eyes, mouth, total face, and entire screen. For emotion recognition, eye gaze was analysed during a three-second segment when the face was presented without emotion options. For empathy, eye gaze was analysed during the six-to-eight-second segment that presented the most intense emotional content in each clip. Percentage dwell time to the eyes was calculated by summing all fixations to the eyes divided by the total duration of time spent looking at the face. A two-way ANOVA was run with emotion as the within-subjects factor and group as the between-subjects factor.d for t test ), fear (t(148) = -2.72, p = 0.007, d = 0.47, 95% CI ), anger (t(147.99) = -3.25, p = 0.001, d = 0.52, 95% CI ), and neutral (t(146.99) = − 3.67, p < 0.001, d = 0.58, 95% CI )  = − 1.84, p = 0.07, d = 0.30).DB participants had significantly lower scores for recognising expressions of sadness (t48 = − 2.t(134) = − 2.80, p = 0.006, d = 0.51, 95% CI ), sadness (t(129.59) = − 4.53, p < 0.001, d = 0.76, 95% CI ), and fear (t(131.11) = − 3.93, p < 0.001, d = 0.66, 95% CI )  = − 2.56, p = 0.012, d = 0.47, 95% CI ), sadness (t(134) = − 2.42, p = 0.02, d = 0.44, 95% CI ), and fear (t(117.97) = − 2.40, p = 0.018, d = 0.42, 95% CI )  = − 1.97, p = 0.05, d = 0.40] and empathy tasks . There was no group difference in dwell time to the eyes during either the emotion recognition  = 0.02, p = 0.90, F = 1.06, p = 0.31, The two groups did not differ in attention to the screen during the emotion recognition [t9 = − 1.97As there were no group differences in happiness recognition or social attention, regressions were not run for these variables. Given its importance in disruptive behaviour, overall negative expression recognition was included in the multiple regression for emotion recognition.Emotion recognition The full model of age, IQ, and total SDQ was statistically significant, R2 = 0.132, F = 6.46, p < 0.001, adj. R2 = 0.112. The addition of age and IQ to the prediction of emotion recognition did not lead to a statistically significant change in R2 of 0.03, F = 2.17, p = 0.12. Full details of all regression models are presented in Table Cognitive empathy The full model of age, IQ, and total SDQ was statistically significant, R2 = 0.119, F = 5.19, p = 0.002, adj. R2 = 0.096. The addition of age and IQ to the model did not lead to a statistically significant change in R2 of 0.04, F = 2.38, p = 0.10  = 1.40, p = 0.248, adj. R2 = 0.010. However, model 1 with just total SDQ score was significant, R2 = 0.033, F = 4.05, p = 0.047, adj.R2 = 0.025  and neutral expressions . These fWe hypothesised that children with disruptive behaviour would show also cognitive and affective empathy impairments compared to the typically developing group, and that affective empathy impairments would be specific to negative emotions. Our hypotheses were largely confirmed and were in line with the previous studies , 38. HowThis study also aimed to understand the relationship between emotion recognition and empathy impairments, hypothesising that there would be a relationship between emotion recognition and cognitive, but not affective empathy, based on the study by Lui and colleagues . ContrarAs hypothesised, problems in social attention did not explain performance on the emotion recognition and empathy tasks. This finding contrasts with Dadds et al. , but conWe predicted that emotion recognition and empathy impairments would be influenced primarily by disruptive behaviour. Regression analyses confirmed that severity of disruptive behaviour uniquely predicted emotion recognition, and cognitive and affective empathy impairments, over and above the influence of IQ and age. These findings support the idea that emotion recognition and empathy abilities are important in disruptive behaviour, thus, further providing evidence for the importance of early and targeted interventions.Our study had some limitations. First, practical limitations prevented the collection of eye tracking data in the full sample and eye movement behaviour was considered across all trials, regardless of accuracy. It is possible that eye movement behaviours would be different when considering correct versus incorrect trials. Some children may have had difficulties verbalising their thoughts and feelings  and futuDisruptive behaviour in childhood is related to later antisocial and criminal behaviour. We have provided evidence that emotion recognition impairments in antisocial and criminal populations are already present in young children who display disruptive behaviour and, indeed, that severity of disruptive behaviour predicted intensity of emotion impairments. The findings from this research support the use of early interventions that improve emotion recognition and empathy development in these children . A targe


The incidence and prevalence of stroke among the young are increasing in the US. Data on healthcare utilization prior to stroke is limited. We hypothesized those < 45 years were less likely than those 45–65 years old to utilize healthcare in the 1 year prior to stroke.Patients 18–65 years old who had a stroke between 2008 and 2013 in MarketScan Commercial Claims and Encounters Databases were included. We used descriptive statistics and logistic regression to examine healthcare utilization and risk factors between age groups 18–44 and 45–65 years. Healthcare utilization was categorized by visit type  during the year prior to stroke hospitalization.Of those 18–44 years old, 14.1% had no visits in the year prior to stroke compared to 11.2% of individuals aged 45–65 [OR = 1.30 ]. Patients 18–44 years old had higher odds of having preventive care procedures associated with an outpatient visit and lower odds of having cardiovascular procedures compared to patients aged 45–65 years. Of stroke patients aged 18–45 and 45–65 years, 16.8 and 13.2% respectively had no known risk for stroke.Patients aged 45–65 were less commonly seeking preventive care and appeared to be seeking care to manage existing conditions more than patients aged 18–44 years. However, as greater than 10% of both age groups had no prior risk, further exploration of potential risk factors is needed.The online version contains supplementary material available at 10.1186/s12913-021-06064-5. With 795,000 strokes occurring in the US annually, stroke is currently the leading cause for long-term adult disability and ranked fifth in cause of death –5. AlthoReducing the burden of stroke in the young population requires identification of modifiable risk factors. However, among all age groups conventional risk factors only account for 80% of risk associated with incident events, leaving a substantial proportion of risk unexplained –13. VascHowever, despite emerging evidence for novel risk factors, there are limited studies examining management of these conditions. Further, prior health statistics have shown, in the general population, that those aged 18–44 to have lower healthcare utilization compared to those aged 45–64 . HoweverWe obtained patient data for our study from the MarketScan Commercial Claims and Encounters database, an administrative dataset containing longitudinal data for approximately 230 million de-identified patients. MarketScan contains data from patients enrolled in employee-sponsored insurance programs. Data is collected, de-identified and standardized, and includes demographic characteristics as well as International Classification of Diseases, 9th Revision (ICD-9) diagnosis and procedure codes for all inpatient, outpatient, and emergency department (ED) visits. Each patient is given a de-identified patient code to allow for linking of data and tracking over time. For this study, patients who had a stroke between 2008 and 2014 while enrolled in MarketScan and those age 65 or younger were included for analysis. Our study was limited to the period between 2008 and 2014 because of licensing and cost constraints related to obtaining access to MarketScan data at our institution. We categorized patients by their age at first stroke, 18–44 and 45–65 years. This study was approved by the institutional review board at Columbia University Medical Center; the need for review was waived as data used were publicly available and did not contain direct personal identifiers.We selected patients with ischemic strokes and intracerebral hemorrhagic strokes defined using ICD-9 codes 433.× 1 , 434.00, 434 (excluding 434.× 0 with exception of 434.00), 436 and 431. Subarachnoid hemorrhagic strokes were excluded from this analysis as they are largely dependent on experiencing trauma or aneurysm, rather than risk factors examined in our study .Additional Table For each age group, we examined the proportions as n (%) who met criteria for each visit type, including those with ED visits only, inpatient visits only, outpatient visits, only, or had some combination of inpatient, outpatient and/or ED visits in the year prior to stroke. Additionally, we examined distributions of demographic characteristics, medical history assessed at time of stroke, and risk groups as mean [standard deviation (SD)] for continuous variables and proportions as n (%) for categorical variables by visit types prior to stroke . For total number of visits prior to stroke and days from last visit, we also examined median [interquartile range (IQR)]. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression comparing those aged 18–44 years to those aged 45–65 years for odds of having no visit in the year prior to stroke and odds of meeting criteria for each risk group. Additionally, for those with outpatient visits only and those with a combination of visits, odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated comparing those aged 18–44 years to those aged 45–65 years to assess odds of having select procedure codes.We identified a total of 169,358 patients with incident stroke for inclusion in this study, consisting of 24,103 patients between ages 18–44 and 145,255 ages 45–65 years. Of those 18–44 years of age, 14.1% had no visits in the year prior to stroke compared to 11.2% of individuals aged 45–65. Those aged 18–44 had 1.30 times the odds of having no visit in the year prior to stroke compared to 45–65  year-olds. Of those 18–44 years of age, 516 (2.1%) had only ED visits, 28 (0.1%) had only inpatient visits, 10,812 (44.9%) had only outpatient visits, and 9356 (38.8%) had some combination of inpatient, outpatient and/or ED visits in the year prior to stroke. Of those 45–65 years of age, 1649 (1.1%) had only ED visits, 113 (0.1%) only had inpatient visits, 76,226 (52.5%) only had outpatient visits and 50,969 (35.1%) had a combination of inpatient, outpatient and ED visits in the year prior to stroke.For those 18–44 years of age, 36.9% of those with no visits, 53.3% of those with outpatient visits only and 59.1% of those with a combination of visits were female ], chiropractic [OR = 1.28 ] or emergent office [OR = 1.96 ] procedure code associated with a visit and decreased odds of having a vaccination [OR = 0.61 ], cardiovascular [OR = 0.40 ] or neurologic [OR = 0.85 ] procedure ], trauma or cancer [OR = 1.15 ], or no known risk factors [OR = 1.33 ] at the time of stroke. Those 18–44 years of age had lower odds of having metabolic syndrome [OR = 0.34 ] or substance use [OR = 0.79 ] compared to those 45–65 years old (Table Our retrospective cohort study using MarketScan data demonstrates commercially insured individuals aged 18–44 years had greater odds of having no inpatient, outpatient or ED visit 1 year prior to stroke compared to those aged 45–65 years. Of those with outpatient or a combination of visits, younger patients had increased odds of having a preventative care visit, but lower odds of having a vaccination compared to older patients. Of all patients who had a visit, half had a visit within 6 days prior to stroke. Importantly, 16.8% of stroke patients aged 18–44 and 13.2% of those 45–65 years had no known risk factor for stroke.Health statistics have previously shown those aged 18–44 have lower healthcare utilization, with 21.9% not having had contact with their physician within the past year compared to 13.6% of those aged 45–64 . SimilarIn both age groups of our study, a nominally greater proportion of females had outpatient visits or a combination of visits than no visits at all Table . This isWhen examining procedure codes associated with an outpatient visit, those aged 18–44 years had increased odds of seeking preventive care procedures than those 45–65 years. While this may not be expected based on prior research indicating decreased healthcare utilization in younger age groups, this is likely driven by differences in comorbidities . InsteadHowever, there was decreased utilization of vaccines among younger populations. While these age differences support existing literature, the percentage of patients who had a vaccine within the year prior to stroke is concerning when considering the need for an annual flu vaccine. Our study captures all types of vaccinations administered at an inpatient, outpatient or emergency department visit, including, but not limited to, the flu vaccine. However, vaccine utilization for all immunizations in our study, ranging from 11.3 to 21.5% depending on age group and visit type, are well below annual estimates of flu vaccine utilization from the CDC. For the 2018–2019 flu year, the CDC estimated a vaccination coverage of 34.9% of 18–49 year olds and 47.3% of 50–64 year olds . This maWhen evaluating risk groups for both age groups, results indicate those with no visits 1 year prior had the highest proportions of patients with prior risk for stroke. A higher percentage of patients with no visits prior to stroke had prior history of hypertension, alcohol abuse, drug abuse/dependence, and smoking than all other visit groups for both age groups. Likely, despite having private insurance, these patients are not reached by current clinical interventions to reduce or manage risk factors, illustrating the need for population-based prevention methods.Not surprisingly, the greatest proportions of stroke patients for each visit type were included in multiple risk groups. Modifiable or manageable risk factors, particularly hypertension, were common suggesting a large portion of strokes may have been preventable. However, it is concerning that 16.8 and 13.2% of those aged 18–44 and 45–65 had no prior risk as seen in Table This study has some limitations. Medical history and risk factors may not be readily captured in MarketScan as it is an administrative database, thus prevalence estimates may be underestimated in our study. Additionally, assessed ICD-9 procedure codes are associated with outpatient visits. As patients may seek care through additional sources, such as through work programs or a pharmacy, our results likely underestimate procedure, particularly vaccination coverage. Finally, MarketScan is a dataset of insurance claims and does not capture un-insured individuals or individuals with insurances that do not participate in MarketScan. However, as this is a descriptive study including a large sample size representative of a national population, we believe our study can inform additional questions pertaining to healthcare utilization and risk factor prevalence among young stroke patients.In conclusion, no prior study had investigated healthcare system utilization prior to a stroke event, particularly in younger patients, though understanding healthcare utilization in this population can inform prevention strategies, such as risk factor management. Our retrospective cohort study including a commercially insured sample aimed to address this gap and found those aged 18–44 years had increased odds of having no inpatient, outpatient or ED visits 1 year prior to stroke compared to those aged 45–65 years. Those with no prior visits accounted for 14.1 and 11.2% of 18–44 and 45–65 year-olds, respectively. This difference between age groups is smaller in our study than the general population, highlighting how our population is distinct. While older patients aged 45–65 years were less commonly seeking preventive care, they had a higher median number of visits and appeared to be seeking care to manage existing conditions more so than patients aged 18–44 years. As vaccine utilization for all immunizations in our study were low, future studies should closely examine differences in vaccination rates among those who do and do not utilize healthcare among at risk populations to determine the relationship between vaccination and stroke risk. Additionally, our study describes the need for population-based interventions to lower modifiable risk factors as a higher percentage of patients with no visits prior to stroke had prior history of hypertension, alcohol abuse, drug abuse/dependence, and smoking for both age groups. However, as greater than 10% of those aged 18–44 and 45–65 years had no known prior risk, further exploration of novel risk factors is needed.Additional file 1: Table 1. International Classification of Diseases, 9th Revision, Clinical Modification Codes Used to Identify Outcome or covariates of interest and MarketScan Procedure Group Codes. Table 2. Definitions used for classifying risk groups.


This was a single‐institution, single‐dose, single‐arm phase 1 study in healthy adult males to evaluate the safety and absorption of dimethyl sulfoxide (DMSO) from the bladder into the body when KRP‐116D (a 50% w/w DMSO solution) was intravesically administered and allowed to remain in the bladder for 15 minutes.Six healthy adult males were enrolled in this study. KRP‐116D (50 mL) was instilled directly into the bladder via a catheter where it was allowed to remain for 15 minutes under lidocaine anesthesia in accordance with the usage of RIMSO‐50 (50% w/w DMSO solution) approved in the USA. The residual DMSO solution in the bladder was collected 15 minutes after instillation. The concentrations of DMSO in the plasma and the recovered solution were analyzed by a validated high‐performance liquid chromatography (HPLC) method. The concentration in the residual DMSO solution was multiplied by the solution volume and divided by the dosage to calculate the recovery rate of DMSO.Plasma DMSO was detected in one of six subjects, and in the remaining five subjects DMSO was not detected (<19.6 μg/mL). The recovery rate of DMSO from the bladder was 60.7% to 93.7%. The only drug‐related adverse event was breath odor (garlic‐like breath) observed in four of six subjects (66.7%).Absorption of DMSO from the bladder was low (16.3%), and the systemic exposure was limited. Most of the DMSO was recovered from the bladder. KRP‐116D 50 mL was well tolerated and safe. KRP‐116D is a 50% w/w DMSO sterile solution manufactured in accordance with good manufacturing practice (GMP) by Kyorin Pharmaceutical Co., Ltd. The study was undertaken at the Department of Clinical Pharmacology, Nishi Kumamoto Hospital, Kumamoto, Japan. The study protocol and informed consent form were approved by the Hakata Clinic Institutional Review Board . All subjects gave written informed consent before the initiation of any study‐specific procedure. The study was conducted in accordance with the ethical principles originating in or derived from the Declaration of Helsinki, Good Clinical Practice Guidelines, and locally applicable laws and regulations.2, and confirmation of health by an investigator based on medical examination, observation, and clinical laboratory tests. Subjects were required to be of Japanese ancestry going back at least two generations (grandparents). IC/BPS is much more common in female patients than male patients,Inclusion criteria were: healthy Japanese male subject, aged 20 to 35 years, a body mass index (BMI) of 18.5 to 25.0 kg/mMajor exclusion criteria were history of severe allergic reactions, atopy, anaphylaxis, or intolerance to drugs or foods; any history of disease or surgery that would preclude being enrolled in the study; hypersensitivities to DMSO or amide‐type local anesthetic agents; excessive alcohol consumption or not abstaining from alcohol during the specified study period; heavy smoking or not abstaining from smoking during the specified study period; excessive coffee intake or ingesting caffeine‐containing foods every day or not abstaining from such foods during the study period; having medical treatment 4 weeks prior to instillation, use of over‐the‐counter drugs 2 weeks prior to instillation, or possible use of prohibited medication during the study; whole blood collection of ≥800 mL within 1 year, ≥400 mL within 12 weeks, or 200 mL within 4 weeks, or blood component donation within 2 weeks before screening; hemoglobin <13.5 g/dL at screening or the first day of hospitalization; and being positive for hepatitis B (HB) antigen, hepatitis C virus (HCV) antibody, HIV antigen or antibody, or syphilis test at screening. The enrollment of six subjects was considered a sufficient number to achieve the study objectives.2.2max), time to maximum plasma concentration (tmax), elimination half‐life (t1/2), and area under the concentration‐time curve (AUC) from time zero to the last measurable concentration (AUClast), all of which were calculated by noncompartmental analysis using Phoenix WinNonlin Version 7.0 .A total of six subjects who met the eligibility criteria were enrolled in the study. The day of study drug administration was designated as “day 1”, and after the screening period (day ‐28 to day ‐2), subjects entered the study unit on day ‐1 and were hospitalized until day 3. Before instillation of KRP‐116D, residual urine in the bladder was removed using a urethral catheter. Lidocaine solution  was instilled directly into the bladder, allowed to remain for 15 minutes for bladder anesthesia, and the residual lidocaine solution was removed from the bladder using a urethral catheter. Subjects received a single dose of KRP‐116D (50 mL) intravesically through a urethral catheter that was then allowed to remain in the bladder for 15 minutes. Next, the residual DMSO solution was collected from the bladder using a urethral catheter, and the recovered volume (mL) was measured. Blood samples for the measurement of plasma DMSO were taken immediately pre dose, and then 0.25, 0.5, 1, 2, 4, 8, 12, 24 (day 2), 36 (day 2), and 48 (day 3) hours post dose. DMSO concentrations in the plasma and recovered DMSO solution were measured by a validated high performance liquid chromatography (HPLC) method. The below lower limit of quantification (BLQ) of DMSO in the plasma and recovered DMSO solution was 19.6 μg/mL and 391 μg/mL, respectively. Pharmacokinetic (PK) parameters for DMSO included maximum plasma concentration (CSafety was assessed in relation to adverse events (AEs), clinical laboratory tests , 12‐lead electrocardiogram (ECG), vital signs , and physical examinations. Hematology consisted of leukocyte count, leukocyte fraction , red blood cell count, hematocrit value, hemoglobin amount, and platelet count. Chemistry consisted of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Al‐P), lactate dehydrogenase (LDH), γ‐glutamyl transpeptidase (γ‐GTP), total bilirubin (T‐Bil), direct bilirubin (D‐Bil), creatine kinase (CK), total protein (TP), triglyceride (TG), blood glucose, total cholesterol (T‐Cho), albumin (Alb), blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), and electrolytes including sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and phosphorus (P). Urinalysis consisted of qualitative analysis including protein, glucose, and urobilinogen and sediments of red blood cells and white blood cells. Criteria for abnormal variation in clinical laboratory tests are shown in Table 32 (range: 18.8–24.9 kg/m2).Six healthy adult male subjects were enrolled and all completed the study. The mean age was 23.8 ± 4.7 years (range: 20–32 years), the mean body weight was 68.43 ± 11.73 kg (range: 47.6–83.5 kg), and the mean BMI was 22.53 ± 2.08 kg/mAll subjects received a single dose (50 mL) of KRP‐116D, corresponding to approximately 27 g of DMSO as an active ingredient, which was allowed to remain in the bladder for 15 minutes, and all subjects were included in the PK analysis set and safety analysis set. There were no major protocol deviations.3.1The amount of recovered DMSO from the bladder and the recovery rate of each subject are shown in Table 3.2max, tmax, t1/2, and AUClast of one subject were 72.1 μg/mL, 0.250 hours, 5.46 hours, and 150 μg･.h/mL, respectively. Summary statistics were not available because plasma PK parameters were obtained in only one subject.Among six subjects, the plasma DMSO concentrations of five subjects were not detected (under BLQ). The C3.3Among six subjects, four AEs occurred in four subjects (66.7%). All these events were breath odor Table . These e4Intravesical instillation of 50% w/w DMSO solution has been a mainstay of pharmacological treatment for IC/BPS in the USA and Canada for nearly 40 years since its approval in 1978 in the USA. Currently, 50% w/w DMSO solution is recommended for use as a second‐line treatment in the AUA Guideline for IC/BPS. Dosage and treatment of DMSO in the US package insert of RIMSO‐50  states “instillation of 50 mL of RIMSO‐50® (dimethyl sulfoxide) directly into the bladder may be accomplished by catheter or asepto syringe and be allowed to remain in situ for 15 minutes. Application of an analgesic lubricant gel such as lidocaine jelly to the urethra is recommended prior to insertion of the catheter to avoid spasm. The medication is expelled by spontaneous voiding.”Among six subjects, four AEs occurred in four subjects. All events were breath odor (garlic‐like breath) and were judged as a drug‐related AE. The breath odor might be due to a metabolite, dimethyl sulfide. It should be noted that the findings for this event were objective, not subjective; in other words, the smell itself was clearly detected by the investigator and clinical staff, but the subjects themselves were not aware of it. In this study, because the subjects were hospitalized during the study, this made it particularly likely that objective findings would to be detected because the study staff was strictly conducted over time in accordance with the study protocol. These findings suggest that the incidence of this AE may differ depending on the subject's environment. Breath odor was not reported in the subject in whom DMSO was detected in plasma. Interestingly, there was no relationships between plasma DMSO concentration and breath odor. Garlic‐like breath odor might be due to a metabolite, dimethyl sulfide. However, the main metabolites, dimethyl sulfone and dimethyl sulfide, were not analyzed in our study.5Plasma DMSO concentration was detected in only one of six subjects and was not detected in the remaining five subjects when the subjects received intravesical instillation with a single dose of 50% w/w DMSO solution. Most DMSO was recovered from the bladder. The absorption rate of DMSO from the bladder was low (16.3%), and the systemic exposure was limited. KRP‐116D 50 mL was well tolerated and safe.Kyorin Pharmaceutical Co., Ltd. received a grant from the National Institutes of Biomedical Innovation, Health and Nutrition. Hideyo Shimada MD received a consultancy fee from Kyorin Pharmaceutical Co., Ltd. Makoto Yono has nothing to declare. Yuya Hojo, Yuka Hamamura, and Atsushi Ootsuki are employees of Kyorin Pharmaceutical Co., Ltd.Table S1. Criteria for abnormal variation in clinical laboratory tests.Click here for additional data file.


To analyse short-term changes in the anterior segment and retina after small incision lenticule extraction (SMILE).Patients with myopia scheduled for SMILE were recruited from Ruijin Hospital, Shanghai, China. Basic patient information such as age, sex, and refractive errors was recorded. Ocular measurements were taken before surgery, and 1 day and 1 week after surgery; they included axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white to white (WTW), pupil diameter (PD), macular thickness (MT), ganglion cell layer thickness (GCL), retinal nerve fiber layer thickness (RNFL), choroidal thickness (CT), macular vessel density, and optic disc vessel density.p < 0.05), while LT was thickened after surgery (p < 0.05). MT at the fovea decreased 1 day and 1 week after surgery (p < 0.05). GCL showed no significant changes after surgery. RNFL was unchanged 1 day after surgery, but the inferior sector was thickened 1 week after surgery. CT was thicker at the fovea 1 day after surgery and 1.0 mm from the fovea in the nasal sector 1 week after surgery. Macular vessel density was significantly decreased 1 day after surgery and most recovered in 1 week. Optic disc vessel density decreased at the peripapillary part 1 day after surgery and recovered after 1 week. ΔACD and ΔLT showed no significant correlation 1 day after surgery. ΔACD was negatively correlated with ΔLT and sphere 1 week after surgery . ΔLT was positively correlated with the sphere 1 week after surgery .Sixty-one eyes of 31 patients were selected for this study. AL, CCT, ACD, and postoperative PD were significantly reduced (The anterior segment was the most affected, while the retina also underwent changes with regard to MT, RNFL, CT, macular vessel density, and peripapillary vessel density. Laser refractive surgery has been developing for more than 30 years since Dr. Steven Trokel and his colleagues first reported photorefractive keratectomy (PRK) in 1983 , 3.As myopia patients grow, the effects of refractive surgeries also attract doctors’ concerns. LASIK and SMILE are so similar that researchers have compared them in different ways. Changes in LASIK have been studied extensively. Cornea biomechanics decrease after both LASIK and SMILE , 5. PostOptical coherence tomography angiography (OCTA) has predominated now-a-days for its deep scan and retinal vascular quantitative analysis. Previous studies have shown that retinal microvascularity decreases in myopia patients , 9. PrioThis was a prospective observational study. The design and procedure of this study adhered to the principles of the Declaration of Helsinki. The Institutional Review Board of Ruijin Hospital authorised this study. Patients who were willing to undergo SMILE at Ruijin Hospital from August 2019 to December 2019 were enrolled. Written informed consent was obtained from each subject.The inclusion criteria were as follows: age > 18 years, corrected distance visual acuity no less than 20/20, without any ophthalmologic or systematic disease, stable myopia for more than two years, and calculated residual stromal bed > 250 μm.All participants underwent a complete ophthalmologic examination before and 1 day, 1 week after the surgery, including visual acuity assessment, intraocular pressure (IOP), and refraction. Axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white to white (WTW), and pupil diameter (PD) were measured using Lenstar (LS 900) and corneal tomography captured with Patencam . Changes of ACD and LT were recorded as ΔACD (ACD after surgery - ACD before surgery) and ΔLT (LT after surgery - LT before surgery).OCT scans were captured with Cirrus HD OCT 5000(Carl Zeiss Meditec) software version 9.5.2, and analysed with a software version of 10.0.0. Five types of protocols were used to obtain images. Macular thickness (MT) and ganglion cell layer thickness (GCL) were obtained with a Macular Cube 512 × 128. Retinal fiber layer thickness (RNFL) was obtained with Optic Disc Cube 200 × 200, and choroidal thickness (CT) was obtained with Angiography 3 × 3 mm enhanced depth imaging (EDI) mode, and the superficial vascular density of the macular and optic disk was obtained with angiography 6 × 6 mm.MT, GCL, and RNFL were calculated automatically by OCT and shown in a map image. An MT map of nine zones from the internal limiting membrane (ILM) to the retinal pigment epithelium (RPE) was automatically calculated and recorded as M1-M9  Fig. . CT was The vessel density map of the fovea and optic disk was a 6 mm diameter circle, divided into nine regions with three concentric circles. The inner one was 1.0 mm in diameter, middle one was 3 mm, and outer one was 6 mm. The circle was centred on the fovea and optic disc; the software automatically calculated values in each region of vessel density. Zones were recorded as A1–A9 and O1–O9, respectively, and the sequence was identical to the MT map Fig. .Fig. 5VOne skilled doctor obtained all the OCT scans. Images with signal strength higher than six were selected for analysis.Surgeries were performed using a VisuMax (Carl Zeiss Meditec) femtosecond laser platform by one experienced surgeon. Before surgery, 0.5% proparacaine hydrochloride  was used for anaesthesia. The suction time was 23 s for lenticule creation. The angle of the lenticule side cut was 90°. The cap depth was 120 μm with a diameter of 7.5 mm and a side cut angle of 120°. After the surgery, topical steroids  was used 6 times a day and reduced every 5–7 days over 30 days. Topical antibiotics  was used 4 times a day for 14 days. Artificial tears  was used 4 times a day for at least 1 month.p < 0.05.Statistical analysis was performed using SPSS 20.0 . All values are expressed as mean ± SD. Analysis of paired Student’s t-test was used to assess the differences in CCT, ACD, LT, WTW, PD, MT, GCL, RNFL, CT, vessel density of macular and optic disk before and after surgery. Correlations between sphere and ΔACD and ΔLT were analysed with the Pearson correlation coefficient. Results were considered statistically significant when This study enrolled 61 eyes of 31 patients, including 21 females and 10 males. The mean age was 28.13 ± 5.84 years, ranging from 19 to 44 years. The mean sphere, astigmatism, and ablation depth are shown in Table AL, CCT, ACD, and PD decreased 1 day and 1 week after surgery. LT was thickened 1 day after surgery and became even thicker after 1 week. WTW did not change at either time point Table .Table 2p < 0.000; r = − 0.398, p = 0.002). ΔLT was positively correlated with the sphere 1 week after surgery   1 day after surgery and recovered after 1 week Table .Table 8In this study, we measured several parameters and found that both the anterior segment and retina were affected by the surgery. Results from previous studies suggested that anterior segment changes would last for a long time, while posterior segment changes are only observed for a short time and then gets resolved. Prior studies have reported that PCE and ACD decreased after surgery and even several years later , 7, and AL shortened by approximately 0.1 mm after surgery due to the ablation part. Corneas were usually oedematous after SMILE so that CCT was thinner 1 week than 1 day after surgery, and another article had the same result .In a previous study regarding the treatment of presbyopia using a femtosecond laser, they found that the crystalline lens moved axially and laterally, and it seemed to be affected by suction . The effThere are few articles reporting retinal or choroidal changes after SMILE, but changes after LASIK have been studied extensively. In previous LASIK studies, MT was thickened , or totaTwenty years ago, RNFL changes after LASIK attracted doctors’ interests, and different results were concluded. RNFL was found to change with scanning laser polarimetry (SLP) but unchanged with OCT . This reCT was observed thickened postoperatively , and theVessel density has been studied extensively in glaucoma and retinal diseases since OCTA emerged. Vessel density changes were assumed by the suction effects during surgery on the retinal microcirculation, and instantaneous changes in suction may cause ischaemia-reperfusion injury . IOP eleDuring the observation period, none of the patients had severe complications, and all of them regained ideal visual acuity. However, 1 day after the surgery, some corneas were not as clear as preoperatively due to mild corneal oedema, and it was difficult to capture high-quality images of the retina. Due to the limitation of the OCTA soft version, only superficial vessel density was analysed. These were the shortcomings of the study, along with the requirement of a longer follow-up period.After SMILE, the anterior segment was the most affected, while the retina also underwent changes with regard to MT, macular vessel density, and peripapillary vessel density. This study can help doctors gain deep insights into changes after refractive surgeries.