The decline in performance of older people includes balance function, physical function, and fear of falling and depression. General cognitive function decline is described in terms of processing speed, working memory, attention, and executive functioning, and video game interventions may be effective.This study evaluates the effect of video game interventions on performance and cognitive function in older participants in terms of 6 indicators: balance function, executive function, general cognitive function, physical function, processing speed, and fear of falling and depression.Electronic databases were searched for studies from inception to June 30, 2020. Randomized controlled trials and case-controlled trials comparing video game interventions versus nonvideo game control in terms of performance and cognitive function outcomes were incorporated into a Bayesian network meta-analysis. All data were continuous variables.In total, 47 studies (3244 participants) were included. In pairwise meta-analysis, compared with nonvideo game control, video game interventions improved processing speed, general cognitive function, and depression scores. In the Bayesian network meta-analysis, interventions with video games improved balance function time , the cognitive function score , processing speed time , and processing speed number , similar to the pairwise meta-analysis. Interventions with video games with strong visual senses and good interactivity ranked first, and these might be more beneficial for the elderly.Our comprehensive Bayesian network meta-analysis provides evidence that video game interventions could be considered for the elderly for improving performance and cognitive function, especially general cognitive scores and processing speed. Games with better interactivity and visual stimulation have better curative effects. Based on the available evidence, we recommend video game interventions for the elderly.PROSPERO CRD42020197158; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197158 Since the mid-20th century, with steady improvements in living standards and the growing affluence of global societies, greater longevity has led to great concern over the decline in performance and cognitive abilities that accompanies normal and neuropathological aging . The decWith the rapid development of computer technology and the video game industry, game types and game experience have greatly improved. A video game is any game played on a digital device, encompassing a wide range of interfaces, including web-based programs and apps for mobile devices . ExergamAlthough off-the-shelf video games were not developed for serious purposes or these specific interventions, many studies have determined that video game interventions may benefit the elderly in terms of serious purposes, including cognitive function, fall prevention, and other benefits ,11,12. NThis systematic review conformed to PRISMA  and the PRISMA extension statement for network meta-analysis ,14. We rWe conducted systematic literature searches of PubMed, EMBASE, and the Cochrane Library from their inception to June 30, 2020. The MeSH search terms were as follows in the full-text search: “active video game,” “active game,” “older adults,” and “elderly.” We included both randomized controlled trials (RCTs) and case-controlled trials (CCTs) that met the following criteria: participants were older adults (aged ≥60 years) without dementia; the interventions were all kinds of active video games , which means that the participants perform the video game intervention in an active state rather than a static state, and the whole body needs to be involved in the video games; and controls included exercise, puzzle games, visual stimulation, and no game play, which means that even patients who play games are still in a static state. The above declared the difference between the intervention group and the control group in order to study the effect of active video games in the intervention group. Comparisons of interventions with video games versus nonvideo game control were made with reported outcomes of performance and cognitive function.We assessed the effectiveness of 6 performance and cognitive outcomes by comparing the intervention group and the control group at the final point. The first outcome was balance function, tested using the Berg Balance Scale (BBS), balance test time (s), and balance test speed (m/s). The second outcome was executive function, tested using performance on the trail-making test B , delta (s), Stroop word (s), attention, working memory, and the Corsi block test. The third outcome was related to general cognition, tested using the Mini-Mental State Exam  and the Montreal Cognitive Assessment . Physical function was the fourth outcome, tested using everyday function and function tests (s and cm). The fifth outcome was processing speed tested using the TMT-A (s) and processing speed (number). The final outcomes were the fear of falling and depression, tested using the Efficacy Scale International (score) and the Geriatric Depression Scale (score). All these outcomes were continuous data.Two investigators (CY and XH) independently conducted the electronic literature search. The reference lists of relevant publications were also checked, and no language restrictions were set. These 2 researchers evaluated eligible titles, abstracts, and full texts, and disagreements between them were resolved by discussion with a third researcher (author YZ [Yingshi Zhang] or PC). A preset table was designed to extract details of potentially relevant papers, including the first author, publishing year, study type, region, sample size, gender, age, body mass index (BMI), education year, MMSE score, video game type, frequency, period, follow-up, control type, other associated diseases, and community or hospital. Two investigators (authors CY and EJ) extracted all continuous data independently onto a Microsoft Excel spreadsheet. The quality of the included RCTs was evaluated according to Cochrane Collaboration’s tool for assessing the risk of bias , and theP≤.05 or I2>50% indicated heterogeneity in the outcome. P<.10 revealed that a grouping method was a source of heterogeneity. The random effects model was used to ensure the accuracy of the summarized data. Publication bias was assessed using the Begg and Egger tests, where P≤.05 indicated the existence of publication bias [We applied standardized mean differences (SMDs) and 95% CIs to summarize the 6 outcomes from pairwise meta-analysis. To determine the efficacy of video game intervention versus nonvideo game control, we performed subgroup analysis and meta-regression of various intervention types , types of activity control activities , and periods . To determine the heterogeneity among our included studies, ion bias ,20.We performed a Bayesian random effects network meta-analysis composed of 4 chains with 100,000 iterations after an initial burnin of 10,000 and a thinning of 2.5 in order to determine the most suitable video game intervention. We calculated the SMDs and corresponding 95% credible intervals (CrIs), and the mean rank and surface under the cumulative ranking curve (SUCRA) values were produced from network meta-analysis estimates with a consistent model. We also produced comparison-adjusted funnel plots to explore publication bias from network meta-analysis. All the aforementioned analyses were performed using StataMP, version 14.0 (StataCorp) and WinBUGS, version 1.4.3 .For the outcomes of balance function, we first compared balance scores  pre- and postintervention. No significant differences were found overall and in subgroups by intervention and control types. Significant differences were only found at 8-12 weeks. Substantial heterogeneity was found overall and in all subgroups. The source of heterogeneity was not determined from meta-regression, and publication bias was occasionally found. For the balance test time (s), no significant differences were found overall and in all subgroup meta-analyses, with frequent substantial heterogeneity and no publication bias. In balance test speed (m/s) assessment, significant differences were found only for no game play as the control type . These findings suggest that video game interventions may improve balance in the elderly ; howeverP=.42, I2=0.0%) with high quality . No significant differences were found in all subgroups, with frequent substantial heterogeneity. Second, no significant difference was found in the outcome of delta (s). Similarly, no significant differences were found in the subgroup and overall outcomes of the Stroop word test (s), with substantial heterogeneity. When we evaluated the attention in video games compared with nonvideo games, significant differences were found only in the period of more than 12 weeks, with only 1 original study. In the evaluation of working memory, significant differences were detected for overall outcomes , other video games as the intervention type , no game play as the control type , and 4-8 weeks as the intervention period , with substantial moderate-grade heterogeneity in these subgroups. For the Corsi block test, significant differences were found for no game play and intervention periods of 0-4 and 8-12 weeks. Only the outcome for 8-12 weeks in 4 studies showed no heterogeneity . No significant difference was found for the function test (s) outcome , with substantial heterogeneity . With re outcome . In summP<.001, I2=95.5%) and for activity control , significant differences were found for overall outcomes , other video games , activity control , and for more than 12 weeks , with substantial heterogeneity. In terms of processing speed (number), significant differences were found overall and in subgroups, while substantial heterogeneity was found overall , compared with no game play as the control group, Xbox 360 as the intervention type ranked first, with a significant difference , followed by other video games , Nintendo Wii, and activity control. Significant differences could also be found in Xbox 360 versus other video games as the intervention type , Nintendo Wii , and activity control. For the BBS, significant differences were found only in other video games compared with Nintendo Wii as the intervention type , with some publication bias . In summFor general cognition, we combined the scores of MMSE and MoCA. Compared with no game play as the control type, which ranked the lowest, other video games as the intervention type ranked the highest, with a significant difference , followed by Xbox 360 , Nintendo Wii , and activity control . Significant differences were found in all comparisons, which suggests that the ordering from our Bayesian network meta-analysis was reasonable. No significant differences were found among the network outcomes from the TMT-B (s) to determine executive function B. In sumIn the assessment of processing speed, the first item examined was the TMT-A (s). Compared with no game play, other video games ranked first, with a significant difference , followed by activity control , virtual reality–based games, and Xbox 360. Significant differences were also found in comparisons of other video games and activity control versus virtual reality–based games and Xbox 360. The second item assessed was processing speed (number). Other video games as the intervention type also ranked first, with a significant difference compared with no game play as the control , followed by virtual reality–based games  and activity control . In general, video game intervention improved processing speed A. For thIn conclusion, based on Bayesian network meta-analysis, we determined that video game intervention improves balance function, cognitive function, and processing speed, which were similar results to those obtained using pairwise meta-analysis.Our Bayesian network meta-analysis quantified the comparative effectiveness of video games based on 47 studies including 3244 elderly participants, with acceptable quality. We comprehensively summarized the comparative efficacy of video games in improving performance and cognitive function in 6 domains: balance function, executive function, general cognition, physical function, processing speed, and fear of falling and depression. The results suggested that, first, on pairwise meta-analysis, video game interventions are beneficial for cognition scores, processing speed, and depression scores. There are tendencies toward benefits for balance function, executive function, and physical function. Second, on Bayesian network meta-analysis, interventions with video games may improve balance function, cognitive scores, and processing speed in the elderly, which was similar to the results of pairwise meta-analysis. Third, from the ranking of the Bayesian network meta-analysis, Xbox 360 and other video games always ranked first, while Nintendo Wii always ranked last of all interventions. This was accompanied by having the most outcomes of moderate GRADE with low publication bias in both pairwise and Bayesian network meta-analyses.In this systematic review, we used a comprehensive search with clear inclusion and exclusion criteria and carefully examined the efficacy of video game interventions in improving performance and cognitive function in 6 domains and 18 outcomes. Generally, the consistency of Bayesian network meta-analysis was similar to that of pairwise meta-analysis. On Bayesian network meta-analysis, compared with no game play as the control type, significant differences were found in balance time (s), cognitive scores, processing speed (TMT-A), and processing speed (number). For expert balance time (s), significant differences were also found in terms of cognitive scores, processing speed (TMT-A), and processing speed (number) on pairwise meta-analysis  and 4. BIn our study, we found that other video games and Xbox 360 are more effective than Nintendo Wii. Other types of video games were defined as exergames, video games, computer-based games, and virtual reality–based games. The main reason for these results may be that Xbox 360 and other video game screens require equipment to play, which have good platforms, a strong visual sense, and good interactivity. However, they are not easy to carry because of the requirement of external equipment.A previous meta-analysis did not distinguish between different video games; therefore, this is an innovation of our study. A previous study suggested that after Nintendo Wii therapy, patients experienced motor learning retention, achieving a sustained benefit using the technique . We obseThe mechanisms underlying changes following video game interventions remain unclear, although they might be related to tonic/phasic activation or inhibition of affected brain regions during video game playing  that makThis study had several limitations. First, we predesigned the inclusion criteria of video game intervention versus nonvideo game control. The definition of “video game” was broad, including Xbox 360, Nintendo Wii, virtual reality–based games, and computer-based games. However, the degree of stimulation, interaction, and pleasure of different video games for participants differed, resulting in clinical heterogeneity. Second, substantial heterogeneity was frequently determined on pairwise meta-analysis. One reason is the existence of clinical heterogeneity (many subgroups included less than 3 studies), and the other is the different types of combined scales for outcomes, leading to methodological heterogeneity. Third, some publication bias was detected in both pairwise and Bayesian network meta-analyses, which may be due to the difficulty in publishing negative outcomes. Lastly, to partially maintain the slight stability of the results under the Bayesian framework, we only chose outcomes that included more studies. Therefore, although the Bayesian network meta-analysis was not comprehensive, the results were more accurate.In summary, impaired cognitive function is a highly prevalent condition that can profoundly influence the quality of life and accounts for major health care expenditures among the elderly. Our comprehensive Bayesian network meta-analysis provided evidence that video game interventions could be considered for the elderly to improve their performance and cognitive function, especially general cognitive scores and processing speed. Video games with better interactivity and visual stimulation have better curative effects. Based on the available evidence, we recommend video game interventions for the elderly. Future studies should be designed as multicenter RCTs, involving more subjects and providing more detailed description of the types of video games, in order to determine the most appropriate type of video game for older adults.


Slc26a4 in the cochleae, and they subsequently phagocytose aggregated pigment granules and possibly degenerated intermediate cells. This review summarizes the current knowledge of characteristic features and proposed roles of PVMs in the stria vascularis. We also address macrophage activation and involvement of pigment granules with the loss of Slc26a4 in the cochleae.Tissue-resident macrophages play an important role in clearance, development, and regulation of metabolism. They also function as sentinel immune cells, initiating inflammatory responses, clearing inflammatory debris, and maintaining homeostatic tissue environment. In the cochlea, the roles of tissue-resident macrophages include maintaining steady-state tissues, immunological defense, and repairing pathological conditions associated with noise, ototoxic drugs, aging, and various pathogens. Perivascular macrophages (PVMs) are a unique subset of tissue-resident macrophages that are closely associated with blood vessels and have unique expression markers in certain tissues. PVMs are found in the inner ear, brain, skin, liver, and retina. The origin of PVMs in the inner ear is unclear, but they are already present during embryonic development. PVMs are members of the blood labyrinth barrier and regulate blood vessel permeability in the stria vascularis, which lies on the lateral wall of the cochlear duct and is crucial for endocochlear potential formation. The cytoplasm of strial PVMs can contain pigment granules that increase in number with age. Strial PVMs are activated by the loss of  Macrophages are present in almost all body tissues and display location-specific functions and gene expression profiles. These “tissue-resident macrophages” play an important role in the clearance, development, and regulation of metabolism depending on the tissue location and environment . They alMacrophages can support angiogenesis — formatiTissue-resident macrophages are present at various locations in the cochlea, including the spiral ganglion, spiral ligament, and stria vascularis. The stria vascularis is located on the lateral wall of the cochlear duct, which is essential for the generation of endocochlear potential and hearing acquisition. In this review, we provide a comprehensive overview of the origins, specifications, possible functions, and activation of tissue-resident macrophages in the stria vascularis. We also relate these with the recent findings of our study in the field of macrophage research and highlight important questions that remain unanswered.During development, Iba1-positive resident macrophages appear in the mouse otocyst as early as embryonic day 10.5, and are distributed in the spiral ganglion and spiral ligament until birth , 13. CsfIn the adult inner ear, bone marrow-derived resident macrophages are present in a steady state in the spiral ligament, the acoustic nerve and stria vascularis , 15. TheFigures 2A,C). This characteristic shape is similar to that of ramified microglia in the central nervous system (CNS). Iba-1 positive macrophages with similar form have also been reported in the human cochlea . Th. ThKcnj1us study , 41. PVMSLC26A4 gene, goiter, hearing loss, and enlargement of the vestibular aqueduct. The stria vascularis is atrophied and hyperpigmented in the ears of Slc26a4-null mice, a model of Pendred syndrome , which is predominantly produced by activated macrophages as a pro-protein, pro-IL-1β. Cochlear resident macrophages secrete pro-IL-1β through NLRP3 inflammasome activation . KnowledSlc26a4-null mice (Tissue-resident macrophages in the stria vascularis are observed only during the postnatal period and are always distributed close to blood vessels. Their possible functions and roles include adjustment of the blood-labyrinth barrier integrity and maintenance of homeostasis in the intrastrial space. The morphology of tissue-resident macrophages in the stria vascularis changes upon activation in the presence of melanin pigments, which might accelerate the degeneration of the stria vascularis in the ears of ull mice .TI and NK wrote the manuscript. YF provided critical feedback. All of the authors should have read and critically reviewed the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To the Editor:et al.,We are honored to receive the pertinent and relevant comments of Céline Julien et al.First, we agree that the long study period between 2001-2019 led to biases especially regarding progress made on MRI, HCA classification and molecular analysis. Imaging modalities and perioperative management dramatically changed, which may have led to substantial biases in the imaging interpretation, with a preoperative MRI missing in 7 cases (18%). While significant progress has been made over the last two decades, particularly in the diagnosis of HCA subtypes on MRI, only two subtypes are well-recognized, HNF1α-mutated HCAs (H-HCA) and inflammatory HCA (I-HCA), and no specific imaging pattern has been identified for the diagnosis of β-catenin subtype (β-HCA) and MT-HCA.TERT promoter mutations, as a molecular marker of malignancy, may be helpful in these cases. For instance, TERT promoter mutations have been reported in only 17% of borderline lesions compared with 60% of HCC.,Second, small foci of malignant transformation HCA (SF-HCA) were defined by the presence of foci of malignancy <1 cm within an HCA and malignant HCA (M-HCA) by the presence of macroscopic malignant HCC nodules larger than 1 cm. The diagnosis of malignant transformation of HCA was achieved on surgical specimens by pathological analysis, and all cases included in this study displayed clear foci of malignant transformation based on cytological and architectural features, including reticulin staining in all cases and immunophenotypical markers (such as Glypican-3) when necessary. Borderline HCA without overt foci of malignant transformation were excluded from the study mainly because of the lack of consensual definition in the literature, and variability in interpretation between pathologists. We acknowledge that the distinction of borderline HCA from degenerated HCA or from a well-differentiated HCC may in some cases be difficult to do.et al., noted that I-HCA was the main subtype in our study, indeed, I-HCA was the main subtype (47% of cases) followed by β-HCA (30%) and β-IHCA in 10%. It is well-admitted that risk of malignant transformation is associated with large tumor size (>50 mm), male sex, and presence of βex3 mutations. The risk of malignant transformation into HCC may reach 40% in β-HCA, an incidence higher than for other molecular HCA subtypes.Third, Céline Julien et al., HCCs can frequently overexpress inflammatory proteins and a low level of LFABP, which can be misleading. In addition to suggestive morphological features, I-HCA were confirmed by immunohistochemical stainings with serum amyloid A  and C-reactive protein (considered positive in case of diffuse and intense pattern). To avoid confusion with well-differentiated HCC, all slides of the tumor were carefully reviewed by a pathologist experienced in liver pathology.As mentioned by Céline Julien In our study, 10 patients experienced recurrence, among them, 4 patients had satellite nodules and 2 had microvascular invasion, but none had poorly differentiated HCC.et al. that long-term outcomes are relevant to improve management strategies of malignant transformation risk in HCA, and that specific adjusted risk factors of malignant transformation for each patient with HCA should be evaluated and should help to determine the most appropriate management.Finally, we totally agree with Céline Julien The authors received no financial support to produce this manuscript.SC, AB, VP wrote the manuscript. FC, OS reviewed and corrected the data and manuscript.The authors declare no conflicts of interest that pertain to this work.Please refer to the accompanying ICMJE disclosure forms for further details.


Many young people in Korea today experience deprivation in various areas of life. The social determinants of health approach maintains that social factors play an important role in an individual’s physical and mental health. This study aimed to investigate the problem drinking trajectory of young Korean people and identify the effects of multidimensional deprivation on problem drinking.The study used data from 2012 to 2018 found in the Korea Welfare Panel Study. Latent class growth analysis was performed to determine the number of trajectories of problem drinking. After identifying latent classes, a multinomial logistic regression analysis was utilized to examine multidimensional deprivation as a predictor of class membership.Latent class analysis yielded three groups: (1) a low-level maintenance group , (2) a moderate-level increasing group (moderate level of problem drinking with a moderate increase in problem drinking), and (3) a risky drinking increasing group (high level of problem drinking with a rapid increase in problem drinking). Results from multinomial logistic regression showed that deprivation in housing and social deprivation increased the probability of belonging to the risky drinking increasing group compared to other reference groups.The study speaks to the need to establish appropriate intervention strategies according to the level and changes in the pattern of alcohol use. The implications of housing and social deprivation concerning problem drinking among young Korean people are also discussed.The online version contains supplementary material available at 10.1186/s13011-021-00426-2. Problem drinking encompasses the level or potential of experiencing physical, emotional, and social problems due to alcohol use and overall social harm caused by drinking . The socBiological and psychosocial factors, developmental tasks, and the environments in which these tasks occur differ in each stage of the human life cycle. Several studies have indicated that drinking behaviors and associated harm are different according to each developmental stage , 9. WhilInequality in Korea has been increasing since the economic crisis in the late 1990s that was followed by the aggravation of various social risks. Young Korean people today have a higher level of education than those of the past; however, they face higher unemployment, lower wages, and more precarious job situations regardless of individual efforts due to labor market instability. They also face unstable housing due to rising prices and economic pressures caused by student loans. As such, they are increasingly placed in unpredictable situations that hinder marriage, childbirth, and having a family , 13. TheThis has resulted in young Koreans voluntarily classifying themselves into different socioeconomic classes based on “spoon discourse”Relative deprivation experienced in daily life, a lack of social support, and a lack of control over one’s life play important roles in an individual’s physical and mental health including alcohol related problems . AccordiIn general, problem drinking is explained from a biopsychosocial perspective . HoweverRecent studies have recognized the impact of deprivation and problem drinking on the Korean population –45. HoweBased on the discussion above, this study examines the influence of deprivation on the development of problem drinking trajectories in young people by utilizing a deprivation index that includes multidimensional deprivation. The purpose is to understand the longitudinal effects of deprivation in different areas on young people’s changing problem drinking patterns.The specific research questions are as follows: (1) What are the trajectories for problem drinking among young people over time? (2) How does multidimensional deprivation among young people affect changes in the problem drinking patterns?www.koweps.re.kr) [This study used data from the 2012 to 2018 Korea Welfare Panel Study compiled by the Korea Institute for Health and Social Affairs. Further details on the sampling design, methods, and data sets can be found elsewhere (s.re.kr) . Consists.re.kr) . For theProblem drinking was measured using the Alcohol Use Disorder Identification Test (AUDIT). AUDIT is a screening tool developed by the World Health Organization (WHO) to screen problem drinking, and it consists of 10 questions. Each item is rated on a five-point scale, with the total score ranging from 0 to 40. Interpretations of the scale include using a cut-off score or using the total score as a continuous value. In this study, responses to 10 items were summed as a total score to classify potential groups of developmental trajectories for problem drinking. The higher the score, the higher the likelihood of problem drinking, which reflects dangerous and harmful drinking.Multidimensional deprivation was measured using the base year data from 2012. Seven areas of deprivation were measured. The experience of deprivation reflects the environment and socio-cultural climate in which one resides; therefore, we reviewed studies examining deprivation in Korea that utilized the same dataset , 54–56. Demographic variables included gender , marital status , religious status , and residential area . Income level was categorized into low income (0) and other (1) based on 60% of the median income threshold, and education level was dummy coded as middle school or less, high school, and college or more.To identify the latent development trajectory classes (type of change) for problem drinking among young people and verify the influence of multidimensional deprivation on this pattern change, latent class growth analysis (LCGA) and multinomial logistic regression analysis were performed. LCGA, a form of growth mixture modeling (GMM), is useful for classifying latent classes over time within populations assumed to have similar characteristics . Generalk potential classes presented by the model should also be examined. Models with classes that include fewer than 5% of the samples can be excluded. After identifying latent classes with different problem drinking trajectories, multinomial logistic regression analysis was performed to identify areas of deprivation that predict these classes. Analyses were performed using STATA 16.0 [Various criteria are used to determine the optimal number of latent classes in latent class growth modeling. The current study used Akaike’s information criterion (AIC) and the Bayesian information criterion (BIC) to determine the number of latent classes. In general, a smaller goodness-of-fit value indicates a better model, and the number of relevant latent classes and the proportion of subjects in each class are examined , 60. TheATA 16.0 .n = 727) were male, and 59.0% (n = 1037) were female. A total of 1181 (72.3%) young people had a college degree or higher, and 26.9% (n = 560) had received a high school education. About half of the respondents (51.2%) were married, 47.3% (n = 721) were single, and 1.6% (38) were divorced/widowed/separated. Among the respondents, 51.9% (n = 731) lived in a metropolitan area, and 48.1% (n = 1033) lived in non-metropolitan areas. Using the 60% of the median income threshold, 6.5% (n = 155) of respondents were categorized as the low-income group.The general characteristics of the young adults in the base year 2012 data are presented in Table The zero-order relationship between independent and dependent variables was examined  in class one, 45.6% (n = 804) in class two, and 18.4% (n = 325) in class three.To determine the final optimal model, latent class growth analysis was performed. Table p < .001) and maintained this level over time (36% of respondents). In other words, no increase or decrease in problem drinking was detected longitudinally. The second latent class (Class 2), called the moderate-level increasing group, showed a moderate level of problem drinking initially  and exhibited a moderate increase over time . Among the respondents, 45.6% were classified into this group. The third latent class (Class 3), named the risky drinking increasing group, showed the highest level of problem drinking at the beginning  and exhibited a rapid increase in problem drinking . About 18% of the young people in the study fell into this category.The course trajectories and statistical significance of the three latent classes identified are presented in Table 2 (30) = 278.78, p = .000), and the explanatory power of the model (Pseudo R2) was .155  and the moderate-level increasing group (Class 2). The model indicated a good fit (LR Chi55 Table .Table 4p < .001) and having religion  were less likely to belong to both classes 2 and 3. Compared to the low-level drinking group, single young people were more at risk of belonging to the moderate-level drinking group with an increase in problem drinking over time . Compared to the low-level drinking group, a low income or poverty predicted young people falling into the risky drinking group with an increase in risky drinking longitudinally .First, the relative risk ratios (RRR) of the moderate-level increasing group (class 2) and risky drinking increasing group (class 3) were examined using the low-level maintenance group (class 1) as the reference group. Compared to the low-level maintenance group, being female , and those who experience social deprivation are 1.712 times more likely (RRR = 1.712 P < .01) to engage in risky drinking that will increase over time.In the context of multidimensional deprivation, none of the deprivation areas experienced by young people predicted moderate-level problem drinking compared to the low-level problem drinking group. However, young people who experienced housing deprivation and social deprivation were more at risk of belonging to the risky drinking increasing group compared to the reference group (Class 2). The findings indicate that compared to young people in the low-level maintenance group, housing deprivation increases the probability of engaging in risky drinking by 1.077 times  and those not in poverty  were less likely to belong to Class 3. In other words, men, and those in the low-income group are more at risk of engaging in problem drinking that continues to grow over time.Next, predictors of Class 3 (risky drinking increasing group) were analyzed using Class 2 as the reference group. The results indicated that women  and 1.425 times  more at risk for engaging in risky drinking longitudinally. The findings indicate that housing and social deprivation among young people are significant predictors of problem drinking.Analysis of multidimensional deprivation factors showed that housing and social deprivation are significant predictors of belonging to the Class 3. Compared to the moderate problem drinking group, those who experience deprivation in housing and social areas were 1.107 times , comprises Korean young adults who had low levels of alcohol use and maintained this low level during the study period. The second group, called the moderate-level increasing group (45.6%), includes young adults who initially showed moderate levels of problem drinking and exhibited a moderate increase in problem drinking over time. The last group, called the risky drinking increasing group (18.4%), consists of young people who had the highest level of problem drinking at the baseline and showed a rapid increase in problem drinking. These developmental trajectories among young people show that there are different patterns of problem drinking development. Previous studies focused on alcohol problems among young people in general , 66; howThese findings suggest that prevention and intervention programs should consider different levels of problem drinking among young people. For instance, for young people who fall within low-level problem drinking, prevention efforts should focus on keeping alcohol use at this low level so that they do not develop a risky drinking habit. Drinking patterns formed during early adulthood are likely to persist in later life , 67, 68.The findings from multinomial logistic regression indicated that being male, poverty, housing deprivation, and social deprivation were significant predictors of belonging to the risky drinking increasing group. Although the effects were statistically significant, it is necessary to consider the effect size of these factors. Examination of the relative risk ratios showed that being male and being in poverty had a larger influence on belonging to the risky drinking increasing group than social deprivation and housing deprivation. This finding is consistent with previous knowledge, which had consistently reported that men experience more drinking problems than women. The fact that poverty, a main socioeconomic indicator, has the most important role in predicting risky drinking confirms the importance of examining social determinants of alcohol related issues. Poverty is closely related to many areas of deprivation. If practice and policy on alcohol-related problems do not take livelihoods into account, the benefits of intervention effects will be limited.Examining the effects of multidimensional deprivation on the latent classes of developmental trajectories of problem drinking among young Korean people, the study results indicate that deprivation in housing and social deprivation increased the probability of belonging to the risky drinking increasing group compared to each reference group (the low-level maintenance group and the moderate-level increasing group). The association between housing deprivation and the change in pattern in problem drinking is consistent with previous studies that maintained that housing is a significant factor of alcohol-related behavior , 69. ThiA residence is a basic living condition in life, but housing has various meanings for young Koreans. Having the means to secure appropriate housing is considered an essential condition for completing developmental tasks, such as marriage and having children, and a way to relieve anxiety about uncertainties in life , 13, 54.Ultimately, housing deprivation reflects inequality for young people, and we may infer that this perceived inequality has contributed to a sharp increase in problem drinking . The proFinally, the study findings reported on the relationship between social deprivation and problem drinking among young people, indicating the social environment young people face today. With the growing instability in the labor market, young Koreans are repeatedly entering and exiting different jobs to seek better placements . Young pIn addition, there is an argument that young people lack formal social welfare resources compared to other generations . There aThis study’s findings suggest that public policies targeting young people should give more attention to their problem drinking and seek ways to expand and improve public social networks and social resources. Comparing the results of this study with change patterns of problem drinking of those in the middle-aged and older generations, we can observe several patterns of problem drinking as well as areas of social deprivation that affect it. A recent study that used similar data showed that for the middle-aged group, social security, work, and income deprivation were significant predictors of problem drinking, whereas social deprivation was the main predictor for the elderly group . For youThis study examined a longitudinal relationship between deprivation and problem drinking using a deprivation index based on different needs in the stages of the human life cycle. Through the study, we were able to identify the social risks young people face today in the process of performing developmental tasks and how these risks affect individual mental health, specifically problem drinking. This study is of value in that it examined specific areas of deprivation to which young people are more sensitive and their association with drinking practices. Furthermore, this work adds to current knowledge in alcohol research by examining longitudinal changes in groups showing different patterns of developmental trajectories.Despite the contributions of this study to the literature on alcohol problems, it is important to identify its limitations. The deprivation index was necessarily formed only from items available in the limited secondary data, and it could not include all the functional and diverse areas of deprivation young people may face in daily life today. Another limitation of the data is that they are correlational, and it is difficult to determine a causal relationship between independent variables. Finally, the study only examined the trajectories of problem drinking and did not follow changes in multidimensional deprivation over time. Because longitudinal changes in deprivation as predictive factors can influence problem drinking, future research should examine changing patterns in different areas of deprivation to understand the more dynamic processes in the relationship.This study examined changes in problem drinking among young Korean people over seven years using the Korea Welfare Panel Study to classify latent classes with different problem drinking trajectories. Furthermore, this study examined how various dimensions of deprivation predict latent class membership. Three latent classes with different trajectories that reflect changing patterns in problem drinking were identified: the low-level maintenance group, the moderate level increasing group, and the risky drinking increasing group. This study provides evidence for the need to establish appropriate intervention strategies according to the level of and patterns of change in alcohol use. The study results also confirmed that deprivation, a relative disadvantage or deficiency, experienced in society influences young people’s level of problem drinking and the patterns of change over time. Specifically, Korean youngsters who are deprived of housing and social connections are more likely to engage in higher levels of problem drinking and exhibit increased risky drinking over time. Drinking practices and high-risk drinking may be an individual’s choice. Still, our study confirmed the role of social factors such as housing and social deprivation, known as the social determinants of health, on problem drinking.Additional file 1. Correlation among the study variables. The table describes correlation coefficients between major variables. * p < 0.05; 1 problem drinking; 2 gender ; 3 age; 4 education; 5 marital status (single); 6 marital status (divorced/widowed/separated); 7 residential area (metropolitan); 8 low income; 9 religion; 10 food deprivation; 11 housing deprivation; 12 education deprivation; 13 work and income deprivation; 14 social security deprivation; 15 social deprivation; 16 health and medical care deprivation.


Access to information via social media is one of the biggest differentiators of public health crises today. During the early stages of the Covid-19 outbreak in January 2020, we conducted an experiment in Wuhan, China to assess the impact of viral social media content on pro-social and trust behaviours and preferences towards risk taking with known and unknown probabilities. Prior to the experiment, participants viewed one of two videos that had been widely and anonymously shared on Chinese social media: a central government leader visiting a local hospital and supermarket, or health care volunteers transiting to Wuhan. In a control condition, participants watched a Neutral video, unrelated to the crisis. Viewing one of the leadership or volunteer videos leads to higher levels of pro-sociality and lesser willingness to take risks in an ambiguous situation relative to the control condition. The leadership video, however, induces lower levels of trust. We provide evidence from two post-experiment surveys that the video’s impact on pro-sociality is modulated by influencing the viewer’s affective emotional state.The online version contains supplementary material available at 10.1007/s40881-021-00104-w. On January 23, 2020, local authorities in China imposed a full lockdown of Wuhan city in response to the emergence of a novel coronavirus and associated disease, Covid-19. This event was followed shortly after by the lockdown of other cities across Hubei province. With the movements of over 50 million people in the centre of China being closely monitored, this represented one of the largest forced quarantines in human history.2Access to information via social media is one of the biggest differentiators of pandemics today from the past . The second of these videos shows health care volunteers from other provinces in transit to Wuhan (henceforth “Volunteer video”). Both videos were circulating widely and anonymously among chat groups on the Chinese social media application WeChat at the time of the experiment. In the control condition, participants watch a neutral product advertisement video, unrelated to the crisis .We find that priming participants with either the Leadership or Volunteer video results in significantly more pro-social behaviour relative to the Neutral video, as measured by participants’ levels of altruism and expectations of reciprocity in the decision tasks. Participants’ also display lesser willingness to take risks in an ambiguous situation in the treatment conditions, although there is no systematic effect of the viral videos on risk preferences in unambiguous situations. The Leadership video alone induces a significant fall in trust, although we caution on drawing generalized conclusions from this result, because we test only one video which involves just one (prominent) government figure.In the two follow-up surveys, we find evidence to support the argument that the videos impact behaviour through the manipulation of affective emotional states. In the first survey, we ask respondents to select five events, from a list of fifteen, which acted as psychologically positive motivating factors during the early stages of the Covid-19 crisis. The two most selected events are health care teams volunteering to assist in Hubei province and national leaders countering the epidemic. In the second survey, we evaluate the impact of viewing the videos in our experiment through a set of questionnaires that assess an inventory of emotional measurements. We find that the Leadership and Volunteer videos each induce a significant rise in positive affect relative to the Neutral video, with underlying increases in joviality and self-assuredness. Those individuals who watch the Volunteer video also report greater attentiveness. There is some evidence that viewers of the Leadership and Volunteer videos feel a comparatively greater sense of guilt.The paper continues in Sect. A timeline of our economic experiment in context of the Covid-19 outbreak in Hubei province is displayed in Fig. Invitations to participate in a session were sent directly to participants’ WeChat accounts, which is the most popular instant messaging app and the largest social media platform in China. At the time of the experiment, participants had already left the university for the semester break, which coincides with the annual spring festival holiday. Thus, participants were residing in twenty-nine different provinces. Forty participants were residing in Hubei province, including seventeen from Wuhan. On average, each session lasted forty-five minutes, and participants earned 63.79 RMB (about 9.5 US dollars), including a participation fee of 10 RMB. Participation in the experiment was completed using a mobile device and we transferred payment to their WeChat account immediately after completion of their experimental session.Four canonical games, multi-persons decision problems, are considered: a dictator game (DG), an ultimatum game (UG), a trust game (TG), and a prisoner’s dilemma game (PD).In the TG, players are again matched into pairs, player 1 is allotted a stake and decides how much of that stake to transfer to player 2. The amount transferred is tripled, which player 1 is aware of, before reaching player 2. After player 2 receives the multiplied transfer, he or she decides how much of it to return to player 1. In the TG, the amount that player 1 sends is a measure of trust and the amount that player 2 returns reflects trustworthiness. The stake used for this game is 8 RMB.The PD is a normal-form game in which each player chooses to either Cooperate or Defect. Choosing Defect yields a player a higher payoff than choosing Cooperate against each of the opponent’s possible choices. However, the pair’s total payoff is highest when both choose to Cooperate. The payoff to mutual cooperation was 6 RMB, to mutual defection 3 RMB, to unilateral cooperation 0 RMB and to unilateral defection 9 RMB.We also include tasks designed to elicit preferences towards risk taking with known and unknown probabilities.Before completing the decision tasks, participants watch a once repeated video of approximately two minutes in length.In the Leadership video treatment, participants are shown excerpts from the visit of a senior central government official to Wuhan Jinyintan Hospital—the first hospital designated to treat patients with Covid-19—and to a local supermarket, on January 27, 2020. In this video, the senior central government official uses morale-boosting words and phrases such as “protect”, “save lives” and “empowered”, to which the doctors and customers alike respond enthusiastically. In the Volunteer video treatment, participants are shown a video of health care volunteers from other provinces in transit to Wuhan. The video pans to teams from various hospitals and acknowledges their place of origin and number, in almost regimental style. Exclamations are heard over the public tannoy such as “go Wuhan!” and “we will carry the burden with you”.We summarize our economic experiment and the data collection process in Table L) and Volunteer (V) videos have marginally significant positive effects on pro-sociality in the experiment relative to the Neutral (N) video. In the DG, both videos increase the average amount sent by dictators . There is also evidence that participants offer higher amounts in the UG. While this increase is not significant at conventional thresholds for the Leadership video versus the Neutral video, it is for the Volunteer video . The corresponding difference between Leadership and Volunteer video conditions, however, is not significant . UG acceptance rates are lower in the Neutral video condition in response to the reduced offers, although higher variability means that the pairwise differences are not significant .The aggregate outcomes of the lab experiment are presented in Table p value = 0.09, nL = 18 and nN = 20). We find no significant negative effect of the Volunteer video on trust  and no significant difference in the raw TG amount sent between the Leadership and Volunteer video . Reciprocity, in terms of amounts returned, adjusts proportionally in each experimental condition.p value = 0.52 and p value = 0.64, respectively, nL = nN = 78 and nV = 76).Interestingly, the Leadership video appears to undermine trust. Amounts sent by first movers in the TG are lower in the Leadership video treatment than in the Neutral video control, although this difference is only marginally significant , both videos reduce participants’ willingness to take risks in an ambiguous situation . We advise against reading into the absolute levels recorded in the ambiguity preference elicitation task, because our implementation did not permit participants to choose the payoff-relevant colour and so this task may also pick up trust in the experimenter.10An ancillary question is how the treatment condition videos influence participants’ preferences towards risk taking with known and unknown probabilities. To examine this question, we use the first row in which the certain option was chosen in the risk and ambiguity preference elicitation tasks. For each task, there were nine rows; risk neutrality corresponds to choosing the certain amount for the first time in row five. While neither the Leadership nor Volunteer video significantly influences risk aversion with known probabilities , our non-parametric analyses above rest on small sample sizes per condition and so lack statistical power to detect effects. To address this issue, we conduct an individual-level regression analysis of our key outcome measures on indicator variables for the two treatment condition videos, while controlling for other demographic and local factors that might be influencing behaviour. We include as covariates the aggregate number of diagnosed virus cases at provincial level, participant gender, cell phone operating system and screen size.The results of the regression analysis are presented in Table 12In Table not the Volunteer video—undermining the component of trust which is unrelated to preferences over risk, ambiguity and pro-sociality. There is, however, no significant difference between the Leadership and Volunteer video coefficient estimates. We will return to discuss these differential effects further in Sect. To estimate the impact of the treatment videos on amounts sent by first movers in the TG, we first conduct a straightforward OLS regression. The Leadership video has a robust negative effect on trust which is significant at the 5% level. The Volunteer video has no significant effect on trust. We then control for subjects’ decisions in the risk and ambiguity tasks, and in the PD game, to isolate the effect of the videos on trust net of pro-sociality, risk and ambiguity aversion.To gain insight into the channels mediating the differential effects observed in our economic experiment, we provide two post-experiment assessments on how the content of the social media videos are perceived. The first assessment is a follow-up survey we administered from March 12 to 20, 2020 to 5,686 non-student individuals around China. Among other questions, we asked respondents to select five events, from a list of fifteen, which acted as psychologically positive motivating factors in the early stages of the Covid-19 crisis . There is some evidence that participants who watched the Volunteer video also feel more attentive than those who watched the Neutral video , and more active, inspired and interested than those who watched the Neutral video  or Leadership video .18We find significant increases in positive affect induced by the Leadership and Volunteer videos relative to the Neutral video Table . Particip value = 0.42) or Volunteer video , and little underlying variability in the negative emotions of fear or hostility. An interesting exception is that participants in both the Leadership and Volunteer video conditions describe feeling a greater sense of guilt than their counterparts in the Neutral video condition . We observe no systematic differences in responses to the IRI or SOC questionnaires.19By contrast, we find no significant difference in negative affect for either the Leadership video  influences. Li et al.  show thacentralization thesis, e.g. 't Hart et al., centralization thesis in times of crisis, postulating that bottom–up communication styles are more effective Below is the link to the electronic supplementary material.


Objective: Avocado/soybean unsaponifiables (ASUs) are commonly used to treat OA symptoms. However, there are many ASU mixtures on the market with differing compositions and pharmacological activities. This study aimed to compare the composition and pharmacological activity of seven commercially available ASU products on human osteoarthritis chondrocytes.Methods: The contents of the lipidic part of ASUs were characterized by gas chromatography analysis using a VARIAN 3400 chromatograph. The pharmacological activity of the ASU products was tested on human osteoarthritis chondrocytes cultured in alginate beads. Their effects were evaluated on aggrecan, interleukin (IL)-6 and -8, and matrix metalloproteases (MMP)-3 using immunoassays and on nitric oxide through measurement of nitrite via spectrometry.Results: PIASCLEDINE-ExpASU® showed a specific profile with the presence of chromatographic peaks corresponding to an alkyl furan fraction and alkyl triols. PIASCLEDINE-ExpASU®, Persemax, Insaponifiable 300, Arthrocen, and Arthocare contained quantifiable amounts of tocopherol, while tocopherol was undetectable in Avovida and Saponic. Squalene was found only in PIASCLEDINE-ExpASU®. The abundance of sterols varied depending on the product. PIASCLEDINE-ExpASU® was the most active of the tested ASU products in inhibiting nitric oxide, IL-6, and IL-8 production by chondrocytes. With the exception of Saponic and Persemax, all the ASU mixtures either slightly or significantly increased aggrecan production. MMP-3 levels were significantly decreased by Insaponifiable 300 and PIASCLEDINE-ExpASU® and significantly increased by Saponic.Conclusion: The composition of PIASCLEDINE-ExpASU® is different to that of the other evaluated ASU mixtures. This specific composition explains its better pharmacological activity, including the higher inhibitory effect on pro-inflammatory and pro-catabolic factors. Our findings are helpful in providing a basis for understanding the symptomatic effect of PIASCLEDINE-ExpASU® in patients with osteoarthritis. Osteoarthritis (OA) affects around 500 million people worldwide  and is o® is commercialized as a drug in many countries . This is the only ASU product that has been rigorously investigated in robust randomized controlled trials (RCTs) . It has been shown that a fraction of native furanic unsaponifiables specific to the avocado pericarp, identified as comprising persin compounds, undergoes cyclization when the fruit is submitted to heating  and inhibit the production of interleukin (IL)-6 and -8, prostaglandin (PG) E2, and some matrix metalloproteases (MMPs) in chondrocytes. It also positively modulates the altered phenotype of OA subchondral bone osteoblasts and reduces the production of collagenases by synovial cells. At this time, four robust RCTs have all demonstrated a beneficial symptomatic effect of PIASCLEDINE-ExpASU® in the treatment of hip or knee OA  . It is as (RCTs) . Indeed, heating . This chifiables . Similarescribed  , and Saponic . All products were presented as 300 mg capsules.The following products were included in the study: Arthocare , Arthrocen , Avovida , Insaponifiable 300 , Persemax , PIASCLEDINE-ExpASUFor each product, the mass of 20 individual capsules was weighed and recorded. The content of the capsules was collected and subjected to Soxhlet extraction using chloroform. Soxhlet extraction is a very standard and well-recognized method that leads to the extraction of water-insoluble and slightly water-soluble organics identified as semi-volatile organic compounds (SVOCs) . The masOA human articular cartilage was obtained from 12 different patients  with knee OA at the time of total knee joint replacement surgery. All the subjects provided their informed consent, and ethical approval  was granted for this study.To allow testing the product on primary human OA chondrocytes, which are one of the therapeutic targets of ASU, we used freshly isolated chondrocytes expressing inflammatory phenotypes defined by a high rate of IL-6 production (up to 40 ng/µg DNA). To obtain OA chondrocytes, the following process was used: 1. On dissection, the femoral, patellar, and tibial articular surfaces were evaluated for gross morphological modifications of cartilage according to the Collins diagram . The severity of lesions was, thus, recorded for each sample. Different grades were considered: 0, normal white cartilage in all areas examined; I, the presence of a yellow–gray area with some superficial fibrillations on one or more articular surfaces; II, irregular surface with deep fibrillations on one or more articular surfaces; III, subchondral bone denudation on one or more articular surfaces, in less than 50% of the most damage compartment; and IV, subchondral bone denudation on more than 50% of the articular surface at least in one tibial plateau. All donors showed OA cartilage lesions of grade III to IV. 2. We evaluated the IL-6 levels produced by cultured chondrocytes using an immunoassay.® or one of the six other nutraceutical products being evaluated in comparison, namely, Arthocare, Avovida, Arthrocen, Insaponifiable 300, Persemax, or Saponic (3 wells/condition). At the end of the culture period, the culture medium was carefully discarded, and the beads were dissolved in 1 ml of 0.1 M citrate for 10 min. The resulting suspension was centrifuged at 1,200 rpm for 10 min. With this method, two fractions were collected: the supernatant containing macromolecules originating from the further-removed matrix (FRM) and a pellet containing cells with their associated matrix (CM).Full-depth articular cartilage was excised and immersed in Dulbecco’s modified Eagle’s medium (DMEM) (with phenol red and 4.5 g/L of glucose) supplemented with N-(2-hydroxyethyl)piperazine-N’-(2-ethanesulfonic acid) (HEPES) 10 mM, penicillin (100 U/ml), and streptomycin (0.1 mg/ml) . After three washes, the chondrocytes were released from the cartilage by sequential enzymatic digestions with 0.5 mg/ml of hyaluronidase type IV-S  for 30 min at 37°C, 1 mg/ml of pronase E  for 1 h at 37°C, and 0.5 mg/ml clostridial collagenase IA (Sigma-Aldrich) for 16–20 h at 37°C. The enzymatically isolated cells were then suspended in alginate beads, as previously described , and mai®. Each product group has been tested on six independent cultures. Each culture condition was performed in triplicates.Twelve cultures have been performed. Each culture was performed with chondrocytes coming from one single cartilage specimen. Given the limited number of cells per specimen, it was not possible to test all products on the same specimen. Therefore, the products were separated into two groups. Each group was composed of 3 products and the reference product PIASCLEDINE-ExpASUThe DNA content of the culture was measured according to the fluorometric method using Hoechst .The total AGG production corresponded to the AGG accumulated in the alginate beads. AGG at D12 and IL-6, IL-8, and MMP-3 only in the supernatant (cumulative production D3_D6_D9 and D12) were measured by specific enzyme-amplified sensitivity immunoassays .Cell viability was estimated by quantifying the release of LDH in the culture supernatant, as previously described . A samplvia a spectrophotometric method based upon the Griess reaction. The absorption was measured at 540 nm. Sodium nitrite (NaNO2) was used for calibration.Nitrite and nitrate are stable end products of nitric oxide. Nitrate was reduced to nitrite by its addition to the supernatant of nitrate reductase (0.25 U/ml) for 20 min at 37°C. The cumulative nitrite concentrations in conditioned culture supernatants after 3, 6, 9, and 12 days of culture were determined in vitro experiments were analyzed and compared using a paired Student’s t-test and bilateral hypothesis followed by Bonferroni adjustment. Differences were considered significant when p < 0.05. Data are presented as histograms. The exact p values are provided, and asterisk representations were also performed. All data were analyzed by R software.Data from ®300, the lipidic part extracted by the Soxhlet device represented less than 300 mg/capsule lipidic part, while the PIASCLEDINE-ExpASU® capsules contained 305.5 mg of the lipidic part  contained quantifiable amounts of tocopherol, while tocopherol was undetectable in Avovida and Saponic. Only PIASCLEDINE-ExpASU® contained squalene (2 mg/capsule). The sterol content varied depending on the product: 102 mg/capsule in Saponic, 106 mg/capsule in PIASCLEDINE-ExpASU®, 124 mg/capsule in Persemax, 126.8 mg/capsule in Arthrocen, 138.4 mg/capsule in Avovida, 154.2 mg/capsule in Insaponifiable 300, and 195.4 mg/capsule in Arthocare.Arthocare (0.1 mg/capsule), Arthrocen (1.5 mg/capsule), Insaponifiable 300 (1.8 mg/capsule), Persemax (1.8 mg/capsule), and PIASCLEDINE-ExpASUPrimary OA human chondrocytes were cultured for 12 days in alginate beads with or without ASU products. Cell viability, evaluated by LDH release and DNA content, were not affected by the tested compounds (data not shown).®, and Persemax significantly decreased NO production . However, the effects of PIASCLEDINE-ExpASU® on NO production were significantly higher than those of other compounds (p < 0.0001). In contrast, Arthrocare, Avovida, Insaponifiable 300, and Saponic had no significant effect on NO production.Under basal conditions, the NO production was 69.11 ± 20.08 nmoL/µg of DNA. As illustrated in ®: p = 0.10116; Ctl vs. Arthrocen: p = 0.04979; Ctl vs. Arthocare: p = 0.00010; Ctl vs. Persemax: p = 0.00063)  .®: p < 0.0001; Ctl vs. Arthrocen: p = 0.00031; Ctl vs. Arthocare: p = 0.00244; Ctl vs. Insaponifiable 300: p = 0.00038; Ctl vs. Persemax: p = 0.00014) (® was significantly higher than that of the other compounds (p < 0.0001).Except for Avovida and Saponic, all other products significantly decreased IL-6 production by human OA chondrocytes (Ctl vs. PIASCLEDINE-ExpASU0.00014) . However®: p < 0.0001; Ctl vs. Arthrocen: p = 0.00711; Ctl vs. Insaponifiable 300: p = 0.00658; Ctl vs. Persemax: p = 0.00192; Ctl vs. Saponic: p = 0.00603). However, the inhibitory effect of PIASCLEDINE-ExpASU® was significantly higher than that of the other compounds (p < 0.0001).As illustrated in ® and Insaponifiable 300 significantly decreased the basal production of MMP-3  while Arthocare, Arthrocen, Avovida, and Persemax had no significant effects, and Saponic significantly increased MMP-3 production (Ctl vs. Saponic: p = 0.04103) (PIASCLEDINE-ExpASU0.04103) .ASU products are commonly used to treat OA patients. They are members of a class of drugs called SYSADOA, which have been recommended by many scientific and medical societies for relieving OA symptoms . However® has a unique composition characterized by the presence of alkyl furans, alkyl triols, and squalene. These compounds were absent in all of the other mixtures, indicating that these molecules could be responsible for the different pharmacological activity profiles of PIASCLEDINE-ExpASU®. Indeed, PIASCLEDINE-ExpASU® was the most effective inhibitor of NO, IL-6, IL-8, and MMP-3. The unique formulation of PIASCLEDINE-ExpASU® is obtained by a particular proprietary-patented process. Our results confirmed those of a previous study conducted by the manufacturer (®300, namely, in the absence of or not having detectable levels of specific molecules from common natural avocado unsaponifiables such as the key molecule citrostadienol, the absence of alkyl furans, alkyl triols, and squalene and finally, the presence of brassicasterol, which is highly specific for rapeseed oil and related unsaponifiables (Our characterization clearly of ASU products shows that PIASCLEDINE-ExpASUfacturer , which difiables .®300 and tested the influence of the sterol content on the upregulation of glycosaminoglycan and collagen synthesis by bovine chondrocytes in vitro and on the upregulation of PGE2 in an IL-1–induced in vitro model of articular cartilage breakdown (® has a different gas chromatographic profile to NMX-1000™ with three additional major unidentified peaks, while the total content of sterols was similar. This confirms our data showing that PIASCLEDINE-ExpASU® has a unique composition. However, in contrast to our study, they showed that both ASU products, equalized to contain equivalent sterol contents, had similar metabolic effects on articular chondrocytes. The two products inhibited prostaglandin synthesis, metalloprotease activity, and the release of radiolabeled sulfate from pre-labeled cartilage. This discrepancy can be explained by differences in the methodological approach used to test the pharmacological activity of ASUs. We used human chondrocytes in alginate beads, while Lippiello et al. used bovine monolayer chondrocytes and cartilage explants. Furthermore, the length of time of cell exposure to the tested components also drastically differed. In our study, cells were treated for 12 days while in the study of Lippiello et al., the exposure time was shorter. Another major difference between the two studies was that we used doses of ASUs by weight in contrast to Lippiello et al. who standardized according to the sterol content. Finally, the investigated parameters were different. We tested the effects of ASUs on NO, IL-6, and IL-8, main inflammatory mediators implicated in OA pathogenesis. Through cytokine-induced MAP kinases, NF-κB activation, and oxidative phosphorylation, these mediators contribute to systemic inflammation (®, Arthocare contained almost twice the amount ofsterols but did not demonstrate effective inhibition of MMP-3, NO, and IL-8 and was significantly less effective on IL-6 than PIASCLEDINE-ExpASU®. Furthermore, surprisingly, there was an absence of effects for Avovida. This can be explained by the absence of four key components in its composition. In addition to the absence of alkyl furans, alkyl triols, and squalene, Avovida does not contain tocopherols. These data suggest that tocopherols could play a role in determining the pharmacological activities of ASU mixtures.Another major constituting element of ASU mixtures are the phytosterols beta-sitosterol, campesterol, and stigmasterol. Lippiello et al. compared the sterol composition of NMX-1000™ and Piasceldinereakdown . They reammation . These p®.There are some limitations to our study with regard to interpreting the impact of composition on the pharmacological activity. One is the lack of definitive identification of the various minor components of the ASUs. Another is the small number of parameters investigated. It is possible that when assessing other parameters, the activity of ASU products would show different trends. Finally, we investigated a limited number of products. We cannot exclude the possibility that other commercially available products not studied here may show effects comparable to PIASCLEDINE-ExpASU® has a unique composition characterized by the presence of alkyl furans, alkyl triols, and squalene. This specific composition can explain its higher efficacy on pro-inflammatory and pro-catabolic mediators compared to other ASU products. Our data also confirm that PIASCLEDINE-ExpASU® shows beneficial effects on the chondrocyte metabolism via AGG, which could explain, in part, its clinical efficacy in OA patients. Therefore, to extrapolate the clinical data obtained with one ASU formulation to another one remains fully speculative. Our findings justify investigating each ASU product in clinical trials before claiming any efficacy with respect to OA symptoms.In conclusion, our study demonstrates that PIASCLEDINE-ExpASU


During the COVID-19 pandemic, the authorities made a change in the classification of malnutrition and concomitant service delivery protocol among the Rohingya children, residing in world’s largest refugee camp, located in Cox’s Bazar, Bangladesh. In this paper, we discussed the potential implications of this updated protocol on the malnutrition status among children residing in the Rohingya camps.This paper reviewed relevant literature and authors’ own experience to provide a perspective of the updated protocol for the classification of malnutrition among the children in the Rohingya camps and its implication from a broader perspective.Rohingya refugee camps, Bangladesh.Children aged less than five years residing in the Rohingya camps.Major adaptation during this COVID-19 was the discontinuation of using weight-for-height z-score (WHZ) and the use of only mid upper arm circumference (MUAC) and presence of oedema for admission, follow-up and discharge of malnourished children in the camps. However, evidence suggests that use of MUAC only can underestimate the prevalence of malnutrition among the children in Rohingya camps. These apparently non-malnourished children are devoid of the rations that they would otherwise receive if classified as malnourished, making them susceptible to more severe malnutrition.Our analysis suggests that policymakers should consider using the original protocol of using both MUAC and WHZ to classify malnutrition and retain the guided ration size. We also believe that it would not take an extra effort to adopt the original guideline as even with MUAC only guideline, certain health measures needed to adopt during this pandemic. Although everyone is at risk of the detrimental effect of COVID-19, it can be a serious concern for children and young people as it may hamper their future growth and development. This is truly expressed by UNICEF Executive Director Henrietta Fore as, ‘Don’t let the children be the hidden victims of COVID-19 pandemic’.COVID-19 pandemic is the greatest public health calamity that the world facing today, which is causing thousands of deaths every day around the globe as well as limited health, sanitation and hygiene facilities available at camps. The Rohingya people, also referred to as Forcibly Displaced Myanmar Nationals, are Muslim minorities of Myanmar who flee in large numbers from their land since August 2017 and are now settled in Cox’s Bazar, Bangladesh, in the largest refugee camp in the world. Like other refugee camps of the world, Rohingya camps are also overpopulated and have limited access to health facilities, making the people residing in these camps vulnerable to coronavirus infection.Displaced and refugee populations are particularly at risk of this jeopardy because of their residence in densely populated refugee camps with social distancing often impossible to follow. The high rate of malnutrition has been a great concern among the young children in Rohingya camps. The most recent Standardized Monitoring and Assessment of Relief and Transitions survey carried out in October 2017 recorded a high (19 %) malnutrition rate as classified by weight-for-height z-score (WHZ score), where the prevalence of severe acute malnutrition and moderate acute malnutrition (MAM) was 3 % and 16 %, respectively.According to UNHCR Operational Data Portal, the total population in Rohingya camps is 889 704, of which nearly one-fifth (18·7 %) are young children aged less than five years, the nutrition sector redefined the classification of malnutrition of the children and related safety measures and service delivery protocols,12. In this paper, we discussed the implications of this new protocol on overall malnutrition status among the young children in Rohingya camps amid this COVID-19 pandemic.In the meantime, considering the social distancing rules imposed by the camp authority due to COVID-19 pandemic, Refugee Relief and Repatriation Commissioner and agreement among the technical advisors of three UN agencies  Before the COVID-19 pandemic, admission and discharge criteria and other services were conducted according to the National Guidelines for Community Based Management of Acute Malnutrition. Ready to use therapeutic food was provided based on weight during every weekly visit in outpatient therapeutic programs, while children are provided with one sachet of ready to use supplementary food in each 14 d according to the therapeutic supplementary feeding programme protocol. The detail admission and discharge criteria are presented in Table Nutrition sector is coordinating and administrating emergency nutrition response since the beginning of the humanitarian crisis in Cox’s Bazar. At present, nutrition service is being provided from forty-six integrated nutrition facilities in thirty-four camps. One-stop-shop approach was taken to ensure access of all nutrition-related services from one place, including outpatient therapeutic programme, therapeutic supplementary feeding programme and blanket supplementary feeding programme.,12  for diagnosis of severe malnutrition on 27 March 2020 because it has the potential to spread contamination during height and weight measurement. Concomitantly, with the guidance of technical advisors of all three UN institutions at headquarters, regional and national levels, and in line with international recommendations, the Nutrition Sector agreed to use only mid upper arm circumference (MUAC) and oedema for testing, admission, tracking and discharge of children aged 6–59 months in all Community Based Management of Acute Malnutrition programs within the camps. Moreover, local decision was made by Nutrition Sector partners to raise the standard of MUAC, influenced by the results of the Cox’s Bazar Standardized Monitoring and Assessment of Relief and Transitions general survey, which showed poor agreement between MUAC and WHZ, and other children with MUAC up to 135 mm were identified as malnourished using WHZ. To ensure that no children were missed, the final MUAC cut-off was agreed to be < 120 mm for outpatient therapeutic program and ≥ 120 mm and < 130 mm for targeted child feeding programs. Therefore, the major adaptation during this COVID-19 was the discontinuation of using weight scales and height board and use of only MUAC and presence of oedema for admission, follow up and discharge in all Community Based Management of Acute Malnutrition programming in both makeshift and registered camps. A recent study carried out in twelve districts of Bangladesh also shows the dis-concordance between MUAC and WHZ and suggests increasing cut-off of the MUAC criteria to increase the chance of covering the malnourishment classified by WHZ. However, it comes with the inclusion of non-wasted children and MAM children in severe acute malnutrition treatment program. According to the Standardized Monitoring and Assessment of Relief and Transitions survey final report of round 4, the Global Acute Malnutrition (GAM) rate by WHZ was 10·9 %, 13·3 % and 12·1 %, respectively, which was only 4·9 %, 2·7 % and 2·2 % respectively by MUAC only, and the combined GAM rate by WHZ and MUAC was 12·2 %, 13·6 % and 12·1 %, respectively, in Rohingya camps. This suggests that the prevalence of GAM by WHZ and combined WHZ and MUAC concordance far better than MUAC only. Other studies carried out in similar setting also support this finding,17. Therefore, it is obvious that many of the children in camps who are not being classified as malnourished according to the MUAC only criteria would have been categorised as malnourished if they are assessed according to the recommended WHZ or combined WHZ and MUAC criteria. It is a great concern that these apparently non-malnourished children are devoid of the rations that they would otherwise receive if classified as malnourished, making them susceptible to more severe malnutrition.The concordance between WHZ and MUAC for assessing malnutrition depends on several factors and varies between countries and regions, and the use of one criterion can both underestimate and overestimate the prevalence of malnutrition. It is recommended for the countries of Southern Asia, and The SAHEL region  to maintain WHZ criteria for assessing malnutritionMoreover, due to the changed ration protocol, the frequency of visiting integrated facilities has been reduced. For example, previously, the severe acute malnutrition children were visited in the facility four times in a month on 7 d interval and MAM children twice in a month on 14 d interval. Due to changed protocol, now the severe acute malnutrition children are visited twice in a month on 14 d interval and MAM children once in a month on 28 d interval. Authors’ own experience from the field suggests that this has led to an increased length of stay that might result in delayed rehabilitation of the children. Furthermore, this low frequency of visits at the facility has limited the monitoring at field level, which might have an effect on programme performance. However, average weight gain and growth monitoring promotion are also being suspended due to MUAC only plus oedema criteria. But both are important indicators for monitoring growth and nutritional status, particularly among older children aged 24–59 months, among whom change of MUAC is less prominent than change of weight compared with those of younger children aged 6–23 months.. Likewise, at the therapeutic feeding centre of the refugee settlements of Yemen, where all the infection, prevention and control material and PPE are available for safe nutritional assessment, WHZ and oedema are assessed, and treatment is provided according to the national protocol. In refugee camps of Uganda, extended MUAC thresholds of 12·0 cm to 13·0 cm are considered ‘at risk’ for admission, and after admission, weight is taken to calculate ration size.Based on the earlier discussion, we believe that it is important that the policymakers immediately consider using the original protocol of using both MUAC and WHZ and ration size after ensuring coronavirus infection control and other necessary arrangements for services delivery amid this pandemic. This would help reduce the risk of underestimating the actual prevalence of malnutrition that may result using MUAC only criteria. It is also important to note that even for the measurement of MUAC, certain health measures need to be taken during this COVID-19 pandemic and therefore, we believe, it is possible to go back to the original guideline with limited extra effort. From authors’ own direct field observation and experience, it was also obvious that replacing the original protocol in the real-world implementation will not incur an extra cost, time, and resources as the institutional arrangements to implement the original protocol is already in place in the field. We also found instances where both WHZ and MUAC have been used in refugee camps amid this pandemic. For example, in the refugee camps of Sudan, the authorities continued to use both measures  for admission of Community Based Management of Acute Malnutrition in case of without any restrictions in population mobility (night curfew)It is conspicuous from the above discussion that MUAC-only protocol adopted for classifying malnutrition during this pandemic can underestimate the prevalence of malnutrition among young children in Rohingya refugee camps, along with other service-level changes that occurred during this pandemic further exacerbate the malnutrition condition of the children in camps. We propose that policymakers and public health practitioners immediately consider adopting the previous guidelines of classifying malnutrition and revise the service delivery modality by considering COVID-19 issue to make it more streamlined and prevent large-scale malnutrition among children in camps. It is also recommended to conduct a study to determine an appropriate cut-off point for child MUAC in the Rohingya camps.