The First Case of Cutaneous Acanthamoebiasis Caused by Acanthamoeba triangularis in Korea.

A 62-year-old man with multiple myeloma visited our clinic with multiple painful erythematous to purpuric nodules on his whole body. He received a skin biopsy which showed septal and lobular inflammation with vasculitis, and multiple amoebic organisms were found. Polymerase chain reaction and culture were performed and an Acanthamoeba triangularis infection was diagnosed. This is the first report on cutaneous acanthamoebiasis caused by A. triangularis, suggesting that A. triangularis should be regarded as a clinical pathogen that can cause ocular as well as disseminated infection.

Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon.

BACKGROUND: Gabon is a malaria-threatened country with a stable and hyperendemic transmission of Plasmodium falciparum monoinfection. Malaria drug resistance is widely spread in many endemic countries around the world, including Gabon. The molecular surveillance of drug resistance to antifolates and artemisinin-based combination therapy (ACT) is one of the strategies for combating malaria. As Plasmodium parasites continue to develop resistance to currently available anti-malarial drugs, this study evaluated the frequency of the polymorphisms and genetic diversity associated with this phenomenon among the parasites isolates in Gabon. METHODS: To assess the spread of resistant haplotypes among the malaria-infected population of Libreville, single nucleotide polymorphisms linked to sulfadoxine-pyrimethamine (SP) and artemisinin drugs resistance were screened for P. falciparum dihydrofolate reductase (Pfdhfr), P. falciparum dihydropteroate synthase (Pfdhps), and P. falciparum kelch 13-propeller domain (Pfk13) point mutations. RESULTS: The analysis of 70 malaria-positive patient samples screened for polymorphism showed 92.65% (n = 63) mutants vs. 7.35% (n = 5) wild parasite population in Pfdhfr, with high prevalence mutations at S108N(88.24%, n = 60), N51I(85.29%, n = 58), C59R(79.41%, n = 54); however, I164L(2.94%, n = 2) showed low frequency mutation. No wild haplotype existed for Pfdhps, and there were no mutations at the K540E, A581G, and A613T/S positions. However, the mutation rate at A437G(93.38%, n = 62) was the highest, followed by S436A/F(15.38%, n = 10). A higher frequency of quadruple IRNI-SGKAA (69.84%) than quintuple IRNI-(A/F)GKAA (7.94%) mutations was observed in the Pfdhfr-Pfdhps combination. Furthermore, none of the mutations associated with ACT resistance, especially those commonly found in Africa, were observed in Pfk13. CONCLUSIONS: High polymorphism frequencies of Pfdhfr and Pfdhps genes were observed, with alternative alanine/phenylalanine mutation at S436A/F (7.69%, n = 5) for the first time. Similar to that of other areas of the country, the patterns of multiple polymorphisms were consistent with selection owing to drug pressure. Although there was no evidence of a medication failure haplotype in the studied population, ACT drug efficacy should be regularly monitored in Libreville, Gabon.

Prevalence and molecular analysis of glucose-6-phosphate dehydrogenase deficiency in Chin State, Myanmar.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by X-linked recessive disorderliness. It induces severe anemia when a patient with G6PD deficiency is exposed to oxidative stress that occurs with administration of an antimalarial drug, primaquine. The distribution of G6PD deficiency remains unknown while primaquine has been used for malaria treatment in Myanmar. This study aimed to investigate the prevalence of G6PD deficiency and its variants in Chin State, Myanmar. Among 322 participants, 18 (11 males and 7 females) demonstrated a G6PD deficiency. Orissa variant was dominant in the molecular analysis. This would be related to neighboring Indian and Bangladeshi population, in which Orissa variant was also reported as the main mutation type. The screening test for G6PD deficiency before primaquine treatment appears to be important in Myanmar.

Genetic diversity of Plasmodium falciparum erythrocyte membrane protein 1 in field isolates from central Myanmar.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the polymorphic var multigene family, is a highly polymorphic antigen that plays a crucial role in the pathology of malaria. The contribution of the genetic diversity of var toward the immune escape of P. falciparum has not yet been fully elucidated. This study aimed to characterize the diversity of var repertoires by screening P. falciparum Duffy-binding-like α domain (PfDBLα) among field isolates from central Myanmar. Genetic analysis revealed that the D-H segments of var in Myanmar populations have an extensive polymorphic repertoire, with high numbers of unique sequence types in each individual. However, var genes from the global population, including Myanmar, shared close genetic lineages regardless of their geographic origins, indicating that they have not undergone rapid evolutionary changes.

Persistent impacts of smoking on resting-state EEG in male chronic smokers and past-smokers with 20 years of abstinence.

Smoking is a severe addictive health risk behavior and notorious for the high likelihood of relapse after attempted cessation. Such an addictive pattern in smoking has been associated with neurobiological changes in the brain. However, little is known whether the neural changes associated with chronic smoking persist after a long period of successful abstinence. To address this question, we examined resting state EEG (rsEEG) in chronic smokers who have been smoking for 20 years or more, past-smokers who have been successfully abstaining for 20 years or more, and never-smokers. Both current-smokers and past-smokers showed significantly decreased relative theta power than never-smokers, showcasing persistent effect of smoking on the brain. Other rsEEG features in alpha frequency band demonstrated distinctive patterns associated with active smoking, such that compared to never-smokers, only current-smokers, but not past-smokers, showed significantly higher relative power, EEG reactivity-power changes between eyes-closed and eyes-open conditions-, and coherence between channels. Furthermore, individual variabilities across these rsEEG biomarkers were accounted for by individuals' self-reported smoking history and nicotine dependence in current- and past- smokers. These data suggest the persistent effect of smoking on the brain even after sustained remission for 20 years.

Evolutionary analysis of Babesia vulpes and Babesia microti-like parasites.

BACKGROUND: The Babesia microti-like parasite is an emerging tick-borne piroplasm that has been detected in a range of hosts worldwide. Babesia vulpes, which is found in dogs and foxes, has been reclassified from B. microti-like parasites. The relationships among these B. microti-like parasites and B. vulpes with respect to host range and geographical origin have not been elucidated. METHODS: Blood samples were collected from 27 raccoon dogs in South Korea and used to screen for B. microti-like parasites based on a PCR assay targeting the 18S rRNA gene of Babesia. For comparative purposes, in addition to 18S rRNA sequences from nine raccoon dogs, we also analyzed 18S rRNA sequences from B. microti-like parasites infecting hosts in different geographical regions worldwide obtained from the GenBank database, giving 123 sequences in total. The genetic variation and evolutionary relationships among these sequences were examined based on analyses using DnaSP, MEGA, Arlequine, and BEAST software. RESULTS: Babesia microti-like parasites were identified in nine raccoon dogs and found to be related to B. vulpes obtained from Spanish dogs. Among the 123 sequences from 14 countries and various hosts, we identified 43 haplotypes with high genetic variance. Based on the genetic variance and phylogenetic analyses, we established that the B. microti-like parasites isolated in different geographical regions and from hosts belonging to five orders showed higher among-population variation than within-population variation. Babesia vulpes parasites infecting carnivore hosts, including raccoon dogs, foxes, skunks and dogs, appear to be genetically distinct from B. microti-like parasites infecting hosts belonging to the other orders. CONCLUSIONS: Our study demonstrated the genetic variation and evolutionary relationships among 18S rRNA sequences obtained from blood samples collected from various hosts and different geographical regions. Babesia vulpes was identified from raccoon dogs in South Korea. In addition, higher genetic variations were observed among populations of different hosts and geographical origins and, in particular, low connectivity was observed among host populations in the order Carnivora and those in other orders. These results suggest the B. vulpes, a piroplasmid species pathogenic in domestic dogs and wild canines, is genetically and evolutionarily different from B. microti-like parasites.

Exploring the impacts of implicit context association and arithmetic booster in impulsivity reduction.

People have a higher preference for immediate over delayed rewards, and it is suggested that such an impulsive tendency is governed by one's ability to simulate future rewards. Consistent with this view, recent studies have shown that enforcing individuals to focus on episodic future thoughts reduces their impulsivity. Inspired by these reports, we hypothesized that administration of a simple cognitive task linked to future thinking might effectively modulate individuals' delay discounting. Specifically, we used one associative memory task targeting intervention of context information, and one working memory task targeting enhancement of individual's ability to construct a coherent future event. To measure whether each type of cognitive task reduces individuals' impulsivity, a classic intertemporal choice task was used to quantify individuals' baseline and post-intervention impulsivity. Across two experiments and data from 216 healthy young adult participants, we observed that the impacts of intervention tasks were inconsistent. Still, we observed a significant task repetition effect such that the participants showed more patient choices in the second impulsivity assessment. In conclusion, there was no clear evidence supporting that our suggested intervention tasks reduce individuals' impulsivity, and that the current results call attention to the importance of taking into account task repetition effects in studying the impacts of cognitive training and intervention.

Characterization of the Core Determinants of Social Influence From a Computational and Cognitive Perspective.

Most human decisions are made among social others, and in what social context the choices are made is known to influence individuals' decisions. Social influence has been noted as an important factor that may nudge individuals to take more risks (e.g., initiation of substance use), but ironically also help individuals to take safer actions (e.g., successful abstinence). Such bi-directional impacts of social influence hint at the complexity of social information processing. Here, we first review the recent computational approaches that shed light on neural and behavioral mechanisms underlying social influence following basic computations involved in decision-making: valuation, action selection, and learning. We next review the studies on social influence from various fields including neuroeconomics, developmental psychology, social psychology, and cognitive neuroscience, and highlight three dimensions of determinants-who are the recipients, how the social contexts are presented, and to what domains and processes of decisions the influence is applied-that modulate the extent to which individuals are influenced by others. Throughout the review, we also introduce the brain regions that were suggested as neural instantiations of social influence from a large body of functional neuroimaging studies. Finally, we outline the remaining questions to be addressed in the translational application of computational and cognitive theories of social influence to psychopathology and health.

Petasites japonicus extract exerts anti-malarial effects by inhibiting platelet activation.

BACKGROUND: New antimalarial agents are needed to combat emerging resistance to the currently available drugs. In the pathology of cerebral malaria, platelets play a central role by binding infected and uninfected red cells and the endothelium. Since Petasites japonicus extract was reported as an effective inhibitor of platelet activation, we examined the antimalarial activities of the P. japonicus extract. PURPOSE: This study aimed to evaluate the impact of P. japonicus extract prepared from whole plants on malarial infection. METHODS: The P. japonicus extract were characterized by high-performance liquid chromatography (HPLC) profiling. Antimalarial activity of the P. japonicus ethanolic extract was evaluated in vitro using chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) P. berghei strains. Also, the in vivo activity of the extract was evaluated in P. berghei-infected mice via oral administration followed by a four-day suppressive test to measure the hematological parameters. In addition, platelet activation signaling induced by the P. japonicus extract in P. berghei infection was evaluated. RESULTS: In HPLC study, catechin, rutin, liquiritin, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid were identified in P. japonicus extract. Exposure to the P. japonicus extract significantly inhibited both CQ-sensitive (3D7) and resistant (Dd2) strains of P. falciparum with IC50 values of 8.48 ± 1.70 and 7.83 ± 6.44 µg/ml, respectively. Administration of the P. japonicus extract also resulted in potent antimalarial activities in P. berghei-infected mice with no associated toxicity. The treatment also improved the hematologic parameters. In addition, the survived mice from P. berghei infection exhibited the inhibition of collagen-induced platelet aggregation by attenuated glycoprotein VI (GPVI) downstream signaling. CONCLUSION: P. japonicus extracts promote antimalarial effects both in vitro and in vivo. In addition, the effects appear to be induced by the inhibition of collagen-induced platelet activation related to attenuated GPVI downstream signaling. Further studies to identify and characterize the antimalarial compounds in P. japonicus will promote the development of new drugs.

Sirtinol Supresses Trophozoites Proliferation and Encystation of Acanthamoeba via Inhibition of Sirtuin Family Protein.

The encystation of Acanthamoeba leads to the development of metabolically inactive and dormant cysts from vegetative trophozoites under unfavorable conditions. These cysts are highly resistant to anti-Acanthamoeba drugs and biocides. Therefore, the inhibition of encystation would be more effective in treating Acanthamoeba infection. In our previous study, a sirtuin family protein-Acanthamoeba silent-information regulator 2-like protein (AcSir2)-was identified, and its expression was discovered to be critical for Acanthamoeba castellanii proliferation and encystation. In this study, to develop Acanthamoeba sirtuin inhibitors, we examine the effects of sirtinol, a sirtuin inhibitor, on trophozoite growth and encystation. Sirtinol inhibited A. castellanii trophozoites proliferation (IC50=61.24 µM). The encystation rate of cells treated with sirtinol significantly decreased to 39.8% (200 µM sirtinol) after 24 hr of incubation compared to controls. In AcSir2-overexpressing cells, the transcriptional level of cyst-specific cysteine protease (CSCP), an Acanthamoeba cysteine protease involved in the encysting process, was 11.6- and 88.6-fold higher at 48 and 72 hr after induction of encystation compared to control. However, sirtinol suppresses CSCP transcription, resulting that the undegraded organelles and large molecules remained in sirtinol-treated cells during encystation. These results indicated that sirtinol sufficiently inhibited trophozoite proliferation and encystation, and can be used to treat Acanthamoeba infections.

Computational mechanisms underlying illusion of control in delusional individuals.

Humans navigate complex situations that require the accurate estimation of the controllability of the environment. Aberrant controllability computation might lead to maladaptive behaviors and poor mental health outcomes. Illusion of control, which refers to a heightened sense of control while the environment is uncontrollable, is one such manifestation and has been conceptually associated with delusional ideation. Nevertheless, this association has not yet been formally characterized in a computational framework. To address this, we used a computational psychiatry approach to quantify illusion of control in human participants with high (n = 125) or low (n = 126) trait delusion. Participants played a two-party exchange game in which their choices either did ("Controllable condition") or did not ("Uncontrollable condition") influence the future monetary offers made by simulated partners. We found that the two groups behaved similarly in model-agnostic measures (i.e., offer size, rejection rate). However, computational modeling revealed that compared to the low trait delusion group, the high delusion group overestimated their influence ("expected influence" parameter) over the offers made by their partners under the Uncontrollable condition. Highly delusional individuals also reported a stronger sense of control than those with low trait delusion in the Uncontrollable condition. Furthermore, the expected influence parameter and self-reported beliefs about controllability were significantly correlated in the Controllable condition in individuals with low trait delusion, whereas this relationship was diminished in those with high trait delusion. Collectively, these findings demonstrate that delusional ideation is associated with aberrant computation of and belief about environmental controllability, as well as a belief-behavior disconnect.

Subjective optimality in finite sequential decision-making.

Many decisions in life are sequential and constrained by a time window. Although mathematically derived optimal solutions exist, it has been reported that humans often deviate from making optimal choices. Here, we used a secretary problem, a classic example of finite sequential decision-making, and investigated the mechanisms underlying individuals' suboptimal choices. Across three independent experiments, we found that a dynamic programming model comprising subjective value function explains individuals' deviations from optimality and predicts the choice behaviors under fewer and more opportunities. We further identified that pupil dilation reflected the levels of decision difficulty and subsequent choices to accept or reject the stimulus at each opportunity. The value sensitivity, a model-based estimate that characterizes each individual's subjective valuation, correlated with the extent to which individuals' physiological responses tracked stimuli information. Our results provide model-based and physiological evidence for subjective valuation in finite sequential decision-making, rediscovering human suboptimality in subjectively optimal decision-making processes.

Humans use forward thinking to exploit social controllability.

The controllability of our social environment has a profound impact on our behavior and mental health. Nevertheless, neurocomputational mechanisms underlying social controllability remain elusive. Here, 48 participants performed a task where their current choices either did (Controllable), or did not (Uncontrollable), influence partners' future proposals. Computational modeling revealed that people engaged a mental model of forward thinking (FT; i.e., calculating the downstream effects of current actions) to estimate social controllability in both Controllable and Uncontrollable conditions. A large-scale online replication study (n=1342) supported this finding. Using functional magnetic resonance imaging (n=48), we further demonstrated that the ventromedial prefrontal cortex (vmPFC) computed the projected total values of current actions during forward planning, supporting the neural realization of the forward-thinking model. These findings demonstrate that humans use vmPFC-dependent FT to estimate and exploit social controllability, expanding the role of this neurocomputational mechanism beyond spatial and cognitive contexts.

Emotional adaptation during a crisis: decline in anxiety and depression after the initial weeks of COVID-19 in the United States.

Crises such as the COVID-19 pandemic are known to exacerbate depression and anxiety, though their temporal trajectories remain under-investigated. The present study aims to investigate fluctuations in depression and anxiety using the COVID-19 pandemic as a model crisis. A total of 1512 adults living in the United States enrolled in this online study beginning April 2, 2020 and were assessed weekly for 10 weeks (until June 4, 2020). We measured depression and anxiety using the Zung Self-Rating Depression scale and State-Trait Anxiety Inventory (state subscale), respectively, along with demographic and COVID-related surveys. Linear mixed-effects models were used to examine factors contributing to longitudinal changes in depression and anxiety. We found that depression and anxiety levels were high in early April, but declined over time. Being female, younger age, lower-income, and previous psychiatric diagnosis correlated with higher overall levels of anxiety and depression; being married additionally correlated with lower overall levels of depression, but not anxiety. Importantly, worsening of COVID-related economic impact and increase in projected pandemic duration exacerbated both depression and anxiety over time. Finally, increasing levels of informedness correlated with decreasing levels of depression, while increased COVID-19 severity (i.e., 7-day change in cases) and social media use were positively associated with anxiety over time. These findings not only provide evidence for overall emotional adaptation during the initial weeks of the pandemic, but also provide insight into overlapping, yet distinct, factors contributing to depression and anxiety throughout the first wave of the pandemic.

Neural correlates of tactile hardness intensity perception during active grasping.

While tactile sensation plays an essential role in interactions with the surroundings, relatively little is known about the neural processes involved in the perception of tactile information. In particular, it remains unclear how different intensities of tactile hardness are represented in the human brain during object manipulation. This study aims to investigate neural responses to various levels of tactile hardness using functional magnetic resonance imaging while people grasp objects to perceive hardness intensity. We used four items with different hardness levels but otherwise identical in shape and texture. A total of Twenty-five healthy volunteers participated in this study. Before scanning, participants performed a behavioral task in which they received a pair of stimuli and they were to report the perceived difference of hardness between them. During scanning, without any visual information, they were randomly given one of the four objects and asked to grasp it. We found significant blood oxygen-level-dependent (BOLD) responses in the posterior insula in the right hemisphere (rpIns) and the right posterior lobe of the cerebellum (rpCerebellum), which parametrically tracked hardness intensity. These responses were supported by BOLD signal changes in the rpCerebellum and rpIns correlating with tactile hardness intensity. Multidimensional scaling analysis showed similar representations of hardness intensity among physical, perceptual, and neural information. Our findings demonstrate the engagement of the rpCerebellum and rpIns in perceiving tactile hardness intensity during active object manipulation.

Depression Symptoms Mediate Mismatch Between Perceived Severity of the COVID-19 Pandemic and Preventive Motives.

The present study monitored changes in beliefs about the coronavirus disease 2019 (COVID-19) pandemic, depressive symptoms, and preventive motives between the first and second waves in South Korea using an online survey administered to 1,144 individuals nationally representative for age, gender, and areas of residence. While participants correctly updated their beliefs about the worsening pandemic situations, the perceived importance of social distancing did not change, and their motives to follow prevention measures shifted toward compulsory rather than voluntary motives. This inconsistency appeared to be mediated by depressive symptoms, such that negative belief changes followed by increased depressive symptoms were associated with the decreased perceived importance of social distancing and decreased voluntary motives. Our data highlights the importance of psychological responses to the dynamically evolving pandemic situations in promoting preventive behaviors.

Moral dilemmas and trust in leaders during a global health crisis.

Trust in leaders is central to citizen compliance with public policies. One potential determinant of trust is how leaders resolve conflicts between utilitarian and non-utilitarian ethical principles in moral dilemmas. Past research suggests that utilitarian responses to dilemmas can both erode and enhance trust in leaders: sacrificing some people to save many others ('instrumental harm') reduces trust, while maximizing the welfare of everyone equally ('impartial beneficence') may increase trust. In a multi-site experiment spanning 22 countries on six continents, participants (N = 23,929) completed self-report (N = 17,591) and behavioural (N = 12,638) measures of trust in leaders who endorsed utilitarian or non-utilitarian principles in dilemmas concerning the COVID-19 pandemic. Across both the self-report and behavioural measures, endorsement of instrumental harm decreased trust, while endorsement of impartial beneficence increased trust. These results show how support for different ethical principles can impact trust in leaders, and inform effective public communication during times of global crisis. PROTOCOL REGISTRATION STATEMENT: The Stage 1 protocol for this Registered Report was accepted in principle on 13 November 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13247315.v1 .

Antimalarial Effect of the Total Glycosides of the Medicinal Plant, Ranunculus japonicus.

In traditional Chinese medicine, Ranunculus japonicus has been used to treat various diseases, including malaria, and the young stem of R. japonicus is consumed as a food in the Republic of Korea. However, experimental evidence of the antimalarial effect of R. japonicus has not been evaluated. Therefore, the antimalarial activity of the extract of the young stem of R. japonicus was evaluated in vitro using both chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains; in vivo activity was evaluated in Plasmodium berghei-infected mice via oral administration followed by a four-day suppressive test focused on biochemical and hematological parameters. Exposure to extracts of R. japonicus resulted in significant inhibition of both chloroquine-sensitive (3D7) and resistant (Dd2) strains of P. falciparum, with IC50 values of 6.29 ± 2.78 and 5.36 ± 4.93 µg/mL, respectively. Administration of R. japonicus also resulted in potent antimalarial activity against P. berghei in infected mice with no associated toxicity; treatment also resulted in improved hepatic, renal, and hematologic parameters. These results demonstrate the antimalarial effects of R. japonicus both in vitro and in vivo with no apparent toxicity.

Containment of COVID-19: Simulating the impact of different policies and testing capacities for contact tracing, testing, and isolation.

Efficient contact tracing and testing are fundamental tools to contain the transmission of SARS-CoV-2. We used multi-agent simulations to estimate the daily testing capacity required to find and isolate a number of infected agents sufficient to break the chain of transmission of SARS-CoV-2, so decreasing the risk of new waves of infections. Depending on the non-pharmaceutical mitigation policies in place, the size of secondary infection clusters allowed or the percentage of asymptomatic and paucisymptomatic (i.e., subclinical) infections, we estimated that the daily testing capacity required to contain the disease varies between 0.7 and 9.1 tests per thousand agents in the population. However, we also found that if contact tracing and testing efficacy dropped below 60% (e.g. due to false negatives or reduced tracing capability), the number of new daily infections did not always decrease and could even increase exponentially, irrespective of the testing capacity. Under these conditions, we show that population-level information about geographical distribution and travel behaviour could inform sampling policies to aid a successful containment, while avoiding concerns about government-controlled mass surveillance.

Genetic polymorphism of vir genes of Plasmodium vivax in Myanmar.

The Plasmodium vivax variant proteins encoded by vir genes are highly polymorphic antigens and are considered as one of key proteins of P. vivax for host immune evasion via antigenic variations. Because genetic diversity of these antigens is a critical hurdle in the development of an effective vaccine, understanding the genetic nature of the vir genes in natural population is important. In this study, we selected four vir genes (vir 4, vir 12, vir 21, and vir 27) previously used for genetic analysis in several studies and evaluated the genetic polymorphisms and phylogenetic relationship of these 4 vir genes in Myanmar P. vivax population. Taken all genetic diversity values, the vir 12 (S = 168, H = 17, Hd = 0.854, Tajima's D value = 2.91524) was the most genetically diverse gene and the vir 4 (S = 9, H = 4, Hd = 0.744, Tajima's D value = -0.49151) was the most conserved gene. All phylogenetic trees showed two clades, and vir 4 and 12 haplotypes from Myanmar were clustered in a distinct clade with those from India and Republic of Korea. These results confirmed the pattern of high genetic polymorphism of vir genes and provided information on vir gene for further functional research and studies focused toward the practical use of vir genes.