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The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.
Methods
We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.
Results
Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.
Conclusions
Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.
There is growing evidence that smoking increases the risk of developing psychiatric disorders, but the underlying mechanisms are largely unknown. We examine brain structure as a potential pathway between smoking and psychiatric disease liability.
Methods
We test associations between smoking (initiation, cigarettes per day, cessation, lifetime use) and depression, bipolar disorder, and schizophrenia, with and without correcting for volume of the amygdala, hippocampus, lateral and medial orbitofrontal cortex, superior frontal context, and cortical thickness and surface area. We use three methods that use summary statistics of genome-wide association studies to investigate genome-wide and local genetic overlap (genomic structural equation modeling, local analysis of (co)variant association), as well as causal associations (Mendelian randomization).
Results
While we find causal effects of smoking on brain volume in different brain areas, and with psychiatric disorders, brain volume did not seem to mediate the effect of smoking on psychiatric disorders.
Conclusions
While these findings are limited by characteristics of the included summary statistics (e.g. sample size), we conclude that brain volume of these areas is unlikely to explain a substantial part of any effect of smoking on psychiatric disorders. Nevertheless, genetic methods are valuable tools for exploring other potential mechanisms, such as brain functional connectivity, foregoing the need to collect all phenotypes in one dataset.
Health insurers’ role in healthcare systems based on managed competition comprises various tasks. Misconceptions about these tasks may result in low public trust, which may hamper health insurers in performing their tasks. This study examines the relationship between enrollees’ perceptions of health insurers’ tasks and their trust in them.
Methods:
A questionnaire in November 2021 asked respondents to indicate to what extent health insurers have to perform certain tasks, whether they actually perform them, and whether they think these tasks are important. Trust was measured using a validated multiple-item scale. The results from 837 respondents (56 per cent response rate) were analysed using multivariate regression models.
Results:
A larger mismatch between enrollees’ expectations about health insurers’ tasks and their actual statutory tasks is related to less trust regarding the categories ‘controlling healthcare costs’ and ‘mediation and quality of care’. Second, a larger mismatch between expectations and actually performed tasks is related to less trust for all categories. Importance of tasks only affects this relationship concerning ‘informing about price and availability of care’.
Conclusions:
This study emphasises the importance of reducing enrollees’ misconceptions as trust in health insurers is necessary to fulfil their role as purchaser of care.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Se is particularly necessary in infants because of their rapid physical growth period in addition to being indispensable for neurodevelopment. Severe deficiency can lead to cardiomyopathy, hypothyroidism and faltering growth. However, Se can be toxic at high doses. In the paediatric age group, plasma/serum and erythrocyte Se levels seem to increase with age, except in the first year of life. Understanding the variability in Se status during this period can help to identify infants at risk of deficiency and develop strategies for controlling and preventing its consequences. This review aimed to identify the extent and characteristics of the variability of Se status during the first year of life. A search was conducted across five databases to find articles published until 30 July 2024, with no limitations on the language or date of publication. Articles were screened, data were extracted independently by two reviewers, and any disagreement was resolved by a third reviewer. A total of 22 studies comprising 1288 participants were included in this review, 21 of which assessed plasma/serum Se and 12 assessed erythrocyte Se. In the first 4 months of age, serum/plasma Se decreased, remained stable or increased depending on feeding, with an increase in supplemented formula-fed infants and breastfed infants of supplemented mothers. Erythrocyte Se levels showed a declining trend, except in infants fed supplemented formula or breastfed by supplemented mothers. Variability of serum/plasma and erythrocyte Se levels in the first year was associated with maternal Se intake/supplementation and the Se content of the infant’s diet.
The stellar age and mass of galaxies have been suggested as the primary determinants for the dynamical state of galaxies, with environment seemingly playing no or only a very minor role. We use a sample of 77 galaxies at intermediate redshift ($z\sim0.3$) in the Middle-Ages Galaxies Properties with Integral field spectroscopy (MAGPI) Survey to study the subtle impact of environment on galaxy dynamics. We use a combination of statistical techniques (simple and partial correlations and principal component analysis) to isolate the contribution of environment on galaxy dynamics, while explicitly accounting for known factors such as stellar age, star formation histories, and stellar masses. We consider these dynamical parameters: high-order kinematics of the line-of-sight velocity distribution (parametrised by the Gauss-Hermite coefficients $h_3$ and $h_4$), kinematic asymmetries $V_{\textrm{asym}}$ derived using kinemetry, and the observational spin parameter proxy $\lambda_{R_e}$. Of these, the mean $h_4$ is the only parameter found to have a significant correlation with environment as parametrised by group dynamical mass. This correlation exists even after accounting for age and stellar mass trends. We also find that satellite and central galaxies exhibit distinct dynamical behaviours, suggesting they are dynamically distinct classes. Finally, we confirm that variations in the spin parameter $\lambda_{R_e}$ are most strongly (anti-)correlated with age as seen in local studies, and show that this dependence is well-established by $z\sim0.3$.
An analysis of the divertor designs for the Infinity Two fusion pilot plant (FPP) baseline plasma design is presented. The divertor uses an $m=5$, $n=4$ magnetic island chain, where m is the poloidal number and n is the toroidal number. Two divertor designs are presented. A classical divertor that is similar to the Wendelstein 7-X island divertor is analyzed using diffusive field-line following and the fluid code EMC3-Lite. For a baseline $800\text{ MW}$ operating point in Infinity Two, the conditions where the heat flux on the divertor plate remains in the acceptable region are analyzed. In addition a related, but different and novel large island backside divertor (LIBD) design is shown. The LIBD promises improved neutral pumping by closing the divertor through the use of baffling and with a structure inside the island, thus preventing neutralized plasma particles from reente ring the plasma.
Calves sold at weaning are the main source of income for cow–calf operations, and their survival should be a priority. Given this, the effective use of management practices for pregnant dams and calves to prevent calf mortality is essential; however, decision-makers often do not have access to information about the effectiveness of many management practices. A systematic review was conducted to summarize the evidence of the effectiveness of biosecurity, vaccination, colostrum management, breeding and calving season management, and nutritional management practices for preventing preweaned beef calf mortality. The population of interest was preweaned beef calves from birth until at least 3 months of age. The outcome of interest was general preweaning calf mortality with stillbirths excluded. Eleven studies were deemed relevant. Ten were observational cross-sectional studies, and one was a randomized controlled trial (RCT). The practices that were statistically significantly associated with calf mortality were intervening with colostrum in case a calf had not nursed from its dam or was assisted at calving, timing and length of the calving season, and injecting selenium and vitamin E at birth. More well-executed RCTs and cohort studies are needed to provide evidence of effectiveness and help support implementation of recommended practices in herds.
This paper reports an expansion of the English as a second language (L2) component of the Multilingual Eye Movement Corpus (MECO L2), an international database of eye movements during text reading. While the previous Wave 1 of the MECO project (Kuperman et al., 2023) contained English as a L2 reading data from readers with 12 different first language (L1) backgrounds, the newly collected dataset adds eye-tracking data on English text reading from 13 distinct L1 backgrounds (N = 660) as well as participants’ scores on component skills of English proficiency and information about their demographics and language background and use. The paper reports reliability estimates, descriptive statistics, and correlational analyses as means to validate the expansion dataset. Consistent with prior literature and the MECO Wave 1, trends in the MECO Wave 2 data include a weak correlation between reading comprehension and oculomotor measures of reading fluency and a greater L1-L2 contrast in reading fluency than reading comprehension. Jointly with Wave 1, the MECO project includes English reading data from more than 1,200 readers representing a diversity of native writing systems (logographic, abjad, abugida, and alphabetic) and 19 distinct L1 backgrounds. We provide multiple pointers to new venues of how L2 reading researchers can mine this rich publicly available dataset.
Though Health Technology Assessment (HTA) has steadily grown over the past decades, less attention has been paid to the way HTA may prove more responsive to the broader economic, social, and environmental challenges that health systems are facing today. In view of climate change, chronic diseases, an aging population, inequalities, and workforce issues, the HTA community’s unique set of skills nonetheless holds great potential to help decision-makers strengthen many publicly funded health systems around the world.
Methods
This article adopts an integrated system-wide perspective guided by the Responsible Innovation in Health (RIH) framework to explore how the HTA community may not only adapt to the speed of innovation but also consider its direction.
Results
Because RIH aims to steer innovation toward a more sustainable pathway, it can help HTA agencies anticipate decision-makers’ informational needs regarding four systemic challenges: (1) equitable access; (2) workforce issues; (3) accountable policy trade-offs; and (4) environmental sustainability. We clarify how key elements of the RIH framework may be used by HTA agencies to: (1) supplement their evaluation process; (2) align their priority-setting or strategic planning activities with their health system challenges; or (3) inform the production of early HTAs, horizon scans, or reports that are broader in scope than a single technology review.
Conclusions
The article concludes with three practical implications that were identified by the Institut National d’Excellence en Santé et Services Sociaux (INESSS) (Québec, Canada) and may inspire other HTA agencies.
The incidence of congenital malformations (CM) among non-Hispanic White American (NHWA) mothers was reviewed to identify and evaluate the geographic differences in the most frequent CM subtypes associated with smoking and other risk factors. Data on CM were obtained from 150,775 children (2000-2004) from the Centers for Disease Control and Prevention. Risk factors associated with CM development were the mother’s age < 21 and > 35 years, body weight gain during pregnancy, anemia, diabetes mellitus, eclampsia (cases of preeclampsia were omitted), smoking, and alcohol use during pregnancy. Among smoking mothers, the most common CM was omphalocele, club foot, cleft lip, and polydactyly. The highest incidences (CM/10,000 births/year) of observed CM in children of smoking mothers were clubfoot, 25.51 cases (Utah), cleft lip, 22.47 (South Dakota), polydactyly, 21.23 (North Dakota), and omphalocele, 13.14 (Montana). The presence of maternal comorbidities, tobacco and alcohol consumption, and their association with other environmental factors can affect the incidence of CM in NHWA mothers. Further comparisons among the American states regarding the overall changes in CM over the last two decades should uncover crucial outcomes in terms of CM and smoking.
Understanding the determinants of malnutrition is pivotal for public health interventions. This study aimed to identify socio-economic, demographic, dietary and maternal determinants of wasting and overweight among Brazilian children between 6 and 59 months. Data from the Brazilian National Survey on Child Nutrition were analysed (n 11 789). Children’s weight-for-height Z-scores were calculated according to the WHO growth standard and classified as wasting (Z < −2), normal weight (–2 ≤ Z ≤ 1), overweight risk (1 < Z ≤ 2) and overweight (Z > 2). Socio-economic, demographic, dietary and maternal covariables were considered. Adjusted multinomial logistic regression (OR and 95 % CI) was employed. The prevalence of overweight and wasting was 9·5 and 2·6 %, respectively. In the adjusted model, younger age (6–23 months: OR: 1·7; 95 % CI: 1·3, 2·2), consumption of ≥ 5 ultra-processed food groups (OR: 1·8; 95 % CI: 1·1, 3·1), maternal underweight (OR: 0·4; 95 % CI: 0·2, 0·9), overweight (OR: 1·5; 95 % CI: 1·2, 1·9) and mild food insecurity (OR: 0·8; 95 % CI: 0·6, 1·0) were associated with child overweight. The Brazilian Northeast (OR: 4·9; 95 % CI: 2·1, 11·3), Southeast (OR: 7·1; 95 % CI: 3·0, 16·6), South (OR: 4·7; 95 % CI: 1·8, 12·1), Midwest regions (OR: 2·7; 95 % CI: 1·2, 6·2) and maternal underweight (OR: 5·4; 95 % CI: 2·7, 10·7) were associated with wasting. Overweight in Brazil is prevalent among children between 6 and 59 months, while wasting is not a major public health problem. The main determinants of these Brazilian children’s nutritional status were age, ultra-processed food consumption and maternal nutritional status.
Following acquired brain injury (ABI), individuals often experience anxiety and/or depressive symptoms. BrainACT is an adapted form of Acceptance and Commitment Therapy (ACT) tailored to this target group. The current study is a trial-based health-economic evaluation comparing BrainACT to a psychoeducation and relaxation control treatment.
Methods
An economic evaluation from a societal perspective was conducted in the Netherlands alongside a multicenter randomized controlled two-armed parallel trial including 72 participants. A cost-utility and cost-effectiveness analysis was conducted where incremental costs, quality-adjusted life-years (QALYs), and anxiety/depression (Hospital Anxiety and Depression Scale (HADS) score) were collected and presented over a 1-year follow-up period. Bootstrapping, scenario, and subgroup analyses were performed to test the robustness of the results.
Results
The BrainACT arm reported non-significant lower total costs (incremental difference of €−4,881; bootstrap interval €−12,139 to €2,330) combined with significantly decreased anxiety/depression (HADS) (3.2; bootstrap intervals 0.7–5.7). However, the total QALYs were non-significantly lower (−0.008; bootstrap interval −0.060 to 0.042) for BrainACT. The probability of the intervention being cost-effective was 86 percent at a willingness-to-accept threshold of €50,000/QALY. The scenario and subgroup analyses confirmed the robustness of the results.
Conclusion
BrainACT may be a more cost-effective alternative to a psychoeducation and relaxation intervention for anxiety and/or depressive symptoms following ABI. Despite limitations, BrainACT appears to be a promising addition to treatment options in the Netherlands. Further research is needed to validate these findings, and consideration should be given to implementing BrainACT in Dutch clinical settings with ongoing monitoring.
This study evaluated the effects of capsaicin (CAP) supplementation on the intake, nutrient digestibility, ruminal fermentation, nitrogen balance, microbial protein synthesis and health traits of bulls managed on pasture. Eight crossbred (Holstein x Zebu) cattle averaging 313 ± 31 kg of body weight (BW) were arranged in a replicated 4 × 4 Latin square design (one square of four bulls, rumen fistulated with 4-inch silicone cannulas and one square of four non-fistulated bulls), which were kept on Pangola grass pasture (Digitaria decumbens). Each experimental period consisted of 21 days, with 7 days for data collection (no washout between periods). Bulls were randomly assigned to the following treatments: CON (control): concentrate supplementation at 0.5% live weight (BW) and no additive (CAPCIN®), or concentrate supplementation at 0.5% BW in association with CAPCIN® (NutriQuest, Campinas, Brazil) fed at the inclusion rates of 150 (CAP150), 300 (CAP300) and 450 (CAP450) mg/animal/day. Digestibilities of dry matter, organic matter and neutral detergent fibre showed quadratic responses to CAP supplementation. Rumen pH linearly increased with CAP supplementation. The numbers of lymphocytes and eosinophils were linearly increased with CAP supplementation. The use of encapsulated pepper in supplements of crossbred (Holstein x Zebu) bulls managed on D. decumbens pasture up to 450 mg/animal/day improves nutrients digestibility and ruminal fermentation and can positively influence the health status of beef cattle managed under tropical conditions.
Recent years show an exponential increased interest (“renaissance”) in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit.
Methods
In this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments.
Results
In addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation.
Conclusions
Four recommendations are formulated for further research and clinical implementation.
In freely decaying stably stratified turbulent flows, numerical evidence shows that the horizontal displacement of Lagrangian tracers is diffusive while the vertical displacement converges towards a stationary distribution, as shown numerically by Kimura & Herring (J. Fluid Mech., vol. 328, 1996, pp. 253–269). Here, we develop a stochastic model for the vertical dispersion of Lagrangian tracers in stably stratified turbulent flows that aims to replicate and explain the emergence of a stationary probability distribution for the vertical displacement of such tracers. More precisely, our model is based on the assumption that the dynamical evolution of the tracers results from the competing effects of buoyancy forces that tend to bring a vertically perturbed fluid parcel (carrying tracers) to its equilibrium position and turbulent fluctuations that tend to disperse tracers. When the density of a fluid parcel is allowed to change due to molecular diffusion, a third effect needs to be taken into account: irreversible mixing. Indeed, ‘mixing’ dynamically and irreversibly changes the equilibrium position of the parcel and affects the buoyancy force that ‘stirs’ it on larger scales. These intricate couplings are modelled using a stochastic resetting process (Evans & Majumdar, Phys. Rev. Lett., vol. 106, issue 16, 2011, 160601) with memory. More precisely, Lagrangian tracers in stratified turbulent flows are assumed to follow random trajectories that obey a Brownian process. In addition, their stochastic paths can be reset to a given position (corresponding to the dynamically changing equilibrium position of a density structure containing the tracers) at a given rate. Scalings for the model parameters as functions of the molecular properties of the fluid and the turbulent characteristics of the flow are obtained by analysing the dynamics of an idealised density structure. Even though highly idealised, the model has the advantage of being analytically solvable. In particular, we show the emergence of a stationary distribution for the vertical displacement of Lagrangian tracers. We compare the predictions of this model with direct numerical simulation data at various Prandtl numbers $Pr$, the ratio of kinematic viscosity to molecular diffusion.
◦ This case study describes price signaling through a third-party data subscription service.
◦ Informed Sources provided a data subscription service to companies operating in the retail gasoline market in Australia. Each subscribing company provided its prices at a high-frequency (on the order of every fifteen to thirty minutes) to the Informed Sources online platform and was given access to all subscribers’ prices on that platform.
◦ The Informed Sources platform was supportive of collusion as it facilitated coordinating on high prices – by allowing for low-cost signaling of future prices – and monitoring for compliance with those high prices. The platform allowed for tacit and indirect communication, and collusion could occur without explicit and direct communication.
◦ Using data from a similar platform, FuelCheck, empirical evidence is provided that supports this type of platform having anticompetitive effects by reducing the risks and costs associated with price leadership while achieving a common understanding among firms as to the prices to charge.
◦ For policymakers, the case study underscores competitive concerns associated with price-sharing platforms. In particular, the speed and reliability with which communication was possible through the Informed Sources platform substantially removed the usual deterrents to firms’ using prices for signaling.
The relevance of education and outreach (E&O) activities about the Antarctic Treaty has been recognized at the Antarctic Treaty Consultative Meetings (ATCM) and at the Committee for Environmental Protection (CEP). This study examines the key topics and the target audiences detailed in papers submitted to the ATCM on E&O. Since the Antarctic Treaty entered into force in 1961, a total of 216 ATCM papers on E&O have been produced. The number of papers has increased substantially since the mid-1990s. ‘Science’ (76.9%) and ‘Wildlife/Biodiversity/Environment’ (75.5%) were the most addressed topics in these papers, while the ‘Public’ (81.0%) and those attending ‘Schools’ (69.0%) are the main target audiences. ‘Science’ in ATCM papers increased ~120-fold from 1961–1997 to 2015–2023, while ATCM papers discussing engagement with the ‘Public’ increased ~40-fold during the same period. ‘Climate change’ was first mentioned in 2006, and the number of papers per year increased fourfold by 2015–2023. This study shows the increasing interest in E&O through time, addressing key topics to relevant audiences related to the Antarctic region. From an educational perspective, attention should be paid to emerging topics (e.g. equity, diversity and inclusion), and the engagement of early-career professionals and educators should be made a priority.
The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
Visceral leishmaniasis (VL) is a tropical disease that can be fatal if acute and untreated. Diagnosis is difficult, the treatment is toxic and prophylactic vaccines do not exist. Leishmania parasites express hundreds of proteins and several of them are relevant for the host's immune system. In this context, in the present study, 10 specific T-cell epitopes from 5 parasite proteins, which were identified by antibodies in VL patients’ sera, were selected and used to construct a gene codifying the new chimeric protein called rCHI. The rCHI vaccine was developed and thoroughly evaluated for its potential effectiveness against Leishmania infantum infection. We used monophosphoryl lipid A (MPLA) and polymeric micelles (Mic) as adjuvant and/or delivery system. The results demonstrated that both rCHI/MPLA and rCHI/Mic significantly stimulate an antileishmanial Th1-type cellular response, with higher production of IFN-γ, TNF-α, IL-12 and nitrite in vaccinated animals, and this response was sustained after challenge. In addition, these mice significantly reduced the parasitism in internal organs and increased the production of IgG2a isotype antibodies. In vivo and in vitro toxicity showed that rCHI is safe for the mammalians, and the recombinant protein also induced in vitro lymphoproliferative response and production of Th1-type cytokines by human cells, which were collected from healthy subjects and treated VL patients. These data suggest rCHI plus MPLA or micelles could be considered as a vaccine candidate against VL.