Exploring the potential of CoMoO4-modified graphitic carbon nitride to boost oxidation of amoxicillin micropollutants in hospital wastewater.

This study investigates the removal of amoxicillin micropollutants (AM) from hospital wastewater using CoMoO4-modified graphitic carbon nitride (CMO/gCN). Consequently, CMO/gCN exhibits notable improvements in visible light absorption and electron-hole separation rates compared to unmodified gCN. Besides, CMO/gCN significantly enhances the removal efficiency of AM, attaining an impressive 96.5%, far surpassing the performance of gCN at 48.6%. Moreover, CMO/gCN showcases outstanding reusability, with AM degradation performance exceeding 70% even after undergoing six cycles of reuse. The removal mechanism of AM employing CMO/gCN involves various photoreactions of radicals (•OH, •O2-) and amoxicillin molecules under light assistance. Furthermore, CMO/gCN demonstrates a noteworthy photodegradation efficiency of AM from hospital wastewater, reaching 92.8%, with a near-complete reduction in total organic carbon levels. Detailed discussions on the practical applications of the CMO/gCN photocatalyst for removal of micropollutants from hospital wastewater are provided. These findings underline the considerable potential of CMO/gCN for effectively removing various pollutants in environmental remediation strategies.

A comprehensive analysis of the immune system in healthy Vietnamese people.

Lifestyle, diet, socioeconomic status and genetics all contribute to heterogeneity in immune responses. Vietnam is plagued with a variety of health problems, but there are no available data on immune system values in the Vietnamese population. This study aimed to establish reference intervals for immune cell parameters specific to the healthy Vietnamese population by utilizing multi-color flow cytometry (MCFC). We provide a comprehensive analysis of total leukocyte count, quantitative and qualitative shifts within lymphocyte subsets, serum and cytokine and chemokine levels and functional attributes of key immune cells including B cells, T cells, natural killer (NK) cells and their respective subpopulations. By establishing these reference values for the Vietnamese population, these data contribute significantly to our understanding of the human immune system variations across diverse populations. These data will be of substantial comparative value and be instrumental in developing personalized medical approaches and optimizing diagnostic strategies for individuals based on their unique immune profiles.

Weather in two climatic regions shapes the diversity and drives the structure of fungal endophytic community of bilberry (Vaccinium myrtillus L.) fruit.

BACKGROUND: Bilberry (Vaccinium myrtillus L.) is one of the most important economic and natural resources in Northern Europe. Despite its importance, the endophytic fungal community of the fruits has rarely been investigated. Biogeographic patterns and determinants of the fungal diversity in the bilberry fruit are poorly understood, albeit fungal endophytes can have a close relationship with the host plants. Here, we investigated the effect of climatic regions, and their weather conditions within growth season and soil properties on fungal endophytic communities of bilberry fruits collected from northern and southern regions of Finland using high-throughput sequencing technology targeting the internal transcribed spacer 2 ribosomal DNA region for fungi. RESULTS: Species richness and beta diversity (variation in community structure) were higher in the southern compared to the studied northern region. The weather condition of the growth season drove both fungal richness and community structure. Furthermore, abundance of the genera Venturia, Cladosporium, and Podosphaera was influenced by the weather, being different between the south and north regions. CONCLUSIONS: We conclude that diversity and assembly structure of the fungal endophytes in bilberry fruits follow similar patterns as for foliar fungal endophytes, being shaped by various environmental factors, such as the climate and surrounding vegetation.

A scanning focus nuclear microscope with multi-pinhole collimation.

Microscopic nuclear imaging down to spatial resolutions of a few hundred microns can already be achieved using low-energy gamma emitters (e.g.125I, ∼30 keV) and a basic single micro-pinhole gamma camera. This has been applied toin vivomouse thyroid imaging, for example. For clinically used radionuclides such as99mTc, this approach fails due to penetration of the higher-energy gamma photons through the pinhole edges. To overcome these resolution degradation effects, we propose a new imaging approach: scanning focus nuclear microscopy (SFNM). We assess SFNM using Monte Carlo simulations for clinically used isotopes. SFNM is based on the use of a 2D scanning stage with a focused multi-pinhole collimator containing 42 pinholes with narrow pinhole aperture opening angles to reduce photon penetration. All projections of different positions are used to iteratively reconstruct a three-dimensional image from which synthetic planar images are generated. SFNM imaging was tested using a digital Derenzo resolution phantom and a mouse ankle joint phantom containing99mTc (140 keV). The planar images were compared with those obtained using a single-pinhole collimator, either with matched pinhole diameter or with matched sensitivity. The simulation results showed an achievable99mTc image resolution of 0.04 mm and detailed99mTc bone images of a mouse ankle with SFNM. SFNM has strong advantages over single-pinhole imaging in terms of spatial resolution.

Oxidative Stress-Induced Silver Nano-Carriers for Chemotherapy.

Recently, silver nanoparticles (AgNPs) have been extensively explored in a variety of biological applications, especially cancer treatment. AgNPs have been demonstrated to exhibit anti-tumor effects through cell apoptosis. This study intends to promote cell apoptosis further by increasing oxidative stress. AgNPs are encapsulated by biocompatible and biodegradable polyaspartamide (PA) (PA-AgNPs) that carries the anti-cancer drug Doxorubicin (Dox) to inhibit cancer cells primarily. PA-AgNPs have an average hydrodynamic diameter of 130 nm, allowing them to move flexibly within the body. PA-AgNPs show an excellent targeting capacity to cancer cells when they are conjugated to biotin. In addition, they release Dox efficiently by up to 88% in cancer environments. The DCFDA experiment demonstrates that the Dox-carried PA-AgNPs generate reactive oxidation species intensively beside 4T1 cells. The MTT experiment confirms that PA-AgNPs with Dox may strongly inhibit 4T1 cancer cells. Furthermore, the in vivo study confirms that PA-AgNPs with Dox successfully inhibit tumors, which are about four times smaller than the control group and have high biosafety that can be applied for chemotherapy.

Knowledge and Attitude Related to Hepatitis C among Medical Students in the Oral Direct Acting Antiviral Agents Era in Vietnam.

BACKGROUND: Medical students play important frontline roles in the prevention, early detection, and treatment of hepatitis C. This study investigated knowledge and attitudes toward hepatitis C among 5th- and 6th-year medical students and possible associated factors. METHODS: A cross-sectional survey was conducted among 2000 students from eight medical universities using a self-administered structured questionnaire. RESULTS: The mean knowledge and attitude scores for hepatitis C were 20.1 ± 4.0 (out of 26) and 10.6 ± 2.9 (out of 20), respectively. Approximately, three-quarters (74.4%) of the participants had a good knowledge score, but only a small proportion (3.1%) obtained a good attitude score. Although the participants had fairly high knowledge about the causes, consequences, and transmission routes of hepatitis C, there were important gaps in their knowledge about hepatitis C screening and treatment. In multivariate analysis, female students, 5th-year students, and students from the central provinces had significantly higher knowledge and attitude scores. There was a low positive correlation between knowledge and attitude scores. CONCLUSION: This study points out the need to update the medical training curriculum to improve the knowledge and attitude of students about hepatitis C infection.

Knowledge, Attitudes and Practices toward Hepatitis B Virus Infection among Students of Medicine in Vietnam.

BACKGROUND: Building capacity in hepatitis B virus prevention and management for medical students and health professionals is one of the pillars of the national viral hepatitis control strategy. METHODS: A cross-sectional study was conducted at eight medical universities from the northern, central and southern regions of the country between May and November 2020 using a systematic random sampling technique. RESULTS: Among 2000 participants, 84.2% reported they had been tested for hepatitis B and 83.9% had received the hepatitis B vaccine. The mean knowledge, attitude, practice score was 40.2 out of 54 (74.4%) with only 19.9% of the study participants obtaining a good score. In multivariate analysis, fifth year students, students from central universities, students who had tested positive for hepatitis B and students who had received hepatitis B vaccine or had encountered patients with chronic hepatitis B had significantly higher knowledge score (p < 0.05). The study showed lack of trust in the hepatitis B vaccine safety and lack of confidence in providing counselling, testing and management of patients with chronic hepatitis B. CONCLUSION: Findings from our research emphasized an immediate need to improve the medical schools' training curriculum in Vietnam to enable students' readiness in hepatitis B prevention and management.

Host species shape the community structure of culturable endophytes in fruits of wild berry species (Vaccinium myrtillus L., Empetrum nigrum L. and Vaccinium vitis-idaea L.).

Wild berries are interesting research subjects due to their rich sources of health-beneficial phenolic compounds. However, the internal microbial communities, endophytes, associated with the wild berry fruits are currently unknown. Endophytes are bacteria or fungi inhabiting inside plant tissues, and their functions vary depending on the host species and environmental parameters. The present study aimed to examine community composition of fungal and bacterial endophytes in fruits of three wild berry species (bilberry Vaccinium myrtillus L., lingonberry Vaccinium vitis-idaea L. and crowberry Empetrum nigrum L.) and the effects of host plant species and their growth sites on shaping the endophytic communities. We found that the endophytic community structures differed between the berry species, and fungi were predominant over bacteria in the total endophytic taxa. We identified previously unknown endophytic fungal taxa including Angustimassarina, Dothidea, Fellozyma, Pseudohyphozyma, Hannaella coprosmae and Oberwinklerozyma straminea. A role of soluble phenolic compounds, the intracellular components in wild berry fruits, in shaping the endophytic communities is proposed. Overall, our study demonstrates that each berry species harbors a unique endophytic community of microbes.

Efficient Monte-Carlo based system modelling for image reconstruction in preclinical pinhole SPECT.

The use of multi-pinhole collimation has enabled ultra-high-resolution imaging of SPECT and PET tracers in small animals. Key for obtaining high-quality images is the use of statistical iterative image reconstruction with accurate energy-dependent photon transport modelling through collimator and detector. This can be incorporated in a system matrix that contains the probabilities that a photon emitted from a certain voxel is detected at a specific detector pixel. Here we introduce a fast Monte-Carlo based (FMC-based) matrix generation method for pinhole imaging that is easy to apply to various radionuclides. The method is based on accelerated point source simulations combined with model-based interpolation to straightforwardly change or combine photon energies of the radionuclide of interest. The proposed method was evaluated for a VECTor PET-SPECT system with (i) a HE-UHR-M collimator and (ii) an EXIRAD-3D 3D autoradiography collimator. Both experimental scans with99mTc,111In, and123I, and simulated scans with67Ga and90Y were performed for evaluation. FMC was compared with two currently used approaches, one based on a set of point source measurements with99mTc (dubbed traditional method), and the other based on an energy-dependent ray-tracing simulation (ray-tracing method). The reconstruction results show better image quality when using FMC-based matrices than when applying the traditional or ray-tracing matrices in various cases. FMC-based matrices generalise better than the traditional matrices when imaging radionuclides with energies deviating too much from the energy used in the calibration and are computationally more efficient for very-high-resolution imaging than the ray-tracing matrices. In addition, FMC has the advantage of easily combining energies in a single matrix which is relevant when imaging radionuclides with multiple photopeak energies (e.g.67Ga and111In) or with a continuous energy spectrum (e.g.90Y). To conclude, FMC is an efficient, accurate, and versatile tool for creating system matrices for ultra-high-resolution pinhole SPECT.

Impacts of Sexually Transmitted Disease/HIV Outreach Sites on the Effectiveness of Detecting New Infections in Baltimore City, 2015 to 2018.

BACKGROUND: Effectiveness of sexually transmitted disease (STD)/HIV mobile van outreach programs has been shown to assist in identifying new cases of syphilis and HIV among high-risk populations. However, specific types of mobile outreach testing and their varying abilities to assist in STD/HIV case identification have not been thoroughly explored. METHODS: We analyzed data from the Baltimore City Health Department syphilis and HIV testing intake interviews and subsequent laboratory results for clients at any of the 6 different Baltimore City Health Department mobile outreach testing setting types between 2015 and 2018. A total of 8098 syphilis and 7946 HIV testing encounters were included. Cross-tabulation and proportion estimates were used to obtain the volume of new syphilis and HIV diagnoses across the different mobile outreach testing setting types. Multivariable firth logistic regressions for rare events were used to obtain odds ratios for new syphilis diagnoses across the different mobile outreach setting categories. RESULTS: Testing at street corners yielded the highest proportion of new syphilis cases (0.83%), whereas at community centers, it produced the highest proportion of new HIV cases (0.48%). The adjusted odds for new syphilis were 2.14 among street corners compared with community centers. CONCLUSIONS: The findings indicated that street corners were the most successful at detecting new syphilis cases, whereas community centers were the most successful at detecting new HIV cases. However, because of the small number of new cases detected and low uptake per testing event between 2015 and 2018, STD/HIV mobile testing does not seem to be effective overall.

RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis.

Inactivation of tumor suppressor Runt-related transcription factor 3 (RUNX3) plays an important role during early tumorigenesis. However, posttranslational modifications (PTM)-based mechanism for the inactivation of RUNX3 under hypoxia is still not fully understood. Here, we demonstrate a mechanism that G9a, lysine-specific methyltransferase (KMT), modulates RUNX3 through PTM under hypoxia. Hypoxia significantly increased G9a protein level and G9a interacted with RUNX3 Runt domain, which led to increased methylation of RUNX3 at K129 and K171. This methylation inactivated transactivation activity of RUNX3 by reducing interactions with CBFß and p300 cofactors, as well as reducing acetylation of RUNX3 by p300, which is involved in nucleocytoplasmic transport by importin-α1. G9a-mediated methylation of RUNX3 under hypoxia promotes cancer cell proliferation by increasing cell cycle or cell division, while suppresses immune response and apoptosis, thereby promoting tumor growth during early tumorigenesis. Our results demonstrate the molecular mechanism of RUNX3 inactivation by G9a-mediated methylation for cell proliferation and antiapoptosis under hypoxia, which can be a therapeutic or preventive target to control tumor growth during early tumorigenesis.

EXIRAD-HE: multi-pinhole high-resolution ex vivo imaging of high-energy isotopes.

We recently developed a dedicated focusing multi-pinhole collimator for a stationary SPECT system that offers down to 120 µm (or 1.7 nL) spatial resolution SPECT images of cryo-cooled tissue samples (EXIRAD-3D). This collimator is suitable for imaging isotopes that are often used in small animal and diagnostic SPECT such as 125I (27 keV), 201Tl (71 keV), 99mTc (140 keV), and 111In (171 and 245 keV). The goal of the present work is to develop high-resolution pinhole imaging of tissue samples containing isotopes with high-energy photon emissions, for example, therapeutic alpha and beta emitters that co-emit high energy gammas (e.g. 213Bi (440 keV) and 131I (364 keV)) or 511 keV annihilation photons from PET isotopes. To this end, we optimise and evaluate a new high energy small-bore multi-pinhole collimator through simulations. The collimator-geometry was first optimised by simulating a Derenzo phantom scan with a biologically realistic activity concentration of 18F at two system sensitivities (0.30% and 0.60%) by varying pinhole placements. Subsequently, the wall thickness was selected based on reconstructions of a Derenzo phantom and a uniform phantom. The obtained collimators were then evaluated for 131I (364 keV), 213Bi (440 keV), 64Cu (511 keV), and 124I (511 + 603 keV) with biologically realistic activity concentrations, and also for some high activity concentrations of 18F, using digital resolution, mouse knee joint, and xenograft phantoms. Our results show that placing pinhole centres at a distance of 8 mm from the collimator inner wall yields good image quality, while a wall thickness of 43 mm resulted in sufficient shielding. The collimators offer resolutions down to 0.35 mm, 0.6 mm, 0.5 mm, 0.6 mm, and 0.5 mm when imaging 131I, 213Bi, 18F, 64Cu, and 124I, respectively, contained in tissue samples at biologically achievable activity concentrations.

EXIRAD-3D: Fast automated three-dimensional autoradiography.

INTRODUCTION: Autoradiography is an established technique for high-resolution imaging of radiolabelled molecules in biological tissue slices. Unfortunately, creating a 3D image from a set of these 2D images is extremely time-consuming and error-prone. MicroSPECT systems provide such 3D images but have a low resolution. Here we present EXIRAD-3D, a fast automated method as an alternative for 3D autoradiography from coupes based on ultra-high resolution microSPECT technology. METHODS: EXIRAD-3D uses a very small bore focusing multi-pinhole collimator mounted in a SPECT system with stationary detectors (U-SPECT/CT, MILabs B.V. The Netherlands) using a sample holder with integrated tissue cooling to avoid activity leaking or tissue deformation during the scan. The system performance was experimentally evaluated using various phantoms and tissue samples of animals in vivo injected with technetium-99m and iodine-123. RESULTS: The reconstructed spatial resolution obtained with a Derenzo hot rod phantom was 120 µm (or 1.7 nl). The voxel values of a syringe phantom image appear to be uniform and scale linearly with activity. Uptake in tiny details of the mouse knee joint, thyroid, and kidney could be clearly visualized. CONCLUSION: EXIRAD-3D opens up the possibility for fast and quantitative 3D imaging of radiolabelled molecules at a resolution far better than in vivo microSPECT and saves tremendous amounts of work compared to obtaining 3D data from a set of 2D autoradiographs. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: EXIRAD-3D offers superior image resolution over microSPECT, and it can be a very efficient alternative for autoradiography in pharmaceutical and biological studies.

Integration of iron oxide nanoparticles and polyaspartamide biopolymer for MRI image contrast enhancement and an efficient drug-delivery system in cancer therapy.

We integrate superparamagnetic iron oxide nanoparticles with polyaspartamide (PA) biopolymer to form a biological construct that functions as a tracking, targeting and drug-delivery system for cancer diagnosis and therapy. Iron oxide nanoparticles with uniformly distributed average spherical diameters of around 10 nm and superparamagnetic characteristics play a key role in increasing the transverse 1/T 2 relaxation rate or darkening the T 2-weighted MR image for cancer diagnosis using MRI. In in vitro MRI testing on cancer cells, the MR images of samples with the bio-constructshow a much clearer contrast effect than those of controls. The PA biopolymer plays an essential role in enhancing the hydrophilicity and biocompatibility of the bio-construct. In addition, as a multifunctional polymer, PA is conjugated with biotin and doxorubicin (Dox) functional groups to enhance targeting and impairment of cancer cells. In in vivo testing on cancer tumors, injection with the bio-construct decreased the magnitude of cancer tumor volume growth by three times compared with that of uninjected controls. The physicochemical characteristics of the bio-construct and the roles of biotin and Dox functional groups are examined and discussed in detail.

Clinical application of hepatocyte transplantation: current status, applicability, limitations, and future outlook.

Introduction: Hepatocyte transplantation (HT) is a promising alternative to liver transplantation for the treatment of liver-based metabolic diseases and acute liver failure (ALF). However, shortage of good-quality liver tissues, early cell loss post-infusion, reduced cell engraftment and function restricts clinical application.Areas covered: A comprehensive literature search was performed to cover pre-clinical and clinical HT studies. The review discusses the latest developments to address HT limitations: cell sources from marginal/suboptimal donors to neonatal livers, differentiating pluripotent stem cells into hepatocyte-like cells, in vitro expansion, prevention of immune response to transplanted cells by encapsulation or using innate immunity-inhibiting agents, and enhancing engraftment through partial hepatectomy or irradiation.Expert opinion: To date, published data are highly encouraging specially the alginate-encapsulated hepatocyte treatment of children with ALF. Hepatocyte functions can be further improved through co-culturing with mesenchymal stromal cells. Moreover, ex-vivo genetic correction will enable the use of autologous cells in future personalized medicine.

Algorithms and Analyses for Joint Spectral Image Reconstruction in Y-90 Bremsstrahlung SPECT.

Quantitative yttrium-90 (Y-90) SPECT imaging is challenging due to the nature of Y-90, an almost pure beta emitter that is associated with a continuous spectrum of bremsstrahlung photons that have a relatively low yield. This paper proposes joint spectral reconstruction (JSR), a novel bremsstrahlung SPECT reconstruction method that uses multiple narrow acquisition windows with accurate multi-band forward modeling to cover a wide range of the energy spectrum. Theoretical analyses using Fisher information and Monte-Carlo (MC) simulation with a digital phantom show that the proposed JSR model with multiple acquisition windows has better performance in terms of covariance (precision) than previous methods using multi-band forward modeling with a single acquisition window, or using a single-band forward modeling with a single acquisition window. We also propose an energy-window subset (ES) algorithm for JSR to achieve fast empirical convergence and maximum-likelihood based initialization for all reconstruction methods to improve quantification accuracy in early iterations. For both MC simulation with a digital phantom and experimental study with a physical multi-sphere phantom, our proposed JSR-ES, a fast algorithm for JSR with ES, yielded higher recovery coefficients (RCs) on hot spheres over all iterations and sphere sizes than all the other evaluated methods, due to fast empirical convergence. In experimental study, for the smallest hot sphere (diameter 1.6cm), at the 20th iteration the increase in RCs with JSR-ES was 66 and 31% compared with single wide and narrow band forward models, respectively. JSR-ES also yielded lower residual count error (RCE) on a cold sphere over all iterations than other methods for MC simulation with known scatter, but led to greater RCE compared with single narrow band forward model at higher iterations for experimental study when using estimated scatter.

Design and performance of a coarse media, high hydraulic load polishing wetland for steel industry wastewater.

This paper presents the design of a constructed wetland (CW) system in an area with limited land availability, resulting in high hydraulic loads. The CW was constructed to act as a buffering/ polishing step after stabilization ponds for steel industry wastewater post-treatment. A pilot test with two different filter media (50-100mm vs 40-60mm diameter) indicated that a flow rate increase from 49.5 m3/h to 122.4 m3/h would lead to a head loss increase from 2.9cm to 8.7cm, and more than double that for the finer gravel. This was substantially higher than the calculated theoretical values, though the relation with flow rate was similar. Four full scale wetland cells (CW1, CW2, CW3 and CW4) were constructed using the coarser gravel. A design value of total head loss of 1.01m over the total system length, with a design flow of 36,000 m3/day, was expected based on pilot test results. During the first operation year (September 2017 to July 2018), the pond-CW system has received wastewater already meeting required discharge standards. The effluent from the CWs had consistently lower concentrations of all measured variables, and met the predicted values for biochemical oxygen demand (BOD5), total nitrogen (TN) and NH4 +-N. Highest removal efficiencies were achieved for NH4 +-N (>90%), Mn (>60%) and Fe (45%) with removal efficiencies for TN (14%), BOD5 and chemical oxygen demand (COD) (around 30%). Concentrations of phenol, CN- and Cr6+ were below 10, 4 and 3µg/l, respectively, in in- and outflows. An appreciated benefit of the wetland was the 'green element' in the industrial landscape.

Evaluation of pinhole collimator materials for micron-resolution ex vivo SPECT.

Pinhole collimation is widely recognized for offering superior resolution-sensitivity trade-off in SPECT imaging of small subjects. The newly developed EXIRAD-3D autoradiography technique (MILabs B.V.) based on a highly focusing multi-pinhole collimator achieves micron-resolution SPECT for cryo-cooled tissue samples. For such high resolutions, the choice of pinhole material may have a significant impact on images. Therefore, this paper aims to compare the performance of EXIRAD-3D with lead, tungsten, gold, and depleted uranium pinhole collimators designed such that they achieve equal sensitivities. Performance in terms of resolution is characterized for several radioisotopes, namely 111In (171 keV and 245 keV), 99mTc (140 keV), 201Tl (71 keV), and 125I (27 keV). Using Monte Carlo simulation, point spread functions were generated and their profiles as well as their full-width-at-half-maximum and full-width-at-tenth-maximum were determined and evaluated for different materials and isotopes. Additionally, simulated reconstructions of a Derenzo resolution phantom, validated with experimental data, were judged by assessment of the resolvable rods as well as a contrast-to-noise ratio (CNR) analysis. Our results indicate that using materials with higher photon-stopping power yields images with better CNR for the studied isotopes with improvements ranging from 1.9% to 36.6%. Visual assessment on the reconstructed images suggests that for EXIRAD-3D, the tungsten collimator is generally a good choice for a wide range of SPECT isotopes. For relatively high-energy isotopes such as 111In, using gold inserts can be beneficial.

Follicular Helper T Cells are Essential for the Elimination of Plasmodium Infection.

CD4+ follicular helper T (Tfh) cells have been shown to be critical for the activation of germinal center (GC) B-cell responses. Similar to other infections, Plasmodium infection activates both GC as well as non-GC B cell responses. Here, we sought to explore whether Tfh cells and GC B cells are required to eliminate a Plasmodium infection. A CD4 T cell-targeted deletion of the gene that encodes Bcl6, the master transcription factor for the Tfh program, resulted in complete disruption of the Tfh response to Plasmodium chabaudi in C57BL/6 mice and consequent disruption of GC responses and IgG responses and the inability to eliminate the otherwise self-resolving chronic P. chabaudi infection. On the other hand, and contrary to previous observations in immunization and viral infection models, Signaling Lymphocyte Activation Molecule (SLAM)-Associated Protein (SAP)-deficient mice were able to activate Tfh cells, GC B cells, and IgG responses to the parasite. This study demonstrates the critical role for Tfh cells in controlling this systemic infection, and highlights differences in the signals required to activate GC B cell responses to this complex parasite compared with those of protein immunizations and viral infections. Therefore, these data are highly pertinent for designing malaria vaccines able to activate broadly protective B-cell responses.