The FES Gene at the 15q26 Coronary-Artery-Disease Locus Inhibits Atherosclerosis.

BACKGROUND: Genome-wide association studies have discovered a link between genetic variants on human chromosome 15q26.1 and increased coronary artery disease (CAD) susceptibility; however, the underlying pathobiological mechanism is unclear. This genetic locus contains the FES (FES proto-oncogene, tyrosine kinase) gene encoding a cytoplasmic protein-tyrosine kinase involved in the regulation of cell behavior. We investigated the effect of the 15q26.1 variants on FES expression and whether FES plays a role in atherosclerosis. METHODS AND RESULTS: Analyses of isogenic monocytic cell lines generated by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that monocytes with an engineered 15q26.1 CAD risk genotype had reduced FES expression. Small-interfering-RNA-mediated knockdown of FES promoted migration of monocytes and vascular smooth muscle cells. A phosphoproteomics analysis showed that FES knockdown altered phosphorylation of a number of proteins known to regulate cell migration. Single-cell RNA-sequencing revealed that in human atherosclerotic plaques, cells that expressed FES were predominately monocytes/macrophages, although several other cell types including smooth muscle cells also expressed FES. There was an association between the 15q26.1 CAD risk genotype and greater numbers of monocytes/macrophage in human atherosclerotic plaques. An animal model study demonstrated that Fes knockout increased atherosclerotic plaque size and within-plaque content of monocytes/macrophages and smooth muscle cells, in apolipoprotein E-deficient mice fed a high fat diet. CONCLUSIONS: We provide substantial evidence that the CAD risk variants at the 15q26.1 locus reduce FES expression in monocytes and that FES depletion results in larger atherosclerotic plaques with more monocytes/macrophages and smooth muscle cells. This study is the first demonstration that FES plays a protective role against atherosclerosis and suggests that enhancing FES activity could be a potentially novel therapeutic approach for CAD intervention.

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.

A flexible implant for acute intrapancreatic electrophysiology.

Microelectrode arrays (MEAs) have proven to be a powerful tool to study electrophysiological processes over the last decades with most technology developed for investigation of the heart or brain. Other targets in the field of bioelectronic medicine are the peripheral nervous system and its innervation of various organs. Beyond the heart and nervous systems, the beta cells of the pancreatic islets of Langerhans generate action potentials during the production of insulin. In vitro experiments have demonstrated that their activity is a biomarker for blood glucose levels, suggesting that recording their activity in vivo could support patients suffering from diabetes mellitus with long-term automated read-out of blood glucose concentrations. Here, we present a flexible polymer-based implant having 64 low impedance microelectrodes designed to be implanted to a depth of 10 mm into the pancreas. As a first step, the implant will be used in acute experiments in pigs to explore the electrophysiological processes of the pancreas in vivo. Beyond use in the pancreas, our flexible implant and simple implantation method may also be used in other organs such as the brain.

The COVID-19 e-lective: using innovation to manage disrupted medical student clinical placements.

BACKGROUND: The COVID-19 pandemic changed the way we work, spend, live, and learn. The impact was felt in the health sector where hospitals cancelled elective surgery, put on hold outpatient services, and implemented new social distancing procedures and telehealth systems, to enable hospitals to increase bed capacity. For medical students, these factors meant significant disruption to their clinical placements, remote delivery of their education, cessation of international and interstate placements, complicated by significant travel restrictions and border closures. There were concerns that final year students might be unable to graduate that year due to this lack of clinical exposure. INNOVATION: As a result of this disruption in late March 2020 we developed an innovative 6 week 'COVID-19 e-lective' rotation, consisting of online modules, virtual clinical tutorials and a COVID project totalling the equivalent of 200 h of work. RESULTS: An evaluation was undertaken that found it to be remarkably successful in meeting the students' learning needs and alleviating concerns about disrupted placements. It was also conducted during 2021 for all Year 4 students to help expand clinical placement opportunities. OUTCOMES: This paper describes the e-lective, its innovations, its challenges, and its evaluation findings, for others to learn from.

HHIPL1, a Gene at the 14q32 Coronary Artery Disease Locus, Positively Regulates Hedgehog Signaling and Promotes Atherosclerosis.

BACKGROUND: Genome-wide association studies have identified chromosome 14q32 as a locus for coronary artery disease. The disease-associated variants fall in a hitherto uncharacterized gene called HHIPL1 (hedgehog interacting protein-like 1), which encodes a sequence homolog of an antagonist of hedgehog signaling. The function of HHIPL1 and its role in atherosclerosis are unknown. METHODS: HHIPL1 cellular localization, interaction with sonic hedgehog (SHH), and influence on hedgehog signaling were tested. HHIPL1 expression was measured in coronary artery disease-relevant human cells, and protein localization was assessed in wild-type and Apoe-/- (apolipoprotein E deficient) mice. Human aortic smooth muscle cell phenotypes and hedgehog signaling were investigated after gene knockdown. Hhipl1-/- mice were generated and aortic smooth muscle cells collected for phenotypic analysis and assessment of hedgehog signaling activity. Hhipl1-/- mice were bred onto both the Apoe-/- and Ldlr-/- (low-density lipoprotein receptor deficient) knockout strains, and the extent of atherosclerosis was quantified after 12 weeks of high-fat diet. Cellular composition and collagen content of aortic plaques were assessed by immunohistochemistry. RESULTS: In vitro analyses revealed that HHIPL1 is a secreted protein that interacts with SHH and increases hedgehog signaling activity. HHIPL1 expression was detected in human smooth muscle cells and in smooth muscle within atherosclerotic plaques of Apoe-/- mice. The expression of Hhipl1 increased with disease progression in aortic roots of Apoe-/- mice. Proliferation and migration were reduced in Hhipl1 knockout mouse and HHIPL1 knockdown aortic smooth muscle cells, and hedgehog signaling was decreased in HHIPL1-deficient cells. Hhipl1 knockout caused a reduction of >50% in atherosclerosis burden on both Apoe-/- and Ldlr-/- knockout backgrounds, and lesions were characterized by reduced smooth muscle cell content. CONCLUSIONS: HHIPL1 is a secreted proatherogenic protein that enhances hedgehog signaling and regulates smooth muscle cell proliferation and migration. Inhibition of HHIPL1 protein function might offer a novel therapeutic strategy for coronary artery disease.

JCAD, a Gene at the 10p11 Coronary Artery Disease Locus, Regulates Hippo Signaling in Endothelial Cells.

Objective- A large number of genetic loci have been associated with risk of coronary artery disease (CAD) through genome-wide association studies, however, for most loci the underlying biological mechanism is unknown. Determining the molecular pathways and cellular processes affected by these loci will provide new insights into CAD pathophysiology and may lead to new therapies. The CAD-associated variants at 10p11.23 fall in JCAD, which encodes an endothelial junction protein, however, its molecular function in endothelial cells is not known. In this study, we characterize the molecular role of JCAD (junctional cadherin 5 associated) in endothelial cells. Approach and Results- We show that JCAD knockdown in endothelial cells affects key phenotypes related to atherosclerosis including proliferation, migration, apoptosis, tube formation, and monocyte binding. We demonstrate that JCAD interacts with LATS2 (large tumor suppressor kinase 2) and negatively regulates Hippo signaling leading to increased activity of YAP (yes-associated protein), the transcriptional effector of the pathway. We also show by double siRNA knockdown that the phenotypes caused by JCAD knockdown require LATS2 and that JCAD is involved in transmission of RhoA-mediated signals into the Hippo pathway. In human tissues, we find that the CAD-associated lead variant, rs2487928, is associated with expression of JCAD in arteries, including atherosclerotic arteries. Gene co-expression analyses across disease-relevant tissues corroborate our phenotypic findings and support the link between JCAD and Hippo signaling. Conclusions- Our results show that JCAD negatively regulates Hippo signaling in endothelial cells and we suggest that JCAD contributes to atherosclerosis by mediating YAP activity and contributing to endothelial dysfunction.

High perinatal mortality rates persist in Kirakira: The sustainable development goals for health remain out of reach in the provinces of Solomon Islands.

AIM: This study aimed to calculate the perinatal mortality rate in Kirakira Hospital, a remote provincial hospital in Solomon Islands, over a 3-year period, from 2014 to 2016. METHODS: A retrospective audit of the labour ward admission books for the years 2014-2016 was conducted. Patient files of all perinatal deaths and caesarean sections were accessed and reviewed. Stillbirths and early neonatal deaths were classified, and results were compared with the national health statistics of Australia (2014). RESULTS: Between 2014 and 2016, there were 1311 births and 40 perinatal deaths (mortality rate of 31 per 1000). This is approximately three times the Australian rate of 9.6 deaths per 1000. Of these deaths, 28 were stillbirths, and 12 were neonatal deaths. Detailed information was available for 88% (35/40) of the perinatal deaths. Only 15 caesarean sections (1.1% of deliveries) were performed, compared to a rate of 32.1% of caesarean sections in Australia (2014). CONCLUSIONS: Kirakira continues to have a very high perinatal mortality rate that has not changed over the last 6 years. The rate is double that reported for Solomon Islands in current World Health Organization data. This discrepancy is likely due to an absence of clinical data outside of the National Referral Hospital in Honiara. This paper identifies clinical indicators that could be targeted to help lower the perinatal mortality rate in this remote and impoverished community.

The Coronary Artery Disease-associated Coding Variant in Zinc Finger C3HC-type Containing 1 (ZC3HC1) Affects Cell Cycle Regulation.

Genome-wide association studies have to date identified multiple coronary artery disease (CAD)-associated loci; however, for most of these loci the mechanism by which they affect CAD risk is unclear. The CAD-associated locus 7q32.2 is unusual in that the lead variant, rs11556924, is not in strong linkage disequilibrium with any other variant and introduces a coding change in ZC3HC1, which encodes NIPA. In this study, we show that rs11556924 polymorphism is associated with lower regulatory phosphorylation of NIPA in the risk variant, resulting in NIPA with higher activity. Using a genome-editing approach we show that this causes an effective decrease in cyclin-B1 stability in the nucleus, thereby slowing its nuclear accumulation. By perturbing the rate of nuclear cyclin-B1 accumulation, rs11556924 alters the regulation of mitotic progression resulting in an extended mitosis. This study shows that the CAD-associated coding polymorphism in ZC3HC1 alters the dynamics of cell-cycle regulation by NIPA.

Quantifying temperature-dependent T1 changes in cortical bone using ultrashort echo-time MRI.

PURPOSE: To demonstrate the feasibility of using ultrashort echo-time MRI to quantify T1 changes in cortical bone due to heating. METHODS: Variable flip-angle T1 mapping combined with 3D ultrashort echo-time imaging was used to measure T1 in cortical bone. A calibration experiment was performed to detect T1 changes with temperature in ex vivo cortical bone samples from a bovine femur. Ultrasound heating experiments were performed using an interstitial applicator in ex vivo bovine femur specimens, and heat-induced T1 changes were quantified. RESULTS: The calibration experiment demonstrated that T1 increases with temperature in cortical bone. We observed a linear relationship between temperature and T1 with a linear coefficient between 0.67 and 0.84 ms/°C over a range of 25-70°C. The ultrasound heating experiments showed increased T1 changes in the heated regions, and the relationship between the temperature changes and T1 changes was similar to that of the calibration. CONCLUSION: We demonstrated a temperature dependence of T1 in ex vivo cortical bone using a variable flip-angle ultrashort echo-time T1 mapping method.

A microphysiological system for parallelized morphological and electrophysiological read-out of 3D neuronal cell culture.

Three-dimensional in vitro models in microfluidic systems are promising tools for studying cell biology, with complex models using multiple cell types combined with high resolution imaging. Neuronal models demand electrical readout of the activity of networks of single neurons, yet classical planar microelectrode arrays struggle to capture extracellular action potentials when neural soma are suspended distant from the microelectrodes. This study introduces sophisticated microfluidic microelectrode arrays, specifically tailored for electrophysiology of 3D neuronal cultures. Using multilayer photolithography of permanent epoxy photoresists, we developed devices having 12 independent culture modules in a convenient format. Each module has two adjacent compartments for hydrogel-based 3D cell culture, with tunnels allowing projection of neurites between compartments. Microelectrodes integrated in the tunnels record action potentials as they pass between the compartments. Mesh ceilings separate the compartments from overlying wells, allowing for simple cell seeding and later nutrient, gas and waste exchange and application of test substances. Using these devices, we have demonstrated 3D neuronal culture, including electrophysiological recording and live imaging. This microphysiological platform will enable high-throughput investigation of neuronal networks for investigation of neurological disorders, neural pharmacology and basic neuroscience. Further models could include cocultures representing multiple brain regions or innervation models of other organs.

Approaches for modelling interstitial ultrasound ablation of tumours within or adjacent to bone: theoretical and experimental evaluations.

PURPOSE: The objectives of this study were to develop numerical models of interstitial ultrasound ablation of tumours within or adjacent to bone, to evaluate model performance through theoretical analysis, and to validate the models and approximations used through comparison to experiments. METHODS: 3D transient biothermal and acoustic finite element models were developed, employing four approximations of 7-MHz ultrasound propagation at bone/soft tissue interfaces. The various approximations considered or excluded reflection, refraction, angle-dependence of transmission coefficients, shear mode conversion, and volumetric heat deposition. Simulations were performed for parametric and comparative studies. Experiments within ex vivo tissues and phantoms were performed to validate the models by comparison to simulations. Temperature measurements were conducted using needle thermocouples or magnetic resonance temperature imaging (MRTI). Finite element models representing heterogeneous tissue geometries were created based on segmented MR images. RESULTS: High ultrasound absorption at bone/soft tissue interfaces increased the volumes of target tissue that could be ablated. Models using simplified approximations produced temperature profiles closely matching both more comprehensive models and experimental results, with good agreement between 3D calculations and MRTI. The correlation coefficients between simulated and measured temperature profiles in phantoms ranged from 0.852 to 0.967 (p-value < 0.01) for the four models. CONCLUSIONS: Models using approximations of interstitial ultrasound energy deposition around bone/soft tissue interfaces produced temperature distributions in close agreement with comprehensive simulations and experimental measurements. These models may be applied to accurately predict temperatures produced by interstitial ultrasound ablation of tumours near and within bone, with applications toward treatment planning.

A mesh microelectrode array for non-invasive electrophysiology within neural organoids.

Organoids are emerging in vitro models of human physiology. Neural models require the evaluation of functional activity of single cells and networks, which is commonly measured by microelectrode arrays. The characteristics of organoids clash with existing in vitro or in vivo microelectrode arrays. With inspiration from implantable mesh electronics and growth of organoids on polymer scaffolds, we fabricated suspended hammock-like mesh microelectrode arrays for neural organoids. We have demonstrated the growth of organoids enveloping these meshes and the culture of organoids on meshes for up to one year. Furthermore, we present proof-of-principle recordings of spontaneous electrical activity across the volume of an organoid. Our concept enables a new class of microelectrode arrays for in vitro models of three-dimensional electrically active tissue.

The N-end rule pathway promotes seed germination and establishment through removal of ABA sensitivity in Arabidopsis.

The N-end rule pathway targets protein degradation through the identity of the amino-terminal residue of specific protein substrates. Two components of this pathway in Arabidopsis thaliana, PROTEOLYSIS6 (PRT6) and arginyl-tRNA:protein arginyltransferase (ATE), were shown to regulate seed after-ripening, seedling sugar sensitivity, seedling lipid breakdown, and abscisic acid (ABA) sensitivity of germination. Sensitivity of prt6 mutant seeds to ABA inhibition of endosperm rupture reduced with after-ripening time, suggesting that seeds display a previously undescribed window of sensitivity to ABA. Reduced root growth of prt6 alleles and the ate1 ate2 double mutant was rescued by exogenous sucrose, and the breakdown of lipid bodies and seed-derived triacylglycerol was impaired in mutant seedlings, implicating the N-end rule pathway in control of seed oil mobilization. Epistasis analysis indicated that PRT6 control of germination and establishment, as exemplified by ABA and sugar sensitivity, as well as storage oil mobilization, occurs at least in part via transcription factors ABI3 and ABI5. The N-end rule pathway of protein turnover is therefore postulated to inactivate as-yet unidentified key component(s) of ABA signaling to influence the seed-to-seedling transition.

Noise versus Resolution in Optical Chemical Imaging-How Reliable Are Our Measurements?

Optical chemical imaging has established itself as a valuable technique for visualizing analyte distributions in 2D, notably in medical, biological, and environmental applications. In particular for image acquisitions on small scales between few millimeter to the micrometer range, as well as in heterogeneous samples with steep analyte gradients, image resolution is essential. When individual pixels are inspected, however, image noise becomes a metric as relevant as image accuracy and precision, and denoising filters are applied to preserve relevant information. While denoising filters smooth the image noise, they can also lead to a loss of spatial resolution and thus to a loss of relevant information about analyte distributions. To investigate the trade-off between image resolution and noise reduction for information preservation, we studied the impact of random camera noise and noise due to incorrect camera settings on oxygen optodes using the ratiometric imaging technique. First, we estimated the noise amplification across the calibration process using a Monte Carlo simulation for nonlinear fit models. We demonstrated how initially marginal random camera noise results in a significant standard deviation (SD) for oxygen concentration of up to 2.73% air under anoxic conditions, although the measurement was conducted under ideal conditions and over 270 thousand sample pixels were considered during calibration. Second, we studied the effect of the Gaussian denoising filter on a steep oxygen gradient and investigated the impact when the smoothing filter is applied during data processing. Finally, we demonstrated the effectiveness of a Savitzky-Golay filter compared to the well-established Gaussian filter.

Development of a bi-layered cryogenic electrospun polylactic acid scaffold to study calcific aortic valve disease in a 3D co-culture model.

Calcified aortic valve disease (CAVD) is the most prevalent valve disease in the elderly. Targeted pharmacological therapies are limited since the underlying mechanisms of CAVD are not well understood. Appropriate 3D in vitro models could potentially improve our knowledge of the disease. Here, we developed a 3D in vitro aortic heart valve model that resembles the morphology of the valvular extracellular matrix and mimics the mechanical and physiological behavior of the native aortic valve fibrosa and spongiosa. We employed cryogenic electrospinning to engineer a bi-layered cryogenic electrospun scaffold (BCES) with defined morphologies that allowed valvular endothelial cell (VEC) adherence and valvular interstitial cell (VIC) ingrowth into the scaffold. Using a self-designed cell culture insert allowed us to establish the valvular co-culture simultaneously by seeding VICs on one side and VECs on the other side of the electrospun scaffold. Proof-of-principle calcification studies were successfully performed using an established osteogenic culture protocol and the here designed 3D in vitro aortic heart valve model. STATEMENT OF SIGNIFICANCE: Three-dimensional (3D) electrospun scaffolds are widely used for soft tissue engineering since they mimic the morphology of the native extracellular matrix. Several studies have shown that cells behave more naturally on 3D materials than on the commonly used stiff two-dimensional (2D) cell culture substrates, which have no biological properties. As appropriate 3D models for the study of aortic valve diseases are limited, we developed a novel bi-layered 3D in vitro test system by using the versatile technique of cryogenic electrospinning in combination with the influence of different solvents to mimic the morphology, mechanical, and cellular distribution of a native aortic heart valve leaflet. This 3D in vitro model can be used to study valve biology and heart valve-impacting diseases such as calcification to elucidate therapeutic targets.

A multimodal 3D neuro-microphysiological system with neurite-trapping microelectrodes.

Three-dimensional cell technologies as pre-clinical models are emerging tools for mimicking the structural and functional complexity of the nervous system. The accurate exploration of phenotypes in engineered 3D neuronal cultures, however, demands morphological, molecular and especially functional measurements. Particularly crucial is measurement of electrical activity of individual neurons with millisecond resolution. Current techniques rely on customized electrophysiological recording set-ups, characterized by limited throughput and poor integration with other readout modalities. Here we describe a novel approach, using multiwell glass microfluidic microelectrode arrays, allowing non-invasive electrical recording from engineered 3D neuronal cultures. We demonstrate parallelized studies with reference compounds, calcium imaging and optogenetic stimulation. Additionally, we show how microplate compatibility allows automated handling and high-content analysis of human induced pluripotent stem cell-derived neurons. This microphysiological platform opens up new avenues for high-throughput studies on the functional, morphological and molecular details of neurological diseases and their potential treatment by therapeutic compounds.

A flexible protruding microelectrode array for neural interfacing in bioelectronic medicine.

Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a low-invasive neural interface with highly selective, micrometer-sized electrodes. This paper reports on the development of a three-dimensional (3D) protruding thin-film microelectrode array (MEA), which is intended to be used for recording low-amplitude neural signals from pelvic nervous structures by penetrating the nerves transversely to reduce the distance to the axons. Cylindrical gold pillars (Ø 20 or 50 µm, ~60 µm height) were fabricated on a micromachined polyimide substrate in an electroplating process. Their sidewalls were insulated with parylene C, and their tips were optionally modified by wet etching and/or the application of a titanium nitride (TiN) coating. The microelectrodes modified by these combined techniques exhibited low impedances (~7 kΩ at 1 kHz for Ø 50 µm microelectrode with the exposed surface area of ~5000 µm²) and low intrinsic noise levels. Their functionalities were evaluated in an ex vivo pilot study with mouse retinae, in which spontaneous neuronal spikes were recorded with amplitudes of up to 66 µV. This novel process strategy for fabricating flexible, 3D neural interfaces with low-impedance microelectrodes has the potential to selectively record neural signals from not only delicate structures such as retinal cells but also autonomic nerves with improved signal quality to study neural circuits and develop stimulation strategies in bioelectronic medicine, e.g., for the control of vital digestive functions.

Contribution of NOTCH1 genetic variants to bicuspid aortic valve and other congenital lesions.

INTRODUCTION: Bicuspid aortic valve (BAV) affects 1% of the general population. NOTCH1 was the first gene associated with BAV. The proportion of familial and sporadic BAV disease attributed to NOTCH1 mutations has not been estimated. AIM: The aim of our study was to provide an estimate of familial and sporadic BAV disease attributable to NOTCH1 mutations. METHODS: The population of our study consisted of participants of the University of Leicester Bicuspid aoRtic vAlVe gEnetic research-8 pedigrees with multiple affected family members and 381 sporadic patients. All subjects underwent NOTCH1 sequencing. A systematic literature search was performed in the NCBI PubMed database to identify publications reporting NOTCH1 sequencing in context of congenital heart disease. RESULTS: NOTCH1 sequencing in 36 subjects from 8 pedigrees identified one variant c.873C>G/p.Tyr291* meeting the American College of Medical Genetics and Genomics criteria for pathogenicity. No pathogenic or likely pathogenic NOTCH1 variants were identified in 381 sporadic patients. Literature review identified 64 relevant publication reporting NOTCH1 sequencing in 528 pedigrees and 9449 sporadic subjects. After excluding families with syndromic disease pathogenic and likely pathogenic NOTCH1 variants were detected in 9/435 (2.1%; 95% CI: 0.7% to 3.4%) of pedigrees and between 0.05% (95% CI: 0.005% to 0.10%) and 0.08% (95% CI: 0.02% to 0.13%) of sporadic patients. Incomplete penetrance of definitely pathogenic NOTCH1 mutations was observed in almost half of reported pedigrees. CONCLUSIONS: Pathogenic and likely pathogenic NOTCH1 genetic variants explain 2% of familial and <0.1% of sporadic BAV disease and are more likely to associate with tetralogy of Fallot and hypoplastic left heart.

High Prevalence of Low-Level Parasitemia With Plasmodium vivax in Makira-Ulawa Province Presents a Challenge for the Diagnosis and Eradication of Malaria in Solomon Islands.

Background: Malaria remains endemic in Solomon Islands, but data on malaria in the provinces of Solomon Islands are limited. This study from Makira-Ulawa Province aimed to identify the most prevalent strain of malaria and assess if the available rapid diagnostic test (RDT) was effective in Kirakira Hospital. Methods: Forty-five patients who presented to Kirakira Hospital with symptoms of fever had a positive malaria parasite smear during a 4-week period in 2017. The parasite count for each smear was calculated. Simultaneous testing using the CareStart Malaria HRP2/pLDH (Pf/pan) Combo RDT was conducted. The data for all malaria parasite smears performed in Makira-Ulawa Province in 2016 were collated for comparison. Results: All 45 patients diagnosed with malaria in a 4-week period in 2017 were positive for Plasmodium vivax. The median parasite load was 280 parasites per µL (range, 160 to 640 parasites per µL). None of the 45 CareStart RDTs performed was positive. In 2016, 5,505 of 17,195 patients (32.0%) screened had malaria parasites detected on a malaria parasite smear. P vivax was detected in 5,212 (94.7%) and Plasmodium falciparum in 285 (5.2%) of patients with malaria. Conclusion: P vivax is the predominant strain of malaria present in Makira-Ulawa Province. RDTs were not helpful in the diagnosis of malaria at Kirakira Hospital. The parasite load detected in the 45 patients diagnosed with malaria in this study was low. A focus on attempting to eradicate P vivax in the community through improved compliance with treatment protocols is suggested as a possible way forward to best manage malaria in Makira-Ulawa Province.