Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages.

New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. In this manuscript we characterize 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv-exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target.

UV-C disinfection of ultrasound probes: Challenges of uneven irradiance on complex surfaces.

Medical devices that contact non-intact skin or mucous membranes are considered semi-critical devices and must undergo high-level disinfection (HLD) before use. Studies have identified several potential limitations of UV-C for HLD of semi-critical medical devices, including a lack of data demonstrating that UV-C irradiance can be uniformly applied to complex surfaces that contain grooves, notches and imperfections. This study focused on ultrasound probes as commonly used medical devices to show the distribution of irradiance on these surfaces.

Factors Associated with Advance Care Planning Engagement Among Community-Dwelling Older Adults: A Cross-Sectional Study.

Aim: To explore the associations between depression, anxiety, decisional conflict and advance care planning engagement and the potential mediating role of decisional conflict in the associations between depression, anxiety and advance care planning among community-dwelling older adults.

Design: A cross-sectional study was conducted with 262 community-dwelling older Australians across metropolitan, regional and rural communities between August and October 2022.

Methods: Validated self-reported questions were used to collect data on anxiety, depression (Hospital Anxiety and Depression Scale), decisional conflict (Decisional Conflict Scale), advance care planning engagement (Advance Care Planning Engagement Survey) and covariates (demographic characteristics, health literacy [Health Literacy Screening Questions]), overall health status (Short form 36).

A 4-Month-Old With Jaundice, Lethargy, and Emesis.

Acute liver failure is rare in the neonatal and infant population; however, when encountered, it requires timely diagnosis, management, and identification of the underlying etiology to provide the best clinical outcomes. Here, we present a case of new-onset liver failure in a 4-month-old infant. She had previously been diagnosed with neonatal mucocutaneous herpes simplex virus disease, but had been healthy in the interval, and was referred to our hospital for evaluation of possible need for liver transplantation because of a rapidly progressing pace of disease.

A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites.

Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led to strain-specific protection, limiting the success of AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, a humanised single-domain antibody-like molecule that recognises a conserved pan-species conformational epitope in AMA1 with low nanomolar affinity and inhibits the binding of the RON2 ligand to AMA1.

Validating care and treatment scenarios for measuring decisional conflict regarding future care preferences among older adults.

Objective: Decisional conflict is used increasingly as an outcome measure in advance care planning (ACP) studies. When the Decisional Conflict Scale (DCS) is used in anticipatory decision-making contexts, the scale is typically tethered to hypothetical scenarios. This study reports preliminary validation data for hypothetical scenarios relating to life-sustaining treatments and care utilisation to inform their broader use in ACP studies.

Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages.

New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. We isolated 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target.

A Diversity Covering (DiCo) Plasmodium vivax apical membrane antigen-1 vaccine adjuvanted with RFASE/RSL10 yields high levels of growth-inhibitory antibodies.

Plasmodium vivax malaria is increasingly recognized as a major global health problem and the socio-economic impact of P.vivax-induced burden is huge. Vaccine development against P.

Attitudes and Perceptions on Advance Care Planning Among Chinese-Speaking Older Australians.

Background: Current literature indicates low uptake of advance care planning (ACP) among the Chinese-speaking community in Australia. To increase the uptake of ACP among the Chinese-speaking community, a better understanding of their attitudes and perceptions on end-of-life (EOL) matters, and ACP is required.

Objective: This study aimed to identify significant events and social and cultural factors that influence participants' values and characterize the attitudes and perceptions towards ACP among older Chinese-speaking Australians.

Defining species-specific and conserved interactions of apical membrane protein 1 during erythrocyte invasion in malaria to inform multi-species vaccines.

Plasmodium falciparum and P. vivax are the major causes of human malaria, and P. knowlesi is an important additional cause in SE Asia.

The direct binding of AMA1 to erythrocytes defines a RON2-independent invasion pathway.

We used a transgenic parasite in which parasites were genetically modified to express apical membrane antigen 1 (PvAMA1) protein in place of PfAMA1 to study PvAMA1-mediated invasion. In , AMA1 interaction with rhoptry neck protein 2 (RON2) is known to be crucial for invasion, and PfRON2 peptides (PfRON2p) blocked the invasion of PfAMA1 wild-type parasites. However, PfRON2p has no effect on the invasion of transgenic parasites expressing PvAMA1 indicating that PfRON2 had no role in the invasion of PvAMA1 transgenic parasites.

Characterisation of PfCZIF1 and PfCZIF2 in Plasmodium falciparum asexual stages.

Plasmodium falciparum exerts strong temporal control of gene expression across its lifecycle. Proteins expressed exclusively during late schizogony of blood stages, for example, often have a role in facilitating merozoite invasion of the host red blood cell (RBC), through merozoite development, egress, invasion or early establishment of infection in the RBC. Here, we characterise P.

RNAseq of Infected Erythrocyte Surface Antigen-Encoding Genes.

Massive parallel sequencing technology has greatly increased the breadth and depth of transcriptomic data that can be captured from P. falciparum samples. This has revolutionized in vitro studies but uptake has been slower in the analysis of clinical samples.

Advances in Plasmodium research, an update: Highlights from the Malaria in Melbourne 2021 conference.

The Malaria in Melbourne 2021 conference was held online in October. This conference aims to provide a platform for students and early career researchers to share their research and develop new collaborative networks. The program covered a broad range of topics including antimalarial drug development, epidemiology, immunology, molecular and cellular biology, and other emerging technologies.

Health-related quality of life of Malaysian patients with chronic non-malignant pain and its associated factors: a cross-sectional study.

Background: Chronic pain has a major impact on a patient's quality of life, affecting physical and psychological functioning. It has debilitating consequences on social and economic aspects too. This study aimed to explore the status of health-related quality of life (HRQoL) of Malaysian patients suffering from chronic non-malignant pain.

Identifying high-risk hospitalised chronic kidney disease patient using electronic health records for serious illness conversation.

Introduction: This study aimed to identify risk factors that are associated with increased mortality that could prompt a serious illness conversation (SIC) among patients with chronic kidney disease (CKD).

Methods: The electronic health records of adult CKD patients admitted between August 2018 and February 2020 were retrospectively reviewed to identify CKD patients with >1 hospitalisation and length of hospital stay ≥4 days. Outcome measures were mortality and the duration of hospitalisation.

New signatures of the spin gap in quantum point contacts.

One dimensional semiconductor systems with strong spin-orbit interaction are both of fundamental interest and have potential applications to topological quantum computing. Applying a magnetic field can open a spin gap, a pre-requisite for Majorana zero modes. The spin gap is predicted to manifest as a field dependent dip on the first 1D conductance plateau.

Histone modifications associated with gene expression and genome accessibility are dynamically enriched at Plasmodium falciparum regulatory sequences.

Background: The malaria parasite Plasmodium falciparum has an unusually euchromatic genome with poorly conserved positioning of nucleosomes in intergenic sequences and poorly understood mechanisms of gene regulation. Variant histones and histone modifications determine nucleosome stability and recruit trans factors, but their combinatorial contribution to gene regulation is unclear.

Results: Here, we show that the histone H3 acetylations H3K18ac and H3K27ac and the variant histone Pf H2A.

Developments in drug design strategies for bromodomain protein inhibitors to target parasites.

: Bromodomains (BRDs) bind to acetylated lysine residues, often on histones. The BRD proteins can contribute to gene regulation either directly through enzymatic activity or indirectly through recruitment of chromatin-modifying complexes or transcription factors. There is no evidence of direct orthologues of the BRD proteins (PfBDPs) outside the apicomplexans.

Decreased K13 Abundance Reduces Hemoglobin Catabolism and Proteotoxic Stress, Underpinning Artemisinin Resistance.

Increased tolerance of Plasmodium falciparum to front-line artemisinin antimalarials (ARTs) is associated with mutations in Kelch13 (K13), although the precise role of K13 remains unclear. Here, we show that K13 mutations result in decreased expression of this protein, while mislocalization of K13 mimics resistance-conferring mutations, pinpointing partial loss of function of K13 as the relevant molecular event. K13-GFP is associated with ∼170 nm diameter doughnut-shaped structures at the parasite periphery, consistent with the location and dimensions of cytostomes.

Alternative splicing is required for stage differentiation in malaria parasites.

Background: In multicellular organisms, alternative splicing is central to tissue differentiation and identity. Unicellular protists lack multicellular tissue but differentiate into variable cell types during their life cycles. The role of alternative splicing in transitions between cell types and establishing cellular identity is currently unknown in any unicellular organism.