Lymphoma follow-up pathway: A 10-year study to guide practice.

Purpose: Lymphoma survivors who have received curative intent treatment are currently followed up at defined time points in medical and nurse-led clinics often indefinitely. The follow up protocol is often at the discretion of the treating physician. The aim of the study was to explore the clinical, biochemical and radiological presentation of patients with Diffuse Large B-cell Lymphoma (DLBCL) and Hodgkin Lymphoma (HL) treated with curative intent at the point of recurrence from first remission, and to understand if recurrence was detected at scheduled follow up.

Mixed alkyl/aryl phosphonates identify metabolic serine hydrolases as antimalarial targets.

Malaria, caused by Plasmodium falciparum, remains a significant health burden. One major barrier for developing antimalarial drugs is the ability of the parasite to rapidly generate resistance. We previously demonstrated that salinipostin A (SalA), a natural product, potently kills parasites by inhibiting multiple lipid metabolizing serine hydrolases, a mechanism that results in a low propensity for resistance.

Peptidic Boronic Acid SUB1 Inhibitors with Improved Selectivity over Human Proteasome.

subtilisin-like serine protease 1 (PfSUB1) is essential for egress of invasive merozoite forms of the parasite, rendering PfSUB1 an attractive antimalarial target. Here, we report studies aimed to improve drug-like properties of peptidic boronic acid PfSUB1 inhibitors including increased lipophilicity and selectivity over human proteasome (H20S). Structure-activity relationship investigations revealed that lipophilic P amino acid side chains as well as -capping groups were well tolerated in retaining PfSUB1 inhibitory potency.

The malaria parasite egress protease SUB1 is activated through precise, plasmepsin X-mediated cleavage of the SUB1 prodomain.

Background: The malaria parasite Plasmodium falciparum replicates within red blood cells, then ruptures the cell in a process called egress in order to continue its life cycle. Egress is regulated by a proteolytic cascade involving an essential parasite subtilisin-like serine protease called SUB1. Maturation of SUB1 initiates in the parasite endoplasmic reticulum with autocatalytic cleavage of an N-terminal prodomain (p31), which initially remains non-covalently bound to the catalytic domain, p54.

Venetoclax Initiation in Chronic Lymphocytic Leukemia: International Insights and Innovative Approaches for Optimal Patient Care.

Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)/mutated- and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age groups. Due to the potent pro-apoptotic effect of venetoclax, treatment initiation carries a risk of tumor lysis syndrome (TLS). Prompt and appropriate management is needed to limit clinical TLS, which may entail serious adverse events and death.

Mixed Alkyl/Aryl Phosphonates Identify Metabolic Serine Hydrolases as Antimalarial Targets.

Malaria, caused by remains a significant health burden. A barrier for developing anti-malarial drugs is the ability of the parasite to rapidly generate resistance. We demonstrated that Salinipostin A (SalA), a natural product, kills parasites by inhibiting multiple lipid metabolizing serine hydrolases, a mechanism with a low propensity for resistance.

A choline-releasing glycerophosphodiesterase essential for phosphatidylcholine biosynthesis and blood stage development in the malaria parasite.

The malaria parasite synthesizes significant amounts of phospholipids to meet the demands of replication within red blood cells. De novo phosphatidylcholine (PC) biosynthesis via the Kennedy pathway is essential, requiring choline that is primarily sourced from host serum lysophosphatidylcholine (lysoPC). LysoPC also acts as an environmental sensor to regulate parasite sexual differentiation.

Subtilisin-like Serine Protease 1 (SUB1) as an Emerging Antimalarial Drug Target: Current Achievements in Inhibitor Discovery.

Widespread resistance to many antimalarial therapies currently in use stresses the need for the discovery of new classes of drugs with new modes of action. The subtilisin-like serine protease SUB1 controls egress of malaria parasites (merozoites) from the parasite-infected red blood cell. As such, SUB1 is considered a prospective target for drugs designed to interrupt the asexual blood stage life cycle of the malaria parasite.

Ambulatory atrioventricular synchronous pacing over time using a leadless ventricular pacemaker: Primary results from the AccelAV study.

Background: Previous studies demonstrated that accelerometer-based, mechanically timed atrioventricular synchrony (AVS) is feasible using a leadless ventricular pacemaker.

Objective: The purpose of this study was to determine the performance of a leadless ventricular pacemaker with accelerometer-based algorithms that provide AVS pacing.

Methods: AccelAV was a prospective, single-arm study to characterize AVS in patients implanted with a Micra AV, which uses the device accelerometer to mechanically detect atrial contractions and promote VDD pacing.

Peptidic boronic acids are potent cell-permeable inhibitors of the malaria parasite egress serine protease SUB1.

Malaria is a devastating infectious disease, which causes over 400,000 deaths per annum and impacts the lives of nearly half the world's population. The causative agent, a protozoan parasite, replicates within red blood cells (RBCs), eventually destroying the cells in a lytic process called egress to release a new generation of parasites. These invade fresh RBCs to repeat the cycle.

Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor.

Malaria parasite egress from host erythrocytes (RBCs) is regulated by discharge of a parasite serine protease called SUB1 into the parasitophorous vacuole (PV). There, SUB1 activates a PV-resident cysteine protease called SERA6, enabling host RBC rupture through SERA6-mediated degradation of the RBC cytoskeleton protein β-spectrin. Here, we show that the activation of Plasmodium falciparum SERA6 involves a second, autocatalytic step that is triggered by SUB1 cleavage.

AMEE Consensus Statement: Planetary health and education for sustainable healthcare.

The purpose of this Consensus Statement is to provide a global, collaborative, representative and inclusive vision for educating an interprofessional healthcare workforce that can deliver sustainable healthcare and promote planetary health. It is intended to inform national and global accreditation standards, planning and action at the institutional level as well as highlight the role of individuals in transforming health professions education. Many countries have agreed to 'rapid, far-reaching and unprecedented changes' to reduce greenhouse gas emissions by 45% within 10 years and achieve carbon neutrality by 2050, including in healthcare.

The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion.

Red blood cell (RBC) invasion by malaria merozoites involves formation of a parasitophorous vacuole into which the parasite moves. The vacuole membrane seals and pinches off behind the parasite through an unknown mechanism, enclosing the parasite within the RBC. During invasion, several parasite surface proteins are shed by a membrane-bound protease called SUB2.

Education for sustainable health care: From learning to professional practice.

A number of planetary boundaries, including climate change as a result of greenhouse gas emissions, has already been exceeded. This situation has deleterious consequences for public health. Paradoxically, 4.

Essentiality of Plasmodium falciparum plasmepsin V.

The malaria parasite replicates within erythrocytes. The pathogenesis of clinical malaria is in large part due to the capacity of the parasite to remodel its host cell. To do this, intraerythrocytic stages of Plasmodium falciparum export more than 300 proteins that dramatically alter the morphology of the infected erythrocyte as well as its mechanical and adhesive properties.

Lymphoma survivors' experiences at the end of treatment.

Aims And Objectives: To explore lymphoma survivors' experiences on their end of treatment and follow-up care at a large urban haematology centre in Ireland.

Methods: This was a qualitative study using semistructured interviews with lymphoma patients post-treatment (n = 14). Thematic analysis guided the analysis of interview data.

Publisher Correction: A protease cascade regulates release of the human malaria parasite Plasmodium falciparum from host red blood cells.

In the version of this Letter originally published, Michele S. Y. Tan was incorrectly listed as Michele Y.

A protease cascade regulates release of the human malaria parasite Plasmodium falciparum from host red blood cells.

Malaria parasites replicate within a parasitophorous vacuole in red blood cells (RBCs). Progeny merozoites egress upon rupture of first the parasitophorous vacuole membrane (PVM), then poration and rupture of the RBC membrane (RBCM). Egress is protease-dependent , but none of the effector molecules that mediate membrane rupture have been identified and it is unknown how sequential rupture of the two membranes is controlled.

The Plasmodium falciparum pseudoprotease SERA5 regulates the kinetics and efficiency of malaria parasite egress from host erythrocytes.

Egress of the malaria parasite Plasmodium falciparum from its host red blood cell is a rapid, highly regulated event that is essential for maintenance and completion of the parasite life cycle. Egress is protease-dependent and is temporally associated with extensive proteolytic modification of parasite proteins, including a family of papain-like proteins called SERA that are expressed in the parasite parasitophorous vacuole. Previous work has shown that the most abundant SERA, SERA5, plays an important but non-enzymatic role in asexual blood stages.

Anthropometric indices of First Nations children and youth on first entry to Manitoba/Saskatchewan residential schools-1919 to 1953.

Background: First Nations people are experiencing increasing rates of obesity and type 2 diabetes but no anthropometric information exists from before the 1950s to provide context to these epidemics.

Objective: To compare anthropometric indices of First Nations children and youth on first entering residential schools with historical and contemporary reference groups.

Methods: This observational cross-sectional study used archival records from the Department of Indian Affairs to calculate body mass index (BMI), height for age (HA) and weight for age (WA) of all known children and youth undergoing physical examinations on first entering residential schools in Saskatchewan and Manitoba from 1919 to 1953.

Development and Application of a Simple Plaque Assay for the Human Malaria Parasite Plasmodium falciparum.

Malaria is caused by an obligate intracellular protozoan parasite that replicates within and destroys erythrocytes. Asexual blood stages of the causative agent of the most virulent form of human malaria, Plasmodium falciparum, can be cultivated indefinitely in vitro in human erythrocytes, facilitating experimental analysis of parasite cell biology, biochemistry and genetics. However, efforts to improve understanding of the basic biology of this important pathogen and to develop urgently required new antimalarial drugs and vaccines, suffer from a paucity of basic research tools.