Improving diagnostics and surveillance of malaria among displaced people in Africa
Int J Equity Health. 2025 Jan 21;24(1):22. doi: 10.1186/s12939-025-02378-6.
ABSTRACT
African communities that have been forced to leave their homes experience a considerably greater susceptibility to malaria as a result of densely populated living conditions, restricted availability of healthcare, and environmental influences. Internally displaced individuals frequently live in large settlements with restricted availability to drinking water, essential sanitation, and medical services, intensifying the spread of malaria. As a result, the occurrence of malaria is significantly more common among refugees and internally displaced individuals compared to those who are not displaced. This leads to greater rates of illness and death, especially among young people. Insufficient monitoring worsens the condition, leading to delayed identification and medical intervention, and contributing to a higher incidence of severe malaria and deaths. Furthermore, these communities are faced with economic consequences that contribute to the continuation of poverty and the worsening of socio-economic inequalities. Furthermore, the psychological impact of malaria, which is marked by feelings of anxiety and uncertainty, is particularly severe in vulnerable populations such as displaced children and pregnant women, aggravating the overall burden. Hence, addressing malaria in displaced populations in Africa requires comprehensive and well-coordinated strategies. Advanced diagnostic and surveillance technologies are essential for promptly identifying and treating malaria, providing chances to monitor and control its spread effectively. Collaboration among healthcare, policy, and humanitarian sectors is crucial for implementing comprehensive solutions that incorporate enhanced diagnostics, surveillance, and socio-psychological support. Active involvement of the community, usage of Community Health Workers, and regular collection of surveillance data are crucial in increasing awareness, directing control efforts, and tackling the specific difficulties encountered by displaced groups. Moreover, the implementation of environmental management, the incorporation of health services, and the utilization of adaptable healthcare interventions are essential for reducing the effects of malaria. To mitigate the impact of malaria and improve health outcomes among displaced populations in Africa, it is crucial to focus on these specific areas.
PMID:39833862 | DOI:10.1186/s12939-025-02378-6
Direct observation of small molecule activator binding to single PR65 protein
NPJ Biosens. 2025;2(1):2. doi: 10.1038/s44328-024-00018-7. Epub 2025 Jan 16.
ABSTRACT
The reactivation of heterotrimeric protein phosphatase 2A (PP2A) through small molecule activators is of interest to therapeutic intervention due to its dysregulation, which is linked to chronic conditions. This study focuses on the PP2A scaffold subunit PR65 and a small molecule activator, ATUX-8385, designed to bind directly to this subunit. Using a label-free single-molecule approach with nanoaperture optical tweezers (NOT), we quantify its binding, obtaining a dissociation constant of 13.6 ± 2.5 μM, consistent with ensemble fluorescence anisotropy results but challenging to achieve with other methods due to low affinity. Single-molecule NOT measurements reveal that binding increases optical scattering, indicating PR65 elongation. This interpretation is supported by all-atom molecular dynamics simulations showing PR65 adopts more extended conformations upon binding. This work highlights NOT's utility in quantifying binding kinetics and structural impact, offering insights valuable for drug discovery.
PMID:39830999 | PMC:PMC11738983 | DOI:10.1038/s44328-024-00018-7
Direct observation of small molecule activator binding to single PR65 protein
NPJ Biosens. 2025;2(1):2. doi: 10.1038/s44328-024-00018-7. Epub 2025 Jan 16.
ABSTRACT
The reactivation of heterotrimeric protein phosphatase 2A (PP2A) through small molecule activators is of interest to therapeutic intervention due to its dysregulation, which is linked to chronic conditions. This study focuses on the PP2A scaffold subunit PR65 and a small molecule activator, ATUX-8385, designed to bind directly to this subunit. Using a label-free single-molecule approach with nanoaperture optical tweezers (NOT), we quantify its binding, obtaining a dissociation constant of 13.6 ± 2.5 μM, consistent with ensemble fluorescence anisotropy results but challenging to achieve with other methods due to low affinity. Single-molecule NOT measurements reveal that binding increases optical scattering, indicating PR65 elongation. This interpretation is supported by all-atom molecular dynamics simulations showing PR65 adopts more extended conformations upon binding. This work highlights NOT's utility in quantifying binding kinetics and structural impact, offering insights valuable for drug discovery.
PMID:39830999 | PMC:PMC11738983 | DOI:10.1038/s44328-024-00018-7
Palliative care needs and quality of life among adults with advanced chronic illnesses in low-income communities of Bangladesh
BMC Palliat Care. 2025 Jan 18;24(1):18. doi: 10.1186/s12904-024-01643-9.
ABSTRACT
OBJECTIVES: Palliative care (PC) is an interdisciplinary approach aimed at improving the physical, psychological, and spiritual well-being of patients and families affected by life-threatening diseases. This study aimed to investigate the need for PC among critically ill patients and their quality of life (QOL) in low-income groups in Bangladesh.
METHODS: This cross-sectional study was conducted at four healthcare facilities from March to April 2023, involving 553 registered patients with advanced chronic conditions. After applying inclusion and exclusion criteria, 183 patients in the advanced stage of illness were included. We collected data on sociodemographic, comorbidities, disabilities, and the 10-item African Palliative Outcome Scale (APOS). The Supportive and Palliative Care Indicators Tool (SPICT) was used to identify individuals requiring PC. The study investigated patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 3-4, indicating significant functional impairment, and explored QOL across four domains: physical health, psychological health, social relationships, and environmental factors.
RESULTS: The mean age of the 183 patients was 53.8 (± 14.53) years, with 69.5% being female. We found that 10.3% of patients with chronic illness required PC, particularly cancer patients (87%) and those with chronic kidney disease (CKD) (53.3%). The APOS scores indicated that family anxiety (48.6%) was the most burdensome issue, followed by severe pain (15.5%), severe worry about illness (22.4%), and feelings of life being unworthy (9.4%). Patients with severe functional limitations (ECOG 3-4) were significantly more likely to need PC (58%) compared to those with moderate or no limitations (ECOG 0-2) (24%). Among those requiring PC, 70.1% rated their QOL as poor or very-poor, while only 23.8% of patients not needing PC reported similar ratings. Female patients had poorer QOL than males across all domains, and those facing financial hardships also experienced significantly lower QOL.
CONCLUSION: In Bangladesh's low-income communities, a significant proportion of patients with chronic illnesses require palliative care (PC) due to advanced conditions. The findings emphasize the importance of integrating PC early in the treatment process for cancer and CKD patients, as it can greatly improve their QOL and provide essential support for both patients and families. The results advocate for a holistic approach to PC that addresses physical, psychological, social, and environmental factors affecting patients' QOL.
PMID:39825369 | DOI:10.1186/s12904-024-01643-9
Coronal alignment in normal individuals and moderate scoliosis: Normative values, variation with age and comparison with sagittal alignment
Brain Spine. 2024 Oct 11;4:103917. doi: 10.1016/j.bas.2024.103917. eCollection 2024.
ABSTRACT
INTRODUCTION: Global coronal alignment is mainly assessed by C7 plumbline and central sacral vertical line (CSVL), pelvic obliquity and shoulder alignment. A detailed analysis is mandatory when treating spinal deformity. It remains unclear to what extent mild scoliosis influences global coronal alignment.
RESEARCH QUESTION: The objective was to define a comprehensive set of coronal alignment parameters and to investigate differences between individuals without spinal deformity and with mild scoliosis. The relationship between coronal and sagittal alignment and the influence of age were studied.
METHODS: Radiographs of 236 normal individuals (Group N) and 140 patients with scoliosis <35° (Group S) were prospectively collected. Coronal parameters were femoral head distance and angle, pelvic obliquity, Maloney angle, L4 and L5 inclinations, coronal T1 pelvic angle, C7-CSVL and odontoid CSVL offset, coracoid distance and angle. Sagittal cervical, spinopelvic, thoracolumbar and global parameters were measured.
RESULTS: There was no significant difference between groups N and S for coronal parameters, except for L4 and L5 inclinations with a mean difference of 3,3° (p < 0,001). Global coronal alignment kept constant throughout age groups in N and S groups. Sagittal parameters varied with age: C2-C7 lordosis (p < 0,001), T1-T12 kyphosis (p < 0,001), pelvic incidence (p < 0,001). There was no correlation between global coronal and sagittal alignment: R-values ranging from -0.2 to 0.2.
CONCLUSION: Global coronal parameters were comparable in normal individuals and in scoliosis <35°. Coronal plane parameters were not influenced by age. Sagittal plane parameters varied significantly with age. There was no direct link between coronal et sagittal alignment.
PMID:39823062 | PMC:PMC11736157 | DOI:10.1016/j.bas.2024.103917
Single-Cell Analysis in the Mouse and Human Mammary Gland
Adv Exp Med Biol. 2025;1464:45-73. doi: 10.1007/978-3-031-70875-6_4.
ABSTRACT
The mammary gland is a complex organ, host to a rich array of different cell types. As the only organ to complete its development in adulthood, it delicately balances both cell intrinsic and external signalling from hormones, growth factors and other stimulants. The gland can undergo vast proliferation, restructuring and functional maturation during pregnancy and undo these gross changes to a nearly identical resting state during involution. The adaptive nature of the mammary gland underpins its function but also increases its susceptibility to cancer. While already characterised at a macro scale, understanding the complexities of mammary gland morphogenesis, development and tumorigenesis requires interrogation of cellular and molecular mechanisms. As outlined below, single-cell analysis is a key approach for this, allowing us to unbiasedly explore and characterise the functions and properties of individual cells from the genome to the proteome. Here, we introduce key single-cell analysis methods and give brief introductions to their respective workflows. We then discuss the structure, cell types and development of the mammary gland from birth, puberty and through pregnancy, as well as cancer formation. Additionally, we highlight the benefits and caveats of implementing single-cell methodologies and mouse models for studying critical time points of human development and disease. Finally, we highlight some limitations and future directions of single-cell techniques. This chapter provides a starting point for users hoping to further their understanding of mammary gland development and its link to cancer as explained by single-cell analysis studies.
PMID:39821020 | DOI:10.1007/978-3-031-70875-6_4
Quantitative approaches for studying G protein-coupled receptor signalling and pharmacology
J Cell Sci. 2025 Jan 1;138(1):JCS263434. doi: 10.1242/jcs.263434. Epub 2025 Jan 15.
ABSTRACT
G protein-coupled receptor (GPCR) signalling pathways underlie numerous physiological processes, are implicated in many diseases and are major targets for therapeutics. There are more than 800 GPCRs, which together transduce a vast array of extracellular stimuli into a variety of intracellular signals via heterotrimeric G protein activation and multiple downstream effectors. A key challenge in cell biology research and the pharmaceutical industry is developing tools that enable the quantitative investigation of GPCR signalling pathways to gain mechanistic insights into the varied cellular functions and pharmacology of GPCRs. Recent progress in this area has been rapid and extensive. In this Review, we provide a critical overview of these new, state-of-the-art approaches to investigate GPCR signalling pathways. These include novel sensors, Förster or bioluminescence resonance energy transfer assays, libraries of tagged G proteins and transcriptional reporters. These approaches enable improved quantitative studies of different stages of GPCR signalling, including GPCR activation, G protein activation, second messenger (cAMP and Ca2+) signalling, β-arrestin recruitment and the internalisation and intracellular trafficking of GPCRs.
PMID:39810711 | DOI:10.1242/jcs.263434
Quantitative approaches for studying G protein-coupled receptor signalling and pharmacology
J Cell Sci. 2025 Jan 1;138(1):JCS263434. doi: 10.1242/jcs.263434. Epub 2025 Jan 15.
ABSTRACT
G protein-coupled receptor (GPCR) signalling pathways underlie numerous physiological processes, are implicated in many diseases and are major targets for therapeutics. There are more than 800 GPCRs, which together transduce a vast array of extracellular stimuli into a variety of intracellular signals via heterotrimeric G protein activation and multiple downstream effectors. A key challenge in cell biology research and the pharmaceutical industry is developing tools that enable the quantitative investigation of GPCR signalling pathways to gain mechanistic insights into the varied cellular functions and pharmacology of GPCRs. Recent progress in this area has been rapid and extensive. In this Review, we provide a critical overview of these new, state-of-the-art approaches to investigate GPCR signalling pathways. These include novel sensors, Förster or bioluminescence resonance energy transfer assays, libraries of tagged G proteins and transcriptional reporters. These approaches enable improved quantitative studies of different stages of GPCR signalling, including GPCR activation, G protein activation, second messenger (cAMP and Ca2+) signalling, β-arrestin recruitment and the internalisation and intracellular trafficking of GPCRs.
PMID:39810711 | DOI:10.1242/jcs.263434