The cryo-EM resolution revolution has heralded a new era in our understanding of eukaryotic lipid flippases with a rapidly growing number of high-resolution structures. Flippases belong to the P4 family of ATPases (type IV P-type ATPases) that largely follow the reaction cycle proposed for the more extensively studied cation-transporting P-type ATPases. However, unlike the canonical P-type ATPases, no flippase cargos are transported in the phosphorylation half-reaction. Instead of being released into the intracellular or extracellular milieu, lipid cargos are transported to their destination at the inner leaflet of the membrane. Recent flippase structures have revealed multiple conformational states during the lipid transport cycle. Nonetheless, critical conformational states capturing the lipid cargo \"in transit\" are still missing. In this review, we highlight the amazing structural advances of these lipid transporters, discuss various perspectives on catalytic and regulatory mechanisms in the literature, and shed light on future directions in further deciphering the detailed molecular mechanisms of lipid flipping.

UNASSIGNED: The National Pressure Injury Advisory Panel, European Pressure Ulcer Advisory Panel, and the Pan Pacific Pressure Injury Alliance are commencing a new (fourth) edition of the Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline . The fourth edition of the International Pressure Injury (PI) Guideline will be developed using GRADE methods to ensure a rigorous process consistent with evolving international standards. Clinical questions will address prevention and treatment of PIs, identification of individuals at risk of PIs, assessment of skin and tissues, and PI assessment. Implementation considerations supporting application of the guidance in clinical practice will be developed. The guideline development process will be overseen by a guideline governance group and methodologist; the guideline development team will include health professionals, educators, researchers, individuals with or at risk of PIs, and informal carers.This article presents the project structure and processes to be used to undertake a systematic literature search, appraise risk of bias of the evidence, and aggregate research findings. The methods detail how certainty of evidence will be evaluated; presentation of relative benefits, risks, feasibility, acceptability, and resource requirements; and how recommendations will be made and graded. The methods outline transparent processes of development that combine scientific research with best clinical practice. Strong involvement from health professionals, educators, individuals with PIs, and informal carers will enhance the guideline\'s relevance and facilitate uptake. This update builds on previous editions to ensure consistency and comparability, with methodology changes improving the guideline\'s quality and clarity.

Illness prevention is essential for athlete health management, but little is known about its uptake in sport. Prior to the pandemic, the International Olympic Committee (IOC) published a consensus statement recommending illness prevention guidelines are implemented in sports. Yet, little is known about guideline uptake. Therefore, this study aimed to explore the (1) illness experiences of rugby players and athlete support personnel and (2) barriers and enablers to illness prevention guideline uptake in rugby, using the lens of behaviour change theory. In a bid to inform and enhance athlete welfare, we sought to amplify the voices of participants through qualitative inquiry. Between August 2020 and May 2021, 16 semi-structured interviews were undertaken with players and athlete support personnel working across rugby. Analysis was conducted using Braun and Clarke\'s reflexive thematic analysis. Prior to COVID-19, participants deemed illness to be of little concern, with experience of illnesses and the global pandemic critical enablers to guideline uptake. The rugby environment was a barrier to illness prevention, particularly in women\'s and academy teams where resource deficiency was highlighted. \'Rugby identity\' acted as both a barrier and enabler with participants\' passion for rugby driving both guideline adherence and non-adherence. Tackling resource inequalities between men\'s and women\'s cohorts is critical to effectively implement guidelines. Coach and player education is essential, and emphasis must be placed on continuing preventative behaviours adopted due to COVID-19. Our findings offer new insight into illness prevention, moving away from prevailing quantitative research, and instead voicing players\' experiences.

Reducing the burden of neonatal sepsis requires timely identification and initiation of suitable antibiotic treatment in primary health care (PHC) settings. Countries are encouraged to adopt simplified antibiotic regimens at the PHC level for treating sick young infants (SYI) with signs of possible serious bacterial infection (PSBI). As countries implement PSBI guidelines, more lessons on effective implementation strategies and outcome measurements are needed. We document pragmatic approaches used to design, measure and report implementation strategies and outcomes while adopting PSBI guidelines in Kenya.
We designed implementation research using longitudinal mixed methods embedded in a continuous regular systematic learning and adoption of evidence in the PHC context. We synthesized formative data to co-create with stakeholders, implementation strategies to incorporate PSBI guidelines into routine service delivery for SYIs. This was followed by quarterly monitoring for learning and feedback on the effect of implementation strategies, documented lessons learned and tracked implementation outcomes. We collected endline data to measure the overall effect on service level outcomes.
Our findings show that characterizing implementation strategies and linking them with implementation outcomes, helps illustrate the pathway between the implementation process and outcomes. Although we have demonstrated that it is feasible to implement PSBI in PHC, effective investment in continuous capacity strengthening of providers through blended approaches, efficient use of available human resources, and improving the efficiency of service areas for managing SYIs optimizes timely identification and management of SYI. Sustained provision of commodities for management of SYI facilitates increased uptake of services. Strengthening facility-community linkages supports adherence to scheduled visits. Enhancing the caregiver\'s preparedness during postnatal contacts in the community or facility will facilitate the effective completion of treatment.
Careful design, and definition of terms related to the measurement of implementation outcomes and strategies enable ease of interpretation of findings. Using the taxonomy of implementation outcomes help frame the measurement process and provides empirical evidence in a structured way to demonstrate causal relationships between implementation strategies and outcomes. Using this approach, we have illustrated that the implementation of simplified antibiotic regimens for treating SYIs with PSBI in PHC settings is feasible in Kenya.

Translating evidence-based guidelines into clinical practice is a complex challenge. This observational study aimed to assess the adherence to the Italian national guidelines on postpartum haemorrhage (PPH) and describe the clinical management of haemorrhagic events in a selection of maternity units (MUs) in six Italian regions, between January 2019 and October 2020. A twofold study design was adopted: (i) a before-after observational study was used to assess the adherence to national clinical and organisational key recommendations on PPH management, and (ii) a cross-sectional study enrolling prospectively 1100 women with PPH ≥ 1000 mL was used to verify the results of the before-after study. The post-test detected an improved adherence to 16/17 key recommendations of the guidelines, with clinical governance and communication with family members emerging as critical areas. Overall, PPH management emerged as appropriate except for three recommended procedures that emphasise different results between the practices adopted and the difference between what is considered acquired and what is actually practised in daily care. The methodology adopted by the MOVIE project and the adopted training materials and tools have proved effective in improving adherence to the recommended procedures for appropriate PPH management and could be adopted in similar care settings in order to move evidence into practice.

Artificial ion-exchange and other charged membranes, such as biomembranes, are self-organizing nanomaterials built from macromolecules. The interactions of fragments of macromolecules results in phase separation and the formation of ion-conducting channels. The properties conditioned by the structure of charged membranes determine their application in separation processes (water treatment, electrolyte concentration, food industry and others), energy (reverse electrodialysis, fuel cells and others), and chlore-alkali production and others. The purpose of this review is to provide guidelines for modeling the transport of ions and water in charged membranes, as well as to describe the latest advances in this field with a focus on power generation systems. We briefly describe the main structural elements of charged membranes which determine their ion and water transport characteristics. The main governing equations and the most commonly used theories and assumptions are presented and analyzed. The known models are classified and then described based on the information about the equations and the assumptions they are based on. Most attention is paid to the models which have the greatest impact and are most frequently used in the literature. Among them, we focus on recent models developed for proton-exchange membranes used in fuel cells and for membranes applied in reverse electrodialysis.

BACKGROUND: Scintigraphic evaluation of the thyroid gland enables determination of the iodine-123 iodide or the 99mTc-pertechnetate uptake and distribution and remains the most accurate method for the diagnosis and quantification of thyroid autonomy and the detection of ectopic thyroid tissue. In addition, thyroid scintigraphy and radioiodine uptake test are useful to discriminate hyperthyroidism from destructive thyrotoxicosis and iodine-induced hyperthyroidism, respectively.
METHODS: Several radiopharmaceuticals are available to help in differentiating benign from malignant cytologically indeterminate thyroid nodules and for supporting clinical decision-making. This joint practice guideline/procedure standard from the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides recommendations based on the available evidence in the literature.
CONCLUSIONS: The purpose of this practice guideline/procedure standard is to assist imaging specialists and clinicians in recommending, performing, and interpreting the results of thyroid scintigraphy (including positron emission tomography) with various radiopharmaceuticals and radioiodine uptake test in patients with different thyroid diseases.

OBJECTIVE: According to the regulatory guidelines, one of the critical steps in using in-vitro permeability methods for permeability classification is to demonstrate the suitability of the method. Here, suitability of the permeability method by using a monolayer of cultured epithelial cells was verified with different criteria.
METHODS: Imaging with a transmission electron microscope was used for characterisation of the cells. Monolayer integrity was confirmed by transepithelial electrical resistance measurements and permeability of zero permeability marker compounds. Real-time polymerase chain reaction was employed to evaluate expression levels of 84 known transporters. Samples for bidirectional permeability determination were quantified by ultra-performance liquid chromatography.
RESULTS: The Caco-2 cells grow in an intact monolayer and morphologically resemble enterocytes. Genes of 84 known transporters were expressed at different levels; furthermore, expression was time depended. Functional expression of efflux transporter P-glycoprotein was confirmed. We established a correlation between permeability coefficients of 21 tested drug substances ranging from low, moderate and high absorption with human fraction absorbed literature data (R2  = 0.84).
CONCLUSIONS: Assay standardisation assures the consistency of experimental data. Only such fully characterised model has the ability to accurately predict drug\'s intestinal permeability at the early stage of research or for the BCS-based biowaiver application.

The strong dependence of retroviruses, such as human immunodeficiency virus type 1 (HIV-1), on host cell factors is no more apparent than when the endosomal sorting complex required for transport (ESCRT) machinery is purposely disengaged. The resulting potent inhibition of retrovirus release underscores the importance of understanding fundamental structure-function relationships at the ESCRT-HIV-1 interface. Recent studies utilizing advanced imaging technologies have helped clarify these relationships, overcoming hurdles to provide a range of potential models for ESCRT-mediated virus abscission. Here, we discuss these models in the context of prior work detailing ESCRT machinery and the HIV-1 release process. To provide a template for further refinement, we propose a new working model for ESCRT-mediated HIV-1 release that reconciles disparate and seemingly conflicting studies.

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