Structure and Function of Stator Units of the Bacterial Flagellar Motor.

Many bacteria use the flagellum for locomotion and chemotaxis. Its bidirectional rotation is driven by a membrane-embedded motor, which uses energy from the transmembrane ion gradient to generate torque at the interface between stator units and rotor. The structural organization of the stator unit (MotAB), its conformational changes upon ion transport, and how these changes power rotation of the flagellum remain unknown. Here, we present ~3 Å-resolution cryoelectron microscopy reconstructions of the stator unit in different functional states. We show that the stator unit consists of a dimer of MotB surrounded by a pentamer of MotA. Combining structural data with mutagenesis and functional studies, we identify key residues involved in torque generation and present a detailed mechanistic model for motor function and switching of rotational direction.

Structural basis of torque generation in the bi-directional bacterial flagellar motor.

The flagellar stator unit is an oligomeric complex of two membrane proteins (MotA5B2) that powers bi-directional rotation of the bacterial flagellum. Harnessing the ion motive force across the cytoplasmic membrane, the stator unit operates as a miniature rotary motor itself to provide torque for rotation of the flagellum. Recent cryo-electron microscopic (cryo-EM) structures of the stator unit provided novel insights into its assembly, function, and subunit stoichiometry, revealing the ion flux pathway and the torque generation mechanism. Furthermore, in situ cryo-electron tomography (cryo-ET) studies revealed unprecedented details of the interactions between stator unit and rotor. In this review, we summarize recent advances in our understanding of the structure and function of the flagellar stator unit, torque generation, and directional switching of the motor.

Diversity and phage sensitivity to phages of porcine enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is a diverse and poorly characterized E. coli pathotype that causes diarrhea in humans and animals. Phages have been proposed for the veterinary biocontrol of ETEC, but effective solutions require understanding of porcine ETEC diversity that affects phage infection. Here, we sequenced and analyzed the genomes of the PHAGEBio ETEC collection, gathering 79 diverse ETEC strains isolated from European pigs with post-weaning diarrhea (PWD). We identified the virulence factors characterizing the pathotype and several antibiotic resistance genes on plasmids, while phage resistance genes and other virulence factors were mostly chromosome encoded. We experienced that ETEC strains were highly resistant to Enterobacteriaceae phage infection. It was only by enrichment of numerous diverse samples with different media and conditions, using the 41 ETEC strains of our collection as hosts, that we could isolate two lytic phages that could infect a large part of our diverse ETEC collection: vB_EcoP_ETEP21B and vB_EcoS_ETEP102. Based on genome and host range analyses, we discussed the infection strategies of the two phages and identified components of lipopolysaccharides ( LPS) as receptors for the two phages. Our detailed computational structural analysis highlights several loops and pockets in the tail fibers that may allow recognition and binding of ETEC strains, also in the presence of O-antigens. Despite the importance of receptor recognition, the diversity of the ETEC strains remains a significant challenge for isolating ETEC phages and developing sustainable phage-based products to address ETEC-induced PWD.IMPORTANCEEnterotoxigenic Escherichia coli (ETEC)-induced post-weaning diarrhea is a severe disease in piglets that leads to weight loss and potentially death, with high economic and animal welfare costs worldwide. Phage-based approaches have been proposed, but available data are insufficient to ensure efficacy. Genome analysis of an extensive collection of ETEC strains revealed that phage defense mechanisms were mostly chromosome encoded, suggesting a lower chance of spread and selection by phage exposure. The difficulty in isolating lytic phages and the molecular and structural analyses of two ETEC phages point toward a multifactorial resistance of ETEC to phage infection and the importance of extensive phage screenings specifically against clinically relevant strains. The PHAGEBio ETEC collection and these two phages are valuable tools for the scientific community to expand our knowledge on the most studied, but still enigmatic, bacterial species-E. coli.

Aridity, availability of drinking water and freshwater foods, and hominin and archeological sites during the Late Pliocene-Early Pleistocene in the western region of the Turkana Basin (Kenya): A review.

Although the Turkana Basin is one of the driest regions of the East African Rift, its Plio-Pleistocene sediments are rich in freshwater vertebrates and invertebrates, providing evidence that freshwater resources were available to hominins in this region during the Plio-Pleistocene (4.2-0.7 Ma). Here we provide an overview of the hydroconnectivity of the Turkana Basin. We then review the period during which freshwater river and lake systems expanded into the western region of the Turkana Basin, where hominin and archeological sites have been discovered in sediments dating back to the Late Pliocene-Pleistocene. Freshwater conditions are reconstructed from river and lake sediments and the flora and micro- and macofauna they contain. Data synthesis suggests that drinking water and freshwater foods prevailed in the western region of the Turkana Basin at 4.20-3.98 Ma, 3.70-3.10 Ma, 2.53-2.22 Ma, then between 2.10 and 1.30 Ma and intermittently from 1.27 to 0.75 Ma. Milestones in hominin evolution occurred in this context, such as the first occurrence of Australopithecus anamensis (4.20-4.10 Ma) and Kenyanthropus platyops (3.50 Ma and 3.30-3.20 Ma), the presence of Paranthropus aethiopicus (2.53-2.45 Ma), early Homo (2.33 Ma), Paranthropus boisei (2.25 Ma and 1.77-1.72 Ma) and Homo ergaster/Homo erectus (1.75 Ma, 1.47-1.42 Ma and 1.10-0.90 Ma). Developments in hominin behavior also occurred during this timeframe, including the first known stone tools (3.30 Ma), the oldest Oldowan sites (2.34 Ma and 2.25 Ma) in the Turkana Basin, the earliest known evidence for the emergence of bifacial shaping in eastern Africa (1.80 Ma), and the first known Acheulean site (1.76 Ma). Our synthesis suggests that, diachronic variation in hydroconnectivity played a role on the amount of drinking water and freshwater foods available in the western region of the Turkana Basin, despite regional aridity.

Role of sentinel lymph node evaluation during hysterectomy for preoperative pathology diagnosis of endometrial intraepithelial neoplasia in a community hospital setting.

OBJECTIVE: To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC). METHODS: We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling. RESULTS: Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups. CONCLUSION: Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC.

Two thirds of patients may not need routine 12-month specialist review in an epilepsy clinic: A cross-sectional study of clinic appointments.

OBJECTIVES: Timely access to specialist outpatient clinics can be difficult to achieve as outpatient services are often oversubscribed leading to unacceptable wait times. New patients, or those with emergent issues may wait for appointments whilst existing patients are booked in for routine reviews "just in case" there is a problem, using considerable clinic resources. We investigated routine 12-month review appointments to assess whether these appointments changed patient management. METHODS: The medical records of 100 randomly selected adult patients attending annual review appointments over 12 months at a publicly-funded specialist outpatient epilepsy clinic in Melbourne, Australia were audited. Demographic and clinical data as well as information about the content of each appointment were analysed to determine whether the appointment resulted in changes to epilepsy management (eg medication change), administrative actions (eg drivers license approval) or the provision of information or education. Logistic regression was performed to assess what clinical factors were associated with changes in patient care arising from the 12-month review appointment. RESULTS: Almost half (47%) of appointments resulted in no change to patient care and 37% had only administrative outcomes, such as the completion of a regulatory driving report. Only 16% of appointments resulted in a change in medical management. The only factor that independently predicted a change in medical management was the occurrence of a seizure in the previous year. The only factor independently associated with not having any change in medical management or administrative action was having an unknown seizure type. CONCLUSIONS/ SIGNIFICANCE: Only a small number of patients experience a change in medical management when attending a 12-month epilepsy clinic appointment, with a need for management change associated with the presence of ongoing seizure. Outpatient services should limit the use of routine annual follow up to those patients most likely to need intervention or support, creating "just in time" capacity for timely access to review as issues arise.

Self-management strategies for people with epilepsy: An overview of reviews.

OBJECTIVE: This overview of systematic reviews aimed to appraise evidence regarding self-management strategies on health-related quality of life, self-efficacy, medication compliance, seizure status and psychosocial outcomes compared to usual care for people with epilepsy. METHODS: Databases were searched until September 2022 using MeSH terms included OVID Medline, Embase and Cochrane. Following application of eligibility criteria, data were extracted and quality of articles was assessed using the AMSTAR2 checklist. A narrative synthesis of evidence included certainty of evidence evaluated using a Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: The 12 selected reviews contained three meta-analyses and 91 unique primary studies. One review considered only epilepsy with intellectual disability and three considered paediatrics. Interventions included technologically-based interventions, small group discussion, or counselling and educational programs. There was high certainty evidence to suggest self-management is associated with improvement in health-related quality of life and moderate certainty evidence to suggest improvement in depression symptoms. There was low certainty evidence to suggest a modest reduction in negative health events and a minimal increase in the satisfaction with life. There was no evidence of benefit favouring self-management on measures of adherence epilepsy self-management, perception of self-efficacy, medication adherence or seizure status. SIGNIFICANCE: Despite high certainty evidence to suggest that self-management strategies for people with epilepsy improve health-related quality of life, benefits have not been demonstrated for outcomes that would be expected to be associated with these improvements, such as seizure status. These results provide support for self-management strategies to supplement usual care for people with epilepsy.

Cryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and substrate-bound states.

ABCG2 is a transporter protein of the ATP-binding-cassette (ABC) family that is expressed in the plasma membrane in cells of various tissues and tissue barriers, including the blood-brain, blood-testis and maternal-fetal barriers1-4. Powered by ATP, it translocates endogenous substrates, affects the pharmacokinetics of many drugs and protects against a wide array of xenobiotics, including anti-cancer drugs5-12. Previous studies have revealed the architecture of ABCG2 and the structural basis of its inhibition by small molecules and antibodies13,14. However, the mechanisms of substrate recognition and ATP-driven transport are unknown. Here we present high-resolution cryo-electron microscopy (cryo-EM) structures of human ABCG2 in a substrate-bound pre-translocation state and an ATP-bound post-translocation state. For both structures, we used a mutant containing a glutamine replacing the catalytic glutamate (ABCG2EQ), which resulted in reduced ATPase and transport rates and facilitated conformational trapping for structural studies. In the substrate-bound state, a single molecule of estrone-3-sulfate (E1S) is bound in a central, hydrophobic and cytoplasm-facing cavity about halfway across the membrane. Only one molecule of E1S can bind in the observed binding mode. In the ATP-bound state, the substrate-binding cavity has collapsed while an external cavity has opened to the extracellular side of the membrane. The ATP-induced conformational changes include rigid-body shifts of the transmembrane domains, pivoting of the nucleotide-binding domains (NBDs), and a change in the relative orientation of the NBD subdomains. Mutagenesis and in vitro characterization of transport and ATPase activities demonstrate the roles of specific residues in substrate recognition, including a leucine residue that forms a 'plug' between the two cavities. Our results show how ABCG2 harnesses the energy of ATP binding to extrude E1S and other substrates, and suggest that the size and binding affinity of compounds are important for distinguishing substrates from inhibitors.

'Making a connection': a qualitative study of experiences from a cancer telerehabilitation program.

PURPOSE: Specialised group-based exercise rehabilitation is beneficial for cancer survivors but access to these services is limited. Telerehabilitation provides an opportunity to expand reach, but we do not know about the experiences of those who participate in this way. This study explored participant experiences of an exercise-based telerehabilitation program for people with cancer. METHOD: A qualitative study using semi-structured interviews was completed. Twenty-two cancer survivors were purposively sampled from the experimental group of a randomised controlled trial evaluating exercise-based cancer telerehabilitation delivered in groups using synchronous videoconferencing. Interviews were audio-recorded and transcribed verbatim. Data were coded independently by two reviewers and analysed inductively by thematic analysis. RESULTS: 'A feeling of connection' was the overarching theme. Participants perceived they connected with the health service, expert health professionals, and peers through participating in the telerehabilitation program. These connections provided a personalised rehabilitation experience and improved perceptions of physical and emotional well-being. Two subthemes suggested connection was facilitated by (1) the acceptability of telerehabilitation and (2) enhanced accountability to exercise. Participants felt disconnected when they were unable to participate in the program due to cancer treatment and side effects (e.g. fatigue), feeling unwell, and co-morbidities. CONCLUSION: We identified that telerehabilitation facilitated connections that enhanced the reach of exercise to cancer survivors. Our findings support using telerehabilitation to deliver specialised group-based exercise programs alongside more traditional models of care to increase participation in exercise among people with cancer.

Hip fracture has profound psychosocial impacts: a systematic review of qualitative studies.

BACKGROUND: Hip fracture is a common and serious traumatic injury for older adults characterised by poor outcomes. OBJECTIVE: This systematic review aimed to synthesise qualitative evidence about the psychosocial impact of hip fracture on the people who sustain these injuries. METHODS: Five databases were searched for qualitative studies reporting on the psychosocial impact of hip fracture, supplemented by reference list checking and citation tracking. Data were synthesised inductively and confidence in findings reported using the Confidence in the Evidence from Reviews of Qualitative research approach, taking account of methodological quality, coherence, relevance and adequacy. RESULTS: Fifty-seven studies were included. Data were collected during the peri-operative period to >12 months post fracture from 919 participants with hip fracture (median age > 70 years in all but 3 studies), 130 carers and 297 clinicians. Hip fracture is a life altering event characterised by a sense of loss, prolonged negative emotions and fear of the future, exacerbated by negative attitudes of family, friends and clinicians. For some people after hip fracture there is, with time, acceptance of a new reality of not being able to do all the things they used to do. There was moderate to high confidence in these findings. CONCLUSIONS: Hip fracture is a life altering event. Many people experience profound and prolonged psychosocial distress following a hip fracture, within a context of negative societal attitudes. Assessment and management of psychosocial distress during rehabilitation may improve outcomes for people after hip fracture.

Preventing Sexual Harm in Nightlife Settings: A Scoping Review.

Sexual harm within nightlife settings is a pervasive global concern; however, little is known about the nature of available interventions. The current study aims to review the literature on the nature and effectiveness of nightlife-related sexual harm interventions. A systematic literature search of six databases was conducted to identify records that were published between 1970 and June 2023 and reported approaches that aimed to reduce or prevent nightlife-related sexual harm. Records were included if they theorized, discussed, or evaluated an intervention, prevention or response strategy; however, individual safety strategies were excluded. Results were categorized according to intervention type. Thirty-five peer-reviewed journal articles and 16 gray literature records were identified. The most common nightlife-related sexual harm intervention strategies covered by the literature included targeted policies, laws, and regulations, bystander interventions, and awareness-raising campaigns. Literature in the area is increasing, with the majority of the articles (77.1%) being published in the previous six years; however, there are very few interventions that have been critically evaluated (22.9%). Promising areas for intervention include targeted alcohol regulations (e.g., lockout policies), venue-level policies, and environmental interventions. However, an increase in rigorous evaluative practices is urgently required to ensure future interventions are based on sound theoretical work and empirical evidence.

Self-management Programs Within Rehabilitation Yield Positive Health Outcomes at a Small Increased Cost Compared With Usual Care: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine if self-management programs, supported by a health professional, in rehabilitation are cost effective. DATA SOURCES: Six databases were searched until December 2023. STUDY SELECTION: Randomized controlled trials with adults completing a supported self-management program while participating in rehabilitation or receiving health professional input in the hospital or community settings were included. Self-management programs were completed outside the structured, supervised therapy and health professional sessions. Included trials had a cost measure and an effectiveness outcome reported, such as health-related quality of life or function. Grading of Recommendations, Assessment, Development, and Evaluations was used to determine the certainty of evidence across trials included in each meta-analysis. Incremental cost-effectiveness ratios were calculated based on the mean difference from the meta-analyses of contributing health care costs and quality of life. DATA EXTRACTION: After application of the search strategy, two independent reviewers determined eligibility of identified literature, initially by reviewing the title and/or abstract before full-text review. Using a customized form, data were extracted by one reviewer and checked by a second reviewer. DATA SYNTHESIS: Forty-three trials were included, and 27 had data included in meta-analyses. Where self-management was a primary intervention, there was moderate certainty of a meaningful positive difference in quality-of-life utility index of 0.03 units (95% confidence interval, 0.01-0.06). The cost difference between self-management as the primary intervention and usual care (comprising usual intervention/therapy, minimal intervention [including education only], or no intervention) potentially favored the comparison group (mean difference=Australian dollar [AUD]90; 95% confidence interval, -AUD130 to AUD310). The cost per quality-adjusted life year (QALY) gained for self-management programs as a stand-alone intervention was AUD3000, which was below the acceptable willingness-to-pay threshold in Australia per QALY gained (AUD50,000/QALY gained). CONCLUSIONS: Self-management as an intervention is low cost and could improve health-related quality of life.

Understanding the influences on hospital discharge decision-making from patient, carer and staff perspectives.

BACKGROUND: Gaps in discharge planning are experienced by 41% of hospital patients in Australia. There is an established body of knowledge regarding the features of the discharge process that need to be improved to avoid subsequent hospital readmission and enhance the discharge experience. However, many of these studies have focused solely on factors related to unplanned hospital readmissions and there has been limited success in operationalising improvements to the discharge process. The aim of this study was to explore and describe the factors that influence the decision to discharge adult medical patients from hospital, from patient, carer and staff perspectives. METHODS: A qualitative descriptive study was conducted in one acute medical ward in Melbourne, Australia. The study data were collected by observations of clinical practice and semi-structured interviews with patients, carers and staff. Participants were: i) English-speaking adults identified for discharge home, ii) patient carers, and iii) staff involved in the discharge process. Observation data were analysed using content analysis and interviews data were analysed using thematic analysis. RESULTS: Twenty-one discharges were observed, and 65 participants were interviewed: 21 patients, two carers, and 42 staff. Most patients (76%) were identified as being ready for discharge during morning medical rounds, and 90% of discharge decisions were made collaboratively by the medical team and the patient. Carers were observed to be notified in 15 discharges by the patient (n = 8), doctors (n = 4), or nursing staff (n = 3). Five themes were constructed from thematic analysis of interviews: Readiness for Home, Fragmented Collaboration, Health Literacy, Unrealistic Expectations, and Care beyond Discharge. A collaborative team and supportive carers were considered to enhance risk assessment and discharge planning, however fragmented communication between clinicians, and between clinicians and patients/carers was a barrier to discharge decision-making. CONCLUSIONS: Our study highlights the need for a more coordinated approach to discharge decision-making that optimises communication with patients and carers and multidisciplinary workflows and reduces fragmentation. The importance of patient-centred care and a personalised approach to care are well established. However, there is a need to design systems to customise the entirety of the patient journey, including the approach to discharge decision making.

An evidence-based demand management strategy using a hub and spoke training model reduces waiting time for children's therapy services: An implementation trial.

BACKGROUND: Waiting lists for community-based paediatric therapy services are common and lead to poorer health outcomes, anxiety and missed opportunities for treatment during crucial developmental stages. The Specific Timely Appointments for Triage (STAT) model has been shown to reduce waiting lists in a range of health settings. AIMS: To determine whether providing training and support in the STAT model to champions within five community health centres using a remote 'hub and spoke' approach could reduce waiting time from referral to first appointment. METHODS: Representatives from five community health centres providing paediatric therapy services (speech therapy, occupational therapy and other allied health services) participated in five online workshops over 6 months. They were guided sequentially through the steps of the STAT model: understanding supply and demand, reducing backlogs, preserving space for new patients based on demand and redesigning models of care to maintain flow. Waiting time was measured in three consecutive years (pre, during and post intervention) and compared using the Kruskal-Wallis test. Employee satisfaction and perception of the model were explored using surveys. RESULTS: Data from 2564 children (mean age 3.2 years, 66% male) showed a 33% reduction in waiting time from the pre-intervention (median 57 days) to the post-intervention period (median 38 days, p < 0.01). The total number of children waiting was observed to reduce from 335 immediately prior to the intervention (mean per centre 67, SD 25.1) to 112 (mean 22, SD 13.6) after implementation (t[8] = 3.56, p < 0.01). There was no impact on employee satisfaction or other aspects of service delivery. CONCLUSION: Waiting lists are a major challenge across the health system. STAT provides a practical, low-cost, data-driven approach to tackling waiting times. This study demonstrates its effectiveness in paediatric therapy services and provides evidence for a 'hub and spoke' approach to facilitate implementation that could be provided at scale.

Structure and transformation of bacteriophage A511 baseplate and tail upon infection of Listeria cells.

Contractile injection systems (bacteriophage tails, type VI secretions system, R-type pyocins, etc.) utilize a rigid tube/contractile sheath assembly for breaching the envelope of bacterial and eukaryotic cells. Among contractile injection systems, bacteriophages that infect Gram-positive bacteria represent the least understood members. Here, we describe the structure of Listeria bacteriophage A511 tail in its pre- and post-host attachment states (extended and contracted, respectively) using cryo-electron microscopy, cryo-electron tomography, and X-ray crystallography. We show that the structure of the tube-baseplate complex of A511 is similar to that of phage T4, but the A511 baseplate is decorated with different receptor-binding proteins, which undergo a large structural transformation upon host attachment and switch the symmetry of the baseplate-tail fiber assembly from threefold to sixfold. For the first time under native conditions, we show that contraction of the phage tail sheath assembly starts at the baseplate and propagates through the sheath in a domino-like motion.

Recommendations for the management of hip and knee osteoarthritis: A systematic review of clinical practice guidelines.

OBJECTIVES: Guideline adherence for hip and knee osteoarthritis management is often poor, possibly related to the quality and/or inconsistent recommendations. This systematic review of hip and knee osteoarthritis guidelines aimed to appraise the quality and consistency in recommendations across higher-quality guidelines. METHODS: Eight databases, guideline repositories, and professional associations websites were searched on 27/10/2022. Guideline quality was appraised using the Appraisal of Guidelines for Research and Evaluation II (AGREE II tool) (six domains). Higher quality was defined as scoring ≥60% for domains 3 (rigour of development), 6 (editorial independence), plus one other. Consistency in recommendations across higher-quality guidelines was reported descriptively. This review was registered prospectively (CRD42021216154). RESULTS: Seven higher-quality and 18 lesser-quality guidelines were included. AGREE II domain scores for higher-quality guidelines were > 60% except for applicability (average 46%). Higher-quality guidelines consistently recommended in favour of education, exercise, and weight management and non-steroidal anti-inflammatory drugs (hip and knee), and intra-articular corticosteroid injections (knee). Higher quality guidelines consistently recommended against hyaluronic acid (hip) and stem cell (hip and knee) injections. Other pharmacological recommendations in higher-quality guidelines (e.g., paracetamol, intra-articular corticosteroid (hip), hyaluronic acid (knee)) and adjunctive treatments (e.g., acupuncture) were less consistent. Arthroscopy was consistently recommended against in higher-quality guidelines. No higher-quality guidelines considered arthroplasty. CONCLUSION: Higher-quality guidelines for hip and knee osteoarthritis consistently recommend clinicians implement exercise, education, and weight management, alongside consideration of Non-Steroidal Anti-Inflammatory Drugs and intra-articular corticosteroid injections (knee). Lack of consensus on some pharmacological options and adjunctive treatments creates challenges for guideline adherence. Future guidelines must prioritise providing implementation guidance, considering consistently low applicability scores.

Limb salvage in octogenarians with critical limb ischemia after lower extremity bypass surgery.

OBJECTIVES: Peripheral artery disease is a worldwide epidemic that affects millions of patients, especially the elderly. It has a prevalence of 20% in individuals >80 years old. Although peripheral artery disease affects >20% of octogenarians, information about limb salvage rates in this patient population is limited. Therefore, this study aims to understand the impact of bypass surgery on limb salvage in patients aged >80 years with critical limb ischemia. METHODS: We conducted a retrospective analysis by querying the electronic medical records at a single institution from 2016 through 2022 to identify the population of interest and analyzed their outcomes after lower extremity bypass. The primary outcomes were limb salvage and primary patency, with hospital length of stay and 1-year mortality as secondary outcomes. RESULTS: We identified 137 patients who met the inclusion criteria. The lower extremity bypass population was divided into two cohorts: <80 years old (n = 111) with a mean age of 66 or ≥80 years old (n = 26) with a mean age of 84 years. The gender distribution was similar (P = .163). No significant difference was found in the two cohorts when it came to coronary artery disease, chronic kidney disease, or diabetes mellitus. However, when current and former smokers were grouped together, they were significantly more common in the younger cohort when compared with nonsmokers (P = .028). The primary end point of limb salvage was not significantly different between the two cohorts. Hospital length of stay was not significantly different between the two cohorts with 4.13 days vs 4.17 days in the younger vs octogenarian cohorts, respectively (P = .95). The 30-day all-cause readmissions were also not found to be significantly different between the two groups. The primary patency at 1 year was 75% and 77% (P = .16) for the <80-year-old and ≥80-year-old cohorts, respectively. Mortality was low in both cohorts, with two and three for the younger and octogenarian populations, respectively; thus, no analysis was performed. CONCLUSIONS: Our study shows that octogenarians who undergo the same preoperative risk assessment as younger populations have similar outcomes when it comes to primary patency, hospital length of stay, and limb salvage when comorbidities were considered. Further studies need to be done to determine the statistical impact on mortality in this population with a larger cohort.

Structure of the human multidrug transporter ABCG2.

ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs and limits the delivery of therapeutics into tumour cells, thus contributing to multidrug resistance. Here we present the structure of human ABCG2 determined by cryo-electron microscopy, providing the first high-resolution insight into a human multidrug transporter. We visualize ABCG2 in complex with two antigen-binding fragments of the human-specific, inhibitory antibody 5D3 that recognizes extracellular loops of the transporter. We observe two cholesterol molecules bound in the multidrug-binding pocket that is located in a central, hydrophobic, inward-facing translocation pathway between the transmembrane domains. Combined with functional in vitro analyses, our results suggest a multidrug recognition and transport mechanism of ABCG2, rationalize disease-causing single nucleotide polymorphisms and the allosteric inhibition by the 5D3 antibody, and provide the structural basis of cholesterol recognition by other G-subfamily ABC transporters.

Professional care workforce: a rapid review of evidence supporting methods of recruitment, retention, safety, and education.

BACKGROUND: Across the care economy there are major shortages in the health and care workforce, as well as high rates of attrition and ill-defined career pathways. The aim of this study was to evaluate current evidence regarding methods to improve care worker recruitment, retention, safety, and education, for the professional care workforce. METHODS: A rapid review of comparative interventions designed to recruit, retain, educate and care for the professional workforce in the following sectors: disability, aged care, health, mental health, family and youth services, and early childhood education and care was conducted. Embase and MEDLINE databases were searched, and studies published between January 2015 and November 2022 were included. We used the Quality Assessment tool for Quantitative Studies and the PEDro tools to evaluate study quality. RESULTS: 5594 articles were initially screened and after applying the inclusion and exclusion criteria, 30 studies were included in the rapid review. Studies most frequently reported on the professional nursing, medical and allied health workforces. Some studies focused on the single domain of care worker education (n = 11) while most focused on multiple domains that combined education with recruitment strategies, retention strategies or a focus on worker safety. Study quality was comparatively low with a median PEDro score of 5/10, and 77% received a weak rating on the Quality Assessment tool for Quantitative Studies. Four new workforce strategies emerged; early career rural recruitment supports rural retention; workload management is essential for workforce well-being; learning must be contextually relevant; and there is a need to differentiate recruitment, retention, and education strategies for different professional health and care workforce categories as needs vary. CONCLUSIONS: Given the critical importance of recruiting and retaining a strong health and care workforce, there is an immediate need to develop a cohesive strategy to address workforce shortfalls. This paper presents initial evidence on different interventions to address this need, and to inform care workforce recruitment and retention. Rapid Review registration PROSPERO 2022 CRD42022371721 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022371721.

A walking programme for adults living in the community after hip fracture: A feasibility randomized controlled trial.

OBJECTIVE: To test the feasibility of a walking programme for community-dwelling adults recovering from hip fracture. DESIGN: A randomized controlled trial with embedded qualitative analysis. SETTING: Community. PARTICIPANTS: Aged at least 60 years and living in the community after hip fracture. INTERVENTIONS: In addition to standard care, the experimental group received weekly home-based physiotherapy for 12 weeks to facilitate 100 minutes/week of moderate-intensity walking. MAIN OUTCOME MEASURES: Feasibility domains of demand, acceptability, implementation, practicality and limited efficacy. RESULTS: Of 158 potentially eligible, 38 participated (23 women, mean age 80 years, SD 9). The recruitment rate of 24% indicated low demand. Participants considered the walking programme highly acceptable. The programme was implemented as intended; the experimental group received a mean of 11 (SD 1) consultations and averaged more than 100 min of walking per week. The programme was practical with no serious adverse events and no between-group difference in risk of falling or hospital readmissions. Demonstrating evidence of efficacy, there were moderate standardized mean differences for physical activity favouring the experimental group, who increased daily moderate-intensity physical activity compared to the control group (MD 8 min, 95% CI 2-13). There were no between-group differences in mobility, walking confidence or quality of life. CONCLUSION: A walking programme for community-dwelling older adults after hip fracture was acceptable, could be implemented as intended and was practical and demonstrated preliminary evidence of efficacy in increasing physical activity. However, low demand would threaten the feasibility of such a programme.