The septin cytoskeleton is required for plasma membrane repair.

Plasma membrane repair is a fundamental homeostatic process of eukaryotic cells. Here, we report a new function for the conserved cytoskeletal proteins known as septins in the repair of cells perforated by pore-forming toxins or mechanical disruption. Using a silencing RNA screen, we identified known repair factors (e.g. annexin A2, ANXA2) and novel factors such as septin 7 (SEPT7) that is essential for septin assembly. Upon plasma membrane injury, the septin cytoskeleton is extensively redistributed to form submembranous domains arranged as knob and loop structures containing F-actin, myosin IIA, S100A11, and ANXA2. Formation of these domains is Ca2+-dependent and correlates with plasma membrane repair efficiency. Super-resolution microscopy revealed that septins and F-actin form intertwined filaments associated with ANXA2. Depletion of SEPT7 prevented ANXA2 recruitment and formation of submembranous actomyosin domains. However, ANXA2 depletion had no effect on domain formation. Collectively, our data support a novel septin-based mechanism for resealing damaged cells, in which the septin cytoskeleton plays a key structural role in remodeling the plasma membrane by promoting the formation of SEPT/F-actin/myosin IIA/ANXA2/S100A11 repair domains.

Venous thromboembolism After Knee Arthroscopy: Incidence, Risk Factors, Prophylaxis, and Management.

Venous thromboembolism (VTE), comprising pulmonary embolism and deep vein thrombosis, is one of the most common complications after knee arthroscopy. Sequelae of VTE include VTE recurrence, postthrombotic syndrome, and potential for loss of limb or life. Given the increasing volume of knee arthroscopy procedures worldwide and the considerable morbidity and mortality associated with VTE, it is important to prevent, diagnose, and treat VTEs efficiently and effectively. Risk factors such as history of VTE, family history of VTE, genetic coagulopathy, oral contraceptive use, cancer history, and old age increase the risk of postoperative VTE and warrant consideration of prophylaxis. Diagnosis and treatment should be initiated rapidly in the setting of concerning symptoms and positive imaging diagnosis, respectively. The purpose of this review was to provide a framework to individualized VTE risk, weigh prophylaxis options, expedite diagnostic pathways, and implement outpatient treatment algorithms.

Management of Massive Flank Hernia After Lateral Lumbar Fusion: Preoperative Botulinum Toxin Injections and Open Repair - A Case Report.

BACKGROUND Incisional flank hernias represent a complication after lateral lumbar spine surgery. Given the increasing rate of lateral lumbar interbody fusions, the rate of incisional flank hernias will increase. Since there are no reports of open massive flank hernia repair utilizing preoperative botulinum injections, we sought to publish this technique to provide surgeons with an innovative method for preoperatively treating patients with massive flank hernias. CASE REPORT A 75-year-old man with a history of coronary artery disease, chronic kidney disease, and abdominal hernia repair presented for evaluation of left lateral abdominal and left lower back bulging for 5 months. The symptoms began after an L2-L4 lateral lumbar spinal fusion. Physical examination revealed a left posterior lateral flank bulge. Computed tomography (CT) showed a fat-containing left posterolateral abdominal hernia. The patient was scheduled for CT-guided lateral abdominal wall botulinum injections, followed by open flank hernia repair. He tolerated the surgery well, was admitted for pain control, and discharged on day 2. Repeat imaging with CT at 3 months showed no evidence of patient's prior hernia defect. CONCLUSIONS Open flank hernia repair, in conjunction with preoperative botulinum toxin injections, allows for optimal visualization and re-approximation of the myofascial components of flank hernia defects. Failure to achieve adequate myofascial and skin closure, along with mesh reinforcement, in open flank hernia repair can result in various surgical site complications, including incisional flank hernia recurrence. We recommend further investigation on the benefits of botulinum injections as an adjunct in management of massive flank hernias.

A Mixed-Methods Cohort Study Evaluating the Impact of a One-Day Well-Being Course for Anesthesia Providers Working in Low-Resource Settings.

BACKGROUND: Burnout, depression, and anxiety are increasingly recognized as common among health care providers. Risks for these conditions are exacerbated in low-resource settings by excessive workload, high disease burden, resource shortage, and stigma against mental health issues. Based on discussions and requests to learn more about burnout during the Vital Anaesthesia Simulation Training (VAST), our team developed VAST Wellbeing, a 1-day course for health care providers in low-resource settings to recognize and mitigate burnout and to promote personal and professional well-being. METHODS: This mixed-methods study used quantitative pre- and postcourse surveys using validated mental health measures and qualitative semistructured interviews to explore participants' experience of VAST Wellbeing during and after the course. Quantitative outcomes included burnout and professional fulfillment as measured by the Professional Fulfillment Index and general well-being as measured by the Warwick-Edinburgh Mental Wellbeing Scale. RESULTS: Twenty-six participants from 9 countries completed the study. In the immediate postcourse survey, study participants rated the course overall as "very good" (60.7%) and "excellent" (28.6%). Quantitative analysis showed no statistical differences in levels of work exhaustion, interpersonal disengagement, burnout, professional fulfillment, or general mental well-being 2 months after the course. Five themes on the impact of VAST Wellbeing were identified during qualitative analysis: (1) raising awareness, breaking taboos; (2) not feeling alone; (3) permission and capacity for personal well-being; (4) workplace empowerment; and (5) VAST Wellbeing was relevant, authentic, and needed. CONCLUSIONS: Causes of burnout are complex and multidimensional. VAST Wellbeing did not change measures of burnout and fulfillment 2 months postcourse but did have a meaningful impact by raising awareness, reducing stigma, fostering connection, providing skills to prioritize personal well-being, and empowering people to seek workplace change.

A simulation-guided approach to the selection of RPLC columns for platform small molecule separations.

Simulations were conducted to evaluate the potential of several hundred reversed-phase columns to separate small molecules. By calculating the retention factor of compounds in randomly generated virtual mixtures via the HSM (hydrophobic subtraction model) and applying basic chromatography theory, the simulation can estimate the retention time and peak width of every virtual compound and calculate the resolution between every adjacent pair of compounds. A preferred column set based on the number of successful separations of randomly generated virtual mixtures was developed. The tandem-column liquid chromatography (TC-LC) approach can separate 53.2 % of the 16-compound samples using 20 tandem-column pairs, while a single-column approach can only separate 42.6 % of the 16-compound samples with 20 single columns. The preferred set of columns obtained from the simulation was almost the same as the empirical set of columns previously obtained. In screening applications, TC-LC can achieve a comparably successful separation factor (selectivity) with a smaller column inventory (nine 50-mm columns) compared to the larger inventory needed by single-column LC (twenty-one 100-mm columns).

Exploring experiences of people with knee osteoarthritis who received a physiotherapist-delivered dietary weight loss and exercise intervention: a mixed methods study.

OBJECTIVE: Explore the experiences of people with knee osteoarthritis who received a very low energy diet (VLED) and exercise program from a physiotherapist. METHODS: Mixed methods study involving questionnaires (n=42) and semi-structured interviews (n=22) with randomized control trial participants with knee osteoarthritis who had received a 6-month physiotherapist-delivered VLED weight loss and exercise intervention. Questionnaires measured participant satisfaction, and perceptions about physiotherapist's skills/knowledge in delivery of the dietary intervention (measured on 5-7 point Likert scales). Interviews explored participant's experiences and were analysed based on the principles of reflexive thematic analysis. RESULTS: Questionnaire response: 90%. Participants were satisfied with the program (95%), confident their physiotherapist had the required skills (84%) and knowledge (79%) to deliver the dietary intervention, felt comfortable talking to the physiotherapist about weight (74%), and would recommend others see a physiotherapist for the intervention they undertook (71%). Four themes were developed from the interviews: 1) one-stop-shop of exercise and diet; 2) physiotherapist-delivered weight loss works (unsure initially; successfully lost weight); 3) physiotherapists knowledge and skills (exercise is forte; most thought physiotherapists had the necessary weight loss skills/knowledge, but some disagreed); 4) physiotherapists have a role in weight loss (physiotherapists are intelligent, credible, and trustworthy; specific training in weight loss necessary). CONCLUSION: This study provides, to our knowledge, the first documented perspectives from people with osteoarthritis who have received a physiotherapist-delivered weight loss intervention. Findings suggest physiotherapists may have a role in delivering a protocolised dietary intervention for some people with knee osteoarthritis with overweight and obesity.

Evaluating surgeon communication of pancreatic cancer prognosis using the VitalTalk ADAPT framework.

BACKGROUND AND OBJECTIVES: Few data exist to guide optimal communication practices for surgical oncologists. VitalTalk, an evidence-based communication skills training model for clinicians, offers the five-step ADAPT tool for discussing prognosis. This study aimed to characterize surgeon communication of pancreatic cancer prognosis using VitalTalk's ADAPT framework. METHODS: Contemporaneous audio recordings from 12 initial surgeon-patient encounters for borderline resectable pancreatic cancer were transcribed. Directed qualitative content analysis based on ADAPT (Ask, Discover, Anticipate, Provide, and Track) was used to deductively code transcripts. RESULTS: All encounters contained at least one ADAPT step while only one (8%) incorporated four or five steps. Surgeons provided prognostic information (Provide) in all but one encounter (92%); most was qualitative and clustered into themes: serious illness, surgical candidacy, prognostic ambiguity, and cancer recurrence. Surgeons elicited understanding (Ask), requested information preferences (Discover), anticipated ambivalence (Anticipate), and responded to emotion (Track) in a minority of encounters (25%-42%); of 15 patient emotional cues, six were not addressed by surgeons. CONCLUSIONS: During an initial encounter for pancreatic cancer, surgeons focus heavily on providing information but omit critical prognostic communication steps. Future studies are needed to investigate if surgeon training in palliative care-based communication is feasible and impacts patient-perceived quality of communication.

Dopamine transmission at D1 and D2 receptors in the nucleus accumbens contributes to the expression of incubation of cocaine craving.

Relapse represents a consistent clinical problem for individuals with substance use disorder. In the incubation of craving model of persistent craving and relapse, cue-induced drug seeking progressively intensifies or 'incubates' during the first weeks of abstinence from drug self-administration and then remains high for months. Previously, we and others have demonstrated that expression of incubated cocaine craving requires strengthening of excitatory synaptic transmission in the nucleus accumbens core (NAcc). However, despite the importance of dopaminergic signaling in the NAcc for motivated behavior, little is known about the role that dopamine (DA) plays in the incubation of cocaine craving. Here we used fiber photometry to measure DA transients in the NAcc of male and female rats during cue-induced seeking tests conducted in early abstinence from cocaine self-administration, prior to incubation, and late abstinence, after incubation of craving has plateaued. We observed DA transients time-locked to cue-induced responding but their magnitude did not differ significantly when measured during early versus late abstinence seeking tests. Next, we tested for a functional role of these DA transients by injecting DA receptor antagonists into the NAcc just before the cue-induced seeking test. Blockade of either D1 or D2 DA receptors reduced cue-induced cocaine seeking after but not before incubation. We found no main effect of sex in our experiments. These results suggest that DA contributes to incubated cocaine seeking but the emergence of this role reflects changes in postsynaptic responsiveness to DA rather than presynaptic alterations.

Implementation and evaluation of a community-based mindful walking randomized controlled trial to sustain cognitive health in older African Americans at risk for dementia.

BACKGROUND: With an increasing proportion of older adults and the associated risk of Alzheimer's Disease and Related Dementias (ADRD) around the globe, there is an urgent need to engage in ADRD risk reduction efforts. African American (AA) older adults in the U.S. are disproportionally impacted by ADRD compared to other races and ethnicities. Mindful walking integrates two potentially protective factors of ADRD by elevating mindfulness and physical activity (i.e., walking), resulting in a synergistic behavioral strategy that is feasible and safe for older adults. However, the efficacy of applying this intervention for cognitive health outcomes has not been evaluated using experimental designs. METHODS: This paper documents the goal and protocol of a community-based, mindful walking randomized controlled trial to examine the short- and longer-term efficacy on cognitive and other health-related outcomes in ADRD at-risk AA older adults. The study outcomes include various brain health determinants, including cognitive function, quality of life, psychological well-being, physical activity, mindfulness, sleep, and overall health status. In addition, the estimated costs of program implementation are also collected throughout the study period. This study will recruit 114 older adults (ages 60+ years) with elevated ADRD risk from the Midlands region of South Carolina. Older adults are randomly assigned to participate in 24 sessions of outdoor mindful walking over three months or a delayed mindful walking group (n=57 in each group). Participants in both groups follow identical measurement protocols at baseline, after 12 weeks, after 18 weeks, and after 24 weeks from baseline. The outcome measures are administered in the lab and in everyday settings. Costs per participant are calculated using micro-costing methods. The eliciting participant costs for mindful walking engagement with expected results are reported using the payer and the societal perspectives. DISCUSSION: This study will generate evidence regarding the efficacy of mindful walking on sustaining cognitive health in vulnerable older adults. The results can inform future large-scale effectiveness trials to support our study findings. If successful, this mindful walking program can be scaled up as a low-cost and viable lifestyle strategy to promote healthy cognitive aging in diverse older adult populations, including those at greatest risk. TRIAL REGISTRATION: ClinicalTrials.gov number NCT06085196 (retrospectively registered on 10/08/2023).

Prophylactic somatostatin analogs for postoperative pancreatic fistulas: a cross-sectional survey of AHPBA surgeons.

BACKGROUND: Postoperative pancreatic fistulas lead to substantially increased morbidity, mortality, and healthcare costs after pancreatectomy. Studies have reported conflicting data on the role of prophylactic somatostatin analogs in the reduction of postoperative pancreatic fistula. Current practice patterns, surgeon beliefs, and barriers to using these drugs in the Americas is not known. METHODS: An online 26-question cross-sectional survey was distributed via email to the members of the Americas Hepato-Pancreato-Biliary Association in April 2023. RESULTS: One hundred and two surgeons responded in spring 2023. 48.0% of respondents reported using prophylactic SSAs during their surgical training, however, only 29.4% do so in their current practice, most commonly when performing Whipple procedures. Octreotide was the most frequently used SSA (34.3%), followed by octreotide LAR (12.7%) and pasireotide (11.8%). Reasons for not prescribing included a lack of high-quality data (62.7%), perception of limited efficacy (34.3%) and high cost (30.4%). CONCLUSION: These results highlight key areas for future study including understanding surgeon rationale for patient and drug selection. Variable practice patterns amongst surgeons also underscore the importance of generalizability in the design of future clinical trials in order to maximize impact.

Correction: Clinical reasoning education in the clerkship years: A cross-disciplinary national needs assessment.

[This corrects the article DOI: 10.1371/journal.pone.0273250.].

Association of Symptoms and Collaborative Care Intervention (TACcare) with Systemic Inflammation Biomarkers in End-Stage Kidney Disease.

BACKGROUND: Patient-reported symptoms are associated with inflammation biomarkers in many chronic diseases. We examined associations of inflammation biomarkers with pain, fatigue, and depression in patients with end-stage kidney disease (ESKD) and the effects of a Technology Assisted stepped Collaborative Care (TACcare) intervention on these biomarkers. METHODS: In the TACcare multi-site randomized control trial, data on patient-reported symptoms were collected at baseline, 3, and 6 months. Anti-inflammatory [interleukin 1 receptor agonist (IL-1RA), IL-10], pro-inflammatory [tumor necrosis factor alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), IL-6] and regulatory [IL-2] biomarkers were assayed. Linear mixed-effects modeling was used to examine within- and between-group differences after adjusting for age, sex, race, and comorbidities. RESULTS: Among the 160 patients (mean age 58±14 years, 55% men, 52% white), there were no significant associations between inflammation biomarkers and pain, fatigue or depression at baseline. Both intervention and control group demonstrated reductions in IL-10 and IL-1RA over 6 months (ß range=-1.22 to -0.40, p range=<0.001 to 0.02) At 3 months, the treatment group exhibited decreases in TNF-α (ß=-0.22, p<0.001) and IL-2 (ß=-0.71, p<0.001), whereas the control group showed increases in IL-6/IL-10 ratio (ß=0.33, p=0.03). At 6 months, both groups exhibited decreases in IL-2 (ß range=-0.66 to -0.57,p<0.001); the control group showed significant increases in the ratio of IL-6/IL-10 (ß=0.75,p<0.001) and decrease in TNF-α (ß=-0.16, p=0.02). Compared to controls, the treatment group demonstrated significantly decreased IL-2 at 3 months (ß=-0.53, p<0.001). Significant interaction effects of treatment were observed on the association between changes in pro-inflammatory biomarkers (TNF-α and hs-CRP) levels and changes in symptom scores from baseline to 6 months. CONCLUSIONS: The TACcare intervention had a short-term impact on reducing inflammatory burden in patients with ESKD. More studies are needed to confirm our findings and to determine if these biomarkers mediate the link between symptoms and disease progression.

Spaceflight-associated pain.

PURPOSE OF REVIEW: Consequences of the expanding commercial spaceflight industry include an increase in total number of spaceflight participants and an accompanying surge in the average number of medical comorbidities compared with government-based astronaut corps. A sequela of these developments is an anticipated rise in acute and chronic pain concerns associated with spaceflight. This review will summarize diagnostic and therapeutic areas of interest that can support the comfort of humans in spaceflight. RECENT FINDINGS: Painful conditions that occur in space may be due to exposure to numerous stressors such as acceleration and vibration during launch, trauma associated with extravehicular activities, and morbidity resulting directly from weightlessness. Without normal gravitational forces and biomechanical stress, the hostile environment of space causes muscle atrophy, bone demineralization, joint stiffness, and spinal disc dysfunction, resulting in a myriad of pain generators. Repeated insults from abnormal environmental exposures are thought to contribute to the development of painful musculoskeletal and neuropathic conditions. SUMMARY: As humanity invests in Lunar and Martian exploration, understanding the painful conditions that will impede crew productivity and mission outcomes is critical. Preexisting pain and new-onset acute or chronic pain resulting from spaceflight will require countermeasures and treatments to mitigate long-term health effects.

Near-Peer Paradigms in Medical School: Integrating Student Teaching Assistants Into a Core Radiology Clerkship.

RATIONALE AND OBJECTIVES: Near-peer paradigms have been demonstrated effective in supporting how students navigate novel clinical environments. In this study, we describe an innovative model of incorporating teaching assistants (TAs) into a core radiology clerkship and investigate both its perceived educational value by clinical-year learners and its perceived impact on professional growth by TAs. MATERIALS AND METHODS: At one U.S. medical school, the core clinical year includes a clerkship in radiology incorporating both reading room exposure and a didactic curriculum. Radiology faculty deliver a variety of traditional and interactive, "dynamic" lectures, while medical student TAs deliver additional dynamic sessions, including a final TA-created review session. The educational value of each didactic session by clerkship students was assessed using a five-point scale survey, and the professional value of the experience by TAs was assessed using a five-point Likert survey. RESULTS: Spanning from 2020 to 2023, 268 (74.4%) clinical-year students submitted the post-clerkship survey, with the didactic review sessions created and led by TAs receiving the highest ratings of any didactic session. Of 16 former TAs, 12 (75%) completed the post-service survey, with all respondents agreeing or strongly agreeing that they enjoyed and would recommend their experience, and that it enhanced their interest in radiology and in academic medicine. CONCLUSION: Near-peer education in a core radiology clerkship enhances the experience of the learner through peer guidance and the experience of the teacher through professional development. These findings may increase student interest in pursuing academic radiology as a career and invite opportunities for broadening medical school education in radiology.

Discriminative Ability of Dye Injected Into a Meat Model to Determine Accuracy of Ultrasound-Guided Injection.

INTRODUCTION: The utility of using meat models for ultrasound-guided regional anesthesia simulation training has been well established. Feedback is considered the most important element of successful simulation-based education, and simulation offers an opportunity for evaluation. The objective of this study was to establish the discriminative ability of dye injected into a meat model to determine whether injectate is properly placed in the perineural (PN) space, thus providing an additional tool for learner feedback and evaluation. METHODS: Meat models containing a beef tendon (simulating a nerve) were injected with dye in one of 3 locations: PN, intraneural, and intramuscular. Blinded assessors then independently interpreted the dye staining on the models, marked the interpreted injection location, ease of interpretation, and whether staining was present on the beef tendon. RESULTS: Thirty meat models were injected with dye and independently assessed. Determining the location of injection was deemed to be easy or very easy in 72% of the models. Assessors correctly identified PN, intraneural, and intramuscular injections 100%, 95%, and 85% of the time, respectively. Assessor agreement was 87%. CONCLUSIONS: The location of dye injected into a meat model, simulating a peripheral nerve blockade, can be accurately and reliably scored to provide feedback to learners. This technique offers a novel means of providing feedback to trainees and assessing block success in ultrasound-guided regional anesthesia simulation.

Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training. METHODS: We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness. RESULTS: Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight). CONCLUSION: Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

Correlation of ablation volume with renal function loss after cryoablation in solitary functioning kidneys.

PURPOSE: The purpose of this study was to retrospectively analyze the degree of renal function deterioration after renal cryoablation in patients with a solitary functioning kidney based on ablation volume. MATERIALS AND METHODS: Over a 15-year period, 81 percutaneous cryoablations were performed in solitary functioning kidneys. After exclusion of patients with baseline end-stage renal disease(ESRD) and insufficient follow up, analysis was performed on 65 procedures in 52 patients (40 male, mean age 63.5 years). The post-cryoablation renal function was based on the lowest serum creatinine within 6 months post-procedure. Renal function change was defined as percentage glomerular filtration rate(GFR) change. Volumetric analysis was performed on the target lesion, renal parenchyma, and ablation zone. RESULTS: The median tumor diameter was 2.0cm (range 0.8-4.7cm). The median baseline GFR decreased from 56.4 mL/min/1.73m2 (range 17.5-89.7) to 46.9 (range 16.5-89.7) at median 95 days (p<0.001), equating to an -7.9% median renal function change (range -45.0 to +30.7). All patients had stage 2 or worse chronic kidney disease and baseline function did not correlate with renal function change. The median volume of ablated parenchyma was 19.7mL (range 2.4-87.3mL), equating to 8.1% (range 0.7-37.2%) of total parenchyma. The volume of parenchymal volume ablated correlated significantly with renal function loss, while age, hypertension, and diabetes mellitus did not. No patients developed ESRD within 1 year after cryoablation. CONCLUSION: Cryoablation in solitary functioning kidneys resulted in a modest reduction in renal function, even in patients with chronic kidney disease and ablations up to 20% of renal parenchymal volume.