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Introduction: Enhanced recovery after surgery (ERAS) protocols have been implemented to decrease opioid use and decrease patient hospital length of stay (LOS, days). Serratus anterior plane (SAP) blocks anesthetize the T2 through T9 dermatomes of the breast and can be applied intraoperatively. The purpose of this study was to compare postoperative opioid (OME) consumption and LOS between a control group, an ERAS group, and an ERAS/local anesthetic cocktail group in patients who underwent implant-based breast reconstruction. Methods: In this study, 142 women who underwent implant-based breast reconstruction between 2004 and 2020 were divided into Group A (46 patients), a historical cohort; Group B (73 patients), an ERAS/no-block control group; and Group C (23 patients), an ERAS/anesthetic cocktail study group. Primary outcomes of interest were postanesthesia care unit (PACU), inpatient and total hospital OME consumption, and PACU LOS. Results: A significant decrease was observed from Group A to C in PACU LOS (103.3 vs. 80.2 vs. 70.5; p = 0.011), OME use (25.1 vs. 11.4 vs. 5.7; p < 0.0001), and total hospital OME (120.3 vs. 95.2 vs. 35.9; p < 0.05). No difference was observed in inpatient OMEs between the three groups (95.2 vs. 83.8 vs. 30.8; p = 0.212). Despite not reaching statistical significance, Group C consumed an average of 50–60 % less opioids per patient than did Group B in PACU, inpatient, and total hospital OMEs. Conclusion: Local anesthetic blocks are important components of ERAS protocols. Our results demonstrate that a combination regional block with a local anesthetic cocktail in an ERAS protocol can decrease opioid consumption in implant-based breast reconstruction.

Summary: Serotonin (5-HT) modulates early development during critical periods when experience drives heightened levels of plasticity in neurons. Here, we investigate the cellular mechanisms by which 5-HT modulates critical period plasticity (CPP) in the olfactory system of Drosophila. We first demonstrate that 5-HT is necessary for experience-dependent structural plasticity in response to chronic CO2 exposure and can re-open the critical period long after it normally closes. Knocking down 5-HT7 receptors in a subset of GABAergic local interneurons was sufficient to block CPP, as was knocking down GABA receptors expressed by CO2-sensing olfactory sensory neurons (OSNs). Furthermore, direct modulation of OSNs via 5-HT2B receptors in CO2-sensing OSNs and autoreceptor expression by serotonergic neurons was also required for CPP. Thus, 5-HT targets individual neuron types in the olfactory system via distinct receptors to enable sensory driven plasticity.

Radiotherapy (RT) is one of major therapeutic modalities in combating breast cancer. In RT, ionizing radiation is employed to induce DNA double-strand breaks (DSBs) as a primary mechanism that causes cancer cell death. However, the induced DNA damage can also trigger the activation of DNA repair mechanisms, reducing the efficacy of RT treatment. Given the pivotal role of RAD50 protein in the radiation-responsive DNA repair pathways involving DSBs, we developed a novel polymer-lipid based nanoparticle formulation containing RAD50-silencing RNA (RAD50-siRNA-NPs) and evaluated its effect on the RAD50 downregulation as well as cellular and tumoral responses to ionizing radiation using human triple-negative breast cancer as a model. The RAD50-siRNA-NPs successfully preserved the activity of the siRNA, facilitated its internalization by cancer cells via endocytosis, and enabled its lysosomal escape. The nanoparticles significantly reduced RAD50 expression, whereas RT alone strongly increased RAD50 levels at 24 h. Pretreatment with RAD50-siRNA-NPs sensitized the cancer cells to RT with ∼2-fold higher level of initial DNA DSBs as determined by a γH2AX biomarker and a 2.5-fold lower radiation dose to achieve 50 % colony reduction. Intratumoral administration of RAD50-siRNA-NPs led to a remarkable 53 % knockdown in RAD50. The pretreatment with RAD50-siRNA-NPs followed by RT resulted in approximately a 2-fold increase in DNA DSBs, a 4.5-fold increase in cancer cell apoptosis, and 2.5-fold increase in tumor growth inhibition compared to RT alone. The results of this work demonstrate that RAD50 silencing by RAD50-siRNA-NPs can disrupt RT-induced DNA damage repair mechanisms, thereby significantly enhancing the radiation sensitivity of TNBC MDA-MB-231 cells in vitro and in orthotopic tumors as measured by colony forming and tumor regrowth assays, respectively.

Purpureocillium lilacinum and Fusarium species are increasingly recognized as significant opportunistic fungal pathogens. We report a rare case of co-infection in a 63-year old heart transplant recipient presenting with nodular skin lesions, treated successfully with voriconazole. We highlight the importance of being vigilant about co-infection with moulds as it impacts on the selection of appropriate antifungal agents. 2012 Elsevier Ltd. All rights reserved.

Invasive fungal infection is a life-threatening complication of chemotherapy and neutropaenia in the haematology population. Trichoderma species rarely cause human disease but have been reported to cause invasive infection in the immunosuppressed. We present a case of invasive Trichoderma longibrachiatum pulmonary infection with fatal outcome in a neutropaenic patient with acute myeloid leukaemia. 2012 Elsevier Ltd. All rights reserved.

Coronary artery disease is the most common cause of heart failure, which is the leading cause of cardiovascular-related death worldwide. There are insufficient data to make strong recommendations for percutaneous coronary intervention (PCI) in patients with severe ischemic left ventricular systolic dysfunction (LVSD). In that context, we performed a meta-analysis to compare the outcomes of PCI with those of optimal medical therapy alone in patients with severe ischemic LVSD. A systematic search was conducted in PubMed, EMBASE, and ClinicalTrials.gov from inception to December 2023. Our outcome of interest was all-cause mortality in patients undergoing PCI vs medical therapy. We used random effects models to aggregate data and to calculate pooled incidence and relative risk with 95% CIs. Four studies including 2 randomized controlled trials with 2080 patients (PCI, 1082; optimal medical therapy, 998) were included. All-cause mortality did not differ significantly between the groups: 168 patients (15.5%) in the PCI group vs 200 patients (20.0%) in the optimal medical therapy group (relative risk, 0.88; 95% CI, 0.75-1.09; P=.25). In conclusion, the available evidence indicates that PCI does not improve all-cause mortality in patients with severe LVSD without lifestyle-limiting anginal symptoms. Further data are needed to identify subgroups of patients better served by each modality.

Background: Proximal humerus fractures are the third most common fracture type for patients between the ages of 65 and 89 and occur more frequently in women than men. Given the variety of surgical treatments for proximal humerus fractures, the aim of this study was to (1) report United States national volume and incidence estimates for surgical management of proximal humerus fractures to better understand the changing practice over the past decade and (2) to analyze differences in volume and incidence among age groups, sex, and geographic region. Methods: Using IBM Marketscan national database, all patients that underwent open reduction internal fixation (ORIF), hemiarthroplasty, or reverse total shoulder arthroplasty (RTSA) between 2010 and 2019 were identified with Current Procedural Terminology codes. The dataset was further stratified to identify patients treated for proximal humerus fractures. IBM Marketscan provided discharge weights that were used to determine estimated national annual volumes of each procedure in IBM SPSS Statistics software (IBM Corp., Armonk, NY, USA). Volume and incidence were adjusted per 1,000,000 persons and calculated for subgroups according to age group, sex, and geographical region. The United States Census Bureau annual population data was used for all incidence calculations. Results: Over the past decade, the total volume and incidence of surgically treated proximal humerus fractures increased by 13% and 5%, respectively. Although overall incidence decreased, ORIF remained the most common surgical treatment. The greatest decrease in volume and incidence of ORIF occurred in patients ≥75. The incidence of ORIF treatment increased in the South and West while it decreased in the Northeast and Midwest. Total volume and incidence of HA decreased between 2010 and 2019 and this trend remained among all subgroups. Total volume and incidence of RTSA increased by over 300%. The incidence of males and females receiving RTSA increased by 266% and 320%, respectively. Volume and incidence of RTSA increased across all age groups. Volume and incidence of RTSA increased in the Midwest, South, and Western regions while it remained unchanged in the Northeast. Conclusion: Surgical management trends of proximal humerus fractures have changed greatly over the past decade. ORIF remains the most common surgical treatment for proximal humerus fractures. HA has fallen out of favor while RTSA has seen significant increases in usage across sex, age groups, and geographic regions. These trends represent a change in practice for treating proximal humerus fractures by considering all patient and fracture characteristics when opting for surgical management.

The burden of noncommunicable chronic diseases has relevant and negative consequences to persons, health care systems, and economies worldwide. Chronic diseases are the leading cause of disability and mortality and are responsible for 90% of health care expenditure. The most common chronic diseases are diabetes mellitus (DM), cardiovascular disease, and cerebrovascular disease (stroke and vascular cognitive impairment). Modifiable risk factors (MRFs) for these conditions include hypertension, hyperlipidemia, smoking, poor diet, and low-physical activity; with hypertension being the most prevalent MRF. Most MRFs can be successfully targeted through lifestyle medicine (LSM), which is a medical specialty that addresses the root causes of chronic diseases through its primary, secondary, and tertiary preventative approaches. Lifestyle medicine comprises 6 pillars (nutrition, physical activity, sleep health, stress reduction, social connections, and substance use) which through various behavioral approaches, focus on regular physical activity, healthy eating, good quality and quantity sleep, and meaningful social connections coupled with the reduction of stress and substance use. This paper will briefly review the evidence and promise of individual LSM pillars in addressing the underlying MRFs of DM, cardiovascular and cerebrovascular disease (specifically stroke and vascular cognitive impairment). Lifestyle medicine holds a great promise for comprehensive and much improved population health. However, the adoption of LSM at the societal scale requires a multifaceted approach and widespread integration would galvanize a paradigm shift to prevent, treat or reverse chronic diseases from the root causes and achieve health equity.

Milk is considered an essential source of protein for people of all ages. However, Bangladeshi people, particularly those living in rural areas, tend to consume less milk and milk products than necessary. Therefore, this study aims to investigate the demand for milk and milk products among rural consumers and the factors affecting their consumption habits. The study utilizes balanced panel data from three waves of the Bangladesh Integrated Household Survey: 2011–12, 2015, and 2018–19, collected by the International Food Policy Research Institute. Both the Almost Ideal Demand System (AIDS) and Fixed Effects Model were employed. The expenditure elasticity for liquid milk, powdered milk, and condensed milk was found to be 1.013, 1.856, and 1.060, respectively, indicating that these products are considered luxury goods in rural Bangladesh. Additionally, powdered milk is more price-sensitive than liquid or condensed milk in these areas. Milk and milk products exhibit a substitutable relationship based on the Slutsky and Cournot cross-price elasticities matrix. Consumption of liquid milk is significantly influenced, either positively or negatively, by several factors, including age, education, family size, ownership of dairy animals, income, expense of food, and year. Furthermore, while the consumption of powdered milk is increasing over time, factors such as family size and livestock ownership negatively impact its consumption. Similarly, the consumption of condensed milk is negatively affected by education and ownership of dairy animals. Based on our study results, we recommend increasing household income through on and off-farm job creation, promoting educational campaigns on the benefits of milk, and supporting livestock ownership to reduce reliance on processed milk products.

This study presents a molecular dynamics analysis focusing on the behavior of interstitial helium (He) clusters in nickel (Ni), examining their formation, stability, and migration energetics. We found that the binding energies of interstitial He with a He cluster are positive and increase with the cluster size, indicating a preference for He atoms to cluster together. While the formation energy increases monotonically with cluster size, binding energy shows non-monotonic. trend Importantly, small He clusters were found to be thermally unstable at reactor operational temperatures (approximately 600 K), with the He2 cluster exhibiting instability even at room temperature. With a binding energy of 0.44 eV for a He4 cluster, we hypothesize that for He bubbles to form via homogeneous nucleation (i.e., through trap mutation) at reactor operating temperatures, the He concentration must be high enough to facilitate the formation of He clusters of at least size 4 or larger. At finite temperatures, He clusters of size 7 and larger trap mutate immediately. However, clusters of size 10 and larger will trap mutate even at 0 K. As expected, interstitial He and small He clusters are highly mobile, and found to be mobile even at temperatures as low as 200 K. Furthermore, the mean squared displacement method has been utilized to determine the activation energies and the corresponding prefactors for clusters ranging from He1 to He6

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Background: Extrahepatic biliary neuroendocrine tumors (EBNETs) are rare. We aimed to characterize EBNETs including factors associated with survival. Methods: The National Cancer Database was queried for patients with EBNETs from 2004 to 2016. Patients who underwent resection were examined using Cox proportional hazards regression and the Kaplan-Meier method. We compared overall survival (OS) among patients with EBNETs to those with NETs from other primary sites. Results: Overall, 223 patients with EBNETs were identified. Patients were predominantly male (n = 113, 50.7 %), white (n = 177, 79.4 %) and presented without distant metastasis (n = 182, 81.6 %). The majority underwent operation (n = 127, 57.9 %) with resection of the primary tumor (n = 89, 70 %). Among patients who underwent resection (n = 71), multivariable regression demonstrated older age (HR 1.11, 95 % C.I. 1.04–1.17), lymph node metastases (HR 1.19, 95 % C.I. 1.02–1.38) and poorly/undifferentiated tumors [HR 22.3, 95 % C.I. 3.78–131]) were associated with worse overall survival. Patients with EBNETs experienced abbreviated OS compared to patients with small bowel or pancreas NETs (p

Rice production is inherently risky and volatile, and farmers in Bangladesh face a wide range of risks, including weather, pest and disease attacks, interruptions to input supply, and market-associated risks. Moreover, poor farm households often perceive risks in adopting new technology, even though it could improve productivity and food security. Such households are thus caught in a “risk-induced trap” that precludes them from realizing the benefits of technological innovation. Extension service is one way to help farmers improve risk management skills and escape risk-induced traps, but there is limited empirical analysis of its impact in Bangladesh. The objective of the study is to measure the nexus between agricultural extension services, technology adoption, and production risks as well as women empowerment in agriculture index. IFPRI utilized stratified random sampling to determine the 5603 households in 2018 (which is nationally called the BIHS-2018 dataset) from rural and pre-urban areas of Bangladesh. Out of these 5603 households, 2663 households were specifically selected for the study related to rice farming to achieve the main objective of the study. Focusing on rice farming, a moment-based Poisson regression model is estimated with 2SLS and identifies risks associated with key technologies and potential productivity and risk-reducing effects. The results revealed that wealthier households are more likely to adopt technology for minimizing production risk and women's empowerment which can positively affect productivity by mitigating risk. The result revealed a positive and significant difference in WEAI between the AES participant and non-participant group. We find that engagement in agricultural extension services was associated with technology adoption and production risk reduction. The agricultural extension services increased, technology adoption by 4.2 % and decreased production risk by 2.4 %. Based on the findings, it is concluded that more comprehensive extension services can enhance rice production and ameliorate farmers' risk in rice production to some extent.

Introduction: Leakage of orogastric secretions past the cuff of a tracheal tube is a contributory factor in ventilator-associated pneumonia. Current bench test methods specified in the International Standard for Anaesthetic and Respiratory Equipment (EN ISO 5361:2023) to test cuff leakage involve using a glass or plastic rigid cylinder model of the trachea. There is a need for more realistic models to inform cuff leakage. Methods: We used human computerised tomography data and additive manufacturing (3D printing), combined with casting techniques to fabricate a bio-inspired synthetic tracheal model with analogous tissue characteristics. We conducted cuff leakage tests according to EN ISO 5361:2023 and compared results for high-volume low-pressure polyvinyl chloride and polyurethane cuffs between the rigid cylinder trachea with our bio-inspired model. Results: The tracheal model demonstrated close agreement with published tracheal tissue hardness for cartilaginous and membranous soft tissues. For high-volume low-pressure polyvinyl chloride cuffs the leakage rate was >50% lower in the bio-inspired tracheal model compared with the rigid cylinder model (151 [8] vs 261 [11] ml h−1). For high-volume low-pressure polyurethane cuffs, much lower leakage rates were observed than polyvinyl chloride cuffs in both models with leakage rates higher for the bio-inspired trachea model (0.1 [0.2] vs 0 [0] ml h−1). Conclusion: A reproducible tracheal model that incorporates the mechanical properties of the human trachea can be manufactured from segmented CT images and additive manufactured moulds, providing a useful tool to inform future cuff development, leakage testing for industrial applications, and clinical decision-making. There are differences between cuff leakage rates between the bio-inspired model and the rigid cylinder recommended in EN ISO 5361:2023. The bio-inspired model could lead to more accurate and realistic cuff leakage rate testing which would support manufacturers in refining their designs. Clinicians would then be able to choose better tracheal tubes based on the outcomes of this testing.

Additive manufacturing is proposed as a novel tool to produce complex scaffold constructs for use in cell cultured meat. The presence of scaffolds in the final cell cultured products raises the need to understand the thermal behavior of biopolymers through culturing and cooking as it relates to the final organoleptic properties. Therefore, the objective of this study was to understand how aqueous and high temperature environments influence plasticization and contraction of biopolymer scaffolds through the physio–chemical mechanisms of hydrolysis and negative thermal expansion. To achieve this objective, scaffolds were printed using a negative thermal expansion stretch–dominated design in both PLA and PLA-TPU material configurations. The samples were evaluated after a simulated cooking experiment (90 °C for 10 mins). The formation of crystals in the single material PLA during cooking led to bend–dominated contraction while the dual-material PLA-TPU experienced stretch–dominated contraction. Furthermore, exceeding the glass transition temperature of PLA during simulated cooking in an aqueous environment caused irreversible deformation to the scaffold structure that has the potential to influence organoleptic properties.

Neosartorya udagawae is a known cause of fungal infection in humans and animals. It is found to be more refractory to antifungal treatment in comparison to other Aspergillus species. With this report we present a case of proven invasive infection with Neosartorya udagawae in a child with chronic myeloid leukaemia after haematopoietic stem cell transplant. The patient received several lines of antifungal therapy including dual therapy appropriate to the antifungal susceptibility profile with progression of the invasive fungal disease requiring left lung upper lobe lobectomy. The case emphasizes the importance of early biopsy with antifungal susceptibility testing for targeted therapy and demonstrates the potential requirement for surgical management in addition to appropriate antifungal treatment.

Background: Increasing evidence suggests that clinician well-being influences patient, workforce, and organizational outcomes. Despite increasing attention to well-being among licensed clinicians (e.g., nurses and physicians), collective evidence about well-being among healthcare assistants, such as nursing and medical assistants, is limited. Healthcare assistants make up a substantial portion of the clinical workforce delivering direct patient care. The well-being of healthcare assistants is critical to ensure an ample workforce supply. The objective of this systematic review was to contribute a reproducible search, summary, appraisal, synthesis, and critique of the literature about well-being among healthcare assistants, including factors that induce or inhibit burnout, and to identify gaps in evidence that warrant future research. Methods: We performed a literature search across 4 databases with keywords using BOOLEAN operators. After an initial title and abstract screen, a search of relevant reference lists, and full text review was peformed independently by 2 researchers. Study quality was evaluated using Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. We extracted study characteristics, results, and deductively analyzed each study's alignment with the United States National Academy of Medicine's Clinician Well-Being Model. Results: We identified 28 articles meeting our inclusion criteria. Our synthesis indicated that most studies investigated personal factors (e.g., financial stressors or physical, emotional, and spiritual health) as opposed to organizational or policy factors (e.g., occupational policies or workplace culture) that may impact well-being. Younger workers and those with fewer years of experience appear to have higher burnout risk. Sleep health, improved unit-based culture (respect and increased decision-making with nurses), shorter shifts, and increased social support appear to be the most protective against burnout. Discussion: There remains a scarcity of evidence about factors impacting well-being among healthcare assistants. Existing literature focuses on individual, as opposed to external or organizational, contributory factors to burnout or well-being risk. Future studies should use specific methods to define and measure healthcare assistant roles, isolate harmful individual and organizational factors, and measure more specific sub-concepts of well-being such as depression. Such studies can contribute greatly to the overall understanding of healthcare assistant health and wellness, which subsequently may promote optimal patient and organizational outcomes. Tweetable abstract: The hidden workforce: Systematic review demonstrates gaps in evidence about wellbeing and burnout among healthcare assistants and aides.

Background: With an aging population, the incidence of olecranon fractures in older patients is increasing. The standard of care has traditionally included operative management for displaced fractures. Recent literature has called this standard of care into question. Older patients may be at increased risk of operative complications and may have satisfactory functional outcomes with nonoperative management. Given recently evolving evidence, the current treatment preferences of orthopedic surgeons for older patients with displaced olecranon fractures are unknown. Methods: We administered a cross-sectional survey of Canadian orthopedic surgeons via e-mail invitation and online survey form to determine treatment preferences for patients aged 65-75 and >75 years with simple displaced and comminuted displaced stable olecranon fractures. Respondents reviewed representative images and were asked to indicate their preferred treatment based on patient age. We also asked respondents to indicate their perceived importance of 11 patient factors on treatment decision-making. Results: We received 200 responses (33.8% response rate). For patients aged 65-75 years with simple displaced fractures, surgeons preferred tension-band wiring (n = 110, 56%) to plating (n = 82, 42%, P = .005), while only 3% (n = 5) preferred nonoperative treatment. For patients aged >75 years with simple displaced fractures, surgeons preferred operative (n = 144, 73%) to nonoperative management (n = 51, 26%; P 75 years (n = 131, 68%). In patients aged >75 years, this was followed by early range of motion (n = 35, 18%) and immobilization (n = 24, 13%). Of the 11 factors surveyed, participation in high-intensity activities (mean rank = 9.4), independent living (mean rank = 8.8), and disrupted extensor mechanism (mean rank = 8.3) were ranked most highly for increasing likelihood of surgical treatment. Conclusion: In patients aged 65 to 75 years, operative management is favored by most surgeons, with tension-band wiring preferred over plating for simple displaced fractures. In patients aged >75 years, operative management is again preferred by most respondents for simple and comminuted fractures. Despite operative preferences, there is a paucity of quality evidence to guide treatment decision-making, particularly in patients aged >75 years.

Objective: Postoperative delirium after cardiac surgery is associated with long-term cognitive decline and mortality. We investigated whether increased ICU Confusion Assessment Method scores were associated with greater 30-day mortality and failure to rescue after cardiac surgery. Methods: We studied 4030 patients who underwent a Society of Thoracic Surgeons index operation at the University of Virginia Health System from 2011 to 2021. We obtained all ICU Confusion Assessment Method scores recorded during patients' admission and summarized scores for the first 7 postoperative days. Univariate and multivariable logistic regression analyzed the association between ICU Confusion Assessment Method score/delirium presence and postoperative complications, operative mortality, and failure to rescue. Results: Any episode of ICU Confusion Assessment Method screen-positive delirium and nearly all components of the score were associated with increased 30-day mortality on univariate analysis. We found that a single episode of delirium was associated with increased mortality. Feature 2 (inattention) had the strongest association with poorer outcomes, including failure to rescue in our analysis, as were patients with higher peak Richmond Agitation Sedation Scale scores. Patients with higher mean Richmond Agitation Sedation Scale scores had an association with decreased failure to rescue. Conclusions: A single episode of delirium, as measured using ICU Confusion Assessment Method scores, is associated with increased mortality. Inattention and higher peak Richmond Agitation Sedation Scale scores were associated with failure to rescue. Screening may clarify diagnosing delirium and assessing its implications on mortality and failure to rescue. Our findings suggest the importance of identifying and managing risk factors for delirium to improve patient outcomes and reduce mortality and failure to rescue rates.

Plasmodium falciparum is the deadliest causative agent of human malaria. This parasite has historically developed resistance to most drugs, including the current frontline treatments, so new therapeutic targets are needed. Our previous work on guanine quadruplexes (G4s) in the parasite's DNA and RNA has highlighted their influence on parasite biology, and revealed G4 stabilising compounds as promising candidates for repositioning. In particular, quarfloxin, a former anticancer agent, kills blood-stage parasites at all developmental stages, with fast rates of kill and nanomolar potency. Here we explored the molecular mechanism of quarfloxin and its related derivative CX-5461. In vitro, both compounds bound to P. falciparum-encoded G4 sequences. In cellulo, quarfloxin was more potent than CX-5461, and could prevent establishment of blood-stage malaria in vivo in a murine model. CX-5461 showed clear DNA damaging activity, as reported in human cells, while quarfloxin caused weaker signatures of DNA damage. Both compounds caused transcriptional dysregulation in the parasite, but the affected genes were largely different, again suggesting different modes of action. Therefore, CX-5461 may act primarily as a DNA damaging agent in both Plasmodium parasites and mammalian cells, whereas the complete antimalarial mode of action of quarfloxin may be parasite-specific and remains somewhat elusive.

Acute cellular rejection (ACR) is one of the main risk factors for chronic allograft dysfunction, the primary contributor to poor long-term survival in lung transplant recipients. We sought to develop a blood-based transcriptomic risk score (TRS) to detect ACR in lung transplant recipients. We tested for the association of the TRS with ACR in a logistic mixed model. We analyzed 101 samples from 75 individuals. We identified 4 genes after application of the least absolute shrinkage and selection operator. The TRS was significantly associated with ACR (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.86-7.14, p

Background: Malignancy is a long-term complication of lung transplantation (LTx); however, contemporary Australian data and detailed evaluation of nonreportable cancers are lacking. Methods: Retrospective review of LTx recipients’ medical records and registry data linkage were performed to identify histologically proven malignancies. Baseline clinico-demographic variables were collected, and cancer incidence was compared with reported data for the general Australian population. Results: There were 1,715 LTx in 1,631 patients between 1989 and 2021, with a follow-up of 9,696 person-years. Eight hundred and ninety-three (54.8%) patients were male, and the median age at first LTx was 54.7 years. There were 886 deaths with a median overall survival of 7.5 years (95% confidence intervals (CI) 6.8-8.3 years). One thousand seven hundred and seventy-four separate invasive cancer events occurred across 407 patients, of which, 1,588 (89.5%) were nonmelanoma skin cancers (NMSCs). This translated to a 9-fold increased incidence of NMSCs and a 4-fold increased incidence of other cancers compared with the general population. Cancer mortality reached parity with chronic lung allograft dysfunction 10 years postfirst transplant and was independently associated with age (hazard ratios (HR) per year increase in age 1.02 [95% CI 1.01-1.03], p = 0.001), Epstein-Barr virus primary mismatch (HR 3.24 [95% CI 1.68-6.25], vs nonmismatch, p = 0.002), and cancer count (HR per cancer event 1.19 [95% CI 1.13-1.24], p

Rural transformation plays a crucial role in enhancing the income and employment prospects of the rural labor force. We investigate the effects of rural transformation on rural income inequality at the district level in Bangladesh using data from five years of nationally representative Household Income and Expenditure Surveys. The Gini coefficient is used to measure rural income inequality. In contrast, the share of high-value agricultural outputs and the share of rural non-farm employment are used as indicators of rural transformation. We find that rural income inequality is positively associated with the share of high-value agricultural outputs and the share of rural non-farm employment. The non-linear regression result shows an inverted U-shaped relationship between rural transformation and income inequality, which indicates that income inequality initially increases with rural transformation but decreases in the long run. Additionally, we find that rural income inequality is positively correlated with the proportion of household education expenditures, agricultural rental activity, and the share of remittances. This study also reveals that income inequality in rural areas of Bangladesh has a significant negative correlation with the government's social safety net program.

A whale fall community of chemosymbiotic invertebrates living on cetacean bones has been identified off southwestern Australia during a Remotely Operated Vehicle (ROV) survey at bathyal depths within the Bremer Marine Park, which is part of important marine mammal areas (IMMA) of the Albany Canyon Region. Cetacean bones on the seafloor of the Hood Canyon, consisted of isolated skulls of three species of beaked whales (family Ziphiidae): Mesoplodon cf. layardii, M. grayi, and M. hectori, a few vertebrae, and lower jaws. One of the beaked whale skulls (Mesoplodon cf. layardii) was sampled and found to be intensely colonised by hundreds of specimens of a bathymodilinae mussel (“Adipicola” s.l.). Live polychaetes (Phyllochaetopterus?), skeneimorph gastropods, and amphipods (Seba, Leptamphopus) colonised the skull bone, which represent a later stage (sulfophilic) of carcass decomposition. The reducing sediment below the skull was inhabited by lucinid (Lucinoma) and vesicomyid (Calyptogena) chemosymbiotic bivalves. Additionally, the sediment thanatocoenosis comprised shells of various other chemosymbiotic bivalves, such as Acharax, thyasirids, lucinids, vesicomyids, and limpets, representing the complex ecological turnover phases through time in this whale fall chemosynthetic habitat. With one exception, all bones recovered were colonized by bathymodiolin mussels. This is the first documented case of a chemosynthetic community and associated chemosymbiotic fauna relating to beaked whales, and the first fully documented record of a whale fall community within the Australian Southern Ocean region.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p

Early and precise detection of solid tumor cancers is critical for improving therapeutic outcomes. In this regard, magnetic resonance imaging (MRI) has become a useful tool for tumor diagnosis and image-guided therapy. However, its effectiveness is limited by the shortcomings of clinically available gadolinium-based contrast agents (GBCAs), i.e. poor tumor penetration and retention, and safety concerns. Thus, we have developed a novel nanoparticulate contrast agent using a biocompatible terpolymer and lipids to encapsulate manganese dioxide nanoparticles (TPL-MDNP). The TPL-MDNP accumulated in tumor tissue and produced paramagnetic Mn2+ ions, enhancing T1-weight MRI contrast via the reaction with H2O2 rich in the acidic tumor microenvironment. Compared to the clinically used GBCA, Gadovist®1.0, TPL-MDNP generated stronger T1-weighted MR signals by over 2.0-fold at 30 % less of the recommended clinical dose with well-defined tumor delineation in preclinical orthotopic tumor models of brain, breast, prostate, and pancreas. Importantly, the MRI signals were retained for 60 min by TPL-MDNP, much longer than Gadovist®1.0. Biocompatibility of TPL-MDNP was evaluated and found to be safe up to 4-fold of the dose used for MRI. A robust large-scale manufacturing process was developed with batch-to-batch consistency. A lyophilization formulation was designed to maintain the nanostructure and storage stability of the new contrast agent.

Introduction: Self-perceived health status data is usually collected using patient-reported outcome measures. Information from the patients’ perspective is one of the important components in planning person-centred care. The study aimed to compare EQ-5D-5L in survivors after out-of-hospital cardiac arrest (OHCA) with data for Norwegian population controls. Secondary aim included comparing characteristics of respondents and non-respondents from the OHCA population. Methods: In this cross-sectional survey, 714 OHCA survivors received an electronic EQ-5D-5L questionnaire 3–6 months following OHCA. EQ-5D-5L assesses for five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with five-point descriptive scales and overall health on a visual analogue scale from 0 (worst) to 100 (best) (EQ VAS). Results are used to calculate the EQ index ranging from −0.59 (worst) to 1 (best). Patient responses were matched for age and sex with existing data from controls, collected through a postal survey (response rate 26%), and compared with Chi-square tests or t-tests as appropriate. Results: Of 784 OHCA survivors, 714 received the EQ-5D-5L, and 445 (62%) responded. Respondents had higher rates of shockable first rhythm and better cerebral performance category scores than the non-respondents. OHCA survivors reported poorer health compared to controls as assessed by EQ-5D-5L dimensions, the EQ index (0.76 ± 0.24 vs 0.82 ± 0.18), and EQ VAS (69 ± 21 vs 79 ± 17), except for the pain/discomfort dimension. Conclusions: Norwegian OHCA survivors reported poorer health than the general population as assessed by the EQ-5D-5L. PROMs use in this population can be used to inform follow-up and health care delivery.

Summary: Postnatal development of the uterus involves the specification of undifferentiated epithelium into uterine-type epithelium. That specification is regulated by stromal-epithelial interactions as well as intrinsic cell-specific transcription factors and gene regulatory networks. Here, we present a co-culture system to study the effects of stromal-derived factors on epithelial cell growth and differentiation into organoids. First, we describe epithelial cell isolation and organoid growth characterization. Second, we detail a co-culture system that allows the study of stromal-derived paracrine factors on epithelial development.For complete details on the use and execution of this protocol, please refer to Rizo et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Color centers in diamond are one of the most promising tools for quantum information science. Of particular interest is the use of single-crystal diamond membranes with nanoscale-thickness as hosts for color centers. Indeed, such structures guarantee a better integration with a variety of other quantum materials or devices, which can aid the development of diamond-based quantum technologies, from nanophotonics to quantum sensing. A common approach for membrane production is what is known as “smart-cut”, a process where membranes are exfoliated from a diamond substrate after the creation of a thin sub-surface amorphous carbon layer by He+ implantation. Due to the high ion fluence required, this process can be time-consuming. In this work, we demonstrated the production of thin diamond membranes by neon implantation of diamond substrates. With the target of obtaining membranes of ∼200 nm thickness and finding the critical damage threshold, we implanted different diamonds with 300 keV Ne+ ions at different fluences. We characterized the structural properties of the implanted diamonds and the resulting membranes through SEM, Raman spectroscopy, and photoluminescence spectroscopy. We also found that a SRIM model based on a two-layer diamond/sp2-carbon target better describes ion implantation, allowing us to estimate the diamond critical damage threshold for Ne+ implantation. Compared to He+ smart-cut, the use of a heavier ion like Ne+ results in a ten-fold decrease in the ion fluence required to obtain diamond membranes and allows to obtain shallower smart-cuts, i.e. thinner membranes, at the same ion energy.

Background: Lower childhood intelligence test scores are reported in some studies to be associated with higher risk of depression in adulthood. The reasons for the association are unclear. This longitudinal data-linkage study explored the relationship between childhood intelligence (at age ∼11) and risk of depression in later-life (up to age ∼85), and whether childhood family structure and adulthood socio-economic and geographical factors accounted for some of this association. Methods: Intelligence test scores collected in the Scottish Mental Survey 1947 were linked to electronic health records (hospital admissions and prescribing data) between 1980 and 2020 (n = 53,037), to identify diagnoses of depression. Mixed-effect Cox regression models were used to explore the relationship between childhood intelligence test scores and risk of depression in later-life. Analyses were also adjusted for childhood family structure (size of family) and adulthood socio-economic and geographical factors (Carstairs index, urban/rural). Results: Twenty-seven percent of participants were diagnosed with depression during follow-up (n = 14,063/53,037). Greater childhood intelligence test scores were associated with a reduced risk of depression in an unadjusted analysis (HR = 0.95, 95% CI = 0.93 to 0.97, P

The integration of digital health into the field of medicine has seen a marked increase with the advancement of technology. Before the pandemic, a marked portion of the adult population, more than 66%, owned smartphones, and approximately 15% owned wearables. The widespread use of such devices, along with the effect of COVID-19 pandemic, has led to a transformation in health care culture that prioritizes cocreation, codesign, and collaboration. This shift promotes a model of health care centered on patient empowerment and self-management. In a recent interview with Dave deBronkart, known as e-Patient Dave, we revisited the possibilities of this new approach aimed at empowering, engaging, and equipping e-patients in the context of the pandemic. This interview with deBronkart was originally used for a graduate course on digital health. However, after noticing many reoccurring themes throughout the discussion, we decided to further explore this matter. It was discovered that participatory medicine is a new paradigm in health care, which challenges the conventional, paternalistic model and emphasizes the importance of a collaborative relationship between patients and providers. The realization of the full potential of health care can be achieved by promoting patient engagement and activation through the adoption of participatory medicine.

ABSTRACT: Objectives: A variety of methods have been developed to detect antimicrobial resistance (AMR) in different environments to better understand the evolution and dissemination of this public health threat. Comparisons of results generated using different AMR detection methods, such as quantitative PCR (qPCR) and whole-genome sequencing (WGS), are often imperfect, and few studies have analysed samples in parallel to evaluate differences. In this study, we compared bacterial culture and WGS to a culture-independent commercially available qPCR assay to evaluate the concordance between methods and the utility of each in answering research questions regarding the presence and epidemiology of AMR in wild bird habitats. Methods: We first assessed AMR gene detection using qPCR in 45 bacterial isolates from which we had existing WGS data. We then analysed 52 wild bird faecal samples and 9 spatiotemporally collected water samples using culture-independent qPCR and WGS of phenotypically resistant indicator bacterial isolates. Results: Overall concordance was strong between qPCR and WGS of bacterial isolates, although concordance differed among antibiotic classes. Analysis of wild bird faecal and water samples revealed that more samples were determined to be positive for AMR via qPCR than via culture and WGS of bacterial isolates, although qPCR did not detect AMR genes in two samples from which phenotypically resistant isolates were found. Conclusions: Both qPCR and culture followed by sequencing may be effective approaches for characterising AMR genes harboured by wild birds, although data streams produced using these different tools may have advantages and disadvantages that should be considered given the application and sample matrix.

Summary: Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3–4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone marrow but during final cDC differentiation in peripheral tissues under the influence of local secondary signals that persist after resolution of SIRS. Vaccination with monoclonal antibodies that target cDC receptors or blockade of transforming growth factor β partially overcomes paralysis and immunosuppression. This work provides insights into the mechanisms of paralysis and describes strategies to restore immunocompetence post-SIRS.

Jute often referred to as Bangladesh's “golden fiber” offers numerous environmental advantages along with significant industrial and economic importance. It is a crucial source of export earnings for Bangladesh. Beyond its use in house decoration materials, jute is employed in the production of twine, mats, carpets, sacks, and hessian clothing, among other products. This study aimed to assess the value chain of jute fiber in Bangladesh. Primary data were collected from 90 jute farmers and 233 chain participants across different stages of the value chain selected through simple random and purposive sampling, respectively, in 2019. Mapping strategies and marketing margins were employed to analyse the value addition of each actor. The benefit-cost ratio of 1.44 demonstrates the profitability of jute cultivation. The study identified that the highest share of the total value addition by farmers was 52.80% through the ‘Farmer-Faria-Kutcha Baler-Mill’ channel in Faridpur district, 59.66% through the ‘Farmer-Faria-Aratdar-Mill’ channel in Rangpur district, 60.52% through the ‘Farmer-Faria-Aratdar-Mill’ channel in Dinajpur district, and 58.87% through the ‘Farmer-Faria-Aratdar-Mill’ channel in Kishoreganj district. Per quintal, gross and net marketing margins for farmers were Taka 569 and Taka 537, respectively. Pucca balers cum exporters accounted for the highest proportion of gross marketing margin (41.30%) and net marketing margin (44.34%), while Farias contributed the lowest share (6.77% and 3.63%). Finally, based on the research findings, several policy measures are recommended to revitalize this potential sector in Bangladesh.

Summary: Background: As countries progress through economic and demographic transition, chronic non-communicable diseases (NCDs) overtake a previous burden of infectious diseases. We investigated the prevalence of hypertension, diabetes, obesity, and multimorbidity in older adults in The Gambia. Methods: We embedded a survey on NCDs into the nationally representative 2019 Gambia National Eye Health Survey of adults aged 35 years or older. We measured anthropometrics, capillary blood glucose, and blood pressure together with sociodemographic information, personal and family health history, and information on smoking and alcohol consumption. Hypertension was defined as systolic blood pressure of 140 mmHg or more, diastolic blood pressure of 90 mmHg or more, or receiving treatment for hypertension. Diabetes was defined as fasting capillary blood glucose of 7 mmol/L or more, random blood glucose of 11·1mmol/L or more, or previous diagnosis or treatment for diabetes. Overweight was defined as BMI of 25–29·9 kg/m2 and obesity as 30 kg/m2 or more. Multimorbidity was defined as the coexistence of two or more conditions. We calculated weighted crude and adjusted estimates for each outcome by sex, residence, and selected sociodemographic factors. Findings: We analysed data from 9188 participants (5039 [54·8%] from urban areas, 6478 [70·5%] women). The prevalence of hypertension was 47·0%; 2259 (49·3%) women, 2052 (44·7%) men. The prevalence increased with age, increasing from 30% in those aged 35–45 years to over 75% in those aged 75 years and older. Overweight and obesity increased the odds of hypertension, and underweight reduced the odds. The prevalence of diabetes was 6·3% (322 [7·0%] women, 255 [5·6%] men), increasing from 3·8% in those aged 35–44 years to 9·1% in those aged 65–75 years, and then declining. Diabetes was much more common among urban residents, especially in women (peaking at 13% by age 65 years). Diabetes was strongly associated with BMI and wealth index. The prevalence of obesity was 12·0% and was notably higher in women than men (880 [20·2%] vs 170 [3·9%]). Multimorbidity was present in 932 (10·7%), and was more common in women than men (694 [15·9] vs 238 [5·5]). The prevalence of smoking was 9·7%; 5 (0·1%) women, 889 (19·3%) men. Alcohol consumption in the past year was negligible. Interpretation: We have documented high levels of NCDs and associated risk factors in Gambian adults. This presents a major stress on the country's fragile health system that requires an urgent, concerted, and targeted mutisectoral strategy. Funding: The Queen Elizabeth Diamond Jubilee Trust and Wellcome Trust.

Summary: Stem cells (SCs) are critical to maintain tissue homeostasis. However, it is currently not known whether signaling through cell junctions protects quiescent epithelial SC reservoirs from depletion during disease-inflicted damage. Using the autoimmune model disease pemphigus vulgaris (PV), this study reveals an unprecedented role for a desmosomal cadherin in governing SC quiescence and regeneration through adhesion signaling in the multipotent mouse hair follicle compartment known as the bulge. Autoantibody-mediated, mechanical uncoupling of desmoglein (Dsg) 3 transadhesion activates quiescent bulge SC which lose their multipotency and stemness, become actively cycling, and finally delaminate from their epithelial niche. This then initiates a self-organized regenerative program which restores Dsg3 function and bulge morphology including SC quiescence and multipotency. These profound changes are triggered by the sole loss of functional Dsg3, resemble major signaling events in Dsg3−/− mice, and are driven by SC-relevant EGFR activation and Wnt modulation requiring longitudinal repression of Hedgehog signaling.

Farmer misperceptions of plot size can potentially lead to greater than intended levels of fertilizer use, which can increase the threat of soil fertility decline and non responsiveness of crops to inorganic fertilizer application. In addition, due to diminishing marginal returns of fertilizer use on grain yields, overestimation of plot size can potentially decrease fertilizer profitability. In this study, we use data collected from randomly selected farmers in rural western Kenya that include both the estimated sizes of the agricultural plots as reported by the farmers and their GPS-measured sizes. We find that 65 percent of plots are overestimated by at least 20 percent. We also find that inorganic nitrogen use is strongly increasing in plot size misestimation: a 10% increase in plot misestimation was associated with a 2.6 percent increase in commercial nitrogen application. Next, we build a random forest model to examine the agronomic efficiency of the farmer intended fertilizer use rates vs. actual rates. We find that misestimation of plot sizes is associated with an average decrease in return on investment of 5% (12%) at application rates of 60 kg N/ha (120 kg N/ha). Building on this exercise, we review the literature linking soil health and plot size misperceptions and conclude by proposing a new research agenda to examine how plot size misperceptions affect soil health and farmer well-being, more broadly.