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Higher levels of nitrated lipoproteins (NT-HDL and NT-LDL) were found in blood and atherosclerotic plaques of patients with coronary artery disease. We aimed to examine the relationship between plasma NT-HDL and NT-LDL and diabetic vascular dysfunction. The study included 125 African-American patients with T2DM. NT-HDL and NT-LDL were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. In univariate analysis, NT-HDL was associated with VRI in total population and in patients with HbA1c ≤7.0% (β= -0.178, p= 0.034; β= -0.265, p= 0.042; respectively). In contrast, NT-LDL was associated with CIMT in total population and in patients with HbA1c >7.0% (β= -0.205, p= 0.022; β= -0.244, p= 0.042; respectively). Multivariable-adjusted regression analysis demonstrated that NT-HDL independently predicted VRI outcome in total population and in well-controlled patients (β= -0.282, p= 0.014; β= -0.400, p= 0.035, respectively). These results suggest that NT-HDL could be used as marker to identify diabetic patients at risk of developing early microvascular complications.

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function. The study included 125 patients with T2DM. Plasma levels of sF11R and ANXA5 were quantified by ELISA. Microvascular function was assessed using the vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. The mean age of patients in the study was 59.7 ± 7.8 years, 78% had hypertension, 76% had dyslipidemia, and 12% had CKD. sF11R correlated positively with ANXA5 levels (β = 0.250, p = 0.005), and correlated inversely with VRI and total nitic oxide (NO), (β = −0.201, p = 0.024; β = −0.357, p = 0.0001, respectively). Multivariate regression analysis revealed that sF11R was independently associated with ANXA5 in the total population and in patients with HbA1c > 6.5% (β = 0.366, p = 0.007; β = 0.425, p = 0.0001, respectively). sF11R and ANXA5 were not associated with vascular outcome, suggesting that they may not be reliable markers of vascular dysfunction in diabetes. The clinical significance of sF11R/ANXA5 association in diabetes warrants further investigation in a larger population.

Collections of biological specimens are fundamental to scientific understanding and characterization of natural diversity-past, present and future. This paper presents a system for liberating useful information from physical collections by bringing specimens into the digital domain so they can be more readily shared, analyzed, annotated and compared. It focuses on insects and is strongly motivated by the desire to accelerate and augment current practices in insect taxonomy which predominantly use text, 2D diagrams and images to describe and characterize species. While these traditional kinds of descriptions are informative and useful, they cannot cover insect specimens "from all angles" and precious specimens are still exchanged between researchers and collections for this reason. Furthermore, insects can be complex in structure and pose many challenges to computer vision systems. We present a new prototype for a practical, cost-effective system of off-the-shelf components to acquire natural-colour 3D models of insects from around 3 mm to 30 mm in length. ("Natural-colour" is used to contrast with "false-colour", i.e., colour generated from, or applied to, gray-scale data post-acquisition.) Colour images are captured from different angles and focal depths using a digital single lens reflex (DSLR) camera rig and two-axis turntable. These 2D images are processed into 3D reconstructions using software based on a visual hull algorithm. The resulting models are compact (around 10 megabytes), afford excellent optical resolution, and can be readily embedded into documents and web pages, as well as viewed on mobile devices. The system is portable, safe, relatively affordable, and complements the sort of volumetric data that can be acquired by computed tomography. This system provides a new way to augment the description and documentation of insect species holotypes, reducing the need to handle or ship specimens. It opens up new opportunities to collect data for research, education, art, entertainment, biodiversity assessment and biosecurity control.

DNA barcoding protocols require the linkage of each sequence record to a voucher specimen that has, whenever possible, been authoritatively identified. Natural history collections would seem an ideal resource for barcode library construction, but they have never seen large-scale analysis because of concerns linked to DNA degradation. The present study examines the strength of this barrier, carrying out a comprehensive analysis of moth and butterfly (Lepidoptera) species in the Australian National Insect Collection. Protocols were developed that enabled tissue samples, specimen data, and images to be assembled rapidly. Using these methods, a five-person team processed 41,650 specimens representing 12,699 species in 14 weeks. Subsequent molecular analysis took about six months, reflecting the need for multiple rounds of PCR as sequence recovery was impacted by age, body size, and collection protocols. Despite these variables and the fact that specimens averaged 30.4 years old, barcode records were obtained from 86% of the species. In fact, one or more barcode compliant sequences (>487 bp) were recovered from virtually all species represented by five or more individuals, even when the youngest was 50 years old. By assembling specimen images, distributional data, and DNA barcode sequences on a web-accessible informatics platform, this study has greatly advanced accessibility to information on thousands of species. Moreover, much of the specimen data became publically accessible within days of its acquisition, while most sequence results saw release within three months. As such, this study reveals the speed with which DNA barcode workflows can mobilize biodiversity data, often providing the first web-accessible information for a species. These results further suggest that existing collections can enable the rapid development of a comprehensive DNA barcode library for the most diverse compartment of terrestrial biodiversity - insects.

Abstract Background Family-based treatment (FBT), the leading intervention for adolescents with anorexia nervosa (AN), is severely understudied in outpatient care settings that serve publicly-insured populations. Many individuals with public insurance are lower-income, racially and ethnically diverse, and experience barriers to accessing evidence-based interventions for eating disorders (EDs). Methods Semi-structured interviews were conducted with ten interdisciplinary providers who provide specialty care to youth with EDs in an inpatient and/or outpatient medical setting. Interview questions were focused on the interdisciplinary providers’ experiences of caring for individuals with EDs, with a focus on differences in care for those with private insurance compared to public insurance. The interviews took place two years after training in FBT was delivered to mental health providers in San Francisco County, which created opportunities to explore provider perspectives on collaborating with newly-trained mental health providers in the community implementing FBT with publicly-insured youth. Results Content analysis converged on three themes: the critical importance of supporting mental health treatment within the context of medical care, complex challenges when helping patients and their families navigate publicly-funded health care systems, and the overall positive impact of the FBT rollout in San Francisco County. Participants emphasized greater confidence in patient outcomes when collaborating with FBT providers and noted discord when working with providers not trained in EDs or FBT. Referral systems, weight-based stigma, and a lack of appropriate services were highlighted as significant barriers to care. To facilitate treatment engagement in publicly-insured populations, participants stressed the importance of clinicians providing psychoeducation and providing services with a high degree of cultural competence. Participants expressed that patients’ ability to access FBT and providers’ ability to collaborate on cases markedly improved following the county training, increasing their sense of efficacy in delivering adequate patient care. Conclusions The discussed themes highlight the importance of access to FBT for individuals in underserved communities, which can significantly reduce both provider and patient burden. Despite various barriers to utilizing FBT in publicly-funded settings, clinicians stressed that cultural adaptations increase the implementation of and facilitate family engagement in FBT, which is consistent with previous literature examining evidence-based intervention implementation science.

Abstract The second-generation antipsychotic clozapine is used as a medication for treatment-resistant schizophrenia. It has previously been associated with epigenetic changes in pre-clinical rodent models and cross-sectional studies of treatment-resistant schizophrenia. Cross-sectional studies are susceptible to confounding, however, and cannot disentangle the effects of diagnosis and medication. We therefore profiled DNA methylation in sequential blood samples (n = 126) from two independent cohorts of patients (n = 38) with treatment-resistant schizophrenia spectrum disorders who commenced clozapine after study enrolment and were followed up for up to six months. We identified significant non-linear changes in cell-type proportion estimates derived from DNA methylation data - specifically B-cells - associated with time on clozapine. Mixed effects regression models were used to identify changes in DNA methylation at specific sites associated with time on clozapine, identifying 37 differentially methylated positions (DMPs) (p

Abstract Our group previously showed that genetic or pharmacological inhibition of the cystine/glutamate antiporter, system xc−, mitigates excitotoxicity after anoxia by increasing latency to anoxic depolarization, thus attenuating the ischaemic core. Hypoxia, however, which prevails in the ischaemic penumbra, is a condition where neurotransmission is altered, but excitotoxicity is not triggered. The present study employed mild hypoxia to further probe ischaemia‐induced changes in neuronal responsiveness from wild‐type and xCT KO (xCT−/−) mice. Synaptic transmission was monitored in hippocampal slices from both genotypes before, during and after a hypoxic episode. Although wild‐type and xCT−/− slices showed equal suppression of synaptic transmission during hypoxia, mutant slices exhibited a persistent potentiation upon re‐oxygenation, an effect we termed ‘post‐hypoxic long‐term potentiation (LTP)’. Blocking synaptic suppression during hypoxia by antagonizing adenosine A1 receptors did not preclude post‐hypoxic LTP. Further examination of the induction and expression mechanisms of this plasticity revealed that post‐hypoxic LTP was driven by NMDA receptor activation, as well as increased calcium influx, with no change in paired‐pulse facilitation. Hence, the observed phenomenon engaged similar mechanisms as classical LTP. This was a remarkable finding as theta‐burst stimulation‐induced LTP was equivalent between genotypes. Importantly, post‐hypoxic LTP was generated in wild‐type slices pretreated with system xc− inhibitor, S‐4‐carboxyphenylglycine, thereby confirming the antiporter's role in this phenomenon. Collectively, these data indicate that system xc− interference enables neuroplasticity in response to mild hypoxia, and, together with its regulation of cellular damage in the ischaemic core, suggest a role for the antiporter in post‐ischaemic recovery of the penumbra.

The osteotome was a hand-cranked medical chainsaw designed in 1830 by the German surgeon Bernhard Heine. Before Heine, surgeons used crude, manual tools, such as hammers, chisels, and handsaws. The osteotome was among the first mechanical tools used in orthopedic surgery, and it preceded the later use of the motorized chainsaw for woodcutting. Due to the small number of units manufactured, questions remain about the osteotome’s usage. To facilitate conservation and assist with investigation, Heine’s osteotome was digitally reconstructed. As with other digital reconstruction attempts in cultural heritage, assumptions were made to facilitate reproduction. To highlight the functional similarities and contrasts between early and contemporary tools, its parts were compared with contemporary chainsaws and surgical tools. Contemporary orthopedic surgeons have largely shifted away from medical chainsaws, such as the osteotome, in favor of reciprocating saws. Due to its small size and medical purpose, the osteotome was designed for greater precision than a modern industrial chainsaw. Based on the reproduction and comparative analysis, the device was likely used in a manner more similar to modern medical reciprocating saws than to its direct descendant, the industrial chainsaw. The Heine osteotome mechanized surgery and its descendants are still used in medicine and the industry. The osteotome model enabled an analysis of its function and use.

Abstract Background Lung perfusion defects, mainly due to endothelial and coagulation activation, are a key contributor to COVID-19 respiratory failure. COVID-19 patients may also develop acute kidney injury (AKI) because of renal perfusion deficit. We aimed to explore AKI-associated factors and the independent prediction of standardized minute ventilation (MV)—a proxy of alveolar dead space—on AKI onset and persistence in COVID-19 mechanically ventilated patients. Methods This is a multicenter observational cohort study. We enrolled 157 COVID-19 patients requiring mechanical ventilation and intensive care unit (ICU) admission. We collected clinical information, ventilation, and laboratory data. AKI was defined by the 2012 KDIGO guidelines and classified as transient or persistent according to serum creatinine criteria persistence within 48 h. Ordered univariate and multivariate logistic regression analyses were employed to identify variables associated with AKI onset and persistence. Results Among 157 COVID-19 patients on mechanical ventilation, 47% developed AKI: 10% had transient AKI, and 37% had persistent AKI. The degree of hypoxia was not associated with differences in AKI severity. Across increasing severity of AKI groups, despite similar levels of paCO2, we observed an increased MV and standardized MV, a robust proxy of alveolar dead space. After adjusting for other clinical and laboratory covariates, standardized MV remained an independent predictor of AKI development and persistence. d-dimer levels were higher in patients with persistent AKI. Conclusions In critically ill COVID-19 patients with respiratory failure, increased wasted ventilation is independently associated with a greater risk of persistent AKI. These hypothesis-generating findings may suggest that perfusion derangements may link the pathophysiology of both wasted ventilation and acute kidney injury in our population.

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with an unpredictable course of recurrent exacerbations alternating with more stable disease. SLE is characterized by broad immune activation and autoantibodies against double-stranded DNA and numerous proteins that exist in cells as aggregates with nucleic acids, such as Ro60, MOV10, and the L1 retrotransposon-encoded ORF1p. Results Here we report that these 3 proteins are co-expressed and co-localized in a subset of SLE granulocytes and are concentrated in cytosolic dots that also contain DNA: RNA heteroduplexes and the DNA sensor ZBP1, but not cGAS. The DNA: RNA heteroduplexes vanished from the neutrophils when they were treated with a selective inhibitor of the L1 reverse transcriptase. We also report that ORF1p granules escape neutrophils during the extrusion of neutrophil extracellular traps (NETs) and, to a lesser degree, from neutrophils dying by pyroptosis, but not apoptosis. Conclusions These results bring new insights into the composition of ORF1p granules in SLE neutrophils and may explain, in part, why proteins in these granules become targeted by autoantibodies in this disease.

Abstract Objectives To determine the functional domains and symptom scales that affect patients most following radical cystectomy (RC) and urinary diversion (UD), and if a single instrument (or combination) adequately captures these bothersome symptoms. It is unclear whether current patient reported outcome (PRO) instruments that have been used to assess quality of life in patients following RC and UD adequately cover the most bothersome symptoms affecting patients. Materials and methods A systematic search of MEDLINE, EMBASE, PubMed, Cinahl and Cochrane was conducted from January 2000 to May 2023 for original articles of patients who had RC and UD since 2000 for muscle invasive bladder cancer. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) process was followed. Extracted data included the PRO measures used, domains reported and scores in the first 12 months post‐surgery (short‐term) and after 12 months (long‐term). A conservative threshold of 30 for symptom domains was used to determine which PRO domains were potentially concerning to patients in each study. Quality assessment was performed using the QUALSYST appraisal tool. Results Thirty‐five studies met the inclusion criteria, including a total of eight unique PRO instruments. The main findings indicated that physical function was the most concerning PRO for patients with both neobladder (NB) and ileal conduit (IC) in the short and long term. Additionally, bowel, urinary and sexual bother were concerning symptoms for patients with NB in the long‐term, but only in the short‐term for those with IC. Conclusions The main issues are adequately addressed using the combination of EORTC QLQ‐C30 and QLQ‐BLM30 instruments.

ABSTRACT Tuberous sclerosis complex (TSC) is a variable multisystem disorder. The “no mutations identified” (NMI) group are reportedly phenotypically milder than those with an identified molecular cause, and often have mosaic or intronic variants not detected by standard sequencing methods. Methods We describe the phenotypes in an Australian TSC NMI group (n = 18) and a molecular testing strategy implementable in a diagnostic laboratory. Massively parallel sequencing (MPS) of the whole genomic regions of TSC1 and TSC2 was performed using DNA extracted from multiple tissue samples per participant. Results Our study showed that the phenotype in TSC NMI individuals can be similar to those with heterozygous, particularly TSC1, variants. Although neurodevelopmental outcomes can be less severe, the number of organ systems involved was similar to the non‐mosaic groups. A diagnostic yield of 72% (13/18) was achieved, with the majority (10/13) being mosaic variants and the remainder heterozygous variants missed on previous testing. Conclusion Testing DNA from multiple tissue samples allowed for validation of otherwise discarded low‐level mosaic variants and detection of mosaic variants by MPS without excessive cost or the need for specialised techniques. Implementing this approach in a diagnostic setting is viable and allows optimal clinical care of patients with NMI TSC.

The aim of the present systematic review is to evaluate the effects of different photobiomodulation therapy (PBMT) approaches in oncological treatment practices. The review follows the PRISMA guidelines. Specifically, the review is composed of laser PBMT and LED PBMT. A total of 23 studies were included, 14 investigating laser PBMT and 9 examining LED PBMT. In vitro studies demonstrated laser PBMT’s potential to induce apoptosis and cytotoxicity in various cancer cell lines while enhancing sensitivity to chemotherapeutics and natural compounds. However, some studies highlighted divergent effects between in vitro (promoted proliferation) and in vivo xenograft models (slowed tumor growth) for certain laser wavelengths. LED PBMT studies showed blue light inhibited melanoma and pancreatic cancer cell growth, potentially via ROS generation, while red light raised concerns about enhancing oral cancer invasiveness. Both modalities mitigated treatment side effects like oral mucositis, xerostomia, peripheral neuropathy, and improved quality of life. While promising, the outcomes varied based on light parameters, cancer type, and experimental setting, necessitating further optimization of PBMT protocols through well-designed studies to establish long-term safety and efficacy across clinical scenarios.

Background: Autologous venous bypasses effectively treat extensive infrainguinal arterial occlusive disease with excellent long-term patency rates. However, one-third of patients will experience significant vein graft stenosis, particularly within the first-year post-bypass. Current endovascular interventions yield suboptimal results, with reported re-stenosis rates of 20–50 %. This study investigates the efficacy of cutting balloon (‘slash’) followed by a drug-eluting balloon (‘splash’) angioplasty in treating vein graft stenosis. Methods: This single-centre retrospective review examines consecutive patients who underwent the ‘Slash and Splash’ technique for treating significant stenosis (>70 % stenosis and/or PSV >300 cm/s) in infrainguinal autologous bypasses from June 2017 to January 2023. Follow-up duplex ultrasound was conducted at three months, six months, and yearly thereafter. Primary outcomes assessed technical success and graft patency. Secondary outcomes included major adverse limb events (MALEs), and major amputations Results: Twenty-three patients (mean age 67.4 ± 8.1 years, 44 % male) with significant vein graft stenoses underwent the ‘Slash and Splash’ method to salvage their bypasses. Most patients (91 %) had critical limb-threatening ischemia. Nine patients received femoral-popliteal grafts and 14 received femoral-tibial grafts, with18 utilizing saphenous in-situ conduits. The average follow-up duration was 26.1 ± 16.7 months, with no losses to follow-up. The median time from initial bypass to angioplasty was 10 months. Primary technical success was 100 % and primary patency was 95 %, with only one restenosis requiring repeat angioplasty during follow-up. Primary-assisted and secondary patency rates were 100 %. Freedom from MALEs was 90 %, with two patients requiring amputations secondary to diabetic foot infections, although bypasses remained patent at the time of amputation. Conclusions: The ‘Slash and Splash’ technique effectively treats severe infrainguinal vein bypass graft stenosis, offering excellent mid-term patency and freedom from MALEs. Adoption of this technique should be considered in the treatment of hemodynamically significant vein graft stenoses.

Background The dynamics of carbon (C), nitrogen (N), and phosphorus (P) in soils determine their fertility and crop growth in agroecosystems. These dynamics depend on microbial metabolism, which in turn depends on nutrient availability. Farmers typically apply either mineral or organic fertilizers to increase the availability of nutrients in soils. Phosphorus, which usually limits plant growth, is one of the most applied nutrients. Our knowledge is limited regarding how different forms of P impact the ability of microbes in soils to produce the enzymes required to release nutrients, such as C, N and P from different substrates. Methods In this study, we used the arable layer of a calcareous soil obtained from an alfalfa cropland in Cuatro Cienegas, México, to perform an incubation experiment, where five different phosphate molecules were added as treatments substrates: three organic molecules (RNA, adenine monophosphate (AMP) and phytate) and two inorganic molecules (calcium phosphate and ammonium phosphate). Controls did not receive added phosphorus. We measured nutrient dynamics and soil microbial activity after 19 days of incubation. Results Different P molecules affected potential microbial C mineralization (CO2-C) and enzyme activities, specifically in the organic treatments. P remained immobilized in the microbial biomass (Pmic) regardless of the source of P, suggesting that soil microorganisms were limited by phosphorus. Higher mineralization rates in soil amended with organic P compounds depleted dissolved organic carbon and increased nitrification. The C:N:P stoichiometry of the microbial biomass implied a change in the microbial community which affected the carbon use efficiency (CUE), threshold elemental ratio (TER), and homeostasis. Conclusion Different organic and inorganic sources of P affect soil microbial community structure and metabolism. This modifies the dynamics of soil C, N and P. These results highlight the importance of considering the composition of organic matter and phosphate compounds used in agriculture since their impact on the microbial activity of the soil can also affect plant productivity.

BackgroundFamily-based treatment (FBT) is the leading intervention for adolescents with anorexia nervosa (AN); however, it is under researched in socioeconomically disadvantaged and racially diverse youth.MethodsSemi-structured interviews were completed with ten FBT clinicians who practice in publicly-funded settings. Interview questions were focused on implementation challenges, overall acceptability and appropriateness of FBT, and naturally-occurring treatment adaptations.ResultsContent analysis revealed common themes relating to the implementation of FBT in publicly-funded, community-based settings: acceptability and appropriateness, complexity and learnability, perceived core components of FBT, cultural adaptations, socioeconomic factors, logistical considerations, organizational and systemic barriers, training acceptability, participant’s self-efficacy, and telehealth accommodations.ConclusionThe discussed themes offer insights into the implementation of FBT for settings with limited resources, aligning with prior research on clinical adaptations for multicultural patients. Recognizing these themes can guide clinical adjustments and refine the adapted treatment model in real-world settings for patients facing systemic barriers.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Aim: The objectives of this study were to assess the return of spontaneous circulation rates and hemodynamic response of large swine (>65Kg) during cardiopulmonary resuscitation after nontraumatic cardiac arrest using the COBRA-OS® aortic occlusion balloon and to address limitations of large swine closed-chest cardiopulmonary resuscitation by comparing closed-chest vs. open-chest cardiopulmonary resuscitation. Methods: Yorkshire pigs (n = 10) weighing >65 kg were anesthetized and ventilated. After 7 min of untreated ventricular fibrillation (VF), animals were randomized to receive mechanical closed-chest cardiopulmonary resuscitation or open-chest cardiac massage. Following a 5-minute low-flow state, advanced cardiac life support algorithms were started and the COBRA-OS® was inflated in the thoracic aorta. Animals that achieved return of spontaneous circulation were re-started on mechanical ventilation and medications, CPR, defibrillation, and aortic occlusion were discontinued. The primary outcome was return of spontaneous circulation and secondary outcomes were mean arterial pressures generated in the low flow and aortic occlusion states before return of spontaneous circulation. Groups were compared with a t-test or Mann-Whitney U test for normal and non-parametric data, respectively, while categorical data was compared with the chi square test. Results: Return of spontaneous circulation was obtained in 4 animals (80%) in the open cardiac massage group and none in the mechanical closed-chest CPR group (p 65 kg) swine models of nontraumatic cardiac arrest. The COBRA-OS® demonstrated feasibility for use in this model.The Keenan Research Center, Li Ka Shing Knowledge Institute of St. Michael’s Hospital Animal Care Committee: ACC Protocol #726.

Abstract Stress shielding and aseptic loosening are complications of short stem total hip arthroplasty, which may lead to hardware failure. Stems with increased porosity toward the distal end were discovered to be effective in reducing stress shielding, however, there is a lack of research on optimized porous distribution in stem’s coating. This study aimed to optimize the distribution of the coefficient of friction of a metaphyseal femoral stem, aiming for reducing stress shielding in the proximal area. A finite element analysis model of an implanted, titanium alloy short-tapered wedge stem featuring a porous coating made of titanium was designed to simulate a static structural analysis of the femoral stem's behavior under axial loading in Analysis System Mechanical Software. For computational feasibility, 500 combinations of coefficients of friction were randomly sampled. Increased strains in proximal femur were found in 8.4% of the models, which had decreased coefficients of friction in middle medial areas of porous coating and increased in lateral proximal and lateral and medial distal areas. This study reported the importance of the interface between bone and middle medial and distal lateral areas of the porous coating in influencing the biomechanical behavior of the proximal femur, and potentially reducing stress shielding.

Abstract Background Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on “focal” or “non-focal” lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish “focal” from “non-focal” lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. Methods The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as “focal” or “non-focal”. Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for “non-focal” ARDS and lower PEEP and prone positioning for “focal” ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. Discussion PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. Trial registration The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

Immunoprecipitation (IP) coupled with mass spectrometry effectively maps protein–protein interactions when genome-wide, affinity-tagged cell collections are used. Such studies have recorded significant portions of the compositions of physiological protein complexes, providing draft ’interactomes’; yet many constituents of protein complexes still remain uncharted. This gap exists partly because high-throughput approaches cannot optimize each IP. A key challenge for IP optimization is stabilizing in vivo interactions during the transfer from cells to test tubes; failure to do so leads to the loss of genuine interactions during the IP and subsequent failure to detect. Our high-content screening method explores the relationship between in vitro chemical conditions and IP outcomes, enabling rapid empirical optimization of conditions for capturing target macromolecular assemblies.

Abstract Background Breakthrough cancer pain (BTCP) is primarily managed at home and can stem from physical exertion and emotional distress triggers. Beyond these triggers, the impact of ambient environment on pain occurrence and intensity has not been investigated. This study explores the impact of environmental factors on the frequency and severity of breakthrough cancer pain (BTCP) in the home context from the perspective of patients with advanced cancer and their primary family caregiver. Methods A health monitoring system was deployed in the homes of patient and family caregiver dyads to collect self-reported pain events and contextual environmental data (light, temperature, humidity, barometric pressure, ambient noise.) Correlation analysis examined the relationship between environmental factors with: 1) individually reported pain episodes and 2) overall pain trends in a 24-hour time window. Machine learning models were developed to explore how environmental factors may predict BTCP episodes. Results Variability in correlation strength between environmental variables and pain reports among dyads was found. Light and noise show moderate association (r = 0.50–0.70) in 66% of total deployments. The strongest correlation for individual pain events involved barometric pressure (r = 0.90); for pain trends over 24-hours the strongest correlations involved humidity (r = 0.84) and barometric pressure (r = 0.83). Machine learning achieved 70% BTCP prediction accuracy. Conclusion Our study provides insights into the role of ambient environmental factors in BTCP and offers novel opportunities to inform personalized pain management strategies, remotely support patients and their caregivers in self-symptom management. This research provides preliminary evidence of the impact of ambient environmental factors on BTCP in the home setting. We utilized real-world data and correlation analysis to provide an understanding of the relationship between environmental factors and cancer pain which may be helpful to others engaged in similar work.

Subsidence refers to the gradual lowering or sudden sinking of the ground surface and is known to impact human lives in terms of damages to the infrastructures, utility lines, and buildings as well as changes in the surficial drainage systems and groundwater conditions. The impacts of land subsidence will be greater in the future, considering the sea level rise, population growth, intensification of coastal erosion and extreme events, as well as increase in flood risk or freshwater salinization, mostly in coastal cities. The main aim of this work is to provide an open-source, peer-reviewed, and comprehensive database identifying the main and secondary causes of land subsidence in 143 coastal cities. We highlight the potential impacts of subsidence that are still unknown in some at-risk cities and non-existence of mitigation measures. The database additionally shows that mitigation measures, specifically those addressing subsidence due to groundwater extraction, have proven successful in the past. The proposed database aims to increase the knowledge on the subsidence phenomenon and also global awareness of land subsidence issues among researchers, the scientific community, stakeholders, and policymakers in terms of urban planning and development.

No abstract available.

Summary: Fasting has emerged as a potent means of preserving tissue function with age in multiple model organisms. However, our understanding of the relationship between food removal and long-term health is incomplete. Here, we demonstrate that in the nematode worm Caenorhabditis elegans, a single period of early-life fasting is sufficient to selectively enhance HSF-1 activity, maintain proteostasis capacity and promote longevity without compromising fecundity. These effects persist even when food is returned, and are dependent on the mitochondrial sirtuin, SIR-2.2 and the H3K27me3 demethylase, JMJD-3.1. We find that increased HSF-1 activity upon fasting is associated with elevated SIR-2.2 levels, decreased mitochondrial copy number and reduced H3K27me3 levels at the promoters of HSF-1 target genes. Furthermore, consistent with our findings in worms, HSF-1 activity is also enhanced in muscle tissue from fasted mice, suggesting that the potentiation of HSF-1 is a conserved response to food withdrawal.

Improve optical band gaps of metal oxides by a suitable doping is very interesting for optoelectronic application. However, the effect of doping is usually affected by the synthesis method. Among the existing synthesis routes, coprecipitation is cheap and offers a possibility to strictly control the stoichiometry, depending on the precipitating agents. Herein cobalt doped manganese oxides were prepared via coprecipitation using succinate ion as precipitating agent and their optical properties have been investigated. The results obtained from a set of instrumental techniques revealed that the main phase formed is Mn3O4 hausmatite with cobalt substituting manganese in the structure. The UV–visible diffuse reflectance results demonstrated that the band gap increases from 1.97 for undoped Mn3O4, to 2.91 eV for 5% Co doping, and therefore decreases to 2.34 eV for 6% Co. This trend can be explained by the difference in the substitution site of cobalt which is either tetrahedral or octahedral.