Impact of an emergency department nurse training intervention on the adequacy of thromboprophylaxis for venous thromboembolism: the PROTESU III study. / Impacto de una intervención formativa en enfermería de urgencias sobre la adecuación de la profilaxis de la enfermedad tromboembólica venosa: estudio PROTESU III.

OBJECTIVE: Objectives. To assess the impact of training for emergency department (ED) nurses on adequate thromboprophylaxis for patients admitted to hospital from the ED for medical conditions. Methods. Multicenter quasiexperimental pre-post study of an ED nurse training intervention in 8 hospitals. Patients were recruited from January 2022 through May 2023 in 3 phases: before nurse training, in the first month after training, and in the sixth month after training. Included were patients attended in the ED for medical conditions. Adequate thromboprophylaxis was defined as 1) use of prophylactic drugs in patients at high risk for venousthromboembolism according to the Padua Prediction Score (PPS), and 2) nonuse in patients at low risk. We compared the percentage of adequate prophylaxis in the first phase to the percentages in the second and third phases. Results. A total of 928 patients were included (326 in phase 1, 295 in phase 2, and 307 in phase 3). PPS scores indicated that 238 (73%) of the patients were at high risk in phase 1 vs 189 (64.1%, P = .016) in phase 2 and 207 (67.4%, P = .125) in phase 3. A total of 187 patients (57.4%, 95% CI, 51.8%-62.8%) were adequatelythromboprophylaxed in phase 1 vs 178 (60.%, 95% CI, 54.5%-66%) in phase 2 (absolute difference in proportions, 3.0% (95% CI, -4.8% to 10.6%; P = .462)]. In phase 3, 166 patients (54.1%, 95% CI, 48.3%-59.7%) received adequate prophylaxis (difference, -3.3% (95% CI, -11.0% to 4.4%; P = .405). Conclusions. A training intervention for ED nurses, implemented as an isolated strategy, had no impact on the adequacy of thromboprophylaxis in patients admitted from the ED for medical conditions.

OBJETIVO: Objetivos. Evaluar el impacto de una intervención formativa en enfermería de urgencias sobre la adecuación de la tromboprofilaxis farmacológica de los pacientes ingresados por patología médica. Método. Estudio cuasiexperimental, multicéntrico (8 hospitales), pre y posintervención, con 3 fases de reclutamiento (enero 2022-mayo 2023): primera,preintervención; segunda, en el primer mes tras la intervención; y tercera, al sexto mes. Se incluyeron los pacientes atendidos en urgencias que requirieron ingreso por enfermedad médica. La adecuación de la tromboprofilaxis farmacológica se definió como: 1) la utilización en pacientes clasificados en el grupo de riesgo alto por la Escala de Padua (PPS); o 2) la no utilización en pacientes clasificados de riesgo bajo. Se compararon los porcentajes de adecuación de las fases 2 y 3 frente a la fase 1. Resultados. Se incluyeron 928 pacientes: 326 en la fase 1; 295 en la fase 2; y 307 en la fase 3. En la fase 1, 238 pacientes (73%) fueron clasificados de riesgo alto por PPS; en la fase 2, 189 (64,1%) (p = 0,016); y en la fase 3, 207 (67,4%) (p = 0,125). La tromboprofilaxis farmacológica fue adecuada en 187 pacientes (57,4%, IC 95% 51,8-62,8%) de la fase 1; en 178 (60,3%, IC 95% 54,5 66%) de la fase 2 [diferencia absoluta proporciones (DAP) 3,0% (IC 95% de ­4,8 a +10,6%), p = 0,462], y en 166 (54,1%, IC 95% 48,3-59,7%) de la fase 3 [DAP 3,3% (IC 95% de ­11,0 a +4,4%, p = 0,405]. Conclusiones. Una intervención formativa aislada en la enfermería de urgencias no tuvo impacto sobre la adecuación de la tromboprofilaxis farmacológica en urgencias de los pacientes que ingresan por enfermedad médica.

Key Clinical and Histopathological Features of a Pterygium-Like Induced Lesion in a Rabbit Model.

Purpose: Surgery is the definitive treatment for pterygium; therefore, reliable animal models are required for translational research. The goal of this investigation was to establish a standardized preclinical model of pterygium-like lesion. Methods: A subconjunctival injection of fibroblasts (NIH3T3) and extracellular matrix was administered to 22 New Zealand rabbits. Clinical evaluation was assessed at different points, the severity of the lesion was scored according to four grades and correlated with the area of hyperemia and the histopathological findings on day 23. Results: Thirteen of 22 eyes (60%) developed pterygium-like lesions after 7 days and progressed through different grades. Initially, grade 3, characterized by an elevated and fleshiness conjunctiva with tortuous hyperemia, was evident on day 7. By day 15, lesion decreased to grade 2, with less elevation and hyperemia. Subsequent improvement was noted, with grade 1 on day 18. Finally, day 23 was marked by a white‒yellow lesion, classified as grade 4. The area of hyperemia increased from grade 2 to grade 3 (P < 0.05) and decreased from grade 3 to grade 4 (P ≤ 0.05). Histopathological analysis revealed a tendency toward increasing inflammation at grades 2, 3, and 4. There was a correlation between clinical features and the degree of inflammation. Conclusions: Subconjunctival injection of NIH3T3 and extracellular matrix induces a pterygium-like lesion that progresses across four grades, beginning with an acute inflammatory process that evolve a chronic form. This study provides a replicable model for simulating pterygium. Translational Relevance: The development of a standardized preclinical model of pterygium to evaluate new pharmacological or surgical treatments.

Tachypnea in response to hypoxemia decreases with age in older patients.

AIM: To investigate if tachypneic response to hypoxia is decreased in older patients. METHODS: We included all patients ≥65 years of age attending 52 Spanish emergency departments (EDs) for whom peripheral arterial oxygen saturation (SatO2) measured by pulsioxymetry and respiratory rate (RR) were registered at ED arrival. We assessed the relationship between SatO2 and RR in different models, and with the best-fitting model, we independently analyzed this relationship in four subgroups according to patient age (65-69, 70-79, 80-89, and ≥90 years). Five sensitivity analyses using different subsets of patients were carried out to check for the consistency of the results. RESULTS: We included 7126 patients, with medians for SatO2 and RR of 97% (interquartile range [IQR]: 94-98) and 15 bpm (IQR: 15-16), respectively. We found significant associations (P < 0.001) between SatO2 and RR in every model tested (P < 0.001 for all), with the quadratic model obtaining the best fit (R2: 0.098) over those obtained with linear (R2: 0.096) and logarithmic (R2: 0.092) models. The same was observed in sensitivity analyses, with R2 for quadratic models ranging from 0.069 in patients with low comorbidity and 0.102 in patients breathing room air. The mean RR for 100% SatO2 was 15 bpm and increased as SatO2 decreased, although with a progressive slowing of the slope, with a mean RR of 27 at 50% SatO2. We detected a decreased RR response to increasing hypoxemia according to age and, while the RR curve was higher and with a progressively steepening slope in the 972 patients aged 65-69 (mean RR of 42 bpm with 50% SatO2), a progressive slowing of slope was observed in the 2693 patients aged 70-79 (mean RR of 28 with 50% SatO2), the 2582 aged 80-89 (mean RR of 25) and the 879 aged ≥90 (mean RR of 23). Sensitivity analyses provided very similar results. CONCLUSION: Tachypneic response to hypoxemia in older patients decreases as age advances, regardless of the reason leading to hypoxemia. Geriatr Gerontol Int 2024; ••: ••-••.

An exploratory analysis of associations of genetic variation with the efficacy of tocilizumab in severe COVID-19 patients. A pharmacogenetic study based on next-generation sequencing.

Background: In the context of the cytokine storm the takes place in severe COVID-19 patients, the Interleukin 6 (IL6) pathway emerges as one of the key pathways involved in the pathogenesis of this hyperinflammatory state. The strategy of blocking the inflammatory storm by targeting the IL6 is a promising therapy to mitigate mortality. The use of Tocilizumab was recommended by the World Health Organization (WHO) to treat severe COVID-19 patients. However, the efficacy of Tocilizumab is variable. We hypothesize that the genetic background could be behind the efficacy of Tocilizumab in terms of mortality. Methods: We performed a targeted-next generation sequencing of 287 genes, of which 264 belong to a community panel of ThermoFisher for the study of genetic causes of primary immunodeficiency disorders, and 23 additional genes mostly related to inflammation, not included in the original community panel. This panel was sequenced in an initial cohort of 425 COVID-19 patients, of which 232 were treated with Tocilizumab and standard therapy, and 193 with standard therapy only. Selected genetic variants were genotyped by single base extension in additional 245 patients (95 treated with Tocilizumab and 150 non-treated with Tocilizumab). Appropriate statistical analyses and internal validation, including logistic regression models, with the interaction between Tocilizumab and genetic variants, were applied to assess the impact of these genetic variants in the efficacy of Tocilizumab in terms of mortality. Results: Age (p < 0.001) and cardiovascular disease (p < 0.001) are risk factors for mortality in COVID-19 patients. The presence of GG and TT genotypes at IL10Rß (rs2834167) and IL1ß (rs1143633) genes significantly associates with a reduced risk of mortality in patients treated with Tocilizumab (OR = 0.111; 95%CI = 0.015-0.829; p = 0.010 and OR = 0.378; 95%CI = 0.154-0.924; p = 0.028 respectively). The presence of CC genotype at IL1RN (rs2234679) significantly associates with an increased risk of mortality, but only in patients not treated with Tocilizumab (OR = 3.200; 95%CI = 1.512-6.771; p = 0.002). Exhaustive internal validation using a bootstrap method (B = 500 replicates) validated the accuracy of the predictive models. Conclusion: We developed a series of predictive models based on three genotypes in genes with a strong implication in the etiopathogenesis of COVID-19 disease capable of predicting the risk of mortality in patients treated with Tocilizumab.

Determination of the internal loads experienced by proximal phalanx fracture fixations during rehabilitation exercises.

Phalangeal fractures are common, particularly in younger patients, leading to a large economic burden due to higher incident rates among patients of working age. In traumatic cases where the fracture may be unstable, plate fixation has grown in popularity due to its greater construct rigidity. However, these metal plates have increased reoperation rates due to inflammation of the surrounding soft tissue. To overcome these challenges, a novel osteosynthesis platform, AdhFix, has been developed. This method uses a light-curable polymer that can be shaped in situ around traditional metal screws to create a plate-like structure that has been shown to not induce soft tissue adhesions. However, to effectively evaluate any novel osteosynthesis device, the biomechanical environment must first be understood. In this study, the internal loads in a phalangeal plate osteosynthesis were measured under simulated rehabilitation exercises. In a human hand cadaver study, a plastic plate with known biomechanical properties was used to fix a 3 mm osteotomy and each finger was fully flexed to mimic traditional rehabilitation exercises. The displacements of the bone fragments were tracked with a stereographic camera system and coupled with specimen specific finite element (FE) models to calculate the internal loads in the osteosynthesis. Following this, AdhFix patches were created and monotonically tested under similar conditions to determine survival of the novel technique. The internal bending moment in the osteosynthesis was 6.78 ± 1.62 Nmm and none of the AdhFix patches failed under the monotonic rehabilitation exercises. This study demonstrates a method to calculate the internal loads on an osteosynthesis device during non-load bearing exercises and that the novel AdhFix solution did not fail under traditional rehabilitation protocols in this controlled setting. Further studies are required prior to clinical application.

Biomechanical and histological evaluation of a prototype bovine pericardial patch for veterinary abdominal surgery: An approximation study.

In veterinary medicine, especially within large animal medical and surgical clinics, addressing cavitary defects is a primary concern. In bovines, umbilical hernias are the most common defect, and surgical repair often necessitates the use of prosthetic materials. However, there is a high rate of recurrence with sutures or synthetic meshes, largely due to tissue contamination. The development of biological patches for such repairs is still in its early stages in veterinary medicine, with no commercially tested prototypes available in Argentina. Tissues derived from the extracellular matrix are considered for this purpose, with bovine pericardium standing out due to its architectural characteristics and mechanical properties. For an ideal membrane, the pericardium must retain its biomechanical properties while being unreactive and safe for the host. This study aimed to biomechanically and histologically characterize a bovine pericardium patch through all stages of processing. The treatment involved fixation with 0.5 % glutaraldehyde, immersion in an antibiotic/antimycotic solution, and detoxification and storage in a 98 % sterile glycerin solution, with three sodium phosphate-buffered washes between steps. Histological examinations and stress-strain tests were performed at each processing stage, using native pericardium as a control. Despite some minor modifications in the histological and mechanical properties, the final patches appear to be a viable alternative for resolving cavitary defects.

Intestinal pathology in goats challenged with Clostridium perfringens type D strain CN1020 wild-type and its genetically modified derivatives.

Clostridium perfringens type D is the causative agent of enterotoxemia in sheep, goats, and cattle. Although in sheep and cattle, the disease is mainly characterized by neurological clinical signs and lesions, goats with type D enterotoxemia frequently have alterations of the alimentary system. Epsilon toxin (ETX) is the main virulence factor of C. perfringens type D, although the role of ETX in intestinal lesions in goats with type D enterotoxemia has not been fully characterized. We evaluated the contribution of ETX to C. perfringens type D enteric pathogenicity using an intraduodenal challenge model in young goats, with the virulent C. perfringens type D wild-type strain CN1020; its isogenic etx null mutant; an etx-complemented strain; and sterile, non-toxic culture medium. The intestinal tract of each animal was evaluated grossly, microscopically, and immunohistochemically for activated caspase-3. Both ETX-producing strains induced extensive enterocolitis characterized by severe mucosal necrosis, apoptosis, and diffuse suppurative infiltrates. No significant gross or microscopic lesions were observed in goats inoculated with the non-ETX-containing inocula. These results confirm that ETX is essential for the production of intestinal lesions in goats with type D disease. Also, our results suggest that the intestinal pathology of type D enterotoxemia in goats is, at least in part, associated with apoptosis.

Advances in prostate cancer treatment: Radionuclide therapy for prostate cancer.

The optimal treatment of metastatic castration-resistant prostate cancer (mCRPC) continues to be challenging, given the multitude of life prolonging treatment options. Radionuclide therapy delivers concentrated doses of radiation via ionizing particles chelated to ligands or antibody-based molecules with specific tumor targets and is approved for patients with treatment resistant mCRPC. Variations of radionuclide therapies within the continuum of prostate cancer treatment are being investigated. Landmark phase III clinical trials of beta-emitting 177Lu-PSMA radionuclide therapy have demonstrated the utility of 177Lu-PSMA in the treatment of mCRPC. Further research into alpha-emitting radionuclide therapy and vectors may provide alternative treatments for patients with treatment resistant mCRPC. As radionuclide therapy treatment options evolve, assessing appropriate patient selection for radionuclide therapy is important and may be facilitated by advances in imaging and blood-based biomarkers. Exploration of other approved life prolonging therapies in combination with radionuclide therapy has shown increasing interest as a potential method of combatting radionuclide therapy resistance. In this chapter, we review various types of radionuclide therapies for mCRPC, patient selection for radionuclide therapy from outcome predictions, ongoing clinical trials of radiopharmaceuticals for treatment of prostate cancer, and the resistance mechanisms and challenges to radionuclide therapy.

One year follow-up of the colon cancer patient cohort treated with a novel miniaturized robotic-assisted surgery device (mRASD).

BACKGROUND: With the proven benefits of minimally invasive surgery, there is steady growth in robotic surgery use and interest in novel robotic platforms. A miniaturized Robotic-Assisted Surgery Device (mRASD) has been in clinical use under a multi-center, investigational device exemption (IDE) study for right and left colectomy. The goal of this work was to report the short-term and 12-month outcomes specifically for the cohort of colon cancer patients that underwent surgery using the mRASD. METHOD: From the IDE study that included both benign and malignant diseases, long-term follow-up was only conducted for patients with colon cancer. The main outcome measures were the oncologic quality metrics (Overall Survival, OS and Disease-free Survival, DFS). Secondary outcomes included incidence of intra-operative, device-related, and procedure-related adverse events. Frequency statistics were performed to assess the measures of central tendency and variability in short (within 30 days) and long-term (1-year) outcomes. RESULTS: Thirty total patients underwent a colectomy with mRASD; 17 (57%) were diagnosed with a malignancy and included in this analysis. The mean patient age was 59.9 ± 13.2 years. There were no intraoperative or device-related adverse events. In 100% of cases (n = 17), the primary dissection was completed and hemostasis maintained using the mRASD, and negative margins were achieved. At 30 days postoperatively, the major complication rate was 6%, and there was one unplanned reoperation for anastomotic leak. At one-year follow-up, the OS and DFS rates were 100 and 94%, respectively. In one patient, omental implants were discovered at the time of surgery, and the patient opted to not undergo additional therapy. CONCLUSIONS: The first experience with mRASD for colectomy in colon cancer demonstrated technical effectiveness and an acceptable surgical safety profile in line with other minimally invasive procedures. The study continues to monitor disease recurrence and survival outcomes in this cohort.

MyofAPPcial: Construct validity of a novel technological aid for improving clinical reasoning in the management of myofascial pain syndrome.

BACKGROUND: Physiotherapists encounter challenges in diagnosing myofascial trigger points (MTrPs), which are crucial for managing myofascial pain but difficult due to their complex referred pain patterns. We aimed to assess if an interactive software (MyofAPPcial) can enhance the ability of physical therapists specialized in musculoskeletal disorders (as clinicians and as researchers and educators) to identify referred pain patterns associated with specific MTrPs and to explore their opinion about incorporating this technology regularly into their professional setting. METHODS: After developing the app, a descriptive cross-sectional survey study was conducted. Participants were asked about their demographic characteristics, professional experience, two knowledge tests (first without and later with MyofAPPcial support) and the 18-item mHealth app usability questionnaire. RESULTS: Fifty-nine participants completed the survey (47.5% clinicians and 62.5% researchers/educators). Groups were comparable in terms of age, gender and professional experience (p > .05). However, clinicians coursed shorter specific MPS trainings (p = .007) and handle more cases a week (p < .001). In the first knowledge test, participants in both the groups were more accurate in identifying pain maps of highly prevalent MTrPs than those with a moderate or low prevalence (p < .001), with no differences between the groups for individual items (all, p > .05) nor the total score (p > .05). In the second knowledge test, perfect scores were obtained for all items in both the groups. Finally, MyofAPPcial scored high satisfaction and app usefulness, with no difference between clinicians and researchers/educators (except greater convenience of use for researchers/educators p = .02). CONCLUSIONS: MyofAPPcial enhances physiotherapists' ability to accurately identify MTrPs, with a good acceptation among clinicians and researchers/educators.

Clinical course in older patients diagnosed with syncope treated in Spanish emergency departments: results from the Emergency Department and Elder Needs-17 study. / Evolución clínica de los pacientes mayores diagnosticados de síncope en servicios de urgencias en España: resultados del estudio EDEN-17.

OBJECTIVE: To study factors associated with hospitalization in an unselected population of patients aged 65 years or older treated for syncope in Spanish hospital emergency departments (EDs). To determine the prevalence of adverse events at 30 days in patients discharged home and the factors associated with such events. METHODS: We included all patients aged 65 years or older who were diagnosed with syncope during a single week in 52 Spanish EDs, recording patient clinical and ED case management data. We compared the findings between hospitalized patients and those discharged home, following the latter for 30 days. In discharged patients, we explored predictors of a composite adverse-event outcome (occurrence of any of the following: ED revisits, hospitalization related to the index visit, or any-cause death). RESULTS: A total of 477 patients with syncope were identified; 67 (14%) were admitted, and 5 (7.5%) died. The median (interquartile range) length of hospital stay was 6 days (3-11 days). Comorbidity increased the probability of hospitalization (odds ratio, 2.172; 95% CI, 1.013-4.655). Among the 410 patients (86%) discharged home from the ED, 9.2% experienced an adverse event within 30 days (ED revisits, 8.,1%; hospitalization, 2.2%; death, 1.5%). No factors were associated with the 30-day composite outcome. CONCLUSIONS: The majority of patients aged 65 years or older are discharged home from EDs, and 30-day adverse events, while infrequent, are difficult to predict. Hospitalization was related to comorbidity and an absence of cognitive decline.

OBJETIVO: Investigar en una muestra no seleccionada de población mayor (65 o más años) atendida en servicios de urgencias hospitalarios (SUH) españoles por síncope los factores que se asociaron con la hospitalización, prevalencia de eventos adversos (EA) a 30 días y los factores asociados a estos entre los pacientes dados de alta desde urgencias. METODO: Se incluyeron todos pacientes con 65 o más años diagnosticados de síncope durante una semana en 52 SUH españoles. Se recogieron datos de la situación clínica y el manejo en urgencias, que se compararon entre los pacientes hospitalizados y los dados de alta directamente desde urgencias. Estos últimos fueron seguidos durante 30 días y se identificaron aquellos que presentaron un EA combinado (reconsulta en urgencias u hospitalización relacionada con el evento índice y muerte por cualquier causa), y se investigaron los factores que predecían dicho EA combinado. RESULTADOS: Se identificaron 477 pacientes con síncope. Hospitalizaron 67 (14%), de los que fallecieron 5 (7,5%) y la estancia mediana fue de 6 días (RIC 3-11). La comorbilidad incrementó la probabilidad de ingreso (OR: 2,172, IC 95%: 1,013-4,655). Entre los 410 pacientes dados de alta de urgencias (86%), el 9,2% tuvo un EA durante los 30 días siguientes (reconsulta a urgencias: 8,1%; hospitalización: 2,2%; muerte: 1,5%). Ningún factor se asoció con el riesgo de EA combinado a 30 días. CONCLUSIONES: La mayoría de los pacientes con 65 años o más atendidos en los SUH por síncope son dados de alta directamente desde urgencias, y los EA a los 30 días fueron poco frecuentes, pero difíciles de predecir. La hospitalización se relacionó con presencia de comorbilidad y ausencia de deterioro cognitivo.

Quantum Effects Explain the Twist Angle in the Helical Structure of DNA.

Why are DNA bases stacked in a double helix structure? We combined three theoretical approaches to demonstrate how one core concept derived from quantum mechanics (Pauli repulsion) annihilates the contribution of dispersion to the π-π stacking. The helical architecture is governed by a combination of exchange and electrostatic forces, a result that is interpreted from both a computational and a biological perspective.

A congenital periocular leiomyosarcoma in a dairy calf.

A mass was removed surgically from the right orbit of a 1-d-old Holstein calf. Grossly, the mass filled the rostral part of an enlarged orbit and compressed the globe toward the caudal pole of the orbit. The brown, 6-cm tumor had central yellow and brown areas, and a smooth, glistening cut surface. Microscopically, the neoplasm was highly cellular and composed of spindle cells arranged in irregular, broad, interlacing streams and bundles, forming a herringbone pattern and supported by a sparse collagenous matrix. Neoplastic cells infiltrated surrounding soft tissues and compressed the globe. The neoplastic cells had positive immunolabeling for α-smooth muscle actin, desmin, and vimentin, and negative immunolabeling for factor VIII, myoglobin, cytokeratin, and skeletal muscle actin. Histopathology and immunohistochemistry results confirmed a diagnosis of leiomyosarcoma. To our knowledge, congenital periocular leiomyosarcoma has not been reported in cattle previously. This rare tumor could be included as a differential diagnosis in newborn calves with periocular masses.

LDL-Cholesterol-Lowering Effects of a Dietary Supplement Containing Onion and Garlic Extract Used in Healthy Volunteers.

Hypercholesterolemia plays a pivotal role in the development and progression of cardiovascular diseases, and its prevention seems to be a crucial healthcare strategy to ameliorate these conditions. Subjects with mild hypercholesterolemia are frequently advised against using cholesterol-lowering drugs due to potential side effects, with an emphasis instead on prioritizing dietary adjustments and lifestyle modifications as the primary strategy. In this context, the use of dietary supplements based on medicinal plants may be recommended as a complementary approach to managing elevated cholesterol levels. The aim of this study was to investigate the safety and potential therapeutic effectiveness of a standardized formulation containing extracts from garlic and onions in addressing the health concerns of individuals with slightly elevated cholesterol levels. A controlled, randomized, double-blind, two parallel-group study was conducted over 8 weeks, with clinical visits scheduled at baseline, weeks 2 and 4, as well as at the end of the study. The results revealed significant reductions in both low-density lipoprotein cholesterol and total cholesterol levels among participants who received the extract. Additionally, improvements in blood pressure, as well as in oxidative and inflammatory markers were observed, thus suggesting its potential as a valuable therapeutic intervention for managing mild hypercholesterolemia.

Acidic Lysosome-Anchoring Croconium-Based Nanoplatform for Enhanced Triple-Mode Bioimaging and Fe3+-Triggered Tumor Synergistic Therapy.

Metal-modulated croconium dyes with multimodal-imaging and synergistic therapy in the tumor microenvironment have exhibited great potential in tumor theranostics. However, their unideal structure optimization always weakened the efficacy of near-infrared fluorescence-photoacoustic (NIRF/PA) imaging and photothermal therapy (PTT). Here, we screened croconium dye containing two indole groups with better NIRF/PA imaging and PTT in their family, linked to two morpholine rings, and obtained CR-736, as a lysosome-targeting and Fe3+-modulated agent. The established CR-736-Fe3+ nanoplatform was accurately delivered to the breast tumor site, released CR-736 and Fe3+ in the lower acidic lysosome microenvironment, and activated pH-responsive NIRF/PA/magnetic resonance imaging and PTT. Furthermore, ferroptosis generated hydroxyl free radicals and lipid peroxide by consuming GSH and H2O2 by dint of the accumulation of Fe3+ in tumor cells, which resulted in the inhibition of the expression of heat shock proteins and the concomitant recovery of PTT. The synergistic therapy of PTT, ferroptosis, and chemodynamics was further optimized to the maximal extent in tumor lysosome acidic microenvironment and proved both in vitro and a mouse tumor model. This study opens a new avenue in designing excellent and unique croconium-based nanoplatforms, synergizing multiple tumor theranostic methods, and further optimizing the theranostic effects in tumor microenvironment.

The Dynastic Benefits of Early-Childhood Education: Participant Benefits and Family Spillovers.

We demonstrate the social efficiency of investing in high-quality early childhood education using newly collected data from the HighScope Perry Preschool Project. The data analyzed are the longest follow-up of any randomized early childhood education program. Annual observations of participant outcomes up to midlife allow us to provide a cost-benefit analysis without relying on forecasts. Adult outcomes on the participants' children and siblings allow us to quantify spillover benefits. The program generates a benefit-cost ratio of 6.0 (p-value = 0.03). Spillover benefits increase this ratio to 7.5 (p-value = 0.00).

Impact of Implementing an Antimicrobial Stewardship Program for Optimizing Antibiotic Treatment in Gram-negative Bacilli Bacteremia.

BACKGROUND: Antibiotic Stewardship Programs (ASP) have improved empirical and directed antibiotic treatment in Gram-negative Bacilli (GNB) bloodstream infections. A decrease in mortality, readmission, and length of hospitalization has been reported. MATERIALS AND METHODS: A pre-post-quasi-experimental study was conducted between November and April 2015-2016 (pre-intervention period), 2016-2017, 2017-2018, and 2018-2019 (post-intervention periods), to analyse the impact of ASP on empirical, directed, and entire treatment optimization, as well as mortality, readmission, and length of hospitalization, in hospitalized patients with Gram-negative bacilli (GNB) bloodstream infections. RESULTS: One hundred seventy-four patients were included (41 in the pre-intervention group, 38 in the first-year post-intervention group, 50 in the second-year post-intervention group, and 45 in the third-year post-intervention group). There was a significant improvement in directed treatment optimization (43.9% in the pre-intervention group, 68.4% in the first-year post-intervention group, 74% in the second-year post-intervention group, and 88.9% in the third-year post-intervention group, P <0.001), as well as in entire treatment optimization (19.5%, 34.2%, 40.0%, and 46.7%, respectively, P=0.013), with increased optimal directed (adjusted odds ratio [aOR], 3.71; 95% confidence interval [CI], 1.60-8.58) and entire treatment (aOR, 3.31; 95% CI, 1.27-8.58). Although a tendency toward improvement was observed in empirical treatment after ASP implementation, it did not reach statistical significance (41.5% vs. 57.9%, P=0.065). No changes in mortality, readmission, or length of hospitalization were detected. CONCLUSION: ASP implementation improved both directed and entire treatment optimization in patients with GNB bloodstream infections over time. Nevertheless, no improvement was found in clinical outcomes such as mortality, readmission, or length of hospitalization.

Plasma Levels of Neuron/Glia-Derived Apoptotic Bodies, an In Vivo Biomarker of Apoptosis, Predicts Infarct Growth and Functional Outcome in Patients with Ischemic Stroke.

Evidence demonstrating the involvement of apoptosis in the death of the potentially salvageable area (penumbra zone) in patients during stroke remains limited. Our aim was to investigate whether apoptotic processes occur in penumbral brain tissue by analyzing circulating neuron- and glia-derived apoptotic bodies (CNS-ApBs), which are vesicles released into the bloodstream during the late stage of apoptosis. We have also assessed the clinical utility of plasma neuronal and glial apoptotic bodies in predicting early neurological evolution and functional outcome. The study included a total of 71 patients with acute hemispheric ischemic stroke (73 ± 10 years; 30 women). Blood samples were collected from these patients immediately upon arrival at the hospital (within 9 h) and at 24 and 72 h after symptom onset. Subsequently, isolation, quantification, and phenotypic characterization of CNS-ApBs during the first 72 h post-stroke were performed using centrifugation and flow cytometry techniques. We found a correlation between infarct growth and final infarct size with the amount of plasma CNS-ApBs detected in the first 72 h after stroke. In addition, patients with neurological worsening (progressive ischemic stroke) had higher plasma levels of CNS-ApBs at 24 h after symptom onset than those with a stable or improving course. Circulating CNS-ApB concentration was further associated with patients' functional prognosis. In conclusion, apoptosis may play an important role in the growth of the cerebral infarct area and plasma CNS-ApB quantification could be used as a predictive marker of penumbra death, neurological deterioration, and functional outcome in patients with ischemic stroke.

Photonic and Nanomechanical Modes in Acoustoplasmonic Toroidal Nanopropellers.

Non-conventional resonances, both acoustic and photonic, are found in metallic particles with a toroidal nanopropeller geometry, which is generated by sweeping a three-lobed 2D shape along a spiral with twisting angle α. For both optical and acoustic cases, the spectral location of resonances experiences a red-shift as a function of α. We demonstrate that the optical case can be understood as a natural evolution of resonances as the spiral length of the toroidal nanopropeller increases with α, implying a huge helicity-dependent absorption cross-section. In the case of acoustic response, two red-shifting breathing modes are identified. Additionally, even a small α allows the appearance of new low-frequency resonances, whose spectral dispersion depends on a competition between the length of the generative spiral and the pitch of the toroidal nanopropeller.