Agriculture and hot temperatures interactively erode the nest success of habitat generalist birds across the United States.

Habitat conversion and climate change are fundamental drivers of biodiversity loss worldwide but are often analyzed in isolation. We used a continental-scale, decades-long database of more than 150,000 bird nesting attempts to explore how extreme heat affects avian reproduction in forests, grasslands, and agricultural and developed areas across the US. We found that in forests, extreme heat increased nest success, but birds nesting in agricultural settings were much less likely to successfully fledge young when temperatures reached anomalously high levels. Species that build exposed cup nests and species of higher conservation concern were particularly vulnerable to maximum temperature anomalies in agricultural settings. Finally, future projections suggested that ongoing climate change may exacerbate the negative effects of habitat conversion on avian nesting success, thereby compromising conservation efforts in human-dominated landscapes.

Comparison between Two Types of 22-Gauge Fine-Needle Biopsy for Solid Pancreatic Tumors.

Background: Tissue sampling using endoscopic ultrasound-guided fine-needle aspiration is the gold standard for diagnosing malignant pancreatic tumors; however, its sensitivity and specificity are highly variable. Thus, fine-needle biopsy using cutting needles has been developed to overcome current limitations and improve diagnostic yield. Our study compared two fine-needle biopsy needles for tissue sampling for pancreatic solid lesions. Materials and Methods: Samples obtained from patients with pancreatic solid lesions using the 22-gauge fine-needle biopsy needles (Franseen needle or reverse bevel needle) were retrospectively analyzed. The primary outcomes were diagnostic yield and sample adequacy. The secondary outcome was diagnostic performance. The analysis was performed using 2 × 2 tables to calculate sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for each needle type. Proportions were compared using the Z test. For quantitative variables, a comparative analysis was performed using Student's t test. Qualitative and unpaired outcome variables were described using Fisher's exact test. Results: Sixty-three patients with pancreatic lesions were included in the analysis. The fine-needle biopsy Franseen and reverse bevel groups included 33 and 30 patients, respectively. An adequate sample was obtained in 97% of patients in the Franseen needle group versus 80% in the reverse bevel needle group; the diagnostic yields in these groups were 93.9 and 66.7%, respectively. Neither differences between needle passes nor complications were noted. The sensitivity and specificity were 93.5 and 100%, respectively, in the fine-needle biopsy Franseen group, versus 71 and 100%, respectively, in the reverse bevel needle group. Conclusions: The Franseen needle was more effective for sampling pancreatic tumors than the reverse bevel needle.

Introdução: A aquisição de tecido através de punção com agulha fina guiada por ecoendoscopia é o padrão para o diagnóstico de neoplasias pancreáticas malignas; contudo, a sua sensibilidade e especificidade é altamente variável. A biópsia por agulha fina (FNB) usando agulhas cortantes foi desenvolvida para ultrapassar as limitações atuais. Este estudo comparou duas agulhas de FNB na aquisição de tecido de lesões pancreáticas sólidas. Métodos: Amostras obtidas de doentes com lesões pancreáticas sólidas utilizando agulha de FND de 22 gauge (Franseen ou reverse bevel) foram avaliadas retrospetivamente. Os outcomes primárias foram a rentabilidade diagnóstica e a adequabilidade das amostras. O outcome secundário foi a performance diagnóstica. A análise estatística foi realizada através de tabelas de contingência 2 × 2 para cálculo da sensibilidade, especificidade, valor preditivo positivo e negativo e acuidade para cada tipo de agulha. As proporções foram calculadas utilizando o teste-Z. Para variáveis quantitativas foi realizada análise comparativa com teste t-Student. Variáveis qualitativas e não pareadas foram comparadas com teste exato de Fisher. Resultados: Foram incluídos 63 doentes com lesões pancreáticas (33 no grupo FNB Franseen e 30 no grupo reverse bevel). Foram obtidas amostras adequadas em 97% do grupo Franseen vs 80% no grupo reverse bevel, sendo a rentabilidade diagnóstica de 93.9 e 66.7%, respetivamente. Não houve diferenças no número de passagens nem nas complicações. A sensibilidade e especificidade foram, respetivamente, de 93.5 e 100% no grupo Franseen versus 71 e 100% no grupo reverse bevel. Conclusões: A agulha Franseen foi mais efetiva na aquisição de amostras de lesões pancreáticas do que a agulha reverse bevel.

Potential to reduce pesticides in intensive apple production through management practices could be challenged by climatic extremes.

Apples are the third most produced fruit in the world, but their production is often pesticide-intensive. Our objective was to identify options for pesticide reduction using farmer records from 2549 commercial apple fields in Austria during five years between 2010 and 2016. Using generalized additive mixed modeling, we examined how pesticide use was related to farm management, apple varieties, and meteorological parameters, and how it affected yields and toxicity to honeybees. Apple fields received 29.5 ± 8.6 (mean ± SD) pesticide applications per season at a rate of 56.7 ± 22.7 kg ha-1, which included a total of 228 pesticide products with 80 active ingredients. Over the years, fungicides accounted for 71 % of the pesticide amounts applied, insecticides for 15 %, and herbicides for 8 %. The most frequently used fungicides were sulfur (52 %), followed by captan (16 %) and dithianon (11 %). Of insecticides, paraffin oil (75 %) and chlorpyrifos/chlorpyrifos-methyl (6 % combined) were most frequently used. Among herbicides, glyphosate (54 %), CPA (20 %) and pendimethalin (12 %) were most often used. Pesticide use increased with increasing frequency of tillage and fertilization, increasing field size, increasing spring temperatures, and drier summer conditions. Pesticide use decreased with increasing number of summer days with maximum temperatures >30 °C and number of warm, humid days. Apple yields were significantly positively related to the number of heat days, warm humid nights, and pesticide treatment frequency, but were not affected by frequency of fertilization and tillage. Honeybee toxicity was not related to insecticide use. Pesticide use and yield were significantly related to apple varieties. Our analysis shows that pesticide use in the apple farms studied can be reduced by less fertilization and tillage, partly because yields were >50 % higher than the European average. However, weather extremes related to climate change, such as drier summers, could challenge plans to reduce pesticide use.

Extracting Thyroid Nodules Characteristics from Ultrasound Reports Using Transformer-based Natural Language Processing Methods.

The ultrasound characteristics of thyroid nodules guide the evaluation of thyroid cancer in patients with thyroid nodules. However, the characteristics of thyroid nodules are often documented in clinical narratives such as ultrasound reports. Previous studies have examined natural language processing (NLP) methods in extracting a limited number of characteristics (<9) using rule-based NLP systems. In this study, a multidisciplinary team of NLP experts and thyroid specialists, identified thyroid nodule characteristics that are important for clinical care, composed annotation guidelines, developed a corpus, and compared 5 state-of-the-art transformer-based NLP methods, including BERT, RoBERTa, LongFormer, DeBERTa, and GatorTron, for extraction of thyroid nodule characteristics from ultrasound reports. Our GatorTron model, a transformer-based large language model trained using over 90 billion words of text, achieved the best strict and lenient F1-score of 0.8851 and 0.9495 for the extraction of a total number of 16 thyroid nodule characteristics, and 0.9321 for linking characteristics to nodules, outperforming other clinical transformer models. To the best of our knowledge, this is the first study to systematically categorize and apply transformer-based NLP models to extract a large number of clinical relevant thyroid nodule characteristics from ultrasound reports. This study lays ground for assessing the documentation quality of thyroid ultrasound reports and examining outcomes of patients with thyroid nodules using electronic health records.

The dinosaurian femoral head experienced a morphogenetic shift from torsion to growth along the avian stem.

Significant evolutionary shifts in locomotor behaviour often involve comparatively subtle anatomical transitions. For dinosaurian and avian evolution, medial overhang of the proximal femur has been central to discussions. However, there is an apparent conflict with regard to the evolutionary origin of the dinosaurian femoral head, with neontological and palaeontological data suggesting seemingly incongruent hypotheses. To reconcile this, we reconstructed the evolutionary history of morphogenesis of the proximal end of the femur from early archosaurs to crown birds. Embryological comparison of living archosaurs (crocodylians and birds) suggests the acquisition of the greater overhang of the femoral head in dinosaurs results from additional growth of the proximal end in the medial-ward direction. On the other hand, the fossil record suggests that this overhang was acquired by torsion of the proximal end, which projected in a more rostral direction ancestrally. We reconcile this apparent conflict by inferring that the medial overhang of the dinosaur femoral head was initially acquired by torsion, which was then superseded by mediad growth. Details of anatomical shifts in fossil forms support this hypothesis, and their biomechanical implications are congruent with the general consensus regarding broader morpho-functional evolution on the avian stem.

Increasing crop field size does not consistently exacerbate insect pest problems.

Increasing diversity on farms can enhance many key ecosystem services to and from agriculture, and natural control of arthropod pests is often presumed to be among them. The expectation that increasing the size of monocultural crop plantings exacerbates the impact of pests is common throughout the agroecological literature. However, the theoretical basis for this expectation is uncertain; mechanistic mathematical models suggest instead that increasing field size can have positive, negative, neutral, or even nonlinear effects on arthropod pest densities. Here, we report a broad survey of crop field-size effects: across 14 pest species, 5 crops, and 20,000 field years of observations, we quantify the impact of field size on pest densities, pesticide applications, and crop yield. We find no evidence that larger fields cause consistently worse pest impacts. The most common outcome (9 of 14 species) was for pest severity to be independent of field size; larger fields resulted in less severe pest problems for four species, and only one species exhibited the expected trend of larger fields worsening pest severity. Importantly, pest responses to field size strongly correlated with their responses to the fraction of the surrounding landscape planted to the focal crop, suggesting that shared ecological processes produce parallel responses to crop simplification across spatial scales. We conclude that the idea that larger field sizes consistently disrupt natural pest control services is without foundation in either the theoretical or empirical record.

The developing bird pelvis passes through ancestral dinosaurian conditions.

Living birds (Aves) have bodies substantially modified from the ancestral reptilian condition. The avian pelvis in particular experienced major changes during the transition from early archosaurs to living birds1,2. This stepwise transformation is well documented by an excellent fossil record2-4; however, the ontogenetic alterations that underly it are less well understood. We used embryological imaging techniques to examine the morphogenesis of avian pelvic tissues in three dimensions, allowing direct comparison with the fossil record. Many ancestral dinosaurian features2 (for example, a forward-facing pubis, short ilium and pubic 'boot') are transiently present in the early morphogenesis of birds and arrive at their typical 'avian' form after transitioning through a prenatal developmental sequence that mirrors the phylogenetic sequence of character acquisition. We demonstrate quantitatively that avian pelvic ontogeny parallels the non-avian dinosaur-to-bird transition and provide evidence for phenotypic covariance within the pelvis that is conserved across Archosauria. The presence of ancestral states in avian embryos may stem from this conserved covariant relationship. In sum, our data provide evidence that the avian pelvis, whose early development has been little studied5-7, evolved through terminal addition-a mechanism8-10 whereby new apomorphic states are added to the end of a developmental sequence, resulting in expression8,11 of ancestral character states earlier in that sequence. The phenotypic integration we detected suggests a previously unrecognized mechanism for terminal addition and hints that retention of ancestral states in development is common during evolutionary transitions.

Parasitoids of Lobesia botrana (Lepidoptera: Tortricidae) in the Douro Demarcated Region vineyards and the prospects for enhancing conservation biological control.

The more restrictive regulations of pesticides in Europe have led to an increase in conservation biological control (CBC) research. However, little attention has been paid to the main determinants of Lobesia botrana parasitism. The Douro Demarcated Region landscape offers scope for the use of CBC. The study was conducted between 2002 and 2015 aiming at: (i) identifying parasitoids associated with L. botrana and evaluating their impact as biological control agents in each generation of the pest, and (ii) evaluating the effect of both the proportion of ecological infrastructures (EI) near the vineyards, and the impact of management practices (chemical treatments and ground cover) on the parasitism of L. botrana. A total of 3226 larvae/pupae of L. botrana were collected (15% were parasitized and 485 parasitoids emerged). A complex of 16 taxa of parasitoids was identified, the majority belonging to Hymenoptera. The most abundant were Elachertus sp. (Eulophidae), Campoplex capitator Aubert (Ichneumonidae), and Brachymeria tibialis (Walker) (Chalcididae), which represented 62.5, 12.6, and 12.0% of the total assemblage of parasitoids which emerged, respectively. The percentage of parasitism ranged from 0.0 to 61.5% (first generation), from 0.0 to 36.8% (second generation), and from 0.0 to 12.1% (third generation). Importantly, it was found that the parasitism rate was higher in vineyards with ground cover. In addition, EI in the area surrounding the vineyards produced a significant increase in parasitism. These results suggest potential for CBC of L. botrana if EI around vineyards, and ground cover with native perennial plants within vineyards, are encouraged.

Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly.

Parkinson's disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays is utilized to validate αS sequences and their structural characteristics that are essential for aggregation and propagation of PD phenotypes. The study aids in developing significant mechanistic and therapeutic insights into various facets of αS aggregation, which will pave the way for effective treatments for PD.

The causes and consequences of pest population variability in agricultural landscapes.

Variability in population densities is key to the ecology of natural systems but also has great implications for agriculture. Farmers' decisions are heavily influenced by their risk aversion to pest outbreaks that result in major yield losses. However, the need for long-term pest population data across many farms has prevented researchers from exploring the drivers and implications of pest population variability (PV). Here, we demonstrate the critical importance of PV for sustainable farming by analyzing 13 years of pest densities across >1300 Spanish olive groves and vineyards. Variable populations were more likely to cause major yield losses, but also occasionally created temporal windows when densities fell below insecticide spray thresholds. Importantly, environmental factors regulating pest variability were very distinct from factors regulating mean density, suggesting variability needs to be uniquely managed. Finally, we found diversifying landscapes may be a win-win situation for conservation and farmers, as diversified landscapes promote less abundant and less variable pest populations. Therefore, we encourage agricultural stakeholders to increase the complexity of the landscapes surrounding their farms through conserving/restoring natural habitat and/or diversifying crops.

Embryonic muscle splitting patterns reveal homologies of amniote forelimb muscles.

Limb muscles are remarkably complex and evolutionarily labile. Although their anatomy is of great interest for studies of the evolution of form and function, their homologies among major amniote clades have remained obscure. Studies of adult musculature are inconclusive owing to the highly derived morphology of modern amniote limbs but correspondences become increasingly evident earlier in ontogeny. We followed the embryonic development of forelimb musculature in representatives of six major amniote clades and found, contrary to current consensus, that these early splitting patterns are highly conserved across Amniota. Muscle mass cleavage patterns and topology are highly conserved in reptiles including birds, irrespective of their skeletal modifications: the avian flight apparatus results from slight early topological modifications that are exaggerated during ontogeny. Therian mammals, while conservative in their cleavage patterns, depart drastically from the ancestral amniote musculoskeletal organization in terms of topology. These topological changes occur through extension, translocation and displacement of muscle groups later in development. Overall, the simplicity underlying the apparent complexity of forelimb muscle development allows us to resolve conflicting hypotheses about homology and to trace the history of each individual forelimb muscle throughout the amniote radiations.

Eficacia del endoscopio frontal asistido por cap como método para la evaluación de la ampolla de Vater / Efficacy of cap-assisted forward-viewing endoscopy as a method for the evaluation of the ampulla of Vater

Introducción: la evaluación endoscópica de la ampolla de Vater (AV), aunque recomendada de forma rutinaria, no siempre es posible debido a su configuración anatómica, que puede ocultarla del campo visual del endoscopio frontal. Se ha propuesto como una alternativa eficaz el usoañadido de un cap distal al endoscopio frontal para facilitar la examinación de esta estructura.Objetivos: determinar la eficacia del uso del endoscopio frontal asistido por cap para la valoración completa del AV. Se valoran la morfología del AV, los tiempos de búsqueda y total del procedimiento, así como la seguridad de la técnica.Métodos: estudio prospectivo de un solo brazo con inclusión de los pacientes en quienes se realizó una endoscopia alta electiva. Se excluyeron los pacientes con neoplasia avanzada, anatomía modificada, diagnóstico de estenosis u obstrucción del tracto digestivo superior.Resultados: se analizaron 90 pacientes, 36 hombres (40 %) y 54 mujeres (60 %), un 15,5 % del total con antecedente de un síndrome hereditario para cáncer de colon. El éxito técnico del endoscopio frontal + cap fue del 98,8 %. El AV se clasificó como tipo 1 (clásica) en el 49,4 %; tipo 2 (plana), en el 16,8 %; tipo 3 (protuberante), en el 11,2 %; y tipo 4 (anillada), en el 22,4 %. El tiempo promedio de búsqueda fue de 37,7 segundos (s) (DE ± 31,6), con un tiempo total procedimiento de 487,4 s (DE ± 206,2). No se reportaron eventos adversos.Conclusiones: el uso combinado del endoscopio frontal y cap distal es una técnica efectiva y segura para la visualización completa y caracterización morfológica del AV. (AU)

Efficacy of cap-assisted forward-viewing endoscopy as a method for the evaluation of the ampulla of Vater.

INTRODUCTION: endoscopic evaluation of the ampulla of Vater (AV), although routinely recommended, is not always possible due to its anatomic configuration, which can hide it from the visual field of the forward-viewing endoscope. Cap-assisted forward-viewing endoscopy has been proposed as a useful alternative to facilitate the examination of this structure. OBJECTIVES: to assess the efficacy of cap-assisted forward-viewing endoscopy for the complete evaluation of the AV. Secondary outcomes were to assess AV morphology, search and total procedure times and technique safety. METHODS: a prospective, single-arm study. Patients who were selected for elective upper endoscopy were included. Patients with advanced neoplasia, modified anatomy, upper gastrointestinal stenosis or obstructions were excluded. OUTCOMES: ninety patients were included, 36 males (40 %) and 54 females (60 %). Fifteen percent had a history of hereditary colon cancer syndrome. Technical success of cap-assisted, forward-viewing endoscopy was 98.8 %. AV was classified as type 1 (classic) in 49.4 %, type 2 (small) in 16.8 %, type 3 (protruding) in 11.2 % and type 4 (ridged) in 22.4 %. The mean search time was 37.7 seconds (s) (SD ± 31.6) and the total procedure time was 487.4 s (SD ± 206.2). No adverse events were reported. CONCLUSIONS: cap-assisted forward-viewing endoscopy is an effective and safe technique for the complete visualization and morphologic characterization of the ampulla of Vater.

[Ocular manifestations associated to CD4+ in patients with human immunodeficiency virus]. / Manifestaciones oculares asociadas a CD4+ en pacientes con virus de inmunodeficiencia humana.

BACKGROUND: Since the first cases of human immunodeficiency virus (HIV), ocular manifestations secondary to infection have been known and these have been related to the CD4+ lymphocyte count. OBJECTIVE: To describe the correlation between ocular manifestations in patients with HIV and the CD4+ lymphocyte count. MATERIAL AND METHODS: Analytical cross-sectional study of patients with HIV whose CD4+ count was correlated with the presence of ophthalmological manifestations. RESULTS: 21 patients between 26 and 67 years were studied. Only 3 patients were not on antiretroviral therapy. 67% of the patients presented some type of ocular manifestation, 42% presented non-infection related manifestations, 47% related manifestations and 24% both. Conjunctival microangiopathy was the most frequent ocular manifestation (35.7%). There was a statistically significant correlation (r = 0.76, p = 0.0001) between eye manifestations related to infection and CD4+ lymphocyte count. CONCLUSIONS: Patients with HIV frequently present ocular manifestations, the majority related to infection; there is a correlation between the presence of these with the CD4+ count. However, a similar number of manifestations not related to infection occurred without correlation with the count; therefore, HIV patients should have periodic ophthalmological examinations, independently of CD4+ count.

INTRODUCCIÓN: desde los primeros casos de virus de inmunodeficiencia humana (VIH), se conocen manifestaciones oculares secundarias a la infección y estas se han relacionado con el conteo de linfocitos CD4+. OBJETIVO: describir la correlación entre las manifestaciones oculares en pacientes con VIH y el conteo de linfocitos CD4+. MATERIAL Y MÉTODOS: estudio transversal analítico de pacientes con VIH, en quienes se analizó la correlación entre conteo de CD4+ y manifestaciones oftalmológicas. RESULTADOS: se incluyeron 21 pacientes entre 26 y 67 años de edad. Solo tres no se encontraban en terapia antirretroviral. El 67% presentó algún tipo de manifestación ocular, 42% presentó manifestaciones no relacionadas con la infección, 47% manifestaciones relacionadas y 24% ambas. La microangiopatía de la conjuntiva fue la manifestación ocular más frecuente (35.7%). Hubo una correlación estadísticamente significativa (r = 0.76, p = 0.0001) entre las manifestaciones oculares relacionadas con la infección y el conteo de linfocitos CD4+. CONCLUSIONES: los pacientes con VIH presentan con frecuencia manifestaciones oculares, la mayoría asociadas a la infección. Existe correlación entre la presencia de estas con el conteo de CD4+; sin embargo, un número similar de manifestaciones no asociadas a la infección se presentaron sin correlación con el conteo, por lo que los pacientes con VIH deberían tener revisiones oftalmológicas periódicas, independientemente del conteo de CD4+.

Manifestaciones oculares asociadas a CD4+ en pacientes con virus de inmunodeficiencia humana / Ocular manifestations associated to CD4+ in patients with human immunodeficiency virus

Introducción: desde los primeros casos de virus de inmunodeficiencia humana (VIH), se conocen manifestaciones oculares secundarias a la infección y estas se han relacionado con el conteo de linfocitos CD4+. Objetivo: describir la correlación entre las manifestaciones oculares en pacientes con VIH y el conteo de linfocitos CD4+. Material y métodos: estudio transversal analítico de pacientes con VIH, en quienes se analizó la correlación entre conteo de CD4+ y manifestaciones oftalmológicas. Resultados: se incluyeron 21 pacientes entre 26 y 67 años de edad. Solo tres no se encontraban en terapia antirretroviral. El 67% presentó algún tipo de manifestación ocular, 42% presentó manifestaciones no relacionadas con la infección, 47% manifestaciones relacionadas y 24% ambas. La microangiopatía de la conjuntiva fue la manifestación ocular más frecuente (35.7%). Hubo una correlación estadísticamente significativa (r = 0.76, p = 0.0001) entre las manifestaciones oculares relacionadas con la infección y el conteo de linfocitos CD4+. Conclusiones: los pacientes con VIH presentan con frecuencia manifestaciones oculares, la mayoría asociadas a la infección. Existe correlación entre la presencia de estas con el conteo de CD4+; sin embargo, un número similar de manifestaciones no asociadas a la infección se presentaron sin correlación con el conteo, por lo que los pacientes con VIH deberían tener revisiones oftalmológicas periódicas, independientemente del conteo de CD4+.

Background: Since the first cases of human immunodeficiency virus (HIV), ocular manifestations secondary to infection have been known and these have been related to the CD4+ lymphocyte count. Objective: To describe the correlation between ocular manifestations in patients with HIV and the CD4+ lymphocyte count. Material and methods: Analytical cross-sectional study of patients with HIV whose CD4+ count was correlated with the presence of ophthalmological manifestations. Results: 21 patients between 26 and 67 years were studied. Only 3 patients were not on antiretroviral therapy. 67% of the patients presented some type of ocular manifestation, 42% presented non-infection related manifestations, 47% related manifestations and 24% both. Conjunctival microangiopathy was the most frequent ocular manifestation (35.7%). There was a statistically significant correlation (r = 0.76, p = 0.0001) between eye manifestations related to infection and CD4+ lymphocyte count. Conclusions: Patients with HIV frequently present ocular manifestations, the majority related to infection; there is a correlation between the presence of these with the CD4+ count. However, a similar number of manifestations not related to infection occurred without correlation with the count; therefore, HIV patients should have periodic ophthalmological examinations, independently of CD4+ count.

Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain.

Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) pathology at a young age, including amyloid plaques and neurofibrillary tangles (NFTs). Tau pathology can spread via extracellular vesicles, such as exosomes. The cargo of neuron-derived small extracellular vesicles (NDEVs) from individuals with DS contains p-Tau at an early age. The goal of the study was to investigate whether NDEVs isolated from the blood of individuals with DS can spread Tau pathology in the brain of wildtype mice. We purified NDEVs from the plasma of patients with DS-AD and controls and injected small quantities using stereotaxic surgery into the dorsal hippocampus of adult wildtype mice. Seeding competent Tau conformers were amplified in vitro from DS-AD NDEVs but not NDEVs from controls. One month or 4 months post-injection, we examined Tau pathology in mouse brains. We found abundant p-Tau immunostaining in the hippocampus of the mice injected with DS-AD NDEVs compared to injections of age-matched control NDEVs. Double labeling with neuronal and glial markers showed that p-Tau staining was largely found in neurons and, to a lesser extent, in glial cells and that p-Tau immunostaining was spreading along the corpus callosum and the medio-lateral axis of the hippocampus. These studies demonstrate that NDEVs from DS-AD patients exhibit Tau seeding capacity and give rise to tangle-like intracellular inclusions.

Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance.

An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model to gain novel insight into changes in the local metabolome and proteome within the islet allograft's immediate microenvironment in association with immune-mediated rejection or tolerance. We performed integrated metabolomics and proteomics analyses in aqueous humor samples representative of the graft's microenvironment under each transplant outcome. The results showed that several free amino acids, small primary amines, and soluble proteins related to the Warburg effect were upregulated or downregulated in association with either outcome. In general, the observed shifts in the local metabolite and protein profiles in association with rejection were consistent with established pro-inflammatory metabolic pathways and those observed in association with tolerance were immune regulatory. Taken together, the current findings further support the potential of metabolic reprogramming of immune cells towards immune regulation through targeted pharmacological and dietary interventions against specific metabolic pathways that promote the Warburg effect to prevent the rejection of transplanted islets and promote their immune tolerance.

Smooth Extubation Techniques in Pediatric Patients After LeFort I Osteotomy.

The anesthetic approach to patients with facial deformities, such as midface hypoplasia (MFH), is complex and requires coordinated work with the surgical team. These patients may have a difficult airway (DA), and hence special considerations must be taken from the anesthetic point of view, and several options have been described by the American Society of Anesthesiology (ASA) related to this. Multiple methods have been described for intubation and maintenance; for extubation in pediatric patients, there are no defined guidelines. Extubation can be performed under deep anesthesia or with the patient awake, taking special considerations by keeping their condition in mind; these approaches have shown varying results. Favorable outcomes have been observed in the literature and personal experiences with smooth extubation techniques in patients at a high risk of reintubation, such as those with dentofacial deformities and the pediatric population. A 15-year-old girl with a diagnosis of severe malar hypoplasia associated with a cleft lip (CL) was admitted to our hospital. She had a history of previous surgeries and had persistent functional disorders, for which surgical placement of facial distractors was scheduled. For the anesthetic approach, a balanced general anesthesia option was chosen. The use of a video laryngoscope was determined to be the proper choice for DA, with the fixation of the oral endotracheal tube (OETT) in a caudal direction, and with mechanical-ventilator settings appropriate for the patient's age. Deep extubation with smooth extubation techniques was performed successfully. No anesthetic complications were observed in this case.