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Abstract Background Worldwide about 2.3 million newborns still die in the neonatal period and the majority occurs in low- and middle-income countries (LMICs). Intrapartum-related events account for 24% of neonatal mortality. Of these events, intrapartum birth asphyxia with subsequent neonatal encephalopathy is the main cause of child disabilities in LMICs. Data on neurodevelopmental outcome and early risk factors are still missing in LMICs. This study aimed at investigating the factors associated with mortality, risk of neurodevelopmental impairment and adherence to follow-up among asphyxiated newborns in rural Tanzania. Methods This retrospective observational cohort study investigated mortality, neurodevelopmental risk and adherence to follow-up among asphyxiated newborns who were admitted to Tosamaganga Hospital (Tanzania) from January 2019 to June 2022. Neurodevelopmental impairment was assessed using standardized Hammersmith neurologic examination. Admission criteria were Apgar score 1500 g. Babies with clinically visible congenital malformations were excluded. Comparisons between groups were performed using the Mann-Whitney test, the Chi-square test, and the Fisher test. Results Mortality was 19.1% (57/298 newborns) and was associated with outborn (p

ABSTRACT Introduction and objectives: Drug-eluting balloons (DEB) are an established treatment option for in-stent restenosis (ISR). This study aimed to assess the safety and efficacy of a novel DEB in patients with ISR. Methods: This prospective, single-center study enrolled a consecutive cohort of patients diagnosed with ISR who underwent coronary angioplasty with a new second-generation paclitaxel-eluting balloon. The 3 main endpoints were myocardial infarction, target lesion revascularization, and target vessel revascularization. Baseline variables were collected, including patient and procedure characteristics. Follow-up data were collected through medical records or telephone contact. Results: The study included 160 consecutive patients with 206 treated lesions (mean age, 71.4 ± 14.9 years, 15.5% women) undergoing percutaneous coronary intervention with DEB for ISR. A total of 53.3% of patients had acute coronary syndrome. The average diameter of the treated vessel was 3.10 ± 0.7 mm. The DEB used had a mean diameter of 3.1 ± 0.6 mm and a mean length of 23.1 ± 6.8 mm. Predilatation was performed in 98% of the lesions, and a noncompliant balloon was used in 80%. Intracoronary imaging was used in 24% of cases. At the end of the procedure, 98.5% of patients had Thrombolysis in Myocardial Infarction flow grade 3, residual stenosis was > 30% in 3.4%, and dissection occurred in 1.4%. Bail-out stenting was required in 4.8% of patients. Mortality was nil during follow-up (maximum 768 days). The incidence of myocardial infarction, target lesion revascularization, and target vessel revascularization were 5.4% (95%CI, 0.69-10.1), 8.4% (95%CI, 0-17.8), and 14.2% (95%CI, 3.61-24.78), respectively. Conclusions: In this cohort of patients with ISR treated with DEB, we observed a low rate of adverse events in both the short- and mid-term. These results support the safety and efficacy of this new generation of DEB for treating ISR.

RESUMEN Introducción y objetivos: El balón farmacoactivo (BFA) es un tratamiento establecido para tratar la reestenosis intrastent (RIS). El objetivo de este estudio fue valorar la eficacia y la seguridad de un nuevo BFA en pacientes con RIS. Métodos: Cohorte prospectiva, unicéntrica y consecutiva de pacientes con RIS tratados con angioplastia coronaria con un nuevo balón liberador de paclitaxel de segunda generación. Los 3 eventos principales del estudio fueron infarto de miocardio, revascularización de la lesión diana y revascularización del vaso diana. Se recogieron variables basales, incluidas las características del paciente y del procedimiento. Los datos referentes al seguimiento se obtuvieron de registros médicos o por contacto telefónico. Resultados: Se incluyeron 160 pacientes consecutivos con 206 lesiones tratadas (71,4 ± 14,9 años, el 15,5% mujeres) que fueron tratados con una intervención coronaria percutánea con BFA debido a RIS. El 53,3% de los pacientes presentaban síndrome coronario agudo. El diámetro medio del vaso tratado fue de 3,1 ± 0,7 mm. El diámetro y la longitud del BFA empleado fueron de 3,1 ± 0,6 mm y 23,1 ± 6,8, respectivamente. El 98% de las lesiones se predilataron y en el 80% se empleó un balón no distensible. El 24% de las angioplastias fueron guiadas por imagen intracoronaria. El 98,5% de los pacientes presentaban un flujo Thrombolysis in Myocardial Infarction de grado 3 al final de la angioplastia. Hubo estenosis residual > 30% en el 3,4%, y el 1,4% presentaron disección. El 4,8% de los pacientes requirieron stent de rescate. Al finalizar el seguimiento (máximo 768 días), ningún paciente había fallecido. Las incidencias de infarto de miocardio, de revascularización de la lesión diana y de revascularización del vaso diana fueron del 5,4% (IC95%, 0,69-10,1), el 8,4% (IC95%, 0-17,8) y el 14,2% (IC95%, 3,61-24,78), respectivamente. Conclusiones: En esta cohorte de pacientes con RIS tratados con BFA se observa una baja tasa de eventos clínicos adversos, tanto a corto como a medio plazo. Estos resultados respaldan la eficacia y la seguridad de esta nueva generación de BFA para pacientes con RIS.

In predator-prey systems, interspecific interactions at the spatial and temporal scale may affect different components of the ecosystem. Despite a growing interest in the topic, little is known about these interactions in many regions, particularly in areas recently recolonized by apex predators, such as the Alps. Using a multidimensional approach, we assessed wolf-wild boar interactions in a recently recolonized protected area of the Western Alps (Gran Paradiso National Park, Italy) by combining camera trapping and wolf scat analyses. First, we quantified the importance of wild boar in the wolf diet by comparing two different periods (October 2018–September 2020 vs. October 2021–September 2022). Second, we evaluated prey selection in 2021–2022, when data on prey availability were collected. Then, we assessed spatiotemporal interactions between the wild boar and the wolf. Finally, we calculated combined spatiotemporal associations between the wolf and the wild boar in comparison to other ungulate prey. We found a remarkable increase in wild boar consumption between the two periods; roe deer and wild boar were consumed in proportion to their availability, while the chamois was positively selected and the red deer and the ibex were less consumed in relation to their availability. Although we found no negative association between wolf and wild boar detection rates, in winter the wild boar limited its temporal overlap with the predator by being less active in sites more frequently used by the wolf, suggesting some spatial modulation of a temporal antipredator response. Among ungulate species, the wild boar had the highest combined spatiotemporal association with the wolf, particularly in autumn-winter. Our results suggest complex interspecific interactions in alpine areas recently recolonized by the wolf.

Abstract Within a shared cytoplasm, filamentous actin (F-actin) plays numerous and critical roles across the cell body. Cells rely on actin-binding proteins (ABPs) to organize F-actin and to integrate its polymeric characteristics into diverse cellular processes. Yet, the multitude of ABPs that engage with and shape F-actin make studying a single ABP’s influence on cellular activities a significant challenge. Moreover, without a means of manipulating actin-binding subcellularly, harnessing the F-actin cytoskeleton for synthetic biology purposes remains elusive. Here, we describe a suite of designed proteins, Controllable Actin-binding Switch Tools (CASTs), whose actin-binding behavior can be controlled with external stimuli. CASTs were developed that respond to different external inputs, providing options for turn-on kinetics and enabling orthogonality and multiplexing. Being genetically encoded, we show that CASTs can be inserted into native protein sequences to control F-actin association locally and engineered into structures to control cell and tissue shape and behavior.

Clathrin-mediated endocytosis is essential for the removal of transmembrane proteins from the plasma membrane in all eukaryotic cells. Many transmembrane proteins are glycosylated. These proteins collectively comprise the glycocalyx, a sugar-rich layer at the cell surface, which is responsible for intercellular adhesion and recognition. Previous work has suggested that glycosylation of transmembrane proteins reduces their removal from the plasma membrane by endocytosis. However, the mechanism responsible for this effect remains unknown. To study the impact of glycosylation on endocytosis, we replaced the ectodomain of the transferrin receptor, a well-studied transmembrane protein that undergoes clathrin-mediated endocytosis, with the ectodomain of MUC1, which is highly glycosylated. When we expressed this transmembrane fusion protein in mammalian epithelial cells, we found that its recruitment to endocytic structures was substantially reduced in comparison to a version of the protein that lacked the MUC1 ectodomain. This reduction could not be explained by a loss of mobility on the cell surface or changes in endocytic dynamics. Instead, we found that the bulky MUC1 ectodomain presented a steric barrier to endocytosis. Specifically, the peptide backbone of the ectodomain and its glycosylation each made steric contributions, which drove comparable reductions in endocytosis. These results suggest that glycosylation constitutes a biophysical signal for retention of transmembrane proteins at the plasma membrane. This mechanism could be modulated in multiple disease states that exploit the glycocalyx, from cancer to atherosclerosis.

The analysis of mechanisms underlying prey use and selection is crucial for understanding the potential for apex predators to shape ecological processes across trophic levels. Significant implications for the conservation and management of ecosystems can ensue, especially in human-modified landscapes characterised by the recent recovery of apex predators, such as those of Europe. Generalist predators may show frequency-dependent prey selection, leading to prey switching; however, there is no ubiquitous support for positive relationships between prey abundance and prey selection. In a protected area recently recolonised by the wolf Canis lupus and hosting abundant wild prey (>20 individuals/km2), we assessed prey use and selection (>3000 wolf scats analysed) throughout 7 years since wolf settlement (April 2016-to-March 2023), during which prey density was relatively stable. Wolf diet was dominated by wild boar Sus scrofa and fallow deer Dama dama (>70 % of occurrences and volume); the roe deer Capreolus capreolus and coypu Myocastor coypus represented main secondary prey. The wolf showed a clear prey switching throughout the study. In the first two years, the fallow deer was the main prey and was positively selected. Then, wild boar replaced fallow deer as main prey, and was positively selected, with a progressive decrease in the use of fallow deer throughout the years. Selection indices of wild boar were negatively associated with those of fallow deer. The relationship between selection indices and population density was inconsistent across species, being negative for the wild boar and weakly positive for the fallow deer, although the latter showed no sharp decline in the area. Concurrent studies showed increased diurnal activity of fallow deer and a consequent reduced temporal overlap with the wolf throughout years since the settlement of this predator, suggesting temporal avoidance. By supporting a minor role of prey density in mediating prey switching, our results suggest a major role of other factors (e.g., antipredator behavioural responses). Alternative substantial prey are important to buffer apex predators not only towards changes in the abundance of main prey, but also towards the effects of other factors potentially reducing prey detectability, e.g., antipredator behaviour.

Abstract Background Despite pediatric acute illnesses being leading causes of death and disability among children, acute and critical care services are not universally available in low-middle income countries, such as Tanzania, even if in this country significant progress has been made in child survival, over the last 20 years. In these countries, the hospital emergency departments may represent the only or the main point of access to health-care services. Thus, the hospitalization rates may reflect both the health system organization and the patients’ health status. The purpose of the study is to describe the characteristics of clinical presentations to a pediatric Outpatient Department (OPD) in Tanzania and to identify the predictive factors for hospitalization. Methods Retrospective cohort study based on 4,324 accesses in the OPD at Tosamaganga Voluntary Agency Hospital (Tanzania). Data were collected for all 2,810 children (aged 0–13) who accessed the OPD services, within the period 1 January − 30 September 2022. The association between the hospitalization (main outcome) and potential confounding covariates (demographic, socio-contextual and clinical factors) was evaluated using univariate and multivariate logistic regression models. Results Five hundred three (11.6%) of OPD accesses were hospitalized and 17 (0.4%) died during hospitalization. A higher (p

Albeit with discontinuity, the history of representation is punctuated by imaginative impulses apparently lacking operational results, and for this reason dismissed as caprices or at most as divertissements, but which conversely, if taken up and developed, could have opened up new horizons. [read more]

A subset of Project FUEL (Forwarding the Understanding of Every Life Lesson), Deepak Ramola and his team created The Wisdom Corridor Project for schools. Creating a Wisdom Corridor is a wonderful opportunity for students to get to know teachers outside of the formal curriculum, learn about their life lessons, and then transform the school corridors into vibrant learning environments that showcase the teachers' powerful life lessons to share with everyone who passes through the school. Project FUEL's training guides a group of 10-12 students (the Wisdom Squad) to become empathic interviewers who can add to the growing repository of life lessons. At a time when social-emotional learning is most critical, the Wisdom Corridor project brings self-awareness, societal perception, and relationship skills. While the Wisdom Squads practice empathic interviewing skills and compassionate communication, the rest of the school gains a wider perspective on the world outside of the classroom walls.

Advancing Social-Communication and Play (ASAP) is a classroom-based intervention targeting the social-communication and play development of preschool-age children with autism spectrum disorder. We used a multimethod approach to measuring intervention fidelity, including adherence, exposure, treatment differentiation, and quality of treatment delivery. Overall, teachers in the ASAP classrooms increased their adherence to the ASAP intervention compared with business-as-usual teachers. Teacher characteristics did not affect the ability to implement ASAP with fidelity. There were no group differences in coded video instructional quality scores. Differences in child engagement between the ASAP and business-as-usual groups were not mediated by fidelity adherence scores, contrary to our hypothesis. Finally, end-of-year summary of treatment delivery ratings did not align with adherence scores. Continued research regarding fidelity of school-based interventions should focus on distinguishing active ingredients from general instructional practices and learning from teachers about the child-level factors they consider when implementing an intervention.

Background Liquid biopsy is mainly used to identify tumor cells in pulmonary neoplasms. It is more often used in research than in clinical practice. The BL-MOL-AR study aims to investigate the efficacy of next-generation sequencing (NGS) and clinical interpretation of the circulating free DNA (cfDNA) levels. This study reports the preliminary results from the first samples analyzed from patients affected by various neoplasms: lung, intestinal, mammary, gastric, biliary, and cutaneous.

El tratamiento del infarto agudo de miocardio con elevación del segmento ST tiene barreras dependiendo de la región geográfica. La angioplastia coronaria primaria es el tratamiento de elección, siempre y cuando sea realizada dentro de tiempo y por operadores experimentados. Sin embargo, cuando no está disponible, la administración de fibrinólisis y el envío para angioplastia de rescate, en caso de reperfusión negativa, es la mejor estrategia. De la misma manera, la angioplastia coronaria, como parte de una estrategia farmacoinvasiva, es la mejor alternativa cuando hay reperfusión positiva. El desarrollo de redes de tratamiento del infarto aumenta el número de pacientes reperfundidos dentro de los tiempos recomendados y mejora los desenlaces. En América Latina, los programas nacionales para el tratamiento del infarto deben centrarse en mejorar los resultados y el éxito a largo plazo depende de trabajar hacia objetivos definidos y obtener métricas de rendimiento, por lo tanto, estos deben desarrollar métricas para cuantificar su desempeño. El siguiente documento discute todas estas alternativas y sugiere oportunidades de mejora.

Abstract Background There is need of information on ecological interactions that keystone species such as apex predators establish in ecosystems recently recolonised. Interactions among carnivore species have the potential to influence community-level processes, with consequences for ecosystem dynamics. Although avoidance of apex predators by smaller carnivores has been reported, there is increasing evidence that the potential for competitive-to-facilitative interactions is context-dependent. In a protected area recently recolonised by the wolf Canis lupus and hosting abundant wild prey (3 ungulate species, 20–30 individuals/km2, together), we used 5-year food habit analyses and 3-year camera trapping to (i) investigate the role of mesocarnivores (4 species) in the wolf diet; (ii) test for temporal, spatial, and fine-scale spatiotemporal association between mesocarnivores and the wolf. Results Wolf diet was dominated by large herbivores (86% occurrences, N = 2201 scats), with mesocarnivores occurring in 2% scats. We collected 12,808 carnivore detections over > 19,000 camera trapping days. We found substantial (i.e., generally ≥ 0.75, 0–1 scale) temporal overlap between mesocarnivores—in particular red fox—and the wolf, with no support for negative temporal or spatial associations between mesocarnivore and wolf detection rates. All the species were nocturnal/crepuscular and results suggested a minor role of human activity in modifying interspecific spatiotemporal partitioning. Conclusions Results suggest that the local great availability of large prey to wolves limited negative interactions towards smaller carnivores, thus reducing the potential for spatiotemporal avoidance. Our study emphasises that avoidance patterns leading to substantial spatiotemporal partitioning are not ubiquitous in carnivore guilds.

Exactly ten years ago, the Pinksummer gallery in Genoa hosted an exhibition in the Cortile Maggiore of the Palazzo Ducale in which two architects’ collectives, Gruppo A12 and Baukuh, questioned the possible future (or perhaps, more appropriately, the possible futures) of the Ligurian capital. And they did so by proposing projects and solutions that synergistically contaminated representational modes as varied as they were unusual: starting with the image chosen for the communication, namely that same angel, present in the Ribaudo family chapel of the Monumental Cemetery of Staglieno, used by the rock band Joy Division for the cover of its single Love will tear us apart. [read more]

The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology, but how proteins localize differentially to these structures within a shared cytoplasm remains unclear. Here, we show that the actin-binding domains of accessory proteins can be sensitive to filament conformational changes. Using a combination of live cell imaging and in vitro single molecule binding measurements, we show that tandem calponin homology domains (CH1-CH2) can be mutated to preferentially bind actin networks at the front or rear of motile cells. We demonstrate that the binding kinetics of CH1-CH2 domain mutants varies as actin filament conformation is altered by perturbations that include stabilizing drugs and other binding proteins. These findings suggest that conformational changes of actin filaments in cells could help to direct accessory binding proteins to different actin cytoskeletal structures through a biophysical feedback loop.

In vertebrates, epithelial permeability is regulated by the tight junction (TJ) formed by specialized adhesive membrane proteins, adaptor proteins, and the actin cytoskeleton. Despite the TJ's critical physiological role, a molecular-level understanding of how TJ assembly sets the permeability of epithelial tissue is lacking. Here, we identify a 28-amino-acid sequence in the TJ adaptor protein ZO-1, which is responsible for actin binding, and show that this interaction is essential for TJ permeability. In contrast to the strong interactions at the adherens junction, we find that the affinity between ZO-1 and actin is surprisingly weak, and we propose a model based on kinetic trapping to explain how affinity could affect TJ assembly. Finally, by tuning the affinity of ZO-1 to actin, we demonstrate that epithelial monolayers can be engineered with a spectrum of permeabilities, which points to a promising target for treating transport disorders and improving drug delivery.

The physical dimensions of proteins and glycans on cell surfaces can critically affect cell function, for example, by preventing close contact between cells and limiting receptor accessibility. However, high-resolution measurements of molecular heights on native cell membranes have been difficult to obtain. Here we present a simple and rapid method that achieves nanometer height resolution by localizing fluorophores at the tip and base of cell surface molecules and determining their separation by radially averaging across many molecules. We use this method, which we call cell surface optical profilometry (CSOP), to quantify the height of key multidomain proteins on a model cell, as well as to capture average protein and glycan heights on native cell membranes. We show that average height of a protein is significantly smaller than its contour length, due to thermally driven bending and rotation on the membrane, and that height strongly depends on local surface and solution conditions. We find that average height increases with cell surface molecular crowding but decreases with solution crowding by solutes, both of which we confirm with molecular dynamics simulations. We also use experiments and simulations to determine the height of an epitope, based on the location of an antibody, which allows CSOP to profile various proteins and glycans on a native cell surface using antibodies and lectins. This versatile method for profiling cell surfaces has the potential to advance understanding of the molecular landscape of cells and the role of the molecular landscape in cell function.

Despite the high performance exhibited by tungsten (W), no material would be able to withstand the huge loads expected with extreme plasma transients in EU-DEMO and future reactors, where the installation of sacrificial first wall limiters is essential to prevent excessive wall degradation. The integration of W lattices in the architecture of such components can allow for meeting their conflictual requirements: indeed, they must ensure the effective exhaust of the nominal thermal load during stationary operation; when transients occur, they must thermally insulate and decouple the surface from the heat sink, promoting prompt vapour shielding formation. Starting from the optimised layouts highlighted in a previous study, in this work, a detailed 3D finite element model was developed to analyse in depth the influence of the actual features of the latticed metamaterial on the overall performance of the EU-DEMO limiter PFC on the basis of a flat tile configuration. Its main goal is to help in identifying the most promising layout as a preconceptual design for the fabrication of a small-scale mock-up. For this purpose, the complex geometry of a W-based lattice armour was faithfully reproduced in the model and analysed. This allowed for a detailed assessment of the thermally induced stresses that develop in the component because of the temperature field in response to a number of plasma scenarios—above all, normal operation and ramp down. Structural integrity was verified through the acceptance criteria established for ITER. The two optimised layouts proposed for the PFC were able to effectively meet the requirements under normal reactor operating conditions, while they missed some requirements in the ramp-down case. However, the first HHF tests will be performed in order to benchmark the analyses.