Effect of silk fibroin microparticles on cellular immunity and liver of gilthead seabream (Sparus aurata L.) with and without experimental skin injuries.

Silk fibroin (SF) microparticles were administered in the diet of gilthead seabream with or without experimental skin wounds to study the effects on cellular immunity and liver. A commercially available diet was enriched with varying amount of SF: 0, 50 and 100 mg kg-1 (representing the control, SF50 and SF100 diets respectively). The animals were fed for 30 days and half of them were sampled. Similar experimental wounds were then performed on the rest of fish, and they continued to be fed the same diet. At 7 days post-wounding, samples were taken from the wounded fish. Cellular immunity was studied on head kidney leucocytes (phagocytosis, respiratory and peroxidase content) and liver status (histological study and gene expression) were studied. Our results showed that experimental wounds affect both cellular immunity (by decreasing leucocyte respiratory burst and peroxidase activity) and altered liver histology (by inducing vascularisation and congestion of blood vessels). In addition, it influences the expression of genes that serve as markers of oxidative stress, endoplasmic reticulum stress and apoptosis. The highest dose of SF (SF100) increased the phagocytic capacity of leucocytes the most, as well as the expression of genes related to blood vessel formation in the liver. Furthermore, increased expression of antioxidant genes (cat and gsr) and decreased expression of genes related to reticulum endoplasmic stress (grp94 and grp170) and apoptosis (nos and jnk) were detected in these fish fed with SF100 and wounded. In conclusion, fed fish with SF100 had many beneficial effects as cellular immunostimulant and hepatoprotection in wounded fish. Its use could be of great interest for stress management in farmed fish conditions.

Automated FerryBox monitoring reveals the first recorded river induced crude oil seep transport to the Strait of Magellan in southern Patagonia.

This study presents the first documented occurrence of a natural crude oil seep plume associated with river discharge along the Strait of Magellan in southern Patagonia in modern times. Between September and December 2022, hydrocarbon signals were detected using a crude oil sensor integrated into a FerryBox system that traversed the Strait of Magellan and several channels of southern Patagonia, covering approximately 510 km. The highest levels of crude oil signals were observed in the mid-basin of the Strait of Magellan. These signals exhibited a strong negative correlation with sea surface salinity, coinciding with the water discharge from the San Juan River. Notably, during periods of high river discharge, typically exceeding 15 m3 s-1, a distinct crude oil plume was detected moving towards the Magellan Strait. Conversely, when river discharge fell below this threshold, no noticeable crude oil signal was observed. As river discharge decreased and winds intensified during the austral summer, the crude oil signal gradually dissipated. This observation suggests that the dispersion of crude oil becomes limited during periods of low river discharge, as buoyant currents remain confined close to the coast. Historical records indicate that this seep has been releasing hydrocarbons into the Strait of Magellan for at least the past 120 years, implying a long history of chronic crude oil input into this relatively isolated region of the world. This finding shows the potential contribution to the understanding of marine ecosystems dynamics and potential pollutants in poorly studied regions through the use of automated monitoring FerryBox system, enabling both spatial and temporal high-resolution surveys.

Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet.

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.

Papel de N-acetilcisteína (NAC) en pacientes con tabaquismo / Role of N-acetylcysteine (NAC) in patients with smoking

Antecedentes y objetivo. El tabaquismo es el principal factor de riesgo de la enfermedad pulmonar obstructiva crónica (EPOC). N-acetilcisteína (NAC) es un agente mucolítico con propiedades antioxidantes y antiinflamatorias que ha demostrado ser eficaz en la reducción de la tasa de exacerbaciones y mejoría clínica de los pacientes con EPOC. El objetivo del trabajo es conocer la opinión de terapeutas expertos acerca del perfil o perfiles de los pacientes fumadores que pueden ser candidatos al uso de NAC. Métodos. Se efectuó una encuesta distribuida a las unidades de tabaquismo de España y una Reunión de Expertos en tabaquismo y EPOC, en la que los Expertos pudieron debatir abiertamente los tópicos seleccionados. Resultados. Los expertos reconocieron el papel del tabaquismo en la generación de estrés oxidativo y concordaron en emplear la terapia mucolítica/antioxidante para fumadores o exfumadores con síntomas respiratorios. Se debatió la necesidad de ampliar las indicaciones de esta terapia a otros perfiles de pacientes. Se señaló también el potencial efecto preventivo de la NAC sobre el daño pulmonar por su acción antioxidante, aunque se necesitaría más evidencia en este ámbito específico del tabaquismo. Se puso énfasis en diferenciar la dosis de NAC como mucolítico (600 mg/día)o antioxidante (1.200 mg/día). Conclusiones. Los expertos valoraron a NAC como un fármaco bien tolerado, de sencillo uso, con un conocido buen perfil de seguridad y un gran potencial para lograr los objetivos terapéuticos por su alta capacidad antioxidante. (AU)

Background and objective. The smoking habit is the main risk factor for chronic obstructive pulmonary disease (COPD). N-Acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties that has been demonstrated to be effective in the reduction of the rate of exacerbations and clinical improvement of patients with COPD. This study aims to know the opinion of the expert therapists on the profile(s) of the patients who smoke and who may be candidates for the use of NAC. Methods. A survey was performed, distributing it to the smoking units in Spain and to a Meeting of Experts on the smoking habit and COPD in which the Experts could openly debate on the selected topics. Results. The experts recognized the role of the smoking habit in the generation of oxidative stress and agreed to use the mucolytic/antioxidant treatment for smokers or ex-smokers with respiratory symptoms. The need to extend the indications of this therapy to other patient profiles was debated. The potential preventive effect of NAC on lung damage due to its antioxidant action was also pointed out, although more evidence in this special area of the smoking habit would be necessary. Emphasis was placed on differentiating the NAC dose as a mucolytic (600 mg/day) or as an antioxidant (1,200 mg/day). Conclusions. The experts evaluated NAC as a drug that is well-tolerated, easy-to-use, with a known good safety profile and having great potential to achieve the therapeutic objectives due to its high antioxidant capacity. (AU)

Nonlinear confocal positioner for micron-scale target alignment.

This paper presents a novel target positioner system that exhibits high sensitivity and accuracy. Specifically, the system is capable of precisely locating rough target surfaces within a micron-scale in the focal plane. The high sensitivity comes from the nonlinear detection scheme which uses the two-photon-absorption process in a Si-photodiode and a CMOS sensor at 1550 [nm]. The setup employs a confocal configuration that is easy to align and does not require a conjugated focal plane selective aperture (pinhole), thus demonstrating its feasibility and tilt tolerance of the target. Moreover, the system offers high accuracy up to 5 [µm], which corresponds to the step size of the focus scanning. The presented positioner system has potential applications in microfabrication with lasers and laser-driven plasma accelerators even at high repetition rates, limited by the detection bandwidth of the photodiode. Additionally, the principle can be extended to cameras if spatial information is needed and the system design can be extended to other spectral ranges with minimal changes.

Effects of bisphenol F, bisphenol S, and bisphenol AF on cultured human osteoblasts.

Bisphenol A (BPA) analogs, like BPA, could have adverse effects on human health including bone health. The aim was to determine the effect of BPF, BPS and BPAF on the growth and differentiation of cultured human osteoblasts. Osteoblasts primary culture from bone chips harvested during routine dental work and treated with BPF, BPS, or BPAF for 24 h at doses of 10-5, 10-6, and 10-7 M. Next, cell proliferation was studied, apoptosis induction, and alkaline phosphatase (ALP) activity. In addition, mineralization was evaluated at 7, 14, and 21 days of cell culture in an osteogenic medium supplemented with BP analog at the studied doses. BPS treatment inhibited proliferation in a dose-dependent manner at all three doses by inducing apoptosis; BPF exerted a significant inhibitory effect on cell proliferation at the highest dose alone by an increase of apoptosis; while BPAF had no effect on proliferation or cell viability. Cell differentiation was adversely affected by treatment with BPA analogs in a dose-dependent, observing a reduction in calcium nodule formation at 21 days. According to the results obtained, these BPA analogs could potentially pose a threat to bone health, depending on their concentration in the organism.

[Prevalence of myasthenia gravis in Colombia]. / Prevalencia de la miastenia grave en Colombia.

TITLE: Prevalencia de la miastenia grave en Colombia.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts' view.

BACKGROUND: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. OBJECTIVE: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. METHODS: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. RESULTS AND CONCLUSIONS: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them.

Niño de 5 años con macrohematuria ¿Sabríamos ante qué glomerulopatía estamos? / Five-year-old with macrohematuria... Would we know what glomerulopathy we’re dealing with?

Presentamos el caso de un escolar de 5 años que consulta en nuestro servicio por macrohematuria. Tras confirmarse el origen glomerular de la misma se sospecha glomerulonefritis aguda postestreptocócica debido al antecedente de infección faringoamigdalar, sin embargo el complemento es normal. Presenta deterioro rápido y progresivo de función renal, por lo que es diagnosticado de glomerulonefritis aguda rápidamente progresiva. Se realiza biopsia renal, donde se evidencia semilunas en un 81% de los glomérulos y depósitos de C3, compatible con glomerulonefritis aguda postinfecciosa. Inmediatamente después, se inicia tratamiento corticoideo presentando una evolución excelente y con recuperación completa de la función renal. Solo el 10-20% de la glomerulonefritis aguda postinfecciosas cursan con niveles de complemento normal, y solo el 0,5% de los casos se manifiesta como una glomerulonefritis rápidamente progresiva. La macrohematuria en niños puede suponer un reto diagnóstico. En ocasiones las manifestaciones son muy variable y superponibles a diferentes causa y hasta la biopsia no podemos llegar a un diagnóstico fiable.(AU)

We present the case of a 5-year-old school boy who consulted our department for asymptomatic macrohematuria. After confirming the glomerular origin, poststreptococcal acute glomerulonephritis was suspected due to a history of pharyngotonsillar infection, however the complement is normal. He presents rapid and progressive deterioration of kidney function, which is why he is diagnosed with rapidly progressive acute glomerulonephritis. A renal biopsy was performed, showing crescents in 81% of the glomeruli and C3 deposits, compatible with acute post-infectious glomerulonephritis. Immediately afterwards, corticosteroid treatment was started, with excellent progress and complete recovery of kidney function. Only 10-20% of acute post-infectious glomerulonephritis present with normal complement levels, and only 0.5% of cases manifest as rapidly progressive glomerulonephritis. Macrohematuria in children can be a diagnostic challenge. Sometimes the manifestations are very variable and can be attributed to different causes and until the biopsy we cannot reach a reliable diagnosis.(AU)

Neutron time-of-flight detectors (nTOF) used at Sandia's Z-Machine.

Neutron time-of-flight (nTOF) detectors have been used on Sandia National Laboratories' Z-Machine for inertial confinement fusion and magnetized liner fusion experiments to infer physics parameters including the apparent fuel-ion temperature, neutron yield, the magnetic-radius product (BR), and the liner rho-r. Single-paddle, dual-paddle, and co-axial scintillation nTOF detectors are used in axial lines-of-sight (LOS) and LOS that are 12° from the midplane. Detector fabrication, characterization, and calibration are discussed.

Inferring neutron yields using indium activation samples for small fractions of tritium added to deuterium fuel in inertial confinement fusion (ICF) experiments.

In inertial confinement fusion experiments, the neutron yield is an important metric for thermonuclear fusion performance. Neutron activation diagnostics can be used to infer neutron yields. The material used for neutron activation diagnostic undergoes a threshold reaction so that only neutrons having energies above the threshold energy are observed. For thermonuclear experiments using deuterium (D) and tritium (T) fuel constituents, neutrons arising from D + D reactions (DD-neutrons) and neutrons resulting from D + T reactions (DT-neutrons) are of primary interest. Indium has two neutron activation reactions that can be used to infer yields of DD-neutrons and DT-neutrons. One threshold is high enough that only DT-neutrons can induce activation, the second reaction can be activated by both DD-neutrons and DT-neutrons. Thus, to obtain the DD-neutron yield, the contribution made by DT-neutrons to the total induced activity must be extracted. In DD-fuel experiments, DT-neutrons arise from secondary reactions, which are significantly lower in number than primary DD-neutrons, and their contribution to the inferred DD-neutron yield can be ignored. When the DD- and DT-neutron yields become comparable, such as when low tritium fractions are added to DD-fuel, the contribution of DT-neutrons must be extracted to obtain accurate yields. A general method is described for this correction to DD-neutron yields.

High accuracy astigmatic-focusing system for laser targets.

An accurate location of the focal position with respect to a solid target is a key task for different applications, for instance, in laser driven plasma acceleration for x-ray generation where minimum required intensities are above 1014W/cm2. For such practical applications, new approaches for focus location and target delivery techniques are needed to achieve the required intensity, repeatability, and stability. There are different techniques to accomplish the focusing and target positioning task such as interferometry-, microscopy-, astigmatism-, and nonlinear-optics-based techniques, with their respective advantages and limitations. We present improvements of a focusing technique based on an astigmatic method with potential applications where maximum intensity at the target position is necessary. The presented technique demonstrates high accuracy up to 5 µm, below the Rayleigh range, and also its capability to work in rough surfaces targets and tilt tolerance of the target, with respect to the normal of the target surface.

Direct Measurement of Resonances in

We have performed the first direct measurement of two resonances of the ^{7}Be(α,γ)^{11}C reaction with unknown strengths using an intense radioactive ^{7}Be beam and the DRAGON recoil separator. We report on the first measurement of the 1155 and 1110 keV resonance strengths of 1.73±0.25(stat)±0.40(syst) eV and 125_{-25}^{+27}(stat)±15(syst) meV, respectively. The present results have reduced the uncertainty in the ^{7}Be(α,γ)^{11}C reaction rate to ∼9.4%-10.7% over T=1.5-3 GK, which is relevant for nucleosynthesis in the neutrino-driven outflows of core-collapse supernovae (νp process). We find no effect of the new, constrained reaction rate on νp-process nucleosynthesis.