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Abstract The CMS detector, including its muon system, has been operating at the CERN LHC in increasingly challenging conditions for about 15 years. The muon detector was designed to provide excellent triggering and track reconstruction for muons produced in proton–proton collisons at an instantaneous luminosity ( $$\mathcal {L}$$ L ) of $$1 \times 10^{34}$$ 1 × 10 34 cm $$^{-2}$$ - 2 s $$^{-1}$$ - 1 . During the Run 2 data-taking period (2015–2018), the LHC achieved an instantaneous luminosity of twice its design value, resulting in larger background rates and making the efficient detection of muons more difficult. While some backgrounds result from natural radioactivity, cosmic rays, and interactions of the circulating protons with residual gas in the beam pipe, the dominant source of background hits in the muon system arises from proton–proton interactions themselves. Charged hadrons leaving the calorimeters produce energy deposits in the muon chambers. In addition, high-energy particles interacting in the hadron calorimeter and forward shielding elements generate thermal neutrons, which leak out of the calorimeter and shielding structures, filling the CMS cavern. We describe the method used to measure the background rates in the various muon subsystems. These rates, in conjunction with simulations, can be used to estimate the expected backgrounds in the High-Luminosity LHC. This machine will run for at least 10 years starting in 2029 reaching an instantaneous luminosity of $$\mathcal {L} = 5 \times \text {10}^\text {34}\,\text {cm}^\text {-2}\,\text {s}^\text {-1}$$ L = 5 × 10 34 cm -2 s -1 and increasing ultimately to $$\mathcal {L} = 7.5 \times \text {10}^\text {34}\,\text {cm}^\text {-2}\,\text {s}^\text {-1}$$ L = 7.5 × 10 34 cm -2 s -1 . These background estimates have been a key ingredient for the planning and design of the muon detector upgrade.

Dopamine tone modulation generates changes in beta oscillation physiology. Here the authors show beta frequency, and not power, coherence, phase-locking, or PAC is monotonically linked to dopamine tone and is likely the key property of pathological oscillations in cortical and basal ganglia networks.

Lazerckerite, ideally Ag3.75Pb4.5(Sb7.75Bi4)S24, is a new mineral species found in medieval mine dumps of the historic Ag–Pb–Zn Kutná Hora ore district, Czech Republic. The mineral is associated with other Sb–Bi lillianite homologues (terrywallaceite, gustavite, holubite) and Ag,Bi-bearing galena, most frequently as grain aggregates and replacement rims of earlier Ag–Pb–Bi minerals, growing together in aggregates of up to 0.6×0.3 mm. Lazerckerite is opaque, is steel grey in colour, and has a metallic lustre; the calculated density is 5.920 g cm−3. In reflected light lazerckerite is greyish white, and bireflectance and pleochroism are weak with grey tints. Anisotropy is weak to moderate with grey to bluish-grey rotation tints. Internal reflections are not observed. Electron microprobe analyses yielded the empirical formula, based on 44 apfu, (Ag3.61Cu0.04)Σ3.65(Pb4.55Fe0.01Cd0.01)Σ4.57(Sb7.87Bi3.75)Σ11.62(S24.15Se0.01)Σ24.16. Its unit cell parameters are a=13.2083(9), b=19.4595(8), c=8.4048(13), β=90.032(7)°, V=2160.3(4) Å3, space group P21/c, and Z=2. The structure of lazerckerite contains two Pb sites (Pb1 and Pb2) in bicapped trigonal prismatic coordination, 8 independent octahedral sites, and 13 distinct sulfur positions. Four of the octahedral sites are mixed (Sb,Bi) and (Bi,Sb) sites, one is a mixed (Ag,Bi) site, and one is a mixed (Sb,Pb) site. The new mineral belongs to the andorite branch of the lillianite homologous series with N=4 and is a new addition to the group of Sb–Bi mixed members of the series. Lazerckerite is defined as a lillianite homologue with the three following requirements: N=4, L (Ag++ (Bi3+, Sb3+) ↔ 2 Pb2+ substitution) ≈ 90 %–95 %, and approximately one-third of atom percentage of antimony is replaced by bismuth (Bi/(Bi+Sb) ≈ 0.30–0.38). The new mineral has been approved by the Commission on New Minerals, Nomenclature and Classification (CNMNC) of the International Mineralogical Association (IMA 2022-113) and named after Lazarus Ercker, the supreme Royal Bergmeister of the Kingdom of Bohemia and the Master of Prague Mint.

Abstract Background Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. Methods Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60–75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. Discussion The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

It was suggested the model of the non-concentric spherical core-shell quantum dot with hydrogenic impurity. It has been defined that the electron energy spectrum as a function of both an impurity and the core location. The splitting and degeneration of energy levels has been discussed. It is shown that displacing the core of a quantum dot or impurity in opposite directions can lead to alternate splitting and degeneracy of the energy levels of excited states. In certain configurations of arrangements, compensatory effects associated with the partial restoration of spherical symmetry in the field are observed.

Fermented Tithonia diversifolia and Persea americana miller or avocado leaves as local alternative forages for goats are potential as protein, mineral, and energy sources. Therefore, this study aimed to evaluate the effect of fermented Tithonia diversifolia (FTD) and avocado leaves (AL) combination on in vitro nutrient digestibility, rumen fluid characteristics, and methane production. This study consisted of 3 trials. Trial 1 evaluated FTD’s nutrient content with Lactobacillus bulgaricus with different durations of fermentation arranged in a completely randomized design consisting of five treatments and four replications. The treatments were T. diversifolia without fermentation and fermentation of T. diversifolia for 2, 3, 4, and 5 days. Trial 2 was in vitro evaluation on different days of fermented T. diversifolia in a completely randomized design consisting of four treatments and four replications. Trial 3 was in vitro evaluation of FTD for 5 days and AL combination, which consisted of four combinations. FTDAL1 = 20% FTD+80% AL; FTDAL2 = 40% FTD+60% AL; FTDAL3 = 60% FTD+40% AL; and FTDAL4 = 80% FTD+20% AL. Experimental diets were incubated using Tilley and Terry method. Fermentation of T. diversifolia using L. bulgaricus significantly increased nutrient components (p

Agricultural landscapes support multiple functions and are of great importance for biodiversity. Heterogeneous agricultural mosaics of cropland and grassland commonly result from variable land use practices and ecosystem service demands. Switzerland's agricultural land use is considerably spatially heterogeneous due to strong variability in conditions, especially topography and climate, thus presenting challenges to automated agricultural mapping. Nationwide knowledge of the location of cropland and grassland is necessary for effective conservation and land use planning. We mapped the distribution of cropland and permanent grassland across Switzerland. We used several indices largely derived from Sentinel-2 satellite imagery captured over multiple growing seasons and parcel-based training data derived from landholder reporting. The mapping was conducted within Google Earth Engine using a random forest classifier. The resulting map has high accuracy in lowlands as well as in mountainous areas. The map will act as a base agricultural land cover dataset for researchers and practitioners working in agricultural areas of Switzerland and interested in land cover and landscape structure. The map as well as the training data and calculation algorithms (using Google Earth Engine) are freely available for download on the EnviDat platform https://doi.org/10.16904/envidat.205 (Pazúr et al., 2021).

The objective of this study was to evaluate the impact of coccidiosis on bone quality and antioxidant status in the liver and bone marrow of broiler chickens. A total of 360 13-day old male broilers (Cobb 500) were randomly assigned to different groups (negative control, low, medium-low, medium-high, and highest dose groups) and orally gavaged with different concentrations of Eimeria oocysts solution. Broiler tibia and tibia bone marrow were collected at 6 days post-infection (6 dpi) for bone 3-D structural analyses and the gene expression related to osteogenesis, oxidative stress, and adipogenesis using micro-computed tomography (micro-CT) and real-time qPCR analysis, respectively. Metaphyseal bone mineral density and content were reduced in response to the increase of Eimeria challenge dose, and poor trabecular bone traits were observed in the high inoculation group. However, there were no significant structural changes in metaphyseal cortical bone. Medium-high Eimeria challenge dose significantly increased level of peroxisome proliferator-activated receptor gamma (PPARG, p < 0.05) and decreased levels of bone gamma-carboxyglutamate protein coding gene (BGLAP, p < 0.05) and fatty acid synthase coding gene (FASN, p < 0.05) in bone marrow. An increased mRNA level of superoxide dismutase type 1 (SOD1, p < 0.05) and heme oxygenase 1 (HMOX1, p < 0.05), and increased enzyme activity of superoxide dismutase (SOD, p < 0.05) were found in bone marrow of Eimeria challenged groups compared with that of non-infected control. Similarly, enzyme activity of SOD and the mRNA level of SOD1, HMOX1 and aflatoxin aldehyde reductase (AKE7A2) were increased in the liver of infected broilers (p < 0.05), whereas glutathione (GSH) content was lower in the medium-high challenge group (p < 0.05) compared with non-challenged control. Moreover, the mRNA expression of catalase (CAT) and nuclear factor kappa B1 (NFKB1) showed dose-depend response in the liver, where expression of CAT and NFKB1 was upregulated in the low challenge group but decreased with the higher Eimeria challenge dosage (p < 0.05). In conclusion, high challenge dose of Eimeria infection negatively affected the long bone development. The structural changes of tibia and decreased mineral content were mainly located at the trabecular bone of metaphyseal area. The change of redox and impaired antioxidant status following the Eimeria infection were observed in the liver and bone marrow of broilers.

This study evaluated the effects of total sulfur amino acid (TSAA) levels on the performance and intestinal health of broilers challenged with Eimeria spp. A total of 432 one-day-old off-sex Cobb 500 male chicks were randomly assigned to a 3 × 2 factorial arrangement (6 replicates/12 birds), with diets and Eimeria challenge as the main factors. The diets were as follows: 70% (no methionine [Met] supplementation), 85, and 100% TSAA, supplemented with L-Met. At day 14, the challenged birds (n = 216) were orally gavaged with a pool of Eimeria acervulina, Eimeria maxima, and Eimeria tenella sporulated oocysts, and the unchallenged birds (n = 216) received water. At 6 and 12 D post inoculation (dpi), performance and intestinal health were evaluated. The challenge, regardless of diets, significantly impaired the performance, intestinal villi height, villus-to-crypt ratio, and ileal digestibility of dry matter, energy, and crude protein (CP) and modulated the tight junction protein (TJP) expression throughout the experiment. Moreover, the superoxide dismutase activity was increased, whereas the reduced glutathione (GSH)-to-oxidized glutathione (GSSG) ratio was decreased by the challenge at 6 dpi. Regardless of the challenge, the 70% TSAA diet reduced the body weight and feed intake in all phases, whereas the ileal digestibility of CP was higher in birds fed with the 70% TSAA diet than in those fed with the 100% TSAA diet at 6 dpi. No major differences were observed among the diets with regard to the intestinal histomorphology and TJP expression, and birds fed with the 100% TSAA diet had the highest GSH concentration at 12 dpi. Few interactions were observed, and the Met supplementation counteracted the negative effects of the Eimeria challenge on GSH concentration when 85 and 100% of TSAA levels were reached. Overall, the Eimeria challenge had a negative impact on growth and intestinal health. Moreover, the supplementation of L-Met until either 85 or 100% of TSAA levels were reached was enough to assure good performance and intestinal health in birds challenged or not challenged with Eimeria spp.

We report a combined theoretical and experimental investigation of magnetic proximity and Hall transport in Pt/Cr bilayers. Density-functional theory indicates that interfacial magnetic moments can be induced in the Pt layer and a strong magnetocrystalline anisotropy with an out-of-plane easy axis arises in the antiferromagnet. A signal ascribed to the anomalous Hall effect is detected and associated to the interface between Pt and Cr layers. We discuss how this effect originates from the Berry curvature of the electronic structure at the interface and the correlation with the character of the proximity-induced magnetic moments.

Abstract Seal lice, unique among insects, show remarkable adaptability to the extreme conditions of the deep sea. Evolving with their seal and sea lion hosts, they have managed to tolerate hypoxia, high salinity, low temperature, and elevated hydrostatic pressure. Given the diving capabilities of their mammalian hosts, which can reach depths of hundreds to thousands of meters, our study examines the morphological variation among closely related seal lice species infesting hosts with different maximum diving depths. In particular, our research reveals a significant morphological difference between lice associated with regular and deep-diving hosts, where lice from deep-diving hosts tend to be rounder. This could be an adaptation to withstand the high hydrostatic pressures found in the deep ocean. The rounded shape optimizes the louse’s ability to withstand external pressure by redistributing it over a larger ventral/dorsal plane. This in turn minimizes the internal energy required to support body deformations, thereby increasing the louse’s resilience in the deep sea environment.

The eclipsing binary NN Vir is a short period system showing an EW-type light curve. Photometric Observations of NN Vir were done by Gomez-Ferrellad & Garcia-Melendo (1997) at Esteve Duran Observatory. We used photometric Data of NN Vir for light curve analysis. The available spectroscopic data of NN Vir is new and we also used the first radial velocity Data of this system obtained by Rusinski & Lu (1999) for analysis. The radial velocity and light curves analysis was made with the Latest version of Wilson program (1998) and the geometric and physical elements of the system are derived. By searching the simultaneous solutions of the system, we have determined the masses and radii of the components : 1.89(Msun) and 1.655(Rsun) for the primary component; O.93(Msun) and 1.230(Rsun) for the secondary component. We estimated effective temperatures of 7030(K) for the primary and 6977(K) for the secondary component.

El conocimiento de las interacciones existentes entre el cambio climático y el manejo del bosque en el decaimiento de ciertas especies forestales es necesario de cara al establecimiento de planes de conservación y gestión. En este trabajo hemos realizado una revisión bibliográfica y una síntesis de trabajos científicos centrados en el estudio de la causas del declive de los cedrales del Atlas (bosques de Cedrus atlantica), norte de Marruecos.Se han revisado trabajos sobre las tendencias climáticas y las propiedades del suelo y estudios dendroecológicos con el objetivo de determinar las relaciones existentes entre el patrón de crecimiento de los árboles, la degradación y el declive del bosque y el clima. Los bosques de cedro han sido severamente afectados por sequías, sobrepastoreo, talas y podas. Eventos recurrentes de intensa sequía, así como un incremento en la temperatura media, han sido identificados desde la década de 1970. El actual decaimiento de las poblaciones de cedro en bosques intensamente talados, podados y sobrepastoreados está propiciando su regresión y su sustitución por especies más resistentes a la sequía y las perturbaciones, como por ejemplo Quercus rotundifolia.

Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO2/FiO2 ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO2/FiO2 ratio, neutrophil density or TGF-β expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-β expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation.

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO2/FiO2 ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.

Objetivo: valorar el efecto de la pentoxifilina (un potente inhibidor del factor de necrosis tumoral alfa) en la supervivencia, en la hemodinámica sistémica y portal y en la función cardiaca en la cirrosis alcohólica avanzada. Diseño: estudio aleatorizado, doble-ciego, controlado con placebo. Contexto: estudio unicéntrico utilizando grupos de pacientes en paralelo para comparar pentoxifilina y placebo. Pacientes: se incluyeron 24 pacientes con cirrosis alcohólica (8 en estadio B de Child-Pugh y 16 en estadio C de Child-Pugh). Intervención: los pacientes fueron aleatorizados a recibir pentoxifilina (400 mg, 3 veces al día, n = 12) o placebo (n = 12) durante 4 semanas. Determinaciones: el objetivo principal fue la supervivencia a corto/largo plazo. Los objetivos secundarios fueron observar beneficios hemodinámicos (mejoría en la función cardiaca y/o en el índice de resistencias vasculares sistémicas o disminución de la presión portal). Resultados: la presión portal y la función cardiaca no se modificaron y no hubo diferencias en la supervivencia a corto y largo plazo entre los grupos tratados y placebo. Los índices de resistencia vascular sistémica y cardiaco cambiaron en el grupo de pentoxifilina (de 1.721 ± 567 a 2.082 ± 622 Din.seg ¹ cm-5 m-2 y de 4,17 ± 1,4 a 3,4 ± 0,9 lm-2, p = 0,05). Conclusiones: aunque la pentoxifilina parece producir algún beneficio hemodinámico a corto plazo en pacientes con cirrosis alcohólica avanzada, no tiene efecto sobre la tasa de supervivencia, la función cardiaca ni sobre la presión portal en estos pacientes.Objective: to assess the effect of pentoxiphylline (a potent inhibitor of tumor necrosis factor alpha) on survival, on systemic and portal hemodynamics, and on cardiac function in patients with alcoholic cirrhosis. Design: a randomized double-blind placebo-controlled trial. Setting: a single center using parallel groups of patients to compare pentoxiphylline with placebo. Patients: we recruited 24 patients with alcoholic cirrhosis (8 Child-Pugh B and 16 Child-Pugh C). Interventions: patients were randomly assigned to receive pentoxiphylline (400 mg tid; n = 12) or placebo (n = 12) over a 4-week period. Outcome measures: the primary outcome was to extend short-term and long-term survival. Secondary outcomes included hemodynamic benefits (improvement in cardiac function and/or systemic vascular resistance index, or decrease in portal pressure). Results: portal pressure and cardiac function remained unchanged and there were no significant differences in short-term or long-term survival between treatment and placebo groups. The group on pentoxiphylline increased systemic vascular resistance and decreased cardiac indices (from 1,721 ± 567 to 2,082 ± 622 dyn.sec-1 cm-5 m-2 and from 4.17 ± 1.4 to 3.4 ± 0.9 l.m-2, p = 0.05). Conclusions: although pentoxiphylline seems to provide some short-term aemodynamic benefits in patients with advanced alcoholic cirrhosis, this drug has no effect on survival or portal pressure in these patients.

No abstract is available

Resumen: La técnica de cuasi-implicación estadística es muy útil para determinar relaciones de causa y efecto (con un número pequeño de excepciones). La aplicación del análisis jerárquico de similitudes, busca constituir particiones cada vez más finas, en el conjunto de variables, construidas de forma ascendente en árbol, mediante un criterio de similitud entre las misma. Su objetivo es descubrir y estructurar en forma de reglas, un conjunto de datos a partir de la modelización estadística de la cuasi-implicación.En éste trabajo se presenta una aplicación de ésta técnica para encontrar grupos de equivalencia existente entre un conjunto completo de imágenes (groundTruth)de resonancia magnética de cerebro (T1-weighted).Los experimentos se han realizado con la serie de lonchas sin cráneo, segmentadas y binarizadas previamente. Los resultados muestran una robusta clasificación de las mismas agrupándolas según un mismo índice de implicación entre dos lonchas en forma cuasi-bicondicional. En cada grupo de similitud el método permite seleccionar a uno de los cortes como representante del grupo generando una lista de patrones los cuales resumen las características encontradas próximas al patrón. Para representar el grado de equivalencia se ha utilizado una probabilidad.tud. Abstract:The quasi-implication statistical technique is very useful for determining cause and effect (with a few exceptions). The application of hierarchical analysis of similarities,seeks to build increasingly fine partitions in the set of variables, built from the bottom up in the tree, using a criterion of similarity between them. Their purpose is to discover and structure, in the form of rules, a set of data from statistical modeling of quasi-implication.An application of this technique is presented in this work to find groups of equivalence between a full set of Brain MRI (T1- weighted)images (ground Truth). Experiments have been performed witha number of slices without skull previously segmented and binarized. The results show a robust classification of the same grouping them with the same rate of engagement between two quasi-biconditional shapedslices. This method allows in each similarity group select one of the images as o representative of the group, generating a list of standards which outline features proximal to the pattern. To represent the degree of equivalence a probability has been used.

Resumen Introducción y objetivo. La lesión de nervio periférico, en todos sus mecanismos, es un evento frecuente entre la población en general. Existen distintos métodos de reparación de la misma, sin embargo, no hay suficiente investigación sobre el injerto más eficaz. El objetivo de este estudio es determinar la superioridad de la combinación de polietilenglicol en tubos de politetrafluoroetileno como injerto sobre el uso aislado del mismo y de un autoinjerto. Material y método. Estudio experimental de casos y controles utilizando ratas Wistar a las que se les indujo, bajo sedación, lesión nerviosa mediante extracción de injerto nervioso de nervio ciático y su posterior reparación, divididas en 3 grupos: autoinjerto, injerto de politetrafluoroetileno e injerto de politetrafluoroetileno con polietilenglicol. Resultados. Analizamos 8 variables histopatológicas con conteo total de axones, encontrando mayor número en las muestras de autoinjerto. Entre las variables clínicas, analizamos la deformidad de la extremidad, la atrofia muscular macroscópica y la alteración en la marcha. El grupo de la combinación de materiales mostró una evolución excelente en las 3 categorías. Conclusiones. La recuperación clínica de la extremidad intervenida en el grupo donde se utilizó la combinación de los materiales en estudio fue notablemente superior; observamos además mucha mejor organización axonal, indicando una superioridad de esta combinación respecto a los otros grupos evaluados.

Background and PurposeLaparoscopic partial nephrectomy (LPN) has been performed at several institutions using oxidized cellulose (OC) as a means of bleeding and urinary fistula (UF) prevention. However, a foreign-body reaction mimicking either abscess or tumor recurrence has been associated with the use of OC. We evaluated renal-defect healing after LPN with and without OC.Materials and MethodsSixteen female Landrace pigs underwent lower-pole excision; all the collecting systems were entered and then closed with absorbable running suture. In group 1, hemostatic U-shaped stitches were the only method of hemostasis. In group 2, a bolster of OC was added to the renal defect. The pigs were sacrificed at 1, 4, 7, or 21 days, and gross findings such as perirenal collection were observed. A catheter was advanced up to the kidney, and methylene blue was injected with collecting system pressure observation; burst pressure was defined as the appearance of extravasation. High risk for UF was defined as burst pressure <10 mm Hg.ResultsNeither hemorrhage nor urinoma was observed during sacrifice. One pig from group 2 had a burst pressure of 4 mm Hg At 7 days (high risk for UF). At 21 days in group 2, the tissue was grossly solid, apparently a granuloma. Suppuration tended to be greater in group 2. The foreign-body reaction was more intense in group 2 and was strongly present at 4, 7, and 21 days.ConclusionsThe use of OC is associated with higher scores of suppuration and foreign-body reaction. After LPN with OC, postoperative day 7 might be a critical time for the development of urinary leakage. [ABSTRACT FROM AUTHOR]

Purpose The Bariatric Experience Long Term (BELONG) prospective study cohort was created to address limitations in the literature regarding the relationship between surgical weight loss and psychosocial, health, behaviour and environmental factors. The BELONG cohort is unique because it contains 70% gastric sleeve and 64% patients with non-white race/ethnicity and was developed with strong stakeholder engagement including patients and providers.Participants The BELONG cohort study included 1975 patients preparing to have bariatric surgery who completed a baseline survey in a large integrated health system in Southern California. Patients were primarily women (84%), either black or Hispanic (59%), with a body mass index (BMI) of 45.1±7.4 kg/m2, age 43.3±11.5 years old, and 32% had at least one comorbidity.Findings to date A total of 5552 patients were approached before surgery between February 2016 and May 2017, and 1975 (42%) completed a baseline survey. A total of 1203 (73%) patients completed the year 1 and 1033 (74%) patients completed the year 3 postoperative survey. Of these survey respondents, 1341 at baseline, 999 at year 1, and 951 at year 3 were included in the analyses of all survey and weight outcome data. A total of 803 (60% of eligible patients) had survey data for all time points. Data collected were self-reported constructs to support the proposed theoretical model. Height, weight and BMI were abstracted from the electronic medical record to obtain the main outcomes of the study: weight loss and regain.Future plans We will collect self-reported constructs and obtain height, weight and BMI from the electronic medical record 5 years after bariatric surgery between April 2022 and January 2023. We will also collect patient experiences using focus groups of 8–12 patients each throughout 2022.

ABSTRACT: Insulin deregulation (ID) is a central player in the pathophysiology of equine metabolic syndrome (EMS), which is associated with generalized and/or regional obesity. The objective of this experiment was to characterize the alterations in the hormonal profile in horses exposed to a hypercaloric diet. A total of nine Mangalarga Marchador adult horses with initial body condition score (BCS) of 2.9±1/9 (mean±SD) were submitted to a high calorie grain-rich diet for 5 months. The data was collected before the start of the experiment and every 15 days until the end of the experiment and glucose and insulin concentrations were measured in the plasma. Proxies G:I, RISQI, HOMA-IR and MIRG were calculated. The low-dose oral glucose tolerance test (OGTT) was performed and the total area under the glucose (GTA) and insulin (ITA) curves at three different timepoints (before inducing obesity, after 90 days and after 150 days) was used. Analysis of variance of the results was performed considering the time effects and the means were compared with repeated measures by the Tukey’s test (P≤0.05). The ID was observed during the first 90 days of the experiment and was characterized as a decompensated ID, showing an increase of basal glucose and insulin plasma levels, changes in all proxies and a significant increase in GTA (P

The tumor stroma plays a relevant role in the initiation and evolution of solid tumors. Tumor-stroma ratio (TSR) is a histological feature that expresses the proportion of the stromal component that surrounds cancer cells. In different studies, the TSR represents a potential prognostic factor: a rich stroma in tumor tissue can promote invasion and aggressiveness. The aim of this study was to evaluate the reproducibility and determine the interobserver agreement in the TSR score. The stromal estimate was evaluated in patients diagnosed with colorectal adenocarcinoma (CRA), who underwent surgical resection. We also evaluated age, gender, and other anatomopathological features. Tumor-stroma ratio was calculated based on the slide used in routine diagnostic pathology to determine the T-status. Stromal percentages were separated into 2 categories: ⩽50%—low stroma and >50%—high stroma. The interobserver agreement in the TSR scoring was evaluated among 4 pathologists at different stages of professional experience, using 2 different ways to learn the scoring system. In total, 98 patients were included in this study; 54.1% were male, with a mean age of 61.9 years. Localized disease was diagnosed in 60.2% of patients. Stromal-poor CRA was predominant. The concordance between the TSR percentages of the 4 pathologists was substantial (Kappa > 0.6). There was greater agreement among pathologists for stromal-poor tumors. Substantial agreement and high reproducibility were observed in the determination of TSR score. The TSR score is feasible, suggesting that the presented methodology can be used to facilitate the determination of the stromal proportion of potential prognostic factor.

Experiential avoidance (EA)—or psychological (in)flexibility—is a central concept in contextual therapies, and it has been proposed as a transdiagnostic dimension of psychopathology. We intended to test whether EA and other coping strategies independently predict both state and trait-anxiety. We administered a set of measures (the AAQ-II, a modified version of the Brief COPE, and the STAI) to 284 undergraduates from a public university in Lima, Peru. Results showed that EA, lack of problem solving, self-blame, and substance use were all significantly related to state and trait-anxiety. However, after submitting these variables to multiple regression analyses, only EA, lack of problem solving, and self-blame remained significant predictors of trait-anxiety; of these, only EA made a significant improvement to the model (ΔR² = .16). On the other hand, none of the variables under study were significant predictors of state-anxiety. We concluded that the effort to avoid unpleasant thoughts and emotions constitutes a central aspect of trait-anxiety. We discussed these findings in light of previous studies, and gave suggestions for future research.

The present study focused on the activity of the palladacycle complex DPPE 1.1 on Leishmania (Leishmania) amazonensis. Promastigotes of L. (L.) amazonensis were destroyed in vitro by nanomolar concentrations of DPPE 1.1, whereas intracellular amastigotes were killed at drug concentrations fivefold less toxic than those harmful to macrophages. L. (L.) amazonensis-infected BALB/c mice were treated by intralesional injection of DPPE 1.1. Animals treated with 3.5 and 7.0 mg/kg of DPPE 1.1 showed a significant decrease of foot lesion sizes and a parasite load reduction of 93 and 99%, respectively, when compared to untreated controls. Furthermore, DPPE 1.1 was non-toxic to treated animals. The cathepsin B activity of L. (L.) amazonensis amastigotes was inhibited by DPPE 1.1 as demonstrated spectrofluorometrically by use of a specific fluorogenic substrate. Analysis of T-cells populations in mice treated with DPPE 1.1 and untreated controls was performed by fluorescence-activated cell sorter (FACS). IFN-γ was measured in supernatants of lymphocytes from popliteal and inguinal lymph nodes isolated from treated and untreated mice and stimulated with L. (L.) amazonensis amastigotes extract and active TGF-β was evaluated in supernatants of foot lesions; both dosages were carried out by means of a double-sandwich ELISA assay. A significant increase of TCD4+ and TCD8+ lymphocytes and IFN-γ secretion was displayed in mice treated with DPPE 1.1 compared to untreated animals, whereas a significant reduction of active TGF-β was observed in treated mice. These findings open perspectives for further investment in DPPE 1.1 as an alternative option for the chemotherapy of cutaneous leishmaniasis.

Este trabajo se centra en la comprensión de la racionalidad de la gestión de los recursos disponibles en la unidad de producción agrícola (UPA), la identificación de sus características técnicas y socioeconómicas con el fin de hacer un diagnóstico para subsidiar el gerente rural en la toma de decisiones en la producción estratégica de la organización rural. Este estudio de caso fue parte del proyecto de extensión empresarial rural, desarrollado en la comunidad de Nhu-Porã, São Borja / RS / Brasil, priorizando como objeto de estudio una unidad de producción familiar, siendo realizado en el período de octubre a noviembre 2014. Se realizó una encuesta de datos cualitativos y cuantitativos, como los recursos naturales, la superficie agrícola utilizada, manada, mejoras, maquinaria y equipo, la disponibilidad de mano de obra y las producciones de los diferentes subsistemas de cultivo, cría y procesamiento. Estos datos fueron organizados en una hoja de cálculo, la cual pertmitó identificar lo sistema de producción adoptado y sus características técnicas y socioeconómicas. En la evaluación económica, teniendo en cuenta los indicadores económicos globales obtenidos, se puede decir que la UPA se encuentra en una situación cómoda, cuya renta agrícola global puede superar el nivel de reproducción social (NRS), estipulado en este estudio en R$ 9,100.00. Como propuesta de la intervención técnica y de gestión, a partir de este diagnóstico, propose estratégicamente intensificar la producción de leche em detrimiento de la producción de soja, hasta su alta contribuición en relación con el valor añadido por unidad de área.

Evapotranspiration (ET) plays an important role in global climate dynamics and in primary production of terrestrial ecosystems; it represents the mass and energy transfer from the land to atmosphere. Limitations to measuring ET at large scales using ground-based methods have motivated the development of satellite remote sensing techniques. The purpose of this work is to evaluate the accuracy of the SEBAL algorithm for estimating surface turbulent heat fluxes at regional scale, using 28 images from MODIS. SEBAL estimates are compared with eddy-covariance (EC) measurements and results from the hydrological model MGB-IPH. SEBAL instantaneous estimates of latent heat flux (LE) yielded r 2= 0.64 and r2 = 0.62 over sugarcane croplands and savannas when compared against in situ EC estimates. At the same sites, daily aggregated estimates of LE were r 2 = 0.76 and r2 = 0.66, respectively. Energy balance closure showed that turbulent fluxes over sugarcane croplands were underestimated by 7% and 9% over savannas. Average daily ET from SEBAL is in close agreement with estimates from the hydrological model for an overlay of 38,100 km2 (r2 = 0.88). Inputs to which the algorithm is most sensitive are vegetation index (NDVI), gradient of temperature (dT) to compute sensible heat flux (H) and net radiation (Rn). It was verified that SEBAL has a tendency to overestimate results both at local and regional scales probably because of low sensitivity to soil moisture and water stress. Nevertheless the results confirm the potential of the SEBAL algorithm, when used with MODIS images for estimating instantaneous LE and daily ET from large areas.

We quantify uncertainty in the impacts of climate change on the discharge of Rio Grande, a major tributary of the Paraná River in South America and one of the most important basins in Brazil for water supply and hydro-electric power generation. We consider uncertainty in climate projections associated with the greenhouse-gas emission scenarios (A1b, A2, B1, B2) and increases in global mean air temperature of 1 to 6° C for the HadCM3 GCM (Global Circulation Model) as well as uncertainties related to GCM structure. For the latter, multimodel runs using 6 GCMs (CCCMA CGCM31, CSIRO Mk30, IPSL CM4, MPI ECHAM5, NCAR CCSM30, UKMO HadGEM1) and HadCM3 as baseline, for a +2° C increase in global mean temperature. Pattern-scaled GCM-outputs are applied to a large-scale hydrological model (MGB-IPH) of Rio Grande Basin. Based on simulations using HadCM3, mean annual river discharge increases, relative to the baseline or control run period (1961–1990), by +5% to +10% under the SRES emissions scenarios and from +8% to +51% with prescribed increases in global mean air temperature of between 1 and 6° C. Substantial uncertainty in projected changes to mean river discharge (−28% to +13%) under the 2° C warming scenario is, however, associated with the choice of GCM. We conclude that, in the case of Rio Grande Basin, the most important source of uncertainty derives from the GCM rather than the emission scenario or the magnitude of rise in mean global temperature.

Libraries of compounds containing heteroaromatic rings and other nitrogen heterocycles were [...]

Este trabajo aborda la comprensión de la racionalidad de la gestión de la producción y los recursos disponibles en la unidad de producción agrícola (UPA), identificando sus principales características técnicas y socioeconómicas con el fin de hacer un diagnóstico sistémico para subsidiar el gestor rural en la toma de decisiones. Este estudio fes parte del proyecto de extensión del Programa Institucional de Incentivo la Extensión del Instituto Federal Farroupilha (Brasil), priorizando como objeto de estudio una UPA familiar en el municipio de Santo Antonio das Missões/RS/Brasil, se llevaron a cabo entre octubre al noviembre de 2014. Como procedimiento metodológico se realizó encuesta de datos cualitativos y cuantitativos, como: los recursos naturales, la superficie agrícola utilizada, rebaño, instalaciones, maquinaria y equipos, la disponibilidad de mano de obra y los rendimientos de los diferentes subsistemas. Estos datos fueron organizados en una hoja de cálculo, identificando el sistema de producción adoptado y sus principales características técnicas y socioeconómicas. Como propuesta de intervención técnica y de gestión en el sistema de producción, se propone estratégicamente intensificar la producción de leche en detrimento de la producción de soja, visto su alta aporte en relación con el valor añadido por unidad de área.

OBJECTIVE: It is controversial whether age is associated with higher grade and worse outcome. Some studies have not found age to be related to outcome nor younger age to be associated with better response to therapy. MATERIALS AND METHODS: The study population consisted of 27 patients aged 55 years or younger and 173 patients 56 years or older submitted to radical prostatectomy. The variables studied were preoperative PSA, time to PSA progression following radical prostatectomy and pathologic findings in surgical specimens: Gleason score, Gleason predominant grade, positive surgical margins, tumor extent, extraprostatic extension (pT3a), and seminal vesicle invasion (pT3b). RESULTS: Comparing patients aged 55 years or younger and 56 years or older, there was no statistically significant difference for all variables studied: preoperative PSA (p = 0.4417), Gleason score (p = 0.3934), Gleason predominant grade (p = 0.2653), tumor extent (p = 0.1190), positive surgical margins (p = 0.8335), extraprostatic extension (p = 0.3447) and seminal vesicle invasion (p > 0.9999). During the study period, 44 patients (22%) developed PSA progression. No difference was found in the time to biochemical progression between men aged 55 years or younger and 56 years or older. CONCLUSION: Our findings suggest that age alone do not influence the biological aggressiveness of prostate cancer.

Muitas famílias utilizam carroça tracionada por equinos como seu meio de trabalho ou suplementação da renda. Preocupando-se com a saúde desses animais, em Pelotas, desde 2006, existe o Ambulatório Veterinário, que presta atendimento clínico gratuito semanalmente aos cavalos de carroceiros. Os objetivos deste trabalho foram avaliar e registrar os padrões biométricos de equinos de tração em Pelotas. Foram avaliados 219 equinos, 129 fêmeas e 90 machos. Largura de peito (LP), perímetro de canela (PC), perímetro torácico (PT), largura de garupa (LG), altura do animal e peso (P) foram mensurados. Baseado nos valores encontrados, foram calculados os índices de Compacidade 1 (ICC1= (P/AC)/100), de compacidade 2 (ICC2=(P/[AC-1]/100) e de conformação (ICF=PT2/AC). Os animais de ambos os sexos apresentaram as seguintes médias: AC - 1,38 ± 0,07 m; PC – 0,19 ± 0,02 cm; PT – 1,56 ± 0,10 m; LP – 0,26 ± 0,05 cm; LG – 0,22 ± 0,05 cm; peso – 308 ± 60 kg. Em relação aos índices ICC1, ICC2 e ICF, as médias encontradas também para ambos os sexos foram, respectivamente, 2,30; 8,39; 1,82. Dessa forma, pelos índices obtidos, os cavalos avaliados foram considerados em sua maioria como inadequados para tração de cargas pesadas e com maior aptidão para tração de cargas leves ou uso como cavalos de sela. PALAVRAS-CHAVE: biometria; carroça; cavalos; índice de compacidade; tração.

The aim of this study was to investigate the effect of aging and timing of left ventricular ischemic injury on the availability and functionality of stem cells. We studied young and aged male inbred Lewis rats that were used as donors of bone marrow mononuclear cells (BM-MNCs), divided in four experimental groups: controls, sham operated, 48 h post-myocardial infarction (MI), and 28 days post-MI. In vitro studies included flow cytometry analysis, hematopoietic colony-forming capacity, and invasion assays of migration capacity. BM-MNCs from these groups were transplanted in female rats after MI induction. Late engraftment was evaluated by real-time PCR of the SRY chromosome. Percentage of CD34 + /CD45 +low cells was similar among different experimental groups in young rats, but was significantly higher in aged animals ( p < 0.001), particularly 28 days post-MI. KDR + /CD34 + cells were increased 48 h after MI and decreased 28 days post-MI in young animals, while they were profoundly reduced in the aged group ( p < 0.001). Triple staining for CD44 + /CD29 + /CD71 + cells was similar in different groups of aged rats, but we observed an intense increase 48 h post-MI in young animals. Colony-forming units and cytokine-induced migration were significantly attenuated 28 days after the MI. Late engraftment in infarcted transplanted female hearts was present, but considerably heterogeneous. Finally, recovery of left ventricular systolic function in transplanted female recipients was significantly influenced by donors' BM-MNCs groups ( p < 0.01). We have demonstrated that aging and timing of myocardial injury are factors that may act synergistically in determining stem cell availability and function. Such interaction should be considered when planning new cell therapy strategies for acute and chronic ischemic heart disease in the clinical arena.

En el trabajo se caracterizan las condiciones extremas por excesivo calor en La Habana (Cuba) y su variabilidade intraestacional, estacional e interanual. Para ello, se determinan las condiciones de calor intenso (CCI), nuevo indicador bioclimático generado a partir de las sensaciones térmicas de las personas en horarios contrastantes (07:00 y 13:00 h - 75º W), según los valores de los índices de temperatura efectiva y temperatura efectiva equivalente. Los cálculos se efectuaron para el período 1975-2004, con datos de las estaciones meteorológicas de Casablanca y Santiago de las Vegas; y para diferentes puntos dentro de la ciudad con información climatológica proveniente de mediciones y observaciones microclimáticas. Los resultados indican que las CCI ilustran coherentemente tanto las condiciones medias como la variabilidad climática de los extremos por calor, al compararse con otros indicadores bioclimáticos. Se establece una diferenciación entre la zona costera, con mayor cantidad de días con CCI, y el interior del territorio, donde es menor. Se reportan tendencias crecientes de alta significación estadística en el número de días anuales con esta condición; puntos de cambio significativos en las series entre los años 1980 y 1994; y el alargamiento de la temporada donde ellas se manifiestan, a cuenta de un final más avanzado en el año, más notables en Santiago de las Vegas. En presencia de CCI en la estación de Casablanca, importantes variaciones pueden producirse dentro de la ciudad, donde influyen la distancia al mar, el efecto del viento y la compactación de las edificaciones. El enfoque y la metodología empleados pueden aplicarse a otras unidades naturales o político-administrativas, en condiciones climáticas similares.

Introduction: Median arcuate ligament syndrome (MALS) is a rarely diagnosed and treated etiology of abdominal pain with no established diagnostic approach. The effectiveness of our institutional protocol in identifying these patients was investigated by analyzing their surgical outcomes., Methods: A retrospective review was conducted of patients treated for MALS at our institution from 2001 to 2022. Patients were considered for a diagnosis of MALS if there was evidence of abdominal pain (unprovoked, provoked by eating and physical activity) and celiac artery dynamic compression on diagnostic imaging. During the study period, an institutionalized management protocol was developed for these patients. Patients were then categorized as having positive surgical outcomes if their symptoms improved or resolved entirely during the latest follow-up visit, while those whose symptoms remained unchanged or worsened were classified as having negative outcomes. Of the patients considered for MALS diagnosis, a patient was confirmed positive if there is either a positive provocative mesenteric angiogram, celiac plexus block, or both, along with a negative gastroenterology workup. Comparative analysis was performed using a chi-square test. Multivariable logistic regression models were performed to evaluate the association between risk factors and symptom relief with the adjusted follow-up length. All tests were two-sided, with p-value <0.05 considered statistically significant., Results: A total of 163 patients with a mean follow-up duration of 17.7 + 23.4 months were included in the study. Patients who were part of the protocol had a higher rate of improvement in their abdominal pain (65.9% vs 50.0 %, p < 0.04). Furthermore, patients diagnosed positive by the protocol experienced greater relief of abdominal pain compared to patients with a negative diagnosis (77.8% vs 52.5%, p = 0.014)., Conclusion: By using a standardized protocol, patients who received a positive diagnosis demonstrated symptomatic improvement in their outcomes. Further investigation is warranted on a larger scale to assess its generalizability for the management of this challenging patient population., (Copyright © 2024. Published by Elsevier Inc.)

Learning from appetitive and aversive stimuli involves interactions between the prefrontal cortex and subcortical structures. Preclinical and theoretical studies indicate that inhibition is essential in regulating the relevant neural circuitry. Here, we demonstrate that GABA, the main inhibitory neurotransmitter in the central nervous system, differentially affects how the dACC interacts with subcortical structures during appetitive and aversive learning in humans. Participants engaged in tasks involving appetitive and aversive learning, while using functional magnetic resonance spectroscopy (MRS) at 7T to track GABA concentrations in the dACC, alongside whole-brain fMRI scans to assess BOLD activation. During appetitive learning, dACC GABA concentrations were negatively correlated with learning performance and BOLD activity measured from the dACC and the Putamen. These correlations were absent during aversive learning, where dACC GABA concentrations negatively correlated with the connectivity between the dACC and the Putamen. Our results show that inhibition in the dACC mediates appetitive and aversive learning in humans through distinct mechanisms.

Adhesions are recognised as one of the most common complications of abdominal surgery; their diagnosis and prevention remains a significant unmet need in surgical therapy, affecting negatively a patient's quality of life and healthcare budgets. In addition, postoperative pelvic adhesions pose a high risk of reduced fertility in women of childbearing age. These 2023 Global Recommendations on Adhesion Prevention in Gynaecological Laparoscopic Surgery provide agreed-upon statements to guide clinical practice, with the ultimate goal of improving patient outcomes.

Purpose: Hepatic venous transplant anastomotic pressure gradient measurement and transjugular liver biopsy are commonly used in clinical decision-making in patients with suspected anastomotic hepatic venous outflow obstruction. This investigation aimed to determine if sinusoidal dilatation and congestion on histology are predictive of hepatic venous anastomotic outflow obstruction, and if it can help select patients for hepatic vein anastomosis stenting., Materials and Methods: This is a single-center retrospective study of 166 transjugular liver biopsies in 139 patients obtained concurrently with transplant venous anastomotic pressure gradient measurement. Demographic characteristics, laboratory parameters, procedure and clinical data, and histology of time-zero allograft biopsies were analyzed., Results: No relationship was found between transplant venous anastomotic pressure gradient and sinusoidal dilatation and congestion (P = 0.92). Logistic regression analysis for sinusoidal dilatation and congestion confirmed a significant relationship with reperfusion/preservation injury and/or necrosis of the allograft at time-zero biopsy (OR 6.6 [1.3-33.1], P = 0.02)., Conclusion: There is no relationship between histologic sinusoidal dilatation and congestion and liver transplant hepatic vein anastomotic gradient. In this study group, sinusoidal dilatation and congestion is a nonspecific histopathologic finding that is not a reliable criterion to select patients for venous anastomosis stenting., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background & Aims: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes., Methods: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection., Results: Among 91 eligible patients, with a median (IQR) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years 0.72, 95% CI 0.53-0.99, p = 0.044) and ICI washout time (aHR per 1 week 0.92, 95% CI 0.86-0.99, p = 0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p = 0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8] vs. 8.0 [9.0]; p = 0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p = 0.032)., Conclusion: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations., Impact and Implications: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitor use prior to liver transplantation suggest acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without immune checkpoint inhibitor exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

This study evaluated the possible use of a fraction of brewers' spent grain rich in arabinoxylans (BSG-AX) as an excipient that modifies the release of class III drugs (Biopharmaceutics Classification System), by determining the release profile of metformin hydrochloride (MH), in a water medium. The cumulative percentage of MH release showed the best linear fit when modeled with the cumulative distribution function (CDF) of the Weibull distribution ( R 2 = 0.993 ± 0.001). According to the Korsmeyer-Peppas model, the first stage of MH release is regulated by a super case-II transport mechanism controlled by the expansion and relaxation of BSG-AX. Finally, with the Hixson-Crowell model, a release rate ( k HC ) of 0.350 ± 0.026 h - 1 3 was obtained ( R 2 = 0.996 ± 0.007). BSG-AX constitutes a suitable material for producing prolonged drug release vehicles; however, additional research is required to provide a better encapsulation of the active ingredients to ensure their optimal applicability and performance.

With all the current misinformation on social media platforms about the COVID-19 vaccine and its potential effects on fertility, it is essential for healthcare providers to have evidenced-based research to educate their patients, especially those who are trying to conceive, of the risks to mothers and fetuses of being unvaccinated. It is well known that COVID-19 infection puts pregnant women at higher risk of complications, including ICU admission, placentitis, stillbirth, and death. In February of 2021, the American College of Obstetricians and Gynecologists (ACOG), the American Society for Reproductive Medicine (ASRM), and the Society for Maternal-Fetal Medicine (SMFM) released a statement denying any link between COVID vaccination and infertility. ASRM later confirmed and stated that "everyone, including pregnant women and those seeking to become pregnant, should get a COVID-19 vaccine". In this review, we aim to provide a compilation of data that denies any link between vaccination and infertility for healthcare providers to be able to educate their patients based on evidence-based medicine. We also reviewed the effect of COVID-19 virus and vaccination on various parameters and processes that are essential to obtaining a successful pregnancy., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: Early diagnosis of knee osteoarthritis (KOA) in asymptomatic stages is essential for the timely management of patients using preventative strategies. We develop and validate a prognostic model useful for predicting the incidence of radiographic KOA (rKOA) in non-radiographic osteoarthritic subjects and stratify individuals at high risk of developing the disease., Methods: Subjects without radiographic signs of KOA according to the Kellgren and Lawrence (KL) classification scale (KL=0 in both knees) were enrolled in the OA initiative (OAI) cohort and the Prospective Cohort of A Coruña (PROCOAC). Prognostic models were developed to predict rKOA incidence during a 96-month follow-up period among OAI participants based on clinical variables and serum levels of the candidate protein biomarkers APOA1, APOA4, ZA2G and A2AP. The predictive capability of the biomarkers was assessed based on area under the curve (AUC), and internal validation was performed to correct for overfitting. A nomogram was plotted based on the regression parameters. Model performance was externally validated in the PROCOAC., Results: 282 participants from the OAI were included in the development dataset. The model built with demographic, anthropometric and clinical data (age, sex, body mass index and WOMAC pain score) showed an AUC=0.702 for predicting rKOA incidence during the follow-up. The inclusion of ZA2G, A2AP and APOA1 data significantly improved the model's sensitivity and predictive performance (AUC=0.831). The simplest model, including only clinical covariates and ZA2G and A2AP serum levels, achieved an AUC=0.826. Both models were internally cross-validated. Predictive performance was externally validated in an independent dataset of 100 individuals from the PROCOAC (AUC=0.713)., Conclusion: A novel prognostic model based on common clinical variables and protein biomarkers was developed and externally validated to predict rKOA incidence over a 96-month period in individuals without any radiographic signs of disease. The resulting nomogram is a useful tool for stratifying high-risk populations and could potentially lead to personalised medicine strategies for treating OA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy., Objectives: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery., Methods: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events., Results: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively., Conclusions: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Exploration is typically motivated by gaining information, with previous research showing that potential information gains drive a "directed" type of exploration. Yet, this research usually studies exploration in the context of learning paradigms and does not directly manipulate multiple levels of information gain. Here, we present a task that isolates learning from decision-making and controls the magnitude of prospective information gains. As predicted, participants explore more with larger future information gains. Both value gains and information gains, at a trial-by-trial level, engage the ventromedial prefrontal cortex (vmPFC), the ventral striatum (VStr), the amygdala, the dorsal anterior cingulate cortex (dACC), and the anterior insula (aINS). Moreover, individual sensitivities to value gains and information gains modulate the vmPFC, dACC, and aINS, but the amygdala and VStr are modulated only by individual sensitivities to information gains. Overall, we identify the neural circuitry of information-based exploration and its relationship with inter-individual exploration biases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)