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Increased cell proliferation most likely plays a key role in peroxisome proliferator-induced liver cancer. Recently, Kupffer cells were shown to be responsible for Wy-14,643-induced cell proliferation. However, the mechanism by which peroxisome proliferators activate Kupffer cells is unknown. Since gut-derived endotoxin is a known activator of Kupffer cells, the hypothesis that it is involved was evaluated. Increased cell proliferation and peroxisome induction were unaffected by gut sterilization. Moreover, endotoxin was not detectable in portal blood following treatment with Wy-14,643. Therefore, it is concluded that gut-derived endotoxin is not responsible for Kupffer cell activation. To test the hypothesis that Kupffer cell activation. To test the hypothesis that Kupffer cells are activated by Wy-14,643 directly, Kupffer cell superoxide production was measured following treatment in vitro. Wy-14,643 increased superoxide production in a dose-dependent manner (0.1 and 50 μM) with half-maximal stimulation at 2.5 μM. Treatment with Wy-14,643 for 21 days caused a 2-fold increase in Kupffer cell superoxide production while DEHP did not. Pretreatment of Kupffer cells with staurosporine (0.01-10 pM) completely blocked generation of superoxide demonstrating that protein kinase C is required. Moreover, Wy-14,643 increased Kupffer cell protein kinase C activity 3-fold. Pretreatment of Kupffer cells with the amino acid glycine (0.01-3 mM), which blunts calcium signaling, inhibited Wy-14,643-stimulated superoxide production and increased protein kinase C activity completely. These data are consistent with the hypothesis that potent peroxisome proliferators (Wy-14,643 and MEHP) directly activate Kupffer cell production of oxidants via mechanisms involving protein kinase C. Further, peroxisome proliferator treatments that sustain elevated rates of cell proliferation (e.g. Wy-14,643) activate Kupffer cell superoxide production following long-term dietary treatment supporting the hypothesis that Kupffer cell-derived oxidants are involved in peroxisome proliferator-induced neoplasia. [ABSTRACT FROM PUBLISHER]

Gran parte de los cultivos de cacao en el país son viejos y necesitan ser renovados debido a sus bajos rendimientos. Por esta razón se aborda la producción masiva de plántulas injertadas con materiales de alta productividad, que sin embargo presentan problemas en el prendimiento y desarrollo de las yemas. En el Centro de Investigación Nataima-Corpoica (Espinal, Tolima), plántulas de cacao del clon IMC67 tratadas con desbrote apical fueron injertadas con yemas de los clones CCN51 e ICS95. El ensayo siguió un diseño completamente aleatorizado con siete tratamientos, tres de ellos correspondientes a concentraciones de 5, 10 y 15 mg L-1 de ácido giberélico (AG3), y otros tres aplicando 6-bencilaminopurina (6BAP) en las mismas concentraciones, más un testigo sin aplicación de hormonas. Cada 3 días se midieron la altura, el diámetro, la longitud, el número de hojas y el área foliar del injerto, además de su masa fresca y seca al final del experimento, el cual duró 30 días. El AG3 permitió alcanzar los mayores valores en longitud, número de hojas, área foliar y masa fresca y seca del injerto. Para los mismos parámetros, los tratamientos con 6BAP alcanzaron valores similares a los obtenidos con AG3 (con diferencias estadísticas en algunos casos), además de los mayores diámetros del injerto. Dentro de las aplicaciones de AG3, la realizada a una concentración de 10 mg L-1 mostró los mejores resultados en ambos clones. Sin la aplicación de hormonas, las yemas del clon ICS95 desarrollaron una mayor área foliar y alcanzaron mayores valores de masa fresca y seca que las yemas del clon CCN51. Sin embargo, después de aplicar los tratamientos, los dos clones presentaron valores similares.

Objetivos: Examinar mediante revisión bibliográfica la morbilidad y mortalidad asociada al acceso vascular, analizar la tendencia actual del tipo de acceso en las unidades de Hemodiálisis españolas, determinar las causas que influyen en su elección y mostrar la importancia de la fístula arteriovenosa como acceso vascular. Metodología: Se ha diseñado un estudio descriptivo transversal mediante una revisión de la literatura científica comprendida entre los años 2008 y 2014. Resultados: Los estudios revisados ponen de manifiesto que en comparación con la fístula arteriovenosa, los catéteres venosos centrales tiene un mayor riesgo relativo de muerte y una comorbilidad más grave y que ésta aumenta con el tiempo. Existe además una relación inversamente proporcional entre la probabilidad de iniciar hemodiálisis mediante un acceso vascular permanente y el tiempo transcurrido entre la remisión del paciente y la evaluación por el cirujano, así como entre la evaluación por el cirujano y la construcción del acceso vascular. Conclusiones: La fístula arteriovenosa ha demostrado ser el acceso vascular más seguro y duradero y por ello el acceso vascular por excelencia. En los últimos años no ha sido posible alcanzar los objetivos planteados en las guías en lo relativo a la prevalencia e incidencia del acceso vascular. La alta morbimortalidad asociada al inicio en hemodiálisis con un catéter venoso central hace necesaria la reducción del uso de éstos. La causa de su actual exceso es multifactorial, por ello es necesario actuar simultáneamente desde varios niveles siendo crucial derivar al paciente con tiempo suficiente para permitir la realización de la fístula arteriovenosa.

Las políticas agrícolas de los últimos veinte años en Colombia presentan evidentes incoherencias, falta de claridad, avances y retrocesos sin sentido. El autor sostiene que ese caos obedece a la carencia de una visión de largo p.lazo del sector rural y, en los medios académicos, a la carencia de una teoría agraria que abarque la complejidad de 10 rural, que aclare -con rigor, un método definodo e instrumentos adecuados- en qué consiste el problema agrario que las politicas deben contribuir a resolver. Luego de recordar algunos fundamentos teóricos se pregunta cómo se llegó a la confusión que hoy existe y, para responderla, hace un seguimiento, en la obra de Jesus Bejarano, de la evolución de la visión del problema agrario, hasta desaparecer de las preocupaciones académicas actuales. Conc 1uyc presentando algunas opciones epistemológicas que tienen la academia y la sociedad para revisar sus fundamentos, partiendo de la necesidad de volver a pensarse como sociedad.Agricultural policy in Colombia during the last two decades has been characterized by incoherence, lack of clarity and a senseless pattern of advances and U-turns. The author sustains that this chaos is due to the lack of a long term vision of the rural sector and, in academic circles, the lack of of an adequate theory capable of encompassing its complexity. Such a theory should clearly establish -with rigor, a definite method and appropiate instruments- what precisely in theagrarian problem to whose solution policies are addressed. After reviewing some basic theoretical concepts, this essay explores the causes of the current confusion. In order to formulate an answer, it follows the evolution, in the work of Bejarano, of the vision of the agrarian problem until it disappeared below the horizon of current academic concerns. It concludes with a discussion some epistemologicaloptions available to society and academia to return to the basics. One of these is the need to thihk once again as a society.

This article presents the nature, bases, and coherence requirements of a plan, in order to specify the methodological criteria of its internal critique of the agricultural chapter. The examination of its diagnosis leads to a different diagnosis, which is inferred by the objective of "integrating the rural sector": the persistence of the agrarian problem, expressed in a bimodal structure, polarized into 'the economic' and 'the social'. The plan's objective reveals a long-term vision: tocontribute to the solution of the agrarian problem. Thus, the policies differentiate between the advanced entrepreneurial and peasant sectors, for which it designs different strategies which assign different roles for the state: to facilitate socioeconomic processes for the former, and to promote rural development for the latter. The article shows that the Plan maintains internal coherence, and illustrates its limitationsdue to the institutional environment, which is manifested in itsdesign and in the possibilities for its execution. It concludes that the most important policies are the weakest, and that rural developmerlt is not only a problem of social design, but above all of the mentality and commitment of society on all levels.Este articulo expone la naturaleza, fundamentos y requerimientos de coherencia de un plan para precisar los criterios metodologicos de su critica interna al capitulo agropecuario. El examen de diagnostico lleva a un diagnostico diferente, que se infiere del objetivo de "integrar al sector rural" la persistencia del problema agrario en el pais, expresada en un estructura bimodal, polarizada en lo economico y en lo social. El objetivo del plan revela una vision de largo plazo: contribuir a resolver el problema agrario. Adi, las politicas diferencian entre sector empresarial avanzado y campesino, para los cuales diseña estrategias distintan que asignan un papel distinto al Estado: facilitar procesos socio-economicos para el primero e impulsar el desarrollo rural para el segundo. El articulo muestra que el plan guarda coherencia interna e ilustra las limitaciones debidas al entorno institucional, que se manifiesta en su diseño y en las posibilidades de ejecutarlo. Concluye que las politicas mas importantes son las mas debiles, y que el desarrrollo rural no es solo un problema de diseño social sino, ante todo, de metalidad y compromiso de la sociedad en todos niveles.

Cabezas duras y dedos inteligentes, Alberto Mayor Mora, Colcutura, Bogotá, 1996.

Abstract Background Sweetpotato (Ipomoea batatas (L.) Lam.), a hexaploid outcrossing crop, is an important staple and food security crop in developing countries in Africa and Asia. The availability of genomic resources for sweetpotato is in striking contrast to its importance for human nutrition. Previously existing sequence data were restricted to around 22,000 expressed sequence tag (EST) sequences and ~ 1,500 GenBank sequences. We have used 454 pyrosequencing to augment the available gene sequence information to enhance functional genomics and marker design for this plant species. Results Two quarter 454 pyrosequencing runs used two normalized cDNA collections from stems and leaves from drought-stressed sweetpotato clone Tanzania and yielded 524,209 reads, which were assembled together with 22,094 publically available expressed sequence tags into 31,685 sets of overlapping DNA segments and 34,733 unassembled sequences. Blastx comparisons with the UniRef100 database allowed annotation of 23,957 contigs and 15,342 singletons resulting in 24,657 putatively unique genes. Further, 27,119 sequences had no match to protein sequences of UniRef100database. On the basis of this gene index, we have identified 1,661 gene-based microsatellite sequences, of which 223 were selected for testing and 195 were successfully amplified in a test panel of 6 hexaploid (I. batatas) and 2 diploid (I. trifida) accessions. Conclusions The sweetpotato gene index is a useful source for functionally annotated sweetpotato gene sequences that contains three times more gene sequence information for sweetpotato than previous EST assemblies. A searchable version of the gene index, including a blastn function, is available at http://www.cipotato.org/sweetpotato_gene_index.

Objective: Maximizing safe resection in neuro-oncology has become paramount to improving patient survival and outcomes. Laser interstitial thermal therapy (LITT) offers similar survival benefits to traditional resection, alongside shorter hospital stays and faster recovery times. The extent of ablation (EOA) achieved using LITT is linked to patient outcomes, with greater EOA correlating with improved outcomes. However, the preoperative predictors for achieving supramaximal ablation (EOA ≥ 100%) are not well understood. By leveraging machine learning (ML) techniques, this study aimed to identify these predictors to enhance patient selection and therefore outcomes. The objective was to explore preoperative predictors for supramaximal EOA using ML in patients with glioblastoma., Methods: A retrospective study was conducted on the medical records of 254 patients undergoing LITT from 2013 to 2023 at a single tertiary center. Cohort criteria included age ≥ 18 years, diagnosis of glioblastoma, single-trajectory ablation, and a complete dataset. The study assessed preoperative clinical and radiographic factors, using EOA ≥ 100% as the endpoint. Five ML models were used: logistic regression, random forest (RF), gradient boosting, Gaussian naive Bayes, and support vector machine. Training and testing cohorts were subsequently assessed across ML models with fivefold cross-validation. Models were optimized using hyperparameter tuning. Performance was primarily quantified using the area under the curve (AUC) of the receiver operating characteristic curve., Results: The final cohort consisted of 72 patients. Among the ML models, RF achieved the highest AUC (mean ± SD 0.94 ± 0.06). The leading models identified that lower preoperative volume, history of prior radiation therapy, history of prior craniotomy, preoperative neurological deficits, history of preoperative seizures, and distance from intracranial heat sinks were predictive of successful ablations in patients. Additionally, RF had the best mean metrics: accuracy 0.88, precision 0.87, specificity 0.87, and sensitivity 0.89., Conclusions: This is the first study to investigate the role of ML for optimizing ablation volumes in LITT. These ML models suggest that low preoperative volumes, previous craniotomy, previous radiation therapy, no previous neurological deficits, larger catheter-heat sink distance, and the presence of preoperative seizures are important prognostic factors for predicting successful supramaximal ablations with LITT.

Background and Objectives: Laser interstitial thermal therapy (LITT) has demonstrated promise in surgical neuro-oncology because of its effectiveness in delivering precise thermal energy to lesions. The extent of ablation (EOA) is a prognostic factor in improving patient outcomes but is often affected by perilesional heatsink structures, which can lead to asymmetric ablations. The purpose of this study was to quantitatively evaluate the impact of various perilesional heatsink structures on the EOA in LITT for brain metastases., Methods: Twenty-seven procedures for 22 unique patients with brain metastases fit the inclusion criteria. Intracranial heatsink structures were identified: sulci, meninges, cerebrospinal fluid (CSF) spaces, and vasculature. Asymmetric ablation was determined by measuring 3 pairs of orthogonal distances from the proximal, midpoint, and distal locations along the laser catheter to the farthest edge of the ablation zone bilaterally. Distances from the same points on the laser catheter to the nearest heatsink were also recorded. The Heatsink Effect Index was created to serve as a proxy for asymmetric ablation. Pearson correlations, t -tests, and analysis of variance were the statistical analyses performed., Results: From the midpoint of the catheter, the 27 heatsinks were meninges (40.7%), sulci (22.2%), vasculature (22.2%), and CSF spaces (14.8%). Across all points along the catheter track, there was a significant generalized heatsink effect on asymmetric ablations ( P < .0001). There was a negative correlation observed between asymmetric ablations and EOA from the midpoint of the laser catheter (r = -0.445, P = .020). Compared with sulci, CSF spaces trended toward a greater effect on asymmetric ablation volumes ( P = .069)., Conclusion: This novel quantitative analysis shows that perilesional heatsinks contribute to asymmetric ablations. CSF spaces trended toward higher degrees of asymmetric ablations. Importantly, neurosurgeons may anticipate asymmetric ablations preoperatively if heatsinks are located within 13.3 mm of the laser probe midpoint. These preliminary results may guide surgical decision-making in LITT for metastatic brain lesions., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Purpose: Recurrence for high-grade gliomas is inevitable despite maximal safe resection and adjuvant chemoradiation, and current imaging techniques fall short in predicting future progression. However, we introduce a novel whole-brain magnetic resonance spectroscopy (WB-MRS) protocol that delves into the intricacies of tumor microenvironments, offering a comprehensive understanding of glioma progression to inform expectant surgical and adjuvant intervention., Methods: We investigated five locoregional tumor metabolites in a post-treatment population and applied machine learning (ML) techniques to analyze key relationships within seven regions of interest: contralateral normal-appearing white matter (NAWM), fluid-attenuated inversion recovery (FLAIR), contrast-enhancing tumor at time of WB-MRS (Tumor), areas of future recurrence (AFR), whole-brain healthy (WBH), non-progressive FLAIR (NPF), and progressive FLAIR (PF). Five supervised ML classification models and a neural network were developed, optimized, trained, tested, and validated. Lastly, a web application was developed to host our novel calculator, the Miami Glioma Prediction Map (MGPM), for open-source interaction., Results: Sixteen patients with histopathological confirmation of high-grade glioma prior to WB-MRS were included in this study, totaling 118,922 whole-brain voxels. ML models successfully differentiated normal-appearing white matter from tumor and future progression. Notably, the highest performing ML model predicted glioma progression within fluid-attenuated inversion recovery (FLAIR) signal in the post-treatment setting (mean AUC = 0.86), with Cho/Cr as the most important feature., Conclusions: This study marks a significant milestone as the first of its kind to unveil radiographic occult glioma progression in post-treatment gliomas within 8 months of discovery. These findings underscore the utility of ML-based WB-MRS growth predictions, presenting a promising avenue for the guidance of early treatment decision-making. This research represents a crucial advancement in predicting the timing and location of glioblastoma recurrence, which can inform treatment decisions to improve patient outcomes., (© 2024. The Author(s).)

Competing Interests: The author has no financial interest to declare in relation to the content of this article.

Maintenance of tissue integrity is a requirement of host survival. This mandate is of prime importance at barrier sites that are constitutively exposed to the environment. Here, we show that exposure of the skin to non-inflammatory xenobiotics promotes tissue repair; more specifically, mild detergent exposure promotes the reactivation of defined retroelements leading to the induction of retroelement-specific CD8 + T cells. These T cell responses are Langerhans cell dependent and establish tissue residency within the skin. Upon injury, retroelement-specific CD8 + T cells significantly accelerate wound repair via IL-17A. Collectively, this work demonstrates that tonic environmental exposures and associated adaptive responses to retroelements can be coopted to preemptively set the tissue for maximal resilience to injury.

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown. Here, we identify a shape-sensing mechanism that increases the expression of the chemokine receptor CCR7 and guides dendritic cell migration from peripheral tissues to lymph nodes at steady state. This mechanism relies on the lipid metabolism enzyme cPLA 2 , requires nuclear envelope tensioning and is finely tuned by the ARP2/3 actin nucleation complex. We also show that this shape-sensing axis reprograms dendritic cell transcription by activating an IKKβ-NF-κB-dependent pathway known to control their tolerogenic potential. These results indicate that cell shape changes experienced by immune cells can define their migratory behavior and immunoregulatory properties and reveal a contribution of the physical properties of tissues to adaptive immunity., (© 2024. The Author(s).)

Background: Blood transfusion reactions may have a negative impact on organ function. It is unknown whether this association holds true for acute kidney injury (AKI). Therefore, we conducted a cohort study to assess the association between transfusion reactions and the incidence of AKI and major adverse kidney events., Methods: In this retrospective cohort study, we included patients who received transfusion of blood products during hospitalization at the Hospital Civil of Guadalajara. We analyzed them according to the development of transfusion reactions, and the aim was to assess the association between transfusion reactions and AKI during long-term follow-up., Results: From 2017 to 2021, 81,635 patients received a blood product transfusion, and 516 were included in our study. The most common transfusion was red blood cell packaging (50.4%), fresh frozen plasma (28.7%) and platelets (20.9%); of the 516 patients, 129 (25%) had transfusion reactions. Patients who had transfusion reactions were older and had more comorbidities. The most common type of transfusion reaction was allergic reaction (70.5%), followed by febrile nonhemolytic reaction (11.6%) and anaphylactoid reaction (8.5%). Most cases were considered mild. Acute kidney injury was more prevalent among those who had transfusion reactions (14.7%) than among those who did not (7.8%), p =  < 0.01; those with AKI had a higher frequency of diabetes, vasopressors, and insulin use. Transfusion reactions were independently associated with the development of AKI (RR 2.1, p =  < 0.02). Major adverse kidney events were more common in those with transfusion reactions. The mortality rate was similar between subgroups., Conclusion: In our retrospective cohort of patients who received blood product transfusions, 25% experienced transfusion reactions, and this event was associated with a twofold increase in the probability of developing AKI and some of the major adverse kidney events during long follow-up., (© 2024. The Author(s).)

Background: Gluteal fat grafting is a common procedure in liposculpture. This study proposes a Doppler ultrasound-guided intramuscular and subcutaneous gluteal lipotransfer technique that allows for visualization of the location of the gluteal vessels, avoiding approaching them during lipotransfer by having the cannula localized during fat infiltration., Methods: This new technique was applied to 24 women after obtaining informed consent and providing them with a clear explanation of potential risks and complications. Doppler ultrasound was used to locate the site and depth of blood vessels, and for quadrant scanning of vessels and superficial intramuscular visualization of the cannula's location. Intramuscular lipotransfer was performed with a volume of 400 mL per gluteus (or less), and 12 patients underwent magnetic resonance imaging before and 3 months after surgery., Results: This technique allowed for visualizing the location of the gluteal vessels, and infiltration could be easily performed in patients. In the 24 glutei reviewed postsurgery, from 12 patients who underwent pre- and postsurgery magnetic resonance imaging, intramuscular fat was found; however, there was no migration outside the gluteus maximus muscle., Conclusions: No local or systemic complications were observed. The results of our report show that fat filtration did not migrate outside the gluteus maximus muscle. This finding seeks to promote new research to create theoretical/practical precedents for the intervention of plastic surgeons and, from there, promote the standardization of a new and safe technique., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.

Background: The field of neurosurgery has consistently represented an area of innovation and integration of technology since its inception. As such, machine learning (ML) has found its way into applications within neurosurgery relatively rapidly. Through this bibliometric review and cluster analysis, we seek to identify trends and emerging applications of ML within neurosurgery., Methods: A bibliometric analysis was carried out in the Web of Science database on publications from January 2000 to March 2023. The full data set of the 200 most cited publications including title, author information, journal, citation count, keywords, and abstracts for each publication was evaluated in CiteSpace. CiteSpace was used to elucidate publication characteristics, trends, and topic clusters via collaborate network analysis using the Kamada-Kawai algorithm., Results: The 25 most cited titles were included in our analysis. Harvard University and its affiliates represented the top institution, contributing nearly 25% of publications in the literature. WORLD NEUROSURGERY was the journal with the highest net citation count of 747 (29%). Collaborative network analysis generated 12 unique clusters, the largest of which was machine learning, followed by feature importance and deep brain stimulation., Conclusion: This review highlights the most impactful articles pertaining to ML in the field of neurosurgery. ML has been applied into several sub-specialties within neurosurgery to optimize patient care, with special attention to outcome predictors, patient selection, and surgical decision making., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The intestine comprises the largest proportion of immune cells in the body. It is continuously exposed to new antigens and immune stimuli from the diet, microbiota but also from intestinal pathogens. In this review, we describe the main populations of immune cells present along the intestine, both from the innate and adaptive immune system. We later discuss how intestinal niches significantly impact the phenotype and function of gut immune populations at steady state and upon infection., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Porophyllum ruderale (Jacq.) Cass. (Asteraceae) has antiprotozoal properties and contains extractable phenolic compounds by the maceration method (M). However, new extraction proposals such as ultrasound (U), microwaves (MW), and ultrasound/microwaves (U/MW) have emerged to optimise yields, but it is unknown if these methods modify effectiveness. Therefore, the study consisted of extracting the aerial part of P. ruderale with ethanol using the M, U, MW and U/MW methods to study its composition by RP-HPLC-ESI-MS, its total polyphenol content and its effect against Entamoeba histolytica . The study showed that U, MW and U/MW did not modify the extraction yield compared to M, but they did change the composition and the total polyphenol content. All extracts contain phloretin, caffeic acid 4-O-glucoside, todolactol A, quercetin 3-O-glucoside, quercetin 3-O-rhamnoside, luteolin and 3,7-dimethylquercetin, and affected the growth of E. histolytica . However, M and U extracts were the most effective at 5 mg/mL.

Traditionally, Equisetum hyemale has been used for wound healing. However, its mechanism of action remains to be elucidated. For this purpose, a 40% ethanolic extract of E. hyemale was prepared. Phytochemical screening revealed the presence of minerals, sterols, phenolic acids, flavonols, a lignan, and a phenylpropenoid. The extract reduced the viability of RAW 264.7 cells and skin fibroblasts at all times evaluated. On the third day of treatment, this reduction was 30-40% and 15-40%, respectively. In contrast, the extract increased the proliferation of skin fibroblasts only after 48 h. In addition, the extract increased IL-10 release and inhibited MCP-1 release. However, the extract did not affect both TGF-β1 and TNF-α released by RAW 264.7 cells. The higher release of IL-10 could be related to the up-/downregulation of inflammatory pathways mediated by the extract components associated with their bioactivity. The extract inhibited the growth of Staphylococcus aureus and Escherichia coli . Topical application of the extract accelerated wound healing in diabetic rats by increasing fibroblast collagen synthesis. These results suggest that E. hyemale extract has great potential for use in the treatment of wounds thanks to its phytochemical composition that modulates cytokine secretion, collagen synthesis, and bacterial growth.

IgA plasma cell myeloma (PCM) has been linked to molecular abnormalities that confer a higher risk for adverse patient outcomes. However, since IgA PCM only accounts for approximately 20% of all PCM, there are very few reports on high-risk IgA PCM. Moreover, no such reports are found on the more infrequent biclonal IgA PCM. Hence, we present a 65-year-old Puerto Rican female with acute abdominal pain, concomitant hypercalcemia, and acute renal failure. Protein electrophoresis with immunofixation found high IgA levels and detected a biclonal IgA gammopathy with kappa specificity. Histomorphologically, bone marrow showed numerous abnormal plasma cells (32%) replacing over 50% of the marrow stroma. Immunophenotyping analysis detected CD45-negative plasma cells aberrantly expressing CD33, CD43, OCT-2, and c-MYC. Chromosomal analysis revealed multiple abnormalities including the gain of chromosome 1q. Thus, we report on an unusual biclonal IgA PCM and the importance of timely diagnosing aggressive plasma cell neoplasms.

Modifiers are commonly used in natural, biological, and synthetic crystallization to tailor the growth of diverse materials. Here, we identify tautomers as a new class of modifiers where the dynamic interconversion between solute and its corresponding tautomer(s) produces native crystal growth inhibitors. The macroscopic and microscopic effects imposed by inhibitor-crystal interactions reveal dual mechanisms of inhibition where tautomer occlusion within crystals that leads to natural bending, tunes elastic modulus, and selectively alters the rate of crystal dissolution. Our study focuses on ammonium urate crystallization and shows that the keto-enol form of urate, which exists as a minor tautomer, is a potent inhibitor that nearly suppresses crystal growth at select solution alkalinity and supersaturation. The generalizability of this phenomenon is demonstrated for two additional tautomers with relevance to biological systems and pharmaceuticals. These findings offer potential routes in crystal engineering to strategically control the mechanical or physicochemical properties of tautomeric materials., (© 2023. The Author(s).)

Background: Gestational diabetes mellitus (GDM) is first diagnosed during pregnancy and it is the most frequent maternal hyperglycemia., Objective: To know fetal and maternal outcomes in an intensive control program in pregnant women with and without DMG at the Instituto Mexicano del Seguro Social (Mexican Institute for Social Security) Regional General Hospital No. 6, in Ciudad Madero, Tamaulipas., Material and Methods: A descriptive and retrospective study, which included 800 outcomes of pregnant women between January 2009 and June 2020. Anthropometric data and pregnancy outcomes were collected. The intensive control program consisted of face-to-face consultations of 1 to 4 weeks, granted according to the degree of metabolic control, with which it was given nutritional counseling, recommendations for physical activity, and in some cases pharmacological treatment., Results: The prevalence of GDM was 36.2%. There were no statistically significant differences between the two groups, except for respiratory distress syndrome, which was more common in GDM (9.4%, p = 0.06). Patients with GDM had a lower prevalence of macrosomy (6.1%) compared to the control group (6.6%). All women admitted to the program in the first trimester had fewer fetal and maternal complications., Conclusions: This study demonstrates the effectiveness and efficiency of implementing an intensive control program in women with GDM, by reducing and equalizing maternal and fetal outcomes compared to a group of women without the disease., (© 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

The relevance of cross-dressing as an antigen presentation mechanism in antitumor responses is not fully understood. In this issue of Immunity, MacNabb et al. (2022) report that dendritic cells use cross-dressing as an effective mechanism to trigger CD8 + T cell antitumor immunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A key feature of the brain is the ability to handle novelty. Anything that is new will stimulate curiosity and trigger exploration. Novelty preference has been proposed to predict increased sensitivity to cocaine. Different brain circuits are activated by novelty, but three specific brain regions are critical for exploring a novel environment: the noradrenergic neurons originating from the locus coeruleus (LC), the dopaminergic neurons from the ventral tegmental area (VTA), and the hippocampus. However, how exploring a novel environment can interfere with the reward system and control cocaine impact on VTA dopamine neuron plasticity is unclear. Here, we first investigated the effects of exposure to a novel environment on the tonic electrophysiological properties of VTA dopamine neurons. Then, we explored how exposure to a novel environment controls cocaine-evoked plasticity in dopamine neurons. Our findings indicate that LC controls VTA dopamine neurons under physiological conditions but also after cocaine., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Dendritic cells (DCs) patrol tissues and transport antigens to lymph nodes to initiate adaptive immune responses. Within tissues, DCs constitute a complex cell population composed of distinct subsets that can exhibit different activation states and functions. How tissue-specific cues orchestrate DC diversification remains elusive. Here, we show that the small intestine included two pools of cDC2s originating from common pre-DC precursors: (1) lamina propria (LP) CD103 + CD11b + cDC2s that were mature-like proinflammatory cells and (2) intraepithelial cDC2s that exhibited an immature-like phenotype as well as tolerogenic properties. These phenotypes resulted from the action of food-derived retinoic acid (ATRA), which enhanced actomyosin contractility and promoted LP cDC2 transmigration into the epithelium. There, cDC2s were imprinted by environmental cues, including ATRA itself and the mucus component Muc2. Hence, by reaching distinct subtissular niches, DCs can exist as immature and mature cells within the same tissue, revealing an additional mechanism of DC functional diversification., Competing Interests: Declaration of interests C.R.S. has an additional appointment as professor in the Faculty of Medicine at Imperial College London. C.R.S. is a founder of Adendra Therapeutics and owns stock options and/or is a paid consultant for Adendra Therapeutics, Bicara Therapeutics, Montis Biosciences, Oncurious NV, Bicycle Therapeutics, and Sosei Heptares, all unrelated to this work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The hyperpolarization-activated cation current (I h ) is a determinant of intrinsic excitability in various cells, including dopaminergic neurons (DA) of the ventral tegmental area (VTA). In contrast to other cellular conductances, I h is activated by hyperpolarization negative to -55 mV and activating I h produces a time-dependent depolarizing current. Our laboratory demonstrated that cocaine sensitization, a chronic cocaine behavioral model, significantly reduces I h amplitude in VTA DA neurons. Despite this reduction in I h , the spontaneous firing of VTA DA cells after cocaine sensitization remained similar to control groups. Although the role of I h in controlling VTA DA excitability is still poorly understood, our hypothesis is that I h reduction could play a role of a homeostatic controller compensating for cocaine-induced change in excitability. Using in vivo single-unit extracellular electrophysiology in isoflurane anesthetized rats, we explored the contribution of I h on spontaneous firing patterns of VTA DA neurons. A key feature of spontaneous excitability is bursting activity; bursting is defined as trains of two or more spikes occurring within a short interval and followed by a prolonged period of inactivity. Burst activity increases the reliability of information transfer. To elucidate the contribution of I h to spontaneous firing patterns of VTA DA neurons, we locally infused an I h blocker (ZD 7288, 8.3 μM) and evaluated its effect. I h blockade significantly reduced firing rate, bursting frequency, and percent of spikes within a burst. In addition, I h blockade significantly reduced acute cocaine-induced spontaneous firing rate, bursting frequency, and percent of spikes within a burst. Using whole-cell patch-clamp, we determine the progressive reduction of I h after acute and chronic cocaine administration (15 mg/k.g intraperitoneally). Our data show a significant reduction (~25%) in I h amplitude after 24 but not 2 h of acute cocaine administration. These results suggest that a progressive reduction of I h could serve as a homeostatic regulator of cocaine-induced spontaneous firing patterns related to VTA DA excitability., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Macropinocytosis is a nonspecific mechanism by which cells compulsively "drink" the surrounding extracellular fluids in order to feed themselves or sample the molecules therein, hence gaining information about their environment. This process is cell-intrinsically incompatible with the migration of many cells, implying that the two functions are antagonistic. The migrating cell uses a molecular switch to stop and explore its surrounding fluid by macropinocytosis, after which it employs the same molecular machinery to start migrating again to examine another location. This cycle of migration/macropinocytosis allows cells to explore tissues, and it is key to a range of physiological processes. Evidence of this evolutionarily conserved antagonism between the two processes can be found in several cell types-immune cells, for example, being particularly adept-and ancient organisms (e.g., the social amoeba Dictyostelium discoideum). How macropinocytosis and migration are negatively coupled is the subject of this chapter., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Stroke is a leading cause of acquired long-term upper extremity motor disability. Current standard of care trajectories fail to deliver sufficient motor rehabilitation to stroke survivors. Recent research suggests that use of brain-computer interface (BCI) devices improves motor function in stroke survivors, regardless of stroke severity and chronicity, and may induce and/or facilitate neuroplastic changes associated with motor rehabilitation. The present sub analyses of ongoing crossover-controlled trial NCT02098265 examine first whether, during movements of the affected hand compared to rest, ipsilesional Mu rhythm desynchronization of cerebral cortical sensorimotor areas [Brodmann's areas (BA) 1-7] is localized and tracks with changes in grip force strength. Secondly, we test the hypothesis that BCI intervention results in changes in frequency-specific directional flow of information transmission (direct path functional connectivity) in BA 1-7 by measuring changes in isolated effective coherence (iCoh) between cerebral cortical sensorimotor areas thought to relate to electrophysiological signatures of motor actions and motor learning. A sample of 16 stroke survivors with right hemisphere lesions (left hand motor impairment), received a maximum of 18-30 h of BCI intervention. Electroencephalograms were recorded during intervention sessions while outcome measures of motor function and capacity were assessed at baseline and completion of intervention. Greater desynchronization of Mu rhythm, during movements of the impaired hand compared to rest, were primarily localized to ipsilesional sensorimotor cortices (BA 1-7). In addition, increased Mu desynchronization in the ipsilesional primary motor cortex, Post vs. Pre BCI intervention, correlated significantly with improvements in hand function as assessed by grip force measurements. Moreover, the results show a significant change in the direction of causal information flow, as measured by iCoh, toward the ipsilesional motor (BA 4) and ipsilesional premotor cortices (BA 6) during BCI intervention. Significant iCoh increases from ipsilesional BA 4 to ipsilesional BA 6 were observed in both Mu [8-12 Hz] and Beta [18-26 Hz] frequency ranges. In summary, the present results are indicative of improvements in motor capacity and behavior, and they are consistent with the view that BCI-FES intervention improves functional motor capacity of the ipsilesional hemisphere and the impaired hand., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Remsik, Gjini, Williams, van Kan, Gloe, Bjorklund, Rivera, Romero, Young, Nair, Caldera, Williams and Prabhakaran.)

In this work, the synthesis of SrB 4 O 7 through solid state reaction and its beta particle excited thermoluminescence (TL) are reported. The glow curves show maxima around 200 and 300 -considered suitable for TL dosimetry-, and a remarkable reproducibility in successive irradiation - TL readout cycles. The integrated TL exhibits a linear dependence upon the irradiation dose in the tested dose range (from 1.0 up to 8.0 Gy). The lower detection limit and the sensitivity relative to the TLD-100 dosimeter are 88 mGy and 0.49, respectively. From the results here presented, we conclude that SrB 4 O 7 synthesized through solid state reaction can be considered a phosphor material interesting to develop TL dosimeters., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Acetaminophen is the most common over-the-counter pain and fever medication used by pregnant women. While European studies suggest acetaminophen exposure in pregnancy could affect childhood asthma development, findings are less consistent in other populations. We evaluated whether maternal prenatal acetaminophen use is associated with childhood asthmatic symptoms (asthma diagnosis, wheeze, dry cough) in a Los Angeles cohort of 1201 singleton births. We estimated risk ratio (RR) and 95% confidence interval (CI) for childhood asthmatic outcomes according to prenatal acetaminophen exposure. Effect modification by maternal race/ethnicity and psychosocial stress during pregnancy was evaluated. The risks for asthma diagnosis (RR = 1.39, 95% CI 0.96, 2.00), wheezing (RR = 1.25, 95% CI 1.01, 1.54) and dry cough (RR =1.35, 95% CI 1.06, 1.73) were higher in children born to mothers who ever used acetaminophen during pregnancy compared with non-users. Black/African American and Asian/Pacific Islander children showed a greater than two-fold risk for asthma diagnosis and wheezing associated with the exposure. High maternal psychosocial stress also modified the exposure-outcome relationships. Acetaminophen exposure during pregnancy was associated with childhood asthmatic symptoms among vulnerable subgroups in this cohort. A larger study that assessed prenatal acetaminophen exposure with other social/environmental stressors and clinically confirmed outcomes is needed.

Alteration to endoplasmic reticulum (ER) proteostasis is observed in a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR target genes. In this study, we designed an ATF6f/XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has a stronger effect in reducing the abnormal aggregation of mutant huntingtin and α-synuclein when compared to XBP1s or ATF6 alone. We developed a gene transfer approach to deliver UPRplus into the brain using adeno-associated viruses (AAVs) and demonstrated potent neuroprotection in vivo in preclinical models of Parkinson's disease and Huntington's disease. These results support the concept in which directing UPR-mediated gene expression toward specific adaptive programs may serve as a possible strategy to optimize the beneficial effects of the pathway in different disease conditions., Competing Interests: Declarations of interest R.L.V. and C.H. protected the use of a gene therapy to deliver UPRplus into the brain to treat Parkinson’s disease and Huntington’s disease. UPRplus is a registered brand in Chile. The patent is licensed to Handl Biotech, Belgium (https://patents.google.com/patent/WO2017075729A1/es)., (Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

The present research focused on evaluating the antibacterial effect and the mechanism of action of partially purified fractions of an extract of Persea americana . Furthermore, both its antioxidant capacity and composition were evaluated. The extract was fractionated by vacuum liquid chromatography. The antimicrobial effect against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 11229), Pseudomonas aeruginosa (ATCC 15442), and Salmonella choleraesuis (ATCC 1070) was analyzed by microdilution and the mechanism of action by the Sytox green method. The antioxidant capacity was determined by DPPH, FRAP, and ABTS techniques and the composition by Rp-HPLC-MS. All fractions showed a concentration-dependent antibacterial effect. Fractions F3, F4, and F5 (1000 µg/mL) showed a better antibacterial effect than the extract against the bacteria mentioned. The F3 fraction showed inhibition of 95.43 ± 3.04% on S. aureus , F4 showed 93.30 ± 0.52% on E. coli , and F5 showed 88.63 ± 1.15% on S. choleraesuis and 86.46 ± 3.20% on P. aeruginosa . The most susceptible strain to the treatment with the extract was S. aureus . Therefore, in this strain, the bacterial membrane damage induced by the extract and fractions was evidenced by light fluorescence microscopy. Furthermore, the extract had better antioxidant action than each fraction. Finally, sinensitin was detected in F3 and cinnamoyl glucose, caffeoyl tartaric acid, and cyanidin 3- O -(6''-malonyl-3''-glucosyl-glucoside) were detected in F4; esculin and kaempferide, detected in F5, could be associated with the antibacterial and antioxidant effect.

In this work, the synthesis through solid state reaction and the thermoluminescence (TL) characterization of pellet shaped CaZrO 3 samples is reported. X-ray diffraction confirms that orthorhombic CaZrO 3 was obtained. The glow curve has two maxima located at 149 and 216 °C as well as a less intense maximum around 350 °C when a 5.0 °C/s heating rate is used after 64 Gy of beta particle exposure. A remarkably reproducibility of the TL response is observed in repeated irradiation - TL readouts cycles. The TL as a function of the dose displays linear dependence in the dose range from 0.5 to 256 Gy. The intensity of the maximum located around 216 °C remains 61% 14 days after irradiation, and then remains closely constant for longer times. The synthesized CaZrO 3 exhibits TL properties potentially of interest for use in radiation detection and dosimetry., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Thiolate-protected metal nanoclusters (TPNCs) have attracted great interest in the last few decades due to their high stability, atomically precise structure, and compelling physicochemical properties. Among their various applications, TPNCs exhibit excellent catalytic activity for numerous reactions; however, recent work revealed that these systems must undergo partial ligand removal in order to generate active sites. Despite the importance of ligand removal in both catalysis and stability of TPNCs, the role of ligands and metal type in the process is not well understood. Herein, we utilize Density Functional Theory to understand the energetic interplay between metal-sulfur and sulfur-ligand bond dissociation in metal-thiolate systems. We first probe 66 metal-thiolate molecular complexes across combinations of M = Ag, Au, and Cu with twenty-two different ligands (R). Our results reveal that the energetics to break the metal-sulfur and sulfur-ligand bonds are strongly correlated and can be connected across all complexes through metal atomic ionization potentials. We then extend our work to the experimentally relevant [M25(SR)18]- TPNC, revealing the same correlations at the nanocluster level. Importantly, we unify our work by introducing a simple methodology to predict TPNC ligand removal energetics solely from calculations performed on metal-ligand molecular complexes. Finally, a computational mechanistic study was performed to investigate the hydrogenation pathways for SCH3-based complexes. The energy barriers for these systems revealed, in addition to thermodynamics, that kinetics favor the break of S-R over the M-S bond in the case of the Au complex. Our computational results rationalize several experimental observations pertinent to ligand effects on TPNCs. Overall, our introduced model provides an accelerated path to predict TPNC ligand removal energies, thus aiding towards targeted design of TPNC catalysts.

Midbrain dopamine neurons communicate signals of reward anticipation and attribution of salience. This capacity is distorted in heroin or cocaine abuse or in conditions such as human mania. A shared characteristic among rodent models of these behavioral disorders is that dopamine neurons in these animals acquired a small size and manifest an augmented spontaneous and burst activity. The biophysical mechanism underlying this increased excitation is currently unknown, but is believed to primarily follow from a substantial drop in K + conductance secondary to morphology reduction. This work uses a dopamine neuron mathematical model to show, surprisingly, that under size diminution a reduction in K + conductance is an adaptation that attempts to decrease cell excitability. The homeostatic response that preserves the intrinsic activity is the conservation of the ion channel density for each conductance; a result that is analytically demonstrated and challenges the experimentalist tendency to reduce intrinsic excitation to K + conductance expression level. Another unexpected mechanism that buffers the raise in intrinsic activity is the presence of the ether-a-go-go-related gen K + channel since its activation is illustrated to increase with size reduction. Computational experiments finally demonstrate that size attenuation results in the paradoxical enhancement of afferent-driven bursting as a reduced temporal summation indexed correlates with improved depolarization. This work illustrates, on the whole, that experimentation in the absence of mathematical models may lead to the erroneous interpretation of the counterintuitive aspects of empirical data., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)