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Research describes the isolation and characterization of two quinones with unique terpenoid skeleton, pycnanthuquinones A and B from Pycnanthus angolensis plant. Data suggest that the quinones possess antihyperglycemic activity.

Los hospitales de referencia nacional ofrecen una alta gama de servicios médicos y cada uno con su complejidad. Los estudios imagenológicos juegan un papel fundamental, puesto que ayuda a garantizar la atención médica integral de los pacientes. Esta investigación está basada en la estimación de los costos aplicando el método ABC (Actividad Basada en Costo) de un servicio de Imagenología en un hospital privado de la ciudad de Managua en Nicaragua, es un hospital de referencia nacional. Se realizó un estudio descriptivo de corte transversal y retrospectivo, tomando los datos registrados en el año 2021 para un total 204,477 de estudios realizados en todas las modalidades, de los cuales 169,793 correspondían a Rayos X 120,579 (58.96%), Tomografía 12,376 (6.05%), Resonancia Magnética 4,952 (2.42%) y Ultrasonido 31, 994 (15.64%), y se tomaron los estudios más frecuentes fueron radiografía de tórax, tomografía de tórax, ultrasonido de abdomen completo y resonancia magnética de columna lumbar. Debido a que el estudio de Resonancia Magnética (RM) de columna lumbar cumplía con todos los procesos asistenciales y se tenía acceso a costos de insumos y mano de obra, sé realizó la estimación del costo de RM como modelo, obteniendo un costo total de: C$ 6,236.72 córdobas equivalente a $170.9308 dólares americanos, según la tasa de cambio de referencia del Banco Central de la República de Nicaragua agosto 2023. Concluyendo que: el costo calculado es equivalente al 50% del costo más barato con relación al mercado nacional y que la metodología de costeo ABC es reproducible y aplicable para este sector del área de salud; además su utilización puede ayudar a los directivos del hospital a tomar mejores decisiones en torno a la competitividad del mercado nacional.

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OBJECTIVE: The mismatch repair (MMR) genes play a central role for the onset of cancer. One of these genes is hMSH2. A differential hMSH2 protein expression has been detected in the mononuclear fraction of peripheral blood of patients with breast cancer when compared to healthy women. This work aims to evaluate the expression of hMSH2 in patients diagnosed with breast cancer undergoing treatment at various stages of the disease to verify its potential use as a prognostic marker. PATIENTS AND METHODS: Immunohistochemical expression of hMSH2 at different stages of breast cancer in 40 patients biopsy samples were analyzed. RESULTS: hMSH2 has a considerable increased expression in all groups of patients with tumors, when compared to patients without tumors. CONCLUSIONS: immunohistochemistry indeed can be a great tool for the diagnosis of breast cancer, as it is an easy and versatile technique. [ABSTRACT FROM AUTHOR]

Abstract Background Cells respond to endoplasmic reticulum stress (ER) stress by activating the unfolded protein response. To study the ER stress response in pancreatic β-cells we developed a model system that allows for pathophysiological ER stress based on the Akita mouse. This mouse strain expresses a mutant insulin 2 gene (C96Y), which prevents normal proinsulin folding causing ER stress and eventual β-cell apoptosis. A double-stable pancreatic β-cell line (pTet-ON INS-1) with inducible expression of insulin 2 (C96Y) fused to EGFP was generated to study the ER stress response. Results Expression of Ins 2 (C96Y)-EGFP resulted in activation of the ER stress pathways (PERK, IRE1 and ATF6) and caused dilation of the ER. To identify gene expression changes resulting from mutant insulin expression we performed microarray expression profiling and real time PCR experiments. We observed an induction of various ER chaperone, co-chaperone and ER-associated degradation genes after 24 h and an increase in pro-apoptotic genes (Chop and Trib3) following 48 h of mutant insulin expression. The latter changes occurred at a time when general apoptosis was detected in the cell population, although the relative amount of cell death was low. Inhibiting the proteasome or depleting Herp protein expression increased mutant insulin levels and enhanced cell apoptosis, indicating that ER-associated degradation is maintaining cell survival. Conclusions The inducible mutant insulin expressing cell model has allowed for the identification of the ER stress response in β-cells and the repertoire of genes/proteins induced is unique to this cell type. ER-associated degradation is essential in maintaining cell survival in cells expressing mutant insulin. This cell model will be useful for the molecular characterization of ER stress-induced genes.

Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency is characterized by elevated plasma and tissue homocysteine levels. There is no cure, but HCU is typically managed by methionine/protein restriction and vitamin B 6 supplementation. Enzyme replacement therapy (ERT) based on human CBS has been developed and has shown significant efficacy correcting HCU phenotype in several mouse models by bringing plasma total homocysteine below the clinically relevant 100 μM threshold. As the reactive nature of homocysteine promotes disulfide formation and protein binding, and ERT is unable to normalize plasma total homocysteine levels, the mechanism of action of ERT in HCU remains to be further characterized. Here we showed that only a reduced homocysteine serves as a substrate for CBS and its availability restricts the homocysteine-degrading capacity of CBS. We also demonstrated that cells export homocysteine in its reduced form, which is efficiently metabolized by CBS in the culture medium. Availability of serine, a CBS co-substrate, was not a limiting factor in our cell-based model. Biological reductants, such as N-acetylcysteine, MESNA or cysteamine, increased the availability of the reduced homocysteine and thus promoted its subsequent CBS-based elimination. In a transgenic I278T mouse model of HCU, administration of biological reductants significantly increased the proportion of protein-unbound homocysteine in plasma, which improved the efficacy of the co-administered CBS-based ERT, as evidenced by significantly lower plasma total homocysteine levels. These results clarify the mechanism of action of CBS-based ERT and unveil novel pharmacological approaches to further increase its efficacy., Competing Interests: Declaration of competing interest TM is an inventor on patents related to pegtibatinase, provides ad-hoc consulting to Travere Therapeutics and receives research support from Travere Therapeutics. TB receives compensation for metabolomic analyses from Travere Therapeutics. WC, KL and SR are current or former employees and stockholders of Travere Therapeutics, which clinically develops pegtibatinase as an enzyme replacement therapy for classical homocystinuria. TMP and CS declare no conflicting interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper presents the implementation of two automated text classification systems for prostate cancer findings based on the PI-RADS criteria. Specifically, a traditional machine learning model using XGBoost and a language model-based approach using RoBERTa were employed. The study focused on Spanish-language radiological MRI prostate reports, which has not been explored before. The results demonstrate that the RoBERTa model outperforms the XGBoost model, although both achieve promising results. Furthermore, the best-performing system was integrated into the radiological company's information systems as an API, operating in a real-world environment., (© 2024. The Author(s).)

Positive reappraisal strategies have been found to reduce negative affect following the recall of negative personal events. This study examined the restorative effect of two mood-repair instructions (self-compassion vs benefit-focused reappraisal) and a control condition with no instructions following a negative Mood Induction Procedure by using the guided recall of a negative autobiographical event. A total of 112 university students participated in the online study (81% women, Mage: 21.0 years). Immediately following the negative memory recall, participants were randomised to each condition [(self-compassion: n  = 36, benefit-focused: n  = 39) or a control condition ( n  = 37)]. Repeated measures ANOVAs 3 (Repair condition) × 3 (Time of mood assessment: pre-recall, post-recall, post-regulation) showed that, as expected, negative mood (sadness, shame, and guilt) worsened significantly after the guided recall in all groups ( p  < .001). After the mood-repair intervention, participants in the self-compassion and benefit-focused conditions showed a significant reduction in negative mood ( p  < .019), while such improvement was not observed in the control group. Self-compassion and benefit-focused reappraisal functioned similarly as mood repair strategies after experiencing negative affect induced by the recall of negative personal memories. Implications in the context of autobiographical memory biases are discussed.

Background: The MDS-UPDRS has been available in English since 2008, showing satisfactory clinimetric results and being proposed as the new official benchmark scale for Parkinson's disease (PD), being cited as a core instrument for PD in the National Institutes of Neurological Disorders and Stroke Common Data Elements program. For this reason, the MDS created guidelines for development of MDS-UPDRS official, clinimetrically validated translations., Objective: This study presents the formal process used to obtain the officially approved Portuguese version of the MDS-UPDRS., Methods: The study consisted of three phases: (1) Independent translation by Portuguese and Brazilian teams followed by a challenging consensus process that this article particularly emphasizes; (2) Cognitive pretest involving raters and patients from both Portugal and Brazil; (3) Validation test with a sample of 367 native Portuguese-speaking PD patients., Results: The overall factor structure of the Portuguese version was consistent with the English version based on a comparative fit index ≥0.96 for all four parts of the MDS-UPDRS., Conclusion: This version can be designated as the official Portuguese version of the MDS-UPDRS., (© 2024 International Parkinson and Movement Disorder Society.)

Introduction: Much research on the treatment of paranoia has involved cognitive-behavioural interventions that address explicit social cognition processes. However, much of human cognition is preverbal or implicit, raising the possibility that such social judgements are implicated in paranoia. One type of implicit social cognition that has been investigated concerning paranoia is implicit self-esteem with some evidence that it may be possible to change implicit self-esteem using techniques based on conditioning theory. Therefore, the primary purpose of this research is to further evaluate the potential of this approach. At the same time, as a secondary purpose, we introduce a novel way of measuring social cognition that, we argue, has utility for investigating the psychological processes involved in paranoia., Method: We conducted two proof-of-concept studies of a novel brief intervention based on evaluative conditioning, targeting implicit cognition. The first study was conducted with a large non-clinical sample, while the second study included a small series of psychotic patients. As part of our proof-of-concept evaluation of the potential of evaluative conditioning, we attempted to probe for neurophysiological changes following the intervention using magnetoencephalography in an exploratory way in the clinical sample., Results: Our results revealed that both non-clinical and clinical participants in the experimental group showed a significant change in how they evaluated themselves in the social cognition task, which could be related to the perception of social information in a less threatening way. In addition, clinical participants in the experimental group showed changes in brain activity during the social cognition task, particularly in regions involved in emotional reactivity and mentalization processes., Discussion: Our results are encouraging, suggesting that implicit cognition is manipulable, that such manipulation affects underlying neurophysiological mechanisms, and that there may be an impact on paranoid symptoms. However, much more work is required to determine whether this approach can produce meaningful clinical change and be delivered in routine clinical settings. Finally, it is important to note that we are not claiming the clinical effectiveness of our intervention, which is in a very early stage of development. Our goal here is to demonstrate clinical possibilities that warrant further investigation., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Trucharte, Carmen, Pacios, Bruña, Espinosa, Peinado, Pascual, Martinez, Maestu and Bentall.)

Background: Tuberculosis (TB) is a highly prevalent chronic infectious disease in developing countries, with Peru being one of the most affected countries in the world. The variants of the N -acetyltransferase 2 ( NAT2 ) gene are related to xenobiotic metabolism and have potential usefulness in TB studies., Aim: To determine whether NAT2 gene variants and acetylator phenotypes are associated with active TB in Peruvian patients., Methods: This study included cases (patients with TB) and controls (population-based data). First, DNA isolation and the rs1799929, rs1799930, and rs1799931 variants of the NAT2 gene were identified using sequencing methods. Subsequently, the acetylator phenotypes, namely slow (SA), intermediate (IA), and rapid acetylation (RA), were also analyzed., Results: The comparison of the frequencies of the rs1799931 variant in the cases and controls revealed significant differences. Risk factors were found for both the A allele (p = 0.00; odds ratio [OR] = 3.04, 95 % confidence interval [CI]: 1.88-4.9) and AG genotype (p = 0.00; OR = 5.94, 95 % CI: 3.17-11.09). In addition, the non-rapid acetylator phenotype (SA + IA) was also found to be a risk factor (p = 0.016; OR = 3.16, 95 % CI: 1.29-7.72)., Conclusion: The A allele, GA heterozygous genotype of the rs1799931 variant of the NAT2 gene, and SA + IA acetylator phenotype showed an association with increased risk for the development of TB. In addition to xenobiotic metabolism, other metabolic and immunological functions of NAT2 have also been postulated to confer susceptibility to TB in the Peruvian population owing to its characteristic high Native American component., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Importance: Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear., Objective: To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajectory prestroke in stroke survivors with the trajectory of individuals without incident stroke over follow-up., Design, Setting, and Participants: The study used harmonized and pooled data from 14 population-based cohort studies included in the Cohort Studies of Memory in an International Consortium collaboration. These studies were conducted from 1993 to 2019 across 11 countries among community-dwelling older adults without a history of stroke or dementia. For this study, linear mixed-effects models were used to estimate trajectories of cognitive function poststroke relative to a stroke-free cognitive trajectory. The full model adjusted for demographic and vascular risk factors. Data were analyzed from July 2022 to March 2024., Exposure: Incident stroke., Main Outcomes and Measures: The primary outcome was global cognition, defined as the standardized average of 4 cognitive domains (language, memory, processing speed, and executive function). Cognitive domain scores were formed by selecting the most commonly administered test within each domain and standardizing the scores., Results: The study included 20 860 participants (12 261 [58.8%] female) with a mean (SD) age of 72.9 (8.0) years and follow-up of 7.51 (4.2) years. Incident stroke was associated with a substantial acute decline in global cognition (-0.25 SD; 95% CI, -0.33 to -0.17 SD), the Mini-Mental State Examination, and all cognitive domains (ranging from -0.17 SD to -0.22 SD), as well as accelerated decline in global cognition (-0.038 SD per year; 95% CI, -0.057 to -0.019 SD per year) and all domains except memory (ranging from -0.020 to -0.055 SD per year), relative to a stroke-free cognitive trajectory. There was no significant difference in prestroke slope in stroke survivors compared with the rate of decline in individuals without stroke in all cognitive measures. The mean rate of decline without a previous stroke was -0.049 SD per year (95% CI, -0.051 to -0.047 SD) in global cognition., Conclusions and Relevance: In this cohort study using pooled data from 14 cohorts, incident stroke was associated with acute and accelerated long-term cognitive decline in older stroke survivors.

Susceptibility-weighted imaging (SWI) has become a standard component of most brain MRI protocols. While traditionally used for detecting and characterising brain hemorrhages typically associated with stroke or trauma, SWI has also shown promising results in glioma assessment. Numerous studies have highlighted SWI's role in differentiating gliomas from other brain lesions, such as primary central nervous system lymphomas or metastases. Additionally, SWI aids radiologists in non-invasively grading gliomas and predicting their phenotypic profiles. Various researchers have suggested incorporating SWI as an adjunct sequence for predicting treatment response and for post-treatment monitoring. A significant focus of these studies is on the detection of intratumoural susceptibility signals (ITSSs) in gliomas, which are indicative of microhemorrhages and vessels within the tumour. The quantity, distribution, and characteristics of these ITSSs can provide radiologists with more precise information for evaluating and characterising gliomas. Furthermore, the potential benefits and added value of performing SWI after the administration of gadolinium-based contrast agents (GBCAs) have been explored. This review offers a comprehensive, educational, and practical overview of the potential applications and future directions of SWI in the context of glioma assessment. CLINICAL RELEVANCE STATEMENT: SWI has proven effective in evaluating gliomas, especially through assessing intratumoural susceptibility signal changes, and is becoming a promising, easily integrated tool in MRI protocols for both pre- and post-treatment assessments. KEY POINTS: • Susceptibility-weighted imaging is the most sensitive sequence for detecting blood and calcium inside brain lesions. • This sequence, acquired with and without gadolinium, helps with glioma diagnosis, characterisation, and grading through the detection of intratumoural susceptibility signals. • There are ongoing challenges that must be faced to clarify the role of susceptibility-weighted imaging for glioma assessment., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Nowadays, the use of advanced MRI sequences such as diffusion-weighted imaging or perfusion-weighted imaging in the field of musculoskeletal radiology remains limited compared to other anatomical regions and subspecialties. Several reasons underpin this, primarily technical challenges, and a longstanding reliance on conventional and morphological evaluations of soft tissue and bone lesions. Experienced radiologists often assert that these advanced sequences do not offer added diagnostic value, claiming that a morphological approach suffices. However, in our opinion, the role of these advanced MRI sequences extends beyond merely naming an MSK lesion. In this commentary, we elucidate how these sequences can aid radiologists in various scenarios, from determining patient prognosis and tracking treatment progress to enhancing clinical-radiological correlations or guiding less experienced radiologists in evaluating soft tissues or bone tumours., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)