MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed. We have compiled a cohort of 850 patients, which has shown a 3.65 % fusion prevalence and represents the largest MAML3-positive series reported to date. While MAML3-fusions mainly cause single pheochromocytomas, we also observed somatic post-zygotic events, resulting in multiple tumours in the same patient. MAML3-tumours show increased expression of neuroendocrine-to-mesenchymal transition markers, MYC-targets, and angiogenesis-related genes, leading to a distinct tumour microenvironment with unique vascular and immune profiles. Importantly, our findings have identified MAML3-tumours specific vulnerabilities beyond Wnt-pathway dysregulation, such as a rich vascular network, and overexpression of PD-L1 and CD40, suggesting potential therapeutic targets.

Astrocytic Ca2+ activation by chemogenetics mitigates the effect of kainic acid-induced excitotoxicity on the hippocampus.

Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry. Astrocytic Ca2+ activation increased the 18F-FDG uptake, but this effect was not found when the study was performed in knock out mice for type-2 inositol 1,4,5-trisphosphate receptor (Ip3r2-/-) nor in floxed mice to abolish glucose transporter 1 (GLUT1) expression in hippocampal astrocytes (GLUT1ΔGFAP). Sustained astrocyte activation after KA injection reversed the brain glucose hypometabolism, restored hippocampal function, prevented neuronal death, and increased hippocampal GABA levels. The findings of our study indicate that astrocytic GLUT1 function is crucial for regulating brain glucose metabolism. Astrocytic Ca2+ activation has been shown to promote adaptive changes that significantly contribute to mitigating the effects of KA-induced damage. This evidence suggests a protective role of activated astrocytes against KA-induced excitotoxicity.

Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy.

Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance. Then, we further studied the effect of chronic metformin treatment (9 months) in Tau-VLW mice from 9 to 18 months of age. Longitudinal PET neuroimaging studies revealed that chronic metformin altered the temporal profile in the progression of brain glucose hypometabolism associated with ageing. Besides, metformin altered the content and/or phosphorylation of key components of the insulin signal transduction pathway in the frontal cortex leading to significant changes in the content of the active forms. Thus, metformin increased the expression of pAKT-Y474 while reducing pmTOR-S2448 and pGSK3ß. These changes might be related, at least partially, to a slow progression of ageing, neurological damage, and cognitive decline. Metformin also improved the peripheral glucose tolerance and the ability of the Tau-VLW mice to maintain their body weight through ageing. Altogether our study shows that the tau-VLW mice could be a useful model to study the potential interrelationship between tauopathy and central and peripheral glucose metabolism alterations. More importantly our results suggest that chronic metformin treatment may have direct beneficial central effects by post-transcriptional modulation of key components of the insulin signal transduction pathway.

Endothelin-1 down-regulates nuclear factor erythroid 2-related factor-2 and contributes to perivascular adipose tissue dysfunction in obesity.

Perivascular adipose tissue (PVAT) negatively regulates vascular muscle contraction. However, in the context of obesity, the PVAT releases vasoconstrictor substances that detrimentally affect vascular function. A pivotal player in this scenario is the peptide endothelin-1 (ET-1), which induces oxidative stress and disrupts vascular function. The present study postulates that obesity augments ET-1 production in the PVAT, decreases the function of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, further increasing reactive oxygen species (ROS) generation, culminating in PVAT dysfunction. Male C57BL/6 mice were fed either a standard or a high-fat diet for 16 weeks. Mice were also treated with saline or a daily dose of 100 mg·kg-1 of the ETA and ETB receptor antagonist Bosentan, for 7 days. Vascular function was evaluated in thoracic aortic rings, with and without PVAT. Mechanistic studies utilized PVAT from all groups and cultured WT-1 mouse brown adipocytes. PVAT from obese mice exhibited increased ET-1 production, increased ECE1 and ETA gene expression, loss of the anticontractile effect, as well as increased ROS production, decreased Nrf2 activity, and downregulated expression of Nrf2-targeted antioxidant genes. PVAT of obese mice also exhibited increased expression of Tyr216-phosphorylated-GSK3ß and KEAP1, but not BACH1 - negative Nrf2 regulators. Bosentan treatment reversed all these effects. Similarly, ET-1 increased ROS generation and decreased Nrf2 activity in brown adipocytes, events mitigated by BQ123 (ETA receptor antagonist). These findings place ET-1 as a major contributor to PVAT dysfunction in obesity and highlight that pharmacological control of ET-1 effects restores PVAT's cardiovascular protective role.

Anxiety in Nursing Students during the COVID-19 Pandemic: Systematic Review and Meta-Analysis.

OBJECTIVES: To analyse the influence of the COVID-19 pandemic on the development of anxiety in nursing students and the factors involved. DESIGN: A systematic review and meta-analysis. DATA SOURCE: PubMed, CINAHL, Scopus and Web of Science. BACKGROUND: Nursing students are at an increased risk of developing mental overload, due to the presence of many sources of stress during their academic training. Therefore, the COVID-19 pandemic has had an impact on the mental health of the general population, especially on healthcare workers and consequently on students undertaking placements in healthcare settings. METHODS: A systematic review was conducted using PubMed, CINAHL, Scopus and Web of Science databases. A total of 24 articles were included in the review, and 20 articles were selected for the meta-analysis. RESULTS: We found that the anxiety scores of nursing students during the COVID-19 pandemic were slightly higher (50%) than before the pandemic. The most influential risk factors for developing anxiety were academics, age, gender, having children, living in urban areas or with family, having an addiction to social networks, and having a fear of becoming infected with COVID-19. Resilience, spiritual support and feelings of happiness protected students against the risk of developing high levels of anxiety. CONCLUSIONS: The COVID-19 pandemic has led to increased levels of anxiety in nursing students. Thirty-five percent of the meta-analytically analysed sample had elevated levels of anxiety.

Factors associated with outcomes following microvascular decompression for the treatment of primary trigeminal neuralgia in adults: a systematic review and meta-analysis.

This study aimed to evaluate pain assessment strategies and factors associated with outcomes after microvascular decompression for the treatment of primary trigeminal neuralgia in adults. We conducted a systematic review and meta-analysis of English, Spanish, and French literature. We searched three databases, PubMed, Ovid, and EBSCO, from 2010 to 2022 and selected studies including patients with primary trigeminal neuralgia, clear pain assessment, and pain outcomes. Population means and standard deviations were calculated. Studies that included factors associated with postoperative outcomes were included in the meta-analysis. A total of 995 studies involving 5673 patients with primary trigeminal neuralgia following microvascular decompression were included. Patients with arteries compressing the trigeminal nerve demonstrated optimal outcomes following microvascular decompression (odds ratio [OR]= 0.39; 95% confidence interval [CI] = 0.19-0.80; X2 = 46.31; Dof = 15; I2 = 68%; P = < 0.0001). Conversely, when comparing arterial vs venous compression of the trigeminal nerve (OR = 2.72; 95% CI = 1.16-6.38; X2 = 23.23; Dof = 10; I2 = 57%; P = 0.01), venous compression demonstrated poor outcomes after microvascular decompression. Additionally, when comparing single-vessel vs multiple-vessel compression (OR = 2.72; 95% CI = 1.18-6.25; X2 = 21.17; Dof = 9; I2 = 57%; P = 0.01), patients demonstrated unfavorable outcomes after microvascular decompression. This systematic review and meta-analysis evaluated factors associated with outcomes following microvascular decompression (MVD) for primary trigeminal neuralgia (PTN). Although MVD is an optimal treatment strategy for PTN, a gap exists in interpreting the results when considering the lack of evidence for most pain assessment strategies.

A one-pot five component reaction for the synthesis of tetrazol-benzofuran hybrids and their inhibitory activity against Mucor lusitanicus.

A synthetic strategy for obtaining a new series of 1,5-disubstituted tetrazole-benzofuran hybrid systems via a one-pot five-component reaction is described. This process involves a Ugi-azide multicomponent reaction coupled to an intramolecular cyclization catalyzed by Pd/Cu, resulting in low to moderate yields from 21 to 67%. This protocol allowed the synthesis of highly substituted benzofurans at the 2-position through an operationally simple process under mild reaction conditions and with high bond forming efficiency due to the formation of six new bonds (two C-C, two C-N, one N-N, and one C-O). Besides, to evaluate the antifungal activity of 1,5-disubstituted tetrazole-benzofurans 9a-n, in vitro studies against Mucor lusitanicus were performed, finding that compound 9b exhibits bioactivity comparable to the commercial antifungal drug Amphotericin B. These results suggest potential for use in controlling mucormycosis infections in animal models, highlighting the importance of these findings given the limited antifungal drug options and high mortality rates associated with this infection.

A Metastable Semiquinone Molecular Switch Modulated by Ascorbate/O2: A Study from a System Far-From-Equilibrium to Biological Assays in Mitochondria.

A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolyl quinone thiocyanate (PQ 9) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13 C NMR. The metastable quinoid species formed by the interaction with F- ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out-of-equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 9 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 9 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 9 reduced ROS production and catalase activity in yeast. The results suggest that PQ 9 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.

Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer.

The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK-positive NSCLC based on the clinical experience of a multidisciplinary panel of experts.

[Overweight and obesity in children aged 5-11 years in Mexico - Why is necessary an interdisciplinary approach?] / Sobrepeso y obesidad en niños de 5 a 11 años en México en el periodo 1999-2021: ¿por qué es necesario un abordaje interdisciplinario?

Introduction: Introduction: overweight and obesity in children are serious public health problems in Mexico. Objective: to analyze the behavior of the prevalence of overweight and obesity in children from 5 to 11 years of age and to present projections on the prevalence for the period 2022-2026. Methodology: ecological and retrospective study whose units of analysis were groups of children of Mexico with overweight and obesity in the period 1999-2021, according to information collected from six National Health and Nutrition Surveys. For the projections the classical method of least squares was used, for a trend analysis of both conditions for the period 2022-2026. Results: overweight in girls and obesity in boys shows a high prevalence in the period 1999-2021, even though the trend analysis for the period 2022-2026 shows a slight decrease in overweight for the group of boys and a slight increase in overweight for girls, as well in obesity for both groups. Conclusions: due to the high prevalence of overweight and obesity in children from 5 to 11 years of age in Mexico, an interdisciplinary approach is required to identify which dimensions (biochemical, psychological, interpersonal and social) participate in the problem, considering three environments contributing for psychological and social development of children, the ecological-social, the family and the school.

Introducción: Introducción: el sobrepeso y la obesidad en niños son serios problemas de salud pública en México. Objetivo: analizar el comportamiento de la prevalencia de sobrepeso y obesidad en niños de 5 a 11 años y presentar proyecciones sobre su prevalencia para el periodo 2022-2026. Metodología: estudio ecológico y retrospectivo cuyas unidades de análisis fueron grupos de niños con sobrepeso y obesidad en el periodo 1999-2021, de acuerdo con información recabada en seis Encuestas Nacionales de Salud y Nutrición en México. Para las proyecciones se utilizó el método clásico de mínimos cuadrados, con el que se realizó un análisis de tendencia de ambas condiciones para el periodo 2022-2026. Resultados: el sobrepeso en niñas y la obesidad en niños muestra una elevada prevalencia en el periodo 1999-2021, aun cuando el análisis de tendencia para el periodo 2022-2026 muestra un ligero decremento en el sobrepeso para el grupo de niños y un ligero incremento en el sobrepeso para las niñas, así como en la obesidad para ambos grupos. Conclusión: Debido a la elevada prevalencia de sobrepeso y obesidad en niños de 5 a 11 años en México, se precisa de su abordaje interdisciplinario para identificar qué dimensiones (bioquímica, psicológica, interpersonal y social) participan en el problema, considerando tres ambientes que contribuyen al desarrollo psicológico y social de los niños, el ecológico-social, el familiar y el escolar.

Understanding electrical and chemical transmission in the brain.

The histochemical Falck-Hillarp method for the localization of dopamine (DA), noradrenaline (NA) and serotonin in the central nervous system (CNS) of rodents was introduced in the 1960s. It supported the existence of chemical neurotransmission in the CNS. The monoamine neurons in the lower brain stem formed monosynaptic ascending systems to the telencephalon and diencephalon and monoamine descending systems to the entire spinal cord. The monoamines were early on suggested to operate via synaptic chemical transmission in the CNS. This chemical transmission reduced the impact of electrical transmission. In 1969 and the 1970s indications were obtained that important modes of chemical monoamine communication in the CNS also took place through the extra-synaptic fluid, the extracellular fluid, and long-distance communication in the cerebrospinal fluid involving diffusion and flow of transmitters like DA, NA and serotonin. In 1986, this type of transmission was named volume transmission (VT) by Agnati and Fuxe and their colleagues, also characterized by transmitter varicosity and receptor mismatches. The short and long-distance VT pathways were characterized by volume fraction, tortuosity and clearance. Electrical transmission also exists in the mammalian CNS, but chemical transmission is in dominance. One electrical mode is represented by electrical synapses formed by gap junctions which represent low resistant passages between nerve cells. It allows for a more rapid passage of action potentials between nerve cells compared to chemical transmission. The second mode is based on the ability of synaptic currents to generate electrical fields to modulate chemical transmission. One aim is to understand how chemical transmission can be integrated with electrical transmission and how putative (aquaporin water channel, dopamine D2R and adenosine A2AR) complexes in astrocytes can significancy participate in the clearance of waste products from the glymphatic system. VT may also help accomplish the operation of the acupuncture meridians essential for Chinese medicine in view of the indicated existence of extracellular VT pathways.

Ceftazidime-Avibactam Use in a Case Series of Difficult-to-Treat or Recurrent Infections in Pediatric Patients with Complex Chronic Conditions: Effectiveness and Absence of Resistance Development.

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime-avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive case series at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. The clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n = 8) and biliary atresia (n = 4). The predominant type of infection for which they received CZA was intra-abdominal infection caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, two patients died, with one case directly linked to the infection's fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA's potential as a primary treatment option against OXA-48-producing infections.

Specific inhibition of α-synuclein oligomer generation and toxicity by the chaperone domain Bri2 BRICHOS.

Protein misfolding and aggregation are involved in several neurodegenerative disorders, such as α-synuclein (αSyn) implicated in Parkinson's disease, where new therapeutic approaches remain essential to combat these devastating diseases. Elucidating the microscopic nucleation mechanisms has opened new opportunities to develop therapeutics against toxic mechanisms and species. Here, we show that naturally occurring molecular chaperones, represented by the anti-amyloid Bri2 BRICHOS domain, can be used to target αSyn-associated nucleation processes and structural species related to neurotoxicity. Our findings revealed that BRICHOS predominantly suppresses the formation of new nucleation units on the fibrils surface (secondary nucleation), decreasing the oligomer generation rate. Further, BRICHOS directly binds to oligomeric αSyn species and effectively diminishes αSyn fibril-related toxicity. Hence, our studies show that molecular chaperones can be utilized as tools to target molecular processes and structural species related to αSyn neurotoxicity and have the potential as protein-based treatments against neurodegenerative disorders.

Pubertal stress in male rats: Effects on juvenile play behavior and adult sexual partner preference.

Puberty is a period of brain organization impacting the expression of social and sexual behaviors. Here, we assessed the effects of an acute pubertal stressor (immune challenge) on the expression of juvenile play (short-term) and sexual partner preference (long-term) in male rats. Juvenile play was assessed over ten trials at postnatal days (PND) (31-40) with age- and sex-matched conspecifics, and at PND35 males received a single injection of lipopolysaccharide (LPS, 1.5 mg/kg i.p.) or saline. Then, sexual partner preference was assessed at PND 60, 64, and 68, in a three-compartment chamber with a sexually receptive female and a male as potential partners simultaneously. The results confirmed that a single injection of LPS during puberty induced sickness signs indicative of an immune challenge. However, juvenile play was not affected by LPS treatment during the following days (PND36-40), nor was sexual behavior and partner preference for females in adulthood. These findings highlight that, while other studies have shown that LPS-induced immunological stress during puberty affects behavior and neuroendocrine responses, it does not affect juvenile play and sexual behavior in male rats. This suggests a remarkable resilience of these behavioral systems for adaptation to stressful experiences mediated by immune challenges during critical periods of development. These behaviors, however, might be affected by other types of stress.

Complications in Patients with Surgically Altered Gastrointestinal Anatomy Undergoing Endoscopic Retrograde Cholangiopancreatography: 15-Year Experience at a Tertiary Care Center in Latin America.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure, but it poses challenges in patients with surgically altered gastrointestinal anatomy (SAGA). Alternative techniques like single-balloon enteroscopy (SBE), double-balloon enteroscopy (DBE), or push enteroscopy (PE) have been used, albeit with potential complications. Limited Latin American data exists on ERCP complications in SAGA patients. Our goal is to describe complications of ERCP in SAGA at a national referral institution. METHODS: Retrospective, single-center cohort study. All SAGA ERCP procedures performed at the Gastrointestinal Endoscopy Department of the National Institute of Medical Sciences and Nutrition Salvador Zubirán from January 2008 to May 2023 were included. Extracted data from records included procedure specifics, endoscope type, success, and complications. Complications were evaluated during procedure and 28-day post-procedure and classified using the AGREE system. RESULTS: A total of 266 procedures in 174 patients were included, 74% were women, and the median age was 44 years. Predominant modified anatomy was Roux-en-Y biliary reconstruction (79%), followed by Whipple procedure (13%) and subtotal gastrectomy with Roux-en-Y reconstruction (6.0%). The main indications were cholangitis with stricture (31%), stricture (19%), and cholangitis (19%). DBE was used in 89%, PE in 7.5%, and SBE in 3.4%. Success rates were 77% endoscopic, 72% technical, and 69% therapeutic; in 30%, the procedure was unsuccessful. Complications happened in 18% of cases, most commonly cholangitis (7.5%), followed by perforation (2.6%) and hemorrhage (1.9%). According to the AGREE classification, 10.9% were grades 1 and 2, 6.4% were grade 3, and 0.4% were grade 4 complications. No significant differences emerged between groups with and without complications. Procedures increased over time, but complications and unsuccessful procedures remained stable. CONCLUSION: ERCP complications align with international data, often not requiring invasive treatment. Enhanced exposure to such cases correlates with fewer complications and failures. Prospective studies are essential to identify complication and failure predictors.

Segment Anything for Comprehensive Analysis of Grapevine Cluster Architecture and Berry Properties.

Grape cluster architecture and compactness are complex traits influencing disease susceptibility, fruit quality, and yield. Evaluation methods for these traits include visual scoring, manual methodologies, and computer vision, with the latter being the most scalable approach. Most of the existing computer vision approaches for processing cluster images often rely on conventional segmentation or machine learning with extensive training and limited generalization. The Segment Anything Model (SAM), a novel foundation model trained on a massive image dataset, enables automated object segmentation without additional training. This study demonstrates out-of-the-box SAM's high accuracy in identifying individual berries in 2-dimensional (2D) cluster images. Using this model, we managed to segment approximately 3,500 cluster images, generating over 150,000 berry masks, each linked with spatial coordinates within their clusters. The correlation between human-identified berries and SAM predictions was very strong (Pearson's r2 = 0.96). Although the visible berry count in images typically underestimates the actual cluster berry count due to visibility issues, we demonstrated that this discrepancy could be adjusted using a linear regression model (adjusted R 2 = 0.87). We emphasized the critical importance of the angle at which the cluster is imaged, noting its substantial effect on berry counts and architecture. We proposed different approaches in which berry location information facilitated the calculation of complex features related to cluster architecture and compactness. Finally, we discussed SAM's potential integration into currently available pipelines for image generation and processing in vineyard conditions.

Use and Outcomes of Dexamethasone in the Management of Malignant Small Bowel Obstruction.

Objective: To describe rates of dexamethasone use in the nonoperative management of malignant small bowel obstruction (mSBO) and their outcomes. Background: mSBO is common in patients with advanced abdominal-pelvic cancers. Management includes prioritizing quality of life and avoiding surgical intervention when possible. The use of dexamethasone to restore bowel function is recommended in the National Comprehensive Cancer Network guidelines for mSBO. Yet, it is unknown how often dexamethasone is used for mSBO and whether results from nonresearch settings support its use. Methods: This is a multicenter retrospective cohort study including unique admissions for mSBO from January 1, 2019 to December 31, 2021. Dexamethasone use and management outcomes were summarized with descriptive statistics and multiple logistic regression. Results: Among 571 admissions (68% female, mean age 63 years, 85% history of abdominal surgery) that were eligible and initially nonoperative, 26% [95% confidence interval (CI) = 23%-30%] received dexamethasone treatment (69% female, mean age 62 years, 87% history of abdominal surgery). Dexamethasone use by site ranged from 13% to 52%. Among dexamethasone recipients, 13% (95% CI = 9%-20%) subsequently required nonelective surgery during the same admission and 4 dexamethasone-related safety-events were reported. Amongst 421 eligible admissions where dexamethasone was not used, 17% (95% CI = 14%-21%) required nonelective surgery. Overall, the unadjusted odds ratio (OR) for nonelective surgery with dexamethasone use compared to without its use was 0.7 (95% CI = 0.4-1.3). Using multiple logistic regression, OR after adjusting for site, age, sex, history of abdominal surgery, nasogastric tube, and Gastrografin use was 0.6 (95% CI = 0.3-1.1). Conclusion: Dexamethasone was used in about 1 in 4 eligible mSBO admissions with high variability of use between tertiary academic centers. This multicenter retrospective cohort study suggested an association between dexamethasone use and lower rates of nonelective surgery, representing a potential opportunity for quality improvement.

The Androgen Dehydroepiandrosterone Sulfate Shows a Greater Relationship with Impulsivity than Testosterone in a Healthy Male Sample.

This study was designed to examine the relationships among the impulsivity construct as a personality trait, the dehydroepiandrosterone sulfate (DHEA-S), and testosterone in a sample of 120 healthy middle-aged males (Mage = 44.39; SD = 12.88). The sum of the three BIS-11 scales, the SR, and the five UPPS-P scales correlated with DHEA-S 0.23 (p < 0.006) and testosterone 0.19 (p < 0.04), controlling for age. Partial correlations showed that DHEA-S was significantly related to motor impulsivity (0.24; p < 0.008), Sensitivity to Reward (0.29; p < 0.002), Lack of Premeditation (0.26; p < 0.05), and, to a lesser extent, Sensation Seeking (0.19; p < 0.04) and Positive Urgency (0.19; p < 0.04). Testosterone correlated with attention impulsivity (0.18; p < 0.04), Sensation Seeking (0.18; p < 0.04), and Positive Urgency (0.22; p < 0.01). Sensitivity to Reward, Negative Urgency, and Positive Urgency were significant predictors of DHEA-S (R2 = 0.28), and Positive Urgency for testosterone (R2 = 0.09). Non-parametric LOESS graphical analyses for local regression allowed us to visualize the non-linear relationships between the impulsivity scales with the two androgens, including non-significant trends. We discuss the implications of these results for impulsive biological personality traits, the limitations of our analyses, and the possible development of future research.

Perceptions of Adulthood and Mental Health.

BACKGROUND: In contrast to conventional definitions, the contemporary conceptualization of adulthood emphasizes psychological characteristics over sociodemographic milestones. At the same time, an increasing number of theorists propose that the way individuals view adulthood may have a significant impact on the mental health of both adolescents and adults. However, empirical examination of this hypothesis has been notably limited to date. The aim of this study is to explore the association between individuals' perceptions of adulthood and multiple dimensions of mental health. METHOD: This study applied some adulthood markers and multiple mental health indexes (including well-being, optimism, Alexithymia, satisfaction with life, Goldberg's index of mental health, the dark triad, and dimensional personality disorders) to a community sample comprising 1772 individuals in Spain, spanning ages from 16 to 93 years. RESULTS: The findings support the overarching hypothesis, as perceptions of adulthood display strong correlations with nearly every assessed index of mental health, particularly those that comprise a dimension of negative emotions. These associations persist even after accounting for age and socio-economic status, and in alignment with the psychological paradigm of adulthood, they show a notable consistency across various age groups. CONCLUSIONS: This study establishes that such perceptions of adulthood represent a modifiable factor contributing to positive mental health. The implications of these findings for the formulation of public policies aimed at promoting mental health in the context of adulthood, as well as a number of future studies, are deliberated.

A Promising Amphotericin B Derivative Induces Morphological Alterations, Mitochondrial Damage, and Oxidative Stress In Vitro and Prevents Mice from Death Produced by a Virulent Strain of Trypanosoma cruzi.

Chagas Disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, affecting 6-8 million people, mainly in Latin America. The medical treatment is based on two compounds, benznidazole and nifurtimox, with limited effectiveness and that produce severe side effects; consequently, there is an urgent need to develop new, safe, and effective drugs. Amphotericin B is the most potent antimycotic known to date. A21 is a derivative of this compound with the property of binding to ergosterol present in cell membranes of some organisms. In the search for a new therapeutic drug against T. cruzi, the objective of this work was to study the in vitro and in vivo effects of A21 derivative on T. cruzi. Our results show that the A21 increased the reactive oxygen species and reduced the mitochondrial membrane potential, affecting the morphology, metabolism, and cell membrane permeability of T. cruzi in vitro. Even more important was finding that in an in vivo murine model of infection, A21 in combination with benznidazole was able to reduce blood parasitemia, diminish the immune inflammatory infiltrate in skeletal muscle and rescue all the mice from death due to a virulent T. cruzi strain.