Inhibition of RhoA prevents Cryptococcus neoformans capsule glucuronoxylomannan-stimulated brain endothelial barrier disruption.

Cryptococcus neoformans (Cn) is an opportunistic fungus that causes severe central nervous system (CNS) disease in immunocompromised individuals. Brain parenchyma invasion requires fungal traversal of the blood-brain barrier. In this study, we describe that Cn alters the brain endothelium by activating small GTPase RhoA, causing reorganization of the actin cytoskeleton and tight junction modulation to regulate endothelial barrier permeability. We confirm that the main fungal capsule polysaccharide glucuronoxylomannan is responsible for these alterations. We reveal a therapeutic benefit of RhoA inhibition by CCG-1423 in vivo. RhoA inhibition prolonged survival and reduced fungal burden in a murine model of disseminated cryptococcosis, supporting the therapeutic potential targeting RhoA in the context of cryptococcal infection. We examine the complex virulence of Cn in establishing CNS disease, describing cellular components of the brain endothelium that may serve as molecular targets for future antifungal therapies to alleviate the burden of life-threatening cryptococcal CNS infection.

SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features.

SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B-cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and SOX11 expression were mutually exclusive in BL. SOX11 expression in EBV- BL was associated with an IG∷MYC translocation generated by aberrant class switch recombination, while in EBV-/SOX11- tumors the IG∷MYC translocation was mediated by mistaken somatic hypermutations. Interestingly, EBV- SOX11 expressing BL showed higher frequency of SMARCA4 and ID3 mutations compared to EBV-/SOX11- cases. By RNA-sequencing, we identified a SOX11-associated gene expression profile, with functional annotations showing partial overlap with the SOX11 transcriptional program of MCL. Contrary to MCL, no differences on cell migration or BCR signaling were found between SOX11- and SOX11+ BL cells. However, SOX11+ BL showed higher adhesion to VCAM-1 than SOX11- BL cell lines. Here we demonstrate that EBV- BL comprises two subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.

SOX11/PRDX2 axis modulates redox homeostasis and chemoresistance in aggressive mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell neoplasm characterized by an aggressive behavior, short responses to conventional therapies and SOX11 overexpression, which is associated with aggressive disease features and inferior clinical outcome of patients. Oxidative stress is known to induce tumorigenesis and tumor progression, whereas high expression levels of antioxidant genes have been associated with chemoresistance in different cancers. However, the role of oxidative stress in MCL pathogenesis and the involvement of SOX11 regulating redox homeostasis in MCL cells are largely unknown. Here, by integrating gene set enrichment analysis of two independent series of MCL, we observed that SOX11+ MCL had higher reactive oxygen species (ROS) levels compared to SOX11- MCL primary tumors and increased expression of Peredoxine2 (PRDX2), which upregulation significantly correlated with SOX11 overexpression, higher ROS production and worse overall survival of patients. SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.

Clinicopathological and Genomic Identification of Breast Cancers with No Impact on Mortality.

BACKGROUND: Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. PATIENTS AND METHODS: To identify them, a retrospective observational study was carried out selecting patients without any palpable tumor and without axillary involvement, and a genomic analysis was performed with PAM50. RESULTS: The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90-0.93) at 20 years and 0.96 (95% CI, 0.92-1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumors and in 9 (9.47%) luminal B tumors smaller than 1 cm, and in HER2 and basal type tumors, there were no metastatic events (20-year DMFI of 1.00). CONCLUSION: Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumor size less than 1 cm. Therefore, de-escalation of treatment should be considered.

Hallazgos histopatológicos en la disección y rotura de la aorta torácica. Estudio de 54 casos de autopsia / Histopathological findings in dissection and rupture of the thoracic aorta. Study of 54 autopsy cases

Introducción la disección/rotura de la aorta torácica tiene una alta mortalidad, constituyendo de 3,9 a 5,4% de las muertes súbitas en series forenses. Los hallazgos histopatológicos de la media asociados a estas entidades han recibido múltiples términos y definiciones. En 2016, la Asociación Europea de Patología Cardiovascular junto con la Sociedad de Patología Cardiovascular publicaron un documento de consenso, aplicado a muestras quirúrgicas, para unificar criterios. El objetivo de este trabajo es valorar su aplicación en las autopsias forenses. Un objetivo secundario es estudiar cambios inflamatorios útiles para la datación. Material y métodos se revisaron las preparaciones histológicas de aorta de 54 casos de muertes súbitas por rotura/disección aórtica estudiados entre 2019 y 2022. Resultados se observó degeneración de la media en 49 casos (90,8%) (severa en 42,9%). Por lesiones, el orden de frecuencia fue: fragmentación y/o pérdida de las fibras elásticas (74,1%); acúmulo de matriz mucoide extracelular (61,1%); pérdida de núcleos de células musculares lisas (48,1%) y colapso de la media (44,4%). Algunas lesiones del documento no pudieron ser valoradas. No se encontraron diferencias significativas por edad; presencia o no de colagenopatías; o válvulas aórticas bi/tricúspides. Se observó tejido de granulación o infiltrado neutrofílico en los fallecidos con dolor de varios días o <24 h antes de la muerte, respectivamente. Conclusión con la aplicación del documento se encuentran lesiones en la media en >90% de los casos y pueden estudiarse las lesiones fundamentales. La respuesta inflamatoria frente a la rotura/disección parece correlacionarse con el momento de la disección/rotura. (AU)

Introduction Thoracic aortic dissection/rupture has a high mortality, constituting 3.9-5.4% of sudden deaths in forensic series. Medial histopathological findings associated with these entities have received multiple terms and definitions. In 2016, the European Association for Cardiovascular Pathology and the Society for Cardiovascular Pathology published a consensus document, applied to surgical specimens, to unify criteria. The aim of this work is to assess its application in forensic autopsies. A secondary objective is to study inflammatory changes useful for dating. Material and methods Aortic histological preparations of the 54 cases of sudden deaths due to aortic rupture/dissection studied between 2019 and 2022 were reviewed. Results Medial degeneration was observed in 49 cases (90.8%) (severe in 42.9%). By lesions, the order of frequency was: fragmentation and/or loss of elastic fibers (74.1%); accumulation of extracellular mucoid matrix (61.1%); loss of smooth muscle cell nuclei (48.1%) and collapse of the media (44.4%). Some lesions of the consensus paper could not be assessed. No significant differences were found by age; presence or not of collagenopathies; or bi/tricuspid aortic valves. Granulation tissue or neutrophilic infiltrate was observed in those deceased with pain several days or <24 h before death, respectively. Conclusion With the application of the document, lesions in the media are found in >90% of cases and fundamental lesions can be studied. The inflammatory response to rupture/dissection appears to correlate with the timing of dissection/rupture. (AU)

Asociación entre la historia reproductiva, el subtipo de cáncer de mama y la supervivencia de mujeres premenopáusicas / Association between reproductive history, breast cancer subtype, and survival in premenopausal women

Antecedentes y objetivo: La historia reproductiva influye en el riesgo de cáncer de mama. Hemos analizado su asociación con el subtipo tumoral y la supervivencia en mujeres premenopáusicas. Pacientes y métodos: Estudio observacional, retrospectivo, de mujeres premenopáusicas con carcinoma de mama, estadios I-III, en los últimos 20 años. Revisión de la historia reproductiva, de los datos clínicos y de los tratamientos en las historias de salud. Resultados: En 661 mujeres premenopáusicas (32,40% de 1.377 totales), la mediana de edad fue de 47 años (19-53), de la menarquia 12 (7-17), del primer parto 28 (16-41) y de número de partos 2 (0-9). Fueron nulíparas 111 (18,20%). Emplearon lactancia natural 359 (58,80%) con mediana de duración de 6 meses. Consumieron anovulatorios 271 (44,40%), con mediana de 36 meses. Se halló asociación entre menarquia <10 años y menos riesgo de subtipo luminal (OR: 0,52; IC 95%: 0,28-0,94; p=0,03), entre menarquia >11 años y menos riesgo de subtipo HER2 (OR: 0,50; IC 95%: 0,26-0,97; p=0,04) y entre primer parto >30 años y menos riesgo de subtipo triple negativo (OR: 0,40; IC 95%: 0,17-0,93; p=0,03). La probabilidad de supervivencia global y libre de enfermedad a 20 años fue de 0,80 (IC 95%: 0,71-0,90) y 0,72 (IC 95%: 0,64-0,79), respectivamente. Las pacientes con uno o más de un parto presentaron mejor supervivencia global que las nulíparas (HR: 0,51; IC 95%: 0,27-0,96, p=0,04). Conclusiones: Los hallazgos sugieren que existe asociación entre edad de la menarquia y del primer parto y subtipo de cáncer de mama. La nuliparidad está asociada con peor supervivencia.(AU)

Background and objective: Reproductive history influences breast cancer risk. We analysed its association with tumour subtype and survival in premenopausal women. Patients and methods: Retrospective, observational study of premenopausal women with stage I-III breast carcinoma in the last 20 years. Review of reproductive history, clinical data, and treatments in health records.Results: In 661 premenopausal women (32.40% of 1377 total cases), median age was 47 years (19-53), menarche 12 (7-17), first delivery 28 (16-41) and number of deliveries 2 (0-9). One hundred and eleven (18.20%) were nulliparous. Three hundred and fifty-nine (58.80%) used natural lactation, with a median duration of 6 months. Anovulatory drugs were used by 271 (44.40%), with a median duration of 36 months. Associations were found between menarche <10 years and lower risk of luminal subtype (OR: 0.52, 95% CI: 0.28-0.94; P=.03), between menarche >11 years and lower risk of HER2 subtype (OR: 0.50, 95% CI: 0.26-0.97; P=.04) and between first birth >30 years and lower risk of triple negative subtype (OR: 0.40, 95% CI: 0.17-0.93; P=.03). The 20-year overall and disease-free survival probabilities were 0.80 (95% CI: 0.71–0.90) and 0.72 (95% CI: 0.64-0.79) respectively. Patients with ≥1 delivery had better overall survival than nulliparous patients (HR: 0.51, 95% CI: 0.27-0.96, P=.04). Conclusions: The findings suggest an association between age at menarche and age at first delivery and breast cancer subtype. Nulliparity is associated with worse survival.(AU)

SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma.

The sterile alpha motif and histidine-aspartate (HD) domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several haematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara-C efficacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMG-box containing protein 11 (SOX11) as a novel direct binding partner and first known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Co-immunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identified SAMHD1 as the top SOX11 interaction partner which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar affinity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara-C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identified SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its first known endogenous inhibitor with potentially important implications for clinical therapy stratification.

Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

PDZome-wide and structural characterization of the PDZ-binding motif of VANGL2.

VANGL2 is a core component of the non-canonical Wnt/Planar Cell Polarity signaling pathway that uses its highly conserved carboxy-terminal type 1 PDZ-binding motif (PBM) to bind a variety of PDZ proteins. In this study, we characterize and quantitatively assess the largest VANGL2 PDZome-binding profile documented so far, using orthogonal methods. The results of our holdup approach support VANGL2 interactions with a large panel of both long-recognized and unprecedented PDZ domains. Truncation and point mutation analyses of the VANGL2 PBM establish that, beyond the strict requirement of the P-0 / V521 and P-2 / T519 amino acids, upstream residues, including E518, Q516 and R514 at, respectively, P-3, P-5 and P-7 further contribute to the robustness of VANGL2 interactions with two distinct PDZ domains, SNX27 and SCRIBBLE-PDZ3. In agreement with these data, incremental amino-terminal deletions of the VANGL2 PBM causes its overall affinity to progressively decline. Moreover, the holdup data establish that the PDZome binding repertoire of VANGL2 starts to diverge significantly with the truncation of E518. A structural analysis of the SYNJ2BP-PDZ/VANGL2 interaction with truncated PBMs identifies a major conformational change in the binding direction of the PBM peptide after the P-2 position. Finally, we report that the PDZome binding profile of VANGL2 is dramatically rearranged upon phosphorylation of S517, T519 and S520. Our crystallographic approach illustrates how SYNJ2BP accommodates a S520-phosphorylated PBM peptide through the ideal positioning of two basic residues, K48 and R86. Altogether our data provides a comprehensive view of the VANGL2 PDZ network and how this network specifically responds to the post-translation modification of distinct PBM residues. These findings should prove useful in guiding future functional and molecular studies of the key PCP component VANGL2.

Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-ß was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.

Association between reproductive history, breast cancer subtype, and survival in premenopausal women. / Asociación entre la historia reproductiva, el subtipo de cáncer de mama y la supervivencia de mujeres premenopáusicas.

BACKGROUND AND OBJECTIVE: Reproductive history influences breast cancer risk. We analysed its association with tumour subtype and survival in premenopausal women. PATIENTS AND METHODS: Retrospective, observational study of premenopausal women with stage I-III breast carcinoma in the last 20 years. Review of reproductive history, clinical data, and treatments in health records. RESULTS: In 661 premenopausal women (32.40% of 1377 total cases), median age was 47 years (19-53), menarche 12 (7-17), first delivery 28 (16-41) and number of deliveries 2 (0-9). One hundred and eleven (18.20%) were nulliparous. Three hundred and fifty-nine (58.80%) used natural lactation, with a median duration of 6 months. Anovulatory drugs were used by 271 (44.40%), with a median duration of 36 months. Associations were found between menarche <10 years and lower risk of luminal subtype (OR: 0.52, 95% CI: 0.28-0.94; P=.03), between menarche >11 years and lower risk of HER2 subtype (OR: 0.50, 95% CI: 0.26-0.97; P=.04) and between first birth >30 years and lower risk of triple negative subtype (OR: 0.40, 95% CI: 0.17-0.93; P=.03). The 20-year overall and disease-free survival probabilities were 0.80 (95% CI: 0.71-0.90) and 0.72 (95% CI: 0.64-0.79) respectively. Patients with ≥1 delivery had better overall survival than nulliparous patients (HR: 0.51, 95% CI: 0.27-0.96, P=.04). CONCLUSIONS: The findings suggest an association between age at menarche and age at first delivery and breast cancer subtype. Nulliparity is associated with worse survival.

Dietary proteins modulate high-density lipoprotein characteristics in a sex-specific way in Apoe-deficient mice.

OBJECTIVES: The type and amount of dietary protein have become a topic of renewed interest, considering their involvement in several diseases. However, little attention has been devoted to the effect of avian proteins despite their wide human consumption. In a previous study, we saw that compared with soybean protein, the consumption of avian proteins, depending on sex, resulted in similar or lower atherosclerosis with a higher paraoxonase 1 activity, an antioxidant enzyme carried by high-density lipoproteins (HDL). This suggests that under these conditions, the HDL lipoproteins may undergo important changes. The aim of this research was to study the influence of soybean, chicken, and turkey proteins on the characteristics of HDL. METHODS: Male and female Apoe-deficient mice were fed purified Western diets based on the AIN-93 diet, differing only in the protein source, for 12 wk. After this period, blood and liver samples were taken for analysis of HDL composition and hepatic expression of genes related to HDL metabolism (Abca1, Lcat, Pltp, Pon1, and Scarb1). Depending on sex, these genes define a different network of interactions. Females consuming the turkey protein-containing diet showed decreased atherosclerotic foci, which can be due to larger very-low-density lipoproteins (VLDLs) calculated by molar ratio triacylglycerols/VLDL cholesterol and higher expression of Lcat. In contrast, in males, a higher ratio of paraoxonase1 to apolipoprotein A1 decreased the oxidative status of the different lipoproteins, and augmented Abca1 expression was observed. CONCLUSIONS: The source of protein has an effect on the development of atherosclerosis depending on sex by modifying HDL characteristics and the expression of genes involved in their properties.

Innovative and potential treatments for fungal central nervous system infections.

Fungal infections of the central nervous system (FI-CNS) are a problematic and important medical challenge considering that those most affected are immunocompromised. Individuals with systemic cryptococcosis (67-84%), candidiasis (3-64%), blastomycosis (40%), coccidioidomycosis (25%), histoplasmosis (5-20%), mucormycosis (12%), and aspergillosis (4-6%) are highly susceptible to develop CNS involvement, which often results in high mortality (15-100%) depending on the mycosis and the affected immunosuppressed population. Current antifungal drugs are limited, prone to resistance, present host toxicity, and show reduced brain penetration, making FI-CNS very difficult to treat. Given these limitations and the rise in FI-CNS, there is a need for innovative strategies for therapeutic development and treatments to manage FI-CNS in at-risk populations. Here, we discuss standards of care, antifungal drug candidates, and novel molecular targets in the blood-brain barrier, which is a protective structure that regulates movement of particles in and out of the brain, to prevent and combat FI-CNS.

Frequency of symptoms and the associated factors of eating disorders in a group of dental students in Medellín, Colombia.

BACKGROUND: Eating disorders (EDs) are considered a public health problem. Scientific research has focused on teenagers due to their higher prevalence in this population. However, other groups, such as university students, may be exposed to suffering from EDs due to their academic, social and personal characteristics. Identifying the magnitude of EDs and the associated characteristics may impact the generation of prevention strategies. OBJECTIVES: The aim of the present study was to establish the prevalence of the risk of EDs (anorexia nervosa (AN) and bulimia nervosa (BN)) and the associated factors in dental students at the University of Antioquia, Medellín, Colombia.. MATERIAL AND METHODS: A cross-sectional study was conducted on 278 students (76 males, 202 females) with the use of a Google-Forms survey. The validated Spanish version of the Eating Attitudes Test-26 (EAT-26) and the Sick, Control, One Stone, Fat, Food (SCOFF) questionnaire were used. Other recorded variables included sociodemographic data, coronavirus disease 2019 (COVID-19)-related factors, health, and social support (the Duke-11 profile). The bivariate analysis of the risk of EDs was conducted according to different variables (95% confidence interval (CI)), followed by the logistic regression models adjusting for different variables (adjusted prevalence ratio (aPR) and 95% CI). RESULTS: According to EAT-26, the risk of EDs was 27.6% (18.8-38.6) for males and 28.7% (22.9-35.3) for females. However, differences between males and females were higher when the SCOFF questionnaire was applied (males: 6.6% (2.8-14.5); females: 22.3% (17.1-28.5); p < 0.01). According to the SCOFF instrument, after adjusting for sociodemographic and health variables, women were more likely to report the symptoms of EDs (aPR: 2.20; 95% CI: 1.06-4.57). Women receiving information from social networks were more likely to report the symptoms of EDs (aPR: 1.85; 95% CI: 1.19-2.88). Multivariate models showed that women reporting poor self-rated health and some symptoms during the mandatory confinement caused by the COVID-19 pandemic were more likely to report the symptoms of EDs. CONCLUSIONS: A higher risk of EDs was found in dental students. Healthcare, psychological and/or psychiatric interviews, and educational/early prevention strategies are required.

Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosis in vivo.

Cryptococcus neoformans (Cn) is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments. Palmitoylethanolamide (PEA) is an immunomodulatory compound capable of promoting neuroprotection and reducing inflammation. To investigate the efficacy of PEA as a therapeutic alternative for CME, we intracerebrally infected mice with Cn and treated them with PEA or AmpB alone or in combination. Our results demonstrate that PEA alone does not significantly prolong survival nor reduce fungal burden, but when combined with AmpB, PEA exerts an additive effect and promotes both survivability and fungal clearance. However, we compared this combination to traditional AmpB and 5-FC treatment in a survivability study and observed lower efficacy. Overall, our study revealed that PEA alone is not effective as an antifungal agent in the treatment of CME. Importantly, we describe the therapeutic capability of PEA in the context of Cn infection and show that its immunomodulatory properties may confer limited protection when combined with an effective fungicidal agent.

Short-term dietary intervention improves endothelial dysfunction induced by high-fat feeding in mice through upregulation of the AMPK-CREB signaling pathway.

AIM: In addition to functioning as an energy sensor switch, AMPK plays a key role in the maintenance of cardiovascular homeostasis. However, obesity disrupts AMPK signaling, contributing to endothelial dysfunction and cardiovascular disease. This study aimed to elucidate if a short-term dietary intervention consisting in replacing the high-fat diet with a standard diet for 2 weeks could reverse obesity-induced endothelial dysfunction via AMPK-CREB activation. METHODS: For this, 5-week-old male C57BL6J mice were fed a standard (Chow) or a high-fat (HF) diet for 8 weeks. The HF diet was replaced by the chow diet for the last 2 weeks in half of HF mice, generating 3 groups: Chow, HF and HF-Chow. Vascular reactivity and western-blot assays were performed in the thoracic aorta. RESULTS: Returning to a chow diet significantly reduced body weight and glucose intolerance. Relaxant responses to acetylcholine and the AMPK activator (AICAR) were significantly impaired in HF mice but improved in HF-Chow mice. The protein levels of AMPKα, p-CREB and antioxidant systems (heme oxygenase-1 (HO-1) and catalase) were significantly reduced in HF but normalized in HF-Chow mice. CONCLUSION: Improving dietary intake by replacing a HF diet with a standard diet improves AMPK-mediated responses due to the upregulation of the AMPK/CREB/HO-1 signaling pathway.

Axillary management in patients with breast cancer and positive axilla at diagnosis. Experience in a Spanish university hospital with a 5-year follow-up.

Background: Axillary lymph node dissection (ALND) was the standard in breast cancer with axillary involvement until recently. Along with the number of metastatic nodes, axillary positivity was considered a main prognostic factor and scientific evidence shows that the administration of radiotherapy on ganglion areas decreases the risk of recurrence even in positive axilla. The objective of this study was to evaluate the axillary treatment in patients with positive axilla at diagnosis, the evolution of them over time, and to assess patient's follow-up with the aim of avoiding the morbidity associated with axillary dissection. Methods: A retrospective observational study of breast cancer patients diagnosed between 2010 and 2017 was performed. In total, 1,100 patients were studied, out of which 168 were women with clinically and histologically positive axilla at diagnosis. Seventy-six percent received primary chemotherapy and subsequent treatment with sentinel node biopsy, axillary dissection, or both. Patients with positive sentinel lymph node biopsy received either radiotherapy or lymphadenectomy depending on the year time they were diagnosed. Results: For 60 patients out of 168, neoadjuvant chemotherapy resulted in a complete pathological axillary response. Axillary recurrence was registered for six patients. No recurrence was detected in the biopsy group associated with radiotherapy. These results support the benefit of lymph node radiotherapy for patients with positive sentinel node biopsy after receiving primary chemotherapy. Conclusion: Sentinel node biopsy provides useful and reliable information about cancer staging and might prevent lymphadenectomy, leading to a decrease in morbidity. Pathological response to systemic treatment came out as the most important predictive factor of disease-free survival of breast cancer.

Borylated Subphthalocyanines: Versatile Precursors for the Preparation of Functional Bowl-Shaped Aromatics.

The peripheral borylation of porphyrinoids has become a key step to prepare advanced functional materials. This study reports the synthesis, electronic properties, and reactivity of borylated subphthalocyanines. These compounds, which are prepared by Suzuki-Miyaura borylation in excellent yields, are easily purified, display a great stability, and serve as powerful starting materials for the post-functionalization of SubPcs via cross-coupling reactions. Remarkably, this novel approach is more efficient than the methodologies already described and enables the preparation of exotic systems, such as SubPc dimeric species linked by C-C bonds, which are not accessible so far and present promising properties for optoelectronic devices.

Production of Dihydrogen Using Ammonia Borane as Reagent and Pyrazole as Catalyst.

Theoretical chemistry (DLPNO-CCSD(T)/def2-TZVP//M06-2x/aug-cc-pVDZ) was used to design a system based on ammonia boranes catalyzed by pyrazoles with the aim of producing dihydrogen, nowadays of high interest as clean fuel. The reactivity of ammonia borane and cyclotriborazane were investigated, including catalytic activation through 1H-pyrazole, 4-methoxy-1H-pyrazole, and 4-nitro-1H-pyrazole. The results point toward a catalytic cycle by which, at the same time, ammonia borane can initially store and then, through catalysis, produce dihydrogen and amino borane. Subsequently, amino borane can trimerize to form cyclotriborazane that, in presence of the same catalyst, can also produce dihydrogen. This study proposes therefore a consistent progress in using environmentally sustainable (metal free) catalysts to efficiently extract dihydrogen from small B-N bonded molecules.

Percepciones sobre salud (física, mental y bucal) en un grupo de mujeres en situación de prostitución en la ciudad de Medellín

Introducción: las mujeres y las personas trans que han ejercido el trabajo sexual se encuentran vulneradas puesto que son víctimas de discriminación por su condición laboral, por su género y por los riesgos que acarrea esta labor, y esto impacta en su situación de salud. Este estudio tuvo como objetivo conocer las percepciones sobre salud (física, mental y bucal) en cuatro mujeres que ejercen la prostitución en Medellín, a partir de sus experiencias de vida y aquellas relacionadas con su contexto social. Métodos: se realizó una investigación cualitativa con enfoque etnográfico para analizar las situaciones mencionadas de acuerdo con el objetivo general. Se contó con la participación de cuatro mujeres: dos de nacionalidad venezolana y dos de nacionalidad colombiana; se llevaron a cabo entrevistas semiestructuradas. Se realizó análisis de contenido cualitativo, lo cual permitió la generación de cuatro categorías (salud mental, salud bucal, salud general y calidad de vida). Resultados: sus discursos permitieron elucidar la conexión entre las condiciones de vida y la situación de salud. La falta de oportunidades laborales, un proceso migratorio de profundos cambios económicos y sociales, y una Colombia con inequidades y barreras de acceso a servicios de salud y sociales, son procesos determinantes de orden general, particular y singular de las precarias condiciones de salud bucal y general. Conclusiones: la población participante se encuentra en situación de vulnerabilidad social y de salud, lo cual evidencia la necesidad de políticas públicas y estrategias basadas en la realidad social que contribuyan a generar equidad en salud.

Introduction: women and trans people who have engaged in sex work are triply vulnerable since they are victims of discrimination due to their employment status, their gender, and the risks that this work entails, this impacts their health situation. This study aimed to know the perceptions about health (physical, mental, and oral) of four women who work in prostitution in Medellin, based on their life experiences and those related to their social context. Methods: qualitative research with an ethnographic approach was conducted to analyze the situations mentioned. Four women participated, two Venezuelans and two Colombians, and semi-structured interviews were conducted. Qualitative content analysis was performed, which allowed the generation of four categories (mental health, oral health, general health, and quality of life). Results: her discourses made it possible to elucidate the connection between the living conditions and the health situation. Lack of job opportunities, a migratory process of profound economic and social changes, and a Colombia with inequities and barriers to access to health and social services are determining processes of a general and singular order of the precarious conditions of oral health and general. Conclusions: the participating population is in a situation of social and health vulnerability, which shows the need for public policies and strategies based on the social reality that contribute to generating equity in health.