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Borderline Ovarian Tumours (BOTs) are an interesting subset of epithelial neoplasms defined histologically by atypical epithelial proliferation without stromal invasion. These tumours typically affect young women in the reproductive age group and have a good prognosis. Although ultrasonography is the primary screening imaging technique in the evaluation of any suspected adnexal mass, grey-scale and colour Doppler have limited value in characterizing BOTs. Thus, a pelvic magnetic resonance imaging (MRI) is recommended for further characterization on account of its multiplanar capabilities, excellent soft-tissue contrast and high spatial resolution. BOTs histological subtypes display specific features on MRI that are useful in differential diagnosis. However, the final diagnosis and staging of BOTs require pathologic evaluation after surgical excision. Therefore, the purpose of this review is to describe, illustrate and compare the imaging characteristics of the different subtypes of BOTs - serous, mucinous and seromucinous - focusing on MRI, as well as to correlate with pathology findings considering the recent 2020 World Health Organization (WHO) classification, in order to improve the accuracy of preoperative diagnosis and facilitate optimal patient management. [ABSTRACT FROM AUTHOR]

A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Portugal. Expression of estrogen receptors alpha (ERα) and beta (ERβ), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ERα and ERβ expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ERα, ERβ and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation. [ABSTRACT FROM AUTHOR]

p53 protein immunoexpression was evaluated in 17 invasive carcinomas arising in pleomorphic adenoma and correlated with the histologic type and tumor grade. Ten tumors had one malignant histologic component: adenocarcinoma NOS (not otherwise specified) (five), undifferentiated carcinoma (two), malignant myoepithelioma (one), epithelial-myoepithelial carcinoma (one), and malignant oncocytoma (one). In the remaining cases, there was a coexistence of areas of adenocarcinoma (seven), adenosquarious (two), epithelial-myoepithelial (two), adenoid cystic (two), undifferentiated carcinoma (one), and low-grade polymorphous adenocarcinoma (one). p53 positivity was found within adenocarcinoma NOS (three) and adenosquamous carcinoma (two) components of four cases. Tumor areas showing low-grade histology, either mono- or bidifferentiated carcinomas, were always negative in this series, in keeping with previous observations on primary neoplasms of the same histologic type. The benign component of the neoplasms was also found to be consistently negative. The results point to a preferential association of the p53 gene dysfunction and its protein accumulation with the malignant transformation of pleomorphic adenomas into salivary adenocarcinomas with features of high-grade malignancy. [ABSTRACT FROM AUTHOR]

Aortic stenosis was once considered a pure isolated valve obstacle challenging left ventricle driving force of contraction and flow generation. Left ventricular (LV) adaptation was merely interpreted as a uniform hypertrophic response to increased afterload. However, in these last 2 decades cardiac imaging research and some histopathology correlation studies brought insight towards the complex interaction between the vasculature, the valve and the myocardium. Verily, LV remodeling in this setting is a complex multidetermined process that goes further beyond myocardial hypertrophy. Ultrastructural changes involving both diffuse and replacement fibrosis of the myocardium take part and might explain the transition of clinical phenotypes with distinct prognosis, from compensated hypertrophy to LV maladaptive dysfunction and heart failure. Presently, the combined appropriate use of echocardiography and cardiac magnetic resonance may better assess the global LV afterload, hypertrophy and geometric remodeling, global and regional LV function, beyond ejection fraction, and structural changes that include the fibrotic burden of the myocardium. As a whole these may not only better stratify individual risk of disease progression but also identify patients benefiting from earlier valve intervention. In this paper, we review the maladaptive response of the LV to chronic pressure overload, describing the different signaling pathways and mechanisms that underly both hypertrophy and remodeling. Histomorphology changes in this setting are described and we try to make sense of the use of new imaging tools for LV characterization. [ABSTRACT FROM AUTHOR]

Ovarian carcinoma (OvC) remains a major therapeutic challenge due to its propensity to develop resistance after an initial response to chemotherapy. Interactions of tumour cells with the surrounding microenvironment play a role in tumour survival, invasion capacity and drug resistance. Cancer models that retain tissue architecture and tumour microenvironment components are therefore essential to understand drug response and resistance mechanisms. Herein, our goal was to develop a long-term OvC patient-derived explant (OvC-PDE) culture strategy in which architecture and cell type heterogeneity of the original tumour would be retained. Samples from 25 patients with distinct OvC types and one with a benign tumour, were cultured for 30 days in agitation-based culture systems with 100% success rate. OvC-PDE cultures retained the original tumour architecture and main cellular components: epithelial cells, fibroblasts and immune cells. Epithelial cells kept their original levels of proliferation and apoptosis. Moreover, the major extracellular components, such as collagen-I and -IV, were retained in explants. OvC-PDE cultures were exposed to standard-of-care chemotherapeutics agents for 2 weeks, attesting the ability of the platform for drug assays employing cyclic drug exposure regimens. We established an OvC-PDE dynamic culture in which tumour architecture and cell type heterogeneity were preserved for the different OvC types, replicating features of the original tumour and compatible with long-term drug exposure for drug efficacy and resistance studies. [ABSTRACT FROM AUTHOR]

The Challenge Hypothesis (Wingfield et al. Am. Nat. 136, 829-846) aims to explain the complex relationship between androgens and social interactions. Despite its well acceptance in the behavioral endocrinology literature, several studies have failed to found an androgen response to staged social interactions. Possible reasons for these inconsistencies are the use of single sampling points that may miss the response peak, and the occurrence of inter-individual variability in the androgen response to social interactions. In this study we addressed these two possible confounding factors by characterizing the temporal pattern of the androgen response to social interactions in the African cichlid, Oreochromis mossambicus, and relating it to inter-individual variation in terms of the individual scope for androgen response (i.e. the difference between baseline and maximum physiological levels for each fish) and behavioral types. We found that the androgen response to territorial intrusions varies between individuals and is related to their scope for response. Individuals that have a lower scope for androgen response did not increase androgens after a territorial intrusion but were more aggressive and exploratory. In contrast males with a higher scope for response had fewer aggressive and exploratory behaviors and exhibited two peaks of KT, an early response 2–15 min after the interaction and a late response at 60–90 min post-interaction. Given that the pharmacological challenge of the Hypothalamic-Pituitary-Gonad axis only elicits the late response, we suggest that these two peaks may be regulated by different physiological mechanisms, with the early response being mediated by direct brain-gonad neural pathways. In summary, we suggest that determining the temporal pattern of the androgen response to social interactions and considering inter-individual variation may be the key to understanding the contradictory results of the Challenge Hypothesis. • The time course of the androgen response to social interaction varies between individuals. • Individuals with a lower scope for androgen response did not increase androgens after a territorial intrusion. • Individuals with a higher scope for androgen response exhibit two waves of KT response. • Responders and non-responders consistently differ in their fewer aggressive and exploratory behaviors. • The two androgen peaks present in responders seem to be regulated by different physiological mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the magnetic resonance imaging (MRI) features that may help distinguish leiomyosarcomas from atypical leiomyomas (those presenting hyperintensity on T2-W images equal or superior to 50% compared to the myometrium). Materials and methods: The authors conducted a retrospective single-centre study that included a total of 57 women diagnosed with smooth muscle tumour of the uterus, who were evaluated with pelvic MRI, between January 2009 and March 2020. All cases had a histologically proven diagnosis (31 Atypical Leiomyomas—ALM; 26 Leiomyosarcomas—LMS). The MRI features evaluated in this study included: age at presentation, dimension, contours, intra-tumoral haemorrhagic areas, T2-WI heterogeneity, T2-WI dark areas, flow voids, cyst areas, necrosis, restriction on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) values, signal intensity and heterogeneity after contrast administration in T1-WI, presence and location of unenhanced areas. The association between the MRI characteristics and the histological subtype was evaluated using Chi-Square and ANOVA tests. Results: The MRI parameters that showed a statistically significance correlation with malignant histology and thus most strongly associated with LMS were found to be: irregular contours (p < 0.001), intra-tumoral haemorrhagic areas (p = 0.028), T2-WI dark areas (p = 0.016), high signal intensity after contrast administration (p = 0.005), necrosis (p = 0.001), central location for unenhanced areas (p = 0.026), and ADC value lower than 0.88 × 10−3 mm2/s (p = 0.002). Conclusion: With our work, we demonstrate the presence of seven MRI features that are statistically significant in differentiating between LMS and ALM. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 55-year-old male truck driver and retired professional boxer who was brought to an emergency hospital due to sudden onset of hemiparesis following a focal complex hemiconvulsion. It outlines the patient's history including obesity and hyperhomocysteinemia. It adds that the brain computed tomography confirms the presence of ganglionic hypertensive hematoma, severe leukoaraiosis and dilated brain perivascular spaces that look like a honeycomb.

Background: Viral rewiring of host bioenergetics and immunometabolism may provide novel targets for therapeutic interventions against viral infections. Here, we have explored the effect on bioenergetics during the infection with the mosquito-borne flavivirus West Nile virus (WNV), a medically relevant neurotropic pathogen causing outbreaks of meningitis and encephalitis worldwide. Results: A systematic literature search and meta-analysis pointed to a misbalance of glucose homeostasis in the central nervous system of WNV patients. Real-time bioenergetic analyses confirmed upregulation of aerobic glycolysis and a reduction of mitochondrial oxidative phosphorylation during viral replication in cultured cells. Transcriptomics analyses in neural tissues from experimentally infected mice unveiled a glycolytic shift including the upregulation of hexokinases 2 and 3 (Hk2 and Hk3) and pyruvate dehydrogenase kinase 4 (Pdk4). Treatment of infected mice with the Hk inhibitor, 2-deoxy-D-glucose, or the Pdk4 inhibitor, dichloroacetate, alleviated WNV-induced neuroinflammation. Conclusions: These results highlight the importance of host energetic metabolism and specifically glycolysis in WNV infection in vivo. This study provides proof of concept for the druggability of the glycolytic pathway for the future development of therapies to combat WNV pathology. [ABSTRACT FROM AUTHOR]

AL-471, the leading exponent of a class of potent HIV and enterovirus A71 (EV-A71) entry inhibitors discovered in our research group, contains four l-tryptophan (Trp) units bearing an aromatic isophthalic acid directly attached to the C2 position of each indole ring. Starting from AL-471, we (i) replaced l-Trp with d-Trp, (ii) inserted a flexible linker between C2 and the isophthalic acid, and (iii) substituted a nonaromatic carboxylic acid for the terminal isophthalic acid. Truncated analogues lacking the Trp motif were also synthesized. Our findings indicate that the antiviral activity seems to be largely independent of the stereochemistry (l- or d-) of the Trp fragment and also that both the Trp unit and the distal isophthalic moiety are essential for antiviral activity. The most potent derivative, 23 (AL-534), with the C2 shortest alkyl urea linkage (three methylenes), showed subnanomolar potency against different EV-71 clinical isolates. This finding was only observed before with the early dendrimer prototype AL-385 (12 l-Trp units) but remained unprecedented for the reduced-size prototype AL-471. Molecular modeling showed the feasibility of high-affinity binding of the novel l-Trp-decorated branches of 23 (AL-534) to an alternative site on the VP1 protein that harbors significant sequence variation among EV-71 strains. [ABSTRACT FROM AUTHOR]