Primary thromboprophylaxis in cancer outpatients - real-world evidence.

INTRODUCTION: Cancer-associated thrombosis (CAT) is a significant concern among patients with malignant diseases, leading to increased mortality. While current guidelines recommend primary thromboprophylaxis for venous thromboembolism (VTE) in medium-to-high-risk outpatients, this practice remains controversial. A better understanding of primary thromboprophylaxis is crucial, yet there is a lack of Real-World Evidence (RWE) in Portugal. AIMS: This RWE study aimed to elucidate primary thromboprophylaxis practices among cancer outpatients in Portugal. METHODS: A five-year observational multicentric study in eight Portuguese health institutions enrolled 124 adult cancer outpatients under primary thromboprophylaxis for VTE. The endpoints were CAT, bleeding, cancer progression and death. RESULTS: High thrombotic risk tumours were prevalent, with 57% (71) of the patients presenting with pancreatic and gastric cancers. Regarding primary thromboprophylaxis, 55% (68) received Low-Molecular-Weight Heparin (LMWH). VTE was presented in 11% (14) of the patients and major bleeding in 2% (2). Vascular compression, elevated D-dimer and previous VTE were significantly associated with VTE occurrence under primary thromboprophylaxis. The Onkotev model was shown to be the best risk assessment model (RAM) in this population (p = 0.007). CAT patients exhibited a lower progression-free survival than non-CAT patients (p = 0.021), while thrombosis did not influence overall survival (p = 0.542). CONCLUSION: Primary thromboprophylaxis in medium-to-high-risk cancer outpatients is a safe and effective practice in real-world settings. This study is the first Portuguese RWE on primary thromboprophylaxis, highlighting evidence for improving prophylactic strategies in this population.

The aconitate decarboxylase 1/itaconate pathway modulates immune dysregulation and associates with cardiovascular disease markers in SLE.

Objective: The Krebs cycle enzyme Aconitate Decarboxylase 1 (ACOD1) mediates itaconate synthesis in myeloid cells.. Previously, we reported that administration of 4-octyl itaconate abrogated lupus phenotype in mice. Here, we explore the role of the endogenous ACOD1/itaconate pathway in the development of murine lupus as well as their relevance in premature cardiovascular damage in SLE. Methods: We characterized Acod1 protein expression in bone marrow-derived macrophages and human monocyte-derived macrophages, following a TLR7 agonist (imiquimod, IMQ). Wild type and Acod1-/- mice were exposed to topical IMQ for 5 weeks to induce an SLE phenotype and immune dysregulation was quantified. Itaconate serum levels were quantified in SLE patients and associated to cardiometabolic parameters and disease activity. Results: ACOD1 was induced in mouse bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages following in vitro TLR7 stimulation. This induction was partially dependent on type I Interferon receptor signaling and specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum anti-dsDNA and proinflammatory cytokine levels, enhanced kidney immune complex deposition and proteinuria, when compared to the IMQ-treated WT mice. Consistent with these results, Acod1-/- BMDM exposed to IMQ showed higher proinflammatory features in vitro. Itaconate levels were decreased in SLE serum compared to healthy control sera, in association with specific perturbed cardiometabolic parameters and subclinical vascular disease. Conclusion: These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in SLE, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.

Sinonasal Adenocarcinoma: Clinicopathological Characterization and Prognostic Factors.

Sinonasal (SN) malignancies are rare. Within SN adenocarcinomas, the most frequent are intestinal-type adenocarcinomas (ITACs). ITAC has been associated with wood and leather dust occupational exposure and TP53 mutations. Not much information is available regarding its characterization and treatment. The aim of this study is to characterize the clinicopathologic and prognostic factors of patients with sinonasal adenocarcinomas (SNACs) treated in our tertiary-level hospital. A retrospective, consecutive study including SNAC patients diagnosed between 2004-2023 was conducted. Clinicopathological data was collected, and p53 status was assessed in the tumor specimens. The association between p53 status and clinicopathological variables, as well as their impact on survival, was evaluated. In total, 35 were included, most of them having ITAC (91.4%) with papillary subtype (37.5%); the majority were subjected to occupational risk exposure (82.9%). Overexpression of p53 was identified in 48.6% of the tumors. Papillary and colonic subtypes were associated with higher median progression-free survival (mPFS) than mucinous and solid subtypes (mPFS 37 months, 95% CI, 20.0-54.0, vs. 9 months, 95% CI, 7.15-10.85, p=0.01); the former was also associated with higher median overall survival (mOS) (mOS 64 months, 95% CI, 37.18-90.81 vs. 14 months, 95% CI, 0-41.58, p=0.02). Histologic grade 1-2 and macroscopic complete resection were associated with higher PFS (PFS of five months of 90.9% vs. 33.3%, p=0.01; mPFS of 37 months, 95% CI, 4.93-69.07 vs. 10 months, 95% CI, 6.43-13.57, p=0.04, respectively). Disease recurrence with distant metastases was associated with lower OS (11 months, 95% CI, 6.1-15.9 vs. 53 months, 95% CI, 22.70-83.30, p=0.04). This study reinforces the importance of protective occupational measures. Future studies will be important to validate the best treatment strategy in the advanced stages of this disease and also to identify new prognostic and/or therapeutic target biomarkers in SNAC.

It's You and Me: Infants' cross-modal communicative signals and mother-infant interactive behavior predict infant regulatory patterns in the still-face paradigm at 3 months.

Infant regulatory behavior develops since birth and impacts their early social interactions. Infants differ in the relative coherence and incoherence of their cross-modal communicative signals during en-face infant-caregiver interactions. We expand this research by evaluating whether different infant regulatory patterns observed during the Face-to-Face Still-Face (FFSF) at 3 months are associated with the coherence or incoherence of infants' cross-modal communicative behaviors during en-face interactions or with multiple dimensions of mother-infant interactive behavior during free-play. Analyses were based on data collected from 100 mother-infant dyads from urban, working- and middle-class backgrounds in Portugal who were videotaped during the FFSF and free play at 3 months. Results confirm that infants' different regulatory behavior patterns in the FFSF at 3 months are associated with the coherence and incoherence of their cross-modal interactive behaviors and specific aspects of mother-infant interaction. Infants with a Social-Positive oriented regulatory pattern during the FFSF displayed more coherent and less incoherent communicative behaviors with their mothers and were more cooperative during free play. In turn, their mothers were more sensitive. Our findings support the perspective that infants' regulatory behavior strategies in the context of caregiver regulatory support and sensitivity are likely to increase dyadic correspondence and infant ability to engage with the world.

Attachment and mother-infant interactions in dyads with infants born full-term, moderate-to-late preterm, and very-to-extreme preterm.

BACKGROUND: The impact of prematurity status on attachment quality remains indeterminate. Some studies found no differences between infants born preterm (PT) and infants born full-term (FT), while other investigations present opposite results. AIMS: We aim to contribute to this body of research by studying mother-infant interactive behaviors and quality of attachment in 3 independent samples: Full-Term (FT), Moderate-to-Late Preterm (MLPT) and Very-to-Extreme Preterm (VEPT). STUDY DESIGN: This is a longitudinal laboratory study conducted from 3 to 12 months of age (corrected-age in the case of infants born PT). SUBJECTS: The participants are 213 Portuguese infants (FT = 105; MLPT = 52; VEPT = 56) and their mothers. OUTCOME MEASURES: Mother-infant interactive behavior was observed in free-play at 3 and 9 months (corrected-age). Infant attachment was observed in Strange Situation at 12 months. RESULTS: Secure attachment is more prevalent in infants born FT, and ambivalent attachment is more prevalent in infants born VEPT. Infants with a secure attachment have higher gestational age and weight at birth. Infant and maternal interactive behavior quality is associated with attachment patterns and varies according to infant prematurity status. Last, the results indicate changes in maternal sensitivity and infant difficult behavior from 3 to 9 months of infant's age. CONCLUSIONS: Our findings indicate that prematurity status impacts attachment quality. Changes in maternal and infant behavior from 3 to 9 months suggest a period of rapid non-linear development, supporting a transactional multilayered approach to the study of mother-infant relationship.

The nuclear receptor Nurr1 is preferentially expressed in human pro-inflammatory macrophages and limits their inflammatory profile.

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1ß, IL-6, IL-8, IL-12 p40, CCL2, IFN-ß, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.

Effect of temperature on growth and yessotoxin production of Protoceratium reticulatum and Lingulodinium polyedra (Dinophyceae) isolates from the Portuguese coast (NE Atlantic).

The dinoflagellates Protoceratium reticulatum and Lingulodinium polyedra are potential yessotoxin (YTX) producers, which have been associated with blooms responsible for economic, social, and ecological impacts around the world. They occur in Iberian waters, but in this region, little is known of their ecophysiology and toxin profiles. This study investigated the growth and toxin production of two strains of each species, from the Portuguese coast, at 15 °C, 19 °C, and 23 °C. Growth curves showed higher growth rates at 19 °C, for both species. YTX and three analogs (homo YTX; 45-OH YTX; 45-OH homo YTX) were investigated by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), and the presence of other analogs was investigated by Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS). No evidence of toxin production was found in L. polyedra. By contrast, YTX and 45,55-diOH-YTX were detected in both strains of P. reticulatum. These results confirm P. reticulatum as a source of yessotoxins along the Portuguese coast and add to the observed high intraspecific variability on YTX production of both species, at a global scale.

Can Grapevine Leaf Water Potential Be Modelled from Physiological and Meteorological Variables? A Machine Learning Approach.

Climate change is affecting global viticulture, increasing heatwaves and drought. Precision irrigation, supported by robust water status indicators (WSIs), is inevitable in most of the Mediterranean basin. One of the most reliable WSIs is the leaf water potential (Ψleaf), which is determined via an intrusive and time-consuming method. The aim of this work is to discern the most effective variables that are correlated with plants' water status and identify the variables that better predict Ψleaf. Five grapevine varieties grown in the Alentejo region (Portugal) were selected and subjected to three irrigation treatments, starting in 2018: full irrigation (FI), deficit irrigation (DI), and no irrigation (NI). Plant monitoring was performed in 2023. Measurements included stomatal conductance (gs), predawn water potential Ψpd, stem water potential (Ψstem), thermal imaging, and meteorological data. The WSIs, namely Ψpd and gs, responded differently according to the irrigation treatment. Ψstem measured at mid-morning (MM) and mid-day (MD) proved unable to discern between treatments. MM measurements presented the best correlations between WSIs. gs showed the best correlations between the other WSIs, and consequently the best predictive capability to estimate Ψpd. Machine learning regression models were trained on meteorological, thermal, and gs data to predict Ψpd, with ensemble models showing a great performance (ExtraTrees: R2=0.833, MAE=0.072; Gradient Boosting: R2=0.830; MAE=0.073).

Extra-Neural Metastases of Glioblastoma: A Case Series.

Glioblastoma (GBM) is the most common brain tumor and has a median survival of less than two years. The current standard of care consists of surgery followed by concomitant radio and chemotherapy with temozolomide. Although it is an aggressive tumor, distant metastases are extremely rare. The dissemination mechanisms are not fully understood and currently there is no standard of care for its treatment. In this study, the authors present a comprehensive analysis of all the existing cases of extra-neural metastases of GBM in a tertiary care center over the last five years, along with the procedures carried out in each case.

Burnout in medical students: A longitudinal study in a Portuguese medical school.

Background: Burnout is highly prevalent among medical students. This study aimed to assess burnout levels over the course of a semester and identify variables that might explain burnout's variance over time. Method: This longitudinal study involved medical students from a Portuguese school. Participants completed the Maslach Burnout Inventory and Mental Health Inventory-5, along with questions related to social support, help-seeking behaviours, academic performance, mental health and lifestyle assessment at the beginning (first phase), middle (second phase) and end (third phase) of the first semester of 2018-2019 academic year. Results: A total of 108 participants provided responses in all phases (paired sample). The prevalence of burnout in the first phase was 28.2%, which increased to 34% in the second and 39.5% in the third. To explore factors contributing to burnout levels, we used the 332 responses obtained in the third phase (non-paired sample). Higher burnout levels were associated with poor academic performance, mental health stigma, consumption of tranquillisers and living away from home. Conversely, they were negatively associated with social support and a healthy lifestyle. Conclusions: The study reveals a high prevalence of burnout among medical students, with burnout levels increasing throughout the semester. These levels are influenced by modifiable variables.

A 15-Year Retrospective Review of Ciguatera in the Madeira Islands (North-East Atlantic, Portugal).

The first ciguatera fish poisoning (CFP) in Portugal dates from 2008 when 11 people reported CFP symptoms after consuming a 30 kg amberjack caught around the Selvagens Islands (Madeira Archipelago). Since then, 49 human poisonings have been reported. The emergence of a new threat challenged scientists and regulators, as methods for toxic microalgae analyses and ciguatoxin (CTX) detection were not implemented. To minimise the risk of ciguatera, the Madeira Archipelago authorities interdicted fisheries in Selvagens Islands and banned the capture of amberjacks weighing more than 10 kg in the entire region of Madeira Archipelago. The accurate identification and quantification of the benthic toxin-producing algae species spreading to new areas require efforts in terms of both microscopy and molecular techniques. Two ciguatera-causing dinoflagellates, Gambierdiscus excentricus and Gambierdiscus australes, were identified in the Madeira Island and Selvagens sub-archipelago, respectively. Regarding the CTX analysis (N2a cell-based assay and LC-MS) in fish, the results indicate that the Selvagens Islands are a ciguatera risk area and that fish vectoring CTX are not limited to top predator species. Nevertheless, advances and improvements in screening methods for the fast detection of toxicity in seafood along with certified reference material and sensitive and selective targeted analytical methods for the determination of CTX content are still pending. This study aims to revise the occurrence of ciguatera cases in the Madeira Archipelago since its first detection in 2008, to discuss the risk management strategy that was implemented, and to provide a summary of the available data on the bioaccumulation of CTX in marine fish throughout the marine food web, taking into consideration their ecological significance, ecosystem dynamics, and fisheries relevance.

Bronchiectasis.

Bronchiectasis is a final common pathway of a wide variety of underlying conditions including infectious, autoimmune, allergic, genetic and inflammatory conditions. Patients experience a chronic disease with variable clinical symptoms and course, but most experience cough, sputum production and recurrent exacerbations. Symptoms of bronchiectasis lead to poor quality of life and exacerbations are the major driver of morbidity and mortality. Patients are often chronically infected with bacteria with the most common being Pseudomonas aeruginosa and Haemophilus influenzae. Treatment of bronchiectasis includes standardised testing to identify the underlying cause with targeted treatment if immune deficiency, allergic bronchopulmonary aspergillosis or non-tuberculous mycobacterial infection, for example, are identified. Airway clearance is the mainstay of therapy for patients with symptoms of cough and sputum production. Frequently exacerbating patients may benefit from long term antibiotic or mucoactive therapies. Bronchiectasis is a heterogeneous disease and increasingly precision medicine approaches are advocated to target treatments most appropriately and to limit the emergence of antimicrobial resistance.

Communication preferences and perceptions of cancer patient during their first medical oncology appointment.

BACKGROUND: The first medical oncology appointment serves as a platform for patients to comprehend their diagnosis and prognostic implications of cancer. This study aimed to determine patients' communication preferences during their first medical oncology appointment and to assess the disparities between patients' preferences and perceptions. METHODS: A total of 169 cancer patients participated by completing the Communication in First Medical Oncology Appointment Questionnaire (C-FAQ), a two-section questionnaire designed to assess patients' preferences and perceptions regarding Content (information provided and its extent), Facilitation (timing and location of information delivery), and Support (emotional support) during their first medical oncology appointment. A comparative analysis was conducted to assess the variations between preferences and perceptions. RESULTS: Content emerged as the most significant dimension compared to Facilitation and Support. The physician's knowledge, honesty, and ability to provide clear information were considered the most important attributes. Patients evaluated most of their preferences as "very important". Patients' perception of the communication dimensions present during their appointment was below preferences for 11 items, indicating significant discrepancies in clinical practice. CONCLUSIONS: Patients highly valued their preferences concerning Content, Facilitation, and Support dimensions of communication. However, patient preferences were more prominently oriented towards the Content dimension. The discrepancies between preferences and perceptions should be viewed as an opportunity for enhancing communication skills through training.

Detection of skin wrinkles and quantification of roughness using a novel image processing technique from a dermatoscope device.

OBJECTIVE: Cutaneous relief analysis is crucial in the development of new skincare products, as well as in the evaluation of dermatological treatments. The analysis can be performed by qualitative or quantitative methods. We propose a new algorithm to detect wrinkles and quantify skin roughness by image processing from a dermatoscope. METHODS: A clinical study was carried out with 33 research participants, and images were collected with the dermatoscope and PRIMOS equipment for wrinkle evaluation at two different times: Day 0 (D0) and 45 days (D45) after the use of a dermocosmetic product. Later, a new algorithm was developed to detect wrinkles in the acquired images by applying filters and image transformations that generate a segmented image highlighting the wrinkles. A roughness calculation method is proposed from the pixels belonging to wrinkles. RESULTS: Correlation between the values obtained by the PRIMOS equipment and the proposed system was verified. No correlation was found for data obtained at D0; however, there was correlation at time D45 by Spearman's similarity coefficient. By comparing roughness between times D0 and D45, the treatment was statistically significant for both PRIMOS and the proposed methodology data. CONCLUSION: The wrinkle detection algorithm, in addition to the roughness calculation, demonstrated a sensitivity comparable to the PRIMOS system in evaluating the effectiveness of the dermocosmetic treatment. SIGNIFICANCE: Considering the simplicity of the dermatoscope design compared to other established devices such as PRIMOS, the proposed system is promising as an alternative for dermatological evaluations.

Acanthosis Nigricans Manifesting as a Paraneoplastic Syndrome Associated With Cholangiocarcinoma.

We present the case of a 64-year-old woman with type 2 diabetes who was diagnosed with early-stage intrahepatic cholangiocarcinoma and underwent partial hepatectomy followed by adjuvant chemotherapy. The patient simultaneously developed skin lesions compatible with acanthosis nigricans (AN). Thirty-seven months after completing chemotherapy, the patient had a recurrence of extensive skin and mucosal lesions compatible with AN. A thoracic-abdominal-pelvic (TAP) CT showed a relapse with hepatic hilar adenopathy. Currently, she is under evaluation to undergo radical treatment. Malignancy is a rare cause of AN and skin lesions can arise before, during, or after the diagnosis. As a paraneoplastic syndrome, it is usually related to gastric adenocarcinoma, with cholangiocarcinoma being a rare entity in this setting. Although an uncommon manifestation, the malignant etiology should be considered among other prevalent causes, such as metabolic disorders, and establishing an association can lead to an early diagnosis and initiation of curative treatment.

Six years of demography data for 11 reef coral species.

Scleractinian corals are colonial animals with a range of life-history strategies, making up diverse species assemblages that define coral reefs. We tagged and tracked ~30 colonies from each of 11 species during seven trips spanning 6 years (2009-2015) to measure their vital rates and competitive interactions on the reef crest at Trimodal Reef, Lizard Island, Australia. Pairs of species were chosen from five growth forms in which one species of the pair was locally rare (R) and the other common (C). The sampled growth forms were massive (Goniastrea pectinata [R] and G. retiformis [C]), digitate (Acropora humilis [R] and A. cf. digitifera [C]), corymbose (A. millepora [R] and A. nasuta [C]), tabular (A. cytherea [R] and A. hyacinthus [C]) and arborescent (A. robusta [R] and A. intermedia [C]). An extra corymbose species with intermediate abundance, A. spathulata was included when it became apparent that A. millepora was too rare on the reef crest, making the 11 species in total. The tagged colonies were visited each year in the weeks prior to spawning. During visits, two or more observers each took two or three photographs of each tagged colony from directly above and on the horizontal plane with a scale plate to track planar area. Dead or missing colonies were recorded and new colonies tagged to maintain ~30 colonies per species throughout the 6 years of the study. In addition to tracking tagged corals, 30 fragments were collected from neighboring untagged colonies of each species for counting numbers of eggs per polyp (fecundity); and fragments of untagged colonies were brought into the laboratory where spawned eggs were collected for biomass and energy measurements. We also conducted surveys at the study site to generate size structure data for each species in several of the years. Each tagged colony photograph was digitized by at least two people. Therefore, we could examine sources of error in planar area for both photographers and outliners. Competitive interactions were recorded for a subset of species by measuring the margins of tagged colony outlines interacting with neighboring corals. The study was abruptly ended by Tropical Cyclone Nathan (Category 4) that killed all but nine of the more than 300 tagged colonies in early 2015. Nonetheless, these data will be of use to other researchers interested in coral demography and coexistence, functional ecology, and parametrizing population, community, and ecosystem models. The data set is not copyright restricted, and users should cite this paper when using the data.

The Role of Cyclin-Dependent Kinase 4/6 Inhibitors Treatment in Oligometastatic Breast Cancer: A Case Report on a Possible Curative Intent Strategy.

A small but important subset of patients with metastatic breast cancer has an oligometastatic disease. Some of these patients are highly responsive to systemic therapy and have the potential to achieve complete remission with treatment. However, it remains to be clarified the best locoregional and systemic treatment strategy for such patients and what features can determine whose patients are the best candidates. We also don't know what will be the role of cyclin-dependent kinase 4/6 inhibitors in those cases. We report the case of a 41-year-old woman with HR-positive/HER2-negative oligometastatic breast cancer who, after an excellent response to systemic treatment with palbociclib, anastrozole, and goserelin, underwent breast surgery and liver metastasectomy. After completing three years of systemic treatment, the CDK inhibitor was discontinued, maintaining the hormone therapy. The patient remained under regular follow-up with no evidence of disease after eight months.

The role of intrasexual competition on the evolution of male-male courtship display: a systematic review.

Background: Evidence of male-male courtship display is widespread across the animal kingdom. Yet, its function and evolutionary origin remain unclear. Here, we hypothesise that male-male courtship display evolved in response to selection pressure exerted by intrasexual competition during male-female courtship interactions. Intrasexual competition can be caused by bystander male pressure through eavesdropping and exploiting on displayer male's courtship interactions with females. This bystander pressure can lead to an audience effect by the displayer, who will change their courtship behaviour in the presence of bystanders and display directly towards them, even in the absence of females, as an intimidation strategy. In species where this selection pressure has taken place, we predict that the male courtship display will have a dual function: attract females and deter competitors. Therefore, we expected to find more evidence of bystander-related behaviours in species for which male-male courtship display is linked to intrasexual competition compared to species for which other explanatory hypotheses are more plausible (e.g., mistaken identity or courtship practice). Methodology: We conducted two systematic reviews to test this hypothesis. First, we conducted a search for studies of species with courtship display between males and of the hypotheses provided to explain this behaviour. Our goal was to identify the species with male-male courtship display and evidence of intrasexual competition. Second, among the species with male-male courtship display, we searched for evidence of bystander-related behaviours, i.e., articles referring to eavesdropping, exploitation, and audience effect during male-female courtship interactions. Our goal was to test whether species with intrasexual competition are also more likely to show bystander-related behaviours. Results: Although most studies reporting male courtship display towards other males do not suggest any explanatory hypothesis for this behaviour, the intrasexual competition hypothesis was largely mentioned and supported by some studies reviewed. Additionally, there is more evidence of eavesdropping and of all three bystander-related behaviours combined in species for which the intrasexual competition hypothesis was suggested. Conclusions: Overall, our review supports the hypothesis that intrasexual competition can play a key role in male courtship display evolution, namely that male-male courtship display may have evolved as a secondary function of male-female courtship interactions via bystander male pressure. However, our review also shows that despite the increasing interest in same-sex sexual behaviours, and male-male courtship display in particular, most studies were found to be merely descriptive, and the hypotheses they suggested to explain courtship display between males mostly speculative. This highlights an important gap in the literature. To clarify both the evolution and the function of male-male courtship display, this behaviour needs to be empirically studied more often. Our review can help advancing this research area, as it makes the 20 species with male-male courtship display for which the intrasexual competition hypothesis was suggested excellent candidates for empirical research.

Priapism Secondary to Low-Molecular-Weight Heparins: A Case Report.

Priapism may be a side effect of low-molecular-weight heparins, and its mechanism remains unknown. The authors present a clinical case of a 51-year-old male patient with oligodendroglioma. The patient presented ischemic priapism on the third month after starting tinzaparin, without other recent changes to his medication and he denied the use of other new medicines. The patient went through surgery and the erection was resolved but presented fibrosis of the cavernous body which left him with erectile dysfunction. Since this event, the patient is no longer receiving Heparin and has had no other episodes of priapism. The prompt recognition of this side effect may decrease its morbidity and consequent impact on the quality of life. More studies are needed to better understand its pathophysiology.

O priapismo pode ser um efeito adverso das heparinas de baixo peso molecular, cuja fisiopatologia não é totalmente compreendida. Os autores apresentam o caso de um doente, do sexo masculino, 51 anos, com diagnóstico de oligodendroglioma. O doente apresentou um episódio de priapismo, no terceiro mês sob tinzaparina, sem nenhuma outra alteração recente da sua medicação habitual e com consumo de outros medicamentos negado. Foi submetido a cirurgia, com resolução do priapismo, mas apresentou fibrose sequelar dos corpos cavernosos, com consequente disfunção eréctil. Desde então o doente não retomou heparina e não apresentou novos episódios de priapismo. Um célere reconhecimento do quadro pode contribuir para menores sequelas, com consequente diminuição da morbilidade e impacto na qualidade de vida. Mais investigação é necessária para aumentar o conhecimento sobre a fisiopatologia desta situação.

The Nurr7 agonist Cytosporone B differentially regulates inflammatory responses in human polarized macrophages.

The orphan nuclear receptor Nur77 is involved in diverse cellular processes such as inflammation, proliferation, differentiation and survival. Stimuli like lipopolysaccharide (LPS) and tumor necrosis factor (TNF) increase Nur77 expression in human and murine macrophages, and it has been proposed that Nur77 plays a major role in dampening the inflammatory response. Here, we evaluated the expression and function of Nur77 in human anti-inflammatory and pro-inflammatory macrophages derived from blood monocytes cultured with macrophage colony-stimulating factor (M-MDMs) or granulocyte/macrophage colony-stimulating factor (GM-MDMs), respectively. Nur77 mRNA expression was significantly enhanced in M-MDMs compared with GM-MDMs, both constitutively and upon exposure to Toll-like receptor (TLR)2, 3, and 4 ligands. Nur77 activation with the agonist Cytosporone B (CsnB) significantly suppressed the production of TNF, interleukin (IL)-1ß, IL-6, and IL-8 in GM-MDMs stimulated with LPS. In contrast, it tended to enhance the production of the anti-inflammatory cytokine IL-10. This effect was associated with reduced NF-κB p65 nuclear translocation. Similarly, Nur77 knockdown enhanced TNF production in GM-MDMs. CsnB effectively stimulated the transactivation activity of Nur77 in M-MDMs, but it did not alter cytokine synthesis or p65 nuclear translocation. However, Nur77 seemed to have a role in maintaining the anti-inflammatory profile of M-MDMs, since Nur77-deficient M-MDMs constitutively produced higher levels of TNF transcripts. Thus, in the absence of exogenous agonists, Nur77 activity favors the anti-inflammatory function of M-MDMs, whereas agonistic activation of this receptor preferentially drives attenuation of inflammation in inflammatory macrophages.