Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity.

Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent tumor growth inhibitory activity with high selectivity index. Mechanistically, it induces perturbation of the spindles through microtubule instability. As a consequence, treated cells exhibit irreversible defects in chromosome congression during mitosis, which induce a prolonged spindle assembly checkpoint-dependent mitotic arrest, followed by massive apoptosis, as revealed by live cell imaging. Collectively, the results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, thereby highlighting its potential as antitumor agent.

Tetracyclic Thioxanthene Derivatives: Studies on Fluorescence and Antitumor Activity.

Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline-chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI50 values below 10 µM for the three tested cell lines, and structure-activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.

Red Ear: Syndrome or Symptom?

Red ear syndrome (RES) is a rare disorder characterized by attacks of unilateral ear pain during which the ear becomes red. Episodes can occur spontaneously, or be triggered, in most cases, by rubbing or touching the ear. Both duration and frequency are variable. RES has been explained by a dysfunction of cervical spinal nerves (C3 root) and a dysregulation with disinhibition of brainstem trigemino-autonomic circuits, leading to sympathetic inhibition and parasympathetic hyperactivity producing vasodilation. We describe 6 new cases of RES with different characteristics. Although all presented the cardinal symptom of red ear, the headache patterns were suggestive of other primary headaches (migraine or cluster headache). Therapeutic response was obtained when directed to the associated primary headache phenotype, suggesting that RES may be a phenomena associated with different headaches, rather than a syndrome in itself.

Comparative phylogeography of endemic Azorean arthropods.

BACKGROUND: For a remote oceanic archipelago of up to 8 Myr age, the Azores have a comparatively low level of endemism. We present an analysis of phylogeographic patterns of endemic Azorean island arthropods aimed at testing patterns of diversification in relation to the ontogeny of the archipelago, in order to distinguish between alternative models of evolutionary dynamics on islands. We collected individuals of six species (representing Araneae, Hemiptera and Coleoptera) from 16 forest fragments from 7 islands. Using three mtDNA markers, we analysed the distribution of genetic diversity within and between islands, inferred the differentiation time-frames and investigated the inter-island migration routes and colonization patterns. RESULTS: Each species exhibited very low levels of mtDNA divergence, both within and between islands. The two oldest islands were not strongly involved in the diffusion of genetic diversity within the archipelago. The most haplotype-rich islands varied according to species but the younger, central islands contributed the most to haplotype diversity. Colonization events both in concordance with and in contradiction to an inter-island progression rule were inferred, while a non-intuitive pattern of colonization from western to eastern islands was also inferred. CONCLUSIONS: The geological development of the Azores has followed a less tidy progression compared to classic hotspot archipelagos, and this is reflected in our findings. The study species appear to have been differentiating within the Azores for <2 Myr, a fraction of the apparent life span of the archipelago, which may indicate that extinction events linked to active volcanism have played an important role. Assuming that after each extinction event, colonization was initiated from a nearby island hosting derived haplotypes, the apparent age of species diversification in the archipelago would be moved closer to the present after each extinction-recolonization cycle. Exploiting these ideas, we propose a general model for future testing.

Knowledge about type 2 diabetes: its impact for future management.

Diabetes can cause several long-term complications. Knowledge about this disease can play an important role in reducing diabetes-related complications. In addition, the lack of awareness leads to misconceptions, which joined with inadequate knowledge, are relevant barriers to proper diabetes management. In this study, we aimed to assess the diabetes knowledge of a type 2 diabetes (T2D) population and identify major knowledge gaps, in order to prevent complications and to increase quality of life. In a cross-sectional, observational study in a convenience sample, we identified individuals diagnosed with T2D attending ambulatory visits from five health settings, older than 18 years, with a time diagnosis of at least 1 year, and attending multidisciplinary visits for at least 3 months. To assess the knowledge of T2D individuals, we applied the Portuguese version of the Diabetes Knowledge Test. The sample included a total of 1,200 persons, of whom almost half were female. The age range of the participants varied from 24 to 94 years old, and the mean age was 65.6 ± 11.4 years. Most of the sample had a level of education under secondary and lived with someone. In our sample, 479 (39.9%) were insulin-treated. The percentage of correct answers was 51.8% for non-insulin vs. 58.7% for insulin treated (p < 0.05). There were three items with a percentage of correct answers lower than 15%; the item with the lower value of correct answers was the one related to the identification of signs of ketoacidosis with only 4.4% of correct answers, the errors presented a random pattern; the item related to the identification of which food should not be used to treat low blood glucose with 11.9%, where 56.9% of the sample's participants considered that one cup of skim milk would be the correct answer (53.1% in non-insulin patients and 62.6% in insulin treated patients; p < 0.001). The item regarding the knowledge of free food presented a 13.3% of correct answers (10.8% non-insulin group vs. 17.1% insulin group; p < 0.01). Two of the three items with lower value of correct answers were related to glycemic control and health status monitoring, the other was related to diet and food.

Assessing nature exposure: a study on the reliability and validity of a Portuguese version of the nature exposure scale.

Introduction: Engaging with nature has been widely acknowledged for its positive impact on well-being. Traditionally, assessments of nature exposure focus on estimating green space exposure and outdoor time. However, the Nature Exposure Scale (NES) offers a unique approach by evaluating the quality of nature experiences, encompassing both deliberate and spontaneous encounters. Methods: This study aimed to assess the validity and reliability of the NES in the context of Portugal. Exploratory Factor Analysis (PCA) and Confirmatory Factor Analysis (CFA) were employed to examine the underlying structure of the scale. Additionally, reliability assessments, along with tests of convergent and divergent validity, were conducted. Data were collected from a sample of 558 adults and 241 adolescents between 2016 and 2018. Results: The findings revealed strong internal consistency of the NES, supported by acceptable correlation values and robust factor loadings within a unidimensional model. The scale effectively predicted variations in nature exposure across diverse professional activities. Discussion: In summary, the 4-item NES emerged as a reliable tool for assessing nature exposure in various settings, effectively bridging a gap in the Portuguese context. The scale demonstrated potential for cross-cultural research and was particularly adept at predicting nature exposure in different professional contexts. The results suggest that the NES can enhance our understanding of the impact of nature on well-being in diverse cultural settings. Conclusion: The study underscores the reliability of the NES in assessing nature exposure in Portugal, paving the way for further exploration in Portuguese-speaking regions. The scale holds promise for advancing research on the relationship between nature and well-being, contributing valuable insights across different cultural contexts.

The BALA project: A pioneering monitoring of Azorean forest invertebrates over two decades (1999-2022).

Globally, there is a concerning decline in many insect populations, and this trend likely extends to all arthropods, potentially impacting unique island biota. Native non-endemic and endemic species on islands are under threat due to habitat destruction, with the introduction of exotic, and potentially invasive, species, further contributing to this decline. While long-term studies of plants and vertebrate fauna are available, long-term arthropod datasets are limited, hindering comparisons with better-studied taxa. The Biodiversity of Arthropods of the Laurisilva of the Azores (BALA) project has allowed gathering comprehensive data since 1997 in the Azorean Islands (Portugal), using standardised sampling methods across islands. The dataset includes arthropod counts from epigean (pitfall traps) and canopy-dwelling (beating samples) communities, enriched with species information, biogeographic origins, and IUCN categories. Metadata associated with the sample protocol and events, like sample identifier, archive number, sampled tree species, and trap type are also recorded. The database is available in multiple formats, including Darwin Core, which facilitates the ecological analysis of pressing environmental concerns, such as arthropod population declines and biological invasions.

A dramatic case of Behçet disease successfully treated with infliximab.

Behçet disease is a chronic relapsing systemic disease with possible life-threatening presentations. Management of this disease can be challenging and reports of the off-label use of anti-TNFα agents for the treatment of severe manifestations are increasing, with good results. The authors report a case of Behçet disease with a sudden and severe multi-systemic onset successfully treated with infliximab.

A new species of Tarphius Erichson, 1845 (Coleoptera: Zopheridae) from North Africa and notes on an Iberian species.

A new species of Tarphius Erichson, 1845 (Coleoptera: Zopheridae, Solier, 1834) is described from Morocco. Tarphius isabelae n. sp. is the fifth Tarphius species recorded in North Africa. In addition, we present some information on the Iberian species, Tarphius kiesenwetteri Heyden, 1870.

Empowerment and Knowledge as Determinants for Quality of Life: A Contribution to a Better Type 2 Diabetes Self-Management.

The purpose of this study was to assess how knowledge and empowerment impact the quality of life (QoL) of a person with type 2 diabetes, leading to better communication and disease management. We conducted a descriptive and observational study of individuals with type 2 diabetes. The Diabetes Empowerment Scale-Short Form (DES-SF), Diabetes Knowledge Test (DKT), and EQ-5D-5L were used, in addition to sociodemographic and clinical characteristics. Evaluating the variability in the DES-SF and DKT in relation to the EQ-5D-5L and identifying possible sociodemographic and clinical determinants were conducted using univariate analyses followed by a multiple linear regression model to test whether the factors significantly predicted QoL. A total of 763 individuals were included in the final sample. Patients aged 65 years or older had lower QoL scores, as well as patients who lived alone, had less than 12 years of education, and experienced complications. The insulin-treated group showed higher scores in DKT than the non-insulin-treated group. It was also found that being male, being under 65 years of age, having no complications present, and having higher levels of knowledge and empowerment predicted higher QoL. Our results show that DKT and DES are still determinants of QoL, even after adjusting for sociodemographic and clinical characteristics. Therefore, literacy and empowerment are important for the improvement of the QoL of people with diabetes, by enabling them to manage their health conditions. New clinical practices focused on education, increasing patients' knowledge, and empowerment may contribute to better health outcomes.

Cultural probes for environmental education: Designing learning materials to engage children and teenagers with local biodiversity.

Direct contact with nature is paramount in deepening children's and teenagers' interest in biodiversity. Learning materials chosen to convey information and engage participants during outings in nature-rich environments are varied and can support rich learning experiences. For this purpose, learning materials can be acquired "off-the-shelf" or developed for site-specific locations or projects. However, there is little guidance on potential techniques for those wishing to generate contextually relevant materials. With the view of responding to this challenge, we propose the cultural probes technique. We demonstrate that the technique, commonly used in qualitative research to generate novel insights in conversation with participants, can instigate innovative and thoughtful approaches to materials designed for children and teenagers to explore nature. We present a toolkit that draws on the literature on cultural probes, inquiry-based learning, and the value of sensory, emotional, and aesthetic experiences in environmental education for structuring interactions with participants. To test our approach, we applied a descriptive research design and mixed-methods approach for collecting questions from youths between the ages of 10 and 18, inspired by a nature walk and a set of exploratory tasks executed through the toolkit. Specifically, we tested our toolkit along a trail in the Nature Park of Terceira, situated in the Azores, a Portuguese volcanic archipelago in the North Atlantic. Here, we present and reflect on the data collected during one visit organized over two days with two groups of participants and one post-trail activity directed at both groups. Results demonstrate that the open-ended and playful nature of cultural probes offers a novel way to engage youths with nature-rich environments through questioning. This contribution further highlights the potential of cultural probes for instigating encounters that tap into the value of sensory, emotional, and aesthetic experience in nature, with positive outcomes for participants.

SLAM Project - Long Term Ecological Study of the Impacts of Climate Change in the natural forest of Azores: IV - The spiders of Terceira and Pico Islands (2019-2021) and general diversity patterns after ten years of sampling.

Background: Long-term studies are key to understand the drivers of biodiversity erosion, such as land-use change and habitat degradation, climate change, invasive species or pollution. The long-term project SLAM (Long Term Ecological Study of the Impacts of Climate Change in the natural forest of Azores) started in 2012 and focuses on arthropod monitoring, using SLAM (Sea, Land and Air Malaise) traps, aiming to understand the impact of the drivers of biodiversity erosion on Azorean native forests (Azores, Portugal). This is the fourth contribution including SLAM project data and the second focused on the spider fauna (Arachnida, Araneae) of native forests on two islands (Pico and Terceira). In this contribution, we describe data collected between 2019 and 2021 and we analyse them together with a previously published database that covered the 2012-2019 period, in order to describe changes in species abundance patterns over the last ten years. New information: We present abundance data of Azorean spider species for the 2019-2021 period in two Azorean Islands (Terceira and Pico). We also present analyses of species distribution and abundance of the whole sampling period. In the period of 2019-2021, we collected a total of 5110 spider specimens, of which 2449 (48%) were adults. Most juveniles, with the exception of some exotic Erigoninae, were also included in the data presented in this paper, since the low diversity of spiders in the Azores allows a relatively precise species-level identification of this life-stage. We recorded a total of 45 species, belonging to 39 genera and 16 families. The ten most abundant species were composed mostly of endemic or native non-endemic species and only two exotic species (Tenuiphantestenuis (Blackwall, 1852) and Dysderacrocata C. L. Koch, 1838). They included 4308 individuals (84%) of all sampled specimens and were the dominant species in Azorean native forests. The family Linyphiidae was the richest and most abundant taxon, with 15 (33%) species and 2630 (51%) specimens. We report Cheiracanthiummildei L. Koch, 1864, a non-native species, from Pico Island for the first time. We found no new species records on Terceira Island. This publication contributes to increasing the baseline information for future long-term comparisons of the spiders on the studied sites and the knowledge of the arachnofauna of the native forests of Terceira and Pico, in terms of species abundance, distribution and diversity across seasons for a 10 years period.

Second-Generation Antimitotics in Cancer Clinical Trials.

Mitosis represents a promising target to block cancer cell proliferation. Classical antimitotics, mainly microtubule-targeting agents (MTAs), such as taxanes and vinca alkaloids, are amongst the most successful anticancer drugs. By disrupting microtubules, they activate the spindle assembly checkpoint (SAC), which induces a prolonged delay in mitosis, expected to induce cell death. However, resistance, toxicity, and slippage limit the MTA's effectiveness. With the desire to overcome some of the MTA's limitations, mitotic and SAC components have attracted great interest as promising microtubule-independent targets, leading to the so-called second-generation antimitotics (SGAs). The identification of inhibitors against most of these targets, and the promising outcomes achieved in preclinical assays, has sparked the interest of academia and industry. Many of these inhibitors have entered clinical trials; however, they exhibited limited efficacy as monotherapy, and failed to go beyond phase II trials. Combination therapies are emerging as promising strategies to give a second chance to these SGAs. Here, an updated view of the SGAs that reached clinical trials is here provided, together with future research directions, focusing on inhibitors that target the SAC components.

[Non-Necrotizing Acute Dermo-Hypodermal Infections: Erysipela and Infectious Cellulitis]. / Dermo-Hipodermites Bacterianas Agudas Não Necrotizantes: Erisipela e Celulite Infeciosa.

Non-necrotizing acute dermo-hypodermal infections are infectious processes that include erysipela and infectious cellulitis, and are mainly caused by group A ß-haemolytic streptococcus. The lower limbs are affected in more than 80% of cases and the risk factors are disruption of cutaneous barrier, lymphoedema and obesity. Diagnosis is clinical and in a typical setting we observe an acute inflammatory plaque with fever, lymphangitis, adenopathy and leucocytosis. Bacteriology is usually not helpful because of low sensitivity or delayed positivity. In case of atypical presentations, erysipela must be distinguished from necrotizing fasciitis and acute vein thrombosis. Flucloxacillin and cefradine remain the first line of treatment. Recurrence is the main complication, so correct treatment of the risk factors is crucial.

As dermo-hipodermites bacterianas agudas não necrotizantes são processos infeciosos que incluem a erisipela e a celulite infeciosa, e são geralmente causadas por estreptococos ß­hemolíticos do grupo A. Em mais de 80% dos casos situam-se nos membros inferiores e são fatores predisponentes a existência de solução de continuidade na pele, o linfedema crónico e a obesidade. O seu diagnóstico é essencialmente clínico e o quadro típico baseia-se na presença de placa inflamatória associada a febre, linfangite, adenopatia e leucocitose. Os exames bacteriológicos têm baixa sensibilidade ou positividade tardia. Nos casos atípicos é importante o diagnóstico diferencial com a fasceíte necrotizante e a trombose venosa profunda. A flucloxacilina ou a cefradina são os fármacos de primeira linha. A recidiva constitui a complicação mais frequente, sendo fundamental o correto tratamento dos fatores de risco.

Wildlife inventory from camera-trapping surveys in the Azores (Pico and Terceira islands).

BACKGROUND: The present publication provides a dataset from five camera-trapping sampling campaigns on two islands of the Azorean archipelago (Pico and Terceira islands), between 2013-2018. This dataset was obtained as a by-product of campaigns designed for different purposes. The sampling campaigns were designed to: (i) study the ecology of introduced mammals; (ii) assess the impact of introduced mammals on native birds (Azores woodpigeon - Columba palumbus azorica and Cory's shearwater - Calonectris diomeda borealis), through nest predation; and (iii) obtain information about the impact of vertebrates on agricultural systems, particularly on Azorean traditional vineyards. A total of 258 sites and 47 nests were sampled using camera traps. These sampling campaigns provided a large data series that allowed the creation of a vertebrate wildlife inventory. NEW INFORMATION: We obtained a total of 102,095 camera-trap records, which allowed us to to identify 30 species of vertebrates: one amphibian, one reptile, 17 birds and ten mammal species. This represented 100% of the amphibians and terrestrial mammals, 58% of the breeding birds and 50% of the reptile species known for Pico and/or Terceira islands. Concerning the colonisation status of the species, we recorded 15 indigenous (native non-endemic or endemic) and three introduced bird species; all known terrestrial amphibians, reptiles and mammals in the Azores are introduced species. The data collected contribute to increasing knowledge on the distribution of vertebrate species on Pico and Terceira islands, where most existing records of some species were only available to Island level (e.g. mustelids and hedgehogs). None of the identified species was previously unknown to the study area.

Modelling the distribution of Mustela nivalis and M. putorius in the Azores archipelago based on native and introduced ranges.

The aims of this study were to predict the potential distribution of two introduced Mustelidae, Mustela nivalis and M. putorius in the Azores archipelago (Portugal), and evaluate the relative contribution of environmental factors from native and introduced ranges to predict species distribution ranges in oceanic islands. We developed two sets of Species Distribution Models using MaxEnt and distribution data from the native and introduced ranges of the species to project their potential distribution in the archipelago. We found differences in the predicted distributions for the models based on introduced and on native occurrences for both species, with different most important variables being selected. Climatic variables were most important for the introduced range models, while other groups of variables (i.e., human-disturbance) were included in the native-based models. Most of the islands of the Azorean archipelago were predicted to have suitable habitat for both species, even when not yet occupied. Our results showed that predicting the invaded range based on introduced range environmental conditions predicted a narrower range. These results highlight the difficulty to transfer models from native to introduced ranges across taxonomically related species, making it difficult to predict future invasions and range expansion.

Gelastic seizures: a retrospective study in five tertiary hospital centres.

This study aimed to characterize, clinically and neurophysiologically, a series of patients with gelastic seizures (GS), including both adults and children. We retrospectively collected patients with GS from epilepsy clinics of five tertiary hospital centres within a single country. Patients were selected through relatives'/caregivers' descriptions, home video and/or video-EEG monitoring. GS were identified through ictal semiology. Thirty-five patients were enrolled; 62.9% had initial GS in infancy, 14.3% in adolescence and 22.8% at adult age. Twenty-six had abnormal MRI: eight presented with hypothalamic hamartoma (HH) and 16 non-HH lesions that included different structural aetiologies and genetic, metabolic and immune aetiologies. All patients with HH had their first GS in infancy or adolescence. For the remaining aetiologies, GS started in infancy in 59.3%, in adolescence in 11.1% and at adult age in 29.6%. Video-EEG data was available for analysis in 11 patients, including seven patients with a non-HH MRI lesion. The ictal onset topography on scalp video-EEG was usually concordant with the MRI lesion (in 6/7 patients) and the most frequent ictal onset was fronto-temporal. In two patients, both video-EEG and MRI suggested a parietal and occipital epileptogenic zone. Aetiologies and patterns of affected topography unrelated to HH are common in patients with GS, and all age groups may manifest with this type of ictal semiology. This ictal manifestation has no lateralizing value and, despite a clear preponderance for hypothalamic, frontal and temporal lobe origins, other brain areas, namely the parietal and occipital lobes, should be considered.