Assessment of the Implementation of the International Health Regulations during the COVID-19 Pandemic: Portugal as a Case Study.

INTRODUCTION: The International Health Regulations (IHR) were developed to prepare countries to deal with public health emergencies. The spread of SARS-CoV-2 underlined the need for international coordination, although few attempts were made to evaluate the integrated implementation of the IHR's core capacities in response to the COVID-19 pandemic. The aim of this study was to evaluate whether IHR shortcomings stem from non-compliance or regulatory issues, using Portugal as a European case study due to its size, organization, and previous discrepancies between self-reporting and peer assessment of the IHR's core capacities. METHODS: Fifteen public health medical residents involved in contact tracing in mainland Portugal interpreted the effectiveness of the IHR's core capabilities by reviewing the publicly available evidence and reflecting on their own field experience, then grading each core capability according to the IHR Monitoring Framework. The assessment of IHR enforcement considered efforts made before and after the onset of the pandemic, covering the period up to July 2021. RESULTS: Four out of nine core IHR capacities (surveillance; response; risk communication; and human resource capacity) were classified as level 1, the lowest. Only two were graded level 3 (preparedness; and laboratory), the highest. The remaining three) (national legislation, policy & financing; coordination and national focal point communication; and points of entry) were classified as level 2. CONCLUSION: Portugal exemplifies the extent to which implementation of the IHR was not fully achieved, which has resulted in the underperformance of several core capacities. There is a need to improve preparedness and international cooperation in order to harmonize and strengthen the global response to public health emergencies, with better political, institutional, and financial support.

[Visceral Leishmaniasis in an Immunocompetent Patient: A Case Report]. / Leishmaniose Visceral em Doente Imunocompetente: Relato de um Caso.

Leishmaniasis is a parasitic disease transmitted by the bite of female sandflies that occurs in tropical and subtropical climate regions. Visceral leishmaniasis is the most serious manifestation of the disease, leading to a 95% mortality rate after two years of infection if untreated. Visceral leishmaniasis is frequently associated with immunocompromised states, with the human immunodeficiency virus being the most prevalent. Most cases of visceral leishmaniasis are caused by the species Leishmania donovani and Leishmania infantum, the latter being the endemic species in the Mediterranean basin. In Portugal, the number of reported cases of visceral leishmaniasis has decreased in the last few years, with 15 cases reported between 2017 and 2021. The authors present a case of visceral leishmaniasis in an immunocompetent patient who manifested the classic pentad: fever, weight loss, hepatosplenomegaly, pancytopenia and hypergammaglobulinemia. The diagnosis was made by the observation of amastigotes of the Leishmania infantum species in the bone marrow aspirate examination, and the patient was successfully treated with liposomal amphotericin B.

A leishmaniose é uma doença parasitária transmitida através da picada de flebotomíneos fêmea e que ocorre em regiões de clima tropical e subtropical. A leishmaniose visceral é a forma mais grave da doença, com uma mortalidade de 95% aos dois anos de infeção, quando não tratada. A leishmaniose visceral associa-se frequentemente a estados de imunossupressão, sendo a coinfeção com o vírus da imunodeficiência humana o mais prevalente. A maioria dos casos de leishmaniose visceral é causada pelas espécies Leishmania donovani e Leishmania infantum, sendo esta última a espécie endémica na bacia do Mediterrâneo. Em Portugal, o número de casos reportados de leishmaniose visceral tem vindo a diminuir nos últimos anos, sendo que entre 2017 e 2021 foram reportados 15 casos. Os autores apresentam um caso de leishmaniose visceral numa doente imunocompetente, que manifestou a pêntade clássica: febre, perda ponderal, hepatoesplenomegalia, pancitopenia e hipergamaglobulinemia. O diagnóstico foi feito pela observação de amastigotas da espécie Leishmania infantum no exame anatomopatológico da medula óssea e a doente foi tratada com sucesso com anfotericina B lipossómica.

Door-to-furosemide time and clinical outcomes in acute heart failure.

BACKGROUND AND IMPORTANCE: Acute heart failure (AHF) is one of the main causes of unplanned hospitalization in patients >65 years of age and is associated with adverse outcomes in this population. Observational studies suggest that intravenous diuretic therapy given in the first hour of presentation for AHF was associated with favorable outcomes. OBJECTIVES: To study the short-term prognostic associations of the timing of intravenous diuretic therapy in patients admitted to the emergency department (ED) for acute AHF. DESIGN, SETTINGS AND PARTICIPANTS: Patients treated in the ED with intravenous diuretics were selected from the Estratificação de Doentes com InsuFIciência Cardíaca Aguda (EDIFICA) registry, a prospective study including AHF hospitalized patients. Early and non-early furosemide treatment groups were considered using the 1-h cutoff: door-to-furosemide ≤1 h and >1 h. OUTCOMES MEASURE AND ANALYSIS: Primary outcomes were a composite of heart failure re-hospitalizations or cardiovascular death at 30- and 90-days. MAIN RESULTS: Four-hundred ninety-three patients were included in the analysis. The median (interquartile range) door-to-furosemide time was 85 (41-220) min, and 210 (43%) patients had diuretics in the first hour. Patients in the ≤1 h group had higher evaluation priority according to the Manchester Triage System, presented more often with acute pulmonary edema, warm-wet clinical profile, higher blood pressure, and signs of left-side heart failure, while >1 h group had higher Get With the Guidelines-heart failure risk score, more frequent signs of right-side heart failure, higher circulating B-type natriuretic peptides and lower albumin. Door-to-furosemide ≤ 1 h was independently associated with lower 30-day heart failure hospitalizations and composite of heart failure hospitalizations or cardiovascular death (adjusted analysis Heart Failure Hospitalizations: odds ratios (OR) 3.65; 95% confidence interval (CI), 1.22-10.9; P = 0.020; heart failure hospitalizations or cardiovascular death: OR 3.15; 95% CI, 1.49-6.64; P < 0.001). These independent associations lost significance at 90 days. CONCLUSION: Door-to-furosemide ≤1 h was associated with a lower short-term risk of heart failure hospitalizations or cardiovascular death in AHF patients. Our findings add to the existing evidence that early identification and intravenous diuretic therapy of AHF patients may improve outcomes.

Presence of metals and metalloids in crumb rubber used as infill of worldwide synthetic turf pitches: Exposure and risk assessment.

Crumb rubber derived from end-of-life tires (ELTs) is frequently used as infill of synthetic turf pitches, promoting circular economy. Although important to reduce the accumulation of waste, the use of recycled ELTs can be a problem to human health and the environment, both by direct contact during pitch use and by the release of these elements to the surroundings, mostly via volatilization and leaching. The present study aimed to evaluate the distribution of metals in ELT-derived crumb rubber collected in artificial turf worldwide and assess possible trends by country, pitch age and type (indoor vs. outdoor). The concentration ranges observed are very wide, especially in outdoor fields and for the most abundant metals, namely Zn (2989-5246 mg/kg), Fe (196-5194 mg/kg), Mg (188-1795 mg/kg) and Al (159-1882 mg/kg). For Zn, the levels were mostly above the safe limits set in European directives for relatable matrices (soils and toy materials), and the same happened for Pb, a much more toxic metal at lower concentrations. A multi-pathway human exposure study was also performed, and the risk assessment shows non-carcinogenic and carcinogenic risks from accidental crumb rubber ingestion (with Cr and Pb as major contributors) above the acceptable values for all the receptors except adult bystanders, with a higher significance to younger individuals. These results bring a different perspective regarding most of the studies reporting low risks related with exposure to metals in crumb rubber.

Transcriptomic response of the intertidal limpet Patella vulgata to temperature extremes.

Global warming is challenging wild species in land and water. In the intertidal zone, species are already living at their thermal limits, being vulnerable even to small increases in maximum habitat temperatures. Knowledge of the mechanisms by which many intertidal zone species cope with elevated temperatures is limited. We analysed the molecular thermal stress response of the limpet Patella vulgata under slight and frequent (one-day), and extreme and rare (three-day) warming events. Using RNA-seq to assess differential gene expression among treatments, differing molecular responses were obtained in the two treatments, with more changes in gene expression after the three-day event; with one-third of the differentially expressed transcripts being down-regulated. However, across treatments we observed shifts in gene expression for common aspects of the heat stress response including intra-cellular communication, protein chaperoning, proteolysis and cell cycle arrest. Of the 71,675 transcripts obtained, only 259 were differentially expressed after both heating events. From these, 218 defined the core group (i.e. genes induced by thermal stress with similar expression patterns irrespective of the magnitude of the warming event). The core group was composed of already well-studied genes in heat stress responses in intertidal organisms (e.g. heat shock proteins), but also genes from less explored metabolic pathways, e.g. the ubiquitin system, which were also fundamental regardless of the magnitude of the imposed warming. Moreover, we have also identified 41 signaling genes (i.e. a set of genes responding to both events and with expression patterns specific to the intensity of thermal stress), principally including genes involved in the maintenance of extracellular structure that have previously not been identified as part of the response to thermal stress in intertidal zone organisms. These signaling genes will be useful heat stress molecular biomarkers for monitoring heat stress in natural populations.

A review of potentially harmful chemicals in crumb rubber used in synthetic football pitches.

Recycling end-of-life tires (ELTs) reduces waste and provides a low-cost source of energy and materials such as crumb rubber, used as infill in artificial turf football pitches. However, some concerns were raised and remain about its safety. The potentially toxic human exposure to chemicals such as polycyclic aromatic hydrocarbons (PAHs), metals and others (volatile organic compounds (VOCs), plasticizers, antioxidants and additives) existing in ELTs (and in the resulting crumb rubber) is being studied, with no definitive conclusions. The literature existing so far suggests the possibility of their release from synthetic turf infill into the environment as water leachates and to the air surrounding the pitches, but there is the need of further research, also to assess the contribution of other materials present in synthetic turf. The database available comprised crumb rubber infill studies from pitches in 6 countries (USA, Norway, Netherlands, Portugal, Italy, Spain) and revealed a myriad of hazardous chemicals, with benzo[a]pyrene (n.d.-4.31 ± 3.95 mg/kg) and zinc (n.d.-14150 ± 1344 mg/kg) often exceeding the established limits. A dependence on indoor/outdoor conditions and the age of the source material was evaluated, often showing significative differences. From this standpoint, this review is intended to add knowledge about the presence of contaminants in this recycled material, aiming to ensure the safety of end-users and the environment.

Antimicrobial and antitumor activity of S-methyl dithiocarbazate Schiff base zinc(II) complexes.

Schiff bases (SB) obtained from S-methyl dithiocarbazate and aromatic aldehydes: salicylaldehyde (H2L1), o-vanillin (H2L2), pyridoxal (H2L3) and 2,6-diformyl-4-methylphenol (H3L4), and their corresponding Zn(II)-complexes (1-4), are synthesized. All compounds are characterized by elemental analyses, infrared, UV-Vis, nuclear magnetic resonance spectroscopy and mass spectrometry. The structures of H2L2 and [Zn2(L1)2(H2O)(DMF)] (1a) (DMF = dimethylformamide) are solved by single crystal X-ray diffraction. The SB coordinates the metal center through the Ophenolate, Nimine and Sthiolate atoms. The radical scavenging activity is tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, with all ligand precursors showing IC50 values ~40 µM. Cytotoxicity studies with several tumor cell lines (PC-3, MCF-7 and Caco-2) as well as a non-tumoral cell line (NHDF) are reported. Interestingly, 1 has relevant and selective antiproliferative effect against Caco-2 cells (IC50 = 9.1 µM). Their antimicrobial activity is evaluated in five bacterial strains (Klebsiella pneumoniae, Acinetobacter baumannii, Listeria monocytogenes, Pseudomonas aeruginosa and Staphylococcus aureus) and two yeast strains (Candida albicans and Candida tropicalis) with some compounds showing bacteriostatic and fungicidal activity. The minimal inhibitory concentration (MIC90) of HnL against Mycobacterium tuberculosis is also reported, with H2L2 and H3L4 showing very high activity (MIC90 < 0.6 µg/mL). The ability of the compounds to bind bovine serum albumin (BSA) and DNA is evaluated for H3L4 and [Zn2(L4)(CH3COO)] (4), both showing high binding constants to BSA (ca. 106 M-1) and ability to bind DNA. Overall, the reported compounds show relevant antitumor and antimicrobial properties, our data indicating they may be promising compounds in several fields of medicinal chemistry.

MedChemTrain e-School 2020: Event Highlights and Insights into Virtual Symposium Organization.

Virtual events are flourishing with the world lockdown due to the COVID-19 pandemic. As a result of the cancelation or postponement of scheduled physical meetings, a revolution in medicinal chemistry scientific meetings occurred, leading to an increase in new strategies to share science. One example are online events, namely e-schools or webinars. Taking this into consideration, we decided to promote the MedChemTrain e-School 2020, a virtual event aiming to bring together the scientific community and share some updates in the medicinal chemistry field. After organizing this free event, with more than 1.4 thousand participants worldwide, we decided to share some insights about the logistics behind organizing a virtual symposium to help scientists with this new challenge in science communication.

Neurovascular Coupling Impairment in Heart Failure with Reduction Ejection Fraction.

The hemodynamic consequences of a persistent reduced ejection fraction and unknown cardiac output on the brain have not been thoroughly studied. We sought to explore the status of the mechanisms of cerebrovascular regulation in patients with heart failure with reduced (HFrEF) and recovered (HFrecEF) ejection fraction. We monitored cerebral blood flow velocity (CBFV) with transcranial Doppler and blood pressure. Cerebral autoregulation, assessed by transfer function from the spontaneous oscillations of blood pressure to CBFV and neurovascular coupling (NVC) with visual stimulation were compared between groups of HFrEF, HFrecEF and healthy controls. NVC was significantly impaired in HFrEF patients with reduced augmentation of CBFV during stimulation (overshoot systolic CBFV 19.11 ± 6.92 vs. 22.61 ± 7.78 vs. 27.92 ± 6.84, p = 0.04), slower upright of CBFV (rate time to overshoot: 1.19 ± 3.0 vs. 3.06 (4.30) vs. 2.90 ± 3.84, p = 0.02); p = 0.023) and reduced arterial oscillatory properties (natural frequency 0.17 ± 0.06 vs. 0.20 ± 0.09 vs. 0.24 ± 0.07, p = 0.03; attenuation 0.34 ±0.24vs 0.48 ± 0.35 vs. 0.50 ± 0.23, p = 0.05). Cerebral autoregulation was preserved. The neurovascular unit of subjects with chronically reduced heart pumping capability is severely dysfunctional. Dynamic testing with transcranial Doppler could be useful in these patients, but whether it helps in predicting cognitive impairment must be addressed in future prospective studies.

Importance of Extraintestinal Manifestations in Early Diagnosis of Gardner Syndrome.

Gardner's syndrome is an autosomal dominant disease caused by a mutation in the APC gene with 20-30% of cases presenting de novo. This entity is a variant of familial adenomatous polyposis, with a prevalence of 3/100,000 habitants. It may present as early as 2 months of age with a variety of both colonic and extracolonic symptoms. We report a case of a 21-year-old man, without any known family history, presenting with microcytic hypochromic anemia and constitutional symptoms for two months. Ultimately, after the etiological study, Gardner syndrome diagnosis was established as an index primary familiar case. Gardner syndrome is a clinical challenge which requires a prompt suspicion in order to reach its diagnosis. Given the malignant evolution of adenomas in 100% of untreated patients, early identification of extraintestinal manifestations (identifiable prior to colonic symptoms) is of the essence. A consequent endoscopic study to confirm gastrointestinal involvement is essential for a more favorable prognosis.

De novo Gastrinoma: A Case Report.

Gastrinomas are neuroendocrine tumors characterized by gastrin overexpression - 80% are sporadic and 20% are associated with multiple endocrine neoplasia type 1. A 75-year-old male patient, surgically treated at the age of 50 years for gastrinoma, followed on an outpatient basis because of chronic non-bloody diarrhea, was admitted to our hospital because of abdominal pain, watery diarrhea, and nonbiliary vomits. He was hypotensive and showed no response to fluids. Blood cultures were positive for Salmonella, and a diagnosis of septic shock due to Salmonella infection was made. The patient's condition improved, but the history of chronic diarrhea was still not explained. To investigate chronic diarrhea, gastrinoma recurrence was considered. Serum gastrin measurement was five times higher than the upper limit of the normal range (536 pg/mL). A positive somatostatin receptor scintigraphy was diagnostic for neuroendocrine tumor. Metastases were excluded. The patient was proposed to curative surgery, and a diagnosis of a well-differentiated neuroendocrine tumor was made.

Gastrinomas são tumores neuroendócrinos caracterizados por hipersecreção de gastrina - 80% são esporádicos e 20% associados a neoplasia endócrina múltipla tipo 1 (MEN1). Apresenta-se o caso de um homem, de 75 anos, tratado cirurgicamente aos 50 anos por gastrinoma, seguido em consulta de Medicina Interna por diarreia crónica não-sanguinolenta, internado no nosso hospital por dor abdominal, diarreia aquosa e vómitos não biliares. À admissão, apresentava-se hipotenso e pouco responsivo a fluidoterapia. As hemoculturas foram positivas para Salmonella e foi feito o diagnóstico de choque séptico por Salmonella. O doente melhorou, mas a história prévia de diarreia crónica não estava esclarecida. Para investigar a diarreia crónica, foi colocada como hipótese recidiva de gastrinoma. A medição de gastrina sérica foi cinco vezes superior ao limite superior do normal (536 pg/mL). A cintigrafia com receptores de somatostatina foi diagnóstica para tumor neuroendócrino. Foram excluídas metástases. O doente foi proposto para cirurgia curativa e foi feito o diagnóstico de tumor neuroendócrino bem diferenciado.

Pyridine-Containing Macrocycles Display MMP-2/9 Inhibitory Activity and Distinct Effects on Migration and Invasion of 2D and 3D Breast Cancer Models.

The role of metalloproteinases (MMPs) on the migration and invasion of cancer cells has been correlated with tumor aggressiveness, namely with the up-regulation of MMP-2 and 9. Herein, two pyridine-containing macrocyclic compounds, [15]pyN5 and [16]pyN5, were synthesized, chemically characterized and evaluated as potential MMP inhibitors for breast cancer therapy using 3D and 2D cellular models. [15]pyN5 and [16]pyN5 (5-20 µM) showed a marked inhibition of MMPs activity (100% at concentrations ≥ 7.5 µM) when compared to ARP-100, a known MMP inhibitor. The inhibitory activity of [15]pyN5 and [16]pyN5 was further supported through in silico docking studies using Goldscore and ChemPLP scoring functions. Moreover, although no significant differences were observed in the invasion studies in the presence of all MMPs inhibitors, cell migration was significantly inhibited by both pyridine-containing macrocycles at concentrations above 5 µM in 2D cells (p < 0.05). In spheroids, the same effect was observed, but only with [16]pyN5 at 20 µM and ARP-100 at 40 µM. Overall, [15]pyN5 and [16]pyN5 led to impaired breast cancer cell migration and revealed to be potential inhibitors of MMPs 2 and 9.

Biosensor for direct bioelectrocatalysis detection of nitric oxide using nitric oxide reductase incorporated in carboxylated single-walled carbon nanotubes/lipidic 3 bilayer nanocomposite.

An enzymatic biosensor based on nitric oxide reductase (NOR; purified from Marinobacter hydrocarbonoclasticus) was developed for nitric oxide (NO) detection. The biosensor was prepared by deposition onto a pyrolytic graphite electrode (PGE) of a nanocomposite constituted by carboxylated single-walled carbon nanotubes (SWCNTs), a lipidic bilayer [1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (DSPE-PEG)] and NOR. NOR direct electron transfer and NO bioelectrocatalysis were characterized by several electrochemical techniques. The biosensor development was also followed by scanning electron microscopy and Fourier transform infrared spectroscopy. Improved enzyme stability and electron transfer (1.96 × 10-4 cm.s-1 apparent rate constant) was obtained with the optimum SWCNTs/(DOPE:DOTAP:DSPE-PEG)/NOR) ratio of 4/2.5/4 (v/v/v), which biomimicked the NOR environment. The PGE/[SWCNTs/(DOPE:DOTAP:DSPE-PEG)/NOR] biosensor exhibited a low Michaelis-Menten constant (4.3 µM), wide linear range (0.44-9.09 µM), low detection limit (0.13 µM), high repeatability (4.1% RSD), reproducibility (7.0% RSD), and stability (ca. 5 weeks). Selectivity tests towards L-arginine, ascorbic acid, sodium nitrate, sodium nitrite and glucose showed that these compounds did not significantly interfere in NO biosensing (91.0 ±â€¯9.3%-98.4 ±â€¯5.3% recoveries). The proposed biosensor, by incorporating the benefits of biomimetic features of the phospholipid bilayer with SWCNT's inherent properties and NOR bioelectrocatalytic activity and selectivity, is a promising tool for NO.

Electroanalytical characterization of the direct Marinobacter hydrocarbonoclasticus nitric oxide reductase-catalysed nitric oxide and dioxygen reduction.

Understanding the direct electron transfer processes between redox proteins and electrode surface is fundamental to understand the proteins mechanistic properties and for development of novel biosensors. In this study, nitric oxide reductase (NOR) extracted from Marinobacter hydrocarbonoclasticus bacteria was adsorbed onto a pyrolytic graphite electrode (PGE) to develop an unmediated enzymatic biosensor (PGE/NOR)) for characterization of NOR direct electrochemical behaviour and NOR electroanalytical features towards NO and O2. Square-wave voltammetry showed the reduction potential of all the four NOR redox centers: 0.095 ±â€¯0.002, -0.108 ±â€¯0.008, -0.328 ±â€¯0.001 and -0.635 ±â€¯0.004 V vs. SCE for heme c, heme b, heme b3 and non-heme FeB, respectively. The determined sensitivity (-4.00 × 10-8 ±â€¯1.84 × 10-9 A/µM and - 2.71 × 10-8 ±â€¯1.44 × 10-9 A/µM for NO and O2, respectively), limit of detection (0.5 µM for NO and 1.0 µM for O2) and the Michaelis Menten constant (2.1 and 7.0 µM for NO and O2, respectively) corroborated the higher affinity of NOR for its natural substrate (NO). No significant interference on sensitivity towards NO was perceived in the presence of O2, while the O2 reduction was markedly and negatively impacted (3.6 times lower sensitivity) by the presence of NO. These results clearly demonstrate the high potential of NOR for the design of innovative NO biosensors.

Commercial octopus species from different geographical origins: Levels of polycyclic aromatic hydrocarbons and potential health risks for consumers.

Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants that have been raising global concern due to their carcinogenic and mutagenic properties. A total of 18 PAHs (16 USEPA priority compounds, benzo(j)fluoranthene and dibenzo(a,l)pyrene) were assessed in the edible tissues of raw octopus (Octopus vulgaris, Octopus maya, and Eledone cirrhosa) from six geographical origins available to Portuguese consumers. Inter- and intra-species comparison was statistically performed. The concentrations of total PAHs (∑PAHs) ranged between 8.59 and 12.8 µg/kg w.w. Octopus vulgaris caught in northwest Atlantic Ocean presented ΣPAHs significantly higher than those captured in Pacific Ocean and Mediterranean Sea, as well as than the other characterized species from western central and northeast Atlantic Ocean. PAHs with 2-3 rings were the predominant compounds (86-92% of ∑PAHs) but diagnostic ratios indicated the existence of pyrogenic sources in addition to petrogenic sources. Known and possible/probable carcinogenic compounds represented 11-21% of ΣPAHs. World and Portuguese per capita ingestion of ∑PAHs due to cephalopods consumption varied between 1.62-2.55 × 10-4 and 7.09-11.2 × 10-4 µg/kg body weight per day, respectively. Potential risks estimated for low and high consumers according to USEPA methodology suggested that a regular consumption of raw octopus does not pose public health risks.

An Unusual Case of Tricuspid Stenosis.

Tricuspid stenosis is an uncommon valvular abnormality commonly associated with other valvular lesions. Ebstein's anomaly is a rare congenital heart malformation characterized primarily by abnormalities of the tricuspid valve and right ventricle. Endomyocardial fibrosis is a restrictive cardiomyopathy observed in tropical and subtropical regions. It may cause right ventricular distortion with apparent apical displacement of the tricuspid valve, mimicking Ebstein's anomaly. Eosinophilia is the most commonly cited aetiological link in endomyocardial fibrosis. Here we report the case of 42-year-old male patient who presented with heart failure and severe tricuspid stenosis where a diagnosis of hypereosinophilic syndrome was also established. This case represented a diagnostic challenge in the search for the definitive cause of the tricuspid stenosis. LEARNING POINTS: Ebstein's anomaly is a rare congenital heart malformation characterized primarily by abnormalities of the tricuspid valve and right ventricle. The tricuspid valve is usually incompetent, and very rarely stenotic.Hypereosinophilic syndromes can be associated with heart damage. The fibrotic stage of eosinophil-mediated heart damage is characterized by altered cardiac function due to either compromise/entrapment of the cordae tendineae and/or restrictive cardiomyopathy.Endomyocardial fibrosis is a restrictive cardiomyopathy observed in tropical and subtropical regions that may be indistinguishable from the Loeffler's endocarditis observed in temperate climates. It may cause right ventricle distortion and apical displacement of the tricuspid valve, mimicking Ebstein's anomaly.

Response of Two Mytilids to a Heatwave: The Complex Interplay of Physiology, Behaviour and Ecological Interactions.

Different combinations of behavioural and physiological responses may play a crucial role in the ecological success of species, notably in the context of biological invasions. The invasive mussel Xenostrobus securis has successfully colonised the inner part of the Galician Rias Baixas (NW Spain), where it co-occurs with the commercially-important mussel Mytilus galloprovincialis. This study investigated the effect of a heatwave on the physiological and behavioural responses in monospecific or mixed aggregations of these species. In a mesocosm experiment, mussels were exposed to simulated tidal cycles and similar temperature conditions to those experienced in the field during a heat-wave that occurred in the summer of 2013, when field robo-mussels registered temperatures up to 44.5°C at low tide. The overall responses to stress differed markedly between the two species. In monospecific aggregations M. galloprovincialis was more vulnerable than X. securis to heat exposure during emersion. However, in mixed aggregations, the presence of the invader was associated with lower mortality in M. galloprovincialis. The greater sensitivity of M. galloprovincialis to heat exposure was reflected in a higher mortality level, greater induction of Hsp70 protein and higher rates of respiration and gaping activity, which were accompanied by a lower heart rate (bradycardia). The findings show that the invader enhanced the physiological performance of M. galloprovincialis, highlighting the importance of species interactions in regulating responses to environmental stress. Understanding the complex interactions between ecological factors and physiological and behavioural responses of closely-related species is essential for predicting the impacts of invasions in the context of future climate change.

Equatorial range limits of an intertidal ectotherm are more linked to water than air temperature.

As climate change is expected to impose increasing thermal stress on intertidal organisms, understanding the mechanisms by which body temperatures translate into major biogeographic patterns is of paramount importance. We exposed individuals of the limpet Patella vulgata Linnaeus, 1758, to realistic experimental treatments aimed at disentangling the contribution of water and air temperature for the buildup of thermal stress. Treatments were designed based on temperature data collected at the microhabitat level, from 15 shores along the Atlantic European coast spanning nearly 20° of latitude. Cardiac activity data indicated that thermal stress levels in P. vulgata are directly linked to elevated water temperature, while high air temperature is only stressful if water temperature is also high. In addition, the analysis of the link between population densities and thermal regimes at the studied locations suggests that the occurrence of elevated water temperature may represent a threshold P. vulgata is unable to tolerate. By combining projected temperatures with the temperature threshold identified, we show that climate change will likely result in the westward expansion of the historical distribution gap in the Bay of Biscay (southwest France), and northward contraction of the southern range limit in south Portugal. These findings suggest that even a minor relaxing of the upwelling off northwest Iberia could lead to a dramatic increase in thermal stress, with major consequences for the structure and functioning of the intertidal communities along Iberian rocky shores.

Loss of thermal refugia near equatorial range limits.

This study examines the importance of thermal refugia along the majority of the geographical range of a key intertidal species (Patella vulgata Linnaeus, 1758) on the Atlantic coast of Europe. We asked whether differences between sun-exposed and shaded microhabitats were responsible for differences in physiological stress and ecological performance and examined the availability of refugia near equatorial range limits. Thermal differences between sun-exposed and shaded microhabitats are consistently associated with differences in physiological performance, and the frequency of occurrence of high temperatures is most probably limiting the maximum population densities supported at any given place. Topographical complexity provides thermal refugia throughout most of the distribution range, although towards the equatorial edges the magnitude of the amelioration provided by shaded microhabitats is largely reduced. Importantly, the limiting effects of temperature, rather than being related to latitude, seem to be tightly associated with microsite variability, which therefore is likely to have profound effects on the way local populations (and consequently species) respond to climatic changes.