Neurotensin (8-13) and Neuromedin N Neuropeptides Radiolabelling with Copper-64 Produced on Solid or Liquid Targets.

On the verge of a theranostic approach to personalised medicine, copper-64 is one of the emerging radioisotopes in nuclear medicine due to its exploitable nuclear and biochemical characteristics. The increased demand for copper-64 for preclinical and clinical studies has prompted the development of production routes. This research aims to compare the (p,n) reaction on nickel-64 solid versus liquid targets and evaluate the effectiveness of [64Cu]CuCl2 solutions prepared by the two routes. As new treatments for neurotensin receptor-overexpressing tumours have developed, copper-64 was used to radiolabel Neurotensin (8-13) and Neuromedin N. High-quality [64Cu]CuCl2 solutions were prepared using ACSI TR-19 and IBA Cyclone Kiube cyclotrons. The radiochemical purity after post-irradiation processing reached 99% (LT) and 99.99% (ST), respectively. The irradiation of a solid target with 11.8 MeV protons and 150 µAh led to 704 ± 84 MBq/µA (17.6 ± 2.1 GBq/batch at EOB). At the end of the purification process (1 h, 90.90% activity yield), the solution for peptide radiolabelling had a radioactive concentration of 1340.4 ± 70.1 MBq/mL (n.d.c.). The irradiation of a liquid target with 16.9 MeV protons and 230 µAh resulted in 3.7 ± 0.2 GBq/batch at EOB, which corresponds to an experimental production yield of 6.89 GBq.cm3/(g.µA)sat. Benefiting from a shorter purification process (40 min), the activity yielded 90.87%, while the radioactive concentration of the radiolabelling solution was lower (492 MBq/mL, n.d.c.). The [64Cu]CuCl2 solutions were successfully used for the radiolabelling of DOTA-NT(8-13) and DOTA-NN neuropeptides, resulting in a high RCP (>99%) and high molar activity (27.2 and 26.4 GBq/µmol for LT route compared to 45 and 52 GBq/µmol for ST route, respectively). The strong interaction between the [64Cu]Cu-DOTA-NT(8-13) and the colon cancerous cell lines HT29 and HCT116 proved that the specificity for NTR had not been altered, as shown by the uptake and retention data.

Cross-modal coherence and incoherence of early infant interactive behavior: links to attachment in infants born very preterm or full-term.

Infants exhibit flexibly organized configurations of facial, vocal, affective, and motor behavior during caregiver-infant interactions that convey convergent messages about their internal states and desires. Prior work documents that greater cross-modal discrepancy at 4 months predicts disorganized attachment. Here, we evaluated whether: very preterm (VPT) or full-term (FT) status predicts cross-modal coherence or incoherence in infants' behavior with the caregiver at 3 months; and, regardless of prematurity, whether cross-modal interactive coherence or incoherence predicts 12-month attachment. Participants included 155 infants (85 FT; 70 VPT), and their mothers followed from birth to 12 months (corrected age). Infants' cross-modal coherent and incoherent responses were scored microanalytically from videotaped en-face interactions. Infants' attachment security was evaluated during Ainsworth's Strange Situation. Infants born VPT exhibited more incoherent cross-modal responses and insecure attachment than infants born FT. Regardless of prematurity, infants' coherent and incoherent cross-modal interactive behaviors at 3 months predicted different attachment patterns at 12 months.

Maternal pre and perinatal experiences with their full-term, preterm and very preterm newborns.

BACKGROUND: Mothers' reports about pregnancy, maternity and their experiences during the perinatal period have been associated with infants' later quality of attachment and development. Yet, there has been little research with mothers of very preterm newborns. This study aimed to explore mothers' experiences related to pregnancy, premature birth, relationship with the newborn, and future perspectives, and to compare them in the context of distinct infants' at-birth-risk conditions. METHODS: A semi-structured interview was conducted with women after birth, within the first 72 h of the newborn's life. A total of 150 women participated and were divided in three groups: (1) 50 mothers of full-term newborns (Gestational Age (GA) ≥ 37 weeks; FT), (2) 50 mothers of preterm newborns (GA 32-36 weeks; PT) and (3) 50 mothers of very preterm newborns (GA < 32 weeks; VPT). RESULTS: Mothers of full-term infants responded more often that their children were calm and that they did not expect difficulties in taking care of and providing for the baby. Mothers of preterm newborns although having planned and accepted well the pregnancy (with no mixed or ambivalent feelings about it) and while being optimistic about their competence to take care of the baby, mentioned feeling frightened because of the unexpected occurrence of a premature birth and its associated risks. Mothers of very preterm newborns reported more negative and distressful feelings while showing more difficulties in anticipating the experience of caring for their babies. CONCLUSION: The results indicate that Health Care Systems and Neonatal Care Policy should provide differentiated psychological support and responses to mothers, babies and families, taking into account the newborns' GA and neonatal risk factors.

An unexpected association in a patient with heart failure presenting a surgical challenge.

Bicuspid aortic valve (BAV) is the most common form of congenital heart disease and frequently leads to premature valvular dysfunction. BAV is associated with aortic wall abnormalities and a high prevalence of ascending aorta dilatation and coarctation of the aorta (CoA). Consequently, in patients with BAV a careful assessment of the valve, and also of the aortic root and the ascending aorta, should be performed. The most feared complication is aortic dissection, however, the actual incidence of this complication is low. We report the case of a 58-year-old man who presented with New York Heart Association class III heart failure. The work-up revealed BAV with severe stenosis and severe compromise of left ventricle systolic function. In addition, CoA in the isthmus region, and type B dissection of the aorta were diagnosed.

The impact of antibiotic exposure in water and zebrafish gut microbiomes: A 16S rRNA gene-based metagenomic analysis.

In order to supply human demand for food, the aquaculture industry has been growing fast in the last years, being fish usually cultivated in overcrowded conditions. Hence, to prevent the rapidly disease spreading, antibiotics may be applied to both sick and healthy animals. Due to its broad spectrum, oxytetracycline (OTC) is one of the most used antibiotics in food-production. Yet, although useful to prevent infections, antibiotics may reshape aquatic animals' microbiome, disturbing hosts' welfare. However, the impact of this exposure to the organism microbiome and its surrounding environment is poorly understood. Then, the objective of this study was to analyze in detail the long-term effect of OTC in both zebrafish gut and water microbiomes. Zebrafish adults were exposed, via water, for two months to three concentrations of OTC (0, 10 and 10000 µg/L). Total DNA was extracted from gut and water samples and the V3-V4 region of the bacterial 16 S rRNA gene was sequenced using Illumina technology. Results of alpha and beta-diversity analyses revealed that long-term exposure to OTC impacted both zebrafish gut and water microbiomes. In water samples, effects were observed even at the lowest (10 µg/L) OTC concentration tested resulting in an increase in Deltaproteobacteria, namely the Myxococcales and Bdellovibrionales orders. On the other hand, effects on zebrafish gut were only observed at the highest concentration with the selection of Alphaproteobacteria and Actinobacteria classes. Although these classes are common in fish gut, the increase of Actinobacteria may represent a health problem since some genera like Gordonia are linked to some human infection disease. Nevertheless, in both gut and water, it was observed a decrease in Gamaproteobacteria, probably due to OTC mode of action. In silico functional metagenomic analysis revealed that OTC exposure selected general detoxification mechanisms. In addition, the abundance of functional genes involved in Quorum Sensing (QS) increased under OTC exposure suggesting that QS may help bacteria to survive OTC stress. Thus, future studies should consider post-exposure scenarios for a deeper analysis of the water and zebrafish gut resistome, since bacteria may react differently after exposure ceased.

Biochemical and behavioral responses of zebrafish embryos to magnetic graphene/nickel nanocomposites.

Graphene nanocomposites are emerging carbon-based materials with interesting electrical, mechanical, optical and magnetic properties, relevant for applications in different fields. Despite this increased use, the impact of graphene nanocomposites residues in the environment has not been properly studied. Thus, the goal of this work was to assess the toxicity of two nickel/graphene nanocomposites (G/Ni1 and G/Ni2) differing in size and shape to Danio rerio embryos. Their toxicity was evaluated using apical (mortality, development and hatching), biochemical [cholinesterase (ChE), glutathione-S-transferase (GST), and catalase (CAT) activities] and behavioral (locomotor activity) endpoints. At the tested concentrations, neither of the nanocomposites presented lethal or developmental effects. Nevertheless, both nanocomposites induced behavioral effects, reducing swimming distances. This effect was, however detected at lower concentrations in the G/Ni1 nanocomposite. At biochemical level, only G/Ni1 nanocomposite showed to interfere with the measured parameters, increasing the activities of ChE, CAT and GST. Differences in the effects induced by the two nanocomposites seem to be related not only with their size, but also with the shape and the ability to continuously release nickel ions to aqueous medium. This work highlights the importance of studying graphene nanocomposites effects to aquatic organisms even when acute toxicity is not expected. The relevance of the effects found in this work need to be further analyzed in light of the consequences to the long-term fitness of the organisms and in light of the environmental concentrations expected for this type of compounds.

Is UV radiation changing the toxicity of compounds to zebrafish embryos?

At ecosystems level, environmental parameters such as temperature, pH, dissolved oxygen concentration and intensity of UV radiation (UVR) have an important role on the efficiency of organisms' physiological and behavioral performances and consequently on the capacity of response to contaminants. Insignificant alterations of these parameters may compromise this response. In addition, these parameters can additionally alter chemical compounds by inducing their degradation, producing thereafter other metabolites. Understanding the combined effects of chemicals and environmental parameters is absolutely necessary for an adequate prediction of risk in aquatic environments. According to this scenario, this work aims at studying the combined toxicity of UVR and three xenobiotics: the biocide triclosan (TCS), the metal chromium (as potassium dichromate, PD) and the fungicide prochloraz (PCZ). To achieve this goal zebrafish (Danio rerio) embryos (3h post fertilization (hpf)) were exposed to several concentrations of each chemical combined with different UV intensities; mortality and eggs were recorded every 24h for the all test duration (96 h). Results showed different response patterns depending on the toxicant, stress levels and duration of exposure. The combination of UVR and TCS indicated a dose ratio deviation where synergism was observed when UVR was the dominant stressor (day 2). The combination of UVR and PD presented a dose level dependency at day 3 indicating antagonism at low stress levels, changing with time where at day 4, a dose ratio deviation showed statistically that synergism occurred at higher PD concentrations. Finally, UVR combined with PCZ indicated a dose ratio at day 3 and dose level deviation at day 4 of exposure, suggesting a synergistic response when PCZ is the dominant stressor in the combination. The obtained results in this study highlighted the importance of taking into account the possible interaction of stressors and time of exposure to better predict environmental risk.

Primary diffuse large B-cell lymphoma of the heart: A rare case of heart failure.

A 65-year-old man with previous history of smoking, controlled HIV infection, treated hepatitis B infection, and type III cryoglobulinemia, was admitted due to right heart failure symptoms and significant weight loss. Despite being haemodynamically stable, he had periods of 1:1 conduction atrial flutter and presented with respiratory alkalosis and metabolic acidosis, as well as acute kidney and hepatic dysfunction, elevated D-dimer and cardiac markers. He underwent imaging with chest computed tomography and echocardiogram that confirmed pulmonary embolism and most notably revealed a significant sized cardiac mass causing almost complete obstruction of the right chambers, with no cleavage plane with the myocardial walls and tricuspid valve. Cardiac magnetic resonance was highly suggestive of malignancy. Cardiac surgery for mass excision and endomyocardial biopsy for diagnosis were considered, but the patient died with obstructive shock unresponsive to medical treatment. The autopsy revealed a primary unspecified diffuse large B-cell lymphoma.

[Dyspnea in aortic stenosis: appearances can be deceptive]. / Dispneia na estenose aórtica: nem tudo o que parece é.

Valvular aortic stenosis is the most common valvular disorder in Europe. Although recommended, stress exams are still underused in its evaluation. We report the case of a 60-year-old man who, following a routine electrocardiogram with abnormal ventricular repolarization, underwent stress testing, which was positive for myocardial ischemia, and an echocardiogram that revealed moderate aortic stenosis. Cardiac catheterization showed no angiographic coronary lesions and an intraventricular gradient of 45 mmHg. In view of the latter, stress echocardiography was performed, which documented an increase in the intraventricular gradient from 30 mmHg to 131 mmHg. Repeat stress echocardiography under treatment with bisoprolol showed an increase in test duration and a maximum intraventricular gradient at peak exercise of 36 mmHg. Stress exams may have an important role in the diagnostic and therapeutic management of patients with aortic stenosis.

[Carcinoid heart - case report]. / Coração carcinóide - a propósito de um caso clínico.

We describe the case of a 76-year-old woman, diagnosed with a neuroendocrine tumor of the cecum in 2004, with liver metastases and carcinoid syndrome since September 2010. The patient had been treated intermittently with chemotherapy cycles, and remained symptomatic, with worsening secondary lesions. In June 2011 she began to present signs and symptoms of right heart failure and was hospitalized in September 2011. Transthoracic two- and three-dimensional echocardiography revealed enlarged right atrium and ventricle and thickened and fixed tricuspid and pulmonary valve leaflets, causing severe tricuspid regurgitation and mild pulmonary regurgitation and stenosis, suggestive of carcinoid heart disease. The authors discuss the clinical importance of transthoracic echocardiography, and the more recent three-dimensional echocardiography, as the diagnostic exam of choice in these cases, as it is especially suitable for assessing the valves and subvalvular apparatus.

A rare cause of chest pain in paediatric age: a teenager with acute myocardial infarction due to spontaneous coronary artery dissection.

A healthy 17-year-old boy was admitted to the emergency department presenting with a pressure-like sternal pain that started during exercise. His physical examination was normal. Twelve-lead ECG and transthoracic echocardiogram suggested a myocardial infarction. The patient was submitted to an invasive coronary angiography, which revealed a distal occlusion of the left anterior descending artery, due to a spontaneous coronary artery dissection. A balloon angioplasty was performed, with good results. Aetiological study did not discover any pathologic condition. Chest pain in paediatric age is a frequent complaint, despite not being usually caused by a serious condition. However, it is important to remember warning signs in order to diagnose life-threatening diseases, as soon as possible.

Photo-catalytic oxidation of cyclohexane over TiO2: a novel interpretation of temperature dependent performance.

The rate of cyclohexane photo-catalytic oxidation to cyclohexanone over anatase TiO(2) was studied at temperatures between 23 and 60 °C by in situ ATR-FTIR spectroscopy, and the kinetic parameters were estimated using a microkinetic model. At low temperatures, surface cyclohexanone formation is limited by cyclohexane adsorption due to unfavorable desorption of H(2)O, rather than previously proposed slow desorption of the product cyclohexanone. Up to 50 °C, the activation energy for photocatalytic cyclohexanone formation is zero, while carboxylates are formed with an activation energy of 18.4 ± 3.3 kJ mol(-1). Above 50 °C, significant (thermal) oxidation of cyclohexanone contributes to carboxylate formation. The irreversibly adsorbed carboxylates lead to deactivation of the catalyst, and are most likely the predominant cause of the non-Arrhenius behavior at relatively high reaction temperatures, rather than cyclohexane adsorption limitations. The results imply that elevating the reaction temperature of photocatalytic cyclohexane oxidation reduces selectivity, and is not a means to suppress catalyst deactivation.

Giant left atrial thrombus: an unexpected finding.

The incidence of left atrial thrombi is higher in patients with mitral valve stenosis. Its presence and location have important implications in deciding on the therapeutic approach, particularly the need for valve repair. We describe the case of a 63-year-old patient, with asymptomatic moderate mitral stenosis, hospitalized due to community-acquired pneumonia, in whom investigation to exclude pulmonary thromboembolism revealed a giant left atrial thrombus, which required urgent surgery.

Zebrafish and water microbiome recovery after oxytetracycline exposure.

Oxytetracycline (OTC) is a broad-spectrum antibiotic widely used in aquaculture, resulting in contamination of aquatic environments. In a previous study, we observed significant effects of OTC sublethal concentrations in zebrafish, its microbiome and the water bacterial community. Here we assessed the extent to which these effects are reversible after a recovery period. Zebrafish adults were exposed to OTC (10,000 µg/L) via water exposure. Effects were analyzed at 5 days (5 dE) and 2 months (2 mE) of exposure and recovery was assessed at 5 days (5dPE) and 1 month (1mPE) after exposure Impacts were observed in fish energetic reserves and in fish and water microbiomes structure, being significant even at 5 dE. At energetic reserves level, the effect in cellular energy allocation (CEA) was dependent on the exposure time: initially CEA increased while after 2 mE CEA decreased. At microbiome level, diversity was not affected but the richness of the water microbiome significantly decreased at 2 mE. Regarding the post-exposure period, at CEA level, organisms seem to recover. In water and gut microbiomes OTC effects were also attenuated after exposure ceases, indicating a recovery. Even so, the structure of water exposed community remained significantly different towards the control, while richness of this community significantly increased at 1mPE. During exposure the relative abundance of 11 and 16 genera was significantly affected in the gut and water microbiomes, respectively, though these numbers decreased to 4 and 8 genera in the post-exposure period. At functional level during exposure 12 and 13 pathways were predicted to be affected in zebrafish gut and water microbiomes respectively, while post-exposure few pathways remained significantly affected. Hence, our results suggest a recovery of the fish fitness as well as of the water and intestine microbiomes after exposure ceases. Even so, some of the effects caused by OTC remain significant after this recovery period.

Tetracycline-Resistant Bacteria Selected from Water and Zebrafish after Antibiotic Exposure.

The emergence of antibiotic-resistant pathogens due to worldwide antibiotic use is raising concern in several settings, including aquaculture. In this work, the selection of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) was evaluated after exposure of zebrafish to oxytetracycline (OTC) for two months, followed by a recovery period. The selection of ARB in water and fish was determined using selective media. The abundance of tetA genes was estimated through qPCR. Higher prevalence of ARB was measured in all samples exposed to the antibiotic when compared to control samples, although statistical significance was only achieved five days after exposure. Isolates recovered from samples exposed to the antibiotic were affiliated with Pseudomonas and Stenotrophomonas. Various antibiotic susceptibility profiles were detected and 37% of the isolates displayed multidrug resistance (MDR). The selection of the tetA gene was confirmed by qPCR at the highest OTC concentration tested. Two MDR isolates, tested using zebrafish embryos, caused significant mortality, indicating a potential impact on fish health and survival. Overall, our work highlights the potential impact of antibiotic contamination in the selection of potential pathogenic ARB and ARGS.

Behçet's disease: a case report about a rare cause of intra-cardiac mass.

BACKGROUND: Intra-cardiac masses are always a challenging diagnosis, especially when it involves the right side of the heart. There are multiples aetiologies that can be responsible for these masses, namely thrombosis, neoplasm, or vegetations. Occasionally, these may be related to an autoimmune process not yet diagnosed. We present a case of a 17-year-old patient with an exuberant right ventricular mass due to a not yet diagnosed Behçet's disease. The best approach and treatment for these patients remains uncertain. CASE SUMMARY: The authors present a case of a 17-year-old patient with a right ventricular mass who presented as an initial manifestation of Behçet's disease. It was firstly assumed as a thrombotic mass and medicated with anticoagulation, with no resolution. After performing a cardiac magnetic resonance, the case was discussed in a multidisciplinary team, including cardiology, paediatrics, and rheumatology, and the diagnosis of Behçet's disease with cardiac complication was established. The patient started immunosuppressive therapy with clinical and echocardiographic response. DISCUSSION: Behçet's disease is a multi-systemic autoimmune vasculitis that usually manifests by recurrent oral and genital ulcers as well as ocular symptoms. Cardiac manifestations are rare but important aspects of the course of the disease, especially in what concerns morbidity burden. The treatment of these cardiovascular complications is generally empirical and involves the treatment of the underlying disease.

The Prognostic Value of Exercise Echocardiography After Percutaneous Coronary Intervention.

BACKGROUND: Exercise echocardiography (EE) is a valuable noninvasive method for diagnostic and prognostic assessment of ischemic cardiac disease. The prognostic value of a negative EE test is well known overall, but its role in patients who undergo percutaneous coronary intervention remains poorly validated. The aim of this study was to ascertain the prognostic value of treadmill EE and to determine predictors of cardiac events in this population, with an emphasis on nonpositive (negative or inconclusive) test results. METHODS: A retrospective single-center study was performed. It included 516 patients (83% man; mean age, 62 ± 9 years) previously subjected to percutaneous coronary intervention who underwent treadmill EE between 2008 and 2017. Demographic, clinical, echocardiographic, and angiographic data were collected. The occurrence of cardiac events (cardiac death, acute coronary syndrome, or coronary revascularization) during follow-up was investigated. A multivariate Cox regression analysis was used to evaluate predictors of cardiac events. The Kaplan-Meier method was used to evaluate event-free survival rates. RESULTS: The results of EE were negative for myocardial ischemia in 245 patients (47.5%), inconclusive in 144 (27.9%), and positive in 127 (24.6%). During a mean follow-up period of 40 ± 34 months, cardiac events occurred in 152 patients (29.5%). The positive and negative predictive values of EE were 81.6% and 85.3%, respectively. The sensitivity of the exercise test was 73.9%, with specificity of 90.1%. Predictors of cardiac events were typical angina (hazard ratio [HR], 1.95; 95% CI, 1.16-3.27; P = .011), a positive ischemic response detected by electrocardiographic monitoring during EE (HR, 2.01; 95% CI, 1.21-3.34; P = .007), and the test result (inconclusive result: HR, 1.06; 95% CI, 0.51-2.19; P = .878; positive result: HR, 4.35; 95% CI, 2.42-7.80; P < .001). Patients with inconclusive (log-rank P = .038) and positive (log-rank P < .001) results had significantly more cardiac events during follow-up than those with negative EE test results. Focusing on those patients with nonpositive results, cardiac event-free survival rates at 1, 3, and 5 years were 96.6 ± 0.9%, 88.3 ± 1.9%, and 79.5 ± 2.6%, respectively. In this subpopulation, an inconclusive test result (HR, 1.67; 95% CI, 1.03-2.70; P = .039), more extensive coronary artery disease (two vessels: HR, 1.37; 95% CI, 0.75-2.30; P = .304; three vessels: HR, 2.59; 95% CI, 1.38-4.87; P = .003), and arterial hypertension (HR, 2.07; 95% CI, 1.10-3.91; P = .025) were significantly associated with the occurrence of cardiac events. CONCLUSION: Patients with known coronary disease with negative results on EE are at low risk for hard events. Patients with inconclusive results are at higher risk for cardiac events than those with negative results. The detection of patients with low-risk results on EE should decrease the number of unnecessary repeat invasive coronary angiographic examinations.

Acute severe mitral regurgitation as an early complication of pacemaker implantation.

A 70-year-old man developed drug refractory acute pulmonary oedema secondary to acute severe mitral regurgitation (MR) immediately after implantation of a dual-chamber pacemaker for complete heart block. Clinical improvement occurred after allowing the patient to resume his native rhythm. A new lead was positioned within the right ventricular outflow tract (RVOT). The echocardiogram during pacing at RVOT showed minimal MR.

Value of treadmill exercise echocardiography in the evaluation of symptomatic hypertrophic cardiomyopathy with latent obstruction. Impact on therapeutic decisions.

The authors report the case of a 64-year-old patient with hypertrophic cardiomyopathy with latent obstruction. The patient complained of fatigue but the left ventricular outflow gradient at rest was not significant. He underwent exercise echocardiography that was stopped after 3 minutes due to exhaustion. The gradient at peak workload was 150 mmHg accompanied by a fall in arterial pressure. After the patient refused surgery, a double chamber pacemaker was implanted. A month later, exercise echocardiography lasted for 12 minutes and the gradient at peak workload was 60 mmHg. The authors highlight the importance of exercise echocardiography in the evaluation of symptomatic patients with hypertrophic cardiomyopathy without significant left ventricular outflow gradient at rest and the possible therapeutic role of pacing in these patients.

Intraventricular gradients and acute coronary syndromes: a case report.

Left ventricular outflow tract obstruction (LVOTO) has traditionally been associated with hypertrophic obstructive cardiomyopathy, but can occur in other clinical scenarios such as acute myocardial infarction (AMI). In some patients, LVOTO is absent at rest, being detectable only with provocation tests such as stress echocardiography. Timely diagnosis of this phenomenon is very important, as it has therapeutic implications, and relies on clinical suspicion and on recognizing substrates in which LVOTO can occur. We report a case of syncope and AMI associated with LVOTO with systolic anterior motion of the mitral valve and a significant intraventricular gradient.