Hereditary angioedema: 24 years of experience in a Portuguese Reference Center.

Summary: Hereditary angioedema (HAE) poses a high burden of disease, being its epidemiological and clinical data heterogeneous among countries, with no recent published studies concerning Portuguese patients. Therefore, we aimed to raise awareness of HAE and to contribute to clinical knowledge. An observational, descriptive, retrospective, and cross-sectional study was performed, that included a cohort of 126 patients followed in a single Portuguese Center. We observed a high prevalence of HAE-C1-INH type II (45.2% of patients). Most HAE patients (67.4%) presented the initial manifestations of the disease before adulthood, at a mean age of 12.6 ± 8.4 years. However, we found a long delay in HAE diagnosis, especially in those without family history (mean 20.7 ± 17.3 years). Stress was the most common trigger, followed by trauma and infection. Symptoms involving different systems were increasingly reported with increased disease duration. Cutaneous symptoms (95.0%) were more frequent, followed by gastrointestinal (80.7%), and respiratory symptoms (50.4%). HAE symptoms led to abdominal surgery in 22 (17.5%) patients and induced laryngeal edema requiring intubation/tracheostomy in 8 (6.3%) patients. Most patients were under long-term prophylaxis, mainly with attenuated androgens (62.7% of patients).The correct distinction between HAE and other common causes of angioedema is critical, allowing reduction of diagnostic delay, improvement of adequate management, and ultimately improving outcomes and quality of life of HAE patients.

Outcome of pregnancies in a large cohort of women with acromegaly.

OBJECTIVE: To assess the outcome of pregnancies in a large cohort of women with acromegaly. DESIGN AND METHODS: This is a retrospective analysis of 31 pregnancies in 20 patients with acromegaly. RESULTS: Twenty-seven pregnancies resulted in healthy offspring, and 4 resulted in abortion. Three patients underwent transsphenoidal surgery during pregnancy. IGF-1 levels remained elevated during pregnancy in 4 pregnancies and normalized in 23 cases. Fifteen cases were followed during pregnancy without any medical or surgical treatment, and 13 of these exhibited normal IGF-1 levels. Before or during pregnancy, somatostatin receptor ligands usage was not associated with higher risk for adverse outcomes. Arterial hypertension worsening (45%) and impairment of glucose levels (32%) were the most common complications during pregnancies. There were no maternal or neonatal deaths. One woman delivered twins. Two cases of congenital malformations and one with foetal macrosomia were observed. Caesarean delivery was performed in sixteen cases. CONCLUSION: Our study confirms the impact of gestation on IGF-1 levels. However, it also indicates that acromegaly still holds an increased risk for worsening of comorbidities, especially in uncontrolled patients.

Omalizumab in chronic spontaneous and inducible urticaria: a 9 year retrospective study in Portugal.

Summary: Objective. Describe the safety and long-term use of omalizumab in chronic urticaria (CU), both spontaneous (CSU) and inducible (CIndU). Methods. Retrospective chart-review (2006-15) of CU patients treated with omalizumab for ≥ 6 months. Statistical analyses: descriptive statistics, Mann-Whitney, generalized linear models. Results. 23 patients with CSU (3 men), 3 with CIndU (2 men). Generalized linear models showed UAS reduction per omalizumab administration of 16% in CIndU and CSU and UAS7, of 15% in CIndU, and 20% in CSU. DLQI score at baseline had a median of 19 (CIndU and CSU) and after omalizumab a median of 0 (in both). Seven CSU patients stopped omalizumab and remain asymptomatic. No side-effects were observed. Conclusion. Omalizumab is safe and efficacious in CU. Stopping omalizumab can be tried, as some patients achieve remission.

Pediatric eosinophilic esophagitis in Portugal.

SUMMARY: Eosinophilic esophagitis (EoE) is an increasingly frequent diagnosis in our clinical practice, mainly in pediatric age. Allergic responses to food and aeroallergens have been increasingly implicated in the etiology of this disease. We describe a retrospective data analysis of pediatric EoE patients followed in our Immunoallergology Department. Of the 25 children (22 male, average 10.8 years), 88% had prior history of rhinoconjunctivitis, 76% asthma, 48% eczema and 36% food allergy. After evaluation, we identified in 76% and 92% of patients food and aeroallergen sensitization, respectively; 68% had simultaneously food and inhalant sensitization and 96% had at least one positive test to aeroallergens or food allergens. The first (44%) and the most frequent (56%) symptom was dysphagia. The time between symptoms onset and the EoE diagnosis averaged 18.6 ± 29.4 months. A multidisciplinary approach is needed for a correct evaluation, intervention and follow-up of these patients.

Molecular and oenological characterization of Touriga Nacional non-Saccharomyces yeasts.

AIMS: The aim of this study was to evaluate non-Saccharomyces yeasts isolated from spontaneous fermenting musts of Touriga Nacional (TN), one of the most important Portuguese red grape variety, to improve and diversify TN wines. METHODS AND RESULTS: Two hundred and seventy nine isolates were assigned to 11 yeast species by conventional molecular and growth tests. Starmerella bacillaris was the most frequently detected yeast species, followed by Hanseniaspora guilliermondii and Hanseniaspora uvarum. Twenty-three isolates from 10 species were selected for oenological study, namely fermentation performance, physicochemical and quantitative descriptive sensory analysis of the wines produced. A significant species effect was observed for most of the variables evaluated, some species generating wines with quite interesting aromas. CONCLUSIONS: Candida diversa and S. bacillaris isolates produced wines with higher overall quality, higher balance and more intense and diverse aroma. Furthermore, S. bacillaris isolates generated wines with enhanced TN typical aroma, such as bergamot, violet and rock-rose, and were thus regarded as the most promising for improving TN wines. SIGNIFICANCE AND IMPACT OF STUDY: This study revealed the diversity of wine aroma profiles generated by non-Saccharomyces yeast isolates. This knowledge is particularly important given the growing trend from industry to use non-Saccharomyces yeasts as a tool for improving and diversifying the sensory characteristics of wine.

Resistance training suppresses intra-abdominal fatty acid synthesis in ovariectomized rats.

Ovarian hormone loss is associated with a shift in fat distribution to intra-abdomin al adipose tissue (intra-AAT) depots and with lipid metabolism disorders, which predisposes individuals to developing insulin resistance. Resistance training (RT) prevents increases in intra-AAT after ovarian hormone loss. However, the molecular mechanisms underlying these changes remain unclear. We investigated the effects of ovariectomy and RT on gene expression related to lipogenesis and fat oxidation in the intra-AAT of ovariectomized rats. Sprague-Dawley rats (n=6/group) were divided into the groups: sham-sedentary, ovariectomized-sedentary, sham-RT and ovariectomized-RT. RT groups performed a 10-week climbing program on a ladder with progressive overload. Intra-AAT was subjected to morphometric and mRNA analysis. Ovariectomized-sedentary group had larger adipocytes and higher expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-CoA desaturase-1 (SCD-1), acetyl-CoA carboxylase (ACC), hormone-sensitive lipase (HSL) and lower expression of the oxidative carnitinepalmitoyltransferase-I (CPT-1). RT counteracted OVX-induced increases in PPAR-γ and SCD-1 and decreased SREBP-1c. ACC and HSL were downregulated in ovariectomized-RT compared with the ovariectomized-sedentary group. Ovariectomized-RT group had the highest CPT-1 gene expression. Adipocyte size decreased in ovariectomized-RT group. Results suggest that RT reduces intra-AAT adipocyte size in ovariectomized rats by suppressing intra-AAT fatty acid synthesis and enhancing fatty acid ß-oxidation.

Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice.

OBJECTIVE: Besides their role in lipid absorption, bile acids (BAs) can act as signalling molecules. Cholic acid was shown to counteract obesity and associated metabolic disorders in high-fat-diet (cHF)-fed mice while enhancing energy expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue (brite cells in WAT), were characterized in dietary-obese mice. RESEARCH DESIGN: To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J mice were fed cHF (35% lipid wt wt(-1), mainly corn oil) for 4 months. Mice were then fed either (i) for 8 weeks with cHF or with cHF with two different doses (0.5%, 1%; wt wt(-1)) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice fed ad libitum; mice on standard chow diet were also used (3-week reversion). RESULTS: In the 8-week reversion, the CDCA intervention resulted in a dose-dependent reduction of obesity, dyslipidaemia and glucose intolerance, which could be largely explained by a transient decrease in food intake. The 3-week reversion revealed mild CDCA-dependent and food intake-independent induction of UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in subcutaneous WAT and a shift from carbohydrate to lipid oxidation. CONCLUSIONS: CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction in food intake, an effect probably occuring but neglected in previous studies using cholic acid. Nevertheless, CDCA-dependent and food intake-independent induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in adiposity and to the stabilization of the lean phenotype.

Leishmania braziliensis amastigotes stimulate production of IL-1ß, IL-6, IL-10 and TGF-ß by peripheral blood mononuclear cells from nonendemic area healthy residents.

Leishmania (Viannia) braziliensis causes cutaneous and mucosal leishmaniasis in several countries in Latin America. In mammals, the parasites live as amastigotes, interacting with host immune cells and stimulating cytokine production that will drive the type of the specific immune responses. Generation of Th17 lymphocytes is associated with tissue destruction and depends on IL-1ß, IL-6, TGF-ß and IL-23 production, whereas IL-10 and TGF-ß are associated with tissue protection. Here, we evaluate whether amastigotes stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors to produce the major cytokines responsible for the generation of Th17. Seven L. (V.) braziliensis isolates from patients with different clinical forms of leishmaniasis were expanded in interferon-γ knockout mice to obtain amastigotes and in culture to get promastigotes. The parasites were used to stimulate PBMCs from healthy donors, and cytokine production was evaluated by ELISA or qPCR. Amastigotes and promastigotes induced IL-10 production in PBMCs; however, only amastigotes induced IL-1ß, IL-6 and TGF-ß. These data demonstrate for the first time that L. (V.) braziliensis amastigotes directly stimulate production of a unique pattern of cytokines that could contribute to the generation of Th17.

Objective analysis of surgeons' ergonomy during laparoendoscopic single-site surgery through the use of surface electromyography and a motion capture data glove.

BACKGROUND: Adding to the ergonomic inconveniences already presented by traditional laparoscopy (LAP), laparoendoscopic single-site (LESS) surgery has been found to entail other more specific problems, including greater reduction in movement freedom, in-line vision with loss of triangulation, and greater proximity of instruments. The objective of this study was to evaluate surgeons' ergonomy during LESS surgery, through the study of muscular activity, wrist angle, and hand movements, and compare it with conventional laparoscopy. METHODS: The study group was composed by 14 experienced laparoscopic surgeons, all right-handed. Each one performed dissection tasks on a physical simulator through LAP and LESS approaches. For LAP, straight laparoscopic scissors and dissector were used, whilst for LESS articulating tip scissors and dissector were chosen. During both tasks, muscular activity of biceps brachii, triceps brachii, forearm flexors and extensors, and trapezius muscles was registered through surface electromyography. Simultaneously right-hand movements and wrist angles were obtained through a motion capture data glove (CyberGlove(®)), which allowed for the use of a modified RULA test applied to the recorded angles with subsequent establishment of risk levels for the wrist joint. RESULTS: Muscular activity for trapezius (LAP 6.94 ± 4.12 vs. LESS 11.32 ± 4.68; p ≤ 0.05) and forearm extensor muscles (LAP 9.2 ± 2.45 vs. LESS 37.07 ≤ 16.05; p ≤ 0.001) was significantly lower in conventional laparoscopy compared with LESS approach. No statistical significance was obtained between the different sensors, except in 3 of the 11 analyzed CyberGlove(®) sensors. The modified RULA test showed a score of 3 for laparoscopy (unacceptable), whereas for LESS a score of 2 was obtained (acceptable), with statistically significant differences between them (p ≤ 0.05). CONCLUSIONS: The LESS approach entails greater level of muscular activity in the trapezius and forearm extensor muscles, but we have found evidences of a better wrist position during LESS compared with traditional laparoscopy.

Human error and violation of rules in industrial safety: A systematic literature review.

BACKGROUND: Human error and violation of rules are perceived as deviations from some desired behavior, appearing variably in literature as either similar or opposing concepts. Behavioral deviations may be linked to accidents or considered a protective factor against them. OBJECTIVE: This article aims to explore definitions, characteristics, classifications, and management approaches for behavioral deviations, specifically human error and violation of rules. METHODS: A systematic literature review was conducted. RESULTS: The authors differ in defining and classifying error and violation, associating them with generation of accidents or their prevention. The management proposals for deviations highlighted by the authors were emphasized. CONCLUSION: The findings of this article reinforce the prominence of authors Jens Rasmussen and James Reason in the field. They assert that deviations are a natural aspect of the work process and even serve as a preventive factor against accidents, although their frequent association with accidents remains common in organizations. This study contributes to theoretical understanding by systematizing prevalent perspectives on deviation, human error, and violation of rules. It proposes a taxonomy and emphasizing the need for managing deviations, rather than combating them, especially in an organizational context.

Curiosity and mesolimbic functional connectivity drive information seeking in real life.

Curiosity reflects an individual's intrinsic motivation to seek information in order to close information gaps. In laboratory-based experiments, both curiosity and information seeking have been associated with enhanced neural dynamics in the mesolimbic dopaminergic circuit. However, it is unclear whether curiosity and dopaminergic dynamics drive information seeking in real life. We investigated (i) whether curiosity predicts different characteristics of real-life information seeking and (ii) whether functional connectivity within the mesolimbic dopaminergic circuit is associated with information seeking outside the laboratory. Up to 15 months before the COVID-19 pandemic, curiosity and anxiety questionnaires and a 10-minute resting-state functional magnetic resonance imaging session were conducted. In a follow-up survey early during the COVID-19 pandemic, participants repeated the questionnaires and completed an additional questionnaire about their COVID-19-related information seeking. Individual differences in curiosity but not anxiety were positively associated with the frequency of information-seeking behaviour. Additionally, the frequency of information seeking was predicted by individual differences in resting-state functional connectivity between the ventral tegmental area and the nucleus accumbens. The present translational study paves the way for future studies on the role of curiosity in real-life information seeking by showing that both curiosity and the mesolimbic dopaminergic functional network support real-life information-seeking behaviour.

TCP Doped with Metal Ions Reinforced with Tetragonal and Cubic Zirconia.

Ceramic biocomposites based on bioactive tricalcium phosphate doped with metal ions are a strategy for obtaining good biomimetics for human bone composition. Manufacturing with PMMA porogen also induces bone-like porosity morphology. The poor strength of tricalcium phosphate can be overcomed by designing ceramic composites reinforced with tetragonal and cubic zirconia. In this work, five different bioceramic composites were manufactured without and with induced porosity and their physical, mechanical, microstructural, and biological properties were studied. With the addition of tetragonal and cubic zirconia, an improvement in strength of 22% and 55%, respectively, was obtained, corresponding to up to 20.7 MPa. PMMA was suitable for adding porosity, up to 30%, with interconnectivity while an excellent hOB cellular viability was achieved for all biocomposites.

Saccharomyces bacillaris is not a synonym of Candida stellata: reinstatement as Starmerella bacillaris comb. nov.

Torulopsis bacillaris (Kroemer and Krumbholz) Lodder (basionym Saccharomyces bacillaris Kroemer and Krumbholz) was frequently detected in oenological works on yeast ecology conducted in the mid-1950s in different wine regions of the world, before its unification with Torulopsis stellata (Kroemer and Krumbholz) Lodder. Most of the phenotypic characteristics pointed out for T. bacillaris are currently attributed to Candida zemplinina Sipiczki. In the present work isoenzyme profiles and rDNA restriction profiles of the neotype of S. bacillaris from two yeast culture collections (CBS 843 and PYCC 3044) and of the type strain of C. zemplinina (CBS 9494) were determined and similar profiles were detected. Moreover, the sequences of the D1/D2 region of the 26S rRNA gene of the three strains were 100 % identical. Different profiles were observed for the type strain of C. stellata (CBS 157) both for isoenzyme and rDNA restriction analysis and only 91 % similarity was found between the D1/D2 sequence of this strain and that of the neotype of S. bacillaris. In view of the newly obtained data and the fact that all above-mentioned species belong to the Starmerella clade, only distantly related to Candida tropicalis (the type species of the genus), S. bacillaris is hereby reinstated as Starmerella bacillaris comb. nov., with C. zemplinina as an obligate synonym.

Positive fluid balance is associated with reduced survival in critically ill patients with cancer.

BACKGROUND: There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients. METHOD: One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, Mann-Whitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality. RESULTS: The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675 ml/24 h (471-2921) vs. 887 ml/24 h (104-557), P = 0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100 ml/24 h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.05-1.26), P = 0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.29-3.87), P = 0.004] and a positive fluid balance higher than 1100 ml/24 h at ICU [OR 5.14; 95% CI (1.45-18.24), P = 0.011]. CONCLUSION: A cumulative positive fluid balance higher than 1100 ml/24 h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy.

[Design and validation of a training model on paediatric and neonatal surgery]. / Diseño y validación de un programa formativo en cirugía laparoscópica pediátrica y neonatal.

We present our experience in the design and development of a training program in paediatric and neonatal laparoscopic surgery, and the determination of face validity by the attendants. Data included in the present study was obtained from five consecutive editions of our Neonatal and Paediatric Laparoscopic Surgery Course. Our training model, with a total duration of 21 hours, begins with acquisition of knowledge in ergonomics and instrument concepts, after which the attendants develop basic laparoscopic dexterity through the performance of hands-on physical simulator tasks. During the second and third days of the course, surgeons undertook various surgical techniques hands-on animal model. At the end of the training program, a subjective evaluation questionnaire was handed out to the attendants, in which different didactic and organizational aspects were considered. We obtained a highly positive score on all questions concerning the different topics and techniques included in the training program (> or = 9 points over 10). 78,5% of the 54 attendants was in accordance with the course total duration, whilst 21,5% considered that it should be of longer duration. Regarding abilities' self assessment, 79,1% considered themselves capacitated to perform trained procedures on live patients. The presented training model has obtained a very positive valuation score, leading to an increase in the attendants' self confidence in the application of learned techniques to their clinical practice.

Delayed biochemical changes induced by mercury intoxication are prevented by zinc pre-exposure.

This work evaluated the delayed effects of mercury and the effectiveness of zinc in preventing such effects. Pups were pre-treated with 1 daily dose of ZnCl(2) (27 mg/kg/day, by subcutaneous injections) from 3rd to 7th postnatal day and received 1 daily dose of 5 mg/kg of HgCl(2), for 5 subsequent days (8-12 days old). Animals were euthanized 21 days after the end of Hg-exposure. Porphobilinogen-synthase activity as well as zinc and mercury contents was determined in the liver and kidneys. Alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase activities as well as urea, creatinine and glucose levels were analyzed in plasma or serum. Some animals were considered more sensitive to mercury, since they did not recover the body weight gain and presented an increase of renal and hepatic mercury content, urea and creatinine levels; a decrease in renal porphobilinogen-synthase and alanine aminotransferase activities, as well as a decrease in the liver and an increase in kidney weights. Some animals were considered less sensitive to mercury because they recovered the body weight and presented no biochemical alterations in spite of mercury in the tissues. Zinc prevents partially or totally the alterations caused by mercury even those that persisted for a long time after the end of exposure. These findings suggest that there is difference among the animals regarding the sensitivity to mercury.

Asymmetric intramolecular aldol reactions of substituted 1,7-dicarbonylic compounds. A mechanistic study.

The diastereo- and enantioselectivity obtained experimentally by List on the proline-catalyzed intramolecular aldol reaction of substituted 1,7-dicarbonylic compounds was accurately predicted using density functional theory methods at the B3LYP/6-31++G** level. A polarizable continuum model was used to describe solvent effects. The theoretical data agree in good extension with List's experimental results, both in enantioselectivity and diastereoselectivity, and allow for the confirmation of our previous rationalization of the main factors contributing to the reaction selectivity. While the enantioselectivity results from an important electrostatic contact between the forming alkoxyde group and the proline moiety, the calculated diasteroselectivity results from several steric contacts that can be established between the different substituents and from their relative orientation in respect to the ring conformation. However, for dialdehydes that can originate two diastereomeric enamine intermediates, the proline attack and the immonium formation steps can also be of major importance in the rationalization of the final reaction selectivity, as is the case in two of the six studied systems. The obtained data allows for a full rationalization of the known experimental systems as well as for the extrapolation to new ones with variable substitution at the carbonylic chain.

[Trigeminal neuralgia caused by contra lateral cerebellopontine angle tumor. A case report]. / Neuralgia del trigémino provocada por un tumor del ángulo ponto-cerebeloso contralateral. Caso clínico.

In most cases, trigeminal neuralgia is due to compression of the trigeminal nerve in the zone of entrance at the pons by vascular structures. About 1% of cases, have trigeminal neuralgia associated with the presence of ipsilateral lesion of cerebellar-pontine angle. Rarely, trigeminal neuralgia may be due to contralateral posterior fossa tumors. We present a case of a 37-year- old patient who presented with right trigeminal neuralgia and harboured a left acoustic neuroma of significant dimension. Facial pain completely disappeared after tumor removal.

Release-Recapture Test of Dispersal and Survival of Sterile Males of Ceratitis capitata (Diptera: Tephritidae).

The sterile insect technique is used around the world to suppress or eradicate populations of Ceratitis capitata (Wiedemann) with successful results. It consists of inundative releases of sterile insects into a wide area to reduce reproduction in a field population of the same species. It is necessary to know the dispersion of the sterile males in the field in order to define the maximum distance between the release points that ensures the distribution of the sterile flies in the entire target area. The release methods may vary depending on the area to be covered and the resources available. Manual ground release requires less technology. The aim of this research was to estimate the ability of sterile males to survive and disperse in the field, in the two main areas of citrus production in Uruguay. A release of 20,000 sterile males of C. capitata TslV8 (-inv D53) was performed at the central point of each area defined for the trials. Around these points, a network of 54 Jackson traps baited with trimedlure was installed forming five concentric rings, which were placed on days 1, 3, 5, and 7 after the release and were removed at 24 h in all cases. The emergence rate, flight ability, dispersion, and longevity were estimated. The standard distances obtained by the regression models were 127 m and 131 m for Salto and San José respectively. In Salto, the traps had catches until the eighth day, and in San José, there were no catches after the sixth day.