IgG4-related disease: Case report and 6-year follow-up of an elusive diagnosis mimicking malignancy.

Key Clinical Message: IgG4-related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. Abstract: IgG4-related disease (IgG4-RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4-positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45-year-old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4-related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second-line therapy with rituximab was initiated. Over the 6 years of follow-up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow-up by reumathology, infectious diseases, and family medicine specialists.

Humulus lupulus aqueous extract and hydrolate as a potential ingredient for cosmetics: chemical characterization and in vitro antimicrobial, cytotoxicity, antioxidant and anti-inflammatory assessment.

Humulus lupulus extracts have in their composition different molecules, such as polyphenols, α-acids, ß-acids, and hydrocarbons, which contribute to the plant's medicinal properties. These molecules are associated with antimicrobial, antioxidant and anti-inflammatory activities. OBJECTIVE: This work focuses on the evaluation of H. lupulus biological activities, with the aim of evaluating its potential for inclusion in cosmetic formulations. METHODS: Two distinct aqueous extracts and two hydrolates obtained via hydrodistillation were evaluated. These include the flower parts (FE, FH) and the mix of aboveground parts (ME, MH). The chemical profiles for both aqueous extracts and hydrolates were identified by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Antimicrobial, antioxidant, cytotoxicity, and anti-inflammatory activity were tested in vitro using standard methods. RESULTS: Rutin was the major compound found in FE (40.041 µg mg-1 of extract) and ME (2.909 µg mg-1 of extract), while humulenol II was the most abundant compound in hydrolates (FH: 20.83%; MH: 46.80%). Furthermore, FE was able to inhibit the growth of Staphylococcus aureus and Staphylococcus epidermis with MIC values of 50% and 25% (v/v), respectively. FH showed the same effect in Staphylococcus aureus (50% v/v). FH evidenced poor antioxidant potential in DPPH scavenging test and demonstrated significant antioxidant and anti-inflammatory effects by reducing (***p < 0.001) intracellular reactive oxygen species (ROS), NO (nitric oxide) levels (***p < 0.001) and cyclooxygenase-2 (COX-2) protein expression (***p < 0.001) in lipopolysaccharide (LPS)-stimulated macrophages. Nevertheless, it is important to note that FH exhibited cytotoxicity at high concentrations in 3T3 fibroblasts and RAW 264.7 macrophages. CONCLUSION: The studied H. lupulus aqueous extracts and hydrolates revealed that FH stands out as the most promising bioactive source for cosmetic formulations. However, future research addressing antimicrobial activity is necessary to confirm its potential incorporation into dermatological and cosmetic formulations.

European value-based healthcare benchmarking: moving from theory to practice.

BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.

A loss-of-function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa.

Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT-1 and POFUT-1 genes have been associated with DDD, and loss-of-function mutations in PSENEN, a subunit of the gamma-secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma-secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four-generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense-mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma-secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co-occurrence in HS patients carrying a mutation in the NCSTN gene.

Zika virus: Critical crosstalk between pathogenesis, cytopathic effects, and macroautophagy.

Zika virus (ZIKV) is a re-emerging positive-sense RNA arbovirus. Its genome encodes a polyprotein that is cleaved by proteases into three structural proteins (Envelope, pre-Membrane, and Capsid) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). These proteins have essential functions in viral replication cycle, cytopathic effects, and host cellular response. When infected by ZIKV, host cells promote macroautophagy, which is believed to favor virus entry. Although several authors have attempted to understand this link between macroautophagy and viral infection, little is known. Herein, we performed a narrative review of the molecular connection between macroautophagy and ZIKV infection while focusing on the roles of the structural and nonstructural proteins. We concluded that ZIKV proteins are major virulence factors that modulate host-cell machinery to its advantage by disrupting and/or blocking specific cellular systems and organelles' function, such as endoplasmic reticulum stress and mitochondrial dysfunction.

Peptide extract from spent yeast improves resistance of Saccharomyces cerevisiae to oxidative stress.

Yeast cells face various stress factors during industrial fermentations, since they are exposed to harsh environmental conditions, which may impair biomolecules productivity and yield. In this work, the use of an antioxidant peptide extract obtained from industrial spent yeast was explored as supplement for Saccharomyces cerevisiae fermentation to prevent a common bottleneck: oxidative stress. For that, a recombinant yeast strain, producer of ß-farnesene, was firstly incubated with 0.5 and 0.7 g/L peptide extract, in the presence and absence of hydrogen peroxide (an oxidative stress inducer), for 1-5 h, and then assayed for intracellular reactive oxygen species, and growth ability in agar spot assays. Results showed that under 2 mM H2O2, the peptide extract could improve cells growth and reduce reactive oxygen species production. Therefore, this antioxidant effect was further evaluated in shake-flasks and 2-L bioreactor batch fermentations. Peptide extract (0.7 g/L) was able to increase yeast resistance to the oxidative stress promoted by 2 mM H2O2, by reducing reactive oxygen species levels between 1.2- and 1.7-fold in bioreactor and between 1.2- and 3-fold in shake-flask fermentations. Moreover, improvements on yeast cell density of up to 1.5-fold and 2-fold, and on biomolecule concentration of up to 1.6-fold and 2.8-fold, in bioreactor and shake-flasks, respectively, were obtained. Thus, culture medium supplementation with antioxidant peptide extracted from industrial spent yeast is a promising strategy to improve fermentation performance while valuing biomass waste. This valorization can promote a sustainable and eco-friendly solution for the biotechnology industry by the implementation of a circular economy model. KEY POINTS: • Peptide extract from spent yeast applied for the first time on yeast fermentation. • Antioxidant peptide extract enhanced S. cerevisiae oxidative stress resistance. • Fermentation performance under stress improved by peptide extract supplementation.

Vaginal Sheets with Thymbra capitata Essential Oil for the Treatment of Bacterial Vaginosis: Design, Characterization and In Vitro Evaluation of Efficacy and Safety.

We aimed to incorporate Thymbra capitata essential oil (TCEO), a potent antimicrobial natural product against bacterial vaginosis (BV)-related bacteria, in a suitable drug delivery system. We used vaginal sheets as dosage form to promote immediate relief of the typical abundant vaginal discharge with unpleasant odour. Excipients were selected to promote the healthy vaginal environment reestablishment and bioadhesion of formulations, while the TCEO acts directly on BV pathogens. We characterized vaginal sheets with TCEO in regard to technological characterization, predictable in vivo performance, in vitro efficacy and safety. Vaginal sheet D.O (acid lactic buffer, gelatine, glycerine, chitosan coated with TCEO 1% w/w) presented a higher buffer capacity and ability to absorb vaginal fluid simulant (VFS) among all vaginal sheets with EO, showing one of the most promising bioadhesive profiles, an excellent flexibility and structure that allow it to be easily rolled for application. Vaginal sheet D.O with 0.32 µL/mL TCEO was able to significantly reduce the bacterial load of all in vitro tested Gardnerella species. Although vaginal sheet D.O presented toxicity at some concentrations, this product was developed for a short time period of treatment, so this toxicity can probably be limited or even reversed when the treatment ends.

Spent Yeast Waste Streams as a Sustainable Source of Bioactive Peptides for Skin Applications.

Spent yeast waste streams are a byproduct obtained from fermentation process and have been shown to be a rich secondary source of bioactive compounds such as phenolic compounds and peptides. The latter are of particular interest for skin care and cosmetics as they have been shown to be safe and hypoallergenic while simultaneously being able to exert various effects upon the epidermis modulating immune response and targeting skin metabolites, such as collagen production. As the potential of spent yeast's peptides has been mainly explored for food-related applications, this work sought to understand if peptide fractions previously extracted from fermentation engineered spent yeast (Saccharomyces cerevisiae) waste streams possess biological potential for skin-related applications. To that end, cytotoxic effects on HaCat and HDFa cells and whether they were capable of exerting a positive effect upon the production of skin metabolites relevant for skin health, such as collagen, hyaluronic acid, fibronectin and elastin, were evaluated. The results showed that the peptide fractions assayed were not cytotoxic up to the highest concentration tested (500 µg/mL) for both cell lines tested. Furthermore, all peptide fractions showed a capacity to modulate the various target metabolites production with an overall positive effect being observed for the four fractions over the six selected targets (pro-collagen IαI, hyaluronic acid, fibronectin, cytokeratin-14, elastin, and aquaporin-9). Concerning the evaluated fractions, the overall best performance (Gpep > 1 kDa) was of an average promotion of 41.25% over the six metabolites and two cell lines assessed at a concentration of 100 µg/mL. These results showed that the peptide fractions assayed in this work have potential for future applications in skin-related products at relatively low concentrations, thus providing an alternative solution for one of the fermentation industry's waste streams and creating a novel and highly valuable bioactive ingredient with encompassing activity to be applied in future skin care formulations.

Vulvovaginal Candida albicans Clinical Isolates' Resistance to Phagocytosis In-Vitro

Previous studies have revealed that Candida albicans isolates involved in chronic vulvovaginal candidosis (cVVC) phenotypically express less virulent traits than clinical isolates involved in sporadic infections. In this study, we aimed to further explore this finding by studying the behaviour of those same clinical isolates in in-vitro models of infection. Eighteen clinical Candida albicans isolates were collected from women suffering sporadic (eight isolates) or chronic infections (ten isolates). Adhesion to HeLa cells (human cervical cancer epithelial cell line) and resistance to phagocytosis by RAW 264.7 cells (murine macrophages cell line) were tested in-vitro. In addition, phenotypic expression of virulence factors related with either adhesion or resistance to phagocytosis was tested in-vitro. Results indicated that yeast isolates involved in sporadic infection adhered in a higher proportion of HeLa cells than those of chronic infections, which was related with their ability to produce biofilm (p < 0.05). The ability to evade phagocytosis was related to an elevated production of proteases (p < 0.05) by chronic isolates, while sporadic isolates' resistance to phagocytosis was related to a higher hydrophobicity of cell walls (p < 0.05). We conclude that the evasion of macrophage-mediated phagocytosis related to the production of proteases might be an important factor involved in the recurrence of vulvovaginal candidosis infection.

Spent brewer's yeast (Saccharomyces cerevisiae) as a potential source of bioactive peptides: An overview.

Bioactive peptides become popular in several economic sectors over the years as they have demonstrated important biological benefits in digestive, immune, cardiovascular, and nervous human systems. Although many commercial peptides are chemically synthesized, they can also be obtained from natural protein sources such as spent brewer's yeast (Saccharomyces cerevisiae). The recovery of this fermentation by-product for production of functional ingredients is an important step in the increasingly demand to implement and promote a circular economy-based industry. Bioactive peptides can be found in protein-rich extracts produced from S. cerevisiae, and several studies have described their positive impact of human body. In this line, the present review highlights and discuss the reported biological properties of S. cerevisiae bioactive peptides in terms of antihypertensive, antioxidant and antimicrobial effects, although other bioactivities are also described. Concerning the growing interest in yeast protein-rich products by agri-food and cosmetic sectors, some of the products currently on the market are also pointed out and their potential source is discussed.

An overview of Zika virus genotypes and their infectivity

ABSTRACT Zika virus (ZIKV) is an enveloped, single-stranded RNA arbovirus belonging to the genus Flavivirus. It was first isolated from a sentinel monkey in Uganda in 1947. More recently, ZIKV has undergone rapid geographic expansion and has been responsible for outbreaks in Southeast Asia, the Pacific Islands, and America. In this review, we have highlighted the influence of viral genetic variants on ZIKV pathogenesis. Two major ZIKV genotypes (African and Asian) have been identified. The Asian genotype is subdivided into Southwest Asia, Pacific Island, and American strains, and is responsible for most outbreaks. Non-synonymous mutations in ZIKV proteins C, prM, E, NS1, NS2A, NS2B, NS3, and NS4B were found to have a higher prevalence and association with virulent strains of the Asian genotype. Consequently, the Asian genotype appears to have acquired higher cellular permissiveness, tissue persistence, and viral tropism in human neural cells. Therefore, mutations in specific coding regions of the Asian genotype may enhance ZIKV infectivity. Considering that mutations in the genomes of emerging viruses may lead to new virulent variants in humans, there is a potential for the re-emergence of new ZIKV cases in the future.

Capacidad vital lenta: diferencias entre la capacidad vital espiratoria y la capacidad vital inspiratoria

Resumen Introducción: La capacidad vital (VC) se puede determinar mediante la capacidad vital espiratoria (EVC) o la capacidad vital ins piratoria (IVC). Obtener el mayor volumen de VC es fundamental para la correcta interpretación de las pruebas de función pulmonar. Objetivos: Determinar las diferencias entre EVC y IVC (EVC-IVC) según el patrón ventilatorio; Caracterizar las relaciones FEV1/EVC y FEV1/IVC en la detección de obstrucción de las vías aéreas; Estudiar los efectos de realizar EVC o IVC en la detección de air trapping o de hiperinflación pulmonar. Materiales y Métodos: Estudio transversal. La muestra incluyó 388 individuos que se dividieron en 3 grupos: sanos, obstrucción de las vías aéreas y restricción pulmonar. Para detectar la obstrucción de las vías aéreas, se estudiaron las relaciones FEV1/EVC y FEV1/IVC. La presencia de air trapping o hiperinflación pulmonar se determinó mediante análisis del volumen pulmonar. As diferencias entre EVC e IVC (EVC-IVC) de acuerdo con el padrón ventilatorio fueron agrupados por clases. Resultados: En el grupo normal, 34.8% tuvo una diferencia EVC-IVC ≥ 200 ml, en el grupo de obstrucción de las vías respirato rias 28.4% y en la restricción pulmonar 22.4%, respectivamente. La relación FEV1/EVC detectó obstrucción de las vías aéreas en el 44.8% de los individuos y la relación FEV1/IVC en el 39.4%. En sujetos con obstrucción de las vías respiratorias, la maniobra de EVC determinó el air trapping en el 21.6% de los sujetos y la hiperinflación pulmonar en el 9.5%. En la maniobra de IVC, los porcentajes fueron 18.2% y 10.8%, respectivamente. Conclusiones: El EVC y el IVC no deben considerarse maniobras intercambiables, debido a las diferencias de volumen obtenidas por cada uno de ellos. Los resultados que provienen de su uso influyeron en la interpretación de la función pulmonar.

Slow Vital Capacity: Differences Between the Expiratory Vital Capacity and the Inspiratory Vital Capacity

ABSTRACT Introduction: The vital capacity (VC) can be determined by means of the expiratory vital capacity (EVC) or the inspiratory vital capacity (IVC). Obtaining the highest VC volume is essential for the correct interpretation of lung function tests. Objectives: To determine the differences between the EVC and the IVC (EVC-IVC) according to the ventilatory pattern; to characterize the FEV1/EVC and FEV1/IVC ratios when an obstruction of the airways is detected; to study the effects of the EVC or IVC on the detec tion of air trapping or lung hyperinflation. Materials and Methods: Cross-sectional study. The sample included 388 individuals divided in 3 groups: healthy, airway obstruc tion, and restrictive lung disease. In order to detect the airway obstruction, we studied the FEV1/EVC and FEV1/IVC ratios. The presence of air trapping or lung hyperinflation was determined by means of a lung volume test. The differences between the EVC and the IVC (EVC-IVC) according to the ventilatory pattern were grouped into classes. Results: In the normal group, there was an EVC-IVC difference of ≥ 200 ml in 34.8% of the individuals; in the airway obstruction group, 28.4%, and in the restrictive lung disease group, 22.4%. The FEV1/EVC ratio detected airway obstruction in 44.8% of the individuals, and the FEV1/IVC ratio in 39.4%. In patients with airway obstruction, the EVC maneuver determined the presence of air trapping in 21.6% of subjects and lung hyperinflation in 9.5%. The IVC maneuver showed 18.2% and 10.8%, respectively. Conclusions: The EVC and IVC should not be used as interchangeable maneuvers, considering the volume differences obtained with each one of them. Their results influenced the interpretation of lung function.

In silico analysis of molecular interactions between HIV-1 glycoprotein gp120 and TNF receptors.

Proinflammatory microenvironmental is crucial for the Human Immunodeficiency Virus Type 1 (HIV-1) pathogenesis. The viral glycoprotein 120 (gp120) must interact with the CD4+ T cell chemokine receptor (CCR5) and a co-receptor C-X-C chemokine receptor type 4 (CXCR4) to let the virus entry into the host cells. However, the interaction of the viral particle with other cell surface receptors is mandatory for its attachment and subsequently entry. Tumor Necrosis Factor receptor type I (TNFR1), type II (TNFR2) and Fas are a superfamily of transmembrane proteins involved in canonical inflammatory pathway and cell death by apoptosis as responses against viral pathogens. In our study, we performed an in silico evaluation of the molecular interactions between viral protein gp120 and TNF receptors (TNFR1, TNFR2 and Fas). Protein structures were retrieved from Protein Databank (PDB), and Molecular Docking and dynamics were performed using ClusPro 2.0 server and GROMACS software, respectively. We observed that gp120 is able to bind TNFR1, TNFR2 and Fas receptors, although only the TNFR2-gp120 complex demonstrated to produce a stable and durable binding. Our findings suggest that gp120 may act as an agonist to TNF-α and also function as an attachment factor in HIV-1 entry process. These molecular interaction by gp120 may be the key to HIV-1 immunopathogenesis. In conclusion, gp120 may stimulate pro-inflammatory and apoptotic signaling transduction pathways mediated by TNFR2 and may act as an attachment factor retaining HIV-1 viral particles on the host cell surface.

A conserved arginine with non-conserved function is a key determinant of agonist selectivity in α7 nicotinic ACh receptors.

BACKGROUND AND PURPOSE: The α7 and α4ß2* ("*" denotes possibly assembly with another subunit) nicotinic acetylcholine receptors (nAChRs) are the most abundant nAChRs in the mammalian brain. These receptors are the most targeted nAChRs in drug discovery programmes for brain disorders. However, the development of subtype-specific agonists remains challenging due to the high degree of sequence homology and conservation of function in nAChRs. We have developed C(10) variants of cytisine, a partial agonist of α4ß2 nAChR that has been used for smoking cessation. The C(10) methyl analogue used in this study displays negligible affinity for α7 nAChR, while retaining high affinity for α4ß2 nAChR. EXPERIMENTAL APPROACH: The structural underpinning of the selectivity of 10-methylcytisine for α7 and α4ß2 nAChRs was investigated using molecular dynamic simulations, mutagenesis and whole-cell and single-channel current recordings. KEY RESULTS: We identified a conserved arginine in the ß3 strand that exhibits a non-conserved function in nAChRs. In α4ß2 nAChR, the arginine forms a salt bridge with an aspartate residue in loop B that is necessary for receptor expression, whereas in α7 nAChR, this residue is not stabilised by electrostatic interactions, making its side chain highly mobile. This lack of constrain produces steric clashes with agonists and affects the dynamics of residues involved in agonist binding and the coupling network. CONCLUSION AND IMPLICATIONS: We conclude that the high mobility of the ß3-strand arginine in the α7 nAChR influences agonist binding and possibly gating network and desensitisation. The findings have implications for rational design of subtype-selective nAChR agents.

Is Cholecystectomy Really Harmful? A Long-Term Quality of Life Study in Living Donor Liver Transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) is an accepted option for patients with end-stage liver disease. However, it potentially carries the risk of donor morbi-mortality, as well as long-term functional impairment. Cholecystectomy is performed routinely in the donor intervention, but the long-term effect on gastrointestinal (GI)-related quality of life (QoL) has never been explored previously. This study evaluated living donors' overall, abdominal wall-related, activity-level, and GI-related QoL. MATERIALS AND METHODS: In total, 21 living liver donors (LLD) (57% women, mean age 45 ± 9 years) were compared to a control group (29 patients) undergoing cholecystectomy for gallbladder polyps (45% women, mean age of 46 ± 7 years). LLD and controls (Ctl) were divided into 2 age groups: LLD-Y and Ctl-Y (25-45 years); and LLD-O and Ctl-O (46-65 years). Generic SF-36, Gastrointestinal Quality of Life Index, EuraHS for abdominal wall status assessment, and International Physical Activity Questionnaire were performed. Standard age-adjusted Portuguese population SF-36 scores were used. RESULTS: Global QoL results were better than Portuguese population scores and not inferior when compared to controls, scoring higher in the LLD-Y group in domains as vitality and mental health (P < .05). The abdominal wall impact was minimal among LLD. The activity level was significantly higher in LLD-Y than in Ctl-Y. Overall GI-related QoL was very close to the maximum score, and GI symptoms were significantly less in LLD-O compared with Ctl-O. CONCLUSION: LDLT had no impact on donors' general, abdominal wall-related QoL or activity level. The performance of cholecystectomy apparently had no impact on the development of GI-related symptoms.

[Diffuse Intraparenchymal Mesothelioma: An Atypical Presentation]. / Mesotelioma Intraparenquimatoso Difuso: Uma Apresentação Rara.

Pleural mesothelioma is a disease associated with exposure to asbestos. Although rare, it is the most common malignant pleural neoplasm. It is difficult to diagnose and it has a poor prognosis. We report the case of a 62-year-old male patient with a history of prolonged occupational exposure to asbestos, with dyspnea for minor exertion and productive cough, for several months. Imaging studies revealed extensive interstitial involvement with marked thickening of the interlobular and centrilobular septa and tenuous pleural involvement. Several differential diagnoses were considered such as, asbestosis, cryptogenic organizing pneumonia, desquamative interstitial pneumonia, pleuropulmonary metastases, and/or bronchopulmonary infection, but the histological and immunohistochemical results were compatible with pleural mesothelioma - a rare malignant neoplasm, with pleural origin, with a high mortality rate.

O mesotelioma pleural é uma doença associada à exposição ao amianto. Embora raro, é a principal neoplasia maligna da pleura, sendo o seu diagnóstico difícil e o seu prognóstico reservado. O caso clínico apresentado refere-se a um doente de 62 anos, do género masculino, com história ocupacional de exposição prolongada a amianto e clínica arrastada, com meses de evolução, de dispneia para pequenos esforços e tosse produtiva. Imagiologicamente, apresentava um envolvimento intersticial extenso com marcado espessamento dos septos interlobulares e centrilobulares, associado a ténues alterações pleurais. Várias hipóteses diagnósticas foram equacionadas tais como, asbestose, pneumonia organizativa criptogénica, pneumonia intersticial descamativa, metástases pleuropulmonares, e/ou patologia infeciosa broncopulmonar, mas o resultado histológico e imunohistoquímico foi compatível com mesotelioma pleural- uma neoplasia maligna rara, de origem pleural, com uma taxa de mortalidade elevada.

Characterization of chemical compounds susceptible to be extracted from cork by the wine using GC-MS and 1H NMR metabolomic approaches.

This work presents a metabolomics study of cork by gas chromatography-mass spectrometry (GC-MS) and 1H nuclear magnetic resonance (NMR) spectroscopy to characterize compounds susceptible to be extracted from cork by the wine in an attempt to find a relationship between the content of these compounds and the geographical origin of cork. Cork from eleven geographical regions was studied, five from Portugal and six from Spain. Unsupervised pattern recognition techniques unveiled three main clusters of regions according to their chemical similarity but not related with geographical proximity. Nineteen compounds were found to be responsible for the clusters, including terpenes (trans-squalene, friedelin, camphene, trans-3-pinanone, 1-terpinen-4-ol, two sesquiterpenes), polyphenols (vescalagin, castalagin), among others (pyrogallol, glucosan, sitost-4-en-3-one, o-cymene, quinic acid, five unknowns). These preliminary results unveiled the potential for a more efficient selection of cork planks for stoppers production based on the compounds susceptible to be extracted from cork by the wine.

Assessment of oxidation compounds in oaked Chardonnay wines: A GC-MS and 1H NMR metabolomics approach.

The oxidation of oaked Chardonnay wine during long-term storage was studied by headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry (HS-SPME-GC/MS) and proton (1H) nuclear magnetic resonance (NMR) spectroscopy. Three distinct groups of wine were defined based on the browning index: control, least oxidized (OX1) and most oxidized (OX2). HS-SPME-GC/MS and 1H NMR spectroscopy enabled the profiling of a total of 155 compounds in all wine samples including aldehydes, ketones, esters, polyphenols, among other classes. Acetaldehyde, 3-methylbutanal, 2-phenylacetaldehyde, methional, 3-penten-2-one, ß-damascenone and four unknown carbonyl compounds showed the highest percentage of variation with oxidation. Novel oxidation markers found in this work include pentanal, 3-methyl-2-butanone, 3-penten-2-one, 2-methyltetrahydrofuran-3-one, ß-damascenone, ethyl 2-methylbutanoate and vinyl decanoate. In addition, several correlations between polyphenols, aroma compounds and absorbance at 420 nm (A420) were observed, suggesting the occurrence of chemical reactions with a possible impact in wine browning.