Attachment and adaptation to breast cancer: The mediating role of avoidant emotion processes.

Attachment insecurity is associated with difficulties in adapting to cancer. Accumulating evidence points to the influence of avoidant emotion processes in this association. This study explored this pathway by examining the association between attachment insecurity and quality of life in women with breast cancer, and by exploring the mediating role of two avoidant emotion processes in this association. Women with breast cancer (N = 155) completed measures of attachment, emotional suppression, emotional awareness and quality of life. Avoidance of attachment was positively associated with emotional suppression (ß = .29, p < .01) and lack of emotional awareness (ß = .27, p < .01), and negatively associated with quality of life (ß = -.22, p < .05). Lack of emotional awareness partially mediated the relationship between attachment avoidance and quality of life (indirect effect ß = -.12, p = .008). Attachment anxiety was not associated with any variable. Attachment avoidance may hinder the process of adaptation to breast cancer and difficulties in identifying and describing emotions may be partly responsible for this influence. Access to and ability to benefit from social and medical supports is likely to depend on being able to engage with others and recognise and process emotions effectively. Research and clinical implications are discussed.

Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia.

Processing of Precursor 1 (POP1) is a large protein common to the ribonuclease-mitochondrial RNA processing (RNase-MRP) and RNase-P (RMRP) endoribonucleoprotein complexes. Although its precise function is unknown, it appears to participate in the assembly or stability of both complexes. Numerous RMRP mutations have been reported in individuals with cartilage-hair hypoplasia (CHH) but, to date, only three POP1 mutations have been described in two families with features similar to anauxetic dysplasia (AD). We present two further individuals, one with severe short stature and a relatively mild skeletal dysplasia and another in whom AD was suspected. Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified, p.[(Asp511Tyr)];[(Asp511Tyr)]. These two individuals show the phenotypic extremes in the clinical presentation of POP1-dysplasias. Although CHH and other skeletal dysplasias caused by mutations in RMRP or POP1 are commonly cited as ribosomal biogenesis disorders, recent studies question this assumption. We discuss the past and present knowledge about the function of the RMRP complex in skeletal development.

Effects of photobiomodulation on experimental models of peripheral nerve injury.

Phototherapy has demonstrated positive effects in the treatment of peripheral nerve injury, but there is a need to investigate the dosimetric parameters. Thus, the aim of the present study was to conduct a literature review on the effects of photobiomodulation with the use of low-level laser therapy (LLLT) on the treatment of peripheral nerve injury in experimental models. The databases of PubMed/MEDLINE, SCOPUS, and SPIE Digital Library were searched for articles on the use of LLLT in experimental models of peripheral nerve injury published in English between January 2007 and March 2016. The laser parameter variability was wavelength (632.8 to 980 nm), power (10 to 190 mW), and total energy (0.15 to 90 J) in pulsed or continuous wave and single or multiple points. Eighteen original articles demonstrating the effects of LLLT on the acceleration of functional recovery, morphological aspects as well as the modulation of the expression inflammatory cytokines, and growth factors were selected. LLLT is a viable phototherapeutic modality for the treatment of peripheral nerve injury, demonstrating positive effects on the neuromuscular repair process using either red or infrared light. The majority of studies used a power of up to 50 mW and total energy of up to 15 J administered to multiple points. The determination of these parameters is important to the standardization of a LLLT protocol to enhance the regeneration process following a peripheral nerve injury.

Analysis of FOXP3 gene in children with allergy and autoimmune diseases.

BACKGROUND: Allergy and autoimmunity are important immunological entities underlying chronic diseases in children. In some cases both entities develop simultaneously in the same patient. FOXP3 gene codes for a transcription factor involved in regulation of the immune system. Considering that regulatory T cells are involved in controlling immunological disease development, and the relevant role of FOXP3 in this kind of T cells, the objective of this study was to analyse the FOXP3 gene in the most prevalent autoimmune diseases and/or allergies in childhood in a European population. METHODS: A total of 255 Caucasian individuals, 95 controls and 160 patients diagnosed with allergic, autoimmune or both diseases were included in this study. The molecular analysis of FOXP3 was performed by DNA sequencing following the recommendations for quality of the European Molecular Genetics Quality Network. Genomic DNA was extracted from peripheral blood of all participants and was amplified using the polymerase chain reaction. After the visualisation of the amplified fragments by agarose gel-electrophoresis, they were sequenced. RESULTS: Thirteen different polymorphisms in FOXP3 gene were found, seven of which had not been previously described. The mutated allele of SNP 7340C>T was observed more frequently in the group of male children suffering from both allergic and autoimmune diseases simultaneously (p=0.004, OR=16.2 [1.34-195.15]). CONCLUSIONS: In this study we identified for first time genetic variants of FOXP3 that are significantly more frequent in children who share allergic and autoimmune diseases. These variants mainly affect regulatory sequences that could alter the expression levels of FOXP3 modifying its function including its role in Treg cells.

Value of sentinel lymph node biopsy in papillary thyroid cancer: initial results of a prospective trial.

The objectives of the study were to evaluate the performance of sentinel lymph node biopsy (SLNB) in detecting occult metastases in papillary thyroid carcinoma (PTC) and to correlate their presence to tumor and patient characteristics. Twenty-three clinically node-negative PTC patients (21 females, mean age 48.4 years) were prospectively enrolled. Patients were submitted to sentinel lymph node (SLN) lymphoscintigraphy prior to total thyroidectomy. Ultrasound-guided peritumoral injections of (99m)Tc-phytate (7.4 MBq) were performed. Cervical single-photon emission computed tomography and computed tomography (SPECT/CT) images were acquired 15 min after radiotracer injection and 2 h prior to surgery. Intra-operatively, SLNs were located with a gamma probe and removed along with non-SLNs located in the same neck compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted to histopathology analysis. Sentinel lymph nodes were located in levels: II in 34.7 % of patients; III in 26 %; IV in 30.4 %; V in 4.3 %; VI in 82.6 % and VII in 4.3 %. Metastases in the SLN were noted in seven patients (30.4 %), in non-SLN in three patients (13.1 %), and in the lateral compartments in 20 % of patients. There were significant associations between lymph node (LN) metastases and the presence of angio-lymphatic invasion (p = 0.04), extra-thyroid extension (p = 0.03) and tumor size (p = 0.003). No correlations were noted among LN metastases and patient age, gender, stimulated thyroglobulin levels, positive surgical margins, aggressive histology and multifocal lesions. Sentinel lymph node biopsy can detect occult metastases in PTC. The risk of a metastatic SLN was associated with extra-thyroid extension, larger tumors and angio-lymphatic invasion. This may help guide future neck dissection, patient surveillance and radioiodine therapy doses.

A role for the mitochondrial-associated protein p32 in regulation of trophoblast proliferation.

p32 is a conserved eukaryotic protein which is primarily expressed in the mitochondria and regulates cell proliferation, migration and metabolism in various tissues. In this study, we sought to examine the expression and function of p32 in the human placenta. p32 was highly expressed in the syncytiotrophoblast, the underlying cytotrophoblast (CTB), the vascular endothelium and by a proportion of cells in the villous stroma in first trimester and term placenta. p32 mRNA and protein expression was significantly higher in the first trimester of pregnancy than at term, and expression in the trophoblast was significantly reduced in placentas from women with fetal growth restriction (FGR). Small interfering RNA (siRNA)-mediated knockdown of p32 in term placental explants significantly reduced the number of Ki67-positive CTB, but did not alter CTB apoptosis or necrosis. p32 knockdown increased lactate production, reduced glucose extraction from culture medium and was associated with reduced MitoTracker dye accumulation in trophoblast mitochondria. p32 knockdown was also associated with a significant reduction in expression of the mitochondrial respiratory complexes I and IV. These data suggest that p32 expression is important for CTB proliferation, via a mechanism involving regulation of normal mitochondrial function. As p32 expression is reduced in FGR placentas, this may contribute to some of the observed placental pathology, such as reduced CTB proliferation and mitochondrial dysfunction.

Antimicrobial synergism against different lineages of methicillin-resistant Staphylococcus aureus carrying SCCmec IV.

AIM: To evaluate the synergistic activity of antimicrobial drugs against lineages of methicillin-resistant Staphylococcus aureus (MRSA) carrying SCCmec IV. The biofilm production and related genes were also detected. METHODS AND RESULTS: Forty two MRSA isolates were tested for biofilm production and related genes. Biofilm/biomass susceptibility to gentamicin (G), linezolid (L), rifampicin (R) and vancomycin (V) was determined for six isolates from three lineages prevalent in Rio de Janeiro hospitals in concentrations ranging from 0·25 to 64 µg ml(-1). Biomass was evaluated by microtitre plate test and number of viable cells (CFU cm(-2)) and inspected by epifluorescence microscopy. All isolates presented the icaA and sasG genes, but only 38% were biofilm producers. There were 50 and 45% biomass reductions when concentrations ≥4 µg ml(-1) of R or L and ≥16 µg ml(-1) of G or V, respectively, were used. Synergism tests produced a 55% biomass reduction with R(2µgml-1) + G(16µgml-1), R(2µgml-1) + L(2µgml-1), R(2µgml-1) + V(4µgml-1), and L(2µgml-1) + V(4µgml-1). Number of viable cells was reduced from 2 to 3 logs with R(2µgml-1) + L(2µgml-1) and R(2µgml-1) + V(4µgml-1). CONCLUSIONS: Synergisms involving R plus L and R plus V caused important reductions in biofilm/biomass and the number of viable cells. Drug combinations should be considered in the chemotherapies of MRSA-SCCmec IV infections. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofilms in MRSA infections restrict the clinical choice of antimicrobials. Thus, knowledge of the best options for monotherapy and drug synergisms could improve clinical results.

Ultrastructure of novel thrombocytes in the dog snapper Lutjanus jocu.

Myxosporean cysts containing spores of Henneguya sp. were observed in the gills of the dog snapper Lutjanus jocu. Adjacent to the cysts were capillaries, allowing observation of peripheral blood cells. Numerous white blood cells displaying uncommon cytoplasmic projections were observed amongst the erythrocytes. Their morphology allowed them to be identified as thrombocytes (TCs). Each TC displayed 18-26 cytoplasmic projections, most of which were in close proximity to erythrocytes. At their apical end, each cytoplasmic projection presented an ellipsoidal vacuole (c. 0·6 µm × 0·3 µm) from which a secretory tubule, 0·3-0·4 µm long and c. 120 nm in total diameter, extended towards the periphery of the TC plasmalemma and fused with the cellular membrane. From this opening, contents of vacuoles were apparently released into the lumen of the capillaries. Other vacuoles with similar features, and containing an electron-lucent matrix, were observed in the cytoplasm of the TC. This is the first description of fish TC with these ultrastructural features and organization, which suggest that they perform a secretory function.

[Neonatal seizures and progression to epilepsy in a tertiary hospital]. / Crisis neonatales y evolución a epilepsia en un hospital de tercer nivel.

INTRODUCTION: Given the immaturity of the newborn, neonatal seizures are a diagnostic challenge. Most of them are secondary to an acute event. A small percentage constitute the onset of epilepsy. AIMS: The aim was to analyse neonates with a diagnosis of seizures admitted to a tertiary hospital between November 2009 and May 2021, and their subsequent progression to epilepsy. MATERIAL AND METHODS: A retrospective observational study was carried out using the hospital database. Information was collected on neonates with a discharge diagnosis of 'seizures' or 'moderate or severe hypoxic-ischaemic encephalopathy'. Different variables were analysed: aetiology of the seizures, type, persistence over time, treatment and electroclinical correlates. RESULTS: Of 165 patients, 55 presented neonatal seizures. As regards aetiology, 43 patients (78%) had seizures secondary to an acute event, of which 19 (34%) were hypoxic-ischaemic encephalopathies, and 22 (40%) had other acute disorders. Genetic alteration was found in six of them (11%). Thirteen patients (24%) progressed to subsequent epilepsy, of whom seven had symptomatic epilepsy, with a period of latency after the acute event in two patients. Six patients had neonatal epilepsy with unprovoked seizures. Twenty-two (62%) showed electroclinical correlates. All of the confirmed crises (100%) were focal. All the seizures were treated. The drug of choice was phenobarbital. CONCLUSIONS: Diagnosis of neonatal seizures requires high clinical suspicion and electroclinical confirmation. Most of them progress favourably, but a percentage constitute the onset of epilepsy, the identification of which will determine their therapeutic management.

TITLE: Crisis neonatales y evolución a epilepsia en un hospital de tercer nivel.Introducción. Las convulsiones neonatales son un reto diagnóstico, dada la inmadurez del recién nacido. La mayoría son secundarias a un evento agudo. Un pequeño porcentaje constituye el inicio de una epilepsia. Objetivos. Analizar a los neonatos ingresados en un hospital de tercer nivel con diagnóstico de crisis entre noviembre de 2009 y mayo de 2021, y su evolución posterior a epilepsia. Material y métodos. Se ha realizado un estudio observacional retrospectivo utilizando la base de datos del hospital. Se ha recogido la información de los neonatos con diagnóstico en el alta de 'convulsiones' o 'encefalopatía hipóxico-isquémica moderada o grave'. Se analizaron distintas variables: etiología de las crisis, tipo, persistencia temporal, tratamiento y correlato electroclínico. Resultados. De 165 pacientes, 55 presentaron crisis neonatales. En cuanto a la etiología, 43 pacientes (78%) tuvieron crisis secundarias a un evento agudo, de las cuales 19 (34%) fueron encefalopatías hipóxico-isquémicas, y 22 (40%), otras alteraciones agudas. En seis (11%) se encontró alteración genética. Trece pacientes (24%) evolucionaron a una epilepsia posterior, de los cuales siete presentaron una epilepsia sintomática, con un período de latencia tras el evento agudo en dos pacientes. Seis pacientes tuvieron epilepsia neonatal con crisis no provocadas. Veintidós (62%) mostraron correlato electroclínico. El 100% de las crisis confirmadas fueron focales. Todas las crisis se trataron. El fármaco de elección fue el fenobarbital. Conclusiones. El diagnóstico de convulsiones neonatales requiere una alta sospecha clínica y una confirmación electroclínica. La mayoría tiene evolución favorable, pero un porcentaje constituye el inicio de una epilepsia, cuya identificación determinará su manejo terapéutico.

Liver histopathology in brown trout (Salmo trutta f. fario) from the Tinhela River, subjected to mine drainage from the abandoned Jales Mine (Portugal).

The objective of this study was to compare the occurrence of toxicopathic liver lesions in brown trout (Salmo trutta fario) from Tinhela River near the Jales Mine, both before implementation (2002) and after completion of the governmental mitigation program (2006). Fish were caught in April 2002 and May 2006, using an electrofishing system at four sites: S0, reference station; S1, S2 and S3 as contaminated stations. In 2002, the hepatosomatic index (HSI) was significantly higher for trout captured at the contaminated sites S2 and S3 than in S0. After the rehabilitation program, the HSI of fish sampled at the contaminated sites did not differ from the reference group. The liver of trout caught at S0 exhibited the normal parenchymal and stromal architecture described for the species and there were no pathological abnormalities. In contrast, fish sampled at S3 and S2 sites had diverse toxicopathic alterations. Specifically, livers from the two contaminated sites showed bile duct hyperplasia, often with mild epithelial dysplasia and fibrotic adventitial sleeve, foci of smaller and more basophilic hepatocytes and foci of hepatocellular necrosis; the latter conditions were frequently associated. Compared with the reference animals, increased hepatocellular vacuolization was found in livers from the polluted sites. Histopathological examination revealed differences among sampling sites in the severity and diversity of hepatic lesions clearly related to the proximity of the tailings. No pathological alterations were observed in the livers of brown trout caught in the same four areas of the Tinhela River after the mitigation program in 2006. In conclusion, our results supported that drainage from the abandoned Jales Mine had deleterious toxicological effects in brown trout. Our data suggested that the governmental mitigation program may have reduced the impact of Jales tailings.

Protein kinase WNK2 inhibits cell proliferation by negatively modulating the activation of MEK1/ERK1/2.

The recently identified subfamily of WNK protein kinases is characterized by a unique sequence variation in the catalytic domain and four related human WNK genes were identified. Here, we describe the cloning and functional analysis of the human family member WNK2. We show that the depletion of endogenous WNK2 expression by RNA interference in human cervical HeLa cancer cells led to the activation of the extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinases but, in contrast to the depletion of WNK1, had no effect on ERK5. Furthermore, expression of a kinase-dead WNK2-K207M mutant also activated ERK1/2 suggesting that WNK2 catalytic activity is required. Depletion of WNK2 expression increased G1/S progression and potentiated the cellular response to low epidermal growth factor concentrations. The molecular mechanism of ERK1/2 activation in WNK2-depleted cells lies downstream of the Raf kinases and involves MEK1 phosphorylation at serine 298 in both HeLa and HT29 colon cancer cells. This modification is linked to the upregulation of MEK1 activity toward ERK1/2. Together, these results provide evidence that WNK2 is involved in the modulation of growth factor-induced cancer cell proliferation through the MEK1/ERK1/2 pathway. The data identify WNK2 as a candidate tumor suppressor gene and suggest a coordinated activity of WNK kinases in the regulation of cell proliferation.

Bioactivity of Acanthus mollis - Contribution of benzoxazinoids and phenylpropanoids.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthus mollis is a plant native to the Mediterranean region, traditionally used as diuretic, anti-inflammatory and soothing of the mucous membranes of the digestive and urinary tract and externally as healing of wounds and burns, also demonstrating analgesic and anti-inflammatory activities. However, studies focused on its phytochemical composition as well as scientific proof of Acanthus mollis efficacy are scarce. AIM OF THE STUDY: The proposed work aims to perform a phytochemical characterization and evaluation of the therapeutic potential of Acanthus mollis, based on biological properties that support its traditional uses. MATERIAL AND METHODS: In this study, an 96% ethanol extract from Acanthus mollis leaves was obtained and its phytochemical composition evaluated using High Performance Liquid Chromatography with Photodiode Array Detector coupled to Electrospray Ionization Mass Spectrometry (HPLC-PDA-ESI/MSn). The chemical structure of the compound isolated was elucidated using 1H and 13C Nuclear Magnetic Resonance (NMR), 1H-correlation spectroscopy (1H-COSY), heteronuclear single quantum correlation (HSQC) and heteronuclear multiple-bond correlation (HMBC). The quantification of the constituents was performed using two external standards (2,4-dihydroxy-1,4-benzoxazin-3-one and verbascoside). The antioxidant activity was determined by the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) assay. Anti-inflammatory activity was determined measuring the inhibition of nitric oxide production by RAW 264.7 macrophages stimulated with the TLR4 agonist lipopolysaccharide (LPS) and through lipoxygenase (LOX) inhibition assay. The cytotoxicity was screened on two lines (RAW 264.7 and HaCaT) using the resazurin assay. RESULTS: Compounds such as verbascoside and its derivatives, as well as benzoxazinoids were found as the main constituents. A percentage of 5.58% was verified for the 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) derivatives. DIBOA was the main compound of the extract. Significant concentrations were also found for phenylpropanoids, which constitute about 4.39% of the total compounds identified. This extract showed antioxidant capacity against DPPH (IC50 = 40.00 ±â€¯1.59 µg/mL) and superoxide anion (IC50 = 29.42 ±â€¯1.99 µg/mL). It also evidenced anti-inflammatory potential in RAW 264.7 macrophages, presenting capacity for nitric oxide reduction (IC50 = 28.01 µg/mL). Moreover, in vitro studies have shown that this extract was able to inhibit the lipoxygenase, with an IC50 of 104.39 ±â€¯4.95 µg/mL. Importantly, all effective concentrations were devoid of cytotoxicity in keratinocytes, thus highlighting the safety of the extract for the treatment of skin inflammatory related diseases. Concerning macrophages it was also possible to disclose concentrations showing anti-inflammatory activity and without cytotoxicity (up to 30 µg/mL). The benzoxazinoid DIBOA demonstrated a considerable anti-inflammatory activity suggesting its important contribution to this activity. CONCLUSIONS: These results corroborate the anti-inflammatory properties traditionally attributed to this plant. Among the compounds identified in this study, benzoxazinoids exhibited a significant anti-inflammatory activity that was never previously described. Ethanol seems to be a good option for the extraction of these bioactive compounds, since relevant antioxidant/anti-radical and anti-inflammatory activities were found for this extract.

Adult bronchiolitis--a clinical and pathological interpretative classification.

INTRODUCTION: Bronchiolitis is a heterogeneous group of diseases of an inflammatory nature, centered on small conducting airways and often associated with other pulmonary disorders. No single classification scheme for bronchiolar diseases has been widely accepted. In this retrospective study, it was decided to apply a new clinical and pathological interpretative classification. OBJECTIVES: To propose a new clinical and pathological interpretative classification for adult bronchiolitis, based on statistical analysis of a population of 193 patients with histopathological diagnosis of bronchiolitis. MATERIALS AND METHODS: A retrospective study analyzed the epidemiological characteristics, co-morbidities and radiological findings present in a group of patients with histopathological diagnosis of bronchiolitis. RESULTS: This trial involved 193 cases collected over a period of eleven years; 48 (24.9%) patients had simultaneous pulmonary disease; non-pulmonary diseases, such as cardiovascular diseases, type II Diabetes mellitus and dyslipidemia were present in 57 cases. The image study was extremely important in order to integrate clinical and pathological aspects. In this study respiratory bronchiolitis related to smoking dominated. The radiological findings confirmed the secondary nature of the histopathological features, with prevalence of ground-glass patterns, pneumothorax and patterns of interstitial involvement, as described in the literature. It was also verified that clinical behavior of different forms of bronchiolitis was important to distinguish the various types, since they could progress without typical anatomopathological aspects. CONCLUSION: This trial showed that the vast majority of diagnosis obtained corresponded to bronchiolitis as secondary to pulmonary pathology. In most cases, morphological findings had to be complemented with clinical and radiological characteristics, in order to obtain the final diagnosis.

Expression of Mcl-1 and Ki-67 in Papillary Thyroid Carcinomas.

UNLABELLED: Studying molecules that are differentially expressed in cancers as well as benign and normal tissues is crucial for identifying novel biomarkers for cancer immunotherapy. This study aimed to investigate the clinical utility of the immunochemical expression of the proliferative cell marker Ki-67 and the apoptotic blocker Mcl-1 in papillary thyroid carcinoma (PTC). METHODS: We built a tissue microarray with 282 thyroid specimens. There were 59 PTCs including 35 classic (CPTC), 3 tall cell (TCPTC) and 21 follicular variants (FVPTC); 79 benign thyroid diseases (22 follicular adenomas; 57 adenomatoid hyperplasia); 33 Hashimoto's thyroiditis (HT) specimens; and 111 normal thyroid tissues. Clinical history and ultrasound data were retrospectively obtained by chart review. RESULTS: Mcl-1 overexpression was evident in 66.7% of the PTC tissues compared to 32% of the benign thyroid diseases. Mcl-1 strong staining distinguished benign from malignant thyroid lesions (sensitivity=61.3%; specificity=72.8%; negative predictive value, NPV=68%; positive predictive value, PPV=66.7% and 67.5% accuracy). Positive nuclear Ki-67 staining was observed in 34% of PTCs vs. 19% of thyroid adenomas (P=0.031). Strong Mcl-1 and Ki-67 co-expression was identified in 57.5% of PTCs with a higher PPV (75.8%). Mcl-1 and Ki-67 expression was not associated with any clinicopathological feature of malignancy. No deaths occurred during the follow-up. CONCLUSIONS: Mcl-1 immunochemical overexpression allowed differentiating low-risk PTC from the benign thyroid lesions. We suggest that Mcl-1 expression may help differentiate follicular patterned thyroid lesions. The influence of the Mcl-1 expression on several features of tumor aggressiveness has to be studied in large series of high-risk thyroid carcinomas.

Alternative functional criteria to assess airflow-limitation reversibility in asthma.

INTRODUCTION: International guidelines define significant bronchodilator response as absolute and percentage change from baseline in forced expiratory volume (FEV1) in the first second and/or forced vital capacity (FVC) ≥12% and 200 mL. However, bronchodilator effects on other lung function parameters have also been correlated to some degree of reversible airflow limitation. OBJECTIVES: To determine whether changes in other lung function parameters apart from FEV1 and FVC detect functional responses to bronchodilator in asthmatic patients. MATERIALS AND METHODS: Spirometry and body plethysmography were performed at baseline conditions and after administration of 400 µg of salbutamol by metered-dose inhaler through a space chamber device in asthmatic patients. Paired t-tests were used to compare lung function parameters between those with and without criteria for reversibility of airway obstruction according to ATS/ERS criteria. Cut-off values were obtained from the corresponding ROC curves. Measurements evaluated were FEV1, FVC, maximum mid-forced expiratory flow (FEF25-75%), residual volume (RV), inspiratory capacity (IC), airway resistance (Raw) and specific airway conductance (sGaw). RESULTS: From a total of 100 consecutive asthmatics patients (46% of them men; average age 58.7±14.1 years; 76% with mild to moderate obstruction), 50 patients had a significant bronchodilator response. All of these had noteworthy variations (p<0.004) in PEF, FEF25-75%, RV, Raw and sGaw. The most accurate in predicting a significant bronchodilator response were the absolute and percentage improvements in PEF (≥0.4 L/s and 8%), FEF25-75% (≥0.087 L/s and 27%) and the percentage of sGaw compared with that at baseline (≥25%). Based on these cut-off values, a sizeable number of the patients defined as non-responders had important changes in airway caliber. 17 patients had significant increments in the percentage of PEF and 10 had changes in absolute volume; 6 patients had increments in percentage and 16 in absolute change of FEF25-75%; 22 patients had increments in the percentage change of sGaw. CONCLUSIONS: Changes of FEV1 and/or FVC may underestimate significant functional response to bronchodilators in asthmatic patients with airway obstruction when considering the change in other lung function parameters.

First report of Kudoa sp. in the palate and pharyngeal musculature of Gobioides grahamae Palmer and Wheeler, 1955 (Perciformes, Gobiidae) from Marajó Island, Brazil / Primeiro registro de Kudoa sp. na musculatura do palato e faringeal de Gobioides grahamae Palmer e Wheeler, 1955 (Perciformes, Gobiidae) da Ilha do Marajó, Brasil

The aim of this study was to describe the first occurrence ofKudoasp. inGobioides grahamae, contributing to the understanding of this group of parasites in the Amazonian ichthyofauna. Forty specimens ofG. grahamaecollected from the natural environment were analyzed. Cysts ofKudoasp. were diffusely distributed through the striated skeletal muscle fibers with severe edema and inflammatory infiltrate composed of lymphocytes were observed in 30% of the specimens. Edema and marked coagulation necrosis of the muscle fibers was associated with infection byKudoasp. spores, which had accumulated inside the skeletal muscle fibers. Although there are no records of foodborne outbreaks caused by Kudoa spp. in Brazil, it is of paramount importance that we evaluate its occurrence, since the consumption of fish, especially raw fish, has increased because of the adoption of Japanese cuisine. To minimize the economic impacts on the fisheries market and the risk of this parasite to public health, it is necessary to initiate a program to monitor the presence of this likely underdiagnosed, emerging parasite.(AU)

O objetivo deste estudo foi descrever a primeira ocorrência de Kudoa sp. em Gobioides grahamae, contribuindo, assim, para a compreensão desse grupo de parasitas na ictiofauna amazônica. Foram analisados 40 espécimes de G. grahamae coletados de ambiente natural. Cistos de Kudoa sp. foram distribuídos difusamente através das fibras musculares esqueléticas estriadas com presença de edema grave e infiltrado inflamatório composto de linfócitos, que foram observados em 30% dos espécimes. Edema e necrose de coagulação acentuada das fibras musculares foram associados com a infecção por esporos de Kudoa sp., acumulados no interior das fibras musculares da faringe. Apesar de não haver registros de surtos de origem alimentar causada por Kudoa spp. no Brasil, é de suma importância a avaliação de sua ocorrência, uma vez que o consumo de peixe, especialmente peixe cru, aumentou por causa da adoção da culinária japonesa. Para minimizar os impactos econômicos no mercado da pesca e o risco desse parasita para a saúde pública, é necessário iniciar um programa para monitorar a presença desse parasita emergente, possivelmente subdiagnosticada.(AU)

Four novel MSH2 / MLH1 gene mutations in portuguese HNPCC families.

Hereditary non-polyposis colorectal cancer (HNPCC) is considered to be determined by germline mutations in the mismatch repair (MMR) genes, especially MSH2 and MLH1. While screening for mutations in these two genes in HNPCC portuguese families, 3 previously unreported MSH2 and 1 MLH1 mutations have been identified in families meeting strict Amsterdam criteria. Hum Mutat 15:116, 2000.