In vitro anthelmintic activity of Siparuna guianensis extract and essential oil against Strongyloides venezuelensis.

New therapeutic approaches are necessary to control strongyloidiasis due to the side effects of, and resistance to, currently available drugs thiabendazole, albendazole, and ivermectin. This study examined the anthelmintic properties of extracts and isolated compounds from Siparuna guianensis against Strongyloides venezuelensis eggs and larvae, using the egg hatching test (EHT) and larval motility test (LMT). Albendazole (0.025 mg/ml) and ivermectin (0.316 mg/ml) were used as the positive controls for the EHT and LMT assays, respectively. Strongyloides venezuelensis eggs or larvae (±50 specimens) were treated with ethanol extract (0.05-1.0 mg/ml), ethyl acetate and aqueous fractions (0.05-0.8 mg/ml), essential oil (0.2-1.0 mg/ml) and α-bisabolol (0.2-1.0 mg/ml) from S. guianensis, and analysed by optical microscopy after 48 h (EHT), or after 24, 48 and 72 h (LMT). All the tested compounds exhibited ovicidal activity equivalent to the positive control and changed the morphology of the eggs. The S. guianensis ethanol extract and aqueous fraction were as effective as the positive control. Phytochemical analysis of the ethanol extract and fractions revealed the presence of phenolic compounds, tannins and flavonoids. Therefore, S. guianensis is effective against S. venezuelensis eggs and larvae in vitro, and can be considered as a potential alternative treatment for strongyloidiasis.

Integrating EM and Patch-seq data: Synaptic connectivity and target specificity of predicted Sst transcriptomic types.

Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between those cell types 1 . Neural cell types have previously been defined by morphology 2, 3 , electrophysiology 4, 5 , transcriptomic expression 6-8 , connectivity 9-13 , or even a combination of such modalities 14-16 . More recently, the Patch-seq technique has enabled the characterization of morphology (M), electrophysiology (E), and transcriptomic (T) properties from individual cells 17-20 . Using this technique, these properties were integrated to define 28, inhibitory multimodal, MET-types in mouse primary visual cortex 21 . It is unknown how these MET-types connect within the broader cortical circuitry however. Here we show that we can predict the MET-type identity of inhibitory cells within a large-scale electron microscopy (EM) dataset and these MET-types have distinct ultrastructural features and synapse connectivity patterns. We found that EM Martinotti cells, a well defined morphological cell type 22, 23 known to be Somatostatin positive (Sst+) 24, 25 , were successfully predicted to belong to Sst+ MET-types. Each identified MET-type had distinct axon myelination patterns and synapsed onto specific excitatory targets. Our results demonstrate that morphological features can be used to link cell type identities across imaging modalities, which enables further comparison of connectivity in relation to transcriptomic or electrophysiological properties. Furthermore, our results show that MET-types have distinct connectivity patterns, supporting the use of MET-types and connectivity to meaningfully define cell types.

Lipid droplet biogenesis and COX-2 pathway activation are triggered by Barrett's esophagus and adenocarcinoma, but not esophageal squamous cell carcinoma risk factors.

Esophageal cancer (EC) is an aggressive disease, presenting two main histological subtypes: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). The two EC subtypes widely differ concerning virtually all factors. ESCC development is mainly associated with tobacco and alcohol abuse, whereas obesity and chronic gastroesophageal reflux disease (GERD) are important risk factors not only for EAC, but also for for Barrett's esophagus (BE), an intestinal metaplasia that precedes EAC. Obesity triggers ectopic lipid droplets (LD) accumulation in non-adipose tissues. LD are organelles involved in cell metabolism, signaling, proliferation and production of inflammatory mediators. Therefore, the aim of this work was to investigate LD occurrence and role in EC. This study shows progressive LD levels increase along EAC development, in esophageal samples from non-obese through obese individuals, as well as BE, and EAC patients, whereas no significant changes were observed in ESCC samples, when compared to non-tumor samples. Additionally, in order to mimic BE and EAC risk factors exposure, a non-tumor esophageal cell line was incubated with oleic acid (OA) and acidified medium and/or deoxycholic acid (DCA), revealing a significant increment in LD amount as well as in COX-2 and CXCL-8 expression, and in IL-8 secretion. Further, COX-2 expression and LD amount presented a significant positive correlation and were detected co-localized in EAC, but not in ESCC, suggesting that LD may be the site for eicosanoid production in EAC. In conclusion, this study shows that obesity, and BE- and EAC-associated inflammatory stimuli result in a gradual increase of LD, that may be responsible for orchestrating inflammatory mediators' production and/or action, thus contributing to BE and EAC genesis and progression.

A large-scale assessment of lakes reveals a pervasive signal of land use on bacterial communities.

Lakes play a pivotal role in ecological and biogeochemical processes and have been described as "sentinels" of environmental change. Assessing "lake health" across large geographic scales is critical to predict the stability of their ecosystem services and their vulnerability to anthropogenic disturbances. The LakePulse research network is tasked with the assessment of lake health across gradients of land use on a continental scale. Bacterial communities are an integral and rapidly responding component of lake ecosystems, yet large-scale responses to anthropogenic activity remain elusive. Here, we assess the ecological impact of land use on bacterial communities from over 200 lakes covering more than 660,000 km2 across Eastern Canada. In addition to community variation between ecozones, land use across Eastern Canada also appeared to alter diversity, community composition, and network structure. Specifically, increasing anthropogenic impact within the watershed lowered diversity. Likewise, community composition was significantly correlated with agriculture and urban development within a watershed. Interaction networks showed decreasing complexity and fewer keystone taxa in impacted lakes. Moreover, we identified potential indicator taxa of high or low lake water quality. Together, these findings point to detectable bacterial community changes of largely unknown consequences induced by human activity within lake watersheds.

Conjugated linoleic acid (CLA): effect modulation of body composition and lipid profile.

Conjugated linoleic acid (CLA) refers to a family of polyunsaturated fatty acids, being represented by a group of isomers of linoleic acid called conjugated for having a double bound after a simple bound. Among its isomers, trans-10,cis-12 and cis-9, cis-12 CLA stand out. These isomers can lead to different effects on the body: anticarcinogenic, antidiabetogenic, antiatherogenesis and positive body composition alteration. The objective of this review is to describe their mechanisms of action, effects on body composition, on plasmatic lipoproteins and supplementation. Studies about CLA supplementation show its capacity of reducing fat percentage, body mass and of promoting an improvement in lipid metabolism. One of the adverse effects attributed to one of the isomers is insulin resistance by body fat redistribution. Limitations in the scientific models used in CLA researches make impossible to draw conclusions about the action of this fatty acid on human metabolism.

[Intricated asthma tracheomalacia: diagnosis and therapeutic aspects]. / Asthme et trachéomalacie associés: aspects diagnostiques et thérapeutiques.

An asthmatic girl was first hospitalized at age 2(9/12) years because of dyspnoea, lung consolidations and/or atelectasis, and rattling. Between ages 2(9/12) and 6(2/12) years, she required three hospitalizations in ICU out of nine hospitalizations for the same symptoms. Differential diagnosis of this difficult to treat asthma disclosed severe tracheomalacia and persistent asthma. Treatments given according to the clinical, radiological and functional findings failed to decrease frequency and severity of acute respiratory episodes. Eventually, positive pressure ventilation delivered at airway opening (via a mouthpiece) associated to active respiratory physiotherapy succeeded in removing atelectasis and quickly cured the five following acute episodes without any further hospitalization. This case report is about diagnosis procedure, intricate asthma and tracheomalacia, and open mind to unusual therapeutics that may disclose potential help.

Criticality of a contact process with coupled diffusive and non-diffusive fields.

We investigate the critical behavior of a model with two coupled critical densities, one of which is diffusive. The model simulates the propagation of an epidemic process in a population, which uses the underlying lattice to leave a track of the recent disease history. We determine the critical density of the population above which the system reaches an active stationary state with a finite density of active particles. We also perform a scaling analysis to determine the order parameter, the correlation length, and critical relaxation exponents. We show that the model does not belong to the usual directed percolation universality class and is compatible with the class of directed percolation with diffusive and conserved fields.

[Management of patients under 18years of age by adult intensive care unit professionals: Level of training, workload, and specific challenges]. / Prise en charge de patients mineurs par les équipes de réanimation pour adultes : expérience pédiatrique, estimation de l'activité et difficultés ressenties par les soignants.

In routine practice, intensive care physicians rarely have to manage children under 18years of age, particularly those under 15. This study's objectives were to assess the quality of training in pediatrics of adult intensive care teams, to document the workload generated by care of pediatric patients, and to identify the difficulties encountered in managing minors as patients. A survey was administered in Lower Normandy from 4 April 2012 to 1 September 2012. Physicians, residents, nurses, and nurses' aides practicing in one of the nine intensive care units of Lower Normandy were asked to complete an electronic or paper format questionnaire. This questionnaire assessed their level of pediatric training, the workload management of pediatric patients entailed, and the challenges posed by these patients. One hundred and nine questionnaires were returned (by 26 attending physicians, 18 residents, 38 nurses, and 27 nurses' aides). Eighty-three of the respondents (76%) had no experience in a pediatric unit of any kind. Forty-two percent thought that the pediatric age range lies between 3months and 15years of age. However, more than 50% of respondents would like the upper limit to be 16years or even older. Ninety-three respondents (85%) estimated having some exposure to pediatric patients in their routine practice, but this activity remained quite low. Seventy-three (67%) reported difficulties with the management of these young patients. This survey provides current information regarding the level of training of adult intensive care unit professionals and their concerns about managing patients under 18years of age, both in terms of workload and specific challenges.

Chronic exposure to inorganic mercury induces biochemical and morphological changes in the salivary glands of rats.

Mercury exposure is considered to be a public health problem due to the generation of toxic effects on human health as a result of environmental and occupational conditions. The inorganic form of mercury (HgCl2) can cause several biological changes in cells and tissues through its cumulative toxic potential, but little has been experimentally proven about the effects of inorganic mercury on salivary glands, an important modulator organ of oral health. This study analyzes the effects of prolonged low dose exposure to HgCl2 on the salivary glands of rats. Adult animals received a dose of 0.375 mg kg-1 day-1 over a period of 45 days. The parotid and submandibular glands were collected for analysis of the mercury levels and evaluation of oxidative stress, histological parameters and immunomodulation for metallothionein I and II (MT-I/II). In this investigation, biochemical and tissue changes in the salivary glands were verified due to the mercury levels, causing reduction in antioxidant capacity against peroxyl radicals, with consequent cellular lipid peroxidation and an increase in nitrite levels, volumetric changes and cytoskeletal damage in the submandibular glands, with less severe damage to the parotid glands. The results also have shown the occurrence of a cytoprotection mechanism due to increased MT-I/II expression, but not enough to avoid the morphology and oxidative damage. This evidence highlights, for the first time, that inorganic mercury is able to alter the morphology and oxidative biochemistry in salivary glands when exposed for a long time in low doses.

Maternal protein restriction during lactation modulated the expression and activity of rat offspring hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1 during development.

Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring's CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8- fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities' alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development.

Bordetella pertussis adenylate cyclase toxin: proCyaA and CyaC proteins synthesised separately in Escherichia coli produce active toxin in vitro.

Bordetella pertussis produces a cell-invasive adenylate cyclase toxin (CyaA) which is related to the RTX family of pore-forming toxins. Like all RTX toxins, CyaA is synthesised as a protoxin (proCyaA), encoded by the cyaA gene. Activation to the mature cell-invasive toxin involves palmitoylation of lysine 983 and is dependent on co-expression of cyaC. The role of the cyaC gene product in the acylation reaction has not been determined. We have developed an efficient T7 RNA polymerase system for over-expression of cyaA and cyaC separately in Escherichia coli. Each protein accumulated intracellularly in an insoluble form and could be collected by centrifugation of lysed cells. A single-step purification was achieved by extraction of the aggregated material with 8 M urea. Active cell-invasive CyaA was produced in vitro when the proCyaA and CyaC proteins were mixed with a cytosolic extract of either E. coli or B. pertussis. Activation was assumed to occur by an acylation reaction requiring acyl carrier protein (ACP) as cofactor, as the cytosolic factor required for toxin activation was lost if the S100 extract was dialysed before use and the cytosolic factor could be replaced in the in vitro reaction by ACP charged separately in vitro with palmitic acid, as reported previously for activation of the homologous E. coli haemolysin (HlyA). The in vitro activation system may be used to investigate the mechanism of the CyaC-dependent acylation of proCyaA and the effect of variation of the modifying fatty acyl group on target cell specificity and toxic activity of CyaA.

Relationships of myosin heavy chain fibre types to meat quality traits in traditional and modern pigs.

Porcine skeletal muscle fibres were molecularly classified, using in situ hybridisation and immunocytochemistry, into four types, according to the isoform of myosin heavy chain (MyHC) that was present in each fibre (MyHC slow/I, MyHC 2a, MyHC 2x and MyHC 2b). The relationship between MyHC fibre types and meat quality traits between two phenotypically divergent muscles [longissimus dorsi (LD) and psoas], and between the same muscles of different breeds (traditional Berkshire and Tamworth, and modern Duroc-based and Large White-based) were examined. We found that the greater abundance of fast oxidative-glycolytic MyHC 2a and 2x fibres in the psoas was associated with superior meat quality traits, and that the greater presence of fast glycolytic MyHC 2b fibres in the LD could account for less favourable quality traits, both in terms of pH, drip loss, grain, colour, yield force and work done. Although significant correlations were found between specific fibre types and quality traits, within either the psoas or LD muscle of some breeds, no consistent correlation was found across both muscles and all breeds. This finding was in line with the view that a given fibre type could have considerable differences in phenotype between breeds, and between muscles. The observed inverse compositional and functional-meat quality relationship between MyHC 2b and 2x fibres, and MyHC 2b and 2a fibres could form a basis of fibre type manipulation to improve meat quality.

Effects of breed, diet and muscle on fat deposition and eating quality in pigs.

A study in 192 entire male pigs examined the effects of breed, diet and muscle on growth, fatness, sensory traits and fatty acid composition. There were four breeds: two modern breeds, Duroc and Large White and two traditional breeds, Berkshire and Tamworth. The diets differed in energy:protein ratio, being conventional (C) and low protein (LP) diets, respectively. Muscles investigated were the `white' longissimus dorsi (LD) and the `red' psoas major (PS). Breed influenced growth rate and fatness, the modern breeds being faster-growing with leaner carcasses. However, the concentrations of neutral lipid fatty acids and marbling fat (neutral lipid+phosopholipid fatty acids) were higher in Berkshire and Duroc, in both LD and PS. Relationships between marbling fat and P2 fat thickness showed clear breed effects, with Duroc having high marbling fat at low P2 and Tamworth low marbling fat at high P2. Breed effects on sensory scores given by the trained taste panel to griddled LD and PS steaks were relatively small. Breed affected the fatty acid composition of intramuscular neutral lipid, with high % values for the saturated fatty acids, 14:0 and 16:0 in Berkshire and Tamworth (fat carcasses) and high values for polyunsaturated fatty acids in Duroc and Large White (lean carcasses). Duroc had particularly high concentrations of the long-chain polyunsaturated fatty acids, 20:5n-3 and 22:6n-3 in phospholipid of both muscles. Diet influenced growth rate and fatness, the LP diet slowing growth and producing fatter meat, more so in the two modern breeds, and particularly in intramuscular rather than subcutaneous fat. This diet produced more tender and juicy meat, although pork flavour and flavour liking were reduced. The PS muscle had higher tenderness, juiciness, pork flavour, flavour liking and overall liking scores than LD. The concentration of phospholipid fatty acids was higher in PS than LD but neutral lipid fatty acid content and marbling fat were higher in LD.

[Prevalence of serologic markers of hepatitis B virus in hospital personnel]. / Prevalência de marcadores sorológicos do vírus da hepatite B em trabalhadores do serviço hospitalar.

OBJECTIVE: To verify the prevalence of the anti-HBc, anti-HBs and HBsAg markers of hepatitis B virus, and to identify the risk factors determining occupational infection with this virus among hospital personnel. METHODS: Samples of serum from 210 persons both male and female who work in different occupations at a hospital university, were analysed. The technique employed was the immunoenzymatic assay using commercial kits. RESULTS: As a control group, samples of serum from 45 volunteer blood donors were utilized. It was verified that 20.5% of the hospital personnel presented a positive reaction to at least one of the markers songht, as against 6.6% of the control group. The prevalence of each marker separately was: anti-HBc 8.1%, anti-HBs 5.2%, and HBsAg 2.9% in the hospital personnel; and 4.4%, 2.2% and 0.0% in the control group. The simultaneous presence of the anti-HBc and anti-HBs markers was detected in 4.3% of the workers. In the control group, the presence of the anti-HBc and anti-HBs markers was detected, isolately, with respective prevalences of 4.4% and 2.2%. Those who presented the highest rates of positivite reaction were: laboratory technicians 24.0%, nurses 23.6%, physicians 20.8%, and cleaning personnel 18.2%. CONCLUSIONS: The findings suggest that direct contact with patients and handling of blood and other body fluids are risk factors related to occupational infection with HBV. Therefore, it is recommended that hospital personnel be vaccinated against hepatitis B.

[Bernard-Soulier syndrome revealed by major neonatal thrombocytopenia]. / Syndrome de Bernard-Soulier révélé par une thrombopénie sévère en période néonatale.

Bernard-Soulier syndrome (BSS) is a congenital autosomal recessive bleeding disorder characterised by giant platelets, the lack of thrombocytopenia or a moderate one, prolongation of skin bleeding time, and absent platelet aggregation in response to ristocetin. We report a case of BSS revealed by major neonatal thrombocytopenia. A newborn was admitted for thrombocytopenic purpura initially believed to be due to a maternal auto-immune thrombocytopenia. Because of the persistence of the thrombopenia till the age of 7 months despite therapy by corticosteroids and immunoglobulins, and because of the detection of anti-1b antiplatelets antibodies after transfusion, BSS diagnosis was evoked. In such a situation of major thrombocytopenia, the main therapeutic measure is prevention. Therapy by DDAVP may be used after the age of 3 years in situations of high haemorrhagic risk. This case report underlines the importance of a precise diagnosis in front of a maternal thrombocytopenia and the possibility of antenatal diagnosis of BSS.

[2 days of drug dependence consultation in Portugal]. / Dois dias de consulta de toxicodependências em Portugal.

This paper reports the results of a survey of all State outpatient clinics for drug addiction in Portugal. Two consecutive days of consultations in November 1992 were considered. The Health Ministry's SPTT--Service for Drug Addiction Prevention and Treatment--coordinates the activity of all the centres and promoted the inquiry. The main objective was to simultaneously evaluate the state of the population under treatment in what concerns the therapeutic methods used, their clinical costs and efficacy. This methodology may allow us to draw an accurate portrait of the Portuguese drug addiction public health program. We received 535 answers which we estimate to be two thirds of the consultations. Heroin abuse is the main problem in 91.3% of all cases plus 3.9% that associate heroin and cocaine abuse. Cannabis comes next with 2.1%, alcohol abuse with 0.8% and benzodiazepines with 0.5%. In what concerns the clinical results, 60% were abstinent: 15.1% were abstinent for longer than six months, 9.9% for longer than three months but less than six months, 19.8% were abstinent for less than that but longer than a month and 14.5% for longer than a week but less than a month. The main therapeutic approaches were psychotherapeutic in 54.1%, psychopharmacologic in 42.1% and socio-therapeutic in 2.3% of the cases. The author presents further data and discusses the results and their clinical implications.

[The physician facing the evolution of ethical concepts in our times]. / O médico perante a evolução das concepções éticas do nosso tempo.

Medical ethics institutionalized with clinical activities being determined by the patient's interests as they developed in the doctor-patient relationship. The ethical nature of the health concept was emphasized in the positive definitions of health such as the one by the W.H.O.. The established goals for clinical intervention surpass the effective medical capabilities. The curricula of medical schools will have to be reviewed in light of these goals. We characterized the contemporary values and the way medicine has adapted to them: superspecialization and doctors' change in social image brought about by the impact of technocracy in clinical activities, increasing costs of medical care, the interference of non medical managers in the process of clinical decision, litigation and breaches of confidentiality. Technical and social developments lead to new ethical problems in which the moral principles of the doctor can be confronted with patients' demands in situations of difficult choice. Contraception, abortion, genetic engineering, transplants, allocation of scarce resources, the expansion of drug dependency and euthanasia are examples of problems that clinicians frequently face today.

[Culture diseases. Brief review on the way characteristics of today's life affect the ways of mental disease]. / As doenças da cultura. Pequena memória sobre a forma como as características da vida contemporânea afectam as formas do adoecer mental.

Culture is expressed in the content of psychiatric symptoms. In this paper we try to establish a relationship between the pathoplasticity of some paradigmatic psychiatric disorders and characteristics of values and life styles in developed societies. We argue that some aspects of a marked hedonism hide a dangerous nihilism and they both articulate, in a discrepant way, with opposing responsible hiperrational and hypercompetitive register. Doctrinaire fanaticisms increase markedly in other places in the globe with endemic shortages while solid values lack in the societies of abundance. This affects mental health.

[Psychotherapy in AIDS]. / Psicoterapia na SIDA.

Infection with human immunodeficiency virus creates the expectation of terrible disease marked by an inexorable physical decline. The majority of the affected patients are relatively young and pleasure plays an important role in their lives which will be marked by the possibility of an early death. This is a peculiar situation with an unpredictable evolution that mandates a reformulation of the psychotherapeutic approach mainly in the achievable goals and the practical way to manage them. We describe our two years psychiatric and psychotherapeutic experience with AIDS patients followed by the H.S.M. Infectious Diseases Department.