Associations, causation and model in psychiatry

This paper discusses models, associations and causation in psychiatry. The different types of association (linear, positive, negative, exponential, partial, U shaped relationship, hidden and spurious) between variables involved in mental disorders are presented as well as the use of multiple regression analysis to disentangle interrelatedness amongst multiple variables. A useful model should have internal consistency, external validity and predictive power; be dynamic in order to accommodate new sound knowledge; and should fit facts rather than they other way around. It is argued that whilst models are theoretical constructs they also convey a style of reasoning and can change clinical practice. Cause and effect are complex phenomena in that the same cause can yield different effects. Conversely, the same effect can have a different range of causes. In mental disorders and human behaviour there is always a chain of events initiated by the indirect and remote cause; followed by intermediate causes; and finally the direct and more immediate cause. Causes of mental disorders are grouped as those: (i) which are necessary and sufficient; (ii) which are necessary but not sufficient; and (iii) which are neither necessary nor sufficient, but when present increase the risk for mental disorders.

Rat hepatocyte invasion by Listeria monocytogenes and analysis of TNF-alpha role in apoptosis

Listeria monocytogenes, etiological agent of severe human foodborne infection, uses sophisticated mechanisms of entry into host cytoplasm and manipulation of the cellular cytoskeleton, resulting in cell death. The host cells and bacteria interaction may result in cytokine production as Tumor Necrosis Factor (TNF) alpha. Hepatocytes have potential to produce pro-inflammatory cytokines as TNF-alpha when invaded by bacteria. In the present work we showed the behavior of hepatocytes invaded by L. monocytogenes by microscopic analysis, determination of TNF-alpha production by bioassay and analysis of the apoptosis through TUNEL technique. The presence of bacterium, in ratios that ranged from 5 to 50,000 bacteria per cell, induced the rupture of cellular monolayers. We observed the presence of internalized bacteria in the first hour of incubation by electronic microscopy. The levels of TNF-alpha increased from first hour of incubation to sixth hour, ranging from 0 to 3749 pg/mL. After seven and eight hours of incubation non-significant TNF-alpha levels decrease occurred, indicating possible saturation of cellular receptors. Thus, the quantity of TNF-alpha produced by hepatocytes was dependent of the incubation time, as well as of the proportion between bacteria and cells. The apoptosis rate increased in direct form with the incubation time (1 h to 8 + 24 h), ranging from 0 to 43%, as well as with the bacteria : cells ratio. These results show the ability of hepatocyte invasion by non-hemolytic L. monocytogenes, and the main consequences of this phenomenon were the release of TNF-alpha by hepatocytes and the induction of apoptosis. We speculate that hepatocytes use apoptosis induced by TNF-alpha for release bacteria to extracellular medium. This phenomenon may facilitate the bacteria destruction by the immune system.

Arboviral diseases in the Western Brazilian Amazon: a perspective and analysis from a tertiary health & research center in Manaus, State of Amazonas

The Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), located in Manaus, the capital of the State of Amazonas (Western Brazilian Amazon), is a pioneering institution in this region regarding the syndromic surveillance of acute febrile illness, including arboviral infections. Based on the data from patients at the FMT-HVD, we have detected recurrent outbreaks in Manaus by the four dengue serotypes in the past 15 years, with increasing severity of the disease. This endemicity has culminated in the simultaneous circulation of all four serotypes in 2011, the first time this has been reported in Brazil. Between 1996 and 2009, 42 cases of yellow fever (YF) were registered in the State of Amazonas, and 71.4% (30/42) were fatal. Since 2010, no cases have been reported. Because the introduction of the yellow fever virus into a large city such as Manaus, which is widely infested by Aedes mosquitoes, may pose a real risk of a yellow fever outbreak, efforts to maintain an appropriate immunization policy for the populace are critical. Manaus has also suffered silent outbreaks of Mayaro and Oropouche fevers lately, most of which were misdiagnosed as dengue fever. The tropical conditions of the State of Amazonas favor the existence of other arboviruses capable of producing human disease. Under this real threat, represented by at least 4 arboviruses producing human infections in Manaus and in other neighboring countries, it is important to develop an efficient public health surveillance strategy, including laboratories that are able to make proper diagnoses of arboviruses.

The use of a modular titanium endoprosthesis in skeletal reconstructions after bone tumor resections: method presentation and analysis of 37 cases

We analyzed 37 patients who underwent segmental wide resection of bone tumors and reconstruction with a modular titanium endoprosthesis at the Orthopaedic Oncology Group, between 1992 and 1998. Twelve patients were male and 25 were female, with a mean age of 30 years (9 - 81). The mean follow-up was 14 months (2 - 48). The diagnoses were: osteosarcoma (14 cases), metastatic carcinoma (10), Ewing's sarcoma (4), giant cell tumor (4), malignant fibrous histiocytoma (3), chondrosarcoma (1), and aneurysmal bone cyst (1). Eleven articulated total knee, 8 partial proximal femur with bipolar acetabulum, 8 partial proximal humerus, 3 total femur, 2 partial proximal tibia, 2 diaphyseal femur, 2 diaphyseal humerus, and 1 total proximal femur with cementless acetabulum endoprosthesis implant procedures were done. The complications related to the procedure included: infection (5 cases), dislocation (3), module loosening (1), and ulnar nerve paresthesia (1). We used the following criteria for the clinical evaluation: presence of pain, range of motion, reconstruction stability, surgical and oncologic complications, and patient acceptance. The results were good in 56.8% of the cases, regular in 32.4% and poor in 10.8%.

Human identification and analysis of DNA in bones

The introduction of molecular biology techniques, especially of DNA analysis, for human identification is a recent advance in legal medicine. Substantial effort has continuously been made in an attempt to identify cadavers and human remains after wars, socio-political problems and mass disasters. In addition, because of the social dynamics of large cities, there are always cases of missing people, as well as unidentified cadavers and human remains that are found. In the last few years, there has also been an increase in requests for exhumation of human remains in order to determine genetic relationships in civil suits and court action. The authors provide an extensive review of the literature regarding the use of this new methodology for human identification of ancient or recent bones.

Plasmodium falciparum CS protein - prime malaria vaccine candidate: definition of the human CTL domain and analysis of its variation

Studies in mice have shown that immunity to malaria sporozoites is mediated primarily by citotoxic T lymphocytes (CTL) specific for epitopes within the circumsporozoite (CS) protein. Humans, had never been shown to generate CTL against any malaria or other parasite protein. The design of a sub-unit vaccine for humans ralies on the epitopes recognized by CTL being identified and polymorphisms therein being defined. We have developed a novel technique using an entire series of overlapping synthetic peptides to define the epitopes of the Plasmodium falciparum CS protein recognized by human CTL and have analyzed the sequence variation of the protein with respect to the identified CTL epitopic domain. We have demonstrated that some humans can indeed generate CTL. against the P. falciparum CS protein. Furthermore, the extent of variation observed for the CTL recognition domain is finite and the combination of peptides necessary for inclusion in a polyvalent vaccine may be small. If ways can be found to increase immune responsiveness, then a vaccine designed to stimulate CS protein-specific CTL activity may prevent malaria.

Clustering of Schistosoma mansoni mRNA sequences and analysis of the most transcribed genes: implications in metabolism and biology of different developmental stages

The study of the Schistosoma mansoni genome, one of the etiologic agents of human schistosomiasis, is essential for a better understanding of the biology and development of this parasite. In order to get an overview of all S. mansoni catalogued gene sequences, we performed a clustering analysis of the parasite mRNA sequences available in public databases. This was made using softwares PHRAP and CAP3. The consensus sequences, generated after the alignment of cluster constituent sequences, allowed the identification by database homology searches of the most expressed genes in the worm. We analyzed these genes and looked for a correlation between their high expression and parasite metabolism and biology. We observed that the majority of these genes is related to the maintenance of basic cell functions, encoding genes whose products are related to the cytoskeleton, intracellular transport and energy metabolism. Evidences are presented here that genes for aerobic energy metabolism are expressed in all the developmental stages analyzed. Some of the most expressed genes could not be identified by homology searches and may have some specific functions in the parasite.

Production of full-length cDNA sequences by sequencing and analysis of expressed sequence tags from Schistosoma mansoni

The number of sequences generated by genome projects has increased exponentially, but gene characterization has not followed at the same rate. Sequencing and analysis of full-length cDNAs is an important step in gene characterization that has been used nowadays by several research groups. In this work, we have selected Schistosoma mansoni clones for full-length sequencing, using an algorithm that investigates the presence of the initial methionine in the parasite sequence based on the positions of alignment start between two sequences. BLAST searches to produce such alignments have been performed using parasite expressed sequence tags produced by Minas Gerais Genome Network against sequences from the database Eukaryotic Cluster of Orthologous Groups (KOG). This procedure has allowed the selection of clones representing 398 proteins which have not been deposited as S. mansoni complete CDS in any public database. Dedicated sequencing of 96 of such clones with reads from both 5' and 3' ends has been performed. These reads have been assembled using PHRAP, resulting in the production of 33 full-length sequences that represent novel S. mansoni proteins. These results shall contribute to construct a more complete view of the biology of this important parasite.

Larval recovery of Toxocara cati in experimentally infected Rattus norvegicus and analysis of the rat as potential reservoir for this ascarid

Toxocara cati is a common feline parasite transmitted by the ingestion of embryonated eggs, by the transmammary route or by predation of paratenic hosts harbouring third-stage larvae in their bodies. In the present study, the larval distribution of T. cati in tissues and organs of Rattus norvegicus experimentally infected with 300 embryonated eggs was analysed. Third-stage larvae were recovered from livers, lungs, kidneys, eyes, brains and carcasses of infected rats, following tissue digestion with HCl 0.5% for 24 h at 37°C. Some differences from the known larval distribution of Toxocara canisin the same rodent species were found.

Silver nanoparticle production by the fungus Fusarium oxysporum: nanoparticle characterisation and analysis of antifungal activity against pathogenic yeasts

The microbial synthesis of nanoparticles is a green chemistry approach that combines nanotechnology and microbial biotechnology. The aim of this study was to obtain silver nanoparticles (SNPs) using aqueous extract from the filamentous fungus Fusarium oxysporum as an alternative to chemical procedures and to evaluate its antifungal activity. SNPs production increased in a concentration-dependent way up to 1 mM silver nitrate until 30 days of reaction. Monodispersed and spherical SNPs were predominantly produced. After 60 days, it was possible to observe degenerated SNPs with in additional needle morphology. The SNPs showed a high antifungal activity against Candida and Cryptococcus , with minimum inhibitory concentration values ≤ 1.68 µg/mL for both genera. Morphological alterations of Cryptococcus neoformans treated with SNPs were observed such as disruption of the cell wall and cytoplasmic membrane and lost of the cytoplasm content. This work revealed that SNPs can be easily produced by F. oxysporum aqueous extracts and may be a feasible, low-cost, environmentally friendly method for generating stable and uniformly sized SNPs. Finally, we have demonstrated that these SNPs are active against pathogenic fungi, such as Candida and Cryptococcus .

Pharmacotherapy and analysis of gaseous mediators in hypertensive patients

OBJECTIVE To evaluate the effect of using antihypertensive classes of drugs of the calcium channel antagonists and inhibitors of angiotensin-converting enzyme in plasma concentrations of hydrogen sulfide and nitric oxide in patients with hypertension. METHODS Cross-sectional study with quantitative approach conducted with hypertensive patients in use of antihypertensive classes of drugs: angiotensin-converting enzyme inhibitors or calcium channel antagonists. RESULTS It was found that the concentration of plasma nitric oxide was significantly higher in hypertensive patients that were in use of angiotensin-converting enzyme inhibitors (p<0.03) and the hydrogen sulphide concentration was significantly higher in hypertensive plasma in use of calcium channel antagonists (p<0.002). CONCLUSION The findings suggest that these medications have as additional action mechanism the improvement of endothelial dysfunction by elevate plasma levels of vasodilatory substances.

Chlorophenols in tap water from wells and surface sources in Rio de Janeiro, Brazil: method validation and analysis

Two analytical methods were validated for determination of trichlorophenols, tetrachlorophenols and pentachlorophenol in drinking water. Limits of quantification were at least ten times lower than maximum permissible levels set by the Brazilian legislation, which are 200 ng mL-1 for 2,4,6-trichlorophenol and 9 ng mL-1 for pentachlorophenol. Chlorophenol levels were determined in tap water collected in the Municipality of Rio de Janeiro. 2,4,6-Trichlorophenol residues were detected in 36% of the samples, varying from 0.008 to 0.238 ng mL-1. All other analytes were below the limit of quantification. The validated methods showed to be suitable for application in routine quality control.

Identification of grain areas replaced by sugarcane and analysis of the relationship with family farming production in the state of Goiás

In Brazil, the State of Goiás is one of sugarcane expansion's frontiers to meet the growing demand for biofuels. The objective of this study was to identify the municipalities where there were replacement of annual crops (mainly grains) by sugarcane in the state of Goiás, as well as indicate correlations between the sugarcane expansion and the family farming production, in the period between 2005 and 2010. For this purpose, grains crop mask and sugarcane crop mask, obtained from satellite images, were intersected using geoprocessing techniques. It was also used IBGE data of sugarcane production and planted area, and data of family farming production linked with the National Food Acquisition Program (PAA), in relation to the number of cooperatives and family farmers. The crops masks and data tables of the National Food Acquisition Program were provided by National Food Supply Agency. There were 95 municipalities that had crops replacement, totaling 281,554 hectares of grains converted to sugarcane. We highlight the municipalities of Santa Isabel, Iaciara, Maurilândia, and Itapaci, where this change represented more than half of their agricultural areas. In relation to family farming, the sugarcane expansion in the state of Goiás has not affected their activities during the period studied.

Histochemical study of the oviducal gland and analysis of the sperm storage tubules of Mustelus schmitti Springer, 1939 (Chondrichthyes, Triakidae)

Abstract: The paired oviducal glands of immature and mature females of Mustelus schmitti were examined macro and microscopically. Findings indicate that these glands possessed the same zonation as in most chondrichthyans from anterior to posterior: club, papillary, baffle and terminal zones. The whole gland is composed by simple tubular glands that connect with transverse grooves all along the organ. The club zone presents a typical indian club shape with a simple columnar and ciliated epithelium including secretory cells PAS (+) and AB (+). The papillary zone is characterized by lamella forming small and long cones in numbers of three. The epithelium of this zone contains ciliated cells with apical nuclei and secretory cells with basal nuclei that stain AB (+)The baffle zone consists of apically flattened lamellae alternating with spinnerets which are small projections disposed by both sides of the plateau. This whole structure is present in number of 8 or 9 units. A simple columnar ciliated epithelium covers the plateau and spinnerets and no AB or PAS staining is observed. The epithelium of the terminal zone is PAS (-) and AB (+), and elongated tubules, that run adjacent to the baffle zone are the site where groups of spermatozoa are clearly observed in the lumen. The epithelium of the sperm storage tubules do not stain with any of the dyes tested. Sperm was also observed in the baffle zone, presumably in its way to the fecundation in the oviduct because it displays no aggregation pattern and was between the folds of the epithelium. By scanning electron microscopy sperm was observed in the club and baffle zones in a gland which belonged to a pregnant female.