A Promising Antiprion Trimethoxychalcone Binds to the Globular Domain of the Cellular Prion Protein and Changes Its Cellular Location.

The search for antiprion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein (PrPC) conversion into protease-resistant forms (protease-resistant PrP [PrPRes] or the scrapie form of PrP [PrPSc]) is a critical step in the development of TSEs and is thus one of the main targets in the screening for antiprion compounds. In this work, three trimethoxychalcones (compounds J1, J8, and J20) and one oxadiazole (compound Y17), previously identified in vitro to be potential antiprion compounds, were evaluated through different approaches in order to gain inferences about their mechanisms of action. None of them changed PrPC mRNA levels in N2a cells, as shown by reverse transcription-quantitative real-time PCR. Among them, J8 and Y17 were effective in real-time quaking-induced conversion reactions using rodent recombinant PrP (rPrP) from residues 23 to 231 (rPrP23-231) as the substrate and PrPSc seeds from hamster and human brain. However, when rPrP from residues 90 to 231 (rPrP90-231), which lacks the N-terminal domain, was used as the substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with the PrPC globular domain. J8 also reduced the fibrillation of mouse rPrP23-231 seeded with in vitro-produced fibrils. Furthermore, most of the compounds decreased the amount of PrPC on the N2a cell surface by trapping this protein in the endoplasmic reticulum. On the basis of these results, we hypothesize that J8, a nontoxic compound previously shown to be a promising antiprion agent, may act by different mechanisms, since its efficacy is attributable not only to PrP conversion inhibition but also to a reduction of the PrPC content on the cell surface.

Structure and diversity of fishes in a freshwater and coastal subtropical lagoon.

This study examined the fish communities of Peri Lagoon in southern Brazil to aid in the development of an effective management plan because the area is under threat from human activities. Sampling of fish fauna, ichthyoplankton and limnological data were compared between sites, differing by habitat type and characteristics such as depth, substratum composition and vegetation type. Results were significantly related to site, with the highest diversity and abundance recorded at shallow vegetated sites. A total of 14 fish species were recorded throughout the lagoon, with the most abundant being Hyphessobrycon luetkenii. Of the 14 species, half were sampled at their larval stage, suggesting a healthy and protected system. Significantly more larvae and eggs were collected during colder months (autumn to winter) and at sites closer to stream flow, possibly owing to increased food sources and habitat protection. This study highlights the importance of Peri Lagoon as a nursery ground for a wide range of fish species, providing essential information for incorporation into the future protection of fish stocks throughout Brazil.

Barriers to patient recruitment in a poststroke neurorehabilitation multicenter trial in Brazil.

There is a high demand for stroke rehabilitation in the Brazilian public health system, but most studies that have addressed rehabilitation for unilateral spatial neglect (USN) after stroke have been performed in high-income countries. Therefore, the aim of this study was to analyze USN patient recruitment in a multicenter noninvasive brain stimulation clinical trial performed in Brazil and to provide study design recommendations for future studies. We evaluated the reasons for exclusion of patients from a multicenter, randomized, double-blinded clinical trial of rehabilitation of USN patients after stroke. Clinical and demographic variables were compared between the included and excluded patients. A descriptive statistical analysis was performed. Only 173 of the 1953 potential neglect patients (8.8%) passed the initial screening. After screening evaluation, 87/173 patients (50.3%) were excluded for clinical reasons. Cognitive impairment led to the exclusion of 21/87 patients (24.1%). Low socioeconomic status led to the exclusion of 37/173 patients (21.4%). Difficulty obtaining transportation to access treatment was the most common reason for their exclusion (16/37 patients, 43.3%). The analyzed Brazilian institutions have potential for conducting studies of USN. The recruitment of stroke survivors with USN was restricted by the study design and limited financial support. A history of cognitive impairment, intracranial stenting or craniectomy, and lack of transportation were the most common barriers to participating in a multicenter noninvasive brain stimulation trial among patients with USN after stroke.

Barriers to patient recruitment in a poststroke neurorehabilitation multicenter trial in Brazil

There is a high demand for stroke rehabilitation in the Brazilian public health system, but most studies that have addressed rehabilitation for unilateral spatial neglect (USN) after stroke have been performed in high-income countries. Therefore, the aim of this study was to analyze USN patient recruitment in a multicenter noninvasive brain stimulation clinical trial performed in Brazil and to provide study design recommendations for future studies. We evaluated the reasons for exclusion of patients from a multicenter, randomized, double-blinded clinical trial of rehabilitation of USN patients after stroke. Clinical and demographic variables were compared between the included and excluded patients. A descriptive statistical analysis was performed. Only 173 of the 1953 potential neglect patients (8.8%) passed the initial screening. After screening evaluation, 87/173 patients (50.3%) were excluded for clinical reasons. Cognitive impairment led to the exclusion of 21/87 patients (24.1%). Low socioeconomic status led to the exclusion of 37/173 patients (21.4%). Difficulty obtaining transportation to access treatment was the most common reason for their exclusion (16/37 patients, 43.3%). The analyzed Brazilian institutions have potential for conducting studies of USN. The recruitment of stroke survivors with USN was restricted by the study design and limited financial support. A history of cognitive impairment, intracranial stenting or craniectomy, and lack of transportation were the most common barriers to participating in a multicenter noninvasive brain stimulation trial among patients with USN after stroke.

Clear-PEM: a dedicated PET camera for improved breast cancer detection.

Positron emission mammography (PEM) can offer a non-invasive method for the diagnosis of breast cancer. Metabolic images from PEM using 18F-fluoro-deoxy-glucose, contain unique information not available from conventional morphologic imaging techniques like X-ray radiography. In this work, the concept of Clear-PEM, the system presently developed in the frame of the Crystal Clear Collaboration at CERN, is described. Clear-PEM will be a dedicated scanner, offering better perspectives in terms of position resolution and detection sensitivity.

Iterative crystal efficiency calculation in fully 3-D PET.

The calculation of the intrinsic efficiency of individual crystals is one of the steps needed to obtain accurate images of the radioisotope distribution in positron emission tomography (PET). These efficiencies can be computed by comparing the number of coincidence counts obtained when the crystals are equally illuminated by the same source. However, because the number of coincidence counts acquired for one crystal also depends on the efficiency of the other crystals in coincidence, most methods of crystal efficiency calculation need to assume that the influence of the other crystals is negligible. If there are large crystal efficiency variations, this approximation may lead to systematic errors. We have recently implemented an iterative method for a single ring of detectors that does not rely on this assumption. In this paper, we describe a fully three-dimensional (3-D) iterative method that better exploits the sensitivity of the tomograph and allows reduced acquisition times or the use of narrow energy windows. We compare the performance of the iterative method (single-ring and extended to fully 3-D) with noniterative techniques for different acquisition times of a uniform cylinder. Two different energy windows were used to assess the performance of each method with different levels of variations of crystal efficiency. The results showed that the iterative methods are more accurate when large efficiency variations exist and that only the fully 3-D methods provided good efficiency estimates with very low duration scans. We, thus, conclude that iterative fully 3-D methods provide the best estimations and can be used in a larger range of situations than can the other methods tested.

Homocysteinaemia after methionine overload as a coronary artery disease risk factor: importance of age and homocysteine levels.

BACKGROUND: Homocysteinaemia is now accepted as an independent risk factor for coronary artery disease (CAD). Our goal was to study the influence of age plasma homocysteine level on the CAD risk attributable to homocysteinaemia. METHODS: We studied a group of 98 patients under 55 years of age who had suffered a myocardial infarction 3-12 months before the study. The patients were matched by sex and age with a group of 98 controls without vascular disease. We measured the plasma homocysteine levels 6h after a methionine overload of 0.1 g/kg body weight in patients and controls. Afterwards, the odds ratio for homocysteinaemia was determined by homocysteine level, and that for hyperhomocysteinaemia (homocysteine level > 34 mumol/l) by age group. RESULTS: After methionine loading, the homocysteine odds ratio varied from 0.47 (homocysteine level < 23 mumol/l) to 2.88 (homocysteine level > 34 mumol/l). In patients under the age of 46 the odds ratio for hyperhomocysteinaemia was 18.6. In patients between 46 and 55 years of age the odds ratio for hyperhomocysteinaemia was 1.2. CONCLUSIONS: Low homocysteine levels are protective against CAD, and the higher the homocysteine level the higher the coronary risk appears to be. This clearly means that heterozygosity for cystathionine beta synthase deficiency alone is not enough to explain the vascular risk associated with homocysteinaemia. Hyperhomocysteinemia was shown to be a significant risk factor only in patients under the age of 46 years old.

A hybrid scatter correction for 3D PET based on an estimation of the distribution of unscattered coincidences: implementation on the ECAT EXACT HR+.

We implemented a hybrid scatter-correction method for 3D PET that combines two scatter-correction methods in a complementary way. The implemented scheme uses a method based on the discrimination of the energy of events (the estimation of trues method (ETM)) and an auxiliary method (the single scatter simulation method (SSSI) or the convolution-subtraction method (CONV)) in an attempt to increase the accuracy of the correction over a wider range of acquisitions. The ETM takes into account the scatter from outside the field-of-view (FOV), which is not estimated with the auxiliary method. On the other hand, the auxiliary method accounts for events that have scattered with small angles, which have an energy that cannot be discriminated from that of unscattered events using the ETM. The ETM uses the data acquired in an upper energy window above the photopeak (550-650 keV) to obtain a noisy estimate of the unscattered events in the standard window (350-650 keV). Our implementation uses the auxiliary method to correct the residual scatter in the upper window. After appropriate scaling, the upper window data are subtracted from the total coincidences acquired in the standard window, resulting in the final scatter estimate, after smoothing. In this work we compare the hybrid method with the corrections used by default in the 2D and 3D modes of the ECAT EXACT HR+ using phantom measurements. Generally, the contrast was better with the hybrid method, although the relative errors of quantification were similar. We conclude that hybrid techniques such as the one implemented in this work can provide an accurate, general-purpose and practical way to correct the scatter in 3D PET, taking into account the scatter from outside the FOV.

A comparison of normalization effects on three whole-body cylindrical 3D PET systems.

Normalization coefficients in three-dimensional positron emission tomography (3D PET) are affected by parameters such as camera geometry and the design and arrangement of the block detectors. In this work, normalization components for three whole-body 3D-capable tomographs (the GE Advance, the Siemens/CTI962/HR+ and the Siemens/CTI951R) are compared by means of a series of scans using uniform cylindrical and rotating line sources. Where applicable, the manufacturers' normalization methods are validated, and it is shown that these methods can be improved upon by using previously published normalization protocols. Those architectural differences between the three tomographs that affect normalization are discussed with a view to drawing more general conclusions about the effect of machine architecture on normalization. The data presented suggest that uniformity of system response becomes easier to achieve as the uniformity of crystal response within the detector block is improved.

Effects of synthetic salmon calcitonin therapy in children with osteogenesis imperfecta.

A total of four children with osteogenesis imperfecta, three with type I and one with type III forms of the disease, were treated with synthetic salmon calcitonin for 18-24 months. The annual fracture rate was decreased during calcitonin therapy compared with the period preceding it. No patient presented a marked inflexion in linear growth and a transient improvement was even noticed in two cases.

[Homocysteinemia as a risk factor for early myocardial infarct--a case-control study]. / A homocisteinemia como factor de risco de enfarte do miocárdio precoce--estudo de casos e controlos.

PURPOSE: To investigate if hyper-homocysteinemia represents an independent risk factor of early coronary disease. METHODS: We studied a group of patients under 45 years old, that suffered a myocardial infarction from 3 months and 1 year before the study. The patients were matched with a group of normal controls of a check-up program, in terms of age, sex, smoking habits, presence of hypertension, obesity, (Quetelet Index), presence of diabetes, basal glycemia, total cholesterol, LDL and HDL cholesterol. Later we measured to patients (Pts) and controls (Cts) the plasmatic basal homocysteinemia (B HC) and 6 hours after a methionine overload of 0.1 g/kg body weight (L HC). RESULTS: [table: see text] CONCLUSIONS: In this study hyper-homocysteinemia appears as an independent risk factor of early coronary disease. The measurement of homocysteinemia after the methionine loading test was more discriminative than the basal measurement.

[The prevention of hereditary erythrocytic diseases]. / Profilaxia das doenças hereditárias do eritrócito.

The authors report the importance of not only all over the world but also in Portugal and, particularly, in Dona Estefânia Hospital. Some considerations are made about the usefulness of molecular biology methods in prenatal diagnosis. With this tool can also be do the origins and migrations of populations, which contributes to the knowledge of aspects of our history. Finally, they present consensual attitudes which should adopt regarding these chronic diseases, with special emphasis to the prophylactic aspects.

[Homocysteinemia as a risk factor in early cerebrovascular disease]. / A homocisteinemia como factor de risco de doença cerebrovascular precoce.

PURPOSE: To determine whether hyperhomocysteinemia represents a risk factor of early thrombotic cerebrovascular disease. METHOD: In a group of patients under 55 years of age (n = 33, 19 males) which had suffered a stroke from 3 months to 1 year before the study, defined by clinical criteria and presence of cerebral infarction confirmed by tomography, without history or predisposition to embolic disease. The patients were matched with a group of normal controls of checkup program, in terms of age, and sex. Patients and controls with a history of alcoholism, clinical or laboratory signs of renal or hepatic insufficiency or with a history of recent ingestion of Group B vitamins were excluded since these conditions would influence homocysteinemia levels. We measured the plasmatic basal homocysteinemia of patients and controls (HC) and 6 hours later a methionine overload of 0.1 g/Kg body weight (LOAD HC). RESULTS: Patients; Controls; Signific.; Age 46.0 +/- 7.7; 45.9 +/- 7.8; NS; Basal HC. 10.1 +/- 3.4; 8.5 +/- 1.7; p < 0.05; Load HC 28.0 +/- 7.6; 22.7 +/- 5.5; p < 0.01. CONCLUSION: In this study hyperhomocysteinemia appears as a risk factor for thrombotic cerebrovascular disease before the age of 55;-The measurement of homocysteinemia after the methionine loading test was more discriminative than the basal measurement;-A larger number of patients and controls will be necessary to establish the relative importance of homocysteinemia among other vascular risk factors in cerebrovascular disease.

[Homocysteinemia as a risk factor for cerebrovascular disorders. The role of age and homocysteine levels]. / A homocisteinemia como factor de risco de doença vascular cerebral. A importância da idade e dos nìveis de homocisteinemia.

PURPOSE: To evaluate importance of homocysteinemia as risk factor of thrombotic cerebrovascular disease, in terms of age and homocysteinemia levels. METHODS: A group of patients under 55 years old (n = 35, 21 males) that had suffered a stroke 3 months to 1 year before the study, defined by clinical criteria and the presence of cerebral infarction confirmed by tomography, without history or predisponents to embolic disease. The patients were matched with a group of controls without vascular pathology of a check-up program, in terms of age and sex. Patients and controls with history of alcoholism, signs or laboratory of renal or hepatic insufficiency or with history of recent ingestion of vitamins of the group B were excluded since these conditions could influence homocysteinemia levels. We measured to patients and controls the plasmatic basal homocysteinemia and homocysteinemia 6 hours after methionine overload of 0.1 g/Kg body weigh. We estimated case-control odds ratio of hyperhomocysteinemia globally and by age groups, and odd ratio of different levels of homocysteinemia. RESULTS AND CONCLUSIONS: Hyperhomocysteinemia case-control global odds ratio was 5.7, being higher in younger patients (8.8 below and 3.5 after the age of 45 years). Homocysteinemia as a risk factor of cerebrovascular disease presented as a continuous effect: low homocysteinemia was protective, and the higher the homocysteinemia, the higher the cerebrovascular risk proved to be. In these circumstances, heterozygozyty of cysthationine beta synthase deficiency, refered as the more important cause of hyperhomocysteinemia, cannot account for most of the cases of hyperhomocysteinemia.

[A case of Schwartz syndrome (author's transl)]. / Síndrome de Schwartz. A propósito dum caso clínico.

Authors described a case of Schwartz syndrome in a two year old child, whose rare and typical clinical picture was characterized by blepharophimosis, myopia, typical facial signs, myotonia, muscular atrophy and articular motility restriction, which microscopical analysis study was requested.