CPAP increases physical activity in obstructive sleep apnea with cardiovascular disease.

STUDY OBJECTIVES: Uncertainty exists over whether continuous positive airway pressure (CPAP) treatment improves moderate to vigorous physical activity levels in those with obstructive sleep apnea. We aimed to determine effects of CPAP on moderate to vigorous physical activity among participants with co-occurring cardiovascular disease and obstructive sleep apnea. METHODS: The Sleep Apnea cardioVascular Endpoints (SAVE) trial recruited participants with confirmed cardiovascular disease history and obstructive sleep apnea, 45-75 years old. The 2,687 participants (1,346 randomized to CPAP plus usual care and 1,341 to usual care alone) were followed up for a mean of 3.7 years. Self-reported physical activity was recorded at baseline, 6, 24, and 48 months using the Godin-Shepard Leisure Time Exercise Questionnaire (LTEQ). We also determined effects on any limitation of physical activity reported on the physical functioning subscale of the 36-item short form questionnaire (SF-36) and proportions of participants reaching guideline recommended physical activity levels. RESULTS: Among 2,601 participants with available data, those in the CPAP group reported significantly more physical activity compared to the usual care group, with approximately 20% higher reported moderate activities on the LTEQ during follow-up (adjusted mean 95% confidence interval) scores: 8.7, 7.5-9.9 vs 7.3, 6.1-8.5; P = .003). Those in the CPAP group also reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score 1.66, 95% confidence interval 0.87-2.45; P < 0.001), and more reported sufficient levels of physical activity to meet recommendations. CONCLUSIONS: CPAP has positive effects on improving physical activity levels, consistent with long-term health benefits. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease (SAVE); URL: https://clinicaltrials.gov/ct2/show/NCT00738179; Identifier: NCT00738179; and Registry: Australian New Zealand Clinical Trials Registry; Name: Sleep Apnea cardioVascular Endpoints study-An investigation of continuous positive airway pressure for the treatment of obstructive sleep apnea to prevent cardiovascular disease; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83062&isReview=true; Identifier: ACTRN12608000409370.

Síndrome de Herlyn-Werner-Wünderlich / Herlyn-Werner-Wünderlich syndrome

El síndrome de Herlyn-Werner-Wünderlich (HWW) es una anomalía congénita del tracto urogenital, causada por un fallo de la fusión de los conductos müllerianos. Presentamos el caso de una paciente de 32 años, en estudio de infertilidad. La resonancia magnética nos conduce al diagnóstico definitivo con los siguientes hallazgos: útero didelfo con hemivagina obstruida, hematocolpos y agenesia renal izquierda. Se resuelve con resección del tabique vaginal y drenaje del hematocolpos secundario

Herlyn-Werner-Wünderlich syndrome is a very rare congenital anomaly of the urogenital tract, involving defective fusion of müllerian ducts. We report the case of a 32-year-old woman with infertility. Magnetic resonance imaging findings revealed a didelphic uterus with obstructed hemivagina, hematocolpos and ipsilateral renal agenesis. The case was successfully resolved through resection of the vaginal septum and drainage of the hematocolpos

Antibody-mediated phagocytosis of the amyloid beta-peptide in microglia is differentially modulated by C1q.

Microglial ingestion of the amyloid beta-peptide (Abeta) has been viewed as a therapeutic target in Alzheimer's disease, in that approaches that enhance clearance of Abeta relative to its production are predicted to result in decreased senile plaque formation, a proposed contributor to neuropathology. In vitro, scavenger receptors mediate ingestion of fibrillar Abeta (fAbeta) by microglia. However, the finding that cerebral amyloid deposition in a transgenic mouse model of Alzheimer's disease was diminished by inoculation with synthetic Abeta has suggested a possible therapeutic role for anti-Abeta Ab-mediated phagocytosis. Microglia also express C1qR(P), a receptor for complement protein C1q, ligation of which in vitro enhances phagocytosis of immune complexes formed with IgG levels below that required for optimal FcR-mediated phagocytosis. The data presented here demonstrate FcR-dependent ingestion of Abeta-anti-Abeta complexes (IgG-fAbeta) by microglia that is a function of the amount of Ab used to form immune complexes. In addition, C1q incorporated into IgG-fAbeta enhanced microglial uptake of these complexes when they contained suboptimal levels of anti-Abeta Ab. Mannose binding lectin and lung surfactant protein A, other ligands of C1qR(P), also enhanced ingestion of suboptimally opsonized IgG-fAbeta, whereas control proteins did not. Our data suggest that C1qR(P)-mediated events may promote efficient ingestion of Abeta at low Ab titers, and this may be beneficial in paradigms that seek to clear amyloid via FcR-mediated mechanisms by minimizing the potential for destructive Ab-induced complement-mediated processes.

Improved differential screening approach to analyse transcriptional variations in organized cDNA libraries.

A cDNA library was generated from rat brain tissues and organized into 1536-well plates, using a fluorescence activated cell sorter (FACS), acting as a single cell deposition system. The organized library containing 10,000 clones, with 60% full-length cDNA inserts, allowed the generation of multiple identical membrane replicas. Each replica was hybridized with a complex probe obtained from a particular brain tissue or a given cultured cell. The signal intensity for each of the clones present on the membrane, quantified with a standard image-analysis software, is proportional both to the abundance of the corresponding mRNA in the probe and to the amount of plasmid template on the membrane. The latter value was thus used to normalize the signals produced with complex probes, to optimize the comparison of mRNA expression levels for the different systems under study. The construction of high-quality cDNA libraries, the generation of identical membrane replicas and comparable probes, and the utilization of an image-analysis software package, coupled with the normalization of the spot intensity by assaying plasmid quantity, significantly improves the differential screening approach. Altogether, these technical improvements open the possibility to compare a great number of different probes and, in consequence, to accumulate biological information for each clone present in an organized cDNA library. The functional information obtained should complement data from DNA sequencing projects.

Identification of proteins of the yeast protein map using genetically manipulated strains and peptide-mass fingerprinting.

In this study we used genetically manipulated strains in order to identify polypeptide spots of the protein map of Saccharomyces cerevisiae. Thirty-two novel polypeptide spots were identified using this strategy. They corresponded to the product of 23 different genes. We also explored the possibilities of using peptide-mass fingerprinting for the identification of proteins separated on our gels. According to this strategy, proteins contained in spots are digested with trypsin and the masses of generated peptides are determined by matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). The peptide masses are then used to search a yeast protein database for proteins that match the experimental data. Application of this strategy to previously identified polypeptide spots gave evidence of the feasibility of this approach. We also report predictions on the identities of nine unknown spots using MALDI-MS.

N-acetyl-heparosan lyase of Escherichia coli K5: gene cloning and expression.

The structure of the capsular polysaccharide of Escherichia coli K5 is identical to that of N-acetyl-heparosan, a nonsulfated precursor of heparin, which makes this E. coli antigen an attractive starting point for the chemical synthesis of analogs of low-molecular-weight heparin. This polysaccharide is synthesized as a high-molecular-weight molecule that can be depolymerized by an enzyme displaying endo-beta-eliminase activity. The eliminase-encoding gene, designated elmA, has been cloned from E. coli K5 by expression in E. coli K-12. The K-12 genome is devoid of the elmA sequence. The elmA gene product is 820 amino acids long. Active recombinant eliminase is produced by K-12 cells in both cell-bound and secreted forms. Deletion analyses have shown that the C terminus and the N terminus are required for activity and secretion, respectively.

Self-organized neural maps of human protein sequences.

We have recently described a method based on artificial neural networks to cluster protein sequences into families. The network was trained with Kohonen's unsupervised learning algorithm using, as inputs, the matrix patterns derived from the dipeptide composition of the proteins. We present here a large-scale application of that method to classify the 1,758 human protein sequences stored in the SwissProt database (release 19.0), whose lengths are greater than 50 amino acids. In the final 2-dimensional topologically ordered map of 15 x 15 neurons, proteins belonging to known families were associated with the same neuron or with neighboring ones. Also, as an attempt to reduce the time-consuming learning procedure, we compared 2 learning protocols: one of 500 epochs (100 SUN CPU-hours [CPU-h]), and another one of 30 epochs (6.7 CPU-h). A further reduction of learning-computing time, by a factor of about 3.3, with similar protein clustering results, was achieved using a matrix of 11 x 11 components to represent the sequences. Although network training is time consuming, the classification of a new protein in the final ordered map is very fast (14.6 CPU-seconds). We also show a comparison between the artificial neural network approach and conventional methods of biosequence analysis.

A hybrid method to cluster protein sequences based on statistics and artificial neural networks.

We have recently proposed a method, based on artificial neural networks (ANNs) to cluster protein sequences into families according to their degree of sequence similarity. The network was trained with an unsupervised learning algorithm, using, as inputs, matrix patterns derived from the bipeptide composition of the protein sequences. We describe here some further improvements to that approach. First, we propose a statistical method to cluster a set of bipeptidic matrices into families. It consists of three stages: (i) principal component analysis, (ii) determination of the optimal number M of clusters and (iii) final classification of the bipeptidic matrices into M clusters. Using a set of 444 protein sequences, we show that the classification given by the statistical method is in agreement with biological knowledge. We also show that the resulting classification is very similar to the one previously obtained with the ANN approach. Finally, we propose a new hybrid method of the statistical and ANN approaches, in which the results of the statistical method are used to choose the number of neurons and inputs of the network. We show that a network built in this way, and fed with a few principal components of the set of bipeptidic matrices as input signals, can be trained in an extremely short computing time. The resulting topological maps do not essentially differ from the ones obtained with the initial ANN approach.

Protein classification using neural networks.

We have recently described a method based on Artificial Neural Networks to cluster protein sequences into families. The network was trained with Kohonen's unsupervised-learning algorithm using, as inputs, matrix patterns derived from the bipeptide composition of the proteins. We show here the application of that method to classify 1758 protein sequences, using as inputs a limited number of principal components of the bipeptidic matrices. As a result of training, the network self-organized the activation of its neurons into a topologically ordered map, in which proteins belonging to a known family (immunoglobulins, actins, interferons, myosins, HLA histocompatibility antigens, hemoglobins, etc.) were usually associated with the same neuron or with neighboring ones. Once the topological map has been obtained, the classification of new sequences is very fast.

Commentary: caring for the indigent mentally ill--new strategies and old problems.

Christianson and his colleagues examine how Medicaid beneficiaries receive mental health services in HMOs by analyzing two important aspects of service delivery: the use of community-based treatment programs by Medicaid beneficiaries enrolled in health maintenance organizations (HMOs) and the reimbursement levels paid to these programs by HMOs. The hypotheses studied are complex issues that concern mental-health advocates and providers. Traditional community-based mental health services have always struggled to maintain their presence in the health care field, having to contend with changing funding priorities and more serious and multiple problems presented by their patients. For prepaid plans to work effectively for the indigent mentally ill, the complex issues have to be made clear and acknowledged as meaningful variables.

Pattern of the mantle adenylate cyclase activity during the reproductive cycle of the female Mytilus galloprovincialis.

In the mantle of the female sea mussel Mytilus galloprovincialis seasonal variations in the adenylate cyclase activity correlate with gonadal development. Two peaks of adenylate cyclase activity were found in spring and autumn, both periods of gonadal development. The lowest enzymatic activities were in summer, a gonadal resting period.

Clustering proteins into families using artificial neural networks.

An artificial neural network was used to cluster proteins into families. The network, composed of 7 x 7 neurons, was trained with the Kohonen unsupervised learning algorithm using, as inputs, matrix patterns derived from the bipeptide composition of 447 proteins, belonging to 13 different families. As a result of the training, and without any a priori indication of the number or composition of the expected families, the network self-organized the activation of its neurons into topologically ordered maps in which almost all the proteins (96.7%) were correctly clustered into the corresponding families. In a second computational experiment, a similar network was trained with one family of the previous learning set (76 cytochrome c sequences). The new neural map clustered these proteins into 25 different neurons (five in the first experiment), wherein phylogenetically related sequences were positioned close to each other. This result shows that the network can adapt the clustering resolution to the complexity of the learning set, a useful feature when working with an unknown number of clusters. Although the learning stage is time consuming, once the topological map is obtained, the classification of new proteins is very fast. Altogether, our results suggest that this novel approach may be a useful tool to organize the search for homologies in large macromolecular databases.

[Trigeminal neuralgia as the first manifestation in Arnold-Chiari deformity]. / Neuralgia del trigémino como primera manifestación en la malformación de Arnold-Chiari.

The association of trigeminal neuralgia and Arnold-Chiari malformation (ACM) is uncommon. We report two cases of trigeminal neuralgia as the first and single clinical feature of an ACM. The pathophysiological relationship between ACM and trigeminal malformation is discussed. Also, the need for magnetic resonance imaging in trigeminal neuralgia is emphasized, as this is a noninvasive study which may provide valuable etiological information and prevent the progression of the disease.

Topological maps of protein sequences.

A new method based on neural networks to cluster proteins into families is described. The network is trained with the Kohonen unsupervised learning algorithm, using matrix pattern representations of the protein sequences as inputs. The components (x, y) of these 20 x 20 matrix patterns are the normalized frequencies of all pairs xy of amino acids in each sequence. We investigate the influence of different learning parameters in the final topological maps obtained with a learning set of ten proteins belonging to three established families. In all cases, except in those where the synaptic vectors remains nearly unchanged during learning, the ten proteins are correctly classified into the expected families. The classification by the trained network of mutated or incomplete sequences of the learned proteins is also analysed. The neural network gives a correct classification for a sequence mutated in 21.5% +/- 7% of its amino acids and for fragments representing 7.5% +/- 3% of the original sequence. Similar results were obtained with a learning set of 32 proteins belonging to 15 families. These results show that a neural network can be trained following the Kohonen algorithm to obtain topological maps of protein sequences, where related proteins are finally associated to the same winner neuron or to neighboring ones, and that the trained network can be applied to rapidly classify new sequences. This approach opens new possibilities to find rapid and efficient algorithms to organize and search for homologies in the whole protein database.

Mild insomnia induced by environmental perturbations in the rat: a study of this new model and of its possible applications in pharmacological research.

This paper describes an experimental model for testing new products in a situation where sleep is impaired by a nonpharmacological procedure. This model consists in studying the effect of hypnogenic substances on sleep perturbations which take place when chronically implanted rats are moved to a novel individual cage, connected for the first time to their recording cable and dosed intragastrically with test products, vehicle or placebo. Continuous polygraphic recordings were taken throughout the daily treatment period (15 days) and scored for the presence of slow wave sleep (SWS), and rapid eye movement sleep (REM). The hourly vigilance stages were also computed to determine the parameters of their nycthemeral rhythms. In vehicle-treated rats, a decrease in SWS and REM values and a delay of SWS and REM phases of nycthemeral rhythms occurred on the first day as compared with the end of the recording period. Phenobarbital (5 mg/kg p.o.), mecloqualone (5 mg/kg p.o.) and a new benzodiazepine CM 7302 (7 mg/kg p.o.) led to an immediate or fast recovery, whereas no improvement was observed with placebo and with clorazepate dipotassium (9 mg/kg p.o.). This model can be considered as an attractive model for studying mild insomnia because it allows "true" hypnogenic drugs to be selected in a minimum amount of time.

Selective percutaneous thermocoagulation rhizotomy in essential glossopharyngeal neuralgia.

Percutaneous radiofrequency (rf) thermocoagulation of the inferior petrous ganglion of Andersch at the jugular foramen has been used to treat three patients with essential glossopharyngeal neuralgia. Two of these patients needed a second rf thermocoagulation, one within 1 week due to an incomplete result, and the other 8 months after the first procedure for recurrence of some neuralgic pain. Thus, a total of five rf thermocoagulations of the ganglion of Andersch have been performed. The patients are now pain-free and without significant side-effects. Deglutition and phonation have remained intact after each rf thermocoagulation. Glossopharyngeal selectivity was obtained by avoiding the risk of injury to the other nerves at the jugular foramen. The surgical technique involves precise x-ray control and constant monitoring of the blood pressure and electrocardiogram findings. Electrode misplacement of any spreading of current to the vagus nerve will be readily detected by bradycardia and hypotension during the physiological testing before a definite rf lesion takes place. This operative technique is described.