Prognostic value of changes in resting-state functional connectivity patterns in cognitive recovery after stroke: A 3T fMRI pilot study.

Resting-state studies conducted with stroke patients are scarce. First objective was to explore whether patients with good cognitive recovery showed differences in resting-state functional patterns of brain activity when compared to patients with poor cognitive recovery. Second objective was to determine whether such patterns were correlated with cognitive performance. Third objective was to assess the existence of prognostic factors for cognitive recovery. Eighteen right-handed stroke patients and eighteen healthy controls were included in the study. Stroke patients were divided into two groups according to their cognitive improvement observed at three months after stroke. Probabilistic independent component analysis was used to identify resting-state brain activity patterns. The analysis identified six networks: frontal, fronto-temporal, default mode network, secondary visual, parietal, and basal ganglia. Stroke patients showed significant decrease in brain activity in parietal and basal ganglia networks and a widespread increase in brain activity in the remaining ones when compared with healthy controls. When analyzed separately, patients with poor cognitive recovery (n=10) showed the same pattern as the whole stroke patient group, while patients with good cognitive recovery (n=8) showed increased activity only in the default mode network and fronto-temporal network, and decreased activity in the basal ganglia. We observe negative correlations between basal ganglia network activity and performance in Semantic Fluency test and Part A of the Trail Making Test for patients with poor cognitive recovery. A reverse pattern was observed between frontal network activity and the above mentioned tests for the same group. .

Genomic comparison of two strains of Mycobacterium avium subsp. paratuberculosis with contrasting pathogenic phenotype.

In a previous study, we evaluated the degree of virulence of Mycobacterium avium subsp. paratuberculosis (Map) strains isolated from cattle in Argentina in a murine model. This assay allowed us to differentiate between high-virulent MapARG1347 and low-virulent MapARG1543 strains. To corroborate whether the differences in virulence could be attributed to genetic differences between the strains, we performed Whole Genome Sequencing and compared the genomes and gene content between them and determined the differences related to the reference strain MapK10. We found 233 SNPs/INDELS in one or both strains relative to Map K10. The two strains share most of the variations, but we found 15 mutations present in only one of the strains. Considering NS-SNP/INDELS that produced a severe effect in the coding sequence, we focus the analysis on four predicted proteins, putatively related to virulence. Survival of MapARG1347 strain in bMDM was higher than MapARG1543 and was more resistant to acidic pH and H2O2 stresses than MapK10. The genomic differences between the two strains found in genes MAP1203 (a putative peptidoglycan hydrolase), MAP0403 (a putative serine protease) MAP1003c (a member of the PE-PPE family) and MAP4152 (a putative mycofactocin binding protein) could contribute to explain the contrasting phenotype previously observed in mice models.

Identifying associations between amino acid changes and meta information in alignments.

MOTIVATION: We present a method that identifies associations between amino acid changes in potentially significant sites in an alignment (taking into account several amino acid properties) with phenotypic data, through the phylogenetic mixed model. The latter accounts for the dependency of the observations (organisms). It is known from previous studies that the pathogenic aspect of many organisms may be associated with a single or just few changes in amino acids, which have a strong structural and/or functional impact on the protein. Discovering these sites is a big step toward understanding pathogenicity. Our method is able to discover such sites in proteins responsible for the pathogenic character of a group of bacteria. RESULTS: We use our method to predict potentially significant sites in the RpoS protein from a set of 209 bacteria. Several sites with significant differences in biological relevant regions were found. AVAILABILITY: Our tool is publicly available on the CRAN network at http://cran.r-project.org/ CONTACT: naya@pasteur.edu.uy SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[From a pathogen's genome to an effective vaccine: the four-component meningococcal serogroup B vaccine]. / Del genoma de un patógeno a una vacuna efectiva: la vacuna de cuatro componentes frente a los meningococos del serogrupo B.

Invasive meningococcal disease (IMD), caused by the bacterium Neisseria meningitidis, entails significant mortality and morbidity. Disease incidence is highest in infants <1 year and young children globally. In Europe, N. meningitidis serogroup B is responsible for over 50% of overall IMD cases, whereas the majority of IMD cases in Latin America is caused either by serogroup B or C. The development of an effective vaccine against serogroup B has challenged the researchers for over half a century. Serogroup B capsular polysaccharide was an inappropriate vaccine antigen, and the success of outer membrane vesicle (OMV) vaccines was restricted to homologous bacterial strains. Reverse vaccinology led to the development of a 4-component meningococcal vaccine including three novel antigens, and OMVs (4CMenB). Each vaccine component has a different target. 4CMenB has been authorised based on its immunogenicity and safety data because the low disease incidence precluded formal clinical efficacy studies. Human serum bactericidal antibody (hSBA) assay tests functional antibodies in the serum of vaccinated individuals (i.e. the vaccine immunogenicity), and is the accepted correlate of protection. Vaccine strain coverage has been assessed both through hSBA assays and a more conservative method named Meningococcal Antigen Typing System (MATS). Effectiveness data of 4CMenB have been collected in the field since 2013. The vaccine proved effective in outbreak control in North America, and recent data from the introduction of the vaccine in the United Kingdom infant national immunisation programme reveal a vaccine effectiveness of 82.9% for the first two doses, with an acceptable safety profile.

[Analysis of the natural radioactivity due to the radon gas in the underground of Rome]. / Analisi della radioattività naturale dovuta al gas radon presente negli ambienti sotterranei della metropolitana di Roma.

BACKGROUND: Radon is a decay product of 238Uranium which is classified by WHO/IARC as group 1 carcinogen, given its causal relationship with lung neoplasia. An annual concentration of this gas higher than 500 Bq/m3 in workplace is considered potentially dangerous by the italian legislation. No data are currently available on radon level in underground tunnels, which are a potentially important source of exposure both for workers and travellers. MATERIAL AND METHODS: Measurements have been performed in a station and within the trains. Two months integrated measures, and 5 days continuous (hourly) assessments have been performed. Integrated measurements have been performed by means of 12 passive dosimeters, containing a detector made of CR39 (polymeric type), whereas active scintillation-type dosimeters have been employed for continuous assessments. RESULTS: Two months integrated measures: radon level in the station was 665 +/- 71 Bq/m3, whereas values within the trains ranged between 96 and 117 Bq/m3. Continuous measurements: Mean radon level during work activities was 783 +/- 536 Bq/m3 and thereafter it rose to 850 +/- 131 Bq/m3 CONCLUSIONS: Radon nelle levels in underground tunnels may exceed attention levels, whereas within trains they remain well below these levels. Further studies focused to assess the risk of underground employers are needed.

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Energy aspects of the synchronization of model neurons.

We have deduced an energy function for a Hindmarsh-Rose model neuron and we have used it to evaluate the energy consumption of the neuron during its signaling activity. We investigate the balance of energy in the synchronization of two bidirectional linearly coupled neurons at different values of the coupling strength. We show that when two neurons are coupled there is a specific cost associated to the cooperative behavior. We find that the energy consumption of the neurons is incoherent until very near the threshold of identical synchronization, which suggests that cooperative behaviors without complete synchrony could be energetically more advantageous than those with complete synchrony.

Platelet activation in patients with colorectal cancer.

Aspirin may reduce the risk of colorectal neoplasia at doses similar to those recommended for the prevention of cardiovascular disease. Thus, we aimed to address whether enhanced platelet activation, as assessed by the measurement of the urinary excretion of 11-dehydro-TXB(2) (a major enzymatic metabolite of TXB(2)), occurs in patients with colorectal cancer. In 10 patients with colorectal cancer, the urinary excretion of 11-dehydro-TXB(2) was significantly higher than in 10 controls, matched for sex, age and cardiovascular risk factors [1001(205-5571) versus 409(113-984) pg/mg creatinine, respectively, median (range), P<0.05]. The administration of aspirin 50 mg daily for 5 consecutive days to colorectal cancer patients caused a cumulative inhibition of platelet cyclooxygenase (COX)-1 activity either ex vivo, as assessed by the measurement of serum TXB(2) levels, or in vivo, as assessed by urinary 11-dehydro-TXB(2) excretion. In conclusion, enhanced platelet activation occurs in colorectal cancer patients. Permanent inactivation of platelet COX-1 by low-dose aspirin might restore anti-tumor reactivity.

Minimization of the energy flow in the synchronization of nonidentical chaotic systems.

We argue that maintaining a synchronized regime between different chaotic systems requires a net flow of energy between the guided system and an external energy source. This energy flow can be spontaneously reduced if the systems are flexible enough as to structurally approach each other through an adequate adaptive change in their parameter values. We infer that this reduction of energy can play a role in the synchronization of bursting neurons and other natural oscillators.

[Abusive head trauma: report of a case]. / Traumatismo craneal no accidental: a propósito de un caso.

The abusive head trauma is a form of child abuse. The most frequent injuries are intracranial lesions, such as subdural hematoma, as well as retinal hemorrhages, usually without other external injuries. Due to its complexity, this problem requires a multidisciplinary medical team, where the role of the radiologist is important, since there are multiple diagnostic methods that are complementary in order to arrive at the correct diagnosis.

A model combining cell physiology and population genetics to explain Escherichia coli laboratory evolution.

BACKGROUND: Laboratory experiments under controlled conditions during thousands of generations are useful tools to assess the processes underlying bacterial evolution. As a result of these experiments, the way in which the traits change in time is obtained. Under these conditions, the bacteria E. coli shows a parallel increase in cell volume and fitness. RESULTS: To explain this pattern it is required to consider organismic and population contributions. For this purpose we incorporate relevant information concerning bacterial structure, composition and transformations in a minimal modular model. In the short time scale, the model reproduces the physiological responses of the traits to changes in nutrient concentration. The decay of unused catabolic functions, found experimentally, is introduced in the model using simple population genetics. The resulting curves representing the evolution of volume and fitness in time are in good agreement with those obtained experimentally. CONCLUSIONS: This study draws attention on physiology when studying evolution. Moreover, minimal modular models appear to be an adequate strategy to unite these barely related disciplines of biology.

A family with the Saethre-Chotzen syndrome.

Acrocephalosyndactyly (ACS) is an inherited syndrome of premature synostosis of the cranial sutures and abnormalities in the distal segments of the limbs. Several forms of ACS have been described. ACS type III (or Saethre-Chotzen syndrome) is characterized by microcephaly, skull asymmetry, mild syndactyly, and facial abnormalities. We describe an Italian family with ACS III in which two sibs are clearly affected; the mother and the maternal grandmother show some features of the syndrome.

Tumor necrosis factor concentrations in hemolytic uremic syndrome patients and children with bloody diarrhea in Argentina.

Hemolytic uremic syndrome (HUS) is thought to be a vascular endothelial injury disease. The mechanism of injury is unknown although verocytotoxins (Shiga-like toxins (SLTs)) are known to be associated with it. Recent evidence suggests that in vitro treatment of some endothelial cells with tumor necrosis factor alpha (TNF-alpha) dramatically increases their susceptibility to SLTs. We studied 25 children with HUS, 63 children with SLT-positive bloody diarrhea, 62 children with bloody diarrhea not associated with SLTs and 39 children admitted for elective surgery, included as an age- and season-matched control group. The TNF-alpha concentrations were found to be significantly elevated in children with HUS (range, 1 to 95 pg/ml; geometric mean, 32.2 pg/ml) compared with the healthy controls (range, 0 to 53 pg/ml; mean, 12.5 pg/ml; P < 0.001). Because it is hypothesized that TNF-alpha elevation might precede development of HUS, we also studied children with blood diarrhea. The TNF-alpha serum concentrations were significantly higher during the first 10 days after onset of bloody diarrhea than after the first 10 days (P < 0.02). Such elevation could be associated with vascular endothelial glycolipid receptor up-regulation and increased susceptibility to the effects of SLTs.

Dissection of atrial septum after mitral valve replacement.

We report a patient who presented with paraprosthetic leak complicated by dissection of the interatrial septum after mitral valve replacement. A review of the literature provides confirmation that only 3 cases have been previously reported of this potential, albeit extremely rare, complication of prosthetic mitral valve replacement. Prosthesis oversizing and improper mitral annular handling appeared to be the predisposing factors of this complication.

Immunoscintigraphy with 131I or 111In labelled OC 125 F(ab')2 fragments in patients with ovarian carcinoma.

To evaluate the clinical usefulness of immunoscintigraphy with OC 125 in ovarian carcinoma, we studied 25 patients suspected of having ovarian carcinoma or in follow-up after surgery. Fourteen patients were studied with 131I-OC 125 F(ab')2 and 11 with 111In-OC 125 F(ab')2. No differences were observed with the use of either radionuclide. Global diagnostic indexes obtained were S = 100%, Sp = 44,5% and A = 81%. The low specificity obtained was remarkable: 5 false positive results in two uterine myomas, one abscess, one follicular cyst and one granulation tissue scar. On the other hand, all lesions of ovarian carcinoma were detected. Analysis of the evolution of tumor/background (T/B) uptake ratios from the first to the second day of exploration revealed a tendency for the ratio to diminish significantly (greater than 15%) in false positive cases with the exception of the abscess while this did not happen in true positive cases, with the exception of a regional recurrence. Analysis of T/B ratio variations could contribute towards elevating the test's specificity.

Survival despite almost complete occlusion by chronic thrombosis of a Björk-Shiley mitral prosthesis.

We report a patient who was successfully reoperated because of almost complete thrombosis of a Björk-Shiley tilting disc mitral prosthesis. Considering the usually acute presentation and the frequently catastrophic consequences of most similar cases in the literature, the unusual feature of this case is that the patient survived until reoperation with minimal symptoms despite almost total prosthetic occlusion by a chronic thrombus.

Reoperation for prosthetic thrombosis and acute neurologic injury.

Open-heart surgery in patients with recent cardiogenic embolic stroke represents a difficult management problem. We present a patient who developed thrombosis of a mitral tilting-disc prosthesis complicated by repeat cerebral embolic episodes that resulted in acute neurologic injury. We believe that in such patients the indication for reoperation must be individually evaluated but it is justified in young subjects, even in the presence of severe neurologic damage.

Energy balance in feedback synchronization of chaotic systems.

In this paper we present a method based on a generalized Hamiltonian formalism to associate to a chaotic system of known dynamics a function of the phase space variables with the characteristics of an energy. Using this formalism we have found energy functions for the Lorenz, Rössler, and Chua families of chaotic oscillators. We have theoretically analyzed the flow of energy in the process of synchronizing two chaotic systems via feedback coupling and used the previously found energy functions for computing the required energy to maintain a synchronized regime between systems of these families. We have calculated the flows of energy at different coupling strengths covering cases of both identical as well as nonidentical synchronization. The energy dissipated by the guided system seems to be sensitive to the transitions in the stability of its equilibrium points induced by the coupling.

Parameter-adaptive identical synchronization disclosing Lorenz chaotic masking.

A parameter-adaptive rule that globally synchronizes oscillatory Lorenz chaotic systems with initially different parameter values is reported. In principle, the adaptive rule requires access to the three state variables of the drive system but it has been readapted to work with the exclusive knowledge of only one variable, a potential message carrier. The rule is very robust and can be used to trace parameter modulation conveying hidden messages. The driven system is defined according to a drive-driven type of coupling that guarantees synchronization if parameters are identical. From any arbitrary initial state, the parameters of the driven system are dynamically adapted to reach convergence to the drive parameter values. At this point, synchronization mismatch or parameter tracing is used to unmask any potential hidden message.

Pefloxacin in the antibacterial treatment of immunodepressed patients.

Pefloxacin 800 to 1200 mg daily was given for 3 to 20 days, orally or intravenously, to 84 immunocompromised patients. Five patients dropped out because of side effects and 2 for other causes. Treatment efficacy was evaluated in 77 patients, 43 men and 34 women, aged 18 to 80 years. Immunodepression resulted from malignancy in 46 patients, LAS/ARC or AIDS in 28, and from unknown causes in 3. Fifty-eight patients had documented infections (respiratory-tract infections 29, urinary-tract infections 13, septicemia 10, other 6) and 19 had a fever of unknown origin (FUO). Cure or significant improvement of symptoms was achieved in 81% of patients with documented infections and in 74% of patients with FUO. Side effects (mainly gastrointestinal disturbances and skin rash) occurred in 7 patients (8.2%), including dropouts. These results suggest that pefloxacin may be useful for the antibacterial treatment of immunodepressed patients.