Hormonal responses to training and its tapering off in competitive swimmers: relationships with performance

During a winter training season, the effects of 12 weeks of intense training and 4 weeks of tapering off (taper) on plasma hormone concentrations and competition performance were investigated in a group of highly trained swimmers (n = 8). Blood samples were collected and the swimmers performed their speciality in competition at weeks 10 (mid-season), 22 (pre-taper) and 26 (post-taper). No statistically significant changes were observed in the concentrations of total testosterone (TT), non-sex hormone binding globulin-boundtestosterone (NSBT), cortisol (C), luteinising hormone, thyroid stimulating hormone, triiodothyronine, thyroxine plasma catecholamines, creatine kinase and ammonia during training and taper. Mid-season NSBT: C ratio and the amount of training were statistically related (r = 0.82,P < 0.05). Competition performance slightly declined during intense training [0.52 (SD 2.51) %, NS] and improved during taper [2.32 (SD 1.69)%,P < 0.01]. Changes in performance during training and taper correlated with changes in ratios TT: C (r = 0.86,P < 0.01andr = 0.81,P < 0.05, respectively) and NSBT: C (r = 0.77,P < 0.05 andr = 0.76,P < 0.05, respectively). In summary, these results showed that the monitored plasma hormones and metabolic indices were unaltered by 12 weeks of intense training and 4 weeks of taper. The TT: C and NSBT: C ratios, however, appeared to be effective markers of the swimmers' performance capacities throughout the training season.     

PCR assays for identification of Coccidioides posadasii based on the nucleotide sequence of the antigen 2/proline-rich antigen

A conventional nested PCR and a real-time LightCycler PCR assay for detection of Coccidioides posadasii DNA were designed and tested in 120 clinical strains. These had been isolated from 114 patients within 10 years in Monterrey, Nuevo Leon, Mexico, known to be endemic for coccidioidomycosis. The gene encoding the specific antigen 2/proline-rich antigen (Ag2/PRA) was used as a target. All strains were correctly identified, whereas DNA from related members of the family Onygenaceae remained negative. Melting curve analysis by LightCycler and sequencing of the 526-bp product of the first PCR demonstrated either 100% identity to the GenBank sequence of the Silveira strain, now known to be C. posadasii (accession number AF013256), or a single silent mutation at position 1228. Length determination of two microsatellite-containing loci (GAC and 621) identified all 120 isolates as C. posadasii. Specific DNA was amplified by conventional nested PCR from three microscopically spherule-positive paraffin-embedded tissue samples, whereas 20 human tissue samples positive for other dimorphic fungi remained negative. Additionally, the safety of each step of a modified commercially available DNA extraction procedure was evaluated by using 10 strains. At least three steps of the protocol were demonstrated to sufficiently kill arthroconidia. This safe procedure is applicable to cultures and to clinical specimens.     

Detection of Trypanosoma cruzi and Trypanosoma rangeli infection by duplex PCR assay based on telomeric sequences

We used the species specificity and repetitious nature of subtelomeric kinetoplastida sequences to generate a duplex PCR assay for the simultaneous detection of Trypanosoma cruzi and Trypanosoma rangeli in experimentally and naturally infected triatomine (Reduviid) bugs and in infected human subjects. The assay was species specific and was capable of detecting 1/20th of T. cruzi and 1/4th of T. rangeli cell equivalents without complementary hybridization. In addition, the PCR-based assay was robust enough for direct application to difficult biological samples such as Reduviid feces or guts and was capable of recognizing all T. cruzi and T. rangeli strains and lineages. Because the assay primers amplify entirely different target sequences, no reaction interference was observed, facilitating future adaptation of this assay to an automated format.     

Synthetic MRI improves radiomics-based glioblastoma survival prediction

Glioblastoma is an aggressive and fast-growing brain tumor with poor prognosis. Predicting the expected survival of patients with glioblastoma is a key task for efficient treatment and surgery planning. Survival predictions could be enhanced by means of a radiomic system. However, these systems demand high numbers of multicontrast images, the acquisitions of which are time consuming, giving rise to patient discomfort and low healthcare system efficiency. Synthetic MRI could favor deployment of radiomic systems in the clinic by allowing practitioners not only to reduce acquisition time, but also to retrospectively complete databases or to replace artifacted images. In this work we analyze the replacement of an actually acquired MR weighted image by a synthesized version to predict survival of glioblastoma patients with a radiomic system. Each synthesized version was realistically generated from two acquired images with a deep learning synthetic MRI approach based on a convolutional neural network. Specifically, two weighted images were considered for the replacement one at a time, a T2w and a FLAIR, which were synthesized from the pairs T1w and FLAIR, and T1w and T2w, respectively. Furthermore, a radiomic system for survival prediction, which can classify patients into two groups (survival >480 days and $\le$ 480 days), was built. Results show that the radiomic system fed with the synthesized image achieves similar performance compared with using the acquired one, and better performance than a model that does not include this image. Hence, our results confirm that synthetic MRI does add to glioblastoma survival prediction within a radiomics-based approach.     

The magnitude and encephalogenic potential of autoimmune response to MOG is enhanced in MOG deficient mice

Myelin oligodendrocyte glycoprotein (MOG) is a minor component of central nervous system myelin presumably implicated in the pathogenesis of Multiple Sclerosis (MS). Immunization with MOG leads to the development of Experimental Autoimmune Encephalomyelitis (EAE), the experimental model of MS. It has been suggested that its encephalitogenic potential may be due to the lack of MOG self-immune tolerance. To clarify this, we have generated a MOG deficient mouse (MOG(-/-)) strain. Surprisingly, MOG(35-55)specific proliferation and Th1-type cytokine production were markedly enhanced in MOG(-/-)mice compared to wild type control. Furthermore, adoptive transfer of MOG(35-55)specific T cells, isolated from MOG deficient mice, into wild-type recipients resulted in the development of a more severe disease, indicating a high capacity of MOG(-/-)T cells to initiate effector responses. Interestingly, T cell reactivity to overlapping MOG peptides in MOG(-/-)mice did not reveal new potential immunodominant epitopes in H-2(b)mice. Taken together, our data suggests that MOG self-tolerance modulates the encephalitogenic potential of autoreactive MOG T cells in the periphery.     

Lemniscal recurrent and transcortical influences on cuneate neurons

Intracellular recordings were obtained from cuneate neurons of chloralose-anesthetized, paralysed cats to study the synaptic responses induced by electrical stimulation of the contralateral medial lemniscus. From a total of 178 cells sampled, 109 were antidromically fired from the medial lemniscus, 82 of which showed spontaneous bursting activity. In contrast, the great majority (58/69) of the non-lemniscal neurons presented spontaneous single spike activity. Medial lemniscus stimulation induced recurrent excitation and inhibition on cuneolemniscal and non-lemniscal cells. Some non-lemniscal neurons were activated by somatosensory cortex and inhibited by motor cortex stimulation. Some other non-lemniscal cells that did not respond to medial lemniscus stimulation in control conditions were transcortically affected by stimulating the medial lemniscus after inducing paroxysmal activity in the sensorimotor cortex. These findings indicate that different sites in the sensorimotor cortex can differentially influence the sensory transmission through the cuneate, and that the distinct available corticocuneate routes are selected within the cerebral cortex. From a total of 92 cells tested, the initial effect induced by low-frequency stimulation of the sensorimotor cortex was inhibition on most of the cuneolemniscal neurons (32/52) and excitation on the majority of the non-lemniscal cells (25/40). The fact that a substantial proportion of cuneolemniscal and non-lemniscal cells was excited and inhibited, respectively, suggests that the cerebral cortex may potentiate certain inputs by exciting and disinhibiting selected groups of cuneolemniscal cells. Finally, evidence is presented demonstrating that the tendency of the cuneolemniscal neurons to fire in high-frequency spike bursts is due to different mechanisms, including excitatory synaptic potentials, recurrent activation through lemniscal axonal collaterals, and via the lemnisco-thalamo-cortico-cuneate loop.A corticocuneate network circuit to explain the results is proposed.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Predicting development of sustained unresponsiveness to milk oral immunotherapy using epitope-specific antibody binding profiles

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Prosthetic mitral valve endocarditis due to Ochrobactrum anthropi: case report

We describe a case of infective endocarditis in a prosthetic mitral valve due to Ochrobactrum anthropi. Although O. anthropi is an emerging pathogen in immunocompromised patients, infections with the bacterium have very rarely been documented in healthy hosts, and endocarditis is rare. To our knowledge, only two cases of O. anthropi endocarditis have been reported in the medical literature.     

Chemoarchitecture and afferent connections of the "olfactostriatum": a specialized vomeronasal structure within the basal ganglia of snakes

The olfactostriatum, a portion of the striatal complex of snakes, is the major tertiary vomeronasal structure in the ophidian brain, receiving substantial afferents from the nucleus sphericus, the primary target of accessory olfactory bulb efferents. In the present study, we have characterized the olfactostriatum of garter snakes (Thamnophis sirtalis) on the basis of chemoarchitecture (distribution of serotonin, neuropeptide Y and tyrosine hydroxylase) and hodology (afferent connections). The olfactostriatum is densely immunoreactive for serotonin and neuropeptide Y and shows moderate-to-weak immunoreactivity for tyrosine hydroxylase. In addition to afferents from the nucleus sphericus, the olfactostriatum receives inputs from the dorsal and lateral cortices, nucleus of the accessory olfactory tract, external and dorsolateral amygdalae, dorsomedial thalamic nucleus, ventral tegmental area and raphe nuclei. Double labeling experiments demonstrated that the distribution of serotonin and neuropeptide Y in this area almost completely overlaps the terminal field of projections from the nucleus sphericus. Also, serotonergic and dopaminergic innervation of the olfactostriatum likely arise, respectively, from the raphe nuclei and the ventral tegmental area, whereas local circuit neurons originate the neuropeptide Y immunoreactivity. These results indicate that the olfactostriatum of snakes could be a portion of the nucleus accumbens, with features characteristic of the accumbens shell, devoted to processing vomeronasal information. Comparative data suggest that a similar structure is present in the ventral striatum of amphibians and mammals.