Modulation of linguistic prediction by TDCS of the right lateral cerebellum.

It has been postulated recently that the cerebellum contributes the same prediction and learning functions to linguistic processing as it does towards motor control. For example, repetitive TMS over posterior-lateral cerebellum caused a significant loss in predictive language processing, as assessed by the latency of saccades to target items of spoken sentences, using the Visual World task. We aimed to assess the polarity-specific effects of cerebellar TDCS, hypothesising that cathodal TDCS should impair linguistic prediction, and anodal TDCS facilitate it. Our design also tested whether TDCS modulated associative learning in this task. A between groups (sham, anodal, cathodal) design was used, with concurrent stimulation during performance of a manual variation of the Visual World paradigm, and with assessment of latency reduction over repeated presentations of the spoken sentences. Mixed model ANOVA was used to analyse change in response latency. Cathodal TDCS decreased participants' response time advantage for the predictable sentence items without change for non-predictable items, consistent with the previous TMS results. Furthermore, anodal stimulation enhanced the response time advantage for the predictable items, again without change in latencies for non-predictive items. We found a clear practice-based effect over 4 blocks. However, this difference was not significantly modulated by either anodal or cathodal stimulation. Our results therefore support the hypothesis that cerebellum contributes to predictive language processing, mirroring its predictive role in motor control, but we do not yet have evidence that the learning process was affected by cerebellar TDCS.

Zygomycosis over-infection during voriconazole therapy for aspergillosis in a heart transplant patient, successfully treated with liposomal amphotericin and posaconazole.

Aspergillosis and zygomycosis are life-threatening fungal infections in immunocompromised patients. We report a heart transplant recipient with an early pulmonary invasive aspergillosis successfully treated with association of voriconazole and caspofungin. Zygomycosis sinusitis, which was diagnosed while he still was on voriconazole therapy, was successfully treated with the use of combination antifungal therapy including liposomal amphotericin plus posaconazole and conservative surgical debridement.

Antioxidant status and biomarkers of oxidative stress in dogs with lymphoma.

BACKGROUND: Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly diagnosed lymphoma before treatment and once in remission, with comparison with healthy controls. HYPOTHESIS: Dogs with lymphoma have increased oxidant and reduced antioxidant concentrations compared with healthy controls, and that these abnormalities normalize once remission is achieved. ANIMALS: Seventeen dogs with lymphoma and 10 healthy controls. METHODS: Prospective, observational study. Measures of oxidative stress [malondialdehyde and total isoprostanes (isoP)] and antioxidants [alpha-tocopherol, gamma-tocopherol, oxygen radical absorbance capacity (ORAC), and glutathione peroxidase (GSHPx)] were assessed in dogs with newly diagnosed lymphoma before treatment compared with healthy control dogs. The same parameters were measured in the dogs with lymphoma on week 7 of the chemotherapy protocol when all dogs were in remission. RESULTS: At baseline, dogs with lymphoma had significantly lower alpha-tocopherol (P <.001) and gamma-tocopherol (P= .003) but higher GSHPx (P= .05), ORAC (P= .001), and isoP (P < .001) compared with healthy controls. In the dogs with lymphoma, alpha-tocopherol concentrations were higher (P= .005) and ascorbic acid were lower (P= .04) after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that dogs with lymphoma have alterations in oxidant and antioxidant concentrations and that the status of some of these biomarkers normalize after remission. Further studies are warranted to determine whether antioxidant interventions to correct these are beneficial in the treatment of canine lymphoma.

Adriana and Luisa Castellucci Award lecture 2001. Hypoxia inducible factor-1: oxygen regulation of trophoblast differentiation in normal and pre-eclamptic pregnancies--a review.

During early pregnancy, trophoblast differentiation occurs in an environment of relative low oxygen tension which is essential for normal embryonic and placental development. At around 10-12 weeks' gestation, when the intervillous space opens to maternal blood, there is an increase in Po(2). This increase correlates with the time of maximal trophoblast invasion into the maternal decidua, which allows extravillous trophoblast cells to access and remodel the maternal spiral arteries. Hypoxia Inducible Factor 1(HIF-1) is a transcription factor which activates gene transcription in response to varying oxygen concentration of cells. HIF-1 is a heterodimer composed of the inducible HIF-1alpha and the constitutively expressed HIF-1beta/ARNT subunits. Using villous explants, we have demonstrated that the oxygen-regulated events of early trophoblast differentiation are in part mediated by TGFbeta(3), an inhibitor of trophoblast differentiation, via HIF-1alpha. Pre-eclampsia is a disease of pregnancy that is characterized by shallow trophoblast invasion. Recently, we have reported that TGFbeta(3) is over-expressed in pre-eclamptic pregnancy and that its down-regulation restores invasive capability to trophoblast cells. Because TGFbeta(3) is downstream of HIF-1alpha, in the present study we investigated the expression of HIF-1alpha in pre-eclamptic placentae and age-matched controls using in situ hybridization and histochemical analyses. We found that HIF-1alpha mRNA and protein expression are abnormally elevated in pre-eclamptic placental tissue when compared to normal placental tissue. We conclude that pre-eclampsia may result from a developmental failure of oxygen to increase or of trophoblast cells to respond and/or sense an increase in oxygen. This will prevent the normal TGFbeta3 down-regulation and will lead to poor trophoblast invasion predisposing the pregnancy to pre-eclampsia.

Are dyslexics' visual deficits limited to measures of dorsal stream function?

We tested the hypothesis that the differences in performance between developmental dyslexics and controls on visual tasks are specific for the detection of dynamic stimuli. We found that dyslexics were less sensitive than controls to coherent motion in dynamic random dot displays. However, their sensitivity to control measures of static visual form coherence was not significantly different from that of controls. This dissociation of dyslexics' performance on measures that are suggested to tap the sensitivity of different extrastriate visual areas provides evidence for an impairment specific to the detection of dynamic properties of global stimuli, perhaps resulting from selective deficits in dorsal stream functions.

Microstimulation of movements from cerebellar-receiving, but not pallidal-receiving areas of the macaque thalamus under ketamine anaesthesia.

The motor thalamic areas receiving input from the globus pallidus (VA) and the cerebellar nuclei (VL) appear to have different roles in the generation and guidance of movements. In order to further test these differences, we used electrical stimulation to map the ventro-anterior and ventro-lateral nuclei of the thalamus in three ketamine anaesthetised monkeys. Movements were readily evoked from VL at currents of down to 10 microA. The movements were typically multijoint, and stimulation could evoke arm and trunk or arm and facial movement at the same current threshold. Evoked arm movements often involved multiple joints, with or without finger movements. Facial movements included the lips, tongue, jaw, eyebrows and, occasionally, the eyes. The thalamic map was topographic, but complex with at least two separate regions related to arm movement. Very few sites within the VA could stimulate movement, even at high currents. We therefore suggest that the cerebellar projections to motor regions of the cortex, which pass through the VL thalamic nuclei, have a different relationship and are closer to movement execution than the projections from basal ganglia via the ventro-anterior nucleus.

Evidence for an error deadzone in compensatory tracking.

Humans and monkeys show intermittent arm movements while tracking moving targets. This intermittency has been explained by postulating either a psychological refractory period after each movement and/or an error deadzone, an area surrounding the target within which movements are not initiated. We present a technique to detect and quantify the size of this deadzone, using a compensatory tracking paradigm that distinguishes it from a psychological refractory period. An artificial deadzone of variable size was added around a visual target displayed on a computer screen. While the subject was within this area, he received visual feedback that showed him to be directly on target. The presence of this artificial deadzone could affect tracking performance only if it exceeded the size of his intrinsic deadzone. Therefore, the size of artificial deadzone at which performance began to be affected revealed the size of the intrinsic deadzone. Measured at the subjects' eye, the deadzone was found to vary between 0.06 and 0.38 degrees, depending on the tracking task and viewing conditions; on the screen, this range was 1.3 mm to 3.3 mm. It increased with increasing speed of the target, with increasing viewing distance, and when the amplitude of the movement required was reduced. However, the deadzone size was not significantly correlated with the subjects' level of performance. We conclude that an intrinsic deadzone exists during compensatory tracking, and we suggest that its size is set by a cognitive process not simply related to the difficulty of the tracking task.

Evaluation of two seminal collection regimens for mature Holstein bulls.

Twenty mature Holstein bulls (3 to 10 yr old) were used to test the effect of two semen collection regimens on spermatozoal output, post-thaw percentage spermatozoal motility, and time needed to make the collections/week. For both regimens, six ejaculates/wk were collected using either three ejaculates/d, 2 d/wk, or two ejaculates/d, 3 d/wk. A three-period switchback experimental design was used. Each collection period for which measurements were taken was 3 wk and was preceded by a 2 wk period of acclimation. The total number of spermatozoa harvested per week was not significantly different (P greater than .05): 33.2 X 10(9) when the bulls were collected two ejaculates 3 d/wk, compared with 33.9 X 10(9) three ejaculates 2 d/wk. Post-thaw progressive spermatozoal motility was 50.3 and 52.1% (P greater than .05), respectively. The average time per week to collect each bull was 73.6 and 83.7 min (P less than .05), respectively.