Plantar pressure distribution analysis in normal weight young women and men with normal and claw feet: a cross-sectional study

We analyzed the plantar support in 72 normal-weight young voluntaries (46 women, 26 men), by a baropodometric platform. We considered subjects with claw foot (CFS) and subjects with normal foot (NFS). We found a significant reduction of total plantar support surface in the CFS (P < 0.0001 for women, P < 0.001 for men), due to the reduction of the forefoot and rear foot areas of both plantar imprints. Indeed, CFS of both sexes exhibited higher values of both plantar pressure and peak pressure, compared to the NFS. Moreover, the load per units of plantar surface increased in CFS compared to the NFS. In conclusion, the reduction of plantar support surfaces in CFS of both sexes was associated to a major load per units of plantar surface in the forefoot and rear foot areas, and this may be a risk factor to lower extremity overuse injuries

Activation of the motor cortex during phasic rapid eye movement sleep

When dreaming during rapid eye movement (REM) sleep, we can perform complex motor behaviors while remaining motionless. How the motor cortex behaves during this state remains unknown. Here, using intracerebral electrodes sampling the human motor cortex in pharmacoresistant epileptic patients, we report a pattern of electroencephalographic activation during REM sleep similar to that observed during the performance of a voluntary movement during wakefulness. This pattern is present during phasic REM sleep but not during tonic REM sleep, the latter resembling relaxed wakefulness. This finding may help clarify certain phenomenological aspects observed in REM sleep behavior disorder

Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS Production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

Lines on projective varieties and applications

The first part of this note contains a review of basic properties of the variety of lines contained in an embedded projective variety and passing through a general point. In particular we provide a detailed proof that for varieties defined by quadratic equations the base locus of the projective second fundamental form at a general point coincides, as a scheme, with the variety of lines. The second part concerns the problem of extending embedded projective manifolds, using the geometry of the variety of lines. Some applications to the case of homogeneous manifolds are included.Comment: 15 pages. One example removed; one remark and some references added; typos correcte

Biomarkers of myocardial injury with different energy sources for atrial fibrillation catheter ablation

Background: Our study aims to compare acute myocardial injury biomarker rise after atrial fibrillation ablation performed with different technologies.Methods and Results: One hundred and ten patients were treated with pulmonary vein isolation with 4 different technologies: open-irrigated tip radiofrequency (RF) catheter in35 patients (Group A), cryoballoon in 35 patients (Group B), visually guided laser balloon in 20 patients (Group C), open-irrigated tip RF catheter with contact-force-sensing technology in 20 patients (Group D). Post-procedure samples of cardiac troponin I (cTnI) and creatinine kinase-MB (CK-MB) were collected at 19 ± 3 h and 43 ± 3 h after ablation. At the first postprocedural sample, cTnI and CK-MB levels were found elevated in all 110 patients with a median value of 2.11 ng/mL and 8.95 ng/mL, respectively. Group B showed cTnI levels increased (median 5.96 ng/mL) compared to other groups (median Group A: 1.72 ng/mL, Group C: 1.54 ng/mL, Group D: 2.0 ng/mL; p &lt; 0.001). Also CK-MB levels resulted higher in cryoablation (median 26.4 ng/mL) compared to other groups (median Group A: 6.40 ng/mL, Group C: 7.15 ng/mL, Group D: 6.50 ng/mL; p &lt; 0.001). No significant association was observed between biomarker levels and recurrences of atrial fibrillation after a mean follow-up of 369 ± 196 days.Conclusions: Highest markers for myocardial injury were observed in the cryoballoon group. It is possible that a longer delivery energy duration and other factors affecting lesion size resulted in higher amount of cardiac injury in cryoablation. The higher levels of cardiac biomarkers did not translate into a better outcome and its physiologic significance is unknown.

Ranolazine attenuates trastuzumab-induced heart dysfunction by modulating ROS production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

A transient third cranial nerve palsy as presenting sign of spontaneous intracranial hypotension

Spontaneous intracranial hypotension is an uncommon cause of sudden and persistent headache: associated symptoms are common, among which there are cranial nerve palsies, especially of the abducens nerve. We report a case of a 21-year-old man with a transient and isolated third nerve palsy due to spontaneous intracranial hypotension. To our knowledge, there are only few reports in the literature of such association

Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program

Objective: This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy. Methods: This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (&gt;= 50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses. Results: A total of 236 subjects with a median age of 38 (Q(1)-Q(3) = 27-49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q(1)-Q(3) = 2.50-4.47) at baseline to 2.50 (Q(1)-Q(3) = 1.67-3.50) at 12 months (p &lt; .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and gamma-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel. Significance: Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam

Sleep in the Human Hippocampus: A Stereo-EEG Study

Background. There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. Methodology/Principal Findings. We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i) a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii) a flattening of the time course of the very low frequencies (up to 1 Hz) across sleep cycles, with relatively high levels of power even during REM sleep; iii) a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. Conclusions/Significance. Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonanc