Bionanotechnology and the Future of Glioma

Designer nanoscaled materials have the potential to revolutionize diagnosis and treatment for glioma. This review summarizes current progress in nanoparticle‑based therapies for glioma treatment including targeting, drug delivery, gene delivery, and direct tumor ablation. Preclinical and current human clinical trials are discussed. Although progress in the field has been significant over the past decade, many successful strategies demonstrated in the laboratory have yet to be implemented in human clinical trials. Looking forward, we provide examples of combined treatment strategies, which harness the potential for nanoparticles to interact with their biochemical environment, and simultaneously with externally applied photons or magnetic fields. We present our notion of the “ideal” nanoparticle for glioma, a concept that may soon be realized

Valsalva maneuver: Insights into baroreflex modulation of human sympathetic activity

Valsalva's maneuver, voluntary forced expiration against a closed glottis, is a well-characterized research tool, used to assess the integrity of human autonomic cardiovascular control. Valsalva straining provokes a stereotyped succession of alternating positive and negative arterial pressure and heart rate changes mediated in part by arterial baroreceptors. Arterial pressure changes result primarily from fluctuating levels of venous return to the heart and changes of sympathetic nerve activity. Muscle sympathetic activity was measured directly in nine volunteers to explore quantitatively the relation between arterial pressure and human sympathetic outflow during pressure transients provoked by controlled graded Valsalva maneuvers. Our results underscore several properties of sympathetic regulation during Valsalva straining. First, muscle sympathetic nerve activity changes as a mirror image of changes in arterial pressure. Second, the magnitude of sympathetic augmentation during Valsalva straining predicts phase 4 arterial pressure elevations. Third, post-Valsalva sympathetic inhibition persists beyond the return of arterial and right atrial pressures to baseline levels which reflects an alteration of the normal relation between arterial pressure and muscle sympathetic activity. Therefore, Valsalva straining may have some utility for investigating changes of reflex control of sympathetic activity after space flight; however, measurement of beat-to-beat arterial pressure is essential for this use. The utility of this technique in microgravity can not be determined from these data. Further investigations are necessary to determine whether these relations are affected by the expansion of intrathoracic blood volume associated with microgravity

Current rectification by simple molecular quantum dots: an ab-initio study

We calculate a current rectification by molecules containing a conjugated molecular group sandwiched between two saturated (insulating) molecular groups of different length (molecular quantum dot) using an ab-initio non-equilibrium Green's function method. In particular, we study S-(CH2)m-C10H6-(CH2)n-S dithiol with Naphthalene as a conjugated central group. The rectification current ratio ~35 has been observed at m = 2 and n = 10, due to resonant tunneling through the molecular orbital (MO) closest to the electrode Fermi level (lowest unoccupied MO in the present case). The rectification is limited by interference of other conducting orbitals, but can be improved by e.g. adding an electron withdrawing group to the naphthalene.Comment: 8 pages, 9 figure

Sleep deficiency and motor vehicle crash risk in the general population: a prospective cohort study

Background: Insufficient sleep duration and obstructive sleep apnea, two common causes of sleep deficiency in adults, can result in excessive sleepiness, a well-recognized cause of motor vehicle crashes, although their contribution to crash risk in the general population remains uncertain. The objective of this study was to evaluate the relation of sleep apnea, sleep duration, and excessive sleepiness to crash risk in a community-dwelling population. Methods: This was a prospective observational cohort study nested within the Sleep Heart Health Study, a community-based study of the health consequences of sleep apnea. The participants were 1745 men and 1456 women aged 40–89 years. Sleep apnea was measured by home polysomnography and questionnaires were used to assess usual sleep duration and daytime sleepiness. A follow-up questionnaire 2 years after baseline ascertained driving habits and motor vehicle crash history. Logistic regression analysis was used to examine the relation of sleep apnea and sleep duration at baseline to the occurrence of motor vehicle crashes during the year preceding the follow-up visit, adjusting for relevant covariates. The population-attributable fraction of motor vehicle crashes was estimated from the sample proportion of motor vehicle crashes and the adjusted odds ratios for motor vehicle crash within each exposure category. Results: Among 3201 evaluable participants, 222 (6.9%) reported at least one motor vehicle crash during the prior year. A higher apnea-hypopnea index (p < 0.01), fewer hours of sleep (p = 0.04), and self-reported excessive sleepiness (p < 0.01) were each significantly associated with crash risk. Severe sleep apnea was associated with a 123% increased crash risk, compared to no sleep apnea. Sleeping 6 hours per night was associated with a 33% increased crash risk, compared to sleeping 7 or 8 hours per night. These associations were present even in those who did not report excessive sleepiness. The population-attributable fraction of motor vehicle crashes was 10% due to sleep apnea and 9% due to sleep duration less than 7 hours. Conclusions: Sleep deficiency due to either sleep apnea or insufficient sleep duration is strongly associated with motor vehicle crashes in the general population, independent of self-reported excessive sleepiness

Boosting Long-term Memory via Wakeful Rest: Intentional Rehearsal is not Necessary, Automatic Consolidation is Sufficient.

<div><p>People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is <i>not</i> dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is <i>sufficient</i> for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.</p></div

Ventriculo-atrial gradient due to first degree atrio-ventricular block: a case report

BACKGROUND: Isolated, asymptomatic first degree AV block with narrow QRS has not prognostic significance and is not usually treated with pacemaker implantation. In some cases, yet, loss of AV synchrony because of a marked prolongation of the PR interval may cause important hemodynamic alterations, with subsequent symptoms of heart failure. Indeed, AV synchrony is crucial when atrial systole, the "atrial kick", contributes in a major way to left ventricular filling, as in case of reduced left ventricular compliance because of aging or concomitant structural heart disease. CASE PRESENTATION: We performed a trans-septal left atrium catheterization aimed at evaluating the entity of a mitral valve stenosis in a 72-year-old woman with a marked first-degree AV block, a known moderate aortic stenosis and NYHA class III symptoms of functional deterioration. We occurred in a deep alteration in cardiac hemodynamics consisting in an end-diastolic ventriculo-atrial gradient without any evidence of mitral stenosis. The patient had a substantial improvement in echocardiographic parameters and in her symptoms of heart failure after permanent pacemaker implantation with physiological AV delay. CONCLUSION: We conclude that if a marked first degree AV block is associated to instrumental signs or symptoms of heart failure, the restoration of an optimal AV synchrony, achieved with dual-chamber pacing, may represent a reasonable therapeutic option leading to a consequent clinical improvement