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Background: Spermidine administration is linked to increased survival in several animal models., Objective: The aim of this study was to test the potential association between spermidine content in diet and mortality in humans., Design: This prospective community-based cohort study included 829 participants aged 45-84 y, 49.9% of whom were male. Diet was assessed by repeated dietitian-administered validated food-frequency questionnaires (2540 assessments) in 1995, 2000, 2005, and 2010. During follow-up between 1995 and 2015, 341 deaths occurred., Results: All-cause mortality (deaths per 1000 person-years) decreased across thirds of increasing spermidine intake from 40.5 (95% CI: 36.1, 44.7) to 23.7 (95% CI: 20.0, 27.0) and 15.1 (95% CI: 12.6, 17.8), corresponding to an age-, sex- and caloric intake-adjusted 20-y cumulative mortality incidence of 0.48 (95% CI: 0.45, 0.51), 0.41 (95% CI: 0.38, 0.45), and 0.38 (95% CI: 0.34, 0.41), respectively. The age-, sex- and caloric ratio-adjusted HR for all-cause death per 1-SD higher spermidine intake was 0.74 (95% CI: 0.66, 0.83; P < 0.001). Further adjustment for lifestyle factors, established predictors of mortality, and other dietary features yielded an HR of 0.76 (95% CI: 0.67, 0.86; P < 0.001). The association was consistent in subgroups, robust against unmeasured confounding, and independently validated in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) Study (age-, sex-, and caloric ratio-adjusted HR per 1-SD higher spermidine intake: 0.71; 95% CI: 0.53, 0.95; P = 0.019). The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7-y (95% CI: 3.6, 8.1 y) younger age., Conclusion: Our findings lend epidemiologic support to the concept that nutrition rich in spermidine is linked to increased survival in humans. This trial was registered at www.clinicaltrials.gov as NCT03378843.

Objective: Pilot study to evaluate computer-guided deep brain stimulation (DBS) programming designed to optimize stimulation settings using objective motion sensor-based motor assessments., Materials and Methods: Seven subjects (five males; 54-71 years) with Parkinson's disease (PD) and recently implanted DBS systems participated in this pilot study. Within two months of lead implantation, the subject returned to the clinic to undergo computer-guided programming and parameter selection. A motion sensor was placed on the index finger of the more affected hand. Software guided a monopolar survey during which monopolar stimulation on each contact was iteratively increased followed by an automated assessment of tremor and bradykinesia. After completing assessments at each setting, a software algorithm determined stimulation settings designed to minimize symptom severities, side effects, and battery usage., Results: Optimal DBS settings were chosen based on average severity of motor symptoms measured by the motion sensor. Settings chosen by the software algorithm identified a therapeutic window and improved tremor and bradykinesia by an average of 35.7% compared with baseline in the "off" state (p < 0.01)., Conclusions: Motion sensor-based computer-guided DBS programming identified stimulation parameters that significantly improved tremor and bradykinesia with minimal clinician involvement. Automated motion sensor-based mapping is worthy of further investigation and may one day serve to extend programming to populations without access to specialized DBS centers., (© 2015 International Neuromodulation Society.)

Misfolded protein aggregates, characterized by a canonical amyloid fold, play a central role in the pathobiology of neurodegenerative diseases. Agents that bind and sequester neurotoxic intermediates of amyloid assembly, inhibit the assembly or promote the destabilization of such protein aggregates are in clinical testing. Here, we show that the gene 3 protein (g3p) of filamentous bacteriophage mediates potent generic binding to the amyloid fold. We have characterized the amyloid binding and conformational remodeling activities using an array of techniques, including X-ray fiber diffraction and NMR. The mechanism for g3p binding with amyloid appears to reflect its physiological role during infection of Escherichia coli, which is dependent on temperature-sensitive interdomain unfolding and cis-trans prolyl isomerization of g3p. In addition, a natural receptor for g3p, TolA-C, competitively interferes with Aβ binding to g3p. NMR studies show that g3p binding to Aβ fibers is predominantly through middle and C-terminal residues of the Aβ subunit, indicating β strand-g3p interactions. A recombinant bivalent g3p molecule, an immunoglobulin Fc (Ig) fusion of the two N-terminal g3p domains, (1) potently binds Aβ fibers (fAβ) (KD=9.4nM); (2); blocks fAβ assembly (IC50~50nM) and (3) dissociates fAβ (EC50=40-100nM). The binding of g3p to misfolded protein assemblies is generic, and amyloid-targeted activities can be demonstrated using other misfolded protein systems. Taken together, our studies show that g3p(N1N2) acts as a general amyloid interaction motif., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

With a view to analyse multiresidues of pesticides in soil samples, a new ultrasonic solvent extraction (USE) was compared to the European Norm DIN 12393 for foodstuff (extraction with acetone, partitioning with ethylacetate/cyclohexane and clean-up with gel permeation chromatography (GPC)), the QuECheRS method and a pressurised liquid extraction (PLE) method. Pesticides were analysed with both GC-MS and HPLC-MS/MS. The reference materials were the EUROSOIL 7 and its subsoil SO26 as well as a sea sand. All the substances were observed to be linear in the range of 4-800 ng g(-1) for the European Norm DIN 12393, 7-1400 ng g(-1) for the USE method and 20-4000 ng g(-1) for the QueCheRS and the PLE methods. Limits of detection (LOD) and limits of quantification (LOQ) were with HPLC between 0.006 and 0.23 ng g(-1) and between 0.022 and 0.77 ng g(-1), respectively, with the exception of diuron (LOD up to 11.8 ng g(-1); LOQ up to 39.2 ng g(-1)). With GC they ranged from 3.0 to 87.5 ng g(-1) and from 10 to 292 ng g(-1), respectively. All substances could be recovered with USE as well as with the QuECheRS method; the European Norm DIN 12393 could not recover carbendazim and metamitron; the PLE carbendazim, metamitron and monolinuron. For the remaining substances, recoveries at a 500 ng g(-1) fortification level ranged from 10.9 to 96.3% with the USE. In comparison, the QuECheRS method was the most efficient extraction method with recoveries from 27.3 to 120.9%. It was followed by the European Norm DIN 12393 with recoveries between 6.8 and 108.1% and the PLE with recoveries from 12.2 to 153.2%. Recoveries were higher from the EUROSOIL 7 than from the SO 26. The repeatability expressed in term of standard deviation was below 20% for all substances and all materials.

The aim of the present experiment was to investigate the influence of hypothermia on transient evoked otoacoustic emissions (TEOAEs) in humans. Hypothermic alterations were brought about directly by cooling the cardiovascular system of young children during open heart bypass surgery. This condition caused TEOAE levels to decrease with a significant positive correlation between total and frequency band TEOAE amplitudes during cooling. TEOAEs were totally abolished at tympanic temperatures around 30 degrees C, without it being possible to find differences in TEOAE alteration among the frequency components. During rewarming, the changes reversed and TEOAEs returned to their initial prehypothermia status, although sometimes only partially. Despite large possible metabolic changes caused by this hypothermic condition at various levels, it is concluded that the motile properties of outer hair cells (OHCs), that are related to TEOAEs, are temperature-sensitive. The total suppression found in deep hypothermia (above 30 degrees C) could conceivably be attributable to a process involving a temperature-dependent energy source.

Evoked otoacoustic emissions (EOAEs) and spontaneous otoacoustic emissions (SOAEs) were compared between neonates and adults. Several differences were seen for EOAEs: (i) the occurrence of EOAEs was significantly greater in adults than in neonates, and in neonates it increased with extra-uterine age; (ii) the high frequency EOAE intensity was greater in neonates than in adults; (iii) the EOAE intensity was significantly greater in neonates than in adults. No age-related differences for SOAEs were found: (i) age was not significantly related to the presence/absence of SOAEs in neonates or adults; (ii) the occurrence of SOAEs was, however, significantly greater in females than in males in both neonates and adults.