Search

Single-molecule level STM observations of chiral complexes generated by the assembly of achiral components and metal centers at a metal surface are reported. The findings indicate that a square planar ML(sub 4) complex can be chiral in two dimensions when symmetric bidentate ligands are employed which link to the metal atom in an organized unidentate fashion.

Our objective was to assess the association between amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD) and Parkinson's disease (PD). From May 2007 through August 2012 we investigated 146 patients with newly diagnosed ALS and 146 age- and gender-matched controls. Each individual was screened for cardinal extrapyramidal signs (neurological examination) and cognitive dysfunction (Mini Mental State Examination, MMSE and Frontal Assessment Battery, FAB). Results demonstrated that rigidity was present in 8.2% of cases and 2.1% of controls (adjusted odds ratio, adjOR 5.7; 95% CI 1.5–22.0). The corresponding percentages for bradykinesia and postural instability were, respectively, 8.2 vs. 2.7% (adjOR 4.8; 95% CI 1.4–16.5) and 2.7 vs. 9.6% (adjOR 0.3; 95% CI 0.1–0.9). FAB ≤ 13.4 was recorded in 24.8 vs. 9.6%; adjOR 2.9; 95% CI 1.5–5.7). Tremor and abnormal FAB score were predicted by an older age at onset while an abnormal FAB score was associated with cramps and family history of neurodegenerative diseases. In conclusion, our data support the notion that newly diagnosed ALS carries a higher than expected risk of extrapyramidal signs and FTD. [ABSTRACT FROM PUBLISHER]

The 23 km long Sulmona normal fault flanks the southwestern slope of the Mount Morrone range in the central Apennines. To date, the recent activity of this structure is uncertain, as the faulting evidence concerns only undated deposits and the fault cannot be associated with any of the strong historical earthquakes (Mw > 6.5) of the region. Our observation from ~ 1 Ma offset slope breccias, coupled with new tephrochronological data on faulted early Last Glacial lacustrine infilling of the Sulmona basin, implies a vertical slip rate of ~0.5 mm/yr over both the long term and middle term. Moreover, at the apex of a Late Pleistocene alluvial fan, radiocarbon dating of offset stratigraphy uncovered in four paleoseismological trenches shows that repeated earthquakes resulted in more than 4 m of vertical offset since ~9 ka, providing again a minimum Holocene vertical slip rate of ~0.5 mm/yr. In combination with the results of the trench exposure, we define four faulting events in the past ~9 ky B.P., and at least one before then. The most recent is constrained by robust radiocarbon dates as the middle of the second century A.D. The penultimate event was around the middle of the fifth millennium B.P., whereas the other two events are dated in a time between 8.5 ky to 6.5 ky B.P. and around 9 ky cal B.P. The oldest occurred before 9.5 ky B.P. As well as revealing the unexpected paleoseismic history of the Sulmona silent fault, our data provide a recurrence time for Mw >6.5 earthquakes of ~2.4 ky versus an elapsed time of ~ 1.85 ky since the last event. The latter matches with an earthquake previously hypothesized through archaeoseismic clues collected from several Roman settlements of the Sulmona Plain, all of which were dated to halfway through the second century A.D. [ABSTRACT FROM AUTHOR]

Background: There is only one small single-center study on the reliability of the diagnosis of focal dystonia. The aim of this study was to assess the inter-rater reliability of dystonia diagnosis among neurologists with different professional experience. Methods: Twenty-nine adults (18 with dystonia, 9 with other movement disorders, and 2 healthy controls) were videotaped while undergoing neurological examination and during the process of collecting information on the history of their condition. Each case was diagnosed by 35 blind raters (12 general neurologists, 21 neurology residents, and 2 experts in movement disorders) from different hospitals. Sensitivity and specificity were calculated confronting raters with the gold standard (the caring physician). Inter-rater agreement was measured by the Kappa statistic. Results: Specificity and sensitivity were 95.2 and 66.7%, 76.3 and 75.2%, 84.6 and 71.6% for experts, general neurologists, and residents, respectively. Kappa values on dystonia diagnosis ranged from 0.30 to 0.46. The agreement was moderate for experts and residents (0.40–0.60) and fair for general neurologists (0.20–0.40). Kappas were the highest among experts for cranial and laryngeal dystonia (0.61–1), but not for cervical dystonia (0.37). Conclusions: The diagnosis of dystonia is difficult and only partially mirrors a physician’s background. [ABSTRACT FROM AUTHOR]

The aim of this study was to verify whether abnormalities in plasma amino acid (AA) levels could be biological correlates of the age of onset in amyotrophic lateral sclerosis (ALS). We undertook plasma AA profiling in a large population comprising 117 newly diagnosed ALS patients and 117 matched controls. ALS patients were stratified in early (58 patients aged < 55 years) versus late onset (59 patients aged > 74 years). We applied a rapid and reproducible method for the analysis of AA using amine reactive isotope coded tags in conjunction with liquid chromatography coupled to Multiple Reaction Monitoring-Mass Spectrometry. Results showed that values of only three AA were significantly different in ALS patients and controls. We found lower levels of leucine and higher levels of glutamate and leucine in early-onset ALS compared to their matched controls. In conclusion, different AA patterns related to the ALS age of onset were found, providing insight into possibly aberrant biochemical pathways that might unlock key pathological pathways. [ABSTRACT FROM AUTHOR]

Background Increased titres of serum IgM antibodies to GM1 ganglioside are often associated with multifocal motor neuropathy (MMN). Testing for IgM antibodies to other antigens including GM2, the mixture of GM1 and galactocerebroside (GM1/GalC) and the disulfated heparin disaccharide NS6S were reported to increase the sensitivity of antibody testing in MMN even if it is unclear whether the specificity and positive (PPV) or negative predictive value (NPV) for MMN were also affected. Methods We measured IgM antibodies to GM1, GM2, galactocerebroside, GM1/GalC and NS6S in 40 consecutive patients with MMN and 142 controls with other neuropathies or related diseases and compared their sensitivity, specificity and PPV for MMN. Results With the only exception of anti-GM2 and, partially, anti-NS6S antibodies, IgM antibodies to the antigens tested were more frequent in MMN than in controls. Increased titres of anti-GM1 IgM were found in 48% of MMN patients with a specificity of 93% and PPV for MMN of 66%. Anti-GM1/GalC antibodies were present in all anti-GM1 positive MMN patients and in 11 additional patients (28%) with MMN raising the sensitivity of antibody testing to 75%. The specificity (85%) and PPV (59%) for MMN was, however, moderately reduced compared to anti-GM1 IgM, even if they rose with increasing anti-GM1/GalC titres. IgM antibodies to GM2, NS6S and galactocerebroside were found in 8%, 23% and 60% of MMN patients but had a low specificity and PPV for MMN. Conclusions Testing for anti-GM1/GalC IgM significantly increased the sensitivity of antibody testing in MMN compared to anti-GM1 alone ( p=0.021) and may represent a preferred option for GM1 reactivity testing in MMN. [ABSTRACT FROM AUTHOR]

ALS is a heterogeneous disease that is not well understood. Epigenetic rearrangements are important in complex disorders including motor neuron diseases. The aim of this study was to determine whether whole-blood DNA methylation (DNA MET %) is a potential modifier of age at onset in ALS. DNA MET % was measured as incorporation of [3H]dCTP following HpaII cut in 96 ALS patients and 87 controls, comprising: early-onset (< 55 years of age) and late-onset (> 74 years of age). Methionine (Met) and homocysteine (Hcy) plasma levels were assessed by liquid chromatography selected reaction monitoring coupled with isotope-dilution mass spectrometry. Results showed that DNA MET % was increased in ALS patients independently of age of onset. Compared to the other three groups, Hcy plasma levels were reduced in early-onset ALS patients but Met levels were similar. ROC analysis reported Met levels and DNA MET %, respectively, with a slight and moderate discriminative power. In conclusion, increased DNA MET % is a possible marker of epigenetic dysfunction in ALS independently of age of onset. Further studies dissecting biological determinants of phenotypic complexity in ALS may help in developing successful therapeutic strategies. [ABSTRACT FROM AUTHOR]

Our objective was to assess the effects of acetyl-L-carnitine (ALC) with riluzole on disability and mortality of amyotrophic lateral sclerosis (ALS). Definite/probable ALS patients, 40−70 years of age, duration 6−24 months, self-sufficient (i.e. able to swallow, cut food/handle utensils, and walk), and with forced vital capacity (FVC) > 80% entered a pilot double-blind, placebo-controlled, parallel group trial and were followed for 48 weeks. ALC or placebo 3 g/day was added to riluzole 100 mg/day. Primary endpoint: number of patients no longer self-sufficient. Secondary endpoints: changes in ALSFRS-R, MRC, FVC and McGill Quality of Life (QoL) scores. Analysis was made in the intention-to-treat (ITT) and per-protocol (PP) population, completers and completers/compliers (i.e. taking > 75% of study drug). Forty-two patients received ALC and 40 placebo. In the ITT population, 34 (80.9%) patients receiving ALC and 39 (97.5%) receiving placebo became non-self-sufficient ( p = 0.0296). In the PP analysis, percentages were 84.4 and 100.0% ( p = 0.0538), respectively. Mean ALSFRS-R scores at 48 weeks were 33.6 (SD 10.4) and 27.6 (9.9) ( p = 0.0388), respectively, and mean FVC scores 90.3 (32.6) and 58.6 (31.2) ( p = 0.0158), respectively. Median survival was 45 months (ALC) and 22 months (placebo) ( p = 0.0176). MRC, QoL and adverse events were similar. In conclusion, ALC may be effective, well-tolerated and safe in ALS. A pivotal phase III trial is needed. [ABSTRACT FROM AUTHOR]

SUMMARY Urgent urban-planning problems related to the 2009 April, Mw 6.3, L'Aquila earthquake prompted immediate excavation of palaeoseismological trenches across the active faults bordering the Aterno river valley; namely, the Mt. Marine, Mt. Pettino and Paganica faults. Cross-cutting correlations amongst existing and new trenches that were strengthened by radiocarbon ages and archaeological constraints show unambiguously that these three investigated structures have been active since the Last Glacial Maximum period, as seen by the metric offset that affected the whole slope/alluvial sedimentary succession up to the historical deposits. Moreover, in agreement with both 18th century accounts and previous palaeoseismological data, we can affirm now that these faults were responsible for the catastrophic 1703 February 2, earthquake ( Mw 6.7). The data indicate that the Paganica-San Demetrio fault system has ruptured in the past both together with the conterminous Mt. Pettino-Mt. Marine fault system, along more than 30 km and causing an Mw 6.7 earthquake, and on its own, along ca. 19 km, as in the recent 2009 event and in the similar 1461 AD event. This behaviour of the L'Aquila faults has important implications in terms of seismic hazard assessment, while it also casts new light on the ongoing fault linkage processes amongst these L'Aquila faults. [ABSTRACT FROM AUTHOR]