Striatal uptake of a novel PET ligand, [18F]beta-CFT, is reduced in early Parkinson's disease

[18F] beta-CFT is a novel PET ligand for dopamine reuptake sites. In this study, [18F]beta-CFT uptake was studied in nine patients with early Parkinson's disease (PD) without antiparkinsonian medication and in six age-matched controls. The uptake of [18F]beta-CFT was calculated as a (region-cerebellum)/cerebellum ratio at 150-210 min after injection. The mean uptake in the putamen contralateral to the predominant symptoms (1.04+/-0.40, mean +/- SD; P<0.001) was reduced to 31% of the mean control value. In the "ipsilateral" putamen, the ratio in PD patients (1.50+/-0.50, P<0.001) was reduced to 45% of the control mean (3.33+/-0.61). Individually, all PD patients had [18F]beta-CFT uptake values below 2 SD from the control mean in the contralateral putamen. The decline in [18F]beta-CFT uptake in the caudate nucleus was milder than that seen in the putamen. The uptake was reduced contralaterally (2.19+/-0.47, P<0.01) to 67% and ipsilaterally (2.49+/-0.54, P<0.05) to 77% of the control mean (3.17+/-0.61). In the medial frontal cortex or dorsolateral prefrontal cortex, no significant difference in [18F]beta-CFT uptake between patients and controls was seen. In conclusion, [18F]beta-CFT is a powerful ligand to demonstrate presynaptic dopaminergic defect in PD and shows a clear separation of patient and control values.     

Variant Alzheimer's disease with spastic paraparesis: clinical characterization

OBJECTIVE: To present the clinical, neuroimaging, and electrophysiologic characteristics of a variant AD phenotype. BACKGROUND: The authors have identified a large Finnish kindred with presenile dementia and spastic paraparesis due to deletion of exon 9 of presenilin 1. Neuropathologic analysis showed unusual cortical "cotton wool" plaques, immunoreactive for the beta-amyloid peptide but lacking congophilic cores. PATIENTS AND METHODS: Twenty-two affected individuals (16 men and 6 women) were identified in four successive generations. All surviving five patients were examined and subjected to molecular genetic analysis. In addition, the neurologic records of nine deceased patients were evaluated. Electrophysiologic investigations were available in eight cases. CT or MRI of the head had been performed on 11 patients and PET was performed on three patients. RESULT: The mean age at onset (+/-SD) was 50.9 +/- 5.2 years (range 40 to 61 years). Memory impairment was present in all patients. Memory impairment appeared simultaneously with or was preceded by walking difficulty due to spasticity of the lower extremities (10/14). Impaired fine coordination of hands (9/14) and dysarthria (6/14) in some patients suggested cerebellar involvement. EEG showed intermittent generalized delta-theta activity. Head MRI showed temporal and hippocampal atrophy; PET showed bilateral temporo-parietal hypometabolism. CONCLUSION: Spastic paraparesis or brisk stretch reflexes of lower extremities or clumsiness of hands combined with dementia suggests this variant of AD.     

Characterisation of the RNA Virome of Nine Ochlerotatus Species in Finland

RNA viromes of nine commonly encountered Ochlerotatus mosquito species collected around Finland in 2015 and 2017 were studied using next-generation sequencing. Mosquito homogenates were sequenced from 91 pools comprising 16–60 morphologically identified adult females of Oc. cantans, Oc. caspius, Oc. communis, Oc. diantaeus, Oc. excrucians, Oc. hexodontus, Oc. intrudens, Oc. pullatus and Oc. punctor/punctodes. In total 514 viral Reverse dependent RNA polymerase (RdRp) sequences of 159 virus species were recovered, belonging to 25 families or equivalent rank, as follows: Aliusviridae, Aspiviridae, Botybirnavirus, Chrysoviridae, Chuviridae, Endornaviridae, Flaviviridae, Iflaviridae, Negevirus, Partitiviridae, Permutotetraviridae, Phasmaviridae, Phenuiviridae, Picornaviridae, Qinviridae, Quenyavirus, Rhabdoviridae, Sedoreoviridae, Solemoviridae, Spinareoviridae, Togaviridae, Totiviridae, Virgaviridae, Xinmoviridae and Yueviridae. Of these, 147 are tentatively novel viruses. One sequence of Sindbis virus, which causes Pogosta disease in humans, was detected from Oc. communis from Pohjois-Karjala. This study greatly increases the number of mosquito-associated viruses known from Finland and presents the northern-most mosquito-associated viruses in Europe to date.     

Aging Effects on Auditory Processing: An Event-Related Potential Study

Abstract

Deviant tones randomly embedded in a sequence of standard tones elicit an event-related potential (ERP) called the mismatch negativity (MMN), which reflects automatic stimulus-change detection in the human auditory system. When the tones are attended, deviant tones elicit also an N2b component that partly overlaps the MMN. Sequences of standard and deviant (probability 0.15) tones were presented to 13 healthy younger and 13 older subjects. Deviant stimuli were, in separate blocks, either occasional shorter duration or higher frequency tones. The interstimulus interval (ISI) was, in separate blocks, either 0.5 s or 1.5 s, and in the frequency-change condition also 4.5 s. Aging affected neither frequency nor duration of MMN with the 0.5 s ISI. This finding indicates that automatic stimulus discrimination per se is not impaired with normal aging. However, with a 4.5-s ISI the MMN/N2b-complex attenuated significantly more in the older than younger subjects. This suggests that the stimulus trace decays faster or that involuntary attention switching is less sensitive with aging.     

Acute Kidney Injury Following Aortic Valve Replacement in Patients Without Chronic Kidney Disease

BackgroundThe data on acute kidney injury (AKI) in patients without chronic kidney disease (CKD) after transcatheter aortic valve replacement (TAVR) are limited. The study sought to compare the incidence of AKI and its impact on 5-year mortality after TAVR and surgical aortic valve replacement (SAVR) in patients without CKD.MethodsThis registry included data from 6463 consecutive patients who underwent TAVR or SAVR. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. For sensitivity analysis, propensity-score matching between TAVR and SAVR was performed.ResultsThe study included 4555 consecutive patients (TAVR, n = 1215 and SAVR, n = 3340) without CKD. Propensity-score matching identified 542 pairs. Patients who underwent TAVR had a significantly lower incidence of AKI in comparison to those who underwent SAVR (unmatched 4.7% vs 16.4%, P < 0.001, multivariable analysis: odds ratio, 0.29, 95% confidence interval [CI], 0.20-0.41; matched 5.9% vs 19.0%, P < 0.001). Patients with AKI had significantly increased 5-year mortality compared with those without AKI (unmatched 36.0% vs 19.1%, log-rank P < 0.001; matched 36.3% vs 24.0%, log-rank P < 0.001). The adjusted hazard ratios for 5-year mortality were 1.58 (95% CI, 1.20-2.08) for AKI grade 1, 3.27 (95% CI, 2.09-5.06) for grade 2, and 4.82 (95% CI, 2.93-8.04) for grade 3.ConclusionsTAVR in patients without CKD was associated with a significantly less frequent incidence of AKI compared with SAVR. AKI significantly increased the risk of 5-year mortality after either TAVR or SAVR, and increasing severity of AKI was incrementally associated with 5-year mortality.     

Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents

This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer's disease (AD). Forty-seven 40–80-year-old NL received positron emission tomography (PET) with ¹¹C-Pittsburgh compound B (PiB) and 18F-fluoro-2-deoxy-d-glucose (FDG). These included 19 NL with a maternal history (MH), 12 NL with a paternal history (PH), and 16 NL with negative family history of AD (NH). Automated regions of interest, statistical parametric mapping, voxel-wise intermodality correlations, and logistic regressions were used to examine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios across groups. The MH group showed higher PiB retention and lower metabolism in AD regions compared with NH and PH, which were negatively correlated in posterior cingulate, frontal, and parieto-temporal regions (Pearson r ≤ −0.57, p ≤ 0.05). No correlations were observed in NH and PH. The combination of Aβ deposition and metabolism yielded accuracy ≥ 69% for MH vs. NH and ≥ 71% for MH vs. PH, with relative risk = 1.9–5.1 (p values < 0.005). NL individuals with AD-affected mothers show co-occurring Aβ increases and hypometabolism in AD-vulnerable regions, suggesting an increased risk for AD.     

A Post‐Hoc Comparison of the Utility of Sanger Sequencing and Exome Sequencing for the Diagnosis of Heterogeneous Diseases

The advent of massive parallel sequencing is rapidly changing the strategies employed for the genetic diagnosis and research of rare diseases that involve a large number of genes. So far it is not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. The current yield of this traditional diagnostic approach depends on a complex of factors that include gene‐specific phenotype traits, and the relative frequency of the involvement of specific genes. To gauge the impact of the paradigm shift that is occurring in molecular diagnostics, we assessed traditional Sanger‐based sequencing (in 2011) and exome sequencing followed by targeted bioinformatics analysis (in 2012) for five different conditions that are highly heterogeneous, and for which our center provides molecular diagnosis. We find that exome sequencing has a much higher diagnostic yield than Sanger sequencing for deafness, blindness, mitochondrial disease, and movement disorders. For microsatellite‐stable colorectal cancer, this was low under both strategies. Even if all genes that could have been ordered by physicians had been tested, the larger number of genes captured by the exome would still have led to a clearly superior diagnostic yield at a fraction of the cost.     

Cone beam computed tomography (CBCT) for diagnosis and treatment planning in periodontology: systematic review update

Clinical Oral Investigations - To update the findings of a systematic review from the year 2016 on the evidence for the accuracy and potential benefits of cone beam computed tomography (CBCT) in...