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In neurodegenerative disorders including Alzheimer's disease (AD), free radical damage to lipids, carbohydrates, proteins and DNA has been demonstrated to play a key pathogenetic role. In vitro studies have suggested a function of the cellular prion protein (PrPc) in the defense against oxidative stress. Therefore, we investigated the distribution of PrPc immunoreactivity in hippocampus (sectors CA4-CA1), subiculum (Sub), entorhinal (EC), and temporal cortex (TC) in sections from AD, human transmissible spongiform encephalopathy (TSE) and control brains. Compared to control cases, AD brains revealed an increase in the proportion of PrPc-immunoreactive neurons, which was statistically significant in CA2, Sub, and TC. In TSEs, a statistically significant increase of PrPc-immunoreactive neurons was observed in CA2, CA1, Sub, EC, and TC. In conclusion, our data show a striking up-regulation of PrPc in neurodegeneration and provide additional support for the concept that PrPc may be involved in the defense against oxidative stress.

There is a distinctive pattern of hippocampal involvement in Creutzfeldt-Jakob disease (CJD) and evidence for selective vulnerability of GABAergic neurons in experimental and human prion disease. We studied hippocampus and temporal cortex from human CJD and control autopsy brains and surgical cryptogenic temporal lobe epilepsy specimens for distribution and density of parvalbumin (PV) and calbindin-D28K (Cal) -positive neurons that are subpopulations of GABAergic neurons. Pathology was evaluated semiquantitatively in 8 regions in 23 CJD brains for severity of spongiform change, astrogliosis and pathological prion protein deposition. In CJD, pathology was severe in pre-parasubiculum and temporal cortex. and little or absent in CA1–4, PV+ neurons were severely reduced or absent in all cases, whereas Cal+ neurons were largely preserved. In controls, the density of PV+ neurons was highest in pre-parasubiculum and temporal cortex, and lowest in CA1–4. In cTLE, loss of PV+ neurons was seen only in CA1–4. The diffuse and severe loss of PV+ neurons in CJD, and the topographical correlation of tissue lesioning in CJD with density of PV+ neurons in controls suggest selective vulnerability and early loss of this subset of inhibitory neurons in CJD. This might relate to characteristic CJD symptoms such as myoclonus and the distinctive EEG pattern.

Prion diseases are characterized by the accumulation of diffuse and aggregated plaques of protease-resistant prion protein (PrP) in the brains of affected individuals and animals. Whereas prion diseases in animals appear to be almost exclusively transmitted by infection, human prion diseases most often occur sporadically and, to a lesser extent, by inheritance or infection. In the sporadic cases (sporadic Creutzfeld-Jakob disease, sCJD), PrP-containing plaques are infrequent, whereas in transmitted (variant CJD) and inherited (Gerstmann-Straussler-Scheinker Syndrome) cases, plaques are a usual feature. In the current study, representative cases from each of the classes of human prion disease were analyzed for the presence of markers of oxidative damage that have been found in other neurodegenerative diseases. Interestingly, we found that the pattern of deposition of PrP, amyloid-beta, and redox active metals was distinct for the various prion diseases. Whereas 8-hydroxyguanosine has been shown to be increased in sCJD, and inducible NOS is increased in scrapie-infected mice, well-studied markers of oxidative damage that accumulate in the lesions of other neurodegenerative diseases (such as Alzheimer's disease, progressive supranuclear palsy, and Parkinson's disease), such as heme oxygenase-1 and lipid peroxidation, were not found around PrP deposits or in vulnerable neurons. These findings suggest an important distinction in prion-related oxidative stress, indicating that different neurodegenerative pathways are involved in different prion diseases.

Human transmissible spongiform encephalopathies (TSEs) or prion diseases are neurodegenerative disorders of infectious, inherited or sporadic origin and include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), kuru and fatal familial insomnia (FFI). Clinicopathologic features of FFI differ markedly from other human TSEs. Previous studies demonstrated selective neuronal vulnerability of parvalbumin positive (PV+) GABAergic inhibitory interneurons in sporadic CJD and experimental TSEs. In this report we show uniform severe loss of PV+ neurons also in other TSEs such as GSS, kuru, new variant and familial CJD. In contrast, these neurons are mostly well preserved, or only moderately reduced, in FFI. Only PV+ neurons surrounded by isolectin-B4 positive perineuronal nets were severely affected in TSEs, suggesting a factor residing in this type of extracellular matrix around PV+ neurons as modulator for the selective neuronal vulnerability.

Between 1969 and 30 September 1995, 79 Austrian patients had Creutzfeldt-Jakob disease (CJD) diagnosed neuropathologically by necropsy or biopsy. The annual incidence has significantly increased in recent years (average 0.18 per million in 1969-85, and 0.67 per million in 1986-94; estimate for 1995: 1.5 per million). Also, the percentage of patients with CJD over 70 years at death increased significantly until 1989 but is since in decline. There is no regional clustering, familial occurrence, or recognised iatrogenic risk. One patient had a 10 year history of intramuscular injection of purified bovine RNA preparation (Regeneresen) from various organs including the brian. The ages at death are symmetrically distributed around the median of 64 years. The median duration of disease is four months. Most patients (76%) died within six months of onset. Retrospectively, 86% of patients fulfilled clinical criteria of probable or possible CJD. Neuropathology showed the classic triad of spongiform change, astrogliosis, and neuronal loss in most cases. Two cases did not show unequivocal tissue alterations, but anti-PrP immunocytochemistry detected PrP deposits also in these cases. It is concluded that the recent rise in incidence of CJD in Austria most likely reflects increased awareness and diagnosis of CJD rather than a real increase. As bovine spongiform encephalopathy (BSE) has not been reported in Austria, the data do not support a link between a rise in incidence of sporadic CJD and BSE.

PRIMAVERA (process-based climate simulation: advances in high-resolution modelling and European climate risk assessments) was a European Union Horizon 2020 project whose primary aim was to generate advanced and well-evaluated high-resolution global climate model datasets for the benefit of governments, business and society in general. Following consultation with members of the insurance industry, we have used a PRIMAVERA multi-model ensemble to generate a European winter windstorm event set for use in insurance risk analysis, containing approximately 1300 years of windstorm data. The data are available at https://doi.org/10.5281/zenodo.6492182. To create the storm footprints for the event set, the storms in the PRIMAVERA models are identified through tracking. A method is developed to separate the winds from storms occurring in the domain at the same time. The wind footprints are bias corrected and converted to 3 s gusts onto a uniform grid using quantile mapping. The distribution of the number of model storms per season as a function of estimated loss is consistent with re-analysis, as are the total losses per season, and the additional event set data greatly reduce uncertainty on return period magnitudes. The event set also reproduces the temporally clustered nature of European windstorms. Since the event set is generated from global climate models, it can help to quantify the non-linear relationship between large-scale climate indices such as the North Atlantic Oscillation (NAO) and windstorm damage. Although we find only a moderate positive correlation between extended winter NAO and storm damage in northern European countries (consistent with re-analysis), there is a large change in risk of extreme seasons between negative and positive NAO states. The intensities of the most severe storms in the event set are, however, sensitive to the gust conversion and bias correction method used, so care should be taken when interpreting the expected damages for very long return periods.

Foodborne diseases have large economic and societal impacts worldwide. To evaluate how the risks of foodborne diseases might change in response to climate change, credible and usable climate information tailored to the specific application question is needed. Global Climate Model (GCM) data generally need to, both, be downscaled to the scales of the application to be usable, and represent, well, the key characteristics that inflict health impacts. This study presents an evaluation of temperature-based heat indices for the Washington D.C. area derived from statistically downscaled GCM simulations for 1971–2000—a necessary step in establishing the credibility of these data. The indices approximate high weekly mean temperatures linked previously to occurrences of Salmonella infections. Due to bias-correction, included in the Asynchronous Regional Regression Model (ARRM) and the Bias Correction Constructed Analogs (BCCA) downscaling methods, the observed 30-year means of the heat indices were reproduced reasonably well. In April and May, however, some of the statistically downscaled data misrepresent the increase in the number of hot days towards the summer months. This study demonstrates the dependence of the outcomes to the selection of downscaled climate data and the potential for misinterpretation of future estimates of Salmonella infections.

Abstract BACKGROUND: We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment. OBJECTIVE: To investigate the long-term (up to 4 years) response rate of this novel treatment. METHODS: Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient. Quality of life, pain, and patient satisfaction were assessed using the Oswestry Disability Index 2.0, Visual Analog Scale (VAS), and International Patient Satisfaction Index. RESULTS: Patients reported a pain reduction from 8.8 to 1.6 (VAS) at 1 year (P < .001), and 13 of 14 patients (92.9%) rated the therapy as effective (International Patient Satisfaction Index score ≤ 2). At 2 years, average pain score was 1.9 (P < .001), and 9 of 10 patients (90.0%) considered the treatment a success. At 3 years, 8 of 9 patients (88.9%) were satisfied with the treatment results, reporting an average VAS of 2.0 (P < .005). At 4 years, 2 of 3 patients were satisfied with the treatment results. CONCLUSION: We have shown for the first time that PNS is a successful long-term therapy for SIJ pain.

While commercial fruit production is a small fraction of the total agricultural output in the United States, it has major economic impacts at the local and regional level. This is particularly true for agricultural sites in the Midwest where the Great Lakes have a moderating influence on climate, allowing for commercial fruit production at relatively high latitudes for a continental location. Tart cherry production is of particular significance in the Great Lakes region. In 2009, 292 million pounds of tart cherries, or 80 percent of the national total, were produced in Michigan, New York, Pennsylvania, and Wisconsin (NASS 2010). Of