Clustering of tau-immunoreactive pathology in chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer’s disease neuropathologic change (ADNC) without CTE. In CTE: (1) all aspects of tau-immunoreactive pathology were clustered and the clusters were frequently regularly distributed parallel to the tissue boundary, (2) clustering was similar in two CTE cases with minimal co-pathology compared with cases with associated ADNC or TDP-43 proteinopathy, (3) in a proportion of cortical gyri, estimated cluster size was similar to that of cell columns of the cortico-cortical pathways, and (4) clusters of the tau-immunoreactive pathology were infrequently spatially correlated with blood vessels. The NFT and NP in ADNC without CTE were less frequently randomly or uniformly distributed and more frequently in defined clusters than in CTE. Hence, the spatial pattern of the tau-immunoreactive pathology observed in CTE is typical of the tauopathies but with some distinct differences compared to ADNC alone. The spread of pathogenic tau along anatomical pathways could be a factor in the pathogenesis of the disease

Dietary and Behavioral Interventions Protect against Age Related Activation of Caspase Cascades in the Canine Brain

Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON – control environment/control diet, AOX– control environment/antioxidant diet, ENR – enriched environment/control diet, AOX/ENR– enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the first to show that lifestyle interventions can regulate caspase pathways in a higher animal model of aging

A fibril-specific, conformation-dependent antibody recognizes a subset of Aβ plaques in Alzheimer disease, Down syndrome and Tg2576 transgenic mouse brain

Beta-amyloid (Aβ) is thought to be a key contributor to the pathogenesis of Alzheimer disease (AD) in the general population and in adults with Down syndrome (DS). Different assembly states of Aβ have been identified that may be neurotoxic. Aβ oligomers can assemble into soluble prefibrillar oligomers, soluble fibrillar oligomers and insoluble fibrils. Using a novel antibody, OC, recognizing fibrils and soluble fibrillar oligomers, we characterized fibrillar Aβ deposits in AD and DS cases. We further compared human specimens to those obtained from the Tg2576 mouse model of AD. Our results show that accumulation of fibrillar immunoreactivity is significantly increased in AD relative to nondemented aged subjects and those with select cognitive impairments (p < 0.0001). Further, there was a significant correlation between the extent of frontal cortex fibrillar deposit accumulation and dementia severity (MMSE r = −0.72). In DS, we observe an early age of onset and age-dependent accumulation of fibrillar OC immunoreactivity with little pathology in similarly aged non-DS individuals. Tg2576 mice show fibrillar accumulation that can be detected as young as 6 months. Interestingly, fibril-specific immunoreactivity was observed in diffuse, thioflavine S-negative Aβ deposits in addition to more mature neuritic plaques. These results suggest that fibrillar deposits are associated with disease in both AD and in adults with DS and their distribution within early Aβ pathology associated with diffuse plaques and correlation with MMSE suggest that these deposits may not be as benign as previously thought

A Method Of Repair Of Thoracic Cage Defects After Separation Of Thoraco-Omphalopagus Twins

Female Thoraco-Omphalopagus Twins Weighing 3,450 G Were Born By Normal, Spontaneous Vaginal Delivery. Though Twin A Was Stable, Twin B Developed Cardiorespiratory Distress Soon After Delivery. Progressive Respiratory Failure Led To Separation At The Age Of 57 Days. In Order To Repair The Large Thoracic Cage Defects A Sheet Of Teflon Felt Was Tailored Into Two 'Tents'. Twin A Who Survived, Had Primary Closure Of The Chest And Abdomen After Extensive Skin Mobilization. Twin B Had A Silon Chimney Inserted In Addition To The Teflon Felt Tent. Both Were Removed 20 Days Post-Operatively Because Of Infection. She Died Of Respiratory Failure 55 Days After Separation.link_to_subscribed_fulltex

Sacrococcygeal Teratoma: Computed Tomography Evaluation

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Why is There Discordance between the Reimbursement of High-Cost ‘Life-Extending’ Pharmaceuticals and Medical Devices? The Funding of Ventricular Assist Devices in Australia

© 2019, Springer Nature Switzerland AG. New health technologies often yield health benefits, but often at a high cost. In Australia, the processes for public reimbursement of high-cost pharmaceuticals and medical devices are different, potentially resulting in inequity in support for new therapies. We explore how reimbursement is different for medical devices compared with pharmaceuticals, including whether higher cost-effectiveness thresholds are accepted for pharmaceuticals. A literature review identified the challenges of economic evaluations for medical devices compared with pharmaceuticals. We used the ventricular assist device as a case study to highlight specific features of medical device funding in Australia. We used existing guidelines to evaluate whether ventricular assist devices would fulfil the requirements for the “Life-Saving Drugs Program”, which is usually reserved for expensive life–extending pharmaceutical treatments of serious and rare medical conditions. The challenges in conducting economic evaluations of medical devices include limited data to support effectiveness, device-operator interaction (surgical experience) and incremental innovations (miniaturisation). However, whilst high-cost pharmaceuticals may be funded by a single source (federal government), the funding of high-cost devices is complex and may be funded via a combination of federal, state and private health insurance. Based on the Life-Saving Drugs Program criteria, we found that ventricular assist devices could be funded by a similar mechanism to that which funds high-cost life-extending pharmaceuticals. This article highlights the complexities of medical device reimbursement. Whilst differences in available evidence affect the evaluation process, differences in funding methods contribute to inequitable reimbursement decisions between medical devices and pharmaceuticals

Perbandingan NaCl 3% dan Manitol pada Cedera Kepala Akibat Trauma di Ruang Rawat Intensif Anak

Latar belakang. Manitol dan NaCL 3% merupakan agen hiperosmolar yang direkomendasikan pada pasien anak dengan cedera kepala akibat trauma. Beberapa penulis memberikan argumen bahwa larutan salin hipertonis lebih efektif, tetapi belum ada konsensus berkaitan dengan indikasi, konsentrasi, dan cara pemberian yang terbaik. Tujuan. Membandingkan pemakaian manitol dan NaCl 3% pada anak dengan cedera kepala akibat trauma yang dirawat di ruang rawat intensif dalam hal lama rawatan, mortalitas, dan gangguan elektrolit. Metode. Penelitian retrospektif dilakukan dengan pengumpulan data rekam medis pasien traumatic brain injury (TBI) yang dirawat di ruang rawat intensif anak RSUP H. Adam Malik selama kurun waktu Juni 2012 sampai dengan Mei 2013. Data dibagi atas dua kelompok, yaitu pasien yang mendapatkan manitol dan NaCl 3% sebagai agen hiperosmolar. Analisis statistik dilakukan dengan Mann Whitney U-test, chisquare, dan fisher exact test. Hasil. Subjek 47 orang pasien TBI, 29 di antaranya mendapatkan manitol dan 18 mendapat NaCl 3%. Perbandingan antara kelompok manitol dan NaCl 3% tidak menunjukkan perbedaan yang bermakna secara statistik dalam hal lama rawatan [(5,79 + 4,37 hari) vs (6,00 + 4,20 hari);p=0,733], mortalitas (44,44% vs 20,69%; p=0,083), dan gangguan elektrolit (37,93% vs 33,33%). Kesimpulan. Tidak ada perbedaan dalam hal lama rawatan, mortalitas dan gangguan elektrolit dengan penggunaan manitol dan NaCl 3% sebagai agen hiperosmolar pada pasien cedera kepala akibat trauma. Dibutuhkan penelitian lebih lanjut dengan metode prospektif dan jumlah sampel yang lebih besar