Medial Temporal Lobe Does Not Tell The Whole Story: Episodic Memory In ‘atypical’ Variants Of Alzheimer’s Disease

Alzheimer’s disease is the most common form of dementia, which is globally epidemic and well-known by the general public. Episodic memory, a conscious recollection of a particular event in spatial and temporal context, is the most prominent deficit in the early stage of clinical amnestic AD, and reflected by the shrinkage of structures in medial temporal lobe (MTL), including the hippocampus. According to Braak staging, tangles begin in the transentorhinal cortex of the MTL, which then spreads to hippocampal subfields, and later to neocortical areas. Cases that are less recognized by the general public are patients with the atypical variants of AD. Interestingly, many of the atypical cases of AD appear to share the same histopathological features with clinical amnestic AD. According to the diagnostic criteria for these atypical variants of AD, episodic memory should be relatively preserved. However, inconsistent reports on the episodic memory performance and the hippocampal involvement in these atypical cases pose challenges for accurately diagnosing these patients. The two kinds of atypical variants of AD that I focused here are logopenic variant of Primary Progressive Aphasia (lvPPA) and posterior cortical atrophy (PCA). The overarching theme of my thesis is to examine 1) whether the atypical cases of AD have episodic memory difficulty, and if so, 2) what brain areas are responsible for this difficulty. Chapter 2 and 3 of the current thesis show that 1) episodic memory difficulty is observed in lvPPA and PCA cases and 2) this impairment is modulated by deficit in other cognitive domains and associated with disease in non-MTL brain regions. This would be consistent with the ‘hippocampal-sparing’ hypothesis that not all AD histopathology begins in the MTL, and these hippocampal-sparing conditions suggest that additional mechanisms must be considered in the genesis of spreading pathology in AD

Neural Correlates of Verbal Episodic Memory and Lexical Retrieval in Logopenic Variant Primary Progressive Aphasia

Objective: Logopenic variant primary progressive aphasia (lvPPA) is commonly associated with Alzheimer's disease (AD) pathology. But lvPPA patients display different cognitive and anatomical profile from the common clinical AD patients, whose verbal episodic memory is primarily affected. Reports of verbal episodic memory difficulty in lvPPA are inconsistent, and we hypothesized that their lexical retrieval impairment contributes to verbal episodic memory performance and is associated with left middle temporal gyrus atrophy.Methods: We evaluated patients with lvPPA (n = 12) displaying prominent word-finding and repetition difficulties, and a demographically-matched cohort of clinical Alzheimer's disease (AD, n = 26), and healthy seniors (n = 16). We assessed lexical retrieval with confrontation naming and verbal episodic memory with delayed free recall. Whole-brain regressions related naming and delayed free recall to gray matter atrophy. Medial temporal lobe (MTL) subfields were examined using high in-plane resolution imaging.Results: lvPPA patients had naming and delayed free recall impairments, but intact recognition memory. In lvPPA, delayed free recall was related to naming; both were associated with left middle temporal gyrus atrophy but not MTL atrophy. Despite cerebrospinal fluid evidence consistent with AD pathology, examination of MTL subfields revealed no atrophy in lvPPA. While AD patients displayed impaired delayed free recall, this deficit did not correlate with naming. Regression analyses related delayed free recall deficits in clinical AD patients to MTL subfield atrophy, and naming to left middle temporal gyrus atrophy.Conclusion: Unlike amnestic AD patients, MTL subfields were not affected in lvPPA patients. Verbal episodic memory deficit observed in lvPPA was unlikely to be due to a hippocampal-mediated mechanism but appeared to be due to poor lexical retrieval. Relative sparing of MTL volume and intact recognition memory are consistent with previous reports of hippocampal-sparing variant cases of AD pathology, where neurofibrillary tangles are disproportionately distributed in cortical areas with relative sparing of the hippocampus. This suggests that AD neuropathology in lvPPA may originate in neuronal networks outside of the MTL, which deviates from the typical Braak staging pattern of spreading pathology in clinical AD

An outbreak of Glasser’s disease from two farms in Malaysia

Haemophilus parasuis is an endemic bacterial pathogen in pig farms worldwide. In this report, we investigated a suspected case of Glasser’s disease in 3-9 weeks old Landrace cross Duroc piglets from two pig farms. The farmers reported the case to the Veterinary Hospital of University Malaysia Kelantan, with the complaint of anorexia, depression and weakness. On physical examination, the piglets were found to be smaller in size and had rough hair coat. Clinical signs included swollen hock joint, labored abdominal breathing and tremors. Post-mortem evaluation of culled moribund piglets showed pneumonic lesions in the lung, polyarthritis of the hock joint, cerebral congestion, meningitis, renal cortical heamorrhage and polyserositis. Histo-pathological examination showed interstitial pneumonia with emphysema, encephalitis, encephalomalacia with gliosis and vacuolar degeneration of the hepatocytes. Bacteriological culture of swab samples from infected organs revealed the growth of satellitic small colonies on blood culture suggestive of H. parasuis. Ceftiofur injection (HIPRA, Malaysia, 3mg kg-1i.m), phenoxymethyl penicillin (Norvatis Animal Health, Australia at 200g T-1 of feed) and amoxicillin (Norvatis Animal Health at 15-30g 100L-1 of water) were effective in reducing morbidity and reversing clinical signs. Prompt diagnosis and treatment of Glasser’s disease in pig farms is paramount in order to curtail its menace and prevent serious economic losses

BOVA is Superior to sPESI in Identification of High Risk Pulmonary Embolism Patients

Introduction: Prognostic models exist for the purpose of stratifying patients with acute pulmonary embolism. Of these, the Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are the most well-known, although more recent composite models, like the BOVA score, are now being studied and implemented. Comparative efficacy of these scores to predict long term mortality is not well established. Methods: We performed a retrospective analysis of all consecutive patients diagnosed with PE using computed tomography scan from 2014-2016 at an urban tertiary-referral medical center. Cox proportional hazard analyses were performed to compare the performance of two prognostic models – sPESI and BOVA – to predict all-cause in-hospital and cumulative one-year mortality. Results: The all-cause in-hospital mortality rate was 6.0%, and cumulative one-year mortality rate was 21.3%. In adjusted analyses, a BOVA score \u3e4 was significantly associated with an increased in-hospital mortality (HR 3.5, 95% CI: 1.4-9.0, p = 0.009) and one-year mortality (HR 2.0, 95% CI: 1.0-3.9, p = 0.04), as compared to a BOVA score \u3c4. However, the sPESI (p = 0.14) did not show a significant association with one-year mortality. In identifying in-hospital mortality, the sPESI had high sensitivity (100%) and low specificity (10.1%), whereas the BOVA score had low sensitivity (20.0%) and high specificity (92.7%). Similar trends were seen for one-year mortality. Conclusion: In this study, a high BOVA score was found to be the best predictor of both short and long-term mortality in PE patients. A low sPESI score identified with high sensitivity patients with low-risk PEs

Integrating Suspended Sediment Flux in Large Alluvial River Channels: Application of a Synoptic Rouse‐Based Model to the Irrawaddy and Salween Rivers

A large portion of freshwater and sediment is exported to the ocean by a small number of major rivers. Many of these megarivers are subject to substantial anthropogenic pressures, which are having a major impact on water and sediment delivery to deltaic ecosystems. Due to hydrodynamic sorting, sediment grain size and composition vary strongly with depth and across the channel in large rivers, complicating flux quantification. To account for this, we modified a semi‐empirical Rouse model, synoptically predicting sediment concentration, grain‐size distribution, and organic carbon (%OC) concentration with depth and across the river channel. Using suspended sediment depth samples and flow velocity data, we applied this model to calculate sediment fluxes of the Irrawaddy (Ayeyarwady) and the Salween (Thanlwin), the last two free‐flowing megarivers in Southeast Asia. Deriving sediment‐discharge rating curves, we calculated an annual sediment flux of urn:x-wiley:jgrf:media:jgrf21236:jgrf21236-math-0001 Mt/year for the Irrawaddy and urn:x-wiley:jgrf:media:jgrf21236:jgrf21236-math-0002 Mt/year for the Salween, together exporting 46% as much sediment as the Ganges‐Brahmaputra system. The mean flux‐weighted sediment exported by the Irrawaddy is significantly coarser (D84 = 193 ± 13 μm) and OC‐poorer (0.29 ± 0.08 wt%) compared to the Salween (112 ± 27 μm and 0.59 ± 0.16 wt%, respectively). Both rivers export similar amounts of particulate organic carbon, with a total of urn:x-wiley:jgrf:media:jgrf21236:jgrf21236-math-0003 Mt C/year, 53% as much as the Ganges‐Brahmaputra. These results underline the global significance of the Irrawaddy and Salween rivers and warrant continued monitoring of their sediment flux, given the increasing anthropogenic pressures on these river basins

Self-Healing Collagen-Based Hydrogel for Brain Injury Therapy

Hydrogels derived from biopolymers, also called biohydrogels, have shown potential for brain injury therapy due to their tunable physical, chemical, and biological properties. Among different biohydrogels, those made from collagen type I are very promising candidates for the reparation of nervous tissues due to its biocompatibility, noncytotoxic properties, injectability, and self-healing ability. Moreover, although collagen does not naturally occur in the brain, it has been demonstrated that collagen type I, which resides in the basal lamina of the subventricular zone in adults, supports neural cell attachment, axonal growth, and cell proliferation due to its intrinsic content of specific cell-signaling domains. This chapter summarizes the most relevant results obtained from both in vitro and in vivo studies using self-healing biohydrogels based on collagen type I as key component in the field of neuroregeneration.University of RegensburgUniversidad de La LagunaMinisterio de Ciencia, Innovación y Universidade

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe