Relationships between Extrapyramidal Signs and Cognitive Function in a Community-Dwelling Cohort of Patients with Parkinson's Disease and Normal Elderly Individuals

The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community-dwelling cohort in northern Manhattan, New York City. Fifiy-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia

Relationships between Extrapyramidal Signs and Cognitive Function in a Community-Dwelling Cohort of Patients with Parkinson's Disease and Normal Elderly Individuals

The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community-dwelling cohort in northern Manhattan, New York City. Fifiy-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia

Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury.

AimThe activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury.MethodsEHD2-sc-mTNFR2 , an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation.ResultsThe activation of TNFR2 protected neurons from glutamate-mediated excitotoxicity through the activation of phosphoinositide-3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2-sc-mTNFR2 , but higher levels of neurofilament H and 2', 3'-cyclic-nucleotide 3'-phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation.ConclusionThe activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation

Mesophotic fish communities of the ancient coastline in Western Australia

Marine diversity across the Australian continental shelf is shaped by characteristic benthic habitats which are determined by geomorphic features such as paleoshorelines. In north-western Australia there has been little attention on the fish communities that inhabit an ancient coastline at ~125 m depth (the designated AC125), which is specified as a key ecological feature (KEF) of the region and is thought to comprise hard substrate and support enhanced diversity. We investigated drivers of fish species richness and assemblage composition spanning six degrees of latitude along sections of the ancient coastline, categorised as ‘on’ and ‘off’ the AC125 based on depth, across a range of habitats and seafloor complexity (~60–180 m depth). While some surveyed sections of the AC125 had hard bottom substrate and supported enhanced fish diversity, including over half of the total species observed, species richness and abundance overall were not greater on the AC125 than immediately adjacent to the AC125. Instead, depth, seafloor complexity and habitat type explained patterns in richness and abundance, and structured fish assemblages at both local and broad spatial scales. Fewer fishes were associated with deep sites characterized by negligible complexity and soft-bottom habitats, in contrast to shallower depths that featured benthic biota and pockets of complex substrate. Drivers of abundance of common species were species-specific and primarily related to sampling Areas, depth and substrate. Fishes of the ancient coastline and adjacent habitats are representative of mesophotic fish communities of the region, included species important to fisheries and conservation, and several species were observed deeper than their currently known distribution. This study provides the first assessment of fish biodiversity associated with an ancient coastline feature, improving our understanding of the function it plays in regional spatial patterns in abundance of mesophotic fishes. Management decisions that incorporate the broader variety of depths and habitats surrounding the designated AC125 could enhance the ecological role of this KEF, contributing to effective conservation of fish biodiversity on Australia’s north west shelf

Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer

Background: While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue. Methods: We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread. Results: We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease. Conclusions: Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease

Chlamydophila (Chlamydia) pneumoniae promotes Ab 1-42 amyloid processing in Neuronal Cells: A Pathogenic Trigger for Alzheimer\u27s Disease

Background: Previously, our laboratory identified Chlamydophila (Chlamydia) pneumoniae (Cpn) in autopsied sporadic AD brains. Furthermore, we have developed a BALB/c mouse model that demonstrated infection-induced amyloid plaques similar to those found in AD, and demonstrated that Cpn infection of neuronal cells inhibited apoptotic pathways of cell death. Hypothesis: Our current studies address whether infection with Cpn in neuronal cells triggers abnormal cleavage of the beta amyloid precursor protein (bAPP) into Ab1-42, thereby contributing to amyloid plaque formation characteristic of the pathology identified in AD. Materials and Methods: Human neuroblastoma cells were infected with the respiratory strain AR39 Cpn in vitro, then amyloid processing was analyzed and quantitated using immunocytochemistry, Western blotting and ELISA assays. Results: Cpn was shown to infect neuronal cells and induce intracellular amyloid processing. Cpn infection yielded cytoplasmic labeling of Ab 1-42 that was increased relative to uninfected cells. The ELISA assay revealed that in neuronal cell lysates, Ab 1-42 in the infected cells was increased 3 to 16-fold over the uninfected cells, from 24 to 72hr post infection. Western blot analysis confirmed an increase in Ab 1-42 in the infected neuronal cell lysates. Conclusions: These data suggest that infection of neuronal cells with Chlamydophila (Chlamydia) pneumoniae alters the processing of bAPP, thereby producing Ab1-42. Therefore, these studies and previous research reported by our laboratory support the implication of Cpn as a pathogenic agent in perpetuating the hallmark amyloid plaque formations observed in AD. This concept holds major therapeutic considerations for future studies.https://digitalcommons.pcom.edu/posters/1004/thumbnail.jp

Pro-inflammatory flagellin proteins of prevalent motile commensal bacteria are variably abundant in the intestinal microbiome of elderly humans

Peer reviewedPublisher PD

From 2000 years of Ganoderma lucidum to recent developments in nutraceuticals

Medicinal mushrooms have been used for centuries as nutraceuticals to improve health and to treat numerous chronic and infectious diseases. One such mushroom is Ganoderma lucidum, commonly known as Lingzhi, a species revered as a medicinal mushroom for treating assorted diseases and prolonging life. The fungus is found in diverse locations, and this may have contributed to confusion regarding the correct taxonomic classification of the genus Ganoderma. G. lucidum was first used to name a specimen found in England and thereafter was naively applied to a different Ganoderma species found in Asia, commonly known as Chinese Lingzhi. Despite the taxonomic confusion, which has largely been uncorrected, the popularity of Lingzhi has escalated across the globe. The current taxonomic situation is now discussed accurately in this Special Issue on Ganoderma. Today it is a multi-billion dollar industry wherein Lingzhi is cultivated or collected from the wild and consumed as a tea, in alcoholic beverages, and as a nutraceutical to confer numerous health benefits. Consumption of nutraceuticals has grown in popularity, and it is becoming increasingly important that active ingredients be identified and that suppliers make substantiated health claims about their products. The objective of this article is to present a review of G. lucidum over the past 2000 years from prized ancient herbal remedy to its use in nutraceuticals and to the establishment of a 2.5 billion $ (US) industry.NZ Focus to BK, MPG and LRF is acknowledged. YX was funded by a Phyllis Paykel Memorial Scholarship, and KSB and LRF were supported by the Auckland Cancer Society Research Centre

New targets for overactive bladder-ICI-RS 2109

Aim: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms. Methods: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB. Results: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide–dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1, TRPV4, TRPA1, and TRPM4) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca2+-activated K+ channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-β pathway—the canonical fibrosis pathway. Conclusions: The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor