1,359 research outputs found
Mortality after emergency department intubation
Introduction The purpose of this study is to identify the rate of emergency department (ED) intubation and the mortality associated with ED intubation. Methods We conducted a retrospective chart review of all patients intubated in the ED between 1 January 2004 an
Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly
Introduction: Periodontal disease is a chronic, inflammatory bacterial dysbiosis that is associated with both Alzheimer's disease (AD) and Down syndrome. /
Methods: A total of 48 elderly cognitively normal subjects were evaluated for differences in subgingival periodontal bacteria (assayed by 16S rRNA sequencing) between cerebrospinal fluid (CSF) biomarker groups of amyloid and neurofibrillary pathology. A dysbiotic index (DI) was defined at the genus level as the abundance ratio of known periodontal bacteria to healthy bacteria. Analysis of variance/analysis of covariance (ANOVA/ANCOVA), linear discriminant effect‐size analyses (LEfSe) were used to determine the bacterial genera and species differences between the CSF biomarker groups. /
Results: At genera and species levels, higher subgingival periodontal dysbiosis was associated with reduced CSF amyloid beta (Aβ)42 (P = 0.02 and 0.01) but not with P‐tau. /
Discussion: We show a selective relationship between periodontal disease bacterial dysbiosis and CSF biomarkers of amyloidosis, but not for tau. Further modeling is needed to establish the direct link between oral bacteria and Aβ
Dynamical tunneling in molecules: Quantum routes to energy flow
Dynamical tunneling, introduced in the molecular context, is more than two
decades old and refers to phenomena that are classically forbidden but allowed
by quantum mechanics. On the other hand the phenomenon of intramolecular
vibrational energy redistribution (IVR) has occupied a central place in the
field of chemical physics for a much longer period of time. Although the two
phenomena seem to be unrelated several studies indicate that dynamical
tunneling, in terms of its mechanism and timescales, can have important
implications for IVR. Examples include the observation of local mode doublets,
clustering of rotational energy levels, and extremely narrow vibrational
features in high resolution molecular spectra. Both the phenomena are strongly
influenced by the nature of the underlying classical phase space. This work
reviews the current state of understanding of dynamical tunneling from the
phase space perspective and the consequences for intramolecular vibrational
energy flow in polyatomic molecules.Comment: 37 pages and 23 figures (low resolution); Int. Rev. Phys. Chem.
(Review to appear in Oct. 2007
Towards the clinical implementation of pharmacogenetics in bipolar disorder.
BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD
Association of Vitamin B12 Deficiency with Fatigue and Depression after Lacunar Stroke
Background: In lacunar stroke patients vitamin B12 deficiency is often found and a relationship with the degree of periventricular white matter lesions (pWMLs) is suggested. Given the known relationships between WMLs and depression and between depression and fatigue after stroke, we studied both depression and fatigue in lacunar stroke patients with and without vitamin B12 deficiency. Methods: In 40 first-ever lacunar stroke patients vitamin B12 levels were determined and self-report questionnaires for fatigue and depression were completed three months after stroke. Results: Lacunar stroke patients with vitamin B12 deficiency (N = 13) reported significantly more fatigue (90.7 versus 59.4; p =.001) and depressive symptoms (6.62 versus 3.89; p,.05) than those without (N = 27). In regression analyses, vitamin B12 deficiency was significantly and independently associated with the presence of severe fatigue and clinically significant depression. Conclusions: Our preliminary results suggest a relationship between vitamin B12 deficiency and increased levels of fatigue and depression in lacunar stroke patients. If these findings could be replicated in a larger and general stroke sample, thi
Plasma tau complements CSF tau and P-tau in the diagnosis of Alzheimer's disease
Introduction: Plasma tau may be an accessible biomarker for Alzheimer’s disease (AD), but the
correlation between plasma and cerebrospinal fluid (CSF) tau and the value of combining plasma
tau with CSF tau and phospho-tau (P-tau) are still unclear.
Methods: Plasma-tau, CSF-tau, and P-tau were measured in 97 subjects, including elderly cognitively normal controls (n 5 68) and patients with AD (n 5 29) recruited at the NYU Center
for Brain Health, with comprehensive neuropsychological and magnetic resonance imaging
evaluations.
Results: Plasma tau was higher in patients with AD than cognitively normal controls (P , .001,
area under the receiver operating characteristic curve 5 0.79) similarly to CSF tau and CSF
P-tau and was negatively correlated with cognition in AD. Plasma and CSF tau measures
were poorly correlated. Adding plasma tau to CSF tau or CSF P-tau significantly increased
the areas under the receiver operating characteristic curve from 0.80 and 0.82 to 0.87 and
0.88, respectively.
Discussion: Plasma tau is higher in AD independently from CSF-tau. Importantly, adding plasma tau
to CSF tau or P-tau improves diagnostic accuracy, suggesting that plasma tau may represent a useful
biomarker for AD, especially when added to CSF tau measures
A Novel Family of Toxoplasma IMC Proteins Displays a Hierarchical Organization and Functions in Coordinating Parasite Division
Apicomplexans employ a peripheral membrane system called the inner membrane complex (IMC) for critical processes such as host cell invasion and daughter cell formation. We have identified a family of proteins that define novel sub-compartments of the Toxoplasma gondii IMC. These IMC Sub-compartment Proteins, ISP1, 2 and 3, are conserved throughout the Apicomplexa, but do not appear to be present outside the phylum. ISP1 localizes to the apical cap portion of the IMC, while ISP2 localizes to a central IMC region and ISP3 localizes to a central plus basal region of the complex. Targeting of all three ISPs is dependent upon N-terminal residues predicted for coordinated myristoylation and palmitoylation. Surprisingly, we show that disruption of ISP1 results in a dramatic relocalization of ISP2 and ISP3 to the apical cap. Although the N-terminal region of ISP1 is necessary and sufficient for apical cap targeting, exclusion of other family members requires the remaining C-terminal region of the protein. This gate-keeping function of ISP1 reveals an unprecedented mechanism of interactive and hierarchical targeting of proteins to establish these unique sub-compartments in the Toxoplasma IMC. Finally, we show that loss of ISP2 results in severe defects in daughter cell formation during endodyogeny, indicating a role for the ISP proteins in coordinating this unique process of Toxoplasma replication
Citrobacter freundii infection after acute necrotizing pancreatitis in a patient with a pancreatic pseudocyst: a case report
<p>Abstract</p> <p>Introduction</p> <p>Infections are the most frequent and severe complications of acute necrotizing pancreatitis with a mortality rate of up to 80 percent. Although experimental and clinical studies suggest that the microbiologic source of pancreatic infection could be enteric, information in this regard is controversial.</p> <p>Case presentation</p> <p>We describe a <it>Citrobacter freundii </it>isolation by endoscopy ultrasound fine needle aspiration in a 80-year-old Caucasian man with pancreatic pseudocyst after acute necrotizing pancreatitis.</p> <p>Conclusion</p> <p>Our case report confirms that this organism can be recovered in patients with a pancreatic pseudocyst. On-site cytology feedback was crucial to the successful outcome of this case as immediate interpretation of the fine needle aspiration sample directed the appropriate cultures and, ultimately, the curative therapy. To the best of our knowledge, this is the first reported case of isolated pancreatic <it>C. freundii </it>diagnosed by endoscopy ultrasound fine needle aspiration.</p
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