Abstract
For almost two decades, researchers have observed the preservation of the quantum statistical properties of bosons in a large variety of plasmonic systems. In addition, the possibility of ...preserving nonclassical correlations in light-matter interactions mediated by scattering among photons and plasmons stimulated the idea of the conservation of quantum statistics in plasmonic systems. It has also been assumed that similar dynamics underlie the conservation of the quantum fluctuations that define the nature of light sources. So far, plasmonic experiments have been performed in nanoscale systems in which complex multiparticle interactions are restrained. Here, we demonstrate that the quantum statistics of multiparticle systems are not always preserved in plasmonic platforms and report the observation of their modification. Moreover, we show that optical near fields provide additional scattering paths that can induce complex multiparticle interactions. Remarkably, the resulting multiparticle dynamics can, in turn, lead to the modification of the excitation mode of plasmonic systems. These observations are validated through the quantum theory of optical coherence for single- and multi-mode plasmonic systems. Our findings unveil the possibility of using multiparticle scattering to perform exquisite control of quantum plasmonic systems.
Abstract Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are ...already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42 ) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD.
The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization ...of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid matabolizers (UMs) will need increased drug dosage to obtain therapeutic response. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. In particular, there is important evidence suggesting association between dopamine 2 receptor (D2) polymorphisms (Taq I and -141-C Ins/Del) and a dopamine 3 receptor (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive dyskinesia. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C polymorphism (-759-T/C) in antipsychotic-induced weight gain. Application of this knowledge to clinical practice is slowly gathering pace, with pretreatment determination of individual's drug metabolic rates, via CYP genotyping, leading the field. Genetic determination of patients' metabolic status is expected to bring clinical benefits by helping to adjust therapeutic doses and reduce adverse reactions. Genetic tests for the pretreatment prediction of antipsychotic response, although still in its infancy, have obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered as successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are far from being realized. Further development of genetic tests is required before the concept of tailored treatment can be applied to psychopharmatherapy. This review aims to summarize the key findings from the last decade of research in the field. Current knowledge on genetic prediction of drug metabolic status, general response and drug-induced side effects will be reviewed and future pharmacogenomic and epigenetic research will be discussed.
The current COVID-19 public health crisis, caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has produced a devastating toll both in terms of human life loss and economic ...disruption. In this paper we present a machine-learning algorithm capable of identifying whether a given patient (actually infected or suspected to be infected) is more likely to survive than to die, or vice-versa. We train this algorithm with historical data, including medical history, demographic data, as well as COVID-19-related information. This is extracted from a database of confirmed and suspected COVID-19 infections in Mexico, constituting the official COVID-19 data compiled and made publicly available by the Mexican Federal Government. We demonstrate that the proposed method can detect high-risk patients with high accuracy, in each of four identified clinical stages, thus improving hospital capacity planning and timely treatment. Furthermore, we show that our method can be extended to provide optimal estimators for hypothesis-testing techniques commonly-used in biological and medical statistics. We believe that our work could be of use in the context of the current pandemic in assisting medical professionals with real-time assessments so as to determine health care priorities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two thirds of all persons with late-onset Alzheimer's disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development ...of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer's disease (AD) biomarker changes brain β-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI and cognitive performance in midlife. Fifty-nine 40-60 year-old cognitively normal participants with clinical, neuropsychological, and brain imaging exams at least 2 years apart were examined. These included 41 women 15 premenopausal controls (PRE), 14 perimenopausal (PERI), and 12 postmenopausal women (MENO) and 18 men. We used targeted minimum loss-based estimation to evaluate AD biomarker and cognitive changes. Older age was associated with baseline Aβ and neurodegeneration markers, but not with rates of change in these biomarkers. APOE4 status influenced change in Aβ load, but not neurodegenerative changes. Longitudinally, MENO and PERI groups showed declines in estrogen-dependent memory tests as compared to men (p < .04). Adjusting for age, APOE4 status, and vascular risk confounds, the MENO and PERI groups exhibited higher rates of CMRglc decline as compared to males (p ≤ .015). The MENO group exhibited the highest rate of hippocampal volume loss (p's ≤ .001), and higher rates of Aβ deposition than males (p < .01). CMRglc decline exceeded Aβ and atrophy changes in all female groups vs. men. These findings indicate emergence and progression of a female-specific hypometabolic AD-endophenotype during the menopausal transition. These findings suggest that the optimal window of opportunity for therapeutic intervention to prevent or delay progression of AD endophenotype in women is early in the endocrine aging process.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating neurological disorders, whose complex relationship is not completely understood. Cerebrovascular pathology, a key element in ...both conditions, could represent a mechanistic link between Aβ/tau deposition after TBI and the development of post concussive syndrome, dementia and chronic traumatic encephalopathy (CTE). In addition to debilitating acute effects, TBI-induced neurovascular injuries accelerate amyloid β (Aβ) production and perivascular accumulation, arterial stiffness, tau hyperphosphorylation and tau/Aβ-induced blood brain barrier damage, giving rise to a deleterious feed-forward loop. We postulate that TBI can initiate cerebrovascular pathology, which is causally involved in the development of multiple forms of neurodegeneration including AD-like dementias. In this review, we will explore how novel biomarkers, animal and human studies with a focus on cerebrovascular dysfunction are contributing to the understanding of the consequences of TBI on the development of AD-like pathology.
•Cerebrovascular dysfunction (CVD) is emerging as a key element in the development of neurodegeneration after TBI.•We propose that TBI initiates CVD, accelerating Aβ/tau deposition and leading to neurodegeneration and dementias.•Clarifying this connection will support the development of novel biomarkers and therapeutic approaches for both TBI and AD.
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.
Plasma-tau, CSF-tau, and P-tau were measured in 97 subjects, including elderly cognitively normal controls (n = 68) and patients with AD (n = 29) recruited at the NYU Center for Brain Health, with comprehensive neuropsychological and magnetic resonance imaging evaluations.
Plasma tau was higher in patients with AD than cognitively normal controls (P < .001, area under the receiver operating characteristic curve = 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.
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.
•Both plasma- and CSF-tau are elevated in patients with AD recruited at the NYU Center for Brain Health.•Plasma tau is correlated with cognition, but not with CSF tau, in AD.•Plasma tau increases diagnostic accuracy (AUC) when added to CSF-tau or P-tau.•SIMOA and ELISA assays performed in the same CSF samples are strongly correlated.•Plasma- and CSF-tau measures appear complementary. The reasons warrant further investigation.
One of the main features of Alzheimer's disease (AD) is the severe reduction of the cerebral metabolic rate for glucose (CMRglc). In vivo imaging using positron emission tomography with ...2‐18Ffluoro‐2‐deoxy‐D‐glucose (FDG–PET) demonstrates consistent and progressive CMRglc reductions in AD patients, the extent and topography of which correlate with symptom severity. Increasing evidence suggests that CMRglc reductions occur at the preclinical stages of AD. CMRglc reductions were observed on FDG–PET before the onset of disease in several groups of at‐risk individuals, including patients with mild cognitive impairment (MCI), often a prodrome to AD; presymptomatic individuals carrying mutations responsible for early‐onset familial AD; cognitively normal elderly individuals followed for several years until they declined to MCI and eventually to AD; normal, middle‐aged individuals who expressed subjective memory complaints and were carriers of the apolipoprotein E epsilon‐4 allele, a strong genetic risk factor for late‐onset AD. However, the causes of the early metabolic dysfunction forerunning the onset of AD are not known. An increasing body of evidence indicates a deficient or altered energy metabolism that could change the overall oxidative microenvironment for neurons during the pathogenesis and progression of AD, leading to alterations in mitochondrial enzymes and in glucose metabolism in AD brain tissue. The present paper reviews findings that implicate hypometabolism and oxidative stress as crucial players in the initiation and progression of synaptic pathology in AD.
Many contemporary theories of memory assume that everyone automatically stores temporal contextual information about all types of encountered information, yet most studies on this topic have used ...words and ignored individual differences. Five experiments accumulated evidence that explicit storage of temporal context information does not appear to occur automatically for all people and types of memoranda. We collected judgments of temporal position (memory-for-when) for words (Experiments 1 & 3), faces (Experiments 2A, 3, 4, and 5), and classrooms (Experiments 2B & 3). At the group level, for each of these memoranda memory-for-when was sensitive to the original input position and showed a temporal primacy effect reflecting better memory for position for items near the beginning of the list, indicating some automatic storage of temporal context information. However, memory-for-when was significantly better for words than classrooms, with faces in the middle. Moreover, individuals varied dramatically in their ability to indicate memory-for-when, especially for classrooms where many people performed at or near chance. Taken together, the data suggest that explicit memory-for-when may be dissociable from the more implicit use of temporal contextual information that is theorised to occur during free recall.
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