Early Diagnosis of Alzheimer's disease by NIRF Spectroscopy and Nuclear Medicine-v.4.0

There is an urgent need for the early detection of diseases such as Alzheimer’s (AD) and Cancers in order to enable their successful treatment. Cancer is the second major cause of death after Heart Disease, and AD is the third major cause of death with major, human and financial/economics trillion dollar consequences for the society. Nuclear Medicine is concerned with applications in Medicine of Nuclear Science and Engineering techniques and knowledge. Three major Nuclear Medicine techniques that are established for diagnostic and research purposes are: Positron Emission Tomography (PET) and CAT/CT, Nuclear Magnetic Resonance Imaging (NMRI/MRI). However, these three techniques have also major limitations in terms of either cost or image resolution, as well as patient irradiation in the case of CAT/CT and PET. On the other hand, Near Infrared Chemical Imaging Microspectroscopy and certain Fluorescence spectroscopic techniques are capable of single cancer cell and/or single molecule detection and/or imaging. Such powerful capabilities, combined with low cost of diagnostics, make these novel techniques very attractive means for early detection of diseases such as cancer and Alzheimer’s, that are promising to reduce the fatality rate of patients through adequate diagnosis and treatment of such diseases at early stages. 
Currently NIH provides only inadequate funding for the clinical and research aspects of these novel investigation and clinical diagnostic techniques by FT-NIRS and Fluorescence spectrocopy for early detection of Alzheimer’s and Cancers.
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Early Diagnosis of Alzheimer's Disease by NIRF Spectroscopy\ud and Nuclear Medicine\ud

Novel approaches to Early Diagnosis of Alzheimer's Disease by NIRF Spectroscopy and Nuclear Medicine are presented and related cognitive, as well as molecular and cellular, models are critically evaluated.\u

Early Diagnosis of Alzheimer's disease by NIRF Spectroscopy and Nuclear Medicine

There is an urgent need for the early detection of diseases such as Alzheimer’s (AD) and Cancers in order to enable their successful treatment. Cancer is the second major cause of death after Heart Disease, and AD is the third major cause of death with major, human and financial/economics trillion dollar consequences for the society. Nuclear Medicine is concerned with applications in Medicine of Nuclear Science and Engineering techniques and knowledge. Three major Nuclear Medicine techniques that are established for diagnostic and research purposes are: Positron Emission Tomography (PET) and CAT/CT, Nuclear Magnetic Resonance Imaging (NMRI/MRI). However, these three techniques have also major limitations in terms of either cost or image resolution, as well as patient irradiation in the case of CAT/CT and PET. On the other hand, Near Infrared Chemical Imaging Microspectroscopy and certain Fluorescence spectroscopic techniques are capable of single cancer cell and/or single molecule detection and/or imaging. Such powerful capabilities, combined with low cost of diagnostics, make these novel techniques very attractive means for early detection of diseases such as cancer and Alzheimer’s, that are promising to reduce the fatality rate of patients through adequate diagnosis and treatment of such diseases at early stages. 
Currently NIH provides only inadequate funding for the clinical and research aspects of these novel investigation and clinical diagnostic techniques by FT-NIRS and Fluorescence spectrocopy for early detection of Alzheimer's and Cancers

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Modelling the future of the Hawaiian honeycreeper : an ecological and epidemiological problem

The Hawaiian honeycreeper (Drepanididae) faces the threat of extinction; this is believed to be due primarily to predation from alien animals, endemic avian malaria (Plasmodium relictum) and climate change. A deterministic SI modelling approach is developed, incorporating these three factors and a metapopulation approach in conjunction with a quasi-equilibrium assumption to simplify the vector populations. This enables the qualitative study of the behaviour of the system. Numerical results suggest that although (partial) resistance to avian malaria may be advantageous for individual birds, allowing them to survive infection, this allows them to become carriers of infection and hence greatly increases the spread of this disease. Predation obviously reduces the life-expectancy of honeycreepers, but in turn this reduces the spread of infection from resistant carriers; therefore the population-level impact of predation is reduced. Various control strategies proposed in the literature are also considered and it is shown that predation control could either help or hinter, depending upon resistance of the honeycreeper species. Captive propagation or habitat restoration may be the best feasible solution to the loss of both heterogeneity within the population and the loss of the species as a whole