Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man.

We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.

Deep Learning-Based Device-Free Localization Scheme for Simultaneous Estimation of Indoor Location and Posture Using FMCW Radars.

Indoor device-free localization (DFL) systems are used in various Internet-of-Things applications based on human behavior recognition. However, the usage of camera-based intuitive DFL approaches is limited in dark environments and disaster situations. Moreover, camera-based DFL schemes exhibit certain privacy issues. Therefore, DFL schemes with radars are increasingly being investigated owing to their efficient functioning in dark environments and their ability to prevent privacy issues. This study proposes a deep learning-based DFL scheme for simultaneous estimation of indoor location and posture using 24-GHz frequency-modulated continuous-wave (FMCW) radars. The proposed scheme uses a parallel 1D convolutional neural network structure with a regression and a classification model for localization and posture estimation, respectively. The two-dimensional location information of the target is estimated for localization, and four different postures, namely standing, sitting, lying, and absence, are estimated simultaneously. We experimentally evaluated the proposed scheme and compared its performance with that of conventional schemes under identical conditions. The results indicate that the average localization error of the proposed scheme is 0.23 m, whereas that of the conventional scheme is approximately 0.65 m. The average posture estimation error of the proposed scheme is approximately 1.7%, whereas that of the conventional correlation, CSP, and SVM schemes are 54.8%, 42%, and 10%, respectively.

Susceptibility to cellular stress in PS1 mutant N2a cells is associated with mitochondrial defects and altered calcium homeostasis.

Presenilin 1 (PS1) mutations are the most common cause of familial Alzheimer's disease (FAD). PS1 also plays a role in cellular processes such as calcium homeostasis and autophagy. We hypothesized that mutant presenilins increase cellular vulnerability to stress. We stably expressed human PS1, mutant PS1E280A and mutant PS1Δ9 in mouse neuroblastoma N2a cells. We examined early signs of stress in different conditions: endoplasmic reticulum (ER) stress, calcium overload, oxidative stress, and Aß 1-42 oligomers toxicity. Additionally, we induced autophagy via serum starvation. PS1 mutations did not have an effect in ER stress but PS1E280A mutation affected autophagy. PS1 overexpression influenced calcium homeostasis and generated mitochondrial calcium overload modifying mitochondrial function. However, the opening of the mitochondrial permeability transition pore (MPTP) was affected in PS1 mutants, being accelerated in PS1E280A and inhibited in PS1Δ9 cells. Altered autophagy in PS1E280A cells was neither modified by inhibition of γ-secretase, nor by ER calcium retention. MPTP opening was directly regulated by γ-secretase inhibitors independent on organelle calcium modulation, suggesting a novel direct role for PS1 and γ-secretase in mitochondrial stress. We identified intrinsic cellular vulnerability to stress in PS1 mutants associated simultaneously with both, autophagic and mitochondrial function, independent of Aß pathology.

Comparing the injectate spread and nerve involvement between different injectate volumes for ultrasound-guided greater occipital nerve block at the C2 level: a cadaveric evaluation.

PURPOSE: The spread patterns between different injectate volumes have not yet been investigated in ultrasound-guided greater occipital nerve (GON) block at the C2 level. This cadaveric study was undertaken to compare the spread pattern and nerve involvements of different volumes of dye using this technique. MATERIALS AND METHODS: After randomization, ultrasound-guided GON blocks with 1 or 5 mL dye solution were performed at the C2 level on the right or left side of five fresh cadavers. The suboccipital regions were dissected, and nerve involvement was investigated. RESULTS: Ten injections were successfully completed. In all cases of 5 mL dye, we observed the deeply stained posterior neck muscles, including the suboccipital triangle space. The suboccipital and third occipital nerves, in addition to GONs, were consistently stained when 5-mL dye was used in all injections (100%). Although all GONs were successfully stained in the 1-mL dye cases, three of five injections (60%) concomitantly stained the third occipital nerves. CONCLUSION: The clinical efficacy of this technique using the 5-mL injectate seems unlikely to arise from the blockade of GON alone. Instead, its efficacy likely arises from the blockade of most nerves originating from the dorsal ramus of the upper cervical spinal nerve at the suboccipital area. Even using 1 mL of injectate may not guarantee blockade of the GON alone.

Health status and related factors in farmers by SF-12.

OBJECTIVES: This study was performed to understand farmers' health status by general characteristic, and to find out the related factors. METHODS: All the 984 subjects were interviewed by means of a structured questionnaire and SF-12. Among them, only 812 were eligible for analysis. Statistical methods used included frequency, t-test, ANOVA, binary logistic regression with SPSS 19.0. RESULTS: In binary logistic regression, marital status, smoking, regular exercise and monthly day off were associated with physical component score. Marital status, smoking and score of pesticide protective device wearing were associated with mental component score. CONCLUSIONS: This study suggests that effort to develop health promotion programs for workers of agricultural industry considering these results can improve their perceived health status.

Non-invasive characterization of the adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells by HS-SPME/GC-MS.

A non-invasive method to characterize human mesenchymal stromal cells during adipogenic differentiation was developed for the first time. Seven fatty acid methyl esters (FAMEs), including methyl laurate, methyl myristate, methyl palmitate, methyl linoleate, methyl oleate, methyl elaidate and methyl stearate, were used for characterizing adipogenic differentiation using headspace solid-phase microextraction (HS-SPME) which is a very simple and non-invasive method for the extraction of volatile compounds. Glassware was used for culturing mesenchymal stromal cells rather than the common plasticware to minimize contamination by volatile impurities. The optimal SPME fiber was selected by comparing diverse fibers containing two pure liquid polymers (PDMS and PA) and two porous solids (PDMS/DVB and CAR/PDMS). Using optimized procedures, we discovered that seven FAMEs were only detected in adipogenic differentiated mesenchymal stromal cells and not in the mesenchymal stromal cells before differentiation. These data could support the quality control of clinical mesenchymal stromal cell culture in the pharmaceutical industry in addition to the development of many clinical applications using mesenchymal stromal cells.