Notes

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health decline in the United States.The present study posits that Alzheimer's disorder is a "fast" disease. This is in sharp contrast to a view, prevailing until now, that Alzheimer's Disease (AD) is a quintessential "slow" disease that develops throughout the life as one prolonged process. According to this view, beta-amyloid (Aβ) is produced and secreted solely by the beta-amyloid precursor protein (βAPP) proteolytic/secretory pathway. As its extracellular levels increase, it triggers neurodegeneration starting relatively early in life. Damages accumulate and manifest, late in life in sporadic Alzheimer's Disease (SAD) cases, as AD symptoms. In familial AD (FAD) cases, where mutations in βAPP gene or in presenilins increase production of either common Aβ isoform or of its more toxic isoforms, neurodegeneration reaches critical threshold sooner and AD symptoms occur earlier in life, mostly in late 40s and 50s. There are currently no preventive AD therapies but if they were available, according to this viewpoint it would be largely futile to ine not susceptible to AD and why only a subset of humans develop the disease. It establishes that Alzheimer's disease is preventable by therapeutic intervention initiated even late in life, details a powerful mechanism underlying the disease, suggests that Aβ produced in the βAPP-independent pathway is retained intracellularly, elaborates why neither BACE inhibition nor Aβ immunotherapy are effective in treatment of AD and why intracellularly retained beta-amyloid could be the primary agent of neuronal death in Alzheimer's disease, necessitates generation of a novel animal AD model capable of producing Aβ via βAPP-independent pathway, proposes therapeutic targets profoundly different from previously pursued components of the βAPP proteolytic pathway, and provides conceptual rationale for design of drugs that could be used not only preemptively but also for treatment and reversal of the early stages of the disease.Thermoresponsive polymers reversibly react to changes in temperature and water content of their environment (i.e., relative humidity, RH). In the present contribution, the thermoresponsiveness of poly(N-vinylcaprolactam) thin films cross-linked by di(ethylene glycol) divinyl ether deposited by initiated chemical vapor deposition are investigated to assess their applicability to sensor and actuator setups. A lower critical solution temperature (LCST) is observed at around 16 °C in aqueous environment, associated with a dramatic change in film thickness (e.g., 200% increase at low temperatures) and refractive index, while only thermal expansion of the polymeric system is found, when ramping the temperature in dry atmosphere. In humid environment, we observed a significant response occurring in low RH (already below 5% RH), with the moisture swelling the thin film (up to 4%), but mainly replacing air in the polymeric structure up to ∼40% RH. Non-temperature-dependent swelling is observed up to 80% RH. Above that, thermoresponsive behavior is also demonstrated to be present in humid environment for the first time, whereas toward 100% RH, film thickness and index appear to approach the values obtained in water at the respective temperatures. The response times are similar in a large range of RH and are faster than the ones of the reference humidity sensor used (i.e., seconds). A sensor/actuator hygromorphic device was built by coating a thin flower-shaped poly(dimethylsiloxane) (PDMS) substrate with the thermoresponsive polymer. The large swelling due to water uptake upon exposure to humid environment at temperatures below the LCST caused the petals to bend, mimicking the capability of plants to respond to environmental stimuli via reversible mechanical motion. Copyright © 2019 American Chemical Society.Background Primary central nervous system lymphoma (PCNSL) is rare and there is limited genomic and immunological information available. Incidental clinical and radiographic responses have been reported in PCNSL patients treated with immune checkpoint inhibitors. Materials and Methods To genetically characterize and ascertain if the majority of PCNSL patients may potentially benefit from immune checkpoint inhibitors, we profiled 48 subjects with PCNSL from 2013 to 2018 with (1) next-generation sequencing to detect mutations, gene amplifications, and microsatellite instability (MSI); (2) RNA sequencing to detect gene fusions; and (3) immunohistochemistry to ascertain PD-1 and PD-L1 expression. Tumor mutational burden (TMB) was calculated using somatic nonsynonymous missense mutations. Results High PD-L1 expression (>5% staining) was seen in 18 patients (37.5%), and intermediate expression (1-5% staining) was noted in 14 patients (29.2%). Sixteen patients (33.3%) lacked PD-L1 expression. PD-1 expression (>1 cell/high-power field) was seen in 12/14 tumors (85.7%), uncorrelated with PD-L1 expression. TMB of greater than or equal to 5 mutations per megabase (mt/Mb) occurred in 41/42 tumors, with 19% (n = 8) exhibiting high TMB (≥17 mt/Mb), 71.4% (n = 30) exhibiting intermediate TMB (7-16 mt/Mb), and 9.5% (n = 4) exhibiting low TMB (≤6 mt/Mb). No samples had MSI. AXL1717 concentration Twenty-six genes showed mutations, most frequently in MYD88 (34/42, 81%), CD79B (23/42, 55%), and PIM1 (23/42, 55%). Among 7 cases tested with RNA sequencing, an ETV6-IGH fusion was found. Overall, 18/48 samples expressed high PD-L1 and 38/42 samples expressed intermediate to high TMB. Conclusions Based on TMB biomarker expression, over 90% of PCNSL patients may benefit from the use of immune checkpoint inhibitors. © The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.Background Ustekinumab was approved for moderate and severe Crohn's disease (CD) in 2016, but little is known about long-term outcomes. Methods A retrospective study evaluated all patients with CD treated with ustekinumab, including patients with reinduction. C-reactive protein (CRP), Harvey-Bradshaw Index (HBI), Short Inflammatory Bowel Disease (SIBDQ), and endoscopy outcomes were collected prospectively. Results Ninety-six patients received ustekinumab, resulting in improvement in CRP, HBI, and SIBDQ scores with 68% endoscopic improvement/remission. link2 Thirty-four patients underwent reinduction, resulting in improved HBI and CRP. Conclusions Ustekinumab in refractory CD results in significant clinical and endoscopic improvement and reinduction may be a viable option to recapture response. © 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.Background Depression is common in patients with inflammatory bowel disease (IBD) and contributes to poor quality of life (QoL). The use of information technology for the remote management of patients with IBD is growing, but little is known about its impact on depressive symptoms (DS) and QoL. We aimed to evaluate the impact of telemedicine on DS and generic QoL in IBD patients. Methods We analyzed data from the Telemedicine for Patients with IBD (TELE-IBD) study. During this 12-month clinical trial, patients were randomized to receive text message-based telemedicine weekly (TELE-IBD W), every other week (TELE-IBD EOW), or to standard care. Depressive symptoms and QoL were assessed over time with the Mental Health Inventory 5 (MHI-5) and the Short Form 12 (SF-12), respectively. We compared the change in MHI-5 and SF-12 (with separate physical (PCS) and mental component summary (MCS) scores) between the study arms. Results A total of 217 participants were included in this analysis. After 1 year, there was no significant difference in the change in MHI-5 (TELE-IBD W +3.0 vs TELE-IBD EOW +0.7 vs standard care +3.4; P = 0.70), MCS (TELE-IBD W +1.4 vs TELE-IBD EOW +1.0 vs standard care +2.5; P = 0.89), and PCS scores (TELE-IBD W +0.4 vs TELE-IBD EOW +0.6 vs standard care +3.7; P = 0.06) between the groups. Conclusions Text message-based telemedicine does not improve DS or QoL when compared with standard care in IBD patients treated at tertiary referral centers. Further studies are needed to determine whether telemedicine improves DS or QoL in settings with few resources. © 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.Background Evidence to support the role of Candida species in oral disease is limited. Often considered a commensal, this opportunistic yeast has been shown to play a role in denture related disease, though whether it is an active participant or innocent bystander remains to be determined. This study sought to understand the role of Candida species alongside the bacterial microbiome in a denture patient cohort, exploring how the microbiology of the denture was affected by oral hygiene practices. Materials and methods In vitro denture cleansing studies were performed on a complex 9-species interkingdom denture biofilm model, with quantitative assessment of retained bacterial and fungal viable bioburdens. Patient hygiene measures were also collected from 131 patients, including OHIP, frequency of denture cleansing, oral hygiene measure and patient demographics. The bacterial microbiome was analysed from each patient, alongside quantitative PCR assessment of ITS (fungal) and 16S (bacterial) bioburden from denturucture and a shift from health to disease when the opportunity arises. © 2019 The Authors.Trauma activity recognition aims to detect, recognize, and predict the activities (or tasks) during a trauma resuscitation. Previous work has mainly focused on using various sensor data including image, RFID, and vital signals to generate the trauma event log. However, spoken language and environmental sound, which contain rich communication and contextual information necessary for trauma team cooperation, are still largely ignored. In this paper, we propose a multimodal attention network (MAN) that uses both verbal transcripts and environmental audio stream as input; the model extracts textual and acoustic features using a multi-level multi-head attention module, and forms a final shared representation for trauma activity classification. We evaluated the proposed architecture on 75 actual trauma resuscitation cases collected from a hospital. We achieved 72.4% accuracy with 0.705 F1 score, demonstrating that our proposed architecture is useful and efficient. These results also show that using spoken language and environmental audio indeed helps identify hard-to-recognize activities, compared to previous approaches. We also provide a detailed analysis of the performance and generalization of the proposed multimodal attention network.Purpose The decision to treat mild obstructive sleep apnea (OSA) often hinges on the presence of subjective daytime sleepiness. This study was done to identify clinical and polysomnographic features which correlate with subjective sleepiness in mild OSA. Methods Utilizing data from the Apnea Positive Pressure Long-term Efficacy Study, 199 participants with mild OSA were identified. Participants were grouped as "sleepy" or "non-sleepy" based on their responses to a question regarding excessive daytime sleepiness, and Epworth Sleepiness Scores. We compared demographic, clinical and baseline polysomnographic data between the groups. Results The prevalence of subjective sleepiness was 74.4%. link3 The sleepy group was younger (46.1 ± 12.6 vs. 53.3 ± 13.1 years, p=0.001), reported lower quality of life (4.5 ± 0.69 vs. 4.9 ± 0.61, p=0.0002), had higher depression scores (5.4 ± 4.7 vs. 3.1 ± 3.5, p=0.003) and reported more naps per week (2.6 ± 2.9 vs. 1.3 ± 1.9, p=0.01). Total sleep time and sleep efficiency were notably higher in the sleepy (254.
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