Radio Signal Sensing and Signal Processing to Monitor Behavioral Symptoms in Dementia: A Case Study.

OBJECTIVES: Alzheimer's Disease (AD)-related behavioral symptoms (i.e. agitation and/or pacing) develop in nearly 90% of AD patients. In this N = 1 study, we provide proof-of-concept of detecting changes in movement patterns that may reflect underlying behavioral symptoms using a highly novel radio sensor and identifying environmental triggers. METHODS: The Emerald device is a Wi-Fi-like box without on-body sensors, which emits and processes radio-waves to infer patient movement, spatial location and activity. It was installed for 70 days in the room of patient 'E', exhibiting agitated behaviors. RESULTS: Daily motion episode aggregation revealed motor activity fluctuation throughout the data collection period which was associated with potential socio-environmental triggers. We did not detect any adverse events attributable to the use of the device. CONCLUSION: This N-of-1 study suggests the Emerald device is feasible to use and can potentially yield actionable data regarding behavioral symptom management. No active or potential device risks were encountered.

The indispensable role of CCR5 for in vivo suppressor function of tumor-derived CD103+ effector/memory regulatory T cells.

CD103 is a marker for identification of effector/memory regulatory T cells (Tregs). CD103(+) Tregs are potent suppressors of tissue inflammation in several infectious diseases, autoimmune diseases, and cancers. However, the underlying mechanisms for this potent suppression ability remain unclear. The current study was designed to clarify this issue. Unexpectedly, we found both CD103(+) and CD103(-) Tregs had similar suppression capacity in vitro. We then chose a murine tumor model for investigation of the in vivo behavior of these Tregs. The suppression ability in vivo against the anti-tumor ability of CD8(+) T cells was restricted to CD103(+) Tregs although both Tregs had equal in vitro suppression ability. In addition, CD103(+) Tregs expressed significantly higher levels of CCR5 than those of CD103(-) Tregs and accumulated more in tumors than did CD103(-) Tregs. Furthermore, blockade of CCR5 signaling, either by CCR5(-/-)CD103(+) Tregs or by CCL5 knockdown tumor, could reduce the migration of CD103(+) Tregs into tumors and impair their in vivo suppression ability. In conclusion, these results indicate that the potent in vivo suppression ability of CD103(+) Tregs is due to the tissue-migration ability through CCR5 expression.

The Aerodynamic Effect of Biomimetic Pigeon Feathered Wing on a 1-DoF Flapping Mechanism.

This study focused on designing a single-degree-of-freedom (1-DoF) mechanism emulating the wings of rock pigeons. Three wing models were created: one with REAL feathers from a pigeon, and the other two models with 3D-printed artificial remiges made using different strengths of material, PLA and PETG. Aerodynamic performance was assessed in a wind tunnel under both stationary (0 m/s) and cruising speed (16 m/s) with flapping frequencies from 3.0 to 6.0 Hz. The stiffness of remiges was examined through three-point bending tests. The artificial feathers made of PLA have greater rigidity than REAL feathers, while PETG, on the other hand, exhibits the weakest strength. At cruising speed, although the artificial feathers exhibit more noticeable feather splitting and more pronounced fluctuations in lift during the flapping process compared to REAL feathers due to the differences in weight and stiffness distribution, the PETG feathered wing showed the highest lift enhancement (28% of pigeon body weight), while the PLA feathered wing had high thrust but doubled drag, making them inefficient in cruising. The PETG feathered wing provided better propulsion efficiency than the REAL feathered wing. Despite their weight, artificial feathered wings outperformed REAL feathers in 1-DoF flapping motion. This study shows the potential for artificial feathers in improving the flight performance of Flapping Wing Micro Air Vehicles (FWMAVs).

Therapeutic Role of Inducible Nitric Oxide Synthase Expressing Myeloid-Derived Suppressor Cells in Acetaminophen-Induced Murine Liver Failure.

Background: Acetaminophen (APAP) overdose is one of the major etiologies of liver failure. Hepatocyte necrosis induced by toxic metabolites of APAP can activate proinflammatory responses, including elastase-expressing neutrophils, to exacerbate liver injury. Myeloid-derived suppressor cells (MDSCs) increased in inflammation can inhibit proinflammatory responses. Our aim is to investigate the role of MDSC in APAP-induced liver failure and the possible therapeutic application. Methods: BLAB/c mice were injected with a sublethal/lethal dose of APAP as the murine model of liver failure. MDSCs were defined as CD11b+Gr-1+ cells with the ability of T-cell suppression. Results: A sublethal challenge of APAP could increase the intrahepatic MDSC and protect mice against subsequent lethal challenge of APAP, lipopolysaccharide (LPS)/D-galatosamine or concanavalin A. This protection was lost if MDSCs were depleted and inducible nitric oxide synthase (iNOS) was the key molecule in this MDSC-mediated protection. Taking advantage of these observations, different bone marrow-derived MDSCs (BM-MDSCs) were generated. Among different cytokine-treated BM-MDSCs, tumor necrosis factor alpha/LPS-primed MDSCs (TNF-α/LPS MDSCs) had the strongest liver-protection ability after adoptive transfer. Further mechanistic explorations showed, iNOS-expressing TNF-α/LPS MDSCs induced the apoptosis of activated neutrophil and decreased the intrahepatic infiltration of elastase-expressing neutrophil. Moreover, we generated MDSCs from human peripheral blood mononuclear cells (PBMCs) with similar phenotype. Conclusion: We demonstrated the protective role of MDSCs and therapeutic effect of TNF-α/LPS MDSCs in APAP-induced liver failure. MDSC might protect against the APAP-induced liver failure by reducing the intrahepatic infiltration of activated neutrophil to limit inflammation. Therefore, a therapeutic role of MDSCs for APAP-induced liver failure was proposed.

Passive Monitoring at Home: A Pilot Study in Parkinson Disease.

We conducted a pilot study using a passive radio-wave-based home monitor in individuals with Parkinson disease (PD) with a focus on gait, home activity, and time in bed. We enrolled 7 ambulatory individuals to have the device installed in the bedroom of their homes over 8 weeks and performed standard PD assessments at baseline. We evaluated the ability of the device to objectively measure gait and time in bed and to generate novel visualizations of home activity. We captured 353 days of monitoring. Mean gait speed (0.39-0.78 m/s), time in bed per day (4.4-12.1 h), and number (1.4-5.9) and duration (15.0-49.8 min) of nightly awakenings varied substantially across and within individuals. Derived gait speed correlated well with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale total (r = -0.88, p = 0.009) and motor sub-score (r = -0.95, p = 0.001). Six of the seven participants agreed that their activity was typical and indicated a willingness to continue monitoring. This technology provided promising new insights into the home activities of those with PD and may be broadly applicable to other chronic conditions.

Induction of liver-specific intrahepatic myeloid cells aggregation expands CD8 T cell and inhibits growth of murine hepatoma.

Toll-Like Receptor 9 (TLR9) stimulation selectively triggers the formation of a cell cluster termed intrahepatic myeloid aggregation for T cell expansion" (iMATE) in a mouse chronic viral hepatitis model. iMATE expands cytotoxic T cells and controls viral hepatitis infection. The liver-specific immune response prompted this investigation of whether the effect could control tumor growth in the murine hepatic tumor model. Murine hepatic BNL cells were used to establish an orthotropic liver tumor model. We found that intravenous infusion of TLR 9 agonist, CpG oligodeoxynucleotide (ODN) induced iMATE formation in non-tumor parts of liver and suppressed the murine BNL tumor growth. The ratio of intra-tumor CD8+ T cells have increased after CpG ODN. These cells expressed higher levels of effector and checkpoint molecules, and produce more Th1 cytokine upon ex vivo stimulation. The CD11b+Ly6ChiLy6G - subset of CD11b+ myeloid cells in the tumor microenvironment has increased. Both CD11b+Ly6ChiLy6G - and CD11b+Ly6CloLy6G+ subsets expressed higher level of interferon-gamma post CpG ODN treatment, although still presented a suppressive phenotype. Their suppressive ability was decreased, instead, the targeted CD8+ T cell proliferation was promoted at a higher dose of CD11b+Ly6ChiLy6G- cells. The phenomenon was further proven in DEN induced liver tumor model. In conclusion, systemic CpG ODN treatment induced iMATE formation that expanded effector CD8+ T cells to control tumor growth in the mouse hepatic tumor model. This novel strategy provides a new rationale for liver-specific tumor immunotherapy.

Apoptosis of tumor infiltrating effector TIM-3+CD8+ T cells in colon cancer.

TIM-3 functions to enforce CD8+ T cell exhaustion, a dysfunctional state associated with the tolerization of tumor microenvironment. Here we report apoptosis of IFN-γ competent TIM-3+ population of tumor-infiltrating CD8+ T cells in colon cancer. In humans suffering from colorectal cancer, TIM-3+ population is higher in cancer tissue-resident relative to peripheral blood CD8+ T cells. Both the TIM-3+ and TIM-3- cancer tissue-resident CD8+ T cells secrete IFN-γ of comparable levels, although apoptotic cells are more in TIM-3+ compared to TIM-3- population. In mouse CT26 colon tumor model, majority of tumor-infiltrating CD8+ T cells express TIM-3 and execute cytolysis function with higher effector cytokine secretion and apoptosis in TIM-3+ compared to TIM-3- population. The tumor cells secrete galectin-9, which increases apoptosis of tumor-infiltrating CD8+ T cells. Galectin-9/TIM-3 signaling blockade with anti-TIM-3 antibody reduces the apoptosis and in addition, inhibits tumor growth in mice. The blockade increases therapeutic efficacy of cyclophosphamide to treat tumor in mice as well. These results reveal a previously unexplored role of TIM-3 on tumor-infiltrating CD8+ T cells in vivo.