Financial capacity is already significantly impaired in mild AD. Patients with mild AD demonstrate deficits in more complex financial abilities and impairment in most financial activities. Patients with moderate AD demonstrate severe impairment of all financial abilities and activities. The Financial Capacity Instrument has promise as an instrument for assessing domain-level financial activities and task-specific financial abilities in patients with dementia. Arch Neurol. 2000.

Soluble carbon nanotubes are promising materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, however, their effects on male reproduction have not been examined. Here we show that repeated intravenous injections of water-soluble multi-walled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress, and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired after 60 and 90 days. The quantity, quality, and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.

Ewing sarcoma (EWS) is a tumor of the bone and soft-tissue that primarily affects adolescents and young adults. With current therapies, 70% of patients with localized disease survive, but patients with metastatic or recurrent disease have a poor outcome. We found that EWS cell lines are defective in DNA break repair and are sensitive to PARP inhibitors (PARPis). PARPi-induced cytotoxicity in EWS cells was 10- to 1,000-fold higher after administration of the DNA-damaging agents irinotecan or temozolomide. We developed an orthotopic EWS mouse model and performed pharmacokinetic and pharmacodynamic studies using 3 different PARPis that are in clinical development for pediatric cancer. Irinotecan administered on a low-dose, protracted schedule previously optimized for pediatric patients was an effective DNA-damaging agent when combined with PARPis; it was also better tolerated than combinations with temozolomide. Combining PARPis with irinotecan and temozolomide gave complete and durable responses in more than 80% of the mice.

This in vivo PET method provided valid measures of central AChE activity in normal subjects and AD patients. Applied in early AD, it should facilitate inhibitor treatment by confirming central inhibition, optimizing drug dosage, identifying likely responders, and testing surrogate markers of therapeutic response.

Exosomes are a potential source of cancer biomarkers. Probing tumor-derived exosomes can offer a potential non-invasive way to diagnose cancer, assess cancer progression, and monitor treatment responses. Novel molecular methods would facilitate exosome analysis and accelerate basic and clinical exosome research.Methods: A standard gold-coated glass microscopy slide was used to develop a miniaturized affinity-based device to capture exosomes in a target-specific manner with the assistance of low-cost 3-D printing technology. Gold nanorods coated with QSY21 Raman reporters were used as the label agent to quantitatively detect the target proteins based on surface enhanced Raman scattering spectroscopy. The expressions of several surface protein markers on exosomes from conditioned culture media of breast cancer cells and from HER2-positive breast cancer patients were quantitatively measured. The data was statistically analyzed and compared with healthy controls.Results: A miniaturized 17 × 5 Au array device with 2-mm well size was fabricated to capture exosomes in a target-specific manner and detect the target proteins on exosomes with surface enhanced Raman scattering gold nanorods. This assay can specifically detect exosomes with a limit of detection of 2×106 exosomes/mL and analyze over 80 purified samples on a single device within 2 h. Using the assay, we have showed that exosomes derived from MDA-MB-231, MDA-MB-468, and SKBR3 breast cancer cells give distinct protein profiles compared to exosomes derived from MCF12A normal breast cells. We have also showed that exosomes in the plasma from HER2-positive breast cancer patients exhibit significantly (P ≤ 0.01) higher level of HER2 and EpCAM than those from healthy donors.Conclusion: We have developed a simple, inexpensive, highly efficient, and portable Raman exosome assay for detection and protein profiling of exosomes. Using the assay and model exosomes from breast cancer cells, we have showed that exosomes exhibit diagnostic surface protein markers, reflecting the protein profile of their donor cells. Through proof-of-concept studies, we have identified HER2 and EpCAM biomarkers on exosomes in plasma from HER2-positive breast cancer patients, suggesting the diagnostic potential of these markers for breast cancer diagnostics. This assay would accelerate exosome research and pave a way to the development of novel cancer liquid biopsy for cancer detection and monitoring.