Background: Available drugs for the global Alzheimer disease (AD) epidemic only treat the symptoms without modifying disease progression. Accumulating evidence supports amyloid-β42 (Aβ42)as the key triggering agent in AD, making it the ideal target for disease-modifying therapies. Preclinical studies provided extensive support for passive Aβ42 immunotherapy, leading to human clinical trials with different antibodies. Objective: Examine the status of clinical trials for passive immunotherapy against Aβ42. Methods: We performed a thorough literature review of passive Aβ42 immunotherapy. Results: Ten anti-Aβ42 antibodies targeting lineal or conformational epitopes have been tested in clinical trials. Antibody engineering and appropriate dosing have overcome undesired side effects, leading to increased safety profiles. Unfortunately, few trials have shown cognitive protection, leading to legitimate questions about the utility of Aβ42 as an AD target. There is still hope that solanezumab, aducanumab, and other ongoing trials will identify antibodies, patient subpopulations, and administration protocols, with consistent clinical benefits. Conclusions: Despite the overall disappointing results, there is still hope that Aβ immunotherapy in presymptomatic patients will prevent neuronal loss and provide significant clinical benefits that can be applied to larger populations as preventive therapies. Advances with other targets may soon provide additional therapeutic options for AD with increased efficacy.

This study comprehensively reviews two HFC MAC protocols: Data-Over-Cable Service Interface Specifications (DOCSIS) and IEEE 802.14a. DOCSIS was approved by the ITU as a standard and is supported by many vendors. However, IEEE 802.14a remains a draft due to the delayed standardization process. After briefly introducing the features of HFC networks, the basic operations and mechanisms of these two MAC protocols are then examined. Both standards view an upstream channel as a stream of minislots and have similar mechanisms for upstream bandwidth management, virtual queue, downstream in MPEG-2 format, data-linklayer security, and ranging. However, the standards adopt different mechanisms for upstream access modes, QoS support, and collision resolution. Moreover, the implementation issues over hardware and software design for DOCSIS networks are investigated. This work also identifies the research issues in HFC MAC protocols, particularly allocation and scheduling issues. S U R V E Y S I E E E C O M M U N I C A T I O N S T h e E l e c t r o n i c M a g a z i n e o f O r i g i n a l P e e r -R e v i e w e d S u r v e y A r t i c l e s

The glycosylation of UDP-glucosyltransferases (UGTs) is of great importance in the control and elimination of both endogenous and exogenous toxins. Bm-UGT10286 (UGT86) is the sole provider of UGT activity against the 5-O position of quercetin and directly influences the formation of green pigment in the Bombyx cocoon. To evaluate whether cocoon coloration evolved for mimetic purposes, we concentrated on the expression pattern of Ugt86 and the activities of the enzyme substrates. The expression of Ugt86 was not only detected in the cocoon absorbing and accumulating tissues such as the digestive tube and silk glands, but also in quantity in the detoxification tissues of the malpighian tubes and fat body, as well as in the gonads. As in the green cocoon strains, Ugt86 was clearly expressed in the yellow and white cocoon strains. In vitro, the fusion protein of UGT86 showed quercetin metabolic activity. Nevertheless, Ugt86 expression of 5th instar larvae was not up-regulated in the silk gland by exogenous quercetin. However, it was significantly up-regulated in the digestive tube and gonads (P < 0.05). A similar result was observed in experiments where larvae were exposed to rutin, an insect resistance inducer and growth inhibitor typically found in plants, and to 20-hydroxylecdysone (20E), an insect endocrine and plant source hormone. On the contrary, up-regulated Ugt86 expression was almost nil in larvae exposed to juvenile hormone III (P > 0.05). The results of HPLC revealed that a new substance was formed by mixing 20E with the recombinant UGT86 protein in vitro, indicating that the effect of Ugt86 on 20E was similar to that on exogenous quercetin derived from plant food, and that the effect probably initiated the detoxification reaction against rutin. The conclusion is that the reaction of Ugt86 on the silkworm cocoon pigment quercetin is not the result of active mimetic ecogenesis, but derives from the detoxification of UGTs.

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What Is Known and Objective: The aim of this study was to evaluate the pharmacokinetics of paclitaxel in cancer patients with hypoalbuminemia following paclitaxelcontaining chemotherapy and to provide a reference for the prevention of adverse events (AEs) after paclitaxel administration.Methods: Peripheral blood was collected from cancer patients treated with paclitaxel.The plasma concentration of paclitaxel was determined by ultra-high performance liquid chromatography after 24 ± 8 h of chemotherapy, and individual paclitaxel time above a threshold concentration of 0.05 μmol/L (T c>0.05 ) was calculated using the population pharmacokinetic model. Haematological and non-haematological toxicities were monitored after chemotherapy, and the correlation between different chemotherapy toxicities and T c>0.05 was evaluated using the Prism software.Results and Discussion: The enrolled patients were divided into the hypoalbuminemia group and normal albumin level group. The mean T c>0.05 values in the normal albumin level and hypoalbuminemia groups were 36.89 and 24.93 h, respectively (P < 0.001). The risk of myelosuppression was positively correlated with T c>0.05 . Due to the lower T c>0.05 , the incidences of immediate AEs such as gastrointestinal reactions and rashes were higher in the hypoalbuminemia group than in the normal albumin level group, and the incidences of delayed AEs such as myelosuppression and neurotoxicity were lower in the hypoalbuminemia group.What Is New and Conclusions: Plasma albumin level has a conclusive effect on T c>0.05 , which can predict the potential clinical toxicity of paclitaxel. The study provides a theoretical basis for administration of paclitaxel.