ALBERT

Description: Background: High shear wet granulation (HSWG) is a shaping process for granulation that has been enhanced for application in the pharmaceutical industry. However, study of HSWG is complex and challenging due to the relatively poor understanding of HSWG, especially for sticky powder-like herbal extracts. Aim: In this study, we used Salvia miltiorrhiza granules to investigate the HSWG process across different scales using quality by design (QbD) approaches. Methods: A Plackett–Burman experimental design was used to screen nine granulation factors in the HSWG process. Moreover, a quadratic polynomial regression model was established based on a Box–Behnken experimental design to optimize the granulation factors. In addition, the scale-up of HSWG was implemented based on a nucleation regime map approach. Results: According to the Plackett–Burman experimental design, it was found that three granulation factors, including salvia ratio, binder amount, and chopper speed, significantly affected the granule size (D50) of S. miltiorrhiza in HSWG. Furthermore, the results of the Box–Behnken experimental design and validation experiment showed that the model successfully captured the quadratic polynomial relationship between granule size and the two granulation factors of salvia ratio and binder amount. At the same experiment points, granules at all scales had similar size distribution, surface morphology, and flow properties. Conclusions: These results demonstrated that rational design, screening, optimization, and scale-up of HSWG are feasible using QbD approaches. This study provides a better understanding of HSWG process under the paradigm of QbD using S. miltiorrhiza granules.

Description: Liveability is an indispensable component in future city planning and is practically linked with the health status of individuals and communities. However, there was nor comprehensive and universal district-level framework for assessing liveability due to geospatial and social discrepancies among different countries. In this study, using Hong Kong, a highly dense and international city as an example, the Liveability and Health Index (LHI-HK) consisting of 30 indicators was established, with 21 of them related to education, economy, housing, walkability/transport, environment, and health facilities aspects, while the health conditions of citizens in individual districts were examined by other 9 indicators. Respective scoring allocation was determined by statistical reasoning, and was applied to quantify the connections between liveability and health among the 18 districts of Hong Kong in both 2016 and 2019. Temporal changes of spatial features could be traced by this quantitative framework, and obvious correlations between liveability and health were attained, with R values of 0.496 and 0.518 in 2016 and 2019, and corresponding slopes of 0.80 and 0.88, respectively. Based on the statistical results, it was found that Sai Kung and Kwun Tong are the most and the least liveable district of Hong Kong in 2019. The LHI-HK index was well-validated by renowned AARP liveability index and The California Healthy Places Index (HPI), with R values of 0.90 and 0.70, and the potential uncertainties due to data projection were less than 2.5% for all districts, which implicates its relevancy and appropriateness in conducting similar spatial assessments in international cities. Further, both favorable and unfavorable spatial arrangements of each of the 3 district types in Hong Kong were identified, namely residential, commercial, and industrial districts. This opens new windows in enhancing liveability and health status within communities, with the aim of promoting the sustainability of cities in the long run.

Description: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory disorder that can lead to serious disability and mortality. Females are predominantly affected, including those within the reproductive age. Most patients develop relapsing attacks of optic neuritis; longitudinally extensive transverse myelitis; and encephalitis, especially brainstem encephalitis. The majority of NMOSD patients are seropositive for IgG autoantibodies against the water channel protein aquaporin-4 (AQP4-IgG), reflecting underlying aquaporin-4 autoimmunity. Histological findings of the affected CNS tissues of patients from in-vitro and in-vivo studies support that AQP4-IgG is directly pathogenic in NMOSD. It is believed that the binding of AQP4-IgG to CNS aquaporin-4 (abundantly expressed at the endfoot processes of astrocytes) triggers astrocytopathy and neuroinflammation, resulting in acute attacks. These attacks of neuroinflammation can lead to pathologies, including aquaporin-4 loss, astrocytic activation, injury and loss, glutamate excitotoxicity, microglial activation, neuroinflammation, demyelination, and neuronal injury, via both complement-dependent and complement-independent pathophysiological mechanisms. With the increased understanding of these mechanisms underlying this serious autoimmune astrocytopathy, effective treatments for both active attacks and long-term immunosuppression to prevent relapses in NMOSD are increasingly available based on the evidence from retrospective observational data and prospective clinical trials. Knowledge on the indications and potential side effects of these medications are essential for a clear evaluation of the potential benefits and risks to NMOSD patients in a personalized manner. Special issues such as pregnancy and the coexistence of other autoimmune diseases require additional concern and meticulous care. Future directions include the identification of clinically useful biomarkers for the prediction of relapse and monitoring of the therapeutic response, as well as the development of effective medications with minimal side effects, especially opportunistic infections complicated by long-term immunosuppression.