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7%) and co-trimoxazole (n = 143, 33.5%) being the most widely implicated drugs. Among patients with reported outcomes, 73 (28.7%) SJS and 3 (10.0%) TEN cases recovered without sequelae, at the time of reporting. Severity of the SCAR was reported for only 171 (69.0%) cases, of which 12 (4.7%) and 8 (26.7%) resulted in death (Grade 5) among SJS and TEN cases, respectively. Conclusions Antiretroviral and antibiotics were the commonly reported offending group of drugs for SJS and TEN cases. Nevirapine and co-trimoxazole were the commonly reported suspect drugs. SJS and TEN were reported most frequently in females and in patients aged 19-40 years, indicating that drug surveillance and counseling in these groups of patients may be beneficial. © The Author(s), 2020.Background The effect of prior hypoglycaemia on cognitive function in type 1 diabetes is an important unresolved clinical question. In this systematic review, we aimed to summarize the studies exploring the impact of prior hypoglycaemia on any aspect of cognitive function in type 1 diabetes. Methods We used a multidatabase search platform Healthcare Database Advanced Search to search Medline, PubMed, EMBASE, EMCARE, CINAHL, PsycINFO, BNI, HMIC, and AMED from inception until 1 May 2019. We included studies on type 1 diabetes of any age. The outcome measure was any aspect of cognitive function. Results The 62 studies identified were grouped as severe hypoglycaemia (SH) in childhood (⩽18 years) and adult-onset (>18 years) diabetes, nonsevere hypoglycaemia (NSH) and nocturnal hypoglycaemia (NH). SH in early childhood-onset diabetes, especially seizures and coma, was associated with poorer memory (verbal and visuospatial), as well as verbal intelligence. Among adult-onset diabetes, SH was associated with poorer cognitive performance in the older age (>55 years) group only. Early versus late exposure to SH had a significant association with cognitive dysfunction (CD). NSH and NH did not have any significant association with CD, while impaired awareness of hypoglycaemia was associated with poorer memory and cognitive-processing speeds. Conclusion The effect of SH on cognitive function is age dependent. Exposure to SH in early childhood (55 years) was associated with a moderate effect on the decrease in cognitive function in type 1 diabetes [PROSPERO ID CRD42019141321]. © The Author(s), 2020.Biomaterial development for clinical applications is currently on the rise. This necessitates adequate in vitro testing, where the structure and composition of biomaterials must be specifically tailored to withstand in situ repair and regeneration responses for a successful clinical outcome. The chorioallantoic membrane of chicken embryos has been previously used to study angiogenesis, a prerequisite for most tissue repair and regeneration. In this study, we report an optimised ex ovo method using a glass-cling film set-up that yields increased embryo survival rates and has an improved protocol for harvesting biomaterials. Furthermore, we used this method to examine the intrinsic angiogenic capacity of a variety of biomaterials categorised as natural, synthetic, natural/synthetic and natural/natural composites with varying porosities. We detected significant differences in biomaterials' angiogenesis with natural polymers and polymers with a high overall porosity showing a greater vascularisation compared to synthetic polymers. Therefore, our proposed ex ovo chorioallantoic membrane method can be effectively used to pre-screen biomaterials intended for clinical application. © The Author(s) 2020.In the contemporary practice of palladium catalysis, a molecular understanding of the role of vital additives used in such reactions continues to remain rather vague. Herein, we disclose an intriguing and a potentially general role for one of the most commonly used silver salt additives, discovered through rigorous computational investigations on four diverse Pd-catalyzed C-H bond activation reactions involving sp2 aryl C-H bonds. The catalytic pathways of different reactions such as phosphorylation, arylation, alkynylation, and oxidative cycloaddition are analyzed, with and without the explicit inclusion of the silver additive in the respective transition states and intermediates. Our results indicate that the pivotal role of silver salts is likely to manifest in the form of a Pd-Ag heterobimetallic species that facilitates intermetallic electronic communication. The Pd-Ag interaction is found to provide a consistently lower energetic span as compared to an analogous pathway devoid of such interaction. Identification of a lower energy pathway as well as enhanced catalytic efficiency due to Pd-Ag interaction could have broad practical implications in the mechanism of transition metal catalysis and the current perceptions on the same. 2-NBDG chemical This journal is © The Royal Society of Chemistry 2020.Although insulin was first purified and used therapeutically almost a century ago, there is still a need to improve therapeutic efficacy and patient convenience. A key challenge is the requirement for refrigeration to avoid inactivation of insulin by aggregation/fibrillation. Here, in an effort to mitigate this problem, we introduced a 4th disulfide bond between a C-terminal extended insulin A chain and residues near the C-terminus of the B chain. Insulin activity was retained by an analog with an additional disulfide bond between residues A22 and B22, while other linkages tested resulted in much reduced potency. Furthermore, the A22-B22 analog maintains the native insulin tertiary structure as demonstrated by X-ray crystal structure determination. We further demonstrate that this four-disulfide analog has similar in vivo potency in mice compared to native insulin and demonstrates higher aggregation stability. In conclusion, we have discovered a novel four-disulfide insulin analog with high aggregation stability and potency. This journal is © The Royal Society of Chemistry 2020.Polymersomes have been extensively used in the delivery of both small and macromolecular payloads. However, the controlled delivery of gaseous therapeutics (e.g., nitric oxide, NO) remains a grand challenge due to its difficulty in loading of gaseous payloads into polymersomes without premature leakage. Herein, NO-releasing vesicles could be fabricated via the self-assembly of NO-releasing amphiphiles, which were synthesized by the direct polymerization of photoresponsive NO monomers (abbreviated as oNBN, pNBN, and BN). These monomers were rationally designed through the integration of the photoresponsive behavior of N-nitrosoamine moieties and the self-immolative chemistry of 4-aminobenzyl alcohol derivatives, which outperformed conventional NO donors such as diazeniumdiolates (NONOates) and S-nitrosothiols (SNOs) in terms of ease of preparation, stability of storage, and controllability of NO release. The unique design made it possible to selectively release NO by a light stimulus and to regulate the NO release rates.

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