Postsynthetic Modification of a Covalent Organic Framework Achieved via Strain-Promoted Cycloaddition.

Two-dimensional covalent organic frameworks (2D COFs) are layered, structurally regular, and permanently porous macromolecules. When reactive groups are embedded into a COF structure, subsequent chemical reactions can be performed following polymerization. As such, a postsynthetic modification (PSM) strategy provides diverse materials from a single set of COF monomers and polymerization protocols. Here, we report the synthesis of an asymmetric dibenzocyclooctyne-containing imine-linked 2D COF, which readily undergoes strain-promoted azide-alkyne cycloaddition (SPAAC) reactions without catalyst under mild and dilute conditions. This approach was used to quantitatively decorate the COF lattice with alkyl chains and amines, all without the need for exogenous species. Functionalization may result in spontaneous delamination of bulk COF materials into solution-stable sheets, demonstrating the utility of this technique. As such, this platform is useful for postsynthetic functionalization with sensitive chemical functionalities that are not amenable to direct polymerization or existing PSM strategies.

Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

BACKGROUND: Abnormal immune function is often an underlying component of illness pathophysiology and symptom presentation. Functional and phenotypic immune-related alterations may play a role in the obscure pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The objective of this study was to investigate the functional ability of innate and adaptive immune cells in moderate and severe CFS/ME patients. The 1994 Fukuda criteria for CFS/ME were used to define CFS/ME patients. CFS/ME participants were grouped based on illness severity with 15 moderately affected (moderate) and 12 severely affected (severe) CFS/ME patients who were age and sex matched with 18 healthy controls. Flow cytometric protocols were used for immunological analysis of dendritic cells, monocytes and neutrophil function as well as measures of lytic proteins and T, natural killer (NK) and B cell receptors. RESULTS: CFS/ME patients exhibited alterations in NK receptors and adhesion markers and receptors on CD4(+)T and CD8(+)T cells. Moderate CFS/ME patients had increased CD8(+) CD45RA effector memory T cells, SLAM expression on NK cells, KIR2DL5(+) on CD4(+)T cells and BTLA4(+) on CD4(+)T central memory cells. Moderate CFS/ME patients also had reduced CD8(+)T central memory LFA-1, total CD8(+)T KLRG1, naïve CD4(+)T KLRG1 and CD56(dim)CD16(-) NK cell CD2(+) and CD18(+)CD2(+). Severe CFS/ME patients had increased CD18(+)CD11c(-) in the CD56(dim)CD16(-) NK cell phenotype and reduced NKp46 in CD56(bright)CD16(dim) NK cells. CONCLUSIONS: This research accentuated the presence of immunological abnormalities in CFS/ME and highlighted the importance of assessing functional parameters of both innate and adaptive immune systems in the illness.

Quality of life and symptom burden in children with neurodegenerative diseases: using PedsQL and SProND, a new symptom-based scale.

BACKGROUND: Children with neurodegenerative conditions (CNDC) often suffer from severe neurodisability and high symptom burden with multisystemic involvement. However, their symptom burden and health-related quality of life (HRQOL) is not systematically documented in the literature, and there is no existing tool for such purposes. We designed our own tool for scoring of symptom burden amongst CNDCs and adopted the PedsQL generic score 4.0 to quantify the impact of overall symptom burden on children's overall HRQOL. METHODS: The Symptom Profile for children with neurodegnerative condition (SProND) questionnaire was developed, which consisted of 14 questions grouped according to 5 categories, namely epilepsy, neurobehavioural, movement and mobility related, breathing and swallowing, and other daily activities. CNDCs were recruited during visits to the Comprehensive Neurometabolic / Neurodegenerative Program of the Duchess of Kent Children's Hospital and Hong Kong Children's Hospital between November 2019 and March 2020. The SProND and PedsQL 4.0 Generic Core Scales were distributed to consenting parents of CNDCs. RESULTS: 36 CNDCs were recruited and matched with community controls. The response rate of subject and control were 99.5% and 98.7% respectively. The Cronbach alpha was 0.61 for the neurobehavioural domain and > = 0.7 for other domains. The greater number of symptoms each subject experiences, the worse his/ her PedsQL scores. Subjects displaying hypersalivation and swallowing difficulties had average physical health summary scores of less than 30% compared with subjects without these symptoms. On the other hand, average psychosocial health summary scores of subjects with involuntary movements, joint stiffness, hypersalivation, sleep problem and anorexia were approximately 70% compared to subjects without these symptoms. DISCUSSION AND CONCLUSION: This is one of the first studies to look at CNDCs as a group. We propose the SProND questionnaire for evaluation of symptom profile amongst CNDCs with satisfactory internal and external validity. It demonstrates how physical symptoms impact both physical and psychosocial HRQOL, and the cumulative effect of individual symptoms on the overall HRQOL. As such, CNDCs should be systematically screened for multi-systemic symptoms as a routine part of their clinical care, and care plans should be individually catered to individual patients' symptom burden and specific needs.

Validation of the Paediatric Hearing Impairment Caregiver Experience (PHICE) Questionnaire.

INTRODUCTION: The paediatric hearing impairment caregiver experience (PHICE) questionnaire is a 68-item instrument that assesses the stress experienced by caregivers of children with hearing impairment (HI). While the questionnaire has been validated in the United States, it may need to be modified for use in the Singapore context due to the differing healthcare system, costing and culture related to caregiving for children with HI. This study aims to modify and validate the PHICE questionnaire to increase its relevance and ease of use in Singapore. MATERIALS AND METHODS: The original PHICE questionnaire was filled out by 127 caregivers of HI children managed at the otolaryngology clinic of the National University Hospital (NUH). An expert panel was convened to assess the questionnaire for its suitability for use in Singapore. Exploratory factor analysis was conducted to evaluate the underlying factor structure of the original PHICE questionnaire. Items with high cross-loadings were removed and a new factor structure was adopted which was further analysed using confirmatory factor analysis (CFA). Cronbach's alpha (α) was computed to determine the internal consistency of the new subscales. RESULTS: Items that are less relevant in Singapore and those with high cross-loadings were removed. A 5-factor structure with only 42 items remaining and corresponding to the factors: " Policy", "Healthcare", "Education", "Support" and "Adaptation" was adopted. CFA suggests a good model fit for the modified questionnaire, improved from the 8-factor structure of the original PHICE. Cronbach's α were high (>0.7) for each new subscale. CONCLUSION: The original PHICE questionnaire has been shortened and reorganised in terms of the subscales composition. The resulting instrument is structurally valid and internally consistent. It is a simple and useful tool for identifying factors related to caregiving that can negatively impact rehabilitation outcomes for children with HI in Singapore. Removal of some sign language items makes this modified version less useful for caregivers, places or countries where sign language is the main focus of rehabilitation for children with HI.

Polyhemoglobin-fibrinogen: a novel oxygen carrier with platelet-like properties in a hemodiluted setting.

Polyhemoglobin (polyHb) is currently being assessed in phase III trials under various formulations. At present, none contain clotting factors or platelet substitutes to aid in hemostasis. We have prepared a novel blood substitute that is an oxygen carrier with platelet-like activity. This is formed by crosslinking fibrinogen to hemoglobin to form polyhemoglobin-fibrinogen (polyHb-Fg). This was studied and compared to polyHb for its effect on coagulation both in vitro and in vivo. In the in vitro experiments, PolyHb-Fg showed similar clotting times as whole blood, whereas polyHb showed significantly higher clotting times. This result was confirmed in in vivo experiments using an exchange transfusion rat-model. Using PolyHb, exchange transfusion of 80% or more increased the normal clotting time (1-2 mins) to > 10 mins. Partial clots formed with PolyHb did not adhere to the tubing wall. With PolyHb-Fg, a normal clotting time is maintained, even with 98% exchange transfusion.