A 72-year-old woman with metastatic lung cancer to bone and brain and with left external iliac vein thrombosis was under the care of a community palliative care provider. She experienced an acute pain crisis due to acute limb ischemia of the left lower limb. Goals-ofcare discussions were held with the patient and her family; she prioritized symptom control and end-of-life care at home. The family and patient were aware of her short prognosis. Her complex pain was managed by the community palliative team, and her family was empowered to give subcutaneous injections. We illustrate a case showing the importance of community health services with palliative care support in providing symptom management and support to patient and family caregivers throughout the course of a life-limiting illness. cIt also highlights family caregivers’ potential psychological distress in delivering subcutaneous injections in terminal care for a patient at home.

INTRODUCTION: The risk for diabetes progression varies greatly in individuals with type 2 diabetes mellitus (T2DM). We aimed to study the clinical determinants of diabetes progression in multiethnic Asians with T2DM. MATERIALS AND METHODS: A total of 2057 outpatients with T2DM from a secondary-level Singapore hospital were recruited for the study. Diabetes progression was defined as transition from non-insulin use to requiring sustained insulin treatment or glycated haemoglobin (HbA1c) ≥8.5% when treated with 2 or more oral hypoglycaemic medications. Multivariable logistic regression (LR) was used to study the clinical and biochemical variables that were independently associated with diabetes progression. Forward LR was then used to select variables for a parsimonious model. RESULTS: A total of 940 participants with no insulin use or indication for insulin treatment were analysed. In 3.2 ± 0.4 (mean ± SD) years' follow-up, 163 (17%) participants experienced diabetes progression. Multivariable LR revealed that age at T2DM diagnosis (odds ratio [95% confidence interval], 0.96 [0.94-0.98]), Malay ethnicity (1.94 [1.19-3.19]), baseline HbA1c (2.22 [1.80-2.72]), body mass index (0.96 [0.92-1.00]) and number of oral glucose-lowering medications (1.87 [1.39-2.51]) were independently associated with diabetes progression. Area under receiver operating characteristic curve of the parsimonious model selected by forward LR (age at T2DM diagnosis, Malay ethnicity, HbA1c and number of glucose-lowering medication) was 0.76 (95% CI, 0.72-0.80). CONCLUSION Young age at T2DM diagnosis, high baseline HbA1c and Malay ethnicity are independent determinants of diabetes progression in Asians with T2DM. Further mechanistic studies are needed to elucidate the pathophysiology underpinning progressive loss of glycaemic control in patients with T2DM.

MHC class II expression is controlled mainly at transcriptional level by class II transactivator (CIITA), which is a non-DNA binding coactivator and serves as a master control factor for MHC class II genes expression. Here, we describe the function of a novel splice-isoform of CIITA, DC-expressed caspase inhibitory isoform of CIITA (or DC-CASPIC), and we show that the expression of DCCASPIC in DC is upregulated upon lipopolysaccharides (LPS) induction. DC-CASPIC localizes to mitochondria, and protein-protein interaction study demonstrates that DC-CASPIC interacts with caspases and inhibits its activity in DC. Consistently, DC-CASPIC suppresses caspases-induced degradation of nitric oxide synthase-2 (NOS2) and subsequently promotes the synthesis of nitric oxide (NO). NO is an essential regulatory molecule that modulates the capability of DC in stimulating T cell proliferation/activation in vitro; hence, overexpression of DC-CASPIC in DC enhances this stimulation. Collectively, our findings reveal that DC-CASPIC is a key molecule that regulates caspases activity and NO synthesis in DC.
Alternative Splicing ; Amino Acid Sequence ; Animals ; Base Sequence ; CARD Signaling Adaptor Proteins ; genetics ; metabolism ; Cell Line ; Dendritic Cells ; drug effects ; immunology ; metabolism ; Humans ; In Vitro Techniques ; Lipopolysaccharides ; pharmacology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mitochondria ; metabolism ; Molecular Sequence Data ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase Type II ; metabolism ; Nuclear Proteins ; genetics ; metabolism ; Protein Isoforms ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; T-Lymphocytes ; immunology ; metabolism ; Trans-Activators ; genetics ; metabolism ; Up-Regulation ; drug effects

Introduction: Children with learning difficulties (LD) have poorer oral health compared to those without LD due to barriers in maintaining oral care. However, the scarcity of data for this population in Malaysia has left a huge gap in understanding their problems and how to overcome those barriers. Therefore, this study was conducted to evaluate the unmet dental needs and barriers to care perceived by the guardians of children with learning difficulties (CWLD) attending the Special Education Integrated Programmes of a mainstream primary school, in comparison to children without learning difficulties. Methods: This cross-sectional study surveyed the guardians of CWLD (case) and those without LD (control), aged 6-12 years old. A total of 225 questionnaires were distributed to the guardians with a response rate of 40.4% (N=91). Unmet dental needs and barriers in both groups were analysed using the chi-square test. Barriers with significant Chi-square results were further tested with logistic regression to investigate possible confounders. Results: Unmet dental needs of 23.1% of CWLD were found. Most of the guardians agreed that regular dental check-ups were the most needed dental treatment (27.1%) compared to other treatments. The child’s behaviour and the unwillingness of the dentists to treat were among the significant barriers to dental care within the CWLD group. Conclusion: Despite regular dental visits, guardians of CWLD perceived that their children had the most unmet dental needs compared to other children without LD, with significant barriers in terms of accessing professional dental services.