Curating wellness during a pandemic in Singapore: COVID-19, museums, and digital imagination.

OBJECTIVES: The COVID-19 pandemic has caused unexpected disruption to the operation of many museums. However, the disruption also presents an opportunity for local museums to explore new modes of audience engagement that could also help to mitigate the negative health impact of COVID-19 through the imaginative use of technology. This article provides a snapshot of the various digital initiatives that were developed by museums in Singapore during the most challenging time of COVID-19 to exemplify the expanded role of museums as a public health resource. It will also offer a brief reflection on the challenges and benefits of curating wellbeing with digital technologies. STUDY DESIGN: A review of creative responses to COVID-19 by museums in Singapore. METHODS: Scoping search. RESULTS: Several local museums have stepped up efforts to support the wellbeing of people by exploring possibilities with digital virtual platforms. Their swift response to develop online contents following an abrupt closure due to the pandemic exemplifies the caring role of museums in offering people a much-needed respite from social isolation by connecting and interacting with others from a safe distance. Moving forward, it is also important for the museums to be mindful of the barriers that digital virtual platforms might present; since access to technology differs amongst population groups, as do digital competency, and literacy. Museums can benefit from further partnerships with sector experts and organisations to learn about the needs and challenges of different groups in future planning and design. This will help them to gather a holistic overview and help ensure inclusionary strategy and practice. CONCLUSIONS: COVID-19 has challenged museums to adapt their programme and keep the public engaged through virtual programmes on online spaces. Online initiatives have offered opportunities for people to remain socially active and meaningfully engaged despite the stringent measures imposed in response to the viral situation. Postpandemic, we can continue to anticipate a highly connected and inclusive society brought together by virtual technologies.

Development and in-vitro characterization of fish oil oleogels containing benzoyl peroxide and salicylic acid as keratolytic agents.

Topical keratolytic agents such as benzoyl peroxide (BP) and salicylic acid (SA) are one of the common treatments for inflammatory skin diseases. However, the amount of drug delivery through the skin is limited due to the stratum corneum. The purposes of this study were to investigate the ability of fish oil to act as penetration enhancer for topical keratolytic agents and to determine the suitable gelator for formulating stable fish oil oleogels. 2 types of gelling agents, beeswax and sorbitan monostearate (Span 60), were used to formulate oleogels. To investigate the efficacy of fish oil oleogel permeation, commercial hydrogels of benzoyl peroxide (BP) and salicylic acid (SA) were used as control, and comparative analysis was performed using Franz diffusion cell. Stability of oleogels was determined by physical assessments at 20°C and 40°C storage. Benzoyl peroxide (BP) fish oil oleogels containing beeswax were considered as better formulations in terms of drug permeation and cumulative drug release. All the results were found to be statistically significant (p<0.05, ANOVA) and it was concluded that the beeswax-fish oil combination in oleogel can prove to be beneficial in terms of permeation across the skin and stability.

Health promotion board-ministry of health clinical practice guidelines: treating tobacco use and dependence.

The Health Promotion Board (HPB) has updated the clinical practice guidelines on Treating Tobacco Use and Dependence to provide health professionals in Singapore with evidence-based interventions for smoking cessation. This article reproduces the introduction and executive summary of key guideline recommendations (with recommendations from the guidelines) from the HPB-MOH Clinical Practice Guidelines on Treating Tobacco Use and Dependence, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Health Promotion Board website: http://www.hpb.gov.sg/cpg-smoking-cessation. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Medical response to the 2009 Sumatra earthquake: health needs in the post-disaster period.

INTRODUCTION: This paper provides an overview of cases seen by the Singapore Armed Forces (SAF) medical and surgical teams in the 2009 Sumatra earthquake and discusses the role of militaries in the acute phase of a disaster. METHODS: Two SAF primary healthcare clinics prospectively collected patient medical information for comparison. Descriptive analysis of the Emergency Department (ED) and surgical case records was performed. RESULTS: 1,015 patients were seen by the two primary healthcare clinics. In both Koto Bangko and Pariaman, respiratory-related conditions were the most common diagnoses (47.2% and 30.6%, respectively), followed by musculoskeletal/joint conditions (31.6% and 20.6%, respectively). In the ED, 55% and 27% of the 113 patients had trauma-related and infective-related diagnoses, respectively. Lacerations and contusions were the most common forms of trauma. Lung infection was the most common infective diagnosis seen at the ED. The number of ED cases was high during the first week and gradually declined in the second week. 56% of the 102 surgical procedures were performed on dirty or infective wounds. Fractures requiring fixation comprised 38% of surgical procedures. CONCLUSION: Medical aid remains an important component of the overall humanitarian response. Militaries could play an important role in disaster response due to their ability to respond in a timely fashion and logistic capabilities. Pre-launch research on the affected area and knowledge on disaster-specific injury patterns would impact the expertise, equipment and supplies required. The increasing evidence base for disaster preparedness and medical response allows for better planning and reduces the impact of disasters on affected populations.

Tyrosine kinase-mediated serine phosphorylation of adenylyl cyclase.

Receptor tyrosine kinase (RTK) activation is associated with modulation of heptahelical receptor-stimulated adenylyl cyclase responses. The mechanisms underlying the RTK-mediated enhancement of adenylyl cyclase function remain unclear. In the present studies, we show that the tyrosine kinase-dependent enhancement of adenylyl cyclase isoform VI function parallels an enhancement in serine phosphorylation of the enzyme. This effect was mediated by both RTK activation, with IGF-1, and by tyrosine phosphatase inhibition, with sodium orthovanadate. This enhancement of adenylyl cyclase function was not attenuated by inhibitors of ERK, PKC, PKA, or PI3 kinase activity but was blunted by inhibition of endogenous p74(raf-1)() activity. To characterize the molecular site of this effect we identified multiple candidate serine residues in and adjacent to the adenylyl cyclase VI C1b catalytic region and performed serine-to-alanine site-directed mutagenesis using adenylyl cyclase VI as a template. Mutation of serine residues 603 and 608 or serine residues 744, 746, 750, and 754 attenuated both the tyrosine kinase-mediated enhancement of enzyme phosphorylation as well as the sensitization of function. Together, these data define a novel tyrosine kinase-mediated mechanism leading to serine phosphorylation of adenylyl cyclase isoform VI and the sensitization of adenylyl cyclase responsiveness.

Arthroscopically-assisted reduction of intra-articular fractures and soft tissue management of distal radius.

Arthroscopy was used to help to reduce intra-articular fractures of the distal radius and treat soft tissue injuries in 33 acute cases. The fractures were treated by reduction under arthroscopic control and percutaneous fixation either with or without external fixation. The triangular fibrocartilage complex (TFCC) was torn in 18 of 33 patients (54%). All tears were peripheral and were repaired with arthroscopic procedures. Scapholunate (SL) ligament injuries prevailed in six (18%) patients; most of them exhibited instability in the SL joint. They received SL ligament debrided and transfixed with K-wires. Four (12%) of the patients suffered lunotriquetral (LT) ligament injuries; three of them also received transfixation with K-wires. Six (18%) of the patients exhibited chondral fractures. All fractures healed without measurable incongruity of joint surface and at follow-up (24 to 36 months), 11 patients displayed excellent results and 22 patients displayed good results according to the Mayo modified wrist score.

Localization of G-protein-coupled receptors in health and disease.

G-protein-coupled receptors (GPCRs) represent a superfamily of proteins, characterized by seven transmembrane alpha-helices, that signal through interactions with a family of heterotrimeric GTP-binding proteins, referred to as G proteins. The broad range of physiological functions associated with GPCRs indicates that a better understanding of these receptors and their regulation can provide a solid foundation for novel pharmacological interventions in a variety of disease states.

Identification of a novel mechanism for endotoxin-mediated down-modulation of CC chemokine receptor expression.

In the present study, we explored the molecular mechanisms by which bacterial endotoxin (LPS) mediates the down-regulation of CCR2 receptors on human monocytes. We found that LPS induced a marked reduction in CCR2 cell surface protein levels which was blocked by pretreatment with the tyrosine kinase inhibitors genistein and herbimycin A. The effector mechanism underlying LPS-induced CCR2 down-modulation appears to involve the enzymatic activity of proteinases since Western blot analysis of LPS-stimulated monocytes revealed the degradation of a 38-kDa species corresponding to the CCR2B monomer. In RBL cells expressing the CCR2B-green fluorescent protein (GFP) fusion chemokine receptor, LPS stimulated the internalization and degradation of CCR2. The serine proteinase inhibitor N-alpha-p-tosyl-L-lysine chloromethyl ketone blocked LPS-induced down-modulation of CCR2 in monocytes and CCR2B-GFP in RBL cells. This work describes a previously uncharacterized mechanism for CC chemokine receptor down-modulation that is dependent upon tyrosine kinase activation and serine proteinase-mediated receptor degradation and may provide further insight into the mechanisms of leukocyte regulation during immunological and inflammatory responses.

Cleaning dental instruments: measuring the effectiveness of an instrument washer/disinfector.

PURPOSE: To analyze the cleaning effectiveness of one type of instrument washer available for use in a dental office. MATERIALS AND METHODS: Dental instruments were heavily contaminated with blood and specific test bacteria. They were placed in cleaning baskets or within instrument cassettes, processed through the instrument washer, and analyzed for remaining blood and viable bacteria. RESULTS: Information obtained indicated that the washer is an effective cleaning system for dental instruments.

Vanadate stimulation of adenylyl cyclase: an index of tyrosine kinase vascular effects.

BACKGROUND: Beyond their mitogenic effects, hormones such as insulin, which activate receptor tyrosine kinases, regulate vascular tone. Further, we have demonstrated that receptor tyrosine kinase activation enhances adenylyl cyclase activation, a prominent mechanism that mediates vasodilation. However, whether tyrosine kinase-mediated human vascular responses parallel tyrosine kinase-mediated cellular effects on adenylyl cyclase activity is unknown. METHODS AND RESULTS: To assess tyrosine kinase-mediated vascular responses, vascular sensitivity to insulin was assessed with the dorsal hand vein linear variable differential transformer technique. Insulin infusion resulted in a dose-dependent relaxation in all subjects. Cellular responses were assessed by means of the insulinomimetic vanadate-mediated sensitization of vascular adenylyl cyclase activity. Vanadate stimulated a tyrosine kinase-dependent enhancement of adenylyl cyclase function in human and rat aortic vascular smooth muscle cells, human lymphocytes, and human aortic endothelial cells. Further, maximal insulin-mediated vasodilation was significantly positively correlated with maximal vanadate-mediated enhancement of human lymphocyte adenylyl cyclase activity. CONCLUSION: Insulin-mediated vasodilation is positively correlated with vanadate-mediated enhancement of adenylyl cyclase activity. Vanadate-mediated enhancement of adenylyl cyclase activity in lymphocytes may represent an index of tyrosine kinase-mediated vascular effects.

beta-arrestins regulate interleukin-8-induced CXCR1 internalization.

The functional role of neutrophils during acute inflammatory responses is regulated by two high affinity interleukin-8 receptors (CXCR1 and CXCR2) that are rapidly desensitized and internalized upon binding their cognate chemokine ligands. The efficient re-expression of CXCR1 on the surface of neutrophils following agonist-induced internalization suggests that CXCR1 surface receptor turnover may involve regulatory pathways and intracellular factors similar to those regulating beta2-adrenergic receptor internalization and re-expression. To examine the internalization pathway utilized by ligand-activated CXCR1, a CXCR1-GFP construct was transiently expressed in two different cell lines, HEK 293 and RBL-2H3 cells. While interleukin-8 stimulation promoted CXCR1 sequestration in RBL-2H3 cells, receptor internalization in HEK 293 cells required co-expression of G protein-coupled receptor kinase 2 and beta-arrestin proteins. The importance of beta-arrestins in CXCR1 internalization was confirmed by the ability of a dominant negative beta-arrestin 1-V53D mutant to block internalization of CXCR1 in RBL-2H3 cells. A role for dynamin was also demonstrated by the lack of CXCR1 internalization in dynamin I-K44A dominant negative mutant-transfected RBL-2H3 cells. Agonist-promoted co-localization of transferrin and CXCR1-GFP in endosomes of RBL-2H3 cells confirmed that receptor internalization occurs via clathrin-coated vesicles. Our data provides a direct link between agonist-induced internalization of CXCR1 and a requirement for G protein-coupled receptor kinase 2, beta-arrestins, and dynamin during this process.

G-protein-coupled receptor kinase expression in hypertension.

In human hypertension we have recently identified an increase in lymphocyte G-protein receptor kinase-2 (GRK-2) protein expression, the key protein regulating the interaction between G-protein-coupled receptors and activation of adenylyl cyclase. However, it was not known whether this increase in GRK-2 protein expression was attributable to regulation at the level of translation. Furthermore, the relationship between extent of GRK-2 expression, receptor activation of adenylyl cyclase, and blood pressure was unclear. We therefore studied lymphocytes from 7 young subjects with borderline hypertension and 14 young normotensive subjects. Immunodetectable GRK-2 protein expression in lymphocytes from subjects with hypertension was increased (155%+/-7% of normotensive subjects; P < .05). In addition, GRK-2 protein expression was positively correlated with blood pressure (r = 0.53; P = .013) and inversely correlated with beta-adrenergic-mediated adenylyl cyclase activity (r = -0.54, P = .012). However, lymphocyte GRK-2 messenger ribonucleic acid (mRNA) content was not altered (110%+/-13% of that observed in normotensive control subjects). Increased GRK-2 protein expression may be an important factor in the impairment of beta-adrenergic-mediated vasodilation, characteristic of the hypertensive state.

G-protein-coupled receptor kinase activity is increased in hypertension.

Impaired vascular beta-adrenergic responsiveness may play an important role in the development and/or maintenance of hypertension. This defect has been associated with an alteration in receptor/guanine nucleotide regulatory protein (G-protein) interactions. However, the locus of this defect remains unclear. G-Protein-coupled receptor kinases (GRKs) phosphorylate serine/threonine residues on G-protein-linked receptors in an agonist-dependent manner. GRK activation mediates reduced receptor responsiveness and impaired receptor/G-protein coupling. To determine whether the impairment in beta-adrenergic response in human hypertension might be associated with altered GRK activity, we studied lymphocytes from younger hypertensive subjects as compared with older and younger normotensive subjects. We assessed GRK activity by rhodopsin phosphorylation and GRK expression by immunoblot. GRK activity was significantly increased in lymphocytes from younger hypertensive subjects and paralleled an increase in GRK-2 (beta ARK-1) protein expression. In contrast, no alterations in cAMP-dependent kinase (A-kinase) activity or GRK-5/6 expression were noted. GRK activity was not increased in lymphocytes from older normotensive subjects who demonstrated a similar impairment in beta-adrenergic-mediated adenylyl cyclase activation. These studies indicate that GRK activity is selectively increased in lymphocytes from hypertensive subjects. The increase in GRK activity may underlie the reduction in beta-adrenergic responsiveness characteristic of the hypertensive state.

G protein alterations in hypertension and aging.

Defective vasodilator function could be important in the pathogenesis and/or maintenance of the hypertensive state and the predisposition of the elderly to hypertension. Impaired beta-adrenergic-mediated vasodilation and reduced lymphocyte beta-adrenergic activation of adenyl cyclase have been demonstrated both in aging and with hypertension. The cellular mechanisms responsible for these alterations remain unclear. To determine if these defects may be due to alterations in guanine nucleotide regulatory proteins (G proteins) that link receptor activation with effector function, we assessed (1) human lymphocyte adenyl cyclase activity, (2) stimulatory G proteins by cholera toxin-mediated [32P]ADP ribosylation and, in hypertensive subjects, with alpha s-specific and beta-subunit antisera, and (3) inhibitory G proteins by pertussis toxin-mediated [32P]ADP ribosylation and, in older subjects, with alpha i,1,2- and beta-subunit-specific antisera. Lymphocytes from older subjects and from hypertensive subjects demonstrated a comparable reduction in isoproterenol-stimulated adenyl cyclase. However, aluminum fluoride-stimulated activity was reduced only in lymphocytes from hypertensive subjects. Furthermore, aluminum fluoride-stimulated activity was inversely correlated with mean arterial pressure. In lymphocytes from younger hypertensive subjects, cholera toxin-mediated labeling was significantly increased. In contrast, inhibitory G protein labeling by immunodetection was unaltered. In lymphocytes from older subjects, cholera toxin-mediated labeling was not altered; however, pertussis toxin-mediated labelling was significantly increased. In contrast, inhibitory G protein labeling by immunodetection was unaltered. Overall, the study suggests alterations of G protein function of adenyl cyclase is impaired. However, these defects are associated with divergent alterations in stimulatory and inhibitory G proteins.

Oxidant stress enhances adenylyl cyclase activation.

The generation of oxygen-derived free radicals has been implicated in the disordered vascular regulation of inflammation and reperfusion. In the vasculature, oxygen-derived free radicals are vasodilatory. The mechanisms underlying this effect remain unclear. To examine the cellular processes involved, we studied the effects of hydrogen peroxide (H2O2) on adenylyl cyclase activity in A10 cells, a murine vascular smooth muscle cell line. Pretreatment with H2O2 caused a dose-dependent enhancement of forskolin-stimulated adenylyl cyclase activity (ED50, 44 mumol/L to a maximum of 166% of control activity; n = 4). This enhancement was attenuated by iron chelation with deferoxamine and by the intracellular hydroxyl scavenger dimethylthiourea and mimicked by preincubation with purine/xanthine oxidase either alone or in the presence of superoxide dismutase. The effects of H2O2 were completely blocked by the tyrosine kinase inhibitors genistein and tyrphostin A9 but not by its inactive analogue tyrphostin A1 (H2O2 alone, 149 +/- 13%; H2O2 + tyrphostin A9, 100 +/- 9%; H2O2 + tyrphostin A1, 171 +/- 21%; n = 4). H2O2 comparably enhanced adenylyl cyclase activity stimulated by isoproterenol (166 +/- 17% of control, n = 5) and sodium fluoride (177 +/- 18% of control, n = 5). Thus oxygen-derived free radicals enhance adenylyl cyclase activation, probably via tyrosine kinase-mediated effects on the catalytic subunit of adenylyl cyclase. Sensitization of adenylyl cyclase activation may be an important mechanism by which free radicals modulate hormone-mediated vasodilation.

A modified Bristow procedure for recurrent anterior shoulder dislocation.

BACKGROUND: Dislocation of the shoulder is one of our earliest frequent injuries. Many procedures have been evaluated for treatment of the condition since the mid 1960s. The modified Bristow procedure was initially described in 1970 by May. Technically easy, the procedure is very effective in prevention of redislocation, and has gained popularity over two decades of use. METHODS: A retrospective study was done of 32 patients with recurrent anterior shoulder dislocation, who had received modified Bristow procedure during the years 1987 through 1991 in this Hospital. Average followup period was 26 months. RESULTS: At postoperative evaluation, average loss of external rotation and abduction as compared to the nonoperated side were 15 and 10 degrees, respectively. There was no limitation on daily activity, but some little restriction in extreme throwing sports was found. Postoperative complications included three patients who had bone block resorption and one patient who had superficial wound infection. There was no redislocation nor implant loosening in the study. CONCLUSIONS: This procedure is technically easy, had a low rate of complication, a high degree of patient satisfaction and very effectively prevents redislocation.

Influence of context and preferred learning environments: approaches to studying physiology.

One hundred and twenty-eight medical students who had experienced a traditional-style preclinical curriculum completed three self-report questionnaires. Using factor analysis of students' responses this study explores interactions between study orientation, preferences for different kinds of learning environment, and evaluations of the physiology course. Such interactions can provide insight into the reasons why students fail to adopt effective learning strategies. Although many students had the intention to understand, they did not adopt a deep approach. Achievement motivation was strong, test anxiety high, and the course was perceived to be competitive. The meaning orientation merged with the achieving orientation; students were thus performance rather than task oriented. These students perceived the course to have been challenging, as did students within the reproducing orientation and who had 'surface' preferences. Students within the non-academic orientation had difficulty coping with the course. The findings suggest that conventional teaching and assessment methods are preventing students from developing appropriate criteria and internal standards for evaluating performance. An illusion of comprehension may prevent students from seeing the need to adopt more effective learning strategies and cause 'good' students with the ability to adopt a deep approach to abort the pursuit of deep understanding. Students' preferences and evaluations of teaching and assessment indicate that students within the different learning orientations have different educational needs. The implications for instruction and evaluation are discussed.