Universities as Intermediary Organizations: Catalyzing the Construction of an Age-Friendly City in Hong Kong.

Background and Objectives: The construction of an Age-Friendly City (AFC) requires active contribution from relevant interest groups including older adults, nonprofit organizations, and policy-makers. However, given that relevant interest groups may have limited resources, knowledge, and skills, as well as unique contextual factors, they often require help from intermediary organizations-actors that aim to build interest groups' capabilities. Our objectives were to examine the functions of universities, as an example of intermediary organizations, in facilitating the construction of an AFC, and identify critical factors that enable intermediary organizations to perform their functions. Research Design and Methods: We conducted three focus groups and one individual interview with multiple interest groups including older adults and social workers from nonprofit organizations and local government involved in a 6-year citywide AFC project in Hong Kong. Participants were asked to share their views on the role of universities in relation to their own experiences and roles in the project. Data generated from the interviews were analyzed using thematic analysis. Results: Four themes pertinent to the functions of universities in facilitating development were identified: facilitating cross-sector collaborations, knowledge diffusion, interest-group building, and mediating divergent interests. We also found that neutrality and reputability are key characteristics for intermediary organizations to wield sufficient legitimacy to perform their functions efficiently. Discussion and Implications: Findings underscore the important yet overlooked role of intermediary organizations in bridging and mediating different interest groups to facilitate AFC development. We advance gerontological scholarship by providing insights into the theoretical mechanisms and practice implications for intermediary organizations in fostering an AFC.

Depressive Symptoms and Coping Strategies in Community-Dwelling Older People Amidst the COVID-19 Pandemic: A Mixed-Method Study.

This study aimed to examine depressive symptoms of community-dwelling older people amidst COVID-19 and explore how naturally occurring coping strategies were associated with depression. A mixed-method cross-sectional telephone survey was conducted with 375 older people aged 60 years and above between March and May 2020 in Hong Kong. Trained social workers interviewed participants and assessed depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9). Attribute coding and thematic analysis were adopted for qualitative data analyses. Generalized linear models (GLM) were used to examine the effects of demographics, self-reported risk factors and coping strategies on PHQ-9 scores. Participants' average PHQ-9 score was 1.9 (SD = 2.9), suggesting a low risk for depression in general. Over half of the participants reported adaptive coping strategies, including learning new things, staying physically, mentally, and socially active, and having a positive mind-set. GLM results indicated that living with family members (other than spouse) and/or others, maladaptive coping, and self-reported risk factors were significantly associated with higher PHQ-9 scores, while adaptive coping was significantly associated with lower PHQ-9 scores. Our study contributed to the growing literature on older people's resilience and adaptive coping during the pandemic, and the results may have implications for mental health promotion and community care.

Safeguarding health equality for the disadvantaged during the COVID-19 pandemic: Lessons learned for the social work profession.

An evaluation of the role played by the social work profession during the outbreak of COVID-19 is necessary. Although social workers have made efforts to address people's needs during the pandemic, it is worth examining the role they have played in safeguarding health equality. Focusing on the case of Hong Kong, we found that the profession was generally ill-prepared for the outbreak, and in particular, for confronting the attendant social inequalities. We identified three possible reasons for these findings: 1) non-governmental organizations were caught off-guard by the outbreak, 2) there was no clearly articulated intervention agenda to inform practitioners of the roles they should play in such a large-scale crisis, and 3) having become more formalized and standardized, social work services may have become less flexible in responding to emerging community needs. We conclude this article by suggesting three directions that could allow the profession to better pursue its mission during large-scale crises.

Associations between Volunteering and Mental Health during COVID-19 among Chinese Older Adults.

Evidence about the association between volunteering and the mental health of older adults during COVID-19 remains underexplored. This study investigated (1) patterns of volunteering among older adults in Hong Kong during COVID-19; (2) associations between volunteering and mental health of older adults during COVID-19; and (3) associations between key psychological resources (e.g., self-efficacy and self-esteem) and volunteering among older adults during COVID-19. This study applied a cross-sectional design with data collected from 128 older adults in June 2020, who were trained as volunteers in a volunteer program that began before COVID-19. The study found that older adults continued to actively contribute to their communities by engaging in volunteering during COVID-19. The specific type of volunteering activities was linked to few depressive and anxiety symptoms. Older adults with increased self-esteem prior to COVID-19 were more likely to participate in volunteering activities related to COVID-19. Our study suggested that encouraging older adults to volunteer during the pandemic is a key pathway to maintain mental health. Social workers are encouraged to engage older adults in volunteerism regularly to offset the risk of depression and anxiety symptoms in times of crisis.

Does Sub-Anesthetic Ketamine Provide Postoperative Analgesia for Third Molar Surgery?

PURPOSE: Despite ketamine's effectiveness as an anesthetic and its known analgesic properties, the role of ketamine in postoperative pain after third molar surgery remains unclear. Therefore, this study aimed to investigate whether patients undergoing third molar surgery who received a sub-anesthetic preoperative dose of intravenous ketamine would experience less postoperative pain. MATERIALS AND METHODS: We implemented a randomized, double-blinded, placebo-controlled trial. The study sample consisted of participants undergoing third molar surgery with procedural sedation anesthesia. Participants were randomized to receive a preoperative intravenous dose of ketamine or placebo, as predictor variables. The primary outcome variable was postoperative pain intensity determined by a 10-point visual analog scale at 6-hour intervals over a period of 48 hours. The secondary outcome variable was the quantity of postoperative non-opioid and opioid consumption. Other variables included the extent and difficulty of surgery performed, patient satisfaction, gender, and age. Data analysis involved descriptive statistics, multivariate analysis, and regression analysis. The P value was set at .05. RESULTS: A total of 134 participants were randomly enrolled into either the ketamine group (n = 74, 55.2%) or placebo group (n = 60, 44.8%). No statistically significant differences in the distribution of study variables were found between the groups. A small yet statistically significant (P < .05) difference was noted in the median pain score at 6 hours postoperatively, with the ketamine group experiencing more pain. However, no further differences were detected at any postoperative time between the 2 groups. Similar results were obtained after adjusting for age, gender, and surgical difficulty. No difference in the amount of postoperative non-opioid or opioid medication use was found between the 2 groups. CONCLUSIONS: This study did not find evidence that a preoperative sub-anesthetic dose of ketamine could reduce pain after third molar surgery or have any effects on non-opioid or opioid analgesic consumption. Nevertheless, ketamine remains a valuable option among sedation medications for oral and maxillofacial surgeons.

An Unusual Case of Mandibular Squamous Cell Carcinoma in Intimacy with an Impacted Wisdom Tooth.

Squamous cell carcinoma is the most common head and neck malignancy. It can occur in the mandible or maxilla without a preexisting oral mucosal lesion. Often, the clinical and radiographic presentation of SCC directs the clinician to favour malignancy over other pathological conditions. However, SCC may also mimic an infectious condition and therefore can pose a diagnostic challenge even for the most experienced clinicians. Herein, we report a case of mandibular squamous cell carcinoma in a 53-year-old male who presented with symptoms of right facial swelling, trismus, pain, and right-sided lip paresthesia. The patient underwent a surgical removal of the presumed infected third molar of the right mandible, but histopathological analysis of the associated soft tissue unexpectedly yielded squamous cell carcinoma. Given the biopsy-proven diagnosis, the patient received a mandibular resection of the tumor followed by primary reconstruction with a fibular free flap. Patients presenting with symptoms mimicking odontogenic infections should receive vigilant attention by clinicians with regard to the disease history, clinical signs, radiographic evidence, and decision for histopathological analysis. This is especially true in the context of impacted dentition, where malignancy must be considered when formulating a differential diagnosis.

MANAGEMENT OF DENTAL EXTRACTIONS IN PATIENTS TAKING WARFARIN AS ANTICOAGULANT TREATMENT: A SYSTEMATIC REVIEW.

OBJECTIVES: The management of patients on anticoagulation therapy is challenging. The objective of this study was to conduct a systematic review to establish the effectiveness of hemostatic interventions to prevent postoperative bleeding following dental extractions among patients taking warfarin. METHODS: A systematic review of the literature was conducted using PubMed, EMBASE and the Cochrane Central Register of Controlled Trials databases and applying relevant MeSH terms. Identified studies were screened independently by 2 reviewers using the following selection criteria: tooth extraction, patients taking warfarin as the only anticoagulant, randomized controlled trials and a hemostatic intervention. RESULTS: Six articles were included in the final review, all evaluating different interventions. Oral or local hemostatic agents were compared in 4 studies where patients continued taking warfarin before and after the procedure; in 3 studies, there were no differences between the agents in preventing postoperative bleeding and, in 1, Histoacryl glue was superior to a gelatin sponge. Two studies compared warfarin continuation with temporary discontinuation and found that continuation did not increase the risk of bleeding in patients who had an international normalized ratio (INR) within the therapeutic range. CONCLUSIONS: Patients with an INR within the therapeutic range can safely continue taking the regular dose of warfarin before dental extractions. There is no evidence to support or reject the superiority of local hemostatic agents over warfarin discontinuation.

Discovery of an iron-regulated citrate synthase in Staphylococcus aureus.

Bacteria need to scavenge iron from their environment, and this is no less important for bacterial pathogens while attempting to survive in the mammalian host. One key strategy is the synthesis of small iron chelators known as siderophores. The study of siderophore biosynthesis systems over the past several years has shed light on novel enzymology and, as such, has identified new therapeutic targets. Staphylococcus aureus, a noted human and animal pathogen, produces two citrate-based siderophores, termed staphyloferrin A and staphyloferrin B. The iron-regulated gene cluster for the biosynthesis of staphyloferrin B, sbnA-I, contains several yet uncharacterized genes. Here, we report on the identification of an enzyme, SbnG, which is annotated in the genome sequence as a metal-dependent class II aldolase. In contrast to this prediction, we report that, instead, SbnG has evolved to catalyze metal-independent citrate synthase activity using oxaloacetate and acetyl-CoA as substrates. We describe an in vitro assay to synthesize biologically active staphyloferrin B from purified enzymes and substrates, and identify several SbnG inhibitors, including metals such as calcium and magnesium.

Mutation of L-2,3-diaminopropionic acid synthase genes blocks staphyloferrin B synthesis in Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus synthesizes two siderophores, staphyloferrin A and staphyloferrin B, that promote iron-restricted growth. Previous work on the biosynthesis of staphyloferrin B has focused on the role of the synthetase enzymes, encoded from within the sbnA-I operon, which build the siderophore from the precursor molecules citrate, alpha-ketoglutarate and L-2,3-diaminopropionic acid. However, no information yet exists on several other enzymes, expressed from the biosynthetic cluster, that are thought to be involved in the synthesis of the precursors (or synthetase substrates) themselves. RESULTS: Using mutants carrying insertions in sbnA and sbnB, we show that these two genes are essential for the synthesis of staphyloferrin B, and that supplementation of the growth medium with L-2,3-diaminopropionic acid can bypass the block in staphyloferrin B synthesis displayed by the mutants. Several mechanisms are proposed for how the enzymes SbnA, with similarity to cysteine synthase enzymes, and SbnB, with similarity to amino acid dehydrogenases and ornithine cyclodeaminases, function together in the synthesis of this unusual nonproteinogenic amino acid L-2,3-diaminopropionic acid. CONCLUSIONS: Mutation of either sbnA or sbnB result in abrogation of synthesis of staphyloferrin B, a siderophore that contributes to iron-restricted growth of S. aureus. The loss of staphyloferrin B synthesis is due to an inability to synthesize the unusual amino acid L-2,3-diaminopropionic acid which is an important, iron-liganding component of the siderophore structure. It is proposed that SbnA and SbnB function together as an L-Dap synthase in the S. aureus cell.

Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by Staphyloferrin A, Staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence.

Staphylococcus aureus is a frequent cause of bloodstream, respiratory tract, and skin and soft tissue infections. In the bloodstream, the iron-binding glycoprotein transferrin circulates to provide iron to cells throughout the body, but its iron-binding properties make it an important component of innate immunity. It is well established that siderophores, with their high affinity for iron, in many instances can remove iron from transferrin as a means to promote proliferation of bacterial pathogens. It is also established that catecholamine hormones can interfere with the iron-binding properties of transferrin, thus allowing infectious bacteria access to this iron pool. The present study demonstrates that S. aureus can use either of two carboxylate-type siderophores, staphyloferrin A and staphyloferrin B, via the transporters Hts and Sir, respectively, to access the transferrin iron pool. Growth of staphyloferrin-producing S. aureus in serum or in the presence of holotransferrin was not enhanced in the presence of catecholamines. However, catecholamines significantly enhanced the growth of staphyloferrin-deficient S. aureus in human serum or in the presence of human holotransferrin. It was further demonstrated that the Sst transporter was essential for this activity as well as for the utilization of bacterial catechol siderophores. The substrate binding protein SstD was shown to interact with ferrated catecholamines and catechol siderophores, with low to submicromolar affinities. Experiments involving mice challenged intravenously with wild-type S. aureus and isogenic mutants demonstrated that the combination of Hts, Sir, and Sst transport systems was required for full virulence of S. aureus.

Specificity of Staphyloferrin B recognition by the SirA receptor from Staphylococcus aureus.

Many organisms use sophisticated systems to acquire growth-limiting iron. Iron limitation is especially apparent in bacterial pathogens of mammalian hosts where free iron concentrations are physiologically negligible. A common strategy is to secrete low molecular weight iron chelators, termed siderophores, and express high affinity receptors for the siderophore-iron complex. Staphylococcus aureus, a widespread pathogen, produces two siderophores, staphyloferrin A (SA) and staphyloferrin B (SB). We have determined the crystal structure of the staphyloferrin B receptor, SirA, at high resolution in both the apo and Fe(III)-SB (FeSB)-bound forms. SirA, a member of the class III binding protein family of metal receptors, has N- and C-terminal domains, each composed of mainly a ß-stranded core and α-helical periphery. The domains are bridged by a single α-helix and together form the FeSB binding site. SB coordinates Fe(III) through five oxygen atoms and one nitrogen atom in distorted octahedral geometry. SirA undergoes conformational change upon siderophore binding, largely securing two loops from the C-terminal domain to enclose FeSB with a low nanomolar dissociation constant. The staphyloferrin A receptor, HtsA, homologous to SirA, also encloses its cognate siderophore (FeSA); however, the largest conformational rearrangements involve a different region of the C-terminal domain. FeSB is uniquely situated in the binding pocket of SirA with few of the contacting residues being conserved with those of HtsA interacting with FeSA. Although both SirA and HtsA bind siderophores from the same α-hydroxycarboxylate class, the unique structural features of each receptor provides an explanation for their distinct specificity.

The Staphylococcus aureus siderophore receptor HtsA undergoes localized conformational changes to enclose staphyloferrin A in an arginine-rich binding pocket.

Staphylococcus aureus uses several efficient iron acquisition strategies to overcome iron limitation. Recently, the genetic locus encoding biosynthetic enzymes for the iron chelating molecule, staphyloferrin A (SA), was determined. S. aureus synthesizes and secretes SA into its environment to scavenge iron. The membrane-anchored ATP binding cassette-binding protein, HtsA, receives the ferric-chelate for import into the cell. Recently, we determined the apoHtsA crystal structure, the first siderophore receptor from gram-positive bacteria to be structurally characterized. Herein we present the x-ray crystal structure of the HtsA-ferric-SA complex. HtsA adopts a class III binding protein fold composed of separate N- and C-terminal domains bridged by a single alpha-helix. Recombinant HtsA can efficiently sequester ferric-SA from S. aureus culture supernatants where it is bound within the pocket formed between distinct N- and C-terminal domains. A basic patch composed mainly of six Arg residues contact the negatively charged siderophore, securing it within the pocket. The x-ray crystal structures from two different ligand-bound crystal forms were determined. The structures represent the first structural characterization of an endogenous alpha-hydroxycarboxylate-type siderophore-receptor complex. One structure is in an open form similar to apoHtsA, whereas the other is in a more closed conformation. The conformational change is highlighted by isolated movement of three loops within the C-terminal domain, a domain movement unique to known class III binding protein structures.

Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus.

Siderophores are iron-scavenging molecules produced by many microbes. In general, they are synthesized using either non-ribosomal peptide synthetase (NRPS) or NRPS-independent siderophore (NIS) pathways. Staphylococcus aureus produces siderophores, of which the structures of staphyloferrin A and staphyloferrin B are known. Recently, the NIS biosynthetic pathway for staphyloferrin A was characterized. Here we show that, in S. aureus, the previously identified sbn (siderophore biosynthesis) locus encodes enzymes required for the synthesis of staphyloferrin B, an alpha-hydroxycarboxylate siderophore comprised of l-2,3-diaminopropionic acid, citric acid, 1,2-diaminoethane and alpha-ketoglutaric acid. Staphyloferrin B NIS biosynthesis was recapitulated in vitro, using purified recombinant Sbn enzymes and the component substrates. In vitro synthesized staphyloferrin B readily promoted the growth of iron-starved S. aureus, via the ABC transporter SirABC. The SbnCEF synthetases and a decarboxylase, SbnH, were necessary and sufficient to produce staphyloferrin B in reactions containing component substrates l-2,3-diaminopropionic acid, citric acid and alpha-ketoglutaric acid. Since 1,2-diaminoethane was not required, this component of the siderophore arises from the SbnH-dependent decarboxylation of a 2,3-diaminoproprionic acid-containing intermediate. Liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analyses of a series of enzyme reactions identified mass ions corresponding to biosynthetic intermediates, allowing for the first proposed biosynthetic pathway for staphyloferrin B.

Demonstration of the iron-regulated surface determinant (Isd) heme transfer pathway in Staphylococcus aureus.

In this study, we report experimental results that provide the first complete challenge of a proposed model for heme acquisition by Staphylococcus aureus via the Isd pathway first put forth by Mazmanian, S. K., Skaar, E. P., Gaspar, A. H., Humayun, M., Gornicki, P., Jelenska, J., Joachmiak, A., Missiakas, D. M., and Schneewind, O. (2003) Science 299, 906-909. The heme-binding NEAT domains of Isd proteins IsdA, IsdB (domain 2), IsdC, and HarA/IsdH (domain 3), and the heme-binding IsdE protein, were overexpressed and purified in apo (heme-free) form. Absorption and magnetic circular dichroism spectral data, together with electrospray ionization mass spectrometry were used to unambiguously identify that heme transfers from NEAT-A through NEAT-C to IsdE. Heme transfer was demonstrated to occur in a unidirectional fashion in the sequence NEAT-B2 --> NEAT-A --> NEAT-C --> IsdE or, alternatively, initiating from NEAT-H3 instead of NEAT-B2: NEAT-H3 --> NEAT-A --> NEAT-C --> IsdE. Under the conditions of our experiments, only NEAT-H3 and NEAT-B2 could transfer bidirectionally, which is in the reverse direction as well, and only with each other. Whereas apo-IsdE readily accepted heme from holo-NEAT-C, it would not accept heme from holo-NEAT-A. Heme transfer to IsdE requires the presence of holo-NEAT-C, in agreement with the proposal that IsdC serves as the central conduit of the heme transfer pathway. These experimental findings corroborate the heme transfer model first proposed by the Schneewind group. Our data show that heme transport from the wall-anchored IsdH/IsdB proteins proceeds directly to IsdE at the membrane and, for this to occur, we propose that specific protein-protein interactions must take place.