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Peri-implantitis is a common complication characterized by inflammation in tissues surrounding dental implants due to plaque accumulation, which can lead to implant failure. While air flow abrasive treatment has been found to be effective for debriding implant surfaces, little is known about the factors that affect its cleaning capacity. This study systematically examined the cleaning capacity of air powder abrasive (APA) treatment with β-tricalcium phosphate (β-TCP) powder, using various powder jetting strengths and different particle sizes. Three sizes of β-TCP powder (S, M, and L) were prepared, and different powder settings (low, medium, and high) were tested. The cleaning capacity was determined by quantifying ink removal, which simulated biofilm removal from the implant surfaces at different time points. The results of the systematic comparisons showed that the most efficient cleaning of implant surfaces was achieved using size M particles with medium setting. Additionally, the amount of powder consumed was found to be critical to cleaning efficiency, and the implant surfaces were altered in all tested groups. These systematically analyzed outcomes may provide insights into the development of potential non-surgical strategies for treating peri-implant diseases.

Several XBB subvariants such as XBB.1.5, XBB.1.9, XBB.1.16 and XBB.2.3 co-circulate in Singapore. Despite the different viral properties of XBB.1.16 as compared to other XBB subvariants, comparison on their severity is limited. In this study, we investigate the outcomes of hospitalisation and severe COVID-19 infection in individuals infected with different XBB subvariants, adjusted for potential confounders such as age and vaccination history. Overall, our preliminary analysis showed no difference in the severity of different XBB variants.

Peri-implantitis is a common complication characterized by inflammation in tissues with plaque accumulation around dental implants, causing dental implantation failures. Among current managements, air flow abrasive treatment was found to be efficient for the debridement of implant surfaces, however, little information is understood about factors affecting cleaning capacity. In particular, this study examined the cleaning capacity of air powder abrasive (APA) treatment with β-tricalcium phosphate (β-TCP) powder systematically by utilizing various powder jetting strength and different particle sizes. β-TCP powder was prepared in three sizes (S, M and L) and strength of different powder setting (low, medium, high) was estimated. The cleaning capacity was determined by quantifying the ink removal simulating biofilm removal from the implant surfaces. In the light of these systematical comparisons, it can be concluded that complete implant surface cleaning could be achieved by higher jetting strength of APA treatment with smaller β-TCP particles. Moreover, the amount of consumed powder seemed critical to the cleaning efficiency. Implant surfaces and sandblast and acid etching (SLA) structure of titanium discs were altered in all tested groups. The systematically analyzed outcomes in this study might provide an insight into the development of potential strategies to treat peri-implant diseases.

Decellularized matrices can effectively reduce severe immune rejection with their cells and eliminated nucleic acid material and provide specific environments for tissue repair or tissue regeneration. In this study, we prepared acellular cartilage matrix (ACM) powder through the decellularization method and developed ACM hydrogels by physical, chemical, and enzymatic digestion methods. The results demonstrated that the small size group of ACM hydrogels exhibited better gel conditions when the concentration of ACM hydrogels was 30 and 20 mg/mL in 1N HCl through parameter adjustment. The data also confirmed that the ACM hydrogels retained the main components of cartilage: 61.18% of glycosaminoglycan (GAG) and 78.29% of collagen, with 99.61% of its DNA removed compared to samples without the decellularization procedure (set as 100%). Through turbidimetric gelation kinetics, hydrogel rheological property analysis, and hydrogel tissue physical property testing, this study also revealed that increasing hydrogel concentration is helpful for gelation. Besides, the ex vivo test confirmed that a higher concentration of ACM hydrogels had good adhesive properties and could fill in cartilage defects adequately. This study offers useful information for developing and manufacturing ACM hydrogels to serve as potential alternative scaffolds for future cartilage defect treatment.

Background Osteoarthritis (OA) has become the most common type of arthritis, and the cellular and molecular mechanisms involved in OA is complex and not fully understood. Inflammation and matrix degradation have been indicated to play vital roles in pathogenesis of OA. Apart from biochemical molecules such as anti-oxidants which have been suggested to reduce inflammatory responses, photobiomodulation has become interesting targets for developing therapeutic strategies of cartilage repair and regeneration. Methods To investigate the effect of photobiomodulation on OA, red light-emitting diode (LED) was preventatively applied to hydrogen peroxide induced OA-like chondrocytes. Lumen density was measured for the level of free radicals and gene expression of IL-1β, TNF-α, MMP-1, MMP-13, and COL-2 was analyzed. Significant Findings Our results showed that pre-treatment of 635-nm LED for 2 h significantly reduced free radical formation (from 100% to 8.25%) and inflammatory gene IL-1β, TNF-α expression in OA-like cells while matrix gene COL-2 was enhanced. Furthermore, combination of preventative LED treatment with anti-oxidant(s) (vitamin E or/and resveratrol) exerted synergistic effects of anti-inflammation and MMP-13 reduction. In conclusion, preventative LED irradiation combined with anti-oxidants provides a novel therapeutic strategy for treating early OA prior to the progression of the disease.

Poloxamers are negatively temperature-sensitive hydrogels and their hydrophilic groups interact with water molecules at lower temperatures (liquid phase) while their hydrophobic groups interact more strongly with increases in temperature causing gelation. To investigate the factors affecting the rheological properties of poloxamers, various parameters including different poloxamer P407 concentrations, poloxamers P407/P188 blending ratios and additives were examined. The results presented a clear trend of decreasing gelling temperature/time when P407 was at higher concentrations. Moreover, the addition of P188 enhanced the gelling temperature regardless of poloxamer concentration. Polysaccharides and their derivatives have been widely used as components of hydrogel and we found that alginic acid (AA) or carboxymethyl cellulose (CMC) reduced the gelling temperature of poloxamers. In addition, AA-containing poloxamer promoted cell proliferation and both AA -and CMC-containing poloxamer hydrogels reduced cell migration. This study investigated the intriguing characteristics of poloxamer-based hydrogel, providing useful information to compounding an ideal and desired thermo-sensitive hydrogel for further potential clinical applications such as development of sprayable anti-adhesive barrier, wound-healing dressings or injectable drug-delivery system for cartilage repair.

IntroductionCOVID-19 has a wide disease spectrum ranging from asymptomatic to severe. While humoral immune responses are critical in preventing infection, the immune mechanisms leading to severe disease, and the identification of biomarkers of disease progression and/or resolution of the infection remains to be determined.MethodsPlasma samples were obtained from infections during the initial wave of ancestral wildtype SARS-CoV-2 and from vaccine breakthrough infections during the wave of Delta variant, up to six months post infection. The spike-specific antibody profiles were compared across different severity groups and timepoints.ResultsWe found an association between spike-specific IgM, IgA and IgG and disease severity in unvaccinated infected individuals. In addition to strong IgG1 and IgG3 response, patients with severe disease develop a robust IgG2 and IgG4 response. A comparison of the ratio of IgG1 and IgG3 to IgG2 and IgG4 showed that disease progression is associated with a smaller ratio in both the initial wave of WT and the vaccine breakthrough Delta infections. Time-course analysis revealed that smaller (IgG1 and IgG3)/(IgG2 and IgG4) ratio is associated with disease progression, while the reverse associates with clinical recovery.DiscussionWhile each IgG subclass is associated with disease severity, the balance within the four IgG subclasses may affect disease outcome. Acute disease progression or infection resolution is associated with a specific immunological phenotype that is conserved in both the initial wave of WT and the vaccine breakthrough Delta infections.

Summary Background Studies have found different waning rates of neutralising antibodies compared with binding antibodies against SARS-CoV-2. The impact of neutralising antibody waning rate at the individual patient level on the longevity of immunity remains unknown. We aimed to investigate the peak levels and dynamics of neutralising antibody waning and IgG avidity maturation over time, and correlate this with clinical parameters, cytokines, and T-cell responses. Methods We did a longitudinal study of patients who had recovered from COVID-19 up to day 180 post-symptom onset by monitoring changes in neutralising antibody levels using a previously validated surrogate virus neutralisation test. Changes in antibody avidities and other immune markers at different convalescent stages were determined and correlated with clinical features. Using a machine learning algorithm, temporal change in neutralising antibody levels was classified into five groups and used to predict the longevity of neutralising antibody-mediated immunity. Findings We approached 517 patients for participation in the study, of whom 288 consented for outpatient follow-up and collection of serial blood samples. 164 patients were followed up and had adequate blood samples collected for analysis, with a total of 546 serum samples collected, including 128 blood samples taken up to 180 days post-symptom onset. We identified five distinctive patterns of neutralising antibody dynamics as follows: negative, individuals who did not, at our intervals of sampling, develop neutralising antibodies at the 30% inhibition level (19 [12%] of 164 patients); rapid waning, individuals who had varying levels of neutralising antibodies from around 20 days after symptom onset, but seroreverted in less than 180 days (44 [27%] of 164 patients); slow waning, individuals who remained neutralising antibody-positive at 180 days post-symptom onset (46 [28%] of 164 patients); persistent, although with varying peak neutralising antibody levels, these individuals had minimal neutralising antibody decay (52 [32%] of 164 patients); and delayed response, a small group that showed an unexpected increase of neutralising antibodies during late convalescence (at 90 or 180 days after symptom onset; three [2%] of 164 patients). Persistence of neutralising antibodies was associated with disease severity and sustained level of pro-inflammatory cytokines, chemokines, and growth factors. By contrast, T-cell responses were similar among the different neutralising antibody dynamics groups. On the basis of the different decay dynamics, we established a prediction algorithm that revealed a wide range of neutralising antibody longevity, varying from around 40 days to many decades. Interpretation Neutralising antibody response dynamics in patients who have recovered from COVID-19 vary greatly, and prediction of immune longevity can only be accurately determined at the individual level. Our findings emphasise the importance of public health and social measures in the ongoing pandemic outbreak response, and might have implications for longevity of immunity after vaccination. Funding National Medical Research Council, Biomedical Research Council, and A*STAR, Singapore.

The demand of bone grafting is increasing as the population ages worldwide. Although bone graft materials have been extensively developed over the decades, only a few injectable bone grafts are clinically available and none of them can be extruded from 18G needles. To overcome the existing treatment limitations, the aim of this study is to develop ideal injectable implants from biomaterials for minimally invasive surgery. An injectable composite bone graft containing calcium sulfate hemihydrate, tetracalcium phosphate, and anhydrous calcium hydrogen phosphate (CSH/CaP paste) was prepared with different CSH/CaP ratios and different concentrations of additives. The setting time, injectability, mechanical properties, and biocompatibility were evaluated. The developed injectable CSH/CaP paste (CSH/CaP 1:1 supplemented with 6% citric acid and 2% HPMC) presented good handling properties, great biocompatibility, and adequate mechanical strength. Furthermore, the paste was demonstrated to be extruded from a syringe equipped with 18G needles and exerted a great potential for minimally invasive surgery. The developed injectable implants with tissue repairing potentials will provide an ideal therapeutic strategy for minimally invasive surgery to apply in the treatment of maxillofacial defects, certain indications in the spine, inferior turbinate for empty nose syndrome (ENS), or reconstructive rhinoplasty.

Objectives We considered how decision making around human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) among gay, bisexual, and other men who have sex with men (GBMSM) is made in the context of one’s perceived risk of HIV acquisition and the availability of condoms. Methods We recruited 648 GBMSM aged 18 years old and residing in Singapore through Grindr. Participants were given information on PrEP and participated in a discrete choice experiment requiring them to choose between 2 baskets of PrEP attributes and compare the chosen “PrEP only” option to default options of “condoms only” or “PrEP with condoms.” Generalized multinomial logit model was used to examine the scaling effect and preference heterogeneity. Latent class analysis was conducted to examine preference heterogeneity in the sample. Results Latent class analysis revealed 3 classes of GBMSM: PrEP conservatives (53.9%), moderates (31.1%), and liberals (14.9%). PrEP conservatives were more likely to report greater utility when using condoms only compared with PrEP only, as well as PrEP with condoms, compared with PrEP only, and more likely to report the lowest utility for PrEP as perceived HIV risk increased. PrEP liberals were more likely to report greatest utilities for PrEP only compared with condoms only, as well as PrEP only compared with PrEP with condoms. The utility for PrEP was not affected by perceived risk of HIV or sexually transmitted infections when risks were low. Conclusion This study provides some evidence for risk compensation among a class of GBMSM who already perceived themselves to be good candidates for PrEP before the discrete choice experiment.

Using barbed thread lifting for facial rejuvenation has become popular these days due to its minimally invasive procedures with reduced complications. However, only limited studies regarding its mechanical properties for face suspension were published. The aim of this study was to evaluate suture-holding ability regarding its facelift property, and different specimens were tested in order to establish an in vitro model. Fresh porcine tissue and the synthetic material polydimethylsiloxane (PDMS) were selected to simulate human skin for evaluating barbed suture pull-out strength by the universal material testing machine. The results showed that the pull-out strength of barbs between different porcine tissues varied without consistency. By contrast, PDMS (30:1) showed more consistent pull-out strength in each testing, and the average maximum load force was close to porcine tissue. Furthermore, after submerging barbed sutures in PBS for 0 days (T0), 7 days (T7) and 14 days (T14), a trend of decreased average maximum load force, displacement and force of 1.5 mm/2 mm/3 mm displacement could be detected by in vitro testing with PDMS (30:1). These results provide support for using PDMS (30:1) to evaluate suture pull-out strength and holding/lifting capacities in vitro to obtain consistent and objective information for evaluating substantial equivalence of devices. The established in vitro method could be used for the future development of barbed thread lifting technology.

BACKGROUND: We hypothesize that comprehensive surveillance of COVID-19 in Singapore has facilitated early case detection and prompt contact tracing and, with community-based measures, contained spread. We assessed the effectiveness of containment measures by estimating transmissibility (effective reproduction number, (Equation is included in full-text article.)) over the course of the outbreak. METHODS: We used a Bayesian data augmentation framework to allocate infectors to infectees with no known infectors and determine serial interval distribution parameters via Markov chain Monte Carlo sampling. We fitted a smoothing spline to the number of secondary cases generated by each infector by respective onset dates to estimate (Equation is included in full-text article.)and evaluated increase in mean number of secondary cases per individual for each day's delay in starting isolation or quarantine. RESULTS: As of April 1, 2020, 1000 COVID-19 cases were reported in Singapore. We estimated a mean serial interval of 4.6 days [95% credible interval (CI) = 4.2, 5.1] with a SD of 3.5 days (95% CI = 3.1, 4.0). The posterior mean (Equation is included in full-text article.)was below one for most of the time, peaking at 1.1 (95% CI = 1.0, 1.3) on week 9 of 2020 due to a spreading event in one of the clusters. Eight hundred twenty-seven (82.7%) of cases infected less than one person on average. Over an interval of 7 days, the incremental mean number of cases generated per individual for each day's delay in starting isolation or quarantine was 0.03 cases (95% CI = 0.02, 0.05). CONCLUSIONS: We estimate that robust surveillance, active case detection, prompt contact tracing, and quarantine of close contacts kept (Equation is included in full-text article.)below one.

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.

Memory T cells induced by previous pathogens can shape susceptibility to, and the clinical severity of, subsequent infections1. Little is known about the presence in humans of pre-existing memory T cells that have the potential to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we studied T cell responses against the structural (nucleocapsid (N) protein) and non-structural (NSP7 and NSP13 of ORF1) regions of SARS-CoV-2 in individuals convalescing from coronavirus disease 2019 (COVID-19) (n = 36). In all of these individuals, we found CD4 and CD8 T cells that recognized multiple regions of the N protein. Next, we showed that patients (n = 23) who recovered from SARS (the disease associated with SARS-CoV infection) possess long-lasting memory T cells that are reactive to the N protein of SARS-CoV 17 years after the outbreak of SARS in 2003; these T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2. We also detected SARS-CoV-2-specific T cells in individuals with no history of SARS, COVID-19 or contact with individuals who had SARS and/or COVID-19 (n = 37). SARS-CoV-2-specific T cells in uninfected donors exhibited a different pattern of immunodominance, and frequently targeted NSP7 and NSP13 as well as the N protein. Epitope characterization of NSP7-specific T cells showed the recognition of protein fragments that are conserved among animal betacoronaviruses but have low homology to 'common cold' human-associated coronaviruses. Thus, infection with betacoronaviruses induces multi-specific and long-lasting T cell immunity against the structural N protein. Understanding how pre-existing N- and ORF1-specific T cells that are present in the general population affect the susceptibility to and pathogenesis of SARS-CoV-2 infection is important for the management of the current COVID-19 pandemic.

Summary Background Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020. Methods We gathered epidemiological and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2. Findings As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3–6). The serial interval between transmission pairs ranged between 3 days and 8 days. Interpretation SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community. Funding None.

Gay, bisexual, and other men who have sex with men (GBMSM) are disproportionately affected by HIV and other sexually transmitted infections (STI). While levels of self-perceived risk of HIV or other STI acquisition has been well-established as a factor that is positively associated with HIV or other STI testing, less effort has been made to identify the processes through which GBMSM assess their perceived risk of HIV or other STI acquisition. We conducted a qualitative study exploring the factors influencing self-perceived risk of HIV or other STI among GBMSM. Semi-structured interviews were conducted with 35 self-identified GBMSM in Singapore from October 2017 to June 2018, and the data were analyzed through inductive thematic analysis. Participants reported drawing on individual factors including their own sexual health knowledge and past experiences of risk, interpersonal factors including their sexual partners' attributes or characteristics and perceived trust and familiarity with their sexual partners, and situational factors including the venue and familiarity with such venues where sexual activity took place, in determining their self-perceived risk of HIV or other STI acquisition. The results of this study have implications for HIV and other STI risk education.

The impact of seasonal influenza has been under-appreciated in Asia and surveillance data lags in most other regions. The variety of influenza circulation patterns in Asia – largely due to the range of climates – has also only recently been recognized and its effect on the burden of disease is not fully understood. Recent reports that clinical protection wanes in the weeks after influenza vaccination emphasize the importance of optimally timing vaccination to local epidemiology. It also raises questions as to whether influenza vaccines should be administered more frequently than annually and what may be the benefits in Asia of access to new vaccines with enhanced immunogenicity and effectiveness. This review will summarize influenza surveillance data from Asian countries over 2011–2018, and consider the implications for vaccination strategies in different parts of Asia.

Background: This study compared the genomes of influenza viruses that caused mild infections among outpatients and severe infections among hospitalized patients in Singapore, and characterized their molecular evolution and receptor-binding specificity. Methods: The complete genomes of influenza A/H1N1, A/H3N2 and B viruses that caused mild infections among outpatients and severe infections among inpatients in Singapore during 2012–2015 were sequenced and characterized. Using various bioinformatics approaches, we elucidated their evolutionary, mutational and structural patterns against the background of global and vaccine strains. Results: The phylogenetic trees of the 8 gene segments revealed that the outpatient and inpatient strains overlapped with representative global and vaccine strains. We observed a cluster of inpatients with A/H3N2 strains that were closely related to vaccine strain A/Texas/50/2012(H3N2). Several protein sites could accurately discriminate between outpatient versus inpatient strains, with site 221 in neuraminidase (NA) achieving the highest accuracy for A/H3N2. Interestingly, amino acid residues of inpatient but not outpatient isolates at those sites generally matched the corresponding residues in vaccine strains, except at site 145 of hemagglutinin (HA). This would be especially relevant for future surveillance of A/H3N2 strains in relation to their antigenicity and virulence. Furthermore, we observed a trend in which the HA proteins of influenza A/H3N2 and A/H1N1 exhibited enhanced ability to bind both avian and human host cell receptors. In contrast, the binding ability to each receptor was relatively stable for the HA of influenza B. Conclusions: Overall, our findings extend our understanding of the molecular and structural evolution of influenza virus strains in Singapore within the global context of these dynamic viruses. Keywords: Influenza, A/H1N1 viruses, A/H3N2 viruses, Influenza B, Evolution, Mutations, Receptor binding, Severity, Singapore

Background: Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore. Methods: Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure. Results: A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20–43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 – 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 – 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 – 15.4%) in Chinese workers to 23.0% (95% CI 17.1 – 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989. Conclusions: The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks. Published version MICC was supported by the Ministry of Health, Singapore, under the Communicable Diseases – Public Health Research Grant (grant number MOHCS‑ 15MAR001) for sample collection. Laboratory testing for the seroprevalence of diphtheria among migrant workers was supported by the National Public Health Laboratory.

Background: In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore. Methods: Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT). Results: A total of 2234 migrant workers aged 20–49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2–91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965–1989 than those born in 1990–1999 (95.3% vs. 86.6%, p < 0.0005), whereas there was no significant difference by gender (90.8% in men vs. 89.9% in women, p = 0.508). 195 out of 213 samples with equivocal or negative ELISA results were tested positive using PRNT. Conclusion: The IgG seroprevalence in migrant workers was below the herd immunity threshold of 95% for measles. Sporadic outbreaks may occur in susceptible individuals due to high transmissibility of measles virus. Seroprevalence surveys can help identify susceptible subgroups for vaccination. Ministry of Health (MOH) Published version Sample collection was supported by the Ministry of Health, Singapore, under the Communicable Diseases—Public Health Research Grant (Grant Number MOHCS15MAR001). Laboratory testing for the seroprevalence of measles in migrant workers was supported by the National Public Health Laboratory.

Objectives. To evaluate the effectiveness of point-of-care informational interventions in general practitioner clinics to improve influenza and pneumococcal vaccination uptake among elderly patients. Methods. We conducted a pragmatic, cluster-randomized crossover trial in 22 private general practitioner clinics in Singapore, from November 2017 to July 2018. We included all patients aged 65 years or older. Clinics were assigned to a 3-month intervention (flyers and posters encouraging vaccination) plus 1-month washout period, and a 4-month control period (usual care). Primary outcomes were differences in vaccination uptake rates between periods. Secondary outcomes were identification of other factors associated with vaccination uptake. Results. A total of 4378 and 4459 patients were included in the intervention and control periods, respectively. Both influenza (5.9% vs 4.8%; P = .047) and pneumococcal (5.7% vs 3.7%; P = .001) vaccination uptake rates were higher during the intervention period compared with the control period. On multilevel logistic regression analysis, follow-up for hypertension, diabetes mellitus, hyperlipidemia, or any combination of the 3 was associated with uptake of both vaccines. Conclusions. Point-of-care informational interventions likely contributed to increased influenza and pneumococcal vaccination uptake. Patients on follow-up for hypertension, diabetes mellitus, hyperlipidemia, or any combination of the 3 were more likely to receive influenza and pneumococcal vaccination and should be actively engaged by physicians. Trial Registration. ClinicalTrials.gov Identifier: NCT03445117.

SUMMARY Background Impact of the Delta variant and vaccination on SARS-CoV-2 transmission remains unclear. In Singapore, quarantine of all close contacts, including entry and exit PCR testing, provided the opportunity to determine risk of infection by the Delta variant compared to other variants, vaccine efficacy against SARS-CoV-2 acquisition, symptomatic or severe COVID-19, and risk factors associated with SARS-CoV-2 acquisition and symptomatic disease. Methods This retrospective cohort study included all close contacts between September 1, 2020 and May 31, 2021. Regardless of symptoms, all were quarantined for 14 days with entry and exit PCR testing. Household contacts were defined as individuals who shared a residence with a Covid-19 index case. Secondary attack rates among household close contacts of Delta variant-infected indexes and other variant-infected indexes were derived from prevalence of diagnosed cases among contacts. Relative risk ratios and bootstrapping at the cluster level was used to determine risk of infection by the Delta variant compared to other variants and vaccine efficacy against SARS-CoV-2 acquisition, symptomatic or severe COVID-19. Logistic regression using generalized estimating equations was used to determine risk factors associated with SARS-CoV-2 acquisition and symptomatic disease Findings Of 1024 household contacts linked to 301 PCR-confirmed index cases, 753 (73.5%) were linked to Delta-infected indexes and 248 (24.2%) were exposed to indexes with other variants. Household secondary attack rate among unvaccinated Delta-exposed contacts was 25.8% (95% boostrap confidence interval [BCI] 20.6–31.5%) compared with 12.9% (95%BCI 7.0–20.0%) among other variant-exposed contacts. Unvaccinated Delta-exposed contacts were more likely to be infected than those exposed to other variants (Relative risk 2.01, 95%CI 1.24–3.84). Among Delta-exposed contacts, complete vaccination had a vaccine effectiveness of 56.4% (95%BCI 32.6–75.8%) against acquisition, 64.1% (95%BCI 37.8–85.4%) against symptomatic disease and 100% against severe disease. Among Delta-exposed contacts, vaccination status (adjusted odds ratio [aOR] 0.33, 95% robust confidence interval [RCI] 0.17–0.63) and older age of the index (aOR 1.20 per decade, 95%RCI 1.03–1.39) was associated with increased risk of SARS-CoV-2 acquisition by the contact. Vaccination status of the index was not associated with a statistically-significant difference for contact SARS-CoV-2 acquisition (aOR 0.73, 95%RCI 0.38–1.40). Interpretation Increased risk of SARS-CoV-2 Delta acquisition compared with other variants was reduced with vaccination. Close-contacts of vaccinated Delta-infected indexes did not have statistically significant reduced risk of acquisition compared with unvaccinated Delta-infected indexes.

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO4, CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical characteristics. This study aims to prepare a DBM/CS composite bone graft material in a moldable putty form without compromising the peculiar properties of DBM and CS. For this purpose, firstly, porcine femur was defatted using chloroform/methanol and extracted by acid for demineralization, then freeze-dried and milled/sieved to obtain DBM powder. Secondly, the α-form and β-form of calcium sulfate hemihydrate (CaSO4·0.5H2O, CSH) were produced by heating gypsum (CaSO4·2H2O). The morphology and particle sizes of α- and β-CSH were obtained by SEM, and their chemical properties were confirmed by EDS, FTIR and XRD. Furthermore, the DBM-based graft was mixed with α- or β-CSH at a ratio of 9:1, and glycerol/4% HPMC was added as a carrier to produce a putty. DBM/CSH putty possesses a low washout rate, good mechanical strength and biocompatibility. In conclusion, we believe that the moldable DBM/CSH composite putty developed in this study could be a promising substitute for the currently available bone grafts, and might have practical application in the orthopedics field as a potential bone void filler.

Summary Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a challenge to the effectiveness of current vaccines. A vaccine that could prevent infection caused by known and future variants of concern as well as infection with pre-emergent sarbecoviruses (i.e., those with potential to cause disease in humans in the future) would be ideal. Here we provide data showing that potent cross-clade pan-sarbecovirus neutralizing antibodies are induced in survivors of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) infection who have been immunized with the BNT162b2 messenger RNA (mRNA) vaccine. The antibodies are high-level and broad-spectrum, capable of neutralizing not only known variants of concern but also sarbecoviruses that have been identified in bats and pangolins and that have the potential to cause human infection. These findings show the feasibility of a pan-sarbecovirus vaccine strategy. (Funded by the Singapore National Research Foundation and National Medical Research Council.)

Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement with considerable morbidity and large economic burdens. Antibiotic-Loaded Bone Cement (ALBC) has been developed as a valuable tool for local administration and is becoming one of the most effective methods for the prevention and treatment of orthopedic infections. Controlling antibiotic release from ALBC is critical to achieve effective infection control, however, the antibiotic elution rates are generally low, and the mechanisms are poorly understood. Thus, the present study aims to investigate the effects of the basic acrylic bone cement components, including liquid/powder (monomer-to-polymer) ratios, radiopacifier, initiator, and doses of antibiotics on the porosity, antibiotic elution rates and mechanical properties of polymethylmethacrylate (PMMA) based ALBC. The obtained results from the in vitro studies suggested that a reduction in the liquid/powder ratio and an increase in the radiopacifier ratio and gentamicin doses led to increased porosity and release of antibiotic, while the initiator ratio exerted no effect on elution rates. In conclusion, we hope that by varying the composition of ALBC, we could considerably enhance the antibiotic elution rates by increasing porosity, while maintaining an adequate mechanical strength of the bone cements. This finding might provide insights into controlling antibiotic release from ALBC to achieve effective infection control after total joint replacement surgery.

We studied the performance of an algorithm combining multiplex polymerase chain reaction with phenotypic detection of extended-spectrum β-lactamases and carbapenemases directly from positive blood culture bottles in patients with gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time to optimal therapy in patients with gram-negative bacteremia.

ObjectivesWHO recommends that low burden countries consider systematic screening and treatment of latent tuberculosis infection (LTBI) in migrants from high incidence countries. We aimed to determine LTBI prevalence and risk factors and evaluate cost-effectiveness of screening and treating LTBI in migrants to Singapore from a government payer perspective.DesignCross-sectional study and cost-effectiveness analysis.SettingMigrants in Singapore.Participants3618 migrants who were between 20 and 50 years old, have not worked in Singapore previously and stayed in Singapore for less than a year were recruited.Primary and secondary outcome measuresCosts, quality-adjusted life-years (QALYs), threshold length of stay, incremental cost-effectiveness ratios (ICERs), cost per active TB case averted.ResultsOf 3584 migrants surveyed, 20.4% had positive interferon-gamma release assay (IGRA) results, with the highest positivity in Filipinos (33.2%). Higher LTBI prevalence was significantly associated with age, marital status and past TB exposure. The cost-effectiveness model projected an ICER of S$57 116 per QALY and S$12 422 per active TB case averted for screening and treating LTBI with 3 months once weekly isoniazid and rifapentine combination regimen treatment compared with no screening over a 50-year time horizon. ICER was most sensitive to the cohort’s length of stay in Singapore, yearly disease progression rates from LTBI to active TB, followed by the cost of IGRA testing.ConclusionsFor LTBI screening and treatment of migrants to be cost-effective, migrants from high burden countries would have to stay in Singapore for ~50 years. Risk-stratified approaches based on projected length of stay and country of origin and/or age group can be considered.

Background This study draws on qualitative insights on the barriers and facilitators to HIV testing, as well as perceptions of HIV self-testing (HIVST), to propose a framework to understand the benefits, but also potential knock-on implications of introducing HIVST in the context of other STI testing. Methods We conducted semi-structured, in-depth interviews with 30 gay, bisexual and other men who have sex with men (GBMSM) aged 18 and 39 years old in Singapore. Interview topics included barriers and facilitators to HIV and other STI testing, as well as perceptions of HIVST. Interviews were audio-recorded, transcribed, coded, and analysed using thematic analysis. Results For HIV testing, participants cited the perceived risk of acquiring, susceptibility to, and symptoms of HIV as internal motivators, while social influence and accessibility of HIV testing services were external motivators. For STI testing, perceived symptoms and partner notification of STI were reported as an internal and external motivator, respectively. Availability of bundle tests, starting a new relationship, and instances of mandatory testing motivated both simultaneous HIV and other STI testing. The fear of a positive diagnosis and lack of confidentiality were cited as internal and external barriers to HIV testing, respectively, while low perceived severity of other STI and the cost of STI tests were cited as internal and external barriers to other STI testing, respectively. We identified pathways to HIV and other STI testing and discussed how the introduction of HIVST may reduce opportunities for other STI testing. Conclusions The findings of this study suggest that introducing HIVST might weaken linkages to other STI testing if alternative strategies of promoting other STI testing are not simultaneously implemented. We recommend that future interventions address both the risks of HIV and other STI simultaneously, and that structural interventions promoting HIV and other STI prevention be balanced accordingly.

Background Gay, bisexual, and other men who have sex with men (GBMSM) are at disproportionately higher risk of acquiring HIV and other sexually transmitted infections (STI). While HIV/STI testing rates among GBMSM are increasing worldwide, they remain suboptimal in a variety of settings. While many studies have attempted to evaluate the efficacy of a variety of community-based campaigns, including peer and reminder-based interventions on HIV/STI testing, however few have attempted to do so for a web drama series. Objective This study evaluates the effectiveness of a popular web drama video series developed by a community-based organization in Singapore for GBMSM on HIV and other STI testing behaviors. Methods The study is a pragmatic, randomized controlled trial to evaluate a popular web drama video series developed by a community-based organization in Singapore for GBMSM. A total of 300 HIV-negative, GBMSM men in Singapore aged 18 to 29 years old were recruited and block-randomized into the intervention (n=150) and control arms (n=150). Primary outcomes included changes in self-reported intention to test for, actual testing for, and regularity of testing for HIV, syphilis, chlamydia or gonorrhea, while secondary outcomes include changes in a variety of other knowledge-based and psychosocial measures at the end of the study period. Results Overall, 83.3% (125/150) of participants in the intervention arm completed the proof of completion survey, compared to 88.7% (133/150) in the control arm. We found improvements in self-reporting as a regular (at least yearly) tester for HIV (15.9% difference, 95% CI, 3.2% to 28.6%; P=.02), as well as chlamydia or gonorrhea (15.5% difference, 95% CI, 4.2% to 26.9%; P=.009), indicating that the intervention had positively impacted these outcomes compared to the control condition. We also found improvements in participants’ intentions to test for HIV (16.6% difference, 95% CI, 4.3% to 28.9%; P=.009), syphilis (14.8% difference, 95% CI, 3.2% to 26.4%; P=.01), as well as chlamydia or gonorrhea (15.4% difference, 95% CI, 4.2% to 26.6%; P=.008), in the next 3 months, indicating that the intervention was effective in positively impacting intention for HIV and other STI testing among participants. Conclusions There are clear benefits for promoting intentions to test regularly and prospectively on a broad scale through this intervention. This intervention also has potential to reach GBMSM who may not have access to conventional HIV and other STI prevention messaging, which have typically been implemented at sex-on-premises venues, bars, clubs, and in sexual health settings frequented by GBMSM. When coupled with community or population-wide structural interventions, the overall impact on testing will likely be significant. Trial Registration ClinicalTrials.gov NCT04021953; https://clinicaltrials.gov/ct2/show/NCT04021953 International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2019-033855

BACKGROUND Gay, bisexual, and other men who have sex with men (GBMSM) are at disproportionately higher risk of acquiring HIV and other sexually transmitted infections (STI). While HIV/STI testing rates among GBMSM are increasing worldwide, they remain suboptimal in a variety of settings. While many studies have attempted to evaluate the efficacy of a variety of community-based campaigns, including peer and reminder-based interventions on HIV/STI testing, however few have attempted to do so for a web drama series. OBJECTIVE This study evaluates the effectiveness of a popular web drama video series developed by a community-based organization in Singapore for GBMSM on HIV and other STI testing behaviors. METHODS The study is a pragmatic, randomized controlled trial to evaluate a popular web drama video series developed by a community-based organization in Singapore for GBMSM. A total of 300 HIV-negative, GBMSM men in Singapore aged 18 to 29 years old were recruited and block-randomized into the intervention (n=150) and control arms (n=150). Primary outcomes included changes in self-reported intention to test for, actual testing for, and regularity of testing for HIV, syphilis, chlamydia or gonorrhea, while secondary outcomes include changes in a variety of other knowledge-based and psychosocial measures at the end of the study period. RESULTS Overall, 83.3% (125/150) of participants in the intervention arm completed the proof of completion survey, compared to 88.7% (133/150) in the control arm. We found improvements in self-reporting as a regular (at least yearly) tester for HIV (15.9% difference, 95% CI, 3.2% to 28.6%; P=.02), as well as chlamydia or gonorrhea (15.5% difference, 95% CI, 4.2% to 26.9%; P=.009), indicating that the intervention had positively impacted these outcomes compared to the control condition. We also found improvements in participants’ intentions to test for HIV (16.6% difference, 95% CI, 4.3% to 28.9%; P=.009), syphilis (14.8% difference, 95% CI, 3.2% to 26.4%; P=.01), as well as chlamydia or gonorrhea (15.4% difference, 95% CI, 4.2% to 26.6%; P=.008), in the next 3 months, indicating that the intervention was effective in positively impacting intention for HIV and other STI testing among participants. CONCLUSIONS There are clear benefits for promoting intentions to test regularly and prospectively on a broad scale through this intervention. This intervention also has potential to reach GBMSM who may not have access to conventional HIV and other STI prevention messaging, which have typically been implemented at sex-on-premises venues, bars, clubs, and in sexual health settings frequented by GBMSM. When coupled with community or population-wide structural interventions, the overall impact on testing will likely be significant. CLINICALTRIAL ClinicalTrials.gov NCT04021953; https://clinicaltrials.gov/ct2/show/NCT04021953 INTERNATIONAL REGISTERED REPORT RR2-10.1136/bmjopen-2019-033855

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion within the ATXN3/MJD1 gene. The expanded CAG repeats encode a polyglutamine (polyQ) tract at the C-terminus of the ATXN3 protein. ATXN3 containing expanded polyQ forms aggregates, leading to subsequent cellular dysfunctions including an impaired ubiquitin-proteasome system (UPS). To investigate the pathogenesis of SCA3 and develop potential therapeutic strategies, we established induced pluripotent stem cell (iPSC) lines from SCA3 patients (SCA3-iPSC). Neurons derived from SCA3-iPSCs formed aggregates that are positive to the polyQ marker 1C2. Treatment with the proteasome inhibitor, MG132, on SCA3-iPSC-derived neurons downregulated proteasome activity, increased production of radical oxygen species (ROS), and upregulated the cleaved caspase 3 level and caspase 3 activity. This increased susceptibility to the proteasome inhibitor can be rescued by a Chinese herbal medicine (CHM) extract NH037 (from Pueraria lobata) and its constituent daidzein via upregulating proteasome activity and reducing protein ubiquitination, oxidative stress, cleaved caspase 3 level, and caspase 3 activity. Our results successfully recapitulate the key phenotypes of the neurons derived from SCA3 patients, as well as indicate the potential of NH037 and daidzein in the treatment for SCA3 patients.

Although factors associated with HIV/sexually transmitted infection (STI) testing among gay, bisexual, and queer (GBQ) men are well-established in the literature, few studies have attempted to delineate the processes underlying different patterns of testing. We conducted a qualitative study involving 35 semistructured interviews with a purposive sample of GBQ men in Singapore from October 2017 to July 2018. Topics explored included formative sexual experiences, relationships, and experiences of HIV/STI testing. Interviews were audio-recorded, transcribed, coded, and analyzed through inductive thematic analysis. A typology comprising four distinct HIV/STI testing patterns was identified from the data, categorized based on the regularity of testing, relative to internal or external factors that motivate testing behaviors. These include triggered episodic testing, influenced episodic testing, institutionalized regular testing, and value-based regular testing. The typology highlights the preconditions that underlie different testing patterns and provides a framework for developing interventions that promote HIV/STI testing among GBQ men.

A particular wafer processing step involves deposition of a Ti thin film (˜6 nm to ˜13 nm) on Si, under processing conditions intended to form a silicide with specific electrical properties. It is difficult, however, to distinguish silicide formation from mere elemental inter-diffusion. Routine laboratory XPS, using an Al X-Ray source(1486.6ev), does have an appropriate probing depth for the film stack involved, but the chemical shifts in Ti (2p) and Si(2p) are too small (

Purpose In recent years, governments around the world are actively promoting the Open Government Data (OGD) to facilitate reusing open data and developing information applications. Currently, there are more than 35,000 data sets available on the Taiwan OGD website. However, the existing Taiwan OGD website only provides keyword queries and lacks a friendly query interface. This study aims to address these issues by defining a DBpedia cloud computing framework (DCCF) for integrating DBpedia with Semantic Web technologies into Spark cluster cloud computing environment. Design/methodology/approach The proposed DCCF is used to develop a Taiwan OGD recommendation platform (TOGDRP) that provides a friendly query interface to automatically filter out the relevant data sets and visualize relationships between these data sets. Findings To demonstrate the feasibility of TOGDRP, the experimental results illustrate the efficiency of the different cloud computing models, including Hadoop YARN cluster model, Spark standalone cluster model and Spark YARN cluster model. Originality/value The novel solution proposed in this study is a hybrid approach for integrating Semantic Web technologies into Hadoop and Spark cloud computing environment to provide OGD data sets recommendation.

ObjectivesTo develop a localised instrument and Bayesian statistical method to generate size estimates—adjusted for transmission error and barrier effects—of at-risk populations in Singapore.MethodsWe conducted indepth interviews and focus group to guide the development of the survey questionnaire. The questionnaire was administered between July and August 2017 in Singapore. Using the network scale-up method (NSUM), we developed a Bayesian hierarchical model to estimate the number of individuals in four hidden populations at risk of HIV. The method accounted for both transmission error and barrier effects using social acceptance measures and demographics.ResultsThe adjusted size estimate of the population of male clients of female sex workers was 72 000 (95% CI 51 000 to 100 000), of female sex workers 4200 (95% CI 1600 to 10 000), of men who have sex with men 210 000 (95% CI 140 000 to 300 000) and of intravenous drug users 11 000 (95% CI 6500 to 17 000).ConclusionsThe NSUM with adjustment for attitudes and demographics allows national-level estimates of multiple priority populations to be determined from simple surveys of the general population, even in relatively conservative societies.

Gay, bisexual and queer men in Singapore are disproportionately represented in prevalent HIV infections, relative to the general population. While anticipated stigma has been found to be a barrier to HIV/STI testing among gay, bisexual and queer men, little effort has been made to contextualise such stigma within the broader sociocultural milieu. We conducted 35 in-depth interviews with a purposively recruited sample of men in Singapore with a focus on topics such as sexual identity development, formative sexual experiences and HIV/STI testing experience. Interviews were analysed through thematic analysis using techniques borrowed from a grounded theory approach. Participants drew on their past interactions with family, friends, religion, the gay, bisexual and queer men's community and the wider society to construct meanings of deviance in the context of their sexuality. Participants articulated how anticipated stigma was rooted in such deviance, and how clinics or other HIV/STI-related health services served as physical spaces of costly disclosure by exposing or imposing 'deviant' identities on individuals who access these physical spaces, which were otherwise concealed. Findings from the study provide a framework for actions and interventions to address the roots of anticipated stigma in the context of HIV/STI testing among gay, bisexual and queer men.

ObjectivesGay, bisexual and other men who have sex with men (GBMSM) in Singapore may fear disclosing their sexual orientation to others due to negative societal attitudes, and the law that criminalises sexual relations between men, which may, in turn, impede access to HIV/sexually transmitted infection (STI)-related health services. This study attempts to determine how selective disclosure to varying social groups, and the extent of disclosure, may serve to impact HIV/STI testing patterns among GBMSM.MethodsIn this observational study, we recruited GBMSM in Singapore through an online cross-sectional survey disseminated via the smartphone app Grindr from 14 January to 11 February 2018. Respondents provided information on their sociodemographic characteristics, disclosure of sexual orientation towards other lesbian, gay, bisexual, transgender and questioning (LGBTQ) individuals, non-LGBTQ family members, non-LGBTQ friends and non-LGBTQ colleagues, along with their HIV/STI testing patterns. Extent of disclosure was defined as the number of social groups that a participant had disclosed his sexual orientation to. Statistical analyses were conducted through descriptive statistics, multivariable binary, ordinal, and multinomial logistic regression models.ResultsWe recruited 1339 respondents, of which 1098 who had provided their response to questions on HIV/STI testing were included in the analytic sample. Multivariable analyses indicated that disclosure towards non-LGBTQ family members (adjusted OR [aOR] 1.85, 95% CI 1.12 to 3.07) and other LGBTQ individuals (aOR 1.63, 95% CI 1.12 to 2.37) were positively associated with recent HIV testing, whereas disclosure towards non-LGBTQ colleagues (aOR 1.56, 95% CI 1.09 to 2.22) was positively associated with regular HIV testing. Extent of disclosure exhibited a positive, dose–response relationship with all testing outcomes.ConclusionsResults indicate how the fear of being identified as an LGBTQ individual may deter GBMSM from getting tested for HIV and other STIs. Health services should bridge the gaps to accessing healthcare among individuals who fear being stigmatised for attending sexual health-specific clinics or being identified as GBMSM.

Identifying the source of an outbreak facilitates its control. Spatial methods are not optimally used in outbreak investigation, due to a mix of the complexities involved (e.g., methods requiring additional parameter selection), imperfect performance, and lack of confidence in existing options. We simulated 30 mock outbreaks and compared 5 simple methods that do not require parameter selection but could select between mock cases’ residential and workplace addresses to localize the source. Each category of site had a unique spatial distribution; residential and workplace address were visually and statistically clustered around the residential neighborhood and city center sites respectively, suggesting that the value of workplace addresses is tied to the location where an outbreak might originate. A modification to centrographic statistics that we propose—the center of minimum geometric distance with address selection—was able to localize the mock outbreak source to within a 500 m radius in almost all instances when using workplace in combination with residential addresses. In the sensitivity analysis, when given sufficient workplace data, the method performed well in various scenarios with only 10 cases. It was also successful when applied to past outbreaks, except for a multisite outbreak from a common food supplier.

Nine autosomal dominant spinocerebellar ataxias (SCAs) are caused by an abnormal expansion of CAG trinucleotide repeats that encodes a polyglutamine (polyQ) tract within different genes. Accumulation of aggregated mutant proteins is a common feature of polyQ diseases, leading to progressive neuronal dysfunction and degeneration. SCA type 3 (SCA3), the most common form of SCA worldwide, is characterized by a CAG triplet expansion in chromosome 14q32.1 ATXN3 gene. As accumulation of the mutated polyQ protein is a possible initial event in the pathogenic cascade, clearance of aggregated protein by ubiquitin proteasome system (UPS) has been proposed to inhibit downstream detrimental events and suppress neuronal cell death. In this study, Chinese herbal medicine (CHM) extracts were studied for their proteasome-activating, polyQ aggregation-inhibitory and neuroprotective effects in GFPu and ATXN3/Q[Formula: see text]-GFP 293/SH-SY5Y cells. Among the 14 tested extracts, 8 displayed increased proteasome activity, which was confirmed by 20S proteasome activity assay and analysis of ubiquitinated and fused GFP proteins in GFPu cells. All the eight extracts displayed good aggregation-inhibitory potential when tested in ATXN3/Q[Formula: see text]-GFP 293 cells. Among them, neuroprotective effects of five selected extracts were shown by analyses of polyQ aggregation, neurite outgrowth, caspase 3 and proteasome activities, and ATXN3-GFP, ubiquitin, BCL2 and BAX protein levels in neuronal differentiated ATXN3/Q[Formula: see text]-GFP SH-SY5Y cells. Finally, enhanced proteasome function, anti-oxidative activity and neuroprotection of catalpol, puerarin and daidzein (active constituents of Rehmannia glutinosa and Pueraria lobata) were demonstrated in GFPu and/or ATXN3/Q[Formula: see text]-GFP 293/SH-SY5Y cells. This study may have therapeutic implication in polyQ-mediated disorders.

IntroductionMeasures to mitigate the COVID-19 outbreak in the migrant worker dormitories in Singapore included lockdown and isolation of residents for prolonged periods. In this paper, we explore efforts to ease tensions and support mental health under these conditions.MethodsCase study of dormitory residents under lockdown from April to August 2020 comprises a nested mixed-method approach using an online questionnaire (n=175) and semistructured interviews (n=23) of migrant workers sampled from the survey (August to September 2020). Logistic regression models were used to analyse survey data. Semistructured interviews were analysed using applied thematic analysis.ResultsSurvey and interview data showed that mental health was largely protected despite initial rising tensions over restrictions during lockdown. Sources of tension negatively affecting low stress responses included job related worries, OR=0.07 (95% CI 0.03 to 0.18, pInterviewees shared how their adaptive capability played a pivotal protective role alongside social support and solidarity; aided by regular use of messaging applications, which supported mental health, OR=4.81 (95% CI 1.54 to 15.21, pConclusionTensions are mapped to protective solutions informing guidelines for future outbreak stress management response.

A novel type of solid-shelled microspheres was prepared by emulsion templating technique through layer-by-layer self assembly. The regulation controlled by different payloads, surfactants, 3-aminopropyltriethoxysilane (APTES) and tetraethoxysilane (TEOS) ratio produced three solid-shelled microspheres with various morphology, sizes, shell thicknesses and brittleness. Such microspheres can be considered as diluent-loaded eggs that can be cracked when forced between narrow rock surfaces or against blocking fluid flow particles. The structural characteristics, size distribution, stability, breakable and release behavior of three payload-in-silica microspheres were investigated by optical microscopy techniques and scanning electron microscopy (SEM) technique, dynamic light scattering (DLS), zeta potential, and ultraviolet-visible (UV–vis) spectroscopy. The results indicated that these three microspheres were relatively uniform in size (1–5 μm) and had a smooth surface with shell thicknesses of 40–120 nm, which also possessed excellent stability. Yet the brittleness of silica shell was obviously different for three solid-shelled microspheres, in detail, the silica shell of toluene microspheres was more brittle and easier to be ruptured than hexane microspheres under external hydrodynamics forces. Sand column tests revealed that the easy-broken toluene-in-silica microspheres prepared from tween-80 template matched the pore throat of reservoir better and achieved higher heavy oil recovery efficiency (94.60%). Such breakable microspheres can provide a selective and targeted diluting approach to extract blockages by heavy-oil and asphaltene precipitates.

PurposeCOVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay.ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.

Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.

Background The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19. Methods This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors. Findings Between Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9–7·1) for 1779 household contacts, 1·3% (0·9–1·9) for 2231 work contacts, and 1·3% (1·0–1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55–69) of COVID-19 diagnoses, and 36% (27–45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio [OR] 5·38 [95% CI 1·82–15·84]; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 [3·86–16·02]; p

BackgroundThe human intestinal microbiome is a complex community that contributes to host health and disease. In addition to normal microbiota, pathogens like carbapenem-resistant Enterobacteriaceae may be asymptomatically present. When these bacteria are present at very low levels, they are often undetectable in hospital surveillance cultures, known as occult or subclinical colonization. Through the use of antibiotics, these subclinical pathogens can increase to sufficiently high levels to become detectable, in a process called outgrowth. However, little is known about the interaction between gut microbiota and Enterobacteriaceae during occult colonization and outgrowth.ResultsWe developed a clinically relevant mouse model for studying occult colonization. Conventional wild-type mice without antibiotic pre-treatment were exposed to K. pneumoniae but rapidly tested negative for colonization. This occult colonization was found to perturb the microbiome as detected by both 16S rRNA amplicon and shotgun metagenomic sequencing. Outgrowth of occult K. pneumoniae was induced either by a four-antibiotic cocktail or by individual receipt of ampicillin, vancomycin or azithromycin, which all reduced overall microbial diversity. Notably, vancomycin was shown to trigger K. pneumoniae outgrowth in only a subset of exposed animals (outgrowth-susceptible). To identify factors that underlie outgrowth susceptibility, we analyzed microbiome-encoded gene functions and were able to classify outgrowth-susceptible microbiomes using pathways associated with mRNA stability. Lastly, an evolutionary approach illuminated the importance of xylose metabolism in K. pneumoniae colonization, supporting xylose abundance as a second susceptibility indicator. We showed that our model is generalizable to other pathogens, including carbapenem-resistant Escherichia coli and Enterobacter cloacae.ConclusionsThis study suggests that microbiota mRNA and small-molecule metabolites may be used to predict outgrowth-susceptibility. Our modeling of occult colonization and outgrowth could help the development of strategies to mitigate the risk of subsequent infection and transmission in medical facilities and the wider community.

Early detection of infections is crucial to limit the spread of coronavirus 2019 disease (COVID-19). Here, we develop a flow cytometry-based assay to detect SARS-CoV-2 Spike protein (S protein) antibodies in COVID-19 patients. The assay detects specific IgM, IgA and IgG in COVID-19 patients and also the acquisition of all IgG subclasses, with IgG1 being the most dominant. The antibody response is significantly higher at a later stage of the infection. Furthermore, asymptomatic COVID-19 patients also develop specific IgM, IgA and IgG, with IgG1 as the most dominant subclass. Although the antibody levels are lower in asymptomatic infections, the assay is highly sensitive and detect 97% of asymptomatic infections. These findings demonstrate that the assay can be used for serological analysis of symptomatic infections, and also asymptomatic infections, which may, otherwise, go undetected., Graphical Abstract, Highlights Flow cytometry assay detects specific antibodies in symptomatic COVID-19 patients. Asymptomatic COVID-19 patients also develop specific antibodies. IgG1 is the dominant IgG subclass in both symptomatic and asymptomatic patients. The assay is highly sensitive and detects 97% of asymptomatic infections., Using a flow cytometry-based assay, Goh et al. finds specific antibodies in symptomatic COVID-19 patients’ plasma samples. IgG1 is the most dominant IgG subclass. Despite lower antibody levels, the assay detects 97% of asymptomatic infections, suggesting the feasibility of the assay to detect asymptomatic infections, which may otherwise go undetected.