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Hongjiang Wu,1,2 Eric SH Lau,3 Alice PS Kong,2,4 Ronald CW Ma,2,4 Risa Ozaki,4 Kitty KT Cheung,4 Elaine Chow,4 Chiu Chi Tsang,5 Kam Piu Lau,6 Eric MT Hui,7 Wing Yee So,8 Danijela Gasevic,1,9 Sarah H Wild,1 Juliana CN Chan,2–4 Andrea Luk2–4 1Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK; 2Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; 3Asia Diabetes Foundation, Prince of Wales Hospital, Hong Kong SAR, China; 4Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; 5Alice Ho Miu Ling Nethersole Hospital, Tai Po, Hong Kong SAR, China; 6Northern District Hospital, Fanling, Hong Kong SAR, China; 7Department of Family Medicine, Prince of Wales Hospital, Hong Kong SAR, China; 8Hospital Authority Head Office, Hong Kong SAR, China; 9School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia Purpose: The aim of this study was to describe the association between educational level and incident cardiovascular disease (CVD) and all-cause mortality in Hong Kong Chinese patients with type 2 diabetes.Patients and methods: We included 12,634 patients with type 2 diabetes who were enrolled into the Joint Asia Diabetes Evaluation Program between June 1, 2007, and June 30, 2017. We classified patients’ educational level into the following three groups: ≤6 years, 6–13 years, and >13 years. Incident CVD events were identified using hospital discharge diagnoses. Death was identified from Hong Kong Death Register. We estimated HRs for incident CVD and all-cause mortality using Cox regression models.Results: Patients with the highest educational level were younger and had shorter diabetes duration and better glycemic control at enrollment than those with the lowest educational level. During the median follow-up of 6.2 years for CVD and 6.4 years for all-cause mortality, 954 CVD events and 833 deaths were recorded. HRs for CVD and all-cause mortality were 0.73 (95% CI: 0.57, 0.94) and 0.71 (95% CI: 0.54, 0.94) for the highest educational level compared to the lowest educational level, after adjustment for age, sex, diabetes duration, and family history of diabetes.Conclusion: Educational level is inversely associated with the risk of CVD and all-cause mortality among Hong Kong Chinese patients with type 2 diabetes. Hong Kong Chinese patients with type 2 diabetes and low educational level should be given special attention for the prevention of key complications of diabetes. Keywords: socioeconomic status, educational level, diabetes, cardiovascular disease, all-cause mortality

Crystal TY Lee, Shinan Zhang, Yiu Yan Leung, Samantha KY Li, Cissy C Tsang, Chun-Hung Chu Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, People’s Republic of China Objectives: To study patients’ satisfaction and prevalence of complications in surgical extraction of impacted third molar by senior dentists and recently graduated dentists in a university dental clinic. Method: Patients who had impacted third molar extraction in a university dental clinic by two associate dentists who had 15 years of experience were evaluated in this study. Patients’ age, sex, history of pericoronitis, tooth extracted, and radiographic assessment of the impacted tooth were recorded. Immediately after suture removal, the patients were invited to indicate their satisfaction on a Likert scale of 1–5. Results: A total of 546 patients received extraction, and 251 patients were operated by associate dentists. Patient satisfaction was higher among those who had noncomplicated surgery (P=0.007), short treatment time (P

Aims/hypothesis: Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes., Methods: We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong. The 'total' type 2 diabetes polygenic risk score (PRS) was summed by genome-wide significant type 2 diabetes signals (n=1289). We examined the associations between psPRSs and cardiometabolic profile, age of onset, two glycaemic deterioration outcomes (clinical requirement of insulin treatment, defined by two consecutive HbA 1c values ≥69 mmol/mol [8.5%] more than 3 months apart during treatment with two or more oral glucose-lowering drugs, and insulin initiation), three renal (albuminuria, end-stage renal disease and chronic kidney disease) outcomes and five cardiovascular outcomes., Results: Although most psPRSs and total type 2 diabetes PRS were associated with an earlier and younger onset of type 2 diabetes, the psPRSs showed distinct associations with clinical outcomes. In particular, individuals with normal weight showed higher psPRSs for beta cell dysfunction and lipodystrophy than those who were overweight. The psPRSs for obesity were associated with faster progression to clinical requirement of insulin treatment (adjusted HR [95% CI] 1.09 [1.05, 1.13], p<0.0001), end-stage renal disease (1.10 [1.04, 1.16], p=0.0007) and CVD (1.10 [1.05, 1.16], p<0.0001) while the psPRSs for beta cell dysfunction were associated with reduced incident end-stage renal disease (0.90 [0.85, 0.95], p=0.0001) and heart failure (0.83 [0.73, 0.93], p=0.0011). Major findings remained significant after adjusting for a set of clinical variables., Conclusions/interpretation: Beta cell dysfunction and lipodystrophy could be the driving pathological pathways in type 2 diabetes in individuals with normal weight. Genetic risks of beta cell dysfunction and obesity represent two major genetic drivers of type 2 diabetes heterogeneity in disease progression and diabetic complications, which are shared across ancestry groups. Type 2 diabetes psPRSs may help inform patient stratification according to aetiology and guide precision diabetes care., Competing Interests: Acknowledgements The authors thank all the participants and investigators of the HKDR and HKDB for their contributions, and the medical and nursing staff of the respective hospitals for their professional input and support. The full lists of team members of the Hong Kong Diabetes Biobank Study Group and the TRANSCEND Consortium are included in the ESM additional information section. Data availability The list of SNPs used to calculate hard- and soft-clustering psPRSs can be found in ESM Tables 6 and 7. HKDR and HKDB data are not publicly available but may be made available upon reasonable request to the corresponding author. Funding This work was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region (CU R4012-18), Research Grants Council Theme-based Research Scheme (T12-402/13N), the University Grants Matching Scheme, a CUHK Direct Grant and the Focused Innovation Scheme. RCWM acknowledges support from a Croucher Foundation Senior Medical Research Fellowship, the Research Committee Postdoctoral Fellowship Scheme, the CUHK Internationalisation Faculty Mobility Scheme and the Provost’s Scheme for PhD scholarship of the Chinese University of Hong Kong. JCNC acknowledges support from the Hong Kong Government Health and Medical Research Fund (CFS-CUHK2), Hong Kong Genome Institute, Chinese University of Hong Kong Research Committee Postdoctoral Fellowship Scheme and Innovation and Technology Commission Research Talent Hub. RAO has a research grant from Randox Ltd on autoimmune disease genetic risk score diagnostics and the University of Exeter licenses know-how to Randox and receives royalties for a type 1 diabetes GRS biochip. Authors’ relationships and activities JCNC received consultancy fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Celltrion, MSD, Pfizer, Servier and Viatris Pharmaceutical; speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, MSD, Merck, Sanofi and Servier; and research grants through her institutions from Applied Therapeutics, Astra Zeneca, Hua Medicine, Lee Powder, Lilly, Merck and Servier. APSK received research grants from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Kyowa Kirin and Merck Serono and honoraria for consultancy or giving lectures from Nestle, Novo Nordisk, Pfizer and Sanofi. EYKNC received speaker fees from Sanofi and Novartis and institutional research funding from Sanofi, Medtronic Diabetes and Powder Pharmaceuticals Inc. RCWM has received research funding from Bayer, Boehringer Ingelheim, Novo Nordisk, Roche Diagnostics and Tricida Inc. for carrying out clinical trials or studies; and from AstraZeneca, Bayer, Boehringer Ingelheim, Diachii Sankyo, Kyowa Kirin and Merck for speaker honoraria or consultancy in advisory boards. All proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. JCNC, CKPL, RCWM and W-yS are co-founders of GemVCare, a biotech start-up supported by the Technology Start-up Support Scheme for Universities of the Hong Kong Government Innovation and Technology Commission. RCWM is an advisory board member of the editorial board of Diabetologia. RAO has performed consulting for Janssen, Provention Bio and Sanofi.The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement GY, CHTT, CKPL, MNW, RAO and RCWM conceptualised and designed the study. CHTT, CKPL, ESHL, RO, H-mL, ACWN, YH, BF, CH, HW, AY, HMC, KFL, SCS, GH, CCT, KPL, JYYL, EYNC, MWT, GK, ITL, JKYL, VTFY, EL, SL, SF, YLC, CCS, EC, APSK, WHT, AOYL, W-yS, JCNC and RCWM contributed to data acquisition. GY, CHTT, ESHL conducted statistical analysis. GY, CHTT, CKPL, MS, ESHL, BF, WHT, MNW, RAO, JCNC and RCWM were involved in data interpretation. GY, RAO and RCWM drafted the manuscript. All authors contributed to the editing, review and critical revision of the manuscript. WHT, W-yS, JCNC, RAO and RCWM contributed to funding acquisition for the study. All authors read and approved the final version to be published. RCWM is the guarantor of this work., (© 2024. The Author(s).)

While mangrove ecosystems are rich in biodiversity, they are increasingly impacted by climate change and urban pollutants. The current study provides first insights into the emergence of potentially pathogenic yeasts in Hong Kong's mangroves. Sediment and water samples were collected from ten urban and rural mangroves sites. Initial CHROMagar TM Candida Plus screening, representing the first application of this differential medium for water and soil samples collected from a non-clinical environment, enabled the rapid, preliminary phenotypic identification of yeast isolates from mangroves. Subsequent molecular profiling (ITS and/or 28S nrDNA sequencing) and antifungal drug susceptibility tests were conducted to further elucidate yeast diversity and drug resistance. A diversity of yeasts, including 45 isolates of 18 distinct species across 13 genera/clades, was isolated from sediments and waters from Hong Kong mangroves. Molecular profiling revealed a dominance of the Candida / Lodderomyces clade (44.4%), a group of notorious opportunistic pathogens. The findings also reveal a rich biodiversity of non- Candida / Lodderomyces yeasts in mangroves, including the first reported presence of Apiotrichum domesticum and Crinitomyces flavificans . A potentially novel Yamadazyma species was also discovered. Remarkably, 14.3% of the ubiquitous Candida parapsilosis isolates displayed resistance to multiple antifungal drugs, suggesting that mangroves may be reservoirs of multi-drug resistance. Wildlife, especially migratory birds, may disseminate these hidden threats. With significant knowledge gaps regarding the environmental origins, drug resistance, and public health impacts of pathogenic yeasts, urgent surveillance is needed from a One Health perspective. This study provides an early warning that unrestrained urbanization can unleash resistant pathogens from coastal ecosystems globally. It underscores the necessity for enhanced surveillance studies and interdisciplinary collaboration between clinicians, ornithologists, and environmental microbiologists to effectively monitor and manage this environmental health risk, ensuring the maintenance of 'One Health'.

In the last few years, next-generation sequencing (NGS) has emerged as a technology for laboratory diagnosis of many culture-negative infections and slow-growing microorganisms. In this study, we describe the use of metagenomic NGS (mNGS) for rapid diagnosis of T. marneffei infection in a 37-year-old renal transplant recipient who presented with chronic pneumonia syndrome. Bronchoalveolar lavage for mNGS was positive for T. marneffei sequence reads. Prolonged incubation of the bronchoalveolar lavage revealed T. marneffei colonies after 6 days of incubation. Analysis of 23 cases of T. marneffei infections in renal transplant recipients from the literature revealed that the number of cases ranged from 1 to 4 cases per five years from 1990 to 2020; but increased rapidly to 9 cases from 2021 to 2023, with 7 of them diagnosed by NGS. Twenty of the 23 cases were from T. marneffei-endemic areas [southern part of mainland China (n = 9); Hong Kong (n = 4); northeastern India (n = 2); Indonesia (n = 1) and Taiwan (n = 4)]. For the 3 patients from non-T. marneffei-endemic areas [United Kingdom (n = 2) and Australia (n = 1)], they had travel histories to China and Vietnam respectively. The time taken for diagnosis by mNGS [median 1 (range 1 to 2) day] was significantly shorter than that for fungal culture [median 6 (range 3 to 15) days] (P = 0.002). mNGS is useful for picking up more cases of T. marneffei infections in renal transplant recipients as well as providing a rapid diagnosis. Talaromycosis is an emerging fungal infection in renal transplant recipients., (© 2024. The Author(s).)

Epizootic lymphangitis (EL) is a highly prevalent and contagious infectious disease affecting horses in many parts of Ethiopia caused by Histoplasma capsulatum sensu lato ('var. farciminosum'). In this study, 12 suspected isolates of H. capsulatum sensu lato or yeasts unidentified by conventional biochemical tests isolated from Ethiopian horses with EL were characterised by internal transcribed spacer sequencing. Six of the 12 isolates were identified to be members of H. capsulatum sensu lato and the other six were Pichia kudriavzevii (synonym: Candida krusei) (n = 3), Trichosporon asahii (n = 1), Geotrichum silvicola (n = 1) and Moesziomyces aphidis (n = 1), respectively. The six H. capsulatum sensu lato isolates were further characterised by multilocus sequence analysis. Four distinct gene loci (arf [462 bases], H-anti [410 bases], ole1 [338 bases] and tub1 [272 bases]) of these six isolates as well as those of two H. capsulatum sensu lato ('var. farciminosum') reference strains (ATCC 58332 and ATCC 28798) were polymerase chain reaction (PCR)-amplified and sequenced. Phylogenetic analyses of their concatenated nucleotide sequences showed that three of the isolates and the reference strain ATCC 58332 were identical and belonged to the Eurasia clade within Latin American (LAm) A (H. suramericanum), and those of the other three isolates and the reference strain ATCC 28798 were identical and belonged to the Africa clade. At least two distinct phylogenetic clades of H. capsulatum sensu lato were circulating in Ethiopian horses with EL. Advanced molecular technologies and bioinformatics tools are crucial for the accurate identification and typing of pathogens as well as the discovery of novel microorganisms in veterinary microbiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Electrochemical nitrate reduction (NO 3 RR) provides a new option to abate nitrate contamination with a low carbon footprint. Restricted by competitive hydrogen evolution, achieving satisfied nitrate reduction performance in neutral media is still a challenge, especially for the regulation of this multielectron multiproton reaction. Herein, facile element doping is adopted to tune the catalytic behavior of IrNi alloy nanobranches with an unconventional hexagonal close-packed ( hcp ) phase toward NO 3 RR. In particular, the obtained hcp IrNiCu nanobranches favor the ammonia production and suppress byproduct formation in a neutral electrolyte indicated by in situ differential electrochemical mass spectrometry, with a high Faradaic efficiency (FE) of 85.6% and a large yield rate of 1253 μg cm -2 h -1 at -0.4 and -0.6 V (vs reversible hydrogen electrode (RHE)), respectively. In contrast, the resultant hcp IrNiCo nanobranches promote the formation of nitrite, with a peak FE of 33.1% at -0.1 V (vs RHE). Furthermore, a hybrid electrolysis cell consisting of NO 3 RR and formaldehyde oxidation is constructed, which are both catalyzed by hcp IrNiCu nanobranches. This electrolyzer exhibits lower overpotential and holds the potential to treat polluted air and wastewater simultaneously, shedding light on green chemical production based on contaminate degradation.

Objectives: To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia., Methods: We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics., Results: Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-β-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved., Conclusion: Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia., (© 2024. The Author(s).)

Aims/hypothesis: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers., Methods: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m 2 ) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts., Results: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts., Conclusions/interpretation: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification., (© 2024. The Author(s).)

Insufficient sleep contributes negatively to child developmental processes and neurocognitive abilities, which argues the need for implementing interventions to promote sleep health in children. In this study, we evaluated the effectiveness of a multimodal and multilevel school-based sleep education program in primary school children using a cluster randomized controlled design. Twelve schools were randomly assigned to either the sleep education or nonactive control groups. The sleep education group included a town hall seminar, small class teaching, leaflets, brochures, and a painting competition for children. Parents and teachers were invited to participate in a one-off sleep health workshop. Parental/caregiver-reported questionnaires were collected at baseline and 1-month follow-up. A total of 3769 children were included in the final analysis. There were no significant improvements observed in the sleep-wake patterns, daytime functioning, and insomnia symptoms between the two groups at follow-up, whereas the intervention group had significantly improved parental sleep knowledge than the controls (paternal: adjusted mean difference: 0.95 [95% confidence interval (CI): 0.18 to 1.71]; maternal: adjusted mean difference: 0.87 [95% CI: 0.17 to 1.57]). In addition, children receiving the intervention had a lower persistence rate of excessive beverage intake (adjusted odds ratio: 0.49 [95% CI: 0.33 to 0.73]), and experienced greater reductions in conduct problems (adjusted mean difference: 0.12 [95% CI: 0.01 to 0.24]) compared with the controls at 1-month of follow-up. Moreover, a marginally significant reduction for emotional problems in the intervention group was also observed (adjusted mean difference: 0.16 [95% CI: -0.00 to 0.32]). These findings demonstrated that school-based sleep education was effective in enhancing parental sleep knowledge and improving behavioral outcomes in children, but not sufficient in altering the children's sleep-wake patterns and sleep problems.

Objective: In this study we aim to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications., Research Design and Methods: We performed a two-stage genome-wide association study for CHD in Chinese patients with T2D (3,596 case and 8,898 control subjects), followed by replications in European patients with T2D (764 case and 4,276 control subjects) and general populations (n = 51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes and its interactions with glycemic, blood pressure (BP), and lipid controls in incident cardiovascular diseases., Results: We identified a novel variant (rs10171703) for CHD (odds ratio 1.21 [95% CI 1.13-1.30]; P = 2.4 × 10-8) and BP (β ± SE 0.130 ± 0.017; P = 4.1 × 10-14) at PDE1A in Chinese T2D patients but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (Pinteraction = 0.0155) and myocardial infarction (MI) (Pinteraction = 5.1 × 10-4). Patients with CC genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9 × 10-8 < P < 3.6 × 10-5), those with CT genotype had no difference (0.0726 < P < 0.2614), and those with TT genotype had a threefold increase in MI risk (P = 6.7 × 10-3)., Conclusions: We discovered a novel CHD- and BP-related variant at PDE1A that interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes, only when our findings are validated., (© 2023 by the American Diabetes Association.)

Objectives: The current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD)., Methods: This cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration., Results: In contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001)., Conclusion: FDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To explore the impact of the COVID-19 pandemic on the sleep-wake patterns of preschool children., Methods: A cohort of preschoolers established before the COVID-19 pandemic was invited to participate in this study. Data including children's demographics, their own and parental sleep-wake patterns, physical activities, and screen time were collected through an online questionnaire from August to September 2020. A comparison was made on the collected data from the same cohort of children before and during the pandemic., Results: The cohort which was established before the pandemic consisted of 3720 preschoolers. For this current study, 642 (17%) participated, and 497 (13%) children who fulfilled the eligibility criteria were included in the final analysis. They showed a delay in their bedtime and wake time on both weekdays and weekends with a 15-30 min increase in nocturnal sleep duration. However, with a reduction in nap time, the average daily sleep duration was shortened by 16.3 ± 64.3 min (p < 0.001) and 27.5 ± 72.9 min (p < 0.001) during weekdays and weekends, respectively. Screen time was increased while outdoor activity duration was decreased. Parental sleep/wake times were also delayed with an increase in sleep duration. Children's sleep habits were associated with screen time and parental sleep/wake patterns., Conclusion: Despite school suspension during the COVID-19 pandemic, preschoolers were not sleeping longer. Screen time and parental sleep/wake patterns were the major factors driving the preschoolers' sleep habits. Health education is required to control screen time in children and to promote sleep hygiene among all family members., Competing Interests: Declaration of competing interest KC Chan has received a research grant from Merck Sharp & Dohme unrelated to the content of this work. Other authors declared no conflicts of interest related to the research work and content of this manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To review existing literature evaluating barriers and facilitators to the use of personal protective equipment (PPE) by health care workers in long-term care (LTC)., Design: Scoping review., Setting and Participants: Health care workers in LTC settings., Methods: Several online databases were searched and a gray literature search was conducted. Study inclusion criteria were (1) conducted in nursing homes or LTC settings, (2) focused on LTC health care workers as the study population, and (3) identified barriers and/or facilitators to PPE use. The Theoretical Domains Framework (TDF), which assesses barriers to implementation across 14 behavioral change domains, was used to extract and organize data about barriers and facilitators to appropriate use of PPE from the included studies., Results: A total of 5216 references were screened for eligibility and 10 studies were included in this review. Eight of the 10 studies were conducted during the COVID-19 pandemic. Several barriers and facilitators to PPE use were identified. The most common TDF domain identified was environmental context and resources, which was observed in 9 of the 10 studies. Common barriers to PPE use included supply issues (n = 7 studies), the cost of acquisition (n = 3 studies), unclear guidelines on appropriate use of PPE (n = 2 studies), difficulty providing care (n = 2 studies), and anxiety about frightening patients (n = 2 studies). Having PPE readily available facilitated the use of PPE (n = 2 studies)., Conclusions and Implications: Further research is necessary to identify barriers and facilitators more extensively across behavior change domains to develop effective strategies to improve PPE use and prevent infection transmission within LTC., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility., Research Design and Methods: HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value., Results: Over median (IQR) 5.2 (5.0-5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD [hazard ratio (HR) 0.65 (95% CI 0.52, 0.81)] and all-cause mortality [0.47 (0.38, 0.59)] (false discovery rate < 0.05). Very large HDL-P were positively associated with all-cause mortality [1.75 (1.19, 2.58)]. Small HDL-P improved prediction of mortality [C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851)] and CVD [IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486)] over the RECODe model., Conclusion: Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D., (© 2022. The Author(s).)

Study Objectives: This study aimed to examine the effect of sleep-corrected social jetlag (SJLsc) on mental health, behavioral problems, and daytime sleepiness in adolescents., Methods: This was a cross-sectional study which included 4787 adolescents (Mean age: 14.83±1.6y, 56.0% girls) recruited from 15 secondary schools in Hong Kong. SJLsc was defined as the absolute difference between sleep-corrected midsleep on weekdays and weekends, at which the sleep debt has been considered. It was classified into three groups: low-level ("LSJLsc", <1h), mid-level ("MSJLsc", ≥1h and <2h), and high-level of SJLsc ("HSJLsc", ≥2h). Adolescents' mental health, behavioral problems and daytime sleepiness were measured by the General Health Questionnaire (GHQ-12), the Strengths and Difficulties Questionnaire (SDQ) and the Pediatric Daytime Sleepiness Scale (PDSS). Logistic regression analysis and restricted cubic spline regression (RCS) analysis were applied with consideration of confounders including age, gender, puberty and sleep problems., Results: Nearly half (46.9%) of adolescents had SJLsc for at least 1 h. Greater SJLsc was associated with more behavioral difficulties (MSJLsc: OR: 1.20, p = 0.03; HSJLsc: OR: 1.34, p = 0.02) when controlling for age, sex, puberty, chronotype, insomnia, and time in bed. There was a dose-response relationship in which higher SJLsc had an increased risk of conduct problems and hyperactivity, while only high-level SJLsc was associated with a peer relationship problem. In RCS analysis, SJLsc was associated with a higher likelihood of behavioral difficulties (p = 0.03) but not poor mental health or daytime sleepiness., Conclusions: Sleep-corrected social jetlag was a unique risk factor for behavioral problems in adolescents. Our findings highlighted the need for interventions to promote healthy sleep-wake patterns in school adolescents., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Drug resistance derived from extracellular vesicles (EVs) is an increasingly important research area but has seldom been described regarding fungal pathogens. Here, we characterized EVs derived from a triazole-resistant but amphotericin B-susceptible strain of Candida auris . Nano- to microgram concentrations of C. auris EVs prepared from both broth and solid agar cultures could robustly increase the yeast's survival against both pure and clinical amphotericin B formulations in a dose-dependent manner, resulting in up to 16-fold changes of minimum inhibitory concentration. Meanwhile, this effect was not observed upon addition of these EVs to C. albicans , nor upon addition of C. albicans EVs to C. auris . No change in susceptibilities was observed upon EV treatment for fluconazole, voriconazole, micafungin, and flucytosine. Mass spectrometry indicated the presence of immunogenic-/drug resistance-implicated proteins in C. auris EVs, including alcohol dehydrogenase 1 as well as C. albicans Mp65-like and Xog1-like proteins in high quantities. Based on these observations, we propose a potential species-specific role for EVs in amphotericin B resistance in C. auris . These observations may provide critical insights into treatment of multidrug-resistant C. auris .

Rationale & Objective: Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes., Study Design: Multicenter prospective cohort study., Settings & Participants: 19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank., Exposures: DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR., Outcomes: All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%)., Analytical Approach: Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates., Results: Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR <30 mL/min/1.73 m 2 yielded similar findings., Limitations: Potential misclassification because of drug use., Conclusions: Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We aim to assess the long-term impact of acute kidney injury (AKI) on progression of diabetic kidney disease (DKD) and all-cause mortality and investigate determinants of AKI in Chinese patients with type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register was followed for 12 years (mean ± SD age 57 ± 13.2 years; 46.9% men; median duration of diabetes 5 years). AKI was defined based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 single nucleotide polymorphisms (SNPs) known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD, and ESRD. Validation was sought in an independent cohort including 6,007 patients (age 61.2 ± 10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (hazard ratio 14.3 [95% CI 12.69-16.11]), for developing ESRD (12.1 [10.74-13.62]), and for all-cause death (7.99 [7.31-8.74]) compared with those without AKI. Incidence rate for ESRD among patients with no episodes of AKI and one, two, and three or more episodes of AKI was 7.1, 24.4, 32.4, and 37.3 per 1,000 person-years, respectively. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts but not ESRD. Elevated SUA may increase the risk of DKD through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a nonmodifiable risk factor may facilitate the identification of individuals at high risk to prevent AKI and its long-term impact in T2D., (© 2022 by the American Diabetes Association.)

Importance: Diabetic kidney disease (DKD) and its comorbidities can be prevented by treating multiple targets. Technology-assisted team-based care with regular feedback and patient empowerment can improve the attainment of multiple targets and clinical outcomes in patients with type 2 diabetes, but the effects of this intervention on patients with DKD are unclear., Objective: To evaluate the effect of the Joint Asia Diabetes Evaluation (JADE) web portal, nurse reminders, and team-based care on multiple risk factors in patients with DKD., Design, Setting, and Participants: This 12-month multinational, open-label randomized clinical trial was conducted between June 27, 2014, and February 19, 2019, at 13 hospital-based diabetes centers in 8 countries or regions in Asia. All patients who participated had DKD. The intention-to-treat data analysis was performed from April 7 to June 30, 2020., Interventions: Patients were randomized in a 1:1:1 ratio at each site to usual care, empowered care, or team-based empowered care. All patients underwent a JADE web portal-guided structured assessment at baseline and month 12. Patients in the usual care and empowered care groups received a medical follow-up. Patients in the empowered care group also received a personalized JADE report and nurse telephone calls every 3 months. Patients in the team-based empowered care group received additional face-to-face reviews every 3 months from a physician-nurse team., Main Outcomes and Measures: The primary outcome was the proportion of patients who attained multiple treatment targets (defined as ≥3 of 5 targets: HbA1c level <7.0% [53 mmol/mol], blood pressure <130/80 mm Hg, low-density lipoprotein cholesterol level <1.8 mmol/L, triglyceride level <1.7 mmol/L, and/or persistent use of renin-angiotensin-aldosterone system inhibitors)., Results: A total of 2393 patients (mean [SD] age, 67.7 [9.8] years; 1267 men [52.9%]) were randomized to the usual care group (n = 795), empowered care group (n = 802), and team-based empowered care group (n = 796). At baseline, 34.7% patients (n = 830) were on 3 treatment targets. On intention-to-treat analysis, the team-based empowered care group had the highest proportion of patients who had further increase in attainment of multiple treatment targets (within-group differences: usual care group, 3.9% [95% CI, 0.0%-7.8%]; empowered care group, 1.3% [95% CI, -2.8% to 5.4%]; team-based empowered care group, 9.1% [95% CI, 4.7%-13.5%]). The team-based empowered care group was more likely to attain multiple treatment targets than the usual care group (risk ratio [RR], 1.17; 95% CI, 1.00-1.37) and the empowered care group (RR, 1.25; 95% CI, 1.06-1.48) after adjustment for site. Compared with the group that did not attain multiple treatment targets, the group that attained multiple treatment targets reported a lower incidence of cardiovascular, kidney, and cancer events (8.4% [n = 51] vs 14.5% [n = 134]; P = .004). Analysis of the per-protocol population yielded similar results., Conclusions and Relevance: This trial found that technology-assisted team-based care for 12 months improved the attainment of multiple treatment targets as well as empowerment in patients with DKD., Trial Registration: ClinicalTrials.gov Identifier: NCT02176278.

Pleurostoma species are wood-inhabiting fungi and emerging opportunistic pathogens causing phaeohyphomycosis. In this study, we isolated a dematiaceous fungus, HKU44 T , from the subhepatic abscess pus and drain fluids of a liver transplant recipient with post-transplant biliary and hepatico-jejunostomy bypass strictures. Histology of the abscess wall biopsy showed abundant fungal hyphae. The patient survived after a second liver transplant and antifungal therapy. On SDA, HKU44 T grew initially as white powdery colonies which turned beige upon maturation. Hyphae were septate and hyaline. Phialides were monophialidic and laterally located, generally closely associated to a cluster of conidia which were usually reniform. Phylogenetic analyses showed that HKU44 T is most closely related to, but distinct from, Pleurostoma ootheca and Pleurostoma repens . These suggested that HKU44 T is a novel Pleurostoma species, for which the name Pleurostoma hongkongense sp. nov. is proposed. Antifungal susceptibility testing showed that Pleurostoma species possessed high MICs/MECs for fluconazole, 5-flucytosine and the echinocandins; whereas they exhibited a high strain-to-strain variability to the susceptibilities to the other triazoles. As for amphotericin B, ∼65% of the Pleurostoma strains had low MICs (≤1 µg/mL). DNA sequencing should be performed to accurately identify fungi with Pleurostoma/Phialophora -like morphologies, so is antifungal susceptibility testing for patients with Pleurostoma infections.

Talaromyce marneffei is an important thermally dimorphic pathogen causing disseminated mycoses in immunocompromised individuals in southeast Asia. Previous studies have suggested that NLRP3 inflammasome plays a critical role in antifungal immunity. However, the mechanism underlying the role of NLRP3 inflammasome activation in host defense against T. marneffei remains unclear. We show that T. marneffei yeasts but not conidia induce potent IL-1β production. The IL-1β response to T. marneffei yeasts is differently regulated in different cell types; T. marneffei yeasts alone are able to induce IL-1β production in human PBMCs and monocytes, whereas LPS priming is essential for IL-1β response to yeasts. We also find that Dectin-1/Syk signaling pathway mediates pro-IL-1β production, and NLRP3-ASC-caspase-1 inflammasome is assembled to trigger the processing of pro-IL-1β into IL-1β. In vivo , mice deficient in NLRP3 or caspase-1 exhibit higher mortality rate and fungal load compared to wild-type mice after systemic T. marneffei infection, which correlates with the diminished recruitment of CD4 T cells into granulomas in knockout mice. Thus, our study first demonstrates that NLRP3 inflammasome contributes to host defense against T. marneffei infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ma, Chan, Tan, Kui, Tsang, Pei, Lau, Woo and Lee.)

Background: Eveningness and insomnia are highly comorbid and closely related to psychopathology in adolescents. We aimed to prospectively investigate the trajectories and associations of eveningness and insomnia with daytime functioning, depression and suicidal risk in adolescents., Methods: A 3-year longitudinal study was conducted among 414 Chinese adolescents. The associations of eveningness and insomnia with daytime functioning, depression and suicidal ideation were analyzed using logistic regressions., Results: The prevalence rates of eveningness were similar at baseline and follow-up (19.3% vs 22.5%; p = 0.27), while the prevalence of insomnia increased at follow-up (29.2% vs 40.8%; p < 0.001). Among those eveningness adolescents (n=80) at baseline, 46.2% remained as stable evening-type at follow-up, and among those insomnia adolescents (n=121) at baseline, 64.5% had persistent insomnia at follow-up. Logistic regressions showed that stable, incident, and resolved eveningness were associated with excessive daytime sleepiness (EDS) at follow-up, while only persistent and incident insomnia increased the risk of EDS. Persistent and incident insomnia, as well as stable eveningness were independently associated with depression at follow-up. Persistent and incident insomnia, but not eveningness, were associated with suicidal ideation., Limitations: The outcome assessments were based on self-reported questionnaires and the sample size is modest., Conclusions: Persistent eveningness and insomnia are significantly associated with greater risks of EDS and depression in adolescents, while both persistent and incident insomnia, but not eveningness, increased the risk of suicidal ideation. These findings underscore the importance of addressing sleep and circadian factors in the management of adolescent mood and daytime functioning., (Copyright © 2021. Published by Elsevier B.V.)

Next-generation sequencing (NGS) technologies have recently developed beyond the research realm and started to mature into clinical applications. Here, we review the current use of NGS for laboratory diagnosis of fungal infections. Since the first reported case in 2014, >300 cases of fungal infections diagnosed by NGS were described. Pneumocystis jirovecii is the predominant fungus reported, constituting ~25% of the fungi detected. In ~12.5% of the cases, more than one fungus was detected by NGS. For P. jirovecii infections diagnosed by NGS, all 91 patients suffered from pneumonia and only 1 was HIV-positive. This is very different from the general epidemiology of P. jirovecii infections, of which HIV infection is the most important risk factor. The epidemiology of Talaromyces marneffei infection diagnosed by NGS is also different from its general epidemiology, in that only 3/11 patients were HIV-positive. The major advantage of using NGS for laboratory diagnosis is that it can pick up all pathogens, particularly when initial microbiological investigations are unfruitful. When the cost of NGS is further reduced, expertise more widely available and other obstacles overcome, NGS would be a useful tool for laboratory diagnosis of fungal infections, particularly for difficult-to-grow fungi and cases with low fungal loads.

BACKGROUND: Previous studies have documented factors influencing medication nonadherence among the Medicare population, but few studies have examined medication nonadherence among the Medicare low-income subsidy (LIS) population. Furthermore, little is known about the factors associated with nonadherence among this population, especially those with prevalent chronic conditions such as type 2 diabetes, hypertension, or heart failure. OBJECTIVE: To examine factors associated with the likelihood of medication nonadherence among Medicare LIS recipients with type 2 diabetes, hypertension, or heart failure. METHODS: This was a retrospective analysis of 2012-2013 Medicare Parts A, B, and D claims (most recent available for this research) linked to the Area Health Resources Files. Beneficiaries aged 65 years or older with continuous Medicare coverage and receiving any LIS were included. Individuals were categorized into full LIS or partial LIS groups. Nonadherence was determined by the proportion of days covered less than 80% for specified oral type 2 diabetes, hypertension, and heart failure medications, as defined by the Pharmacy Quality Alliance. A multivariate logistic regression was used to determine and compare individual-level and community-level characteristics associated with nonadherence among the entire study sample, the full LIS group, and the partial LIS group. RESULTS: The study sample included 505,771 Medicare beneficiaries, with 448,509 (88.7%) receiving full LIS and 57,262 (11.3%) receiving partial LIS. The proportion of individuals nonadherent was higher among the full LIS population (33.2%) than that of the partial LIS population (30.8%). Among the entire population, younger age was associated with nonadherence (OR = 0.98; 95% CI = 0.98-0.99). Men were more likely to be nonadherent than women (OR = 1.12; 95% CI = 1.11-1.14). Compared with non-Hispanic Whites, racial/ethnic minorities had higher nonadherence. Compared with beneficiaries who were non-Hispanic White, the ORs for those who were Black, Hispanic, Asian, and other were 1.41 (95% CI = 1.38-1.43), 1.58 (95% CI = 1.55-1.61), 1.08 (95% CI = 1.05-1.11), and 1.63 (95% CI = 1.56-1.70), respectively. There were higher nonadherence rates among patients living in communities with lower socioeconomic characteristics, such as a metropolitan statistical area (MSA vs non-MSA; OR = 1.05, 95% CI = 1.04-1.07). A higher risk adjustment summary score, indicating worse health status, was associated with an increased likelihood of medication nonadherence (OR = 1.21; 95% CI = 1.20-1.22). These patterns were similar among the full and partial LIS groups. CONCLUSIONS: Individual- and community-level characteristics were associated with the likelihood of medication nonadherence among Medicare LIS recipients with type 2 diabetes, hypertension, or heart failure. These characteristics included younger age, male sex, racial/ethnic minorities, living in lower socioeconomic communities, and a higher risk adjustment summary score. This study provided insight into medication nonadherence within the Medicare LIS population and identified the need to consider these factors when developing future policies to improve medication adherence. DISCLOSURES: This study was funded by the Pharmaceutical Research & Manufacturers of America (PhRMA), which was involved in the preparation and revision of the manuscript. Dougherty is employed by PhRMA. Todor was a PQA-CVS Health Foundation Scholar who was funded to work on this study. Hines is employed by Pharmacy Quality Alliance. Wang reports grants from AbbVie, Curo, Bristol Myers Squibb, and Pfizer, during the time of this study, and fees from the PhRMA Foundation for work on its Heath Outcomes Research Advisor Committee. The other authors have nothing to disclose. This study was presented as a poster at the online 2020 PQA Annual Meeting, May 7, 2020.

Background: Previous literature reported racial/ethnic disparities in the measure assessment of diabetes medication adherence in the Medicare Part D Star Ratings program., Objective: This study examined the likelihood of inclusion in measure calculation across racial/ethnic groups for adherence metrics in Part D Star Ratings among individuals with diabetes, hypertension, and/or hyperlipidemia., Methods: This was a retrospective cross sectional analysis of a 10% random sample of 2017 Medicare claims linked to Area Health Resources Files. Inclusion in measure calculation was determined based on inclusion/exclusion criteria in adherence metrics for adherence medications for diabetes, hypertension, and hyperlipidemia in Part D Star Ratings developed by the Pharmacy Quality Alliance. Logistic regression and multinomial logistic regression were used to adjust for patient/community characteristics., Results: The study sample size was 2 707 216. Compared to Non-Hispanic White (White) beneficiaries, minorities were more likely to be excluded from measure calculation among individuals with 1 condition. For example, among individuals with hypertension, compared to White individuals, the adjusted odds ratios for exclusion for Black, Hispanic, Asian/Pacific Islander and other individuals were 1.46 (95% confidence interval, or CI = 1.42-1.50), 1.38 (95% CI = 1.33-1.43), 1.28 (95% CI = 1.21-1.35), and 1.08 (95% CI = 1.02-1.15), respectively. Among individuals with more than 1 chronic condition, minorities were more likely to be included in fewer calculations for medication adherence measures. For example, among individuals with all 3 conditions, the adjusted relative risk ratios for Black, compared to White, beneficiaries for being included in 0, 1, and 2 measures, versus all 3 measures, were 2.14 (95% CI = 1.99-2.30), 1.49 (95% CI = 1.41-1.56), 1.20 (95% CI = 1.18-1.23), respectively., Conclusions: Compared to White beneficiaries, racial/ethnic minorities are more likely to be excluded from the calculation for adherence measures among individuals with diabetes, hypertension, and/or hyperlipidemia. Future studies should examine whether such disparities exacerbate existing racial/ethnic disparities in health outcomes and devise solutions for these disparities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In addition to human cases, cases of COVID-19 in captive animals and pets are increasingly reported. This raises the concern for two-way COVID-19 transmission between humans and animals. Here, we developed a SARS-CoV-2 nucleocapsid protein-based competitive enzyme-linked immunosorbent assay (cELISA) for serodiagnosis of COVID-19 which can theoretically be used in virtually all kinds of animals. We used 187 serum samples from patients with/without COVID-19, laboratory animals immunized with inactive SARS-CoV-2 virions, COVID-19-negative animals, and animals seropositive to other betacoronaviruses. A cut-off percent inhibition value of 22.345% was determined and the analytical sensitivity and specificity were found to be 1:64-1:256 and 93.9%, respectively. Evaluation on its diagnostic performance using 155 serum samples from COVID-19-negative animals and COVID-19 human patients showed a diagnostic sensitivity and specificity of 80.8% and 100%, respectively. The cELISA can be incorporated into routine blood testing of farmed/captive animals for COVID-19 surveillance.

Background: The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear., Methods: We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients., Results: Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10 - 103  < P < 1.3 × 10 - 75 ) and 3-year lipid changes (1.4 × 10 - 6  < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (β ± SE = 0.052 ± 0.002), 11.7% in TG (β ± SE = 0.111 ± 0.006), 5.8% in HDL-C (β ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (β ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10 - 3  < P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10 - 10  < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (β ± SE = 0.011 ± 0.005, P trend  = 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI) = 1.07 (1.03-1.11)], TG [OR (95% CI) = 1.05 (1.01-1.09)], and LDL-C [OR (95% CI) = 1.05 (1.01-1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8 × 10 - 4  < P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association., Conclusions: The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

Background: The number of patients infected with Aspergillus rose dramatically in recent years. However, studies on the clinical spectrum and antifungal susceptibilities of non-classical (non-fumigatus, non-flavus, non-niger and non-terreus) pathogenic Aspergillus species are very limited., Objectives: We examined the clinical spectrum and antifungal susceptibilities of 34 non-duplicated, non-classical Aspergillus isolates collected from Hong Kong, Shenzhen and Shanghai., Methods: The Aspergillus isolates were identified by internal transcribed spacer, partial BenA and partial CaM sequencing and phylogenetic analyses. Susceptibility testing against eight antifungals was performed following the European Committee for Antimicrobial Susceptibility Testing's methodology., Results: The 34 Aspergillus isolates were identified as 14 different rare/cryptic species of four sections (Flavi [n = 8], Nidulantes [n = 8], Nigri [n = 17] and Restricti [n = 1]). Except for one patient whose clinical history could not be retrieved, 72.7% of the remaining patients had underlying conditions predisposing them to Aspergillus infections. The most common diseases were pulmonary infections (n = 15), followed by skin/nail infections (n = 6), chronic otitis externa and/or media (n = 5), wound infections (n = 2) and mastoiditis/radionecrosis (n = 1), while three were colonisations. Five patients succumbed due to the infections during the admission, and another two died 5 years later because of chronic pulmonary aspergillosis. Antifungal susceptibility testing showed that they possessed different susceptibility profiles compared to the classical Aspergillus species. The majority of isolates characterised were sensitive or wild-type to amphotericin B. The minimum effective concentrations for all the three echinocandins were also low., Conclusion: Susceptibility testing should be performed for infections due to these rare/cryptic Aspergillus species to guide proper patient management., (© 2020 Wiley-VCH GmbH.)

Background: Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings., Methods and Findings: The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15-1.30) and 0.70 (95% CI 0.66-0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score-matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias., Conclusions: ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JCNC is the Chief Executive Officer (on a pro-bono basis) of ADF, a charitable foundation established under the CUHK Foundation for developing the JADE Technology. JCNC, WYS, and RCWM are co-founders of GemVCare, a biotechnology company, supported by the Hong Kong Government Technology Start-up Support Scheme for Universities, which licenses the JADE Technology to provide diabetes risk evaluation and management program, in collaboration with other healthcare organizations. RCWM is a member of the editorial board for PLOS Medicine. RCWM has received research grants for clinical trials from AstraZeneca, Bayer, MSD, Novo Nordisk, Sanofi, and Tricida and honoraria for consultancy or lectures from AstraZeneca and Boehringer Ingelheim.

Objectives: To investigate the association of insomnia and chronotype preference with daytime impairment and psychopathology in a community sample of adolescents in Hong Kong., Methods: This was a cross-sectional study that included seven local secondary schools in Hong Kong. A total of 1667 adolescents (mean age: 14.8 ± 1.6 years old; boys: 56.5%) returned a battery of self-report questionnaires including Insomnia Severity Index (ISI) and reduced Horne and Östberg Morningness and Eveningness Questionnaire (rMEQ) for assessing insomnia symptoms and chronotype preference, respectively. A subset of adolescent samples (n = 768) were additionally assessed for suicidal ideation. Potential confounders including age, gender and sleep duration were controlled for in the analyses., Results: The prevalence of insomnia symptoms and eveningness chronotype was 37% and 25.6%, respectively. Regression models indicated that insomnia and eveningness were independently associated with excessive daytime sleepiness (insomnia: adjusted OR [AdjOR] = 3.8; 95% confidence interval [C.I.] = 2.9-5.0; eveningness: AdjOR = 2.6; 95% C.I. = 1.9-3.7), and an increased risk of depression (insomnia: AdjOR = 3.5, 95% C.I. = 2.5-5.0; eveningness: AdjOR = 2.0, 95% C.I. = 1.3-3.2). The odds ratio increased to 8.7 (95% C.I. = 6.1-12.3, p < 0.001) for excessive daytime sleepiness and 4.8 (95% C.I. = 3.2-7.2, p < 0.001) for depression among adolescents with both insomnia and eveningness. Insomnia symptoms, but not eveningness, were associated with anxiety symptoms (AdjOR = 5.8; 95% C.I. = 3.6-9.4) and suicidal ideation (AdjOR = 2.1, 95% C.I. = 1.4-3.2)., Conclusions: The present study provided further evidence that insomnia and eveningness uniquely contributed to poor daytime functioning and mood related outcomes, while the co-existence of these two conditions could confer a greater risk in adolescents. However, insomnia, but not eveningness, was significantly linked to suicidality after controlling for mood symptoms. Our findings highlighted the necessity of timely management of sleep and circadian issues in adolescents., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing., Results: While the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate., Conclusions: We demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract.

Objectives: Significant literature exists on the effects of medication adherence on reducing healthcare costs, but less is known about the effect of medication adherence among Medicare low-income subsidy (LIS) recipients. This study examined the effects of medication adherence on healthcare costs among LIS recipients with diabetes, hypertension, and/or heart failure., Methods: This retrospective study analyzed Medicare claims data (2012-2013) linked to the Area Health Resources Files. Using measures developed by the Pharmacy Quality Alliance, adherence to 11 medication classes was studied among patients with 7 possible combinations of the diseases mentioned. Adherence was measured in 8 categories of proportion of days covered (PDC): ≥95%, 90% to <95%, 85% to <90%, 80% to <85%, 75% to <80%, 50% to <75%, 25% to <50%, and <25%. Annual Medicare costs were compared across adherence categories. A generalized linear model was used to control for patient/community characteristics., Results: Among patients with only one disease, such as diabetes, patients with the lowest adherence (PDC < 25%) had $3152/year higher Medicare costs than patients with the highest adherence (PDC ≥ 95%; $11 101 vs $7949; P < .05). The adjusted costs among patients with PDC < 25% was $1893 higher than patients with PDC ≥ 95% ($9919 vs $8026; P < .05). Among patients with multiple chronic conditions, patients' adherence to medications for fewer diseases had higher costs., Conclusions: Greater medication adherence is associated with lower Medicare costs in the Medicare LIS population. Future policy affecting the LIS program should encourage better medication adherence among patients with chronic diseases., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 ( n = 223) and other respiratory virus infections ( n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission.

Background: Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D., Methods and Findings: In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1-9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03-1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06-1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10-8) but not glycemic progression (HR: 1.01 [95% CI 0.96-1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort., Conclusions: Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RCWM acknowledges receiving research support (outside of this work) from AstraZeneca, Bayer, and Pfizer and honoraria or consultancy fees from AstraZeneca and Boehringer Ingelheim, all of which have been donated to the Chinese University of Hong Kong to support diabetes research. CKPL, WYS, JCNC, and RCWM are cofounders of GemVCare, a diabetes genetic testing laboratory, which was established through support from the Technology Start-up Support Scheme for Universities (TSSSU) from the Hong Kong Government Innovation and Technology Commission (ITC). RCWM is a member of the editorial board of PLOS Medicine. JCNC has received research grants and/or honoraria for consultancy or giving lectures, from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Eli-Lilly, GlaxoSmithKline, Merck Serono, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Sanofi. APSK has received research grants and/or speaker honoraria from Abbott, AstraZeneca, Eli-Lilly, Merck Serono, Nestle, Sanofi, and Novo Nordisk. AOL has served as an advisory committee member for AstraZeneca, Boehringer Ingelheim, Sanofi, and Amgen and has received research grants and travel grants from AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk, Sanofi, and Amgen.

Although case series of talaromycosis have been reported in China, their detailed clinical and microbiological characteristics have never been systematically profiled. In this study, we report the clinical characteristics, molecular epidemiology, rapid identification and antifungal susceptibilities of talaromycosis in The University of Hong Kong-Shenzhen Hospital in Shenzhen. Seven cases of talaromycosis were observed since commencement of hospital service in 2012. Three patients were local Shenzhen residents, whereas the other four were immigrants from other parts of China. Two patients were HIV-negative, but with underlying diseases requiring immunosuppressive therapy. Two of the seven patients succumbed. All the seven isolates were successfully identified as T. marneffei by MALDI-TOF MS using Bruker database expanded with in-house generated T. marneffei mass spectra. MLST showed that the seven strains belonged to six different, novel sequences types. Phylogenetic analyses of the concatenated five-locus sequence revealed that the seven strains were scattered amongst other T. marneffei strains. The MICs of itraconazole, isavuconazole, posaconazole and voriconazole against the seven clinical isolates were low but MICs of anidulafungin were high. Underlying diseases other than HIV infection are increasingly important risk factors of talaromycosis. MALDI-TOF MS is useful for rapid identification. Highly diverse T. marneffei sequence types were observed., (© 2018 Blackwell Verlag GmbH.)

With new or emerging fungal infections, human and animal fungal pathogens are a growing threat worldwide. Current diagnostic tools are slow, non-specific at the species and subspecies levels, and require specific morphological expertise to accurately identify pathogens from pure cultures. DNA barcodes are easily amplified, universal, short species-specific DNA sequences, which enable rapid identification by comparison with a well-curated reference sequence collection. The primary fungal DNA barcode, ITS region, was introduced in 2012 and is now routinely used in diagnostic laboratories. However, the ITS region only accurately identifies around 75% of all medically relevant fungal species, which has prompted the development of a secondary barcode to increase the resolution power and suitability of DNA barcoding for fungal disease diagnostics. The translational elongation factor 1α ( TEF1α ) was selected in 2015 as a secondary fungal DNA barcode, but it has not been implemented into practice, due to the absence of a reference database. Here, we have established a quality-controlled reference database for the secondary barcode that together with the ISHAM-ITS database, forms the ISHAM barcode database, available online at http://its.mycologylab.org/ . We encourage the mycology community for active contributions.

Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-Aspergillus fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these 24 nail isolates, 17 were confidently identified as 13 different known fungal species, using a polyphasic approach. These 13 species belonged to 11 genera and ≥9 families. For the remaining seven isolates, multilocus sequencing did not reveal their definite species identities. These seven potentially novel species belonged to four different known and three potentially novel genera of seven families. 33.3%, 41.7% and 95.8% of the 24 fungal isolates possessed minimum inhibitory concentrations of >1 µg/mL to terbinafine, itraconazole and fluconazole, respectively, the first line treatment of onychomycosis. A high diversity of moulds was associated with onychomycosis. A significant proportion of the isolates were potentially novel fungal species. To guide proper treatment, molecular identification and antifungal susceptibility testing should be performed for these uncommonly isolated fungal species.

Aims/introduction: Biosimilar insulin can reduce treatment costs, although the extent of its use is largely unknown. We examined biosimilar insulin use and its associations with the quality of glycemic control using the Joint Asia Diabetes Evaluation register., Materials and Methods: We carried out a cross-sectional analysis in 81,531 patients with type 1 and type 2 diabetes enrolled into the Joint Asia Diabetes Evaluation Program from 2007 to 2014. All insulin related terms are extracted from the Joint Asia Diabetes Evaluation portal, and compared clinical profiles between biosimilar and originator insulin users. Multivariate analysis was performed to assess the association of biosimilar insulin compared with originator insulin with dosage, glycated hemoglobin and hypoglycemia events., Results: Amongst 81,531 patients, 20.5% (n = 16,738) were insulin-treated. In four countries with high use of biosimilar insulin, 4.7% (n = 719) of insulin users (n = 10,197) were treated with biosimilar insulin (India n = 507, 70.3%; the Philippines n = 90, 12.5%; China n = 62, 8.6%; Vietnam n = 60, 8.3%). Biosimilar insulin users were younger and had higher body mass index, glycated hemoglobin, insulin dosage and more frequent hypoglycemia than originator insulin users. These associations were non-significant after adjustment for confounders. Only age, college education, diabetes education, lipid control, physical activity and history of cardiovascular complications were independently associated with these quality measures., Conclusions: Biosimilar insulin use is not uncommon in Asia. Data exclusion due to incomplete capturing of brand names suggests possibly higher use. The multiple determinants of the quality of glycemic control call for establishment of prospective cohorts and diabetes registers to monitor the safety and efficacy of different brands of biosimilar insulin and their impacts on clinical outcomes., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Five bacterial strains, UAE-HKU57 T , UAE-HKU58, UAE-HKU59, UAE-HKU60 and UAE-HKU61, were isolated in Dubai, UAE, from necrotic foot tissue samples of four dromedaries (Camelus dromedarius) and associated maggots (Wohrlfartia species). They were non-sporulating, Gram-negative, non-motile bacilli. They grew well under aerobic conditions at 37 °C, but not anaerobically. The pH range for growth was pH 7.0-9.0 (optimum, pH 7.5-8.0) and the strains could tolerate NaCl concentrations (w/v) up to 2 % (optimum, 0.5 %). They were catalase- and cytochrome oxidase-positive, but caseinase-, gelatinase- and urease-negative. Their phenotypic characters were distinguishable from other closely related species. Phylogenetic analyses of the almost-complete 16S rRNA gene and partial 23S rRNA gene, gyrB, groEL and recA sequences revealed that the five isolates were most closely related to undescribed Ignatzschineria strain F8392 and Ignatzschineria indica, but in most phylogenies clustered separately from these close relatives. Average nucleotide identity analysis showed that genomes of the five isolates (2.47-2.52 Mb, G+C content 41.71-41.86 mol%) were 98.00-99.97% similar to each other, but ≤87.18 % similar to other Ignatzschineriaspecies/strains. Low DNA relatedness between the five isolates to other Ignatzschineriaspecies/strains was also supported by Genome-to-Genome Distance Calculator analysis. The chemotaxonomic traits of the five strains were highly similar. They were non-susceptible (intermediate or resistant) to tetracycline and resistant to trimethoprim/sulphamethoxazole. The name Ignatzschineria cameli sp. nov. is proposed to accommodate these five strains, with strain UAE-HKU57 T (=CCOS1165 T =NBRC 113042 T ) as the type strain.

No study has comprehensively evaluated the performance of 28S nrDNA and ITS sequencing, commercial biochemical test kits, MALDI-TOF MS platforms, and the emerging rep-PCR DNA fingerprinting technology using a cohort of yeast strains collected from a clinical microbiology laboratory. In this study, using 71 clinically important yeast isolates (excluding Candida albicans) collected from a single centre, we determined the concordance of 28S nrDNA and ITS sequencing and evaluated the performance of two commercial test kits, two MALDI-TOF MS platforms, and rep-PCR DNA fingerprinting. 28S nrDNA and ITS sequencing showed complete agreement on the identities of the 71 isolates. Using sequencing results as the standard, 78.9% and 71.8% isolates were correctly identified using the API 20C AUX and Vitek 2 YST ID Card systems, respectively; and 90.1% and 80.3% isolates were correctly identified using the Bruker and Vitek MALDI-TOF MS platforms, respectively. Of the 18 strains belonging to the Candida parapsilosis species complex tested by DiversiLab automated rep-PCR DNA fingerprinting, all were identified only as Candida parapsilosis with similarities ≥93.2%, indicating the misidentification of Candida metapsilosis and Candida orthopsilosis. However, hierarchical cluster analysis of the rep-PCR DNA fingerprints of these three species within this species complex formed three different discrete clusters, indicating that this technology can potentially differentiate the three species. To achieve higher accuracies of identification, the databases of commercial biochemical test kits, MALDI-TOF MS platforms, and DiversiLab automated rep-PCR DNA fingerprinting needs further enrichment, particularly for uncommonly encountered yeast species.