Long-range air dispersion of Candida auris in a cardiothoracic unit outbreak in Hong Kong.

BACKGROUND: Nosocomial outbreaks of Candida auris, a multidrug-resistant fungus, are increasingly reported worldwide; the mode of transmission has usually been reported to be via direct contact. Some studies previously suggested potential short-distance air dispersal during high-turbulence activities, but evidence on long-range air dispersal remains scarce. AIM: To describe a C. auris nosocomial outbreak involving two wards (H7, 5E) in two local hospitals. METHODS: Samples were taken from patients, ward surfaces (frequently touched items and non-reachable surfaces) while settle plates were used for passive air sampling to investigate possible contributions by direct contact and air dispersal. Epidemiological and phylogenetic analyses were also performed on the C. auris isolates from this outbreak. FINDINGS: Eighteen patients were confirmed to have asymptomatic C. auris skin colonization. C. auris was expectedly identified in samplings from frequently touched ward items but was also isolated in two samples from ceiling supply air grilles which were 2.4 m high and inaccessible by patients. Moreover, one sample from a corridor return air grille as far as 9.8 m away from the C. auris cohort area was also positive. Two passive air samplings were positive, including one from a cubicle with no confirmed cases for four days, suggesting possible air dispersal of C. auris. Whole-genome sequencing confirmed clonality of air, environment, and patients' isolates. CONCLUSION: This is the first study to demonstrate potential long-range air dispersal of C. auris in an open-cubicle ward setting. Ventilation precautions and decontamination of out-of-reach high-level surfaces should be considered in C. auris outbreak management.

Efficacy of Silkworm Pupae Extract on Muscle Strength and Mass in Middle-Aged and Older Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: We investigated the efficacy and safety of silkworm pupae extract (SWP) consumption for 12 weeks on muscle mass and strength in middle-aged and older individuals with relatively low skeletal muscle mass who do regular low-intensity exercise. DESIGN: A randomized double-blinded placebo-controlled trial. PARTICIPANTS: The study was conducted with 54 participants with relatively low skeletal muscle mass (SMM) (64.4 ± 6.1 years; body mass index, 23.8 ± 2.4 kg/m2). INTERVENTION AND MEASUREMENTS: Participants were randomly assigned to one of two groups: 1000 mg of SWP/day plus regular exercise (SWP group, n=27) or placebo plus regular exercise (placebo group, n=27). All participants were required to engage in 30-60 minutes/day of walking for ≥3 days/week for 12 weeks. The primary outcome was knee extension/flexion strength (Nm), measured at the velocity of 60°/s. Secondary outcomes included body composition, biomarkers (creatine kinase and creatinine), handgrip strength, and quality of life questionnaire. RESULTS: Both the intention-to-treat (ITT) and per-protocol (PP) analyses revealed no significant impact of SWP on knee strength compared to the placebo group over 12 weeks. On the other hand, the SWP group had significantly greater increases in right-handgrip strength by 1.94 kg (95% CI: 0.08-3.79; p = 0.041) and left-handgrip strength by 1.83 kg (0.25-3.41; p = 0.024) compared to the placebo group in the ITT population, after 12 weeks. Moreover, in the PP population, the SWP group revealed an even greater increase in right-handgrip strength by 2.07 kg (0.15-3. 98; p = 0.035) and left-handgrip strength by 2.21 kg (0.60-3.83; p = 0.008) for the 12-week period. However, this study resulted in a failure to detect significant differences in the body composition, biomarkers, quality of life questionnaire, physical activity, and caloric intake between the groups. None of the participants in the SWP group experienced any significant adverse events. In the placebo group, two participants experienced urticaria and allergic side effects, leading to their withdrawal from the study and two exhibited elevated levels of liver enzyme and increased diastolic blood pressure, respectively at 12 weeks. CONCLUSION: SWP, in addition to low-intensity exercise, may enhance handgrip strengths in middle-aged and older adults with relatively lower SMM. Future studies need to use a large sample size over longer periods to validate our findings. This trial was registered at clinicaltrials.gov as NCT04994054.

Clinical and Immunological Characterization of Perilla Seed Allergy in Children.

BACKGROUND AND OBJECTIVES: Perilla seeds are known to cause immediate allergic reactions. However, reports on perilla seed allergy are limited to a few case reports worldwide, and there is currently no diagnostic test for this allergy. Our objective was to analyze the clinical and immunological characteristics of perilla seed allergy and to identify allergens for the development of diagnostic methods. METHODS: Twenty-one children with clinical perilla seed allergy were enrolled from 2 tertiary hospitals between September 2016 and June 2019. Using perilla seed extract, we developed a skin prick test (SPT) and an IgE enzyme-linked immunosorbent assay (ELISA) for diagnosis of perilla seed allergy. IgE immunoblotting was performed to identify putative allergenic components, and amino acid composition analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The median age of children with perilla seed allergy was 3 years; the proportion of children with anaphylaxis was 28.6%. SPT was performed with perilla seed in 15 of 21 children, all of whom tested positive. On ELISA, 85.7% of children tested positive for perilla seed-specific IgE. Proteins with molecular weights of 50, 31-35, and 14-16 kDa bound to the sera of >50% of children with perilla seed allergy. LC-MS/MS analysis of these 3 protein fractions showed 8 putative proteins, including perilla oleosin (Accession No. 9963891), to be allergens. CONCLUSIONS: This study documented the clinical characteristics and immunological profiles of 21 children with perilla seed allergy. Our results suggest that oleosin is one of the major allergens in perilla seeds.

Erythema annulare centrifugum induced by COVID-19 vaccination.

With the expansion of the COVID-19 vaccination drive, an increasing number of adverse effects are surfacing. A 74-year-old woman presented with multiple erythematous and itchy patches on several sites. She had no relevant medical history, apart from the first AZD1222 vaccination 1 month previously. Microscopically, epidermal changes, including mild spongiosis and parakeratosis, were observed. Tight perivascular lymphocytic infiltration (coat-sleeve pattern) was also observed in the dermis. The final diagnosis was erythema annulare centrifugum (EAC) induced by SARS-CoV-2 vaccination. Based on this report, dermatologists should be aware of the possibility of EAC from the AZD1222 vaccination.

Lactobacillus intestinalis YT2 restores the gut microbiota and improves menopausal symptoms in ovariectomized rats.

There are many studies focusing on the alleviation of menopausal symptoms; however, little is known about the role of gut microorganisms in menopausal symptoms. Ovariectomized (OVX) rats were administered a novel strain (YT2) of Lactobacillus intestinalis (a species with significantly reduced abundance in OVX rats) and the potential probiotic effect on the improvement of menopausal symptoms was evaluated. Of note, the gut microbial composition completely shifted after ovariectomy in rats. Treatment with L. intestinalis YT2 significantly alleviated menopausal symptoms, such as increased fat mass, decreased bone mineral density, increased pain sensitivity, depression-like behaviour, and cognitive impairment. Additionally, the administration of L. intestinalis YT2 restored the intestinal microbial composition, including an increased Firmicutes/Bacteroides ratio. L. intestinalis YT2 also promoted gut barrier integrity by increasing the mRNA levels of tight junction-related markers. In conclusion, L. intestinalis YT2 treatment alleviated menopausal symptoms via the modulation of the gut microbiota. Importantly, these results suggest that L. intestinalis YT2 should be considered as a therapeutic probiotic agent for menopausal women.

Potential role of CMPK1, SLC29A1, and TLE4 polymorphisms in gemcitabine-based chemotherapy in HER2-negative metastatic breast cancer patients: pharmacogenetic study results from the prospective randomized phase II study of eribulin plus gemcitabine versus paclitaxel plus gemcitabine (KCSG-BR-13-11).

BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.

Prevalence of Anemia and Its Association with Frailty, Physical Function and Cognition in Community-Dwelling Older Adults: Findings from the HOPE Study.

OBJECTIVES: The prevalence of anemia and its impact on frailty and physical function amongst the multiethnic older populations in the Southeast Asian (SEA) countries are often not well studied. Singapore, a nation comprised of multiethnic communities, is one of the most rapidly aging population globally. We aim to evaluate the prevalence of anemia and its impact on frailty, and physical function in Healthy Older People Everyday (HOPE)- an epidemiologic population-based study on community-dwelling older adults in Singapore. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: 480 adults ≥ 65 years old. MEASUREMENTS: Data were collected from interviewers-administered questionnaires on socio-demographics, FRAIL scale, Mini-Mental State Examination, EQ-5D, Barthel Index, and Lawton index. Hemoglobin concentration and physical assessments, including anthropometry, grip strength, timed up-and-go (TUG) were measured. RESULTS: The overall prevalence of anemia was 15.2% (73 out of 480). The Indian ethnic group had the highest prevalence of anemia (32%, OR=3.02; 95%CI= 1.23-7.41) with the lowest hemoglobin concentration compared to the overall population (13.0±1.3g/L and 13.5±1.4g/L, p=0.02). Hemoglobin levels and anemia were significantly associated with frailty (OR=2.28; 95% CI=1.02-5.10), low grip strength (OR=1.79; 95% CI=1.01-3.03), ≥ one IADL impairment (OR=2.35; 95% CI=1.39-3.97). Each 1 g/dL increase in hemoglobin was associated with a 6% decrease in frailty odds after adjusting for potential covariates (OR = 0.94, 95% CI: 0.90-0.99). There was a significant difference in the mean TUG between the non-anemic (11.0±3.4 seconds) and anemic (12.3±6.0 seconds, p=0.01) counterparts, but no difference in the number of falls. CONCLUSION: In our multiethnic Asian population, anemia was adversely associated with frailty, decreased muscle strength, and IADL impairment. Health policies on anemia screening should be employed to avoid or potentially delay or reverse these adverse outcomes associated with anemia. Recognition, evaluation, and treatment of anemia amongst this vulnerable population is warranted.

A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis.

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations in thirteen CLN genes. Mutations in one CLN gene, CLN5, cause variant late-infantile NCL, with an age of onset between 4 and 7 years. The CLN5 protein is ubiquitously expressed in the majority of tissues studied and in the brain, CLN5 shows both neuronal and glial cell expression. Mutations in CLN5 are associated with the accumulation of autofluorescent storage material in lysosomes, the recycling units of the cell, in the brain and peripheral tissues. CLN5 resides in the lysosome and its function is still elusive. Initial studies suggested CLN5 was a transmembrane protein, which was later revealed to be processed into a soluble form. Multiple glycosylation sites have been reported, which may dictate its localisation and function. CLN5 interacts with several CLN proteins, and other lysosomal proteins, making it an important candidate to understand lysosomal biology. The existing knowledge on CLN5 biology stems from studies using several model organisms, including mice, sheep, cattle, dogs, social amoeba and cell cultures. Each model organism has its advantages and limitations, making it crucial to adopt a combinatorial approach, using both human cells and model organisms, to understand CLN5 pathologies and design drug therapies. In this comprehensive review, we have summarised and critiqued existing literature on CLN5 and have discussed the missing pieces of the puzzle that need to be addressed to develop an efficient therapy for CLN5 Batten disease.

Associations between Chewing Difficulty, Subjective Cognitive Decline, and Related Functional Difficulties among Older People without Dementia: Focus on Body Mass Index.

OBJECTIVE: This study aimed to determine whether chewing difficulty is associated with subjective cognitive decline (SCD) and related functional difficulties by body mass index. DESIGN: A population-based cross-sectional study. SETTING AND PARTICIPANTS: A nationwide sample of 54,004 individuals aged ≥65 years from the 2018 Korea Community Health Survey. MEASUREMENTS: SCD and SCD-related functional difficulties were measured using the cognitive decline module of the Behavioral Risk Factor Surveillance System. Chewing difficulty was assessed based on a self-report questionnaire from an oral health-related behaviors interview survey. BMI was calculated from objective values by measuring height and weight through a physical meter. RESULTS: Among the 54,004 individuals, the prevalence of SCD in underweight, overweight, and obesity group was 33.6% (n = 806), 30.3% (n = 9,691), and 28.7% (n=5,632) respectively. Chewing difficulty was associated with SCD and SCD-related functional difficulties. This association was more pronounced in underweight (BMI: <18.5 kg/m2) people [underweight: (odds ratio [OR] = 1.68, 95% confidence interval [CI] 1.48-1.92); normal weight: OR = 1.13, 95% CI 1.04-1.22; obese: OR = 1.15, 95% CI 1.05-1.27]. Similar trends were demonstrated for SCD-related functional difficulties (underweight: OR = 1.53, 95% CI 1.17-2.01; normal weight: OR = 1.36, 95% CI 1.15-1.63; obese: OR = 1.50, 95% CI 1.22-1.86). CONCLUSIONS: Chewing difficulty was associated with SCD and SCD-related functional difficulties in older people. Our results suggest that underweight status may play roles in the associations between chewing difficulty and SCD and SCD-related functional difficulties.

Seed dormancy and germination of Asarum sieboldii, a disjunct relict species in East Asia.

Disjunct species in the same genus are a common feature of the flora in the temperate forests of East Asia and eastern North America. This study aimed to evaluate whether the kind of seed dormancy was maintained after species in the genus Asarum (Aristolochiaceae) were separated from their common ancestor. We classified the seed dormancy of Asarum sieboldii, an East Asian species, based on a phenology study and experiments in controlled temperature conditions, and then compared it to that of the previously studied A. canadense, an eastern North American species. The underdeveloped embryo of A. sieboldii grew and germinated (radicle emergence) in autumn but shoot emergence did not occur until the following spring. The seeds of A. sieboldii had deep simple epicotyl morphophysiological dormancy because the seeds with emerged radicle required a relatively long period of cold stratification to break epicotyl dormancy and produce a shoot. Although the seed of A. sieboldii had weaker radicle dormancy and stronger epicotyl dormancy compared to A. canadense, the kind of seed dormancy was the same for the two species. The trait of seed dormancy was inherited from a shared common ancestor and maintained in populations well after the two species (or their ancestors) separated. However, quantitative differences in temperature requirements for radicle and shoot emergence suggest the possibility of adaptation to the environment.

A Participatory, Mixed Methods Approach to Define and Measure Partnership Synergy in Long-standing Equity-focused CBPR Partnerships.

Understanding what contributes to success of community-based participatory research (CBPR) partnerships is essential to ensuring their effectiveness in addressing health disparities and health inequities. Synergy, the concept of accomplishing more together than separately, is central to partnership effectiveness. However, synergy specific to long-standing, equity-focused CBPR partnerships has not been closely examined. To address this, we defined and developed measures of partnership synergy as one dimension of a participatory mixed methods study, Measurement Approaches to Partnership Success (MAPS), to develop a validated instrument to measure success in long-standing CBPR partnerships. Framed by a conceptual model and scoping literature review, we conducted in-depth interviews with a national panel of academic and community experts in CBPR and equity to develop partnership synergy measures. Items were refined through an iterative process, including a three-stage Delphi process, comparison with existing measures, cognitive interviews, and pilot testing. Seven questionnaire items were developed to measure synergy arising from equitable partnerships bringing together diverse partners across power differences to promote equity. Defining and measuring synergy in the context of long-standing partnership success is central to understanding the role of synergy in collaborative approaches to research and action and can strengthen CBPR partnerships to promote healthy communities and advance health equity.

A new aortoiliac calcification scoring system to predict grade C anastomotic leak following rectal cancer surgery.

BACKGROUND: Aortoiliac calcification may be a surrogate marker of decreased visceral perfusion causing anastomotic leak (AL). The aim of this study was to evaluate the predictive role of aortoiliac calcification for AL after rectal cancer surgery. METHODS: We enrolled patients with primary rectal cancer who had restorative resection at our institution between January 2013 and December 2015. An aortoiliac calcification score was calculated as the sum of calcification scores at the infrarenal aorta (0: no, 1: ≤ 3 cm, 2: > 3 cm) and the common iliac arteries (0: no, 1: unilateral, 2: bilateral). AL was classified into three grades: grade A, requiring no intervention; grade B, requiring therapeutic intervention without re-laparotomy; and grade C, requiring re-laparotomy. Clinicopathological characteristics were analyzed to identify risk factors for AL. RESULTS: There were 583 patients. Three-hundred forty-five (59.2%) had an aortoiliac calcification score ≥ 3, and 37 (6.3%) patients experienced AL, in 30 cases (5.1%) grade C AL. Patients with an aortoiliac calcification score ≥ 3 had a higher incidence of grade C AL (6.7% vs. 2.9%, p = 0.045). Multivariate logistic regression analysis revealed that an aortoiliac calcification score ≥ 3 was an independent risk factor for grade C AL (odds ratio = 2.669, 95% confidence interval 1.066-6.686, p = 0.036). CONCLUSIONS: Aortoiliac calcification may be considered a risk factor for grade C AL after rectal cancer surgery.

Risk of nosocomial transmission of coronavirus disease 2019: an experience in a general ward setting in Hong Kong.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in Wuhan in December 2019 and has rapidly spread across different cities within and outside China. Hong Kong started to prepare for COVID-19 on 31st December 2019 and infection control measures in public hospitals were tightened to limit nosocomial transmission within healthcare facilities. However, the recommendations on the transmission-based precautions required for COVID-19 in hospital settings vary from droplet and contact precautions, to contact and airborne precautions with placement of patients in airborne infection isolation rooms. AIM: To describe an outbreak investigation of a patient with COVID-19 who was nursed in an open cubicle of a general ward before the diagnosis was made. METHOD: Contacts were identified and risk categorized as 'close' or 'casual' for decisions on quarantine and/or medical surveillance. Respiratory specimens were collected from contacts who developed fever, and/or respiratory symptoms during the surveillance period and were tested for SARS-CoV-2. FINDINGS: A total of 71 staff and 49 patients were identified from contact tracing, seven staff and 10 patients fulfilled the criteria of 'close contact'. At the end of 28-day surveillance, 76 tests were performed on 52 contacts and all were negative, including all patient close contacts and six of the seven staff close contacts. The remaining contacts were asymptomatic throughout the surveillance period. CONCLUSION: Our findings suggest that SARS-CoV-2 is not spread by an airborne route, and nosocomial transmissions can be prevented through vigilant basic infection control measures, including wearing of surgical masks, hand and environmental hygiene.