Circ_0068481 Affects the Human Pulmonary Artery Smooth Muscle Cells' Progression by miR-361-3p/KLF5 Axis.

BACKGROUND: Uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). In this work, we defined the precise part of circ_0068481 in PASMC proliferation and migration induced by hypoxia. We hypothesized that circ_0068481 enhanced hypoxia-induced PASMC proliferation, invasion, and migration through the microRNA (miR)-361-3p/Krüppel-like factor 5 (KLF5) pathway. METHODS: Human PASMCs (hPASMCs) were exposed to hypoxic (3% O2) conditions. Circ_0068481, miR-361-3p, and KLF5 levels were gauged by qRT-PCR and western blot. Cell viability, proliferation, invasion, and migration were detected by XTT, EdU incorporation, transwell, and wound-healing assays, respectively. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were performed to confirm the direct relationship between miR-361-3p and circ_0068481 or KLF5. RESULTS: Circ_0068481 expression was increased in the serum of PAH patients and hypoxia-induced hPASMCs. Downregulation of circ_0068481 attenuated hypoxia-induced promotion in hPASMC proliferation, invasion, and migration. Circ_0068481 directly targeted miR-361-3p, and miR-361-3p downregulation reversed the inhibitory effects of circ_0068481 silencing on hypoxia-induced hPASMC proliferation, invasion, and migration. KLF5 was a direct miR-361-3p target, and miR-361-3p upregulation mitigated hypoxia-induced hPASMC proliferation, invasion, and migration by inhibiting KLF5 expression. Moreover, circ_0068481-induced KLF5 expression by binding to miR-361-3p in hypoxic hPASMCs. CONCLUSIONS: Circ_0068481 knockdown ameliorated hypoxia-induced hPASMC proliferation, invasion, and migration at least in part through the miR-361-3p/KLF5 axis.

Neo-Antigen-Reactive T Cells Immunotherapy for Colorectal Cancer: A More Personalized Cancer Therapy Approach.

Colorectal cancer (CRC) is the second most common malignancy in women and the third most frequent cancer in men. Evidence has revealed that the survival of patients with metastatic CRC is very low, between one and three years. Neoantigens are known proteins encoded by mutations in tumor cells. It is theorized that recognizing neoantigens by T cells leads to T cell activation and further antitumor responses. Neoantigen-reactive T cells (NRTs) are designed against the mentioned neoantigens expressed by tumor cells. NRTs selectively kill tumor cells without damage to non-cancerous cells. Identifying patient-specific and high immunogen neoantigens is important in NRT immunotherapy of patients with CRC. However, the main challenges are the side effects and preparation of NRTs, as well as the effectiveness of these cells in vivo. This review summarized the properties of neoantigens as well as the preparation and therapeutic outcomes of NRTs for the treatment of CRC.

[Chemical composition and antioxidant activity of different parts of Prunella vulgaris by UPLC-Q-TOF-MS/MS and UPLC].

Prunellae Spica is the dried spica of Prunella vulgaris belonging to Labiatae and it is widely used in pharmaceutical and general health fields. As a traditional Chinese medicine cultivated on a large scale, it produces a large amount of non-medicinal parts, which are discarded because they are not effectively used. To analyze the chemical constituents in the different samples from spica, seed, stem, and leaf of P. vulgaris, and explore the application value and development prospect of these parts, this study used ultrahigh performance liquid chromatography-tandem quadrupoles time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) to detect chemical constituents in different parts of P. vulgaris. As a result, 117 compounds were detected. Among them, 87 compounds were identified, including 32 phenolic acids, 8 flavonoids, and 45 triterpenoid saponins. Some new triterpenoid saponins containing the sugar chain with 4-6 sugar units were found. Further, multivariate statistical analysis was conducted on BPI chromatographic peaks of multiple batches of different parts, and the results showed that spica had the most abundant chemical constituents, including salviaflaside and linolenic acid highly contained in the seed and phenolic acids, flavonoids, and triterpenoid saponins in the stem and leaf. In general, the constituents in the spica were composed of those in the seed, stem, and leaf. UPLC was used to determine the content of 6 phenolic acids(danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, salviaflaside, and rosmarinic acid) in different parts. The content of other phenolic acids in the seed was generally lower than that in the spica except that of salviaflaside. The content of salviaflaside in the spica was higher than that in the stem and leaf, but the content of other phenolic acids in the spica was not significantly different from that in the stem. The content of protocatechuic aldehyde and caffeic acid in the spica was lower than that in the leaf. DPPH free radical scavenging method was used to detect the antioxidant activity of four parts, and there was no significant difference in the antioxidant activity between the spica and the stem and leaf, but that was significantly higher than the seed. Moreover, the antioxidant activity of these parts was correlated with the content of total phenolic acids. Based on the above findings, the stem and leaf of P. vulgaris have potential application value. Considering the traditional medication rule, it is feasible to use the whole plant as a medicine. Alternatively, salviaflaside, occurring in the seed, can be used as a marker compound for the quality evaluation of Prunellae Spica, if only using spica as the medicinal part of P. vulgaris, as described in the Chinese Pharmacopoeia(2020 edition).

[New steroidal saponins from aerial parts of Paris polyphylla var. chinensis].

The shortage of Paridis Rhizoma promotes comprehensive utilization and development research of waste aerial parts of the original plant. The chemical compositions of the aerial parts of Paris polyphylla var. chinensis were clarified based on the ultrahigh performance liquid chromatography tandem quadrupoles time of flight mass spectrometry(UPLC-QTOF-MS/MS) in the previous investigation, and a series of flavonoids and steroidal saponins were isolated. The present study continued the isolation and structure identification of the new potential compounds discovered based on UPLC-QTOF-MS/MS. By using silica gel, ODS, flash rapid preparation, and other column chromatography techniques, combined with prepared high performance liquid chromatography, five compounds were isolated from the 75% ethanol extract of the aerial parts of P. polyphylla var. chinensis, and their structures were identified by spectral data combined with chemical transformations, respectively, as(23S,25R)-23,27-dihydroxy-diosgenin-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→3)]-ß-D-glucopyranoside(1),(25R)-26-O-ß-D-glucopyranosyl-furost-5-en-3ß,22α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(2),(25R)-27-O-ß-D-glucopyranosyl-5-en-3ß,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(3),(25R)-27-O-ß-D-glucopyranosyl-5-en-3ß,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→3)]-ß-D-glucopyranoside(4), and aculeatiside A(5). Among them, compounds 1-4 were new ones, and compound 5 was isolated from P. polyphylla var. chinensis for the first time.

[Discovery, isolation and structural identification of alkaloid glycosides in six traditional Chinese medicine such as Coptis chinensis].

Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.

Simulation education utilizing phantom and angle reference guide in pulmonary nodule CT localization.

Objective: The incidence of sub-centimeter pulmonary nodules has been increasing along with the use of low-dose computed tomography (LDCT) as a screening tool for early lung cancer detection. In our institution, pulmonary nodule computed tomography-guided localization (PNCL) is performed preoperatively with the laser angle guided assembly (LAGA), an angle reference device. This study aims to investigate the efficacy of postgraduate education in a phantom simulation of PNCL, with or without LAGA. Setting design: This prospective study was conducted in an academic hospital in Taiwan. Seven thoracic surgery residents and three experienced senior physicians were recruited to perform PNCL using a phantom simulation, with or without LAGA, for five nodules each and complete a questionnaire. Performance data were collected. χ2 tests, Mann-Whitney U test, univariate and multivariate linear regression were used for statistical analyses. Results: The confidence level increased from median 7[range 1, 9] to 8, range [6,9] (p = 0.001) before and after the simulation education course. The scores of enhanced PNCL ability and course satisfaction were as high as 8 [5,9], and 9 [7,9]. LAGA enabled broader puncture angles (with 27.5° [0°,80°]; without 14° [0°, 80°], p = 0.003), a lower puncture frequency (with 1 [1,4]; without 2 [1,5], p < 0.001), and a smaller angle deviation (with 3°[ 0°,8°]; without 5°[ 0°,19°], p = 0.002). Pleural depth in millimeters was associated with increased puncture frequency (0.019[0,010,0.028]) and procedure time (0.071'[ 0.018,0.123']. The PNCL-experienced physicians performed the procedure in less time (-2.854'[-4.646',1.061']. The traverse direction toward the mediastinum diminished the frequency (toward 1[ 1,3]; away 1 [1,5], p = 0.003) and time (toward 7.5'[2',18]'; away 9'[ 3',31'], p = 0.027). The learning curve did not improve procedure performance after ten PNCL simulation rounds. Conclusions: The phantom PNCL simulation education course increased the confidence level, enhanced residents' skill acquisition, and promoted learning satisfaction. The angle reference device helped improve the outcomes of the puncture frequency and reduced angle deviation.

The Association of DNA Ligase 1 Rs20579 Polymorphism With Lung Cancer Risk Among Taiwanese.

BACKGROUND/AIM: Impaired DNA repair capacity may play a critical role in genome instability and carcinogenesis. However, the impact of DNA ligase 1 (Lig1) genotypes on tumorigenesis remains unclear. This study aimed to investigate the contribution of Lig1 rs20579 genotypes to the risk of developing lung cancer, and review the related literature. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genotypes of Lig1 rs20579 and evaluate their association with lung cancer risk among 358 lung cancer cases and 716 age- and sex-matched cancer-free control subjects. RESULTS: The distribution of GG, AG, and AA genotypes for Lig1 rs20579 was 77.1%, 20.8%, and 2.1% among the controls, and 76.0%, 21.5%, and 2.5% among the lung cancer cases (p for trend=0.8686). There was no significant difference in the distribution of AG and AA genotypes between the two groups (p=0.8257 and 0.8098, respectively). Allelic frequency analysis indicated that individuals carrying the variant A allele for Lig1 rs20579 had a non-significant 1.07-fold higher risk of developing lung cancer than those carrying the wild-type G allele [95% confidence interval (CI)=0.82-1.40, p=0.6639]. Furthermore, no differential distribution of the Lig1 rs20579 genotype was found among non-smokers (p=0.9910) or smokers (p=0.9001). CONCLUSION: In contrast to Americans, Lig1 rs20579 genotypes do not appear to play a critical role in determining susceptibility to lung cancer among Taiwanese individuals.

Surface-Enhanced Raman Spectroscopic Investigation of PAHs at a Fe3O4@GO@Ag@PDA Composite Substrates.

A method for surface-enhanced Raman spectroscopy (SERS) sensing of polycyclic aromatic hydrocarbons (PAHs) is reported. Fe3O4@PDA@Ag@GO is developed as the SERS substrate prepared by classical electrostatic attraction method based on the enrichment of organic compounds by graphene oxide (GO) and polydopamine (PDA) and the good separation and enrichment function of Fe3O4. The morphology and structure of the SERS substrate were represented by transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD) and the UV-visible absorption spectrum (UV-vis spectra). The effect of different temperatures on SERS during synthesis was investigated, and it was found that the best effect was achieved when the synthesis temperature was 90 °C. The effect of each component of Fe3O4@PDA@Ag@GO nanocomposites on SERS was explored, and it was found that Ag NPs are of great significance to enhance the Raman signal based on the electromagnetic enhancement mechanism; apart from enriching the polycyclic aromatic hydrocarbons (PAHs) through π-π interaction, GO also generates strong chemical enhancement to the Raman signal, and PDA can prevent Ag from shedding and agglomeration. The existence of Fe3O4 is favored for the fast separation of substrate from the solutions, which greatly simplifies the detection procedure and facilitates the cycle use of the substrate. The experimental procedure is simplified, and the substrate is reused easily. Three kinds of PAHs (phenanthrene, pyrene and benzanthene) are employed as probe molecules to verify the performance of the composite SERS substrate. The results show that the limit of detection (LOD) of phenanthrene pyrene and benzanthene detected by Fe3O4@PDA@Ag@GO composite substrate are 10-8 g/L (5.6 × 10-11 mol/L), 10-7 g/L (4.9 × 10-10 mol/L) and 10-7 g/L (4.4 × 10-10 mol/L), respectively, which is much lower than that of ordinary Raman, and it is promising for its application in the enrichment detection of trace PAHs in the environment.

Genomics and morphometrics reveal the adaptive evolution of pikas.

Pikas (Lagomorpha: Ochotonidae) are small mouse-like lagomorphs. To investigate their adaptation to different ecological environments during their dispersal from the Qinghai-Xizang (Tibet) Plateau (QTP), we collected 226 pikas and measured 20 morphological characteristics and recorded habitat information. We also sequenced the genome of 81 specimens, representing 27 putative pika species. The genome-wide tree based on 4 090 coding genes identified five subgenera, i.e., Alienauroa, Conothoa, Lagotona, Ochotona, and Pika, consistent with morphometric data. Morphologically, Alienauroa and Ochotona had similar traits, including smaller size and earlier divergence time compared to other pikas. Consistently, the habitats of Alienauroa and Ochotona differed from those of the remaining subgenera. Phylogenetic signal analysis detected 83 genes significantly related to morphological characteristics, including several visual and hearing-related genes. Analysis of shared amino acid substitutions and positively selected genes (PSGs) in Alienauroa and Ochotona identified two genes, i.e., mitochondrial function-related TSFM (p.Q155E) and low-light visual sensitivity-related PROM1 (p.H419Y). Functional experiments demonstrated that TSFM-155E significantly enhanced mitochondrial function compared to TSFM-155Q in other pikas, and PROM1-419Y decreased the modeling of dynamic intracellular chloride efflux upon calcium uptake. Alienauroa and Ochotona individuals mostly inhabit different environments (e.g., subtropical forests) than other pikas, suggesting that a shift from the larger ancestral type and changes in sensory acuity and energy enhancement may have been required in their new environments. This study increases our understanding of the evolutionary history of pikas.

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events.

Objective: To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up. Methods: A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models. Results: The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL. Conclusion: Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.

Preparation of Fe3O4@PDA@Au@GO Composite as SERS Substrate and Its Application in the Enrichment and Detection for Phenanthrene.

In this study, highly active Fe3O4@PDA@Au@GO surface-enhanced Raman spectroscopy (SERS) active substrate was synthesized for application in the enrichment and detection of trace polycyclic aromatic hydrocarbons (PAHs) in the environment. The morphology and structure were characterized by transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD) and UV-visible absorption spectrum (UV-vis spectra). The effect of each component of Fe3O4@PDA@Au@GO nanocomposites on SERS was explored, and it was found that gold nanoparticles (Au NPs) are crucial to enhance the Raman signal based on the electromagnetic enhancement mechanism, and apart from enriching the PAHs through π-π interaction, graphene oxide (GO) also generates strong chemical enhancement of Raman signals, and polydopamine (PDA) can prevent Au from shedding and agglomeration. The existence of Fe3O4 aided the quick separation of substrate from the solutions, which greatly simplified the detection procedure and facilitated the reuse of the substrate. The SERS active substrate was used to detect phenanthrene in aqueous solution with a detection limit of 10-7 g/L (5.6 × 10-10 mol/L), which is much lower than that of ordinary Raman, it is promising for application in the enrichment and detection of trace PAHs.

Pulmonary fungal ball due to Trichophyton successfully managed with oral itraconazole: a case report.

Pulmonary fungal balls are caused by long-term fungal infection of the lung. They are sometimes a complication of previous cavitary pulmonary tuberculosis. Pulmonary fungal balls caused by Trichophyton are extremely rare. A 65-year-old man who worked in a leather recycling factory was admitted because of a productive cough and shortness of breath. He had a history of tuberculosis with lung destruction. A chest radiograph showed an opacity surrounding an air lucency over the left lung field, and chest computed tomography showed a mass within a cavity, producing a ball-in-hole appearance, over the left upper lung lobe. Bronchoalveolar lavage was performed, and fungal culture of the lavage fluid yielded Trichophyton. After 6 months of treatment with oral itraconazole, the patient's general condition improved. This case emphasizes the importance of awareness of fungal infection within cavitary lesions of the lung and shows that Trichophyton may be the etiologic organism in such cases. Itraconazole is a recommended treatment of pulmonary fungal balls.

[Qualitative and quantitative analysis of Paris polyphylla var. chinensis by UPLC-Q-TOF-MS/MS and HPLC].

Paridis Rhizoma(PR) is prepared from the dried rhizome of Paris polyphylla var. yunnanensis(PPY) or P. polyphylla var. chinensis(PPC) in Liliaceae family. The rapid development of PPY or PPC planting industry resulted from resource shortage has caused the waste of a large number of non-medicinal resources. To clarify the chemical compositions in rhizomes, fibrous roots, stems, leaves, seeds and pericarps of PPC, and explore the comprehensive application value and development prospect of these parts, the qualitative and quantitative analyses on the different parts of PPC were carried out by ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) and high performance liquid chromatography(HPLC). A total of 136 compounds were identified, including 112 steroidal saponins, 6 flavonoids, 11 nitrogen-containing compounds and 7 phytosterols. Rhizomes, fibrous roots, and seeds mainly contained protopennogenyl glycosides and pennogenyl glycosides; leaves and stems mainly contained protodiosgenyl glycosides and diosgenyl glycosides; pericarps mainly contained pennogenyl glycosides, followed by diosgenyl glycosides. The total level of four saponins was the highest in fibrous roots and rhizomes, followed by those in the pericarps and arillate seeds, and the lowest in the stems and exarillate seeds. This study can provide data support for the comprehensive development and rational application of non-medicinal parts of PPC.

[Separation and structural elucidation of C25 epimers of furostanol saponin from aerial parts of Paris polyphylla var. chinensis].

Paris polyphylla var. chinensis(PPC) is used as one of the origin plants of Paridis Rhizoma described in the Chinese Pharmacopoeia(2020 edition). Its resources shortage makes the planting scale gradually expand, and plenty of aerial parts are abandoned because of not being effectively used. On the basis of previous research, this study separated steroidal saponins to further clarify the chemical composition of the aerial parts of PPC. As a result, three pairs of 25R or 25S epimers of furostanol saponins were obtained by various column chromatography techniques. Their structures were identified as neosolanigroside Y6(1), solanigroside Y6(2), neoprotogracillin(3), protogracillin(4), neoprotodioscin(5) and protodioscin(6) by spectral data combining with chemical transformation. Compound 1 is a new compound, and compounds 2, 3 and 5 are isolated from Paris plants for the first time. Compounds 4 and 6 are isolated from this plant for the first time. Previously, only several spirostanol glycosides with 25S configuration were isolated from Paris plants. Guided by mass spectrometry, the present study isolated the furostanol saponins with 25S configuration from this genus for the first time, which further enriches the chemical information of Paris genus and provides a reference for the isolation of similar compounds.

A Study to Analyze Narrative Feedback Record of an Emergency Department.

BACKGROUND: This study adopts the Situation-Behavior-Impact-Action (SBIA) model to examine the compliance of narrative feedback in the Entrustable Professional Activities (EPAs)-based e-Portfolio system for clinical preceptors in the emergency department of a regional teaching hospital, and analyzes the applicability of its application in emergency clinical training to increase the feasibility of improving the quality of clinical preceptors' feedback content. METHODS: Application of data mining technique to analyze 928 data points was recorded by 14 clinical teachers from April 2017 to May 2019. These data points were narrative feedback from workplace direct observation, which was recorded in the EPAs-based e-Portfolio. RESULTS: The majority of the narrative feedback consisted of only one component, behavior observed (53.99%) and action suggestion (17.24%). Some feedback consisted of two to three components; which were behavior observed-action suggestion (20.37%) and situation description-behavior observed- action suggestion (1.29%). Only a few feedbacks consisted of all four components: situation description- behavior observed-possible impact-action suggestion (0.75%). CONCLUSIONS: The current narrative feedback is from the basic appearance of SBIA, but there still got room for improvement. The narrative feedback should be given according to SBIA model in order to provide a comprehensive and constructive learning outcome. The narrative feedback recorded in EPAsbased e-Portfolio provides the delay of feedback effect. Thus, multiple feedbacks from various clinical teachers could make the assessments more concrete and outline the authentic clinical condition of the trainees.

The impact of COVID-19 pandemic on the health-seeking behaviour of an Asian population with acute respiratory infections in a densely populated community.

BACKGROUND: The COVID-19 pandemic led to the implementation of various non-pharmaceutical interventions (NPI) as the Singapore government escalated containment efforts from DORSCON Orange to Circuit Breaker. NPI include mandatory mask wearing, hand hygiene, social distancing, and closure of schools and workplaces. Considering the similar mode of transmission of COVID-19 and other pathogens related to acute respiratory infections (ARI), the effects of NPI could possibly lead to decreased ARI attendances in the community. This study aims to determine the year-on-year and weekly changes of ARI attendances across a cluster of polyclinics following the implementation of NPI. METHODS: The effect of the nation-wide measures on the health-seeking behaviour of the study population was examined over three periods: (1) 9 weeks prior to the start of Circuit Breaker (DORSCON Orange period), (2) 8 weeks during the Circuit Breaker, and (3) 9 weeks after easing of Circuit Breaker. Data on ARI attendances for the corresponding periods in 2019 were also extracted for comparison and to assess the seasonal variations of ARI. The average weekly workday ARI attendances were compared with those of the preceding week using Wilcoxon signed rank test. RESULTS: ARI attendances dropped steadily throughout the study period and were 50-80% lower than in 2019 since Circuit Breaker. They remained low even after Circuit Breaker ended. Positivity rate for influenza-like illnesses samples in the community was 0.0% from the last week of Circuit Breaker to end of study period. CONCLUSIONS: NPI and public education measures during DORSCON Orange and Circuit Breaker periods appear to be associated with the health-seeking behaviour of the public. Changing levels of perceived susceptibility, severity, benefits and barriers, and widespread visual cues based on the Health Belief Model may account for this change. Understanding the impact of NPI and shifts in the public's health-seeking behaviour will be relevant and helpful in the planning of future pandemic responses.

What are the measures taken to prevent COVID-19 infection among healthcare workers? A retrospective study in a cluster of primary care clinics in Singapore.

OBJECTIVE: To examine factors contributing to the low COVID-19 infectivity rate among healthcare workers in SingHealth Polyclinics (SHP), Singapore, from February to July 2020. DESIGN: Retrospective description, analysis and discussion of the factors and their contribution. SETTING: Single-institution study. METHODS: We describe and discuss the healthcare policies, infrastructure, people and processes contributing to the low COVID-19 infectivity rate in SHP.There were 1212 full-time and 198 contract staff. Of these, 171 SHP employees also supported the work in dormitories, isolation and community care facilities. During the review period, healthcare workers (HCWs) in SHP managed about 867 076 patient attendances, including 63 503 for upper respiratory tract infections, across its cluster of eight polyclinics. 29 642 swabs for COVID-19 were performed in SHP, with 126 positive results. 395 swabs were carried out in the dormitories and 59 were positive. Despite the high exposure, only two SHP staff were infected with COVID-19. Both have recovered well. RESULTS: Provision of adequate personal protection equipment, zonal segregation of high-risk patients, reduction in physical patient visits, effective staff communication, implementation of self-declared temperature monitoring and the maintenance of sustainable workload and work hours of HCWs contributed to the mitigation of COVID-19 infection risk among our staff. CONCLUSIONS: Until the widespread uptake of safe and effective vaccines against COVID-19, these measures are important in protecting HCWs. They are also important when managing future pandemics of similar nature to COVID-19.

Variations in the Antithyroid Antibody Titre During Pregnancy and After Delivery.

BACKGROUND: Immunosuppression occurs during pregnancy, and the antithyroid antibody titre drops, rebounding after delivery. We aimed to determine variations in antithyroid antibody titres during pregnancy and after delivery. METHODS: This retrospective study was conducted in a single centre. Antibody titres of 142 patients were measured to assess variations in the levels of thyroid-stimulating hormone receptor antibodies (TRAbs), thyroid peroxidase antibodies (TPOAbs), and thyroid globulin antibodies (TgAbs). We compared the titres of each antibody between adjacent time periods (eg, first trimester (T1) vs second trimester (T2), T2 vs third trimester (T3), T3 vs the postpartum period (PP)) by paired t-test or the Wilcoxon test. Then, we analysed data from patients with complete laboratory examination results in all four periods with the Friedman test, performing comparisons among groups. RESULTS: In the TgAb group, significant differences existed between T1 and T2 and between T2 and T3 in the LT4 subgroup and between T1 and T2 in the no-medication subgroup. In the TRAb group, significant differences existed between T1 and T2 in the LT4 subgroup. In the TPOAb group, significant differences existed among each group in the LT4 subgroup, and there were significant differences between T1 and T2 and between T2 and T3 in the no-medication subgroup. The Friedman test showed that the P-values were 0.013 and 0.004 in the LT4 and no-medication subgroups of the TgAb group, respectively; 0.122 in the LT4 subgroup of the TRAb group; and <0.001 and 0.272 in the LT4 and no-medication subgroups of the TPOAb group, respectively. In the LT4 subgroup of the TgAb group, the P-values for comparisons of time periods were 0.602 between T1 and T2, 0.602 between T2 and T3, 0.006 between T1 and T3, and 0.602 between T3 and PP. In the no-medication subgroup of the TgAb group, the P-values were 0.078 between T1 and T2, 1.000 between T2 and T3, 0.011 between T1 and T3, and 0.078 between T3 and PP. In the LT4 subgroup of the TPOAb group, the P-values were 0.09 between T1 and T2, 0.014 between T2 and T3, <0.001 between T1 and T3, and 0.772 between T3 and PP. CONCLUSION: We can conclude that the TgAb and TPOAb titres dropped during pregnancy.

Significant Association of Chitinase 3-like 1 Genotypes to Asthma Risk in Taiwan.

BACKGROUND/AIM: Chitinase 3-like 1 (CHI3L1) is overexpressed in asthma, and negatively associated with forced expiratory volume in the first second. This study aimed at evaluating whether CHI3L1 genotypes affect asthma risk. MATERIALS AND METHODS: The blood samples of 198 asthma patients and 453 control subjects were collected, and the genotypic patterns of CHI3L1 -131C/G (rs4950928) and -247G/A (rs1262491437) were examined. RESULTS: The percentages of CG and GG at CHI3L1 -131C/G were 32.8% and 7.6% among the asthma cases, respectively, significantly higher than the 23.8% and 3.1% among the non-asthmatic healthy subjects (p for trend=0.0009). The allelic frequency distribution analysis showed that the G allele at CHI3L1 - 131C/G conferred a significantly higher asthma risk than the wild-type C allele (p<0.0001). The genotypic and allelic frequency analyses for CHI3L1 -247G/A did not show any significant difference. CONCLUSION: The G allele at CHI3L1-131C/G serves as a biomarker in determining personal susceptibility to asthma in Taiwan.

Mycoplasma pneumoniae and Chlamydia pneumoniae Coinfection with Acute Respiratory Distress Syndrome: A Case Report.

Community-acquired pneumonia caused by Mycoplasma pneumoniae or Chlamydia pneumoniae is usually mild. Mycoplasma pneumoniae-related and C. pneumoniae-related acute respiratory distress syndromes (ARDSs) are rare. Moreover, to our knowledge, there are no published reports on ARDS caused by M. pneumoniae and C. pneumoniae coinfection. Here, we report a case of an immunocompetent young woman who was co-infected with M. pneumoniae and C. pneumoniae and was started on treatment with piperacillin and clarithromycin. Two days later, she developed ARDS. She recovered rapidly following a change of antibiotic treatment to levofloxacin and was discharged on day 12. We conducted exome sequencing followed by alternative filtering to search for candidate ARDS-related genes. We identified an intronic variant of unknown significance within leucine-rich repeat-containing 16A (LRRC16A), a gene previously identified as a significant locus for platelet count with a possible role in ARDS. This is a rare case of ARDS in a young adult caused by M. pneumoniae and C. pneumoniae coinfection. This case suggests that ARDS in young adults may be correlated with variants in LRRC16A. This requires confirmation by further case reports.