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This rapid review aims to present a comprehensive overview of barriers, facilitators, and effective interventions that promote vaccination uptake by older adults in the Asia-Pacific region. Rapid review methodology was applied, using two databases (PubMed, Embase). Articles were included if studies were conducted in Australia, Singapore, Indonesia, and the Philippines; included human population ≥50 years of age, and was published from 2016 to August 2022. Related articles were not found from Indonesia and Philippines. A total of 23 articles met the inclusion criteria, with 19 reporting on barriers and facilitators, whereas, four articles reported effective interventions to promote vaccination uptake. Among the 19 studies that identified barriers and facilitators to vaccination uptake, the more common factors were social influences (n = 8/19), perceived benefits of vaccine (n = 7/19), and perceived vaccine safety (n = 6/19). Interventions that focused on supporting clinicians were found to be effective in leading them to recommend vaccinations among older adults, such as creating awareness on the low baseline vaccination rates among older adults, provision of structured health assessment, and nurse reminders. More studies are needed to ascertain the barriers and facilitators to uptake, as well as to identify effective interventions influencing vaccine uptake among older adults in the Asia-Pacific region., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia., Methods: Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis., Results: Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index., Conclusions: In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease., Competing Interests: Disclosures None.

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background/purpose: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics., Methods: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways., Results: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved., Conclusion: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Parathyroid adenoma (PA) sometimes recurs after surgery, how to improve the surgical success rate of PA is the key to the treatment of this disease., Aim: To investigate the clinical features, diagnosis, and surgical treatment of patients with PA., Methods: Patients who were pathologically confirmed with PA and had undergone surgery for the first time between January 2010 and December 2017 at the Beijing Shijitan Hospital affiliated to Capital Medical University were included in the study. The clinical features, localization diagnosis, and surgical treatment of these patients were analyzed., Results: Of the 140 patients, 32 were male and 108 were female; 132 cases had one adenoma, and 8 had two adenomas. In addition, 114 cases had clinical symptoms, among which 51, 28, 23, 8, and 4 had urinary system, skeletal system, digestive system, neuromuscular system, and neuropsychiatric symptoms, respectively, while 26 cases had no obvious symptoms. The median level of preoperative parathyroid hormone (PTH) was 201.0 pg/mL. The positive detection rate of technetium-99m sestamibi (Tc-99m MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT), ultrasound examination, and the combined use of Tc-99m MIBI SPECT/CT and ultrasound examination was 92.9%, 85.5%, and 96.4%, respectively. Open surgery was performed in all patients, and PTH was monitored during surgery. The success rate of surgery was 98.6%. After surgery, 21 cases developed hypocalcemia, 1 case developed temporary hoarseness, and 19 cases had transient hypoparathyroidism but there was no permanent hypoparathyroidism, postoperative hemorrhage, or hematoma in the surgical area., Conclusion: For patients with clinically unexplained skeletal system, urinary system, and neuropsychiatric symptoms, the possibility of PA should be considered. Imaging examinations such as ultrasound and Tc-99m MIBI SPECT/CT could be integrated before surgery to obtain accurate localization diagnosis. Precise preoperative localization, intraoperative PTH monitoring, and delicate surgery to protect the integrity of the PA capsule ensure a minimally invasive and successful surgery., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

A curated database of shark and ray biological data is increasingly necessary both to support fisheries management and conservation efforts, and to test the generality of hypotheses of vertebrate macroecology and macroevolution. Sharks and rays are one of the most charismatic, evolutionary distinct, and threatened lineages of vertebrates, comprising around 1,250 species. To accelerate shark and ray conservation and science, we developed Sharkipedia as a curated open-source database and research initiative to make all published biological traits and population trends accessible to everyone. Sharkipedia hosts information on 58 life history traits from 274 sources, for 170 species, from 39 families, and 12 orders related to length (n = 9 traits), age (8), growth (12), reproduction (19), demography (5), and allometric relationships (5), as well as 871 population time-series from 202 species. Sharkipedia relies on the backbone taxonomy of the IUCN Red List and the bibliography of Shark-References. Sharkipedia has profound potential to support the rapidly growing data demands of fisheries management, international trade regulation as well as anchoring vertebrate macroecology and macroevolution., (© 2022. The Author(s).)

Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs) which is potentially fatal. In some studies, chronic kidney disease (CKD) was also implicated to compound the risk of SCARs. We aim to investigate if pre-treatment HLA-B*58:01 screening can prevent allopurinol-induced SCARs in Chinese patients with CKD and its cost-effectiveness. We prospectively recruited Chinese CKD patients who required allopurinol during 2011-2015 and performed pre-treatment HLA testing (HLA screening group). Patients tested positive for HLA-B*58:01 were refrained from allopurinol while those tested negative were prescribed allopurinol. The incidence of SCARs in the HLA screening group was compared with the historical control in previous 5 years and the cost-effectiveness of HLA testing was analyzed. In the historical control (2006-2010), 3605 patients on allopurinol were screened, 22 out of 1027 (2.14%) CKD Chinese patients newly started on allopurinol developed SCARs, including 6 SJS/TEN. In the HLA screening group, 28 out of 192 patients (14.6%) tested HLA-B*58:01 positive were advised to avoid allopurinol; 156 out of 164 HLA-B*58:01-negative patients received allopurinol and none developed SCARs. The incidence rate of SCARs was significantly lower in the HLA screening group compared with controls (0% vs 2.14% respectively, p = 0.037*). The targeted HLA screening approach was associated with lower healthcare costs compared with no HLA screening (US$ 92,430 vs US$ 281,226). Pre-treatment HLA-B*58:01 screening is cost-effective to target on patients with CKD in Chinese to prevent allopurinol-induced SCARs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI., 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 © 2022 Chan, Wong, Leung, Yang, Fok, Mak, Yao, Ma, Mao, Zhao, Liang, Singh, Barbouche, He, Jiang, Liew, Le, Muktiarti, Santos-Ocampo, Djidjik, Belaid, Ismail, Abdul Latiff, Lee, Chen, Liu, Jin, Wang, Chien, Yu, Raj, Raj, Vaughan, Urban, Berg, Eley, Lee, Isa, Ang, Lee, Yeoh, Shek, Quynh Le, Nguyen, Phan Nguyen Lien, Capulong, Mallillin, Villanueva, Camonayan, Vera, Casis-Hao, Lobo, Foronda, Binas, Boushaki, Kechout, Phongsamart, Wongwaree, Jiratchaya, Lao-Araya, Trakultivakorn, Suratannon, Jirapongsananuruk, Chantveerawong, Kamchaisatian, Chan, Koh, Wong, Fong, Thong, Latiff, Noh, Silva, Jouhadi, Al-Saad, Vignesh, Jindal, Rawat, Gupta, Suri, Yang, Au, Kwok, Chan, Hui, Chua, Duque, Cheong, Chong, Ho, Lee, Wong, Yang, Lee, Tu, Yang and Lau.)

Competing Interests: The authors declare no conflict of interest.

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.

Cancer cells are high in heterogeneity and versatility, which can easily adapt to the external stresses via both primary and secondary resistance. Targeting of tumour microenvironment (TME) is a new approach and an ideal therapeutic strategy especially for the multidrug resistant cancer. Recently, we invented AANG, a natural compound formula containing traditional Chinese medicine (TCM) derived Smad3 inhibitor Naringenin (NG) and Smad7 activator Asiatic Acid (AA), for rebalancing TGF-β/Smad signalling in the TME, and its implication on the multidrug resistance is still unexplored. Here, we observed that an equilibrium shift of the Smad signalling in patients with hepatocellular carcinoma (HCC), which was dramatically enhanced in the recurrent cases showing p-glycoprotein overexpression. We optimized the formula ratio and dosage of AANG that effectively inhibit the proliferation of our unique human multidrug resistant subclone R-HepG2. Mechanistically, we found that AANG not only inhibits Smad3 at post-transcriptional level, but also upregulates Smad7 at transcriptional level in a synergistic manner in vitro. More importantly, AANG markedly suppressed the growth and p-glycoprotein expression of R-HepG2 xenografts in vivo. Thus, AANG may represent a novel and safe TCM-derived natural compound formula for overcoming HCC with p-glycoprotein-mediated multidrug resistance., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Mincle is essential for tumor-associated macrophage (TAM)-driven cancer progression and represents a potential immunotherapeutic target for cancer. Nevertheless, the lack of a specific inhibitor has largely limited its clinical translation. Here, we successfully developed a gene therapeutic strategy for silencing Mincle in a virus-free and tumor-specific manner by combining RNA interference technology with an ultrasound-microbubble-mediated gene transfer system (USMB). We identified a small hairpin RNA (shRNA) sequence shMincle that can silence not only Mincle expression but also the protumoral effector production in mouse bone marrow- and human THP-1-derived macrophages in the cancer setting in vitro . By using our well-established USMB system (USMB-shMincle), the shMincle-expressing plasmids were delivered in a tissue-specific manner into xenografts of human lung carcinoma A549 and melanoma A375 in vivo . Encouragingly, we found that USMB-shMincle effectively inhibited the protumoral phenotypes of TAMs as well as the progression of both A549 and A375 xenografts in a dose-dependent manner in mice without significant side effects. Mechanistically, we identified that USMB-shMincle markedly enhanced the anticancer M1 phenotype of TAMs in the A549 and A375 xenografts by blocking the protumoral Mincle/Syk/nuclear factor κB (NF-κB) signaling axis. Thus, USMB-shMincle may represent a clinically translatable novel and safe gene therapeutic approach for cancer treatment., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Overfishing is the primary cause of marine defaunation, yet declines in and increasing extinction risks of individual species are difficult to measure, particularly for the largest predators found in the high seas 1-3 . Here we calculate two well-established indicators to track progress towards Aichi Biodiversity Targets and Sustainable Development Goals 4,5 : the Living Planet Index (a measure of changes in abundance aggregated from 57 abundance time-series datasets for 18 oceanic shark and ray species) and the Red List Index (a measure of change in extinction risk calculated for all 31 oceanic species of sharks and rays). We find that, since 1970, the global abundance of oceanic sharks and rays has declined by 71% owing to an 18-fold increase in relative fishing pressure. This depletion has increased the global extinction risk to the point at which three-quarters of the species comprising this functionally important assemblage are threatened with extinction. Strict prohibitions and precautionary science-based catch limits are urgently needed to avert population collapse 6,7 , avoid the disruption of ecological functions and promote species recovery 8,9 .

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18-45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N = 557 censored). Women who successfully conceived (N = 475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N = 373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts. This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition, the S-PRESTO study draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

Background: Allergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs., Methods: Artemisia pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. Artemisia specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders., Results: Artemisia specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A 4 hydrolase (LTA 4 H) was consistent with the proteomics data. The LTA 4 H level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTA 4 H generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTA 4 H might be a potential biomarker for predicting the efficiency of AIT., Conclusion: Serum LTA 4 H may be a potential biomarker for early prediction of an effective AIT., 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 © 2020 Ma, Cao, Yu, Shi, Yan, Liu, Pan, Sun, Wei, Wang, Wei, Wang and Yin.)

Objectives: To evaluate cost-effectiveness of a novel screening strategy using a microRNA (miRNA) blood test as a screen, followed by endoscopy for diagnosis confirmation in a 3-yearly population screening program for gastric cancer., Methods: A Markov cohort model has been developed in Microsoft Excel 2016 for the population identified to be at intermediate risk (Singaporean men, aged 50-75 years with Chinese ethnicity). The interventions compared were (1) initial screening using miRNA test followed by endoscopy for test-positive individuals and a 3-yearly follow-up screening for test-negative individuals (proposed strategy), and (2) no screening with gastric cancer being diagnosed clinically (current practice). The model was evaluated for 25 years with a healthcare perspective and accounted for test characteristics, compliance, disease progression, cancer recurrence, costs, utilities, and mortality. The outcomes measured included incremental cost-effectiveness ratios, cancer stage at diagnosis, and thresholds for significant variables., Results: The miRNA-based screening was found to be cost-effective with an incremental cost-effectiveness ratio of $40 971/quality-adjusted life-year. Key drivers included test costs, test accuracy, cancer incidence, and recurrence risk. Threshold analysis highlights the need for high accuracy of miRNA tests (threshold sensitivity: 68%; threshold specificity: 77%). A perfect compliance to screening would double the cancer diagnosis in early stages compared to the current practice. Probabilistic sensitivity analysis reported the miRNA-based screening to be cost-effective in >95% of iterations for a willingness to pay of $70 000/quality-adjusted life-year (approximately equivalent to 1 gross domestic product/capita) CONCLUSIONS: The miRNA-based screening intervention was found to be cost-effective and is expected to contribute immensely in early diagnosis of cancer by improving screening compliance., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify how monetary incentives affect influenza vaccination uptake rate using a randomized control experiment and to subsequently design an optimal incentive program in Singapore, a high-income country with a market-based healthcare system., Methods: 4000 people aged ≥65 were randomly assigned to 4 treatment groups (1000 each) and were offered a monetary incentive (in shopping vouchers) if they chose to participate. The baseline group was invited to complete a questionnaire with incentives of 10 Singapore dollars (SGD; where 1 SGD ≈ 0.73 USD), whereas the other three groups were invited to complete the questionnaire and be vaccinated against influenza at their own cost of around 32 SGD, in return for incentives of 10, 20, or 30 SGD., Results: Increasing the total incentive for vaccination and reporting from 10 to 20 SGD increased participation in vaccination from 4.5% to 7.5% (P < .001). Increasing the total incentive from 20 to 30 SGD increased the participation rate to 9.2%, but this was not statistically significantly different from a 20-SGD incentive. The group of nonworking elderly were more sensitive to changes in incentives than those who worked. In addition to working status, the effects of increasing incentives on influenza vaccination rates differed by ethnicity, socio-economic status, household size, and a measure of social resilience. There were no significant differential effects by age group, gender, or education, however. The cost of the program per completed vaccination under a 20-SGD incentive is 36.80 SGD, which was the lowest among the three intervention arms. For a hypothetical population-level financial incentive program to promote influenza vaccination among the elderly, accounting for transmission dynamics, an incentive between 10 and 20 SGD minimizes the cost per completed vaccination from both governmental and health system perspectives., Conclusions: Appropriate monetary incentives can boost influenza vaccination rates. Increasing monetary incentives for vaccination from 10 to 20 SGD can improve the influenza vaccination uptake rate, but further increasing the monetary incentive to 30 SGD results in no additional gains. A partial incentive may therefore be considered to improve vaccination coverage in this high-risk group., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: The lack of seasonality in influenza epidemics in the tropics makes the application of well-established temperate zone national vaccination plans challenging., Objectives: We developed an individual-based simulation model to study optimal vaccination scheduling and assess cost-effectiveness of these vaccination schedules in scenarios of no influenza seasonality and the seasonality regimes of Singapore, Taipei, and Tokyo., Methods: The simulation models heterogeneities in human contact networks, levels of protective antibodies following infection, the effectiveness of the influenza vaccine, and seasonality. Using a no intervention baseline, we consider 3 alternative vaccination strategies: (1) annual vaccination for a percentage of the elderly, (2) biannual vaccination for a percentage of the elderly, and (3) annual vaccination for all elderly and a fraction of the remaining population. We considered 5 vaccination uptake rates for each strategy and modeled the estimated costs, quality-adjusted life years, and incremental cost-effectiveness ratios (ICERs), indicating the cost-effectiveness of each scenario., Results: In Singapore, annual vaccination for a proportion of elderly is largely cost-effective. However, with fixed uptake rates, partial biannual vaccination for the elderly yields a higher ICER than partial annual vaccination for the elderly, resulting in a cost-ineffective ICER. The most optimal strategy is the total vaccination of all the elderly and a proportion of individuals from other age groups, which results in a cost-saving ICER. This finding is consistent across different seasonality regimes., Conclusions: Tropical countries like Singapore can have comparably cost-effective vaccination strategies as found in countries with winter epidemics. The vaccination of all the elderly and a proportion of other age groups is the most cost-effective strategy, supporting the need for an extensive national influenza vaccination program., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Infectious pancreatic necrosis virus (IPNV) and infectious hematopoietic necrosis virus (IHNV) are two common viral pathogens that cause severe economic losses in all salmonid species in culture, but especially in rainbow trout. Although vaccines against both diseases have been commercialized in some countries, no such vaccines are available for them in China. In this study, a recombinant virus was constructed using the IHNV U genogroup Blk94 virus as a backbone vector to express the antigenic gene, VP2, from IPNV via the reverse genetics system. The resulting recombinant virus (rBlk94-VP2) showed stable biological characteristics as confirmed by virus growth kinetic analyses, pathogenicity analyses, indirect immunofluorescence assays and western blotting. Rainbow trout were immunized with rBlk94-VP2 and then challenged with the IPNV ChRtm213 strain and the IHNV Sn1203 strain on day 45 post-vaccination. A significantly higher survival rate against IHNV was obtained in the rBlk94-VP2 group on day 45 post-vaccination (86%) compared with the PBS mock immunized group (2%). Additionally, IPNV loads decreased significantly in the rBlk94-VP2 immunized group in the liver (28.6-fold to 36.5-fold), anterior kidney (21.7-fold to 44.2-fold), and spleen (14.9-fold to 22.7-fold), as compared with the PBS mock control group. The mRNA transcripts for several innate and adaptive immune-related proteins (IFN-γ, IFN-1, Mx-1, CD4, CD8, IgM, and IgT) were also significantly upregulated after rBlk94-VP2 vaccination, and neutralizing antibodies against both IHNV and IPNV were induced on day 45 post-vaccination. Collectively, our results suggest that this recombinant virus could be developed as a vaccine vector to protect rainbow trout against two or more diseases, and our approach lays the foundations for developing live vaccines for rainbow trout., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Infectious hematopoietic necrosis virus (IHNV) was developed as a vector to aid the construction of vaccines against viral diseases such as viral hemorrhagic septicemia virus, spring viremia of carp virus, and influenza virus H1N1. However, the optimal site for foreign gene expression in the IHNV vector has not been determined. In the present study, five recombinant viruses with the green fluorescence protein (GFP) gene inserted into different genomic junction regions of the IHNV genomic sequence were generated using reverse genetics technology. Viral growth was severely delayed when the GFP gene was inserted into the intergenic region between the N and P genes. Real-time fluorescence quantitative PCR assays showed that the closer the GFP gene was inserted towards the 3' end, the higher the GFP mRNA levels. Measurement of the GFP fluorescence intensity, which is the most direct method to determine the GFP protein expression level, showed that the highest GFP protein level was obtained when the gene was inserted into the intergenic region between the P and M genes. The results of this study suggest that the P and M gene junction region is the optimal site within the IHNV vector to express foreign genes, providing valuable information for the future development of live vector vaccines.

Objective: To investigate the self-reported prevalence, clinical characteristics, complications of allergic rhinitis (AR) and the sensitization of outdoor air pollen allergens in children in the Inner mongolia grassland region. Methods: A multistage, stratified and random clustered sampling with a face-to-face interview survey study in children from 0 to 17 years old was performed together with 10 common allergen skin prick tests (SPT) and measurements of the daily pollen count in 6 regions in the Inner mongolia grassland region from May to August of 2015. SAS 9.4 software was used for data analysis. Results: A total of 2 443 subjects completed the study. The self-reported prevalence of AR was 26.6%. The prevalence of boys was higher than that of girls (28.8% vs 24.3%, χ(2)=6.157, P< 0.05). Subjects from urban areas showed higher prevalence than rural areas (34.7% vs 18.8%, χ(2)=79.107, P< 0.05). There was significant regional difference in the prevalence of AR among the six areas investigated (χ(2)=221.416, P< 0.05). The main clinical symptoms of AR were sneezing (88.2%) and nasal congestion (78.6%). Among combined diseases, asthma accounted for 16.5% (107/650), rhinoconjunctivitis accounted for 47.9% (311/650). The peak season of AR was April and July, with the top SPT positive allergens of Artemisia species and chenopodium in this area. Conclusions: The prevalence AR in children in the Inner mongolia grassland region is extremely high. Sneezing is the main clinical symptom. Rhinoconjunctivitis is the most common combined disease. High summer and autumn pollen exposure is the main cause of AR.

Aim: Medication non-adherence influences outcomes of therapies for chronic diseases. Allopurinol is a cornerstone therapy for patients with gout; however, non-adherence to allopurinol is prevalent in Singapore and limits its effectiveness. Between 2008-2010, an adherence-enhancing program was implemented at the rheumatology division of a public tertiary hospital. The cost-effectiveness of this program has not been fully evaluated. With healthcare resources being finite, the value of investing in adherence-enhancing interventions should be ascertained. This study aims to evaluate the cost-effectiveness of this adherence-enhancing program to inform optimal resource allocation toward better gout management., Method: Adopting a real-world data approach, we utilized patient clinical and financial records generated in their course of routine care. Intervention and control groups were identified in a standing database and matched on nine risk factors through propensity score matching. Cost and effect data were followed through 1-2 years. A decision tree was developed in TreeAge using a societal perspective. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty., Results: At an assumed willingness-to-pay threshold of $50 000 USD ($70 000 SGD) per quality-adjusted life year (QALY), the intervention had an 85% probability of being cost-effective compared to routine care. The incremental cost-effectiveness ratio was $12 866 USD per QALY for the base case and ranged from $4 139 to $21 593 USD per QALY in sensitivity analyses., Conclusion: The intervention is cost-effective in the short-term, although its long-term cost-effectiveness remains to be evaluated., (© 2018 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: To cope with rising demand for healthcare services in Singapore, Regional Health Systems (RHS) comprising of health and social care providers across care settings were set up to integrate service delivery. Tasked with providing care for the western region, in 2012, the National University Health System (NUHS) - RHS developed a transitional care program for elderly patients with complex healthcare needs who consumed high levels of hospital resources. Through needs assessment, development of personalized care plans and care coordination, the program aimed to: (i) improve quality of care, (ii) reduce hospital utilization, and (iii) reduce healthcare-related costs. In this study, recognizing the need for process evaluation in conjunction with outcome evaluation, we aim to evaluate the implementation fidelity of the NUHS-RHS transitional care program to explain the outcomes of the program and to inform further development of (similar) programs., Methods: Guided by the modified version of the Conceptual Framework for Implementation Fidelity (CFIF), adherence and moderating factors influencing implementation were assessed using non-participatory observations, reviews of medical records and program databases., Results: Most (10 out of 14) components of the program were found to be implemented with low or moderate level of fidelity. The frequency or duration of the program components were observed to vary based on the needs of users, availability of care coordinators (CC) and their confidence. Variation in fidelity was influenced predominantly by: (1) complexity of the program, (2) extent of facilitation through guiding protocols, (3) facilitation of program implementation through CCs' level of training and confidence, (4) evolving healthcare participant responsiveness, and (5) the context of suboptimal capability among community providers., Conclusion: This is the first study to assess the context-specific implementation process of a transitional care program in the context of Southeast Asia. It provides important insights to facilitate further development and scaling up of transitional care programs within the NUHS-RHS and beyond. Our findings highlight the need for greater focus on engaging both healthcare providers and users, training CCs to equip them with the relevant skills required for their jobs, and building the capability of the community providers to implement such programs.

Reverse genetics systems are powerful tools for understanding the virulence mechanisms and gene functions of negative-sense RNA viruses. The reverse genetics systems commonly used for recombinant infectious hematopoietic necrosis virus (IHNV) are based on vaccinia virus infection. To avoid the potential biological safety risks associated with vaccinia virus, a recombinant IHNV virus strain Sn1203 (rIHNV-Sn1203) was rescued in this study using a mammalian cell line, BHK-21. The genome sequence authenticity of rIHNV-Sn1203 was confirmed using two silent genetic tags introduced by site-directed mutagenesis. Indirect immunofluorescence assays and transmission electron microscopy revealed that rIHNV-Sn1203 and wild-type IHNV-Sn1203 (wtIHNV-Sn1203) had identical immunogenicity and virion morphology. The virulence and pathogenicity of rIHNV-Sn1203 were assessed in vitro and in vivo. Although rIHNV-Sn1203 displayed trends toward delayed intracellular viral replication and lower virion yields compared with wtIHNV-Sn1203, statistical analyses revealed no significant differences between these two viruses. Moreover, rainbow trout challenged with rIHNV-Sn1203 and wtIHNV-Sn1203 showed indistinguishable mortality. Together, these results show that IHNV was successfully rescued using BHK-21 cells. This method is very convenient and may also be suitable for use in the recovery of other Novirhabdoviruses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To investigate the incidence of plant food allergy in patients with pollinosis and the effect of food allergens on the clinical symptoms of pollinosis patients. Method: A total of 40 patients with pollinosis and food allergy attended to the allergy Department of Duolun People's Hospital of Inner Mongolia were accepted skin prick test of inhaled allergens while the rhino conjunctivitis quality of life questionnaire(RQLQ) were also completed. The patients were divided into A and B groups randomly. Patients in group A were required for avoiding allergic plant foods intake but not them in group B. The two groups of patients with RQLQ, VAS and clinical symptom scores were statistically analyzed by P <0.05, the difference was statistically significant. Result: Forty cases were allergic to Artemisia. The most common allergic plant foods was peach, which accounted for 47.5%. Twenty-four patients were allergic to multiple foods simultaneously. Seventeen cases of pollinosis were preceded by food allergy, and 23 cases of food allergy were preceded by pollinosis. The mean values of RQLQ, VAS and symptom scores in group A were 81.44±14.31, 6.02±1.39, 10.60±3.68, respectively. The mean values of group B patients after 1 years were 100.73±21.66, 8.30±1.00, 13.45±3.51, the difference was statistically significant ( P <0.01). The patients in group A complained that the symptoms were better than before. The mean values of RQLQ, VAS and symptom scores before intervention were 105.2±26.69, 7.00±1.71, 14.83±3.66, with significant difference ( P <0.01). There was no significant improvement in the symptoms of Group B patients ( P >0.05). Conclusion: Patients with pollinosis are often associated with food allergies. Reducing the intake of allergic plant foods should help alleviate symptoms., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To analyze the dynamic changes of the clinical features of chronic rhinosinusitis in recent 10 years, so as to deeply understand the characteristics of chronic rhinosinusitis, and to provide new ideas for treatment of chronic rhinosinusitis. Method: This retrospective study was performed in patients who were diagnosed as chronic rhinosinusitis and enrolled. General information, clinical examination and pathological results were all collected, then patients' age, gender, the incidence of asthma and allergic rhinitis, peripheral eosinophil percentage, olfactory dysfunction and pathological results were statistically analyzed. Result: 1 955 patients who were diagnosed as chronic rhinosinusitis(CRS) were enrolled in this study, including 570 patients in 2006, 583 patients in 2010, and 802 patients in 2015. There were no obvious changes of age structure in these patients in three years. And there was no significant change in sex ratio as well. The proportions of patients with CRS concomitant with asthma were obviously increased in 10 years, which was 3.51% in 2006, 7.55% in 2010, and 17.58% in 2015. The proportions of patients with allergic rhinitis were also increased, which was 10.35% in 2006, 8.75% in 2010, and 14.09% in 2015. Peripheral eosinophil ratio was increased significantly in these patients after 2010. The proportions of ECRS in CRS were elevated in 2015 and almost doubled compared to 2006. Olfactory dysfunction increased significantly in 2015. Conclusion: In recent 10 years, there were obvious changes of clinical features of CRS. The proportion of patients with CRS concomitant with asthma showed a gradual increasing trend. ECRS significantly increased than it was 10 years ago. Olfactory dysfunction also increased significantly. In order to improve the therapeutic effect of CRS, it is necessary to strengthen the treatment of upper and lower airway inflammation related with eosinophil., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: The aim of this study is to observe the clinical efficacy of pollen specific immunotherapy with Artemisia in allergic rhinitis. Method: A total of 139 patients with allergic rhinitis who were positive for Artemisia pollen were selected for allergen skin pricking. All of them were treated with Artemisia pollen-specific immunotherapy. The patients were followed-up for 3 months, respectively before treatment (N), after treatment start interval. 3 months (D1, D2, D3) followup fill in the total score of nasal symptoms (TNSS), visual analogue scale (VAS) score, olfactory function grading, ocular symptom score (TOSS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) )score. Result: TNSS：N>D1，N>D2，N>D3，D1,D2,D3 two of the three compared to no difference.VAS：N>D1，N>D2，N>D3，among D1,D2,D3, two of the three compared to no difference. Olfactory function classification:N>D1，N>D2，N>D3，among D1,D2,D3, two of the three compared to no difference.TOSS：N>D1，N>D2，N>D3，among D1,D2,D3,D1>D2,the rest had no difference. RQLQ: N>D1, N>D2, N>D3, D1>D2, D3>D1, D3>D2. Conclusion: The specific pollen immunotherapy of artemisia is effective in the treatment of allergic rhinitis, and the symptoms are obviously improved., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To investigate whether there were differences between the three stains for eosinophil counting in nasal polyps. Method: Three serial sections of formalin-fxed, paraffn-embedded tissues of 23 cases of nasal polyps were stained with Congo red,Chromotrope 2R and conventional HE staining, respectively. The stained sections were converted to digital pathology using a digital slice scanner. The qualitative assessment of the staining results was made in terms of specificity, contrast and background staining. Eosinophils were quantitatively evaluated and statistically analyzed using the Image J Analysis System and GraphPad Prism 5 statistical software. Result: Congo red staining and Chromotrope 2R staining were more specific than conventional HE staining. Chromotrope 2R had the lowest background staining. The majority of Congo red staining ( n =20) was lighter in the background than in the conventional HE, while a small number of cases ( n =3) background staining slightly stronger. Both Congo red staining and Chromotrope 2R staining had statistically significant differences compared with conventional HE staining ( P <0.05), but there was no significant difference between Congo red staining and Chromotrope 2R staining ( P >0.05). Conclusion: Congo red staining and Chromotrope 2R staining are more suitable for accurate counting of eosinophils, and the use of these two methods contributes to the harmonization of eosinophil count criteria in the ECRSwNP definition.

Background: Drug resistance is a growing challenge to tuberculosis (TB) control worldwide, but particularly salient to countries such as Myanmar, where the health system is fragmented across the public and private sector. A recent systematic review has identified a critical lack of evidence for local policymaking, particularly in relation to drivers of drug-resistance that could be the target of preventative efforts. To address this gap from a health systems perspective, our study investigates the healthcare-seeking behavior and preferences of recently diagnosed patients with drug-resistant tuberculosis (DR-TB), focusing on the use of private versus public healthcare providers., Methods: The study was conducted in ten townships across Yangon with high DR-TB burden. Patients newly-diagnosed with DR-TB by GeneXpert were enrolled, and data on healthcare-seeking behavior and socio-economic characteristics were collected from patient records and interviews. A descriptive analysis of healthcare-seeking behavior was followed by the investigation of relationships between socio-economic factors and type of provider visited upon first feeling unwell, through univariate logistic regressions., Results: Of 202 participants, only 8% reported first seeking care at public facilities, while 88% reported seeking care at private facilities upon first feeling unwell. Participants aged 25-34 (Odds Ratio = 0.33 [0.12-0.95]) and males (Odds Ratio = 0.39 [0.20-0.75]) were less likely to visit a private clinic or hospital than those aged 18-24 and females, respectively. In contrast, participants with higher income were more likely to utilize private providers. Prior to DR-TB diagnosis, 86% of participants took medications from private providers. After DR-TB diagnosis, only 7% of participants continued to take medications from private providers., Conclusion: In urban Myanmar, most patients shifted to being managed exclusively in the public sector after being formally diagnosed with DR-TB. However, since the vast majority of DR-TB patients first visited private providers in the period leading to diagnosis, related issues such as unregulated quality of care, potential delays to diagnosis, and lack of care continuity may greatly influence the emergence of drug-resistance. A greater understanding of the health system and these healthcare-seeking behaviors may simultaneously strengthen TB control programmes and reduce government and out-of-pocket expenditures on the management of DR-TB.

Taimen ( Hucho taimen ) is an important ecological and economic species that is classified as vulnerable by the IUCN Red List of Threatened Species; however, limited genomic information is available on this species. RNA-Seq is a useful tool for obtaining genetic information and developing genetic markers for nonmodel species in addition to its application in gene expression profiling. In this study, we performed a comprehensive RNA-Seq analysis of taimen. We obtained 157 M clean reads (14.7 Gb) and used them to de novo assemble a high-quality transcriptome with a N50 size of 1,060 bp. In the assembly, 82% of the transcripts were annotated using several databases, and 14,666 of the transcripts contained a full open reading frame. The assembly covered 75% of the transcripts of Atlantic salmon and 57.3% of the protein-coding genes of rainbow trout. To learn about the genome evolution, we performed a systematic comparative analysis across 11 teleosts including eight salmonids and found 313 unique gene families in taimen. Using Atlantic salmon and rainbow trout transcriptomes as the background, we identified 250 positive selection transcripts. The pathway enrichment analysis revealed a unique characteristic of taimen: It possesses more immune-related genes than Atlantic salmon and rainbow trout; moreover, some genes have undergone strong positive selection. We also developed a pipeline for identifying microsatellite marker genotypes in samples and successfully identified 24 polymorphic microsatellite markers for taimen. These data and tools are useful for studying conservation genetics, phylogenetics, evolution among salmonids, and selective breeding for threatened taimen.

Infectious hematopoietic necrosis virus (IHNV) is a common pathogen that causes severe disease in the salmonid aquaculture industry. Recent work demonstrated that autophagy plays an important role in pathogen invasion by activating innate and adaptive immunity. This study investigated the relationship between IHNV and autophagy in epithelioma papulosum cyprini cells. The electron microscopy results show that IHNV infection can induce typical autophagosomes which are representative structures of autophagy activation. The punctate accumulation of green fluorescence-tagged microtubule-associate protein 1 light chain 3 (LC3) and the protein conversion from LC3-I to LC3-II were respectively confirmed by confocal fluorescence microscopy and western blotting. Furthermore, the effects of autophagy on IHNV replication were also clarified by altering the autophagy pathway. The results showed that rapamycin induced autophagy can inhibit both intracellular viral replication and extracellular viral yields, while autophagy inhibitor produced the opposite results. These findings demonstrated that autophagy plays an antiviral role during IHNV infection., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Platelet aggregation and inflammation are both implicated in coronary artery disease (CAD). Thrombin induced platelet-fibrin clot strength (MA Thrombin ) measured by thrombelastography (TEG) has been proved to be a novel marker of platelet aggregation. The aim of this study was to investigate the correlation of MA Thrombin to platelet volume indices (PVIs) or to inflammatory markers in different types of CAD. 206 patients with different types of CAD were enrolled. MA Thrombin , PVIs, including mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR) as well as inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP) and fibrinogen (Fbg) were measured. Multiple linear regression models were used to analyze the association between MA Thrombin , PVIs, and inflammatory markers. MA Thrombin and inflammatory markers both varied with CAD types (P<0.001). MA Thrombin was correlated to PVIs in NSTEMI individuals (MPV, r=0.393, P=0.007; PDW, r=0.334, P=0.023; P-LCR, r=0.382, P=0.008), but had inner-link with inflammatory markers in STEMI cases (hs-CRP, r=0.499, P<0.001; Fbg, r=0.500, P<0.001). These findings may suggest different mechanisms of platelet aggregation in different types of CAD. Moreover, MA Thrombin may be used as a potential parameter to evaluate platelet aggregation and inflammation together., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Infectious hematopoietic necrosis virus (IHNV) is a common pathogen that causes severe disease in the salmonid aquaculture industry. Because oral vaccines induce more efficient mucosal immunity than parenteral immunization, an oral vaccine was developed with an improved yeast cell surface display technology to induce an immune response to IHNV. The oral yeast vaccine, designated EBY100/pYD1-bi-G, was delivered orally to rainbow trout (Oncorhynchus mykiss) on days 1 and 32, and the nonspecific and specific immune responses were measured 50days after the first vaccination. In the hindgut, spleen, and head kidney, the expression of IFN-1 and Mx-1 was significantly upregulated after oral vaccination with EBY100/pYD1-bi-G, and the highest expression of IFN-1 and Mx-1 was observed in the spleen (7.5-fold higher than the control group) and head kidney (3.9-fold higher than the control group), respectively. Several markers of the adaptive immune response (IgM, IgT, CD4, and CD8) were also significantly upregulated, and the highest expression of these markers was observed in the hindgut, suggesting that the mucosal immune response was successfully induced by oral vaccination with EBY100/pYD1-bi-G. Sera from the orally vaccinated rainbow trout showed higher anti-IHNV neutralizing antibody titers (antibody titer 81±4) than the control sera (antibody titer 7±3), and the relative percentage survival after IHNV challenge was 45.8% compared with 2% in the control group. Although the protection afforded by this orally delivered vaccine was lower than that of a DNA vaccine (83%-98%), it is a promising candidate vaccine with which to protect larval fish against IHNV, which are most susceptible to the virus and difficult to inject with a DNA vaccine., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Patients with diverticulitis are predisposed to hepatic abscesses via seeding through the portal circulation. Hepatic abscesses are well-documented sequelae of diverticulitis, however instances of progression to hepato-bronchial fistulization are rare. We present a case of diverticulitis associated with hepatic abscess leading to hepato-bronchial fistulization, which represents a novel disease course not yet reported in the literature., Case Presentation: A 61-year-old Caucasian man presented with a history of unintentional weight loss and dyspnea both at rest and with exertion. He had a significant tobacco and alcohol misuse history. A massive right-sided pleural effusion was found on chest X-ray, which responded partially to chest tube insertion. A computed tomography scan of his thorax confirmed the presence of innumerable lung abscesses as well as a complex pleural effusion. An indeterminate tiny air pocket at the dome of the liver was also noted. A follow-up computed tomography scan of his abdomen revealed a decompressed hepatic abscess extending into the right pleural space and the right lower lobe. A sigmoid-rectal fistula was also revealed with focal colonic thickening, presumed to be the sequelae of remote or chronic diverticulitis. An interventional radiologist inserted a percutaneous drain into the decompressed hepatic abscess and the instillation of contrast revealed immediate filling of the right pleural space, lung parenchyma, and bronchial tree, confirming a hepato-bronchial fistula. After two concurrent chest tube insertions failed to drain the remaining pleural effusion completely, surgical lung decortication was conducted. Markedly thickened pleura were seen and a significant amount of gelatinous inflammatory material was debrided from the lower thoracic cavity. He recovered well and was discharged 10 days post-thoracotomy on oral antibiotics. The percutaneous liver abscess tube was removed 3 weeks post-discharge from hospital after the drain check revealed that the fistula and abscess had entirely resolved., Conclusions: Refractory right-sided pleural effusion combined with constitutional symptoms should alert clinicians to search for possible hepatic abscess, especially in the context of diverticulitis. The rupture of an untreated hepatic abscess could lead to death from profound sepsis or rarely, as in this case, a hepato-bronchial fistula. Timely investigation and a multidisciplinary treatment approach can lead to improved patient outcomes.

Background: The development of oral vaccines using yeast surface display technology is an area of intensive study in vaccine development, but the protein level displayed on yeast surfaces is not currently high enough to obtain a robust immune response., Methods: To address this issue, we established an efficient and simple method of increasing the level of displayed protein on the yeast cell surface. We used the single chain variable fragment (scFv) of an antibody against the infectious hematopoietic necrosis virus isolate Sn1203 as a target display protein. The yeast-derived scFv was first displayed on the yeast surface by galactose induction, and then Escherichia coli-derived scFv was also displayed on the same yeast via an artificial anchoring condition to increase the total scFv level on the yeast surface., Results: The levels of yeast- and E. coli-derived scFv displayed on the yeast cell surface were analyzed by flow cytometry, western blotting, and fluorescent microscopy. The flow cytometry results indicated that when the cells were suspended in phosphate-buffered saline with 1mmol/L glutathione, 0.2mmol/L oxidized glutathione, and 5% dimethyl sulfoxide at 4°C for 6h, the E. coli-derived scFv protein was stably anchored to the yeast cell surface. The mean fluorescence intensity in these experiments, which is an indirect quantitative representation of the surface scFv expression, was three times higher in the treated cells than that in control cells. The western blotting results show two specific protein bands, the smaller of which was identified as the E. coli-derived scFv that was displayed on the yeast cell surface. Cell immunofluorescence is a more direct way to detect differentially produced proteins that are displayed on the yeast cell surface. The fluorescence microscopy results show that both fluorescence corresponding to the yeast-derived scFv and fluorescence corresponding to the E. coli-derived scFv can exist on the cell surface of same yeast cell. This confirms that the E. coli-derived scFv protein was successfully displayed on the yeast cell surface., Conclusions: This method provides a rapid, simple, and high-efficiency strategy to increase the level of displayed protein on the yeast cell surface. Application of this technique may allow the yeast surface display system to be used to generate potential oral vaccines., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Infectious pancreatic necrosis is a significant disease of farmed salmonids in China. In this study, a single chain variable fragment (scFv) antibody library derived from rainbow trout (Oncorhynchus mykiss) and viral protein VP2 of a Chinese infectious pancreatic necrosis virus (IPNV) isolate ChRtm213 were co-expressed by a bacterial display technology. The library was subjected to three rounds of screening by flow cytometry (FCM) to select IPNV specific antibodies. Six antibody clones with different mean fluorescence intensities (MFI) were obtained by picking colonies at random. The antibody clones were expressed and purified. The purified IPNV-specific scFv antibodies were used successfully in Western blotting, enzyme linked immunosorbent assay (ELISA) and an immunofluorescence antibody test (IFAT). This method provides a high throughput means to screen an antibody library by flow cytometry, and isolate a panel of antibody that can be used as potential reagents for the detection and study of IPNV that are prevalent in China., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We aimed to investigate the differences in incidence of nasal anatomic abnormalities between patients with and without headache and the outcome of surgical treatment for the headache patients with mucosal contact points. We conducted the observational study and recruited 107 subjects without headache (nonheadache group) and 78 patients with recurrent headache for more than 2 years (headache group). Study participants underwent high-resolution sinus computed tomography scans, and the incidence of nasal anatomic abnormalities was calculated in both groups. An additional 25 patients with recurrent headache underwent endoscopic surgical treatment. Mucosal contact points were observed in 85.9% of patients with recurrent headache and also in 80.4% of participants without headache. The most common mucosal contact point was between a deviated nasal septum and lateral nasal wall (41.1%). The incidence of deviated nasal septum contacting with lateral nasal wall was significantly different between the headache group (55.1%) and the nonheadache group (40.2%) (p < 0.05). The postoperative pain scores of the additional 25 headache patients with recurrent headache and mucosal contact point who were treated with endoscopic surgery decreased significantly compared with their preoperative measurements (p < 0.001), but only 44% of patients had recovered from headache 7 days postoperatively. We conclude that some patients with recurrent headache may not have a mucosal contact point, and some patients with mucosal contact points may not meet the diagnostic criteria of mucosal contact point headache since pain was not resolved within 7 days after surgical treatment. The diagnostic criteria of mucosal contact point headache before surgery should be reevaluated.

Cases of gastric fistula secondary to drainage tube penetration have rarely been reported. The current study presents a case of gastric penetration caused by misplacement of a drainage tube after a splenectomy. The patient was admitted to the Department of Hepatobiliary Surgery, (Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, China) for blunt abdominal trauma due to injuries sustained in an automobile accident. A ruptured spleen was found and successfully removed surgically. On post-operative day 7, the patient complained of slight discomfort and tenderness in the left upper quadrant of the abdomen. In addition, 500 ml of bile-colored fluid with small food particles was noted in the drainage tube. Barium X-ray revealed a gastric fistula in the upper gastrointestinal tract. Gastroscopy indicated infiltration of the drainage tube into the gastric cavity. No significant peritoneal effusion was observed, as revealed by abdominal ultrasound examination. These results confirmed the diagnosis of a gastric fistula secondary to perforation by the drainage tube. Following conservative treatment with antibiotics and total parenteral nutrition, the general condition of the patient improved significantly. The drainage tube was withdrawn progressively, as the amount of fluid being discharged was decreasing. Gastroenterography confirmed perforation closure and the tube was finally removed on post-operative day 44.

Unlabelled: Tolerance after treatment and recovery from posttransplant lymphoproliferative disease (PTLD) have been described but little is known about the immunology. The objective of this study is to evaluate the immunity of pediatric recipients who recovered from PTLD., Materials and Methods: Pediatric recipients who recovered from PTLD after liver transplant and twice the number of recipients who never had PTLD were recruited. Their immune statuses were measured by ImmuKnow (measurement of adenosine 5-triphospate level produced CD4+ T helper cells), and the results were divided into 3 groups, "low" (≤225 ng/mL), "moderate" (226 to 524 ng/mL), and "high" (≥525 ng/mL). The results of both groups were compared and analyzed., Results: Nine PTLD recipients and 20 non-PTLD recipients were recruited. There were no significant differences in terms of sex and age between the 2 groups. The majority of PTLD recipients (88.9%) had "low" immune status responses, and none of them had "high" responses. For non-PTLD recipients, more than half (55%) had "moderate" immune status responses. The median value of adenosine 5-triphospate levels was significantly lower in the PTLD group (119 ng/mL vs 380.5 ng/mL P = 0.014), and their trough immunosuppressant level was also lower (3.8 μg/L vs 7.7 μg/L; P = 0.004). None of the patients in either group had abnormal liver enzymes (aspartate aminotransferase/alanine aminotransferase) to suggest graft rejection., Conclusions: Patients who recovered from PTLD have a lower CD4 T-cell activity compared with those who have not suffered from PTLD. Under careful monitoring, their immunosuppressant levels can be kept at low levels to prevent recurrence of PTLD.

Background: The increasing number of cancer patients and inadequate communication in clinics are posing challenges to cancer patients receiving outpatient-based chemotherapy and healthcare providers. A nurse-led care program was proposed as one way of dealing with at least some of these challenges., Objective: The objectives of the pilot study were to assess the feasibility of the subject recruitment, care, and data collection procedures and to explore the acceptability of this program., Methods: A pilot study with a 1-group pretest-posttest design was conducted. Five cancer patients receiving chemotherapy in a chemotherapy day center participated. Each patient had a nurse consultation before chemotherapy and received 2 telephone calls after the first and second cycles of chemotherapy. Four questionnaires were adopted to evaluate the subjects' quality of life, self-efficacy, symptom experiences, and satisfaction with care. Questionnaires were completed before the chemotherapy and after the second cycle. The subjects were also interviewed to understand their comments on the service., Results: The recruitment, care, and data collection procedures were completed smoothly. Slight changes were observed in quality of life and self-efficacy. All 5 subjects were highly satisfied with the care., Conclusions: The nurse-led care program is feasible and acceptable., Implications for Practice: The effect of the nurse-led care program will be evaluated in a single-center, open, randomized controlled trial. If the encouraging results can be confirmed, it may be an effective approach to improving the quality of ambulatory chemotherapy care. It would also shed light on the development of nurse-led care in other areas.