Exploring the ageing methylome in the model insect, Nasonia vitripennis.

BACKGROUND: The ageing process is a multifaceted phenomenon marked by the gradual deterioration of cellular and organismal functions, accompanied by an elevated susceptibility to diseases. The intricate interplay between genetic and environmental factors complicates research, particularly in complex mammalian models. In this context, simple invertebrate organisms have been pivotal, but the current models lack detectable DNA methylation limiting the exploration of this critical epigenetic ageing mechanism. This study introduces Nasonia vitripennis, the jewel wasp, as an innovative invertebrate model for investigating the epigenetics of ageing. Leveraging its advantages as a model organism and possessing a functional DNA methylation system, Nasonia emerges as a valuable addition to ageing research. RESULTS: Whole-genome bisulfite sequencing unveiled dynamic alterations in DNA methylation, with differentially methylated CpGs between distinct time points in both male and female wasps. These changes were associated with numerous genes, enriching for functions related to telomere maintenance, histone methylation, and mRNA catabolic processes. Additionally, other CpGs were found to be variably methylated at each timepoint. Sex-specific effects on epigenetic entropy were observed, indicating differential patterns in the loss of epigenetic stability over time. Constructing an epigenetic clock containing 19 CpGs revealed a robust correlation between epigenetic age and chronological age. CONCLUSIONS: Nasonia vitripennis emerges as a promising model for investigating the epigenetics of ageing, shedding light on the intricate dynamics of DNA methylation and their implications for age-related processes. This research not only expands the repertoire of ageing models but also opens avenues for deeper exploration of epigenetic mechanisms in the context of ageing.

A millimeter water-in-oil droplet as an alternative back exchange prevention strategy for hydrogen/deuterium exchange mass spectrometry of peptides/proteins.

Hydrogen/deuterium exchange mass spectrometry (HDX-MS) is a versatile bioanalytical technique for protein analysis. Since the reliability of HDX-MS analysis considerably depends on the retention of deuterium labels in the post-labeling workflow, deuterium/hydrogen (D/H) back exchange prevention strategies, including decreasing the pH, temperature, and exposure time to protic sources of the deuterated samples, are widely adopted in the conventional HDX-MS protocol. Herein, an alternative and effective back exchange prevention strategy based on the encapsulation of a millimeter droplet of a labeled peptide solution in a water-immiscible organic solvent (cyclohexane) is proposed. Cyclohexane was used to prevent the undesirable uptake of water by the droplet from the atmospheric vapor through the air-water interface. Using the pepsin digest of deuterated myoglobin, our results show that back exchange kinetics of deuterated peptides is retarded in a millimeter droplet as compared to that in the bulk solution. Performing pepsin digestion directly in a water-in-oil droplet at room temperature (18-21 °C) was found to preserve more deuterium labels than that in the bulk digestion with an ice-water bath. Based on the present findings, it is proposed that keeping deuterated peptides in the form of water-in-oil droplets during the post-labelling workflow will facilitate the preservation of deuterium labels on the peptide backbone and thereby enhance the reliability of the H/D exchange data.

Enhanced neural mechanisms of set shifting in musically trained adolescents and young adults: converging fMRI, EEG, and behavioral evidence.

Musically trained individuals have been found to outperform untrained peers in various tasks for executive functions. Here, we present longitudinal behavioral results and cross-sectional, event-related potential (ERP), and fMRI results on the maturation of executive functions in musically trained and untrained children and adolescents. The results indicate that in school-age, the musically trained children performed faster in a test for set shifting, but by late adolescence, these group differences had virtually disappeared. However, in the fMRI experiment, the musically trained adolescents showed less activity in frontal, parietal, and occipital areas of the dorsal attention network and the cerebellum during the set-shifting task than untrained peers. Also, the P3b responses of musically trained participants to incongruent target stimuli in a task for set shifting showed a more posterior scalp distribution than control group participants' responses. Together these results suggest that the musician advantage in executive functions is more pronounced at an earlier age than in late adolescence. However, it is still reflected as more efficient recruitment of neural resources in set-shifting tasks, and distinct scalp topography of ERPs related to updating and working memory after childhood.

Diagnostic accuracy of a prehospital electrocardiogram rule-based algorithm for ST-elevation myocardial infarction: results from a population-wide project.

INTRODUCTION: This study reviewed the diagnostic accuracy of the prehospital electrocardiogram (PHECG) rule-based algorithm for ST-elevation myocardial infarction (STEMI) universally utilised in Hong Kong. METHODS: This prospective observational study was linked to a population-wide project. We analysed 2210 PHECGs performed on patients who presented to the emergency medical service (EMS) with chest pain from 1 October to 31 December 2021. The diagnostic accuracy of the adopted rulebased algorithm, the Hannover Electrocardiogram System, was evaluated using the adjudicated blinded rating by two investigators as the primary reference standard. Diagnostic accuracy was also evaluated using the attending emergency physician's diagnosis and the diagnosis on hospital discharge as secondary reference standards. RESULTS: The prevalence of STEMI was 5.1% (95% confidence interval [CI]=4.2%-6.1%). Using the adjudicated blinded rating by investigators as the reference standard, the rule-based PHECG algorithm had a sensitivity of 94.6% (95% CI=88.2%-97.8%), specificity of 87.9% (95% CI=86.4%-89.2%), positive predictive value of 29.4% (95% CI=24.8%-34.4%), and negative predictive value of 99.7% (95% CI=99.3%-99.9%) [all P<0.05]. CONCLUSION: The rule-based PHECG algorithm that is widely used in Hong Kong demonstrated high sensitivity and fair specificity for the diagnosis of STEMI.

Management of overactive bladder: consensus statements from the Hong Kong Urological Association and the Hong Kong Geriatrics Society.

Overactive bladder (OAB) is a common urological disease with a high prevalence in older adult populations. Antimuscarinic drugs have been the most common treatment for OAB for more than a decade, but their anticholinergic side-effects and potential impact on cognitive function among older patients are usually underestimated. This consensus aimed to provide practical recommendations concerning OAB management, with a particular emphasis on older patients. A joint consensus panel was formed by representatives of the Hong Kong Urological Association and the Hong Kong Geriatrics Society. Literature searches regarding OAB and its management were performed in PubMed and Ovid. Several working meetings were held to present and discuss available evidence, develop consensus statements, and vote for the statements. A modified Delphi method was used in this consensus process. To address questions regarding various aspects of OAB, 29 consensus statements were proposed covering the following areas: diagnosis, initial assessment, non-pharmacological treatments, considerations before administration of pharmacological treatments, various pharmacological treatments, combination therapy, and surgical treatment. Twenty-five consensus statements were accepted.

Peptide Oxidation Induced by Liquid-Solid Contact Electrification as Revealed in Liquid Microjunction-Surface Sampling Probe Mass Spectrometry.

Reproducible peptide oxidation was observed using a homebuilt liquid microjunction-surface sampling probe (LMJ-SSP) platform for analyzing peptide standards. Although electrochemical oxidation and corona discharges have previously been associated with analyte oxidation in electrospray ionization (ESI) and ESI-related ambient ionization mass spectrometry (MS) methods, they were unlikely the causes for the peptide oxidation observed in the LMJ-SSP studies. A systematic investigation demonstrated that analyte oxidation was induced during the droplet drying on a solid surface through liquid-solid electrification processes. To minimize unwanted analyte oxidation, the water content in the sample solution should be decreased and the use of hydroxyl-functionalized substrates, such as glass slides, should be avoided. In addition, if water is an essential solvent component, adding an antioxidant, such as ascorbic acid, to the sample solution before droplet evaporation on the solid surface could lower the percentage of analyte oxidation. The present findings apply to all the MS methods that involve drying microliters of sample solution onto a suitable substrate in their sample preparation protocols.

Use of group IIB metal ions as charge carriers for collision-induced dissociation of glycopeptide and glycan.

RATIONALE: Dissociation of biomolecules by tandem mass spectrometry (MS/MS) generates a variety of fragment ions which provide useful information for the structural characterization of biomolecules. Different fragmentation strategies result in different mass spectra for the same molecule and thus provide distinct features. Charge carriers play important roles in determining the dissociation pathways of the target precursor ions. The use of various transition metals ions as charge carriers of glycopeptide and glycan might provide additional structural information and needs to be investigated. METHODS: A 9.4 T SolariX FTICR mass spectrometer was used for collision-induced dissociation (CID) of glycopeptide and glycan. Group IIB metal ions, including Zn2+ , Cd2+ and Hg2+ , were used as charge carriers. Glycopeptide NLTK-M5 G2 and glycan G1F were used as the model systems. RESULTS: For Zn2+ - and Cd2+ -adducted species, cross-ring cleavages, glycosidic cleavages and cleavages along the peptide backbone could be obtained. There is a high degree of similarity in their CID spectra with that of Mg2+ ion-adducted glycopeptide species. For Hg2+ -adducted species, only glycosidic cleavages were observed in high abundance. The formation of doubly-charged ions (M2+ ) and a series of [f-H]+ fragments indicated unique dissociation pathways for Hg2+ -adducted glycopeptide. CONCLUSIONS: Zn2+ and Cd2+ -adducted glycopeptide species produced similar dissociation CID spectra, whereas Hg2+ -adducted species produced significantly different CID spectra. Similar CID dissociation features were also observed for Group IIB metal ions adducted glycan species. These results demonstrated that different metal ions might be used to tune the dissociation behaviors of glycopeptides and glycans.

Cross-Course Harmonized Assignments in Neuroscience.

Neuroscience is inherently interdisciplinary. This interdisciplinarity can be lost due to the self-contained nature of each course in most undergraduate neuroscience programs, leaving students to draw these cross-course relationships on their own. We sought to address this by using short, creative research assignments on a topic of the student's choice ("Deep Dive" assignments) that provided students with the opportunity to explore common applications across two concurrently run core neuroscience courses housed in different departments. We tested whether unifying the available Deep Dive topics across the two courses improved student outcomes. Specifically, students were asked to select a topic of interest from a shortlist shared in the two courses. Our results show that harmonized, concurrent creative assignments across dissimilar neuroscience courses improved outcomes related to student interest in material, confidence in creative problem solving, content recall for the other course, and applicability to real life. To our surprise, there was no added benefit to be in the same topic for both courses. Instead, the addition of harmonized Deep Dive assignments themselves, even if assigned on different topics across the two courses, drove the outcome improvement.

Implications for patient follow-up of changes in inferior vena cava filter removal plan practices.

AIM: To assess the improvements during patient follow-up after implementing a proactive plan for retrieval of inferior vena cava (IVC) filters. MATERIALS AND METHODS: A retrospective study was undertaken including all patients who had a temporary IVC filter inserted over a 10-year period. Patient demographics, insertion dates, retrieval dates, retrieval rates, and complications were recorded. Patients were categorised into three groups as follows: group A, no intervention where retrieval was not suggested; group B, passive intervention where retrieval was suggested but no appointment made; and group C, proactive intervention where a retrieval date was booked by the radiologist. RESULTS: Five hundred and nine patients had a temporary IVC filter inserted at Royal Liverpool University Hospital over the study period. One per cent of patients in group C were lost to follow-up compared to 41% and 29% in groups A and B respectively (p<0.001). The number of patients who had an IVC retrieval attempt also increased to 80% in group C compared to 53% and 64% in groups A and B (p<0.001). CONCLUSION: Incorporation of a proactive retrieval booking system has significantly reduced the number of patients lost to follow-up to 1%, leading to an increased number of IVC filter retrieval attempts.

A study on clinical outcomes of Rathke's cleft cyst in patients managed conservatively.

OBJECTIVES: The primary objective was to investigate the clinical presentation, hormonal dysfunction, imaging characteristics and natural history of RCCs that were managed conservatively. Secondary objective was to identify factors associated with cyst progression. METHODS: A retrospective review of patients with the clinical diagnosis of RCC-identified from word search from radiology reports that were followed up from January 1999 to March 2019 was performed. The demographics, clinical data, radiological features and outcomes were reviewed and analyzed. RESULTS: 105 patients were identified with a median follow up of 6 years. 68 patients (64.8%) were managed conservatively from diagnosis till last follow up while 37 patients (35.2%) underwent surgery, with 26 operated at time of diagnosis and 11 operated upon monitoring. For patients managed conservatively from diagnosis till last follow up, incidental finding was the most common presentation. 19.1% had either one or more axes of hormonal dysfunction, with hypogonadism and hypocortisolemia being the commonest ones. Imaging features were variable. 66.2% of patients had T2W hyperintensity on MRI. Pathognomonic feature of intracystic nodule was present in only 14.7% of patients. Among the 79 patients with repeated MRI imaging (68 from conservative group and 11 from surgical group), 32.9% of patients developed cyst progression while 67.1% had either static disease or regression in size of RCC. Median time to progression of cyst was 14 months. Longer median follow up duration and presence of pituitary stalk displacement at presentation were associated with cyst progression. Only one patient developed new endocrine dysfunction. CONCLUSION: 2/3 of the RCCs had static disease or even regression in the size of the cyst. They rarely gave rise to additional endocrine dysfunction by adopting observant approach. Cyst progression was demonstrated in 1/3 of patients. Conservative treatment remained a reasonable treatment for patients without significant symptoms.

Effects of temporal order and intentionality on reflective attention to words in noise.

Speech perception in noise is a cognitively demanding process that challenges not only the auditory sensory system, but also cognitive networks involved in attention. The predictive coding theory has been influential in characterizing the influence of prior context on processing incoming auditory stimuli, with comparatively less research dedicated to "postdictive" processes and subsequent context effects on speech perception. Effects of subsequent semantic context were evaluated while manipulating the relationship of three target words presented in noise and the temporal position of targets compared to the subsequent contextual cue, demonstrating that subsequent context benefits were present regardless of whether the targets were related to each other and did not depend on the position of the target. However, participants instructed to focus on the relation between target and cue performed worse than those who did not receive this instruction, suggesting a disruption of a natural process of continuous speech recognition. We discuss these findings in relation to lexical commitment and stimulus-driven attention to short-term memory as mechanisms of subsequent context integration.

Assessing the Association Between Pre-operative Feeding and the Development of Oral Feeding Skills in Infants with Single Ventricle Heart Disease: An Analysis of the NPC-QIC Dataset.

Pre-operative feeding may improve long-term feeding outcomes in single ventricle patients, including weaning from supplemental tube feedings in infancy. This study examines the association between pre-operative enteral feeding and subsequent long-term feeding outcomes while also assessing the counterbalancing risk of necrotizing enterocolitis (NEC). Secondary analysis of the National Pediatric Cardiology Quality Improvement Collaborative database was performed. The association between pre-operative feeding practice and achieving all oral feeds through the first year of life was examined using a multivariable regression model. Similarly, the association between pre-operative oral feeding and NEC was also assessed. Of 944 patients with 1-year feeding outcomes available, 58% were fed preoperatively (41.3% exclusively oral) and 12.3% were not fed per institutional approach. At hospital discharge after Stage 1 palliation, 57% required a feeding tube, while 39% required a feeding tube at their first birthday. In infants who were orally fed, the odds ratio to achieving tube-free feeding at 1 year was not significantly increased (1.3, confidence interval 0.8-2.0). Of 1740 infants with pre-operative feeding and Stage 1 there was no statistically significant difference in NEC among patients who were preoperatively fed versus those that were not fed per institutional approach (p = 0.2). Pre-operative feeding of infants with single ventricle heart disease was not associated with early achievement of tube-free feeding in the first year of life. However, pre-operative oral feeding was also not associated with increased risk of NEC, suggesting that it can be safely offered among appropriate patients.

Health behaviour practices and expectations for a local cancer survivorship programme: a cross-sectional study of survivors of childhood cancer in Hong Kong.

INTRODUCTION: Lifestyle choices may influence health outcomes in cancer survivors. This study of childhood cancer survivors in Hong Kong investigated factors associated with health-protective and health-damaging behaviours; it also examined expectations of a survivorship programme. METHODS: This cross-sectional study recruited survivors of childhood cancer ≥2 years after treatment. Survivors completed a structured questionnaire to report their health practices and the perceived values of survivorship programme components. Multivariable logistic regression analysis was conducted to identify factors associated with health behaviours. RESULTS: Two hundred survivors were recruited (mean age=23.4 ± 8.8 years; mean duration since treatment, 13.4 ± 7.6 years). Comparatively few survivors exercised ≥4 days/week (16.0%), used sun protection (18.0%), and had a balanced diet (38.5%). Furthermore, comparatively few survivors reported that they had not undergone any immunisation (24.5%) or were unsure (18.5%) about their immunisation history. Most adult survivors were never-drinkers (71.0%) and never-smokers (93.0%). Brain tumour survivors were more likely to have unhealthy eating habits, compared with haematological malignancy survivors (odds ratio [OR]=2.45; 95% confidence interval [CI]=1.29-4.68). Lower socioeconomic status was associated with inadequate sun protection (OR=0.20; 95% CI=0.05-0.83), smoking (OR=5.13; 95% CI=1.48-17.75), and exposure to second-hand smoke (OR=3.52; 95% CI=1.42-8.69). Late-effects screening (78.5%) and psychosocial services to address psychological distress (77%) were considered essential components of a survivorship programme. CONCLUSIONS: Despite the low prevalences of health-damaging behaviours, local survivors of childhood cancer are not engaging in health-protective behaviours. A multidisciplinary programme addressing late effects and psychosocial aspects may address the multifaceted needs of this special population.

The "men in grief" phenomenon among suicide bereaved Chinese men in Hong Kong.

This qualitative study addressed the intersectionality between masculine grief and gender role expectations during the grief process among men. The sample comprised 10 Chinese men in Hong Kong who had lost their wife or child to suicide. The study found that the "men in grief" phenomenon comprised three themes: making sense of hidden grief, processing grief-related guilt, and removing the stigma of masculine grieving. Future research on the masculine grieving process can focus on the association between perceived weaknesses and expected help-seeking behaviors in men who experience multiple losses after a suicide death in the family.

Application of virtual reality for peritoneal dialysis exchange learning in patients with end-stage renal disease and cognitive impairment.

Cognitive impairment is not uncommon in patients with end-stage renal disease and can make it more difficult for these patients to carry out peritoneal dialysis (PD) on their own. Their attempts to do so may result in adverse consequences such as peritonitis. PD exchange is a complex procedure demanding knowledge and skill which requires close supervision and guidance by a renal nurse specialist. In this study, a non-immersive virtual reality (VR) training program using a Leap motion hand tracking device was developed to facilitate patients' understanding and learning of the PD exchange procedure before attempting real task practice. This study was a two-center single-blinded randomized controlled trial on 23 incident PD patients. Patients in the experimental group received 8 sessions of VR training, while patients in the control were provided with printed educational materials. The results showed that there were significant differences between the two groups in performance of the overall PD exchange sequence, especially on the crucial steps. VR had a patient satisfaction rate of 89%, and all patients preferred to have the VR aid incorporated in PD training. Our findings conclude VR can be a useful aid in the training and reinforcement of PD exchange procedures, with distinct merits of being free from restrictions of time, space, and manpower.

Development of a Matrix Sublimation Device with Controllable Crystallization Temperature for MALDI Mass Spectrometry Imaging.

The size and distribution of matrix crystals deposited on the surface of a tissue section play a key role in the performance of MALDI mass spectrometry imaging (MALDI-MSI). In this study, uniform distribution and a restricted size of matrix crystals were achieved via a homemade matrix sublimation device with controllable crystallization temperature. The crystallization temperature was stably controlled at a subzero temperature, and homogeneous matrix crystals with diameters <0.2 µm were generated on the sample surface. Typical MALDI-MSI experiments of endogenous and exogenous components in the tissues of strawberries, kidneys, and mussels were conducted to examine the performance of the sublimator. Good reproducibility of MALDI-MSI was achieved, and the quality of ion images was significantly improved. These results demonstrate that the developed sublimator should have potential in matrix deposition for further high resolution MALDI-MSI application.

ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19.

BACKGROUND: COVID-19 is caused by the coronavirus SARS-CoV-2, which uses angiotensin-converting enzyme 2 (ACE-2) as a receptor for cellular entry. It is theorized that ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration. OBJECTIVE: To determine whether ACE-I and ARB use is associated with acute kidney injury (AKI), macrovascular thrombosis and in-hospital mortality. METHODS: A retrospective, single-centre study of 558 hospital inpatients with confirmed COVID-19 admitted from 1 March to 30 April 2020, followed up until 24 May 2020. AKI and macrovascular thrombosis were primary end-points, and in-hospital mortality was a secondary end-point. RESULTS: AKI occurred in 126 (23.1%) patients, 34 (6.1%) developed macrovascular thrombi, and 200 (35.9%) died. Overlap propensity score-weighted analysis showed no significant effect of ACE-I/ARB use on the risk of occurrence of the specified end-points. On exploratory analysis, severe chronic kidney disease (CKD) increases odds of macrovascular thrombi (OR: 8.237, 95% CI: 1.689-40.181, P = 0.009). The risk of AKI increased with advancing age (OR: 1.028, 95% CI: 1.011-1.044, P = 0.001) and diabetes (OR: 1.675, 95% CI: 1.065-2.633, P = 0.025). Immunosuppression was associated with lower risk of AKI (OR: 0.160, 95% CI: 0.029-0.886, P = 0.036). Advancing age, dependence on care, male gender and eGFR < 60 mL min-1 /1.73 m2 increased odds of in-hospital mortality. CONCLUSION: We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi or mortality. This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic.

Single-cell RNA sequencing identifies molecular targets associated with poor in vitro maturation performance of oocytes collected from ovarian stimulation.

STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

Risk of cancer in patients with ankylosing spondylitis: a nationwide cohort study in Taiwan.

Objective: To estimate the incidence of cancer among patients with ankylosing spondylitis (AS) and compare this risk with that of the general population.Method: We obtained data from Taiwan's National Health Insurance database on 19 289 patients with a first diagnosis of AS registered between 2000 and 2012 with no history of cancer before the diagnosis of AS. Standardized incidence ratios (SIRs) for all cancers and for site-specific cancers were used to assess whether AS was associated with an increased risk of cancer.Results: During the follow-up period, 485 patients developed cancer. The incidence rate was therefore 256.3 per 100 000 person-years. Compared with the general population, patients with AS had an increased risk of cancer [SIR 1.33, 95% confidence interval (CI) 1.20-1.47]. The SIR of cancer was higher in older patients; the risk increased from 8 years after initial diagnosis. Among solid tumours, the risk of melanoma was the highest (SIR 4.64, 95% CI 1.93-11.15), followed by prostate (SIR 2.53, 95% CI 2.01-3.19), thyroid (SIR 2.09, 95% CI 1.45-3.00), and bone cancer (SIR 2.00, 95% CI 1.01-3.99). Among haematological cancers, the risk of leukaemia was the highest (SIR 1.94, 95% CI 1.21-3.12). By contrast, the risks of oesophageal and oral cancers decreased in patients with AS.Conclusion: This nationwide population-based cohort study demonstrated that patients with AS in Taiwan are at an increased risk of cancer, particularly melanoma; prostate, thyroid, and bone cancers; and haematological malignancies.

Changes of the intestinal microbiota along the gut of Japanese Eel (Anguilla japonica).

Fish intestine contains different types of microbiomes, and bacteria are the dominant microbiota in fishes. Studies have identified various core gut bacteria in fishes. However, little is known about the composition and their relative functions of gut microbial community along the intestine. To explore this, the current study investigated the microbial community distribution along the gut in Anguilla japonica. By 16S rRNA gene sequencing, we profiled the gut microbiota in eel along the three regions (anterior intestine (AI), the middle intestine (MI) and the posterior intestine (PI)). Results suggested that the three regions did not have significant differences on the observed species and diversities. The cluster tree analysis showed that the bacteria community in MI was closer to PI than the AI. The dominant bacteria in AI were the Proteobacteria, in which the majority was graduated replaced by Bacteroidetes along the gut to PI region. Through PICRUSt analysis, shifts in the bacterial community along the gut were found to affect the genetic information processing pathways. Higher levels of translation and transcriptional pathway activities were found in MI and PI than in AI. The dominant bacterial species were different among the regions and contributed to various biological functions along the gut.