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Introduction Studies on economic evaluations of the 13-valent pneumococcal conjugate vaccine (PCV13) have been increasing over the last decade. No systematic reviews have synthesized the evidence of economic evaluations of the PCV13. Areas covered We systematically searched the literature which published on peer-reviewed journals from January 2010 to June 2022. The literature search was conducted in the following electronic databases: PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database. We identified 1827 records from the database search. After excluding 511 duplicates, 1314 records were screened, of which 156 records were retained for the full-text reviews. A total of 44 studies were included in the review. Among the included studies, 33 studies were economic evaluations of PCV13 among children, and 11 studies were conducted among adults. The literature search initiated in April, 2022, and updated in June 2022. Expert opinion Vaccination with PCV13 was found to significantly reduce the mortality and morbidity of pneumococcal diseases and was cost-effective compared to no vaccine or several other pneumococcal vaccines (e.g. PCV10, PPV23). Future research is advised to expand economic evaluations of PCV13 combined with dynamic model to enhance methodologic rigor and prediction accuracy.

Abstract Background Lignocellulose is the most abundant natural biomass resource for the production of biofuels and other chemicals. The efficient degradation of cellulose by cellulases is a critical step for the lignocellulose bioconversion. Understanding the structure-catalysis relationship is vital for rational design of more stable and highly active enzymes. Glycoside hydrolase (GH) family 5 is the largest and most functionally diverse group of cellulases, with a conserved TIM barrel structure. The important roles of the various loop regions of GH5 enzymes in catalysis, however, remain poorly understood. Results In the present study, we investigated the relationship between the loops surrounding active site architecture and its catalytic efficiency, taking TfCel5A, an enzyme from GH5_2 subfamily of Thermobifida fusca, as an example. Large-scale computational simulations and site-directed mutagenesis experiments revealed that three loops (loop 8, 3, and 7) around active cleft played diverse roles in substrate binding, intermediate formation, and product release, respectively. The highly flexible and charged residue triad of loop 8 was responsible for capturing the ligand into the active cleft. Severe fluctuation of loop 3 led to the distortion of sugar conformation at the − 1 subsite. The wobble of loop 7 might facilitate product release, and the enzyme activity of the mutant Y361W in loop 7 was increased by approximately 40%. Conclusion This study unraveled the vital roles of loops in active site architecture and provided new insights into the catalytic mechanism of the GH5_2 cellulases.

Abstract Background Keratin, the main component of chicken feather, is the third most abundant material after cellulose and chitin. Keratin can be converted into high-value compounds and is considered a potential high-quality protein supplement; However, its recalcitrance makes its breakdown a challenge, and the mechanisms of action of keratinolytic proteases-mediated keratinous substrates degradation are not yet fully elucidated. Bacillus sp. CN2, having many protease-coding genes, is a dominant species in keratin-rich materials environments. To explore the degradation patterns of feather keratin, in this study, we investigated the characteristics of feather degradation by strain CN2 based on the functional-degradomics technology. Results Bacillus sp. CN2 showed strong feather keratin degradation activities, which could degrade native feathers efficiently resulting in 86.70% weight loss in 24 h, along with the production of 195.05 ± 6.65 U/mL keratinases at 48 h, and the release of 0.40 mg/mL soluble proteins at 60 h. The extracellular protease consortium had wide substrate specificity and exhibited excellent biodegradability toward soluble and insoluble proteins. Importantly, analysis of the extracellular proteome revealed the presence of a highly-efficient keratin degradation system. Firstly, T3 γ-glutamyltransferase provides a reductive force to break the dense disulfide bond structure of keratin. Then S8B serine endopeptidases first hydrolyze keratin to expose more cleavage sites. Finally, keratin is degraded into small peptides under the synergistic action of proteases such as M4, S8C, and S8A. Consistent with this, high-performance liquid chromatography (HPLC) and amino acid analysis showed that the feather keratin hydrolysate contained a large number of soluble peptides and essential amino acids. Conclusions The specific expression of γ-glutamyltransferase and co-secretion of endopeptidase and exopeptidase by the Bacillus sp. CN2 play an important role in feather keratin degradation. This insight increases our understanding of the keratinous substrate degradation and may inspire the design of the optimal enzyme cocktails for more efficient exploration of protein resources in industrial applications.

Poor health behaviours in childhood, including sedentary behaviour, low physical activity levels, inadequate sleep, and unhealthy diet, are established risk factors for both chronic diseases and mental illness. Scant studies have examined the importance of such health behaviour patterns for health-related quality of life (HRQoL). This study aimed to examine the association of health behaviour patterns with HRQoL among Canadian children. Data from 2866 grade five students were collected through a provincially representative school-based survey of the 2014 Raising Healthy Eating and Active Living Kids in Alberta study. Latent class analysis was used to identify health behaviour patterns based on 11 lifestyle behaviours: sedentary behaviour (using a computer, playing video games, watching TV), physical activity (with and without a coach), sleep (bedtime on weekdays and weekends), and diet (fruit and vegetables intake, grain products, milk and alternatives, meat and alternatives). Multivariable multilevel logistic regression was applied to examine the associations of health behaviour patterns with HRQoL. Three groupings with distinct health behaviour patterns were identified: the first grouping (55%) is characterized by relatively healthy levels of sedentary behaviour, physical activity, and sleep, but a less healthy diet (“activity-focused” group). The second grouping (24%) is characterized by a relatively healthy diet, but moderately healthy levels of sedentary behaviour, physical activity, and sleep (“diet-focused” group). The third grouping (21%) is characterized by mostly unhealthy behaviours (“not health-focused” group). Students in the third and second groupings (“not health-focused” and “diet-focused”) were more likely to report lower HRQoL relative to students in the first grouping (“activity-focused”). The findings suggest that health promotion strategies may be more effective when considering the patterns of health behaviours as distinct targets in the efforts to improve HRQoL. Future research should include prospective observational and intervention studies to further elucidate the relationship between health behaviour patterns and HRQoL among children.

IntroductionPostoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary.MethodsThis is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention (n = 186) and placebo (n = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes.DiscussionTo our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test’s power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.

Objectives: The COVID-19 pandemic has negatively affected children's lifestyle behaviours and mental health and wellbeing, and concerns have been raised that COVID-19 has also increased health inequalities. No study to date has quantified the impact of COVID-19 on health inequalities among children. We compared pre-pandemic vs. post-lockdown inequalities in lifestyle behaviours and mental health and wellbeing among children living in rural and remote northern communities. Methods: We surveyed 473 grade 4–6 students (9–12 years of age) from 11 schools in rural and remote communities in northern Canada in 2018 (pre-pandemic), and 443 grade 4–6 students from the same schools in 2020 (post-lockdown). The surveys included questions on sedentary behaviours, physical activity, dietary intake, and mental health and wellbeing. We measured inequality in these behaviors using the Gini coefficient, a unitless measure ranging from 0 to 1 with a higher value indicating greater inequality. We used temporal changes (2020 vs. 2018) in Gini coefficients to assess the impact of COVID-19 on inequalities in lifestyle behaviours and mental health and wellbeing separately among girls and boys. Results: Inequalities in all examined lifestyle behaviours increased between 2018 and 2020. Inequalities in watching TV, playing video games, and using a cell phone increased among girls, while inequalities in playing video games, using computers and tablets, and consumption of sugar, salt, saturated fat and total fat increased among boys. Changes in inequalities in mental health and wellbeing were small and not statistically significant. Conclusion: The findings suggest that the COVID-19 pandemic has exacerbated inequalities in lifestyle behaviours among children living in rural and remote northern communities. If not addressed, these differences may translate into exacerbated inequalities in future health. The findings further suggest that school health programs can help mitigate the negative impact of the pandemic on lifestyle behaviours and mental health and wellbeing.

Enhancer of zeste homolog 2 (EZH2) is the lysine methyltransferase of polycomb repressive complex 2 (PRC2) that catalyzes H3K27 tri-methylation. Aberrant expression and loss-of-function mutations of EZH2 have been demonstrated to be tightly associated with the pathogenesis of various myeloid malignancies characterized by ineffective erythropoiesis, such as myelodysplastic syndrome (MDS). However, the function and mechanism of EZH2 in human erythropoiesis still remains largely unknown. Here, we demonstrated that EZH2 regulates human erythropoiesis in a stage-specific, dual-function manner by catalyzing histone and non-histone methylation. During the early erythropoiesis, EZH2 deficiency caused cell cycle arrest in the G1 phase, which impaired cell growth and differentiation. Chromatin immunoprecipitation sequencing and RNA sequencing discovered that EZH2 knockdown caused a reduction of H3K27me3 and upregulation of cell cycle proteindependent kinase inhibitors. In contrast, EZH2 deficiency led to the generation of abnormal nuclear cells and impaired enucleation during the terminal erythropoiesis. Interestingly, EZH2 deficiency downregulated the methylation of HSP70 by directly interacting with HSP70. RNA-sequencing analysis revealed that the expression of AURKB was significantly downregulated in response to EZH2 deficiency. Furthermore, treatment with an AURKB inhibitor and small hairpin RNAmediated AURKB knockdown also led to nuclear malformation and decreased enucleation efficiency. These findings strongly suggest that EZH2 regulates terminal erythropoiesis through a HSP70 methylation-AURKB axis. Our findings have implications for improved understanding of ineffective erythropoiesis with EZH2 dysfunction.

Objective The aim of this study was to investigate the role of deubiquitinase (DUB) 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in patients with bladder cancer. Methods From 2016 to 2018, 181 patients diagnosed with primary bladder cancer at the Affiliated Hospital of Qingdao University were recruited. The expression of PSMD14 in bladder cancer tissues was tested by immunochemistry. The association between PSMD14 expression and clinical and pathological data and outcomes of bladder cancer patients was determined. Overexpression and knockdown cells were constructed to evaluate the effects of PSMD14 on proliferation of bladder cancer cells. Results Our results showed that PSMD14 was significantly overexpressed in bladder cancer tissues compared to adjacent non-tumor tissues (76.24% vs 23.76%, P = 0.02). The expression of PSMD14 was significantly higher in patients with larger tumor diameters (85.14% vs 70.09%, P = 0.019) and patients with a family history of cancer (92.16% vs 70.00%, P = 0.002). Patients with high expression of PSMD14 had poor disease-free survival (DFS) (HR = 2.89, 95% CI [1.247–6.711], P = 0.013). Gain and loss of function experiments demonstrated that PSMD14 deficiency inhibited bladder cancer cell proliferation. Additionally, depletion of PSMD14 suppressed bladder cancer cell growth via down-regulation of GPX4, and the promotion of PSMD14-induced cell growth was observably reversed by the GPX4 inhibitor RSL3. Conclusion We determined that PSMD14 is highly expressed in bladder cancer tissues, and that PSMD14 expression correlated with poor disease-free survival. Depletion of PSMD14 could inhibit the proliferation of bladder cancer cells through the downregulation of GPX4. Therefore, PSMD14 may be an effective target for the treatment of bladder cancer.

Xylanases have the potential to be used as bio-deinking and bio-bleaching materials and their application will decrease the consumption of the chlorine-based chemicals currently used for this purpose. However, xylanases with specific properties could act effectively, such as having significant thermostability and alkali resistance, etc. In this study, we found that TfXyl10A, a xylanase from Thermobifida fusca, was greatly induced to transcript by microcrystalline cellulose (MCC) substrate. Biochemical characterization showed that TfXyl10A is optimally effective at temperature of 80 °C and pH of 9.0. After removing the carbohydrate-binding module (CBM) and linker regions, the optimum temperature of TfXyl10A-CD was reduced by 10°C (to 70°C), at which the enzyme’s temperature tolerance was also weakened. While truncating only the CBM domain (TfXyl10AdC) had no significant effect on its thermostability. Importantly, polysaccharide-binding experiment showed that the auxiliary domain CBM2 could specifically bind to cellulose substrates, which endowed xylanase TfXyl10A with the ability to degrade xylan surrounding cellulose. These results indicated that TfXyl10A might be an excellent candidate in bio-bleaching processes of paper industry. In addition, the features of active-site architecture of TfXyl10A in GH10 family were further analyzed. By mutating each residue at the -2 and -1 subsites to alanine, the binding force and enzyme activity of mutants were observably decreased. Interestingly, the mutant E51A, locating at the distal -3 subsite, exhibited 90% increase in relative activity compared with wild-type (WT) enzyme TfXyl10A-CD (the catalytic domain of TfXyl110A). This study explored the function of a GH10 xylanase containing a CBM2 domain and the contribution of amino acids in active-site architecture to catalytic activity. The results obtained provide guidance for the rational design of xylanases for industrial applications under high heat and alkali-based operating conditions, such as paper bleaching.

Abstract Background Xylan is the most abundant hemicellulose polysaccharide in nature, which can be converted into high value-added products. However, its recalcitrance to breakdown requires the synergistic action of multiple enzymes. Aspergillus niger, possessing numerous xylan degrading isozyme-encoding genes, are highly effective xylan degraders in xylan-rich habitats. Therefore, it is necessary to explore gene transcription, the mode of action and cooperation mechanism of different xylanase isozymes to further understand the efficient xylan-degradation by A. niger. Results Aspergillus niger An76 encoded a comprehensive set of xylan-degrading enzymes, including five endo-xylanases (one GH10 and four GH11). Quantitative transcriptional analysis showed that three xylanase genes (xynA, xynB and xynC) were up-regulated by xylan substrates, and the order and amount of enzyme secretion differed. Specifically, GH11 xylanases XynA and XynB were initially secreted successively, followed by GH10 xylanase XynC. Biochemical analyses displayed that three GH11 xylanases (XynA, XynB and XynD) showed differences in catalytic performance and product profiles, possibly because of intricate hydrogen bonding between substrates and functional residues in the active site architectures impacted their binding capacity. Among these, XynB had the best performance in the degradation of xylan and XynE had no catalytic activity. Furthermore, XynA and XynB showed synergistic effects during xylan degradation. Conclusions The sequential secretion and different action modes of GH11 xylanases were essential for the efficient xylan degradation by A. niger An76. The elucidation of the degradation mechanisms of these xylanase isozymes further improved our understanding of GH-encoding genes amplification in filamentous fungi and may guide the design of the optimal enzyme cocktails in industrial applications.

Abstract Background Psychological resilience and coping strategies have been found to be related to various psychological and mental health problems. Evaluations of the relationship between resilience and coping style among university students are important for developing effective health promotion strategies focused on resilience intervention to benefit students’ health and well-being. The relationship between psychological resilience and coping styles has usually been examined among adults and patients. Very few studies have investigated the relationship between resilience and coping style in university students. The present study aimed to investigate the associations between psychological resilience, students’ characteristics (gender, major and grade) and coping styles among undergraduate students. Methods A cross-sectional survey was conducted among undergraduate students in Shandong Province, China. Undergraduate students were randomly selected from 6 universities in 3 cities of the province using a stratified random sampling method. The questionnaire included questions on the participants’ demographic information, including gender, grade and major, measures of psychological resilience and coping style. Coping style was measured by the Simplified Coping Style Questionnaire (SCSQ). The Asian Resilience Scale (ARS) was applied to evaluate undergraduates’ psychological resilience. Multivariable regression analysis was used to examine the relationships between resilience, students’ characteristics and positive coping styles. Results A sample of 1743 undergraduates was analysed. The mean psychological resilience score was 70.41. The mean score for positive coping style was 24.72. Multiple regression analysis showed that three factors of psychological resilience, mood control, self-plasticity and coping flexibility, were all significant factors for positive coping styles (regression coefficient = 0.34, 0.35, 0.14, p

Human smooth pursuit eye movements and motion perception behave similarly when observers track and judge the motion of simple objects, such as dots. But moving objects in our natural environment are complex and contain internal motion. We ask how pursuit and perception integrate the motion of objects with motion that is internal to the object. Observers (n = 20) tracked a moving random-dot kinematogram with their eyes and reported the object's perceived direction. Objects moved horizontally with vertical shifts of 0, ±3, ±6, or ±9° and contained internal dots that were static or moved ±90° up/down. Results show that whereas pursuit direction was consistently biased in the direction of the internal dot motion, perceptual biases differed between observers. Interestingly, the perceptual bias was related to the magnitude of the pursuit bias (r = 0.75): perceptual and pursuit biases were directionally aligned in observers that showed a large pursuit bias, but went in opposite directions in observers with a smaller pursuit bias. Dissociations between perception and pursuit might reflect different functional demands of the two systems. Pursuit integrates all available motion signals in order to maximize the ability to monitor and collect information from the whole scene. Perception needs to recognize and classify visual information, thus segregating the target from its context. Ambiguity in whether internal motion is part of the scene or contributes to object motion might have resulted in individual differences in perception. The perception-pursuit correlation suggests shared early-stage motion processing or perception-pursuit interactions.

Cordyceps militaris, a traditional medicinal ingredient with a long history of application in China, is regarded as a high-value fungus due to its production of various bioactive ingredients with a wide range of pharmacological effects in clinical treatment. Several typical bioactive ingredients, such as cordycepin, D-mannitol, cordyceps polysaccharides, and N6-(2-hydroxyethyl)-adenosine (HEA), have received increasing attention due to their antitumor, antioxidant, antidiabetic, radioprotective, antiviral and immunomodulatory activities. Here, we systematically sorted out the latest research progress on the chemical characteristics, biosynthetic gene clusters and pathways of these four typical bioactive ingredients. This summary will lay a foundation for obtaining low-cost and high-quality bioactive ingredients in large amounts using microbial cell factories in the future.

The parasitoid fungus Cordyceps cicadae, whose fruiting bodies are known in China as “chan hua,” literally “cicada flower,” has been used as a traditional Chinese medicinal ingredient for centuries. However, systematic disclosure of the vital factors responsible for the formation of wild cicada flower is limited. Here, we determined the physicochemical properties of soil and simultaneously analyzed the diversities and the structures of microbial community inhabiting the coremia, sclerotia, and soil around wild cicada flowers through high-throughput sequencing. Our results indicated that cicada flower more preferentially occurred in acidic soil (pH 5.9) with abundant moisture content (MC), total nitrogen (TN), and organic matter (OM). The dominant fungal genera in soil mainly included Isaria, f__Clavariaceae_Unclassified, Umbelopsis, f__Chaetomiaceae_Unclassified, Mortierella, f__Sordariaceae_Unclassified, and Arcopilus. Among them, C. cicadae was the only fungus that was massively detected in both the coremia and sclerotia with abundance of 83.5 and 53.6%, respectively. Based on this, a C. cicadae strain named AH10-4 with excellent adenosine- and N6-(2-hydroxyethyl)-adenosine (HEA)-producing capability was successfully isolated. However, to the aspect of bacteria, Burkholderia–Caballeronia–Paraburkholderia, Bacillus, Acidibacter, f__Xanthobacteraceae_Unclassified, and Candidatus_Solibacter were the dominant genera in soil. Pedobacter, f__Enterobacteriaceae_Unclassified, Pandoraea, Achromobacter, Stenotrophomonas, Burkholderia–Caballeronia–Paraburkholderia, and Chitinophaga were the dominant genera in the coremia and sclerotia. Notably, Burkholderia–Caballeronia–Paraburkholderia was the shared bacteria among them with high abundance of 3.1, 11.4, and 5.2% in the sclerotia, coremia, and soil, respectively. However, the possible role of these bacteria to the occurrence of cicada flower has been unclear to our knowledge. By analyzing the correlation between physicochemical properties and microbial community of soil, we found that MC, Fe, and Zn were significantly negatively correlated with soil Isaria and that Cu was significantly negatively correlated with most dominant soil bacterial genera. But Mg was significantly positively correlated with most dominant taxa. This study provides new insight into the formation mechanisms of cicada flower and may contribute to the large-scale cultivation of cicada flowers.

Objective: Studies that have reported the associations of diet quality, physical activity (PA), sedentary behavior (SB), and health-related quality of life (HRQoL) with mental health among children and adolescents are predominantly cross-sectional in design. Very few studies have examined the longitudinal relationship of mental health with health behavior and HRQoL among children. This study aimed to investigate the associations of diet quality, PA, SB, and HRQoL among children with mental health disorders throughout childhood.Methods: We linked data from grade five students aged primarily 10 and 11 years who participated in the Raising Healthy Eating and Active Living (REAL) Kids Alberta survey in 2012 in the Canadian province of Alberta with their administrative health care data from birth to 2012. Mental health outcomes included internalizing disorder and attention deficit and hyperactivity disorder (ADHD) defined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or Tenth Revision, Canadian version (ICD-10-CA). The HRQoL was measured by the EQ-5D-Y, a five-dimensional descriptive system for children and youth. We applied negative binomial regressions to examine the associations between health behaviors, HRQoL, and mental health.Results: Of the 1,352 participating students, 12.31 and 8.32% had a diagnosis of internalizing disorders and ADHDs, respectively, during childhood from birth to the ages of 10–11 years. Students in the highest tertile for diet quality, relative to the lowest tertile, were 56% less likely to have diagnoses of internalizing disorders (incidence rate ratio, IRR = 0.44, 95% CI = 0.23–0.85). Students engaged in less PA (vs. more PA) were more likely to be diagnosed for internalizing disorders (IRR = 1.98, 95% CI = 1.19–3.30). Poorer diet quality, low PA, excessive use of computers/video games, and watching TV were significantly associated with more diagnoses of ADHDs. Children who experienced some or a lot of problems in “feeling worried, sad, or unhappy” and “having pain or discomfort” were more likely to receive diagnoses of internalizing disorders and ADHDs, respectively.Conclusions: These observed associations suggest that health promotion programs targeting promoting diet quality, PA, and HRQoL and reducing SB among children may contribute to improving mental health.

Thermostable and alkaline- or acid-stable xylanases are more advantageous in agricultural and industrial fields. In this study, a rational structure-based design was conducted based on a thermostable GH11 xylanase TlXynA from Thermomyces lanuginosus to improved pH-tolerance. Four mutant enzymes (P1, P2, P3, and P4) and five variants (N1, N2, N3, N4, and N5) were constructed by substituting surface charged residue combinations using site-directed mutagenesis. Compared to the native enzyme, two mutants P1 and P2 showed higher acid tolerance, especially at pH 3.0, presented 50 and 40% of their maximum activity, respectively. In addition, four mutants N1, N2, N3 and N4 had higher tolerance than the native enzyme to alkaline environments (pH 7.0–9.0). At pH 9.0, the residual activities of N1, N2, N3, and N4 were 86, 78, 77, and 66%, respectively. In summary, an improved pH-tolerance design principle is being reported.

Abstract Background Comparisons of population health status using self-report measures such as the SF-36 rest on the assumption that the measured items have a common interpretation across sub-groups. However, self-report measures may be sensitive to differential item functioning (DIF), which occurs when sub-groups with the same underlying health status have a different probability of item response. This study tested for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scales in population-based data using latent variable mixture models (LVMMs). Methods Data were from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective national cohort study. LVMMs were applied to the ten PF and five MH SF-36 items. A standard two-parameter graded response model with one latent class was compared to multi-class LVMMs. Multivariable logistic regression models with pseudo-class random draws characterized the latent classes on demographic and health variables. Results The CaMos cohort consisted of 9423 respondents. A three-class LVMM fit the PF sub-scale, with class proportions of 0.59, 0.24, and 0.17. For the MH sub-scale, a two-class model fit the data, with class proportions of 0.69 and 0.31. For PF items, the probabilities of reporting greater limitations were consistently higher in classes 2 and 3 than class 1. For MH items, respondents in class 2 reported more health problems than in class 1. Differences in item thresholds and factor loadings between one-class and multi-class models were observed for both sub-scales. Demographic and health variables were associated with class membership. Conclusions This study revealed DIF in population-based SF-36 data; the results suggest that PF and MH sub-scale scores may not be comparable across sub-groups defined by demographic and health status variables, although effects were frequently small to moderate in size. Evaluation of DIF should be a routine step when analysing population-based self-report data to ensure valid comparisons amongst sub-groups.

DNA methylation is associated with gene silencing in eukaryotic organisms. Although pathways controlling the establishment, maintenance and removal of DNA methylation are known, relatively little is understood about how DNA methylation influences gene expression. Here we identified a METHYL-CpG-BINDING DOMAIN 7 (MBD7) complex in Arabidopsis thaliana that suppresses the transcriptional silencing of two LUCIFERASE (LUC) reporters via a mechanism that is largely downstream of DNA methylation. Although mutations in components of the MBD7 complex resulted in modest increases in DNA methylation concomitant with decreased LUC expression, we found that these hyper-methylation and gene expression phenotypes can be genetically uncoupled. This finding, along with genome-wide profiling experiments showing minimal changes in DNA methylation upon disruption of the MBD7 complex, places the MBD7 complex amongst a small number of factors acting downstream of DNA methylation. This complex, however, is unique as it functions to suppress, rather than enforce, DNA methylation-mediated gene silencing.

BackgroundSelf-reported health status measures, like the Short Form 36-item Health Survey (SF-36), can provide rich information about the overall health of a population and its components, such as physical, mental, and social health. However, differential item functioning (DIF), which arises when population sub-groups with the same underlying (i.e., latent) level of health have different measured item response probabilities, may compromise the comparability of these measures. The purpose of this study was to test for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scale items in a Canadian population-based sample.MethodsStudy data were from the prospective Canadian Multicentre Osteoporosis Study (CaMos), which collected baseline data in 1996-1997. DIF was tested using a multiple indicators multiple causes (MIMIC) method. Confirmatory factor analysis defined the latent variable measurement model for the item responses and latent variable regression with demographic and health status covariates (i.e., sex, age group, body weight, self-perceived general health) produced estimates of the magnitude of DIF effects.ResultsThe CaMos cohort consisted of 9423 respondents; 69.4% were female and 51.7% were less than 65 years. Eight of 10 items on the PF sub-scale and four of five items on the MH sub-scale exhibited DIF. Large DIF effects were observed on PF sub-scale items about vigorous and moderate activities, lifting and carrying groceries, walking one block, and bathing or dressing. On the MH sub-scale items, all DIF effects were small or moderate in size.ConclusionsSF-36 PF and MH sub-scale scores were not comparable across population sub-groups defined by demographic and health status variables due to the effects of DIF, although the magnitude of this bias was not large for most items. We recommend testing and adjusting for DIF to ensure comparability of the SF-36 in population-based investigations.

Attention-deficit and hyperactivity disorder (ADHD) in children and adolescents is a global public health burden. Identification of health-related behavioral risk factors including diet quality and physical and sedentary activities for ADHD is important for prioritizing behavioral intervention strategies to improve mental health. This study aimed to examine the association of diet quality, physical activity, and sedentary behaviours in childhood with ADHD throughout adolescence. We linked data from grade five students aged primarily 10 and 11 years old who participated in a population-based lifestyle survey in the Canadian province of Nova Scotia with their administrative health care data. We applied negative binomial regression methods to examine the associations between health behaviours and ADHD. Of the 4875 students, 9.7% had one or more diagnoses of ADHD between the ages of 10/11 and 18 years. The number of primary diagnoses with ADHD was statistically significantly lower among students with better diet quality, higher levels of physical activity, and those that spent less time playing computers and video games (p < 0.05). These findings suggest that health promotion programs aiming to improve children’s diets and active lifestyles may also reduce the public health burden of ADHD.

Crowding is a major limitation of visual perception. Because of crowding, a simple object, like a letter, can only be recognized if clutter is a certain critical spacing away. Crowding is only weakly associated with acuity. The critical spacing of crowding is lowest in the normal fovea, and grows with increasing eccentricity in peripheral vision. Foveal crowding is more prominent in certain patient groups, including those with strabismic amblyopia and apperceptive agnosia. Crowding may lessen with age during childhood as reading speed increases. The range of crowding predicts much of the slowness of reading in children with developmental dyslexia. There is tantalizing evidence suggesting that the critical spacing of crowding indicates neural density (participating neurons per square deg) in the visual cortex. Thus, for basic and applied reasons, it would be very interesting to measure foveal crowding clinically in children and adults with normal and impaired vision, and to track the development of crowding during childhood. While many labs routinely measure peripheral crowding as part of their basic research in visual perception, current tests are not well suited to routine clinical testing because they take too much time, require good fixation, and are mostly not applicable to foveal vision. Here we report a new test for clinical measurement of crowding in the fovea. It is quick and accurate, works well with children and adults, and we expect it to work well with dementia patients as well. The task is to identify a numerical digit, 1-9, using a new “Pelli” font that is identifiable at tiny width (0.02 deg, about 1 minarc, in normal adult fovea). This allows quick measurement of the very small (0.05 deg) critical spacing in the normal adult fovea, as well as with other groups that have higher critical spacing. Preliminary results from healthy adults and children are presented.