Tag: pubmed

Pilot Feasibility Stud. 2022 May 23;8(1):108. doi: 10.1186/s40814-022-01058-4.

ABSTRACT

BACKGROUND: Dietary interventions have been previously explored in children with ADHD. Elimination diets and supplementation can produce beneficial behaviour changes, but little is known about the mechanisms mediating change. We propose that these interventions may work, in part, by causing changes in the gut microbiota. A microbiome-targeted dietary intervention was developed, and its feasibility assessed.

METHODS: A non-randomised feasibility study was conducted on nine non-medicated children with ADHD, aged 8-13 years (mean 10.39 years), using a prospective one-group pre-test/post-test design. Participants were recruited from ADHD support groups in London and took part in the 6-week microbiome-targeted dietary intervention, which was specifically designed to impact the composition of gut bacteria. Children were assessed pre- and post-intervention on measures of ADHD symptomatology, cognition, sleep, gut function and stool-sample microbiome analysis. The primary aim was to assess the study completion rate, with secondary aims assessing adherence, adverse events (aiming for no severe and minimal), acceptability and suitability of outcome measures.

RESULTS: Recruitment proved to be challenging and despite targeting 230 participants directly through support groups, and many more through social media, nine families (of the planned 10) signed up for the trial. The completion rate for the study was excellent at 100%. Exploration of secondary aims revealed that (1) adherence to each aspect of the dietary protocol was very good; (2) two mild adverse events were reported; (3) parents rated the treatment as having good acceptability; (4) data collection and outcome measures were broadly feasible for use in an RCT with a few suggestions recommended; (5) descriptive data for outcome measures is presented and suggests that further exploration of gut microbiota, ADHD symptoms and sleep would be helpful in future research.

CONCLUSIONS: This study provides preliminary evidence for the feasibility of a microbiome-targeted dietary intervention in children with ADHD. Recruitment was challenging, but the diet itself was well-tolerated and adherence was very good. Families wishing to trial this diet may find it an acceptable intervention. However, recruitment, even for this small pilot study, was challenging. Because of the difficulty experienced recruiting participants, future randomised controlled trials may wish to adopt a simpler dietary approach which requires less parental time and engagement, in order to recruit the number of participants required to make meaningful statistical interpretations of efficacy.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03737877 . Registered 13 November 2018-retrospectively registered, within 2 days of the first participant being recruited.

PMID:35606889 | DOI:10.1186/s40814-022-01058-4

Genome Med. 2022 May 24;14(1):55. doi: 10.1186/s13073-022-01058-2.

ABSTRACT

BACKGROUND: Genome-wide association studies of asthma have revealed robust associations with variation across the human leukocyte antigen (HLA) complex with independent associations in the HLA class I and class II regions for both childhood-onset asthma (COA) and adult-onset asthma (AOA). However, the specific variants and genes contributing to risk are unknown.

METHODS: We used Bayesian approaches to perform genetic fine-mapping for COA and AOA (n=9432 and 21,556, respectively; n=318,167 shared controls) in White British individuals from the UK Biobank and to perform expression quantitative trait locus (eQTL) fine-mapping in immune (lymphoblastoid cell lines, n=398; peripheral blood mononuclear cells, n=132) and airway (nasal epithelial cells, n=188) cells from ethnically diverse individuals. We also examined putatively causal protein coding variation from protein crystal structures and conducted replication studies in independent multi-ethnic cohorts from the UK Biobank (COA n=1686; AOA n=3666; controls n=56,063).

RESULTS: Genetic fine-mapping revealed both shared and distinct causal variation between COA and AOA in the class I region but only distinct causal variation in the class II region. Both gene expression levels and amino acid variation contributed to risk. Our results from eQTL fine-mapping and amino acid visualization suggested that the HLA-DQA1*03:01 allele and variation associated with expression of the nonclassical HLA-DQA2 and HLA-DQB2 genes accounted entirely for the most significant association with AOA in GWAS. Our studies also suggested a potentially prominent role for HLA-C protein coding variation in the class I region in COA. We replicated putatively causal variant associations in a multi-ethnic cohort.

CONCLUSIONS: We highlight roles for both gene expression and protein coding variation in asthma risk and identified putatively causal variation and genes in the HLA region. A convergence of genomic, transcriptional, and protein coding evidence implicates the HLA-DQA2 and HLA-DQB2 genes and HLA-DQA1*03:01 allele in AOA.

PMID:35606880 | DOI:10.1186/s13073-022-01058-2

Hum Resour Health. 2022 May 23;20(1):46. doi: 10.1186/s12960-022-00743-y.

ABSTRACT

BACKGROUND: Given the demands for public health and infectious disease management skills during COVID-19, a shortage of the public health workforce, particularly with skills and competencies in epidemiology and biostatistics, has emerged at the Centers for Disease Controls (CDCs) in China. This study aims to investigate the employment preferences of doctoral students majoring in epidemiology and biostatistics, to inform policy-makers and future employers to address recruitment and retention requirements at CDCs across China.

METHODS: A convenience sampling approach for recruitment, and an online discrete choice experiment (DCE) survey instrument to elicit future employee profiles, and self-report of their employment and aspirational preferences during October 20 and November 12, 2020. Attributes included monthly income, employment location, housing benefits, children’s education opportunities, working environment, career promotion speed and bianzhi (formally established post).

RESULTS: A total of 106 doctoral epidemiology and biostatistics students from 28 universities completed the online survey. Monthly income, employment location and bianzhi was of highest concern in the seven attributes measured, though all attributes were statistically significant and presented in the expected direction, demonstrating preference heterogeneity. Work environment was of least concern. For the subgroup analysis, employment located in a first-tier city was more likely to lead to a higher utility value for PhD students who were women, married, from an urban area and had a high annual family income. Unsurprisingly, when compared to single students, married students were willing to forgo more for good educational opportunities for their children. The simulation results suggest that, given our base case, increasing only monthly income from 10,000 ($ 1449.1) to 25,000 CNY ($ 3622.7) the probability of choosing the job in the third-tier city would increase from 18.1 to 53.8% (i.e., the location choice is changed).

CONCLUSION: Monthly income and employment location were the preferred attributes across the cohort, with other attributes then clearly ranked and delineated. A wider use of DCEs could inform both recruitment and retention of a public health workforce, especially for CDCs in third-tier cities where resource constraints preclude all the strategies discussed here.

PMID:35606873 | DOI:10.1186/s12960-022-00743-y

J Otolaryngol Head Neck Surg. 2022 May 23;51(1):22. doi: 10.1186/s40463-022-00580-y.

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease that may require biological therapy. Omalizumab is an anti-IgE biologic that was recently approved by the FDA and Health Canada for use in severe CRS with nasal polyps (CRSwNP) recalcitrant to intranasal corticosteroids. Dosing is based on weight and pre-treatment serum IgE, with elevated levels of the latter being an indication for biologic treatment according to EPOS and EUFOREA guidelines. The goal of this study was to identify variables that predict IgE-high type 2 inflammation and serve as indicators for biologic treatment in CRS.

METHODS: Patients ≥ 19 yo diagnosed with CRS undergoing functional endoscopic sinus surgery were included retrospectively. Demographics, past medical history, preoperative blood work, Lund-Mackay (LM), Lund Kennedy (LK), and SNOT-22 scores were extracted. Descriptive statistics and binary logistic regression analyses were conducted. Model superiority was based on Nagelkerke R2 scores and receiver operating characteristic curves.

RESULTS: Sixty-five patients, average age 49.96 ± 13.59 years, were included. Sixty-one binary logistic regression models for elevated serum IgE were created. Among the top 3 models, the best model had sensitivity, specificity, positive predictive value and negative predictive values of 82.1, 69.2, 80.0, and 72.0. All performance measures except sensitivity exceeded the Canadian Biologics Guideline model. Serum eosinophils ≥ 300 cell/uL, CRSwNP and LM ≥ 17 increased the odds of elevated IgE.

CONCLUSIONS: IgE-high type-2 inflammation can be predicted by a model that includes eosinophil ≥ 300 cell/uL, CRSwNP, LM ≥ 17, asthma diagnosis and SNOT-22 ≥ 40. Patients meeting these parameters have a high pretest probability for elevated IgE and would benefit from IgE serology to determine qualification for omalizumab. This could reduce unwarranted IgE serology in patients with CRSwNP but also target a patient population for further workup that will lead to optimization of resource allocation and improve healthcare equity in rural and remote areas within Canada.

PMID:35606866 | DOI:10.1186/s40463-022-00580-y

Breast Cancer Res. 2022 May 23;24(1):35. doi: 10.1186/s13058-022-01528-w.

ABSTRACT

BACKGROUND: CCR5 is a motility chemokine receptor implicated in tumor progression, whose activation and subsequent endocytosis may identify highly aggressive breast cancer cell subtypes likely to spread into the circulatory system.

METHODS: The MDA-MB-231 cell line was used to model and visualize CCR5 activation by stimulation with RANTES, in an effort to quantify CCR5 endocytosis from the cell surface to the perinuclear space. CCR5 expression was then examined in tumor-associated cells (TACs), consisting of circulating tumor cells and circulating stromal cells, isolated from the peripheral blood of 54 metastatic breast cancer (mBC) patients to evaluate these CCR5 pooling patterns as they relate to progression and survival over 2 years.

RESULTS: In MB231 experiments, it was observed that CCR5 formed ~ 1 micron clusters identified as “CCR5 pools” on the surface of the cell, which in the presence of RANTES were endocytosed and translocated to the cell cytoplasm. When TACs from patients were analyzed, CCR5 pools were observed on the cell surface and translocating to the nuclear area, with CCR5 also having a positive statistical correlation between increased numbers of TACs and increased CCR5 pools on the cells. Further, it was determined that patients with very high numbers of CCR5 (> 10 CCR5 pools), specifically in the circulating stromal cells, were associated with worse progression-free survival (hazard ratio = 4.5, p = 0.002) and worse overall survival (hazard ratio = 3.7, p = 0.014).

CONCLUSIONS: Using a liquid biopsy approach, we evaluated two populations of tumor-associated cells emanating from primary tumors, with data suggesting that upregulation of the motility chemokine CCR5 in TACs provides clinically relevant opportunities for treating and tracking drug targetable receptors in mBC.

PMID:35606863 | DOI:10.1186/s13058-022-01528-w

Child Adolesc Psychiatry Ment Health. 2022 May 23;16(1):38. doi: 10.1186/s13034-022-00466-x.

ABSTRACT

BACKGROUND: Previous work has examined the association of aggression levels and callous-unemotional traits with outcome expectations and values regarding the consequences of aggression. Less work has examined the outcome expectations and values regarding the consequences of aggression of adolescents with Conduct Disorder (CD). Also, no studies have examined links between irritability (a second socio-affective trait associated with CD) and these social cognitive processes despite the core function of anger in retaliatory aggression and establishing dominance.

METHOD: The current study, investigating these issues, involved 193 adolescents (typically developing [TD; N = 106], 87 cases with CD [N = 87]). Participants completed an adaptation of the Outcomes Expectations and Values Questionnaire and were assessed for CU traits and irritability via the Inventory of Callous-Unemotional traits and the Affective Reactivity Index.

RESULTS: While CD was associated with atypical outcome expectations this was not seen within statistical models including CU traits and irritability. CU traits were associated with decreased expectation that aggression would result in feelings of remorse and victim suffering, as well as decreased concern that aggressive acts would result in punishment and victim suffering. Irritability was associated with increased expectations and concern that aggression would result in dominance and forced respect.

CONCLUSIONS: The results suggest that CU traits and irritability, often present in youth with CD, are associated with different forms of maladaptive outcome expectations and values regarding the consequences of aggression. This suggests that the atypical social cognitive processes underlying aggressive behavior among youth exhibiting CU traits may differ from those exhibiting problems regulating anger.

PMID:35606814 | DOI:10.1186/s13034-022-00466-x

Pediatr Rheumatol Online J. 2022 May 23;20(1):38. doi: 10.1186/s12969-022-00696-5.

ABSTRACT

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease that can have conduction disturbances and cardiac rhythm disorders as manifestations of cardiac involvement. The aim of the study is to assess the susceptibility of children with FMF to cardiac repolarization abnormalities and therefore arrhythmia in children with FMF.

METHODS: A cross sectional study conducted on 60 children had FMF and 40 age and sex matched healthy controls. Cardiac repolarization markers, cardiac dimensions and functions were assessed by electrocardiogram (ECG) and conventional echocardiography in patients and controls.

RESULTS: The mean ± SD age of the patients was 10.43 ± 3.472 years, corrected QT (QTc) and the ratio of peak to end T wave (Tpe) over QTc interval (Tpe /QTc) increased significantly in FMF patients more than healthy control (p value 0.023 and 0.022 respectively). P wave dispersion (Pd) was significantly higher in FMF patients with amyloidosis (p value 0.030). No significant difference was found in cardiac dimensions and functions between the two groups. We found a statistically negative correlation between Pd and age of patients at time of study, age of disease onset and age at diagnosis. On the other hand, we found a statistically significant positive correlation between Pd with number of attacks per year and disease severity score. Furthermore, Tpe/QTc ratio correlated with FMF 50 score, QTc correlated with 24 hours proteinuria. QT, JT intervals correlated with fibrinogen.

CONCLUSIONS: FMF Patients may have increased risk of arrhythmia and should be monitored on regular basis. Compliance to colchicine therapy and better disease control might play a role in decreasing this risk.

PMID:35606812 | DOI:10.1186/s12969-022-00696-5

Arthritis Res Ther. 2022 May 23;24(1):120. doi: 10.1186/s13075-022-02801-1.

ABSTRACT

BACKGROUND: Osteoarthritis (OA) is a slowly developing and debilitating disease, and there are no validated specific biomarkers for its early detection. To improve therapeutic approaches, identification of specific molecules/biomarkers enabling early determination of this disease is needed. This study aimed at identifying, with the use of proteomics/mass spectrometry, novel OA-specific serum biomarkers. As obesity is a major risk factor for OA, we discriminated obesity-regulated proteins to target only OA-specific proteins as biomarkers.

METHODS: Serum from the Osteoarthritis Initiative cohort was used and divided into 3 groups: controls (n=8), OA-obese (n=10) and OA-non-obese (n=10). Proteins were identified and quantified from the liquid chromatography-tandem mass spectrometry analyses using MaxQuant software. Statistical analysis used the Limma test followed by the Benjamini-Hochberg method. To compare the proteomic profiles, the multivariate unsupervised principal component analysis (PCA) followed by the pairwise comparison was used. To select the most predictive/discriminative features, the supervised linear classification model sparse partial least squares regression discriminant analysis (sPLS-DA) was employed. Validation of three differential proteins was performed with protein-specific assays using plasma from a cohort derived from the Newfoundland Osteoarthritis.

RESULTS: In total, 509 proteins were identified, and 279 proteins were quantified. PCA-pairwise differential comparisons between the 3 groups revealed that 8 proteins were differentially regulated between the OA-obese and/or OA-non-obese with controls. Further experiments using the sPLS-DA revealed two components discriminating OA from controls (component 1, 9 proteins), and OA-obese from OA-non-obese (component 2, 23 proteins). Proteins from component 2 were considered related to obesity. In component 1, compared to controls, 7 proteins were significantly upregulated by both OA groups and 2 by the OA-obese. Among upregulated proteins from both OA groups, some of them alone would not be a suitable choice as specific OA biomarkers due to their rather non-specific role or their strong link to other pathological conditions. Altogether, data revealed that the protein CRTAC1 appears to be a strong OA biomarker candidate. Other potential new biomarker candidates are the proteins FBN1, VDBP, and possibly SERPINF1. Validation experiments revealed statistical differences between controls and OA for FBN1 (p=0.044) and VDPB (p=0.022), and a trend for SERPINF1 (p=0.064).

CONCLUSION: Our study suggests that 4 proteins, CRTAC1, FBN1, VDBP, and possibly SERPINF1, warrant further investigation as potential new biomarker candidates for the whole OA population.

PMID:35606786 | DOI:10.1186/s13075-022-02801-1

J Orthop Surg Res. 2022 May 23;17(1):287. doi: 10.1186/s13018-022-03177-3.

ABSTRACT

BACKGROUND: Arthrometry has been introduced to evaluate the laxity of ankle joint in recent years. However, its role in the diagnosis of chronic ankle instability is still debatable. Therefore, we assessed the diagnostic accuracy of a digital arthrometer in terms of sensitivity and specificity.

METHODS: According to the inclusion and exclusion criteria proposed by the International Ankle Consortium, we recruited 160 uninjured ankles (control group) and 153 ankles with chronic ankle instability (CAI group). Ankle laxity was quantitively measured by a validated digital arthrometer. Data of loading force and joint displacement were recorded in a continuous manner. Differences between the control and CAI groups were compared using 2-tailed independent t test. A receiver operating characteristic curve analysis was used to calculate area under a curve, sensitivity and specificity.

RESULTS: Load-displacement curves of the two groups were depicted. Differences of joint displacement between the control and CAI groups were compared at 30, 45, 60, 75, 90, 105 and 120 N, which were all of statistical significance (all p < 0.001) with the largest effect size at 90 N. Statistical significance was found in the differences between the two groups in load-displacement ratio at 10-120 N, 10-40 N, 40-80 N and 80-120 N (all p < 0.001), with the largest effect size at 10-40 N. Load-displacement ratio at the interval of 10-40 N had the highest area under a curve (0.9226), with sensitivity and specificity of 0.804 and 0.863, respectively, when the cutoff point was 0.1582 mm/N.

CONCLUSION: The digital arthrometer measurement could quantitively analyze the ankle laxity with high diagnostic accuracy. The load-displacement ratio would be a reliable and promising approach for chronic ankle instability diagnosis. Level of evidence level II.

PMID:35606774 | DOI:10.1186/s13018-022-03177-3

BMC Endocr Disord. 2022 May 23;22(1):136. doi: 10.1186/s12902-022-01047-x.

ABSTRACT

BACKGROUND: Microvascular complications lead to disability, dependency, and accelerated morbidity and mortality. This study aimed to identify predictors of blood glucose change and time to microvascular complications among patients with type 2 diabetes.

METHODS: A retrospective cohort study was conducted among type 2 diabetes mellitus patients enrolled between December 2014 and December 2015 at Felege Hiwot and Debre Markos Referral Hospital. A total of 318 T2DM patients were included in the study. Joint modelling of longitudinal and survival analysis was employed to identify predictors of Blood Glucose Change and Microvascular Complications in Type 2 Diabetes Mellitus Patients.

RESULTS: The prevalence of microvascular complications in Type 2 diabetes patients was 26.3%, 95%confidence interval(CI):(21.5, 31.1). Of which, half of the patients developed a microvascular complication after 30 months from the onset of the follow-up. The significant predictors of developing microvascular complication were positive proteinurea (adjusted hazard ratio (AHR) = 1.418, 95%CI: 1.080, 1.861), Serum creatinine (AHR = 3.704, 95%CI: 1.992, 6.887), Weight (AHR = 1.058, 95%CI: 1.023, 1.094), and log fasting blood glucose(log(FBS))(AHR = 1.013, 95%CI: 1.010, 1.015). The predictors of fasting blood glucose progression were higher baseline FBS(est(estimate) = 0.002,95%CI:0.0018, 0.0022), Systolic blood pressure (SBP) (est = 0.003, 95%CI: 0.002, 0.004), diastolic blood pressure (DBP) (est = 0.002, 95%CI: 0.0002, 0.004), and age (est = 0.003, 95%CI: 0.001, 0.004).

CONCLUSION: The progression of the fasting blood glucose level for rural patients was faster than for urban patients. Patients having higher baseline FBS, previous hypertension history, higher SBP, higher DBP, older age, and fewer visits to the hospital have a relatively more progressive change in blood sugar levels. Patients having higher triglyceride levels, positive proteinuria, higher fasting blood sugar, higher weight, and a lesser number of hospital visits have a higher risk of developing a complication. In response to this finding, an aggressive intervention that targets to prevent microvascular complications is required.

PMID:35606785 | DOI:10.1186/s12902-022-01047-x