Nevin Manimala

Biomed Chromatogr. 2022 Apr 7:e5381. doi: 10.1002/bmc.5381. Online ahead of print.

ABSTRACT

This research developed and validated a highly sensitive and selective UPLC-MS/MS approach using a triple quadrupole mass spectrometer for quantifying favipiravir (FAV). Moreover, we introduced a study evaluating bioequivalence using two drugs, favibrivix and avigan- containing favipiravir. Lean Six Sigma verified the capacity and performance of the process. Protein precipitation extraction was utilized to extract FAV from the collected human matrices. We used an ACQUITY UPLCr BEH HILIC column and valproic acid as an internal standard (IS). Furthermore, we conducted the procedure using an isocratic elution comprising acetonitrile and 0.005% ammonia in water (75:25, v/v), a flow rate of 0.25ml/min, a temperature-controlled at 10 ⁰ C, and an injection volume of 1.0μl. Our UPLC-MS/MS process has a broad range (50-10,000) ng/ml with a determination coefficient (r² ) of 0.9980. We validated the method in line with the FDA. The findings revealed that the test, favibrivix 200mg/tablet, and the reference, avigan® 200mg/tablet, were statistically bioequivalent regarding healthy Egyptian participants.

PMID:35393721 | DOI:10.1002/bmc.5381

Bioessays. 2022 Apr 7:e2200020. doi: 10.1002/bies.202200020. Online ahead of print.

ABSTRACT

There is much discussion in the media and some of the scientific literature of how many of the conclusions from scientific research should be doubted. These critiques often focus on studies, typically in non-experimental spheres of biomedical and social sciences – that search large datasets for novel correlations, with a risk that inappropriate statistical evaluations might yield dubious conclusions. By contrast, results from experimental biological research can often be interpreted largely without statistical analysis. Typically: novel observation(s) are reported, and an explanatory hypothesis is offered; multiple labs undertake experiments to test the hypothesis; interpretation of the results may refute the hypothesis, support it or provoke its modification; the test/revise sequence is reiterated many times; and the field moves forward. I illustrate this experimental/non-experimental dichotomy by examining the contrasting recent histories of: (a) our remarkable and growing understanding of how several inositol-containing phospholipids contribute to the lives of eukaryote cells; and (b) the difficulty of achieving any agreed mechanistic understanding of why consuming dietary supplements of inositol is clinically beneficial in some metabolic diseases.

PMID:35393713 | DOI:10.1002/bies.202200020

ANZ J Surg. 2022 Apr 8. doi: 10.1111/ans.17649. Online ahead of print.

ABSTRACT

BACKGROUND: Our aims were to determine if the diagnostic threshold for diagnosing hypertrophic pyloric stenosis (HPS) on ultrasound scan (USS) should be adjusted based on birth weight (BW), current weight (CW), gestational age (GA), chronological age (CA) or corrected gestational age (CGA).

METHODS: All patients who underwent either an USS and pyloromyotomy (Group 1) or an USS for possible HPS (Group 2) at our tertiary centre between July 2013 and June 2019 were identified. Ideal threshold values are identified by measuring Youden’s Index (J = sensitivity + specificity – 1; higher is better). Mean maximum Youden’s Index for stratified results was compared to that for combined results.

RESULTS: Two hundred and eighty-four patients were included (142 patients in both Group 1 and Group 2). Combined maximum Youden’s Index for all patients was 0.92 for pyloric canal thickness (PMT) and 0.87 for pyloric canal length (PCL). Mean maximum Youden’s Index was higher when patients were stratified by GA, CGA, BW or CW, and equivalent for CA. For pyloric canal length (PCL), mean maximum Youden’s Index was lower for all variables when stratified compared to combined. There was no visual trend observed in the diagnostic thresholds between groups.

CONCLUSION: Stratifying USS PMT diagnostic thresholds values based on age and weight is statistically more accurate than a single threshold in diagnosing HPS. However, the lack of visual correlation indicates a larger dataset is required to validate these results.

PMID:35393697 | DOI:10.1111/ans.17649

Int J Urol. 2022 Apr 7. doi: 10.1111/iju.14887. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to develop models to predict new-onset overactive bladder in 5 years using a large prospective cohort of the general population.

METHODS: This is a secondary analysis of a longitudinal cohort study in Japan. The baseline characteristics were measured between 2008 and 2010, with follow-ups every 5 years. We included subjects without overactive bladder at baseline and with follow-up data 5 years later. Overactive bladder was assessed using the overactive bladder symptom score. Baseline characteristics (demographics, health behaviors, comorbidities, and overactive bladder symptom scores) and blood test data were included as predictors. We developed two competing prediction models for each sex based on logistic regression with penalized likelihood (LASSO). We chose the best model separately for men and women after evaluating models’ performance in terms of discrimination and calibration using an internal validation via 200 bootstrap resamples and a temporal validation.

RESULTS: We analyzed 7218 participants (male: 2238, female: 4980). The median age was 60 and 55 years, and the number of new-onset overactive bladder was 223 (10.0%) and 288 (5.8%) per 5 years in males and females, respectively. The in-sample estimates for C-statistic, calibration intercept, and slope for the best performing models were 0.77 (95% confidence interval 0.74-0.80), 0.28 and 1.15 for males, and 0.77 (95% confidence interval 0.74-0.80), 0.20 and 1.08 for females. Internal and temporal validation gave broadly similar estimates of performance, indicating low optimism.

CONCLUSION: We developed risk prediction models for new-onset overactive bladder among men and women with good predictive ability.

PMID:35393696 | DOI:10.1111/iju.14887

Biomed Chromatogr. 2022 Apr 7:e5362. doi: 10.1002/bmc.5362. Online ahead of print.

ABSTRACT

Chicken Colibacillosis (CC) is one of the most severe diseases in the chicken industry. Ceftiofur sodium (CS) is often used to treat CC in clinical practice, and lipopolysaccharide (LPS) accumulates in the chicken body. Previous experimental studies found that CS combined with LPS could induce liver injury in layer chickens, and polysaccharides from charred Angelica Sinensis (CASP) had a better hepatoprotective effect than polysaccharides from unprocessed Angelica Sinensis (UASP). However, the intervention mechanism was unclear. Thus, UPLC-Q/TOF-MS/MS-based metabonomics and transcriptomics were used in this study to clarify the hepatoprotective effect mechanism of CASP and UASP on the layer chicken. Transcriptomics and enzyme-linked immunosorbent assay (ELISA) was used to make the biological verification on some critical mutual metabolic pathways screened with metabonomics. The comprehensive analysis results showed that after the layer chicken liver injury model built with LPS and CS, twelve critical metabolic pathways were disturbed, involving ten important differential metabolites. The hepatoprotective effect mechanism of CASP is related to the arachidonic acid metabolism pathway and mTOR signaling pathway, involving nine important differential metabolites. By contrast, the hepatoprotective effect mechanism of UASP is related to the arachidonic acid metabolism pathway, involving four important differential metabolites.

PMID:35393691 | DOI:10.1002/bmc.5362

Int J Health Plann Manage. 2022 Apr 7. doi: 10.1002/hpm.3469. Online ahead of print.

ABSTRACT

INTRODUCTION: The relationships among health expenditure, health outcome, and economic growth have been given significant consideration in the current literature. Nevertheless, there are potential gaps in the nature of health-growth nexus that current empirical studies have not thoroughly considered.

METHODOLOGY: This study explores Granger causality and cointegration relationships in a trivariate framework among, health expenditure, health outcome, and economic growth. We used three health outcome measures and a panel vector autoregressive model to study 45 countries in Sub-Saharan Africa between 1990 and 2018. Our innovative panel data evaluation technique allows to ascertain significant causal relationships among the studied variables in the short and long run.

RESULTS: Findings from the study include (1) health expenditure and health outcome Granger-cause economic growth in the long run; (2) economic growth Granger-cause health expenditure in the short run; (3) no causal relationship was found running from health expenditure and health outcome to economic growth in the short-run. The former result (1) may not be surprising, given that the countries considered in this study are relatively less developed countries from Sub-Saharan Africa. Hence, further health improvement may play a statistically significant role in spurring further economic growth.

CONCLUSION: Based on the results, the study presents interesting and possible effective policy perspectives for health improvement in the studied countries. Policies that stimulate health spending are needed to create a better and more industrious society that can support SSA’s economic progress. This is because a healthy person may be more productive than someone who is sick, allowing them to produce greater output.

PMID:35393680 | DOI:10.1002/hpm.3469

Dev Med Child Neurol. 2022 Apr 8. doi: 10.1111/dmcn.15237. Online ahead of print.

ABSTRACT

AIM: This study aimed to explore eye movements and stress during eye-tracking gaming performance in children with dyskinetic cerebral palsy (CP) compared with typically developing children, and associations between eye-tracking performance, eye movements, stress, and participants’ characteristics.

METHOD: This cohort study included 12 children with dyskinetic CP aged 5 to 12 years (mean age 8 years 7 months, standard deviation [SD] 2 years 3 months) and 23 typically developing children aged 5 to 13 years (mean age 9 years 0 months, SD 2 years 7 months). Participants played 10 eye-tracking games. Tobii X3-120 and Tobii Pro Lab were used to record and analyse eye movements. Stress was assessed through heart rate variability (HRV), recorded during rest, and eye-tracking performance using the Bittium Faros360° ECG Holter device. Eye-tracking performance was measured using gaming completion time. Fixation and saccade variables were used to quantify eye movements, and time- and frequency-domain variables to quantify HRV. Non-parametric statistics were used.

RESULTS: Gaming completion time was significantly different (p < 0.001) between groups, and it was negatively correlated with experience (r_s = -0.63, p = 0.029). No significant differences were found between groups in fixation and saccade variables. HRV significantly changed from rest to eye-tracking performance only in typically developing children and not in children with dyskinetic CP.

INTERPRETATION: Children with dyskinetic CP took longer to perform the 10 games, especially the inexperienced users, indicating the importance of the early provision of eye-tracking training opportunities. It seems that eye-tracking tasks are not a source of increased stress and effort in children with dyskinetic CP.

PMID:35393636 | DOI:10.1111/dmcn.15237

Eur Heart J. 2022 Apr 8:ehac179. doi: 10.1093/eurheartj/ehac179. Online ahead of print.

ABSTRACT

AIMS: Aspirin is widely used in cardiovascular disease prevention but is also associated with an increased risk of bleeding. The net effect of aspirin on dementia and cognitive impairment is uncertain.

METHODS AND RESULTS: In the ASCEND trial, 15 480 people from the UK with diabetes and no history of cardiovascular disease were randomized to aspirin 100 mg daily or matching placebo for a mean of 7.4 years. The 15 427 ASCEND participants with no recorded dementia prior to baseline were included in this cognitive study with a primary pre-specified outcome of ‘broad dementia’, comprising dementia, cognitive impairment, or confusion. This was ascertained through participant, carer, or general practitioner report or hospital admission diagnosis, by 31 March 2019 (∼2 years beyond the scheduled treatment period). The broad dementia outcome occurred in a similar percentage of participants in the aspirin group and placebo group: 548 participants (7.1%) vs. 598 (7.8%), rate ratio 0.91 [95% confidence interval (CI), 0.81-1.02]. Thus, the CI excluded proportional hazards of >2% and proportional benefits of >19%.

CONCLUSION: Aspirin does not have a large proportional effect on the risk of dementia. Trials or meta-analyses with larger total numbers of incident dementia cases to increase statistical power are needed to assess whether any modest proportional 10-15% benefits of 5-7 years of aspirin use on dementia exist.

CLINICAL TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN60635500; ClinicalTrials.gov number: NCT00135226.

PMID:35393614 | DOI:10.1093/eurheartj/ehac179

Nat Genet. 2022 Apr 7. doi: 10.1038/s41588-022-01036-9. Online ahead of print.

ABSTRACT

Polygenic risk scores suffer reduced accuracy in non-European populations, exacerbating health disparities. We propose PolyPred, a method that improves cross-population polygenic risk scores by combining two predictors: a new predictor that leverages functionally informed fine-mapping to estimate causal effects (instead of tagging effects), addressing linkage disequilibrium differences, and BOLT-LMM, a published predictor. When a large training sample is available in the non-European target population, we propose PolyPred⁺, which further incorporates the non-European training data. We applied PolyPred to 49 diseases/traits in four UK Biobank populations using UK Biobank British training data, and observed relative improvements versus BOLT-LMM ranging from +7% in south Asians to +32% in Africans, consistent with simulations. We applied PolyPred⁺ to 23 diseases/traits in UK Biobank east Asians using both UK Biobank British and Biobank Japan training data, and observed improvements of +24% versus BOLT-LMM and +12% versus PolyPred. Summary statistics-based analogs of PolyPred and PolyPred⁺ attained similar improvements.

PMID:35393596 | DOI:10.1038/s41588-022-01036-9

Nat Genet. 2022 Apr 7. doi: 10.1038/s41588-022-01039-6. Online ahead of print.

ABSTRACT

The human brain forms functional networks of correlated activity, which have been linked with both cognitive and clinical outcomes. However, the genetic variants affecting brain function are largely unknown. Here, we used resting-state functional magnetic resonance images from 47,276 individuals to discover and validate common genetic variants influencing intrinsic brain activity. We identified 45 new genetic regions associated with brain functional signatures (P < 2.8 × 10^-11), including associations to the central executive, default mode, and salience networks involved in the triple-network model of psychopathology. A number of brain activity-associated loci colocalized with brain disorders (e.g., the APOE ε4 locus with Alzheimer’s disease). Variation in brain function was genetically correlated with brain disorders, such as major depressive disorder and schizophrenia. Together, our study provides a step forward in understanding the genetic architecture of brain functional networks and their genetic links to brain-related complex traits and disorders.

PMID:35393594 | DOI:10.1038/s41588-022-01039-6