Nevin Manimala

PLoS One. 2022 Jul 6;17(7):e0270232. doi: 10.1371/journal.pone.0270232. eCollection 2022.

ABSTRACT

BACKGROUND: Intraocular treatment with antibodies targeting vascular endothelial growth factor (anti-VEGF) inhibits pathological vessel growth in adults and preterm infants. Recently, concerns regarding the impact of anti-VEGF treatment on systemic VEGF levels in preterm infants have been raised. Earlier studies suggest that preanalytical and methodological parameters impact analytical VEGF concentrations, but we have not found a comprehensive systematic review covering preanalytical procedures and methods for VEGF measurements.

OBJECTIVE: This review aimed to evaluate the most critical factors during sample collection, sample handling, and the analytical methods that influence VEGF levels and therefore should be considered when planning a prospective collection of samples to get reproducible, comparable results.

MATERIAL AND METHODS: PubMed and Scopus databases were searched 2021/Nov/11. In addition, identification of records via other methods included reference, citation, and Google Scholar searches. Rayyan QCRI was used to handle duplicates and the selection process. Publications reporting preanalytical handling and/or methodological comparisons using human blood samples were included. Exclusion criteria were biological, environmental, genetic, or physiological factors affecting VEGF. The data extraction sheets included bias assessment using the QUADAS-2 tool, evaluating patient selection, index-test, reference standard, and flow and timing. Concentrations of VEGF and results from statistical comparisons of analytical methods and/or preanalytical sample handling and/or different sample systems were extracted. The publications covering preanalytical procedures were further categorized based on the stage of the preanalytical procedure. Meta-analysis was used to visualize VEGF concentrations among healthy individuals. The quality of evidence was rated according to GRADE.

RESULTS: We identified 1596 publications, and, after the screening process, 43 were considered eligible for this systematic review. The risk of bias estimation was difficult for 2/4 domains due to non-reported information. Four critical steps in the preanalytical process that impacted VEGF quantification were identified: blood drawing and the handling before, during, and after centrifugation. Sub-categorization of those elements resulted in nine findings, rated from moderate to very low evidence grade. The choice of sample system was the most reported factor. VEGF levels (mean [95% CI]) in serum (n = 906, 20 publications), (252.5 [213.1-291.9] pg/mL), were approximated to ninefold higher than in plasma (n = 1122, 23 publications), (27.8 [23.6-32.1] pg/mL), based on summarized VEGF levels with meta-analysis. Notably, most reported plasma levels were below the calibration range of the used method.

CONCLUSION: When measuring circulating VEGF levels, choice of sample system and sample handling are important factors to consider for ensuring high reproducibility and allowing study comparisons. Protocol: CRD42020192433.

PMID:35793362 | DOI:10.1371/journal.pone.0270232

PLoS Negl Trop Dis. 2022 Jul 6;16(7):e0010588. doi: 10.1371/journal.pntd.0010588. Online ahead of print.

ABSTRACT

Zika virus (ZIKV) is a mosquito-borne flavivirus with maternal infection associated with preterm birth, congenital malformations, and fetal death, and adult infection associated with Guillain-Barré syndrome. Recent widespread endemic transmission of ZIKV and the potential for future outbreaks necessitate the development of an effective vaccine. We developed a ZIKV vaccine candidate based on virus-like-particles (VLPs) generated following transfection of mammalian HEK293T cells using a plasmid encoding the pre-membrane/membrane (prM/M) and envelope (E) structural protein genes. VLPs were collected from cell culture supernatant and purified by column chromatography with yields of approximately 1-2mg/L. To promote increased particle yields, a single amino acid change of phenylalanine to alanine was made in the E fusion loop at position 108 (F108A) of the lead VLP vaccine candidate. This mutation resulted in a modest 2-fold increase in F108A VLP production with no detectable prM processing by furin to a mature particle, in contrast to the lead candidate (parent). To evaluate immunogenicity and efficacy, AG129 mice were immunized with a dose titration of either the immature F108A or lead VLP (each alum adjuvanted). The resulting VLP-specific binding antibody (Ab) levels were comparable. However, geometric mean neutralizing Ab (nAb) titers using a recombinant ZIKV reporter were significantly lower with F108A immunization compared to lead. After virus challenge, all lead VLP-immunized groups showed a significant 3- to 4-Log10 reduction in mean ZIKV RNAemia levels compared with control mice immunized only with alum, but the RNAemia reduction of 0.5 Log10 for F108A groups was statistically similar to the control. Successful viral control by the lead VLP candidate following challenge supports further vaccine development for this candidate. Notably, nAb titer levels in the lead, but not F108A, VLP-immunized mice inversely correlated with RNAemia. Further evaluation of sera by an in vitro Ab-dependent enhancement assay demonstrated that the F108A VLP-induced immune sera had a significantly higher capacity to promote ZIKV infection in FcγR-expressing cells. These data indicate that a single amino acid change in the fusion loop resulted in increased VLP yields but that the immature F108A particles were significantly diminished in their capacity to induce nAbs and provide protection against ZIKV challenge.

PMID:35793354 | DOI:10.1371/journal.pntd.0010588

PLoS Biol. 2022 Jul 6;20(7):e3001712. doi: 10.1371/journal.pbio.3001712. Online ahead of print.

ABSTRACT

People of all ages display the ability to detect and learn from patterns in seemingly random stimuli. Referred to as statistical learning (SL), this process is particularly critical when learning a spoken language, helping in the identification of discrete words within a spoken phrase. Here, by considering individual differences in speech auditory-motor synchronization, we demonstrate that recruitment of a specific neural network supports behavioral differences in SL from speech. While independent component analysis (ICA) of fMRI data revealed that a network of auditory and superior pre/motor regions is universally activated in the process of learning, a frontoparietal network is additionally and selectively engaged by only some individuals (high auditory-motor synchronizers). Importantly, activation of this frontoparietal network is related to a boost in learning performance, and interference with this network via articulatory suppression (AS; i.e., producing irrelevant speech during learning) normalizes performance across the entire sample. Our work provides novel insights on SL from speech and reconciles previous contrasting findings. These findings also highlight a more general need to factor in fundamental individual differences for a precise characterization of cognitive phenomena.

PMID:35793349 | DOI:10.1371/journal.pbio.3001712

PLoS One. 2022 Jul 6;17(7):e0270643. doi: 10.1371/journal.pone.0270643. eCollection 2022.

ABSTRACT

The objective of this paper is to analyze the association between the job placement results of graduates and the satisfaction that, retrospectively, they express about their university education. Despite the fact that, in Spain, 47.0% of the population aged 25 to 34 has a higher education degree, we have little knowledge of the determinants of university student satisfaction. In addition, most studies have focused on evaluating the university experience (teaching activity, study plans, counselling for students, or facilities) and very few of them have taken into account the influence of graduates’ labour market outcomes on their satisfaction. This issue is of particular interest in the Spanish case, considering the dysfunctional nature of the youth labor market, which has high rates of overqualification, excessive job turnover and high unemployment. The sources of statistical information used in this work include the first two editions of the “University Graduate Job Placement Survey”, carried out by the Spanish National Institute of Statistics (INE) in 2014 and 2019. The methodology used in the empirical work is the propensity score matching estimator. The results of empirical analysis indicate that graduates’ job placement difficulties have a significant association with their dissatisfaction with their university experience. In particular, educational mismatch (horizontal and vertical) and, to a lesser extent, unemployment and low wages significantly increase the probability of graduates stating that, if they had to start over, they would not return to university or they would not study the same degree.

PMID:35793347 | DOI:10.1371/journal.pone.0270643

PLoS One. 2022 Jul 6;17(7):e0268396. doi: 10.1371/journal.pone.0268396. eCollection 2022.

ABSTRACT

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

PMID:35793346 | DOI:10.1371/journal.pone.0268396

PLoS One. 2022 Jul 6;17(7):e0270428. doi: 10.1371/journal.pone.0270428. eCollection 2022.

ABSTRACT

BACKGROUND: Previous study showed that both melatonin supplement and physical exercise intervention could improve sleep quality in children with autism spectrum disorders (ASD) with the increase in endogenous melatonin level. However, none of the studies have directly compared the effectiveness between the two interventions on treating sleep disturbance in children with ASD. Without direct comparison, we do not know which intervention is better. Thus, we designed a study to compare which intervention is more effective to treat sleep disturbance in children with ASD and to examine whether the combination of the two could be the most efficacious. We present a protocol for conducting a randomized controlled trial to compare the effectiveness of physical exercise and melatonin supplement on treating sleep disturbance in children with ASD.

STUDY DESIGN: The proposed study will be a four-group randomised control trial (RCT) design, with equal allocation of participants to the three intervention groups and one control group.

METHODS: All eligible participants will be randomly allocated to a morning jogging group, a melatonin supplement group, a combination group and a control group. Changes in sleep quality will be monitored through actigraphic assessment and parental sleep logs. Melatonin levels represented by 6-sulfoxymelatonin will be measured from the participants’ 24-h and the first morning void urinary samples. All the assessments will be carried out before the intervention (T1), in the mid of the study (5 weeks after the commencement of the study) (T2) and after the 10-week intervention (T3). Level of statistical significance will be set at 5% (i.e. p < .05). The results of this trial will be submitted for publication in peer-reviewed journal.

FINDINGS: The findings will provide evidence to determine whether physical exercise or melatonin supplement or the combination of interventions is the most effective to treat sleep disturbance in children with ASD.

PMID:35793342 | DOI:10.1371/journal.pone.0270428

PLoS One. 2022 Jul 6;17(7):e0268594. doi: 10.1371/journal.pone.0268594. eCollection 2022.

ABSTRACT

Birdwatching is considered one of the fastest growing nature-based tourism sectors in the world. Tourists who identify as birdwatchers tend to be well-educated and wealthy travellers with a specific interest in the places they visit. Birdwatchers can bring economic resources to remote communities diversifying their economies and contribute to biodiversity conservation in areas of bird habitat with global significance. Alaska plays a critical role in understanding the link between bird conservation and bird tourism as it supports the world’s largest concentration of shorebirds and is a global breeding hotspot for hundreds of migratory species, including many species of conservation concern for their decline across their ranges. Alaska is also a global destination for birders due to the large congregations of birds that occur during the spring, summer and fall seasons. Despite its global importance, relatively little information exists on the significance of bird tourism in Alaska or on opportunities for community development that align with conservation. This study used ebird data to look at trends in Alaska birdwatching and applied existing information from the Alaska Visitor Statistics Program to estimate visitor expenditures and the impact of that spending on Alaska’s regional economies. In 2016, nearly 300,000 birdwatchers visited Alaska and spent $378 million, supporting approximately 4,000 jobs. The study describes bird tourism’s contributions to local jobs and income in remote rural and urban economies and discusses opportunities for developing and expanding the nature-based tourism sector. The study points toward the importance of partnering with rural communities and landowners to advance both economic opportunities and biodiversity conservation actions. The need for new data collection addressing niche market development and economic diversification is also discussed.

PMID:35793337 | DOI:10.1371/journal.pone.0268594

PLoS One. 2022 Jul 6;17(7):e0266521. doi: 10.1371/journal.pone.0266521. eCollection 2022.

ABSTRACT

BACKGROUND: Spatiotemporal modelling techniques allow one to predict injury across time and space. However, such methods have been underutilised in injury studies. This study demonstrates the use of statistical spatiotemporal modelling in identifying areas of significantly high injury risk, and areas witnessing significantly increasing risk over time.

METHODS: We performed a retrospective review of hospitalised major trauma patients from the Victorian State Trauma Registry, Australia, between 2007 and 2019. Geographical locations of injury events were mapped to the 79 local government areas (LGAs) in the state. We employed Bayesian spatiotemporal models to quantify spatial and temporal patterns, and analysed the results across a range of geographical remoteness and socioeconomic levels.

RESULTS: There were 31,317 major trauma patients included. For major trauma overall, we observed substantial spatial variation in injury incidence and a significant 2.1% increase in injury incidence per year. Area-specific risk of injury by motor vehicle collision was higher in regional areas relative to metropolitan areas, while risk of injury by low fall was higher in metropolitan areas. Significant temporal increases were observed in injury by low fall, and the greatest increases were observed in the most disadvantaged LGAs.

CONCLUSIONS: These findings can be used to inform injury prevention initiatives, which could be designed to target areas with relatively high injury risk and with significantly increasing injury risk over time. Our finding that the greatest year-on-year increases in injury incidence were observed in the most disadvantaged areas highlights the need for a greater emphasis on reducing inequities in injury.

PMID:35793336 | DOI:10.1371/journal.pone.0266521

Laryngoscope. 2022 Jul 6. doi: 10.1002/lary.30273. Online ahead of print.

ABSTRACT

PURPOSE: The effects of general anesthetics on cognitive impairment are unclear and complicated. Laser laryngeal surgery (LLS) requires the administration of low levels of oxygen, which may increase the risk of desaturation and brain function impairment. This prospective randomized trial aimed to compare the effects of desflurane and propofol-based general anesthesia on the occurrence of early postoperative cognitive decline in elderly patients undergoing LLS.

METHODS: Seventy-three patients classified as American Society of Anesthesiologists grade I or II and at least 65 years of age were randomly allocated to receive either desflurane-based (Group D) or propofol-based (Group P) anesthesia during LLS. The standard anesthesia protocol was performed, with a bispectral index between 40 and 60 and a mean arterial pressure within 20% of baseline values. Intraoperative regional oxygen saturation values were recorded. Each patient was assessed using the mini-mental state examination (MMSE) test during the preoperative period (baseline), 30 min after extubation in the postanesthesia care unit, and 1, 3, and 24 h after surgery.

RESULTS: MMSE scores improved slightly in both groups compared to baseline during the early postoperative period, but these increases were not statistically significant. No significant differences were identified in MMSE scores between groups. Only three patients (9.6%) in group D and one patient (3.1%) in group P developed cognitive impairment (p = 0.583).

CONCLUSION: Low intraoperative inspired oxygen concentration during short-duration LLS did not reduce early postoperative cognitive function in elderly patients. Desflurane or propofol-based anesthesia had similar effects on early neurocognition after LLS.

LEVEL OF EVIDENCE: 2 Laryngoscope, 2022.

PMID:35791905 | DOI:10.1002/lary.30273

J Biopharm Stat. 2022 Jul 6:1-16. doi: 10.1080/10543406.2022.2065502. Online ahead of print.

ABSTRACT

Non-inferiority (NI) clinical trials are widely used to evaluate whether the new experimental treatment is not unacceptably worse than the current active-control treatment by more than a pre-specified non-inferiority margin (NI margin). However, choosing either an absolute difference [risk difference (RD)] or a relative difference [relative risk (RR) and odds ratio (OR)] to evaluate efficacy in NI clinical trials is still controversial. In this study, we aim to evaluate the performance of abovementioned three metrics for testing NI clinical trials with risk rate endpoint. Herein, extensive Monte Carlo simulations based on various parameter settings (NI margin as well as risk rates in the experimental group and active-control group) are conducted to compare the Type I error rate, statistical power, and the necessary sample size to achieve a desired power for testing NI using RD, RR, and OR. We show that testing NI using RD not only controls well the Type I error and achieves the highest statistical power but also requires the smallest sample size compared to RR and OR. In practice, however, the choice among three metrics still needs to be based upon clinical interpretations and regulatory perspectives.

PMID:35791856 | DOI:10.1080/10543406.2022.2065502