Category: Nevin Manimala

J Dent. 2021 May 30:103708. doi: 10.1016/j.jdent.2021.103708. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the effect of rapid high-intensity light-curing on the marginal integrity of four bulk-fill composites, including two materials specifically designed for high-intensity curing.

METHODS: Class V cavities were prepared on buccal surfaces of intact human molars with simulated pulpal pressure, filled in a single increment and light-cured using a conventional (10 s @ 1,340 mW/cm²) or high-intensity (3 s @ 3,440 mW/cm²) protocol. The restorations were subjected to thermo-mechanical loading (TML) comprising 1,200,000 mechanical loading cycles and 3,000 thermocycles. Quantitative margin analysis was performed before and after TML using a scanning electron microscope, and the marginal integrity was expressed as percentage of continuous margin (PCM).

RESULTS: All PCM values measured before TML were statistically similar regardless of the material and curing protocol (p>0.05). A statistically significant effect of the curing protocol (p=0.021) was identified only after TML for one material. PCM was significantly diminished by TML (p<0.001) for most combinations of material and curing protocol. The PCM values of the sculptable composites after TML were statistically similar regardless of the curing protocol (p>0.05). Compared to these values, significantly lower PCM after TML was identified for the flowable composites cured with the high-intensity protocol (p=0.001-0.045).

CONCLUSION: In most cases, high-intensity and conventional curing generally led to similar marginal integrity. Although all of the investigated composites initially performed similarly well, the flowable composites light-cured using the high-intensity protocol showed a significantly inferior marginal integrity compared to the sculptable composites after loading.

CLINICAL SIGNIFICANCE: Rapid high-intensity light-curing cannot be recommended for flowable bulk-fill composites since it may compromise the tooth-restoration interface.

PMID:34077801 | DOI:10.1016/j.jdent.2021.103708

Am J Hum Genet. 2021 May 25:S0002-9297(21)00189-0. doi: 10.1016/j.ajhg.2021.05.005. Online ahead of print.

ABSTRACT

Cupping of the optic nerve head, a highly heritable trait, is a hallmark of glaucomatous optic neuropathy. Two key parameters are vertical cup-to-disc ratio (VCDR) and vertical disc diameter (VDD). However, manual assessment often suffers from poor accuracy and is time intensive. Here, we show convolutional neural network models can accurately estimate VCDR and VDD for 282,100 images from both UK Biobank and an independent study (Canadian Longitudinal Study on Aging), enabling cross-ancestry epidemiological studies and new genetic discovery for these optic nerve head parameters. Using the AI approach, we perform a systematic comparison of the distribution of VCDR and VDD and compare these with intraocular pressure and glaucoma diagnoses across various genetically determined ancestries, which provides an explanation for the high rates of normal tension glaucoma in East Asia. We then used the large number of AI gradings to conduct a more powerful genome-wide association study (GWAS) of optic nerve head parameters. Using the AI-based gradings increased estimates of heritability by ∼50% for VCDR and VDD. Our GWAS identified more than 200 loci associated with both VCDR and VDD (double the number of loci from previous studies) and uncovered dozens of biological pathways; many of the loci we discovered also confer risk for glaucoma.

PMID:34077762 | DOI:10.1016/j.ajhg.2021.05.005

Can J Cardiol. 2021 May 30:S0828-282X(21)00285-3. doi: 10.1016/j.cjca.2021.05.009. Online ahead of print.

ABSTRACT

The COVID-19 crisis led to a flurry of clinical trials activity. The COVID-Evidence database shows 2,814 COVID-19 randomized trials registered as of February 16, 2021. Most were small (only 18% have a planned sample size >500) and the rare completed ones have not provided published results promptly (only 283 trial publications as of 2/2021). Small randomized trials and observational, non-randomized analyses have not had a successful track record and have generated misleading expectations. Different large trials on the same intervention have generally been far more efficient in producing timely and consistent evidence. The rapid generation of evidence and accelerated dissemination of results have led to new challenges for systematic reviews and meta-analyses (e.g. rapid, living, and scoping reviews). Pressure to regulatory agencies has also mounted with massive emergency authorizations, but some of them have had to be revoked. Pandemic circumstances have disrupted the way trials are conducted; therefore, new methods have been developed and adopted more widely to facilitate recruitment, consent, and overall trial conduct. Based on the COVID-19 experience and its challenges, planning of several large, efficient trials, and wider use of adaptive designs may change the future of clinical research. Pragmatism, integration in clinical care, efficient administration, promotion of collaborative structures, and enhanced integration of existing data and facilities may be several of the legacies of COVID-19 on future randomized trials.

PMID:34077789 | DOI:10.1016/j.cjca.2021.05.009

Acta Paediatr. 2021 Jun 2. doi: 10.1111/apa.15964. Online ahead of print.

ABSTRACT

AIM: Malnutrition is a major public health issue that has been associated with high susceptibility for impaired brain development and mental functioning. However, to date studies on this topic have not been collated and appraised. This systematic review and meta-analysis investigated the association between malnutrition and cognitive development.

METHODS: We searched the MEDLINE, Scopus, CINAHL, Embase PsycINFO and Cochrane Library databases in English up to 8 December 2020. All studies reporting an association between nutritional status and cognitive development were included. P values of less than 0.05 were considered statistically significant and the results are reported as standardised mean differences (SMD), 95% confidence intervals (95%) and I² statistics.

RESULTS: We included 12 studies comprising 7,607 participants aged 1 to 12 years. Children with malnutrition had worse scores than controls for the Wechsler Intelligence Scale (SMD -0.40; 95% CI -0.60 to -0.20; p<0.0001; I² 77.1%), the Raven’s Coloured Progressive Matrices (SMD -3.75; 95% CI -5.68 to -1.83; p<0.0001; I² 99.2%), visual processing (SMD -0.85; 95% CI -1.23 to -0.46; p 0.009; I² 11.0%) and short memory (SMD 0.85; 95% CI -1.21 to -0.49; p<0.0001; I² 0%) tests.

CONCLUSION: Normal cognitive development requires access to good and safe nutrition.

PMID:34077582 | DOI:10.1111/apa.15964

Plant Biotechnol J. 2021 Jun 2. doi: 10.1111/pbi.13645. Online ahead of print.

ABSTRACT

Starch is the most abundant storage carbohydrate in maize kernels and provides calories for humans and other animals as well as raw materials for various industrial applications. Decoding of the genetic basis of natural variation in kernel starch content is needed to manipulate starch quantity and quality via molecular breeding to meet future needs. Here, we identified 50 unique single quantitative trait loci (QTLs) for starch content with 18 novel QTLs via single linkage mapping, joint linkage mapping, and a genome-wide association study in a multi-parent population containing six recombinant inbred line populations. Only five QTLs explained over 10% of phenotypic variation in single populations. In addition to a few large-effect and many small-effect additive QTLs, limited pairs of epistatic QTLs also contributed to the genetic basis of the variation in kernel starch content. A regional association study identified five non-starch-pathway genes that were the causal candidate genes underlying the identified QTLs for starch content. The pathway-driven analysis identified ZmTPS9, which encodes a trehalose-6-phosphate synthase in the trehalose pathway, as the causal gene for the QTL qSTA4-2, which was detected by all three statistical analyses. Knockout of ZmTPS9 increased kernel starch content and, in turn, kernel weight in maize, suggesting potential applications for ZmTPS9 in maize starch and yield improvement. These findings extend our knowledge about the genetic basis of starch content in maize kernels and provide valuable information for maize genetic improvement of starch quantity and quality.

PMID:34077617 | DOI:10.1111/pbi.13645

Ann Bot. 2021 Jun 2:mcab065. doi: 10.1093/aob/mcab065. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Secondary metabolites are integral to multiple key plant processes: growth regulation, pollinator attraction, interactions with conspecifics, competitors and symbionts, yet their role in plant adaptation remains an underexplored area of research. Carnivorous plants use secondary metabolites to acquire nutrients from prey, but the extent of the role of secondary metabolites in plant carnivory is not known. We aimed to determine the extent of the role of secondary metabolites in facilitating carnivory of the Cape sundew, Drosera capensis.

METHODS: We conducted metabolomic analysis of 72 plants in a time-series experiment before and after simulated prey capture. We used UHPLC-MS/MS and retention time index to identify compounds in the leaf trap tissue which changed up to 72 hrs following simulated prey capture. We identified associated metabolic pathways, and cross-compared these compounds to metabolites previously known to be involved in carnivorous plants across taxa.

KEY RESULTS: For the first time in a carnivorous plant, we have profiled the whole-leaf metabolome response to prey capture. Reliance on secondary plant metabolites was higher than previously thought-2383 out of 3257 compounds in fed leaves had statistically significant concentration changes in comparison to unfed controls. Of these, ~34 compounds are also associated with carnivory in other species; 11 are unique to Nepenthales. At least 20 compounds had 10-fold changes in concentration, 12 of which had 30-fold changes and are typically associated with defence or attraction in non-carnivorous plants.

CONCLUSIONS: Secondary plant metabolites are utilised in plant carnivory to an extent greater than previously thought-we found a whole metabolome response to prey capture. Plant carnivory, at the metabolic level, likely evolved from at least two distinct functions-attraction and defence. Findings of this study support the hypothesis that secondary metabolites play an important role in plant diversification and adaptation to new environments.

PMID:34077503 | DOI:10.1093/aob/mcab065

Int J Gynaecol Obstet. 2021 Jun 2. doi: 10.1002/ijgo.13775. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study is to assess the effect of cesarean section (CS) timing, elective versus unplanned, on the residual myometrial thickness (RMT) and CS scars.

METHODS: This is a prospective single-blinded observational cohort study with 186 observations. Patients indicated to undergo first singleton CS were preoperatively recruited. Exclusion criteria are history of repeated CS, vertical hysterotomy, diabetes and additional uterine surgeries. Sonographic examination was performed for assessing the RMT ratio, the presence of a niche, fibrosis, and the distance from the scar to the internal os (SO) one year after CS. Power analysis was performed with 0.05 α, 0.1 β, and all statistical analysis was conducted with Stata^® .

RESULTS: Wilcoxon rank-sum test for the association between CS timing, RMT ratio and SO showed -0.59 and -4.94 Z values (0.553, <0.001 p-values) respectively. There was no association between CS timing and niches and fibrosis (>0.99, 0.268 p-values). Linear regression between SO and the extent of cervical dilatation showed a -0.45 β (95% CI: -0.68 to -0.21) and a 10.22 mm intercept (< 0.001 p-value).

CONCLUSION: RMT is independent of the timing of cesarean section, but the SO distance shows a negative linear relationship with the cervical dilatation.

PMID:34077556 | DOI:10.1002/ijgo.13775

Int J Gynaecol Obstet. 2021 Jun 2. doi: 10.1002/ijgo.13777. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the indirect impact of the COVID-19 pandemic on patterns of pregnancy-related venous thromboembolism (VTE) events, mediated by population mobility restrictions during lockdown periods.

METHODS: Pregnancy-related VTE hospitalizations were identified through a code-targeted search of the Hadassah Medical Center’s computerized database. A manual analysis of relevant medical records was performed, and cases diagnosed throughout the year 2020 were compared to those diagnosed during 2019 and 2018. Statistical analyses studied obstetrical outcomes, as well as the extent and treatment of VTE events during the COVID-19 pandemic compared to those of preceding years, stratified by pre-, intra-, and post-lockdown periods.

RESULTS: The incidence of pregnancy-related thromboembolic events during 2020 was 0.16% of all deliveries, significantly higher than in 2018 and 2019 (0.06% and 0.1%, respectively; P<0.05). Higher rates of VTE events were found during post-lockdown periods in 2020, compared with corresponding time periods in 2019 and 2018.

CONCLUSION: The present data suggest that lockdown periods impact pregnancy-related VTE hospitalizations, possibly as a result of restricted population mobility. Increased awareness of this undesirable outcome may aid health policymakers in the continuing struggle with epidemics.

PMID:34077561 | DOI:10.1002/ijgo.13777

Am J Health Syst Pharm. 2021 Jun 2:zxab232. doi: 10.1093/ajhp/zxab232. Online ahead of print.

ABSTRACT

PURPOSE: Our aim was to review key methodological concepts and provide a practical guide to employing mixed methods research to enhance pharmacy practice research.

SUMMARY: Mixed methods research provides multiple organized analytic perspectives to thoroughly investigate complex social and scientific problems in a methodologically rigorous manner. This research design incorporates collection and analysis of both qualitative and quantitative data components to create a thorough understanding of a complex question. The 5 most commonly identified reasons for conducting mixed methods research include triangulation, complementarity, development, initiation, and expansion of results. For research questions that benefit from mixed methods research, we review how to structure the study, including timing, sequencing, and prioritization of methods. Illustrative examples from the literature highlight the utility of this methodology for clinical and operational pharmacy research questions.

CONCLUSION: Mixed methods designs can enhance pharmacy research inquiry, provide a means to understand complicated issues, and uncover optimal interventions.

PMID:34077491 | DOI:10.1093/ajhp/zxab232

JAMA. 2021 Jun 2. doi: 10.1001/jama.2021.6530. Online ahead of print.

ABSTRACT

IMPORTANCE: Continuous glucose monitoring (CGM) is recommended for patients with type 1 diabetes; observational evidence for CGM in patients with insulin-treated type 2 diabetes is lacking.

OBJECTIVE: To estimate clinical outcomes of real-time CGM initiation.

DESIGN, SETTING, AND PARTICIPANTS: Exploratory retrospective cohort study of changes in outcomes associated with real-time CGM initiation, estimated using a difference-in-differences analysis. A total of 41 753 participants with insulin-treated diabetes (5673 type 1; 36 080 type 2) receiving care from a Northern California integrated health care delivery system (2014-2019), being treated with insulin, self-monitoring their blood glucose levels, and having no prior CGM use were included.

EXPOSURES: Initiation vs noninitiation of real-time CGM (reference group).

MAIN OUTCOMES AND MEASURES: Ten end points measured during the 12 months before and 12 months after baseline: hemoglobin A1c (HbA1c); hypoglycemia (emergency department or hospital utilization); hyperglycemia (emergency department or hospital utilization); HbA1c levels lower than 7%, lower than 8%, and higher than 9%; 1 emergency department encounter or more for any reason; 1 hospitalization or more for any reason; and number of outpatient visits and telephone visits.

RESULTS: The real-time CGM initiators included 3806 patients (mean age, 42.4 years [SD, 19.9 years]; 51% female; 91% type 1, 9% type 2); the noninitiators included 37 947 patients (mean age, 63.4 years [SD, 13.4 years]; 49% female; 6% type 1, 94% type 2). The prebaseline mean HbA1c was lower among real-time CGM initiators than among noninitiators, but real-time CGM initiators had higher prebaseline rates of hypoglycemia and hyperglycemia. Mean HbA1c declined among real-time CGM initiators from 8.17% to 7.76% and from 8.28% to 8.19% among noninitiators (adjusted difference-in-differences estimate, -0.40%; 95% CI, -0.48% to -0.32%; P < .001). Hypoglycemia rates declined among real-time CGM initiators from 5.1% to 3.0% and increased among noninitiators from 1.9% to 2.3% (difference-in-differences estimate, -2.7%; 95% CI, -4.4% to -1.1%; P = .001). There were also statistically significant differences in the adjusted net changes in the proportion of patients with HbA1c lower than 7% (adjusted difference-in-differences estimate, 9.6%; 95% CI, 7.1% to 12.2%; P < .001), lower than 8% (adjusted difference-in-differences estimate, 13.1%; 95% CI, 10.2% to 16.1%; P < .001), and higher than 9% (adjusted difference-in-differences estimate, -7.1%; 95% CI, -9.5% to -4.6%; P < .001) and in the number of outpatient visits (adjusted difference-in-differences estimate, -0.4; 95% CI, -0.6 to -0.2; P < .001) and telephone visits (adjusted difference-in-differences estimate, 1.1; 95% CI, 0.8 to 1.4; P < .001). Initiation of real-time CGM was not associated with statistically significant changes in rates of hyperglycemia, emergency department visits for any reason, or hospitalizations for any reason.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, insulin-treated patients with diabetes selected by physicians for real-time continuous glucose monitoring compared with noninitiators had significant improvements in hemoglobin A1c and reductions in emergency department visits and hospitalizations for hypoglycemia, but no significant change in emergency department visits or hospitalizations for hyperglycemia or for any reason. Because of the observational study design, findings may have been susceptible to selection bias.

PMID:34077502 | DOI:10.1001/jama.2021.6530