pH-responsive i-motif-conjugated nanoparticles for MRI analysis.

Gadolinium (Gd)-based contrast agents (CAs) are widely used to enhance anatomical details in magnetic resonance imaging (MRI). Significant research has expanded the field of CAs into bioresponsive CAs by modulating the signal to image and monitor biochemical processes, such as pH. In this work, we introduce the modular, dynamic actuation mechanism of DNA-based nanostructures as a new way to modulate the MRI signal based on the rotational correlation time, τR. We combined a pH-responsive oligonucleotide (i-motif) and a clinical standard CA (Gd-DOTA) to develop a pH-responsive MRI CA. The i-motif folds into a quadruplex under acidic conditions and was incorporated onto gold nanoparticles (iM-GNP) to achieve increased relaxivity, r1, compared to the unbound i-motif. In vitro, iM-GNP resulted in a significant increase in r1 over a decreasing pH range (7.5-4.5) with a calculated pKa = 5.88 ± 0.01 and a 16.7% change per 0.1 pH unit. In comparison, a control CA with a non-responsive DNA strand (T33-GNP) did not show a significant change in r1 over the same pH range. The iM-GNP was further evaluated in 20% human serum and demonstrated a 28.14 ± 11.2% increase in signal from neutral pH to acidic pH. This approach paves a path for novel programmable, dynamic DNA-based complexes for τR-modulated bioresponsive MRI CAs.

Nucleic acid nanostructures for in vivo applications: The influence of morphology on biological fate.

The development of programmable biomaterials for use in nanofabrication represents a major advance for the future of biomedicine and diagnostics. Recent advances in structural nanotechnology using nucleic acids have resulted in dramatic progress in our understanding of nucleic acid-based nanostructures (NANs) for use in biological applications. As the NANs become more architecturally and functionally diverse to accommodate introduction into living systems, there is a need to understand how critical design features can be controlled to impart desired performance in vivo. In this review, we survey the range of nucleic acid materials utilized as structural building blocks (DNA, RNA, and xenonucleic acids), the diversity of geometries for nanofabrication, and the strategies to functionalize these complexes. We include an assessment of the available and emerging characterization tools used to evaluate the physical, mechanical, physiochemical, and biological properties of NANs in vitro. Finally, the current understanding of the obstacles encountered along the in vivo journey is contextualized to demonstrate how morphological features of NANs influence their biological fates. We envision that this summary will aid researchers in the designing novel NAN morphologies, guide characterization efforts, and design of experiments and spark interdisciplinary collaborations to fuel advancements in programmable platforms for biological applications.

Association of internet gaming disorder to depression, anxiety and stress among Filipino adolescents in selected public high schools in Pasay City / The Health Sciences Journal

Introduction@#This study determined the relationship of personal factors and gaming factors with Internet Gaming Disorder (IGD). It aimed to provide information on the association of IGD with depression, anxiety, stress and both depression and anxiety among adolescent gamers.@*Methods@#This was an analytic cross-sectional study among 560 14-18-year-old adolescents from two public high schools in Pasay City that used the Internet Gaming Disorder Scale–Short-Form (IGDS9-SF), Depression, Anxiety and Stress Scale-21 items (DASS-21) and gamer profile questionnaires.@*Results@#The prevalence of Internet Gaming Disorder (IGD) was low at 1.1%, while moderate depression was observed in 67%, stress in 46.8%, both depression and anxiety in 64.8%, and high anxiety in 89.3% among adolescents. Using multiple logistic regression to control the effects of possible confounders, the association of IGD with depression (OR 0.971, 95% CI 0.085-11.084, p-value .981), anxiety (OR 6.0x107, p-value .999), stress (OR 6.135, 95% CI 0.373-100.991, p-value .204) and both depression and anxiety (OR 1.027, 95% CI 0.089-11.846, p-value .983) were not statistically significant. @*Conclusion@#The odds of depression, anxiety, stress and both depression and anxiety were higher among those with IGD as compared to those without IGD. However, it is not statistically significant. This study recommended further validation of the new IGD definition in the local setting and longitudinal studies with a larger population to determine other factors associated with mental disorders.

Effect of Vitamin D Supplementation in Early Life on Children's Growth and Body Composition: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Vitamin D deficiency during pregnancy or infancy is associated with adverse growth in children. No systematic review has been conducted to summarize available evidence on the effect of vitamin D supplementation in pregnancy and infancy on growth and body composition in children. OBJECTIVE: We aim to summarize the available evidence on the effect of vitamin D supplementation in pregnancy and infancy on child growth and body composition. METHOD: A systematic review and meta-analysis were performed on the effects of vitamin D supplementation during early life on children's growth and body composition (bone, lean and fat). A literature search of randomized controlled trials (RCTs) was conducted to identify relevant studies on the effects of vitamin D supplementation during pregnancy and infancy on children's body composition (bone, lean and fat) in PubMed, EMBASE and Cochrane Library from inception to 31 December 2020. A Cochrane Risk Assessment Tool was used for quality assessment. The comparison was vitamin D supplementation vs. placebo or standard care. Random-effects and fixed-effect meta-analyses were conducted. The effects are presented as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 3960 participants from eleven randomized controlled trials were eligible for inclusion. Vitamin D supplementation during pregnancy was associated with higher triceps skinfold thickness (mm) (MD 0.33, 95% CI, 0.12, 0.54; I2 = 34%) in neonates. Vitamin D supplementation during pregnancy or infancy was associated with significantly increased length for age z-score in infants at 1 year of age (MD 0.29, 95% CI, 0.03, 0.54; I2 = 0%), and was associated with lower body mass index (BMI) (kg/m2) (MD -0.19, 95% CI -0.34, -0.04; I2 = 0%) and body mass index z-score (BMIZ) (MD -0.12, 95% CI -0.21, -0.04; I2 = 0%) in offspring at 3-6 years of age. Vitamin D supplementation during early life was not observed to be associated with children's bone, lean or fat mass. CONCLUSION: Vitamin D supplementation during pregnancy or infancy may be associated with reduced adiposity in childhood. Further large clinical trials of the effects of vitamin D supplementation on childhood body composition are warranted.

A DNA-Based MRI Contrast Agent for Quantitative pH Measurement.

Extracellular pH is important in clinical measurements due to its correlation to cell metabolism and disease progression. In MRI, T1/T2 ratiometric analysis and other methods have been previously applied to quantify pH using conventional pulse sequences. However, for nanoparticle-based approaches, heterogeneity in size and surface functionalization tends toward qualitative rather than quantitative results. To address this limitation, we developed a novel DNA-based MRI contrast agent, pH-DMRCA, which utilizes a highly programmable and reproducible nanostructure. The pH-DMRCA is a dendritic DNA scaffold that is functionalized with a pH-responsive MRI-sensitive construct, Gd(NP-DO3A), at the end of each DNA arm. We first evaluated the r1 and r2 response of our pH-DMRCA over a range of pH values (pH = 5-9) to establish a relaxometric model of pH. These MRI-based assessments of pH were validated in a separate set of samples using a pH electrode (n = 18) and resulted in a good linear correlation (R2 = 0.99, slope = 0.98, intercept = 0). A Bland-Altman analysis of the results also showed reasonable agreement between the calculated pH and measured pH. Moreover, these pH comparisons were consistent across three different pH-DMRCA concentrations, demonstrating concentration-independence of the method. This MRI-based pH quantification methodology was further verified in human blood plasma. Given the versatility of the DNA-based nanostructures, the contrast agent has a potential to be applied to a wide variety of imaging applications where extracellular pH is important including cancer, stroke, cardiovascular disease, and other important diseases.

The Philippine Coronavirus Disease 2019 (COVID-19) profile study: Clinical profile and factors associated with mortality of hospitalized patients

Introduction@#The coronavirus disease 2019 (COVID-19) have spread globally and reached the Philippines in late January 2020. This study is the first local and nationwide research on admitted COVID-19 adult patients: their clinic-demographic profiles, managements, and clinical outcomes. We aim to determine the associated factors with mortality among COVID-19 patients.@*Methods@#This was a retrospective, multicenter, observational cohort study of rt-PCR confirmed and admitted COVID-19 adult patients in 89 hospitals in the Philippines from February to July, 2020. The data on admission of patient’s demographic, clinical, laboratory, pre-hospital and during hospital treatment management and in-hospital clinical outcomes were gathered. The data were described and analyzed using multiple logistic regression analysis.@*Results@#There were 2884 rt-PCR confirmed and admitted COVID-19 adult patients included in the study. Majority were Filipinos (99·4%), with slightly more males (54.4%) than females. 21% were healthcare workers (HCWs). Mortality was higher among non-HCWs at 16% versus 2% among HCWs. 63% of the patients had a co-morbidity, which included hypertension (69%), diabetes mellitus (48%) and chronic kidney disease (26%). The significantly associated factors with mortality in this Philippine cohort were: age >60 years, hypertension as co-morbidity, tachypnea (> 22/minute), WBC count > 10 x 109 /L, and elevated serum lactate dehydrogenase (LDH) (all p<0.05). Elevated serum LDH was the strongest factor associated with mortality (OR of 8.74, p=0.004).@*Conclusion@#This study identified that age, hypertension, tachypnea, elevated WBC count, and elevated serum LDH were associated with mortality among COVID-19 adult patients and results were consistent with results from studies done in other countries. We recommend that early detection and awareness of exposures and symptoms will improve the management and clinical outcomes of COVID-19 adult patients. Also, a long follow-up of the outcomes of COVID-19 to determine the effectiveness of treatment is recommended for further study.

Mycotic aneurysm in pregnancy: A case report / Philippine Journal of Obstetrics and Gynecology

Reported is a case of a 20-year old G2P1 (1001) Pregnancy Uterine 22 weeks age of gestation (AOG), who suffered three episodes of aneurysmal rupture over a period of almost 8 weeks, the last being fatal occurring on the 27th week AOG, despite aggressive antimicrobial treatment, insertion of ventriculo-peritoneal shunt and clinically improving neurologic status. The patient succumbed to subarachnoid hemorrhage resulting from the third aneurysmal rupture. Mycotic aneurysm is a serious and catastrophic clinical condition, more so in a pregnant patient wherein management options are limited in order to preserve pregnancy.This report will discuss the first documented case in the Philippines of mycotic aneurysm in pregnancy secondary to a valvular heart disease, to increase awareness on such cases for timely diagnosis and management.