Protocol for CARES-HAPIN: an ambidirectional cohort study on exposure to environmental tobacco smoke and risk of early childhood caries.

INTRODUCTION: Prenatal and postnatal exposure to environmental tobacco smoke (ETS) has been linked with early childhood caries (ECC), but the specific molecular mechanisms and pathways remain largely unknown. The Caries Risk from exposure to Environmental tobacco Smoke (CARES) within the Household Air Pollution Intervention Network (HAPIN) study aims to establish the association between ETS and ECC by employing epidemiological and novel biomarker-based approaches. Here, we outline the overall design and rationale of the project. METHODS AND ANALYSIS: We will leverage the infrastructure and data from the HAPIN trial (India) to mount the CARES study. In this ambidirectional cohort study, children (n=735, aged: 3-5 years) will undergo ECC examination by a trained dentist using standard criteria and calibrated methods. Structured questionnaires will be used to gather information on sociodemographic variables, dietary habits, oral hygiene, oral health-related quality of life and current exposure to ETS. We will collect non-invasive or minimally invasive biospecimens (i.e., saliva, buccal cells, dried blood spots and urine) from a subset of HAPIN children (n=120) to assess a battery of biomarkers indicative of exposure to ETS, early biological effect and epigenetic modifications. Both self-reported and objective measures of ETS exposure collected longitudinally during in utero and early postnatal periods will be accessed from the HAPIN database. We will apply current science data techniques to assess the association and interrelationships between ETS, ECC, and multiple biomarkers. ETHICS AND DISSEMINATION: Information gathered in this research will be published in peer-reviewed journals and summaries will be shared with the key stakeholders as well as patients and their parents/guardians involved in this study. Sri Ramachandra Institute of Higher Education and Research Ethics Board has approved the study protocol (IEC-NI22/JUL/83/82). TRIAL REGISTRATION NUMBER: NCT02944682.

Exploring combined effects of DNA methylation and copy number on gene expression with a two-stage approach.

DNA methylation and copy number may be associated with each other to some extent, in positive or negative ways. Whether differential methylation and copy number variation have combined effects on gene expression is largely unknown. We use a multivariate linear model to formulate the relationship among the three genomic measurements, gene expression, copy number, and methylation levels. We propose a method that combines a distance covariance measure and the group LASSO to analyze multiple types of genomic data collectively for the purpose of insightfully revealing how gene expression is potentially affected by both copy number variation and differential methylation levels in cellular process. Our approach is of two stages, the first is a variable screening process in which a variable selection method is utilized by employing the concept of joint distance covariance (JdCov) of random vectors, and the second is to implement a penalized regression approach, a group LASSO, on the screened data of much lower dimension. The two-stage approach is tested in extensive simulation studies and shown to be effective. The approach is then applied to the TCGA Melanoma data, which consists of gene expression, methylation and copy number measurements of more than 300 patients and relationship of some genes with methylation and copy number measurements were revealed for the involved subjects.

Sepsis-Induced Myocardial Dysfunction in Pediatric Septic Shock: Prevalence, Predictors, and Outcome-A Prospective Observational Study.

There is a paucity of literature on the prevalence, predictors, prognostic markers, and outcomes of sepsis-induced myocardial dysfunction (SMD) in pediatric septic shock. The objectives of our study were to estimate the prevalence of SMD in pediatric septic shock by point-of-care functional echocardiography (POCFE) and to study the association of SMD with severity of illness, organ dysfunctions, and outcomes. This prospective, observational study was conducted over a period of 1 year (from July 2018 to July 2019) in a 12-bed, tertiary pediatric intensive care unit (PICU) of an academic and referral hospital in South India. Children presenting with septic shock were enrolled in the study. POCFE was done within 6 hours of PICU admission and patients were categorized as having SMD based on POCFE findings. The prevalence of SMD (left ventricle ± right ventricle) was 32% (32/100). More than half of the children (54.5%) died in SMD group, whereas only 7.5% died in non-SMD group ( p < 0.001). SMD was associated with higher organ dysfunctions, worse patient outcomes, and was found to be an independent predictor of mortality. The median lactate levels were higher in SMD group (3.15 [2.7, 5] vs. 2 [1.3, 2.7], p < 0.001) as compared with non-SMD group. We observed significantly lower median lactate clearance at 6 hours in SMD than non-SMD (30.0% [-14.44, 44.22] vs. 59.8% [45.83, 71.43], p < 0.001). Lactate levels at 6 hours with a threshold of 2.4 mmol/L was a good predictor of SMD with sensitivity and specificity of 73 and 80%, respectively. SMD is not an uncommon entity in children with septic shock. SMD was associated with worse patient outcomes, organ dysfunction, and mortality. Serum lactate trends may predict SMD and can be used as prognosticate markers as well.

Anthropometric Growth Reference for Indian Children and Adolescents.

OBJECTIVE: We aimed to develop anthropometric growth references for Indian children and adolescents, based on available 'healthy' child data from multiple national surveys. METHODOLOGY: Data on 'healthy' children, defined by comparable WHO's Multicentre Growth Reference Study (MGRS) selection criteria, were extracted from four Indian surveys over the last 2 decades, viz, NFHS-3, 4, and 5 and Comprehensive National Nutrition Survey (CNNS). Reference distributions of height-for-age for children up to 19 years, weight-for-age for children up to 9y, weight-for-height for children less than 5 years and BMI for age for children between 5-19 y were estimated by GAMLSS with Box-Cox Power Exponential (BCPE) family. The national prevalence of growth faltering was also estimated by the NFHS-5 and CNNS data. RESULTS: The distributions of the new proposed Indian growth references are consistently lower than the WHO global standard, except in the first 6 months of age. Based on these references, growth faltering in Indian children and adolescents reduced > 50% in comparison with the WHO standard. CONCLUSION: The study findings revealed that the WHO one-standard-fits-all approach may lead to inflated estimates of under nutrition in India and could be a driver of misdirected policy and public health expenditure in the Indian context. However, these findings need validation through prospective and focussed studies for more robust evidence base.

Improving adolescents' dietary behavior through teacher-delivered cancer prevention education: a school-based cluster randomized intervention trial in urban Rajasthan.

BACKGROUND: Dietary practices are one of the most common modifiable risk factors for cancers. Foods rich in dietary fibers are considered protective, meanwhile fast & junk foods are risk for common cancers. Adolescence period is marked by habit formation and is thus suited for delivering behavioral intervention. Schools offer an optimal setting for planning and executing these interventions to a large number of adolescents. OBJECTIVE: To assess the effectiveness of a teacher-delivered cancer-prevention education in changing dietary behaviors of school going adolescents. METHODS: A cluster randomized trial was conducted in government secondary and senior secondary schools with schools as clusters. A minimum required sample of 1032 students was estimated from 16 schools with 1:1 allocation in intervention and non-intervention groups. Dietary behaviors were recorded as dichotomous variable. The determinants were recorded as per theory of planned behavior framework using Likert-scale. Two teachers from each intervention school were trained to deliver cancer prevention education with focus on role of dietary behavior. Pre-post training assessment of teachers' knowledge towards common cancers was done using a self-administered questionnaire. Gender adjusted difference-in-difference analysis was done to assess intervention effect on both healthy and unhealthy behaviors. RESULTS: In selected schools all students from classes 8 to 10 were approached and a total of 1224 students were enrolled, of whom 1096 completed the study. The study recorded significant improvement in scores of students from intervention group compared to non-intervention group for their attitude, subjective norms, perceived behavioral control and intention towards consuming healthy and avoiding unhealthy foods. The intervention was effective in significantly improving the proportion of students limiting fried/fast/packed food & sugar sweetened beverages (OR:1.51, 95%CI:1.08,2.12,p:0.017), and consuming fruits & vegetables daily (OR:1.55, 95%CI:1.08,2.22, p:0.017) while adjusting effect of gender. CONCLUSION: Classroom-based cancer prevention education delivered through teachers during regular working hours is effective in improving dietary behaviors and its determinants among adolescent students. Thus, we recommend integrating a section focusing on the role of diet in cancer prevention and other lifestyle diseases in the existing school curriculum. TRIAL REGISTRATION: The trial was registered under Clinical Trial Registry-India with registration number CTRI/2018/12/016586, dated-10/12/2018.

Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

Arginine Surface Density of Nanoparticles Controls Nonendocytic Cell Uptake and Autophagy Induction.

Nonendocytic cell uptake of nanomaterials is challenging, which requires specific surface chemistry and smaller particle size. Earlier works have shown that an arginine-terminated nanoparticle of <10-20 nm size shows nonendocytic uptake via direct membrane penetration. However, the roles of surface arginine density and the arginine-arginine distance at the nanoparticle surface in controlling such nonendocytic uptake mechanism is not yet explored. Here we show that a higher arginine density at the nanoparticle surface with an arginine-arginine distance of <3 nm is the most critical aspect for such nonendocytic uptake. We have used quantum dot (QD)-based nanoparticles as a model for fluorescent tracking inside cells and for quantitative estimation of cellular uptake. We found that arginine-terminated nanoparticles of 10 nm size can opt for the energy-dependent endocytosis pathway if the arginine-arginine distance is >3 nm. In contrast, nanoparticles with <3 nm arginine-arginine distance rapidly enter into the cell via the nonendocytic approach, are freely available in the cytosol in large amounts to capture the cellular adenosine triphosphate (ATP), generate oxidative stress, and induce ATP-deficient cellular autophagy. This work shows that arginine-arginine distance at the nanoparticle surface is another fundamental parameter, along with the particle size, for the nonendocytic cell uptake of foreign materials and to control intracellular activity. This approach may be utilized in designing nanoprobes and nanocarriers with more efficient biomedical performances.

Perfusion Index Variations in Children With Septic Shock: Single-Center Observational Cohort Study in India.

OBJECTIVES: To study in children with septic shock: 1) variation in peripheral perfusion index (PI), which is a derived variable from pulse oximetry; 2) correlation between PI and lactate concentration; and 3) exploratory diagnostic evaluation between mortality and PI. DESIGN: Prospective observational study (from October 2018 to March 2020). SETTING: Pediatric emergency department and PICU of a tertiary hospital in India. PATIENTS: Children (1 mo to 16 yr old) with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data collected included demographic, clinical, laboratory, and outcome-related variables. Hemodynamic variables like heart rate, mean arterial pressure, and PI, along with serum lactate were recorded at specified intervals. A total of 112 children with septic shock were recruited, with median (interquartile range [IQR]) age of 50 (IQR 12,118.5) months and 65 of 112 (58%) were male children. Overall mortality was 25 of 112 (22%). At admission, the median PI was 0.6 (IQR -0.30, 0.93), and we used PI less than or equal to 0.6 to define a "critical PI." Of 61 children with critical PI at admission, 26 of 61 increased above this threshold by 6 hours. We observed a negative correlation between PI and lactate, at admission ( r = -0.27; 95% CI, -0.44 to -0.08; p = 0.006) and at 6 hours ( r = -0.21; 95% CI, -0.39 to -0.02; p = 0.03). In the exploratory analysis, a PI cutoff of less than or equal to 0.6 at 6 hours had area under the receiver operating curve of 0.74 (95% CI, 0.60-0.88). That is, with a 70% sensitivity and 81% specificity for mortality, the performance of such a test in our population (pre-to-post-test probability) for mortality would be 0.22-0.51. CONCLUSIONS: We have used pulse oximetry-derived PI in children presenting with septic shock and found that the value is negatively correlated with a rise in serum lactate concentration. However, the utility of using a critical threshold value in PI (≤ 0.6) after 6 hours of treatment to be indicative of later mortality has considerable uncertainty.

Effect of 3 different disinfection methods on the image quality of photostimulable phosphor plates.

OBJECTIVE: The aim of this study was to assess the effects of 3 disinfection protocols on the quality of images acquired with a photostimulable phosphor (PSP) plate system. STUDY DESIGN: Thirty DIGORA Optime PSP plates were divided into 3 groups of 10. Group 1 was disinfected with 95% ethanol. Group 2 was disinfected using germicidal disposable wipes. Group 3 was disinfected with 95% ethanol, followed by hydrogen peroxide gas sterilization. Images of a quality assurance phantom were acquired on each plate before disinfection (baseline images). Disinfection and imaging cycles were repeated 45 times for each plate. Changes in image quality were assessed between baseline and final images. Image quality was evaluated for dynamic range, spatial resolution, and contrast perceptibility. The Fisher exact test was used to detect statistically significant differences among the 3 disinfection methods relative to decreases in image quality parameters between the baseline and final radiographs. Additionally, for each group, the Z-test was used to detect statistically significant decreases in image quality parameters between baseline and final images. The significance level was established at P < .05. RESULTS: No statistically significant differences were detected among the disinfection groups or relative to baseline values for any group at a 5% significance level. CONCLUSIONS: Hydrogen peroxide gas may be considered to prevent cross-contamination while preserving image quality. Regular quality assurance testing is recommended to maintain image quality over time.

A Fluorescent Carbon Nanoparticle for Photodynamic Cell Therapy via Rapid Non-Endocytic Uptake.

Although photodynamic therapy is a promising approach for cancer treatment, it has limited clinical application due to the poor performance of conventional photosensitizers. In this study, we present a carbon nanoparticle-based photosensitizer for efficient photodynamic cell therapy. The nanoparticles have been synthesized from a steel industry-based waste material, exhibiting strong fluorescence in the visible region, rapidly entering the cell via non-endocytic uptake, and localizing within the mitochondria. Light exposure of nanoparticle-labeled cells offers efficient photodynamic therapy and induces cytotoxicity. Overall, this study highlights the utility of carbon nanoparticles in efficient photodynamic therapy via rapid cellular uptake and subcellular targeting.

Excess Mortality Risk Due to Heat Stress in Different Climatic Zones of India.

India is at a high risk of heat stress-induced health impacts and economic losses owing to its tropical climate, high population density, and inadequate adaptive planning. The health impacts of heat stress across climate zones in India have not been adequately explored. Here, we examine and report the vulnerability to heat stress in India using 42 years (1979-2020) of meteorological data from ERA-5 and developed climate-zone-specific percentile-based human comfort class thresholds. We found that the heat stress is usually 1-4 °C higher on heatwave (HW) days than on nonheatwave (NHW) days. However, the stress on NHW days remains considerable and cannot be neglected. We then showed the association of a newly formulated India heat index (IHI) with daily all-cause mortality in three cities - Delhi (semiarid), Varanasi (humid subtropical), and Chennai (tropical wet and dry), using a semiparametric quasi-Poisson regression model, adjusted for nonlinear confounding effects of time and PM2.5. The all-cause mortality risk was enhanced by 8.1% (95% confidence interval, CI: 6.0-10.3), 5.9% (4.6-7.2), and 8.0% (1.7-14.2) during "sweltering" days in Varanasi, Delhi, and Chennai, respectively, relative to "comfortable" days. Across four age groups, the impact was more severe in Varanasi (ranging from a 3.2 to 7.5% increase in mortality risk for a unit rise in IHI) than in Delhi (2.6-4.2% higher risk) and Chennai (0.9-5.7% higher risk). We observed a 3-6 days lag effect of heat stress on mortality in these cities. Our results reveal heterogeneity in heat stress impact across diverse climate zones in India and call for developing an early warning system keeping in mind these regional variations.

Cumulative effect of PM2.5 components is larger than the effect of PM2.5 mass on child health in India.

While studies on ambient fine particulate matter (PM2.5) exposure effect on child health are available, the differential effects, if any, of exposure to PM2.5 species are unexplored in lower and middle-income countries. Using multiple logistic regression, we showed that for every 10 µg m-3 increase in PM2.5 exposure, anaemia, acute respiratory infection, and low birth weight prevalence increase by 10% (95% uncertainty interval, UI: 9-11), 11% (8-13), and 5% (4-6), respectively, among children in India. NO3-, elemental carbon, and NH4+ were more associated with the three health outcomes than other PM2.5 species. We found that the total PM2.5 mass as a surrogate marker for air pollution exposure could substantially underestimate the true composite impact of different components of PM2.5. Our findings provide key indigenous evidence to prioritize control strategies for reducing exposure to more toxic species for greater child health benefits in India.

Intake of ultra-processed food, dietary diversity and the risk of nutritional inadequacy among adults in India.

OBJECTIVE: This study assessed diet diversity and consumption of ultra-processed foods and explored its impact on macronutrient intake and risk of micronutrient inadequacy. DESIGN: Cross-sectional, non-probability snowball sampling. SETTING: Nutrient intake was assessed using 24-h dietary recall method and diet diversity through FAO-diet diversity score (DDS). Mann-Whitney U test was used to assess differences in risk of inadequacy across gender. Spearman's rank correlation assessed associations between energy contributed by ultra-processed food and risk of nutrient inadequacy. PARTICIPANTS: A total of 589 adults (20-40 years) belonging to upper-middle and high-income groups. RESULTS: The average individual DDS was 4·4 ± 0·6. Most of the participants (>80 %) had intakes less than national recommendations of pulses/eggs/flesh foods, milk/milk products, fruits, vegetables and nuts. Ultra-processed foods contributed to 17 % of total energy intake, 12 % of protein, 17 % of carbohydrate, 29 % of added sugar, 20 % of total fat and 33 % of Na intake. The average risk of nutrient inadequacies for Zn (98 % v. 75 %), folate (67 % v. 22 %) and niacin (83 % v. 44 %) was higher among males than females (P < 0·001). The average risk of nutrient inadequacies for Fe (58 % v. 7 %), vitamin B6 (95 % v. 90 %) and vitamin A (68 % v. 44 %) was higher among females than males (P < 0·001). There was a positive correlation between energy contributed by ultra-processed food and risk of niacin (ρ = 0·136, P = 0·001) and folate (ρ = 0·089, P = 0·049) inadequacy. CONCLUSION: Reformulating ultra-processed food to reduce fat, sugar and salt and increase micronutrients and behaviour change communication strategies that promote dietary diversity will improve micronutrient adequacy and diet quality.

Haemoglobin diagnostic cut-offs for anaemia in Indian women of reproductive age.

BACKGROUND: The persistent high prevalence of anaemia among Indian women of reproductive age (WRA) despite aggressive long-term iron supplementation could be related to over-diagnosis from an inappropriately high haemoglobin (Hb) diagnostic cut-off. To develop an appropriate cut-off for Indian WRA, we hypothesized that during iron-folic acid (IFA) supplementation to a mixed (anaemic/non-anaemic) WRA population, the positive slope of the Hb-plasma ferritin (PF) response in anaemic women would inflect into a plateau (zero-response) as a non-anaemic status is reached. The 2.5th percentile of the Hb distribution at this inflection point will be the diagnostic Hb cut-off for iron-responsive anaemia. METHOD: A hierarchical mixed effects model, with a polynomial mean and variance model to account for intraclass correlation due to repeated measures, was used to estimate the response curve of Hb to PF, or body iron stores, in anaemic and non-anaemic WRA (without inflammation), who were receiving a 90-day IFA supplementation. RESULTS: The Hb response curve at low PF values showed a steep increase, which inflected into a plateau at a PF of 10.1 µg/L and attained a steady state at a PF of 20.6 µg/L. The Hb distribution at the inflection was a normal probability distribution, with a mean of 12.3 g/dL. The 2.5th percentile value of this distribution, or the putative diagnostic Hb cut-off for anaemia, was 10.8 g/dL (~11 g/dL). CONCLUSION: The derived Hb cut-off is lower than the current adult values of 12 g/dL and could partly explain the persistently high prevalence of anaemia.

Customization of WHO Under-five Growth Standards for an Appropriate Quantification of Public Health Burden of Growth Faltering in India.

OBJECTIVE: To examine the accuracy of World Health Organization (WHO) growth standard in under-5 year Indian children, and identify a method to contextualize the WHO standard for India. PARTICIPANTS: Data of Healthy children, defined by WHO selection criteria, extracted from nationally representative Indian surveys (National Family Health Surveys, NFHS-3, NFHS-4, NFHS-5 and Comprehensive National Nutrition Survey, CNNS). DESIGN: Height for age z score (HAZ) and weight for age z score (WAZ) and weight for height z score (WHZ) distributions in healthy sample were compared against the standard normal. If deviant, age-specific correction factors for z scores were estimated by hierarchical linear mixed effects mean and variance polynomial models. A new term, excess mean risk of growth faltering (EMRGF), was introduced to describe growth faltering. MAIN OUTCOME: Measure of deviation of HAZ, WAZ and WHZ from standard normal distribution. Correction of WHO growth standards for India leading to accurate prevalence of stunting, underweight and wasting in Indian children using NFHS-5 data. RESULTS: Data on 10,384 healthy under-5 year children were extracted, of which 5377 were boys. Across surveys and metrics, the mean z scores were significantly lower than zero (-0.52 to -0.79). HAZ and WHZ variability (1.16, 1.07) were significantly higher than 1. Derived age-specific corrections reduced the NFHS-5 prevalence of growth faltering by 50%. The national EMRGF (after applying the age-specific correction) for height for age was 15.5% (95%CI:15.3-15.8), and weight for age was 15.0% (95%CI:14.8-15.3), respectively, in NFHS-5. CONCLUSION: The WHO growth standards need contextual customization for accurate estimation of the burden of growth faltering in under-5 year children in India. When corrected, the burden of growth faltering is lower, by half or more, in all the three indices.

Prevalence of Vitamin B12 and Folate Deficiencies in Indian Children and Adolescents.

Deficiencies of vitamin B12 (B12) and folate (FA) are of particular interest due to their pleiotropic role in 1-carbon metabolism. In addition to adverse birth outcomes, deficiencies of B12 and FA, or an imbalance in FA/B12 status, are linked to metabolic disorders. Indian diets that are predominantly plant food-based could be deficient in these vitamins, but there are no national estimates of the prevalence of B12 and FA deficiency in Indian children and adolescents, nor their associations with age, sex and growth indicators. The recent Comprehensive National Nutrition Survey (CNNS-2016-18) provided estimates of the prevalence of B12 and FA deficiency at the national and state levels among preschool (1-4 years: 9976 and 11,004 children, respectively), school-age children (5-9 years: 12,156 and 14,125) and adolescents (10-19 years: 11,748 and 13,621). Serum B12 and erythrocyte FA were measured by the direct chemiluminescence method and their deficiency was defined using WHO cut-offs. The prevalence of B12 and FA deficiency was high among adolescents (31.0%, CI: 28.7-33.5 and 35.6%, CI: 33.1-8.2) compared to school-age (17.3%, CI: 15.4-19.3 and 27.6%, CI: 25.5-29.9) and preschool children (13.8%, CI: 11.7-16.2 and 22.8%, CI: 20.5-25.2, respectively). The prevalence of both B12 and FA deficiency was significantly higher by 8% and 5%, respectively, in adolescent boys compared to girls. There was no association between anthropometric undernutrition and B12 and FA deficiency. There was wide regional variation in the prevalence of B12 and FA deficiency, but no rural-urban differences were observed across all age groups. The national prevalence of B12 deficiency among preschool or school-age children was <20% (the cut-off that indicates a public health problem). However, FA deficiency in these age groups and both FA and B12 deficiencies in adolescents were >20%, warranting further investigation.

Rapid Mitochondria Targeting by Arginine-Terminated, Sub-10 nm Nanoprobe via Direct Cell Membrane Penetration.

Although mitochondria have been identified as a potential therapeutic target for the treatment of various diseases, inefficient drug targeting to mitochondria is a major limitation for related therapeutic applications. In the current approach, drug loaded nanoscale carriers are used for mitochondria targeting via endocytic uptake. However, these approaches show poor therapeutic performance due to inefficient drug delivery to mitochondria. Here, we report a designed nanoprobe that can enter the cell via a nonendocytic approach and label mitochondria within 1 h. The designed nanoprobe is <10 nm in size and terminated with arginine/guanidinium that offers direct membrane penetration followed by mitochondria targeting. We found five specific criteria that need to be adjusted in a nanoscale material for mitochondria targeting via the nonendocytic approach. They include <10 nm size, functionalization with arginine/guanidinium, cationic surface charge, colloidal stability, and low cytotoxicity. The proposed design can be adapted for mitochondria delivery of drugs for efficient therapeutic performance.

Routine Diaper Change Alters Kidney Oxygenation in Premature Infants: A Non-A Priori Analysis.

BACKGROUND: Reduction in oxygen delivery to developing kidneys of premature infants may be an important source for acute kidney injury in premature infants. PURPOSE: To describe changes in continuous kidney oxygenation (RrSO 2 ) measures before, during, and after routine diaper changes. METHODS: Non-a priori analysis of a prospective cohort that received continuous measurement of RrSO 2 with near-infrared spectroscopy (NIRS) over the first 14 days of life demonstrating acute RrSO 2 drops surrounding diaper changes. RESULTS: In total, 26 of 38 (68%) infants (≤1800 g) from our cohort exhibited acute drops in RrSO 2 that temporally correlated with diaper changes. Mean (SD) RrSO 2 baseline prior to each diaper change event was 71.1 (13.2), dropped to 59.3 (11.6) during diaper change, and recovered to 73.3 (13.2). There was a significant difference between means when comparing baseline to diaper change ( P < .001; 95% CI, 9.9 to 13.8) and diaper change to recovery ( P < .001; 95% CI, -16.9 to -11.2). The mean decrease in RrSO 2 during diaper change averaged 12 points (17%) below 15-minute RrSO 2 mean prior to diaper change, with quick recovery to prediaper change levels. No decreases in SpO 2 , blood pressure, or heart rate were documented during the intermittent kidney hypoxic events. IMPLICATIONS FOR PRACTICE AND RESEARCH: Routine diaper changes in preterm infants may increase the risk for acute reductions in RrSO 2 as measured by NIRS; however, the impact on kidney health remains unknown. Larger prospective cohort studies assessing kidney function and outcomes related to this phenomenon are needed.