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ObjectivePreterm infants frequently receive red cell transfusions; however, the effect of transfusions on cognition is unclear. We evaluated the relationship between transfusions and cognitive outcomes in preterm infants enrolled in a randomized trial of erythropoiesis stimulating agents (ESAs).Study designPreterm infants were randomized to ESAs or placebo during initial hospitalization, and transfusions recorded. Children were evaluated using standard developmental tests of cognition at 18–22 months (56 ESA, 24 placebo) and 3.5–4 years (39 ESA, 14 placebo).ResultsCognitive scores at 18–22 months were inversely correlated with transfusion volume (p = 0.02). Among those receiving ≥1 transfusion, cognitive scores were significantly higher in the ESA-treated group (p = 0.003). At 3.5–4 years, transfusions were not correlated with cognitive scores.ConclusionsIn the placebo group, transfused children had lower cognitive scores than did non-transfused children at 18–22 months. In the ESA group, cognitive scores did not differ by transfusion status, suggesting ESAs might provide neuroprotection.

A variant of the toll-like receptor 3 (TLR3) provides protection against geographic atrophy, or “dry” age-related macular degeneration, and reduces apoptosis of cultured retinal pigment epithelial cells on exposure to TLR3 ligand. Because double-stranded RNA is a ligand of TLR3, this finding gives rise to the hypothesis that viral infection causes this disease and to concerns about therapeutic intraocular injection of short interfering RNA. A variant of the toll-like receptor 3 (TLR3) provides protection against geographic atrophy, or “dry” age-related macular degeneration, and reduces apoptosis of cultured retinal pigment epithelial cells on exposure to TLR3 ligand. Age-related macular degeneration is the leading cause of irreversible blindness in the developed world. The disease is broadly classified according to its severity and likelihood of progression. The hallmark of the condition is the presence of drusen, or deposits in the macula (central retina). When the drusen are confluent and “soft” in appearance, the affected person is considered to have early-to-intermediate age-related macular degeneration, even though vision is usually unaffected. The greater the number and size of the drusen, the greater the risk of progression to either form of advanced age-related macular degeneration: extensive atrophy of the retinal pigment epithelium . . .

ObjectiveOur hypothesis was that among infants with hypoxic-ischemic encephalopathy (HIE), venoarterial (VA), compared to venovenous (VV), extracorporeal membrane oxygenation (ECMO) is associated with an increased risk of mortality or intracranial hemorrhage (ICH).Design/methodsRetrospective cohort analysis of infants in the Children’s Hospitals Neonatal Database from 2010 to 2016 with moderate or severe HIE, gestational age ≥36 weeks, and ECMO initiation <7 days of age. The primary outcome was mortality or ICH.ResultsSevere HIE was more common in the VA ECMO group (n = 57), compared to the VV ECMO group (n = 53) (47.4% vs. 26.4%, P = 0.02). VA ECMO was associated with a significantly higher risk of death or ICH [57.9% vs. 34.0%, aOR 2.39 (1.08–5.28)] and mortality [31.6% vs. 11.3%, aOR 3.06 (1.08–8.68)], after adjusting for HIE severity.ConclusionsIn HIE, VA ECMO was associated with a higher incidence of mortality or ICH. VV ECMO may be beneficial in this population.

Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. However, the precise gene(s) and genetic variant(s) involved remain largely unknown. Erythropoietin (EPO) is a potent angiogenic factor observed in the diabetic human and mouse eye. By a combination of case-control association and functional studies, we demonstrate that the T allele of SNP rs1617640 in the promoter of the EPO gene is significantly associated with PDR and ESRD in three European-American cohorts [Utah: P = 1.91 x 10⁻³; Genetics of Kidneys in Diabetes (GoKinD) Study: P = 2.66 x 10⁻⁸; and Boston: P = 2.1 x 10⁻²]. The EPO concentration in human vitreous body was 7.5-fold higher in normal subjects with the TT risk genotype than in those with the GG genotype. Computational analysis suggests that the risk allele (T) of rs1617640 creates a matrix match with the EVI1/MEL1 or AP1 binding site, accounting for an observed 25-fold enhancement of luciferase reporter expression as compared with the G allele. These results suggest that rs1617640 in the EPO promoter is significantly associated with PDR and ESRD. This study identifies a disease risk-associated gene and potential pathway mediating severe diabetic microvascular complications.

Soil organic carbon (SOC) up to 1 m depth originates from contemporary vegetation cover dating from past millennia. Deforestation and reforestation with economically important species is influencing soil carbon sequestration. An attempt has been made in this study to evaluate the impact of vegetation cover change (due to replacement of natural heterogeneous cover by teak and bamboo) on SOC using carbon isotopes (δ 13 C, 14 C) in a tropical system (India). A litter decomposition study was carried out to understand the impact of differences in vegetation characteristics (specifically of leaves) on decomposition. Both experiments were carried out to look at the impact of changes in vegetation characteristics (specifically of leaves) on litter decomposition, and how these influence near term litter decomposition rates ( k values) and long-term SOC content of the soil system beneath. Leaves of teak, bamboo and eight other species were selected for this study. The proportion of structural carbohydrates (lignin and cellulose) in leaves significantly (at 5 % level) influenced k values. The SOC and carbon isotope data collected in this study indicate that C 3 vegetation cover in the study area could be contemporary and dominant for the past few centuries. This can be extended up to ~2,200 years from the recorded 14 C values of teak cover. The study confirms that k values of leaf litter influence SOC present beneath the vegetation cover at the decadal/century time scale.

Background In premature children, erythropoiesis-stimulating agents (ESAs) may improve developmental outcome. It is not clear which of the several potential mechanisms are responsible for this improvement. High-resolution MRI and diffusion tensor imaging characterize brain structure and white matter organization, offering possible insight into the long-term effect of ESAs on brain development. Methods MRI scans were performed at 3.5–4 years of age on former preterm infants treated with ESAs or placebo, and on healthy term controls. Mean cortical thickness, surface area, and fractional anisotropy (FA) were compared across study groups, and were correlated with general IQ measures. Results Univariate analysis found no significant effect of ESAs on cortical thickness ( P =0.366), surface area ( P =0.940), or FA ( P =0.150); however, there was a greater increase in FA among ESA-treated girls. Group analysis found significant correlations between FA and Full-Scale IQ ( P =0.044) and Verbal IQ ( P =0.036), although there was no significant relationship between Full-Scale IQ and FA among just the preterm children. Conclusion ESA treatment may have a preferential effect on white matter development in girls, although factors other than just whole-brain FA are involved in mediating cognitive outcome.

Importance Intercenter variation exists in the management of hypoxic-ischemic encephalopathy (HIE). It is unclear whether increased resource utilization translates into improved neurodevelopmental outcomes. Objective To determine if higher resource utilization during the first 4 days of age, quantified by hospital costs, is associated with survival without neurodevelopmental impairment (NDI) among infants with HIE. Design, Setting, and Participants Retrospective cohort analysis of neonates with HIE who underwent therapeutic hypothermia (TH) at US children’s hospitals participating in the Children’s Hospitals Neonatal Database between 2010 and 2016. Data were analyzed from December 2021 to December 2022. Exposures Infants who survived to 4 days of age and had neurodevelopmental outcomes assessed at greater than 11 months of age were divided into 2 groups: (1) death or NDI and (2) survived without NDI. Resource utilization was defined as costs of hospitalization including neonatal neurocritical care (NNCC). Data were linked with Pediatric Health Information Systems to quantify standardized costs by terciles. Main Outcomes and Measures The main outcome was death or NDI. Characteristics, outcomes, hospitalization, and NNCC costs were compared. Results Among the 381 patients who were included, median (IQR) gestational age was 39 (38-40) weeks; maternal race included 79 (20.7%) Black mothers, 237 (62.2%) White mothers, and 58 (15.2%) mothers with other race; 80 (21%) died, 64 (17%) survived with NDI (combined death or NDI group: 144 patients [38%]), and 237 (62%) survived without NDI. The combined death or NDI group had a higher rate of infants with Apgar score at 10 minutes less than or equal to 5 (65.3% [94 of 144] vs 39.7% [94 of 237];P < .001) and a lower rate of infants with mild or moderate HIE (36.1% [52 of 144] vs 82.3% [195 of 237];P < .001) compared with the survived without NDI group. Compared with low-cost centers, there was no association between high– or medium–hospitalization cost centers and death or NDI. High– and medium–EEG cost centers had lower odds of death or NDI compared with low-cost centers (high vs low: OR, 0.30 [95% CI, 0.16-0.57]; medium vs low: OR, 0.29 [95% CI, 0.13-0.62]). High– and medium–laboratory cost centers had higher odds of death or NDI compared with low-cost centers (high vs low: OR, 2.35 [95% CI, 1.19-4.66]; medium vs low: OR, 1.93 [95% CI, 1.07-3.47]). High–antiseizure medication cost centers had higher odds of death or NDI compared with low-cost centers (high vs. low: OR, 3.72 [95% CI, 1.51-9.18]; medium vs low: OR, 1.56 [95% CI, 0.71-3.42]). Conclusions and Relevance Hospitalization costs during the first 4 days of age in neonates with HIE treated with TH were not associated with neurodevelopmental outcomes. Higher EEG costs were associated with lower odds of death or NDI yet higher laboratory and antiseizure medication costs were not. These findings serve as first steps toward identifying aspects of NNCC that are associated with outcomes.

Diabetes continues to be a major source of morbidity and mortality among working-age adults nationally and internationally. The microvascular complications of diabetes, including diabetic retinopathy, account for a major proportion of disease-associated morbidity and likely contribute to macrovascular complications. Although glycemic control contributes to susceptibility for diabetic complications, some people with strict control develop these complications, whereas others with poor control remain complication free. This suggests a genetic contribution to disease development. Although many genes and proteins of vascular growth have been studied in association with diabetic retinopathy, no definitive major predisposing genes or functional consequences of genetic variants have been identified for microvascular complications of the disease. In this article, we review the studies done on candidate genes.