Miracle-dz/UniFAR-FTUs huggingface dataset:
Racial differences in gene-specific DNA methylation levels are present at birth.

BACKGROUND DNA methylation patterns differ among children and adults and play an unambiguous role in several disease processes, particularly cancers. The origin of these differences is inadequately understood, and this is a question of specific relevance to childhood and adult cancer. METHODS DNA methylation levels at 26,485 autosomal CpGs were assayed in 201 newborns (107 African American and 94 Caucasian). Nonparametric analyses were performed to examine the relation between these methylation levels and maternal parity, maternal age, newborn gestational age, newborn gender, and newborn race. To identify the possible influences of confounding, stratification was performed by a second and third variable. For genes containing CpGs with significant differences in DNA methylation levels between races, analyses were performed to identify highly represented gene ontological terms and functional pathways. RESULTS 13.7% (3623) of the autosomal CpGs exhibited significantly different levels of DNA methylation between African Americans and Caucasians; 2% of autosomal CpGs had significantly different DNA methylation levels between male and female newborns. Cancer pathways, including four (pancreatic, prostate, bladder, and melanoma) with substantial differences in incidence between the races, were highly represented among the genes containing significant race-divergent CpGs. CONCLUSIONS At birth, there are significantly different DNA methylation levels between African Americans and Caucasians at a subset of CpG dinucleotides. It is possible that some of the epigenetic precursors to cancer exist at birth and that these differences partially explain the different incidence rates of specific cancers between the races.
Comparison of formation of thiolactones and active metabolites of prasugrel and clopidogrel in rats and dogs

Prasugrel and clopidogrel are antiplatelet prodrugs that are converted to their respective active metabolites through thiolactone intermediates. Prasugrel is rapidly hydrolysed by esterases to its thiolactone intermediate, while clopidogrel is oxidized by cytochrome P450 (CYP) isoforms to its thiolactone. The conversion of both thiolactones to the active metabolites is CYP mediated. This study compared the efficiency, in vivo, of the formation of prasugrel and clopidogrel thiolactones and their active metabolites. The areas under the plasma concentration versus time curve (AUC) of the thiolactone intermediates in the portal vein plasma after an oral dose of prasugrel (1 mg kg−1) and clopidogrel (0.77 mg kg−1) were 15.8 ± 15.9 ng h ml−1 and 0.113 ± 0.226 ng h ml−1, respectively, in rats, and 454 ± 104 ng h ml−1 and 23.3 ± 4.3 ng h ml−1, respectively, in dogs, indicating efficient hydrolysis of prasugrel and little metabolism of clopidogrel to their thiolactones in the intestine. The relative bioavailability of the active metabolites of prasugrel and clopidogrel calculated by the ratio of active metabolite AUC (prodrug oral administration/active metabolite intravenous administration) were 25% and 7%, respectively, in rats, and 25% and 10%, respectively, in dogs. Single intraduodenal administration of prasugrel showed complete conversion of prasugrel, resulting in high concentrations of the thiolactone and active metabolite of prasugrel in rat portal vein plasma, which demonstrates that these products are generated in the intestine during the absorption process. In conclusion, the extent of in vivo formation of the thiolactone and the active metabolite of prasugrel was greater than for clopidogrel’s thiolactone and active metabolite.
Bimodal rhythms of general conceptions and the birth-month phenomenon in schizophrenia, neural tube defects, and laterality: a solstitial hypothesis.

BACKGROUND Studies of early to mid-20th century birth records found that people with schizophrenia had been born most often in late winter (February–March) and least often in late summer (August–September). A late-winter birth peak coinciding with the schizophrenia peak also occurred during those times in the non-schizophrenic general populations. Odegard suggested in 1977 that the schizophrenia and general-birth rhythms represented the same phenomenon, with the former being a mere exaggeration of the latter. However, unlike the schizophrenia rhythm, the general-population birth rhythm was bimodal, with a second peak occurring in August–September and coinciding with the schizophrenia dip. METHODS We reexamined those intriguing coincidences in light of newer findings including evidence of a schizophrenia-like rhythm of births in neural tube defects (NTDs) and extreme left-handedness. RESULTS Based on U.S. data, we found that for all three anomalies (schizophrenia, NTDs, and sinistrality) the maximum risk and the minimum risk (a resistance peak) coincided with, respectively, the February–March and August–September peaks of general-population births. We also found that, while superficially similar, the two general-birth peaks were more likely to represent different phenomena with opposite causes (possibly the June vs December sunlight) and radically different mechanisms of enhanced embryonic survival (increased post-implantation viability in the February–March case and increased implantation rates in the August–September case). CONCLUSIONS We propose a mechanism of selective embryonic survival whereby the birth-month-associated risk levels for the various anomalies would all represent traits genetically or epigenetically inherent to the two differently selected populations of surviving embryos. Birth Defects Research (Part A) 2011. © 2011 Wiley-Liss, Inc.
Methylphenidate modifies the motion of the circadian clock Lamotrigine in mood disorders and cocaine dependence Cortical glutamate in postpartum depression Involvement of Infralimbic Prefrontal Cortex but Not Lateral Habenula in Dopamine Attenuation after Chronic Mild Stress

This is a PDF file of an unedited peer-reviewed manuscript that has been accepted for publication. NPG are providing this early version of the manuscript as a service to our customers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.
Colostrum as Oral Immune Therapy to Promote Neonatal Health

It is well known that the immune response is blunted and underdeveloped in the premature infant, but human milk supports the infant's growth, function, and effectiveness. Thus, own mother's colostrum (OMC) administered oropharyngeally has potential to deliver oral immune therapy (C-OIT) even before enteral feedings have begun. Colostrum interacts with lymphoid tissue in the oropharynx and gut. Colostrum as oral immune therapy is delivered by swabbing the cheeks in the first days of life. Little formal study has evaluated its effectiveness. However, small studies demonstrate that it is a practice that is safe, feasible, and well tolerated even by the smallest premature infants. Encouraging preliminary evidence supports the effect of C-OIT to reduce the time to full enteral feedings. Effects on other outcomes is unclear, in part because existing studies are underpowered to detect significant differences on outcomes like necrotizing enterocolitis, sepsis, and death. Another limitation in the evidence base is that adherence to the intervention and the number of doses of colostrum infants received in the studies is not consistently made clear. More well-designed studies are needed to demonstrate the impact on neonatal complications and how C-OIT supports the infant's immune development. Quality improvement and time series reports of differences pre- and postimplementation of OMC given orally should minimally include statistics for adherence to the intervention and/or the number of doses an infant received as a covariate. Even so, OMC is an immune therapy that poses little risk yet offers likely cost-effective benefit for vulnerable infants.
Methylphenidate modifies the motion of the circadian clock Lamotrigine in mood disorders and cocaine dependence Cortical glutamate in postpartum depression Chronic Exposure to Methamphetamine Disrupts Reinforcement-Based Decision-Making in Rats

This is a PDF file of an unedited peer-reviewed manuscript that has been accepted for publication. NPG are providing this early version of the manuscript as a service to our customers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.
Assessment Tools for Evaluation of Oral Feeding in Infants Younger Than 6 Months

Background:Feeding difficulty is common in infants younger than 6 months. Identification of infants in need of specialized treatment is critical to ensure appropriate nutrition and feeding skill development. Valid and reliable assessment tools help clinicians objectively evaluate feeding. Purpose:To identify and evaluate assessment tools available for clinical assessment of bottle- and breastfeeding in infants younger than 6 months. Methods/Search Strategy:CINAHL, HaPI, PubMed, and Web of Science were searched for “infant feeding” and “assessment tool. ” The literature (n = 237) was reviewed for relevant assessment tools. A secondary search was conducted in CINAHL and PubMed for additional literature on identified tools. Findings/Results:Eighteen assessment tools met inclusion criteria. Of these, 7 were excluded because of limited available literature or because they were intended for use with a specific diagnosis or in research only. There are 11 assessment tools available for clinical practice. Only 2 of these were intended for bottle-feeding. All 11 indicated that they were appropriate for use with breastfeeding. None of the available tools have adequate psychometric development and testing. Implications for Practice:All of the tools should be used with caution. The Early Feeding Skills Assessment and Bristol Breastfeeding Assessment Tool had the most supportive psychometric development and testing. Implications for Research:Feeding assessment tools need to be developed and tested to guide optimal clinical care of infants from birth through 6 months. A tool that assesses both bottle- and breastfeeding would allow for consistent assessment across feeding methods.
Metabolic map of osthole and its effect on lipids

Abstract 1. Osthole, a coumarin compound from plants, is a promising agent for the treatment of metabolic diseases, including hyperglycemia, fatty liver, and cancers. Studies indicate that the peroxisome proliferator-activated receptors (PPAR) α and γ are involved in the pharmacological effects of osthole. The in vitro and in vivo metabolism of osthole and its biological activity are not completely understood. 2. In this study, ultra-performance chromatography electrospray ionization quadrupole time-of-ﬂight mass spectrometry (UPLC–ESI–QTOFMS)-based metabolomics was used to determine the metabolic pathway of osthole and its influence on the levels of endogenous metabolites. Forty-one osthole metabolites, including 23 novel metabolites, were identified and structurally elucidated from its metabolism in vitro and in vivo. Recombinant cytochrome P450s (CYPs) screening showed that CYP3A4 and CYP3A5 were the primary enzymes contributing to osthole metabolism. 3. More importantly, osthole was able to decrease the levels of lysophosphatidylethanolamine (LPE) and lysophosphatidylcholine (LPC) in the plasma, which explains in part its modulatory effects on metabolic diseases. 4. This study gives the insights about the metabolic pathways of osthole in vivo, including hydroxylation, glucuronidation, and sulfation. Furthermore, the levels of the lipids regulated by osthole indicated its potential effects on adipogenesis. These data contribute to the understanding of the disposition and pharmacological activity of osthole in vivo.
Validation of the cell line LS180 as a model for study of the gastrointestinal toxicity of mycophenolic acid

Abstract 1. Gastrointestinal (GI) intolerability is a concern for drugs such as mycophenolic acid (MPA) and drug metabolism may play a role. Few in vitro models exist that allow for the preclinical evaluation of a potential role of drug metabolism in intestinal drug toxicity. Thus, we sought to develop an in vitro model based on the human colon adenocarcinoma cell line LS180 to investigate MPA’s negative effects on intestinal cells. 2. Stability of expression of key enzymes of MPA metabolism (UGT1A7, UGT1A9, UGT1A10, UGT2B7, CYP3A4 and CYP3A5), transporters (OATP1B1, OATP1B3, OATP2B1, MRP1, MRP2 and MDR1) and the nuclear receptor PXR over 12 passages in combination with guanosine supplementation to counter MPA’s antiproliferative effects (determined by western blot analysis and proliferation assays, respectively) was established. 3. Expression of LS180 key enzymes remained stable over passages 47–59 and MPA-induced growth inhibition was circumvented by exogenous guanosine over a period of three days. MPA was not cytotoxic at concentrations up to 250 μM, a concentration that intestinal cells adjacent to the dissolving capsule or tablet are exposed to. 4. We concluded that LS180 cells are suitable to study the potential association between MPA metabolism and its negative effects on intestinal cells.
Oxidative stress in alcoholic liver disease: Role of NADPH oxidase complex

Alcohol is a well‐known risk factor for liver damage and is one of the major causes of liver disease worldwide. Chronic intake of alcohol, over a certain limit, inevitably leads to hepatic steatosis. If the injury persists, steatosis with concomitant tumor necrosis factor‐α and other cytokines, progresses to steatohepatitis, fibrosis and finally cirrhosis. Among the multiple factors involved in the process of alcohol‐induced liver injury, a crucial role is played by oxidative stress. Several mechanisms during ethanol metabolism result in reactive oxygen species (ROS) production. Although the main site of ethanol metabolism is hepatocytes, other mechanisms are involved in alcohol‐induced liver injury. Specifically, in the ROS production activity, an important role is played by the NADPH oxidase complex. NADPH oxidase is expressed in hepatocytes, hepatic stellate cells and Kupffer cells in the liver. Studying NADPH oxidase gives new insights into alcohol‐induced liver damage and provides new direction for future therapeutic strategies.
Smartphone and Internet Preferences of Parents: Information Needs and Desired Involvement in Infant Care and Pain Management in the NICU

Background: Despite an abundance of research that identifies the benefits for both parent and child when parents are actively involved in their infant's care, challenges related to the best methods to engage families persist. Purpose: To conduct a feasibility study that aims to understand the preferences of smartphone and Internet use by parents of infants admitted to the neonatal intensive care unit (NICU) related to information seeking and active participation in infant care, with a focus on pain management interventions. Methods: A paper-based survey was distributed to 90 parents in a tertiary-level NICU from September to November 2013. Results: Response rate was 80% (72 of the 90). Ninety-seven percent accessed the Internet daily, 87% using their smartphone, and ranked it as an important source of NICU information (81%), more than books (56%) and brochures (33%). Participants reported a desire to have more information on how they could provide general comfort (96%), as well as greater participation in comforting their baby during painful procedures (94%). Implications for Practice: Parents in the NICU want more information and greater involvement in their infant's care and pain management and place a higher value on the Internet compared with traditional resources. Implications for Research: Researchers and clinicians should work together to determine the quality of online resources to better support and evaluate parent use of the Internet as a health information resource. Future studies should examine parental preference regarding the optimal balance between online sources and face-to-face interactions.
Valproate prescriptions for nonepilepsy disorders in reproductive-age women.

BACKGROUND Scientific evidence has consistently shown taking valproate during pregnancy increases risks of congenital malformations and cognitive impairment. As such, elimination of its use would be an important step in birth defects prevention. There are guidelines discouraging its use among women with epilepsy, but none exists for women without epilepsy, nor is the prevalence of valproate for nonepilepsy indications known. METHODS Using de-identified data from the National Hospital and Ambulatory Medical Care Surveys (1996-2007), we examined individual prescriptions for reproductive-age adolescent girls and adult women ages 15 to 44 years in the United States, and estimated the number of antiepileptic drug and valproate prescriptions in the aggregate. We classified our study population using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, as women with epilepsy and women without epilepsy. The prevalence of antiepileptic drug and valproate prescriptions among women without epilepsy was estimated as prescriptions per 1000 patient visits for every 3-year time interval and the overall study period. RESULTS We found 83% of valproate prescriptions were issued to women without epilepsy and 74% of these were for psychiatric diagnoses. The prevalence of antiepileptic drug prescriptions among women without epilepsy tripled during the study period (10.3 [1996-1998] vs. 34.9 [2005-2007] per 1000 patient visits), whereas valproate prescriptions remained relatively stable (3.1 [1996-1998] vs. 3.7 [2005-2007] per 1000 patient visits). CONCLUSION Most women of reproductive age who receive a valproate prescription do not have epilepsy. Valproate prescriptions did not decline, despite increasing knowledge of its teratogenicity. Reducing valproate use among women of reproductive age, especially among those who use the drug for psychiatric indications, would prevent birth defects and cognitive deficits.
Alcohol, cofactors and the genetics of hepatocellular carcinoma

Heavy alcohol consumption, chronic infection with the hepatitis B virus (HBV) or the hepatitis C virus (HCV), tobacco smoking, and diabetes are risk factors for hepatocellular carcinoma (HCC). In the Los Angeles Non‐Asian HCC Study, heavy alcohol intake was shown to exhibit synergistic effects with viral hepatitis (HBV, HCV) and diabetes in the causation of HCC among individuals with joint exposures. Although chronic infection with HBV is recognized as the most important causal factor for HCC in humans, only a minority of HBV carriers eventually develop HCC, suggesting the presence of important cofactors in HBV‐related HCC. In the Guangxi/China HCC Study, a 20‐fold difference in HCC risk was observed between individuals possessing the least versus the most favorable cytokine genotypes for hepatitis B viral clearance. Experimental studies have indicated an important role for one‐carbon metabolism in HCC development. In both the Los Angeles and Guangxi studies, low‐activity genotypes (reduced enzymatic activities) of methylenetetrahydrofolate reductase (MTHFR) and high‐activity genotypes (enhanced enzymatic activities) of thymidylate synthase (TYMS), both of which discourage the misincorporation of uracil into DNA, were shown to be associated with a reduced risk for HCC.
Inhalation exposure of nano diamond induced oxidative stress in lung, heart and brain

Abstract 1. Today, diamond nanoparticles have several industrial applications. Nano diamond (ND) as a carbon allotrope diffuses in the air easily during producing and processing procedures. 2. In this study, we investigated sub-acute exposed to ND at the exposure chamber in mice. The animals were divided into two groups (control and exposed group to ND at the concentration of 3 µg/m3 for 3 h/day, 5 days/week for 30 days) in a whole-body inhalation chamber. 3. Our results showed that exposure to ND induced the hematological and biochemical changes. The target organs for ND were the lungs, brain and heart in the mice, respectively. Also, ND increased reactive oxygen species (ROS) generation, lipid peroxidation (LPO), the collapse of mitochondrial membrane potential (MMP), decreased a level of reduced glutathione (GSH) and finally increased a level of glutathione disulfide (GSSG) in lung, brain and heart tissues. Our results suggest that exposure to ND can induce oxidative stress in the tissue mentioned. 4. These results suggest that exposure of researchers and workers with diamond nanoparticles probably increase a risk of respiratory, cardiovascular and cerebral disorders through oxidative stress. However, good ventilation, appropriate personal protective equipment and using of anti-oxidant compounds in daily diet of worker are suggested.
A Fortified Donor Milk Policy is Associated With Improved In-Hospital Head Growth and Weight Gain in Very Low-Birth-Weight Infants

Background: Previous research has reported that infants fed donor milk grow slower than those fed formula. However, most of the trials used unfortified donor milk, which limits the ability to generalize the results to current clinical practice. Purpose: To evaluate the impact of early human milk feeding (donor milk and/or mother's own milk) with standard fortification on in-hospital growth of very low-birth-weight infants. Methods: This pre-/postretrospective study included selected newborn infants less than 1500 g admitted to a level IV neonatal intensive care unit before and after the introduction of a policy providing donor milk when mother's own milk was not available in sufficient quantity to meet her infant's need. When enteral feeds reached 80 mL/kg per day, all human milk was fortified. Results: Seventy-two “before” (any formula-fed) and 114 “after” (human milk-fed) infants were enrolled in this study. Infant characteristics and neonatal morbidity were similar in both groups. Outcomes revealed that an initial human milk diet with standard fortification was associated with significantly higher early extrauterine weight gain and head growth in very low-birth-weight infants than a formula-fed diet. Implications for Practice: Very early initiation of fortified breast and/or donor milk feeding can help promote in-hospital head growth and weight gain of preterm infants. Formula may not be appropriate for early use among preterm infants. Implications for Research: Further large-scale clinical trials are needed to determine the best initiation and composition of enteral feeding for preterm infants.