Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental toxicity of glyceryl trinitrate in quail embryos.

BACKGROUND Although glyceryl trinitrate (GTN) is used extensively to treat angina and heart failure, little is known about its effects on the conceptus during organogenesis. The goal of these studies was to investigate the effects of GTN in a model organism, the quail (Coturnix coturnix japonica) embryo. METHODS To identify the effects of GTN on quail embryo development, fertilized quail eggs (n = 10-12 eggs/group) were injected with GTN (0, 4.4, 44, or 440 μM) at Hamburger-Hamilton (HH) stage 0, 9, or 19 and examined 7 days later. Next, HH 9 embryos were injected with GTN (0, 0.88, 4.4, 8.8, 44, 88, and 440 μM, in 20 μL per egg) and examined 24-hours, 48-hours, or 72-hours postinjection. Finally, the developing eye on one side was exposed to GTN (44 μM) ex ovo and the tissue was probed for the presence of nitrated proteins. RESULTS In ovo GTN exposure induced a dose-dependent increase in the number of malformed viable quail embryos with a maximal effect in HH 9 embryos. Microphthalmia, craniofacial, heart, and neural tube defects were elevated in GTN-exposed embryos. An increase in nitrated proteins was observed in the developing eye region of embryos exposed ex ovo to GTN. CONCLUSIONS GTN treatment induced a variety of malformations in quail embryos. The presence of nitrated proteins suggests that organic nitrates, such as GTN, generate reactive nitrogen species. We hypothesize that GTN perturbations in the redox status of the embryo may underlie its developmental toxicity.
Semiconductor quantum dots: synthesis and water-solubilization for biomedical applications

Background: Quantum dots (QDs) are generally nanosized inorganic particles. They have distinctive size-dependent optical properties due to their very small size (mostly < 10 nm). QDs are regarded as promising new fluorescent materials for biological labeling and imaging because of their superior properties compared with traditional organic molecular dyes. These properties include high quantum efficiency, long-term photostability and very narrow emission but broad absorption spectra. Objective/methods: Recent developments in synthesizing high quality semiconductor QDs (mainly metal-chalcogenide compounds) and forming biocompatible structures for biomedical applications are discussed in this paper. Results/conclusions: This information may facilitate the research to create new materials/technologies for future clinical applications.
SEMA3A rs7804122 polymorphism is associated with Hirschsprung disease in the Northeastern region of China.

BACKGROUND Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon. Our previous results showed increased semaphorin 3A (SEMA3A) expression may be the risk factor for HSCR pathology in a subset of patients. Therefore, the association between polymorphisms in SEMA3A and the risk of HSCR was examined. METHODS The genotypes of two SNPs (rs7804122 and rs797821) in the SEMA3A gene in 119 patients with HSCR and 93 controls were examined using PCR-sequencing to determine the contribution of SEMA3A to the HSCR phenotype. PCR reaction with cDNA template was also used to find out whether a novel mutation (Chr7:83634610A→T) influences the SEMA3A pre-mRNA splicing. RESULTS Genotypes comprising allele G of rs7804122 (GG or AG) were over-represented in patients (48.74 vs. 24.8%; p = 0.0013) which indicated that the risk of HSCR was significantly higher among subjects with the GG or AG genotype than among the subjects with the AA genotype. No statistically significant associations were found for SNP rs797821 at the allele or genotype levels. The differences in genotypes and allele distributions of rs7804122 and rs797821 between various clinical classifications were not statistically significant. The novel heterozygous mutation (Chr7:83634610A→T) 30bp away from an intron/exon boundary, had no detectable effect on splicing efficiency. CONCLUSION Our results for rs7804122 provided preliminary evidence that the SEMA3A gene is involved in the susceptibility to HSCR in the Northeastern Chinese population.
Dificuldades enfrentadas pelos enfermeiros no cuidado de enfermagem a indivíduos portadores de feridas / Difficulties faced by nurses in nursing care for individuals with wounds

A atuacao do enfermeiro esta diretamente relacionada ao cuidado a individuos portadores de feridas, nos diversos niveis de atencao a saude. O estudo objetivou conhecer as dificuldades enfrentadas pelos enfermeiros no cuidado de enfermagem a individuos portadores de feridas, no âmbito da atencao basica em saude. Trata-se de uma pesquisa qualitativa, do tipo descritiva e exploratoria. Foi realizada junto a quinze enfermeiros atuantes em unidades basicas de saude de um municipio do sul do Brasil. Os dados foram coletados pela tecnica do grupo focal, sendo aplicada a analise tematica para a interpretacao destes. Evidenciaram-se tres categorias tematicas, sendo elas: dificuldades institucionais no cuidado a individuos portadores de feridas; dificuldades profissionais no cuidado a individuos portadores de feridas; e aspectos socioculturais e economicos que geram dificuldades no cuidado a individuos portadores de feridas. Os resultados sugerem que o acesso dos profissionais a recursos materiais adequados, a treinamentos especificos e ao desenvolvimento de um trabalho interdisciplinar sao fatores indispensaveis para que sejam viabilizadas as condicoes necessarias para o estabelecimento de condutas terapeuticas eficazes no processo de cuidado a individuos portadores de feridas. Alem disso, e fundamental que o enfermeiro compreenda os determinantes socioculturais e economicos que influenciam no cuidado a tais individuos.
Intestinal transport of HDND-7, a novel hesperetin derivative, in in vitro MDCK cell and in situ single-pass intestinal perfusion models

Abstract 1. Hesperetin (HDND) possesses extensive bioactivities, however, its poor solubility and low bioavailability limit its application. HDND-7, a derivative of HDND, has better solubility and high bioavailability. In this study, we investigated the intestinal absorption mechanisms of HDND-7. 2. MDCK cells were used to examine the transport mechanisms of HDND-7 in vitro, and a rat in situ intestinal perfusion model was used to characterize the absorption of HDND-7. The concentration of HDND-7 was determined by HPLC. 3. In MDCK cells, HDND-7 was effectively absorbed in a concentration-dependent manner in both directions. Moreover, HDND-7 showed pH-dependent and TEER-independent transport in both directions. The transport of HDND-7 was significantly reduced at 4 °C or in the presence of NaN3. Furthermore, the efflux of HDND-7 was apparently reduced in the presence of MRP2 inhibitors MK-571 or probenecid. However, P-gp inhibitor verapamil had no effect on the transport of HDND-7. The in situ intestinal perfusion study indicated HDND-7 was well-absorbed in four intestinal segments. Furthermore, MRP2 inhibitors may slightly increase the absorption of HDND-7 in jejunum. 4. In summary, all results indicated that HDND-7 might be absorbed mainly by passive diffusion via transcellular pathway, MRP2 but P-gp may participate in the efflux of HDND-7.
Mental health service use in the community and schools: Results from the four-community MECA study

ABSTRACT Objective To describe the use of mental health and substance abuse services by children and adolescents as reported from the four community sites included in the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Method As part of the MECA survey, questions were developed to identify children and adolescents utilizing mental health and substance abuse services. Youths aged 9 through 17 years and a parent/ caretaker were interviewed. Because the investigators had concerns about the capacities of the younger children in the study to describe their use of mental health services, more extensive questions were asked of parents than of youths. Results The procedures developed by the MECA project identified patterns of service use that varied in the four communities surveyed. Agreement between reports of parents and youths regarding the use of mental health and substance abuse services showed substantial Inconsistencies, similar to reports of psychiatric disorders. At three of the four sites, the majority of children meeting criteria for a psychiatric disorder and scoring 60 or less on the Children's Global Assessment Scale reported some mental health–related service in the previous year, although at two of the sites fewer than 25% of these youths were seen in the mental health specialty sector. Conclusion Community surveys show great promise for monitoring the need for mental health and substance abuse services and for identifying patterns of use.
Dimethylarsinic acid modulates the aryl hydrocarbon receptor-regulated genes in C57BL/6 mice: in vivo study

Abstract 1. Dimethylarsinic acid (DMA(V)) is the major metabolite of inorganic arsenic in human body. Thus we investigated the effect of DMA(V) on the alteration of phase I (typified by Cyp1a) and phase II (typified by Nqo1) AhR-regulated genes in vivo. C57BL/6 mice received DMA(V) (13.3 mg/kg, i.p.) with or without TCDD (15 μg/kg, i.p.), thereafter the liver, lung, and kidney were harvested at 6 and 24 h post-treatment. 2. Results demonstrated that DMA(V) has no significant effect on Cyp1a mRNA and protein expression or catalytic activity in the liver. On the other hand, DMA(V) significantly potentiated the TCDD-mediated induction of Cyp1a mRNA and protein expression, with a subsequent potentiation of catalytic activity in the lung. Moreover, DMA(V) significantly inhibited the TCDD-mediated induction of Cyp1a mRNA and protein expression with subsequent inhibition of catalytic activity in the kidney. 3. Regarding to phase II AhR-regulated genes, DMA(V) has no significant effect on Nqo1 mRNA and protein expression, or activity neither in the liver, lung, or kidney. 4. In conclusion, the present work demonstrates for the first time that DMA(V) modulates AhR-regulated genes in a tissue- and enzyme-specific manner. This modulation may play a crucial role in arsenic-induced toxicity and carcinogenicity.
The permeability characteristics and interaction of main components from Si-Ni-San in a MDCK epithelial cell monolayer model

Abstract 1. Si-Ni-San (SNS) possesses extensive therapeutic effects, however, the extent to which main components are absorbed and the mechanisms involved are controversial. 2. In this study, MDCK cell model was used to determine the permeability characteristics and interaction between the major components of Si-Ni-San, including saikosaponin a, paeoniflorin, naringin and glycyrrhizic acid. 3. The transport of the major components was concentration-dependent in both directions. Moreover, the transport of paeoniflorin, naringin and glycyrrhizic acid was significantly reduced at 4 °C or in the presence of NaN3. Additionally, the efflux of paeoniflorin and naringin were apparently reduced in the presence of P-gp inhibitor verapamil. The transport of glycyrrhizic acid was clearly inhibited by the inhibitors of MRP2, indicating that MRP2 may be involved in the transport of glycyrrhizic acid. However, the results indicated that saikosaponin a was absorbed mainly by passive diffusion. Furthermore, the combined incubation of four major components had a powerful sorbefacient effect than a single drug used alone which may be regulated by tight junctions. 4. Taken together, our study provides useful information for pharmacological applications of Si-Ni-San and offers new insights into this ancient decoction for further researches, especially in drug synergism.
Quantitative prediction of the extent of drug–drug interaction using a physiologically based pharmacokinetic model that includes inhibition of drug metabolism determined in cryopreserved hepatocytes

Abstract 1. A physiologically based pharmacokinetic (PBPK) model that includes inhibition constant evaluated in cryopreserved hepatocytes was used to predict drug–drug interactions (DDIs) between orally administered nifedipine, a CYP substrate, and fluconazole or ketoconazole, CYP inhibitors, in rats. 2. The Kp,uu, ratio of unbound inhibitor concentration in liver ([I]liver,u) to that in plasma ([I]sys,u), of fluconazole and ketoconazole was 1.0 and 13.0, indicating that ketoconazole accumulates in liver. The ratios of inhibition constants in rat liver microsomes (Ki,mic,u) to that in rat cryopreserved hepatocytes (Ki,hep,u) for fluconazole and ketoconazole were 1.5 and 25.5, which were similar to the Kp,uu and suggested that cryopreserved hepatocytes could mimic the hepatic accumulation of inhibitors. 3. The increases in AUC of nifedipine predicted by the minimal PBPK model using [I]liver,u/Ki,mic,u and [I]sys,u/Ki,hep,u were within 1.5-fold of the observed values for both inhibitors, whereas the model using [I]sys,u/Ki,mic,u underestimated the AUC increase caused by ketoconazole 21-fold. 4. These results indicated that hepatic accumulation factor of an inhibitor is required for a precise DDI projection and that cryopreserved hepatocytes would be useful to obtain the Ki including hepatic accumulation factor. It was demonstrated that PBPK model using Ki,hep,u could be a valuable approach for quantitative DDI projection.
Evaluation of EORTC QLQ‐C30 questionnaire in patients undergoing in‐hospital chemotherapy for gastrointestinal cancer in Japan

Background and Aim: There have been few studies in Japan of the utility of quality of life (QOL) questionnaires as an evaluation of chemotherapy for gastrointestinal (GI) cancer. The present study investigated whether QOL can be an indicator of the clinical benefit of chemotherapy, by analyzing the changes in the QOL scores of patients who underwent in‐hospital chemotherapy for GI cancer.
Heterozygous DLX5 nonsense mutation associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated families.

BACKGROUND Split-hand/foot malformation (SHFM) is a clinically and genetically heterogeneous limb abnormality characterized by the absence or hypoplasia of the central rays of the autopod. SHFM1, which is one out of seven known SHFM loci, maps to 7q21.2-q21.3. SHFM1 is usually inherited as an autosomal dominant trait with reduced penetrance, although recessive inheritance has been described for a single family carrying a homozygous DLX5 missense variant. In most cases, SHFM1 results from heterozygous deletions encompassing DLX5/DLX6 genes or from inversions and translocations separating the genes from their limb specific enhancers. Recently, a single Chinese family with dominant SHFM1 was shown to result from a heterozygous DLX5 missense mutation. METHODS In this study, we report on four male individuals from two unrelated Polish families (one sporadic and one familial case) presenting with isolated SHFM. We tested both probands for known molecular causes of SHFM, including TP63, WNT10B, DLX5 mutations and copy number changes using 1.4 M array CGH. RESULTS Sanger sequencing of DLX5 revealed a novel heterozygous nonsense mutation c.G115T(p.E39X) in both index patients. Segregation studies demonstrated that the variant was present in all affected family members but also in three apparently healthy relatives (two females and one male). CONCLUSION This is the first report of a heterozygous DLX5 nonsense mutation resulting in incompletely penetrant autosomal dominant isolated SHFM1. Data shown here provides further evidence for the contribution of DLX5 point mutations to the development of ectrodactyly and suggest the possibility of sex-related segregation distortion with an excess of affected males.
Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort.

BACKGROUND Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. METHODS We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. RESULTS We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). CONCLUSION Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240-249, 2016. © 2016 Wiley Periodicals, Inc.
Antibiotic Timing in Neonates With Suspected Hospital-Acquired Infections

There exists general agreement within neonatology that antibiotics should be administered promptly to neonates with possible bacterial sepsis and meningitis. We initiated a series of quality improvement cycles designed to reduce delays in the initiation of antibiotic therapy to less than 2 hours when hospital-acquired infection (HAI) was suspected. All infants in this study were in neonatal intensive care (level II or III) who were started on antibiotics for a suspected HAI (defined as an infection that occurred 72 hours after admission to the NICU) were audited. Through a series of quality improvement cycles, we analyzed sources of delays in the initiation of antibiotic therapy from the time the order was written through administration. In subsequent cycles, we intervened to reduce delays through education, standardize the evaluation process, and develop an online ordering system that streamlined the workflow patterns in the nurseries and pharmacy. Using a prospective cohort design, we compared antibiotic delivery times after each process improvement cycle. Antibiotic delivery time was reduced from a median of 137.5 minutes to 75 minutes and variation of practice was reduced in terms of standard deviation and range (P < .001). The use of computerized physician order entry significantly improved the writing of STAT orders (P < .0001). A systematic analysis of workflow patterns and efficiencies, coupled with improvement cycles targeting delays and development of a computerized physician order entry system, allowed us to improve antibiotic delivery time in neonates with suspected HAI in an intensive care nursery system.
Every Second Counts

Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects patients with a loss of speech and mobility. The aim of this study was to describe patients’ experiences of living with ALS in the end-of-life situations. A manifest content analysis was chosen for analysis narratives from four biographies by women who had ALS. The categories Suffering, Meaningfulness, and Experiences of a Limited life were identified as describing patients’ understanding of living with ALS. Nurses need to be trained in communication skills to maintain human dignity for patients who lost their speech regarding an intellect in shape. There is a need for information among family members about severe diseases, such as ALS, to improve high quality of care and well-being for all involved. Home health care has to invite and facilitate patients’ and relatives’ participation regarding the end-of-care processes to improve a sense of coherence to handle everyday life situation in the future.
Rehabilitation and management of behavioral disturbances following frontal lobe injury

Because of the complex functions of the human frontal lobes, rehabilitation of persons with frontal lobe injury presents a unique set of challenges. Evaluation of behavioral disturbances associated with frontal damage must be individualized and contextually based; neuropsychological assessment is helpful, but not sufficient. Treatment planning should be highly specific as to expected outcomes. Prosthetic environments and prosthetic supports, skill-based learning approaches, and other behavioral programming methods may be effective singly, or in combination, for minimizing the impact of frontal lobe deficits.
Soul Murder: The Effects of Childhood Abuse and Deprivation

There is great promise in the title and the timing of this book, but great disappointment in the telling. It is rare for an author, in his introduction, to point out the major and pervasive flaw in his work, yet not repair it: "I am fond of meandering designs; this book proceeds more by associations than by orderly progression, and some motifs recur throughout. " Material from George Orwell's 1984 and quotes from Freud, Dickens, Chekhov, and Kipling are liberally used. However, these are interspersed in long, convoluted sentences about the author's case histories. Several readings are needed to establish some connections or even whether patient x or Orwell's Winston or a cannibalistic rat is being described. The author, apparently unaware of the contradictions, states: Soul murder is my dramatic designation for a certain category of traumatic experiences: instances of repetitive and chronic overstimulation alternating with emotional deprivation that are deliberately
Longitudinale Körperentwicklung gesunder Kinder von 0 bis 18 Jahren

In addition to the Dortmunder longitudinal growth study we investigated development of height, weight and height velocity in 213 healthy boys and girls 15-18 years old. Number of children decreased in the age group of 17 and 18 years old to 143. The study was performed in a longitudinal way, the measurements were taken in an one year distance. The median height gain in boys between 15 and 18 years amounted to 9.3 cm, in girls to 2.1 cm, respectively. 18 years old boys are 180.1 cm tall, girls 167.9 cm. The median increment of body weight in boys from 15-18 years amounted to 7.3 kg, in girls 4.4 kg, respectively. Median weight in 18 years old boys amounted to 65.2 kg, in girls to 58.0 kg. International comparison with other longitudinal growth studies shows a trend of somewhat higher weight, height and height velocity of the children from our study.