Miracle-dz/UniFAR-FTUs huggingface dataset:
Omeprazole preferentially inhibits the metabolism of (+)-(S)-citalopram in healthy volunteers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Citalopram (CITA) pharmacokinetics are enantioselective in healthy volunteers and the metabolism of (+)-(S)-CITA to (+)-(S)-DCITA is dependent on CYP2C19. Omeprazole is a potent CYP2C19 inhibitor. WHAT THIS STUDY ADDS This study indicates that omeprazole induces a loss of enantioselectivity in the CITA pharmacokinetics because of the selective inhibition of (+)-(S)-CITA metabolism. AIM The study assessed the influence of omeprazole on the kinetic disposition of the (+)-(S)-citalopram (CITA) and (-)-(R)-CITA enantiomers in healthy volunteers. METHODS In a cross-over study, healthy volunteers (n = 9) phenotyped as extensive metabolizers of CYP2C19 and CYP2D6 and with an oral midazolam clearance ranging from 10.9 to 149.3 ml min(-1) kg(-1) received a single dose of racemic CITA (20 mg orally) in combination or not with omeprazole (20 mg day(-1) for 18 days). Serial blood samples were collected up to 240 h after CITA administration. CITA and demethylcitalopram (DCITA) enantiomers were analyzed by LC-MS/MS using a Chiralcel OD-R column. RESULTS The kinetic disposition of CITA was enantioselective in the absence of treatment with omeprazole, with the observation of a greater proportion of plasma (-)-(R)-CITA [AUC S:R ratio of 0.53 (95% CI 0.41, 0.66) for CITA and 1.08 (95% CI 0.80, 1.76) for DCITA] than (+)-(S)-CITA. Racemic CITA administration to healthy volunteers in combination with omeprazole showed a loss of enantioselectivity in CITA pharmacokinetics with an increase of approximately 120% in plasma (+)-(S)-CITA concentrations [AUC S:R ratio of 0.95 (95% CI 0.72, 1.10) for CITA and 0.95 (95% CI 0.44, 1.72) for DCITA]. CONCLUSIONS The administration of multiple doses of omeprazole preferentially inhibited (+)-(S)-CITA metabolism in healthy volunteers. Although omeprazole increased plasma concentrations of (+)-(S)-CITA by approximately 120%, it is difficult to evaluate the clinical outcome because the range of plasma CITA concentrations related to maximum efficacy and minimum risk of adverse effects has not been established.
Comparison of two antibiotic regimens in the treatment of perforated appendicitis in pediatric patients.

BACKGROUND AND PURPOSE An increased incidence of post-surgical infectious complications in children admitted with a diagnosis of perforated appendicitis led to development of a disease-specific antibiogram and modification of our post-operative antibiotic regimen. METHODS A historical control group comprised of 32 pediatric patients receiving ampicillin, gentamicin, and clindamycin (group AGC) was compared to a cohort of 32 children receiving ticarcillin/clavulanate plus gentamicin (group TG). The surgical procedure, peri-operative management, and inclusion, exclusion and discharge criteria were the same for each group. Outcome measures including length of stay, time to defervesce, incidence of infectious complications, and clinical failures to the antibiotic regimen were compared. RESULTS The groups were similar with respect to gender, age, weight, surgical time, pre-operative leukocytes, and number of intra-operative bacterial isolates cultured per patient. Length of stay was 10.1 days in group TG and 12.5 days for group AGC (p = 0.0197). The number of clinical failures was reduced from 9 (28.1%) to 2 (6.3%) in group TG (p = 0.02). The time to defervesce was decreased by 1.4 days, and the number of infectious complications was reduced to 2.5-fold in group TG patients. CONCLUSIONS Ticarcillin/clavulanate plus gentamicin was clinically more effective than ampicillin, gentamicin, and clindamycin combination therapy in the management of perforated appendicitis in our pediatric population.
Insights into the Renal Pathogenesis in Schimke Immuno-Osseous Dysplasia

Schimke immuno-osseous dysplasia (SIOD) is a pleiotropic disorder caused by mutations in the SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like-1 (SMARCAL1) gene, with multiple clinical features, notably end-stage renal disease. Here we characterize the renal pathology in SIOD patients. Our analysis of SIOD patient renal biopsies demonstrates the tip and collapsing variants of focal segmental glomerulosclerosis (FSGS). Additionally, electron microscopy revealed numerous glomerular abnormalities most notably in the podocyte and Bowman’s capsule. To better understand the role of SMARCAL1 in the pathogenesis of FSGS, we defined SMARCAL1 expression in the developing and mature kidney. In the developing fetal kidney, SMARCAL1 is expressed in the ureteric epithelium, stroma, metanephric mesenchyme, and in all stages of the developing nephron, including the maturing glomerulus. In postnatal kidneys, SMARCAL1 expression is localized to epithelial tubules of the nephron, collecting ducts, and glomerulus (podocytes and endothelial cells). Interestingly, not all cells within the same lineage expressed SMARCAL1. In renal biopsies from SIOD patients, TUNEL analysis detected marked increases in DNA fragmentation. Our results highlight the cells that may contribute to the renal pathogenesis in SIOD. Further, we suggest that disruptions in genomic integrity during fetal kidney development contribute to the pathogenesis of FSGS in SIOD patients.
Cutting Edge: DNA Immunization with Minigenes of Carbohydrate Mimotopes Induce Functional Anti-Carbohydrate Antibody Response1

To date, the generation of anti-carbohydrate Th1 immune responses, which would be useful for both tumor immunotherapy as well as in pathogen vaccine strategies, has been elusive. To augment Th1 immune responses to carbohydrate Ags, we describe results of DNA vaccination studies in mice using plasmids encoding designed peptide mimotopes (minigenes) of the neolactoseries Ag Lewis Y (LeY). In contrast to LeY immunization, immunization with mimotope-encoded plasmids induced LeY cross-reactive IgG2a Abs. Minigene immunization primed for a LeY-specific response that is rapidly activated upon encounter with nominal Ag upon subsequent boost. The resulting IgG2a response mediated complement-dependent cytotoxicity of a LeY-expressing human tumor cell line in the presence of human complement. These studies establish that peptide mimotopes of carbohydrate Ags encoded as DNA plasmids are novel immunogens providing a means to manipulate carbohydrate cross-reactive Th1 responses.
Technique and proof of patency of microsurgical lympho‐lymphonodular anastomoses: A study in the rat model

Background: Lymphedemas due to local lymphatic blocks can be treated by microsurgical transplantation or transposition of lymphatic vessels. Here, the anastomoses are usually made end‐to‐end between lymphatics, but occasionally appropriate lymphatic recipient vessels are missing. In such cases, reconstructing lymph drainage by connection to a lymph node could be another technical option. The purpose of this study was to examine the patency rate of such lympho‐lymphonodular anastomoses in an experimental animal model. Methods: Male Sprague–Dawley rats were anesthetized, and the retroperitoneum was exposed. Patent blue dye was injected into the left foot to stain lymphatic structures. In group A (n = 8), the left lumbar trunk was cut centrally, the distal part was turned over to the right lumbar lymph node, and a microsurgical lympho‐lymphonodular anastomosis was performed. In group B (n = 8), the left lumbar trunk was cut. After 8 weeks, the lumbar region was surgically re‐explored, and the lymphatic drainage was examined by injection of Patent blue dye into the left lumbar lymph node. Results: In 8/8 animals of group A, patent transposed lymphatics were found. The patency of the anastomosis was proven directly by observation of blue dye transit and indirectly by observation of blue staining of the right lumbar lymph node. In 6/8 animals of group B, no lymphatic connection to the right lumbar lymphatic system was observed. Conclusions: This is the first report of the microsurgical technique and the proof of patency of lympho‐lymphonodular anastomoses. The novel animal model for testing the patency of transposed lymphatics is discussed. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.
Vitamin D intake and dietary sources in a representative sample of Spanish adults.

BACKGROUND Vitamin D plays an essential role in bone mineralisation and its deficiency is associated with several chronic diseases. Some studies have reported a deficient status of vitamin D in Spanish and European population. The present study aimed to assess vitamin D intake, dietary sources of this nutrient and its adequacy with respect to the dietary reference intakes (DRI) in a representative sample of Spanish adults. METHODS Four hundred and eighteen adults (aged 18-60 years) from 15 Spanish provinces were studied. They constituted a representative sample of the Spanish adult population. Energy and nutrient intake were determined using a 24-h dietary recall questionnaire for two consecutive days. Vitamin D intake was compared with the DRI for this vitamin. RESULTS Mean (SD) vitamin D intake was 3.5 (4.0) μg day(-1) (69.5% of the DRI). Of the participants studied, 81.6% had vitamin D intakes below the DRI and 68.7% had intakes below 67% of the DRI. Of the vitamin D, 91.4% came from food sources and 8.6% came from dietary supplements. The main food sources of vitamin D were fish, eggs, dairy products, cereals, oils and meat. In addition, those subjects who met the DRI for vitamin D had a higher consumption of fish, vegetables and fruits and a lower consumption of meats than those subjects who did not meet the DRI. CONCLUSIONS Vitamin D intake was inadequate in the sample of the adult Spanish population. Therefore, an increase in the consumption of oily fish, as well as fortified dairy products and cereals, might help to improve vitamin D intake.
The impact of frequent attenders on a UK emergency department

Background Previous studies have identified that there is a cohort of frequent attenders to the emergency department (ED). Recent initiatives aim to provide care closer to home and alternatives to ED attendance. This study aims to identify what impact frequent attenders still have on the ED. Methods A chart review of frequent attenders to the ED was carried out over a 12-month period. Inclusion criterion was 10 or more attendances. Information collected comprised age, sex, postcode, next of kin, number of attendances, day of the week, time, referral source, mode of arrival, triage category, disposal, association with alcohol and drug use, presenting complaint, and diagnosis. Results Forty-four frequent users met the study criterion accounting for 1.9% of departmental activity. Sixty-four percent of frequent attenders were male with an average age of 49 years (range 19–83). The majority lived within 5 miles of the ED. Sixty percent of attendances arrived at the ED through ambulance. Documentation of either concurrent alcohol use or history of alcohol dependence and illicit drug use was reported in 54.6 and 15.9% of patients. The admission rate of this group was 38.5% higher than the total ED admission rate of 22%. Conclusion There remains a cohort of frequent attenders that use the ED for their healthcare needs. A significant proportion of these attendances are associated with alcohol use, chronic disease or mental health problems. Reduction of attendances may be achieved by case management strategies and improving access to primary care and drug and alcohol services.
Gene-polymorphisms of angiotensin converting enzyme and endothelial nitric oxide synthase in patients with primary glomerulonephritis.

UNLABELLED The ACE D- and the ecNOS a-allele have been associated with an adverse prognosis in patients with glomerulonephritis (GN). Using genomic DNA we investigated by RT-PCR whether the two polymorphisms are useful prognostic markers in GN patients. In patients with primary GN (IgA-GN n = 70, membranous GN n = 23, FSGS n = 17, MPGN n = 6) neither the whole group nor disease-specific subgroups exhibited any alterations from the normal ACE genotype distribution. No significant associations were detected between the ACE genotype and the development of hypertension, antihypertensive therapy required, progression rate of the disease, age of diagnosis and the antiproteinuric response to ACE-inhibition. In 40 IgA-GN patients with ESRD no increased prevalence of the D-allele was noted. The distribution of the ecNOS-alleles in the above patients (a-allele 22%, b-allele 78%) was comparable to that of the normal controls. No association with any of the parameters mentioned above were detected in the case of the ecNOS-alleles. CONCLUSIONS In our Caucasian patients neither the determination of the ACE nor the ecNOS genotype offered any diagnostic or prognostic help.
Sulthiame in the Primary Therapy of West Syndrome: A Randomized Double‐blind Placebo‐controlled Add‐on Trial on Baseline Pyridoxine Medication

Summary: Purpose: West syndrome (WS) is still one of the most difficult to treat epilepsies in infancy. Sulthiame (STM), which is commonly used in some countries in the treatment of benign focal epilepsies in childhood, has been suggested to be effective in WS too. This prospective, randomized placebo‐controlled study was designed to prove or refute this hypothesis.
Moderators of unemployment and wage scarring during the transition to young adulthood: evidence from Norway

Entering the labour force is one of the most significant life events for young adults and is a central element of the transition to adulthood. Employment ideally provides − in addition to material security − social integration, identity and status. The experience of unemployment or employment instability during young adulthood may have long-term negative effects on labour market integration – so called scarring effects – as well as on subjective and objective well-being (Bell and Blanchflower, 2011; Gregg and Tominey, 2005; Luijkx and Wolbers, 2009; Nilsen and Reiso, 2011; Nordström Skans, 2004; Schmillen and Umkehrer, 2013). The effect of scarring is well documented in the research literature, but less is known about the mechanisms behind such effects amongst young workers. The state of scarring on the individual has been explained by either exposure to early unemployment or observed and/ or unobserved individual and family characteristics affecting the job offers or employment possibilities available to young people over time. Individual and family characteristics related to multiple domains may reveal direct and indirect pathways that suggest causal mechanisms of labour market outcomes for young people (Caspi et al., 1998). The direct pathway proposes that personal characteristics may directly affect job-search behaviour and job performance, which in turn influence opportunities for job offers and employment stability in later life. The indirect pathway proposes that individual and family characteristics may negatively affect other life events, such as education – highschool completion and college attendance – that are vital for securing employment (Caspi et al., 1998).
Finance pathways for young innovative small- and medium-size enterprises: A demand-side examination of finance gaps and policy implications for the post-global financial crisis finance escalator

The paper addresses the persistent finance gaps facing young, innovative SMEs, by examining the financing pathways of 40 UK businesses in a post global financial crisis (GFC) environment. Using a unique combination of finance escalator and resource-based view theories four propositions are tested by examining: (i) early and growth stage development; (ii) innovation RD (iii) the management resource base; (iv) finance gaps and their implications. The paper finds that successful financing strategies are emerging, using a mix of bootstrapping, collaboration and new emerging post-GFC finance escalator funding, which is heavily reliant on government interventions. It also pinpoints remaining finance gaps and the need for more cohesive financing and support policy to address these.
Comprehensive family‐based association study of the glutamate transporter gene SLC1A1 in obsessive‐compulsive disorder

SLC1A1 encodes a neuronal glutamate transporter and is a promising candidate gene for obsessive‐compulsive disorder (OCD). Several independent research groups have reported significant associations between OCD and single nucleotide polymorphisms (SNPs) in this gene. Previously, we evaluated 13 SNPs in, or near, SLC1A1 and reported a strong association signal with rs301443, a SNP 7.5 kb downstream of the gene [Shugart et al. (2009); Am J Med Genet Part B 150B:886–892]. The aims of the current study were first, to further investigate this finding by saturating the region around rs301443; and second, to explore the entire gene more thoroughly with a dense panel of SNP markers. We genotyped an additional 111 SNPs in or near SLC1A1, covering from 9 kb upstream to 84 kb downstream of the gene at average spacing of 1.7 kb per SNP, and conducted family‐based association analyses in 1,576 participants in 377 families. We found that none of the surrounding markers were in linkage disequilibrium with rs301443, nor were any associated with OCD. We also found that SNP rs4740788, located about 8.8 kb upstream of the gene, was associated with OCD in all families (P = 0.003) and in families with male affecteds (P = 0.002). A three‐SNP haplotype (rs4740788–rs10491734–rs10491733) was associated with OCD in the total sample (P = 0.00015) and in families with male affecteds (P = 0.0007). Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD. © 2011 Wiley‐Liss, Inc.
Determination of the excited-state lifetimes of the tryptophan residues in barnase, via multifrequency phase fluorometry of tryptophan mutants.

A multifrequency phase fluorometric study is described for wild-type barnase and engineered mutant proteins in which tryptophan residues have been replaced by less fluorescent residues which do not interfere with the determination of the tryptophan emission spectra and lifetimes. The lifetimes of the three tryptophans in the wild-type protein have been resolved. Trp-35 has a single fluorescence lifetime, which varies in the different proteins between 4.3 and 4.8 ns and is pH-independent between pH 5.8 and 8.9. Trp-71 and Trp-94 behave as an energy-transfer couple with both forward and reverse energy transfer. The couple shows two fluorescence lifetimes: 2.42 (+/-0.2) and 0.74 (+/-0.1) ns at pH 8.9, and 0.89 (+/-0.05) and 0.65 (+/-0.05) ns at pH 5.8. In the mutant Trp-94----Phe the lifetime of Trp-71 is 4.73 (+/-0.008) ns at high pH and 4.70 (+/-0.004) ns at low pH. In the mutant Trp-71----Tyr, the lifetime of Trp-94 is 1.57 (+/-0.01) ns at high pH and 0.82 (+/-0.025) ns at low pH. From these lifetimes, one-way energy-transfer efficiencies can be calculated according to Porter [Porter, G.B. (1972) Theor. Chim. Acta 24, 265-270]. At pH 8.9, a 71% efficiency was found for forward transfer (from Trp-71 to Trp-94) and 36% for reverse transfer. At pH 5.8 the transfer efficiency was 86% for forward and 4% for reverse transfer (all +/-2%). These transfer efficiencies correspond fairly well with the ones calculated according to the theory of Förster [Förster, T. (1948) Ann. Phys. (Leipzig) 2, 55-75]. (ABSTRACT TRUNCATED AT 250 WORDS)
Three Essays on International Trade and Migration

OF THE DISSERTATION THREE ESSAYS ON INTERNATIONAL TRADE AND MIGRATION by Yun Wang Florida International University, 2018 Miami, Florida Professor Hakan Yilmazkuday, Major Professor This dissertation encompasses three different topics on international trade and migration. The first chapter is the introduction. The second chapter investigates the short run effects of regional trade agreements on trade costs. It is widely accepted that the reinforcement of Regional Trade Agreements (RTAs) aiming at trade costs reduction among trade partners requires time. This paper investigates the effects of RTAs on trade costs over time by using unique micro-price data. As a key factor compared to the literature, excluding the local distribution costs, the trade costs we calculated are based on the arbitrage condition to equalize traded input prices across international cities. We confirm that having an RTA on average lowers trade costs significantly. Furthermore, data shows significant and negative effects of RTAs on trade costs over time. Specifically, besides the initial impact on trade costs, having an RTA continuously lower trade costs every year after the commencement of the RTA. Gravity variables such as distance, common language, colonial ties, free trade agreements, and adjacency are used to capture the effects of trade costs in empirical studies. The third chapter decomposes the overall effects of gravity variables on trade through three gravity channels: duties/tariffs (DC), transportation-costs (TC), and dyadic-preferences (PC). When PC is ignored as is typical in the literature, it is shown that nearly all gravity effects are trough distance; 29 percent
Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers.

OBJECTIVE The authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder. METHOD In 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium. RESULTS The dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (Z(LR))=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum Z(LR) for European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20% or less populationwide increase in risk to siblings of cases. CONCLUSIONS This region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.
The First 2,000 Days and Child Skills

Using a randomized experiment, this study investigates the impact of sustained investment in parenting, from pregnancy until age 5, in the context of extensive welfare provision. Providing the Preparing for Life program, incorporating home visiting, group parenting, and baby massage, to disadvantaged Irish families raised children’s cognitive and socioemotional/behavioral scores by two-thirds and one-quarter of a standard deviation, respectively. There were few differential effects by gender and stronger gains for firstborns and lower-resource households. The program also narrowed the socioeconomic gap in children’s skills. Analyses account for small sample size, differential attrition, multiple testing, contamination, and performance bias.