Miracle-dz/UniFAR-FTUs huggingface dataset:
Smoking, the xenobiotic pathway, and clubfoot.

BACKGROUND Isolated clubfoot is a common orthopedic birth defect that affects approximately 135,000 newborns worldwide. It is characterized by ankle equinus, hindfoot varus, and forefoot adductus. Although numerous studies suggest a multifactorial etiology, the specific genetic and environmental components have yet to be delineated. Maternal smoking during pregnancy is the only common environmental factor consistently shown to increase the risk for clubfoot. Moreover, a positive family history of clubfoot, in conjunction with maternal smoking, increases the risk 20-fold. These findings suggest that genetic variation in smoking metabolism (xenobiotic) genes may increase susceptibility to clubfoot. Based on this reasoning, we interrogated eight candidate genes from the xenobiotic metabolism. METHODS Twenty-two single-nucleotide polymorphisms and two null alleles in these genes (CYP1A1, CYP1A2, CYP1B1, CYP2A6, EPHX1, NAT2, GSTM1, and GSTT1) were genotyped in a dataset composed of non-Hispanic white and Hispanic multiplex and simplex families. RESULTS Only rs1048943/CYP1A1 had significantly altered transmission in the aggregate and multiplex non-Hispanic white datasets (p = 0.003 and p = 0.009, respectively). Perturbation of CYP1A1 can cause an increase in harmful, adduct-forming metabolic intermediates. A significant interaction between EPHX1 and NAT2 was also found (p = 0.007). Importantly, for CYP1A2, significant maternal (p = 0.03; relative risk [RR] = 1.24; 95% confidence interval [CI], 1.04-1.44) and fetal (p = 0.01; RR = 1.33; 95% CI, 1.13-1.54) genotypic effects were identified, suggesting that both maternal and fetal genotypes can negatively impact limb development. No association was found between maternal smoking status and variation in xenobiotic metabolism genes. CONCLUSION Together, these results suggest that xenobiotic metabolism genes are unlikely to play a major role in clubfoot; however, perturbation of this pathway may still play a contributory role.
Race differences in a sample of vocational rehabilitation clients with traumatic brain injury

Objective : To evaluate race differences in demographics, injury severity, and vocational outcomes for persons with TBI. Participants : Seventy-five individuals with TBI (13 African American, 62 Caucasian) who requested services from the Missouri Division of Vocational Rehabilitation (VR) over a 2-year period. Measures : Demographics (i.e. age, race, level of education), injury severity (i.e. LOC, PTA, length of hospitalization, neuropsychological test scores), VR services provided (e.g. transportation, maintenance, on-the-job training, etc.), and VR outcomes (successfully vs unsuccessfully employed; cost per case). Procedure : All participants completed a standard neuropsychological evaluation and completed VR services (i.e. were followed from enrolment to case closure). Hypotheses : African Americans and Caucasians would not differ in demographics or injury severity, although fewer African Americans would be successfully employed through DVR. Analyses : Chi-squares and non-parametric MANOVAs to evaluate race differences in terms of demographics, injury severity, vocational services provided and vocational outcomes. Results : As hypothesized, there were few race differences in demographics or injury severity, although African Americans received significantly more transportation services (62 vs 21%). Contrary to hypotheses, there was no difference in the number of successfully employed African Americans (23%) vs Caucasians (18%). Conclusions : African Americans and Caucasians with TBI achieve similar vocational successes if they receive state VR services
Non‐invasive measurements of arterial compliance in hypertensive compared with normotensive adults

Aim To determine differences in arterial compliance attributable to hypertension. Methods Since measurements of arterial compliance have tended to vary in the past according to the method used, a new technique comprising carotid ultrasound and simultaneous, calibrated, carotid pressure waveform measurements was tested in 43 hypertensives and 43 control subjects matched for age, gender and body size. Results There was a significant reduction in compliance among the hypertensive patients, as estimated by the elastic modulus and the ratio of stroke volume to pulse pressure. However, when the non-linearity of the pressure-volume relationship and the impact of distending pressure were taken into account, by the arterial stiffness index and by the increase in arterial wall thickness associated with hypertension by Young's modulus, there were no significant differences in arterial compliance between the two groups.
Banking net income and macroeconomics, from multicollinearity to Granger causality using US data

We select six macroeconomic variables and study their relation with (aggregate) net banking income. The aggregate net banking income was reconstructed from US banking sector authorities' data. Usefulness may be twofold, it provides aggregate insight and the methodology can be replicated at bank institution level. We use standard tools such as linear regression analysis (to study multicollinearity) and Granger causality. The obtained results suggest a highly changing relation between all variables in time and an increase of causality and feedback relations after the 2008 crisis.
Dissociation of tubular cell detachment and tubular cell death in clinical and experimental "acute tubular necrosis".

"Acute tubular necrosis" in humans is often characterized histologically by tubular cell loss and nonreplacement rather than by frank cellular necrosis. It has been assumed that tubular cells detach from the tubular basement membrane after the occurrence of irreversible cell injury and/or cell death. We examined voided urine from patients with native kidney and transplant kidney "acute tubular necrosis" and found significant tubular cell shedding with up to 100% viability of voided tubular cells, as determined by exclusion of trypan blue. Histochemical stains for the brush border enzyme gamma-glutamyl transpeptidase and electron microscopy of cell isolates demonstrated that 30 to 100% of the voided cells were of proximal tubule origin. Moreover, epithelial cell cultures were readily established from noncontaminated voided specimens, and more than 80% of the cells in monolayers expressed gamma-glutamyl transpeptidase activity in vitro. Electron microscopy of cell monolayers confirmed proximal tubular differentiation in the majority of cells in the monolayer, with the remainder having an appearance more consistent with distal origin. In rabbit models of acute ischemic (pedicle clamp) and toxic (HgCl2 and glycerol-induced) injury, tubular cell shedding was also significant, with a mean of 25 to 30% of the voided cells viable. Epithelial cells were successfully cultured and passed from animals with ischemic renal injury. In vitro studies were carried out in cultured human proximal tubular cells to assess suitability of this system for more direct study of the phenomenon of cell detachment in response to injury. We found significant changes in cell shape in response to exposure to anoxia and HgCl2 in these cultures, with extensive cell rounding and retraction at times when cell viability remained high. This in vitro system could prove useful for defining mechanisms of renal tubular cell detachment in response to injury and for examining potential interventions to prevent epithelial disruption and loss of functional integrity. These strategies may ultimately have clinical relevance in patients with "acute tubular necrosis".
Developing an Evaluation Capacity Building Network in the Field of Early Childhood Development

This reflective essay traces the development of an evaluation capacity building network within the early childhood development field. First, we describe the context for building the network using a community-based participatory approach and provide rationale for our specific focus on early childhood development. Second, we provide an explanation of the purpose and processes involved in three areas of significant engagement: partner, stakeholder, and student. We reflect on the methods of engagement used across these three areas and their impact on the outcomes that we achieved. Finally, we conclude the paper with some final considerations for guiding engaged scholars and with the next steps in our own work.
The Relationship between Economic Freedom and FDI versus Economic Growth: Evidence from the GCC Countries

This study aims to explain the role of economic freedom in attracting foreign investments and thus raising the level of economic growth. Through a study based on a sample composed of the Gulf Cooperation Council (GCC) countries. A standard model consisting of GCC countries (Saudi Arabia, United Arab Emirates, Qatar, Kuwait, and Oman) was used during the period from 1995 to 2017. We based on the analytical descriptive and secondly, we used a multivariate analysis based on the panel unit root test, the cointegration and finally the regression Fully Modified Ordinary Least Squares (FMOLS) and Dynamic Ordinary Least Squares (DOLS) following the existence of a long-term integration, which includes the modern standard methods to determine the role of economic freedom in raising foreign direct investment and thus economic growth in the second stage. The research findings from GCC countries support the literature, suggesting that there are indeed some indications that greater levels of economic freedom support higher rates of economic growth in a country.
Melatonin Levels during the First Week of Life and Their Relation with the Antioxidant Response in the Perinatal Period

Aim: Melatonin is a potent free radical scavenger and an indirect antioxidant. Knowledge about the behavior of melatonin secretion in the early neonatal period, which may relate to its properties at a vital stage during very high antioxidant demands, is limited. Patients and Methods: We studied 35 newborns admitted to the Neonatal Unit with respiratory distress syndrome (RDS) and with no signs of sepsis, severe anemia, hemodynamic compromise or malformation. The gestational age of the newborns was 26–40 weeks (mean value 32.5 weeks) and the weight at birth was 870–4,400 g (mean value 1,800 g). They were classified into two groups: ≤1,500 g or >1,500 g birthweight. In all cases, at 09:00 h on their 1st, 3rd and 7th days of life, serum melatonin was measured by RIA. The clinical history was recorded and treatment and follow-up were performed according to established neonatology practice, and the resultant data recorded. Informed consent from the parents or guardians was obtained in accordance with the Declaration of Helsinki. Statistical analysis was carried out using ANOVA-II (factor I: day of sample; factor II: birthweight). Results: There were significant increases in melatonin levels with increasing birthweight (p = 0.017), but no changes by day of sample. Although in both study groups melatonin levels increased during the first few days this was not statistically significant. Conclusions: In newborns of low birthweight, we report high melatonin concentrations in the morning and during the first week of life. These increase with maturation, and at full-term were similar to nocturnal levels during the acrophase of pineal gland secretion in toddlers and schoolage children, when pineal gland secretion is maximal and takes place reflecting environmental variations. In the early neonatal period these high levels of melatonin seem to derive from extrapineal sources, which mature to provide antioxidant protection in accordance with other elements of the antioxidant network to compensate for the high levels of oxidative stress that are present in the perinatal period.
The Arabidopsis thaliana Knockout Mutant for Phytochelatin Synthase1 (cad1-3) Is Defective in Callose Deposition, Bacterial Pathogen Defense and Auxin Content, But Shows an Increased Stem Lignification

The enzyme phytochelatin synthase (PCS) has long been studied with regard to its role in metal(loid) detoxification in several organisms, i.e., plants, yeasts, and nematodes. It is in fact widely recognized that PCS detoxifies a number of heavy metals by catalyzing the formation of thiol-rich oligomers, namely phytochelatins, from glutathione and related peptides. However, recent investigations have highlighted other possible roles played by the PCS enzyme in the plant cell, e.g., the control of pathogen-triggered callose deposition. In order to examine novel aspects of Arabidopsis thaliana PCS1 (AtPCS1) functions and to elucidate its possible roles in the secondary metabolism, metabolomic data of A. thaliana wild-type and cad1-3 mutant were compared, the latter lacking AtPCS1. HPLC-ESI-MS analysis showed differences in the relative levels of metabolites from the glucosinolate and phenylpropanoid pathways between cad1-3 and wild-type plants. Specifically, in control (Cd-untreated) plants, higher levels of 4-methoxy-indol-3-ylmethylglucosinolate were found in cad1-3 plants vs. wild-type. Moreover, the cad1-3 mutant showed to be impaired in the deposit of callose after Cd exposure, suggesting that AtPCS1 protects the plant against the toxicity of heavy metals not only by synthesizing PCs, but also by contributing to callose deposition. In line with the contribution of callose in counteracting Cd toxicity, we found that another callose-defective mutant, pen2-1, was more sensitive to high concentrations of Cd than wild-type plants. Moreover, cad1-3 plants were more susceptible than wild-type to the hemibiotrophic bacterial pathogen Pseudomonas syringae. The metabolome also revealed differences in the relative levels of hydroxycinnamic acids and flavonols, with consequences on cell wall properties and auxin content, respectively. First, increased lignification in the cad1-3 stems was found, probably aimed at counteracting the entry of Cd into the inner tissues. Second, in cad1-3 shoots, increased relative levels of kaempferol 3,7 dirhamnoside and quercetin hexoside rhamnoside were detected. These flavonols are endogenous inhibitors of auxin transport in planta; auxin levels in both roots and shoots of the cad1-3 mutant were in fact lower than those of the wild-type. Overall, our data highlight novel aspects of AtPCS1 functions in A. thaliana.
Aeromonas veronii, a new ornithine decarboxylase-positive species that may cause diarrhea

In 1983, the vernacular name Enteric Group 77 was coined for a group of strains that had been referred to our laboratory as "possible Vibrio cholerae except for gas production. " By DNA-DNA hybridization (hydroxyapatite, 32P), 8 of 10 strains of Enteric Group 77 were very highly related to the labeled strain 1169-83 (74 to 100% at 60 degrees C and 75 to 100% at 75 degrees C; percent divergence, 0.0 to 2.5). Type strains of six other Aeromonas species were 45 to 66% related (60 degrees C) to strain 1169-83, but type strains of 27 Vibrio species were only 2 to 6% related. The name Aeromonas veronii is proposed for the highly related group of nine strains formerly known as Enteric Group 77. The type strain is designated as ATCC 35604 (CDC 1169-83). Strains of A. veronii grew well at 36 degrees C and had positive reactions at this temperature for indole, methyl red, Voges-Proskauer, citrate, lysine and ornithine decarboxylases, DNase, lipase, and motility; the strains had negative reactions for arginine decarboxylase, H2S, urea, and malonate. The following sugars were fermented: D-glucose (acid and gas), cellobiose (seven of nine strains), D-galactose, maltose, D-mannitol, D-mannose, alpha-methyl-D-glucoside (eight of nine strains), salicin, sucrose, and trehalose. The following sugars were not fermented: adonitol, L-arabinose, D-arabitol, dulcitol, erythritol, myo-inositol, lactose, raffinose, L-rhamnose, D-sorbitol, and D-xylose. The positive ornithine decarboxylase reaction differentiates A. veronii from other Aeromonas species. The antibiogram of A. veronii is typical of other Aeromonas strains (resistance to ampicillin and carbenicillin and susceptibility to most other agents). A. veronii strains were isolated from three clinical sources: respiratory secretions of four victims of drowning or near drowning in fresh water (probably not clinically significant); infected wounds of two patients previously exposed to fresh water (unknown clinical significance); and stools from three patients with diarrhea (probably clinically significant).
INFECTIOUS ADAPTATION: POTENTIAL HOST RANGE OF A DEFENSIVE ENDOSYMBIONT IN DROSOPHILA

Maternally transmitted symbionts persist over macroevolutionary timescales by undergoing occasional lateral transfer to new host species. To invade a new species, a symbiont must survive and reproduce in the new host, undergo maternal transmission, and confer a selective benefit sufficient to overcome losses due to imperfect maternal transmission. Drosophila neotestacea is naturally infected with a strain of Spiroplasma that restores fertility to nematode‐parasitized females, which are otherwise sterilized by parasitism. We experimentally transferred Spiroplasma from D. neotestacea to four other species of mycophagous Drosophila that vary in their ability to resist and/or tolerate nematode parasitism. In all four species, Spiroplasma achieved within‐host densities and experienced rates of maternal transmission similar to that in D. neotestacea. Spiroplasma restored fertility to nematode‐parasitized females in one of these novel host species. Based on estimates of maternal transmission fidelity and the expected benefit of Spiroplasma infection in the wild, we conclude that Spiroplasma has the potential to spread and become abundant within Drosophila putrida, which is broadly sympatric with D. neotestacea and in which females are rendered completely sterile by nematode parasitism. Thus, a major adaptation within D. putrida could arise via lateral transmission of a heritable symbiont from D. neotestacea.
Local distribution of mepivacaine after distal interphalangeal joint injection in horses.

OBJECTIVE To evaluate the distribution of mepivacaine hydrochloride after distal interphalangeal (DIP) joint injection in horses. DESIGN Prospective, uncontrolled study. ANIMALS 10 adult horses. PROCEDURE 30 minutes before euthanasia, 8 ml of 2% mepivacaine hydrochloride was injected into the dorsal pouch of a forelimb DIP joint. Synovial tissue from the DIP joint and podotrochlear (navicular) bursa and bone tissue from the medullary cavity of the distal sesamoid (navicular) bone were taken from both forelimbs immediately after death. All synovial and bone specimens were analyzed for tissue concentration of mepivacaine by high-performance liquid chromatography. Synovial tissue and bone specimen concentrations from the injected forelimb were compared with corresponding specimens from the noninjected forelimb. All synovial tissue and bone specimen concentrations were compared with an estimated effective tissue concentration of mepivacaine (0.3 microgram/mg) for local anesthesia. RESULTS Specimen concentrations of mepivacaine from the injected forelimb were significantly greater (P < 0.05) than those in the corresponding tissues of the contralateral noninjected forelimb. All DIP joint and navicular bursa synovial tissue specimens from the injected forelimb had greater than the estimated effective tissue concentration of mepivacaine for local anesthesia. Of the 10 navicular bone specimens from the injected forelimb, 4 were higher and 2 were within 20% of the estimated effective tissue concentration of mepivacaine for local anesthesia. CONCLUSIONS Mepivacaine hydrochloride deposited into the DIP joint should anesthetize pain arising from navicular bursa synovia and may decrease pain arising from the medullary cavity of the navicular bone. CLINICAL RELEVANCE DIP joint injection of mepivacaine hydrochloride is not specific for DIP joint pain.
Studies of U.S. radium dial workers: an epidemiological classic.

The tragic history of the exposure during the second and third decades of this century in the United States of radium dial workers, patients and members of the public to ionizing radiation from internally deposited isotopes of radium is well documented. Recognition of abnormal health outcomes among female dial workers and determination of a causal association between these outcomes among the workers and their exposure to radium leading to the development of protection standards is a classic example of an epidemiological process whereby knowledge and understanding of "the distribution and determinants of disease" evolve. Health effects studies involving U.S. female dial workers began in the early 1920s and continued into the present decade. These studies are discussed in the context of the epidemiological process whereby cause-effect relationships may be postulated, evaluated and refined to the benefit of workers and the general public.
Amelioration of collagen-induced arthritis in rats by adenovirus-mediated PTEN gene transfer.

OBJECTIVE The phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway is known to be activated in rheumatoid arthritis (RA) synovial tissue, which impacts cell growth, proliferation, survival, and migration. Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) functions as a negative regulator of PI 3-kinase signaling, thus blocking Akt activation. The aim of this study was to examine the effect of PTEN gene transfer in rats with collagen-induced arthritis (CIA). METHODS Adenoviral vectors encoding human PTEN (AdPTEN) or beta-galactosidase (AdLacZ) were injected intraarticularly into rats with CIA, and their treatment responses were monitored by measures of clinical, radiographic, and histologic changes. The expression of phosphorylated Akt, total Akt, vascular endothelial growth factor (VEGF), proinflammatory cytokines, and chemokines, as well as the extent of microvessel density in the ankle joints were determined. RESULTS AdPTEN treatment reduced Akt phosphorylation and decreased VEGF production in human RA synovial fibroblasts. Compared with AdLacZ treatment of the rats with CIA, AdPTEN treatment significantly reduced ankle circumference, articular index scores, radiography scores, and histology scores, and also decreased microvessel density and levels of VEGF and interleukin-1beta. Furthermore, PTEN gene transfer led to down-regulation of Akt activation and increased apoptosis in the ankle joints. CONCLUSION This study is the first to demonstrate the in vivo effect of intraarticular gene delivery of PTEN on amelioration of arthritis symptoms in rats with CIA, which involved antiangiogenic, antiproliferative, and antiinflammatory effects of PTEN via inhibition of the PI 3-kinase/Akt signaling pathway. Our findings also implicate the PI 3-kinase/Akt pathway as a therapeutic target for the treatment of RA or other inflammatory diseases.