Miracle-dz/UniFAR-FTUs huggingface dataset:
Craniofacial features in osteogenesis imperfecta: A cephalometric study

Osteogenesis imperfecta (OI) is a heterogeneous group of connective tissue diseases that mainly manifest as bone fragility and skeletal deformity. In most families it segregates as a dominant trait and results from mutations in type I collagen genes. In this study we analyzed the size and form of the bony structures in heads of 59 consecutive patients with OI types I, III, or IV (Sillence classification), using lateral radiographs. Paired controls were matched for gender and age. The purpose was to obtain baseline information of craniofacial development in OI patients that have not received bisphosphonate treatment. In OI type I we found smaller than normal linear measurements, indicating a general growth deficiency, but no remarkable craniofacial deformity. In OI types III and IV, the growth impairment was pronounced, and the craniofacial form was altered as a result of differential growth deficiency and bending of the skeletal head structures. We found strong support both for an abnormally ventral position of the sella region due to bending of the cranial base, and for a closing mandibular growth rotation. Vertical underdevelopment of the dentoalveolar structures and the condylar process were identified as the main reasons for the relative mandibular prognathism in OI. Despite of the widespread intervention with bisphosphonates, the facial growth impairment will probably remain characteristic for many OI patients, and their orthodontic treatment should be further developed. © 2005 Wiley‐Liss, Inc.
The human burn wound as a primary source of interleukin-1 activity.

It has been suggested that interleukin 1 (IL-1) may be elevated systemically after major burn injury. Several metabolic changes commonly observed in patients with burns can be attributed in part to elevated IL-1 production; these include temperature elevation, skeletal muscle proteolysis, and alterations in the production of certain serum proteins by the hepatocyte (e.g., albumin and acute phase reactants). In this article we describe a likely source of this elevated IL-1 activity: the burn wound. Fluid taken from blisters on thermally injured skin early after burn injury contains substantial amounts of IL-1. This activity is less apparent in certain blister fluid (BF) samples, probably because of the presence of an inhibitor(s) of lymphocyte proliferation. However, after gel filtration high-performance liquid chromatography, the IL-1 actively elutes at a molecular weight of 15,000 to 20,000 daltons and can be blocked with an antibody to IL-1. We suggest that the source of this IL-1 activity is the injured keratinocyte and that release of this IL-1 systemically is inevitable. We postulate that release of IL-1 from the wound into the systemic circulation accounts in part for the metabolic changes outlined above. Furthermore, since epidermal IL-1 is a potent T cell chemoattractant, we believe that burn wound IL-1 may affect sequestration of T cells near the burn wound, resulting in T cell lymphopenia.
The effects of a low-carbohydrate versus low-fat diet on adipocytokines in severely obese adults: three-year follow-up of a randomized trial.

BACKGROUND Adipocytokines are associated with insulin resistance and cardiovascular disease and can be modified with weight loss. While we previously demonstrated weight loss and a reduction in leptin in obese adults who followed a low-carbohydrate diet for 6 months, the long-term effects of this diet on adipocytokines are unknown. METHODS 132 obese adults with a body mass index of > or = 35 kg/m2 were randomized to receive one year of dietary counseling to follow either a low-carbohydrate diet < 30 g/day (LC) or a caloric-restricted diet (reduced by 500 calories/day with < 30% of calories from fat) (LF). Weight, leptin, adiponectin, TNF-alpha, CRP, and insulin were measured at 0, 6, and 36 months (24 months post-counseling). Follow-up data at was collected for 53 participants who returned at 36 months. RESULTS Mean weight change from baseline was not different between the groups at 36 months. Between 6 and 36 months weight was unchanged for LF, while LC appeared to regain weight [+ 4.84 +/- 35.6 kg (+ 3.0%)]. This difference, however, was not significant (p = 0.08). Leptin was unchanged in LF at both 6 and 36 months. In LC leptin decreased by 8.49 +/- 6.4 ng/mL or 22.7% at 6 months (p < 0.001) and increased by 10.68 +/- 25.2 ng/mL or 41.9% between 6 and 36 months (p = 0.02). There were no differences in insulin, adiponectin, TNF-alpha, or CRP between the groups. CONCLUSIONS Favorable changes in leptin that accompany weight loss are not sustained in individuals who followed a low-carbohydrate diet for one year. A low-carbohydrate diet had no significant effect on insulin, adiponectin, TNF-alpha, or CRP compared to a low-fat diet at 36 months.
Missed opportunities for the prevention of cardiovascular disease among British hypertensives in primary care.

BACKGROUND High-risk strategies for the prevention of cardiovascular disease (CVD) among hypertensive patients require knowledge of the prevalence and interaction of modifiable risk factors to ensure effective targeting of interventions. Comparatively little is known of risk-factor profiles and their modification among hypertensives in primary care. AIM The present study was designed to explore relationships between patients' knowledge of CVD risk factors, their perception of personal risk and health behaviours, and their use of lifestyle interventions. METHOD A cross-sectional survey of 2676 men and women with mild to moderate hypertension (diastolic blood pressure 95-115 mmHg), and their general practitioners, recruited from 1044 general practices throughout the UK, was conducted. RESULTS Levels of modifiable risk factors were high, although there was considerable variation by age and sex; most (98.5%) patients had at least one additional CVD risk factor. A lower standard of living was associated with a higher prevalence of 'unhealthy' behaviours. Out of those with a current lifestyle problem, 85% of obese patients, 59% of smokers, 47% of excess drinkers, 49% of those with dietary risk factors and 32% of inactive patients claimed to have adopted healthier behaviours within the past 3 months. Older subjects and those with a lower standard of living were less likely to acknowledge risks, and those who did were less likely to report improving their lifestyles. While 71% of patients recalled receiving lifestyle advice, the coverage and targeting of specific interventions was generally poor. Overall, 60% of the sample had received advice on weight control, 47% on diet, 38% on exercise, 38% on smoking and 36% on alcohol. Women and older people were less likely to be given relevant counseling, and there was no evidence of targeting with respect to subjects' social class, level of hypertension or duration of diagnosis. CONCLUSION Lifestyle interventions are welcomed and are viewed as helpful by patients receiving them. Potential health gains among high-risk hypertensives are being lost because of poor targeting and coverage of those at greatest risk.
Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1–derived reactive oxygen species

The alcohol‐inducible cytochrome P450 2E1 (CYP2E1) is expressed mainly in hepatocytes and generates reactive oxygen species (ROS). To better understand how hepatic stellate cells (HSC) become activated in the presence of oxidative stress and evaluate whether CYP2E1‐derived ROS activate stellate cells, we coincubated primary stellate cells with HepG2 cells, which do (E47 cells) or do not (C34 cells) express CYP2E1. Morphologic changes and loss of lipid droplets were more apparent in the stellate cells cocultured with E47 cells. There was a more pronounced increase in α‐smooth muscle actin (α‐sma), intracellular and secreted collagen type I protein, and intra‐ and extracellular H2O2 and lipid peroxidation products in stellate cells coincubated with E47 cells. Expression of collagen in stellate cells did not change when cocultured with HepG2 cells expressing a different P450, CYP3A4. Stellate cells cultured on Matrigel expressed increased α‐sma and collagen when incubated with E47 cells. The increase in collagen production by coculture with E47 cells was prevented by antioxidants, by CYP2E1 inhibitors, and by transfected antisense CYP2E1. The addition of arachidonic acid plus ferric nitrilotriacetate (Fe‐NTA), agents that potentiate oxidative stress, further induced collagen protein in the E47 coculture. Stellate cell proliferation was greater in the E47 coculture, and this was partially abrogated by catalase and vitamin E. These results show that hepatocytes containing CYP2E1 release diffusible mediators including ROS, which can activate HSC. Thus, besides perturbing the homeostasis of hepatocytes, CYP2E1‐derived diffusible oxidants may also interact with stellate cells and contribute to hepatic fibrosis.
Genetic heterogeneity in Rubinstein–Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300

Background: Rubinstein–Taybi syndrome (RSTS) is a congenital disorder characterised by growth retardation, facial dysmorphisms, skeletal abnormalities and mental retardation. Broad thumbs and halluces are the hallmarks of the syndrome. RSTS is associated with chromosomal rearrangements and mutations in the CREB-binding protein gene (CREBBP), also termed CBP, encoding the CREB-binding protein. Recently, it was shown that mutations in EP300, coding for the p300 protein, also cause RSTS. CBP and EP300 are highly homologous genes, which play important roles as global transcriptional coactivators. Objective: To report the phenotype of the presently known patients with RSTS (n = 4) carrying germline mutations of EP300. Results: The patients with EP300 mutations displayed the typical facial gestalt and malformation pattern compatible with the diagnosis of RSTS. However, three patients exhibited much milder skeletal findings on the hands and feet than typically observed in patients with RSTS. Conclusions: Part of the clinical variability in RSTS is explained by genetic heterogeneity. The diagnosis of RSTS must be expanded to include patients without broad thumbs or halluces.
The Domain Organization of Human Topoisomerase I (*)

Using limited proteolysis, we show that the domain boundaries of human topoisomerase I closely parallel those predicted from sequence comparisons with other cellular Topo I enzymes. The enzyme is comprised of (i) an NH-terminal domain (24 kDa), which is known to be dispensable for activity, (ii) the core domain (54 kDa), (iii) a linker region (3 kDa), and (iv) the COOH-terminal domain (10 kDa), which contains the active site tyrosine. The highly conserved core and COOH-terminal domains are resistant to proteolysis, while the unconserved NH-terminal and linker domains are sensitive. Noncovalent binding of Topo I to plasmid DNA or to short duplex oligonucleotides decreases the sensitivity of the linker to proteolysis by approximately a factor of 10 but has no effect on proteolysis of the NH-terminal domain. When the enzyme is covalently complexed to an 18 base pair single-stranded oligonucleotide, the linker region is sensitive to proteolysis whether or not duplex DNA is present. The net positive charge of the linker domain suggests that at a certain point in catalysis the linker may bind directly to DNA. Further, we show that limited subtilisin cleavage can generate a mixture of 60-kDa core and 10-kDa COOH-terminal fragments, which retain a level of topoisomerase activity that is nearly equal to undigested control samples, presumably because the two fragments remain associated after proteolytic cleavage. Thus, despite its potential role in DNA binding, the linker domain (in addition to the NH-terminal domain) appears to be dispensable for topoisomerase activity. Finally, the limited proteolysis pattern of the human enzyme differs substantially from the limited proteolysis pattern of the vaccinia viral Topo I, indicating that the two enzymes belong to separate eukaryotic topoisomerase I subfamilies.
MTR 2756 A > G polymorphism is associated with the risk of systemic lupus erythematosus in the Polish population

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overexpression of cytokines and T cell accessory molecules, which is due to a reduction of DNA regulatory region methylation in T cells. It has been shown that polymorphic variants of genes encoding key enzymes of folate and methionine metabolism may have an effect on DNA methylation. Therefore, in patients with SLE (n = 106) and controls (n = 141) we examined the distribution of polymorphisms of genes encoding methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1); and methylenetetrahydrofolate reductase (MTHFR). We found that MTR 2756AG (919DG) or GG (919GG) genotype exhibited 2.005-fold increased risk of SLE (95% CI = 1.177—3.416, P = 0.0146). However, MTHFR 677C > T (A222V) and MTHFD1 1958G > A (R653Q) allele and genotype frequencies did not exhibit statistical differences between SLE patients and controls. Since MTR is located on 1q43, our findings confirm the significance of the role of 1q region and the methyl cycle in etiopathogenesis of SLE. Lupus (2007) 16, 450—454.
QUALITY MANAGEMENT IN SLOVENE PUBLIC ADMINISTRATION – OPPORTUNITIES FOR LEARNING FROM EXPERIENCE

Public administrations in practically all countries face challenges with respect to the efficiency and quality of their services. In their endeavours for better performance, they progressively implement general public management principles and quality management. Countries exercise different approaches which have a common aim: to build the institutional and administrative capacity to adequately support their political management and national economies. The paper will present the broader context of how countries could or should manage their public administrations to strengthen their administrative capacity for quality management and achieve sustainable public administration. Secondly, the paper will present the results of a comparative analysis of quality management in EU member states and the trends observed, and, thirdly, the case of
Capital market internationalization and equity financing costs: firm-level evidence from China*

Abstract In recent years, the Chinese capital market has been increasingly integrated into the international capital market, although the level of integration remains low. We exploit the unique variations in China’s capital market integration to study the effect of capital market internationalization on the cost of equity financing. Using firm-level panel data from China, we measure capital market integration at the corporate level using the degree of co-movement between a company’s share price and the international capital market. After controlling for year effects and industry effects, we find that the growing integration of the capital market is significantly increasing Chinese companies’ equity financing costs. This surprising result still holds after controlling for the endogeneity problem. One possible explanation is the asymmetric approach of China’s capital market internationalization, i.e. while the Chinese capital market is increasingly open to international investors, it remains difficult for Chinese investors to invest abroad. Consequently, while international investors bring more risk into the Chinese market, domestic investors in China lack effective ways to diversify the risk in the global market. This additional source of non-diversifiable risk demands a higher return to capital, which raises the equity financing costs in China.
Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques.

CONTEXT Longitudinal studies of risk factors for hypothyroidism are required to inform debate regarding the TSH reference range. There are limited longitudinal data on the predictive value of thyroid antibodies measured by automated immunoassay (as opposed to semiquantitative methods). METHODS We measured TSH, free T(4), thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs) using the Immulite platform on sera from 1184 participants in the 1981 and 1994 Busselton Health Surveys. Outcome measures at follow-up were hypothyroidism, defined as TSH greater than 4.0 mU/liter or on thyroxine treatment; and overt hypothyroidism, defined as TSH above 10.0 mU/liter or on thyroxine treatment. Receiver-operator characteristic analysis was used to determine optimal cutoffs for baseline TSH, TPOAbs, and TgAbs as predictors of hypothyroidism. RESULTS At 13 yr follow-up, 110 subjects (84 women) had hypothyroidism, of whom 42 (38 women) had overt hypothyroidism. Optimal cutoffs for predicting hypothyroidism were baseline TSH above 2.5 mU/liter, TPOAbs above 29 kIU/liter, and TgAbs above 22 kIU/liter, compared with reference range upper limits of 4.0 mU/liter, 35 kIU/liter, and 55 kIU/liter, respectively. In women with positive thyroid antibodies (TPOAbs or TgAbs), the prevalence of hypothyroidism at follow-up (with 95% confidence intervals) was 12.0% (3.0-21.0%) when baseline TSH was 2.5 mU/liter or less, 55.2% (37.1-73.3%) for TSH between 2.5 and 4.0 mU/liter, and 85.7% (74.1-97.3%) for TSH above 4.0 mU/liter. CONCLUSIONS The use of TSH cutoffs of 2.5 and 4.0 mU/liter, combined with thyroid antibodies, provides a clinically useful estimate of the long-term risk of hypothyroidism.
The pharmacist's role in the medicinal management of depression.

AIM To elicit pharmacists' perceptions of medication management for people who have been prescribed medication for depression. METHOD A questionnaire survey of 103 mainly community pharmacists was used. RESULTS People frequently approached pharmacists for information about a range of issues concerning antidepressant medication. Although pharmacists were knowledgeable about all aspects of pharmacological interventions, many felt their location in the commercial sector inhibited the amount of assistance they could provide. Barriers to providing information were identified, and the paucity of pharmacists' links with primary care teams exposed. CONCLUSION The survey supports other studies that have suggested pharmacists could provide considerable assistance in helping people to understand their medication and its benefits. There is also discussion of the ways in which the future role of pharmacists could be developed so that they collaborate more closely with other healthcare professionals.
Fiscal Policy Learning from Crisis: Comparative Analysis of the Baltic Countries

Abstract The experience of a major crisis is often expected to lead to policy learning but the empirical evidence about this is limited. The goal of the paper is to explore comparatively whether the crisis of 2008–2010 has led to fiscal policy learning by civil servants in the three Baltic countries. Despite some differences in the crisis experience, the finance ministry officials in all three countries have identified the same lesson from the crisis: fiscal policy should be counter-cyclical and help to stabilize the economy. The paper also discusses how various factors have influenced policy learning, including the acknowledgment of failure, blame shifting, and analytical tractability.
Quantification of the optical surface reflection and surface roughness of articular cartilage using optical coherence tomography

Optical coherence tomography (OCT) is a promising new technique for characterizing the structural changes of articular cartilage in osteoarthritis (OA). The calculation of quantitative parameters from the OCT signal is an important step to develop OCT as an effective diagnostic technique. In this study, two novel parameters for the quantification of optical surface reflection and surface roughness from OCT measurements are introduced: optical surface reflection coefficient (ORC), describing the amount of a ratio of the optical reflection from cartilage surface with respect to that from a reference material, and OCT roughness index (ORI) indicating the smoothness of the cartilage surface. The sensitivity of ORC and ORI to detect changes in bovine articular cartilage samples after enzymatic degradations of collagen and proteoglycans using collagenase and trypsin enzymes, respectively, was tested in vitro. A significant decrease (p < 0.001) in ORC as well as a significant increase (p < 0.001) in ORI was observed after collagenase digestion. After trypsin digestion, no significant changes in ORC or ORI were observed. To conclude, the new parameters introduced were demonstrated to be feasible and sensitive to detect typical OA-like degenerative changes in the collagen network. From the clinical point of view, the quantification of OCT measurements is of great interest since OCT probes have been already miniaturized and applied in patient studies during arthroscopy or open knee surgery in vivo. Further studies are still necessary to demonstrate the clinical capability of the introduced parameters for naturally occurring early OA changes in the cartilage.
The case for feedforward multisensory convergence during early cortical processing

The prevailing hierarchical model of sensory processing in the brain holds that different modalities of sensory information emanating from a single object are analyzed extensively during passage through their respective unisensory processing streams before they are combined in higher-order ‘multisensory’ regions of the cortex. Because of this view, multisensory interactions that have been found at early, putatively ‘unisensory’ cortical processing stages during hemodynamic imaging studies have been assumed to reflect feedback modulations that occur subsequent to multisensory processing in the higher-order multisensory areas. In this paper, we consider findings that challenge an exclusively feedback interpretation of early multisensory integration effects. First, high-density electrical mapping studies in humans have shown that multisensory convergence and integration effects can occur so early in the time course of sensory processing that purely feedback mediation becomes extremely unlikely. Second, direct neural recordings in monkeys show that, in some cases, convergent inputs at early cortical stages have physiological profiles characteristic of feedforward rather than feedback inputs. Third, damage to higher-order integrative regions in humans often spares the ability to integrate across sensory modalities. Finally, recent anatomic tracer studies have reported direct anatomical connections between primary visual and auditory cortex. These findings make it clear that multisensory convergence at early stages of cortical processing results from feedforward as well as feedback and lateral connections, thus using the full range of anatomical connections available in brain circuitry.