Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel functionally deficient MYH variant in individuals with colorectal adenomatous polyposis

Inherited biallelic mutations in the base excision repair gene MYH confer susceptibility to colorectal adenomas and carcinoma. Approximately 85% of Caucasians with MYH mutations carry the (c.494A>G) p.Y165C and (c.1145G>A) p.G382D variants. Only a few other clearly pathogenic mutations have been identified, and mutation analyses tend to focus on the two founder mutations rather than the whole coding region of the gene. We sequenced the entire coding region of MYH in a population‐based series of 24 Finnish APC‐mutation negative polyposis patients in order to identify novel pathogenic MYH variants. A population‐based series of 1,042 Finnish colorectal cancer patients and 85 cancer‐free controls were available for further evaluation. A functional cleavage assay was designed to evaluate consequences of possible novel variants to protein function. Three novel MYH variants, (c.270C>T) p.Y90Y, (c.1376C>A) p.A459D, and (c.1389G>C) p.T469T, were observed. p.A459D variant in exon 14 was identified in two patients from the polyposis series, once in homozygosity and once in compound heterozygosity with p.Y165C. In the population‐based series of 1,042 colorectal cancer patients, the p.A459D mutation was identified once, in homozygosity (allele frequency 0.1%). No p.A459D mutations were identified in the control individuals. In vitro cleavage assay showed significantly reduced repair activity in p.A459D cells. Interestingly, another variant in the same codon has previously been described in a British study, supporting a key role for the codon 459 in MYH function. We therefore suggest that screening of mutations in MYH exon 14 should be added to the molecular analysis at‐risk individuals. © 2005 Wiley‐Liss, Inc.
{N,N′-Bis[1-(2-pyridyl)ethylidene]ethane-1,2-diamine-κ4 N,N′,N′′,N′′′}(thiocyanato-κN)zinc(II) perchlorate

In the title compound, [Zn(NCS)(C16H18N4)]ClO4, the ZnII atom is five-coordinated by four N atoms of the Schiff base ligand N,N′-bis[1-(2-pyridyl)ethylidene]ethane-1,2-diamine in the basal plane, and by the N atom of a thiocyanate ligand at the apical position, forming a distorted square-pyramidal geometry. The r.m.s. deviation from a plane through the four N atoms of the Schiff base is 0.015 (3) Å, and the deviation of the Ni atom from that plane is 0.591 (2) Å. Bond lengths are comparable with those observed in similar zinc(II) complexes with Schiff bases. The two methylene C atoms of the ethane-1,2-diamine bridge of the Schiff base ligand are disordered over two sites with occupancies of 0.587 (3) and 0.413 (3).
Bronchial responsiveness in a Norwegian community.

Bronchial responsiveness to methacholine was examined in a Norwegian general population sample (n = 490) 18 to 73 yr of age. Altogether, 20 and 6% of the sample had PC20 less than or equal to 32 mg/ml and PC20 less than or equal to 8 mg/ml, respectively. The relationship of bronchial responsiveness to the following potential predictors were examined: sex, age, smoking habits, airway caliber (FEV1), FEV1 percent predicted (%FEV1), urban-rural area of residence, occupational airborne exposure in present job, and total serum IgE. After adjusting for age and FEV1, the odds ratio for PC20 less than or equal to 32 mg/ml was higher for men than for women in smokers and in ex-smokers, but did not vary by sex in nonsmokers, the adjusted odds ratio for PC20 less than or equal to 32 mg/ml in male compared with female smokers being 8.4 (95% Cl: 2.5-37.4). Irrespective of smoking status the sex- and FEV1-adjusted odds ratio for PC20 less than or equal to 32 mg/ml fell with increasing age. For every 10-yr increase in age the adjusted odds ratio for PC20 less than or equal to 32 mg/ml methacholine in nonsmokers decreased by 2.0 (95% Cl: 1.3-3.3). Also FEV1 and %FEV1 were predictors of PC20 less than or equal to 32 mg/ml after adjusting for sex and age irrespective of smoking status. Bronchial responsiveness (PC20 less than or equal to 8 mg/ml) was more prevalent in rural than in urban areas, the adjusted odds ratio being 2.5 (95% Cl: 1.1-5.9) for bronchial responsiveness in rural compared with urban residents after adjusting for sex, age, smoking habits, and FEV1. (ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of GABAA receptor binding in human brain by neuroactive steroids: Species and brain regional differences

Allosteric modulation by neuroactive steroids of radioligand binding sites on the GABAA receptor complex was demonstrated by autoradiography in vitro in several regions of human brain and the effects compared to those in rat brain. Comparing human and rat, two steroids known to be active in enhancing GABA‐mediated postsynaptic inhibition, 5α‐pregnane‐3α21‐diol‐20‐one (tetrahydro‐deoxycorticosterone, THDOC) and alphaxalone (5α‐pregnane‐3α‐hdyroxy‐11,20‐dione), allosterically inhibited [35S]TBPS binding to the picrotoxin/convulsant site in both species in several regions including the hippocampus. Unlike rat, human brain binding of [3]Hlflunitrazepam to the benzodiazepine site was not enhanced by alphaxalone (at any concentration), but was unaffected in many regions and inhibited in others. Binding of [3H]muscimol to high and low affinity GABA sites were enhanced by both steroids in all tested regions of rat brain, although to varying degrees. However, several lobes of human cortex showed no modulation of muscimol binding by either steroid, and THDOC, but not alphaxolone, inhibited in some areas. Comparing regions, THDOC at high concentrations (10 μM) enhanced in human frontal lobe and primary sensory and motor cortex, with greater effect in deep layers than superficial. This steroid had no effect in other parts of parietal lobe and inhibited muscimol binding in temporal lobe, primary visual cortex, and other parts of occipital lobe. Concentration‐dependence curves for THDOC showed regional variation, e.g., in the hippocampal formation and surrounding neocortex. These regional and species differences are consistent with the existence of multiple GABAA receptor subtypes that differ in pharmacology. This heterogeneity provides both the opportunity and the difficulty of targeting clinically useful medications such as antiepileptic drugs to the appropriate human brain regions, and the species differences in regional subtype expression suggest caution in use of animal models. © 1995 Wiley‐Liss, Inc.
Spectral-Temporal Modulated Ripple Discrimination by Children With Cochlear Implants

Objectives: A postlingually implanted adult typically develops hearing with an intact auditory system, followed by periods of deafness (or near deafness) and adaptation to the implant. For an early implanted child whose brain is highly plastic, the auditory system matures with consistent input from a cochlear implant. It is likely that the auditory system of early implanted cochlear implant users is fundamentally different than postlingually implanted adults. The purpose of this study is to compare the basic psychophysical capabilities and limitations of these two populations on a spectral resolution task to determine potential effects of early deprivation and plasticity. Design: Performance on a spectral resolution task (Spectral-temporally Modulated Ripple Test [SMRT]) was measured for 20 bilaterally implanted, prelingually deafened children (between 5 and 13 years of age) and 20 hearing children within the same age range. Additionally, 15 bilaterally implanted, postlingually deafened adults, and 10 hearing adults were tested on the same task. Cochlear implant users (adults and children) were tested bilaterally, and with each ear alone. Hearing listeners (adults and children) were tested with the unprocessed SMRT and with a vocoded version that simulates an 8-channel cochlear implant. Results: For children with normal hearing, a positive correlation was found between age and SMRT score for both the unprocessed and vocoded versions. Older hearing children performed similarly to hearing adults in both the unprocessed and vocoded test conditions. However, for children with cochlear implants, no significant relationship was found between SMRT score and chronological age, age at implantation, or years of implant experience. Performance by children with cochlear implants was poorer than performance by cochlear implanted adults. It was also found that children implanted sequentially tended to have better scores with the first implant compared with the second implant. This difference was not observed for adults. An additional finding was that SMRT score was negatively correlated with age for adults with implants. Conclusions: Results from this study suggest that basic psychophysical capabilities of early implanted children and postlingually implanted adults differ when assessed in the sound field using their personal implant processors. Because spectral resolution does not improve with age for early implanted children, it seems likely that the sparse representation of the signal provided by a cochlear implant limits spectral resolution development. These results are supported by the finding that postlingually implanted adults, whose auditory systems matured before the onset of hearing loss, perform significantly better than early implanted children on the spectral resolution test.
Pretreatment with Soluble Thrombomodulin Prevents Intrasinusoidal Coagulation and Liver Dysfunction following Extensive Hepatectomy in Cirrhotic Rats

Summary The major cause of posthepatectomy liver dysfunction is supposed to be microcirculatory disturbance caused by imbalance of intrasinusoidal coagulation equilibrium. Thrombomodulin (TM) is a potent anticoagulant expressed on the endothelial cell surface that regulates the coagulation system by binding thrombin and accelerating the thrombin-catalyzed activation of protein C. Therefore, we examined the effect of soluble TM purified from human urine (UTM) on intrasinusoidal coagulation in cirrhotic rats. Dimethylnitrosamine-induced cirrhotic rats underwent 70% hepatectomy and received endotoxin 48 h after. UTM or vehicle alone was intravenously administered to each rat 30 min before endotoxin injection. UTM treatment attenuated the increases in cytosolic enzymes and serum hyaluronic acid level. The UTM supply improved the survival rate of the rats at 12 h after endotoxin challenge. Histologically, intrasinusoidal fibrin depositions and massive hepatocellular necrosis observed in control rats were scarcely found in UTM-treated rats. Immunohistochemical examination revealed that marked TM stains in sinusoidal endothelial cells were well preserved in UTM-treated rats. In conclusion, UTM administration prevented intrasinusoidal fibrin depositions and attenuated posthepatectomy liver dysfunction in cirrhotic rats.
Cardiovascular Screening in Young Athletes: Evidence for the Electrocardiogram

&NA;The objective of this study is to review the evidence for cardiovascular screening inclusive of an electrocardiogram (ECG) in young athletes. Sudden cardiac death (SCD) in athletes is the leading cause of death during exercise and occurs at a rate that is substantially higher than initially recognized. There is widespread agreement that cardiovascular screening should be performed prior to athletic competition. The primary purpose of preparticipation cardiovascular screening is to identify athletes with conditions that predispose them to SCD. Unfortunately, the traditional model in the United States of a medical history and a physical examination has limited sensitivity to detect cardiovascular disease and provides false reassurance to athletes, parents, and team officials. The addition of an ECG enhances the ability to identify disease, and modern athlete-specific ECG interpretation standards used by experienced physicians provide low false-positive rates, improving the cost-effectiveness while preserving sensitivity. The evidence is clear that if athletes are screened, ECG-inclusive strategies are most likely to meet the primary aim of preparticipation cardiovascular screening. These advanced protocols have the potential to improve health and safety during sport events and should be considered the best practice in high-risk athletes when the sports cardiology infrastructure and oversight are readily available.
Simian Immunodeficiency Virus Containing Mutations in N-Terminal Tyrosine Residues and in the PxxP Motif in Nef Replicates Efficiently in Rhesus Macaques

ABSTRACT SIVmac Nef contains two N-terminal tyrosines that were proposed to be part of an SH2-ligand domain and/or a tyrosine-based endocytosis signal and a putative SH3-ligand domain (P104xxP107). In the present study, we investigated the effects of combined mutations in these tyrosine and proline residues on simian immunodeficiency virus (SIV) Nef interactions with the cellular signal transduction and endocytic machinery. We found that mutation of Y28F, Y39F, P104A, and P107A (FFAA-Nef) had little effect on Nef functions such as the association with the cellular tyrosine kinase Src, downregulation of cell surface expression of CD4 and class I major histocompatibility complex, and enhancement of virion infectivity. However, mutations in the PxxP sequence reduced the ability of Nef to stimulate viral replication in primary lymphocytes. Three macaques infected with the SIVmac239 FFAA-Nef variant showed high viral loads during the acute phase of infection. Reversions in the mutated prolines were observed between 12 and 20 weeks postinfection. Importantly, reversion of A107→P, which restored the ability of Nef to coprecipitate a 62-kDa phosphoprotein in in vitro kinase assays, did not precede the development of a high viral load. The Y28/Y39→F28/F39substitutions did not revert. In conclusion, mutations in both the tyrosine residues and the putative SH3 ligand domain apparently do not disrupt major aspects of SIV Nef function in vivo.
Total antioxidant capacity and superoxide dismutase activity levels in serum and gingival crevicular fluid in post-menopausal women with chronic periodontitis.

OBJECTIVES Menopause has been linked with oxidative stress and decreased antioxidant (AO) defence. A connection has been established between menopause and certain periodontal conditions. The objective of this study is to compare serum and gingival crevicular fluid (GCF) total antioxidant capacity (TAOC) and superoxide dismutase (SOD) concentrations in post-menopausal patients with chronic periodontitis (PMCP) with those of pre-menopausal chronic periodontitis patients (CP). MATERIAL AND METHODS Thirty-two PMCP patients, 31 CP patients, 25 post-menopausal periodontally healthy controls (PMPH) and 26 pre-menopausal controls (PH) were studied. After clinical measurements and samplings, serum and GCF TAOC and SOD concentrations were established in turn using an automated TAOC assay and spectrophotometric end point measurement. The results were analysed statistically. RESULTS Serum and GCF TAOC and SOD concentrations were significantly lower in menopause and periodontitis (p<0.05). The lowest values were in the PMCP group, whereas the highest values were in the PH group. While the effect of menopause was more evident in serum antioxidant analysis, the effect of periodontitis was observed to be more apparent in GCF. CONCLUSIONS A decrease in systemic and local AO defence was observed owing to both menopause and periodontitis. The lowest AO values in the PMCP group suggest that menopause may be a risk factor for periodontitis.
Craniofacial computed tomography scanning: technology, applications and future trends.

OBJECTIVES Craniofacial imaging in three dimensions depends on computed tomography (CT) and related technologies. This paper explains the state-of-the-art for medical and dedicated craniofacial cone-beam CT scanners. METHOD Current medical CT scanners are surveyed, especially the recently announced 16 simultaneous slice models with subsecond source-detector rotation times and spiral/helical third generation geometry. The medical scanner technology is contrasted with dedicated low-cost craniofacial cone-beam CT scanners to delineate the relevant technologies and clarify the differences. RESULTS CT scanners performance in any task is determined by their detectors and reconstruction algorithm primarily and to a lesser extent by the X-ray source, dose utilization, computational and display electronics, and software for post-processing. Each of these components differs between medical and low-cost cone-beam scanners, and the differences are tabulated and explained. CONCLUSION Low-cost craniofacial CT scanners are significantly different from general purpose medical CT scanners, with compromises in technical performance. Despite their limitations, these instruments are remarkably useful for their intended application domain and should improve as computers continue to increase their performance.
Quality assessment of platelet rich plasma during anti-platelet therapy

Platelet rich plasma (PRP) is being used with increased frequency in many surgical procedures for its known benefits of accelerated surgical wound site healing. Speculations in its efficacy in the presence of anti-platelet therapy have been proposed. To aid in defining a quality platelet rich plasma product in the presence of acetylsalicylic acid (ASA) and Plavix (clopidogrel bisulfate), we investigated three (3) groups (n=18) of cardiac surgical patients receiving PRP. Platelet function test, platelet concentration, and quantification of growth factors (PDGF-bb and TGF-b1) were evaluated. Results showed no statistical evidence of decreased growth factors delivered to the surgical wound site in the presence of acetylsalicylic acid (ASA) and/or Plavix (clopidogrel bisulfate). Evidence in this pilot study supports the use of PRP for patients receiving Plavix and aspirin therapy without compromising the quantity of specific growth factors delivered to a wound site. Perfusion (2007) 22, 41—50.
Identification of the Binding Site for an Alloantibody to von Willebrand Factor which Inhibits Binding to Glycoprotein Ib within the Amino-terminal Region Flanking the A1 Domain

Summary An alloantibody to von Willebrand factor (vWF) which developed in a Japanese boy with type 3 von Willebrand disease has been characterized. The antibody was non-precipitating IgG and the main subclasses were IgG2 and IgG4. The antibody inhibited completely ristocetin-induced platelet aggregation (RIPA) and high shear stress-induced platelet aggregation (SIPA). Its predominant inhibitory role was focused, therefore, on the interaction between vWF and platelet gycoprotein Ib. The antibody reacted with a 52/48 kDa tryptic fragment of vWF (residues 449-728). No reaction was seen, however, with either a 39/34 kDa dispase fragment (480-718) or a recombinant vWF fragment (residues 465-728). These findings suggested that the essential epitope resided in the amino-terminal flanking region of the A1 domain. We synthesized overlapping peptides corresponding to the region containing D3/A1 boundary. A peptide, residues 458-472, bound to the antibody and dose-dependently blocked the antibody binding to the 52/48 kDa fragment. The same peptide neutralized the inhibitory effect of the alloanti-body on SIPA. The data are consistent with the presence of an epitope within residues 458-472 which reacted with the 52/48 kDa fragment. Furthermore, the specific component of the antibody, directed against residues 458-472, blocked vWF binding to GPIb in absence of exogenous agonist. Our results suggest that the region flanking the A1 domain plays an important role in regulating vWF binding to GPIb.
Current Status of Spirituality in Cardiac Rehabilitation Programs: A REVIEW OF LITERATURE

PURPOSE: Strong spiritual experiences in life are a protective, positive, prognostic factor in cardiovascular diseases. However, spirituality is often neglected in cardiac rehabilitation (CR) programs. The purpose of this article was to review studies that investigated spirituality in CR programs. METHODS: The electronic databases PubMed, CINHAL, PsycINFO, and Cochrane Library of Systematic Reviews were searched for studies that measured spirituality in a CR population. The search included studies with and without spiritual interventions in CR settings. RESULTS: Five quantitative studies and 1 qualitative study that enrolled a total of 1636 patients in phase 2 CR programs were reviewed. The spiritual interventions found were relaxation responses and spiritual classes. Two studies showed preliminary evidence that supports the further exploration of spiritual interventions in CR programs. CONCLUSIONS: Evidence supporting the use of spiritual interventions for medical and psychological outcomes in CR programs is very limited because of a lack of controlled clinical trials. However, the descriptive and observational studies provide some empirical support to further explore spiritual interventions in CR programs, with the goal of enhancing the psychosocial and emotional status of CR participants. Further rigorous research design and procedures are needed to establish the contribution of spirituality in CR programs for cardiac patients.
Experimental Yersinia-triggered reactive arthritis: effect of a 3-week course of ciprofloxacin.

Lewis rats were injected i.v. with live Yersinia enterocolitica, resulting in 1-2 weeks in an arthritis greatly resembling human reactive arthritis. Starting on day 3, 5, 10 or 13 after the bacterial inoculation, the rats were treated for 3 weeks with 20 mg/kg/day of ciprofloxacin. The development of arthritis was completely prevented if the antibiotic treatment was started on day 3. In a group of rats treated with ciprofloxacin from day 5 onwards, 2/14 rats already showed mild arthritis at the time when the treatment was started. Antibiotic treatment cured the arthritis of these rats as well as that of one additional individual in this group which developed arthritis. No later exacerbations occurred. If the antibiotic treatment was started on day 10 or 13, i.e. at the time of well-developed arthritis, no effect on arthritis was observed; rather, increased faecal excretion of Yersinia occurred following the antibiotic treatment. We conclude that experimental Yersinia reactive arthritis can be cured by antibiotics introduced at an early phase of arthritic development. Regarding acute human enterogenic arthritis, the decision on antibiotic treatment is not a straightforward matter. Our experimental results indicate that the earlier the treatment is started, the better the result, whereas late treatments seem to favour bacterial persistence.