Miracle-dz/UniFAR-FTUs huggingface dataset:
Adjusting Flow-Mediated Dilation for Shear Stress Stimulus Allows Demonstration of Endothelial Dysfunction in a Population with Moderate Cardiovascular Risk

Background/Aims: Although normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress (FMD:shear stress ratio) has been proposed to improve this measure of endothelial function, the clinical utility of FMD normalization has not yet been demonstrated. We tested (1) whether following conventional 5-min forearm occlusion, the FMD:shear stress ratio would discriminate a population with moderate cardiovascular risk (MR) from a low-risk (LR) population, and (2) whether the dose-response profile relating shear stress to FMD would be different between the 2 populations. Methods: Five different magnitudes of reactive hyperemia-induced shear stress were applied to 20 MR and 20 LR subjects by manipulating forearm cuff occlusion duration. Brachial artery diameters and velocities were measured via high-resolution ultrasound. To quantify the hyperemic stimulus, shear stress area under the curve was individually calculated for the duration of time-to-peak dilation. Results: Following 5-min of forearm occlusion, FMD:shear stress ratio (p = 0.041), but not FMD (p = 0.286), discriminated MR from LR. The slope of the shear stress-FMD regression line was lower in MR compared to the LR (p <0.001). Conclusion: The FMD:shear stress ratio distinguished reduced endothelial function in a population with MR. The dose-response profile of the shear stress-FMD relationship appears to differ between populations of distinct cardiovascular risk.
Influence of mastication and edentulism on mandibular bone density

The aim of this study was to demonstrate that external loading due to daily activities, including mastication, speech and involuntary open–close cycles of the jaw contributes to the internal architecture of the mandible. A bone remodelling algorithm that regulates the bone density as a function of stress and loading cycles is incorporated into finite element analysis. A three-dimensional computational model is constructed on the basis of computerised tomography (CT) images of a human mandible. Masticatory muscle activation involved during clenching is modelled by static analysis using linear optimisation. Other loading conditions are approximated by imposing mandibular flexure. The simulations predict that mandibular bone density distribution results in a tubular structure similar to what is observed in the CT images. Such bone architecture is known to provide the bone optimum strength to resist bending and torsion during mastication while reducing the bone mass. The remodelling algorithm is used to simulate the influence of edentulism on mandibular bone loss. It is shown that depending on the location and number of missing teeth, up to one-third of the mandibular bone mass can be lost due to lack of adequate mechanical stimulation.
Bone mineral density, body composition, and height in long-term survivors of acute lymphoblastic leukemia in childhood.

BACKGROUND Childhood leukemia has increasing numbers of survivors, so more emphasis is being placed on long-term effects. The ALL-6 protocol of the Dutch Childhood Leukemia Study Group involved high-dose dexamethasone and methotrexate and no cranial irradiation. Therefore, we studied the long-term effects on bone mineral density (BMD), body composition, and growth in survivors of non-high-risk ALL treated with the ALL-6 protocol. PROCEDURE Twenty-three subjects (12.2-25.4 years) participated in this cross-sectional study. Mean follow-up was 9.6 years (range 7.9-11.4 years). BMD of lumbar spine (LS) and total body (TB) and body composition were measured by dual energy X-ray absorptiometry; results are expressed as standard deviation scores (SDS). Bone mineral apparent density (BMAD(LS)) was calculated to correct for bone size. A questionnaire was administered to determine physical activity, calcium intake, and medical history. RESULTS Mean SDS for BMD(LS), BMD(TB), and BMAD(LS) were normal. None of the subjects had BMD below -2 SDS; one subject had BMAD(LS) below -2 SDS. Mean SDS for lean body mass, percentage fat, and height were not significantly different from zero. Calcium intake correlated positively with BMD. Nine subjects reported traumatic fractures (eight during or shortly after therapy). CONCLUSIONS Ten years after ALL-6 treatment, no long-term side effects on height, BMD, or body composition were found in this small group of patients, despite high-dose dexamethasone and methotrexate. This study suggests that ALL treatment without cranial irradiation might not be associated with long-term side effects on growth and BMD.
Children Experiencing First-Time or Prolonged Febrile Seizure Are Prone to Stress Hyperglycemia

The risk factors and clinical implications of stress hyperglycemia in children with febrile seizure remain uncertain. Among 479 children with febrile seizure, the prevalence of the stress hyperglycemia (blood glucose concentration ≥ 150 mg/dL) was 10.0%. Stress hyperglycemia group included larger proportion of first-time febrile seizure, prolonged febrile seizure, and smaller proportion of short febrile seizure in comparison with the non–stress hyperglycemia group. Stress hyperglycemia group demonstrated a lower pH and higher lactate levels than the non–stress hyperglycemia group. Multivariate analysis revealed that first-time febrile seizure (aOR = 3.741, P = .004) and prolonged febrile seizure (aOR = 12.855, P < .001) were significant risk factors for stress hyperglycemia. The rate of early febrile seizure recurrence in the emergency department was not different between the groups. These findings suggest that children experiencing first-time or prolonged febrile seizure are prone to stress hyperglycemia, and this can be related to febrile seizure severity. However, stress hyperglycemia is not predictive of early febrile seizure recurrence in the emergency department.
The contribution of pinna to the discriminate the vertical angle for virtual reality technology

How to present auditory information with high performance and low cost is a very important technology for developing a new virtual reality system. In this study, we focus on human auditory characteristic on vertical angle discrimination in sagittal planes, and try to get basic research results for virtual reality technology. We measured the ability of human listeners to discriminate white noise bursts in the absence of binaural discrimination cues. The minimum audible angle (MAA) thresholds were obtained for five subjects in a two-alternative, forced-choice, adaptive paradigm as a function of the orientation of the array of sources on the vertical plane (elevation). The subjects were normal hearing students, and wore a monaural earplug to reduce cues in sound level and timing. Experiments measured discrimination of the vertical angle in eight planes parallel to the median plane (0deg position). Experimental results showed that the sound source position can discriminate by the vertical plane when subject of normal monaural hearing condition wore a monaural earplug. However, the discriminate ability has remarkable worsened then normal hearing condition. The under hemi-field sound source orientation discriminate the ability to be higher than the upper hemi-field at the 0deg, 45deg, 90deg, 135deg and 180deg reference positions, but the under hemi-field and sound source orientation discriminate the ability is similarly with upper hemi-field at the 180deg, 225deg, 270deg, 315degand 0deg reference positions in the horizontal plane. Furthermore, the means MAA thresholds was not statistically significant differences at the small and big pinna mold conditions.
Gingipains from Porphyromonas gingivalis W83 Synergistically Disrupt Endothelial Cell Adhesion and Can Induce Caspase-Independent Apoptosis

ABSTRACT We have shown previously that gingipains from Porphyromonas gingivalis W83 can induce cell detachment, cell adhesion molecule (CAM) cleavage, and apoptosis in endothelial cells; however, the specific roles of the individual gingipains are unclear. Using purified gingipains, we determined that each of the gingipains can cleave CAMs to varying degrees with differing kinetics. Kgp and HRgpA work together to quickly detach endothelial cells. Interestingly, in the absence of active caspases, both gingipain-active W83 extracts and purified HRgpA and RgpB induce apoptotic morphology, suggesting that the gingipains can induce both caspase-dependent and caspase-independent apoptosis. Using z-VAD-FMK to inhibit Kgp activity and leupeptin to inhibit Rgp activity in gingipain-active W83 extracts, we investigated the relative significance of the synergistic role of the gingipains. z-VAD-FMK or leupeptin delayed, but did not inhibit, cell detachment induced by gingipain-active W83 extracts or purified gingipains. There was partial cleavage of N-cadherin and cleavage of VE-cadherin was not inhibited. Degradation of integrin β1 was inhibited only in the presence of z-VAD-FMK. These results further clarify the role P. gingivalis plays in tissue destruction occurring in the periodontal pocket.
The Contribution of GJB2 (Connexin 26) 35delG to Age-Related Hearing Impairment and Noise-Induced Hearing Loss

Hypothesis: The common GJB2 (Connexin 26) 35delG mutation might contribute to the development of age-related hearing impairment (ARHI) and noise-induced hearing loss (NIHL). Background: GJB2, a gene encoding a gap junction protein expressed in the inner ear, has been suggested to be involved in the potassium recycling pathway in the cochlea. GJB2 mutations account for a large number of individuals with nonsyndromic recessive hearing loss, with 35delG being the most frequent mutation in populations of European origin. Other genes involved in potassium homeostasis have been suggested to be associated with ARHI and NIHL, and distortion product otoacoustic emission distortions indicative of hearing loss alterations have been found in 35delG carriers. Method: We genotyped 35delG in two distinct sample sets: an ARHI sample set, composed of 2,311 Caucasian samples from nine different centers originating from seven different countries with an age range between 53 and 67 years, and an NIHL sample set consisting of 702 samples from the two extremes of a noise-exposed Polish sample. Results: After statistical analysis, we were unable to detect an association between 35delG and ARHI, nor between 35delG and NIHL. Conclusion: Our findings indicate that there is no increased susceptibility in 35delG carriers for the development of ARHI or NIHL.
Relationship of Leukoaraiosis to Cognitive Decline and Cognitive Aging

Objective:Leukoaraiosis (LA) is a common finding on MRI scans of the elderly. However, its exact relationship to cognitive decline and dementia is in dispute. Because LA involves the paracallosal white matter, we sought to determine if LA, uncomplicated by ischemic lesions or complaints of cognitive impairment, is associated with cognitive loss or difficulties with interhemispheric integration of behavioral functions. Methods:Two hundred fifty-seven MRI scans with deep white matter changes were screened. After a chart review, 38 patients had uncomplicated LA, and 31 gave informed consent to undergo cognitive and behavioral testing. Results:LA severity was not related to any of the cognitive or behavioral assessments. However, some dependent measures showed medium effect sizes that were in keeping with published findings, indicating that LA has a marginal impact on cognition. In comparison, robust relationships with age were found for certain tasks, suggesting that our cohort size was sufficient to detect meaningful clinical relationships. Conclusion:Based on statistical interpretations using effect sizes, LA severity may be better viewed as a biomarker for physiological brain aging that is in advance of chronological age, leaving the elderly individual at greater risk for developing dementia.
A Cointegrate-Like Plasmid That Facilitates Dissemination by Conjugation of the Extended-Spectrum β-Lactamase CTX-M-17

CTX-M enzymes are class A extended-spectrum -lactamases that encompass about 10% of known -lactamases and are highly prevalent in Enterobacteriaceae, particularly in Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (1, 2). K. pneumoniae is known to host large and small plasmids that usually harbor resistance genes, including those belonging to the blaCTX-M class (3). A 7-kbp ColE1-type plasmid, pIP843, that includes blaCTX-M-17, was isolated in 1996 from a clinical K. pneumoniae strain obtained from an 8-month-old child with acute pneumonia in Ho Chi Minh City, Vietnam, and characterized (4). The plasmid includes an oriT locus in its sequence, but all other conjugation functions are lacking. Attempts by the authors to mobilize it from the original K. pneumoniae isolate were unsuccessful (4). This is consistent with the fact that the proteins that form the specific relaxosome (5, 6) are missing in pIP843. While it is usual that other plasmids can act as helpers providing the components of the tranferosome (a type IV secretion system), the relaxosome components tend to be specific and present in cis with oriT (7). The presence of oriT loci without the cognate relaxosome genes has been observed before in small K. pneumoniae plasmids, and in the case of pJHCMW1, which possesses a ColE1-like oriT, mobilization was experimentally shown when the specific relaxosome functions were provided in trans together with heterologous RK2 components of the transferosome (8). However, it is expected that mobilization under these conditions must occur at a very low frequency in nature. In looking for other means of dissemination of blaCTX-M-17, we identified a large conjugative plasmid, pE66An, from an E. coli clinical strain isolated in the same geographical region as pIP843 (9). The pE66An plasmid has the structure of a cointegrate of an original 73-kbp plasmid and pIP843 (Fig. 1). The point of cointegration in pIP843 is the gene coding for RNA II, the molecule that upon RNase H cleavage becomes the primer for initiation of replication. Hence, the ColE1-type replicon must not be functional in pE66An (Fig. 1). We think that pE66An originated after cointegration of an original large plasmid and pIP843, as opposed to the possibility that the latter plasmid was formed by excision from pE66An because (i) the probability of recombinational excision using direct repeats as small as 8 nucleotides as found in pE66An is extremely low (10, 11) and (ii) the ColE1-type replicon is disrupted in pE66An. Thus, it is most probable that the two plasmids cointegrated and disrupted the pIP843 ColE1-type replicon during the process, a desirable outcome because large plasmids are not stable at high copy numbers, a characteristic of plasmids with this type of replicon (12). In conclusion, we identified a conjugative plasmid that can be a specific example of plasmid cointegration that facilitates dissemination of an extended-spectrum -lactamase gene.
Homopolymer mutational hot spots mediate herpes simplex virus resistance to acyclovir

In the majority of cases, the mechanism underlying the resistance to acyclovir (ACV) of herpes simplex viruses (HSVs) is thymidine kinase (TK) deficiency. Plaque isolates from eight ACV-resistant (ACVr) clinical isolates from AIDS patients, of which five reactivated, were sequenced to determine the genetic lesion within the tk gene conferring resistance and whether this may have correlated with reactivation potential. Mutations were clustered within two homopolymer nucleotide stretches. Three plaque isolates (1737-14, 90-150-3, and 89-650-5) had insertion mutations within a stretch of 7 guanosines, while two isolates (89-063-1 and 89-353-1) had frameshift mutations within a stretch of 6 cytosines (a deletion and an insertion, respectively). Mutations resulted in premature termination codons, and the predicted 28- and 32-kDa truncated TK products were detected by Western blot analysis of virus-infected cell extracts. The repair of one homopolymer frameshift mutation (in isolate 1737-14) restored TK activity, demonstrating that this mutation is the basis of TK deficiency. Of the five reactivated isolates, four were TK deficient and contained frameshift mutations while the fifth retained TK activity because of its altered-TK or Pol- phenotype. These data demonstrate that the majority of ACVr clinical isolates contain frameshift mutations within two long homopolymer nucleotide stretches which function as hot spots within the HSV tk gene and produce nonfunctional, truncated TK proteins.
Description and Phylogenetic Relationships of Spumochlamys perforata n. sp. and Spumochlamys bryora n. sp. (Amoebozoa, Arcellinida)

ABSTRACT. Spumochlamys perforata n. sp. and Spumochlamys bryora n. sp. were isolated and described from dry epiphytic moss. The morphology and ultrastructure of both species clearly demonstrate that they belong to the genus Spumochlamys (family Microchlamyiidae). They differ from its only described member, Spumochlamys iliensis (as well as from species of Microchlamys), in the relief of the dorsal surface of the test, revealed by scanning electron microscopy, which can represent a good characteristic for species identification. They also differ in the structure of the dorsal part of the test wall (especially S. perforata). Small subunit ribosomal DNA‐based molecular phylogenetic analyses show that Spumochlamys is a deeply branching lineage of the Arcellinida, without any close affinities. Actin gene sequence analysis places this genus within the Tubulinea, close to two other arcellinid lineages but without forming a monophyletic group with them. These data together strongly suggest that the lack of resolution in the arcellinid molecular phylogenies is due to serious undersampling of taxa, a limited number of sequence data, and high divergence rates in most of the species.
Discovery in toxicology: Mediation by gene expression array technology

Toxicogenomics is a term that represents the merging of toxicology with novel genomics techniques. Data generated in the new‐age era of toxicology is relatively complex, requires new bioinformatics tools for adequate interpretation, and allows for the rapid generation of testable hypotheses. Hazard identification and risk assessment processes will advance from the use of genomics techniques, which will lead to greater understanding of mechanism(s) of action of toxicants, development of novel biomarkers of exposure and effect, and better identification of sensitive subpopulations. © 2001 John Wiley & Sons, Inc. * This article is a US Government work and, as such, is in the public domain in the United States of America. J Biochem Mol Toxicol 15:231–242, 2001
Lipid Paradox in Acute Myocardial Infarction—The Association With 30-Day In-Hospital Mortality

Objectives:Elevated low-density lipoprotein cholesterol and triglycerides are major risk factors for coronary artery disease. However, fatty acids from triglycerides are a major energy source, low-density lipoprotein cholesterol is critical for cell membrane synthesis, and both are critical for cell survival. This study was designed to clarify the relationship between lipid profile, morbidity as assessed by Killip classification, and 30-day mortality in patients with acute myocardial infarction. Design:A noninterventional observational study. Setting:Coronary care unit in a university hospital. Patients:Seven hundred twenty-four patients with acute myocardial infarction in the coronary care program of the Bureau of Health Promotion were analyzed. Interventions:None. Measurements and Main Results:Low-density lipoprotein cholesterol and triglyceride levels were significantly lower in high-Killip (III + IV) patients compared with low-Killip (I + II) patients and in those who died compared with those who survived beyond 30 days (both p < 0.001). After adjustment for risk factors, low-density lipoprotein cholesterol less than 62.5 mg/dL and triglycerides less than 110 mg/dL were identified as optimal threshold values for predicting 30-day mortality and were associated with hazard ratios of 1.65 (95% CI, 1.18–2.30) and 5.05 (95% CI, 1.75–14.54), and the actual mortality rates were 23% in low low-density lipoprotein, 6% in high low-density lipoprotein, 14% in low triglycerides, and 3% in high triglycerides groups, respectively. To test the synergistic effect, high-Killip patients with triglycerides less than 62.5 mg/dL and low-density lipoprotein cholesterol less than 110 mg/dL had a 10.9-fold higher adjusted risk of mortality than low-Killip patients with triglycerides greater than or equal to 62.5 mg/dL and low-density lipoprotein cholesterol greater than or equal to 110 mg/dL (p < 0.001). The lipid paradox also improved acute myocardial infarction short-term outcomes prediction on original Killip and thrombolytic in myocardial infarction scores. Conclusions:Low low-density lipoprotein cholesterol, low triglycerides, and high Killip severity were associated with significantly higher 30-day in-hospital mortality in patients presenting with acute myocardial infarction. The initial lipid profile of patients with acute myocardial infarction may therefore hold prognostic value.
Mast Cells, Histamine, and IL-6 Regulate the Selective Influx of Dendritic Cell Subsets into an Inflamed Lymph Node

In response to bacterial stimuli, multiple dendritic cell (DC) populations accumulate within the draining lymph node, thus enhancing opportunities for effective T cell–DC interaction. DC subpopulations, such as plasmacytoid, CD8+, and CD11b+ subsets, have distinct roles in determining the nature of the immune response. The mechanisms whereby individual DC subpopulations are mobilized and the extent to which these processes are linked to increases in overall lymph node cellularity have not been determined. In the current study, the mechanisms of DC subset mobilization to the draining auricular lymph node were examined after intradermal injection of Staphylococcus aureus-derived peptidoglycan. Using mast cell-deficient mice and local mast cell reconstitution, plasmacytoid and CD8+ DC responses were shown to be mast cell dependent, whereas the CD11b+ DC response was not. A histamine H2 receptor-dependent, CXCL9-independent pathway controlled the selective influx of both plasmacytoid and CD11b+ DC into the lymph node, but not lymph node cellularity. In contrast, IL-6 was important for the mobilization of CD8+ and CD11b+ DC. TNF and IL-1 receptor were dispensable for plasmacytoid, CD11b+, and CD8+ DC responses. These findings provide novel opportunities for the selective mobilization of specific DC subsets to lymph nodes and demonstrate critical roles for both histamine and IL-6 in this process.