Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Bacteria in the Caries Process

Dental biofilms produce acids from carbohydrates that result in caries. According to the extended caries ecological hypothesis, the caries process consists of 3 reversible stages. The microflora on clinically sound enamel surfaces contains mainly non-mutans streptococci and Actinomyces, in which acidification is mild and infrequent. This is compatible with equilibrium of the demineralization/remineralization balance or shifts the mineral balance toward net mineral gain (dynamic stability stage). When sugar is supplied frequently, acidification becomes moderate and frequent. This may enhance the acidogenicity and acidurance of the non-mutans bacteria adaptively. In addition, more aciduric strains, such as ‘low-pH’ non-mutans streptococci, may increase selectively. These microbial acid-induced adaptation and selection processes may, over time, shift the demineralization/remineralization balance toward net mineral loss, leading to initiation/progression of dental caries (acidogenic stage). Under severe and prolonged acidic conditions, more aciduric bacteria become dominant through acid-induced selection by temporary acid-impairment and acid-inhibition of growth (aciduric stage). At this stage, mutans streptococci and lactobacilli as well as aciduric strains of non-mutans streptococci, Actinomyces, bifidobacteria, and yeasts may become dominant. Many acidogenic and aciduric bacteria are involved in caries. Environmental acidification is the main determinant of the phenotypic and genotypic changes that occur in the microflora during caries.
Systemic and cell intrinsic roles of Gqα signaling in the regulation of innate immunity, oxidative stress, and longevity in Caenorhabditis elegans

Signal transduction pathways that regulate longevity, immunity, and stress resistance can profoundly affect organismal survival. We show that a signaling module formed by the G protein alpha subunit, Gqα, and one of its downstream signal transducer phospholipase C β (PLCβ) can differentially affect these processes. Loss of Gqα and PLCβ functions result in increased sensitivity to pathogens and oxidative stress but confer life span extension. Gqα and PLCβ modulate life span and immunity noncell autonomously by affecting the activity of insulin/IGF1 signaling (IIS). In addition, Gqα and PLCβ function cell autonomously within the intestine to affect the activity of the p38 MAPK pathway, an important component of Caenorhabditis elegans immune and oxidative stress response. p38 MAPK activity in the intestine is regulated by diacylglycerol levels, a product of PLCβ’s hydrolytic activity. We provide genetic evidence that life span is largely determined by IIS, whereas p38 MAPK signaling is the primary regulator of oxidative stress in PLCβ mutants. Pathogen sensitivity of Gqα and PLCβ mutants is a summation of the beneficial effects of decreased IIS through reduced neuronal secretion and the detrimental effects of reduced activity of intestinal p38 MAPK. We propose a model whereby Gqα signaling differentially regulates pathogen sensitivity, oxidative stress, and longevity through cell autonomous and noncell autonomous effects on p38 MAPK and insulin/IGF1 signaling, respectively.
Functional magnetic resonance imaging of single motor events reveals human presupplementary motor area

Conventional functional imaging paradigms use periods of repetitive task performance to generate sustained functional signal changes. We have developed a technique of imaging the small, transient signal changes that occur after single cognitive events. The technique uses echo‐planar imaging at 3 T to generate functional images of the whole brain with a temporal resolution of 3 seconds. It uses a signal averaging technique to create time sweeps of functional activity. After a single cognitive event, widely distributed patterns of brain activation can be detected and their time course measured. This technique enables the individual cognitive tasks that constitute a paradigm to be analyzed separately and compared. We describe the application of this new technique to separate the cognitive elements in a simple “go/no‐go” motor paradigm. Comparison of activation patterns during “go” and “no‐go” responses reveals hierarchical subdivision of the medial premotor cortex into an anterior region (presupplementary motor area) involved in movement decision making and a posterior region (supplementary motor area proper) directly involved in motor execution.
Post-traumatic growth and its relationship to quality of life up to 9 years after liver transplantation: a cross-sectional study in Spain

Objective Little is known concerning post-traumatic growth (PTG) after liver transplantation. Against this backdrop the current study analysed the relationship between PTG and time since transplantation on quality of life. Furthermore, it compared PTG between liver transplant recipients and their caregivers. Design Cross-sectional case–control study. Setting University Hospital in Spain. Participants 240 adult liver transplant recipients who had undergone only one transplantation, with no severe mental disease, were the participants of the study. Specific additional analyses were conducted on the subset of 216 participants for whom caregiver data were available. Moreover, results were compared with a previously recruited general population sample. Outcome measures All participants completed the Posttraumatic Growth Inventory, and recipients also filled in the 12-Item Short-Form Health Survey. Relevant sociodemographic and clinical parameters were also assessed. Results In the sample of 240 recipients, longer time since transplantation (>9 years) was associated with more pain symptoms (p=0.026). Regardless of duration, recipients showed lower scores on most quality of life dimensions than the general population. However, high PTG was associated with a significantly higher score on the vitality quality of life dimension (p=0.021). In recipients with high PTG, specific quality of life dimensions, such as bodily pain (p=0.307), vitality (p=0.890) and mental health (p=0.353), even equalled scores in the general population, whereas scores on general health surpassed them (p=0.006). Furthermore, liver transplant recipients (n=216) compared with their caregivers showed higher total PTG (p<0.001) and higher scores on the subscales relating to others (p<0.001), new possibilities (p<0.001) and appreciation of life (p<0.001). Conclusions Our findings highlight the protective role of PTG in the long-term outcome of liver transplant recipients. Future studies should analyse and develop psychosocial interventions to strengthen PTG in transplant recipients and their caregivers.
Not just vicariance: phylogeography of a Sonoran Desert euphorb indicates a major role of range expansion along the Baja peninsula

To examine the generality of population‐level impacts of ancient vicariance identified for numerous arid‐adapted animal taxa along the Baja peninsula, we tested phylogeographical hypotheses in a similarly distributed desert plant, Euphorbia lomelii (Euphorbiaceae). In light of fossil data indicating marked changes in the distributions of Baja floristic assemblages throughout the Holocene and earlier, we also examined evidence for range expansion over more recent temporal scales. Two classes of complementary analytical approaches — hypothesis‐testing and hypothesis‐generating — were used to exploit phylogeographical signal from chloroplast DNA sequence data and genotypic data from six codominant nuclear intron markers. Sequence data are consistent with a scenario of mid‐peninsular vicariance originating c. 1 million years ago (Ma). Alternative vicariance scenarios representing earlier splitting events inferred for some animals (e.g. Isthmus of La Paz inundation, c. 3 Ma; Sea of Cortez formation, c. 5 Ma) were rejected. Nested clade phylo‐geographical analysis corroborated coalescent simulation‐based inferences. Nuclear markers broadened the temporal spectrum over which phylogeographical scenarios could be addressed, and provided strong evidence for recent range expansions along the north–south axis of the Baja peninsula. In contrast to previous plant studies in this region, however, the expansions do not appear to have been in a strictly northward direction. These findings contribute to a growing appreciation of the complexity of organismal responses to past climatic and geological changes — even when taxa have evolved in the same landscape context.
Role of mink cell focus-inducing virus in leukemias induced by Friend ecotropic virus

Recombinant viruses have been implicated in the pathogenesis of murine leukemias induced by a variety of long-latency retroviruses. Neonatal mice of several strains were inoculated with Friend ecotropic virus (F-Eco) and analyzed for the presence of mink cell focus-inducing (MCF) virus or DNA restriction enzyme fragments which were specific for Friend MCF virus (F-MCF). MCF virus was detected within 2 weeks of inoculation in NFS /N mice and at about 2 months after inoculation in BALB/c mice. Both of these strains developed erythroblastosis after inoculation with F-Eco. In contrast, MCF virus was not detected in F-Eco-inoculated C57BL mice. These mice were resistant to erythroblastosis but developed lymphoma or myelogenous leukemia or both at about 5 months after inoculation. Thus, although MCF viruses were associated with F-Eco erythroblastosis in NFS /N and BALB/c mice, they were not necessary for F-Eco-induced lymphoid or myeloid leukemias in C57BL mice. To investigate the association between resistance to erythroblastosis and absence of MCF virus, C57BL mice were inoculated with pseudotypic mixtures of F-Eco plus F-MCF; MCF virus replicated well in these mice, but the mice remained resistant to erythroblastosis. Furthermore, in genetic crosses between C57BL and NFS /N or BALB/c, some mice inherited resistance to F-Eco erythroblastosis without inheriting the C57BL resistance to the generation of MCF viruses. These results indicate that C57BL mice carry a gene for resistance to F-Eco erythroblastosis which is distinct from the C57BL genes which interfere with the generation of MCF viruses.
Sensitivity analysis of a human finger model

The main objective of the presented work is to do a preliminary sensitivity analysis of the simplified neuromusculoskeletal model of the human middle finger that we have already developed [1], [2]. The importance of this study is to improve the model by well estimating internal parameters, which are the most affecting the model output, and by adapting it to each individual. The sensitivity analysis presented in this study is preliminary; it is based on the computing of the elementary effect (EE) of the 3 signal features of the muscular force. We get significant results to indicate the most important parameters among those chosen; these are the most influential parameters on system output, and good estimation of them leads to a more realistic model. These results encourage us to do a deeper sensitivity analysis for the most complex model where the sensitivity analysis will be on all internal parameters of the model in order to improve it.
Perceptual Learning at a Conceptual Level

Humans can learn to abstract and conceptualize the shared visual features defining an object category in object learning. Therefore, learning is generalizable to transformations of familiar objects and even to new objects that differ in other physical properties. In contrast, visual perceptual learning (VPL), improvement in discriminating fine differences of a basic visual feature through training, is commonly regarded as specific and low-level learning because the improvement often disappears when the trained stimulus is simply relocated or rotated in the visual field. Such location and orientation specificity is taken as evidence for neural plasticity in primary visual cortex (V1) or improved readout of V1 signals. However, new training methods have shown complete VPL transfer across stimulus locations and orientations, suggesting the involvement of high-level cognitive processes. Here we report that VPL bears similar properties of object learning. Specifically, we found that orientation discrimination learning is completely transferrable between luminance gratings initially encoded in V1 and bilaterally symmetric dot patterns encoded in higher visual cortex. Similarly, motion direction discrimination learning is transferable between first- and second-order motion signals. These results suggest that VPL can take place at a conceptual level and generalize to stimuli with different physical properties. Our findings thus reconcile perceptual and object learning into a unified framework. SIGNIFICANCE STATEMENT Training in object recognition can produce a learning effect that is applicable to new viewing conditions or even to new objects with different physical properties. However, perceptual learning has long been regarded as a low-level form of learning because of its specificity to the trained stimulus conditions. Here we demonstrate with new training tactics that visual perceptual learning is completely transferrable between distinct physical stimuli. This finding indicates that perceptual learning also operates at a conceptual level in a stimulus-invariant manner.
Kinetics of drug action in disease states. XIV. Effect of infusion rate on pentylenetetrazol concentrations in serum, brain and cerebrospinal fluid of rats at onset of convulsions.

The purpose of this investigation was to develop a method which can be used to determine the effect of various diseases on the concentration-pharmacologic activity relationship of the central nervous system stimulant pentylenetetrazol (PTZ, Metrazol) in a manner that excludes or accounts for pharmacokinetic variables. Adult female rats (approximately 170 g) received an i.v. infusion of PTZ at one of four different rates (0.155-1.53 mg/min) until the animals exhibited the first myoclonic jerk. This occurred after an average of 4.9 to 52 min of infusion. The PTZ concentrations in serum, brain and cerebrospinal fluid at this pharmacologic endpoint were independent of infusion rate. Other groups of rats were infused at three different rates (0.155-1.53 mg/min) to the onset of maximal seizures. Again, the PTZ concentrations in serum, brain and cerebrospinal fluid were not significantly affected by the rate of infusion of the drug. The average (+/- S.D.) PTZ concentration in cerebrospinal fluid was 46 +/- 5 mg/l (n = 22) at the onset of the first myoclonic jerk and 109 +/- 13 mg/l (n = 12) at the onset of maximal seizure. PTZ concentrations in brain and serum were similar to those in cerebrospinal fluid. The total serum clearance of a 20-mg/kg i.v. bolus dose of PTZ was 5.36 +/- 0.34 ml/min/kg, the terminal half-life was 116 +/- 25 min and the apparent volume of distribution was 896 +/- 134 ml/kg (all values are mean +/- S.D.). Serum protein binding was negligible (less than 10%). (ABSTRACT TRUNCATED AT 250 WORDS)
Clinical characteristics and prognosis of patients with retinoblastoma: 8-year follow-up.

BACKGROUND/AIM The aim of this study was to investigate the potential correlation between clinical characteristics and prognosis of patients with retinoblastoma (Rb). MATERIALS AND METHODS This retrospective study included 314 Rb patients. Clinical data including laterality of eyes, sex, age, presenting signs, lag time, and survival were recorded and analyzed. RESULTS Leukocoria is the most common clinical presentation of Rb. Patients with isolated leukocoria had shorter lag time and exhibited a high survival rate (85%, 5 years). Patients with strabismus and blurred vision, and who were older and had longer lag time, exhibited an excellent survival rate (100% and 92.3%, respectively, 5 years). Patients with exophthalmos had the longest lag time and the lowest survival rate (17.8%, 5 years). The 5-year survival rate of patients with a lag time of 6 months was 84.7%, which was significantly higher than that of patients with a lag time of > 6 months (64.7%). CONCLUSION Leukocoria, strabismus, and blurred vision are mild clinical manifestations of Rb that are associated with better disease prognosis, whereas exophthalmos is an indicator of poor prognosis. Long lag time is a risk factor for the survival of Rb, which can be avoided. Early detection and treatment can greatly improve the survival of Rb patients.
Improved Lymphocyte Function-associated Antigen-1 (LFA-1) Inhibition by Statin Derivatives

The integrin lymphocyte function-associated antigen-1 (LFA-1) (αLβ2; CD11a/CD18) plays an important role in leukocyte migration and T cell activation. LFA-1 is inhibited by the cholesterol-lowering drug lovastatin, which binds to an allosteric site of the αL I domain termed the lovastatin site (L-site). Here we report for the first time the x-ray structures of the LFA-1 I domain complexed with derivatives of lovastatin optimized for LFA-1 inhibition. This analysis identified two new subpockets within the L-site occupied by chemical groups of the statin derivatives but not by lovastatin itself. Occupancy of these L-site subpockets led to distinct conformational changes in LFA-1, which were detectable by an epitope-monitoring assay. We utilized this assay to demonstrate improved LFA-1 inhibition in human blood in vitro and in blood samples from treated animals ex vivo. Moreover, we demonstrate that the novel lovastatin-derived LFA-1 inhibitor LFA878 exhibits potent anti-inflammatory effects in carrageenan-induced rat paw edema. In summary, the findings reported here extend the understanding of LFA-1 inhibition at the molecular level, allow for the identification and design of LFA-1 inhibitors of further enhanced potency, and support the expectation that LFA-1 inhibitors binding to the L-site will be of therapeutic value in treating inflammatory diseases.
Changes in glutathione homeostasis during liver regeneration in the rat

We have shown previously that plating primary cultures of rat hepatocytes under low density, which stimulates hepatocytes to shift from the G0 to the G1phase of the cell cycle, resulted in increased levels of glutathione (GSH) and cysteine, and increased activity of γ‐glutamylcysteine synthetase (GCS), the rate‐limiting enzyme in GSH synthesis (Lu et al., Am. J. Physiol. 1992;263:C1181‐C1189). In the current work we examined changes in GSH homeostasis after two‐thirds partial hepatectomy (PH). Male Sprague‐Dawley rats underwent two‐thirds PH or sham operation. GSH, oxidized glutathione (GSSG), cysteine, GSH efflux, DNA synthesis, changes in GCS subunit messenger RNA (mRNA), and protein levels were measured 12 and 24 hours after PH. Both liver GSH and cysteine levels were doubled at 12 hours and remained elevated at 24 hours after PH. GSSG levels also increased, but the ratio of GSH to GSSG levels remained unchanged. The increase in GSH and cysteine levels preceded the increase in DNA synthesis. Sinusoidal GSH efflux was unchanged after two‐thirds PH, but biliary GSH efflux decreased. However, total GSH efflux was minimally altered after two‐thirds PH. The increase in GSH can be largely accounted for by the increase in both cysteine availability and the activity of GCS. The steady‐state mRNA and protein levels of the GCS heavy subunit were increased at 12 hours after PH. The mRNA level of the GCS light subunit was unchanged. In summary, early in the course of liver regeneration the steady‐state hepatic GSH levels double because of an increase in the biosynthesis of GSH.
Rapid Mycobacterium species assignment and unambiguous identification of mutations associated with antimicrobial resistance in Mycobacterium tuberculosis by automated DNA sequencing.

OBJECTIVE To develop and demonstrate the utility of automated DNA sequencing strategies for rapid and unambiguous identification of Mycobacterium species and mutations associated with antimicrobial resistance in Mycobacterium tuberculosis. DESIGN AND SPECIMENS: A 360-base pair segment of the gene (hsp65) encoding a 65-kd heat shock protein was characterized from 91 isolates assigned to 24 Mycobacterium species by traditional biochemical techniques. Areas of seven genes recently shown to contain mutations associated with antimicrobial resistance in M tuberculosis strains were also sequenced in a sample of 128 resistant organisms. Early positive BACTEC 460 cultures and acid-fast, bacterium-positive sputum specimens from patients with tuberculosis were also studied. RESULTS Automated DNA sequencing identified species-specific polymorphism in the target segment of hsp65, successfully identified organisms to the species level in smear-positive sputum samples, and unambiguously characterized seven genes associated with antimicrobial resistance in M tuberculosis. CONCLUSIONS Rapid identification of M tuberculosis and other Mycobacterium species is possible by automated DNA sequencing of a portion of hsp65. The technique is also feasible for analysis of some smear-positive sputum specimens. Unambiguous characterization of target segments of genes harboring mutations associated with antimicrobial resistance in M tuberculosis is possible from primary patient specimens. Taken together, the data demonstrate the feasibility of mycobacterial species identification and potential to identify mutations associated with antimicrobial resistance in less than 48 hours.
Glucose-insulin-potassium infusion as adjunctive therapy in myocardial infarction: current evidence and potential mechanisms.

BACKGROUND In ST-elevation myocardial infarction (STEMI) there is conflicting evidence that mortality, morbidity and infarct size is reduced by therapies influencing myocardial metabolism, such as infusion of glucose-insulin-potassium (GIK). Several clinical trials with GIK have already provided insight into the magnitude of this effect. The aim of this article was to review randomized trials on adjunctive GIK infusion in STEMI. METHODS Randomized trials comparing GIK with placebo or untreated controls in patients with STEMI were identified by electronic and manual searches. A systematic analysis of all data was performed, with regard to inclusion criteria, dose of GIK and additional use of reperfusion therapy. Thirteen trials, involving 4992 patients, were included. RESULTS Overall, hospital mortality was 10.8% after GIK compared to 12.9% in controls (p = 0.02). GIK infusions were in particular effective when a high dose was used and if given as an adjunct to reperfusion therapy. In patients with heart failure on admission, GIK may have worse effects. In all analyzed trials, GIK infusion caused only mild adverse effects, although fluid overload may be a problem in certain patients. CONCLUSIONS GIK may reduce mortality in patients with STEMI, particularly if a high dose is used and when GIK is administered as an adjunct to reperfusion therapy. However, all studies had a relative small sample size and additional large randomized trials are certainly needed before a definite conclusion can be made. The limited evidence currently available does not warrant GIK therapy to be applied in patients at the present time.