Miracle-dz/UniFAR-FTUs huggingface dataset:
LuxS-Mediated Signaling in Streptococcus mutans Is Involved in Regulation of Acid and Oxidative Stress Tolerance and Biofilm Formation

ABSTRACT LuxS-mediated quorum sensing has recently been shown to regulate important physiologic functions and virulence in a variety of bacteria. In this study, the role of luxS of Streptococcus mutans in the regulation of traits crucial to pathogenesis was investigated. Reporter gene fusions showed that inactivation of luxS resulted in a down-regulation of fructanase, a demonstrated virulence determinant, by more than 50%. The LuxS-deficient strain (TW26) showed increased sensitivity to acid killing but could still undergo acid adaptation. Northern hybridization revealed that the expression of RecA, SmnA (AP endonuclease), and Nth (endonuclease) were down-regulated in TW26, especially in early-exponential-phase cells. Other down-regulated genes included ffh (a signal recognition particle subunit) and brpA (biofilm regulatory protein A). Interestingly, the luxS mutant showed an increase in survival rate in the presence of hydrogen peroxide (58.8 mM). The luxS mutant formed less biofilm on hydroxylapatite disks, especially when grown in biofilm medium with sucrose, and the mutant biofilms appeared loose and hive-like, whereas the biofilms of the wild type were smooth and confluent. The mutant phenotypes were complemented by exposure to supernatants from wild-type cultures. Two loci, smu486 and smu487, were identified and predicted to encode a histidine kinase and a response regulator. The phenotypes of the smu486 smu487 mutant were, in almost all cases, similar to those of the luxS mutant, although our results suggest that this is not due to AI-2 signal transduction via Smu486 and Smu487. This study demonstrates that luxS-dependent signaling plays critical roles in modulating key virulence properties of S. mutans.
Ketorolac-based analgesia improves outcomes for living kidney donors.

BACKGROUND To reduce the morbidity of living kidney donors we introduced ketorolac-based analgesia for patients undergoing open donor nephrectomy in August 1999. There are no prior reports on the use of ketorolac for patients undergoing donor nephrectomy. METHODS We conducted a retrospective review of all 198 consecutive patients who underwent open living donor nephrectomy between January 1998 and July 2000 at our institution. We compared patients who underwent surgery before and after introduction of ketorolac-based analgesia. RESULTS The introduction of ketorolac-based analgesia resulted in a reduction in length of postoperative stay from 3.7+/-0.1 to 3.1+/-0.1 days (P<0.001). Patients who underwent surgery after ketorolac introduction required 58% less narcotics (P<0.001), recalled having less postoperative pain, and stopped taking pain medications sooner than patients before routine ketorolac use. Moreover, these patients drank 38% more liquids on the first postoperative day (P<0.001) and were able to resume a regular diet sooner than patients who were not managed with ketorolac. Patients who received ketorolac had a slightly lower creatinine clearance on the second postoperative day relative to patients who did not (66 vs. 72% of preoperative calculated creatinine clearance, P=0.05). However at a minimum of 3 months postoperatively, creatinine clearance did not differ between the two groups (70 vs. 73%, P=0.92). There were no differences in the rates of complications between the two groups. CONCLUSIONS The use of ketorolac to control postoperative pain for patients undergoing open donor nephrectomy reduced morbidity and was not associated with any effect on long-term renal function or increased risk of complications. This is the first study to demonstrate the safety of using ketorolac at the time of donor nephrectomy.
Subunit Interactions of Yeast NAD+-specific Isocitrate Dehydrogenase*

Yeast mitochondrial NAD+-specific isocitrate dehydrogenase is an octamer composed of four each of two nonidentical but related subunits designated IDH1 and IDH2. IDH2 was previously shown to contain the catalytic site, whereas IDH1 contributes regulatory properties including cooperativity with respect to isocitrate and allosteric activation by AMP. In this study, interactions between IDH1 and IDH2 were detected using the yeast two-hybrid system, but interactions between identical subunit polypeptides were not detected with this or other methods. A model for heterodimeric interactions between the subunits is therefore proposed for this enzyme. A corollary of this model, based on the three-dimensional structure of the homologous enzyme from Escherichia coli, is that some interactions between subunits occur at isocitrate binding sites. Based on this model, two residues (Lys-183 and Asp-217) in the regulatory IDH1 subunit were predicted to be important in the catalytic site of IDH2. We found that individually replacing these residues with alanine results in mutant enzymes that exhibit a drastic reduction in catalysis both in vitro and in vivo. Also based on this model, the two analogous residues (Lys-189 and Asp-222) of the catalytic IDH2 subunit were predicted to contribute to the regulatory site of IDH1. A K189A substitution in IDH2 was found to produce a decrease in activation of the enzyme by AMP and a loss of cooperativity with respect to isocitrate. A D222A substitution in IDH2 produces similar regulatory defects and a substantial reduction inV max in the absence of AMP. Collectively, these results suggest that the basic structural/functional unit of yeast isocitrate dehydrogenase is a heterodimer of IDH1 and IDH2 subunits and that each subunit contributes to the isocitrate binding site of the other.
A qualitative study of the consequences of 'hidden dysfunctions' one year after a mild stroke in persons <?75 years

Background and purpose: Increased mental fatiguability, concentration and memory difficulties, irritability, emotional instability, impaired stress tolerance, and sound and light sensitivity, in this paper operationalized through the astheno-emotional syndrome (AE syndrome) are known consequences of stroke. The aim of this study was to explore how persons with AE syndrome, one year after a mild stroke, experienced the consequences of the syndrome in everyday life. Method: A qualitative design was used. Fifteen respondents were chosen by strategic sampling and interviewed. The analysis was done using a grounded theory method. Results: Data analysis yielded harmed/threatened self as the core category with four main categories covering the dimensions of: hidden-apparent dysfunction, predictability-unpredictability, independence-dependence and active life-passive life. The model grounded in data shows the structural properties and the processes that verify the dynamics and interactions of the everyday life consequences of AE syndrome. Conclusions: AE syndrome with mental fatiguability as the most common symptom affected many dimensions of everyday life, which in turn affected performance of activities and independence. The symptoms were 'hidden' in many ways, not only indetectable in the appearance of the person, but also on a more symbolic level not apparent to the patient and persons in their environment. The symptoms changed with environmental circumstances and were experienced as unpredictable.
Atrial natriuretic peptide modulates sodium and potassium-activated adenosine triphosphatase through a mechanism involving cyclic GMP and cyclic GMP-dependent protein kinase.

Prior studies indicate that the natriuretic effects of atrial natriuretic peptide (ANP) are due, in part, to an inhibition of the passive movement of sodium ions from tubular lumen through apical cation channels into renal tubular epithelium. The present work demonstrates that ANP also exerts a potent inhibitory effect on the active pumping of sodium ions by renal tubular sodium and potassium-activated adenosine triphosphatase (Na, K-ATPase). This action of ANP is relatively long lasting, is due to a change in enzyme Vmax and is specific for ouabain-sensitive activity. Enzyme modulation occurs with an EC50 for ANP of 0.1 nM, is independent of intracellular [Na+] and is associated with an increase in tissue cyclic GMP (cGMP), but not cyclic AMP (cAMP). Modulation of Na, K-ATPase by ANP is mimicked by 8-bromo-cGMP and okadaic acid (OA) and is blocked by KT 5823, a selective inhibitor of cGMP-dependent protein kinase (PKG), but not by KT 5720, a selective inhibitor of cyclic AMP-dependent protein kinase (PKA), which suggests that the action of ANP on the sodium pump involves cGMP-mediated changes in protein phosphorylation. Regulation of renal Na, K-ATPase activity also occurs with nitric oxide-generating compounds, such as nitroglycerin and sodium nitroprusside (SNP). However, the ability of ANP to modulate Na, K-ATPase does not appear to involve this latter pathway because the effects of ANP on the sodium pump cannot be blocked by either N omega-nitro-L-arginine, an inhibitor of NO synthase, or hemoglobin, which blocks NO through binding. (ABSTRACT TRUNCATED AT 250 WORDS)
Assess and interpret the visual fields at the bedside

Understanding and applying a bedside visual field assessment is an important skill for the neurologist. By appreciating some basic anatomical and physiological principles it is possible to target the examination appropriately, thus gaining important diagnostic information with the minimum of fuss. Specific patterns of visual loss are caused by damage at various sites within the visual pathway. This review focuses on techniques that can be used at the bedside to identify common visual field defects and cites examples by dividing the visual system into its component parts. We urge the use of an appropriately sized red pin and berate the well worn “waggling finger” technique.
The psycho-pedagogical counselling of the future teachers students during pedagogical training stages

In the process of training the professional competences of the students who will become teachers, the pedagogical practice coordinator in the university (tutor) has a key role in the years of initial training for these students' didactic career. The pedagogical practice coordinator in the university has to have counselling psycho-pedagogical competences for the future teachers in order to sustain and motivate students during their pedagogical training and for the process of assimilating the basic skills for the teaching profession. The relation that establishes between the pedagogical practice coordinator in the university and each student is a relation of tutorship, based on a reciprocal harness of this, in which the transfer of experience from the tutor to the student is a real gain for the latter as he is initiated in the didactic profession. The present article emphasizes especially this type of competence associated to the profile of competences pedagogical practice coordinator in the university and offers a useful pedagogical tool for the students' activity of educational counselling.
The impact of social grant-dependency on agricultural entrepreneurship among rural households in Kwazulu-Natal, South Africa

Developing entrepreneurship is key to achieving the rural poverty reduction goals in South Africa. The concern that social grants, which benefit millions of the poor, may inhibit the growth of entrepreneurship among rural households should be empirically investigated. This study assess the extent to which dependency on social grants influences the development of agricultural entrepreneurship among rural farming households. The study adopts the competency approach in understanding agricultural entrepreneurship, as this approach is readily applicable to firms that are smaller in size and dominated by the entrepreneur such as smallholder farming units. A total of 513 rural farming households were randomly selected in three purposively chosen districts of KwaZulu-Natal. The data were analyzed using the factor score regression method, which was estimated in two steps. The first step involved generating the agricultural entrepreneurship index using principal component analysis, while the second step involved using the computed agricultural entrepreneurship index as a dependent variable in a linear regression. The empirical results indicated that dependency on social grants, in line with the disincentive hypothesis, was negatively associated with agricultural entrepreneurship. This suggests that social grants are spilling-over to unintended groups, creating disincentive effects which inhibit entrepreneurial development among the rural farming households. The study results further indicated that the household's risk-bearing ability through asset endowment (land size, livestock size), access to government support services (extension, credit and training), and institutional and/or infrastructural support (tenure security, market access and irrigation access) had positive effects on agricultural entrepreneurship. The disincentives effects of social grants on entrepreneurship have negative implications on the government's drive to increase production and commercialization levels of smallholder farmers. Given that the entrepreneurial competencies can be learned and changed, the study identified a number of policy variables to enhance agricultural entrepreneurship. In particular, the study recommends that policy-makers should prioritize increasing the risk-bearing abilities of households as well as access to government support services to increase agricultural entrepreneurship.
Serum Insulin-Like Growth Factor-1 Levels Predict Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy

Purpose: Patients with liver cirrhosis or hepatocellular carcinoma (HCC) have decreased serum insulin-like growth factor (IGF)-1 levels. We evaluated whether IGF-1 levels were associated with the outcomes of patients with advanced HCC treated with systemic antiangiogenic therapy. Experimental Design: The study was based on patients with advanced HCC who were enrolled in two clinical trials evaluating first-line combination antiangiogenic therapy. Serum samples were collected before treatment and four to six weeks after the start of treatment. The levels of IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP3) were analyzed for their associations with treatment outcomes. Results: A total of 83 patients were included in the study. Patients who had high (≥the median level) baseline IGF-1 levels had significantly higher disease control rate (DCR) than patients who had low (<the median level) levels (71% vs. 39%, P = 0.003). The levels of posttreatment IGF-1, and pre- or posttreatment IGF-2 and IGFBP3 were not associated with DCR. Patients with high baseline IGF-1 levels, compared with patients with low levels, had significantly longer progression-free survival (PFS; median, 4.3 vs. 1.9 months, P = 0.014) and overall survival (OS; median, 10.7 vs. 3.9 months, P = 0.009). The high baseline IGF-1 level remains an independent factor associated with favorable PFS and OS in multivariate analysis. Conclusions: High pretreatment IGF-1 levels were associated with better DCR, PFS, and OS of patients who received antiangiogenic therapy for advanced HCC. This finding warrants validation in large studies. Clin Cancer Res; 18(14); 3992–7. ©2012 AACR.
A single-surgeon randomized trial comparing sutures, N-butyl-2-cyanoacrylate and human fibrin glue for mesh fixation during primary inguinal hernia repair.

BACKGROUND We sought to determine the efficacy of sutures, human fibrin glue and N-butyl-2-cyanoacrylate for mesh fixation in patients undergoing the plug and mesh procedure for groin hernia. METHODS A total of 156 patients with 167 inguinal hernias (11 bilateral) underwent a plug and mesh procedure and were randomly assigned to received either sutures (n = 59 hernias), human fibrin glue (n = 52) or N-butyl-2-cyanoacrylate (n = 56) for mesh fixation. RESULTS The overall morbidity rate was 38.98% in the suture group, 9.62% in the fibrin glue group and 10.71% in the N-butyl-2-cyanoacrylate group (suture v. fibrin glue, p < 0.001; suture v. N-butyl-2-cyanoacrylate, p < 0.001). There was no significant difference in morbidity between the fibrin glue and N-butyl-2-cyanoacrylate groups. Overall, short-term morbidity was significantly higher in the suture group (27.12%) than in the fibrin glue (9.62%, p = 0.01) or N-butyl-2-cyanoacrylate (8.93%, p = 0.004) groups, but there was no significant difference between the fibrin glue and N-butyl-2-cyanoacrylate groups. There was no significant difference between the groups in terms of mean postoperative stay (32.6 h in the suture group v. 30.8 h in the fibrin glue group v. 32.0 h in the N-butyl-2-cyanoacrylate group) or mean time to return to work (20.4 d in the suture group v. 20.3 d in the fibrin glue group v. 19.8 d in the N-butyl-2-cyanoacrylate group). Overall, long-term morbidity was significantly higher in the suture group (11.86%) than in the fibrin glue (0%, p = 0.001) or N-butyl-2-cyanoacrylate (1.78%, p = 0.03) groups. There was no recurrence in any of the groups. Two cases (3.39%) of chronic groin pain were reported in patients in the suture group. A sensation of extraneous body was reported in 5 (8.47%) patients who received sutures and in 1 (1.78%) patient in the N-butyl-2-cyanoacrylate group; there were no reported cases in the fibrin glue group (suture v. fibrin glue, p = 0.01; suture v. N-butyl-2-cyanoacrylate, p = 0.03; fibrin glue v. N-butyl-2-cyanoacrylate, p = 0.30). CONCLUSION The use of human fibrin glue or N-butyl-2-cyanoacrylate is better tolerated than sutures in tension-free inguinal open repair using the plug and mesh technique in terms of overall immediate results, and there is a better trend in the long-term data.
Whistleblowing As a Failure of Organizational Ethics

The move toward managed care and increased competition in health care exacerbates the conditions leading to instances of whistleblowing. We believe that cases of whistleblowing are indicative of an ethical failure at the organizational level. In this paper, we provide an analysis of whistleblowing in health care organizations. We argue that neither the codes of professional nursing associations nor the standards of the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) provide, in their current forms, mechanisms to overcome the need for whistleblowing. We believe that JCAHO is in a unique position to require health care organizations (HCOs) to address concerns of organizational ethics in ways that go beyond mere compliance related to business practices. We conclude with recommendations addressing the need to refine approaches to organizational ethics and to protect staff who speak out in the defense of patient health and welfare.
Filopodia of spreading 3T3 cells. Do they have a substrate-exploring function?

Freshly plated 3T3 cells send out radial projections or filopodia. We observed cells which happended to settle on glass near the borderline of a gold-plated area. When some of the filopodia contacted the gold- plated area and others the glass substratum and remained attached for a few minutes, lamellipodia then extended preferentially toward the gold- plated area. 1-2 h later, most of the cells were found in the gold- plated area. When the filopodia of a spreading 3T3 cell contacted another already spread 3T3 cell and also the glass substratum, the first lamellipodia extended preferentially towards the glass. These observations suggest a directionally differentiated extension of lamellipodia after the filopodia of a spreading 3T3 cell have contacted different substrates in their environment. Before filopodia contact a substrate, they perform a rapid "scanning" motion. Therefore, we suggest that the filopodia of a spreading 3T3 cell serve as organs which explore the nonfluid environment and react to a certain quality of the substrate that is presently unknown. Subsequently, they mediate the extension of lamellipodia into the direction in which this quality is found. The described phenomena are reversibly inhibited by Cytochalasin B at concentrations above 5 mug/ml although filopodia are produced.
A Direct Utility Model with Dynamic Constraint

The goal of the study is to understand how consumers’ constraint as opposed to utility structure gives rise to final decision when consumers purchase more than one variant of product at a time, i.e., horizontal variety seeking or multiple-discreteness. Purchase and consumption decision not only produces utility but also involves some sort of cognitive pressure. Past consumption or last purchase is likely to be linked to this burden we face such as concern for obesity, risk of harm, and guilt for mischief. In this research, the existence and the role of dynamic constraint are investigated through a microeconomic utility model with multiple dynamic constraint. The model is applied to the salty snacks data collected from field study where burden for spiciness serves as a constraint. The results are compared to the conventional multiple discreteness choice models of static constraints, and policy implications on price discounts is explored. The major findings are that first, one would underestimate the level of consumer preference for product offerings when ignoring the carry-over of the concern from the past consumption, and second, the impact of price promotion on demand would be properly evaluated when the model allows for the role of constraint as both multiple and dynamic. The current study is different from the existing studies in two ways. First, it captures the effect of ‘mental constraint’ on demand in formal economic model. Second, unlike the state dependence well documented in the literature, the study proposes the notion of state dependence in different way, via constraint rather than utility.
Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects.

Deep breaths taken before inhalation of methacholine attenuate the decrease in forced expiratory volume in 1 s and forced vital capacity in healthy but not in asthmatic subjects. We investigated whether this difference also exists by using measurements not preceded by full inflation, i.e., airway conductance, functional residual capacity, as well as flow and residual volume from partial forced expiration. We found that five deep breaths preceding a single dose of methacholine 1) transiently attenuated the decrements in forced expiratory volume in 1 s and forced vital capacity in healthy (n = 8) but not in mild asthmatic (n = 10) subjects and 2) increased the areas under the curve of changes in parameters not preceded by a full inflation over 40 min, during which further deep breaths were prohibited, without significant difference between healthy (n = 6) and mild asthmatic (n = 16) subjects. In conclusion, a series of deep breaths preceding methacholine inhalation significantly enhances bronchoconstrictor response similarly in mild asthmatic and healthy subjects but facilitates bronchodilatation on further full inflation in the latter.