Miracle-dz/UniFAR-FTUs huggingface dataset:
M1 PROTEIN FROM STREPTOCOCCUS PYOGENES INDUCES NITRIC OXIDE-MEDIATED VASCULAR HYPORESPONSIVENESS TO PHENYLEPHRINE: INVOLVEMENT OF TOLL-LIKE RECEPTOR ACTIVATION

Streptococcus pyogenes carrying M1 protein causes the severe and increasingly prevalent streptococcal toxic shock syndrome and necrotizing fasciitis. M1 protein is an important virulence factor of S. pyogenes and induces an inflammatory response in human monocytes. We wanted to investigate if purified M1 protein in solution could induce vascular NO production leading to vasopressor hyporesponsiveness. Rat aortic segments were incubated with M1 protein or LPS in vitro. M1 protein (10 &mgr;g mL−1) and LPS (1 ng mL−1) to a similar extent induced NO production and hyporesponsiveness to the vasoconstrictor phenylephrine. Immunogold electron microscopy demonstrated that M1 protein binds to Toll-like receptor 2 (TLR2) as well as TLR4 in mouse aorta but only to TLR2 in human omental artery. Incubation with M1 protein caused a reduction in the contractile response to phenylephrine in aortic segments from wild-type and TLR2-knockout but not from TLR4-knockout mice. In conclusion, M1 protein causes vascular NO production leading to hyporesponsiveness to vasopressors via a mechanism involving TLR, but the subtypes may be species dependent. M1 protein could contribute to the circulatory disturbances accompanying severe invasive streptococcal infections.ABBREVIATIONS-KRS-Krebs-Ringer solution; l-NAME-N&ohgr;-nitro-l-arginine methyl ester hydrochloride; PAMPs-pathogen-associated microbial patterns; PE-phenylephrine; TLR-Toll-like receptor
Complement Regulator-Acquiring Surface Protein 1 Imparts Resistance to Human Serum in Borrelia burgdorferi1

Factor H and factor H-like protein 1 (FH/FHL-1) are soluble serum proteins that negatively regulate the alternative pathway of complement. It is now well recognized that many pathogenic bacteria, including Borrelia burgdorferi, bind FH/FHL-1 on their cell surface to evade complement-mediated destruction during infection. Recently, it was suggested that B. burgdorferi open reading frame bbA68, known as complement regulator-acquiring surface protein 1 (CRASP-1), encodes the major FH/FHL-1-binding protein of B. burgdorferi. However, because several other proteins have been identified on the surface of B. burgdorferi that also can bind FH/FHL-1, it is presently unclear what role CRASP-1 plays in serum resistance. To examine the contribution of CRASP-1 in serum resistance, we generated a B. burgdorferi mutant that does not express CRASP-1. The B. burgdorferi CRASP-1 mutant, designated B31cF-CRASP-1, was found to be as susceptible to human serum as a wild-type strain of Borrelia garinii 50 known to be sensitive to human serum. To further examine the role of CRASP-1 in serum resistance, we also created a shuttle vector that expresses CRASP-1 from the native B. burgdorferi gene, which was designated pKFSS-1::CRASP-1. When the pKFSS-1::CRASP-1 construct was transformed into the B. burgdorferi B31cF-CRASP-1 mutant, wild-type levels of serum resistance were restored. Additionally, when pKFSS-1::CRASP-1 was transformed into the serum-sensitive B. garinii 50 isolate, human serum resistance was imparted on this strain to a level indistinguishable from wild-type B. burgdorferi. The combined data led us to conclude that CRASP-1 expression is necessary for B. burgdorferi to resist killing by human serum.
Exploring the Abnormal Modulation of the Autonomic Systems during Nasal Flow Limitation in Upper Airway Resistance Syndrome by Hilbert–Huang Transform

Patients with nasal flow limitation and upper airway resistance syndrome (UARS) during sleep can present with low blood pressure and disturbing symptoms associated with hypervagotony. We hypothesized that the dynamic changes of the autonomic system related to inspiratory flow limitation can be quantified by the developed analytic technique applied on beat-to-beat heart rate (RR intervals) and finger photoplethysmography (PPG). Method A breath-by-breath investigation based on the Hilbert–Huang transform was performed to explore autonomic nervous system changes observed during inspiratory flow limitation. Autonomic status was quantified from beat-to-beat heart rate analysis by high frequency (RRHF; 0.15–0.4 Hz), low frequency (RRLF; 0.04–0.15 Hz), and LF/HF ratio of each respiratory cycle. Based on respiratory-related mechanisms contained in the PPG signal, we further quantified the respiratory-related oscillations (PPGres). Based on esophageal pressure and nasal flow measurements, each respiratory cycle was identified and breathing patterns were classified into one of four groups: normal, inspiratory flow limitation cycles without increased effort [FL(−)], minimal inspiratory flow limitation with effort, and inspiratory flow limitation cycles with increased effort [FL(+)]. The resulting quantitative parameters of the identified cycles were calculated. Results 49 UARS patients (12 males; aged 26.8 ± 5.8 years) with apnea–hypopnea index (AHI) 3.1 ± 1.5 per hour and nine aged matched control subjects (3 males; aged 27.8 ± 4.0 years) with AHI 0.8 ± 1.1 per hour were retrospectively identified. Compared to the control group, hyperactivation of the parasympathetic system was noted during stage 2 NREM sleep by RRHF (27.8 ± 18.2 vs 22.5 ± 11.12, p < 0.05) in 49 UARS patients. Analysis of the different classifications of respiratory cycles indicated that during “high” (increased) respiratory efforts, the RRHF and PPGres were significantly higher compared to “normal cycle” and “FL(−)” groups. The RRLF/RRHF (an index of sympathetic activity) was significantly lower in the “FL(+)” group (1.66 ± 0.80) than in the “normal cycle” (1.93 ± 0.97, p < 0.05) and “FL(−)” groups (2.01 ± 1.01, p < 0.05). Conclusion The proposed algorithm allows quantifying the temporal changes of specific mechanisms of the autonomic system on breath-by-breath basis. With no or very limited impact on oxygen saturation, the hyperactivation of parasympathetic system in associated with inspiratory flow limitation or increased respiratory efforts during stage 2 NREM sleep has been presented in this study.
Pathoplasticity of bulimic features and interpersonal problems.

OBJECTIVE Recent research suggests that interpersonal problems and some forms of psychopathology are pathoplastic, or that they mutually affect one another in nonetiological ways. In the current study, the pathoplasticity of bulimic features and interpersonal problems was tested. METHOD Inventory of Interpersonal Problems-64 data from 130 women with scores in the top quartile on the Bulimia scale of the Eating Disorder Inventory-2 from a sample of 517 college undergraduates were cluster analyzed. Age, weight, and scores on psychopathology scales were tested for mean differences across the four quadrants of the interpersonal problems circumplex. RESULTS Consistent with the pathoplasticity hypothesis, cluster means did not differ on external variables. Furthermore, bulimic features and interpersonal problems independently predicted depression in the total sample. CONCLUSION The interpersonal problems reported in the current study suggest differential treatment process that could inform the therapeutic relationship and help prevent premature termination.
Polyomavirus BK Neutralizing Activity in Human Immunoglobulin Preparations

Background. Polyomavirus BK (BKV) infection can cause nephropathy in the allograft kidney. No well-established drug treatment is available at this time. Human intravenous immunoglobulins (IVIG) have been used as an empiric therapy without proof of effectiveness. Methods. We tested five lots of commercially available IVIG preparations from two different suppliers for polyomavirus neutralizing activity. BKV and mouse polyomavirus were used to infect human and murine host cells, respectively, with or without prior treatment with IVIG. Neutralization activity was measured by quantitation of viral DNA after 7 days in culture. Results. Coincubation of BKV but not mouse polyomavirus with clinically relevant concentrations of IVIG derived from healthy and hepatitis B vaccinated subjects caused more than 90% inhibition of viral DNA yield after 7 days in culture. Consistent with a direct neutralizing mechanism, this effect was significantly diminished if viral infection was performed in immunoglobulin pretreated cells or if immunoglobulin treatment was delayed 2 hr after addition of infectious virus. Conclusion. Human IVIG preparations contain BKV neutralizing antibodies. Data on neutralizing capacity of these antibodies are presented to aid dose exploration in clinical trials seeking to validate the use of IVIG in patients with BKV infection.
Effect of protein concentration and protein source on the degradability of dry matter and protein in situ.

Degradability of DM and CP was determined in situ for barley, canola meal, corn gluten meal, barley silage, and four concentrate mixtures. Crude protein percent of concentrate mixtures 1 to 4, respectively, were barley plus canola 1, 15.1; barley plus canola 2, 21.0; barley plus corn gluten 1, 17.1; and barley plus corn gluten 2, 19.6. Degradability of each feedstuff was measured on each of four basal diets consisting of barley silage and one of the above concentrate mixtures fed in the proportion 40:60 (DM). The resulting CP percent of diets containing concentrates 1 to 4 were 12.3, 16.1, 13.8, and 16.4. Effective degradability for DM and CP, assuming a rumen outflow rate of . 08 h-1, were: barley 77.7 and 79.8; canola meal 60.9 and 66.6; corn gluten meal 18.9 and 11.0; barley silage 47.0 and 81.1; barley plus canola 1, 76.4 and 77.4; barley plus canola 2, 72.5 and 71.8; barley plus corn gluten 1, 72.8 and 55.8; barley plus corn gluten 2, 70.2 and 47.4. With two exceptions (DM degradability of concentrate 4 and CP degradability of concentrate 2), basal diet had no significant effect on effective CP or effective DM degradability. Crude protein degradability of concentrate mixtures 1 to 4, respectively, as measured (77.4, 71.8, 55.8, and 47.4) was similar to degradability estimated on the basis of their ingredient content (75.7, 72.1, 49.6, and 43.0).
Self-Reported Sleep Duration in Patients with Neovascular Age-Related Macular Degeneration

ABSTRACT Purpose: To examine the relationship between self-reported sleep duration and neovascular age-related macular degeneration (nAMD). Methods: This case-control study comprised 165 subjects (57 patients with nAMD and 108 controls). Controls were matched to cases by age and sex. Participants completed a questionnaire that included questions about sleep duration and quality. Four categories of sleep duration were established; <6 hours, 6–7 hours, 7–8 hours and >8 hours. Association of sleep duration and nAMD was assessed by logistic regression analysis. Multiple logistic regression models were performed to control for possible confounders. Results: We found a significant association between short sleep duration and nAMD (for <6 hours, odds ratio, OR, 3.29, 95% confidence interval, CI, 1.32–8.27; for 6–7 hours, OR 2.25, 95% CI 0.80–6.32; and for >8 hours, OR 1.39, 95% CI 0.53–3.73) compared with the reference category of 7–8 hours. This association remained significant after adjustment for confounders (<6 hours, OR 3.09, 95% CI 1.20–7.97). In addition, a borderline significant association was observed between self-reported very bad sleep quality and nAMD (OR 2.84, 95% CI 1.02–7.88). The highest rate of sleep medication use was found in the nAMD group (p < 0.001). Conclusion: Our findings provide evidence to support an association between short sleep duration and nAMD. Considering strategies to improve sleep in these patients may prevent the negative effects of sleep deficiency.
Reversing facial fillers: interactions between hyaluronidase and commercially available hyaluronic-acid based fillers.

INTRODUCTION Hyaluronidase (HA) degrades hyaluronic acid, allowing flexibility in the use of hyaluronic acid-based fillers commonly used in facial correction. Potentially differing properties of available hyaluronidases and fillers may influence their interaction, leading to important differences in ultimate cosmetic results. This study examines the physical properties of various fillers after exposure to commonly available hyaluronidases in vitro to better inform their in vivo clinical use. METHODS Four commonly used HA fillers were exposed to varying concentrations of Vitrase (ovine testicular hyaluronidase) and Hylenex (human recombinant hyaluronidase) in vitro. The gross properties of these fillers were then observed to evaluate time- and dose-response; photographs were obtained to allow visual comparison at 1 minute and 5 minutes post-exposure. RESULTS At a concentration of 0.1 mL Vitrase to 0.2 mL filler, Restylane dissipated most followed by Juvéderm; Belotero most retained its form. Hylenex at the same concentration showed similar results, again affecting Restylane most and Belotero least. Response to treatment with both hyaluronidases increased substantially over time, increasing progressively from exposure to 5 minutes post-exposure. When exposed to Hylenex at 15 U and 30 U to 0.2 mL filler, Belotero retained its form most, followed by Juvéderm, Juvéderm Voluma, and then Restylane. The effects on filler structure increased with 30 U concentration vs 15 U concentration of Hylenex. DISCUSSION Available hyaluronidases and HA fillers appear to have differing physical properties that influence their interaction in a time and dose-dependent manner. Knowledge of the ways in which specific fillers interact with different hyaluronidases may help achieve desired cosmesis when aiming to adjust delicate facial fillers.
A Structurally Altered Human Reduced Folate Carrier with Increased Folic Acid Transport Mediates a Novel Mechanism of Antifolate Resistance*

CEM/MTX is a subline of human CCRF-CEM leukemia cells which displays >200-fold resistance to methotrexate (MTX) due to defective transport via the reduced folate carrier (RFC). CEM/MTX-low folate (LF) cells, derived by a gradual deprivation of folic acid from 2.3 μm to 2 nm (LF) in the cell culture medium of CEM/MTX cells, resulted in a >20-fold overexpression of a structurally altered RFC featuring; 1) a wild typeK m value for MTX transport but a 31-fold and 9-fold lower K m values for folic acid and leucovorin, respectively, relative to wild type RFC; 2) a 10-fold RFC1 gene amplification along with a >20-fold increased expression of the main 3.1-kilobase RFC1 mRNA; 3) a marked stimulation of MTX transport by anions (i.e. chloride); and 4) a G → A mutation at nucleotide 227 of the RFC cDNA in both CEM/MTX-LF and CEM/MTX, resulting in a lysine for glutamate substitution at amino acid residue 45 predicted to reside within the first transmembrane domain of the human RFC. Upon transfer of CEM/MTX-LF cells to folate-replete medium (2.3 μm folic acid), the more efficient folic acid uptake in CEM/MTX-LF cells resulted in a 7- and 24-fold elevated total folate pool compared with CEM and CEM/MTX cells, respectively (500 versus 69 and 21 pmol/mg of protein, respectively). This markedly elevated intracellular folate pool conferred a novel mechanism of resistance to polyglutamatable (e.g. ZD1694, DDATHF, and AG2034) and lipophilic antifolates (e.g. trimetrexate and pyrimethamine) by abolishing their polyglutamylation and circumventing target enzyme inhibition.
Effects of an intermittent exercise fatigue protocol on biomechanics of soccer kick performance

The purpose of this study was to examine the effects of fatigue on biomechanical indices of soccer kick performance. Ten male amateur soccer players performed maximal instep kicks prior to, in the middle and after the implementation of a 90 min intermittent exercise protocol. Three‐dimensional data, ground reaction forces (GRFs) and segmental moments were measured during the kick while blood lactate and ammonia concentrations were monitored throughout the protocol. Analysis of variance designs with repeated measures indicated a significant increase in ammonia (P<0.01) and lactate levels (P<0.01) following fatigue. The GRFs and joint displacement curves during the kick remained unaltered after fatigue (P>0.01). However, post‐fatigue maximum angular velocity of the shank, the net moments acting on the shank and the resultant joint moments were significantly lower compared with the corresponding pre‐exercise values (P<0.01). The velocity of the ball was 24.69 m/s prior to the protocol and significantly decreased to 21.78 m/s after (P<0.01). Similarly, the ball/foot speed ratio significantly (P<0.01) declined from 1.40±0.12 (pre‐fatigue) to 1.33±0.18 (post‐fatigue). The present results suggest that an exercise protocol that simulates soccer game conditions results in significant impairment of soccer kick performance. This could be attributed to alterations of the function of the neuromuscular system and force generation capacity, which may have altered the mechanics of soccer kick performance.
Craniofacial morphology in preschool children with obstructive sleep apnoea syndrome.

AIM Obstructive sleep apnoea syndrome (OSAS) is a common problem in children. It is characterised by a combination of partial airway obstruction associated with hypoxemia and hypoventilation and intermittent obstructive apnoea, which disrupts normal ventilation and sleep. The aim of the study was to evaluate the craniofacial features of preschool children with polysomnographic diagnosis of OSAS, using measurements from standardized lateral cephalograms according to the floating norms cephalometric analysis. MATERIALS AND METHODS 21 untreated caucasian children (mean age of 4.57 +/-0.6) with complete deciduous dentition were included in this study. All the subjects had diagnosis of OSAS with a positive RDI. Pretreatment cephalometric radiographs were evaluated. Statistical method Descriptive statistics includes mean and standard deviation of the cephalometric variables. CONCLUSION The present study showed that OSAS preschool children showed a skeletal Class II pattern with retrognathic mandible and increased skeletal divergency.
Outcomes of Blunt Trauma Victims Transported by HEMS from Rural andUrban Scenes

Objective. Mortality differences exist between victims of urban andrural trauma; however, it is unknown if these differences persist in those patients who survive to HEMS transport. This study examined the in-hospital mortality, length of hospital stay, anddischarge status of adult blunt trauma victims transported by HEMS from rural andurban scenes to regional trauma centers. Methods. Retrospective review of all adult (age ≥ 15) HEMS transports in 2001; 271 urban and141 rural blunt trauma patients were identified from HEMS transport records andthe trauma registries at three level one trauma centers. Demographic data, scene andhospital interventions, as well as discharge status of the two groups were examined. Results. Total mileage [27 ± 12 vs. 119 ± 64, p < 0.001], total flight times (minutes) [30 ± 10 vs. 79 ± 40, p < 0.001], andscene times (minutes) [16 ± 8 vs. 21 ± 14, p < 0.001] were significantly longer for rural flights. There were no significant differences between the groups with regard to age, gender, receiving hospital, andinitial HEMS vitals. Injury Severity Score, ICU length of stay (LOS), total hospital LOS, andhospital mortality did not differ between the two groups. After controlling for age, gender, andISS, there were no significant mortality differences between the two groups (p = 0.074). Conclusions. Despite longer flight andscene times for rural patients, adjusted in-hospital mortality rates were similar for patients transported from urban andrural scenes. Factors prior to HEMS arrival may contribute to increased mortality rates of rural blunt trauma victims documented nationally.
Modulation discrimination interference and auditory grouping.

The detection of a change in the modulation pattern of a (target) carrier frequency, fc (for example a change in the depth of amplitude or frequency modulation, AM or FM) can be adversely affected by the presence of other modulated sounds (maskers) at frequencies remote from fc, an effect called modulation discrimination interference (MDI). MDI cannot be explained in terms of interaction of the sounds in the peripheral auditory system. It may result partly from a tendency for sounds which are modulated in a similar way to be perceptually 'grouped', i.e. heard as a single sound. To test this idea, MDI for the detection of a change in AM depth was measured as a function of stimulus variables known to affect perceptual grouping, namely overall duration and onset and offset asynchrony between the masking and target sounds. In parallel experiments, subjects were presented with a series of pairs of sounds, the target alone and the target with maskers, and were asked to rate how clearly the modulation of the target could be heard in the complex mixture. The results suggest that two factors contribute to MDI. One factor is difficulty in hearing a pitch corresponding to the target frequency. This factor appears to be strongly affected by perceptual grouping. Its effects can be reduced or abolished by asynchronous gating of the target and masker. The second factor is a specific difficulty in hearing the modulation of the target, or in distinguishing that modulation from the modulation of other sounds that are present. This factor has effects even under conditions promoting perceptual segregation of the target and masker.
Longitudinal Changes in Patient-reported Dyspnea in Patients with COPD

Abstract Background: Although guidelines recommend monitoring symptoms in patients with chronic obstructive pulmonary disease (COPD), there is limited information on the longitudinal changes in patient-reported dyspnea (PRD) related to activities of daily living. The hypothesis was that PRD scores on the modified Medical Research Council (mMRC) scale, the self-administered computerized (SAC) transition dyspnea index (TDI), and the University of California San Diego Shortness of Breath questionnaire (UCSD SOBQ) would demonstrate progression over two years. Methods: Observational cohort study of symptomatic patients with stable COPD evaluated every 6 months for 2 years. Patients rated the impact of activities of daily living on dyspnea using three patient-reported instruments presented in random order, and then performed post-bronchodilator (pBD) spirometry. Results: Seventy patients (37 female/33 male; age: 66 ± 9 years; and pBD forced expiratory volume in one second [(FEV1): 51 ± 16% predicted] participated. Using fixed effects regression modeling, there was significant worsening in the PRD scores with the SAC TDI (–0.9 ± 2.7; p = 0.03) and UCSD SOBQ (+5.7 ± 18.3; p = 0.001), but not with the mMRC scale (p = 0.52). Both pBD FEV1 (p = 0.19) and pBD forced vital capacity (p = 0.65) were unchanged. Conclusions: Multidimensional instruments (SAC TDI and UCSD SOBQ) demonstrated the frequently observed decline in PRD experienced by patients with COPD. The progression in PRD occurred despite stable lung function. Monitoring PRD provides unique clinical information and should be considered along with measuring lung function to assess patient status over time.