Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequential Treatment of Biofilms with Aztreonam and Tobramycin Is a Novel Strategy for Combating Pseudomonas aeruginosa Chronic Respiratory Infections

ABSTRACT Traditional therapeutic strategies to control chronic colonization in cystic fibrosis (CF) patients are based on the use of a single nebulized antibiotic. In this study, we evaluated the therapeutic efficacy and dynamics of antibiotic resistance in Pseudomonas aeruginosa biofilms under sequential therapy with inhaled aztreonam (ATM) and tobramycin (TOB). Laboratory strains PAO1, PAOMS (hypermutable), PAOMA (mucoid), and PAOMSA (mucoid and hypermutable) and two hypermutable CF strains, 146-HSE (Liverpool epidemic strain [LES-1]) and 1089-HSE (ST1089), were used. Biofilms were developed using the flow cell system. Mature biofilms were challenged with peak and 1/10-peak concentrations of ATM (700 mg/liter and 70 mg/liter), TOB (1,000 mg/liter and 100 mg/liter), and their alternations (ATM/TOB/ATM and TOB/ATM/TOB) for 2 (t = 2), 4 (t = 4), and 6 days (t = 6). The numbers of viable cells (CFU) and resistant mutants were determined. Biofilm structural dynamics were monitored by confocal laser scanning microscopy and processed with COMSTAT and IMARIS software programs. TOB monotherapy produced an intense decrease in CFU that was not always correlated with a reduction in biomass and/or a bactericidal effect on biofilms, particularly for the CF strains. The ATM monotherapy bactericidal effect was lower, but effects on biofilm biomass and/or structure, including intense filamentation, were documented. The alternation of TOB and ATM led to an enhancement of the antibiofilm activity against laboratory and CF strains compared to that with the individual regimens, potentiating the bactericidal effect and/or the reduction in biomass, particularly at peak concentrations. Resistant mutants were not documented in any of the regimens at the peak concentrations and only anecdotally at the 1/10-peak concentrations. These results support the clinical evaluation of sequential regimens with inhaled antibiotics in CF, as opposed to the current maintenance treatments with just one antibiotic in monotherapy.
Potential impact of novel diagnostics and treatments on the burden of antibiotic resistant in Escherichia coli

The rising threat of antibiotic resistance in Europe and beyond is of increasing concern and is prompting renewed effort to better understand and mitigate their impact. Escherichia Coli blood stream infections are a more major concern in Europe given their incidence and severe associated outcomes. Additionally the level of 3rd generation cephalosporins and carbapenems resistance among those bacteraemia has significantly increased, limiting available treatment options. We estimated the current burden associated with E. coli blood stream infections in Europe at 17,000 (95%CI [8,000; 30,000]) excess deaths and 960,000 (95%CI [600,000; 1,450,000]) extra hospital bed days. From those, the contribution due to 3rd generation cephalosporins and carbapenems resistant strains reached 6,000 (95%CI [2,000; 12,000]) excess deaths, and 200,000 (95%CI [76,000; 420,000]) extra hospital bed stay. In the worst case scenario, we estimated the burden of E. coli blood stream infection in 2026 could increase over 4-fold, mostly resulting from an increase in the level of resistance rather than an increase in the incidence of blood stream infections. Finally, we estimated that the impact of combined novel diagnostics and treatments could substantially reduce the excess mortality by 18.5% to 55.5%, and length of stay by 13.2% to 75.6%.
Effects of Amplification on Neural Phase Locking, Amplitude, and Latency to a Speech Syllable

Objective: Older adults often have trouble adjusting to hearing aids when they start wearing them for the first time. Probe microphone measurements verify appropriate levels of amplification up to the tympanic membrane. Little is known, however, about the effects of amplification on auditory-evoked responses to speech stimuli during initial hearing aid use. The present study assesses the effects of amplification on neural encoding of a speech signal in older adults using hearing aids for the first time. It was hypothesized that amplification results in improved stimulus encoding (higher amplitudes, improved phase locking, and earlier latencies), with greater effects for the regions of the signal that are less audible. Design: Thirty-seven adults, aged 60 to 85 years with mild to severe sensorineural hearing loss and no prior hearing aid use, were bilaterally fit with Widex Dream 440 receiver-in-the-ear hearing aids. Probe microphone measures were used to adjust the gain of the hearing aids and verify the fitting. Unaided and aided frequency-following responses and cortical auditory-evoked potentials to the stimulus /ga/ were recorded in sound field over the course of 2 days for three conditions: 65 dB SPL and 80 dB SPL in quiet, and 80 dB SPL in six-talker babble (+10 signal to noise ratio). Results: Responses from midbrain were analyzed in the time regions corresponding to the consonant transition (18 to 68 ms) and the steady state vowel (68 to 170 ms). Generally, amplification increased phase locking and amplitude and decreased latency for the region and presentation conditions that had lower stimulus amplitudes—the transition region and 65 dB SPL level. Responses from cortex showed decreased latency for P1, but an unexpected decrease in N1 amplitude. Previous studies have demonstrated an exaggerated cortical representation of speech in older adults compared to younger adults, possibly because of an increase in neural resources necessary to encode the signal. Therefore, a decrease in N1 amplitude with amplification and with increased presentation level may suggest that amplification decreases the neural resources necessary for cortical encoding. Conclusion: Increased phase locking and amplitude and decreased latency in midbrain suggest that amplification may improve neural representation of the speech signal in new hearing aid users. The improvement with amplification was also found in cortex, and, in particular, decreased P1 latencies and lower N1 amplitudes may indicate greater neural efficiency. Further investigations will evaluate changes in subcortical and cortical responses during the first 6 months of hearing aid use.
Pathogenesis of peritonsillar abscess

The pathogenesis of peritonsillar abscess is described in textbooks as being a direct communication and progression of acute exudative tonsillitis. Little study has been done on the true etiology and pathogenesis of peritonsillar abscess. This paper focuses on the pathogenesis of peritonsillar abscess. A group of salivary glands (Weber's glands) proven to be located in the supratonsillar space have been shown to be implicated in the pathogenesis of peritonsillar abscess. A review of peritonsillar abscess has been undertaken, and evidence has been presented to support the premise that the true cause for peritonsillar abscess is not necessarily an extension of an acute exudative tonsillitis, but an abscess formation of Weber's salivary glands in the supratonsillar fossa.
GC-MS analysis of phytocomponents in the ethanol extract of Polygonum chinense L

Background: The presence of diverse secondary metabolites has been reported from species of the genus Polygonum. However, there has been not much information available on phytochemical components and biological activity in the whole plant ethanol extract of Polygonum chinense L. Objective: This study was designed to determine the phytocomponents in the whole plant ethanol extract of P. chinense. Materials and Methods: GC-MS analysis of the whole plant ethanol extract of P. chinense was performed using a Perkin-Elmer GC Clarus 500 system comprising an AOC-20i auto-sampler and a gas chromatograph interfaced to a mass spectrometer (GC-MS). Results: This investigation was carried out to determine the possible chemical components from P. chinense by GC-MS. This analysis revealed that the ethanol extract of P. chinense (whole plant) contained mainly a triterpene compound–squalene (47.01%), and a plasticizer compound–1,2-benzenedicarboxylic acid, mono[2-ethylhexyl]ester (40.30%). All identified compounds were, generally, reported as having antimicrobial activity. In addition, the squalene compound also having anti-cancer, anti-oxidant, anti-tumor, chemo-preventive, pesticidal and sun-screen properties, while the plasticizer compound –1,2-benzenedicarboxylic acid, mono[2-ethylhexyl] ester reported to have anti-oxidant and anti-inflammatory properties. No activity was reported in the alcoholic compound-4-hexene-1-ol, 5-methyl-2-(1-methylethanyl)-acetate-(R)-. Conclusions: From the results, it is evident that P. chinense contains various bioactive compounds and is recommended as a plant of phytopharmaceutical importance.
Negotiating Agents and Bargaining Processes: Maximizing Member State Interests in COREPER

How can rational political actors maximize their interests when bargaining through representatives? This project challenges the conventional argument of the canonical principalagent and rationalist international relations (IR) bargaining literatures, arguing that the importance of constraining representatives’ actions and choices varies depending on the type of bargaining process in which they are involved. I argue that in “cooperative bargaining processes”, giving representatives a high degree of autonomy will lead to the maximization of interests. On the other hand, in more “competitive bargaining processes”, constraining one’s representatives will lead to the maximization of interests in decision-making outcomes. Using original interview evidence with member state representatives in COREPER, I demonstrate that agent autonomy is crucial for the ability of deputy and permanent representatives to forward the interests of their principals – the various ministries of their member state – within a cooperative bargaining process.
T-Norms on Bounded Lattices: t-norm Morphisms and Operators

Triangular norms or t-norm, in short, and automorphisms are very useful to fuzzy logics in the narrow sense. Moreover, these notions are usually limited to the set [0,1]. In this paper we will consider a well known generalization of the t-norm for arbitrary bounded lattices and provide a generalization of automorphism notion for this same structure. We consider several typical lattice constructors and introduce versions of them for t-norms and morphisms. We also analyze some properties of these constructions.
Fostering Sustainable Nutrition Behavior through Gamification

The food choices consumers make have considerable consequences for the environment. In the Western world, about one-third of all negative environmental impact is directly related to food consumption. Although many consumers are concerned about environmental issues, this frequently has little effect on actual nutritional behavior and new approaches are needed to convert good intentions into action. Gamification could be a possible way to encourage both self-efficacy on the part of the consumer as well as normalizing such behavior socially. In this paper, central elements of the behavioral change model HAPA (health action process approach) are introduced to a gamification concept. The underlying frameworks of both concepts are then analyzed in order to develop propositions for use in the design of an effective gamification setting to promote sustainable nutritional behavior (SNB).
Lopinavir/Ritonavir Pharmacokinetic Profile: Impact of Sex and Other Covariates Following a Change From Twice‐Daily to Once‐Daily Therapy

The aim of this study was to determine the impact of sex on the pharmacokinetics of lopinavir/ritonavir. Interaction between lopinavir/ritonavir and tenofovir was also evaluated. Steady‐state plasma samples were obtained from virologically suppressed HIV‐infected patients on lopinavir/ritonavir 800/200‐mg soft gel capsule taken once daily. Drug assays were performed by high‐performance liquid chromatography. Pharmacokinetic parameters estimated by noncompartmental method were reported as 90% confidence intervals (CIs) about the geometric mean ratio (GMR). There were 9 males and 11 females. No sex differences were observed in lopinavir/ritonavir pharmacokinetics profile. The GMRsex (women compared with men) for lopinavir area under the concentration‐time curve (AUC24), maximum concentration (Cmax), and minimum concentration (Cmin) was 0.95 (90% CI, 0.70–1.29), 0.88 (90% CI, 0.67–1.15), and 1.27 (90% CI, 0.60–2.66), respectively. Similarly, the GMRsex for ritonavir AUC24, Cmax, and Cmin was 0.84 (90% CI, 0.57–1.24), 0.79 (90% CI, 0.50–1.22), and 1.02 (90% CI, 0.58–1.80), respectively. Tenofovir coadministration led to a reduction in lopinavir/ritonavir plasma exposure, giving a lopinavir GMRtenofovir for Cmax of 0.72 (90% CI, 0.57–0.93) and AUC24 of 0.74 (90% CI, 0.56–0.98), respectively. No difference in lopinavir/ritonavir plasma concentrations between sexes was demonstrated in this study. However, tenofovir coadministration lowered lopinavir/ritonavir plasma exposure.
Transthoracic needle biopsy using a C-arm cone-beam CT system: diagnostic accuracy and safety.

OBJECTIVE The purpose of this study was to evaluate the diagnostic accuracy and safety of performing transthoracic needle biopsy (TNB) under combined fluoroscopy and CT guidance using a C-arm cone-beam CT (CBCT) system. METHODS We evaluated the diagnostic accuracy and safety of performing TNB using a C-arm CBCT system. We retrospectively evaluated 99 TNB cases performed in 98 patients using a C-arm CBCT system with an 18-gauge automated cutting needle. We reviewed the diagnostic accuracy according to the size and depth of the lesion, incidence of complications, additional treatment for complications, procedure time, number of needle passes per biopsy and radiation dose. RESULTS The final diagnoses revealed 72 malignant and 27 benign lesions. The overall malignancy sensitivity, malignancy specificity and diagnostic accuracy were 95.8%, 100% and 97.0%, respectively, and those for small pulmonary nodules <20 mm in size were 94.1%, 100% and 96.6%, respectively. There was no significant difference in the correct diagnosis of malignancy according to lesion size (p = 0.634) or depth (p = 0.542). For benign lesions, a specific diagnosis was obtained in 14 cases (51.9%). TNB induced complications in 19 out of 99 procedures (19.2%), including pneumothorax (16.2%), immediate haemoptysis (2.0%) and subcutaneous emphysema (1.0%). Among these, four patients with pneumothorax required chest tube insertion (2.0%) or pig-tail catheter drainage (2.0%). The mean procedure time, number of needle passes and radiation doses were 11.9 ± 4.0 min, 1.2 ± 0.5 times and 170.0 ± 67.2 mGy, respectively. CONCLUSION TNB using a C-arm CBCT system provides high diagnostic accuracy with a low complication rate and a short procedure time, particularly for small pulmonary nodules.
Expression of Neisseria meningitidis iron-regulated outer membrane proteins, including a 70-kilodalton transferrin receptor, and their potential for use as vaccines

The iron-regulated proteins (IRPs) of five group B meningococcal strains expressing class 2 outer membrane proteins were compared with those of five strains expressing class 3 proteins. Three to four high-molecular-weight IRPs were expressed by each strain, but their molecular sizes varied between strains and were not related to class 2 or 3 protein expression. Transferrin and hemoglobin could be used as a sole iron source. By using anti-human transferrin antibodies, it was shown that meningococcal cells and purified outer membranes bound transferrin. Growth under conditions of iron limitation caused a several-fold increase in the amount of transferrin bound to the cell surface. The transferrin-binding protein was detergent solubilized from outer membranes and partially purified. The isolated protein bound human transferrin and had an apparent molecular mass of 70 kilodaltons. To evaluate the potential of vaccines containing IRPs, we prepared outer membrane vaccines from strains M986-NCV-1 (M986) (--:2a: P1.2) and 44/76-M25 (44/76) (--:15:P1.15) grown to fully express their IRPs. Both vaccines induced significant anti-IRP antibodies as measured by enzyme immunoassay and by Western immunoblot with both M986 and 44/76 outer membranes. By Western blot analysis, the M986 vaccine induced antibodies to two different IRPs, one of which was shared with 44/76. Since the IRPs are major in vivo-expressed outer membrane proteins and are required for survival in vivo, these proteins should be evaluated for their usefulness in a group B meningococcal vaccine.
Leisure-Time Physical Activity Is Associated With the Metabolic Syndrome in Type 1 Diabetes

The metabolic syndrome varies in prevalence among different populations. A common feature, however, is a steep increase in prevalence along with a decrease in glucose tolerance (1–2). We have shown that 39% of adult type 1 diabetic patients have the metabolic syndrome (3), and similar data were recently reported from Italy (4). However, whether the metabolic syndrome observed in type 1 diabetes is the same as in nondiabetic and type 2 diabetic patients is unclear. Both lifestyle (5–8) and hereditary factors (9) seem to be involved in the development of the metabolic syndrome in nondiabetic and type 2 diabetic subjects. The PPARγ (peroxisome proliferator-activated receptor γ) Pro12Ala polymorphism has been associated with type 2 diabetes, the Ala allele being associated with a lower risk (10), and with the metabolic syndrome in some (11–12) but not all (13) studies. However, whether lifestyle or genetic factors also play a role in the development and treatment of the metabolic syndrome in patients with type 1 diabetes is unknown. Therefore, to further study the metabolic syndrome in type 1 diabetes, we investigated whether physical activity and/or the PPARγ Pro12Ala polymorphism are associated with metabolic syndrome in patients with type 1 diabetes in the Finnish Diabetic Nephropathy (FinnDiane) …
IFN-β1a Inhibits the Secretion of Th17-Polarizing Cytokines in Human Dendritic Cells via TLR7 Up-Regulation1

IFN-β, an effective therapy against relapsing-remitting multiple sclerosis, is naturally secreted during the innate immune response against viral pathogens. The objective of this study was to characterize the immunomodulatory mechanisms of IFN-β targeting innate immune response and their effects on dendritic cell (DC)-mediated regulation of T cell differentiation. We found that IFN-β1a in vitro treatment of human monocyte-derived DCs induced the expression of TLR7 and the members of its downstream signaling pathway, including MyD88, IL-1R-associated kinase 4, and TNF receptor-associated factor 6, while it inhibited the expression of IL-1R. Using small interfering RNA TLR7 gene silencing, we confirmed that IFN-β1a-induced changes in MyD88, IL-1R-associated kinase 4, and IL-1R expression were dependent on TLR7. TLR7 expression was also necessary for the IFN-β1a-induced inhibition of IL-1β and IL-23 and the induction of IL-27 secretion by DCs. Supernatant transfer experiments confirmed that IFN-β1a-induced changes in DC cytokine secretion inhibit Th17 cell differentiation as evidenced by the inhibition of retinoic acid-related orphan nuclear hormone receptor C and IL-17A gene expression and IL-17A secretion. Our study has identified a novel therapeutic mechanism of IFN-β1a that selectively targets the autoimmune response in multiple sclerosis.
Projection of North Pacific Tropical Upper-Tropospheric Trough in CMIP5 Models: Implications for Changes in Tropical Cyclone Formation Locations

AbstractThe strong westerly shear to the south flank of the tropical upper-tropospheric trough (TUTT) limits the eastward extension of tropical cyclone (TC) formation over the western North Pacific (WNP) and thus the zonal shift of the TUTT in warming scenarios has an important implication for the mean formation location of TCs. The impact of global warming on the zonal shift of the TUTT is investigated by using output from phase 5 of the Coupled Model Intercomparison Project (CMIP5) of 36 climate models in this study. It is found that considerable spread exists in the zonal position, orientation, and intensity of the simulated-climatologic TUTT in the historical runs, which is forced by observed conditions such as changes in atmospheric composition, solar forcing, and aerosols. The large spread is closely related to the diversity in the simulated SST biases over the North Pacific. Based on the 15 models with relatively high skill in their historical runs, the near-term (2016–35) projection shows no signi.
Extensive psoriasis induced by interferon alfa treatment for chronic hepatitis

Primary laryngeal amyloidosis is a rare benign disease of unknown aetiology. It can present with dysphonia or stridor. A woman presenting with airway compromise, who required a tracheostomy, is reported. (Postgrad Med J 2000;76:364–365)
Maintaining efficacy in the treatment of diabetic peripheral neuropathic pain: role of duloxetine

Introduction Neuropathy is one of the most frequent complications of diabetes. Of all the symptoms associated with diabetic neuropathy, pain has the largest impact on sleep and quality of life. In the past few years further medications have been added to the available therapies for neuropathic pain. One of these medications, duloxetine hydrochloride (duloxetine), is a balanced and potent selective serotonin and norepinephrine reuptake inhibitor. Methods Medline was searched from January 2005 to September 2009 using the key words duloxetine and peripheral neuropathy for clinical trials limited to human research published in English and duloxetine and pharmacology in the nervous system. Results Duloxetine has been shown to effectively reduce diabetic peripheral neuropathic pain compared to placebo at doses of 60 mg/day and 120 mg/day with minimal to moderate side effects. This effect is seen with minimal effects on glycemic control and without any clinically relevant effects on lipid control, or cardiovascular parameters. In addition, its efficacy and tolerability is comparable to other medications commonly used in the management of neuropathic pain. Furthermore, duloxetine performs favorably both in terms of quality of life and in cost utility analyses. Discussion and conclusion This article reviewed the issues related to management of diabetic peripheral neuropathic pain, the pharmacology and rationale for use of duloxetine, efficacy studies, and the safety and tolerability of treatment with duloxetine. Duloxetine is an acceptable initial or alternative treatment for patients with diabetic neuropathic pain.
Telocytes in human oesophagus

Telocytes (TCs), a new type of interstitial cells, were identified in many different organs and tissues of mammalians and humans. In this study, we show the presence, in human oesophagus, of cells having the typical features of TCs in lamina propria of the mucosa, as well as in muscular layers. We used transmission electron microscopy (TEM), immunohistochemistry (IHC) and primary cell culture. Human oesophageal TCs present a small cell body with 2–3 very long Telopodes (Tps). Tps consist of an alternation of thin segments (podomers) and thick segments (podoms) and have a labyrinthine spatial arrangement. Tps establish close contacts (‘stromal synapses’) with other neighbouring cells (e.g. lymphocytes, macrophages). The ELISA testing of the supernatant of primary culture of TCs indicated that the concentrations of VEGF and EGF increased progressively. In conclusion, our study shows the existence of typical TCs at the level of oesophagus (mucosa, submucosa and muscular layer) and suggests their possible role in tissue repair.