bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monte Carlo simulations of the dose from imaging with GE eXplore 120 micro‐CT using gate
Authors: Bretin Florian , Bahri Mohamed Ali , Luxen André , Phillips Christophe , Plenevaux Alain , Seret Alain 
Published: September 2015

Purpose:Small animals are increasingly used as translational models in preclinical imaging studies involving microCT, during which the subjects can be exposed to large amounts of radiation. While the radiation levels are generally sublethal, studies have shown that low‐level radiation can change physiological parameters in mice. In order to rule out any influence of radiation on the outcome of such experiments, or resulting deterministic effects in the subjects, the levels of radiation involved need to be addressed. The aim of this study was to investigate the radiation dose delivered by the GE eXplore 120 microCT non‐invasively using Monte Carlo simulations in gate and to compare results to previously obtained experimental values.Methods:Tungsten X‐ray spectra were simulated at 70, 80, and 97 kVp using an analytical tool and their half‐value layers were simulated for spectra validation against experimentally measured values of the physical X‐ray tube. A Monte Carlo model of the microCT system was set up and four protocols that are regularly applied to live animal scanning were implemented. The computed tomography dose index (CTDI) inside a PMMA phantom was derived and multiple field of view acquisitions were simulated using the PMMA phantom, a representative mouse and rat.Results:Simulated half‐value layers agreed with experimentally obtained results within a 7% error window. The CTDI ranged from 20 to 56 mGy and closely matched experimental values. Derived organ doses in mice reached 459 mGy in bones and up to 200 mGy in soft tissue organs using the highest energy protocol. Dose levels in rats were lower due to the increased mass of the animal compared to mice. The uncertainty of all dose simulations was below 14%.Conclusions:Monte Carlo simulations proved a valuable tool to investigate the 3D dose distribution in animals from microCT. Small animals, especially mice (due to their small volume), receive large amounts of radiation from the GE eXplore 120 microCT, which might alter physiological parameters in a longitudinal study setup.
The Effects of Sex, Limb Dominance, and Soccer Participation on Knee Proprioception and Dynamic Postural Control
Authors: Cug Mutlu , Wikstrom Erik A. , Golshaei Bahman , Kirazci Sadettin 
Published: September 2015

Context:Both female athletes’ participation in soccer and associated injuries have greatly increased in recent years. One issue is the 2–9 times greater incidence of noncontact anterior cruciate ligament (ACL) injuries in female athletes relative to male athletes in comparable sports. Several factors such as limb dominance and sporting history have been proposed to play a role in ACL incidence rates between male and female athletes. However, evidence about the effects of these factors and how they interact with sex is mixed, and thus no consensus exists.Objective:To quantify the effects of sports participation, limb dominance, and sex on dynamic postural control and knee-joint proprioception.Design:Cross-sectional study.Setting:University research laboratory.Participants:19 male soccer players, 17 female soccer players, 19 sedentary men, and 18 sedentary women.Intervention:Joint-position sense was tested using reproduction of passive positioning on a Biodex isokinetic dynamometer (30°, 45°, and 60° from 90° of knee flexion). Three Star Excursion Balance Test directions were used to assess dynamic postural control.Main Outcome Measure:Normalized reach distance (% of leg length) in the anterior, posteromedial, and posterolateral directions on each leg quantified dynamic postural control. Average absolute error and constant error for both limbs quantified joint-position sense.Results:Posteromedial reach distance was significantly better in soccer players than sedentary individuals (P = .006). Anterior reach distance was significantly better (P = .04) in sedentary individuals than soccer players. No limb-dominance or sex differences were identified for dynamic postural control, and no differences in absolute- or constant-error scores were identified.Conclusion:Sporting history has a direction-specific impact on dynamic postural control. Sporting history, sex, and limb dominance do not influence knee-joint proprioception when tested in an open kinetic chain using passive repositioning.
Prediction of Dynamic Postural Stability During Single-Leg Jump Landings by Ankle and Knee Flexibility and Strength
Authors: Williams Valerie J. , Nagai Takashi , Sell Timothy C. , Abt John P. , Rowe Russell S. , McGrail Mark A. , Lephart Scott M. 
Published: September 2015

Context:Dynamic postural stability is important for injury prevention, but little is known about how lower-extremity musculoskeletal characteristics (range of motion [ROM] and strength) contribute to dynamic postural stability. Knowing which modifiable physical characteristics predict dynamic postural stability can help direct rehabilitation and injury-prevention programs.Objective:To determine if trunk, hip, knee, and ankle flexibility and strength variables are significant predictors of dynamic postural stability during single-leg jump landings.Design:Cross-sectional study.Setting:Laboratory.Participants:94 male soldiers (age 28.2 ± 6.2 y, height 176.5 ± 2.6 cm, weight 83.7 ± 26.0 kg).Intervention:None.Main Outcome Measures:Ankle-dorsiflexion and plantar-flexion ROM were assessed with a goniometer. Trunk, hip, knee, and ankle strength were assessed with an isokinetic dynamometer or handheld dynamometer. The Dynamic Postural Stability Index (DPSI) was used to quantify postural stability. Simple linear and backward stepwise-regression analyses were used to identify which physical characteristic variables were significant predictors of DPSI.Results:Simple linear-regression analysis revealed that individually, no variables were significant predictors of the DPSI. Stepwise backward-regression analysis revealed that ankle-dorsiflexion flexibility, ankle-inversion and -eversion strength, and knee-flexion and -extension strength were significant predictors of the DPSI (R2 = .19, P = .0016, adjusted R2 = .15).Conclusion:Ankle-dorsiflexion ROM, ankle-inversion and -eversion strength, and knee-flexion and -extension strength were identified as significant predictors of dynamic postural stability, explaining a small amount of the variance in the DPSI.
Athletes’ Expectations About Sport-Injury Rehabilitation: A Cross-Cultural Study
Authors: Arvinen-Barrow Monna , Clement Damien , Hamson-Utley Jennifer Jordan , Kamphoff Cindra , Zakrajsek Rebecca , Lee Sae-Mi , Hemmings Brian , Lintunen Taru , Martin Scott B. 
Published: September 2015

Context:Athletes enter injury rehabilitation with certain expectations about the recovery process, outcomes, and the professional providing treatment. Their expectations influence the effectiveness of the assistance received and affect the overall rehabilitation process. Expectations may vary depending on numerous factors such as sport experience, gender, sport type, and cultural background. Unfortunately, limited information is available on athletes’ expectations about sport-injury rehabilitation.Objective:To examine possible differences in athletes’ expectations about sport-injury rehabilitation based on their country of residence and type of sport (contact vs noncontact).Design:Cross-sectional.Setting:Recreational, college, and professional athletes from the US, UK, and Finland were surveyed.Participants:Of the 1209 athletes ranging from 12 to 80 y of age (mean 23.46 ± 7.91), 529 US [80%], 253 UK [86%], and 199 Finnish [82%] athletes provided details of their geographical location and were included in the final analyses.Main Outcome Measures:The Expectations About Athletic Training (EAAT) questionnaire was used to determine athletes’ expectations about personal commitment, facilitative conditions, and the expertise of the sports-medicine professional (SMP).Results:A 3 × 2 MANCOVA revealed significant main effects for country (P = .0001, ηp2 = .055) and sport type (P = .0001, ηp2 = .023). Specifically, US athletes were found to have higher expectations of personal commitment and facilitative conditions than their UK and Finnish counterparts. Athletes participating in contact sports had higher expectations of facilitative conditions and the expertise of the SMP than did athletes participating in noncontact sports.Conclusions:SMPs, especially those in the US, should consider the sport and environment when providing services. In addition, SMPs need to highlight and demonstrate their expertise during the rehabilitation process, especially for those who compete in contact sports.
Intrinsic Carbapenem-Hydrolyzing Oxacillinases from Members of the Genus Pandoraea
Authors: Schneider Ines , Bauernfeind Adolf 
Published: September 2015

ABSTRACT

We analyzed the oxacillinases of isolates of six different species of
Pandoraea
, a genus that colonizes the respiratory tract of cystic fibrosis patients. The isolates produced carbapenem-hydrolyzing enzymes causing elevated MICs for amoxicillin, piperacillin, meropenem, and imipenem when expressed in an
Escherichia coli
host strain. Sequencing revealed nine new oxacillinases (OXA-151 to OXA-159) with a high degree of identity among isolates of the same species; however, they had much lower interspecies similarities. The intrinsic oxacillinase genes might therefore be helpful for correct identification of
Pandoraea
isolates.
Combinations of Alkaloids Affecting Different Molecular Targets with the Saponin Digitonin Can Synergistically Enhance Trypanocidal Activity against Trypanosoma brucei brucei
Authors: Krstin Sonja , Peixoto Herbenya Silva , Wink Michael 
Published: September 2015

ABSTRACT

The flagellate
Trypanosoma brucei
causes sleeping sickness in humans and nagana in animals. Only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. Also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. An underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. In this study, the potential synergism of mutual combinations of bioactive alkaloids and alkaloids with a membrane-active steroidal saponin, digitonin, was explored with regard to their effect on
T. b. brucei
. Alkaloids were selected that affect different molecular targets: berberine and chelerythrine (intercalation of DNA), piperine (induction of apoptosis), vinblastine (inhibition of microtubule assembly), emetine (intercalation of DNA, inhibition of protein biosynthesis), homoharringtonine (inhibition of protein biosynthesis), and digitonin (membrane permeabilization and uptake facilitation of polar compounds). Most combinations resulted in an enhanced trypanocidal effect. The addition of digitonin significantly stimulated the activity of almost all alkaloids against trypanosomes. The strongest effect was measured in a combination of digitonin with vinblastine. The highest dose reduction indexes (DRI) were measured in the two-drug combination of digitonin or piperine with vinblastine, where the dose of vinblastine could be reduced 9.07-fold or 7.05-fold, respectively. The synergistic effects of mutual combinations of alkaloids and of alkaloids with digitonin present a new avenue to treat trypanosomiasis but one which needs to be corroborated in future animal experiments.
Baicalin Inhibits the Lethality of Shiga-Like Toxin 2 in Mice
Authors: Dong Jing , Zhang Yong , Chen Yutao , Niu Xiaodi , Zhang Yu , Yang Cheng , Wang Quan , Li Xuemei , Deng Xuming 
Published: September 2015

ABSTRACT

Shiga-like toxins (Stxs), produced by pathogenic
Escherichia coli
, are a major virulence factor involved in severe diseases in human and animals. These toxins are ribosome-inactivating proteins, and treatment for diseases caused by them is not available. Therefore, there is an urgent need for agents capable of effectively targeting this lethal toxin. In this study, we identified baicalin, a flavonoid compound used in Chinese traditional medicine, as a compound against Shiga-like toxin 2 (Stx2). We found that baicalin significantly improves renal function and reduces Stx2-induced lethality in mice. Further experiments revealed that baicalin induces the formation of oligomers by the toxin by direct binding. We also identified the residues important for such interactions and analyzed their roles in binding baicalin by biophysical and biochemical analyses. Our results establish baicalin as a candidate compound for the development of therapeutics against diseases caused by Stxs.
Structure-Activity Relationship of the Aminomethylcyclines and the Discovery of Omadacycline
Authors: Honeyman Laura , Ismail Mohamed , Nelson Mark L. , Bhatia Beena , Bowser Todd E. , Chen Jackson , Mechiche Rachid , Ohemeng Kwasi , Verma Atul K. , Cannon E. Pat , Macone Ann , Tanaka S. Ken , Levy Stuart 
Published: September 2015

ABSTRACT

A series of novel tetracycline derivatives were synthesized with the goal of creating new antibiotics that would be unaffected by the known tetracycline resistance mechanisms. New C-9-position derivatives of minocycline (the aminomethylcyclines [AMCs]) were tested for
in vitro
activity against Gram-positive strains containing known tetracycline resistance mechanisms of ribosomal protection (Tet M in
Staphylococcus aureus
,
Enterococcus faecalis
, and
Streptococcus pneumoniae
) and efflux (Tet K in
S. aureus
and Tet L in
E. faecalis
). A number of aminomethylcyclines with potent
in vitro
activity (MIC range of ≤0.06 to 2.0 μg/ml) were identified. These novel tetracyclines were more active against one or more of the resistant strains than the reference antibiotics tested (MIC range, 16 to 64 μg/ml). The AMC derivatives were active against bacteria resistant to tetracycline by both efflux and ribosomal protection mechanisms. This study identified the AMCs as a novel class of antibiotics evolved from tetracycline that exhibit potent activity
in vitro
against tetracycline-resistant Gram-positive bacteria, including pathogenic strains of methicillin-resistant
S. aureus
(MRSA) and vancomycin-resistant enterococci (VRE). One derivative, 9-neopentylaminomethylminocycline (generic name omadacycline), was identified and is currently in human trials for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP).
Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis
Authors: Bicanic Tihana , Bottomley Christian , Loyse Angela , Brouwer Annemarie E. , Muzoora Conrad , Taseera Kabanda , Jackson Arthur , Phulusa Jacob , Hosseinipour Mina C. , van der Horst Charles , Limmathurotsakul Direk , White Nicholas J. , Wilson Douglas , Wood Robin , Meintjes Graeme , Harrison Thomas S. , Jarvis Joseph N. 
Published: September 2015

ABSTRACT

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3;
P
= 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11;
P
= 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.
Meropenem-RPX7009 Concentrations in Plasma, Epithelial Lining Fluid, and Alveolar Macrophages of Healthy Adult Subjects
Authors: Wenzler Eric , Gotfried Mark H. , Loutit Jeffrey S. , Durso Stephanie , Griffith David C. , Dudley Michael N. , Rodvold Keith A. 
Published: September 2015

ABSTRACTThe steady-state concentrations of meropenem and the β-lactamase inhibitor RPX7009 in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations were obtained in 25 healthy, nonsmoking adult subjects. Subjects received a fixed combination of meropenem (2 g) and RPX7009 (2 g) administered every 8 h, as a 3-h intravenous infusion, for a total of three doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject at 1.5, 3.25, 4, 6, or 8 h after the start of the last infusion. Meropenem and RPX7009 achieved a similar time course and magnitude of concentrations in plasma and ELF. The mean pharmacokinetic parameters ± the standard deviations of meropenem and RPX7009 determined from serial plasma concentrations were as follows:Cmax= 58.2 ± 10.8 and 59.0 ± 8.4 μg/ml,Vss= 16.3 ± 2.6 and 17.6 ± 2.6 liters; CL = 11.1 ± 2.1 and 10.1 ± 1.9 liters/h, andt1/2= 1.03 ± 0.15 and 1.27 ± 0.21 h, respectively. The intrapulmonary penetrations of meropenem and RPX7009 were ca. 63 and 53%, respectively, based on the area under the concentration-time curve from 0 to 8 h (AUC0–8) values of ELF and total plasma concentrations. When unbound plasma concentrations were considered, ELF penetrations were 65 and 79% for meropenem and RPX7009, respectively. Meropenem concentrations in AMs were below the quantitative limit of detection, whereas median concentrations of RPX7009 in AMs ranged from 2.35 to 6.94 μg/ml. The results from the present study lend support to exploring a fixed combination of meropenem (2 g) and RPX7009 (2 g) for the treatment of lower respiratory tract infections caused by meropenem-resistant Gram-negative pathogens susceptible to the combination of meropenem-RPX7009.
TIR Domain-Containing Adapter-Inducing Beta Interferon (TRIF) Mediates Immunological Memory against Bacterial Pathogens
Authors: Kanagavelu Saravana , Flores Claudia , Termini J. M. , Romero Laura , Riveron Reldy , Ruiz Jose , Arditi Moshe , Schesser Kurt , Fukata Masayuki 
Published: September 2015

ABSTRACTInduction of adaptive immunity leads to the establishment of immunological memory; however, how innate immunity regulates memory T cell function remains obscure. Here we show a previously undefined mechanism in which innate and adaptive immunity are linked by TIR domain-containing adapter-inducing beta interferon (TRIF) during establishment and reactivation of memory T cells against Gram-negative enteropathogens. Absence of TRIF in macrophages (Mϕs) but not dendritic cells led to a predominant generation of CD4+central memory T cells that express IL-17 during enteric bacterial infection in mice. TRIF-dependent type I interferon (IFN) signaling in T cells was essential to Th1 lineage differentiation and reactivation of memory T cells. TRIF activated memory T cells to facilitate local neutrophil influx and enhance bacterial elimination. These results highlight the importance of TRIF as a mediator of the innate and adaptive immune interactions in achieving the protective properties of memory immunity against Gram-negative bacteria and suggest TRIF as a potential therapeutic target.
Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host
Authors: Bandyopadhyay Syamdas , Bhattacharjee Amrita , Banerjee Sayantan , Halder Kuntal , Das Shibali , Paul Chowdhury Bidisha , Majumdar Subrata 
Published: September 2015

ABSTRACT

CD11b
+
Gr1
+
myeloid-derived suppressor cells (MDSCs), a heterogeneous population of precursor cells, modulate protective immunity against visceral leishmaniasis by suppressing T cell functions. We observed that CD11b
+
Gr1
+
MDSCs, which initially expanded in soluble leishmanial antigen (SLA)-immunized mice and later diminished, suppressed proliferation of T cells isolated from SLA-immunized mice, but to a lesser extent than the case in naive mice. This lesser suppression of MDSCs accompanied the expression of F4/80 and the production of Cox-2, arginase I, nitric oxide, and PGE2. However, with SLA immunization, there was no difference in the expression of interleukin-2 (IL-2) or gamma interferon (IFN-γ) by T cells, in contrast to the case in nonimmunized mice, in which there is an influence. Glycyrrhizic acid (a triterpenoid compound)-mediated inhibition of Cox-2 in myeloid-derived suppressor cells influenced the capacity of T cells to proliferate and the expression of IL-2 and IFN-γ in
Leishmania donovani
-infected BALB/c mice. Further characterization confirmed that administration of glycyrrhizic acid to
L. donovani
-infected BALB/c mice results in an impairment of the generation of MDSCs and a reciprocal organ-specific proliferation of IFN-γ- and IL-10-expressing CD4
+
and CD8
+
T cells. Comprehensive knowledge on the Cox-2-mediated regulation of myeloid-derived suppressor cells might be involved in unlocking a new avenue for therapeutic interventions during visceral leishmaniasis.