bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): Extending the CONSORT Statement
Authors: MacPherson Hugh , Altman Douglas G. , Hammerschlag Richard , Youping Li , Taixiang Wu , White Adrian , Moher David ,   on behalf of the STRICTA Revision Group
Published: July 2010

AbstractThe STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal editors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision. To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group, and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face‐to‐face meeting in Freiburg, a group of 21 participants further revised the STRICTA checklist and planned dissemination. The new STRICTA checklist, which is an official extension of CONSORT, includes six items and 17 sub‐items. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background, and the control or comparator interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word “controlled” in STRICTA is replaced by “clinical,” to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, including uncontrolled outcome studies and case reports. It is intended that the revised STRICTA, in conjunction with both the main CONSORT Statement and extension for nonpharmacologic treatment, will raise the quality of reporting of clinical trials of acupuncture.
Theoretical approach to the hit probability of lung‐cancer‐sensitive epithelial cells by mineral fibers with various aspect ratios
Authors: Sturm Robert 
Published: July 2010

AbstractBackground:  Inhalation of fibers may lead to the damage and, as a further consequence, to the malignant transformation of specific (most of all non‐ciliated) cells of the bronchial and bronchiolar airway epithelium. In order to accurately estimate the cancer risk induced by inhaled fibers, hit probabilities of non‐ciliated (secretory) cells by mineral fibers (asbestos and chrysotile) were computed.Methods:  Besides the use of a stochastic lung geometry and a particle transport/deposition model being based upon the random‐walk algorithm, histological data of cell distributions in the human lungs were applied for the theoretical calculations. Diameters of computer‐generated fibers ranged from 0.1 µm to 10 µm, whilst two values (3 and 100) were selected for the aspect ratios (ratios of fiber length to fiber diameter), thereby simulating the behavior of short and very long fibrous particles.Results:  According to the modeling results, the highest regional hit probabilities (up to 10%) are available for fibers with a diameter of 1.0 µm, whereby cells of the bronchiolar compartment represent a preferential target of these particles. For fibers with a diameter of 0.1 µm, bronchiolar hit probabilities reach 2–3%, whereas fibers with a diameter of 10 µm penetrate to the peripheral lung parts with only low amounts (<0.1%). A change of the inhalation conditions from sitting to light‐work breathing enhances the extrathoracic and bronchial filtering of large particles (diameter ≥1 µm), whilst penetration of small particles towards distal lung airways is subject to a reinforcement. Further refinement of hit probabilities by considering single airway generations results in the circumstance that fibers with diameters ≤1.0 µm preferably collide with cancer‐sensitive cells of airway generations 12–15. In contrast, fibers with a diameter of 10 µm mainly represent a hazard for cancer‐sensitive cells being located in the uppermost airways. A change of breathing conditions both supports the effect of short fibers and enhances the filtering of long ones.Conclusion:  Based upon the results of this contribution it can be concluded that highest cancer risk is generated by the inhalation of mineral fibers with diameters ≤1.0 µm, whereby fiber length has to be classified as a parameter with lower importance.
Relationship between urinary sodium excretion and pioglitazone‐induced edema
Authors: Nakamura Akinobu , Osonoi Takeshi , Terauchi Yasuo 
Published: July 2010

AbstractTo investigate the factors contributing to pioglitazone‐induced edema, we analyzed sodium excretion and several clinical parameters before and after administration of pioglitazone. We analyzed these parameters before and after 8 weeks of administration of pioglitazone to female subjects with type 2 diabetes. When we evaluated whether a significant correlation was found between salt excretion and blood pressure, six patients showed such correlation and 20 patients did not. After 8 weeks of pioglitazone administration, five patients had developed edema, and, surprisingly, such correlation was not found in all five subjects. Salt excretion after administration of pioglitazone was significantly lower in subjects who developed edema and those who showed the correlation, and the hematocrit was significantly lower after administration in the subjects who showed the correlation, but not in the edema group. Pioglitazone‐induced edema would be caused not only by fluid retention, but also by other factors, such as vascular permeability. (J Diabetes Invest, doi: 10.1111/ j.2040‐1124.2010.00046.x, 2010)
Effects of blood pressure and the renin‐angiotensin system on platelet activation in type 2 diabetes
Authors: Uzu Takashi , Sakaguchi Masayoshi , Tsuda Atsuko , Kadota Aya , Yokomaku Yukiyo , Kume Shinji , Kanasaki Masami , Isshiki Keiji , Araki Shin‐ichi , Sugiomoto Toshiro , Maegawa Hiroshi , Kashiwagi Atsunori 
Published: July 2010

AbstractAims/Introduction: Platelet‐derived microparticles (PDMP) are released from the platelets either after activation or in response to physical stimulationin vivo. The present study examined the association between blood pressure and PDMP, and the effects of high‐dose angiotensin receptor blockers (ARB) on PDMP in patients with type 2 diabetes.Materials and Methods: The study subjects consisted of 28 type 2 diabetes patients with blood pressure ≥130/80 mmHg who were treated with valsartan (80 mg daily). The patients were randomly assigned to take either 80 mg of telmisartan (Tel group) or 160 mg of valsartan (Val group) and then were followed up for 24 weeks. Thereafter, the patients were switched to combination therapy (5 mg of amlodipine with 40 mg of telmisartan [Tel group] or 80 mg of valsartan [Val group]) for 12 weeks.Results: Although the ambulatory blood pressure did not change, the PDMP levels were significantly decreased from baseline to week 24 (high dose ARB). In contrast, combination therapy reduced both blood pressure and PDMP levels compared with the baseline. Although the PDMP level was significantly correlated with the morning BP elevation at baseline and week 36 (combination therapy), this same relationship was not found at week 24. There were no significant differences in the blood pressure and PDMP levels between the two groups.Conclusions: Patients with morning hypertension might be at risk for cardiovascular diseases. High‐dose renin‐angiotensin system inhibition and blood pressure control are both considered to reduce cardiovascular events in patients with type 2 diabetes.(J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00048.x, 2010)
Multicenter Study for Defining the Breakpoint for Rifampin Resistance in
Neisseria meningitidis
by
rpoB
Sequencing
Authors: Taha Muhamed-Kheir , Thulin Hedberg Sara , Szatanik Marek , Hong Eva , Ruckly Corinne , Abad Raquel , Bertrand Sophie , Carion Francoise , Claus Heike , Corso Alejandra , Enríquez Rocío , Heuberger Sigrid , Hryniewicz Waleria , Jolley Keith A. , Kriz Paula , Mollerach Marta , Musilek Martin , Neri Arianna , Olcén Per , Pana Marina , Skoczynska Anna , Sorhouet Pereira Cecilia , Stefanelli Paola , Tzanakaki Georgina , Unemo Magnus , Vázquez Julio A. , Vogel Ulrich , Wasko Izabela 
Published: July 2010

ABSTRACT

Identification of clinical isolates of
Neisseria meningitidis
that are resistant to rifampin is important to avoid prophylaxis failure in contacts of patients, but it is hindered by the absence of a breakpoint for resistance, despite many efforts toward standardization. We examined a large number (
n
= 392) of clinical meningococcal isolates, spanning 25 years (1984 to 2009), that were collected in 11 European countries, Argentina, and the Central African Republic. The collection comprises all clinical isolates with MICs of ≥0.25 mg/liter (
n
= 161) received by the national reference laboratories for meningococci in the participating countries. Representative isolates displaying rifampin MICs of <0.25 mg/liter were also examined (
n
= 231). Typing of isolates was performed, and a 660-bp DNA fragment of the
rpoB
gene was sequenced. Sequences differing by at least one nucleotide were defined as unique
rpoB
alleles. The geometric mean of the MICs was calculated for isolates displaying the same allele. The clinical isolates displaying rifampin MICs of >1 mg/liter possessed
rpoB
alleles with nonsynonymous mutations at four critical amino acid residues, D542, H552, S548, and S557, that were absent in the alleles found in all isolates with MICs of ≤1 mg/liter. Rifampin-susceptible isolates could be defined as those with MICs of ≤1 mg/liter. The
rpoB
allele sequence and isolate data have been incorporated into the PubMLST
Neisseria
database (
http://pubmlst.org/neisseria/
). The rifampin-resistant isolates belonged to diverse genetic lineages and were associated with lower levels of bacteremia and inflammatory cytokines in mice. This biological cost may explain the lack of clonal expansion of these isolates.
Characterization of Dengue Virus Resistance to Brequinar in Cell Culture
Authors: Qing Min , Zou Gang , Wang Qing-Yin , Xu Hao Ying , Dong Hongping , Yuan Zhiming , Shi Pei-Yong 
Published: July 2010

ABSTRACT

Brequinar is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for
de novo
pyrimidine biosynthesis. Here we report that brequinar has activity against a broad spectrum of viruses. The compound not only inhibits flaviviruses (dengue virus, West Nile virus, yellow fever virus, and Powassan virus) but also suppresses a plus-strand RNA alphavirus (Western equine encephalitis virus) and a negative-strand RNA rhabdovirus (vesicular stomatitis virus). Using dengue virus serotype 2 (DENV-2) as a model, we found that brequinar suppressed the viral infection cycle mainly at the step of RNA synthesis. Supplementing the culture medium with pyrimidines (cytidine or uridine) but not purines (adenine or guanine) could be used to reverse the inhibitory effect of the compound. Continuous culturing of DENV-2 in the presence of brequinar generated viruses that were partially resistant to the inhibitor. Sequencing of the resistant viruses revealed two amino acid mutations: one mutation (M260V) located at a helix in the domain II of the viral envelope protein and another mutation (E802Q) located at the priming loop of the nonstructural protein 5 (NS5) polymerase domain. Functional analysis of the mutations suggests that the NS5 mutation exerts resistance through enhancement of polymerase activity. The envelope protein mutation reduced the efficiency of virion assembly/release; however, the mutant virus became less sensitive to brequinar inhibition at the step of virion assembly/release. Taken together, the results indicate that (i) brequinar blocks DENV RNA synthesis through depletion of intracellular pyrimidine pools and (ii) the compound may also exert its antiviral activity through inhibition of virion assembly/release.
Screen for Inducers of Autolysis in
Bacillus subtilis
Authors: Falk Shaun P. , Noah James W. , Weisblum Bernard 
Published: July 2010

ABSTRACT

We describe a primary high-throughput screen that uses the reporter strain
Bacillus subtilis
BAU-102 to identify antibiotics that induce autolysis. The screen measures autolysis in terms of the incipient release of recombinant
Escherichia coli
β-galactosidase (β-Gal) from the periplasmic space of
B. subtilis
owing to a loss of integrity of the cell wall. In a model screen, β-Gal release values for 79 members of a library consisting of antibiotics and related compounds were collected, sorted, and plotted as a function of rank. Inducers of autolysis, which included compounds that inhibit cell wall synthesis and those that do not, were readily differentiated from other members of the library on the basis of their elevated β-galactosidase release responses. The results of the BAU-102 model screen called attention to the antibacterial activity of drugs normally used in other applications, describable as “repurposed.” Thus, the screen independently identified the potential antibacterial properties of the antifungal drug miconazole and of the antileishmaniasis drug miltefosine. Daptomycin-induced release of β-Gal was also detected and occurred in a Ca
2+
-dependent manner.
Unpredictable Effects of Rifampin as an Adjunctive Agent in Elimination of Rifampin-Susceptible and -Resistant
Staphylococcus aureus
Strains Grown in Biofilms
Authors: Croes Sander , Beisser Patrick S. , Neef Cees , Bruggeman Cathrien A. , Stobberingh Ellen E. 
Published: July 2010

ABSTRACT

The use of rifampin as an adjunct in biofilm-associated infections is based on the ability to penetrate into biofilms and a presumed activity against dormant bacteria. Yet, its efficacy remains contradictory, and rifampin-resistant strains frequently emerge during therapy. Therefore, the efficacy against rifampin-susceptible and isogenic rifampin-resistant methicillin-susceptible
Staphylococcus aureus
(MSSA) strains was evaluated. Biofilms were generated under static conditions using MSSA with various genetic backgrounds. Oxacillin alone or with rifampin at various concentrations was subsequently added, and after 24 h biomass and viable cell counts were determined. Upon rifampin addition, interstrain variations in viable count change, ranging from a tendency toward antagonism to synergy, were observed among all strains tested, irrespective of the genetic background of the strain. Similar variations were observed in changes in biomass. The decrease in viable count upon rifampin addition was negatively correlated to formation of large amounts of biomass, since strains embedded by more biomass showed a diminished reduction in viable count. Rifampin (1 μg/ml) as adjunct to oxacillin achieved greater reductions in biomass produced by most rifampin-susceptible isolates, ranging from 17 to 54%, compared to 4% for oxacillin alone. In contrast, rifampin had no additional value in reduction of biomass of isogenic rifampin-resistant mutants. At subinhibitory concentrations of rifampin (0.008 μg/ml), none of the strains tested yielded an extra reduction in biomass that was ≥40%. In conclusion, the effects of rifampin as adjunct on biomass and viable count were unpredictable, and the use of rifampin against biofilm containing rifampin-resistant strains seems unwarranted.
Avirulent Uracil Auxotrophs Based on Disruption of Orotidine-5′-Monophosphate Decarboxylase Elicit Protective Immunity to
Toxoplasma gondii
Authors: Fox Barbara A. , Bzik David J. 
Published: July 2010

ABSTRACT

The orotidine-5′-monophosphate decarboxylase (OMPDC) gene, encoding the final enzyme of the
de novo
pyrimidine biosynthesis pathway, was deleted using
Toxoplasma gondii
KU80 knockouts to develop an avirulent nonreverting pyrimidine auxotroph strain. Additionally, to functionally address the role of the pyrimidine salvage pathway, the uridine phosphorylase (UP) salvage activity was knocked out and a double knockout of UP and OMPDC was also constructed. The nonreverting ΔOMPDC, ΔUP, and ΔOMPDC ΔUP knockout strains were evaluated for pyrimidine auxotrophy, for attenuation of virulence, and for their ability to elicit potent immunity to reinfection. The ΔUP knockout strain was replication competent and virulent. In contrast, the ΔOMPDC and ΔOMPDC ΔUP strains were uracil auxotrophs that rapidly lost their viability during pyrimidine starvation. Replication of the ΔOMPDC strain but not the ΔOMPDC ΔUP strain was also partially rescued
in vitro
with uridine or cytidine supplementation. Compared to their hypervirulent parental type I strain, the ΔOMPDC and ΔOMPDC ΔUP knockout strains exhibited extreme attenuation in murine virulence (∼8 logs). Genetic complementation of the ΔOMPDC strain using a functional OMPDC allele restored normal replication and type I parental strain virulence phenotypes. A single immunization of mice with either the live critically attenuated ΔOMPDC strain or the ΔOMPDC ΔUP knockout strain effectively induced potent protective immunity to lethal challenge infection. The avirulent nonreverting ΔOMPDC and ΔOMPDC ΔUP strains provide new tools for the dissection of the host response to infection and are promising candidates for safe and effective Th1 vaccine platforms that can be easily genetically engineered.
Immunization with a Combination of Integral Chlamydial Antigens and a Defined Secreted Protein Induces Robust Immunity against Genital Chlamydial Challenge
Authors: Li Weidang , Murthy Ashlesh K. , Guentzel M. Neal , Chambers James P. , Forsthuber Thomas G. , Seshu J. , Zhong Guangming , Arulanandam Bernard P. 
Published: July 2010

ABSTRACTWe have previously demonstrated the efficacy of recombinant chlamydial protease-like activity factor (rCPAF; a secreted chlamydial protein) in inducing antigen-specific CD4+T cell/gamma interferon (IFN-γ)-mediated but not antibody-mediated chlamydial clearance and reduction of upper genital tract (UGT) pathological sequelae. Since chlamydial integral antigens may induce neutralizing antibody protection, we further evaluated induction of protective immunity using a combination of rCPAF and UV-inactivated chlamydial elementary bodies (UV-EB) against vaginal chlamydial challenge in comparison to immunization with the individual components or live EB. The rCPAF-UV-EB immunization induced a significantly enhanced anti-UV-EB cellular and antibody response and a reduced anti-CPAF cellular and antibody response, compared to immunization with the respective individual components. Moreover, vaccination with UV-EB and rCPAF-UV-EB induced serum antibodies that neutralized chlamydial infectivity. The rCPAF-UV-EB immunization resulted in a significant reduction of vaginal chlamydial shedding and induced earlier bacterial clearance than vaccination of mice with the individual components. Importantly, the UGT sequelae were significantly reduced in mice immunized with rCPAF or rCPAF-UV-EB, but not in those immunized with UV-EB alone, and approached the levels of protection induced by live EB. These results collectively suggest that a combination of neutralizing antibodies induced by integral chlamydial antigens and cell-mediated responses induced by secreted proteins such as CPAF induces optimal protective immunity against genital chlamydial infections.
Activation of the CpxRA System by Deletion of
cpxA
Impairs the Ability of
Haemophilus ducreyi
To Infect Humans
Authors: Spinola Stanley M. , Fortney Kate R. , Baker Beth , Janowicz Diane M. , Zwickl Beth , Katz Barry P. , Blick Robert J. , Munson Robert S. 
Published: July 2010

ABSTRACT

Haemophilus ducreyi
must adapt to the environment of the human host to establish and maintain infection in the skin. Bacteria generally utilize stress response systems, such as the CpxRA two-component system, to adapt to hostile environments. CpxRA is the only obvious two-component system contained in the
H. ducreyi
genome and negatively regulates the
lspB-lspA2
operon, which encodes proteins that enable the organism to resist phagocytosis. We constructed an unmarked, in-frame
H. ducreyi cpxA
deletion mutant, 35000HPΔ
cpxA
. In human inoculation experiments, 35000HPΔ
cpxA
formed papules at a rate and size that were significantly less than its parent and was unable to form pustules compared to the parent. CpxA usually has kinase and phosphatase activities for CpxR, and the deletion of CpxA leads to the accumulation of activated CpxR due to the loss of phosphatase activity and the ability of CpxR to accept phosphate groups from other donors. Using a reporter construct, the
lspB-lspA2
promoter was downregulated in 35000HPΔ
cpxA
, confirming that CpxR was activated. Deletion of
cpxA
downregulated DsrA, the major determinant of serum resistance in the organism, causing the mutant to become serum susceptible. Complementation in
trans
restored parental phenotypes. 35000HPΔ
cpxA
is the first
H. ducreyi
mutant that is impaired in its ability to form both papules and pustules in humans. Since a major function of CpxRA is to control the flow of protein traffic across the periplasm, uncontrolled activation of this system likely causes dysregulated expression of multiple virulence determinants and cripples the ability of the organism to adapt to the host.
The Lung Is an Important Site for Priming CD4 T-Cell-Mediated Protective Immunity against Gastrointestinal Helminth Parasites
Authors: Harvie Marina , Camberis Mali , Tang Shiau-Choot , Delahunt Brett , Paul William , Le Gros Graham 
Published: July 2010

ABSTRACTThe rodent hookwormNippostrongylus brasiliensistypically infects its host by penetrating the skin and rapidly migrating to the lungs and gut. Following primary infection, immunocompetent mice become highly protected from reinfection withN. brasiliensis, with the numbers of worms gaining access to the lungs and gut being reduced by up to 90%. We used green fluorescent protein/interleukin-4 (IL-4) reporter mice and truncated infection studies to identify both the tissue site and mechanism(s) by which the host protects itself from reinfection withN. brasiliensis. Strikingly, we demonstrated that the lung is an important site for priming immune protection. Furthermore, a lung-initiated, CD4 T-cell-dependent, and IL-4- and STAT6-dependent response was sufficient to confer protection against reinfection. In conclusion, vaccination strategies which seek to break the cycle of reinfection and egg production by helminths such as hookworms can include strategies which directly stimulate Th2 responses in the lung.