bluuebunny/crossref_metadata_2025_split huggingface dataset:
Der schweizerische Bundesstaat von 1848 bis 1874: Mehrheits‐ oder Konsensusdemokratie?
Authors: Wirz Rolf 
Published: February 2014

Abstract (deutsch)Der vorliegende Beitrag geht der Frage nach, ob die schweizerische Demokratie bereits ab der Bundesstaatsgründung im Jahr 1848 eine ausgeprägte Konsensusdemokratie war. Zur Beantwortung dieser Fragestellung bedient sich die Studie des Konzepts von Arend Lijphart () mit der Unterscheidung von Mehrheits‐ und Konsensusdemokratie. Anhand von Literatur‐ und Dokumentenanalysen wurden Lijpharts Indikatoren für den schweizerischen Bundesstaat von 1848–1874 codiert. Die Ergebnisse zeigen, dass das politische System der neu gegründeten Schweiz auf Lijpharts Demokratiekarte insbesondere auf der horizontalen Machtteilungsdimension wie erwartet sehr nahe an der Position der USA zu liegen kommt.
Evaluating linkage to care for hypertension after community‐based screening in rural Uganda
Authors: Kotwani Prashant , Balzer Laura , Kwarisiima Dalsone , Clark Tamara D. , Kabami Jane , Byonanebye Dathan , Bainomujuni Bob , Black Douglas , Chamie Gabriel , Jain Vivek , Thirumurthy Harsha , Kamya Moses R. , Geng Elvin H. , Petersen Maya L. , Havlir Diane V. , Charlebois Edwin D. 
Published: February 2014

AbstractObjectivesTo determine the frequency and predictors of hypertension linkage to care after implementation of a linkage intervention in rural Uganda.MethodsDuring a multidisease screening campaign for HIV, diabetes and hypertension in rural Uganda, hypertensive adults received education, appointment to a local health facility and travel voucher. We measured frequency and predictors of linkage to care, defined as visiting any health facility for hypertension management within 6 months. Predictors of linkage to care were calculated using collaborative‐targeted maximum likelihood estimation (C‐TMLE). Participants not linking were interviewed using a standardised instrument to determine barriers to care.ResultsOver 5 days, 2252 adults were screened for hypertension and 214 hypertensive adults received a linkage intervention for further management. Of these, 178 (83%) linked to care within 6 months (median = 22 days). Independent predictors of successful linkage included older age, female gender, higher education, manual employment, tobacco use, alcohol consumption, hypertension family history and referral to local vs. regional health centre. Barriers for patients who did not see care included expensive transport (59%) and feeling well (59%).ConclusionsA community health campaign that offered hypertension screening, education, referral appointment and travel voucher achieved excellent linkage to care (83%). Young adults, men and persons with low levels of formal education were among those least likely to seek care.
Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat
Authors: Pamenter Matthew E. , Carr J. Austin , Go Ariel , Fu Zhenxing , Reid Stephen G. , Powell Frank L. 
Published: February 2014

Key points
Ventilation increases more with chronic than acute hypoxia and does not return to control levels when normoxia is restored, indicating plasticity in the reflexes that control breathing.
Glutamate is the primary excitatory neurotransmitter between arterial chemoreceptors that sense hypoxia and neural circuits that control breathing in the brainstem.
We microinjected specific glutamate receptor antagonists into the brainstem of awake unrestrained rats and found NMDA‐type glutamate receptors explain increased ventilatory sensitivity to hypoxia after chronic hypoxia. AMPA‐type glutamate receptors mediate increased ventilatory drive in normoxia after chronic hypoxia, as well as increased ventilation in acute hypoxia after chronic hypoxia and in control conditions.
Phosphorylation of AMPA and NMDA receptors is increased by chronic hypoxia.
The results indicate that plasticity in different glutamate receptors have unique effects on the reflexes that control breathing in chronic hypoxia and may share cellular mechanisms with other models of neural plasticity.
AbstractWhen exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time‐dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. Currently these mechanisms of HVR plasticity are unknown and we hypothesized that they involve glutamatergic synapses in the nucleus tractus solitarius (NTS), where afferent endings from arterial chemoreceptors terminate. To test this, we treated rats held in normoxia (CON) or 10% O2 (CSH) for 7 days and measured ventilation in conscious, unrestrained animals before and after microinjecting glutamate receptor agonists and antagonists into the NTS. In normoxia, AMPA increased ventilation 25% and 50% in CON and CSH, respectively, while NMDA doubled ventilation in both groups (P < 0.05). Specific AMPA and NMDA receptor antagonists (NBQX and MK801, respectively) abolished these effects. MK801 significantly decreased the HVR in CON rats, and completely blocked the acute HVR in CSH rats but had no effect on ventilation in normoxia. NBQX decreased ventilation whenever it was increased relative to normoxic controls; i.e. acute hypoxia in CON and CSH, and normoxia in CSH. These results support our hypothesis that glutamate receptors in the NTS contribute to plasticity in the HVR with CSH. The mechanism underlying this synaptic plasticity is probably glutamate receptor modification, as in CSH rats the expression of phosphorylated NR1 and GluR1 proteins in the NTS increased 35% and 70%, respectively, relative to that in CON rats.
In Vitro
Activities of Dermaseptins K
4
S
4
and K
4
K
20
S
4
against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa Planktonic Growth and Biofilm Formation
Authors: Zaïri Amira , Ferrières Lionel , Latour-Lambert Patricia , Beloin Christophe , Tangy Frédéric , Ghigo Jean-Marc , Hani Khaled 
Published: February 2014

ABSTRACT

The rising number of infections caused by biofilm formation and the difficulties associated with their treatment by conventional antimicrobial therapies have led to an intensive search for novel antibiofilm agents. Dermaseptins are antimicrobial peptides with a number of attractive properties that might offer alternative therapies against resistant microorganisms. In this study, we synthesized a set of dermaseptin-derived peptides and evaluated their activities against Gram-positive and Gram-negative bacterial biofilm formation. All dermaseptin-derived peptides demonstrated concentration-dependent antibiofilm activities at microgram concentrations, and their activities were dependent on the nature of the peptides, with the highest levels of activity being exhibited by highly charged molecules. Fluorescent binding and confocal microscopy demonstrated that dermaseptin K
4
S
4
, a substituted derivative of the native molecule S
4
, significantly decreased the viability of planktonic and surface-attached bacteria and stopped biofilm formation under dynamic flow conditions. Cytotoxicity assays with HeLa cells showed that some of the tested peptides were less cytotoxic than current antibiotics. Overall, these findings indicate that dermaseptin derivatives might constitute new lead structures for the development of potent antibiofilm agents.
Factors That Cause Trimethoprim Resistance in Streptococcus pyogenes
Authors: Bergmann René , van der Linden Mark , Chhatwal Gursharan S. , Nitsche-Schmitz D. Patric 
Published: February 2014

ABSTRACT

The use of trimethoprim in treatment of
Streptococcus pyogenes
infections has long been discouraged because it has been widely believed that this pathogen is resistant to this antibiotic. To gain more insight into the extent and molecular basis of trimethoprim resistance in
S. pyogenes
, we tested isolates from India and Germany and sought the factors that conferred the resistance. Resistant isolates were identified in tests for trimethoprim or trimethoprim-sulfamethoxazole (SXT) susceptibility. Resistant isolates were screened for the known horizontally transferable trimethoprim-insensitive dihydrofolate reductase (
dfr
) genes
dfrG
,
dfrF
,
dfrA
,
dfrD
, and
dfrK
. The nucleotide sequence of the intrinsic
dfr
gene was determined for resistant isolates lacking the horizontally transferable genes. Based on tentative criteria, 69 out of 268 isolates (25.7%) from India were resistant to trimethoprim. Occurring in 42 of the 69 resistant isolates (60.9%),
dfrF
appeared more frequently than
dfrG
(23 isolates; 33.3%) in India. The
dfrF
gene was also present in a collection of SXT-resistant isolates from Germany, in which it was the only detected trimethoprim resistance factor. The
dfrF
gene caused resistance in 4 out of 5 trimethoprim-resistant isolates from the German collection. An amino acid substitution in the intrinsic dihydrofolate reductase known from trimethoprim-resistant
Streptococcus pneumoniae
conferred resistance to
S. pyogenes
isolates of
emm
type 102.2, which lacked other aforementioned
dfr
genes. Trimethoprim may be more useful in treatment of
S. pyogenes
infections than previously thought. However, the factors described herein may lead to the rapid development and spread of resistance of
S. pyogenes
to this antibiotic agent.
Phenethyl Isothiocyanate Inhibits Shiga Toxin Production in Enterohemorrhagic Escherichia coli by Stringent Response Induction
Authors: Nowicki Dariusz , Maciąg-Dorszyńska Monika , Kobiela Wioletta , Herman-Antosiewicz Anna , Węgrzyn Alicja , Szalewska-Pałasz Agnieszka , Węgrzyn Grzegorz 
Published: February 2014

ABSTRACT

The pathogenicity of enterohemorrhagic
Escherichia coli
(EHEC) depends on production of Shiga toxins, which are encoded by
stx
genes located in the genomes of lambdoid prophages. Efficient expression of these genes requires prophage induction and lytic development of phages. Treatment of EHEC infections is problematic due to not only the resistance of various strains to antibiotics but also the fact that many antibiotics cause prophage induction, thus resulting in high-level expression of
stx
genes. Here we report that
E. coli
growth, Shiga toxin-converting phage development, and production of the toxin by EHEC are strongly inhibited by phenethyl isothiocyanate (PEITC). We demonstrate that PEITC induces the stringent response in
E. coli
that is mediated by massive production of a global regulator, guanosine tetraphosphate (ppGpp). The stringent response induction arises most probably from interactions of PEITC with amino acids and from amino acid deprivation-mediated activation of ppGpp synthesis. In mutants unable to synthesize ppGpp, development of Shiga toxin-converting phages and production of Shiga toxin are significantly enhanced. Therefore, ppGpp, which appears at high levels in bacterial cells after stimulation of its production by PEITC, is a negative regulator of EHEC virulence and at the same time efficiently inhibits bacterial growth. This is in contrast to stimulation of virulence of different bacteria by this nucleotide reported previously by others.
Sustained Delivery of Commensal Bacteria from Pod-Intravaginal Rings
Authors: Gunawardana Manjula , Mullen Madeline , Yoo Jennifer , Webster Paul , Moss John A. , Baum Marc M. 
Published: February 2014

ABSTRACT

Topical administration of live commensal bacteria to the vaginal tract holds significant potential as a cost-effective strategy for the treatment of sexually transmitted infections and the delivery of mucosal vaccines. Probiotic-releasing intravaginal rings (IVRs) embody significant theoretical advantages over traditional daily-dosage forms, such as sustained and controlled delivery leading to improved adherence to therapy compared to that of frequent dosing. The conventional IVR designs, however, are not amenable to the delivery of live bacteria. We have developed a novel pod-IVR technology where polymer-coated tablets (“pods”) of
Lactobacillus gasseri
strain ATCC 33323, a commensal microorganism of human origin, are embedded in silicone IVRs. The release rate of bacterial cells is controlled by the diameter of a delivery channel that exposes a portion of the pod to external fluids.
In vitro
studies demonstrated that the prototype devices released between 1.1 × 10
7
and 14 × 10
7
cells per day for up to 21 days in a controlled sustained fashion with stable burst-free release kinetics. The daily release rates were correlated with the cross-sectional area of the delivery channel. Bacteria in the IVR pods remained viable throughout the
in vitro
studies and formed biofilms on the surfaces of the devices. This proof-of-principle study represents the first demonstration of a prolonged, sustained release of bacteria from an intravaginal device and warrants further investigation of this device as a nonchemotherapeutic agent for the restoration and maintenance of normal urogenital flora.
Mutations within the
rplD
Gene of Linezolid-Nonsusceptible Streptococcus pneumoniae Strains Isolated in the United States
Authors: Dong W. , Chochua S. , McGee L. , Jackson D. , Klugman K. P. , Vidal J. E. 
Published: February 2014

ABSTRACT

Three invasive
Streptococcus pneumoniae
strains nonsusceptible to linezolid were isolated in the United States between 2001 and 2012 from the CDC's Active Bacterial Core surveillance. Linezolid binds ribosomal proteins where structural changes within its target site may confer resistance. Our study identified mutations and deletions near the linezolid binding pocket of two of these strains within the
rplD
gene, which encodes ribosomal protein L4. Mutations in the 23S rRNA alleles or the
rplV
gene were not detected.
Bactericidal Activity of
N
-Chlorotaurine against Biofilm-Forming Bacteria Grown on Metal Disks
Authors: Coraça-Huber Débora C. , Ammann Christoph G. , Fille Manfred , Hausdorfer Johann , Nogler Michael , Nagl Markus 
Published: February 2014

ABSTRACT

Many orthopedic surgeons consider surgical irrigation and debridement with prosthesis retention as a treatment option for postoperative infections. Usually, saline solution with no added antimicrobial agent is used for irrigation. We investigated the activity of
N
-chlorotaurine (NCT) against various biofilm-forming bacteria
in vitro
and thereby gained significant information on its usability as a soluble and well-tolerated active chlorine compound in orthopedic surgery. Biofilms of
Staphylococcus aureus
were grown on metal alloy disks and in polystyrene dishes for 48 h. Subsequently, they were incubated for 15 min to 7 h in buffered solutions containing therapeutically applicable concentrations of NCT (1%, 0.5%, and 0.1%; 5.5 to 55 mM) at 37°C. NCT inactivated the biofilm in a time- and dose-dependent manner. Scanning electron microscopy revealed disturbance of the biofilm architecture by rupture of the extracellular matrix. Assays with reduction of carboxanilide (XTT) showed inhibition of the metabolism of the bacteria in biofilms. Quantitative cultures confirmed killing of
S. aureus
,
Staphylococcus epidermidis
, and
Pseudomonas aeruginosa
biofilms on metal alloy disks by NCT. Clinical isolates were slightly more resistant than ATCC type strains, but counts of CFU were reduced at least 10-fold by 1% NCT within 15 min in all cases. NCT showed microbicidal activity against various bacterial strains in biofilms. Whether this can be transferred to the clinical situation should be the aim of future studies.
PrtR Homeostasis Contributes to Pseudomonas aeruginosa Pathogenesis and Resistance against Ciprofloxacin
Authors: Sun Ziyu , Shi Jing , Liu Chang , Jin Yongxin , Li Kewei , Chen Ronghao , Jin Shouguang , Wu Weihui 
Published: February 2014

ABSTRACT

Pseudomonas aeruginosa
is an opportunistic pathogen that causes acute and chronic infections in humans. Pyocins are bacteriocins produced by
P. aeruginosa
that are usually released through lysis of the producer strains. Expression of pyocin genes is negatively regulated by PrtR, which gets cleaved under SOS response, leading to upregulation of pyocin synthetic genes. Previously, we demonstrated that PrtR is required for the expression of type III secretion system (T3SS), which is an important virulence component of
P. aeruginosa
. In this study, we demonstrate that mutation in
prtR
results in reduced bacterial colonization in a mouse acute pneumonia model. Examination of bacterial and host cells in the bronchoalveolar lavage fluids from infected mice revealed that expression of PrtR is induced by reactive oxygen species (ROS) released by neutrophils. We further demonstrate that treatment with hydrogen peroxide or ciprofloxacin, known to induce the SOS response and pyocin production, resulted in an elevated PrtR mRNA level. Overexpression of PrtR by a
tac
promoter repressed the endogenous
prtR
promoter activity, and electrophoretic mobility shift assay revealed that PrtR binds to its own promoter, suggesting an autorepressive mechanism of regulation. A high level of PrtR expressed from a plasmid resulted in increased T3SS gene expression during infection and higher resistance against ciprofloxacin. Overall, our results suggest that the autorepression of PrtR contributes to the maintenance of a relatively stable level of PrtR, which is permissive to T3SS gene expression in the presence of ROS while increasing bacterial tolerance to stresses, such as ciprofloxacin, by limiting pyocin production.
Type I Interferons Promote Severe Disease in a Mouse Model of Lethal Ehrlichiosis
Authors: Zhang Yubin , Thai Vinh , McCabe Amanda , Jones Maura , MacNamara Katherine C. 
Published: February 2014

ABSTRACT

Human monocytic ehrlichiosis (HME) is caused by a tick-borne obligate intracellular pathogen of the order
Rickettsiales
. HME disease can range from mild to a fatal, toxic shock-like syndrome, yet the mechanisms regulating pathogenesis are not well understood. We define a central role for type I interferons (alpha interferon [IFN-α] and IFN-β) in severe disease in a mouse model of fatal ehrlichiosis caused by
Ixodes ovatus
Ehrlichia
(IOE). IFN-α and IFN-β were induced by IOE infection but not in response to a less virulent strain,
Ehrlichia muris
. The major sources of type I IFNs during IOE infection were plasmacytoid dendritic cells and monocytes. Mice lacking the receptor for type I IFNs (
Ifnar
deficient) or neutralization of IFN-α and IFN-β resulted in a reduced bacterial burden.
Ifnar
-deficient mice exhibited significantly increased survival after IOE infection, relative to that of wild-type (WT) mice, that correlated with increased type II IFN (IFN-γ) production. Pathogen-specific antibody responses were also elevated in
Ifnar
-deficient mice, and this required IFN-γ. Remarkably, increased IFN-γ and IgM were not essential for protection in the absence of type I IFN signaling. The direct effect of type I IFNs on hematopoietic and nonhematopoietic cells was evaluated in bone marrow chimeric mice. We observed that chimeric mice containing
Ifnar
-deficient hematopoietic cells succumbed to infection early, whereas
Ifnar
-deficient mice containing WT hematopoietic cells exhibited increased survival, despite having a higher bacterial burden. These data demonstrate that IFN-α receptor signaling in nonhematopoietic cells is important for pathogenesis. Thus, type I IFNs are induced during a rickettsial infection
in vivo
and promote severe disease.
At return to play following hamstring injury the majority of professional football players have residual isokinetic deficits
Authors: Tol Johannes L , Hamilton Bruce , Eirale Cristiano , Muxart Patrice , Jacobsen Philipp , Whiteley Rod 
Published: February 2014

BackgroundThere is an ongoing debate regarding the optimal criteria for return to sport after an acute hamstring injury. Less than 10% isokinetic strength deficit is generally recommended but this has never been documented in professional football players after rehabilitation. Our aim was to evaluate isokinetic measurements in MRI-positive hamstring injuries.MethodsIsokinetic measurements of professional football players were obtained after completing a standardised rehabilitation programme. An isokinetic strength deficit of more than 10% compared with the contralateral site was considered abnormal. Reinjuries within 2 months were recorded.Results52 players had a complete set of isokinetic testing before clinical discharge. There were 27 (52%) grade 1 and 25 (48%) grade 2 injuries. 35 of 52 players (67%) had at least one of the three hamstring-related isokinetic parameters that display a deficit of more than 10%. The percentage of players with 10% deficit for hamstring concentric 60°/s, 300°/s and hamstring eccentric was respectively 39%, 29% and 28%. There was no significant difference of mean isokinetic peak torques and 10% isokinetic deficits in players without reinjury (N=46) compared with players with reinjury (N=6).ConclusionsWhen compared with the uninjured leg, 67% of the clinically recovered hamstring injuries showed at least one hamstring isokinetic testing deficit of more than 10%. Normalisation of isokinetic strength seems not to be a necessary result of the successful completion of a football-specific rehabilitation programme. The possible association between isokinetic strength deficit and increased reinjury risk remains unknown.
Treatment of ruptured blood blister-like aneurysms with flow diverter SILK stents
Authors: Aydin Kubilay , Arat Anil , Sencer Serra , Hakyemez Bahattin , Barburoglu Mehmet , Sencer Altay , İzgi Nail 
Published: February 2014

IntroductionBlood blister-like aneurysms (BBAs) are fragile and difficult to treat. Routine surgical and endovascular treatment methods, such as clipping, clip wrapping, primary coiling, or stent assisted coiling, have relatively high morbidity and mortality rates. In this study, we report clinical and angiographic results for treatment of ruptured BBAs using flow diverter stents.MethodsWe retrospectively reviewed patients who presented with subarachnoid hemorrhages caused by rupture of BBAs and who were treated using flow diverter stents at three neurointervention centers between January 2009 and January 2013. Clinical and angiographic findings, together with the procedural data and follow-up results, are reported.Results11 patients were identified in this study. BBAs were located on the supraclinoid internal carotid artery (nine patients) and basilar arteries (two patients). Eight patients were treated by implantation of a single flow diverter stent. Two flow diverter stents were telescopically deployed in each of three patients. The procedures were successful in all cases. No acute complications developed in any case. One patient who had an initial Hess–Hunt grade 4 died of septicemia 2 weeks after the procedure (9%). Another patient developed a minor stroke caused by parent artery thrombosis (9%). Control angiographies performed 3 and 6 months post stenting revealed complete occlusion of the aneurysms in all of the remaining nine patients (82%). 10 of the 11 patients (92%) had good clinical outcomes (modified Rankin Scale score ≤2).ConclusionsImplantation of flow diverter stents seems to be a safe and feasible alternative for treatment of ruptured BBAs.