bluuebunny/crossref_metadata_2025 huggingface dataset:
Diet, gut microbiome and indoxyl sulphate in chronic kidney disease patients
Authors: Yang Chih‐Yu , Tarng Der‐Cherng
Published: October 2018

Emerging evidence suggests that intestinal dysbiosis plays an important role in host inflammation locally and systemically. Such pathological condition is even more prevailing in patients with chronic kidney disease (CKD). Of note, indoxyl sulphate (IS), a gut‐derived uremic toxin, is notorious for its pro‐inflammatory feature in CKD patients. IS accumulates in the body as the urinary excretion of uremic toxins is impaired, and further worsens the kidney function in a vicious cycle to CKD. Dietary restriction in vegetables, fruits and yogurt leads to the predominance of indole‐producing intestinal microbial flora and further exaggerates the accumulation of IS in CKD patients. Recently, interventional studies have shown that circulating IS can be reduced by dietary prebiotic and/or probiotic supplements. However, further randomized controlled trials are warranted to examine whether such beneficial effect of dietary prebiotic/probiotic supplements could be extrapolated to better hard outcomes in CKD population. In this review, we would also like to emphasize the importance of achieving sufficient intake of dietary fibre by proper vegetable pre‐treatment and accurate fruit selection, instead of directly avoiding these potassium‐rich yet fibre‐rich and base‐producing foods.
Role of renin‐angiotensin system in acute kidney injury‐chronic kidney disease transition
Authors: Chou Yu‐Hsiang , Chu Tzong‐Shinn , Lin Shuei‐Liong
Published: October 2018

Acute kidney injury (AKI) can increase the risk of developing incident chronic kidney disease (CKD). The severity, frequency and duration of AKI are crucial predictors of poor renal outcome. A repair process after AKI can be adaptive and kidney recovers completely after a mild injury. However, severe injury will lead to a maladaptive repair, which frequently progresses to nephron loss, vascular rarefaction, chronic inflammation and fibrosis. Although different mechanisms underlying AKI‐CKD transition have been extensively discussed, no definite intervention has been proved effective to block or to retard the transition until recently. In CKD, renin‐angiotensin system (RAS) inhibitor has been proved effective to slow down disease progression. Furthermore, RAS needs to be highlighted again in AKI‐CKD transition because recent animal studies have shown the activation of intra‐renal RAS after AKI, and RAS blockade can reduce the ensuing CKD and mortality. In patients with the complete renal recovery after AKI, administration of RAS inhibitor is associated with reduced risk of subsequent CKD as well. In this article, we will demonstrate the role of RAS in AKI‐CKD transition comprehensively. We will then emphasize the promising effect of RAS inhibitor on CKD prevention in patients recovering from AKI based on evidence from the bench to clinical research. All of these discussions will contribute to the establishment of reliable monitoring and therapeutic strategies for patients with functional recovery from AKI who can be most easily ignored.
Characterization and development of SAPP as a specific peptidic inhibitor that targets Porphyromonas gingivalis
Authors: Ho Meng‐Hsuan , Lamont Richard J. , Chazin Walter J. , Chen Huiqing , Young Daphne F. , Kumar Prashant , Xie Hua
Published: October 2018

Porphyromonas gingivalis is a keystone bacterium in the oral microbial communities that elicits a dysbiosis between the microbiota and the host. Therefore, inhibition of this organism in dental plaques has been one of the strategies for preventing and treating chronic periodontitis. We previously identified a Streptococcal ArcA derived Anti‐P gingivalils Peptide (SAPP) that in vitro, is capable of repressing the expression of several virulence genes in the organism. This leads to a significant reduction in P gingivalis virulence potential, including its ability to colonize on the surface of Streptococcus gordonii, to invade human oral epithelial cells, and to produce gingipains. In this study, we showed that SAPP had minimal cytotoxicity to human oral keratinocytes and gingival fibroblasts. We observed that SAPP directly bound to the cell surface of P gingivalis, and that alterations in the sequence at the N‐terminus of SAPP diminished its abilities to interact with P gingivalis cells and repressed the expression of virulence genes. Most strikingly, we demonstrated using an ex‐vivo assay that besides its inhibitory activity against P gingivalis colonization, SAPP could also reduce the levels of several other oral Gram‐negative bacteria strongly associated with periodontitis in multispecies biofilms. Our results provide a platform for the development of SAPP‐targeted therapeutics against chronic periodontitis.
“Mississippi Phenomenon”: Reinterpreting the 1970 Jackson State Shootings in the Era of Black Lives Matter
Authors: Chura Patrick
Published: October 2018

The Kent State and Jackson State shootings of May 1970 were not directly related, yet the two atrocities have become “indelibly linked” in popular memory. This article draws from recent oral histories and ethnographic observations of commemorative events to shift the analytical frame toward attention to essential differences in the shooting contexts, arguing that Jackson State was not “the South's Kent State” but a “Mississippi phenomenon” best understood as a portent of ideologies at the core of the current Black Lives Matter movement.

The long overdue attention now being given antiblack police brutality offers a vocabulary for reinterpreting Jackson State, enabling new conclusions. First, Kent State did not cause Jackson state, but the killings in Ohio did prompt a false equating of events in Kent and Jackson as similar antiwar protests. Second, this process of collective remembering, furthered by some discourses emanating from Kent State University, obfuscates intrinsic truths about race in America. Finally, conversation surrounding Black Lives Matter offers the chance to reassess the tragedies and remember them in ways that bring clarity to political and cultural structures of the present day.
Modeling Undetected Live Poliovirus Circulation After Apparent Interruption of Transmission: Pakistan and Afghanistan
Authors: Kalkowska Dominika A. , Duintjer Tebbens Radboud J. , Pallansch Mark A. , Thompson Kimberly M.
Published: October 2018

Since most poliovirus infections occur with no paralytic symptoms, the possibility of silent circulation complicates the confirmation of the end of poliovirus transmission. Based on empirical field experience and theoretical modeling results, the Global Polio Eradication Initiative identified three years without observing paralytic cases from wild polioviruses with good acute flaccid paralysis surveillance as an indication of sufficient confidence that poliovirus circulation stopped. The complexities of real populations and the imperfect nature of real surveillance systems subsequently demonstrated the importance of specific modeling for areas at high risk of undetected circulation, resulting in varying periods of time required to obtain the same level of confidence about no undetected circulation. Using a poliovirus transmission model that accounts for variability in transmissibility and neurovirulence for different poliovirus serotypes and characterizes country‐specific factors (e.g., vaccination and surveillance activities, demographics) related to wild and vaccine‐derived poliovirus transmission in Pakistan and Afghanistan, we consider the probability of undetected poliovirus circulation for those countries once apparent die‐out occurs (i.e., in the absence of any epidemiological signals). We find that gaps in poliovirus surveillance or reaching elimination with borderline sufficient population immunity could significantly increase the time to reach high confidence about interruption of live poliovirus transmission, such that the path taken to achieve and maintain poliovirus elimination matters. Pakistan and Afghanistan will need to sustain high‐quality surveillance for polioviruses after apparent interruption of transmission and recognize that as efforts to identify cases or circulating live polioviruses decrease, the risks of undetected circulation increase and significantly delay the global polio endgame.
Online peer consulting for health professionals
Authors: Bientzle Martina , Lechner Christine , Cress Ulrike , Kimmerle Joachim
Published: October 2018

Background

Many health care professionals specialise in particular medical fields. Nevertheless, they often encounter patients with other indications for which they have only limited experience. In such situations it is helpful to consult colleagues who have specialised in the respective areas. The Internet provides the opportunity to connect with other specialists that can be used for peer consulting. We argue that health professionals should learn to make use of online peer consulting during vocational training.

Methods

We used an open‐source platform that provided the opportunity to chat and upload documents. We recruited 45 first‐year physiotherapy students as participants. The training for online peer consulting was integrated into courses where students were taught basic principles of gait analysis and learned how to document the findings of their examinations. Subsequently, the students evaluated the course and the online collaboration.

Findings

Students were highly motivated to use the online platform and perceived the online peer consulting and the atmosphere of collaboration on the platform to be very positive. In addition, students had a significant increase in content knowledge and were more confident in their own knowledge than they were before the online peer consulting.

Discussion

It seems appropriate to provide training for giving and gathering online peer feedback. This opportunity, provided at an early stage of training, could help prepare students for continuing co‐operative exchange in their professional lives.

Health care professionals should learn how to gather information from colleagues and how to provide adequate feedback
Calculated democracy—Explorations in gerrymandering
Authors: McCune David , Tunstall Samuel Luke
Published: October 2018

This paper describes a lesson centered around a metric for measuring partisan gerrymandering: the efficiency gap. We situate the efficiency gap in the current US political climate, describe the activity itself, and then provide recommendations for readers interested in adapting the lesson for their own classrooms.
Rescaling low‐carbon transformations: Towards a relational ontology
Authors: Bouzarovski Stefan , Haarstad Håvard
Published: October 2018

Scale is an emergent theme in current scientific and policy debates on low‐carbon urban transformations. Yet notions of scale employed in such contexts are typically based on linear and hierarchical ontologies, and miss out on the long‐standing development of more nuanced conceptions of scale within Human Geography. This paper aims to advance a relational understanding of scale in the analysis and evaluation of low‐carbon urban initiatives (LCUIs). We wish to lay the path towards an innately geographical conceptualisation of low‐carbon urban transformations more generally, in which cities are not seen as rigid and passive physical containers for decarbonisation initiatives, but rather as key nodes within vibrant socio‐technical networks operating across multiple material sites. Using a case study of the transnational and translocal REACH (Reduce Energy use And Change Habits) project funded by the European Union as illustration, we argue that low‐carbon urban transformations are immanently constituted of three sets of relational processes across scale, involving (1) politicisation, (2) enrolment and (3) the hybridisation of human and material agencies.
ACVECC‐Veterinary Committee on Trauma Registry Report 2013–2017
Authors: Hall Kelly E. , Boller Manuel , Hoffberg Jayme , McMichael Maureen , Raffe Marc R. , Sharp Claire R. ,   on behalf of ACVECC's Veterinary Committee on Trauma (VetCOT) Registry Subcommittee
Published: October 2018

Objective

To report summative data from the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma (VetCOT) registry.

Design

Multi‐institutional veterinary trauma registry data report.

Setting

VetCOT identified veterinary trauma centers (VTCs).

Animals

Dogs and cats with evidence of trauma presented to VTCs with data entered in the VetCOT registry September 1, 2013–March 31, 2017.

Interventions

VetCOT created a standardized data collection methodology for dog and cat trauma. Data were input to a web‐based data capture system (REDCap) by data entry personnel trained in data software use and operational definitions of data variables. Data on demographics, trauma type (blunt vs penetrating), preadmission care, hospitalization and intensive care requirement, trauma severity assessment at presentation (eg, modified Glasgow coma scale and animal trauma triage score), key laboratory parameters, necessity for surgical intervention, and case outcome were collected. Summary descriptive data for each species are reported.

Measurements and Main Results

Twenty‐nine VTCs in North America, Europe, and Australia contributed information from 17,335 dog and 3,425 cat trauma cases during the 42‐month reporting period. A large majority of cases presented directly to the VTC after injury (80.4% dogs and 78.1% cats). Blunt trauma was the most common source for injury in cats (56.7%); penetrating trauma was the most common source for injury in dogs (52.3%). Note that 43.8% of dogs and 36.2% of cats were reported to have surgery performed. The proportion surviving to discharge was 92.0% (dogs) and 82.5% (cats).

Conclusions

The VetCOT registry proved to be a powerful resource for collection of a large dataset on trauma in dogs and cats seen at VTCs. While overall survival to discharge was quite high, further evaluation of data on subsets of injury types, patient assessment parameters, interventions, and associated outcome are warranted.
Intercultural (mis)communication in teacher‐student interaction
Authors: Anderson Fred E.
Published: October 2018

This article explores communication and miscommunication in Japanese university settings, in English‐medium classroom situations where the students are Japanese and the instructor is a ‘native’, generally Inner Circle, speaker of English. The focus of the analysis is on two aspects of classroom style that are affected by teacher's and students’ divergent norms of interaction and interpretation: (1) turn‐taking behavior, especially student non‐responsiveness represented by an abundance of silence; and (2) forms of address, particularly the names, with or without a title, that students use in calling their teachers. The article is influenced by, and seen as an extension of, Larry E. Smith's work on English for cross‐cultural communication and discourse across cultures.
Accent, intelligibility, mental health, and trauma
Authors: Bhatia Tej K.
Published: October 2018

The aim of this article is fourfold: (1) to define the notion of ‘accent’ from two linguistic and socio‐psychological perspectives; (2) to examine the multi‐faceted dimensions of accent in terms of the (bio‐)linguistic mind and the social mind; (3) to throw a spotlight on the convergence of mental health and accent trauma by presenting a forensic case study of mass murder and suicide committed by an Asian‐American, Jiverly Wong, who was traumatized by social exclusion and bullying, possibly due to his limited English proficiency in the form of non‐native speech traits exhibited in his accent; and (4) to present evidence from neurolinguistic (f‐MRI) studies of social pain caused by social exclusion. The discussion here is framed particularly in the context of intelligibility and interpretability of speech in cross‐cultural communication through world Englishes and the wide‐ranging negative reactions to people who speak English with a foreign accent.
Extracellular Hsp70 modulates the inflammatory response of cigarette smoke extract in NCI‐H292 cells
Authors: Hulina‐Tomašković Andrea , Rajković Marija Grdić , Somborac‐Bačura Anita , Čeri Andrea , Dabelić Sanja , Rumora Lada
Published: October 2018

New Findings

What is the central question of this study?

Does extracellular heat shock protein 70 (eHsp70) alter cigarette smoke extract (CSE)‐induced inflammatory responses in NCI‐H292 bronchial epithelial cells?

What is the main finding and its importance?

eHsp70 modulates inflammatory responses and TLR2, TLR4 and Hsp70 gene expression, and protects NCI‐H292 cells against CSE‐induced cytotoxicity. eHsp70 might be implicated in development of inflammatory diseases affected by cigarette smoke, such as COPD.

One of the major risk factors for development of chronic obstructive pulmonary disease (COPD) is cigarette smoke. Extracellular Hsp70 (eHsp70) is increased in sera of COPD patients, and can act as damage‐associated molecular pattern (DAMP). In this study, we explored inflammatory parameters (cytokine concentrations, Toll‐like receptor (TLR) 2 and 4 and Hsp70 expression, mitogen‐activated protein kinases (MAPKs) and nuclear factor κB (NF‐κB) activation, and cytotoxicity) after exposure of bronchial‐epithelial NCI‐H292 cells to cigarette smoke extract (CSE) alone (2.5 and 15%) and in combinations with recombinant human (rh) Hsp70 (0.3, 1 and 3 μg ml−1). We applied specific MAPKs, NF‐κB and Hsp70 inhibitors to elucidate rhHsp70 inflammation‐associated responses. CSE alone and combinations of 15% CSE with rhHsp70 stimulated IL‐1α, IL‐6 and IL‐8 release. However, rhHsp70 applied with 2.5% CSE decreased secretion of cytokines indicating antagonistic effects. Individual and combined treatments with 2.5% CSE suppressed TLR2 expression. CSE at 15% induced TLR2 and TLR4 gene expression, whereas rhHsp70 abolished that effect. rhHsp70 and 15% CSE alone reduced, while their combination increased, intracellular Hsp70 mRNA level. CSE alone and in combination with rhHsp70 activated extracellular signal‐regulated kinase and p38 MAPKs, while inhibition of MAPKs, NF‐κB and Hsp70 attenuated IL‐6 and IL‐8 secretion. CSE at 15% reduced cell viability and induced apoptosis, as shown by MTS and caspases‐3/7 assays. CSE at 2.5% alone stimulated lactate dehydrogenase release, but cellular membrane integrity remained intact in co‐treatments with rhHsp70. rhHsp70 might modulate the inflammatory response of CSE and could also protect NCI‐H292 cells against CSE cytotoxicity. Those effects are implemented via MAPK and NF‐κB signalling pathways.
Sports Foods and Dietary Supplements for Optimal Function and Performance Enhancement in Track-and-Field Athletes
Authors: Peeling Peter , Castell Linda M. , Derave Wim , de Hon Olivier , Burke Louise M.
Published: October 2018

Athletes are exposed to numerous nutritional products, attractively marketed with claims of optimizing health, function, and performance. However, there is limited evidence to support many of these claims, and the efficacy and safety of many products is questionable. The variety of nutritional aids considered for use by track-and-field athletes includes sports foods, performance supplements, and therapeutic nutritional aids. Support for sports foods and five evidence-based performance supplements (caffeine, creatine, nitrate/beetroot juice, β-alanine, and bicarbonate) varies according to the event, the specific scenario of use, and the individual athlete’s goals and responsiveness. Specific challenges include developing protocols to manage repeated use of performance supplements in multievent or heat-final competitions or the interaction between several products which are used concurrently. Potential disadvantages of supplement use include expense, false expectancy, and the risk of ingesting banned substances sometimes present as contaminants. However, a pragmatic approach to the decision-making process for supplement use is recommended. The authors conclude that it is pertinent for sports foods and nutritional supplements to be considered only where a strong evidence base supports their use as safe, legal, and effective and that such supplements are trialed thoroughly by the individual before committing to use in a competition setting.
Differences in Sprint Mechanical Force–Velocity Profile Between Trained Soccer and Futsal Players
Authors: Jiménez-Reyes Pedro , García-Ramos Amador , Cuadrado-Peñafiel Victor , Párraga-Montilla Juan A. , Morcillo-Losa José A. , Samozino Pierre , Morin Jean-Benoît
Published: October 2018

Purpose: To compare the sprint mechanical force–velocity (F–V) profile between soccer and futsal players. A secondary aim was, within each sport, to study the differences in sprint mechanical F–V profile between sexes and players of different levels. Methods: A total of 102 soccer players (63 men) and 77 futsal players (49 men) who were competing from the elite to amateur levels in the Spanish league participated in this investigation. The testing procedure consisted of 3 unloaded maximal 40-m sprints. The velocity–time data recorded by a radar device were used to calculate the variables of the sprint acceleration F–V profile (maximal theoretical force [F0], maximal theoretical velocity [V0], maximal power [Pmax], decrease in the ratio of horizontal to resultant force [DRF], and maximal ratio of horizontal to resultant force [RFpeak]). Results: Futsal players showed a higher F0 than soccer players (effect size [ES] range: 0.11–0.74), while V0 (ES range: −0.48 to −1.15) and DRF (ES range: −0.75 to −1.45) was higher for soccer players. No significant differences were observed between soccer and futsal players for Pmax (ES range: −0.43 to 0.19) and RFpeak (ES range: −0.49 to 0.30). Men and high-level players presented an overall enhanced F–V profile compared with women and their lower-level counterparts, respectively. Conclusions: The higher F0 and lower V0 of futsal players could be caused by the game’s specific demands (larger number of accelerations but over shorter distances than in soccer). These results show that the sprint mechanical F–V profile is able to distinguish between soccer and futsal players.
Heart-Rate Variability in Elite Synchronized Swimmers
Authors: Solana-Tramunt Mònica , Morales Jose , Buscà Bernat , Carbonell Marina , Rodríguez-Zamora Lara
Published: October 2018

Purpose: To determine whether heart-rate variability (HRV) was correlated with other training-load and training-tolerance markers for monitoring the effect of a training session on elite synchronized swimmers. Methods: The authors recorded the resting HRV of 12 elite swimmers (mean age = 21.5 [3.5] y) 3 times over 1 wk with a cadence of 48 h prior to the 2015 World Swimming Championships. They continuously monitored heart rate and obtained salivary cortisol (SC) samples before and after the last training session of the week. The authors measured capillary blood lactate (La) 2, 4, and 8 min after the last training session and monitored recovery HRV. They assessed rating of perceived exertion (RPE) over the entire session and tested the association between the highest La concentration (Lapeak), SC, and RPE and relative changes (Δ%) in the natural logarithm of the root-mean-square successive difference of intervals (LnRMSSD). The authors also calculated the smallest worthwhile change of the averaged pre and post LnRMSSD measurements. Results: There were periods of pronounced bradycardia (60.5 [16.7] beats/min) during training exercises corresponding to apneic exercise. The magnitude-based inferences showed nonclinically meaningful changes of LnRMSSD. Lapeak (6.8 [2.7] mmol/L) correlated positively with Δ%LnRMSSD and Δ%SC (r = .89, P = .001 and r = .61, P = .04, respectively). Conclusions: There was no change in LnRMSSD and Lapeak, Δ%SC, and RPE indicated reduced sympathetic activation and positive adaptation to the stress imposed by the session. Isolated HRV assessment may reveal a controversial interpretation of autonomic nervous system status or the training tolerance in elite synchronized swimming athletes due to the influence of the diving response.
Blood Flow Restriction Therapy Versus Standard Care for Reducing Quadriceps Atrophy After Anterior Cruciate Ligament Reconstruction
Authors: Lipker Lauren Anne , Persinger Caitlyn Rae , Michalko Bradley Steven , Durall Christopher J.
Published: October 2018

Clinical Scenario: Quadriceps atrophy and weakness are common after anterior cruciate ligament reconstruction (ACLR). Blood flow restriction (BFR) therapy, alone or in combination with exercise, has shown some promise in promoting muscular hypertrophy. This review was conducted to ascertain the extent to which current evidence supports the use of BFR for reducing quadriceps atrophy following ACLR in comparison with standard care. Clinical Question: Is BFR more effective than standard care for reducing quadriceps atrophy after ACLR? Summary of Key Findings: The literature was searched for studies that directly compared BFR treatment to standard care in patients with ACLR. Three level I randomized control trial studies retrieved from the literature search met the inclusion criteria. Clinical Bottom Line: Reviewed data suggest that a short duration (13 d) of moderate-pressure BFR combined with low-resistance muscular training does not appear to measurably affect quadriceps cross-sectional area. However, a relatively long duration (15 wk) of moderate-pressure BFR combined with low-resistance muscular training may increase quadriceps cross-sectional area to a greater extent than low-resistance muscular training alone. The results of the third randomized control trial suggest that employing BFR while immobilized in the early postoperative period may reduce quadriceps atrophy following ACLR. Additional data are needed to establish if the benefits of BFR on quadriceps atrophy after ACLR outweigh the inherent risks and costs. Strength of Recommendation: All evidence for this review was level 1 (randomized control trial) based on the Centre for Evidence-Based Medicine criteria. However, the findings were inconsistent across the 3 studies regarding the effects of BFR on quadriceps atrophy resulting in a grade “B” strength of recommendation.
The Effect of Body Checking Policy Changes on Concussion Incidence in Canadian Male Youth Ice Hockey Players: A Critically Appraised Topic
Authors: Ingram Brittany M. , Kay Melissa C. , Vander Vegt Christina B. , Register-Mihalik Johna K.
Published: October 2018

Clinical Scenario:Current studies have identified body checking as the most common cause of sports-related concussion in ice hockey across all divisions and levels. As a result, many hockey organizations, particularly in youth sports, have implemented rules making body checking to the head, face, and/or neck illegal. Such a rule, in Canada, makes age 13 the first age in which individuals can engage in body checking. Despite these changes, effectiveness of their implementation on the incidence of concussion in Canadian male youth ice hockey players remains unclear.Clinical Question:What is the effect of body checking policy changes on concussion incidence in male youth ice hockey players?Summary of Key Findings:Of the 3 included studies, 2 studies reported a decrease in the incidence of concussion once a body checking policy change was implemented. The third study showed an increase; however, it is important to note that this may be due, in part, to increased awareness leading to better reporting of injuries.Clinical Bottom Line:Current evidence supports a relationship between body checking policy implementation and decreased concussion incidence; however, more research is needed to understand the long-term implications of policy change and the effects in other leagues. In addition, further data are needed to differentiate between increased concussion incidence resulting from concussion education efforts that may improve disclosure and increased concussion incidence as a direct result of policy changes.Strength of Recommendation:Grade B evidence exists that policy changes regarding body checking decrease concussion incidence in male youth ice hockey players.
Static Stretching Intensity Does Not Influence Acute Range of Motion, Passive Torque, and Muscle Architecture
Authors: Santos Camila Ximenes , Beltrão Natália Barros , Pirauá André Luiz Torres , Durigan João Luiz Quagliotti , Behm David , de Araújo Rodrigo Cappato
Published: October 2018

Context: Although stretching exercises are commonly used in clinical and athletic practice, there is a lack of evidence regarding the methodological variables that guide the prescription of stretching programs, such as intensity. Objective: To investigate the acute effects of different stretching intensities on the range of motion (ROM), passive torque, and muscle architecture. Design: Two-group pretest–posttest design. Setting: Laboratory. Participants: Twenty untrained men were allocated into the low- or high-intensity group. Main Outcome Measures: Subjects were evaluated for initial (ROMinitial) and maximum (ROMmax) discomfort angle, stiffness, viscoelastic stress relaxation, muscle fascicle length, and pennation angle. Results: The ROM assessments showed significant changes, in both groups, in the preintervention and postintervention measures both for the ROMinitial (P < .01) and ROMmax angle (P = .02). There were no significant differences for stiffness and viscoelastic stress relaxation variables. The pennation angle and muscle fascicle length were different between the groups, but there was no significant interaction. Conclusion: Performing stretching exercises at high or low intensity acutely promotes similar gains in flexibility, that is, there are short-term/immediate gains in ROM but does not modify passive torque and muscle architecture.
Arid5a makes the IL-17A/F–responsive pathway less arid
Authors: Puel Anne , Casanova Jean-Laurent
Published: October 2018

The RNA binding protein Arid5a augments the response to IL-17 cytokine stimulation (Amatya
et al
., in 9 October 2018 issue).
Promoting cytokine production
Authors: Foley John F.
Published: October 2018

The helicase DHX9 is required for production of the cytokine IL-6 in response to Toll-like receptor stimulation.
TEM-28 from an Escherichia coli clinical isolate is a member of the His-164 family of TEM-1 extended-spectrum beta-lactamases
Authors: Bradford P A , Jacobus N V , Bhachech N , Bush K
Published: October 2018

TEM-28 (pI 6.1), expressed by an Escherichia coli clinical isolate, is a novel beta-lactamase which hydrolyzed ceftazidime, cefotaxime, and aztreonam with rates of 25, 1.1, and 5.6, respectively, relative to that for benzylpenicillin (100). The nucleotide sequence of blaTEM-28 differed from that of blaTEM-1 by two base changes, resulting in amino acid substitutions of Arg-164 to His and Glu-240 to Lys.
Efficacy of vancomycin and teicoplanin alone and in combination with streptomycin in experimental, low-level vancomycin-resistant, VanB-type Enterococcus faecalis endocarditis
Authors: Nicolau D P , Marangos M N , Nightingale C H , Patel K B , Cooper B W , Quintiliani R , Courvalin P , Quintiliani R
Published: October 2018

The efficacy of vancomycin (VM) and teicoplanin (TE), alone and in combination with streptomycin (SM), against enterococci that express low-level VanB-type VM resistance was investigated in experimental endocarditis using isogenic strains of Enterococcus faecalis susceptible to glycopeptides and aminoglycosides or inducibly resistant to low levels of VM (MIC = 16 micrograms/ml). VM was significantly less active against the resistant strain than against the susceptible strain, establishing that low-level VanB-type VM resistance can influence therapeutic efficacy. By contrast, TE had equally good activity against both strains. VM or TE combined with SM was synergistic and bactericidal against the resistant strain in vitro. While both combinations were efficient in reducing bacterial density in vivo, TE plus SM was significantly superior to VM plus SM if valve sterilization was considered. These data suggest that despite the presence of low-level VanB-type resistance, combination therapy with a glycopeptide and SM (and presumably other aminoglycosides to which there is not high-level resistance) will nevertheless provide effective bactericidal activity.
Synergistic effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein and cefamandole in treatment of rabbit gram-negative sepsis
Authors: Lin Y , Leach W J , Ammons W S
Published: October 2018

As a consequence of their bactericidal actions, many antibiotics cause the release of endotoxin, a primary mediator of gram-negative sepsis. Bactericidal/permeability-increasing protein (BPI) has bactericidal activity and neutralizes endotoxin in vitro and in vivo. We sought to examine the effect of a recombinant N-terminal fragment of BPI (rBPI21) in conjunction with cefamandole, a cephalosporin antibiotic, in the treatment of Escherichia coli bacteremia and septic shock in rabbits. Cefamandole (100 mg/kg of body weight) was injected intravenously. This was followed by simultaneous 10-min infusions of E. coli O7:K1 (9 x 10(9) CFU/kg) and rBPI21 (10 mg/kg). rBPI21 was continuously infused for an additional 110 min at 10 mg/kg/h. The administration of rBPI21 in conjunction with the administration of cefamandole prevented the cefamandole-induced increase of free endotoxin in plasma, accelerated bacterial clearance, ameliorated cardiopulmonary dysfunction, and thereby, prevented death, whereas neither agent alone was protective in this animal model. The efficacy of the combined treatment with rBPI21 and cefamandole suggests a synergistic interaction between the two agents. The data indicate that rBPI21 may be useful in conjunction with traditional antibiotic therapy.
Pharmacokinetics and safety of multiple-dose valaciclovir in geriatric volunteers with and without concomitant diuretic therapy
Authors: Wang L H , Schultz M , Weller S , Smiley M L , Blum M R
Published: October 2018

A randomized, double-blind study was conducted to evaluate the safety and pharmacokinetics of acyclovir following multiple-dose oral administration of valaciclovir (three times a day for 8 days) in geriatric volunteers (65 to 83 years of age). Pharmacokinetic evaluation was performed for three groups: normotensive subjects given 500-mg doses of valaciclovir (n = 11), normotensive subjects given, 1,000-mg doses of valaciclovir (n = 9), and thiazide diuretic-treated hypertensive subjects given 500-mg doses of valaciclovir (n = 9). Valaciclovir, the l-valyl ester of acylclovir, was rapidly absorbed and converted to acyclovir, with plasma valaciclovir concentrations generally undetectable or < or = 0.4 microgram/ml. The peak concentration of drug in plasma (Cmax) for acyclovir occurred at 1 to 2 h, and the half-life of acyclovir was 3 to 4 h in all three elderly groups. The Cmax and area under the concentration-time curve from 0 h to infinity (AUC0-infinity) values of acyclovir obtained on days 1 and 8 indicated no unexpected accumulation at steady state. The steady-state acyclovir Cmax (4.30 and 5.98 micrograms/ml) and daily AUC0-infinity (44 and 74 h.micrograms/ml) following dosing of valaciclovir (500 and 1,000 mg) three times a day were two to three times greater than those expected after high-dose oral acyclovir treatment (800 mg, five times daily). There were no valaciclovir-related changes or abnormalities in safety parameters and no reports of serious adverse experiences in these elderly volunteers. The plasma acyclovir concentration-time curves for the hypertensive and normotensive (500-mg valaciclovir treatment) elderly groups were almost superimposable, and acyclovir pharmacokinetic parameters for the two groups were not significantly different, indicating that concomitant thiazide diuretics do not alter acyclovir pharmacokinetics following valaciclovir dosing in the elderly. Compared with historical data for younger volunteers (creatinine clearance [CLCR] > 75 ml/min/1.73 m2), the elderly subjects (CLCR = 40 to 65 ml/min/1.73 m2) showed higher (approximately 15 to 20%) mean Cmaxs and higher (approximately 30 to 50%) mean AUC(0-infinity)s of acyclovir (P < 0.01), which were consistent with age-related decreases in CLCR. The increased acyclovir exposure from valaciclovir dosing will permit reduced dosing frequency and may result in improved efficacy in the management of herpesvirus diseases.
Once-versus thrice-daily netilmicin combined with amoxicillin, penicillin, or vancomycin against Enterococcus faecalis in a pharmacodynamic in vitro model
Authors: Schwank S , Blaser J
Published: October 2018

Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.
Inhibition of peptidoglycan biosynthesis in vancomycin-susceptible and -resistant bacteria by a semisynthetic glycopeptide antibiotic
Authors: Allen N E , Hobbs J N , Nicas T I
Published: October 2018

LY191145 is a p-chlorobenzyl derivative of LY264826 (A82846B) with activity against both vancomycin-susceptible and -resistant enterococci. Incorporation of L-[14C]lysine into peptidoglycan of intact vancomycin-susceptible and -resistant Enterococcus faecium was inhibited by LY191145 (50% inhibitory concentrations of 1 and 5 microgram/ml, respectively). Inhibition was accompanied by accumulation of UDP-muramyl-peptide precursors in the cytoplasm. This agent inhibited late-stage steps in peptidoglycan biosynthesis in permeabilized E. faecium when either the UDP-muramyl-pentapeptide precursor from vancomycin-susceptible E. faecium or the UDP-muramyl-pentadepsipeptide precursor from vancomycin-resistant E. faecium was used as a substrate. Inhibition of late-stage steps led to accumulation of an N-acetyl-[14C]glucosamine-labeled lipid intermediate indicative of inhibition of the transglycosylation step. Inhibition of peptidoglycan polymerization without affecting cross-linking in a particulate membrane-plus-wall-fragment assay from Aerococcus viridans was consistent with this explanation. The fact that inhibition of peptidoglycan biosynthesis by LY191145 was not readily antagonized by an excess of free acyl-D-alanyl-D-alanine or acyl-D-alanyl-D-lactate ligands indicates that the manner in which this compound inhibits transglycosylation may not be identical to that of vancomycin.
Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin
Authors: Patel K B , Xuan D , Tessier P R , Russomanno J H , Quintiliani R , Nightingale C H
Published: October 2018

The bronchopulmonary and plasma pharmacokinetics of clarithromycin (CLA; 500 mg given twice daily for nine doses) or azithromycin (AZ; 500 mg for the first dose and then 250 mg once daily for four doses) were assessed in 41 healthy nonsmokers. Bronchoalveolar lavage was performed at 4, 8, 12, or 24 h after administration of the last dose. The concentrations (mean +/- standard deviation) of CLA, 14-hydroxyclarithromycin, and AZ were measured in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) cells by high-performance liquid chromatography assay. The concentrations of CLA achieved in ELF were 34.02 +/- 5.16 micrograms/ml at 4 h, 20.63 +/- 4.49 micrograms/ml at 8 h, 23.01 +/- 11.9 micrograms/ml at 12 h, and 4.17 +/- 0.29 microgram/ml at 24 h, whereas at the same time points AZ concentrations remained below the limit of assay sensitivity (0.01 microgram/ml) for all but two subjects. The concentrations of CLA in the AM cells were significantly higher than those of AZ at 8 h (703 +/- 235 and 388 +/- 53 micrograms/ml, respectively). However, the ratio of the concentration in AM cells/concentration in plasma was significantly higher for AZ than for CLA for all time points because of the lower concentration of AZ in plasma. These results indicate that while AZ has higher tissue concentration to plasma ratios, as shown by other investigators, the absolute concentrations of CLA in AM cells and ELF are higher for up to 8 and 12 h, respectively, after administration of the last dose.
Enhanced in vitro activity of pyrimethamine in combination with dapsone against Mycobacterium avium complex
Authors: Shah L M , Meyer S C , Cynamon M H
Published: October 2018

The in vitro activities of pyrimethamine and dapsone alone and in combination were evaluated against 23 clinical isolates of Mycobacterium avium complex. The broth dilution MICs of dapsone and pyrimethamine alone ranged from 16 to > 64 micrograms/ml. Pyrimethamine in combination with a fixed concentration of dapsone at 0.5 microgram/ml showed enhanced activity, with an MIC range of 0.5 to 16 micrograms/ml.
Correlation of molecular resistance mechanisms and phenotypic resistance levels in streptomycin-resistant Mycobacterium tuberculosis
Authors: Meier A , Sander P , Schaper K J , Scholz M , Böttger E C
Published: October 2018

Quantitative susceptibility testing of clinical isolates of streptomycin-resistant Mycobacterium tuberculosis demonstrated that there is a close correlation between the molecular resistance mechanism and the in vitro activity of streptomycin: mutations in rpsL were mainly associated with high-level resistance, mutations in rrs were associated with an intermediate level of resistance, and streptomycin-resistant isolates with wild-type rpsL and rrs exhibited a low-level resistance phenotype. Investigations of streptomycin-resistant isolates with wild-type rpsL and rrs revealed that (i) there is no cross-resistance to other drugs and (ii) a permeability barrier may contribute to resistance, because resistance was significantly lowered in the presence of a membrane-active agent.
Inhibition of Trypanosoma cruzi growth in mammalian cells by purine and pyrimidine analogs
Authors: Nakajima-Shimada J , Hirota Y , Aoki T
Published: October 2018

Trypanosoma cruzi, the causative agent of Chagas' disease, exhibits two different developmental stages in mammals, the amastigote, an intracellular form that proliferates in the cytoplasm of host cells, and the trypomastigote, an extracellular form that circulates in the bloodstream. We have already established an in vitro culture system using mammalian host cells (HeLa) infected with T. cruzi in which the time course of parasite growth is determined quantitatively. We adopted this system for the screening of anti-T. cruzi agents that would ideally prove to be effective against trypanosomes with no toxicity to the host cell. Of the purine analogs tested, allopurinol markedly inhibited the growth of amastigotes in a dose-dependent manner, with no lethal effect on trypomastigotes. 3'-Deoxyinosine and 3'-deoxyadenosine also suppressed T. cruzi growth inside the host cell, with the concentrations causing 50% growth inhibition being 10 and 5 microM, respectively, in contrast to a concentration causing 50% growth inhibition of 3 microM for allopurinol. Among the pyrimidine analogs examined, 3'-azido-3'-deoxythymidine (zidovudine) significantly reduced the growth of the parasite at concentrations as low as 1 microM. The anti-human immunodeficiency virus agents 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine caused a decrease in amastigote growth, while 2',3'-dideoxycytidine and 2',3'-dideoxyuridine had no inhibitory effect. When Swiss 3T3 fibroblasts were used as host cells, allopurinol, 3'-deoxyinosine, 3'-deoxyadenosine, and 3'-azid-3'-deoxythymidine also markedly inhibited T. cruzi proliferation. These results indicate that our culture system is useful as a primary screening method for candidate compounds against T. cruzi on the basis of two criteria, namely, intracellular replication by the parasite and host-cell infection rate.
Effects of isoniazid on ultrastructure of Mycobacterium aurum and Mycobacterium tuberculosis and on production of secreted proteins
Authors: Bardou F , Quémard A , Dupont M A , Horn C , Marchal G , Daffé M
Published: October 2018

Isoniazid (INH), one of the most effective antimycobacterial drugs, specifically inhibits, at an early stage of its action, the biosynthesis of mycolic acids, specific mycobacterial lipids which play a central role in the cell envelope architecture of mycobacteria. In the present study, the consequences of the action of INH on the cell morphology of Mycobacterium tuberculosis and Mycobacterium aurum were examined. Electron microscopy was used to observe bacilli which were previously treated with either subinhibitory concentrations of INH or the MIC of the drug, leading to a decrease of 20 to 35% (by weight) of their mycolic acid contents. The earlier effect of INH on the ultrastructure of mycobacteria, as revealed by negative staining of bacilli, was the alteration of the bacterial poles; this event was observed prior to the bacteriostatic action of the drug and was accompanied by a release of material from the poles into the extracellular medium. In a later stage of the drug's action, cell deformation occurred and more extracellular material was seen. The material released following the action of the drug on susceptible mycobacterial cells was identified as being almost exclusively composed of proteins. Labeling of amino acids with 35S prior to and during the action of INH on M. aurum and subsequent analysis of the labeled proteins led to the conclusion that they consisted of secreted proteins which were up to 20-fold oversecreted in the presence of the drug. Competitive enzyme-linked immunosorbent assay with the secreted 45/47-kDa antigen complex of M. tuberculosis demonstrated up to 20-fold oversecretion of these proteins. Taken together, the production of oversecreted proteins following the decrease of the cell envelope mycolate content by INH strongly suggests that mycolic acids may act as a barrier in the export of proteins secreted by mycobacteria.