bluuebunny/crossref_metadata_2025 huggingface dataset:
The peroneocuboid joint: morphogenesis and anatomical study
Authors: Guimerá V. , Lafuente A. , Zambrana L. , Rodriguez‐Niedenführ M. , Sañudo J. R. , Vazquez T.
Published: November 2014

The peroneocuboid joint, between the peroneus longus tendon and the cuboid bone, has not been anatomically well‐defined and no embryological study has been published. Furthermore, the ossification of the os peroneum (a sesamoid inside the peroneus longus tendon) and its associated pathology has been considered to be generated by orthostatic and/or mechanical loads. A light microscopy analysis of serially sectioned human embryonic and fetal feet, the analysis of human adult feet by means of standard macroscopic dissection, X‐ray and histological techniques have been carried out. The peroneus longus tendon was fully visible until its insertion in the 1st metatarsal bone already at embryonic stage 23 (56–57 days). The peroneocuboid joint cavity appeared at the transition of the embryonic to the fetal period (8–9th week of gestation) and was independent of the proximal synovial sheath. The joint cavity extended from the level of the calcaneocuboid joint all the way to the insertion of the peroneus longus tendon in the 1st metatarsal bone. The frenular ligaments, fixing the peroneus longus tendon to the 5th metatarsal bone or the long calcaneocuboid ligament, developed in the embryonic period. The peroneus longus tendon presented a thickening in the area surrounding the cuboid bone as early as the fetal period. This thickening may be considered the precursor of the os peroneum and was similar in shape and in size relation to the tendon, to the os peroneum observed in adults. To the best of our knowledge, this is the first study to show that the os peroneum, articular facets of the peroneus longus tendon and cuboid bone, the peroneocuboid joint and the frenular ligaments appear during the embryonic/fetal development period and therefore they can not be generated exclusively by orthostatic and mechanical forces or pathological processes.
Telbivudine is associated with improvement of renal function in patients transplanted for HBV liver disease
Authors: Cholongitas E. , Vasiliadis T. , Goulis I. , Fouzas I. , Antoniadis N. , Papanikolaou V. , Akriviadis E.
Published: November 2014

Recent studies showed that telbivudine in patients with hepatitis B virus (HBV) infection improved their glomerular filtration rate (GFR), but data regarding its impact on renal function in liver transplant (LT) recipients are very limited. We evaluated 17 consecutive recipients who received at baseline nucleos(t)ide analogue(s) (NAs) other than telbivudine for 12 months, and then they were switched to telbivudine prophylaxis for another 12 months. In each patient, laboratory data including evaluation of GFR (using MDRD and CKD‐EPI) were prospectively recorded. The changes in GFR (ΔGFR) between baseline and after 12 months (1st period) and between telbivudine initiation and 24 months (2nd period) were evaluated. All patients remained serum HBsAg and HBV‐DNA negative. GFR‐MDRD at baseline, 12 months and 24 months were 72 ± 18, 67.8 ± 16 and 70.3 ± 12mL/min, respectively, (P = 0.025 for comparison between 12 months and 24 months). ΔGFR at the 1st period was significantly lower, compared with ΔGFR at the 2nd period [mean ΔGFR‐MDRD: −4.2 (range: −24–9) vs 2.5 (range: −7–22) mL/min, P = 0.013; mean ΔGFR‐CKD‐EPI: −4.2 (range: −19–10) vs 4.0 (range: −7–23) mL/min, P = 0.004], although the serum levels of calcineurin inhibitors were similar between the two periods. A second group of recipients (n = 17) who remained under the same nontelbivudine NA(s) for 24 months had a decline in the mean eGFR during the total follow‐up period. In conclusion, we showed that telbivudine administration in LT recipients for HBV cirrhosis was effective and it was associated with significant improvement in renal function, but this remains to be confirmed in larger well‐designed studies.
IV. THE COGNITIVE IMPLICATIONS OF OBESITY AND NUTRITION IN CHILDHOOD
Authors: Khan Naiman A. , Raine Lauren B. , Donovan Sharon M. , Hillman Charles H.
Published: November 2014

The prevalence of childhood obesity in the United States has tripled since the 1980s and is strongly linked to the early onset of several metabolic diseases. Recent studies indicate that lower cognitive function may be another complication of childhood obesity. This review considers the research to date on the role of obesity and nutrition on childhood cognition and brain health. Although a handful of studies point to a maladaptive relationship between obesity and aspects of cognitive control, remarkably little is known regarding the impact of fat mass on brain development and cognitive function. Further, missing from the literature is the role of nutrition in the obesity‐cognition interaction. Nutrition may directly or indirectly influence cognitive performance via several pathways including provision of key substrates for optimal brain health, modulation of gut microbiota, and alterations in systemic energy balance. However, in the absence of malnutrition, the functional benefits of specific nutrient intake on particular cognitive domains are not well characterized. Here, we examine the literature linking childhood obesity and cognition while considering the effects of nutritional intake. Possible mechanisms for these relationships are discussed and suggestions are made for future study topics. Although childhood obesity prevalence rates in some developed countries have recently stabilized, significant disparities remain among groups based on sex and socioeconomic status. Given that the elevated prevalence of pediatric overweight and obesity may persist for the foreseeable future, it is crucial to develop a comprehensive understanding of the influence of obesity and nutrition on cognition and brain health in the pediatric population.
Analysis of impact of geographic characteristics on suicide rate and visualization of result with Geographic Information System
Authors: Oka Mayumi , Kubota Takafumi , Tsubaki Hiroe , Yamauchi Keita
Published: November 2014

Aim

The aim of our study was to understand the geographic characteristics of Japanese communities and the impact of these characteristics on suicide rates.

Methods

We calculated the standardized mortality ratio from suicide statistics of 3318 municipalities from 1972 to 2002. Correlation analysis, multi‐regression analysis and generalized additive model were used to find the relation between topographic and climatic variables and suicide rate. We visualized the relation between geographic characteristics and suicide rate on the map of Wakayama Prefecture, using the Geographic Information System.

Results

Our study showed that the geographic characteristics of each community are related with its suicide rate. The strongest factor among the geographic characteristics to increase the suicide rate was the slope of the habitable land.

Conclusions

It is necessary to take the characteristics of each community into consideration when we work out measures of suicide prevention. Visualization of the findings on the local map should be helpful to promote understanding of problems and to share the information among various parties in charge of suicide prevention.
The Transformation of organic regulation: The ambiguous effects of publicization
Authors: Arcuri Alessandra
Published: November 2014

The regulatory regime for organic products is different from other non‐state‐market driven (NSMD) regimes because it is the only one that evolved from a purely private into a regime where the establishment of minimum standards has become the monopoly of public powers. This article is the first to study the effects of the process of publicization, a term coined to characterize the transformation of private into public standards. The central hypothesis studied is that the process of publicization has empowerment and containment effects at the same time. To test the hypothesis the article analyses the effects of publicization on regulatory capabilities of private regulators as well as on the quality of the standards. The effects of publicization are further explored by comparing the legal and institutional architecture that shapes the coexistence of private and public regimes in the EU and the US, showing important differences between the two systems. The article offers a new perspective to look at the dynamic interaction between private and public regulation and its findings are of general relevance for the debate on the desirability of governmental intervention on private regulatory schemes.
Clinical features of 280 hospitalized patients with lymphangioleiomyomatosis in Japan
Authors: Hasegawa Wakae , Yamauchi Yasuhiro , Yasunaga Hideo , Sunohara Mitsuhiro , Jo Taisuke , Matsui Hiroki , Fushimi Kiyohide , Takami Kazutaka , Nagase Takahide
Published: November 2014

Background and objective

Lymphangioleiomyomatosis (LAM) is rare, but potentially life threatening owing to respiratory failure. However, knowledge is limited about the condition of hospitalized LAM patients. The objectives of this study were to investigate patient characteristics, comorbidities and causes of death among hospitalized LAM patients in Japan.

Methods

Using a national inpatient database in Japan, information on 280 LAM patients hospitalized between July 2010 and March 2013 was retrospectively collected. We divided the 280 patients into three groups according to their status regarding lung transplantation.

Results

For the study period, we identified 32 patients who had undergone lung transplantation (‘after‐transplantation’ group), 12 patients admitted for lung transplantation (‘for‐transplantation’) and 236 patients who had not undergone transplantation (‘no‐transplantation’). Although the clinical features of LAM patients in the ‘no‐transplantation’ group were similar to previously reported findings, patients hospitalized in connection with transplantation showed the following: the activities of daily living score using the Barthel Index in the ‘after‐transplantation’ group (89.4) was significantly higher than in the ‘for‐transplantation’ group (64.6); the mortality rates in the after‐transplantation group (3.1%) were significantly lower than in the for‐transplantation group (25%). The most frequent comorbidity was pneumothorax, followed by respiratory failure and angiomyolipoma, although there was no significant difference in the prevalence among the three groups.

Conclusions

We determined the clinical features, comorbidities and fatalities in hospitalized LAM patients. Patients with LAM after transplantation had higher activities of daily living scores than those before transplantation, which suggests that lung transplantation may improve activities of daily living.
Socioeconomic Strain, Family Ties, and Adolescent Health in a Rural Northeastern County
Authors: Van Gundy Karen T. , Mills Meghan L. , Tucker Corinna Jenkins , Rebellon Cesar J. , Sharp Erin Hiley , Stracuzzi Nena F.
Published: November 2014

In adolescence, vital sources of support come from family relationships; however, research that considers the health‐related impact of ties to both parents and siblings is sparse, and the utility of such ties among at‐risk teens is not well understood. Here we use two waves of panel data from the population of 8th and 12th grade students in a geographically isolated, rural, northeastern U.S. county to assess whether socioeconomic status (SES) moderates the effects of parental and sibling attachments on three indicators of adolescent health: obesity, depression, and problem substance use. Our findings indicate that, net of stressful life events, prior health, and sociodemographic controls, increases in parental and sibling attachment correspond with reduced odds of obesity for low‐SES adolescents, reduced odds of depression for high‐SES adolescents, and reduced odds of problem substance use for low‐SES adolescents. Results suggest also that sibling and maternal ties are more influential than paternal ties, at least with regard to the outcomes considered. Overall, the findings highlight the value of strong family ties for the physical, psychological, and behavioral health of socioeconomically strained rural teens, and reveal the explanatory potential of both sibling and parental ties for adolescent health.
Appropriating Iconicity: Why Tank Man Still Matters
Authors: Hubbert Jennifer
Published: November 2014

This article explores the reappropriation of iconic photographs, examining what happens when the iconic “Tank Man” image is modified and repurposed to new political ends. It argues that such reappropriations push viewers to read against the grain of ontological security because the ubiquity of the originals motivates the questioning of taken‐for‐granted meaning in new contexts. In this case, the 21st‐century reappropriated Tank Man images speak less about the absence of political liberalism and democracy in China that were encapsulated in the original Tank Man image and more about their absence in the contemporary United States. At the same time, they also reflect changing global hierarchies in which the United States no longer automatically occupies a position of power relative to China. As such, reappropriations of iconic photographs have the potential to mobilize collective memory and political imaginations to new ends.
Bootlegged: Unauthorized Circulation and the Dilemmas of Collaboration in the Digital Age
Authors: Stout Noelle
Published: November 2014

Recent innovations in digital technologies have exponentially increased the opportunities for collaborative ethnographic filmmaking between anthropologists and our interlocutors. In this article, I focus on a relatively unexplored aspect of these emergent forms of collaboration: the unruliness of circulation in the digital age. I draw on long‐standing anthropological debates about controlling the dissemination of taboo cultural motifs to consider how the rapid and promiscuous circulation of digital images and video intensifies these concerns. Reflecting on my experience of collaborative video production with Cuban sex workers and the subsequent unauthorized circulation of these politicized images outside of Cuba, I show how an inability to control distribution presents pressing concerns regarding consent for a growing cadre of anthropologists working in digital mediums.
MRI CHARACTERISTICS OF FOURTH VENTRICLE ARACHNOID DIVERTICULA IN FIVE DOGS
Authors: Bazelle Julien , Caine Abby , Palus Viktor , Summers Brian A. , Cherubini Giunio B.
Published: November 2014

Intracranial arachnoid diverticula (cysts) are rare accumulations of cerebrospinal fluid (CSF) within the arachnoid membrane. The purpose of this retrospective study was to describe magnetic resonance imaging (MRI) characteristics of fourth ventricle arachnoid diverticula in a group of dogs. The hospital's medical records were searched for dogs with MRI studies of the brain and a diagnosis of fourth ventricle arachnoid diverticulum. Clinical characteristics were recorded from medical records and MRI studies were reinterpreted by a board‐certified veterinary radiologist. Five pediatric dogs fulfilled inclusion criteria. Clinical signs included cervical hyperaesthesia, obtundation, tetraparesis, and/or central vestibular syndrome. In all five dogs, MRI findings were consistent with obstructive hydrocephalus, based on dilation of all ventricles and compression of the cerebellum and brainstem. All five dogs also had cervical syringohydromyelia, with T2‐weighted hyperintensity of the gray matter of the cord adjacent to the syringohydromyelia. A signal void, interpreted as flow disturbance, was observed at the mesencephalic aqueduct in all dogs. Four dogs underwent surgical treatment with occipitalectomy and durotomy. A cystic lesion emerging from the fourth ventricle was detected in all four dogs during surgery and histopathology confirmed the diagnosis of arachnoid diverticula. Three dogs made excellent recovery but deteriorated shortly after surgery and were euthanized. Repeat MRI in two dogs revealed improved hydrocephalus but worsening of the syringohydromyelia. Findings from the current study supported theories that fourth ventricle arachnoid diverticula are secondary to partial obstruction of the central canal or lateral apertures and that arachnoid diverticula are developmental lesions in dogs.
DEVELOPING AN ACCURATE METHOD FOR ESTIMATING THYROID VOLUME IN CALVES USING ULTRASONOGRAPHY
Authors: Metzner Moritz , Uebelhack Sandra , Sauter‐Louis Carola , Reese Sven , Klee Wolfgang
Published: November 2014

Diseases of the thyroid gland with struma formation can occur in calves suffering from iodine deficiency. The aim of the study was to develop a guideline for standardized ultrasonographic examination of the thyroid gland in order to determine its volume. Sonographic measurements of the thyroid lobes were carried out on three standardized axes in calves up to 3 months of age (n= 83). Total volume (VSON) was calculated using the formula for an ellipsoid body. Forty three of the enrolled animals were euthanized. The lobes of their thyroid glands were dissected and measured with a slide gauge, and VSLGwas calculated accordingly. In addition, thyroid volume was measured using the method of water displacement (VAQU) and this was used as a gold standard in correlation and regression analyses with sonographic and slide gauge values. Intraobserver variability of sonographic measurements was dependent on side and axis, and ranged between 3.04% and 7.35%. In the euthanized calves with a body mass of 52.4 ± 17.1 kg, VSLGwas 4.5 ± 1.4 ml, VSONwas 6.5 ± 1.7 ml, and VAQUwas 7.9 ± 2.4 ml (mean ± standard deviation). Instead of the formula for ellipsoid bodies which underestimates thyroid volume, we developed a new formula derived from regression analysis. Body mass and thyroid volume correlated significantly. With the formula presented, thyroid volume of calves can be estimated by ultrasonographic measurement of three axes and compared to predicted values based on body mass.
Loss of β2‐laminin alters calcium sensitivity and voltage‐gated calcium channel maturation of neurotransmission at the neuromuscular junction
Authors: Chand Kirat K. , Lee Kah Meng , Schenning Mitja P. , Lavidis Nickolas A. , Noakes Peter G.
Published: November 2014

Key points

Neuromuscular junctions from β2‐laminin‐deficient mice exhibit lower levels of calcium sensitivity.

Loss of β2‐laminin leads to a failure in switching from N‐ to P/Q‐type voltage‐gated calcium channel (VGCC)‐mediated transmitter release that normally occurs with neuromuscular junction maturation.

The motor nerve terminals from β2‐laminin‐deficient mice fail to up‐regulate the expression of P/Q‐type VGCCs clusters and down‐regulate N‐type VGCCs clusters, as they mature.

There is decreased co‐localisation of presynaptic specialisations in β2‐laminin‐deficient neuromuscular junctions as a consequence of lesser P/Q‐type VGCC expression.

These findings support the idea that β2‐laminin is critical in the organisation and maintenance of active zones at the neuromuscular junction via its interaction with P/Q‐type VGCCs, which aid in stabilisation of the synapse.

β2‐laminin is a key mediator in the differentiation and formation of the skeletal neuromuscular junction. Loss of β2‐laminin results in significant structural and functional aberrations such as decreased number of active zones and reduced spontaneous release of transmitter. In vitro β2‐laminin has been shown to bind directly to the pore forming subunit of P/Q‐type voltage‐gated calcium channels (VGCCs). Neurotransmission is initially mediated by N‐type VGCCs, but by postnatal day 18 switches to P/Q‐type VGCC dominance. The present study investigated the changes in neurotransmission during the switch from N‐ to P/Q‐type VGCC‐mediated transmitter release at β2‐laminin‐deficient junctions. Analysis of the relationship between quantal content and extracellular calcium concentrations demonstrated a decrease in the calcium sensitivity, but no change in calcium dependence at β2‐laminin‐deficient junctions. Electrophysiological studies on VGCC sub‐types involved in transmitter release indicate N‐type VGCCs remain the primary mediator of transmitter release at matured β2‐laminin‐deficient junctions. Immunohistochemical analyses displayed irregularly shaped and immature β2‐laminin‐deficient neuromuscular junctions when compared to matured wild‐type junctions. β2‐laminin‐deficient junctions also maintained the presence of N‐type VGCC clustering within the presynaptic membrane, which supported the functional findings of the present study. We conclude that β2‐laminin is a key regulator in development of the NMJ, with its loss resulting in reduced transmitter release due to decreased calcium sensitivity stemming from a failure to switch from N‐ to P/Q‐type VGCC‐mediated synaptic transmission.
Origami-Based Self-Folding Structure Design and Fabrication Using Projection Based Stereolithography
Authors: Deng Dongping , Chen Yong
Published: November 2014

Self-folding structures have unique capability such as reconfiguration during their usage. Such capability can be beneficial for a wide variety of applications including biomedical and electronics products. In this paper, a novel fabrication approach based on a three-dimensional (3D) printing process is presented for fabricating self-folding structures that can be actuated in a heating environment. The thermo-actuating structures that are designed and fabricated by our method are two-dimensional (2D) origami sheets, which have multiple printed layers. The middle layer of an origami sheet is a prestrained polystyrene film with large shrinkage ratios when heated. Both its top and bottom surfaces are covered with cured resin that is printed in designed shapes. A foldable hinge is achieved by constraining the shrinkage of the film on one side while allowing the shrinkage of the film on another side when the origami sheet is exposed to a heating environment. Heuristic models of hinge's folding angles are developed based on the related folding mechanism. A 2D origami sheet design and fabrication method is presented for a given 3D structure. Various experimental tests are performed to verify the self-folding performance of the designed and fabricated origami sheets. Techniques on improving folding angle control are also discussed with possible applications.
Study on a Vapor-Feed Air-Breathing Direct Methanol Fuel Cell Assisted by a Catalytic Combustor
Authors: Yuan Wei , Xia Hong-Rong , Hu Jin-Yi , Zhang Zhao-Chun , Tang Yong
Published: November 2014

Feeding vaporized methanol to the direct methanol fuel cell (DMFC) helps reduce the effects of methanol crossover (MCO) and facilitates the use of high-concentration or neat methanol so as to enhance the energy density of the fuel cell system. This paper reports a novel system design coupling a catalytic combustor with a vapor-feed air-breathing DMFC. The combustor functions as an assistant heat provider to help transform the liquid methanol into vapor phase. The feasibility of this method is experimentally validated. Compared with the traditional electric heating mode, the operation based on this catalytic combustor results in a higher cell performance. Results indicate that the values of methanol concentration and methanol vapor chamber (MVC) temperature both have direct effects on the cell performance, which should be well optimized. As for the operation of the catalytic combustor, it is necessary to optimize the number of capillary wicks and also catalyst loading. In order to fast trigger the combustion reaction, an optimal oxygen feed rate (OFR) must be used. The required amount of oxygen to sustain the reaction can be far lower than that for methanol ignition in the starting stage.
Effects of spin‐lock field direction on the quantitative measurement of spin‐lattice relaxation time constant in the rotating frame (T1ρ) in a clinical MRI system
Authors: Yee Seonghwan , Gao Jia‐Hong
Published: November 2014

Purpose:

To investigate whether the direction of spin‐lock field, either parallel or antiparallel to the rotating magnetization, has any effect on the spin‐lock MRI signal and further on the quantitative measurement of T1ρ, in a clinical 3 T MRI system.

Methods:

The effects of inverted spin‐lock field direction were investigated by acquiring a series of spin‐lock MRI signals for an American College of Radiology MRI phantom, while the spin‐lock field direction was switched between the parallel and antiparallel directions. The acquisition was performed for different spin‐locking methods (i.e., for the single‐ and dual‐field spin‐locking methods) and for different levels of clinically feasible spin‐lock field strength, ranging from 100 to 500 Hz, while the spin‐lock duration was varied in the range from 0 to 100 ms.

Results:

When the spin‐lock field was inverted into the antiparallel direction, the rate of MRI signal decay was altered and the T1ρ value, when compared to the value for the parallel field, was clearly different. Different degrees of such direction‐dependency were observed for different spin‐lock field strengths. In addition, the dependency was much smaller when the parallel and the antiparallel fields are mixed together in the dual‐field method.

Conclusions:

The spin‐lock field direction could impact the MRI signal and further the T1ρ measurement in a clinical MRI system.
The Test-retest Reliability of Knee Joint Center Location Techniques
Authors: Sinclair Jonathan , Hebron Jack , Taylor Paul J.
Published: November 2014

The principal source of measurement error in three-dimensional analyses is the definition of the joint center about which segmental rotations occur. The hip joint has received considerable attention in three-dimensional modeling analyses yet the reliability of the different techniques for the definition of the knee joint center has yet to be established. This study investigated the reliability of five different knee joint center estimation techniques: femoral epicondyle, femoral condyle, tibial ridge, plugin-gait, and functional. Twelve male participants walked at 1.25 m·s−1 and three-dimensional kinetics/kinematics of the knee and ankle were collected. The knee joint center was defined twice using each technique (test-and-retest) and the joint kinetic/kinematic data were applied to both. Wilcoxon rank tests and intraclass correlation coefficients (ICCs) were used to compare test and retest angular parameters and kinematic waveforms. The results show significant differences in coronal and transverse planes angulation using the tibial ridge, plug-in-gait, and functional methods. The strongest test-retest ICCs were observed for the femoral epicondyle and femoral condyle configurations. The findings from the current investigation advocate that the femoral epicondyle and femoral condyle techniques for the estimation of the knee joint center are currently the most reliable techniques.
Using Nonlinear Tools to Evaluate Movement of Fragile Objects
Authors: Madansingh Stefan , Gorniak Stacey L.
Published: November 2014

We investigated the movement strategies of young, healthy participants (7 men/7 women) during the movement of a fragile object using nonlinear analysis. The kinematic variables of position, velocity, and acceleration were quantified using largest Lyapunov exponent (LyE) and approximate entropy (ApEn) analysis to identify the structure of their movement variability and movement predictability, respectively. Subjects performed a total of 15 discrete trials of an upper extremity movement task without crushing the object at each fragility condition, using each hand (left/right). We tested four fragility conditions hypothesizing that an increase in fragility would result in higher movement predictability and decreased temporal variability. Comparisons between the structure of movement variability and movement predictability were based on fragility condition, handedness, and kinematic measures. In this specific population, object fragility and participant handedness did not significantly impact the structure of movement variability (LyE) in the primary direction of movement (Z direction), although some effects were observed in the anterior/posterior directions. ApEn values were minimized across conditions, showing increased movement predictability, and is suggested for the analysis of discrete kinematic movements. In healthy populations, the results of this study suggest minimal effects on task performance and movement predictability as a result of object fragility.
Evaluating the Coupling between Foot Pronation and Tibial Internal Rotation Continuously Using Vector Coding
Authors: Rodrigues Pedro , Chang Ryan , TenBroek Trampas , van Emmerik Richard , Hamill Joseph
Published: November 2014

Excessive pronation, because of its coupling with tibial internal rotation (TIR), has been implicated as a risk factor in the development of anterior knee pain (AKP). Traditionally, this coupling has been expressed as a ratio between the eversion range of motion and the TIR range of motion (Ev/TIR) that occurs during stance. Currently, this technique has not been used to evaluate specific injuries or the effects of sex. In addition, Ev/TIR is incapable of detecting coupling changes that occur throughout stance. Therefore, the purpose of this study was to compare the coupling between eversion and TIR in runners with (n = 19) and without AKP (n = 17) and across sex using the Ev/TIR ratio, and more continuously using vector coding. When using vector coding, significant coupling differences were noted in runners with AKP (34% to 38% stance), with runners with AKP showing relatively more TIR than eversion. Similarly significant differences were noted across sex (14%–25% and 36%–47% stance), with males transitioning from a loading to propulsive coordination pattern using a proximal to distal strategy, and female runners using a distal to proximal strategy. These differences were only detected when evaluating this coupling relationship using a continuous technique such as vector coding.
Comparative Electromyography Analysis of the Upper Extremity between Inexperienced and Elite Water Polo Players during an Overhead Shot
Authors: Yaghoubi Mostafa , Esfehani Mohamad Mahdi , Hosseini Hossein Asghar , Alikhajeh Yaser , Shultz Sarah P.
Published: November 2014

The aim of this study was to compare muscle activity patterns between inexperienced and experienced water polo players while taking an overhead shot. The study was carried out with a group of 12 water polo players and an inexperienced group of 10 healthy participants. Signals were recorded by surface electromyography from six different muscles. The average and standard deviation of the normalized electrical activity, time to peak, time broadness, and muscle sequencing during the overhead shot were determined for each muscle in both groups and compared with each other. In water polo players, the normalized electrical activities of triceps brachii, pectoralis major, and wrist flexors were greater than other muscles, while in the inexperienced group the triceps brachii specifically played an important role. There was minimal activation of the middle deltoid and biceps brachii in water polo players. Increased times to peak and time broadness of muscles were found in the inexperienced group compared to experienced water polo players; this difference may be explained by different neuromuscular proprioception. Only experienced water polo players activated the observed muscles in a specific sequence, from proximal to distal. Therefore, coaches should emphasize smooth and quick transitions from proximal to distal segments, with less importance placed on individual muscle strengthening.
Pharmacokinetics, Microbial Response, and Pulmonary Outcomes of Multidose Intravenous Azithromycin in Preterm Infants at Risk for Ureaplasma Respiratory Colonization
Authors: Merchan L. Marcela , Hassan Hazem E. , Terrin Michael L. , Waites Ken B. , Kaufman David A. , Ambalavanan Namasivayam , Donohue Pamela , Dulkerian Susan J. , Schelonka Robert , Magder Laurence S. , Shukla Sagar , Eddington Natalie D. , Viscardi Rose M.
Published: November 2014

The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for
Ureaplasma
respiratory colonization. Fifteen subjects (7 of whom were
Ureaplasma
positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for
Ureaplasma
culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [
n
= 12] or a single 20-mg/kg dose [
n
= 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg
0.75
, 1.88 liters · kg, 1.79 liters/h · kg
0.75
, and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC
24
)/MIC
90
value was ∼4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One
Ureaplasma
-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating
Ureaplasma
spp. from the preterm respiratory tract.
Clostridium difficile Isolates with High Linezolid MICs Harbor the Multiresistance Gene
cfr
Authors: Marín Mercedes , Martín Adoración , Alcalá Luis , Cercenado Emilia , Iglesias Cristina , Reigadas Elena , Bouza Emilio
Published: November 2014

We studied the molecular mechanisms of linezolid resistance in 9 isolates of toxigenic
Clostridium difficile
with high linezolid MICs. The activity of linezolid was determined against 891 clinical isolates of toxigenic
C. difficile
. The MIC
50
and MIC
90
of linezolid were 0.75 μg/ml and 1.5 μg/ml, respectively. Nine strains (1%) showed high linezolid MICs (6 μg/ml to 16 μg/ml) and also were resistant to clindamycin, erythromycin, and chloramphenicol. These strains were selected for molecular studies: sequencing of domain V of the
23 rRNA
gene, detection of the
cfr
methyltransferase gene, and sequencing of the ribosomal protein genes
rplC
and
rplD
. Molecular relatedness between strains was assessed using PCR ribotyping and MLVA (multilocus variable-number tandem-repeat analysis) typing. The strains belonged to ribotypes 001 (2/9), 017 (6/9), and 078 (1/9). MLVA showed that strains of ribotype 001 and 017 belonged to the same clonal complex in each ribotype. We did not detect mutations in the 23S rRNA gene. The
cfr
gene was detected in 7 of 9 strains. Sequencing of
cfr
amplicons revealed a similarity of 100% to a fragment of transposon Tn
6218
of
C. difficile
, which was annotated as a putative chloramphenicol/florfenicol resistance protein. We were unable to detect mechanisms of resistance to linezolid in the 2 strains belonging to ribotype 001. While the relevance of our results lies in the detection of the
cfr
gene as a possible mechanism of resistance to linezolid in
C. difficile
, our findings should be assessed by further investigations to characterize these possible
cfr
genes and their contribution to linezolid resistance.
In Vitro
Resistance Selection with Doravirine (MK-1439), a Novel Nonnucleoside Reverse Transcriptase Inhibitor with Distinct Mutation Development Pathways
Authors: Feng Meizhen , Wang Deping , Grobler Jay A. , Hazuda Daria J. , Miller Michael D. , Lai Ming-Tain
Published: November 2014

Doravirine (DOR, formerly known as MK-1439) is a human immunodeficiency type 1 virus (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) that is currently in phase 2b clinical trials.
In vitro
resistance selection of subtype B virus (MT4-green fluorescent protein [GFP] cells), as well as subtype A and C viruses (MT4-GFP/CCR5 cells) was conducted with DOR, rilpivirine (RPV), and efavirine (EFV) under low-multiplicity-of-infection conditions in a 96-well format. Resistance selection was performed with escalating concentrations of the NNRTIs ranging from the 95% effective concentration (1× EC
95
) to 1,000× EC
95
in the presence of 10% fetal bovine serum. In the resistance selection of subtype B virus with DOR, a V106A mutant virus led to two mutation pathways, followed by the emergence separately of either F227L or L234I. In the resistance selection of subtype A and C viruses, similar mutation development pathways were detected, in which a V106A or V106M mutant was also the starting virus in the pathways. Mutations that are commonly associated with RPV and EFV in clinical settings were also identified in subtype B viruses such as the E138K and K103N mutants, respectively, in this
in vitro
resistance selection study. The susceptibility of subtype B mutant viruses selected by DOR, RPV, and EFV to NNRTIs was evaluated. Results suggest that mutant viruses selected by DOR are susceptible to RPV and EFV and mutants selected by RPV and EFV are susceptible to DOR. When the replication capacity of the V106A mutant was compared with that of the wild-type (WT) virus, the mutant virus was 4-fold less fit than the WT virus.
Trends in Serotype Distribution and Antimicrobial Susceptibility in Salmonella enterica Isolates from Humans in Belgium, 2009 to 2013
Authors: Ceyssens Pieter-Jan , Mattheus Wesley , Vanhoof Raymond , Bertrand Sophie
Published: November 2014

The Belgian National Reference Centre for
Salmonella
received 16,544 human isolates of
Salmonella enterica
between January 2009 and December 2013. Although 377 different serotypes were identified, the landscape is dominated by
S. enterica
serovars Typhimurium (55%) and Enteritidis (19%) in a ratio which is inverse to European Union averages. With outbreaks of
Salmonella
serotypes Ohio, Stanley, and Paratyphi B variant Java as prime examples, 20 serotypes displayed significant fluctuations in this 5-year period. Typhoid strains account for 1.2% of Belgian salmonellosis cases. Large-scale antibiotic susceptibility analyses (
n
= 4,561; panel of 12 antibiotics) showed declining resistance levels in
S
. Enteritis and Typhimurium isolates for 8 and 3 tested agents, respectively. Despite low overall resistance to ciprofloxacin (4.4%) and cefotaxime (1.6%), we identified clonal lineages of
Salmonella
serotypes Kentucky and Infantis displaying rising resistance against these clinically important drugs. Quinolone resistance is mainly mediated by serotype-specific mutations in GyrA residues Ser83 and Asp87 (92.2% not wild type), while an additional ParC_Ser80Ile mutation leads to ciprofloxacin resistance in 95.5%
S
. Kentucky isolates, which exceeds European averages. Plasmid-mediated quinolone resistance (PMQR) alleles
qnrA1
(
n
= 1),
qnrS
(
n
= 9),
qnrD1
(
n
= 4), and
qnrB
(
n
= 4) were found in only 3.0% of 533 isolates resistant to nalidixic acid. In cefotaxime-resistant isolates, we identified a broad range of Ambler class A and C β-lactamase genes (e.g.,
bla
SHV-12
,
bla
TEM-52
,
bla
CTX-M-14
, and
bla
CTX-M-15
) commonly associated with members of the family
Enterobacteriaceae
. In conclusion, resistance to fluoroquinolones and cefotaxime remains rare in human
S. enterica
, but clonal resistant serotypes arise, and continued (inter)national surveillance is mandatory to understand the origin and routes of dissemination thereof.
Disparities in Capreomycin Resistance Levels Associated with the
rrs
A1401G Mutation in Clinical Isolates of Mycobacterium tuberculosis
Authors: Reeves Analise Z. , Campbell Patricia J. , Willby Melisa J. , Posey James E.
Published: November 2014

As the prevalence of multidrug-resistant and extensively drug-resistant tuberculosis strains continues to rise, so does the need to develop accurate and rapid molecular tests to complement time-consuming growth-based drug susceptibility testing. Performance of molecular methods relies on the association of specific mutations with phenotypic drug resistance and while considerable progress has been made for resistance detection of first-line antituberculosis drugs, rapid detection of resistance for second-line drugs lags behind. The
rrs
A1401G allele is considered a strong predictor of cross-resistance between the three second-line injectable drugs, capreomycin (CAP), kanamycin, and amikacin. However, discordance is often observed between the
rrs
A1401G mutation and CAP resistance, with up to 40% of
rrs
A1401G mutants being classified as CAP susceptible. We measured the MICs to CAP in 53 clinical isolates harboring the
rrs
A1401G mutation and found that the CAP MICs ranged from 8 μg/ml to 40 μg/ml. These results were drastically different from engineered A1401G mutants generated in isogenic
Mycobacterium tuberculosis
, which exclusively exhibited high-level CAP MICs of 40 μg/ml. These data support the results of prior studies, which suggest that the critical concentration of CAP (10 μg/ml) used to determine resistance by indirect agar proportion may be too high to detect all CAP-resistant strains and suggest that a larger percentage of resistant isolates could be identified by lowering the critical concentration. These data also suggest that differences in resistance levels among clinical isolates are possibly due to second site or compensatory mutations located elsewhere in the genome.
Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish
Authors: Peterman E. M. , Sullivan C. , Goody M. F. , Rodriguez-Nunez I. , Yoder J. A. , Kim C. H.
Published: November 2014

Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death.
Pseudomonas aeruginosa
is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with
P. aeruginosa
are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to
P. aeruginosa
infection.
sod2
is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide
in vitro
, and
sod2
knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections.
Enterococcus faecalis 6-Phosphogluconolactonase Is Required for Both Commensal and Pathogenic Interactions with Manduca sexta
Authors: Holt Jonathan F. , Kiedrowski Megan R. , Frank Kristi L. , Du Jing , Guan Changhui , Broderick Nichole A. , Dunny Gary M. , Handelsman Jo
Published: November 2014

Enterococcus faecalis
is a commensal and pathogen of humans and insects. In
Manduca sexta
,
E. faecalis
is an infrequent member of the commensal gut community, but its translocation to the hemocoel results in a commensal-to-pathogen switch. To investigate
E. faecalis
factors required for commensalism, we identified
E. faecalis
genes that are upregulated in the gut of
M. sexta
using recombinase-based
in vivo
expression technology (RIVET). The RIVET screen produced 113 clones, from which we identified 50 genes that are more highly expressed in the insect gut than in culture. The most frequently recovered gene was locus OG1RF_11582, which encodes a 6-phosphogluconolactonase that we designated
pglA
. A
pglA
deletion mutant was impaired in both pathogenesis and gut persistence in
M. sexta
and produced enhanced biofilms compared with the wild type in an
in vitro
polystyrene plate assay. Mutation of four other genes identified by RIVET did not affect persistence in caterpillar guts but led to impaired pathogenesis. This is the first identification of genetic determinants for
E. faecalis
commensal and pathogenic interactions with
M. sexta
. Bacterial factors identified in this model system may provide insight into colonization or persistence in other host-associated microbial communities and represent potential targets for interventions to prevent
E. faecalis
infections.
What Is a Host? Incorporating the Microbiota into the Damage-Response Framework
Authors: Casadevall Arturo , Pirofski Liise-anne
Published: November 2014

Since proof of the germ theory of disease in the late 19th century, a major focus of the fields of microbiology and infectious diseases has been to seek differences between pathogenic and nonpathogenic microbes and the role that the host plays in microbial pathogenesis. Remarkably, despite the increasing recognition that host immunity plays a role in microbial pathogenesis, there has been little discussion about what constitutes a host. Historically, hosts have been viewed in the context of their fitness or immunological status and characterized by adjectives such as immune, immunocompetent, immunosuppressed, immunocompromised, or immunologically impaired. However, in recent years it has become apparent that the microbiota has profound effects on host homeostasis and susceptibility to microbial diseases in addition to its effects on host immunity. This raises the question of how to incorporate the microbiota into defining a host. This definitional problem is further complicated because neither host nor microbial properties are adequate to predict the outcome of host-microbe interaction because this outcome exhibits emergent properties. In this essay, we revisit the damage-response framework (DRF) of microbial pathogenesis and demonstrate how it can incorporate the rapidly accumulating information being generated by the microbiome revolution. We use the tenets of the DRF to put forth the following definition of a host: a host is an entity that houses an associated microbiome/microbiota and interacts with microbes such that the outcome results in damage, benefit, or indifference, thus resulting in the states of symbiosis, colonization, commensalism, latency, and disease.