bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes
Authors: Loftsson Thorsteinn , Moya-Ortega Maria D , Alvarez-Lorenzo Carmen , Concheiro Angel
Published: June 2015

Objectives

The objective of the present study was to shed some light on pharmacokinetics of cyclodextrins (CDs) and drugs after oral and parenteral administration of inclusion complexes.

Key findings

The complex binding constant in water can predict pharmacokinetics after parenteral administration, but it has to be considered in the context of the physiological environment, where plasma proteins compete with CDs for drug binding. Neither drug/CD nor drug/protein complexes can extravasate, but differently from proteins, CDs are readily cleared through glomerular filtration. In such intricate interrelationships, for complexes with low-to-mid binding constant, binding of drug to plasma proteins will mainly dictate the pharmacokinetics. Oppositely, for drugs showing large CD complex binding constant and low protein binding, significant decrease in distribution volume and enhanced excretion of unmetabolized drug are observed; thus, relevant changes in bioavailability can be predicted. In the case of oral administration, volume for dilution/dissolution of the complexes is relatively low and hence excess CD can hamper drug absorption from the gastrointestinal (GI) tract.

CDs are well-established multipurpose excipients for overcoming organoleptic and biopharmaceutical deficiencies of a variety of drugs. Balances between free and complexed drug in the GI tract and between drug–CD binding and drug–protein binding in plasma seem to play a relevant role in drug pharmacokinetics.
Sex Offenders Seeking Treatment for Sexual Dysfunction—Ethics, Medicine, and the Law
Authors: Phillips Elizabeth A. , Rajender Archana , Douglas Thomas , Brandon Ashley F. , Munarriz Ricardo
Published: June 2015

Introduction

The treatment of sexual dysfunction in patients with prior sexual offenses poses ethical and legal dilemmas. Sex offenders are not obligated by law to disclose this history to medical professionals. Over 20% of sex offenders experience sexual dysfunction; however, the number of sex offenders seeking evaluation for sexual dysfunction is unknown.

Aims

The aims of this study were to determine the incidence and characteristics of sex offenders seeking treatment in our clinic; and to review data regarding sex offender recidivism and ethics pertaining to the issue as it relates to treating physicians.

Methods

Sex offenders were identified via three methods: new patient screening in a dedicated sexual medicine clinic, chart review of those on intracavernosal injection (ICI) therapy for erectile dysfunction (ED), and review of patient's status-post placement of penile prosthesis. Charts were cross-referenced with the U.S. Department of Justice National Sex Offender Public Website. Patient characteristics and details of offenses were collected.

Main Outcome Measures

The main outcome measures used were a self-reported sexual offense and national registry data.

Results

Eighteen male sex offenders were identified: 13 via new patient screening; 3 by review of ICI patients; 1 by review of penile prosthesis data; and 1 prior to penile prosthesis placement. All were primarily referred for ED. Of those with known offenses, 64% were level 3 offenders (most likely to re-offend). The same number had committed crimes against children. All those with complete data had multiple counts of misconduct (average 3.6). Ninety-four percent (17/18) had publicly funded health care. Twelve (67%) were previously treated for sexual dysfunction.

Conclusions

Registered sex offenders are seeking and receiving treatment for sexual dysfunction. It is unknown whether treatment of sexual dysfunction increases the risk of recidivism of sexual offenses. Physicians currently face a difficult choice in deciding whether to treat sexual dysfunction in sex offenders.
Phylogenetic structure of plant species pools reflects habitat age on the geological time scale
Authors: Lososová Zdeňka , Šmarda Petr , Chytrý Milan , Purschke Oliver , Pyšek Petr , Sádlo Jiří , Tichý Lubomír , Winter Marten
Published: June 2015

Question

Patterns of phylogenetic relatedness of species within community types (phylogenetic structure; PS) are often used to infer processes of community assembly, yet the causes of these patterns remain poorly understood. Here we ask whether PS of extant plant species pools is related to availability of correspoding habitats in the geological history.

Location

Czech Republic.

Methods

We characterized PS of recent species pools of 88 major vascular plant community types occurring in the country, comprising a total of 2306 species, using the mean phylogenetic distance (MPD) between all pairs of species found in each species pool, and compared the PS of these species pools with the relative ages of their habitats.

Results

Clustered PS was observed consistently in species pools of historically younger community types of grasslands and other open habitats, which were formed mainly during the late Tertiary as a consequence of climate aridization and cooling, and to which only a limited number of lineages had enough time to adapt. Clustered PS was also typical of species pools of the recent human‐made habitats, in which it probably resulted from environmental filtering of pre‐adapted lineages. In contrast, overdispersed PS was observed in forests and other plant community types occurring in habitats that are assumed to have existed continuously since the Mesozoic.

Conclusions

Our analyses suggest that habitat age has a strong effect on PS of species pools of extant plant community types. Based on these results, we argue that history of the analysed species pools at a geological time scale should be considered whenever differences in PS are discussed and interpreted.
Relapses from acute malnutrition and related factors in a community‐based management programme in Burkina Faso
Authors: Somassè Yassinmè Elysée , Dramaix Michèle , Bahwere Paluku , Donnen Philippe
Published: June 2015

Community‐based management of acute malnutrition (CMAM) is effective in treating acute malnutrition. However, post‐discharge follow‐up often lacks. We aimed at assessing the relapse rate and the associated factors in a CMAM programme in Burkina Faso. Discharged children from the community nutrition centre were requested to return at least every 3 months for follow‐up. The data of recovered children (weight‐for‐height z‐score ≥−2) who were discharged between July 2010 and June 2011 were collected in 45 villages, randomly selected out of 210 in January 2012. Sociodemographic data, economic variables, information on household food availability and the child's food consumption in the last 24 h were collected from the parents. A multivariate Cox proportional hazards regression was used to identify the factors associated to relapse. Of the 637 children, 14 (2.2%) died and 218 (34.2%) were lost to follow‐up. The relapse rate [95% confidence interval] among the children who returned for follow‐up was 15.4 [11.8–19.0] per 100 children‐years. The associated factors to relapses in multivariate Cox regression model were mid‐upper arm circumference (MUAC) at discharge below 125 mm, no oil/fat consumption during the last 24 h and incomplete vaccination. To limit relapses, CMAM programmes should avoid premature discharge before a MUAC of at least 125 mm. Nutrition education should emphasize fat/oil as inexpensive energy source for children. Promoting immunization is essential to promote child growth. Periodic monitoring of discharged children should be organized to detect earlier those who are at risk of relapse. The relapse rate should be a CMAM effectiveness indicator.
First recovery of Rasamsonia argillacea species complex isolated in adolescent patient with cystic fibrosis in Slovenia – case report and review of literature
Authors: Matos Tadeja , Cerar Tjaša , Praprotnik Marina , Krivec Uroš , Pirš Mateja
Published: June 2015

We report the isolation of the emerging fungal pathogen Rasamsonia aegroticola, which belongs Rasamsonia argillacea species complex, from a respiratory sample of a patient with cystic fibrosis. This filamentous fungus, resembling members of a Penicillium and Paecilomyces spp., was identified by morphology and confirmed by DNA sequence analysis. Susceptibility pattern showed high minimal inhibitory concentration of voriconazole and amphotericin B but low minimal inhibitory concentration of caspofungin, micafungin and itraconazole.
Memecylon trunciflorum sp. nov. (Melastomataceae–Olisbeoideae) from the Udzungwa Mountains, southern Tanzania
Authors: Stone Robert Douglas
Published: June 2015

Described and illustrated is Memecylon trunciflorum R. D. Stone, an evidently localized endemic of the Udzungwa Mountains in southern Tanzania. The new species was previously confused with the vegetatively similar but distantly related M. erythranthum Gilg and M. semseii A. Fern. & R. Fern., from which it is distinguished by its anther connectives bearing a dorsal oil‐gland and by its ellipsoid to obovoid fruits (vs anther connective gland absent and fruits globose in M. erythranthum and M. semseii). The new species is placed in M. sect. Magnifoliata R. D. Stone together with M. magnifoliatum A. Fern. & R. Fern., from which it differs by its smaller leaves mostly 9.5–15.0 × 3.5–6.0 cm (vs 18–35 × 8–13 cm), transverse veins 8–18 pairs (vs 25–28 pairs), short‐pedunculate inflorescences with secondary axes well developed (vs peduncles and secondary axes absent), white flowers (vs bluish purple), and smaller fruits mostly 11.5–14.5 × 9–11 mm on longer fruiting pedicels 8.0–13.5 mm (vs fruits 17–20 × 12–14 mm on pedicels 5.0–7.5 mm). Despite its local endemism, Memecylon trunciflorum has been assessed as ‘Least Concern’ according to IUCN criteria, although this assessment is dependent on the continued safeguarding of the Udzungwa Mountains National Park.
The Arabidopsis mitogen‐activated protein kinase 6 is associated with γ‐tubulin on microtubules, phosphorylates EB1c and maintains spindle orientation under nitrosative stress
Authors: Kohoutová Lucie , Kourová Hana , Nagy Szilvia K. , Volc Jindřich , Halada Petr , Mészáros Tamás , Meskiene Irute , Bögre László , Binarová Pavla
Published: June 2015

Stress‐activated plant mitogen‐activated protein (MAP) kinase pathways play roles in growth adaptation to the environment by modulating cell division through cytoskeletal regulation, but the mechanisms are poorly understood.

We performed protein interaction and phosphorylation experiments with cytoskeletal proteins, mass spectrometric identification of MPK6 complexes and immunofluorescence analyses of the microtubular cytoskeleton of mitotic cells using wild‐type, mpk6‐2 mutant and plants overexpressing the MAP kinase‐inactivating phosphatase, AP2C3.

We showed that MPK6 interacted with γ‐tubulin and co‐sedimented with plant microtubules polymerized in vitro. It was the active form of MAP kinase that was enriched with microtubules and followed similar dynamics to γ‐tubulin, moving from poles to midzone during the anaphase‐to‐telophase transition. We found a novel substrate for MPK6, the microtubule plus end protein, EB1c. The mpk6‐2 mutant was sensitive to 3‐nitro‐l‐tyrosine (NO2‐Tyr) treatment with respect to mitotic abnormalities, and root cells overexpressing AP2C3 showed defects in chromosome segregation and spindle orientation.

Our data suggest that the active form of MAP kinase interacts with γ‐tubulin on specific subsets of mitotic microtubules during late mitosis. MPK6 phosphorylates EB1c, but not EB1a, and has a role in maintaining regular planes of cell division under stress conditions.
Healthcare professionals under pressure in involuntary admission processes
Authors: van den Hooff Susanne , Leget Carlo , Goossensen Anne
Published: June 2015

The main objective of this paper is to describe how quality of care may be improved during an involuntary admission process of patients suffering from Korsakoff's syndrome. It presents an empirically grounded analysis with different perspectives on ‘doing good’ during this process. Family carers', healthcare professionals' and legal professionals' ways of understanding and ordering this problematic situation appear very different. This could prevent patients from getting the proper care they need, with risk of more suffering and quality of life below the minimum acceptable. All this possibly lead to immoral dehumanizing situations. Firstly, the background of our empirical study is sketched. Secondly, the different perspectives on ‘doing good’ are summarized and compared. Thirdly, the tensions arising from the different conceptualizations of autonomy and different types of responsibilities of the actors are clarified. A common ‘doing good’ during involuntary admission necessitates removal of any tensions within the relational network by weighing and balancing the different perspectives on autonomy and the resulting responsibilities. With this in mind, we propose a renewed time/action table for involuntary admission, which tends to address all patients' needs at the right time. The solution presented might help healthcare professionals, who are squeezed in between patients, family carers, legal professionals and overall rules, to create practices in which patients suffering from Korsakoff's syndrome can maintain their dignity and receive the care they need. Earlier interventions, timely and adequate diagnosis, and diminishment of tensions between the different actors by fine‐tuning their paradigmatic frameworks are suggested to be part of a solution.
Pediatric Lichen Planopilaris: Clinicopathologic Study of Four New Cases and a Review of the Literature
Authors: Christensen Kevin N. , Lehman Julia S. , Tollefson Megha M.
Published: June 2015

Lichen planopilaris (LPP) is a rare form of cicatricial alopecia that has occasionally been reported in children. Because of the limited number of patients reported, little information is available about demographic characteristics, clinical presentation, or treatment options for these patients. A retrospective chart review of LPP cases in patients under 18 years of age from 1976 to 2013 was performed to further define clinicopathologic features of pediatric LPP. Four pediatric LPP patients ages 13 to 16 years were identified (three male, one female). One patient had scalp pruritus and one had other cutaneous findings of lichen planus (LP). Perifollicular scale and scarring were the most common physical examination findings, although changes mimicking those of alopecia areata were observed. Three patients were treated with topical or intralesional steroids. One patient was treated with minocycline. Histopathologic findings included perifollicular interface and perifollicular fibrosis in all cases. There was focal interfollicular interface in two cases and mild dermal mucin in one case. LPP is exceedingly rare in children. It may be misdiagnosed as alopecia areata in children because of the lack of symptoms and other features of LP. There should be a high index of suspicion for LPP in children with alopecia that is unresponsive to standard treatment or who have findings that are atypical for more common childhood alopecias.
Influence of Asian dust storms on daily acute myocardial infarction hospital admissions
Authors: Teng Joshua Chen‐Yuan , Chan Yun‐Shan , Peng Yu‐I , Liu Tsai‐Ching
Published: June 2015

Objective

This study was the first to explore the relationship between Asian dust storm events (ADS) and acute myocardial infarction (AMI) hospital admissions by applying time series models.

Design and Sample

Nationwide population‐based hospitalization claims data in Taiwan were used. There were 143,063 AMI admissions during 2000–2009.

Measures

An autoregressive with exogenous variables (ARX) time series model was used to investigate the dynamic connection between AMI hospital admissions and ADS events.

Results

AMI hospitalizations significantly spiked on post‐ADS day three. Among the total population, 3.2 more cases of AMI admissions occurred on post‐ADS day three. When the data were stratified by age and gender, the same delayed effect was present in the male population, especially those aged 45–64 and over 74.

Conclusions

Our study shows that although an ADS event does not cause an immediate incidence of AMI, storms may increase AMI incidence through a delayed effect. Hence, AMI prevention is not only important during a dust storm, but particularly so in subsequent days. During the days after an ADS, exposure to dust should be minimized by staying indoors as much as possible and by wearing a mask when exposure to dust is unavoidable. This is especially true for working and older adults. Nurses at local public health centers can increase awareness and promote public safety by providing health information to local communities regarding the link between dust storms and AMI.
An examination of quality of care in Norwegian nursing homes – a change to more activities?
Authors: Kjøs Bente Ø. , Havig Anders K.
Published: June 2015

Background

Studies on Norwegian nursing homes have shown that the general care is at a relatively high level, while the level of physical and social activities is relatively low. As a response to these findings, the Norwegian government has stressed the importance of activities in various white papers and circulars and, in recent years, has launched several campaigns specifically aimed at increasing the level of activities.

Aim

The aim of the study was to examine the following: (i) how the government has succeeded in increasing the level of physical and social activities in Norwegian nursing homes; (ii) how the level of activities compares to the general care; and (iii) how the level of activities and the general care are influenced by the following facility characteristics: residents’ mobility level, total staffing levels, ratio of RNs, ratio of unlicensed staff and ward size.

Method

A cross‐sectional survey of forty nursing home wards throughout Norway was used to collect the data.

Results

On a scale ranging from 1 to 7, the staff members assess the activity dimension to be 4.31 and the general care dimension to be 5.66. The activity dimension was significantly negatively correlated with the ratio of unlicensed staff, the ratio of Registered Nurses and the residents’ mobility level, while the general care dimension was significantly negatively correlated with the ratio of unlicensed staff.

Conclusion

The study shows that the level of physical and social activities offered to the residents is relatively low, while the general care level is significantly higher, in line with earlier studies. Consequently, the government has not succeeded with its current policy to increase the level of activities in nursing homes. The relationship between the two quality dimensions and the explanatory variables shows that nursing home quality is a complicated phenomenon.
McMahan on Speciesism and Deprivation
Authors: Grau Christopher
Published: June 2015

Jeff McMahan has long shown himself to be a vigorous and incisive critic of speciesism, and in his essay “Our Fellow Creatures” he has been particularly critical of speciesist arguments that draw inspiration from Wittgenstein. In this essay I consider his arguments against speciesism generally and the species‐norm account of deprivation in particular. I argue that McMahan's ethical framework (as outlined in The Ethics of Killing) is more nuanced and more open to the incorporation of speciesist intuitions regarding deprivation than he himself suggests. Specifically, I argue that, given his willingness to include a comparative dimension in his “Intrinsic Potential Account” he ought to recognize species as a legitimate comparison class. I also argue that a sensible speciesism can be pluralist and flexible enough to accommodate many of McMahan's arguments in defense of “moral individualist” intuitions. In this way, I hope to make the case for at least a partial reconciliation between McMahan and the “Wittgensteinian speciesists”, e.g. Cora Diamond, Stephen Mulhall, and Raimond Gaita.
Positive impact of dietary water on in vivo epidermal water physiology
Authors: Palma M. L. , Tavares L. , Fluhr J. W. , Bujan M. J. , Rodrigues L. M.
Published: June 2015

Background/purpose

The importance of water in human physiology is well known, also for skin functionality. This study was conducted to assess the effects of dietary water on epidermal skin hydration in healthy females.

Methods

Thirty‐four healthy females (mean 24.5 ± 6.34 years old) were selected and characterized according to their dietary daily habits, by a previously validated Food Frequency Questionnaire. For 1 month, these subjects were asked to add 2 L/day of water to their regular dietary habits. Measurements took place at day D0, D15, and D30, and involved general variables (body weight, blood pressure, Body Mass Index) and specific skin physiological variables in five anatomical sites (ventral forearm, anterior leg, dorsal hand, zygomatic area, and forehead) involving epidermal superficial and deep hydration, by capacitance and transepidermal water loss (TEWL).

Results

This water overload (2 L/day/30 days) did not change the blood volume or weight of the individuals. However, both superficial and deep skin hydration were clearly in those individuals that regularly consumed lees water per day. No significant effect was observed in the TEWL.

Conclusions

This study clearly suggests that dietary water intake seems to influence skin water content. Nevertheless further in vivo investigations involving other variables, such as biomechanical descriptors, should follow to look deeper into this aspect of skin physiology.
Elimination of Thermal Bridges in the Construction of a Flat Low-Pressure Solar Collector by Means of a Vacuum Thermal Insulation Bushing
Authors: Rybár Radim , Kudelas Dušan , Beer Martin , Horodníková Jana
Published: June 2015

The paper deals with the elimination of heat losses in a flat low-pressure solar collector caused by direct contact of outlet pipefitting and the Al–Mg collector box. This is manifested by reduced thermal efficiency of the solar collector, especially in cold season, which is in direct conflict with its application, i.e., high-temperature application and application in cold conditions. The solution lies in the proposed new structural element—the vacuum thermal insulation bushing, which is able to simultaneously provide vacuum tightness of the collector box and interrupt the existing thermal conductive connection. The design philosophy was to transfer the vacuum insulating function component from the original pipe—collector box connection to the thermally insulated place bushing—collector box. Two prototypes were constructed and built into experimental vacuum chamber. Significant increase in the temperature gradient was found in performed experiments. Thermal insulation function, vacuum tightness, and resistance to thermomechanical stress have been demonstrated. The thermal insulation function has also been described through the simulations on a computational model, using finite volume method. The proposed solution of bushing has also successfully become the subject of patent protection.
Characterization of Pulsating Submerged Jet—A Particle Image Velocimetry Study
Authors: Yadav Harekrishna , Srivastava Atul , Agrawal Amit
Published: June 2015

An experimental investigation has been performed to determine the flow characteristics of an axisymmetric submerged water jet with superimposed periodically oscillating flow. The objective of the study is to quantify in detail the near field of a pulsating jet using the particle image velocimetry (PIV) technique. The amplitude and frequency of oscillations are varied separately and the effect of each parameter is determined for a range of Reynolds numbers (ReD = 1602, 2318, and 3600). The experimental results indicate that for a given Reynolds number and amplitude, with an increase in the frequency of pulsation, the vortex formation shifts toward the nozzle exit. The number of vortices also increases with an increase in the jet pulsation frequency. Broadening of the jet and shortening of the potential core length are also observed. This indicates that mixing with the surrounding fluid is higher with pulsating jet even at relatively low Reynolds numbers. It is observed that frequency up to a critical frequency helps increase entrainment of the surrounding fluid. An upper critical frequency beyond which pulsation does not affect the entrainment is also determined. These results should eventually lead to a better understanding of the physical phenomena responsible for enhanced heat transfer rates in the presence of pulsating jets.
Amid panic, a chance to learn about MERS
Authors: Kupferschmidt Kai
Published: June 2015

South Korea's explosive outbreak gives scientists fresh opportunities to study the virus.
Luminance-dependent visual processing enables moth flight in low light
Authors: Sponberg Simon , Dyhr Jonathan P. , Hall Robert W. , Daniel Thomas L.
Published: June 2015

Not too fast and not too slow

Moths are typically active during dawn and dusk when light levels are low and vision is challenging. Slower visual response times can allow for greater light sensitivity, but flying insects are both moving and tracking moving targets, making such tradeoffs potentially problematic. Using a combination of modeling and experiments, Sponberg
et al.
show that moths are able to avoid this potential decrease in visual acuity (see the Perspective by Warrant). This is because the point at which their perception of movement would be compromised is just above the natural frequency at which flowers sway. Thus, insect vision is precisely adapted to the light and movement conditions of their environment.

Science
, this issue p.
1245
; see also p.
1212
Kinetochore attachment sensed by competitive Mps1 and microtubule binding to Ndc80C
Authors: Ji Zhejian , Gao Haishan , Yu Hongtao
Published: June 2015

How cells sense connected chromosomes

Cells have a “checkpoint” that pauses cell division until all chromosomes are properly arranged on the mitotic spindle to allow precise distribution of one copy of each chromosome to each daughter cell. Hiruma
et al.
and Ji
et al.
explain the molecular mechanism by which cells sense that they are ready to divide. The protein kinase MPS1 associates with a protein complex at the kinetochore of the chromosome. Its activity produces signals that pause the cell cycle. When the chromosome becomes properly attached to the mitotic spindle, microtubules of the spindle physically compete for binding to the same site on the kinetochore where MPS1 is bound. Thus, once the kinetochore is properly attached, MPS1 dissociates, the inhibitory signal is lost, and cell division is allowed to proceed.

Science
, this issue pp.
1264
and
1260
Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity
Authors: Gaudet Ryan G. , Sintsova Anna , Buckwalter Carolyn M. , Leung Nelly , Cochrane Alan , Li Jianjun , Cox Andrew D. , Moffat Jason , Gray-Owen Scott D.
Published: June 2015

Detecting Gramnegative bacteria

Invariant molecules specific to different classes of microbes, but not expressed by eukaryotic cells, alert the immune system to a potential invader. Gaudet
et al.
identified one such molecule expressed by a variety of Gram-negative bacteria: the monosaccharide heptose-1,7-bisphosphate (HBP) (see the Perspective by Brubaker and Monack). HBP is an intermediate in the synthesis of lipopolysaccharide, a major component of bacterial cell walls. Rather than alerting the immune system through traditional pathogen detection pathways, such as Toll-like receptors, HBP signals through the host protein TIFA (TRAF-interacting protein with forkhead-associated domain), which activates both innate and adaptive immune responses to control the infection.

Science
, this issue p.
1251
; see also p.
1207
Global Epidemiology of Campylobacter Infection
Authors: Kaakoush Nadeem O. , Castaño-Rodríguez Natalia , Mitchell Hazel M. , Man Si Ming
Published: June 2015

Campylobacter jejuni
infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of campylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that campylobacteriosis is endemic in these areas, especially in children. In addition to
C. jejuni
, there is increasing recognition of the clinical importance of emerging
Campylobacter
species, including
Campylobacter concisus
and
Campylobacter ureolyticus
. Poultry is a major reservoir and source of transmission of campylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, campylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of
Campylobacter
infection.
Transmitted Extended-Spectrum Extensively Drug-Resistant Tuberculosis in Beijing, China, with Discordant Whole-Genome Sequencing Analysis Results
Authors: Li Hao , Kayani Masood ur Rehman , Gu Yunting , Wang Xiaobo , Zhu Ting , Duan Hongfei , Ma Yifeng , Huang Hairong , Javid Babak
Published: June 2015

Drug resistance to tuberculosis remains a major public health threat. Here, we report two cases of extended-spectrum extensively drug-resistant (XXDR) tuberculosis showing resistance to most first- and second-line agents. The results of a correlation of whole-genome sequencing (WGS) and phenotypic testing were discordant, suggesting that overreliance on WGS may miss clinically relevant resistance in extensively drug-resistant disease.
Brown-Pigmented Mycobacterium mageritense as a Cause of Prosthetic Valve Endocarditis and Bloodstream Infection
Authors: McMullen Allison R. , Mattar Caline , Kirmani Nigar , Burnham Carey-Ann D.
Published: June 2015

Mycobacterium
spp. are a rare cause of endocarditis. Herein, we describe a case of
Mycobacterium mageritense
prosthetic valve endocarditis. This organism produced an unusual brown pigment on solid media. Cultures of valve tissue for acid-fast bacilli might be considered in some cases of apparently culture-negative prosthetic valve endocarditis.
Evaluation of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Identification of Nontuberculous Mycobacteria from Clinical Isolates
Authors: Rodríguez-Sánchez Belén , Ruiz-Serrano María Jesús , Marín Mercedes , López Roa Paula , Rodríguez-Créixems Marta , Bouza Emilio
Published: June 2015

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for the identification of nontuberculous mycobacterial (NTM) isolates was evaluated in this study. Overall, 125 NTM isolates were analyzed by MALDI-TOF and GenoType CM/AS. Identification by 16S rRNA/
hsp65
sequencing was considered the gold standard. Agreements between MALDI-TOF and GenoType CM/AS with the reference method were, respectively, 94.4% and 84.0%. In 17 cases (13.6%), results provided by GenoType and MALDI-TOF were discordant; however, the reference method agreed with MALDI-TOF in 16/17 cases (94.1%;
P
= 0.002).
Restriction of HIV-1 Requires the N-Terminal Region of MxB as a Capsid-Binding Motif but Not as a Nuclear Localization Signal
Authors: Schulte Bianca , Buffone Cindy , Opp Silvana , Di Nunzio Francesca , De Souza Aranha Vieira Daniel Augusto , Brandariz-Nuñez Alberto , Diaz-Griffero Felipe
Published: June 2015

The interferon alpha (IFN-α)-inducible restriction factor MxB blocks HIV-1 infection after reverse transcription but prior to integration. Fate-of-capsid experiments have correlated the ability of MxB to block HIV-1 infection with stabilization of viral cores during infection. We previously demonstrated that HIV-1 restriction by MxB requires capsid binding and oligomerization. Deletion and gain-of-function experiments have mapped the HIV-1 restriction ability of MxB to its N-terminal 25 amino acids. This report reveals that the N-terminal 25 amino acids of MxB exhibit two separate functions: (i) the ability of MxB to bind to HIV-1 capsid and (ii) the nuclear localization signal of MxB, which is important for the ability of MxB to shuttle into the nucleus. To understand whether MxB restriction of HIV-1 requires capsid binding and/or nuclear localization, we genetically separated these two functions and evaluated their contributions to restriction. Our experiments demonstrated that the
11
RRR
13
motif is important for the ability of MxB to bind capsid and to restrict HIV-1 infection. These experiments suggested that capsid binding is necessary for the ability of MxB to block HIV-1 infection. Separately from the capsid binding function of MxB, we found that residues
20
KY
21
regulate the ability of the N-terminal 25 amino acids of MxB to function as a nuclear localization signal; however, the ability of the N-terminal 25 amino acids to function as a nuclear localization signal was not required for restriction.

IMPORTANCE
MxB/Mx2 blocks HIV-1 infection in cells from the immune system. MxB blocks infection by preventing the uncoating process of HIV-1. The ability of MxB to block HIV-1 infection requires that MxB binds to the HIV-1 core by using its N-terminal domain. The present study shows that MxB uses residues
11
RRR
13
to bind to the HIV-1 core during infection and that these residues are required for the ability of MxB to block HIV-1 infection. We also found that residues
20
KY
21
constitute a nuclear localization signal that is not required for the ability of MxB to block HIV-1 infection.
Rotavirus NSP3 Is a Translational Surrogate of the Poly(A) Binding Protein-Poly(A) Complex
Authors: Gratia Matthieu , Sarot Emeline , Vende Patrice , Charpilienne Annie , Baron Carolina Hilma , Duarte Mariela , Pyronnet Stephane , Poncet Didier
Published: June 2015

Through its interaction with the 5′ translation initiation factor eIF4G, poly(A) binding protein (PABP) facilitates the translation of 5′-capped and 3′-poly(A)-tailed mRNAs. Rotavirus mRNAs are capped but not polyadenylated, instead terminating in a 3′ GACC motif that is recognized by the viral protein NSP3, which competes with PABP for eIF4G binding. Upon rotavirus infection, viral, GACC-tailed mRNAs are efficiently translated, while host poly(A)-tailed mRNA translation is, in contrast, severely impaired. To explore the roles of NSP3 in these two opposing events, the translational capabilities of three capped mRNAs, distinguished by either a GACC, a poly(A), or a non-GACC and nonpoly(A) 3′ end, have been monitored after electroporation of cells expressing all rotavirus proteins (infected cells) or only NSP3 (stably or transiently transfected cells). In infected cells, we found that the magnitudes of translation induction (GACC-tailed mRNA) and translation reduction [poly(A)-tailed mRNA] both depended on the rotavirus strain used but that translation reduction not genetically linked to NSP3. In transfected cells, even a small amount of NSP3 was sufficient to dramatically enhance GACC-tailed mRNA translation and, surprisingly, to slightly favor the translation of both poly(A)- and nonpoly(A)-tailed mRNAs, likely by stabilizing the eIF4E-eIF4G interaction. These data suggest that NSP3 is a translational surrogate of the PABP-poly(A) complex; therefore, it cannot by itself be responsible for inhibiting the translation of host poly(A)-tailed mRNAs upon rotavirus infection.

IMPORTANCE
To control host cell physiology and to circumvent innate immunity, many viruses have evolved powerful mechanisms aimed at inhibiting host mRNA translation while stimulating translation of their own mRNAs. How rotavirus tackles this challenge is still a matter of debate. Using rotavirus-infected cells, we show that the magnitude of cellular poly(A) mRNA translation differs with respect to rotavirus strains but is not genetically linked to NSP3. Using cells expressing rotavirus NSP3, we show that NSP3 alone not only dramatically enhances rotavirus-like mRNA translation but also enhances poly(A) mRNA translation rather than inhibiting it, likely by stabilizing the eIF4E-eIF4G complex. Thus, the inhibition of cellular polyadenylated mRNA translation during rotavirus infection cannot be attributed solely to NSP3 and is more likely the result of global competition between viral and host mRNAs for the cellular translation machinery.
Mobile Whole Slide Imaging (mWSI): a low resource acquisition and transport technique for microscopic pathological specimens
Authors: Auguste Louis , Palsana Dhaval
Published: June 2015

The Open Mobile Telepathology System (OMT) is a combination of two components, the Pocket Electronic Health Record (pEHR) and the Mobile Whole Slide Imaging (mWSI) app. This system was created over the course of this study to help reduce the cost of telepathology in developing countries. The affordable system as described will help to expedite the diagnostic process in low-resource environments and provide more patients with better health outcomes. The OMT system offers a number of advantages to the standard Whole Slide Imaging machines. It can be deployed at a fraction of the cost, the images are more easily transportable at an average image size of less than 500 MBs and any worker, even someone without any knowledge of pathology, can perform the scans; also, components can be replaced and upgraded at a minimal cost, offering a large advantage to low resource and rural environments. The OMT system utilises a standard light microscope with a custom built 3D adaptor and the iPhone 5s. Acquired mWSIs can be transported through the cloud using the pEHR database and accessed through web and mobile platforms. Therefore it can be used in any part of the world with an Internet connection. The study follows the step-by-step process used to acquire mWSIs of various stains including H&E stains, and thin preps. The results of the tests have been found to be of a diagnostic quality and the imaging process as described has been optimised and standardised over the course of the 2-year study.
Ignoring floor and ceiling effects may underestimate the effect of carotid artery stenting on cognitive performance
Authors: Scherr Martin , Kunz Alexander , Doll Anselm , Mutzenbach Johannes Sebastian , Broussalis Erasmia , Bergmann Hans Jürgen , Kirschner Margarita , Trinka Eugen , Killer-Oberpfalzer Monika
Published: June 2015

Introduction

Data on neuropsychological outcome after carotid artery stenting (CAS) remain inconsistent, furthermore cognitive outcome seems to be unpredictable in the individual case. Previous studies reporting improvement or decline might be due to ceiling and floor effects of the applied cognitive tests. We applied cognitive testing before and after CAS, avoiding the pitfall of ceiling and floor effects.

Methods

In our prospective database, we identified 72 patients free of clinical stroke with ≥70% carotid artery stenosis, who were treated with CAS. They were administered a neurocognitive test battery before and 3 months after CAS to compare cognitive performance before and after CAS. To avoid ceiling and floor effects of test performances, we additionally analysed subgroups of patients without baseline floor and ceiling cognitive performance.

Results

Pre-interventional to post-interventional cognitive performance improved significantly in the subtests measuring verbal episodic memory; deterioration was observed in spatial memory. The subgroups of patients without baseline floor and ceiling cognitive performance improved in measures of global cognition, verbal episodic memory (patients with left-sided CAS) and divided attention (patients with right-sided CAS); we observed no significant effects in the other domains.

Conclusions

Ignoring floor and ceiling effects may underestimate the impact of CAS on cognitive performance.
Republished: A novel route of revascularization in basilar artery occlusion and review of the literature
Authors: Morales Alejandro , Parry Phillip Vaughan , Jadhav Ashutosh , Jovin Tudor
Published: June 2015

Ischemia of the basilar artery is one of the most devastating types of arterial occlusive disease. Despite treatment of basilar artery occlusions (BAO) with intravenous tissue plasminogen activator, antiplatelet agents, intra-arterial therapy or a combination, fatality rates remain high. Aggressive recanalization with mechanical thrombectomy is therefore often necessary to preserve life. When direct access to the basilar trunk is not possible, exploration of chronically occluded vessels through collaterals with angioplasty and stenting creates access for manual aspiration. We describe the first report of retrograde vertebral artery (VA) revascularization using thyrocervical collaterals for anterograde mechanical aspiration of a BAO followed by stenting of the chronically occluded VA origin. Our novel retrograde–anterograde approach resulted in resolution of the patient's clinical stroke syndrome.
Finite BRST–BFV transformations for dynamical systems with second-class constraints
Authors: Batalin Igor A. , Lavrov Peter M. , Tyutin Igor V.
Published: June 2015

We study finite field-dependent BRST–BFV transformations for dynamical systems with first- and second-class constraints within the generalized Hamiltonian formalism. We find explicitly their Jacobians and the form of a solution to the compensation equation necessary for generating an arbitrary finite change of gauge-fixing functionals in the path integral.
TOWARD MULTISCALE MODELING OF WAVE PROPAGATION IN ARTERIES
Authors: RAUSTIN RYAN , MOHAMMADI HADI
Published: June 2015

In this study, we apply a novel numerical technique for modeling the propagation of mechanical wave in the human arteries using the multiscale method. We define a particle region characterized by molecular dynamics (MD) method which is surrounded by a continuous region characterized by a finite element (FE) method. The interface between the two models are defined so as to minimize spurious reflections at the interface. This is a preliminary work for the modeling of the mechanical stability of atherosclerosis plaques using multiscale method. The model offered has extensive application in cell mechanics.
β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade
Authors: Karimi Galougahi Keyvan , Liu Chia-Chi , Garcia Alvaro , Fry Natasha A. , Hamilton Elisha J. , Figtree Gemma A. , Rasmussen Helge H.
Published: June 2015

Dysregulated nitric oxide (NO)- and superoxide (O2·−)-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na+-K+ pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na+-K+ pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47 phox and membranous p22 phox NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47 phox to p22 phox with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na+-K+ pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22 phox with p47 phox, abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na+-K+ pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na+-K+ pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes.
Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure
Authors: Pandit Sudip , Jo Ji Yoon , Lee Sang Ung , Lee Young Jae , Lee So Yeong , Ryu Pan Dong , Lee Jung Un , Kim Hyun-Woo , Jeon Byeong Hwa , Park Jin Bong
Published: June 2015

γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents ( Itonic) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABAA receptors (GABAARs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of Itonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The Itonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced Itonic sensitivity to THIP argued for the decreased function of GABAAR δ subunits in HF, whereas similar Itonic sensitivity to benzodiazepines argued against the difference of γ2 subunit-containing GABAARs in SHAM and HF rats. HF Itonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal Itonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF Itonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABAARs function, the enhanced astroglial GABA uptake-induced attenuation of Itonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure.
Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia
Authors: Massaro An N. , Govindan R. B. , Vezina Gilbert , Chang Taeun , Andescavage Nickie N. , Wang Yunfei , Al-Shargabi Tareq , Metzler Marina , Harris Kari , du Plessis Adre J.
Published: June 2015

Impaired cerebral autoregulation may contribute to secondary injury in newborns with hypoxic-ischemic encephalopathy (HIE). Continuous, noninvasive assessment of cerebral pressure autoregulation can be achieved with bedside near-infrared spectroscopy (NIRS) and systemic mean arterial blood pressure (MAP) monitoring. This study aimed to evaluate whether impaired cerebral autoregulation measured by NIRS-MAP monitoring during therapeutic hypothermia and rewarming relates to outcome in 36 newborns with HIE. Spectral coherence analysis between NIRS and MAP was used to quantify changes in the duration [pressure passivity index (PPI)] and magnitude (gain) of cerebral autoregulatory impairment. Higher PPI in both cerebral hemispheres and gain in the right hemisphere were associated with neonatal adverse outcomes [death or detectable brain injury by magnetic resonance imaging (MRI), P < 0.001]. NIRS-MAP monitoring of cerebral autoregulation can provide an ongoing physiological biomarker that may help direct care in perinatal brain injury.