bluuebunny/crossref_metadata_2025 huggingface dataset:
Heme-iron plays a key role in the regulation of the Ess/Type VII secretion system ofStaphylococcus aureusRN6390
Authors: Casabona M. Guillermina , Kneuper Holger , de Lima Daniela Alferes , Harkins Catriona P. , Zoltner Martin , Hjerde Erik , Holden Matthew T.G. , Palmer Tracy
Published: June 2017

TheStaphylococcus aureusType VII protein secretion system (T7SS) plays important roles in virulence and intra-species competition. Here we show that the T7SS in strain RN6390 is activated by supplementing the growth medium with hemoglobin, and its cofactor hemin (heme B). Transcript analysis and secretion assays suggest that activation by hemin occurs at a transcriptional and a post-translational level. Loss of T7 secretion activity by deletion ofessCresults in upregulation of genes required for iron acquisition. Taken together these findings suggest that the T7SS plays a role in iron homeostasis in at least someS. aureusstrains.
High current optogenetic channels for stimulation and inhibition of primary rat cortical neurons
Authors: Jin Lei , Joest Eike Frank , Li Wenfang , Gao Shiqiang , Offenhäusser Andreas , Maybeck Vanessa
Published: June 2017

ChR2-XXL and GtACR1 are currently the cation and anion ends of the optogenetic single channel current range. These were used in primary rat cortical neuronsin vitroto manipulate neuronal firing patterns. ChR2-XXL provides high cation currents via elevated light sensitivity and a prolonged open state. Stimulating ChR2-XXL expressing putative presynaptic neurons induced neurotransmission. Moreover, stable depolarisation block could be generated in single neurons using ChR2-XXL, proving that ChR2-XXL is a promising candidate forin vivoapplications of optogenetics, for example to treat peripheral neuropathic pain. We also addressed an anion channelrhodopsin (GtACR1) for the next generation of optogenetic neuronal inhibition in primary rat cortical neurons. GtACR1‘s light-gated chloride conduction was verified in primary neurons and the efficient photoinhibition of action potentials, including spontaneous activity, was shown. Our data also implies that the chloride concentration in neurons decreases during neural development. In both cases, we find surprising applications of these high current channels. For ChR2-XXL inhibition and stimulation are possible, while for GtACR1 the role of Cl−during neural development becomes a new optogenetic target.
Bacterial communication and relevance of quantum theory
Authors: Majumdar Sarangam , Roy Sisir
Published: June 2017

The recent findings confirm that bacteria communicate each other through chemical and electrical signals. Bacteria use chemical signaling molecules which are called as quorum sensing molecules(QSMs) or autoinducers. Moreover, the ion channels in bacteria conduct a long-range electrical signaling within biofilm communities through propagated waves of potassium ions and biofilms attracts other bacterial species too. Both communication process are used by bacteria to make their own survival strategies. In this article, we model this bacterial communication mechanism by complex Ginzburg- Landau equation and discuss the formation of patterns depending on kinematic viscosity associated with internal noise. Again, the potassium wave propagation is described by the non-linear Schrödinger equation in a dissipative environment. By adding perturbation to non-linear Schrödinger equation one arrives at Complex Ginzburg-Landau equation. In this paper we emphasize that at the cellular level(bacteria) we use Complex Ginzburg - Landau equation as a perturbed Nonlinear Schrödinger equation to understand the bacterial communication as well as pattern formation in Biofilms for certain range of kinematic viscosity which can be tested in laboratory experiment. Here, the perturbation is due to the existence of non thermal fluctuations associated to the finite size of the bacteria. It sheds new light on the relevance of quantum formalism in understanding the cell to cell communication.
Haplotype and Repeat Separation in Long Reads
Authors: Tischler German
Published: June 2017

Resolving the correct structure and succession of highly similar sequence stretches is one of the main open problems in genome assembly. For non haploid genomes this includes determining the sequences of the different haplotypes. For all but the smallest genomes it also involves separating different repeat instances. In this paper we discuss methods for resolving such problems in third generation long reads by classifying alignments between long reads according to whether they represent true or false read overlaps. The main problem in this context is the high error rate found in such reads, which greatly exceeds the amount of difference between the similar regions we want to separate. Our methods can separate read classes stemming from regions with as little as 1% difference.
A Cross-Sectional Study ofStaphylococcus AureusColonization and the Nasal and Oropharyngeal Microbiomes
Authors: Kates Ashley E. , Dalman Mark , Torner James C. , Smith Tara C.
Published: June 2017

Background

Staphylococcus aureusis a frequent cause of both infections globally. Colonization with the organism is known to increase the risk of developing infections and occurs in roughly one third of the general population. While many factors influence colonization, it has been demonstrated other members of the microbiome influence colonization withS. aureus. Here, we assessed the nasal and oropharyngeal microbiomes of healthy participants in relation toS. aureuscolonization in a cross-sectional study using 16s rRNA sequencing of the v1-v3 region. As livestock workers have also been shown to be at an increased risk of carriage, we have also assessed microbiota differences in colonization status in a population of livestock workers.

Results

In both the nares and oropharynx, there were no microbiota differentially abundant between colonized and non-colonized persons. However, there was a significant difference in the beta diversity (Bray-Curtis distances) between carriers and non-carriers (P=0.002). When considering carriage stratified by livestock exposure, there were a number of differences. Most notably, colonized livestock workers had significantly morePorphyomonas(2-fold change = -8.54,P= 0.03) than the non-colonized livestock workers.

Conclusions

S. aureusis a frequent colonizer of the human upper respiratory tract, including the nares and oropharynx and causes a wide range of infections. Livestock workers are at increased risk for carriage. Interventions such as improving oral hygiene may lead to decreasedS. aureuscarriage by reducing other bacterial species such asPorphyomonas. Larger, longitudinal studies are needed to better explore what microorganisms may be associated withS. aureuscolonization.
Objective (Real-world) Motion Responses in Scene Responsive Regions
Authors: Hacialihafiz Didem Korkmaz , Bartels Andreas
Published: June 2017

We perceive scenes as stable even when eye movements induce retinal motion, for example during pursuit of a moving object. Mechanisms mediating perceptual stability have primarily been examined in motion regions of the dorsal visual pathway. Here we examined whether motion responses in human scene regions are encoded in eye- or world centered reference frames. We recorded brain responses in human participants using fMRI while they performed a well-controlled visual pursuit paradigm previously used to examine dorsal motion regions. In addition, we examined effects of content by using either natural scenes or their Fourier scrambles. We found that parahippocampal place area (PPA) responded to motion only in world- but not in eye-centered coordinates, regardless of scene content. The occipital place area (OPA) responded to both, objective and retinal motion equally, and retrosplenial cortex (RSC) had no motion responses but responded to pursuit. Only PPA’s objective motion responses were higher during scenes than scrambled images, although there was a similar trend in OPA. These results indicate a special role of PPA in representing its content in real-world coordinates. Our results question a strict subdivision of dorsal “what” and ventral “where” streams, and suggest a role of PPA in contributing to perceptual stability.
On the Number of Siblings andp-th Cousins in a Large Population Sample
Authors: Shchur Vladimir , Nielsen Rasmus
Published: June 2017

1.

The number of individuals in a random sample with close relatives in the sample is a quantity of interest when designing Genome Wide Association Studies (GWAS) and other cohort based genetic, and non-genetic, studies. In this paper, we develop expressions for the distribution and expectation of the number ofp-th cousins in a sample from a population of sizeNunder two diploid Wright-Fisher models. We also develop simple asymptotic expressions for large values ofN. For example, the expected proportion of individuals with at least onep-th cousin in a sample ofKindividuals, for a diploid dioecious Wright-Fisher model, is approximately 1 −e−(22p−1)K/N. Our results show that a substantial fraction of individuals in the sample will have at least a second cousin if the sampling fraction (K/N) is on the order of 10−2. This confirms that, for large cohort samples, relatedness among individuals cannot easily be ignored.
Multiplexed live-cell visualization of endogenous proteins with nanometer precision by fluorobodies
Authors: Klein Alina , Hank Susanne , Raulf Anika , Tissen Felicitas , Heilemann Mike , Wieneke Ralph , Tampé Robert
Published: June 2017

The visualization of endogenous proteins in living cells is a major challenge. A fundamental requirement for spatiotemporally precise imaging is a minimal disturbance of protein function at high signal-to-background ratio. Current approaches for visualization of native proteins in living cells are limited by dark emitting, bulky fluorescent proteins and uncontrollable expression levels. Here, we demonstrate the labeling of endogenous proteins using nanobodies with site-specifically engineered bright organic fluorophores, named fluorobodies. Their fast and fine-tuned intracellular transfer by microfluidic cell squeezing allowed for low background, low toxicity, and high-throughput. Multiplexed imaging of distinct cellular structures was facilitated by specific protein targeting, culminating in live-cell super-resolution imaging of protein networks. The high-throughput delivery of engineered nanobodies will open new avenues in visualizing native cellular structures with unprecedented accuracy in cell-based screens.
Organizing for Radical Innovation: Exploring Novel Insights
Authors: Colombo Massimo G. , von Krogh Georg , Rossi‐Lamastra Cristina , Stephan Paula E.
Published: June 2017

While radical innovation brings extensive economic rewards to firms, it is an activity fraught with risk. Prior research has shown that such risks mainly stem from organizational arrangements (at the level of individuals, teams, firms, and inter firm collaborations), which are inadequate or inefficient to support radical innovation. The papers in this special issue on “Organizing for Radical Innovation: Exploring Novel Insights” take stock of past work and provide novel insights about how to organize for radical innovation. The overarching idea linking them is that radical innovation hinges on the creation of fundamentally new knowledge and the continuous stimulation of creativity. Thus, organizational arrangements that support such processes play a crucial role in explaining and predicting the successful commercialization of breakthrough ideas, radically new technologies, and solutions. In particular, the field of science, which in essence aims for the systematic production of new knowledge, can be a valid source of inspiration for how individuals, teams, firms, and interfirm collaborations should organize for radical innovation. Moving from these premises, in this introductory paper, we offer an overview of the topic of organizing for radical innovation and highlight possible linkages with the organizing principles. Then, we summarize the main insights from the papers in this special issue and use their core ideas to sketch a novel research agenda for scholars working at the intersection of organization theory, economics of science, and management of innovation.
Mathermycin, a Lantibiotic from the Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652
Authors: Chen Erquan , Chen Qi , Chen Shaoming , Xu Bing , Ju Jianhua , Wang Huan
Published: June 2017

Lantibiotics are antimicrobial peptides belonging to the family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and feature thioether linkages in their structures. In this study, we identified the biosynthetic gene cluster of a cinnamycin analog, named mathermycin, from
Marinactinospora thermotolerans
SCSIO 00652 and reconstituted its biosynthesis in
Streptomyces lividans
and
Escherichia coli
. Key posttranslational modification enzymes of mathermycin were characterized. Mathermycin exhibited antimicrobial activity and therefore represents an example of cinnamycin-like lantibiotics from
Marinactinospora
species.

IMPORTANCE
The discovery of new antimicrobial compounds that can be used as potential drugs is in urgent need due to increasing bacterial resistance to current antibiotics. Lantibiotics are important antimicrobial compounds that have found applications in both the clinic setting and food industry. We report here the discovery of a new lantibiotic, mathermycin, from a marine-derived
Marinactinospora thermotolerans
strain and elucidation of its biosynthesis. We also demonstrate that mathermycin possesses antimicrobial activity toward a
Bacillus
strain.
Multiple supratentorial subependymomas causing obstructive hydrocephalus
Authors: Schroeder Jason , LeFever Devon , Entezami Pouya , Mrak Robert E
Published: June 2017

Introduction

Subependymomas are benign intraventricular tumours that most often occur asymptomatically and are found incidentally on autopsy. Symptomatic examples requiring surgical intervention are exceedingly rare.

Case presentation

A 55-year-old man with no history of neurological symptoms presented with multiple episodes of loss of consciousness and increasing headaches. MRI revealed a lobulated intraventricular mass centred at the right Foramen of Monro. Obstructive hydrocephalus with localised midline shift and a second lesion were noted. Right frontal craniotomy with total removal via transcortical resection was performed.

Discussion

Symptomatic subependymomas generally present with signs of hydrocephalus due to obstruction of cerebrospinal fluid pathways. There is only one other reported case of multifocal subependymomas in a symptomatic patient. An example of multiple supratentorial subependymomas causing obstructive hydrocephalus has not been previously reported.

Conclusions

Multiple subependymomas are rare. Judicious surgical management with full excision led to symptomatic improvement in our patient.
A 15-year-old Nepali boy with metastasised colorectal cancer
Authors: Pinto Chloe , Perry Zvi Howard
Published: June 2017

Nepal suffers from vast inequalities in modern healthcare. The low-income country wrestles with far-reaching insufficiencies in minimal preventative medicine, health awareness, limited infrastructure and difficult topography—all of which contribute to poor access and poor care-seeking behaviour. Our patient came from rural Nepal, where primary healthcare outposts are frequently understaffed and underequipped. He received supportive treatment in his village from the time symptoms presented until he was diagnosed 2 years later, at a tertiary medical centre, with colorectal cancer. An examination of the relevant literature indicates that younger patients often present in later stages of the disease due to initial misdiagnosis or overlooking colorectal cancer as a possibility. Beyond the rarity of the patient’s condition, the logistical and financial obstacles he faced in Nepal, particularly outside of the capital of Kathmandu, deterred his access to a higher level of care and delayed his correct diagnosis and treatment.
Out-of-pocket expenditures for prevention and treatment of cardiovascular disease in general and specialised cardiac hospitals in Addis Ababa, Ethiopia: a cross-sectional cohort study
Authors: Tolla Mieraf Taddesse , Norheim Ole Frithjof , Verguet Stéphane , Bekele Abebe , Amenu Kassahun , Abdisa Senbeta Guteta , Johansson Kjell Arne
Published: June 2017

Background

Cardiovascular disease poses a great financial risk on households in countries without universal health coverage like Ethiopia. This paper aims to estimate the magnitude and intensity of catastrophic health expenditure and factors associated with catastrophic health expenditure for prevention and treatment of cardiovascular disease in general and specialised cardiac hospitals in Addis Ababa.

Methods and findings

We conducted a cross-sectional cohort study among individuals who sought cardiovascular disease care in selected hospitals in Addis Ababa during February to March 2015 (n=589, response rate 94%). Out-of-pocket payments on direct medical costs and direct non-medical costs were accounted for. Descriptive statistics was used to estimate the magnitude and intensity of catastrophic health expenditure within households, while logistic regression models were used to assess the factors associated with it.

About 27% (26 .7;95% CI 23.1 to 30.6) of the households experienced catastrophic health expenditure, defined as annual out-of-pocket payments above 10% of a household’s annual income. Family support was the the most common coping mechanism. Low income, residence outside Addis Ababa and hospitalisation increased the likelihood of experiencing catastrophic health expenditure. The bottom income quintile was about 60 times more likely to suffer catastrophic health expenditure compared with the top quintile (adjusted OR=58.6 (16.5–208.0), p value=0.00). Of those that experienced catastrophic health expenditure, the poorest and richest quintiles spent on average 34% and 15% of households’ annual income, respectively. Drug costs constitute about 50% of the outpatient care cost.

Conclusions

Seeking prevention and treatment services for cardiovascular disease in Addis Ababa poses substantial financial burden on households, affecting the poorest and those who reside outside Addis Ababa more. Economic and geographical inequalities should also be considered when setting priorities for expanding coverage of these services. Expanded coverage has to go hand-in-hand with implementation of sound prepayment and risk pooling arrangements to ensure financial risk protection to the most needy.
Perceived challenges to achieving universal health coverage: a cross-sectional survey of social health insurance managers/administrators in China
Authors: Shan Linghan , Wu Qunhong , Liu Chaojie , Li Ye , Cui Yu , Liang Zi , Hao Yanhua , Liang Libo , Ning Ning , Ding Ding , Pan Qingxia , Han Liyuan
Published: June 2017

Objective

China has achieved over 96% health insurance coverage. However, universal health coverage (UHC) entails population coverage and the range of services covered and the extent to which health service costs are covered. This study aimed to determine the performance of the health insurance system in China in terms of its role in UHC and to identify challenges in the progress of UHC as perceived by health insurance managers/administrators.

Methods

A cross-sectional questionnaire survey was conducted in Beijing, Ningbo, Harbin and Chongqing over the period of 2014 and 2015. A stratified cluster random sampling strategy was adopted to select study participants. A total of 1277 (64.8%) respondents who reported familiarity with the current health insurance system and the requirements of UHC provided valid data for analyses. They gave a rating on the role of the current health insurance system in achieving UHC. A multivariate logistic regression model was developed to determine the associations between the rating and the features of insurance arrangements.

Results

There was consensus among the respondents on the performance of the current health insurance system in terms of its role in UHC, regardless who they were and what responsibility they held in their organisation (ie, policy development, managing fund transactions, and so on). Overall, about 45% of the respondents believed that there is a long way to go to achieve UHC. The low rating was found to be associated with limited financial protection (OR=1.656, 95% CI 1.279 to 2.146), healthcare inequity (OR=1.607, 95% CI 1.268 to 2.037), poor portability (OR=1.347, 95% CI 1.065 to 1.703) and ineffective supervision and administration of funds (OR=1.339, 95% CI 1.061 to 1.692) as perceived by the respondents.

Conclusion

Health insurance managers/administrators in China are pessimistic about the achievements of the current health insurance system. They are concerned about the overall lack of benefit that insurance programmes bring to members, including low levels of entitlements, large healthcare inequity, limited financial protection and poor portability. A singular amendment of the structural design of the existing funds may not be enough to offer a satisfactory solution to these identified barriers. There is a need to increase funding capacities, to develop unified and consistent policies and to increase the level of fund pooling.
Has the NHS 111 urgent care telephone service been a success? Case study and secondary data analysis in England
Authors: Pope Catherine , Turnbull Joanne , Jones Jeremy , Prichard Jane , Rowsell Ali , Halford Susan
Published: June 2017

Objectives

To explore the success of the introduction of the National Health Service (NHS) 111 urgent care service and describe service activity in the period 2014–2016.

Design

Comparative mixed method case study of five NHS 111 service providers and analysis of national level routine data on activity and service use.

Settings and data

Our primary research involved five NHS 111 sites in England. We conducted 356 hours of non-participant observation in NHS 111 call centres and the urgent care centres and, linked to these observations, held 6 focus group interviews with 47 call advisors, clinical and managerial staff. This primary research is augmented by a secondary analysis of routine data about the 44 NHS 111 sites in England contained in the NHS 111 Minimum Data Set made available by NHS England.

Results

Opinions vary depending on the criteria used to judge the success of NHS 111. The service has been rolled out across 44 sites. The 111 phone number is operational and the service has replaced its predecessor NHS Direct. This new service has led to changes in who does the work of managing urgent care demand, achieving significant labour substitution. Judged against internal performance criteria, the service appears not to meet some targets such as call answering times, but it has seen a steady increase in use over time. Patients appear largely satisfied with NHS 111, but the view from some stakeholders is more mixed. The impact of NHS 111 on other health services is difficult to assess and cost-effectiveness has not been established.

Conclusion

The new urgent care service NHS 111 has been brought into use but its success against some key criteria has not been comprehensively proven.
Association between exposure to the Chinese famine during infancy and the risk of self-reported chronic lung diseases in adulthood: a cross-sectional study
Authors: Wang Zhenghe , Zou Zhiyong , Yang Zhongping , Dong Yanhui , Ma Jun
Published: June 2017

Objective

To examine the association between early-life exposure to the Chinese famine and the risk of chronic lung diseases in adulthood.

Design

Data analysis from a cross-sectional survey.

Setting and participants

4135 subjects were enrolled into the study from the China Health and Retirement Longitudinal Study (CHARLS) 2011–2012 baseline survey to analyse the associations between prenatal and early postnatal famine exposure and the risk of chronic lung diseases in adulthood.

Main outcome measures

Chronic lung diseases were defined based on self-reported information.

Results

The prevalence of self-reported chronic lung diseases in fetus-exposed, infant-exposed, preschool-exposed, and non-exposed groups was 6.5%, 7.9%, 6.8%, and 6.1%, respectively. The risk of chronic lung diseases in the infant-exposed group was significantly higher (OR 1.95, 95% CI 1.10 to 3.44) than the non-exposed group in severely affected areas, even after adjusting for gender, smoking, and drinking, family economic status, and the highest educational attainment of the parents (OR 2.57, 95% CI 1.26 to 5.25). In addition, after stratification by gender and famine severity, we found that only infant exposure to the severe famine was associated with the elevated risk of chronic lung diseases among male adults (OR 3.16, 95% CI 1.17 to 8.51).

Conclusions

Severe famine exposure during the period of infancy might increase the risk of chronic lung diseases in male adults.
Application of pharmacogenomics to investigate adverse drug reactions to the disease-modifying treatments for multiple sclerosis: a case–control study protocol for dimethyl fumarate-induced lymphopenia
Authors: Kowalec Kaarina , Kingwell Elaine , Carruthers Robert , Marrie Ruth Ann , Bernatsky Sasha , Traboulsee Anthony , Ross Colin J D , Carleton Bruce , Tremlett Helen
Published: June 2017

Introduction

Adverse drug reactions (ADRs) are a global public health issue. The potential for pharmacogenomic biomarkers has been demonstrated in several therapeutical areas, including HIV infection and oncology. Dimethyl fumarate (DMF) is a licensed disease-modifying therapy for the treatment of multiple sclerosis (MS). The use of DMF in MS has been associated with a severe reduction in lymphocyte counts and reports of progressive multifocal leukoencephalopathy. Here, we outline the protocol for a case–control study designed to discover genomic variants associated with DMF-induced lymphopenia. The ultimate goal is to replicate these findings and create an efficient and adaptable approach towards the identification of genomic markers that could assist in mitigating adverse drug reactions in MS.

Methods and analysis

The population sample will comprise DMF-exposed patients with MS, with cases representing those who developed lymphopenia and controls who did not. DNA genotyping will take place using a high-throughput genome-wide array. Fine mapping and imputation will be performed to focus in on the potentially causal variants associated with lymphopenia. Multivariable logistic regression will be used to compare genotype and allele frequencies between the cases and the controls, with consideration of potential confounders. The association threshold will be set at p<1.0×10−5for the discovery of genomic association analyses to select variants for replication.

Ethics and dissemination

Ethics approval has been obtained from the respective research ethics board, which includes written informed consent. Findings will be disseminated widely, including at scientific conferences, via podcasts (targeted at both healthcare professionals as well as patients and the wider community), through patient engagement and other outreach community events, written lay summaries for all participants and formal publication in peer-reviewed scientific journals.
High-intensity flywheel exercise and recovery of atrophy after 90 days bed-­rest­
Authors: Belavý Daniel L , Ohshima Hiroshi , Rittweger Jörn , Felsenberg Dieter
Published: June 2017

Aims

To investigate differential muscle atrophy during bed-rest, the impact of a high-intensity concentric-eccentric (flywheel) resistance exercise countermeasure and muscle recovery after bed-rest.

Methods

Twenty-five healthy male subjects underwent 90 dayshead-down tilt bed-rest. Volume of individual lower-limb muscles was measured via MRI before, twice during and four times up to 1 year after bed-rest. Subjects were either inactive (n=16) or performed flywheel exercise every third day of bed-rest (n=9). Functional performance was assessed via countermovement jump.

Results

On ‘intent-to-treat’ analysis, flywheel prevented atrophy in the vasti (p<0.001) and reduced atrophy in the hip adductor/extensor adductor magnus (p=0.001) and ankle dorsiflexors/toe flexors (soleus (p<0.001), gastrocnemius medialis (p<0.001), gastrocnemius lateralis (p=0.02), and tibialis posterior with flexor digitorum longus (p=0.04)). Flywheel exercise was not effective for the hamstrings, gracilis, sartorius, peroneals and anterior tibial muscles. Muscle atrophy in vasti, soleus, gastrocnemius medialis, gastrocnemius lateralis and adductor magnus correlated with losses in countermovement jump performance. Muscle volume recovered within 90 days after bed-rest, however long-term after bed-rest, the inactive subjects only showed significantly increased muscle volume versus prebed-rest in a number of muscles including soleus (+4.3%), gastrocnemius medialis (+3.9%) and semimembranosus (+4.3%). This was not associated with greater countermovement jump performance.

Conclusion

The exercise countermeasure was effective in preventing or reducing atrophy in the vasti, adductor magnus and ankle dorsiflexors/toe flexors but not the hamstrings, medial thigh muscles or peroneals and dorsiflexor muscles.

Trial registration number

NCT00311571; results.
Leisure time physical activity and quality of life in medical students: results from a multicentre study
Authors: Peleias Munique , Tempski Patricia , Paro Helena BMS , Perotta Bruno , Mayer Fernanda B , Enns Sylvia C , Gannam Silmar , Pereira Maria Amelia D , Silveira Paulo S , Santos Itamar S , Carvalho Celso RF , Martins Milton A
Published: June 2017

Background/aim

We evaluated the association between leisure time physical activity (PA) and quality of life (QoL) in medical students. Our hypothesis was that there was a positive association between volume of PA and various domains of perception of QoL.

Methods

Data were evaluated from a random sample of 1350 medical students from 22 Brazilian medical schools. Information from participants included the WHO Quality of Life questionnaire-short form (WHOQOL-BREF), a questionnaire specifically designed to evaluate QoL in medical students (VERAS-Q) and questions for both global QoL self-assessment and leisure time PA. According to the amount of metabolic equivalents (METs) spend during PA, volunteers were divided into four groups, according to the volume of PA: (a) no PA; (b) low PA, ≤540 MET min/week; (c) moderate PA, from 541 to 1260 MET min/week and (d) high PA, > 1261 MET min/week.

Results

Forty per cent of the medical students reported no leisure time PA (46.0% of females and 32.3% of males). In contrast, 27.2% were classified in the group of high PA (21.0% of females and 34.2% of males). We found significant associations between moderate and high levels of PA and better QoL for all measurements. For low levels of PA, this association was also significant for most QoL measurements, with the exceptions of WHOQOL physical health (p=0.08) and social relationships (p=0.26) domains.

Conclusion

We observed a strong dose-effect relationship between the volume of leisure time PA and QoL in both male and female medical students.
Association between fasting insulin and high-sensitivity C reactive protein in Korean adults
Authors: Yang June S , Gerber Jeffry N , You Hyun J
Published: June 2017

Background

High-sensitivity C reactive protein (hs-CRP) is a reliable indicator of atherosclerotic diseases and is associated with hyperinsulinaemia. The purpose of this study is to examine the association between hs-CRP and fasting insulin levels in Korean adults not taking medication for hypertension, dyslipidaemia or diabetes, nor provided with specific dietary advice.

Methods

This cross-sectional study included 2588 subjects who participated in the 2015 Korean National Health and Nutrition Examination Survey. High-risk hs-CRP was defined as hs-CRP>2 mg/L. Subjects were divided into four groups with fasting insulin (<5, 5–10, 10–15,>15 uIU/mL)

Results

The mean hs-CRP in our sample was 1.22 mg/L. hs-CRP was positively associated with fasting insulin level. The occurrence of high-risk hs-CRP with increasing fasting insulin levels was 7.6%, 9.8%, 19.1% and 28.2%, respectively. In comparing high-risk hs-CRP between the highest (>15 µIU/mL) and lowest (<5 µIU/mL) insulin groups, the OR (95% CI) was 4.59 (2.77–7.58). triglycerides/high-density lipoprotein ratio was also associated with hs-CRP. Low-density lipoprotein cholesterol was not associated with hs-CRP.

Conclusions

Higher level of fasting insulin is positively associated with high-risk hs-CRP.
Effect of a gluteal activation warm-up on explosive exercise performance
Authors: Parr Matt , Price Phil DB , Cleather Daniel J
Published: June 2017

Objectives

To evaluate the effect of a gluteal activation warm-up on the performance of an explosive exercise (the high hang pull (HHP)).

Methods

Seventeen professional rugby union players performed one set of three HHPs (with 80% of their one repetition maximum load) following both a control and activation warm-up. Peak electrical activity of the gluteus maximus and medius was quantified using electromyography (EMG). In addition, the kinematics and kinetics of nine players was also recorded using force plate and motion capture technology. These data were analysed using a previously described musculoskeletal model of the right lower limb in order to provide estimates of the muscular force expressed during the movement.

Results

The mean peak EMG activity of the gluteus maximus was significantly lower following the activation warm-up as compared with the control (p<0.05, effect size d=0.30). There were no significant differences in the mean peak estimated forces in gluteus maximus and medius, the quadriceps or hamstrings (p=0.053), although there was a trend towards increased force in gluteus maximus and hamstrings following the activation warm-up. There were no differences between the ground reaction forces following the two warm-ups.

Conclusion

This study suggests that a gluteal activation warm-up may facilitate recruitment of the gluteal musculature by potentiating the glutes in such a way that a smaller neural drive evokes the same or greater force production during movement. This could in turn potentially improve movement quality.
Mortality and oral anticoagulants in the Food and Drug Administration Adverse Event Reporting System
Authors: Serebruany Victor , Cherepanov Vasily , Fortmann Seth , Kim Moo Hyun
Published: June 2017

Objective

The comparative crude death rates (CDR) among non-vitamin K antagonist oral anticoagulants (NOACs) are unknown. Further, whether NOACs improve survival when compared with warfarin is also unclear. We compared CDR co-reported for four NOACs combined or separately versus warfarin within the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.

Methods

We selected CDR from the FAERS database linked to four NOACs and warfarin. The primary endpoints were differences in proportional reporting ratios (PRRs), and Chi-Square (χ2)for dabigatran, rivaroxaban, apixaban and edoxaban when compared with warfarin.

Results

The FAERS database contains significantly less death reports associated with all NOACs combined (14 917 out of 128 267 reports (11.63%); PRR=1.089; χ2=70.0; p=6.05e−17) than for warfarin (19 493 out of 153 911 reports (12.67%)). The numbers for rivaroxaban (6318 out of 64 512 reports or (9.79%); PRR=1.293; χ2=359.4; p=3.72e−80), apixaban (1693 out of 17 789 reports (9.52%); PRR=1.331; χ2=145.8; p=1.43e−33) and edoxaban (53 out of 755 reports (7.02%); PRR=1.804; χ2=21.18; p=4.18e−06) were favourable as compared with warfarin, while the numbers of fatalities co-reported with dabigatran (6989 out of 46 250 reports (15.11%); PRR=0.838; χ2=185.2; p=3.61e−42) were higher than for warfarin.

Conclusion

Overall, based on these CDR, NOACs appear to be associated with a mortality benefit over warfarin. Among NOACs, we observed remarkably similar for factor Xa inhibitors (rivaroxiban, apixaban and edoxaban) but unfavourable signal for the direct thrombin inhibitor (dabigatran). However, these data are clearly not sufficient to change the prescription patterns.
Metagenomic analysis of oomycete communities from the rhizosphere of field pea on the Canadian prairies
Authors: Esmaeili Taheri A. , Chatterton S. , Gossen B.D. , McLaren D.L.
Published: June 2017

Oomycetes are a diverse group of microorganisms; however, little is known about their composition and biodiversity in agroecosystems. Illumina MiSeq was used to determine the type and abundance of oomycetes associated with pea root rot in the Canadian prairies. Additional objectives of the study were to identify differences in oomycete communities associated with pea root health and compare oomycete communities among the 3 prairie provinces, where field peas are commonly cultivated. Samples of soil from the rhizosphere of field pea (Pisum sativum L.) were collected from patches of asymptomatic or diseased plants from 26 commercial fields in 2013 and 2014. Oomycete communities were characterized using metagenomic analysis of the ITS1 region on Illumina MiSeq. From 105 identified operational taxonomic units (OTUs), 45 and 16 oomycete OTUs were identified at species and genus levels, respectively. Pythium was the most prevalent genus and Pythium heterothallicum the most prevalent species in all 3 provinces in both 2013 and 2014. Aphanomyces euteiches, a very important pea root rot pathogen in regions of the prairies, was detected in 57% of sites but at very low abundance (<0.2%). Multivariate analysis revealed differences in the relative abundance of species in oomycete communities between asymptomatic and diseased sites, and among years and provinces. This study demonstrated that deep amplicon sequencing can provide information on the composition and diversity of oomycete communities in agricultural soils.
Mdm2 Is Required for Survival and Growth of p53-Deficient Cancer Cells
Authors: Feeley Kyle P. , Adams Clare M. , Mitra Ramkrishna , Eischen Christine M.
Published: June 2017

p53 deletion prevents the embryonic lethality of normal tissues lacking Mdm2, suggesting that cells can survive without Mdm2 if p53 is also absent. Here we report evidence challenging this view, with implications for therapeutically targeting Mdm2. Deletion of Mdm2 in T-cell lymphomas or sarcomas lacking p53 induced apoptosis and G2 cell-cycle arrest, prolonging survival of mice with these tumors. p53−/− fibroblasts showed similar results, indicating that the effects of Mdm2 loss extend to premalignant cells. Mdm2 deletion in p53−/− cells upregulated p53 transcriptional target genes that induce apoptosis and cell-cycle arrest. Mdm2 deletion also increased levels of p73, a p53 family member. RNAi-mediated attenuation of p73 rescued the transcriptional and biological effects of Mdm2 loss, indicating that p73 mediates the consequences of Mdm2 deletion. In addition, Mdm2 deletion differed from blocking Mdm2 interaction with p53 family members, as Nutlin-3 induced G1 arrest but did not activate apoptosis in p53−/− sarcoma cells. Our results indicate that, in contrast to current dogma, Mdm2 expression is required for cell survival even in the absence of p53. Moreover, our results suggest that p73 compensates for loss of p53 and that targeting Mdm2 in p53-deficient cancers has therapeutic potential. Cancer Res; 77(14); 3823–33. ©2017 AACR.
Pigs, Unlike Mice, Have Two Distinct Colonic Stem Cell Populations Similar to Humans That Respond to High-Calorie Diet prior to Insulin Resistance
Authors: Charepalli Venkata , Reddivari Lavanya , Radhakrishnan Sridhar , Eriksson Elisabeth , Xiao Xia , Kim Sung Woo , Shen Frank , Vijay-Kumar Matam , Li Qunhua , Bhat Vadiraja B. , Knight Rob , Vanamala Jairam K.P.
Published: June 2017

Basal colonic crypt stem cells are long lived and play a role in colon homeostasis. Previous evidence has shown that high-calorie diet (HCD) enhances colonic stem cell numbers and expansion of the proliferative zone, an important biomarker for colon cancer. However, it is not clear how HCD drives dysregulation of colon stem cell/colonocyte proliferative kinetics. We used a human-relevant pig model and developed an immunofluorescence technique to detect and quantify colonic stem cells. Pigs (n = 8/group) were provided either standard diet (SD; 5% fat) or HCD (23% fat) for 13 weeks. HCD- and SD-consuming pigs had similar total calorie intake, serum iron, insulin, and glucose levels. However, HCD elevated both colonic proliferative zone (KI-67) and stem cell zone (ASCL-2 and BMI-1). Proliferative zone correlated with elevated innate colonic inflammatory markers TLR-4, NF-κB, IL6, and lipocalin-2 (r ≥ 0.62, P = 0.02). Elevated gut bacterial phyla proteobacteria and firmicutes in HCD-consuming pigs correlated with proliferative and stem cell zone. Colonic proteome data revealed the upregulation of proteins involved in cell migration and proliferation and correlated with proliferative and stem cell zone expansion. Our study suggests that pig colon, unlike mice, has two distinct stem cells (ASCL-2 and BMI-1) similar to humans, and HCD increases expansion of colonic proliferative and stem cell zone. Thus, pig model can aid in the development of preventive strategies against gut bacterial dysbiosis and inflammation-promoted diseases, such as colon cancer. Cancer Prev Res; 10(8); 442–50. ©2017 AACR.
Shifting the Balance of Activating and Inhibitory Natural Killer Receptor Ligands on BRAFV600E Melanoma Lines with Vemurafenib
Authors: Frazao Alexandra , Colombo Marina , Fourmentraux-Neves Emmanuelle , Messaoudene Meriem , Rusakiewicz Sylvie , Zitvogel Laurence , Vivier Eric , Vély Frédéric , Faure Florence , Dréno Brigitte , Benlalam Houssem , Bouquet Fanny , Savina Ariel , Pasmant Eric , Toubert Antoine , Avril Marie-Françoise , Caignard Anne
Published: June 2017

Over 60% of human melanoma tumors bear a mutation in the BRAF gene. The most frequent mutation is a substitution at codon 600 (V600E), leading to a constitutively active BRAF and overactivation of the MAPK pathway. Patients harboring mutated BRAF respond to kinase inhibitors such as vemurafenib. However, these responses are transient, and relapses are frequent. Melanoma cells are efficiently lysed by activated natural killer (NK) cells. Melanoma cells express several stress-induced ligands that are recognized by activating NK-cell receptors. We have investigated the effect of vemurafenib on the immunogenicity of seven BRAF-mutated melanoma cells to NK cells and on their growth and sensitivity to NK-cell–mediated lysis. We showed that vemurafenib treatment modulated expression of ligands for two activating NK receptors, increasing expression of B7-H6, a ligand for NKp30, and decreasing expression of MICA and ULBP2, ligands for NKG2D. Vemurafenib also increased expression of HLA class I and HLA-E molecules, likely leading to higher engagement of inhibitory receptors (KIRs and NKG2A, respectively), and decreased lysis of vemurafenib-treated melanoma cell lines by cytokine-activated NK cells. Finally, we showed that whereas batimastat (a broad-spectrum matrix metalloprotease inhibitor) increased cell surface ULBP2 by reducing its shedding, vemurafenib lowered soluble ULBP2, indicating that BRAF signal inhibition diminished expression of both cell-surface and soluble forms of NKG2D ligands. Vemurafenib, inhibiting BRAF signaling, shifted the balance of activatory and inhibitory NK ligands on melanoma cells and displayed immunoregulatory effects on NK-cell functional activities. Cancer Immunol Res; 5(7); 582–93. ©2017 AACR.
Electrocardiographic Preexcitation and Risk of Cardiovascular Morbidity and Mortality
Authors: Skov Morten W. , Rasmussen Peter V. , Ghouse Jonas , Hansen Steen M. , Graff Claus , Olesen Morten S. , Pietersen Adrian , Torp-Pedersen Christian , Haunsø Stig , Køber Lars , Svendsen Jesper H. , Holst Anders G. , Nielsen Jonas B.
Published: June 2017

Background—

The majority of available data on the clinical course of patients with ventricular preexcitation in the ECG originates from tertiary centers. We aimed to investigate long-term outcomes in individuals from a primary care population with electrocardiographic preexcitation.

Methods and Results—

Digital ECGs from 328 638 primary care patients were collected during 2001 to 2011. We identified 310 individuals with preexcitation (age range, 8–85 years). Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. The median follow-up time was 7.4 years (quartiles, 4.6–10.3 years). Compared with the remainder of the population, patients with preexcitation had higher adjusted hazards of atrial fibrillation (hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.07–4.70) and heart failure (HR, 2.11; 95% CI, 1.27–3.50). Subgroup analysis on accessory pathway location revealed a higher adjusted hazard of heart failure for a right anteroseptal accessory pathway (HR, 5.88; 95% CI, 2.63–13.1). There was no evidence of a higher hazard of death among individuals with preexcitation when looking across all age groups (HR, 1.07; 95% CI, 0.68–1.68). However, a statistically significant (
P
=0.01) interaction analysis (<65 versus ≥65 years) indicated a higher hazard of death for patients with preexcitation ≥65 years (HR, 1.85; 95% CI, 1.07–3.18).

Conclusions—

In this large ECG study, individuals with preexcitation had higher hazards of atrial fibrillation and heart failure. The higher hazard of heart failure seemed to be driven by a right anteroseptal accessory pathway. Among elderly people, we found a statistically significant association between preexcitation and a higher hazard of death.