bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus Macaques
Authors: Carnathan Diane , Lawson Benton , Yu Joana , Patel Kalpana , Billingsley James M. , Tharp Gregory K. , Delmas Olivia M. , Dawoud Reem , Wilkinson Peter , Nicolette Charles , Cameron Mark J. , Sekaly Rafick-Pierre , Bosinger Steven E. , Silvestri Guido , Vanderford Thomas H. 
Published: February 2018

ABSTRACT

Pathogenic human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection of humans and rhesus macaques (RMs) induces persistently high production of type I interferon (IFN-I), which is thought to contribute to disease progression. To elucidate the specific role of interferon alpha (IFN-α) in SIV pathogenesis, 12 RMs were treated prior to intravenous (i.v.) SIV
mac239
infection with a high or a low dose of an antibody (AGS-009) that neutralizes most IFN-α subtypes and were compared with six mock-infused, SIV-infected controls. Plasma viremia was measured postinfection to assess the effect of IFN-α blockade on virus replication, and peripheral blood and lymphoid tissue samples were analyzed by immunophenotypic staining. Consistent with the known antiviral effect of IFN-I, high-dose AGS-009 treatment induced a modest increase in acute-phase viral loads versus controls. Four out of 6 RMs receiving a high dose of AGS-009 also experienced an early decline in CD4
+
T cell counts that was associated with progression to AIDS. Interestingly, 50% of the animals treated with AGS-009 (6/12) developed AIDS within 1 year of infection compared with 17% (1/6) of untreated controls. Finally, blockade of IFN-α decreased the levels of activated CD4
+
and CD8
+
T cells, as well as B cells, as measured by PD-1 and/or Ki67 expression. The lower levels of activated lymphocytes in IFN-α-blockaded animals supports the hypothesis that IFN-α signaling contributes to lymphocyte activation during SIV infection and suggests that this signaling pathway is involved in controlling virus replication during acute infection. The potential anti-inflammatory effect of IFN-α blockade should be explored as a strategy to reduce immune activation in HIV-infected individuals.

IMPORTANCE
Interferon alpha (IFN-α) is a member of a family of molecules (type I interferons) that prevent or limit virus infections in mammals. However, IFN-α production may contribute to the chronic immune activation that is thought to be the primary cause of immune decline and AIDS in HIV-infected patients. The study presented here attempts to understand the contribution of IFN-α to the natural history and progression of SIV infection of rhesus macaques, the primary nonhuman primate model system for testing hypotheses about HIV infection in humans. Here, we show that blockade of IFN-α action promotes lower chronic immune activation but higher early viral loads, with a trend toward faster disease progression. This study has significant implications for new treatments designed to impact the type I interferon system.
Ethanolamine Utilization in Bacteria
Authors: Kaval Karan Gautam , Garsin Danielle A. 
Published: February 2018

ABSTRACT

Ethanolamine (EA) is a valuable source of carbon and/or nitrogen for bacteria capable of its catabolism. Because it is derived from the membrane phospholipid phosphatidylethanolamine, it is particularly prevalent in the gastrointestinal tract, which is membrane rich due to turnover of the intestinal epithelium and the resident microbiota. Intriguingly, many gut pathogens carry the
eut
(ethanolamine utilization) genes. EA utilization has been studied for about 50 years, with most of the early work occurring in just a couple of species of
Enterobacteriaceae
. Once the metabolic pathways and enzymes were characterized by biochemical approaches, genetic screens were used to map the various activities to the
eut
genes. With the rise of genomics, the diversity of bacteria containing the
eut
genes and surprising differences in
eut
gene content were recognized. Some species contain nearly 20 genes and encode many accessory proteins, while others contain only the core catabolic enzyme. Moreover, the
eut
genes are regulated by very different mechanisms, depending on the organism and the
eut
regulator encoded. In the last several years, exciting progress has been made in elucidating the complex regulatory mechanisms that govern
eut
gene expression. Furthermore, a new appreciation for how EA contributes to infection and colonization in the host is emerging. In addition to providing an overview of EA-related biology, this minireview will give special attention to these recent advances.
Microbial Functional Gene Diversity Predicts Groundwater Contamination and Ecosystem Functioning
Authors: He Zhili , Zhang Ping , Wu Linwei , Rocha Andrea M. , Tu Qichao , Shi Zhou , Wu Bo , Qin Yujia , Wang Jianjun , Yan Qingyun , Curtis Daniel , Ning Daliang , Van Nostrand Joy D. , Wu Liyou , Yang Yunfeng , Elias Dwayne A. , Watson David B. , Adams Michael W. W. , Fields Matthew W. , Alm Eric J. , Hazen Terry C. , Adams Paul D. , Arkin Adam P. , Zhou Jizhong 
Published: February 2018

ABSTRACT

Contamination from anthropogenic activities has significantly impacted Earth’s biosphere. However, knowledge about how environmental contamination affects the biodiversity of groundwater microbiomes and ecosystem functioning remains very limited. Here, we used a comprehensive functional gene array to analyze groundwater microbiomes from 69 wells at the Oak Ridge Field Research Center (Oak Ridge, TN), representing a wide pH range and uranium, nitrate, and other contaminants. We hypothesized that the functional diversity of groundwater microbiomes would decrease as environmental contamination (e.g., uranium or nitrate) increased or at low or high pH, while some specific populations capable of utilizing or resistant to those contaminants would increase, and thus, such key microbial functional genes and/or populations could be used to predict groundwater contamination and ecosystem functioning. Our results indicated that functional richness/diversity decreased as uranium (but not nitrate) increased in groundwater. In addition, about 5.9% of specific key functional populations targeted by a comprehensive functional gene array (GeoChip 5) increased significantly (
P
< 0.05) as uranium or nitrate increased, and their changes could be used to successfully predict uranium and nitrate contamination and ecosystem functioning. This study indicates great potential for using microbial functional genes to predict environmental contamination and ecosystem functioning.

IMPORTANCE
Disentangling the relationships between biodiversity and ecosystem functioning is an important but poorly understood topic in ecology. Predicting ecosystem functioning on the basis of biodiversity is even more difficult, particularly with microbial biomarkers. As an exploratory effort, this study used key microbial functional genes as biomarkers to provide predictive understanding of environmental contamination and ecosystem functioning. The results indicated that the overall functional gene richness/diversity decreased as uranium increased in groundwater, while specific key microbial guilds increased significantly as uranium or nitrate increased. These key microbial functional genes could be used to successfully predict environmental contamination and ecosystem functioning. This study represents a significant advance in using functional gene markers to predict the spatial distribution of environmental contaminants and ecosystem functioning toward predictive microbial ecology, which is an ultimate goal of microbial ecology.
Comparative activity of antimicrobials againstPseudomonas aeruginosa,Achromobacter xylosoxidansandStenotrophomonas maltophiliakeratitis isolates
Authors: Spierer Oriel , Miller Darlene , O’Brien Terrence P 
Published: February 2018

Background/aimsAchromobacter xylosoxidansandStenotrophomonas maltophiliaare emerging corneal pathogens, which are closely related toPseudomonas aeruginosa, and have intrinsic resistance to many commonly available antimicrobials. The purpose of this study is to compare the in vitro efficacy of 12 antimicrobial agents againstA. xylosoxidans,S. maltophiliaandP. aeruginosaisolates recovered from clinical cases of keratitis.MethodsRecovered corneal isolates (n=58) were identified and extracted from the Microbiology Data Bank of the Bascom Palmer Eye Institute. Comparative in vitro minimum inhibitory concentration (MIC) susceptibility profiles for fluoroquinolones, aminoglycosides, beta-lactams and miscellaneous antibiotics were recorded using the E-test methodology. Pharmacodynamic indices (Cmax/MIC) were calculated.ResultsA. xylosoxidansandS. maltophiliaisolates were resistant to fluoroquinolones, aminoglycosides and ceftazidime (susceptibility rate ranging from 0% to 30%) whileP. aeruginosaisolates showed a susceptibility rate of 95%–100% to these antimicrobials (P<0.00001 for the various antimicrobials). Exception was moxifloxacin with 80% of susceptibility rate toS. maltophiliaisolates and Cmax/MIC=10.19. Ninety to 100% susceptibility rates were found for minocycline and trimethoprim/sulfamethoxazole for bothA. xylosoxidansandS. maltophilia. One hundred per cent of theA. xylosoxidansisolates were susceptible to piperacillin/tazobactam and ticarcillin/clavulanic acid.ConclusionsThere is a significant difference in susceptibility patterns betweenA. xylosoxidans,S. maltophiliaandP. aeruginosa. Fluoroquinolones and aminoglycosides may not be effective againstA. xylosoxidansandS. maltophilia. Antibiotics that are not commercially available as eye drops, such as beta-lactams forA. xylosoxidans, and trimethoprim/sulfamethoxazole and minocycline for bothA. xylosoxidansandS. maltophiliashould be considered.
Impact of provision of time in therapeutic range value on anticoagulation management in atrial fibrillation patients on warfarin
Authors: Huang Duo , Wong Chi-Lap , Cheng Kwan-Wa , Chan Pak-Hei , Yue Wen-Sheng , Wong Chun-Ka , Ho Chi-Wai , Wong Ian C K , Chan Esther W , Siu Chung Wah 
Published: February 2018

AbstractIntroductionThe importance of time in therapeutic range (TTR) in patients prescribed warfarin therapy for stroke prevention in atrial fibrillation (AF) cannot be overemphasised.AimTo evaluate the impact of provision of TTR results during clinic visits on anticoagulation management.DesignSingle-centred, randomised controlled study.SettingFifteen arrhythmia clinics in Hong Kong.PatientsAF patients prescribed warfarin.InterventionsProvision of TTR or no provision of TTR.Main outcome measuresA documented discussion between doctors and patients about switching warfarin to a non-vitamin K oral anticoagulant (NOAC).ResultsFour hundred and eighty one patients with AF prescribed warfarin were randomly assigned to (1) a TTR provision group or (2) control. Their mean age was 73.6±12.0 years and 60.7% were men. The mean CHA2DS2-VASc score was 3.2±1.6 and the mean HASBLED score was 1.7±1.2. The mean TTR was 63.9%±29.9%. At the index clinic visit, 71 of 481 patients (14.8%) had a documented discussion about switching warfarin to a NOAC. Patients with provision of TTR results were more likely to discuss switching warfarin to a NOAC than controls (19.1% vs 10.6%, P=0.03), especially those with a TTR &lt;65% (35.2% vs 10.6%, P&lt;0.001). A higher proportion of patients with provision of TTR results switched to a NOAC (5.9% vs 4.1%, P=0.49).ConclusionsThe provision of TTR among patients on warfarin was associated with a discussion about switching from warfarin to a NOAC in those with TTR &lt;65%, but did not result in actual switching to a NOAC, suggesting additional barriers.
UK news media representations of smoking, smoking policies and tobacco bans in prisons
Authors: Robinson Amy , Sweeting Helen , Hunt Kate 
Published: February 2018

BackgroundPrisoner smoking rates remain high, resulting in secondhand smoke exposures for prison staff and non-smoker prisoners. Several jurisdictions have introduced prison smoking bans with little evidence of resulting disorder. Successful implementation of such bans requires staff support. As news media representations of health and other issues shape public views and as prison smoking bans are being introduced in the UK, we conducted content analysis of UK news media to explore representations of smoking in prisons and smoke-free prisons.MethodsWe searched 64 national and local newspapers and 5 broadcast media published over 17 months during 2015–2016, and conducted thematic analysis of relevant coverage in 106 articles/broadcasts.ResultsCoverage was relatively infrequent and lacked in-depth engagement with the issues. It tended to reinforce a negative view of prisoners, avoid explicit concern for prisoner or prison staff health and largely ignore the health gains of smoke-free policies. Most coverage failed to discuss appropriate responses or support for cessation in the prison context, or factors associated with high prisoner smoking rates. Half the articles/broadcasts included coverage suggesting smoke-free prisons might lead to unrest or instability.ConclusionsNegative news media representations of prisoners and prison smoking bans may impact key stakeholders’ views (eg, prison staff, policy-makers) on the introduction of smoke-free prison policies. Policy-makers’ communications when engaging in discussion around smoke-free prison policies should draw on the generally smooth transitions to smoke-free prisons to date, and on evidence on health benefits of smoke-free environments and smoking cessation.
Heart Failure Stimulates Tumor Growth by Circulating Factors
Authors: Meijers Wouter C. , Maglione Manuel , Bakker Stephan J.L. , Oberhuber Rupert , Kieneker Lyanne M. , de Jong Steven , Haubner Bernhard J. , Nagengast Wouter B. , Lyon Alexander R. , van der Vegt Bert , van Veldhuisen Dirk J. , Westenbrink B. Daan , van der Meer Peter , Silljé Herman H.W. , de Boer Rudolf A. 
Published: February 2018

Background:
Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer.

Methods:

HF was induced by inflicting large anterior myocardial infarction in APC
min
mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post–myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort.

Results:

The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APC
min
mice (all
P
<0.0001). The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth (
P
=0.002 and
P
=0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human patients with chronic HF (n=101) compared with healthy subjects (n=180;
P
<0.001). Functionally, serpinA3 resulted in marked proliferation effects in human colon cancer (HT-29) cells, associated with Akt-S6 phosphorylation. Finally, elevated cardiac and inflammation biomarkers in apparently healthy humans (n=8319) were predictive of new-onset cancer (n=1124) independently of risk factors for cancer (age, smoking status, and body mass index).

Conclusions:
We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.
Mental Stress–Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction
Authors: Vaccarino Viola , Sullivan Samaah , Hammadah Muhammad , Wilmot Kobina , Al Mheid Ibhar , Ramadan Ronnie , Elon Lisa , Pimple Pratik M. , Garcia Ernest V. , Nye Jonathon , Shah Amit J. , Alkhoder Ayman , Levantsevych Oleksiy , Gay Hawkins , Obideen Malik , Huang Minxuan , Lewis Tené T. , Bremner J. Douglas , Quyyumi Arshed A. , Raggi Paolo 
Published: February 2018

Background:
Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infarction (MI), a group with unexplained higher mortality than men of comparable age, have shown elevated rates of MSIMI, but the mechanisms are unknown.

Methods:

We studied 306 patients (150 women and 156 men) ≤61 years of age who were hospitalized for MI in the previous 8 months and 112 community controls (58 women and 54 men) frequency matched for sex and age to the patients with MI. Endothelium-dependent flow-mediated dilation and microvascular reactivity (reactive hyperemia index) were measured at rest and 30 minutes after mental stress. The digital vasomotor response to mental stress was assessed using peripheral arterial tonometry. Patients received
99m
Tc-sestamibi myocardial perfusion imaging at rest, with mental (speech task) and conventional (exercise/pharmacological) stress.

Results:

The mean age of the sample was 50 years (range, 22–61). In the MI group but not among controls, women had a more adverse socioeconomic and psychosocial profile than men. There were no sex differences in cardiovascular risk factors, and among patients with MI, clinical severity tended to be lower in women. Women in both groups showed a higher peripheral arterial tonometry ratio during mental stress but a lower reactive hyperemia index after mental stress, indicating enhanced microvascular dysfunction after stress. There were no sex differences in flow-mediated dilation changes with mental stress. The rate of MSIMI was twice as high in women as in men (22% versus 11%,
P
=0.009), and ischemia with conventional stress was similarly elevated (31% versus 16%,
P
=0.002). Psychosocial and clinical risk factors did not explain sex differences in inducible ischemia. Although vascular responses to mental stress (peripheral arterial tonometry ratio and reactive hyperemia index) also did not explain sex differences in MSIMI, they were predictive of MSIMI in women only.

Conclusions:
Young women after MI have a 2-fold likelihood of developing MSIMI compared with men and a similar increase in conventional stress ischemia. Microvascular dysfunction and peripheral vasoconstriction with mental stress are implicated in MSIMI among women but not among men, perhaps reflecting women’s proclivity toward ischemia because of microcirculatory abnormalities.
Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction
Authors: Lichtman Judith H. , Leifheit Erica C. , Safdar Basmah , Bao Haikun , Krumholz Harlan M. , Lorenze Nancy P. , Daneshvar Mitra , Spertus John A. , D’Onofrio Gail 
Published: February 2018

Background:
Some studies report that women are less likely to present with chest pain for acute myocardial infarction (AMI). Information on symptom presentation, perception of symptoms, and care-seeking behaviors is limited for young patients with AMI.

Methods:
We interviewed 2009 women and 976 men aged 18 to 55 years hospitalized for AMI at 103 US hospitals participating in the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Structured patient interviews during the index AMI hospitalization were used to collect information on symptom presentation, perception of symptoms, and care-seeking behaviors. We compared patient characteristics and presentation information by sex. Multivariable hierarchical logistic regression was used to evaluate the association between sex and symptom presentation.

Results:

The majority of women (87.0%) and men (89.5%) presented with chest pain (defined as pain, pressure, tightness, or discomfort). Women were more likely to present with ≥3 associated symptoms than men (eg, epigastric symptoms, palpitations, and pain or discomfort in the jaw, neck, arms, or between the shoulder blades; 61.9% for women versus 54.8% for men,
P
<0.001). In adjusted analyses, women with an ST-segment–elevation AMI were more likely than men to present without chest pain (odds ratio, 1.51; 95% confidence interval, 1.03–2.22). In comparison with men, women were more likely to perceive symptoms as stress/anxiety (20.9% versus 11.8%,
P
<0.001) but less likely to attribute symptoms to muscle pain (15.4% versus 21.2%,
P
=0.029). Approximately 29.5% of women and 22.1% of men sought medical care for similar symptoms before their hospitalization (
P
<0.001); however, 53% of women reported that their provider did not think these symptoms were heart-related in comparison with 37% of men (
P
<0.001).

Conclusions:
The presentation of AMI symptoms was similar for young women and men, with chest pain as the predominant symptom for both sexes. Women presented with a greater number of additional non–chest pain symptoms regardless of the presence of chest pain, and both women and their healthcare providers were less likely to attribute their prodromal symptoms to heart disease in comparison with men.
American Heart Association's Life's Simple 7 at Middle Age and Prognosis After Myocardial Infarction in Later Life
Authors: Mok Yejin , Sang Yingying , Ballew Shoshana H. , Rebholz Casey M. , Rosamond Wayne D. , Heiss Gerardo , Folsom Aaron R. , Coresh Josef , Matsushita Kunihiro 
Published: February 2018

Background

The American Heart Association recommends focusing on 7 health factors (Life's Simple 7) for primordial prevention of cardiovascular health. However, whether greater adherence to Life's Simple 7 in midlife improves prognosis after myocardial infarction (
MI
) in later life is unknown.

Methods and Results

In 1277 participants who developed
MI
during the ARIC (Atherosclerosis Risk in Communities) Study follow‐up, a 14‐point score of Life's Simple 7 was constructed according to the status (2 points for ideal, 1 point for intermediate, and 0 points for poor) of each of 7 factors (smoking, adiposity, physical activity, diet, total cholesterol, blood pressure, and fasting glucose) at baseline (1987–1989). Hazard ratios for composite and individual adverse outcomes of all‐cause mortality, cardiovascular mortality, recurrent
MI
, heart failure, and stroke were calculated according to Life's Simple 7 score. During a median follow‐up of 3.3 years, 918 participants (72%) had subsequent adverse outcomes after
MI
. Life's Simple 7 score at middle age was inversely associated with adverse outcomes after
MI
(adjusted hazard ratios of composite outcome, 0.57 [95% confidence interval, 0.39–0.84] if score is ≥10, 0.78 [95% confidence interval, 0.57–1.07] if score is 7–9, and 0.82 [95% confidence interval, 0.60–1.11] if score is 4–6 versus ≤3). The association was largely independent of access to care and
MI
severity. Individual factors related to better prognosis after
MI
were ideal nonsmoking, body mass index, blood pressure, and fasting glucose.

Conclusions

Optimal Life's Simple 7 at middle age was associated with better prognosis after
MI
in later life. Our findings suggest a secondary prevention benefit of having better cardiovascular health status in midlife.