bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and feasibility of a community‐partnered nutrition intervention targeting rural migrant communities in the Dominican Republic
Authors: Maliszewski Genevieve , Enriquez Maithe , Cheng An‐Lin , Logan Pamela , Watts Jennifer 
Published: March 2017

AbstractObjectiveResearch on health initiatives for rural batey communities in the Dominican Republic is needed.Design and SampleThis study utilized a pretest‐posttest design to examine the feasibility and acceptability of a nutritional intervention targeting rural migrant sugarcane families. Participants (N = 310) were primarily female (61%) and ranged in age from 13 to 64 years (M = 25.9; SD = 10.4). A convenience sample was recruited from six rural bateyes in the southern region of the Dominican Republic.InterventionThe intervention was developed for the target population in partnership with a grass‐roots organization. The intervention consisted of a short video in the participant's preferred language (Spanish or Creole) describing the importance of consuming a diverse diet. Participants then completed an interactive meal‐planning activity to enhance skills learned in the video. The main outcome variable was knowledge and a secondary outcome was participants’ performance on the interactive activity.ResultsResults showed that the intervention was well received by the target population and participants demonstrated a significant increase in nutrition knowledge (p < .001). Higher postintervention knowledge scores were positively correlated with higher activity skills scores.ConclusionThis novel intervention may have promise as a practical program to enhance the nutritional status of a vulnerable population of migrant sugarcane workers.
Potential for mitigating atmospheric ammonia in Canada
Authors: Bittman S. , Sheppard S. C. , Hunt D. 
Published: March 2017

AbstractMost ammonia (NH3) emissions (85%) in Canada come from agricultural sources (400 kt/yr). There are international conventions that require countries to mitigate NH3 emissions but there are no federal or provincial guidelines in Canada stipulating emission targets or best practices for agriculture. This study examines the potential for mitigating atmospheric NH3 using a range of approaches. Taking current farm practices into account, employing proven low‐cost measures (low‐emission slurry application and slurry storage covers) would reduce annual emissions from livestock operations by 16 kt NH3‐N, while using all available low‐cost measures would reduce emissions by 79 kt NH3‐N or 26% of livestock emissions. Another 36 kt/yr could be avoided by improving fertilizer practices, so that the total potential reduction would be about 29% of all agricultural emissions. Emissions from beef cattle and pig production could be reduced by 18% if consumption was cut by 50%, with greater mitigation if production for export was reduced, although the economic and social consequences need to be considered. Mitigation practices must be viewed in the context of possible pollution swapping especially in surplus nitrogen situations. Emissions must also be considered in terms of atmospheric NH3 transport to and from the USA, therefore bi‐national agreements to jointly reduce emissions might be needed. It may be more cost‐effective in Canada to strategically reduce emissions to minimize risks to health (from particulate matter) and the environment rather than to reduce annual national emission targets.
Melatonin and IL‐25 modulate apoptosis and angiogenesis mediators in metastatic (CF‐41) and non‐metastatic (CMT‐U229) canine mammary tumour cells
Authors: Gelaleti G. B. , Borin T. F. , Maschio‐Signorini L. B. , Moschetta M. G. , Hellmén E. , Viloria‐Petit A. M. , Zuccari D. A. P. C. 
Published: March 2017

BackgroundMelatonin has oncostatic actions and IL‐25 is active in inflammatory processes that induce apoptosis in tumor cellsAimThe aim of this study was to evaluate melatonin and IL‐25 in metastatic (CF‐41) and non‐metastatic (CMT‐U229) canine mammary tumor cells cultured as monolayers and tridimensional structures.Materials and MethodsThe cells were treated with melatonin, IL‐25 and IL‐17B silencing gene and performed cell viability, gene and protein expression of caspase‐3 and VEGFA (Vascular endothelial growth factor A) and an apoptosis membrane protein array.ResultsTreatment with 1 mM of melatonin reduced cell viability of both tumor cell lines, all treatments alone and combined significantly increased caspase‐3 cleaved and proteins involved in the apoptotic pathway and reduced pro‐angiogenic VEGFA, confirming the effectiveness of these potential promising treatments.ConclusionThis is the first study evaluating the potential use of these strategies in CF‐41 and CMT‐U229 cell lines and together encourages subsequent in vitro and in vivo studies for further exploration of clinical applications.
Experimental Models of Short Courses of Liposomal Amphotericin B for Induction Therapy for Cryptococcal Meningitis
Authors: Lestner Jodi , McEntee Laura , Johnson Adam , Livermore Joanne , Whalley Sarah , Schwartz Julie , Perfect John R. , Harrison Thomas , Hope William 
Published: March 2017

ABSTRACT
Cryptococcal meningoencephalitis is a rapidly lethal infection in immunocompromised patients. Induction regimens are usually administered for 2 weeks. The shortest effective period of induction therapy with liposomal amphotericin B (LAMB) is unknown. The pharmacodynamics of LAMB were studied in murine and rabbit models of cryptococcal meningoencephalitis. The concentrations of LAMB in the plasma and brains of mice were measured using high-performance liquid chromatography (HPLC). Histopathological changes were determined. The penetration of LAMB into the brain was determined by immunohistochemistry using an antibody directed to amphotericin B. A dose-dependent decline in fungal burden was observed in the brains of mice, with near-maximal efficacy achieved with LAMB at 10 to 20 mg/kg/day. The terminal elimination half-life in the brain was 133 h. The pharmacodynamics of a single dose of 20 mg/kg was the same as that of 20 mg/kg/day administered for 2 weeks. Changes in quantitative counts were reflected by histopathological changes in the brain. Three doses of LAMB at 5 mg/kg/day in rabbits were required to achieve fungicidal activity in cerebrospinal fluid (cumulative area under the concentration-time curve, 2,500 mg · h/liter). Amphotericin B was visible in the intra- and perivascular spaces, the leptomeninges, and the choroid plexus. The prolonged mean residence time of amphotericin B in the brain suggests that abbreviated induction regimens of LAMB are possible for cryptococcal meningoencephalitis.
3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H
Authors: Huber Andrew D. , Michailidis Eleftherios , Tang Jing , Puray-Chavez Maritza N. , Boftsi Maria , Wolf Jennifer J. , Boschert Kelsey N. , Sheridan Megan A. , Leslie Maxwell D. , Kirby Karen A. , Singh Kamalendra , Mitsuya Hiroaki , Parniak Michael A. , Wang Zhengqiang , Sarafianos Stefan G. 
Published: March 2017

ABSTRACT
Hepatitis B virus (HBV) RNase H (RNH) is an appealing therapeutic target due to its essential role in viral replication. RNH inhibitors (RNHIs) could help to more effectively control HBV infections. Here, we report 3-hydroxypyrimidine-2,4-diones as novel HBV RNHIs with antiviral activity. We synthesized and tested 52 analogs and found 4 that inhibit HBV RNH activity in infected cells. Importantly, 2 of these compounds inhibited HBV replication in the low micromolar range.
Impact of Mutations at Arg220 and Thr237 in PER-2 β-Lactamase on Conformation, Activity, and Susceptibility to Inhibitors
Authors: Ruggiero Melina , Curto Lucrecia , Brunetti Florencia , Sauvage Eric , Galleni Moreno , Power Pablo , Gutkind Gabriel 
Published: March 2017

ABSTRACT

PER-2 accounts for up to 10% of oxyimino-cephalosporin resistance in
Klebsiella pneumoniae
and
Escherichia coli
in Argentina and hydrolyzes both cefotaxime and ceftazidime with high catalytic efficiencies (
k
cat
/

K
m

). Through crystallographic analyses, we recently proposed the existence of a hydrogen bond network connecting Ser70-Gln69-oxyanion water-Thr237-Arg220 that might be important for the activity and inhibition of the enzyme. Mutations at Arg244 in most class A β-lactamases (such as TEM and SHV) reduce susceptibility to mechanism-based inactivators, and Arg220 in PER β-lactamases is equivalent to Arg244. Alterations in the hydrogen bond network of the active site in PER-2, through modifications in key residues such as Arg220 and (to a much lesser extent) Thr237, dramatically impact the overall susceptibility to inactivation, with up to ∼300- and 500-fold reductions in the rate constant of inactivation (
k
inact
)/

K
i

values for clavulanic acid and tazobactam, respectively. Hydrolysis on cephalosporins and aztreonam was also affected, although to different extents compared to with wild-type PER-2; for cefepime, only an Arg220Gly mutation resulted in a strong reduction in the catalytic efficiency. Mutations at Arg220 entail modifications in the catalytic activity of PER-2 and probably local perturbations in the protein, but not global conformational changes. Therefore, the apparent structural stability of the mutants suggests that these enzymes could be possibly selected
in vivo
.
Library of Seleno-Compounds as Novel Agents against Leishmania Species
Authors: Martín-Montes Álvaro , Plano Daniel , Martín-Escolano Rubén , Alcolea Verónica , Díaz Marta , Pérez-Silanes Silvia , Espuelas Socorro , Moreno Esther , Marín Clotilde , Gutiérrez-Sánchez Ramón , Sanmartín Carmen , Sánchez-Moreno Manuel 
Published: March 2017

ABSTRACT

The
in vitro
leishmanicidal activities of a series of 48 recently synthesized selenium derivatives against
Leishmania infantum
and
Leishmania braziliensis
parasites were tested using promastigotes and intracellular amastigote forms. The cytotoxicity of the tested compounds for J774.2 macrophage cells was also measured in order to establish their selectivity. Six of the tested compounds (compounds 8, 10, 11, 15, 45, and 48) showed selectivity indexes higher than those of the reference drug, meglumine antimonate (Glucantime), for both
Leishmania
species; in the case of
L. braziliensis
, compound 20 was also remarkably selective. Moreover, data on infection rates and amastigote numbers per macrophage showed that compounds 8, 10, 11, 15, 45, and 48 were the most active against both
Leishmania
species studied. The observed changes in the excretion product profile of parasites treated with these six compounds were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds were potent inhibitors of Fe superoxide dismutase (Fe-SOD) in the two parasite species considered, whereas their impact on human CuZn-SOD was low. The high activity, low toxicity, stability, low cost of the starting materials, and straightforward synthesis make these compounds appropriate molecules for the development of affordable antileishmanicidal agents.
In Vitro
Study of Antimicrobial Percutaneous Nephrostomy Catheters for Prevention of Renal Infections
Authors: Vargas-Cruz Nylev , Reitzel Ruth A. , Rosenblatt Joel , Jamal Mohamed , Szvalb Ariel D. , Chaftari Anne-Marie , Hachem Ray , Raad Issam 
Published: March 2017

ABSTRACT

Percutaneous nephrostomy (PCN) catheters are the primary method for draining ureters obstructed by malignancy and preventing a decline of renal function. However, PCN catheter-related infections, such as pyelonephritis and urosepsis, remain a significant concern. Currently, no antimicrobial PCN catheters are available for preventing infection complications. Vascular catheters impregnated with minocycline-rifampin (M/R) and M/R with chlorhexidine coating (M/R plus CHD) have previously demonstrated antimicrobial activity. Therefore, in this study, we examined whether these combinations could be applied to PCN catheters and effectively inhibit biofilm formation by common uropathogens. An
in vitro
biofilm colonization model was used to assess the antimicrobial efficacy of M/R and M/R-plus-CHD PCN catheters against nine common multidrug-resistant Gram-positive and Gram-negative uropathogens as well as
Candida glabrata
and
Candida albicans
. Experimental catheters were also assessed for durability of antimicrobial activity for up 3 weeks. PCN catheters coated with M/R plus CHD completely inhibited biofilm formation for up to 3 weeks for all the organisms tested. The reduction in colonization compared to uncoated PCN catheters was significant for all Gram-positive, Gram-negative, and fungal organisms (
P
< 0.05). M/R-plus-CHD PCN catheters also produced significant reductions in biofilm colonization relative to M/R PCN catheters for
Enterobacter
spp.,
Escherichia coli
,
Pseudomonas aeruginosa
, methicillin-resistant
Staphylococcus aureus
, vancomycin-resistant enterococci,
C. glabrata
, and
C. albicans
(
P
< 0.05). M/R-plus-CHD PCN catheters proved to be highly efficacious in preventing biofilm colonization when exposed to multidrug-resistant pathogens common in PCN catheter-associated pyelonephritis. M/R-plus-CHD PCN catheters warrant evaluation in a clinical setting to assess their ability to prevent clinically relevant nephrostomy infections.
Amoebicidal Activity of Caffeine and Maslinic Acid by the Induction of Programmed Cell Death in Acanthamoeba
Authors: Martín-Navarro Carmen M. , López-Arencibia Atteneri , Sifaoui Ines , Reyes-Batlle María , Fouque Emilie , Osuna Antonio , Valladares Basilio , Piñero José E. , Héchard Yann , Maciver Sutherland K. , Lorenzo-Morales Jacob 
Published: March 2017

ABSTRACT

Free-living amoebae of the genus
Acanthamoeba
are the causal agents of a sight-threatening ulceration of the cornea called
Acanthamoeba
keratitis, as well as the rare but usually fatal disease granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of
Acanthamoeba
infections, they are generally lengthy and/or have limited efficacy. For the best clinical outcome, treatments should target both the trophozoite and the cyst stages, as cysts are known to confer resistance to treatment. In this study, we document the activities of caffeine and maslinic acid against both the trophozoite and the cyst stages of three clinical strains of
Acanthamoeba
. These drugs were chosen because they are reported to inhibit glycogen phosphorylase, which is required for encystation. Maslinic acid is also reported to be an inhibitor of extracellular proteases, which may be relevant since the protease activities of
Acanthamoeba
species are correlated with their pathogenicity. We also provide evidence for the first time that both drugs exert their anti-amoebal effects through programmed cell death.
Early Intracellular Trafficking of Granulibacter bethesdensis in Human Macrophages
Authors: Chu Jessica , Smelkinson Margery G. , Dorward David W. , Zarember Kol A. , Gallin John I. 
Published: March 2017

ABSTRACT

Granulibacter bethesdensis
is a Gram-negative bacterium that infects patients with chronic granulomatous disease (CGD), a primary immunodeficiency marked by a defect in NOX2, the phagocyte NADPH oxidase. Previous studies have shown that NOX2 is essential for killing of
G. bethesdensis
by neutrophils and monocytes and that the bacteriostatic activity of monocyte-derived macrophages (MDM) requires NOX2 and gamma interferon (IFN-γ) pretreatment. To determine whether
G. bethesdensis
evades phagolysosomal killing, a host defense pathway intact in both normal and CGD MDM, or whether it occupies a distinct intracellular niche in CGD MDM, we assessed the trafficking patterns of this organism. We observed colocalization of
G. bethesdensis
with an early endosome antigen 1 (EEA1)-positive compartment, followed by colocalization with lysosome-associated membrane protein 1 (LAMP1)-positive and LysoTracker-positive late phagosomes; these characteristics were similar in both normal and CGD MDM. Despite localization to acidified late phagosomes, viable
G. bethesdensis
cells were recovered from viable MDM in numbers greater than in the initial input up to 6 days after infection.
G. bethesdensis
remains, and in some cases appears to divide, within a membrane-bound compartment for the entire 6-day time course. These findings indicate that this organism resists both oxygen-dependent and oxygen-independent phagolysosomal antimicrobial systems of human macrophages.
Functional Analysis of the Alternative Sigma-28 Factor FliA and Its Anti-Sigma Factor FlgM of the Nonflagellated Legionella Species L. oakridgensis
Authors: Tlapák Hana , Rydzewski Kerstin , Schulz Tino , Weschka Dennis , Schunder Eva , Heuner Klaus 
Published: March 2017

ABSTRACT

Legionella oakridgensis
causes Legionnaires' disease but is known to be less virulent than
Legionella pneumophila
.
L. oakridgensis
is one of the
Legionella
species that is nonflagellated. The genes of the flagellar regulon are absent, except those encoding the alternative sigma-28 factor (FliA) and its anti-sigma-28 factor (FlgM). Similar to
L. oakridgensis
,
Legionella adelaidensis
and
Legionella londiniensis
, located in the same phylogenetic clade, have no flagellar regulon, although both are positive for
fliA
and
flgM
. Here, we investigated the role and function of both genes to better understand the role of FliA, the positive regulator of flagellin expression, in nonflagellated strains. We demonstrated that the FliA gene of
L. oakridgensis
encodes a functional sigma-28 factor that enables the transcription start from the sigma-28-dependent promoter site. The investigations have shown that FliA is necessary for full fitness of
L. oakridgensis
. Interestingly, expression of FliA-dependent genes depends on the growth phase and temperature, as already shown for
L. pneumophila
strains that are flagellated. In addition, we demonstrated that FlgM is a negative regulator of FliA-dependent gene expression. FlgM seems to be degraded in a growth-phase- and temperature-dependent manner, instead of being exported into the medium as reported for most bacteria. The degradation of FlgM leads to an increase of FliA activity.

IMPORTANCE
A less virulent
Legionella
species,
L. oakridgensis
, causes Legionnaires' disease and is known to not have flagella, even though
L. oakridgensis
has the regulator of flagellin expression (FliA). This protein has been shown to be involved in the expression of virulence factors. Thus, the strain was chosen for use in this investigation to search for FliA target genes and to identify putative virulence factors of
L. oakridgensis
. One of the five major target genes of FliA identified here encodes the anti-FliA sigma factor FlgM. Interestingly, in contrast to most homologs in other bacteria, FlgM in
L. oakridgensis
seems not to be transported from the cell so that FliA gets activated. In
L. oakridgensis
, FlgM seems to be degraded by protease activities.
Identification of the Lyso-Form
N
-Acyl Intramolecular Transferase in Low-GC Firmicutes
Authors: Armbruster Krista M. , Meredith Timothy C. 
Published: March 2017

ABSTRACT

Bacterial lipoproteins are embedded in the cell membrane of both Gram-positive and Gram-negative bacteria, where they serve numerous functions central to cell envelope physiology. Lipoproteins are tethered to the membrane by an
N
-acyl-
S
-(mono/di)-acyl-glyceryl-cysteine anchor that is variously acylated depending on the genus. In several low-GC, Gram-positive firmicutes, a monoacyl-glyceryl-cysteine with an N-terminal fatty acid (known as the lyso form) has been reported, though how it is formed is unknown. Here, through an intergenic complementation rescue assay in
Escherichia coli
, we report the identification of a common orthologous transmembrane protein in both
Enterococcus faecalis
and
Bacillus cereus
that is capable of forming lyso-form lipoproteins. When deleted from the native host, lipoproteins remain diacylated with a free N terminus, as maturation to the
N
-acylated lyso form is abolished. Evidence is presented suggesting that the previously unknown gene product functions through a novel intramolecular transacylation mechanism, transferring a fatty acid from the diacylglycerol moiety to the α-amino group of the lipidated cysteine. As such, the discovered gene has been named
l
ipoprotein
i
ntramolecular
t
ransacylase (
lit
), to differentiate it from the gene for the intermolecular
N
-acyltransferase (
lnt
) involved in triacyl lipoprotein biosynthesis in Gram-negative organisms.

IMPORTANCE
This study identifies a new enzyme, conserved among low-GC, Gram-positive bacteria, that is involved in bacterial lipoprotein biosynthesis and synthesizes lyso-form lipoproteins. Its discovery is an essential first step in determining the physiological role of N-terminal lipoprotein acylation in Gram-positive bacteria and how these modifications impact bacterial cell envelope function.
Statin Use and the Risk of Cataracts: A Systematic Review and Meta‐Analysis
Authors: Yu Shandong , Chu Yanpeng , Li Gang , Ren Lu , Zhang Qing , Wu Lin 
Published: March 2017

Background
Cataracts are the main cause of poor vision and blindness worldwide. The effects of statin administration on cataracts remain debated. Therefore, we conducted a systematic review and meta‐analysis to determine whether statin use affects the risk of cataracts.

Methods and Results

We performed a systematic search of the electronic databases PubMed,
EMBASE
, and the Cochrane Library through January 2016. Weighted averages were reported as relative risk values with 95%
CI
s. Statistical heterogeneity scores were assessed with the standard Cochran's Q test and the I
2
statistic. A total of 6 cohort studies, 6 case–control studies, and 5 randomized controlled trials, together involving more than 313 200 patients, were included in our study. The pooled estimates of cohort studies indicated that the use of statins moderately increases the risk of cataracts (relative risk, 1.13; 95%
CI
, 1.01–1.25). The pooled estimates of case–control studies (relative risk=1.10, 95%
CI
, 0.99–1.23) and randomized controlled trials (relative risk, 0.89; 95%
CI
, 0.72–1.10) indicated that the use of statins does not increase the risk of cataracts. The sensitivity analysis confirmed the stability of the results. Heterogeneity was found among the cohort and case–control studies.

Conclusions
Based on the present meta‐analysis of these studies, we could only conclude that there is no clear evidence showing that statin use increases the risk of cataracts. The most likely case is that there is no association between statin use and cataracts. Because of the considerable benefits of statins in cardiovascular patients, this issue should not deter their use.