bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal nutrient restriction during pregnancy and lactation leads to impaired right ventricular function in young adult baboons
Authors: Kuo Anderson H. , Li Cun , Huber Hillary F. , Schwab Matthias , Nathanielsz Peter W. , Clarke Geoffrey D.
Published: April 2017

Key points

Maternal nutrient restriction induces intrauterine growth restriction (IUGR) and leads to heightened cardiovascular risks later in life.

We report right ventricular (RV) filling and ejection abnormalities in IUGR young adult baboons using cardiac magnetic resonance imaging.

Both functional and morphological indicators of poor RV function were seen, many of which were similar to effects of ageing, but also with a few key differences.

We observed more pronounced RV changes compared to our previous report of the left ventricle, suggesting there is likely to be a component of isolated RV abnormality in addition to expected haemodynamic sequelae from left ventricular dysfunction. In particular, our findings raise the suspicion of pulmonary hypertension after IUGR.

This study establishes that IUGR also leads to impairment of the right ventricle in addition to the left ventricle classically studied.

Maternal nutrient restriction induces intrauterine growth restriction (IUGR), increasing later life chronic disease including cardiovascular dysfunction. Our left ventricular (LV) CMRI studies in IUGR baboons (8 M, 8 F, 5.7 years – human equivalent approximately 25 years), control offspring (8 M, 8 F, 5.6 years), and normal elderly (OLD) baboons (6 M, 6 F, mean 15.9 years) revealed long‐term LV abnormalities in IUGR offspring. Although it is known that right ventricular (RV) function is dependent on LV health, the IUGR right ventricle remains poorly studied. We examined the right ventricle with cardiac magnetic resonance imaging in the same cohorts. We observed decreased ejection fraction (49 ± 2 vs. 33 ± 3%, P < 0.001), cardiac index (2.73 ± 0.27 vs. 1.89 ± 0.20 l min−1 m−2, P < 0.05), early filling rate/body surface area (BSA) (109.2 ± 7.8 vs. 44.6 ± 7.3 ml s−1 m−2, P < 0.001), wall thickening (61 ± 3 vs. 44 ± 5%, P < 0.05), and longitudinal shortening (26 ± 3 vs. 15 ± 2%, P < 0.01) in IUGR animals with increased chamber volumes. Many, but not all, of these changes share similarities to normal older animals. Our findings suggest IUGR‐induced pulmonary hypertension should be further investigated and that atrial volume, pulmonic outflow and interventricular septal motion may provide valuable insights into IUGR cardiovascular physiology. Overall, our findings reaffirm that gestational and neonatal challenges can result in long‐term programming of poor offspring cardiovascular health. To our knowledge, this is the first study reporting IUGR‐induced programmed adult RV dysfunction in an experimental primate model.
Papers of note in
Science
356
(6335)
Authors: VanHook Annalisa M.
Published: April 2017

This week’s articles highlight a peptide that controls myoblast fusion; a metabolic adaptation that enables naked mole-rats to resist the detrimental effects of anoxia; a transcription factor that coordinates signaling in the mammary epithelial stem cell niche; and transgenerational epigenetic inheritance of the response to an environmental stimulus.
Identification of Antifungal H
+
-ATPase Inhibitors with Effect on Plasma Membrane Potential
Authors: Kjellerup Lasse , Gordon Sandra , Cohrt Karen O'Hanlon , Brown William Dalby , Fuglsang Anja Thoe , Winther Anne-Marie L.
Published: April 2017

The plasma membrane H
+
-ATPase (Pma1) is an essential fungal protein and a proposed target for new antifungal medications. The compounds in a small-molecule library containing ∼191,000 commercially available compounds were screened for their ability to inhibit
Saccharomyces cerevisiae
plasma membranes containing Pma1. The overall hit rate was 0.2%, corresponding to 407 compounds. These hit compounds were further evaluated for ATPase selectivity and broad-spectrum antifungal activity. Following this work, one Pma1 inhibitor series based on compound 14 and analogs was selected for further evaluation. This compound series was able to depolarize the membrane and inhibit extracellular acidification in intact fungal cells concomitantly with a significant increase in intracellular ATP levels. Collectively, we suggest that these effects may be a common feature of Pma1 inhibitors. Additionally, the work uncovered a dual mechanism for the previously identified cationic peptide BM2, revealing fungal membrane disruption, in addition to Pma1 inhibition. The methods presented here provide a solid platform for the evaluation of Pma1-specific inhibitors in a drug development setting. The present inhibitors could serve as a starting point for the development of new antifungal agents with a novel mode of action.
New Macrolide-Lincosamide-Streptogramin B Resistance Gene
erm
(48) on the Novel Plasmid pJW2311 in Staphylococcus xylosus
Authors: Wipf Juliette R. K. , Riley Matthew C. , Kania Stephen A. , Bemis David A. , Andreis Sabrina , Schwendener Sybille , Perreten Vincent
Published: April 2017

Whole-genome sequencing of
Staphylococcus xylosus
strain JW2311 from bovine mastitis milk identified the novel 49.3-kb macrolide-lincosamide-streptogramin B (MLS
B
) resistance plasmid pJW2311. It contained the macrolide resistance gene
mph
(C), the macrolide-streptogramin B resistance gene
msr
(A), and the new MLS
B
resistance gene
erm
(48) and could be transformed into
Staphylococcus aureus
by electroporation. Functionality of
erm
(48) was demonstrated by cloning and expression in
S. aureus
.
Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media
Authors: Hoberman Alejandro , Paradise Jack L. , Rockette Howard E. , Jeong Jong-Hyeon , Kearney Diana H. , Bhatnagar Sonika , Shope Timothy R. , Muñiz Gysella , Martin Judith M. , Kurs-Lasky Marcia , Haralam MaryAnn , Pope Marcia A. , Nagg Jennifer P. , Zhao Wenchen , Miah Mohammad Kowser , Beumer Jan , Venkataramanan Raman , Shaikh Nader
Published: April 2017

Amoxicillin-clavulanate (A/C) is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but the standard dosage of 90 mg amoxicillin/6.4 mg clavulanate/kg of body weight/day commonly causes diarrhea. We examined whether an A/C formulation containing lower concentrations of clavulanate would result in less diarrhea while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and to achieve clinical success. We conducted an open-label study in children with AOM who were 6 to 23 months of age. In phase 1, we treated 40 children with a reduced-clavulanate A/C formulation providing 90 mg amoxicillin/3.2 mg clavulanate/kg/day for 10 days. In phase 2, we treated 72 children with the same formulation at a dosage of 80 mg amoxicillin/2.85 mg clavulanate/kg/day for 10 days. We compared the rates of protocol-defined diarrhea (PDD), diaper dermatitis, and AOM clinical response in these children with rates we had reported in children who received the standard A/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving phase 2 and standard regimens were 17% and 26%, respectively (
P
= 0.10). The corresponding rates of diaper dermatitis were 21% and 33% (
P
= 0.04) and of AOM treatment failure were 12% and 16% (
P
= 0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit β-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side effects without reducing clinical efficacy. (This study has been registered at ClinicalTrials.gov under registration no. NCT02630992.)
Multihospital Occurrence of Pan-Resistant Klebsiella pneumoniae Sequence Type 147 with an IS
Ecp1
-Directed
bla
OXA-181
Insertion in the
mgrB
Gene in the United Arab Emirates
Authors: Sonnevend Ágnes , Ghazawi Akela , Hashmey Rayhan , Haidermota Aliasgher , Girgis Safinaz , Alfaresi Mubarak , Omar Mohammed , Paterson David L. , Zowawi Hosam M. , Pál Tibor
Published: April 2017

The emergence of pan-resistant
Klebsiella pneumoniae
strains is an increasing concern. In the present study, we describe a cluster of 9 pan-resistant
K. pneumoniae
sequence type 147 (ST147) isolates encountered in 4 patients over nearly 1 year in 3 hospitals of the United Arab Emirates (UAE). The isolates exhibited highly similar genotypes. All produced chromosomally encoded OXA-181, and the majority also produced the NDM-5 carbapenemase. As with the previously described single isolate from the UAE, MS6671, the
mgrB
was disrupted by a functional, IS
Ecp1
-driven
bla
OXA-181
insertion causing resistance to carbapenems. The mutation was successfully complemented with an intact
mgrB
gene, indicating that it was responsible for colistin resistance.
bla
NDM-5
was located within a resistance island of an approximately 100-kb IncFII plasmid carrying
ermB
,
mph
(A),
bla
TEM-1B
,
rmtB
,
bla
NDM-5
,
sul1
,
aadA2
, and
dfrA12
resistance genes. Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly identical to that of plasmid pMS6671E from which several resistance genes, including
bla
NDM-5
, had been deleted. More extensive similarities of the backbone and the resistance island were found between pABC143C-NDM and the
bla
NDM-5
-carrying IncFII plasmids of two
K. pneumoniae
ST147 isolates from South Korea, one of which was colistin resistant, and both also produced OXA-181. Notably, one of these strains was isolated from a patient transferred from the UAE. Our data show that this pan-resistant clone has an alarming capacity to maintain itself over an extended period of time and is even likely to be transmitted internationally.
Identification of Mycobacterial Genes Involved in Antibiotic Sensitivity: Implications for the Treatment of Tuberculosis with β-Lactam-Containing Regimens
Authors: Viswanathan Gopinath , Yadav Sangya , Raghunand Tirumalai R.
Published: April 2017

In a
Mycobacterium smegmatis
mutant library screen, transposon mutants with insertions in
fhaA
,
dprE2
,
rpsT
, and
parA
displayed hypersusceptibility to antibiotics, including the β-lactams meropenem, ampicillin, amoxicillin, and cefotaxime. Sub-MIC levels of octoclothepin, a psychotic drug inhibiting ParA, phenocopied the
parA
insertion and enhanced the bactericidal activity of meropenem against
Mycobacterium tuberculosis
in combination with clavulanate. Our study identifies novel factors associated with antibiotic resistance, with implications in repurposing β-lactams for tuberculosis treatment.
Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in
In Vitro
and
In Vivo
Studies
Authors: Wen Xiang , Zhang Xiaoshen , Szewczyk Grzegorz , El-Hussein Ahmed , Huang Ying-Ying , Sarna Tadeusz , Hamblin Michael R.
Published: April 2017

Rose bengal (RB) is a halogenated xanthene dye that has been used to mediate antimicrobial photodynamic inactivation for several years. While RB is highly active against Gram-positive bacteria, it is largely inactive in killing Gram-negative bacteria. We have discovered that addition of the nontoxic salt potassium iodide (100 mM) potentiates green light (540-nm)-mediated killing by up to 6 extra logs with the Gram-negative bacteria
Escherichia coli
and
Pseudomonas aeruginosa
, the Gram-positive bacterium methicillin-resistant
Staphylococcus aureus
, and the fungal yeast
Candida albicans
. The mechanism is proposed to be singlet oxygen addition to iodide anion to form peroxyiodide, which decomposes into radicals and, finally, forms hydrogen peroxide and molecular iodine. The effects of these different bactericidal species can be teased apart by comparing the levels of killing achieved in three different scenarios: (i) cells, RB, and KI are mixed together and then illuminated with green light; (ii) cells and RB are centrifuged, and then KI is added and the mixture is illuminated with green light; and (iii) RB and KI are illuminated with green light, and then cells are added after illumination with the light. We also showed that KI could potentiate RB photodynamic therapy in a mouse model of skin abrasions infected with bioluminescent
P. aeruginosa
.
Evaluation of the Ability of a Novel Miconazole Formulation To Penetrate Nail by Using Three
In Vitro
Nail Models
Authors: Christensen Luisa , Turner Rob , Weaver Sean , Caserta Francesco , Long Lisa , Ghannoum Mahmoud , Brown Marc
Published: April 2017

In an effort to increase the efficacy of topical medications for treating onychomycosis, several new nail penetration enhancers were recently developed. In this study, the ability of 10% (wt/wt) miconazole nitrate combined with a penetration enhancer formulation to permeate the nail is demonstrated by the use of a selection of
in vitro
nail penetration assays. These assays included the bovine hoof, TurChub zone of inhibition, and infected-nail models.
Position of O-Acetylation within the Capsular Repeat Unit Impacts the Biological Properties of Pneumococcal Serotypes 33A and 33F
Authors: Spencer Brady L. , Saad Jamil S. , Shenoy Anukul T. , Orihuela Carlos J. , Nahm Moon H.
Published: April 2017

Streptococcus pneumoniae
(pneumococcus) produces many capsule types that differ in their abilities to evade host immune recognition. To explain these serotype-dependent protective capacities, many studies have investigated capsular thickness or the interaction of the capsule with complement proteins, but the effects of small chemical modifications of the capsule on its function have not been studied. One small chemical modification found frequently among pneumococcal capsules is O-acetylation. Pneumococcal serotype 33A has two membrane-bound
O
-acetyltransferase genes,
wciG
and
wcjE
. A 33A
wcjE
-deficient variant, 33F, occurs naturally and is increasing in prevalence in the wake of widespread conjugate vaccine use, but no
wciG
-deficient variants have been reported. To study the biological consequence of the loss of O-acetylation, we created
wciG
-deficient variants in both serotypes 33A and 33F, which we named 33X1 (Δ
wciG
) and 33X2 (Δ
wciG
Δ
wcjE
). Serotypes 33X1 and 33X2 express novel capsule types based on serological and biochemical analyses. We found that loss of WcjE-mediated O-acetylation appears not to affect cell wall shielding, since serotypes 33A and 33F exhibit comparable nonspecific opsonophagocytic killing, biofilm production, and adhesion to nasopharyngeal cells, though serotype 33F survived short-term drying better than serotype 33A. Loss of WciG-mediated O-acetylation in serotypes 33X1 and 33X2, however, resulted in a phenotype resembling that of nonencapsulated strains: increased cell wall accessibility, increased nonspecific opsonophagocytic killing, enhanced biofilm formation, and increased adhesion to nasopharyngeal cells. We conclude that WciG-mediated, but not WcjE-mediated, O-acetylation is important for producing protective capsules in 33A and that small chemical changes to the capsule can drastically affect its biological properties.
Bacillus anthracis Edema Toxin Increases Fractional Free Water and Sodium Reabsorption in an Isolated Perfused Rat Kidney Model
Authors: Jaswal Dharmvir S. , Cui Xizhong , Torabi-Parizi Parizad , Ohanjanian Lernik , Sampath-Kumar Hannish , Fitz Yvonne , Li Yan , Xu Wanying , Eichacker Peter Q.
Published: April 2017

Bacillus anthracis
edema toxin (ET) consists of protective antigen (PA), necessary for host cell toxin uptake, and edema factor (EF), the toxic moiety which increases host cell cyclic AMP (cAMP). Since vasopressin stimulates renal water and sodium reabsorption via increased tubular cell cAMP levels, we hypothesized the ET would also do so. To test this hypothesis, we employed an isolated perfused rat kidney model. Kidneys were isolated and perfused with modified Krebs-Henseleit buffer. Perfusate and urine samples were obtained at baseline and every 10 min over 150 min following the addition of challenges with or without treatments to the perfusate. In kidneys perfused under constant flow or constant pressure, compared to PA challenge (
n
= 14 or 15 kidneys, respectively), ET (13 or 15 kidneys, respectively) progressively increased urine cAMP levels, water and sodium reabsorption, and urine osmolality and decreased urine output (
P
≤ 0.04, except for sodium reabsorption under constant pressure [
P
= 0.17]). In ET-challenged kidneys, compared to placebo treatment, adefovir, an EF inhibitor, decreased urine cAMP levels, water and sodium reabsorption, and urine osmolality and increased urine output, while raxibacumab, a PA-directed monoclonal antibody (MAb), decreased urine cAMP levels, free water reabsorption, and urine osmolality and increased urine output (
P
≤ 0.03 except for urine output with raxibacumab [
P
= 0.17]). Upon immunohistochemistry, aquaporin 2 was concentrated along the apical membrane of tubular cells with ET but not PA, and urine aquaporin 2 levels were higher with ET (5.52 ± 1.06 ng/ml versus 1.51 ± 0.44 ng/ml [means ± standard errors of the means {SEM};
P
= 0.0001). Edema toxin has renal effects that could contribute to extravascular fluid collection characterizing anthrax infection clinically.
Pulmonary Interleukin-17-Positive Lymphocytes Increase during Pneumocystis murina Infection but Are Not Required for Clearance of Pneumocystis
Authors: Ripamonti Chiara , Bishop Lisa R. , Kovacs Joseph A.
Published: April 2017

Pneumocystisremains an important pathogen of immunosuppressed patients, causing a potentially life-threatening pneumonia. Despite its medical importance, the immune responses required to control infection, including the role of interleukin-17 (IL-17), which is important in controlling other fungal infections, have not been clearly defined. Using flow cytometry and intracellular cytokine staining after stimulation with phorbol myristate acetate and ionomycin, we examined gamma interferon (IFN-γ), IL-4, IL-5, and IL-17 production by lung lymphocytes in immunocompetent C57BL/6 mice over time following infection withPneumocystismurina. We also examined the clearance ofPneumocystisinfection in IL-17A-deficient mice. The production of both IFN-γ and IL-17 by pulmonary lymphocytes increased during infection, with maximum production at approximately days 35 to 40, coinciding with peakPneumocystislevels in the lungs, while minimal changes were seen in IL-4- and IL-5-positive cells. The proportion of cells producing IFN-γ was consistently higher than for cells producing IL-17, with peak levels of ∼25 to 30% of CD3+T cells for the former compared to ∼15% for the latter. Both CD4+T cells and γδ T cells produced IL-17. Administration of anti-IFN-γ antibody led to a decrease in IFN-γ-positive cells, and an increase in IL-5-positive cells, but did not impact clearance ofPneumocystisinfection. Despite the increases in IL-17 production during infection, IL-17A-deficient mice clearedPneumocystisinfection with kinetics similar to C57BL/6 mice. Thus, while IL-17 production in the lungs is increased duringPneumocystisinfection in immunocompetent mice, IL-17A is not required for control ofPneumocystisinfection.
Peptoanaerobacter stomatis Primes Human Neutrophils and Induces Granule Exocytosis
Authors: Jimenez Flores E. , Tian S. , Sizova M. , Epstein S. S. , Lamont R. J. , Uriarte S. M.
Published: April 2017

Peptoanaerobacter stomatisis a newly appreciated taxon associated with periodontal diseases; however, little is known about the organism's pathogenic potential or its interaction with the host immune response. Neutrophils are the most abundant innate immune cell present in the gingival tissue and function to constrain the oral microbial challenge. However, some periodontal pathogens have developed strategies to evade phagocytosis and killing by neutrophils. Therefore, to begin to understand the role ofP. stomatisin periodontitis, we studied its interactions with human neutrophils. Our data showed that after 30 min of incubation, neutrophils failed to engulfP. stomatisefficiently; however, whenP. stomatiswas internalized, it was promptly eradicated.P. stomatischallenge induced a robust intracellular respiratory burst; however, this response did not contribute to bacterial killing. Minimal superoxide release was observed by direct bacterial challenge; however,P. stomatissignificantly increasedN-formyl-methionyl-leucyl phenylalanine (fMLF)-stimulated superoxide release to an extent similar to that of cells primed with tumor necrosis factor alpha (TNF-α). When neutrophils were challenged withP. stomatis, 52% of the bacterium-containing phagosomes were enriched for the specific granule marker lactoferrin and 82% with the azurophil granule marker elastase.P. stomatischallenge stimulated exocytosis of the four neutrophil granule subtypes. Moreover,P. stomatissusceptibility to extracellular killing could be attributed to the exocytosis of antimicrobial components present in neutrophil granules. Priming neutrophils for an enhanced respiratory burst together with promoting granule content release could contribute to the chronic inflammation and tissue destruction that characterize periodontal diseases.
Inactivation of Transcriptional Regulators during Within-Household Evolution of Escherichia coli
Authors: Kisiela Dagmara I. , Radey Matthew , Paul Sandip , Porter Stephen , Polukhina Kseniya , Tchesnokova Veronika , Shevchenko Sofiya , Chan Diana , Aziz Maliha , Johnson Timothy J. , Price Lance B. , Johnson James R. , Sokurenko Evgeni V.
Published: April 2017

We analyzed the within-household evolution of two household-associated
Escherichia coli
strains from pandemic clonal group ST131-
H
30, using isolates recovered from five individuals within two families, each of which had a distinct strain. Family 1's strain was represented by a urine isolate from the index patient (older sister) with recurrent cystitis and a blood isolate from her younger sister with fatal urosepsis. Family 2's strain was represented by a urine isolate from the index patient (father) with pyelonephritis and renal abscesses, blood and kidney drainage isolates from the daughter with emphysematous pyelonephritis, and urine and fecal isolates from the mother with cystitis. Collectively, the several variants of each family's strain had accumulated a total of 8 (family 1) and 39 (family 2) point mutations; no two isolates were identical. Of the 47 total mutations, 36 resulted in amino acid changes or truncation of coded proteins. Fourteen such mutations (39%) targeted genes encoding transcriptional regulators, and 9 (25%) involved DNA-binding transcription factors (TFs), which significantly exceeded the relative contribution of TF genes to the isolates' genomes (∼6%). At least one-half of the transcriptional regulator mutations were inactivating, based on phenotypic and/or transcriptional analysis. In particular, inactivating mutations in the global regulator LrhA (repressor of type 1 fimbriae and flagella) occurred in the blood isolates from both households and increased the virulence of
E. coli
strains in a murine sepsis model. The results indicate that
E. coli
undergoes adaptive evolution between and/or within hosts, generating subpopulations with distinctive phenotypes and virulence potential.

IMPORTANCE
The clonal evolution of bacterial strains associated with interhost transmission is poorly understood. We characterized the genome sequences of clonal descendants of two
Escherichia coli
strains, recovered at different time points from multiple individuals within two households who had different types of urinary tract infection. We found evidence that the
E. coli
strains underwent extensive mutational diversification between and within these individuals, driven disproportionately by inactivation of transcriptional regulators. In urosepsis isolates, the mutations observed in the global regulator LrhA increased bacterial virulence in a murine sepsis model. Our findings help in understanding the adaptive dynamics and strategies of
E. coli
during short-term natural evolution.
Impact of Membrane Phospholipid Alterations in Escherichia coli on Cellular Function and Bacterial Stress Adaptation
Authors: Rowlett Veronica W. , Mallampalli Venkata K. P. S. , Karlstaedt Anja , Dowhan William , Taegtmeyer Heinrich , Margolin William , Vitrac Heidi
Published: April 2017

Bacteria have evolved multiple strategies to sense and rapidly adapt to challenging and ever-changing environmental conditions. The ability to alter membrane lipid composition, a key component of the cellular envelope, is crucial for bacterial survival and adaptation in response to environmental stress. However, the precise roles played by membrane phospholipids in bacterial physiology and stress adaptation are not fully elucidated. The goal of this study was to define the role of membrane phospholipids in adaptation to stress and maintenance of bacterial cell fitness. By using genetically modified strains in which the membrane phospholipid composition can be systematically manipulated, we show that alterations in major
Escherichia coli
phospholipids transform these cells globally. We found that alterations in phospholipids impair the cellular envelope structure and function, the ability to form biofilms, and bacterial fitness and cause phospholipid-dependent susceptibility to environmental stresses. This study provides an unprecedented view of the structural, signaling, and metabolic pathways in which bacterial phospholipids participate, allowing the design of new approaches in the investigation of lipid-dependent processes involved in bacterial physiology and adaptation.

IMPORTANCE
In order to cope with and adapt to a wide range of environmental conditions, bacteria have to sense and quickly respond to fluctuating conditions. In this study, we investigated the effects of systematic and controlled alterations in bacterial phospholipids on cell shape, physiology, and stress adaptation. We provide new evidence that alterations of specific phospholipids in
Escherichia coli
have detrimental effects on cellular shape, envelope integrity, and cell physiology that impair biofilm formation, cellular envelope remodeling, and adaptability to environmental stresses. These findings hold promise for future antibacterial therapies that target bacterial lipid biosynthesis.
Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis
Authors: Northey Joseph Michael , Cherbuin Nicolas , Pumpa Kate Louise , Smee Disa Jane , Rattray Ben
Published: April 2017

Background

Physical exercise is seen as a promising intervention to prevent or delay cognitive decline in individuals aged 50 years and older, yet the evidence from reviews is not conclusive.

Objectives

To determine if physical exercise is effective in improving cognitive function in this population.

Design

Systematic review with multilevel meta-analysis.

Data sources

Electronic databases Medline (PubMed), EMBASE (Scopus), PsychINFO and CENTRAL (Cochrane) from inception to November 2016.

Eligibility criteria

Randomised controlled trials of physical exercise interventions in community-dwelling adults older than 50 years, with an outcome measure of cognitive function.

Results

The search returned 12 820 records, of which 39 studies were included in the systematic review. Analysis of 333 dependent effect sizes from 36 studies showed that physical exercise improved cognitive function (0.29; 95% CI 0.17 to 0.41; p<0.01). Interventions of aerobic exercise, resistance training, multicomponent training and tai chi, all had significant point estimates. When exercise prescription was examined, a duration of 45–60 min per session and at least moderate intensity, were associated with benefits to cognition. The results of the meta-analysis were consistent and independent of the cognitive domain tested or the cognitive status of the participants.

Conclusions

Physical exercise improved cognitive function in the over 50s, regardless of the cognitive status of participants. To improve cognitive function, this meta-analysis provides clinicians with evidence to recommend that patients obtain both aerobic and resistance exercise of at least moderate intensity on as many days of the week as feasible, in line with current exercise guidelines.
Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction
Authors: Gerassy-Vainberg Shiran , Blatt Alexandra , Danin-Poleg Yael , Gershovich Katya , Sabo Edmond , Nevelsky Alex , Daniel Shahar , Dahan Aviva , Ziv Oren , Dheer Rishu , Abreu Maria T , Koren Omry , Kashi Yechezkel , Chowers Yehuda
Published: April 2017

Objective

Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model.

Design

We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial–epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1β correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice.

Results

A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology. Increased colonic tumor necrosis factor (TNF)α, IL-1β and IL-6 expression was observed at two different time points. Adherent microbiota from RP differed from those in uninvolved segments and was associated with tissue damage. Using bacterial–epithelial co-cultures, postradiation microbiota enhanced IL-1β and TNFα expression compared with naïve microbiota. GF mice colonisation by irradiated microbiota versus controls predisposed mice to both radiation injury and DSS-induced colitis. IL-1 receptor antagonist administration ameliorated intestinal radiation injury.

Conclusions

The results demonstrate that rectal radiation induces dysbiosis, which transmits radiation and inflammatory susceptibility and provide evidence that microbial-induced radiation tissue damage is at least in part mediated by IL-1β. Environmental factors may affect the host via modifications of the microbiome and potentially allow for novel interventional approaches via its manipulation.
Mistakes and missed opportunities regarding cosmetic surgery and conscientious objection
Authors: Saad Toni C
Published: April 2017

In her paper ‘Cosmetic surgery and conscientious objection’, Minerva rightly identifies cosmetic surgery as an interesting test case for the question of conscientious objection in medicine. Her treatment of this important subject, however, seems problematic. It is argued that Minerva's suggestion that a doctor has a prima facie duty to satisfy patient preferences even against his better clinical judgment, which we call Patient Preference Absolutism, must be regarded with scepticism. This is because (1) it overlooks an important distinction regarding autonomy's meaning and place in clinical practice, and (2) it makes obsolete the important concepts of expert clinical judgment and beneficence. Finally, we discuss two ideas which emerge from consideration of cosmetic surgery in relation to conscientious objection. These are the possible analogy between clinical judgment and conscientious objection, and the possible role the goals of medicine can play in defining the scope of conscientious objection.
A Novel Weighted Variational Model for Image Denoising
Authors: Islam Md. Robiul , Xu Chen , Han Yu , Ashfaq Rana Aamir Raza
Published: April 2017

Image denoising as a part of pre-processing in image analysis is a challenging area of research since noise removal and image detail preservation need a tradeoff. For classical denoising models, the convex total variation (TV) or some nonconvex regularizers are used to achieve the tradeoff. However, the denoising performance of classical models is still inadequate. To overcome this problem, this paper proposes a new variational model for image restoration, where a weighted regularizer is designed to protect more geometric structural details of images from over-smoothing and to remove much noise simultaneously. To solve the model efficiently, a novel algorithm based on Chambolle’s dual projection method and the iteratively reweighting method is presented. Numerical results prove that the proposed denoising method can show better performance than the classical TV-based and the nonconvex regularizer-based denoising methods.
On the autonomous norm on the group of Hamiltonian diffeomorphisms of the torus
Authors: Brandenbursky Michael , Kędra Jarek , Shelukhin Egor
Published: April 2017

We prove that the autonomous norm on the group of Hamiltonian diffeomorphisms of the two-dimensional torus is unbounded. We provide examples of Hamiltonian diffeomorphisms with arbitrarily large autonomous norm. For the proofs we construct explicit quasimorphisms on [Formula: see text] some of them are [Formula: see text]-continuous and vanish on all autonomous diffeomorphisms, and some of them are Calabi.
On the Chern numbers and the Hilbert polynomial of an almost complex manifold with a circle action
Authors: Sabatini Silvia
Published: April 2017

Let [Formula: see text] be a compact, connected, almost complex manifold of dimension [Formula: see text] endowed with a [Formula: see text]-preserving circle action with isolated fixed points. In this paper, we analyze the “geography problem” for such manifolds, deriving equations relating the Chern numbers to the index [Formula: see text] of [Formula: see text]. We study the symmetries and zeros of the Hilbert polynomial, which imply many rigidity results for the Chern numbers when [Formula: see text]. We apply these results to the category of compact, connected symplectic manifolds. A long-standing question posed by McDuff and Salamon asked about the existence of non-Hamiltonian actions with isolated fixed points. This question was answered recently by Tolman, with an explicit construction of a 6-dimensional manifold with such an action. One issue that this raises is whether one can find topological criteria that ensure the manifold can only support a Hamiltonian or only a non-Hamiltonian action. In this vein, we are able to deduce such criteria from our rigidity theorems in terms of relatively few Chern numbers, depending on the index. Another consequence is that, if the action is Hamiltonian, the minimal Chern number coincides with the index and is at most [Formula: see text].
Catalytic Oxidation of Vanillyl Alcohol Using FeMCM-41 Nanoporous Tubular Reactor
Authors: Elamathi P. , Kolli Murali Krishna , Chandrasekar G.
Published: April 2017

Iron containing nanoporous MCM-41 (FeMCM-41) with different Si/Fe ratios of 50, 100 and 150 was synthesized by hydrothermal synthesis process. The materials obtained from hydrothermal synthesis were characterized by various physico chemical techniques such as XRD, N2 adsorption, DR UV-vis, EPR and FTIR spectroscopy. XRD analyses of FeMCM-41 materials confirmed the presence of well-ordered crystalline structure. N2 isotherm of FeMCM-41 materials showed type IV adsorption isotherm. EPR and DR UV-vis analysis of FeMCM-41 samples indicates the presence of high tetrahedral coordination at the Si/Fe ratios of 100 and 150. The catalytic performance of FeMCM-41 nano tubular reactor was tested in the liquid phase oxidation of vanillyl alcohol into vanillin using H2O2 (50[Formula: see text]wt% in water). The reaction products were analyzed by gas chromatography in DB-5 capillary column with flame ionization detector. The products were confirmed by 1H NMR, [Formula: see text]C NMR and LC-Mass spectroscopy. The maximum conversion of vanillyl alcohol (85%) and selectivity towards vanillin (82%) were observed using the catalyst FeMCM-41(100) in 30[Formula: see text]min at 60[Formula: see text]C. The influence of reaction temperature, reaction time, reactants molar ratio, Si/Fe ratio and amount of catalyst were investigated.
Preparation of Magnesium-Based Cobalt-Ferrites (Co1−xMgxFe2O4) Nanoparticles by Sol–Gel Auto Combustion Method
Authors: Gowreesan S. , Ruban Kumar A.
Published: April 2017

The scope of the present work is in enhancing the particle size, and dielectric properties of Mg-substituted Cobalt ferrites nanoparticles prepared by sol–gel auto combustion method. The different ratios of Mg-substituted Co Ferrites (Co[Formula: see text]MgxFe2O4([Formula: see text], 0.05, 0.10, 0.15, 0.20 and 0.30)) are calcinated at 850[Formula: see text]C. The synthesized nanoparticles were characterized by powder XRD, FTIR, FE-SEM, EDX techniques and dielectric behavior. The structural parameters were confirmed from powder XRD and the average particle size is obtained from 39 to 67 nm due to the substitution of Mg[Formula: see text] which was calculated by Debye Scherrer’s formula. FE-SEM showed the surface morphology of the different ratio of the sample. The dielectric loss has measured the frequency range of 50[Formula: see text]Hz–5[Formula: see text]MHz. From electrical modulus, conductivity relaxation and thermal activation of charge carriers has been discussed.
Slag-Based Nanomaterial in the Removal of Hexavalent Chromium
Authors: Baalamurugan J. , Ganesh Kumar V. , Govindaraju K. , Naveen Prasad B. S. , Bupesh Raja V. K. , Padmapriya R.
Published: April 2017

Slag-based nanomaterial is a by-product obtained during steel production and has wide range of components in the form of oxides. In this study, Induction Furnace (IF) steel slag-based application in adsorption of hexavalent chromium is investigated. IF slag has mixture of oxides mainly Fe2O3 and Chromium (VI) a highly toxic pollutant leads to environmental pollution and causes problem to human health mainly, carcinogenetic diseases. Slag-based nanomaterial is characterized using High Resolution Scanning Electron Microscope (HR-SEM) in which the size was around 100[Formula: see text]nm and X-ray Fluorescence (XRF) spectroscopy. Further inductively coupled plasma mass spectroscopy and Fourier transform infrared spectroscopy were used for adsorption studies. Slag activation using NaOH (alkali activation) to the intent of surface hydroxyl ([Formula: see text]OH) group attachment will be a cost-effective process in the removal of hexavalent chromium. Cr(VI) ions are adsorbed on the surface of alkali activated slag material. The core-shell formation of Fe(II)/Fe(III)/Cr(VI) and the adsorption are investigated in detail in the present study.
Synthesis of Zn1−xCdxO Nanoparticles by Co-Precipitation: Structural, Optical and Photodetection Analysis
Authors: Jacob Anju Anna , Balakrishnan L. , Meher S. R. , Shambavi K. , Alex Z. C.
Published: April 2017

Zinc oxide (ZnO) is a wide bandgap semiconductor with excellent photoresponse in ultra-violet (UV) regime. Tuning the bandgap of ZnO by alloying with cadmium can shift its absorption cutoff wavelength from UV to visible (Vis) region. Our work aims at synthesis of Zn[Formula: see text]CdxO nanoparticles by co-precipitation method for the fabrication of photodetector. The properties of nanoparticles were analyzed using X-ray diffractometer, UV–Vis spectrometer, scanning electron microscope and energy dispersive spectrometer. The incorporation of cadmium without altering the wurtzite structure resulted in the red shift in the absorption edge of ZnO. Further, the photoresponse characteristics of Zn[Formula: see text]CdxO nanopowders were investigated by fabricating photodetectors. It has been found that with Cd alloying the photosensitivity was increased in the UVA-violet as well in the blue region.
Complex symmetric operators and semiclassical resonances
Authors: Messirdi Bekkai , Messirdi Sofiane , Messirdi Miloud
Published: April 2017

Unbounded complex symmetric operators on Hilbert space are discussed and various spectral results on these operators are presented in this paper. In addition, we show that the technique of complex scaling allows one to identify the quantum resonances of complex self-adjoint Schrödinger Hamiltonians.
Novel preparation of multiwalled carbon nanotubes/bacterial cellulose nanocomposite for phthalocyanine immobilization
Authors: Chen Shiliang , Huang Yijun , Huang Jiachi
Published: April 2017

Electrically conducting multiwalled carbon nanotubes (MWCNT) incorporated bacterial cellulose (BC) nanocomposite (MWCNT/BC) was prepared by briefly sonicating MWCNT-DMF/H2O dispersion immersed with BC, no addition of surfactant was required during the process. The conductivity of MWCNT/BC, as measured by a four-probe instrument, was up to 0.32 S[Formula: see text]cm[Formula: see text]. Tetraamino cobalt (II) phthalocyanine (CoPc) catalyst was decorated onto the surface of pre-oxidized MWCNT/BC with covalent bonding. The resulting BC-based functional nanomaterial, CoPc decorated, MWCNT incorporated BC (CoPc@MWCNT/BC), is able to efficiently decolorize dye wastewater. The catalytic oxidation activity of CoPc was greatly improved with the incorporation of MWCNT.
The dielectric studies on sol–gel routed molybdenum oxide thin film
Authors: Arasu P. Adal , Williams R. Victor
Published: April 2017

The influence of temperature on the dielectric properties of sol-gel routed spin-coated molybdenum trioxide (MoO[Formula: see text] thin film has been investigated. Prepared films were annealed at temperatures 250[Formula: see text]C, 350[Formula: see text]C and 400[Formula: see text]C. The phase transformation from amorphous to [Formula: see text]-orthorhombic phase with preferential orientation (0 2 2) has been found by XRD for the film annealed above 250[Formula: see text]C. The vibration modes of [Formula: see text]-orthorhombic MoO3 have been examined by Raman spectrum. The predominant Raman’s band of [Formula: see text]-orthorhombic MoO3 thin film has been found at the frequency range 1000–600[Formula: see text]cm[Formula: see text]. Using the UV–Vis spectrum, the band gap of the film is found to be 3.3–3.8[Formula: see text]eV. The surface morphology of the MoO3 films has been examined by scanning electron microscope. The AC conductivity measurement of the MoO3 film has been carried out in the frequency range 10–106 Hz. The frequency dependence of the impedance has been plotted in the complex plane. The variation of the capacitance and dielectric constant of MoO3 film with respect to temperature and frequency has been analyzed. Tunability of capacitance and figure of merit of the film are also determined.
Largest eigenvalue of large random block matrices: A combinatorial approach
Authors: Banerjee Debapratim , Bose Arup
Published: April 2017

We study the largest eigenvalue of certain block matrices where the number of blocks and the block size both increase with suitable conditions on their relative growth. In one of them, we employ a symmetric block structure with large independent Wigner blocks and in the other we have the Wigner block structure with large independent symmetric blocks. The entries are assumed to be independent and identically distributed with mean [Formula: see text] variance [Formula: see text] with an appropriate growth condition on the moments. Under our conditions the limit spectral distribution of these matrices is the standard semi-circle law. It is natural to ask if the extreme eigenvalues converge to the extreme points of its support, namely [Formula: see text]. We exhibit models where this indeed happens as well as models where the spectral norm converges to [Formula: see text]. Our proofs are based on combinatorial analysis of the behavior of the trace of large powers of the matrix.
Precisely Where Are We Going? Charting the New Terrain of Precision Prevention
Authors: Meagher Karen M. , McGowan Michelle L. , Settersten Richard A. , Fishman Jennifer R. , Juengst Eric T.
Published: April 2017

In addition to genetic data, precision medicine research gathers information about three factors that modulate gene expression: lifestyles, environments, and communities. The relevant research tools—epidemiology, environmental assessment, and socioeconomic analysis—are those of public health sciences rather than molecular biology. Because these methods are designed to support inferences and interventions addressing population health, the aspirations of this research are expanding from individualized treatment toward precision prevention in public health. The purpose of this review is to explore the emerging goals and challenges of such a shift to help ensure that the genomics community and public policy makers understand the ethical issues at stake in embracing and pursuing precision prevention. Two emerging goals bear special attention in this regard: (a) public health risk reduction strategies, such as screening, and (b) the application of genomic variation studies to understand and reduce health disparities among population groups.
Neural Circuitry of Reward Prediction Error
Authors: Watabe-Uchida Mitsuko , Eshel Neir , Uchida Naoshige
Published: April 2017

Dopamine neurons facilitate learning by calculating reward prediction error, or the difference between expected and actual reward. Despite two decades of research, it remains unclear how dopamine neurons make this calculation. Here we review studies that tackle this problem from a diverse set of approaches, from anatomy to electrophysiology to computational modeling and behavior. Several patterns emerge from this synthesis: that dopamine neurons themselves calculate reward prediction error, rather than inherit it passively from upstream regions; that they combine multiple separate and redundant inputs, which are themselves interconnected in a dense recurrent network; and that despite the complexity of inputs, the output from dopamine neurons is remarkably homogeneous and robust. The more we study this simple arithmetic computation, the knottier it appears to be, suggesting a daunting (but stimulating) path ahead for neuroscience more generally.
Structure-function relations in physiology education: Where’s the mechanism?
Authors: Lira Matthew E. , Gardner Stephanie M.
Published: April 2017

Physiology demands systems thinking: reasoning within and between levels of biological organization and across different organ systems. Many physiological mechanisms explain how structures and their properties interact at one level of organization to produce emergent functions at a higher level of organization. Current physiology principles, such as structure-function relations, selectively neglect mechanisms by not mentioning this term explicitly. We explored how students characterized mechanisms and functions to shed light on how students make sense of these terms. Students characterized mechanisms as 1) processes that occur at levels of organization lower than that of functions; and 2) as detailed events with many steps involved. We also found that students produced more variability in how they characterized functions compared with mechanisms: students characterized functions in relation to multiple levels of organization and multiple definitions. We interpret these results as evidence that students see mechanisms as holding a more narrow definition than used in the biological sciences, and that students struggle to coordinate and distinguish mechanisms from functions due to cognitive processes germane to learning in many domains. We offer the instructional suggestion that we scaffold student learning by affording students opportunities to relate and also distinguish between these terms so central to understanding physiology.