bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insight into Daptomycin Bioavailability and Localization in Staphylococcus aureus Biofilms by Dynamic Fluorescence Imaging
Authors: Boudjemaa Rym , Briandet Romain , Revest Matthieu , Jacqueline Cédric , Caillon Jocelyne , Fontaine-Aupart Marie-Pierre , Steenkeste Karine
Published: June 2016

Staphylococcus aureus
is one of the most frequent pathogens responsible for biofilm-associated infections (BAI), and the choice of antibiotics to treat these infections remains a challenge for the medical community. In particular, daptomycin has been reported to fail against implant-associated
S. aureus
infections in clinical practice, while its association with rifampin remains a good candidate for BAI treatment. To improve our understanding of such resistance/tolerance toward daptomycin, we took advantage of the dynamic fluorescence imaging tools (time-lapse imaging and fluorescence recovery after photobleaching [FRAP]) to locally and accurately assess the antibiotic diffusion reaction in methicillin-susceptible and methicillin-resistant
S. aureus
biofilms. To provide a realistic representation of daptomycin action, we optimized an
in vitro
model built on the basis of our recently published
in vivo
mouse model of prosthetic vascular graft infections. We demonstrated that at therapeutic concentrations, daptomycin was inefficient in eradicating biofilms, while the matrix was not a shield to antibiotic diffusion and to its interaction with its bacterial target. In the presence of rifampin, daptomycin was still present in the vicinity of the bacterial cells, allowing prevention of the emergence of rifampin-resistant mutants. Conclusions derived from this study strongly suggest that
S. aureus
biofilm resistance/tolerance toward daptomycin may be more likely to be related to a physiological change involving structural modifications of the membrane, which is a strain-dependent process.
Association between the Presence of Aminoglycoside-Modifying Enzymes and
In Vitro
Activity of Gentamicin, Tobramycin, Amikacin, and Plazomicin against Klebsiella pneumoniae Carbapenemase- and Extended-Spectrum-β-Lactamase-Producing Enterobacter Species
Authors: Haidar Ghady , Alkroud Ammar , Cheng Shaoji , Churilla Travis M. , Churilla Bryce M. , Shields Ryan K. , Doi Yohei , Clancy Cornelius J. , Nguyen M. Hong
Published: June 2016

We compared the
in vitro
activities of gentamicin (GEN), tobramycin (TOB), amikacin (AMK), and plazomicin (PLZ) against 13
Enterobacter
isolates possessing both
Klebsiella pneumoniae
carbapenemase and extended-spectrum β-lactamase (KPC+/ESBL+) with activity against 8 KPC+/ESBL−, 6 KPC−/ESBL+, and 38 KPC−/ESBL− isolates. The rates of resistance to GEN and TOB were higher for KPC+/ESBL+ (100% for both) than for KPC+/ESBL− (25% and 38%, respectively), KPC−/ESBL+ (50% and 17%, respectively), and KPC−/ESBL− (0% and 3%, respectively) isolates. KPC+/ESBL+ isolates were more likely than others to possess an aminoglycoside-modifying enzyme (AME) (100% versus 38%, 67%, and 5%;
P
= 0.007, 0.06, and <0.0001, respectively) or multiple AMEs (100% versus 13%, 33%, and 0%, respectively;
P
< 0.01 for all). KPC+/ESBL+ isolates also had a greater number of AMEs (mean of 4.6 versus 1.5, 0.9, and 0.05, respectively;
P
< 0.01 for all). GEN and TOB MICs were higher against isolates with >1 AME than with ≤1 AME. The presence of at least 2/3 of KPC, SHV, and TEM predicted the presence of AMEs. PLZ MICs against all isolates were ≤4 μg/ml, regardless of KPC/ESBL pattern or the presence of AMEs. In conclusion, GEN and TOB are limited as treatment options against KPC+ and ESBL+
Enterobacter
. PLZ may represent a valuable addition to the antimicrobial armamentarium. A full understanding of AMEs and other aminoglycoside resistance mechanisms will allow clinicians to incorporate PLZ rationally into treatment regimens. The development of molecular assays that accurately and rapidly predict antimicrobial responses among KPC- and ESBL-producing
Enterobacter
spp. should be a top research priority.
Comparative Efficacies of Tedizolid Phosphate, Linezolid, and Vancomycin in a Murine Model of Subcutaneous Catheter-Related Biofilm Infection Due to Methicillin-Susceptible and -Resistant Staphylococcus aureus
Authors: Bayer Arnold S. , Abdelhady Wessam , Li Liang , Gonzales Rachelle , Xiong Yan Q.
Published: June 2016

Tedizolid, a novel oxazolidinone, exhibits bacteriostatic activity through inhibition of protein synthesis. The efficacies of tedizolid, linezolid, and vancomycin were compared in a murine catheter-related biofilm infection caused by methicillin-susceptible and -resistant
Staphylococcus aureus
(MSSA and MRSA, respectively) strains engineered for bioluminescence. We observed significantly improved efficacy in terms of decreased
S. aureus
densities and bioluminescent signals in the tedizolid-treated group versus the linezolid- and vancomycin-treated groups in the model of infection caused by the MSSA and MRSA strains.
Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 5. Oseltamivir Carboxylate
Authors: Galindo Bedor Danilo Cesar , Marchand Sandrine , Lamarche Isabelle , Laroche Julian , Pereira de Santana Davi , Couet William
Published: June 2016

The aim of this study was to determine the biopharmaceutical characteristics of oseltamivir carboxylate (OC) after pulmonary delivery. After OC bolus and intratracheal nebulization (NEB) in rats, blood was collected and bronchoalveolar lavages (BALs) were performed. Epithelial lining fluid (ELF) concentrations were estimated from BAL fluid. The area under the curve (AUC) ratio for ELF to plasma was 842 times higher after NEB than after intravenous (i.v.) administration, indicating that OC nebulization offers a biopharmaceutical advantage over i.v. administration.
The Spiroindolone KAE609 Does Not Induce Dormant Ring Stages in Plasmodium falciparum Parasites
Authors: Chavchich Marina , Van Breda Karin , Rowcliffe Kerryn , Diagana Thierry T. , Edstein Michael D.
Published: June 2016

In vitro
drug treatment with artemisinin derivatives, such as dihydroartemisinin (DHA), results in a temporary growth arrest (i.e., dormancy) at an early ring stage in
Plasmodium falciparum
. This response has been proposed to play a role in the recrudescence of
P. falciparum
infections following monotherapy with artesunate and may contribute to the development of artemisinin resistance in
P. falciparum
malaria. We demonstrate here that artemether does induce dormant rings, a finding which further supports the class effect of artemisinin derivatives in inducing the temporary growth arrest of
P. falciparum
parasites. In contrast and similarly to lumefantrine, the novel and fast-acting spiroindolone compound KAE609 does not induce growth arrest at the early ring stage of
P. falciparum
and prevents the recrudescence of DHA-arrested rings at a low concentration (50 nM). Our findings, together with previous clinical data showing that KAE609 is active against artemisinin-resistant K13 mutant parasites, suggest that KAE609 could be an effective partner drug with a broad range of antimalarials, including artemisinin derivatives, in the treatment of multidrug-resistant
P. falciparum
malaria.
Control of Clostridium difficile Physiopathology in Response to Cysteine Availability
Authors: Dubois Thomas , Dancer-Thibonnier Marie , Monot Marc , Hamiot Audrey , Bouillaut Laurent , Soutourina Olga , Martin-Verstraete Isabelle , Dupuy Bruno
Published: June 2016

The pathogenicity ofClostridium difficileis linked to its ability to produce two toxins: TcdA and TcdB. The level of toxin synthesis is influenced by environmental signals, such as phosphotransferase system (PTS) sugars, biotin, and amino acids, especially cysteine. To understand the molecular mechanisms of cysteine-dependent repression of toxin production, we reconstructed the sulfur metabolism pathways ofC. difficilestrain 630in silicoand validated some of them by testingC. difficilegrowth in the presence of various sulfur sources. High levels of sulfide and pyruvate were produced in the presence of 10 mM cysteine, indicating that cysteine is actively catabolized by cysteine desulfhydrases. Using a transcriptomic approach, we analyzed cysteine-dependent control of gene expression and showed that cysteine modulates the expression of genes involved in cysteine metabolism, amino acid biosynthesis, fermentation, energy metabolism, iron acquisition, and the stress response. Additionally, a sigma factor (SigL) and global regulators (CcpA, CodY, and Fur) were tested to elucidate their roles in the cysteine-dependent regulation of toxin production. Among these regulators, onlysigLinactivation resulted in the derepression of toxin gene expression in the presence of cysteine. Interestingly, thesigLmutant produced less pyruvate and H2S than the wild-type strain. Unlike cysteine, the addition of 10 mM pyruvate to the medium for a short time during the growth of the wild-type andsigLmutant strains reduced expression of the toxin genes, indicating that cysteine-dependent repression of toxin production is mainly due to the accumulation of cysteine by-products during growth. Finally, we showed that the effect of pyruvate on toxin gene expression is mediated at least in part by the two-component system CD2602-CD2601.
Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain
Authors: Satchell Karla J. F. , Jones Christopher J. , Wong Jennifer , Queen Jessica , Agarwal Shivani , Yildiz Fitnat H.
Published: June 2016

Vibrio cholerae
O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature
ctxB7
allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including
hns
and
vieA
, diguanylate cyclase genes, and genes belonging to the
lysR
and
gntR
regulatory families. Overall, the studies presented here revealed that
V. cholerae
virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates.
Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae
Authors: Schenk Mirjam , Mahapatra Sebabrata , Le Phuonganh , Kim Hee Jin , Choi Aaron W. , Brennan Patrick J. , Belisle John T. , Modlin Robert L.
Published: June 2016

The innate immune system recognizes microbial pathogens via pattern recognition receptors. One such receptor, NOD2, via recognition of muramyl dipeptide (MDP), triggers a distinct network of innate immune responses, including the production of interleukin-32 (IL-32), which leads to the differentiation of monocytes into dendritic cells (DC). NOD2 has been implicated in the pathogenesis of human leprosy, yet it is not clear whetherMycobacterium leprae, which has a distinct MDP structure, can activate this pathway. We investigated the effect of MDP structure on the innate immune response, finding that infection of monocytes withM. lepraeinduces IL-32 and DC differentiation in a NOD2-dependent manner. The presence of the proximall-Ala instead of Gly in the common configuration of the peptide side chain ofM. lepraedid not affect recognition by NOD2 or cytokine production. Furthermore, amidation of thed-Glu residue did not alter NOD2 activation. These data provide experimental evidence that NOD2 recognizes naturally occurring structural variants of MDP.
A Subset of Protective γ9δ2T Cells Is Activated by Novel Mycobacterial Glycolipid Components
Authors: Xia Mei , Hesser Danny C. , De Prithwiraj , Sakala Isaac G. , Spencer Charles T. , Kirkwood Jay S. , Abate Getahun , Chatterjee Delphi , Dobos Karen M. , Hoft Daniel F.
Published: June 2016

γ9δ2T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ9δ2T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ9δ2T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellularMycobacterium tuberculosisinfection. Based on this premise, we have been searching forM. tuberculosisantigens specifically capable of inducing a unique subset of mycobacterium-protective γ9δ2T cells. Our screening strategy includes the identification ofM. tuberculosisfractions that expand γ9δ2T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments ofM. tuberculosiswhole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as theM. tuberculosisantigens inducing protective γ9δ2T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity ofM. tuberculosiswhole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB.
A Sinorhizobium meliloti RpoH-Regulated Gene Is Involved in Iron-Sulfur Protein Metabolism and Effective Plant Symbiosis under Intrinsic Iron Limitation
Authors: Sasaki Shohei , Minamisawa Kiwamu , Mitsui Hisayuki
Published: June 2016

In
Sinorhizobium meliloti
, RpoH-type sigma factors have a global impact on gene expression during heat shock and play an essential role in symbiosis with leguminous plants. Using mutational analysis of a set of genes showing highly RpoH-dependent expression during heat shock, we identified a gene indispensable for effective symbiosis. This gene, designated
sufT
, was located downstream of the
sufBCDS
homologs that specify the iron-sulfur (Fe/S) cluster assembly pathway. The identified transcription start site was preceded by an RpoH-dependent promoter consensus sequence. SufT was related to a conserved protein family of unknown molecular function, of which some members are involved in Fe/S cluster metabolism in diverse organisms. A
sufT
mutation decreased bacterial growth in both rich and minimal media, tolerance to stresses such as iron starvation, and activities of some Fe/S cluster-dependent enzymes. These results support the involvement of SufT in SUF (sulfur mobilization) system-mediated Fe/S protein metabolism. Furthermore, we isolated spontaneous pseudorevertants of the
sufT
mutant with partially recovered growth; each of them had a mutation in
rirA
. This gene encodes a global iron regulator whose loss increases the intracellular iron content. Deletion of
rirA
in the original
sufT
mutant improved growth and restored Fe/S enzyme activities and effective symbiosis. These results suggest that enhanced iron availability compensates for the lack of SufT in the maintenance of Fe/S proteins.

IMPORTANCE
Although RpoH-type sigma factors of the RNA polymerase are present in diverse proteobacteria, their role as global regulators of protein homeostasis has been studied mainly in the enteric gammaproteobacterium
Escherichia coli
. In the soil alphaproteobacterium
Sinorhizobium meliloti
, the
rpoH
mutations have a strong impact on symbiosis with leguminous plants. We found that
sufT
is a unique member of the
S. meliloti
RpoH regulon;
sufT
contributes to Fe/S protein metabolism and effective symbiosis under intrinsic iron limitation exerted by RirA, a global iron regulator. Our study provides insights into the RpoH regulon function in diverse proteobacteria adapted to particular ecological niches and into the mechanism of conserved Fe/S protein biogenesis.
Heterologous Expression of Der Homologs in an Escherichia coli der Mutant and Their Functional Complementation
Authors: Choi Eunsil , Kang Nalae , Jeon Young , Pai Hyun-Sook , Kim Sung-Gun , Hwang Jihwan
Published: June 2016

The unique
Escherichia coli
GTPase Der (double Era-like GTPase), which contains tandemly repeated GTP-binding domains, has been shown to play an essential role in 50S ribosomal subunit biogenesis. The depletion of Der results in the accumulation of precursors of 50S ribosomal subunits that are structurally unstable at low Mg
2+
concentrations. Der homologs are ubiquitously found in eubacteria. Conversely, very few are conserved in eukaryotes, and none is conserved in archaea. In the present study, to verify their conserved role in bacterial 50S ribosomal subunit biogenesis, we cloned Der homologs from two gammaproteobacteria,
Klebsiella pneumoniae
and
Salmonella enterica
serovar Typhimurium; two pathogenic bacteria,
Staphylococcus aureus
and
Neisseria gonorrhoeae
; and the extremophile
Deinococcus radiodurans
and then evaluated whether they could functionally complement the
E. coli
der
-null phenotype. Only
K. pneumoniae
and
S
. Typhimurium Der proteins enabled the
E. coli der
-null strain to grow under nonpermissive conditions. Sucrose density gradient experiments revealed that the expression of
K. pneumoniae
and
S
. Typhimurium Der proteins rescued the structural instability of 50S ribosomal subunits, which was caused by
E. coli
Der depletion. To determine what allows their complementation, we constructed Der chimeras. We found that only Der chimeras harboring both the linker and long C-terminal regions could reverse the growth defects of the
der
-null strain. Our findings suggest that ubiquitously conserved essential GTPase Der is involved in 50S ribosomal subunit biosynthesis in various bacteria and that the linker and C-terminal regions may participate in species-specific recognition or interaction with the 50S ribosomal subunit.

IMPORTANCE
In
Escherichia coli
, Der (double Era-like GTPase) is an essential GTPase that is important for the production of mature 50S ribosomal subunits. However, to date, its precise role in ribosome biogenesis has not been clarified. In this study, we used five Der homologs from gammaproteobacteria, pathogenic bacteria, and an extremophile to elucidate their conserved function in 50S ribosomal subunit biogenesis. Among them,
Klebsiella pneumoniae
and
Salmonella enterica
serovar Typhimurium Der homologs implicated the participation of Der in ribosome assembly in
E. coli
. Our results show that the linker and C-terminal regions of Der homologs are correlated with its functional complementation in
E. coli der
mutants, suggesting that they are involved in species-specific recognition or interaction with 50S ribosomal subunits.
Emerging Tick-Borne Bacterial Pathogens
Authors: Kernif Tahar , Leulmi Hamza , Raoult Didier , Parola Philippe
Published: June 2016

A vast number of novel tick-related microorganisms and tick-borne disease agents have been identified in the past 20 years, and more are being described due to several factors, from the curiosity of clinicians faced with unusual clinical syndromes to new tools used by microbiologists and entomologists. Borrelioses, ehrlichioses, anaplasmosis, and tick-borne rickettsial diseases are some of the emerging diseases that have been described throughout the world in recent years. In this article, we focus on the bacterial agents and diseases that have been recognized in the past 3 years and refer to major recent reviews of other recognized infections.
The Emergence of Enterovirus-D68
Authors: Messacar Kevin , Abzug Mark J. , Dominguez Samuel R.
Published: June 2016

Enterovirus-D68 (EV-D68) is a unique enterovirus, similar to human rhinoviruses, spread via the respiratory route and primarily causing respiratory disease. Increasing clusters of EV-D68 associated respiratory disease have been reported since 2008, with the largest reported outbreak occurring in North America in 2014. Epidemiologic data and biological plausibility support an association of EV-D68 with the neurologic condition, acute flaccid myelitis. Diagnosis requires EV-D68 specific PCR or viral sequencing of respiratory specimens. Treatment consists of supportive care, as there are no currently available effective vaccines or antiviral therapies. Further research is needed to prepare for future EV-D68 outbreaks of respiratory or neurologic disease.
Middle East Respiratory Syndrome (MERS)
Authors: Rasmussen Sonja A. , Watson Amelia K. , Swerdlow David L.
Published: June 2016

Since the identification of the first patients with Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, over 1,600 cases have been reported as of February 2016. Most cases have occurred in Saudi Arabia or in other countries on or near the Arabian Peninsula, but travel-associated cases have also been seen in countries outside the Arabian Peninsula. MERS-CoV causes a severe respiratory illness in many patients, with a case fatality rate as high as 40%, although when contacts are investigated, a significant proportion of patients are asymptomatic or only have mild symptoms. At this time, no vaccines or treatments are available. Epidemiological and other data suggest that the source of most primary cases is exposure to camels. Person-to-person transmission occurs in household and health care settings, although sustained and efficient person-to-person transmission has not been observed. Strict adherence to infection control recommendations has been associated with control of previous outbreaks. Vigilance is needed because genomic changes in MERS-CoV could result in increased transmissibility, similar to what was seen in severe acute respiratory syndrome coronavirus (SARS-CoV).
West Nile Virus Infection
Authors: Sejvar James J.
Published: June 2016

Although long recognized as a human pathogen, West Nile virus (WNV) emerged as a significant public health problem following its introduction and spread across North America. Subsequent years have seen a greater understanding of all aspects of this viral infection. The North American epidemic resulted in a further understanding of the virology, pathogenesis, clinical features, and epidemiology of WNV infection. Approximately 80% of human WNV infections are asymptomatic. Most symptomatic people experience an acute systemic febrile illness; less than 1% of infected people develop neuroinvasive disease, which typically manifests as meningitis, encephalitis, or anterior myelitis resulting in acute flaccid paralysis. Older age is associated with more severe illness and higher mortality; other risk factors for poor outcome have been challenging to identify. In addition to natural infection through mosquito bites, transfusion- and organ transplant–associated infections have occurred. Since there is no definitive treatment for WNV infection, protection from mosquito bites and other preventative measures are critical. WNV has reached an endemic pattern in North America, but the future epidemiologic pattern is uncertain.
West Africa 2013: Re-examining Ebola
Authors: Bausch Daniel G. , Rojek Amanda
Published: June 2016

The outbreak of Ebola virus disease (EVD) that occurred from 2013 to 2016 in the West African countries of Guinea, Liberia, and Sierra Leone, with imported cases to three neighboring African countries as well as to the United States and Europe, constituted a major humanitarian disaster. The outbreak numbered over 28,500 cases, more than 10 times the number cumulatively registered from all previous EVD outbreaks combined, with at least 11,000 deaths, and resulted in billions of dollars of lost economic growth to an already impoverished region. The unprecedented scale of West Africa 2013 took the world by surprise and laid bare deficiencies in our response capacity to complex humanitarian disasters of highly infectious and lethal pathogens. However, the magnitude of West Africa 2013 also provided an, albeit unwelcome, unique opportunity and obligation to better understand the biology and epidemiology of EVD and, equally as important, the many scientific, economic, social, political, ethical, and logistical challenges in confronting emerging diseases in the modern era. Here we re-examine EVD, reviewing the unique challenges and scientific advances of West Africa 2013, contrasting them with the prior assumptions and classical teachings, identifying what they have taught us and what we still have to learn.
I've got 99 problems but a phone ain't one: Electronic and mobile health in low and middle income countries
Authors: Kumar Pratap , Paton Chris , Kirigia Doris
Published: June 2016

Mobile technology is very prevalent in Kenya—mobile phone penetration is at 88% and mobile data subscriptions form 99% of all internet subscriptions. While there is great potential for such ubiquitous technology to revolutionise access and quality of healthcare in low-resource settings, there have been few successes at scale. Implementations of electronic health (e-Health) and mobile health (m-Health) technologies in countries like Kenya are yet to tackle human resource constraints or the political, ethical and financial considerations of such technologies. We outline recent innovations that could improve access and quality while considering the costs of healthcare. One is an attempt to create a scalable clinical decision support system by engaging a global network of specialist doctors and reversing some of the damaging effects of medical brain drain. The other efficiently extracts digital information from paper-based records using low-cost and locally produced tools such as rubber stamps to improve adherence to clinical practice guidelines. By bringing down the costs of remote consultations and clinical audit, respectively, these projects offer the potential for clinics in resource-limited settings to deliver high-quality care. This paper makes a case for continued and increased investment in social enterprises that bridge academia, public and private sectors to deliver sustainable and scalable e-Health and m-Health solutions.
Positive effects on bone mineralisation and muscular fitness after 10 months of intense school-based physical training for children aged 8–10 years: the FIT FIRST randomised controlled trial
Authors: Larsen Malte Nejst , Nielsen Claus Malta , Helge Eva Wulff , Madsen Mads , Manniche Vibeke , Hansen Lone , Hansen Peter Riis , Bangsbo Jens , Krustrup Peter
Published: June 2016

Objectives

We investigated whether musculoskeletal fitness of school children aged 8–10 years was affected by frequent intense PE sessions.

Design and participants

295 Danish school children aged 8–10 years were cluster randomised to a small-sided ball game group (SSG) (n=96, four schools, five classes), a circuit strength training group (CST) (n=83, four schools, four classes) or a control group (CON, n=116, two schools, five classes).

Intervention

SSG or CST was performed 3×40 min/week over 10 months. Whole-body dual-energy X-ray absorptiometry (DXA) scans were used to determine areal bone mineral density (aBMD), bone mineral content (BMC) and lean body mass (LBM). Flamingo balance, standing long jump and 20-m sprint tests were used to determine muscular fitness.

Results

Analysis of baseline-to-10 months change scores showed between-group differences in favour of the interventions in whole-body aBMD (SSG vs CON: 8 mg/cm2, 95% CI 3 to 13; CST vs CON: 7 mg/cm2, 95% CI 2 to 13, p<0.05) and leg BMC (SSG vs CON: 11 g, 95% CI 4 to 18; CST vs CON: 11 g, 95% CI 3 to 18, p<0.05). SSG had higher change scores in leg aBMD compared with CON and CST (SSG vs CON: 19 mg/cm2, 95% CI 11 to 39, p<0.05; SSG vs CST: 12 mg/cm2, 95% CI 3 to 21, p<0.05), and CST had higher change scores in whole-body BMC compared with CON (CST vs CON: 25 g, 95% CI 10 to 39, p<0.05). Both training types resulted in higher change scores in postural balance (SSG vs CON: 2.4 fewer falls/min, 95% CI 0.3 to 4.5, CST vs CON: 3.6 fewer falls/min, 95% CI 1.3 to 5.9, p<0.05) and jump length (SSG vs CON: 10%, 95% CI 5 to 16%; CST vs CON: 9%, 95% CI 3 to 15%, p<0.05). No between-group differences were observed for sprint performance or LBM (p>0.05).

Conclusions

In conclusion, 3×40 min/week with SSG or CST over a full school year improves bone mineralisation and several aspects of muscular fitness of children aged 8–10 years, suggesting that well-organised intense physical education classes can contribute positively to develop musculoskeletal health in young children.

Trial registration number

NCT02000492, post results.
Gender-based violence and absent fathers: a scoping review protocol
Authors: Sikweyiya Yandisa , Nduna Mzikazi , Khuzwayo Nelisiwe , Mthombeni Andile , Mashamba-Thompson Tivani Phosa
Published: June 2016

Introduction

Gender-based violence (GBV) and absent fathers are two epidemics that affect women and children in sub-Saharan Africa. However, the understanding of the complex links between GBV and absent fathers is currently inadequate. The aim of the study is to provide an overview of documented evidence that links GBV and absent fathers as well as identifies areas that require systematic review and where more primary research is needed.

Methods and analysis

The search strategy for this scoping review study will involve electronic databases including: Academic Search Premier, Ingenta, Kluwer Online, PsycARTICLES (EBSCO), PsycINFO (EBSCO), Social Work Abstracts and Sociological Collection. The studies will be mapped in 2 stages: stage 1 will map studies descriptively by focus and method; stage 2 will involve additional inclusion criteria, quality assessment and data extraction undertaken by two reviewers in parallel. A thematic analysis of the studies will be carried out to extract relevant outcomes using NVIVO.

Discussion

We anticipate finding a large number of studies on GBV diagnostic interventions in sub-Saharan Africa which, once summarised, will be useful to guide future research. The protocol for the scoping review has been registered in PROSPERO.

Dissemination

The study will be disseminated electronically and in print. It will also be presented to conferences related to GBV, Father Connections and Children's Health.

PROSPERO registration number

CRD42015022094.
Systematic review of the association between dietary acid load, alkaline water and cancer
Authors: Fenton Tanis R , Huang Tian
Published: June 2016

Objectives

To evaluate the evidence for a causal relationship between dietary acid/alkaline and alkaline water for the aetiology and treatment of cancer.

Design

A systematic review was conducted on published and grey literature separately for randomised intervention and observational studies with either varying acid–base dietary intakes and/or alkaline water with any cancer outcome or for cancer treatment.

Outcome measures

Incidence of cancer and outcomes of cancer treatment.

Results

8278 citations were identified, and 252 abstracts were reviewed; 1 study met the inclusion criteria and was included in this systematic review. No randomised trials were located. No studies were located that examined dietary acid or alkaline or alkaline water for cancer treatment. The included study was a cohort study with a low risk of bias. This study revealed no association between the diet acid load with bladder cancer (OR=1.15: 95% CI 0.86 to 1.55, p=0.36). No association was found even among long-term smokers (OR=1.72: 95% CI 0.96 to 3.10, p=0.08).

Conclusions

Despite the promotion of the alkaline diet and alkaline water by the media and salespeople, there is almost no actual research to either support or disprove these ideas. This systematic review of the literature revealed a lack of evidence for or against diet acid load and/or alkaline water for the initiation or treatment of cancer. Promotion of alkaline diet and alkaline water to the public for cancer prevention or treatment is not justified.
Competence of health workers in emergency obstetric care: an assessment using clinical vignettes in Brong Ahafo region, Ghana
Authors: Lohela Terhi Johanna , Nesbitt Robin Clark , Manu Alexander , Vesel Linda , Okyere Eunice , Kirkwood Betty , Gabrysch Sabine
Published: June 2016

Objectives

To assess health worker competence in emergency obstetric care using clinical vignettes, to link competence to availability of infrastructure in facilities, and to average annual delivery workload in facilities.

Design

Cross-sectional Health Facility Assessment linked to population-based surveillance data.

Setting

7 districts in Brong Ahafo region, Ghana.

Participants

Most experienced delivery care providers in all 64 delivery facilities in the 7 districts.

Primary outcome measures

Health worker competence in clinical vignette actions by cadre of delivery care provider and by type of facility. Competence was also compared with availability of relevant drugs and equipment, and to average annual workload per skilled birth attendant.

Results

Vignette scores were moderate overall, and differed significantly by respondent cadre ranging from a median of 70% correct among doctors, via 55% among midwives, to 25% among other cadres such as health assistants and health extension workers (p<0.001). Competence varied significantly by facility type: hospital respondents, who were mainly doctors and midwives, achieved highest scores (70% correct) and clinic respondents scored lowest (45% correct). There was a lack of inexpensive key drugs and equipment to carry out vignette actions, and more often, lack of competence to use available items in clinical situations. The average annual workload was very unevenly distributed among facilities, ranging from 0 to 184 deliveries per skilled birth attendant, with higher workload associated with higher vignette scores.

Conclusions

Lack of competence might limit clinical practice even more than lack of relevant drugs and equipment. Cadres other than midwives and doctors might not be able to diagnose and manage delivery complications. Checking clinical competence through vignettes in addition to checklist items could contribute to a more comprehensive approach to evaluate quality of care.

Trial registration number

NCT00623337.
Medication double-checking procedures in clinical practice: a cross-sectional survey of oncology nurses' experiences
Authors: Schwappach D L B , Pfeiffer Yvonne , Taxis Katja
Published: June 2016

Background

Double-checking is widely recommended as an essential method to prevent medication errors. However, prior research has shown that the concept of double-checking is not clearly defined, and that little is known about actual practice in oncology, for example, what kind of checking procedures are applied.

Objective

To study the practice of different double-checking procedures in chemotherapy administration and to explore nurses' experiences, for example, how often they actually find errors using a certain procedure. General evaluations regarding double-checking, for example, frequency of interruptions during and caused by a check, or what is regarded as its essential feature was assessed.

Methods

In a cross-sectional survey, qualified nurses working in oncology departments of 3 hospitals were asked to rate 5 different scenarios of double-checking procedures regarding dimensions such as frequency of use in practice and appropriateness to prevent medication errors; they were also asked general questions about double-checking.

Results

Overall, 274 nurses (70% response rate) participated in the survey. The procedure of jointly double-checking (read-read back) was most commonly used (69% of respondents) and rated as very appropriate to prevent medication errors. Jointly checking medication was seen as the essential characteristic of double-checking—more frequently than ‘carrying out checks independently’ (54% vs 24%). Most nurses (78%) found the frequency of double-checking in their department appropriate. Being interrupted in one's own current activity for supporting a double-check was reported to occur frequently. Regression analysis revealed a strong preference towards checks that are currently implemented at the responders' workplace.

Conclusions

Double-checking is well regarded by oncology nurses as a procedure to help prevent errors, with jointly checking being used most frequently. Our results show that the notion of independent checking needs to be transferred more actively into clinical practice. The high frequency of reported interruptions during and caused by double-checks is of concern.
Compendium of models from a gauge U(1) framework
Authors: Ma Ernest
Published: June 2016

A gauge U(1) framework was established in 2002 to extend the supersymmetric Standard Model. It has many possible realizations. Whereas all have the necessary and sufficient ingredients to explain the possible 750 GeV diphoton excess, observed recently by the ATLAS and CMS Collaborations at the large hadron collider (LHC), they differ in other essential aspects. A compendium of such models is discussed.
A DFT study of pressure-induced phase transitions, structural and electronic properties of Cu2ZnSnS4
Authors: Zhao Yifen , Li Decong , Liu Zuming
Published: June 2016

The structural properties, phase transitions, and electronic structures of Cu2ZnSnS4 (CZTS) in the three structures have been researched using the first-principles density functional theory (DFT). The results indicate that the energies of stannite (ST) and pre-mixed Cu–Au (PMCA) CZTS are higher than those of kesterite (KS) CZTS, indicating that the KS CZTS is more stable. We found the phase transition pressure between the KS and ST structures of CZTS is about 32 GPa. Moreover, for KS- and PMCA-CZTS, there exists in the mischcrystal phase between 52 GPa and 65 GPa. The band structures show that the KS- and ST-CZTS are direct band gap semiconductors. The band gaps of three-type CZTS increase with increasing pressure, and the maximum band gap of KS and ST structures for CZTS occurs at 50 GPa. However, PMCA CZTS possesses metal property. Furthermore, the PMCA CZTS translates from metal to the indirect semiconductor with increasing pressure. The results play an important role in future experimental and theoretical work for CZTS materials.
Design of Low Leakage Variability Aware ONOFIC CMOS Standard Cell Library
Authors: Sharma Vijay Kumar , Pattanaik Manisha
Published: June 2016

In this research paper, a minimum set of low leakage variability aware ONOFIC CMOS digital standard cell library is developed. The developed standard cell library contains basic cells such as inverter, NAND, NOR, AND, OR and buffer logic cells and characterized at 32 nm bulk CMOS process technology. All cells are designed, at 32 nm technology node under TT process corner at room temperature with power supply of 0.8[Formula: see text]V by using Silvaco’s EDA tools. All generated cells have same cell height of 1.58 [Formula: see text]m. The proposed logic cells attain large leakage and power delay product (PDP) reduction. ISCAS’85 benchmark circuits 74181 and c17 are designed and verified with developed logic cells at transistor level. The ONOFIC standard cell library reduces 34.40% and 42.74% leakage power and improves PDP by 18.34% and 16.46% for 74181 and c17 circuits, respectively. The result of generated standard cell library shows that it is a good choice for low leakage applications.
On rigidity of factorial trinomial hypersurfaces
Authors: Arzhantsev Ivan
Published: June 2016

An affine algebraic variety [Formula: see text] is rigid if the algebra of regular functions [Formula: see text] admits no nonzero locally nilpotent derivation. We prove that a factorial trinomial hypersurface is rigid if and only if every exponent in the trinomial is at least [Formula: see text].
Nilpotent symplectic alternating algebras II
Authors: Sorkatti Layla , Traustason Gunnar
Published: June 2016

In this paper and its sequel we continue our study of nilpotent symplectic alternating algebras. In particular we give a full classification of such algebras of dimension 10 over any field. It is known that symplectic alternating algebras over GF(3) correspond to a special rich class [Formula: see text] of 2-Engel 3-groups of exponent 27 and under this correspondence we will see that the nilpotent algebras correspond to a subclass of [Formula: see text] that are those groups in [Formula: see text] that have an extra group theoretical property that we refer to as being powerfully nilpotent and can be described also in the context of [Formula: see text]-groups where [Formula: see text] is an arbitrary prime.
Double coverings of twisted links
Authors: Kamada Naoko , Kamada Seiichi
Published: June 2016

Twisted links are a generalization of virtual links. As virtual links correspond to abstract links on orientable surfaces, twisted links correspond to abstract links on (possibly non-orientable) surfaces. In this paper, we introduce the notion of the double covering of a twisted link. It is defined by considering the orientation double covering of an abstract link or alternatively by constructing a diagram called a double covering diagram. We also discuss links in thickened surfaces, their diagrams and their stable equivalence classes. Bourgoin’s twisted knot group is understood as the virtual knot group of the double covering.
Enabling computations for link invariants coming from the Yokonuma–Hecke algebras
Authors: Karvounis K.
Published: June 2016

We describe an algorithm for computing the invariants of classical links arising from the Yokonuma–Hecke algebras. A detailed overview of the algorithm is given, following closely its implementation, a program used to calculate the invariants on several Homflypt-equivalent pairs of links.
Study of knots in material culture
Authors: Scanlon Lauren A.
Published: June 2016

In this paper we will discuss knots in material culture, giving an overview of their importance and range of usage. We will then discuss a method of characterization for these knots and a method to study these knots through cultural evolution. We then give some preliminary results and ideas for further study.
The consistent histories approach to loop quantum cosmology
Authors: Craig David A.
Published: June 2016

We review the application of the consistent (or decoherent) histories formulation of quantum theory to canonical loop quantum cosmology. Conventional quantum theory relies crucially on “measurements” to convert unrealized quantum potentialities into physical outcomes that can be assigned probabilities. In the early universe and other physical contexts in which there are no observers or measuring apparatus (or indeed, in any closed quantum system), what criteria determine which alternative outcomes may be realized and what their probabilities are? In the consistent histories formulation it is the vanishing of interference between the branch wave functions describing alternative histories — as determined by the system’s decoherence functional — that determines which alternatives may be assigned probabilities. We describe the consistent histories formulation and how it may be applied to canonical loop quantum cosmology, describing in detail the application to homogeneous and isotropic cosmological models with scalar matter. We show how the theory may be used to make definite physical predictions in the absence of “observers”. As an application, we demonstrate how the theory predicts that loop quantum models “bounce” from large volume to large volume, while conventional “Wheeler–DeWitt”-quantized universes are invariably singular. We also briefly indicate the relation to other work.
A frame-dependent gravitational effective action mimics a cosmological constant, but modifies the black hole horizon
Authors: Adler Stephen L.
Published: June 2016

A frame-dependent effective action motivated by the postulates of three-space general coordinate invariance and Weyl scaling invariance exactly mimics a cosmological constant in Robertson–Walker spacetimes. However, in a static spherically symmetric Schwarzschild-like geometry it modifies the black hole horizon structure within microscopic distances of the nominal horizon, in such a way that [Formula: see text] never vanishes. This could have important implications for the black hole “information paradox”.
Prospects for strangelet detection with large-scale cosmic ray observatories
Authors: Pshirkov M. S.
Published: June 2016

Quark matter which contains [Formula: see text]-quarks in addition to [Formula: see text]- and [Formula: see text]- could be stable or metastable. In this case, lumps made of this strange matter, called strangelets, could occasionally hit the Earth. When travelling through the atmosphere they would behave not dissimilar to usual high-velocity meteors with only exception that, eventually, strangelets reach the surface. As these encounters are expected to be extremely rare events, very large exposure is needed for their observation. Fluorescence detectors utilized in large ultra-high energy cosmic ray observatories, such as the Pierre Auger observatory and the Telescope Array are well suited for a task of the detection of these events. The flux limits that can be obtained with the Telescope Array fluorescence detectors could be as low as 2.5 × 10−22 cm−2s−1sr−1 which would improve by two orders of magnitude of the strongest present limits obtained from ancient mica crystals.
Sharp comparison theorems for the Klein–Gordon equation in d dimensions
Authors: Hall Richard L. , Zorin Petr
Published: June 2016

We establish sharp (or ’refined’) comparison theorems for the Klein–Gordon equation. We show that the condition [Formula: see text], which leads to [Formula: see text], can be replaced by the weaker assumption [Formula: see text] which still implies the spectral ordering [Formula: see text]. In the simplest case, for [Formula: see text], [Formula: see text], [Formula: see text] or [Formula: see text] and for [Formula: see text], [Formula: see text], [Formula: see text] or [Formula: see text]. We also consider sharp comparison theorems in the presence of a scalar potential [Formula: see text] (a ‘variable mass’) in addition to the vector term [Formula: see text] (the time component of a four-vector). The theorems are illustrated by a variety of explicit detailed examples.