bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial genotype and phenotypic plasticity of gene expression in response to cold acclimation in killifish
Authors: Healy Timothy M. , Bryant Heather J. , Schulte Patricia M.
Published: December 2016

Adjustments of aerobic metabolic processes are critical components of organismal responses to environmental change that require tight coordination between the nuclear and mitochondrial genomes. Intraspecific differences in mitochondrial genotype can affect gene transcription in both genomes. Thus, variation in mitochondrial genotype may be associated with differences in the plasticity of gene expression when organisms are faced with changes in environmental conditions. Cold acclimation is known to result in metabolic responses involving increases in mitochondrial amount and capacity, suggesting that low temperatures may pose a particular challenge when coordinating the functions of the nuclear and mitochondrial genomes. In this study, we utilized RNA‐seq to assess transcriptome‐wide gene expression in the muscle of Atlantic killifish (Fundulus heteroclitus) from a population that contains segregating variation in mitochondrial genotype. We examined gene expression plasticity in response to 5 °C acclimation and the effects of mitochondrial genotype on this plasticity. Cold acclimation resulted in changes in gene expression consistent with up‐regulation of genes involved in many cellular functions, including spliceosomal and proteasomal processes, and with down‐regulation of genes involved in extracellular matrix, muscle contraction and oxidative phosphorylation functions. There were few differences in gene expression between killifish with different mitochondrial genotypes: 14 genes demonstrated significant interactions between mitochondrial genotype and acclimation temperature and three genes demonstrated effects of mitochondrial genotype alone. These results indicate that variation in mitochondrial genotype has modest effects on gene expression; the majority of which are revealed as differences in plasticity as a result of environmental change.
The genetic architecture of tristyly and its breakdown to self‐fertilization
Authors: Arunkumar Ramesh , Wang Wei , Wright Stephen I. , Barrett Spencer C. H.
Published: December 2016

The floral polymorphism tristyly involves three style morphs with a reciprocal arrangement of stigma and anther heights governed by two diallelic loci (S and M). Tristyly functions to promote cross‐pollination, but modifications to stamen position commonly cause transitions to selfing. Here, we integrate whole‐genome sequencing and genetic mapping to investigate the genetic architecture of the M locus and the genetic basis of independent transitions to selfing in tristylous Eichhornia paniculata. We crossed independently derived semi‐homostylous selfing variants of the long‐ and mid‐styled morph fixed for alternate alleles at the M locus (ssmm and ssMM, respectively), and backcrossed the F1 to the parental ssmm genotype. We phenotyped and genotyped 462 backcross progeny using 1450 genotyping‐by‐sequencing (GBS) markers and performed composite interval mapping to identify quantitative trait loci (QTL) governing style‐length and anther‐height variation. A QTL associated with the primary style‐morph differences (style length and anther height) mapped to linkage group 5 and spanned ~13–27.5 Mbp of assembled sequence. Bulk segregant analysis identified 334 genes containing SNPs potentially linked to the M locus. The stamen modifications characterizing each selfing variant were governed by loci on different linkage groups. Our results provide an important step towards identifying the M locus and demonstrate that transitions to selfing have originated by independent sets of mating‐system modifier genes unlinked to the M locus, a pattern inconsistent with a recombinational origin of selfing variants at a putative supergene.
Positive feelings during pregnancy, early feeding practices, and infant health
Authors: McManus Melissa A , Khalessi Ali A , Lin Joyce , Ashraf Jahanzeb , Reich Stephanie M
Published: December 2016

Background

Early parenting practices, such as infant feeding, can affect children's physical health. Additionally, negative prenatal maternal affect can influence feeding choices, such as breast‐feeding, and can have a detrimental effect on children's health. Little is known, however, about the contribution of positive maternal affect during pregnancy on feeding practices and children's health.

Methods

This study explored whether positive prenatal feelings influenced children's health during the first 18 months, and whether early feeding practices mediated the relationship between these two variables. Low‐income, ethnically diverse, primiparous women (n = 114) reported their feelings of pregnancy uplifts and hassles during their third trimester. These women were interviewed again at 2, 4, 6, 9, 12, and 18 months post‐partum about their feeding practices. A retrospective audit of their infants’ medical charts was completed from birth to 18 months.

Results

Using structural equation modeling, having more uplifts than hassles during pregnancy was associated with longer breast‐feeding duration and greater adherence to recommended schedules for introducing fruits and vegetables, solids, and baby cereal. These feeding practices were linked to better child health outcomes, including reduced risk of upper respiratory tract infections, conjunctivitis, otitis media, and thrush.

Conclusions

Positive maternal feelings during pregnancy were associated with better feeding practices, and these better feeding practices were associated with fewer common childhood illnesses. Helping expectant women focus on the positive aspects of their pregnancy may lead to postnatal care methods that are fiscally advantageous, preventive of detrimental postnatal choices, and medically beneficial for children.
Clinical feasibility of brain‐computer interface based on steady‐state visual evoked potential in patients with locked‐in syndrome: Case studies
Authors: Hwang Han‐Jeong , Han Chang‐Hee , Lim Jeong‐Hwan , Kim Yong‐Wook , Choi Soo‐In , An Kwang‐Ok , Lee Jun‐Hak , Cha Ho‐Seung , Hyun Kim Seung , Im Chang‐Hwan
Published: December 2016

Although the feasibility of brain‐computer interface (BCI) systems based on steady‐state visual evoked potential (SSVEP) has been extensively investigated, only a few studies have evaluated its clinical feasibility in patients with locked‐in syndrome (LIS), who are the main targets of BCI technology. The main objective of this case report was to share our experiences of SSVEP‐based BCI experiments involving five patients with LIS, thereby providing researchers with useful information that can potentially help them to design BCI experiments for patients with LIS. In our experiments, a four‐class online SSVEP‐based BCI system was implemented and applied to four of five patients repeatedly on multiple days to investigate its test‐retest reliability. In the last experiments with two of the four patients, the practical usability of our BCI system was tested using a questionnaire survey. All five patients showed clear and distinct SSVEP responses at all four fundamental stimulation frequencies (6, 6.66, 7.5, 10 Hz), and responses at harmonic frequencies were also observed in three patients. Mean classification accuracy was 76.99% (chance level = 25%). The test‐retest reliability experiments demonstrated stable performance of our BCI system over different days even when the initial experimental settings (e.g., electrode configuration, fixation time, visual angle) used in the first experiment were used without significant modifications. Our results suggest that SSVEP‐based BCI paradigms might be successfully used to implement clinically feasible BCI systems for severely paralyzed patients.
Short‐term trained lexical categories affect preattentive shape perception: Evidence from vMMN
Authors: Yu Mengxia , Mo Ce , Zeng Tianyu , Zhao Sasa , Mo Lei
Published: December 2016

Perceptual processing of colors and shapes in the right visual field is modulated by the lexical category information of the stimuli, a phenomenon known as the lateralized Whorfian effect. For color stimuli, lateralized Whorfian effect is characterized by preattentive occurrence and dependency on acquired lexical information, but it remains unknown whether these key features are generalizable to other domains of perceptual processing. Here, we investigated whether lateralized Whorfian effect in the shape perception domain also depends on acquired lexical category and occurs preattentively using ERPs. Participants were trained to associate novel, irregular polygons with lexical category labels via short‐term intensive training. Using the visual oddball paradigm, we found stronger visual mismatch negativity (vMMN) component elicited by the deviant stimuli whose lexical category differed from the standard stimuli when the deviant was presented in the right visual field, indicating higher perceptual conspicuity for between‐category stimuli. These findings provide direct evidence of similar preattentive lexical category‐contingent modulation on shape perception akin to color perception, suggesting that the lateralized Whorfian effect is not epiphenomenal but rather might reflect the interaction between higher‐level lexical processing and the lower‐level perceptual processing more broadly.
Statistical considerations for reporting and planning heart rate variability case‐control studies
Authors: Quintana Daniel S.
Published: December 2016

The calculation of heart rate variability (HRV) is a popular tool used to investigate differences in cardiac autonomic control between population samples. When interpreting effect sizes to quantify the magnitude of group differences, researchers typically use Cohen's guidelines of small (0.2), medium (0.5), and large (0.8) effects. However, these guidelines were originally proposed as a fallback for when the effect size distribution (ESD) was unknown. Despite the availability of effect sizes from hundreds of HRV studies, researchers still largely rely on Cohen's guidelines to interpret effect sizes and to perform power analyses to calculate required sample sizes for future research. This article describes an ESD analysis of 297 HRV effect sizes from between‐group/case‐control studies, revealing that the 25th, 50th, and 75th effect size percentiles correspond with effect sizes of 0.26, 0.51, and 0.88, respectively. The analyses suggest that Cohen's guidelines may underestimate the magnitude of small and large effect sizes and that HRV studies are generally underpowered. Therefore, to better reflect the observed ESD, effect sizes of 0.25, 0.5, and 0.9 should be interpreted as small, medium, and large effects (after rounding to the closest 0.05). Based on power calculations using the ESD, suggested sample sizes are also provided for planning suitably powered studies that are more likely to replicate. Researchers are encouraged to use the ESD data set or their own collected data sets in tandem with the provided analysis script to perform custom ESD and power analyses relevant to their specific research area.
Mathematical detection of aortic valve opening (B point) in impedance cardiography: A comparison of three popular algorithms
Authors: Árbol Javier Rodríguez , Perakakis Pandelis , Garrido Alba , Mata José Luis , Fernández‐Santaella M. Carmen , Vila Jaime
Published: December 2016

The preejection period (PEP) is an index of left ventricle contractility widely used in psychophysiological research. Its computation requires detecting the moment when the aortic valve opens, which coincides with the B point in the first derivative of impedance cardiogram (ICG). Although this operation has been traditionally made via visual inspection, several algorithms based on derivative calculations have been developed to enable an automatic performance of the task. However, despite their popularity, data about their empirical validation are not always available. The present study analyzes the performance in the estimation of the aortic valve opening of three popular algorithms, by comparing their performance with the visual detection of the B point made by two independent scorers. Algorithm 1 is based on the first derivative of the ICG, Algorithm 2 on the second derivative, and Algorithm 3 on the third derivative. Algorithm 3 showed the highest accuracy rate (78.77%), followed by Algorithm 1 (24.57%) and Algorithm 2 (13.82%). In the automatic computation of PEP, Algorithm 2 resulted in significantly more missed cycles (48.57%) than Algorithm 1 (6.3%) and Algorithm 3 (3.5%). Algorithm 2 also estimated a significantly lower average PEP (70 ms), compared with the values obtained by Algorithm 1 (119 ms) and Algorithm 3 (113 ms). Our findings indicate that the algorithm based on the third derivative of the ICG performs significantly better. Nevertheless, a visual inspection of the signal proves indispensable, and this article provides a novel visual guide to facilitate the manual detection of the B point.
Distinct Anaerobic Bacterial Consumers of Cellobiose-Derived Carbon in Boreal Fens with Different CO
2
/CH
4
Production Ratios
Authors: Juottonen Heli , Eiler Alexander , Biasi Christina , Tuittila Eeva-Stiina , Yrjälä Kim , Fritze Hannu
Published: December 2016

Northern peatlands in general have high methane (CH
4
) emissions, but individual peatlands show considerable variation as CH
4
sources. Particularly in nutrient-poor peatlands, CH
4
production can be low and exceeded by carbon dioxide (CO
2
) production from unresolved anaerobic processes. To clarify the role anaerobic bacterial degraders play in this variation, we compared consumers of cellobiose-derived carbon in two fens differing in nutrient status and the ratio of CO
2
to CH
4
produced. After [
13
C]cellobiose amendment, the mesotrophic fen produced equal amounts of CH
4
and CO
2
. The oligotrophic fen had lower CH
4
production but produced 3 to 59 times more CO
2
than CH
4
. RNA stable-isotope probing revealed that in the mesotrophic fen with higher CH
4
production, cellobiose-derived carbon was mainly assimilated by various recognized fermenters of
Firmicutes
and by
Proteobacteria
. The oligotrophic peat with excess CO
2
production revealed a wider variety of cellobiose-C consumers, including
Firmicutes
and
Proteobacteria
, but also more unconventional degraders, such as
Telmatobacter
-related
Acidobacteria
and subphylum 3 of
Verrucomicrobia
. Prominent and potentially fermentative
Planctomycetes
and
Chloroflexi
did not appear to process cellobiose-C. Our results show that anaerobic degradation resulting in different levels of CH
4
production can involve distinct sets of bacterial degraders. By distinguishing cellobiose degraders from the total community, this study contributes to defining anaerobic bacteria that process cellulose-derived carbon in peat. Several of the identified degraders, particularly fermenters and potential Fe(III) or humic substance reducers in the oligotrophic peat, represent promising candidates for resolving the origin of excess CO
2
production in peatlands.

IMPORTANCE
Peatlands are major sources of the greenhouse gas methane (CH
4
), yet in many peatlands, CO
2
production from unresolved anaerobic processes exceeds CH
4
production. Anaerobic degradation produces the precursors of CH
4
production but also represents competing processes. We show that anaerobic degradation leading to high or low CH
4
production involved distinct sets of bacteria. Well-known fermenters dominated in a peatland with high CH
4
production, while novel and unconventional degraders could be identified in a site where CO
2
production greatly exceeds CH
4
production. Our results help identify and assign functions to uncharacterized bacteria that promote or inhibit CH
4
production and reveal bacteria potentially producing the excess CO
2
in acidic peat. This study contributes to understanding the microbiological basis for different levels of CH
4
emission from peatlands.
Development of an Improved System for the Generation of Knockout Mutants of Amycolatopsis sp. Strain ATCC 39116
Authors: Meyer Florian , Pupkes Hilke , Steinbüchel Alexander
Published: December 2016

The Gram-positive actinomycete
Amycolatopsis
sp. strain ATCC 39116 is used for the industrial production of natural vanillin. Previously, the only gene deletion performed in this strain targeted the gene
vdh
, coding for a vanillin dehydrogenase. The generation of this mutant suffered from a high number of illegitimate recombinations and a low rate of homologous recombination. To alleviate this, we constructed an optimized deletion system based on a modified suicide vector. Thereby, we were able to increase the rate of homologous integration from less than 1% of the analyzed clones to 20% or 50%, depending on the targeted gene. We were furthermore able to reduce the screening effort needed to identify homogenotes through the use of the
rpsL
gene from
Saccharopolyspora erythraea
, which confers streptomycin sensitivity on clones still carrying the suicide vector. The new suicide vector is p6SUI5ERPSL, and its applicability was demonstrated by the deletion of three
Amycolatopsis
gene clusters. The deletion of the first of the gene clusters, coding for an aldehyde oxidase (
yagRST
), led to no altered phenotype compared to the parent strain; deletion of the second, coding for a vanillic acid decarboxylase (
vdcBCD
), led to a phenotype that was strongly impaired in its growth with vanillic acid as the sole carbon source and also unable to form guaiacol; and deletion of the third, coding for a vanillate demethylase (
vanAB
), led to only a negligible impact in comparison. Therefore, we showed that decarboxylation of vanillic acid is the main degradation pathway in
Amycolatopsis
sp. ATCC 39116 while the demethylation plays only a minor role and does not compensate the deletion of
vdcBCD
.

IMPORTANCE
Amycolatopsis
sp. ATCC 39116 is an important microorganism used for the production of natural vanillin from ferulic acid. In contrast to this importance, it has previously been shown that this strain is hard to manipulate on a genetic level. We therefore generated an optimized system to facilitate the deletion of genes in this strain. This allowed us to greatly reduce the time and work requirements for generating deletions. This could allow the improvement of vanillin production in the future and also the elucidation of metabolic pathways. To test our deletion system, we deleted three gene clusters in
Amycolatopsis
sp. ATCC 39116. One showed no involvement in the metabolism of vanillin, while the second proved to be the main pathway of vanillic acid degradation and completely stopped the formation of the off-flavor guaiacol. The third appeared to have only a negligible impact on the degradation of vanillic acid.
A Novel Rhamnose-Rich Hetero-exopolysaccharide Isolated from Lactobacillus paracasei DG Activates THP-1 Human Monocytic Cells
Authors: Balzaretti Silvia , Taverniti Valentina , Guglielmetti Simone , Fiore Walter , Minuzzo Mario , Ngo Hansel N. , Ngere Judith B. , Sadiq Sohaib , Humphreys Paul N. , Laws Andrew P.
Published: December 2016

Lactobacillus paracasei
DG is a bacterial strain with recognized probiotic properties and is used in commercial probiotic products. However, the mechanisms underlying its probiotic properties are mainly unknown. In this study, we tested the hypothesis that the ability of strain DG to interact with the host is at least partly associated with its ability to synthesize a surface-associated exopolysaccharide (EPS). Comparative genomics revealed the presence of putative EPS gene clusters in the DG genome; accordingly, EPS was isolated from the surface of the bacterium. A sample of the pure EPS from strain DG (DG-EPS), upon nuclear magnetic resonance (NMR) and chemical analyses, was shown to be a novel branched hetero-EPS with a repeat unit composed of
l
-rhamnose,
d
-galactose, and
N
-acetyl-
d
-galactosamine in a ratio of 4:1:1. Subsequently, we demonstrated that DG-EPS displays immunostimulating properties by enhancing the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and particularly that of the chemokines IL-8 and CCL20, in the human monocytic cell line THP-1. In contrast, the expression of the cyclooxygenase enzyme COX-2 was not affected. In conclusion, DG-EPS is a bacterial macromolecule with the ability to boost the immune system either as a secreted molecule released from the bacterium or as a capsular envelope on the bacterial cell wall. This study provides additional information about the mechanisms supporting the cross talk between
L. paracasei
DG and the host.

IMPORTANCE
The consumption of food products and supplements called probiotics (i.e., containing live microbial cells) to potentially prevent or treat specific diseases is constantly gaining popularity. The lack of knowledge on the precise mechanisms supporting their potential health-promoting properties, however, greatly limits a more appropriate use of each single probiotic strain. In this context, we studied a well-known probiotic,
Lactobacillus paracasei
DG, in order to identify the constitutive molecules that can explain the documented health-promoting properties of this bacterium. We found a novel polysaccharide molecule, named DG-EPS, that is secreted by and covers the bacterium. We demonstrated that this molecule, which has a chemical structure never identified before, has immunostimulatory properties and therefore may contribute to the ability of the probiotic
L. paracasei
DG to interact with the immune system.
New Arsenate Reductase Gene (
arrA
) PCR Primers for Diversity Assessment and Quantification in Environmental Samples
Authors: Mirza Babur S. , Sorensen Darwin L. , Dupont R. Ryan , McLean Joan E.
Published: December 2016

The extent of arsenic contamination in drinking water and its potential threat to human health have resulted in considerable research interest in the microbial species responsible for arsenic reduction. The arsenate reductase gene (
arrA
), an important component of the microbial arsenate reduction system, has been widely used as a biomarker to study arsenate-reducing microorganisms. A new primer pair was designed and evaluated for quantitative PCR (qPCR) and high-throughput sequencing of the
arrA
gene, because currently available PCR primers are not suitable for these applications. The primers were evaluated
in silico
and empirically tested for amplification of
arrA
genes in clones and for amplification and high-throughput sequencing of
arrA
genes from soil and groundwater samples.
In silico
, this primer pair matched (≥90% DNA identity) 86% of
arrA
gene sequences from GenBank. Empirical evaluation showed successful amplification of
arrA
gene clones of diverse phylogenetic groups, as well as amplification and high-throughput sequencing of independent soil and groundwater samples without preenrichment, suggesting that these primers are highly specific and can amplify a broad diversity of
arrA
genes. The
arrA
gene diversity from soil and groundwater samples from the Cache Valley Basin (CVB) in Utah was greater than anticipated. We observed a significant correlation between
arrA
gene abundance, quantified through qPCR, and reduced arsenic (As
III
) concentrations in the groundwater samples. Furthermore, we demonstrated that these primers can be useful for studying the diversity of arsenate-reducing microbial communities and the ways in which their relative abundance in groundwater may be associated with different groundwater quality parameters.

IMPORTANCE
Arsenic is a major drinking water contaminant that threatens the health of millions of people worldwide. The extent of arsenic contamination and its potential threat to human health have resulted in considerable interest in the study of microbial species responsible for the reduction of arsenic, i.e., the conversion of As
V
to As
III
. In this study, we developed a new primer pair to evaluate the diversity and abundance of arsenate-reducing microorganisms in soil and groundwater samples from the CVB in Utah. We observed significant
arrA
gene diversity in the CVB soil and groundwater samples, and
arrA
gene abundance was significantly correlated with the reduced arsenic (As
III
) concentrations in the groundwater samples. We think that these primers are useful for studying the ecology of arsenate-reducing microorganisms in different environments.
Mutagenesis of NosM Leader Peptide Reveals Important Elements in Nosiheptide Biosynthesis
Authors: Jin Liang , Wu Xuri , Xue Yanjiu , Jin Yue , Wang Shuzhen , Chen Yijun
Published: December 2016

Nosiheptide, a typical member of the ribosomally synthesized and posttranslationally modified peptides (RiPPs), exhibits potent activity against multidrug-resistant Gram-positive bacterial pathogens. The precursor peptide of nosiheptide (NosM) is comprised of a leader peptide with 37 amino acids and a core peptide containing 13 amino acids. To pinpoint elements in the leader peptide that are essential for nosiheptide biosynthesis, a collection of mutants with unique sequence features, including N- and C-terminal motifs, peptide length, and specific sites in the leader peptide, was generated by mutagenesis
in vivo
. The effects of various mutants on nosiheptide biosynthesis were evaluated. In addition to the necessity of a conserved motif LEIS box, native length and the N-terminal 12 amino acid residues were indispensable, and single-site substitutions of these 12 amino acid residues resulted in changes ranging from a greater-than-5-fold decrease to a 2-fold increase of nosiheptide production, depending on the sites and substituted residues. Moreover, although the C-terminal motif is not conservative, significant effects of this portion on nosiheptide production were also evident. Taken together, the present results further highlight the importance of the leader peptide in nosiheptide biosynthesis, and provide new insights into the diversity and specificity of leader peptides in the biosynthesis of various RiPPs.

IMPORTANCE
As a representative thiopeptide, nosiheptide exhibits excellent antibacterial activity. Although the biosynthetic gene cluster and several modification steps have been revealed, the presence and roles of the leader peptide within the precursor peptide of the nosiheptide gene cluster remain elusive. Thus, identification of specific elements in the leader peptide can significantly facilitate the genetic manipulation of the gene cluster for increasing nosiheptide production or generating diverse analogues. Given the complexity of the biosynthetic process, the instability of the leader peptide, and the unavailability of intermediates, cocrystallization of intermediates, leader peptide, and modification enzymes is currently not feasible. Therefore, a mutagenesis approach was used to construct a series of leader peptide mutants to uncover a number of crucial and characteristic elements affecting nosiheptide biosynthesis, which moves a considerable distance toward a thorough understanding of the biosynthetic machinery for thiopeptides.
A Highly Expressed High-Molecular-Weight S-Layer Complex of Pelosinus sp. Strain UFO1 Binds Uranium
Authors: Thorgersen Michael P. , Lancaster W. Andrew , Rajeev Lara , Ge Xiaoxuan , Vaccaro Brian J. , Poole Farris L. , Arkin Adam P. , Mukhopadhyay Aindrila , Adams Michael W. W.
Published: December 2016

Cell suspensions of
Pelosinus
sp. strain UFO1 were previously shown, using spectroscopic analysis, to sequester uranium as U(IV) complexed with carboxyl and phosphoryl group ligands on proteins. The goal of our present study was to characterize the proteins involved in uranium binding. Virtually all of the uranium in UFO1 cells was associated with a heterodimeric protein, which was termed the uranium-binding complex (UBC). The UBC was composed of two S-layer domain proteins encoded by UFO1_4202 and UFO1_4203. Samples of UBC purified from the membrane fraction contained 3.3 U atoms/heterodimer, but significant amounts of phosphate were not detected. The UBC had an estimated molecular mass by gel filtration chromatography of 15 MDa, and it was proposed to contain 150 heterodimers (UFO1_4203 and UFO1_4202) and about 500 uranium atoms. The UBC was also the dominant extracellular protein, but when purified from the growth medium, it contained only 0.3 U atoms/heterodimer. The two genes encoding the UBC were among the most highly expressed genes within the UFO1 genome, and their expressions were unchanged by the presence or absence of uranium. Therefore, the UBC appears to be constitutively expressed and is the first line of defense against uranium, including by secretion into the extracellular medium. Although S-layer proteins were previously shown to bind U(VI), here we showed that U(IV) binds to S-layer proteins, we identified the proteins involved, and we quantitated the amount of uranium bound.

IMPORTANCE
Widespread uranium contamination from industrial sources poses hazards to human health and to the environment. Herein, we identified a highly abundant uranium-binding complex (UBC) from
Pelosinus
sp. strain UFO1. The complex makes up the primary protein component of the S-layer of strain UFO1 and binds 3.3 atoms of U(IV) per heterodimer. While other bacteria have been shown to bind U(VI) on their S-layer, we demonstrate here an example of U(IV) bound by an S-layer complex. The UBC provides a potential tool for the microbiological sequestration of uranium for the cleaning of contaminated environments.
Size and vitreomacular attachment of primary full-thickness macular holes
Authors: Philippakis Elise , Amouyal Franck , Couturier Aude , Boulanger-Scemama Elise , Gaudric Alain , Tadayoni Ramin
Published: December 2016

Purpose

To study the relationship between the size of primary full-thickness macular hole (MH) and the vitreomacular attachment status.

Design

Single-centre retrospective observational case series.

Methods

The records of 100 consecutive eyes operated for primary full-thickness MH were retrospectively reviewed. The vitreous status and MH diameter were assessed on the preoperative optical coherence tomography scans. MH were classified depending on the presence or absence of vitreomacular traction (VMT) and their size as small (<250 µm), medium (250–400 µm) and large (>400 µm), as suggested in the International VMT Study Group Classification.

Results

22% of MH had VMT and 13% had both VMT and a diameter <400 µm. The MH diameter was not significantly different depending on the presence or absence of VMT (respectively, 339±134 and 423±191 µm (p=0.094)), with large overlap between groups. Small, medium and large MH were similarly distributed regardless of the presence or absence of VMT (p=0.69).

Conclusions

Our series of 100 MH did not reveal any significant relationship between the MH size and the presence or absence of VMT. Only 13% of MH had VMT and a diameter <400 mm, then were eligible for intravitreal ocriplasmin as a possible treatment.
Comparison of anti-VEGF therapies on fibrovascular pigment epithelial detachments in age-related macular degeneration
Authors: Au Adrian , Parikh Vishal S , Singh Rishi P , Ehlers Justis P , Yuan Alex , Rachitskaya Aleksandra V , Sears Jonathan E , Srivastava Sunil K , Kaiser Peter K , Schachat Andrew P , Martin Daniel F , Modi Yasha
Published: December 2016

Background

The aim is to compare the therapeutic effects of three antivascular endothelial growth factor (VEGF) drugs (bevacizumab, aflibercept and ranibizumab) on fibrovascular pigment epithelial detachments (fvPEDs) in age-related macular degeneration (AMD).

Methods

This was a retrospective, comparative, consecutive case series of 88 unique eyes with fvPEDs in neovascular AMD treated with anti-VEGF monotherapy for a minimum of 6 months. All eyes were treatment naive. Diagnosis was confirmed retrospectively by fluorescein angiography and spectral-domain optical coherence tomography. Exclusion criteria included serous/drusenoid PEDs or patients who switched anti-VEGF. Mean follow-up across all therapies was 313.9±85.3 days.

Results

Average age of all patients was 80.6 years. Baseline maximum subfoveal PED height was 326.8±185.1 μm, 394.5±238.6 μm and 258.0±145.3 μm for bevacizumab, aflibercept and ranibizumab, respectively (p=0.05). All patients had subretinal fluid, intraretinal fluid or a combination of the two at an initial presentation. Central retinal thickness decreased at all time points compared with baseline across all three anti-VEGF therapies. Subfoveal PED height decreased in patients treated with aflibercept at all time points and decreased in patients treated with bevacizumab at 1-month, 3-month and 6-month time points. Aflibercept reduced PED height more than bevacizumab at 1-month and 12-month follow-ups (p=0.02 and p=0.03, respectively) and ranibizumab at 1-month and 6-month follow-ups (p=0.03 and p=0.02, respectively). No differences in best-corrected visual acuity were appreciated at any time point between drugs.

Conclusions

There was a significant reduction in subfoveal PED height for aflibercept and bevacizumab compared with baseline. A direct comparison of drugs demonstrated a beneficial reduction of PED height, albeit inconsistently, favouring aflibercept. There were no differences in visual acuity across the groups at any time point.
Addressing the challenges of diagnostics demand and supply: insights from an online global health discussion platform
Authors: Engel Nora , Wachter Keri , Pai Madhukar , Gallarda Jim , Boehme Catharina , Celentano Isabelle , Weintraub Rebecca
Published: December 2016

Several barriers challenge development, adoption and scale-up of diagnostics in low and middle income countries. An innovative global health discussion platform allows capturing insights from the global health community on factors driving demand and supply for diagnostics. We conducted a qualitative content analysis of the online discussion ‘Advancing Care Delivery: Driving Demand and Supply of Diagnostics’ organised by the Global Health Delivery Project (GHD) (http://www.ghdonline.org/) at Harvard University. The discussion, driven by 12 expert panellists, explored what must be done to develop delivery systems, business models, new technologies, interoperability standards, and governance mechanisms to ensure that patients receive the right diagnostic at the right time. The GHD Online (GHDonline) platform reaches over 19 000 members from 185 countries. Participants (N=99) in the diagnostics discussion included academics, non-governmental organisations, manufacturers, policymakers, and physicians. Data was coded and overarching categories analysed using qualitative data analysis software. Participants considered technical characteristics of diagnostics as smaller barriers to effective use of diagnostics compared with operational and health system challenges, such as logistics, poor fit with user needs, cost, workforce, infrastructure, access, weak regulation and political commitment. Suggested solutions included: health system strengthening with patient-centred delivery; strengthened innovation processes; improved knowledge base; harmonised guidelines and evaluation; supply chain innovations; and mechanisms for ensuring quality and capacity. Engaging and connecting different actors involved with diagnostic development and use is paramount for improving diagnostics. While the discussion participants were not representative of all actors involved, the platform enabled a discussion between globally acknowledged experts and physicians working in different countries.
Community health workers in Ghana: the need for greater policy attention
Authors: Baatiema Leonard , Sumah Anthony Mwinkaara , Tang Prosper Naazumah , Ganle John Kuumuori
Published: December 2016

From the 1970s to the 1990s, the WHO, United Nations and other agencies mooted the idea of formally training and recognising community health workers (CHWs) to complement efforts to improve primary healthcare delivery in low and middle income countries. Recently, CHWs have been recognised as important players in the achievement of the health-related Millennium Development Goals (MDGs). Despite this recognition, little understanding exists in Ghana about the activities of CHWs: who they are; how they are recruited; what they do; level of health policy support; contribution to healthcare delivery and the challenges they face. Based on a rapid scoping review of the existing literature, and our experience working in Ghana, this paper reflects on the role of CHWs in healthcare delivery in Ghana. We argue that CHWs have played critical roles in improving health service delivery and outcomes, including guinea worm eradication, expanded immunisation coverage, maternal and child health, and HIV/AIDS treatment and management. However, these achievements notwithstanding, CHWs face challenges which prevent them from being optimally productive, including capacity problems, neglect by the healthcare system, high attrition rates and inadequate supervision. Policymakers in Ghana therefore need to give increased attention to CHWs, provide remuneration for their activities, create career opportunities and other means of motivations to boost their productivity and sustain gains associated with their activities.
How does age-related macular degeneration affect real-world visual ability and quality of life? A systematic review
Authors: Taylor Deanna J , Hobby Angharad E , Binns Alison M , Crabb David P
Published: December 2016

Objectives

To review systematically the evidence of age-related macular degeneration (AMD) affecting real-world visual ability and quality of life (QoL). To explore trends in specific topics within this body of the literature.

Design

Systematic review.

Methods

A systematic literature search was carried out using MEDLINE, EMBASE, CINAHL, PsycINFO, PsychARTICLES and Health and Psychosocial Instruments for articles published up to January 2015 for studies including people diagnosed with AMD, assessing real-world visual ability or QoL as an outcome. Two researchers screened studies for eligibility. Details of eligible studies including study design, characteristics of study population and outcomes measured were recorded in a data extraction table. All included studies underwent quality appraisal using the Mixed Methods Appraisal Tool 2011 Version (MMAT).

Results

From 5284 studies, 123 were eligible for inclusion. A range of approaches were identified, including performance-based methods, quantitative and qualitative patient-reported outcome measures (PROMs). AMD negatively affects tasks including mobility, face recognition, perception of scenes, computer use, meal preparation, shopping, cleaning, watching TV, reading, driving and, in some cases, self-care. There is evidence for higher rates of depression among people with AMD than among community dwelling elderly. A number of adaptation strategies have been associated with AMD of varying duration. Much of the research fails to report the type of AMD studied (59% of included studies) or the duration of disease in participants (74%). Of those that do report type studied, the breakdown is as follows: wet AMD 20%, dry AMD 4% and both types 17%.

Conclusions

There are many publications highlighting the negative effects of AMD in various domains of life. Future research should focus on delivering some of this research knowledge into patient management and clinical trials and differentiating between the types of AMD.
Providing additional information about the benefits of statins in a leaflet for patients with coronary heart disease: a qualitative study of the impact on attitudes and beliefs
Authors: Dickinson Rebecca , Raynor David K , Knapp Peter , MacDonald Jan
Published: December 2016

Objective

To explore the impact of providing additional information about the potential benefits of simvastatin in a patient leaflet on attitudes and beliefs.

Design

Interview-based study using a generic qualitative approach and framework analysis.

Participants

21 participants receiving a prescription for simvastatin were recruited from a general practitioner practice (from a total of 120). 8 participants were women; the age range was 55–92.

Intervention

Participants were provided with leaflets showing one of 3 types of additional benefit information: (1) textual statement, (2) number needed to treat (NNT) or (3) natural frequency. Semistructured interviews explored patient's attitudes and beliefs.

Results

A descriptive narrative of preferences for format suggested patients prefer textual as opposed to numerical benefit information. Significant barriers to the acceptance of numerical benefit information included difficulty in understanding the numbers. Patients overestimated the benefits of statins and expressed surprise at the numerical information.

Conclusions

Textual information was preferred but numerical information, in particular in the form of a natural frequency, may help patients make judgements about their medicines. NNTs were found to be very difficult to understand. This raises the prospect that some patients might reject medicines because of disappointment with the perceived low benefits of their medicines. The self-reported impact on behaviour appeared minimal with reports of intentions to ‘do what the doctor tells me’. Further research is needed to explore the impact of such statements on people who are yet to be prescribed a statin.
Cohort profile: the diabetes-tuberculosis treatment outcome (DITTO) study in Pakistan
Authors: Mukhtar Fatima , Butt Zahid A
Published: December 2016

Purpose

Pakistan is faced with an increasing prevalence of diabetes in addition to its existing high burden of tuberculosis (TB). Diabetes has a detrimental effect on treatment outcomes of patients with TB, which may hinder achieving the goals of the End-TB strategy by 2030. We conducted a prospective cohort study to determine difference between treatment outcomes among patients with diabetes and new pulmonary tuberculosis (PTB) and patients without diabetes and new PTB. This would help generate contextual and valid scientific evidence from a developing country like Pakistan with its unique interplay of sociocultural, economic and health system factors to inform policy and practice.

Participants

This paper outlines the baseline characteristics of 614 new cases of PTB, aged 15 years and older, which were followed up prospectively at 2nd, 5th and 6th months while on antituberculosis treatment and at 6 months after treatment completion.

Findings to date

We ascertained patients' diabetic status by conducting random and fasting blood glucose tests and their glycaemic control by determining glycosylated haemoglobin. Treatment outcomes were established using standardised definitions provided by WHO. The assessment of 614 respondents' diabetic status revealed that 113 (18%) were diabetic and 501 (82%) were non-diabetic. A greater proportion of patients with diabetes and PTB were illiterate (n=74/113, 65.5%) as compared to patients without diabetes and PTB (n=249/501, 50%) (p=0.035). More patients with diabetes and PTB gave a history of heart disease (n=14/113, 12%) and hypertension (n=26/113, 23%) as compared to patients without diabetes and PTB (n=2/501, 0.4% (heart disease) and n=13 501, 3% (hypertension)) (p<0.001). Unfavourable treatment outcome was more likely among patients with diabetes and PTB (n=23/93, 25%) as opposed to patients without diabetes and PTB (n=46/410, 11%) (p=0.001).

Future plans

We are negotiating with the government regarding funding for a further 2-year follow-up of the cohort to ascertain death and relapse in the post-treatment period and also differentiate between re-infection and recurrence among these patients with respect to their diabetic status.
Relationship between maternal hypoglycaemia and small-for-gestational-age infants according to maternal weight status: a retrospective cohort study in two hospitals
Authors: Shinohara Satoshi , Uchida Yuzo , Hirai Mitsuo , Hirata Shuji , Suzuki Kohta
Published: December 2016

Objective

The relationship between pre-pregnancy body mass index (BMI) and low glucose challenge test (GCT) results by maternal weight status has not been examined. This study aimed to clarify the relationship between a low GCT result and small for gestational age (SGA) by maternal weight status.

Design

A retrospective cohort study in 2 hospitals.

Setting

This study evaluated the obstetric records of women who delivered in a general community hospital and a tertiary perinatal care centre.

Participants

The number of women who delivered in both hospitals between January 2012 and December 2013 and underwent GCT between 24 and 28 weeks of gestation was 2140. Participants with gestational diabetes mellitus or diabetes during pregnancy, and GCT results of ≥140 mg/dL were excluded. Finally, 1860 women were included in the study.

Primary and secondary outcome measures

The participants were divided into low-GCT (≤90 mg/dL) and non-low-GCT groups (91–139 mg/dL). The χ2tests and multivariate logistic regression analyses were conducted to investigate the association between low GCT results and SGA by maternal weight status.

Results

The incidence of SGA was 11.4% (212/1860), and 17.7% (330/1860) of the women showed low GCT results. The patients were divided into 3 groups according to their BMI (underweight, normal weight and obese). When the patients were analysed separately by their weight status after controlling for maternal age, pre-pregnancy maternal weight, maternal weight gain during pregnancy, pregnancy-induced hypertension, thyroid disease and difference in hospital, low GCT results were significantly associated with SGA (OR 2.10; 95% CI 1.14 to 3.89; p=0.02) in the underweight group.

Conclusions

Low GCT result was associated with SGA at birth among underweight women. Examination of maternal glucose tolerance and fetal growth is necessary in future investigations.
Describing visible acute injuries: development of a comprehensive taxonomy for research and practice
Authors: Rosen Tony , Reisig Christopher , LoFaso Veronica M , Bloemen Elizabeth M , Clark Sunday , McCarthy Thomas J , Mtui Estomih P , Flomenbaum Neal E , Lachs Mark S
Published: December 2016

Background

Little literature exists classifying and comprehensively describing intentional and unintentional acute injuries, which would be valuable for research and practice. In preparation for a study of injury patterns in elder abuse, our goal was to develop a comprehensive taxonomy of relevant types and characteristics of visible acute injuries and evaluate it in geriatric patients.

Methods

We conducted an exhaustive review of the medical and forensic literature focusing on injury types, descriptions, patterns and analyses. We then prepared iteratively, through consensus with a multidisciplinary, national panel of elder abuse experts, a comprehensive classification system to describe these injuries.

Results

We designed a three-step process to fully describe and classify visible acute injuries: (1) determining the type of injury, (2) assigning values to each of the characteristics common to all geriatric injuries and (3) assigning values to additional characteristics relevant for specific injuries. We identified nine unique types of visible injury and seven characteristics critical to describe all these injuries, including body region(s) and precise anatomic location(s). For each injury type, we identified two to seven additional critical characteristics, such as size, shape and cleanliness. We pilot tested it on 323 injuries on 83 physical elder abuse victims and 45 unintentional fall victims from our ongoing research to ensure that it would allow for the complete and accurate description of the full spectrum of visible injuries encountered and made modifications and refinements based on this experience. We then used the classification system to evaluate 947 injuries on 80 physical elder abuse victims and 195 unintentional fall victims to assess its practical utility.

Conclusions

Our comprehensive injury taxonomy systematically integrates and expands on existing forensic and clinical research. This new classification system may help standardise description of acute injuries and patterns among clinicians and researchers.