bluuebunny/crossref_metadata_2025 huggingface dataset:
Sympathy for low blood sugar is felt in your gut
Authors: Moore Daniel J.
Published: September 2016

Sympathetic input into ghrelin-producing cells is required to prevent life-threatening hypoglycemia, especially in individuals with limited nutritional stores.
The Development of Drugs against Acanthamoeba Infections
Authors: Siddiqui Ruqaiyyah , Aqeel Yousuf , Khan Naveed Ahmed
Published: September 2016

For the past several decades, there has been little improvement in the morbidity and mortality associated with
Acanthamoeba
keratitis and
Acanthamoeba
encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies.
Comparative Evaluation of the Predictive Performances of Three Different Structural Population Pharmacokinetic Models To Predict Future Voriconazole Concentrations
Authors: Farkas Andras , Daroczi Gergely , Villasurda Phillip , Dolton Michael , Nakagaki Midori , Roberts Jason A.
Published: September 2016

Bayesian methods for voriconazole therapeutic drug monitoring (TDM) have been reported previously, but there are only sparse reports comparing the accuracy and precision of predictions of published models. Furthermore, the comparative accuracy of linear, mixed linear and nonlinear, or entirely nonlinear models may be of high clinical relevance. In this study, models were coded into individually designed optimum dosing strategies (ID-ODS) with voriconazole concentration data analyzed using inverse Bayesian modeling. The data used were from two independent data sets, patients with proven or suspected invasive fungal infections (
n =
57) and hematopoietic stem cell transplant recipients (
n =
10). Observed voriconazole concentrations were predicted whereby for each concentration value, the data available to that point were used to predict that value. The mean prediction error (ME) and mean squared prediction error (MSE) and their 95% confidence intervals (95% CI) were calculated to measure absolute bias and precision, while ΔME and ΔMSE and their 95% CI were used to measure relative bias and precision, respectively. A total of 519 voriconazole concentrations were analyzed using three models. MEs (95% CI) were 0.09 (−0.02, 0.22), 0.23 (0.04, 0.42), and 0.35 (0.16 to 0.54) while the MSEs (95% CI) were 2.1 (1.03, 3.17), 4.98 (0.90, 9.06), and 4.97 (−0.54 to 10.48) for the linear, mixed, and nonlinear models, respectively. In conclusion, while simulations with the linear model were found to be slightly more accurate and similarly precise, the small difference in accuracy is likely negligible from the clinical point of view, making all three approaches appropriate for use in a voriconazole TDM program.
Molecular Epidemiology and Genome Dynamics of New Delhi Metallo-β-Lactamase-Producing Extraintestinal Pathogenic Escherichia coli Strains from India
Authors: Ranjan Amit , Shaik Sabiha , Mondal Agnismita , Nandanwar Nishant , Hussain Arif , Semmler Torsten , Kumar Narender , Tiwari Sumeet K. , Jadhav Savita , Wieler Lothar H. , Ahmed Niyaz
Published: September 2016

The global dissemination and increasing incidence of carbapenem-resistant, Gram-negative organisms have resulted in acute public health concerns. Here, we present a retrospective multicenter study on molecular characterization of metallo-β-lactamase (MBL)-producing clinical
Escherichia coli
isolates recovered from extraintestinal infections in two hospitals in Pune, India. We screened a large sample size of 510
E. coli
isolates for MBL production wherein we profiled their molecular determinants, antimicrobial resistance phenotypes, functional virulence properties, genomic features, and transmission dynamics. Approximately 8% of these isolates were MBL producers, the majority of which were of the NDM-1 (69%) type, followed by NDM-5 (19%), NDM-4 (5.5%), and NDM-7 (5.5%). MBL producers were resistant to all antibiotics tested except for colistin, fosfomycin, and chloramphenicol, which were effective to various extents. Plasmids were found to be an effective means of dissemination of NDM genes and other resistance traits. All MBL producers adhered to and invaded bladder epithelial (T24) cells and demonstrated significant serum resistance. Genomic analysis of MBL-producing
E. coli
isolates revealed higher resistance but a moderate virulence gene repertoire. A subset of NDM-1-positive
E. coli
isolates was identified as dominant sequence type 101 (ST101) while two strains belonging to ST167 and ST405 harbored NDM-5. A majority of MBL-producing
E. coli
strains revealed unique genotypes, suggesting that they were clonally unrelated. Overall, the coexistence of virulence and carbapenem resistance in clinical
E. coli
isolates is of serious concern. Moreover, the emergence of NDM-1 among the globally dominant
E. coli
ST101 isolates warrants stringent surveillance and control measures.
Ceftriaxone-Resistant Neisseria gonorrhoeae Isolates (2010 to 2014) in France Characterized by Using Whole-Genome Sequencing
Authors: de Curraize Claire , Kumanski Sylvain , Micaëlo Maïté , Fournet Nelly , La Ruche Guy , Meunier Fabienne , Amarsy Rishma , Jacquier Hervé , Cambau Emmanuelle , Goubard Agathe , Bercot Béatrice
Published: September 2016

Two extended-spectrum cephalosporin-resistant
Neisseria gonorrhoeae
isolates were discovered among 6,340 (0.03%) French isolates between 2010 and 2014. One isolate corresponded to the F89 multidrug-resistant
N. gonorrhoeae
isolate harboring a
penA
mosaic; whole-genome sequencing highlighted an additional R251H substitution in the
ftsX
gene recently involved in cephalosporin resistance. The other, ceftriaxone-resistant isolate (MIC, 0.25 mg/liter) harbored the PBP2 pattern XXXVI plus a P551S substitution and belonged to sequence type ST1579 (multilocus sequence typing [MLST]).
Conserved Arginines at the P-Protein Stalk Binding Site and the Active Site Are Critical for Ribosome Interactions of Shiga Toxins but Do Not Contribute to Differences in the Affinity of the A1 Subunits for the Ribosome
Authors: Basu Debaleena , Kahn Jennifer N. , Li Xiao-Ping , Tumer Nilgun E.
Published: September 2016

The A1 subunits of Shiga toxin 1 (Stx1A1) and Shiga toxin 2 (Stx2A1) interact with the conserved C termini of ribosomal-stalk P-proteins to remove a specific adenine from the sarcin/ricin loop. We previously showed that Stx2A1 has higher affinity for the ribosome and higher catalytic activity than Stx1A1. To determine if conserved arginines at the distal face of the active site contribute to the higher affinity of Stx2A1 for the ribosome, we mutated Arg172, Arg176, and Arg179 in both toxins. We show that Arg172 and Arg176 are more important than Arg179 for the depurination activity and toxicity of Stx1A1 and Stx2A1. Mutation of a single arginine reduced the depurination activity of Stx1A1 more than that of Stx2A1. In contrast, mutation of at least two arginines was necessary to reduce depurination by Stx2A1 to a level similar to that of Stx1A1. R176A and R172A/R176A mutations eliminated interaction of Stx1A1 and Stx2A1 with ribosomes and with the stalk, while mutation of Arg170 at the active site reduced the binding affinity of Stx1A1 and Stx2A1 for the ribosome, but not for the stalk. These results demonstrate that conserved arginines at the distal face of the active site are critical for interactions of Stx1A1 and Stx2A1 with the stalk, while a conserved arginine at the active site is critical for non-stalk-specific interactions with the ribosome. Arginine mutations at either site reduced ribosome interactions of Stx1A1 and Stx2A1 similarly, indicating that conserved arginines are critical for ribosome interactions but do not contribute to the higher affinity of Stx2A1 for the ribosome.
Gamma Interferon Is Required for Optimal Antibody-Mediated Immunity against Genital Chlamydia Infection
Authors: Naglak Elizabeth K. , Morrison Sandra G. , Morrison Richard P.
Published: September 2016

Defining the mechanisms of immunity conferred by the combination of antibody and CD4+T cells is fundamental to designing an efficacious chlamydial vaccine. Using theChlamydia muridarumgenital infection model of mice, which replicates many features of humanC. trachomatisinfection and avoids the characteristic low virulence ofC. trachomatisin the mouse, we previously demonstrated a significant role for antibody in immunity to chlamydial infection. We found that antibody alone was not protective. Instead, protection appeared to be conferred through an undefined antibody-cell interaction. Using gene knockout mice andin vivocellular depletion methods, our data suggest that antibody-mediated protection is dependent on the activation of an effector cell population in genital tract tissues by CD4+T cells. Furthermore, the CD4+T cell-secreted cytokine gamma interferon (IFN-γ) was found to be a key component of the protective antibody response. The protective function of IFN-γ was not related to the immunoglobulin class or to the magnitude of theChlamydia-specific antibody response or to recruitment of an effector cell population to genital tract tissue. Rather, IFN-γ appears to be necessary for activation of the effector cell population that functions in antibody-mediated chlamydial immunity. Our results confirm the central role of antibody in immunity to chlamydia reinfection and demonstrate a key function for IFN-γ in antibody-mediated protection.
Type II Secretion Is Necessary for Optimal Association of the Legionella-Containing Vacuole with Macrophage Rab1B but Enhances Intracellular Replication Mainly by Rab1B-Independent Mechanisms
Authors: White Richard C. , Cianciotto Nicholas P.
Published: September 2016

Previously, we documented that type II secretion (T2S) promotes intracellular infection of macrophages by
Legionella pneumophila
. In the present study, we identified infection events that are modulated by T2S by comparing the behaviors of wild-type and T2S mutant bacteria in murine bone marrow-derived macrophages and human U937 cells. Although the two strains behaved similarly for entry into the host cells and evasion of lysosomal fusion, the mutant was impaired in the ability to initiate replication between 4 and 8 h postentry and to grow to large numbers in the
Legionella
-containing vacuole (LCV), as evident at 12 h. At 4 h postinoculation, mutant LCVs had a significantly reduced association with Rab1B, a host GTPase that facilitates the tethering of endoplasmic reticulum (ER)-derived vesicles to LCVs. The mutant did not lose expression or translocation of six type IV secretion effectors (e.g., SidM) that are well known for mediating Rab1B association with the LCV, indicating that T2S promotes the interaction between the LCV and Rab1B via a novel mechanism. Interestingly, the mutant's growth defect was exacerbated in macrophages that had been depleted of Rab1B by short hairpin RNA (shRNA) treatment, indicating that T2S also potentiates events beyond Rab1B association. In support of this, a
sidM lspF
double mutant had an intracellular growth defect that was more dramatic than that of the
lspF
mutant (and a
sidM
mutant) and showed a growth difference of as much as a 400-fold compared to the wild type. Together, these data reveal a new role for T2S in intracellular infection that involves both Rab1B-dependent and Rab1B-independent processes.
A Putative Bacterial ABC Transporter Circumvents the Essentiality of Signal Peptidase
Authors: Morisaki J. Hiroshi , Smith Peter A. , Date Shailesh V. , Kajihara Kimberly K. , Truong Chau Linda , Modrusan Zora , Yan Donghong , Kang Jing , Xu Min , Shah Ishita M. , Mintzer Robert , Kofoed Eric M. , Cheung Tommy K. , Arnott David , Koehler Michael F. T. , Heise Christopher E. , Brown Eric J. , Tan Man-Wah , Hazenbos Wouter L. W.
Published: September 2016

The type I signal peptidase of
Staphylococcus aureus
, SpsB, is an attractive antibacterial target because it is essential for viability and extracellularly accessible. We synthesized compound 103, a novel arylomycin-derived inhibitor of SpsB with significant potency against various clinical
S. aureus
strains (MIC of ~1 µg/ml). The predominant clinical strain USA300 developed spontaneous resistance to compound 103 with high frequency, resulting from single point mutations inside or immediately upstream of
cro
/
cI
, a homolog of the lambda phage transcriptional repressor
cro
. These
cro
/
cI
mutations led to marked (>50-fold) overexpression of three genes encoding a putative ABC transporter. Overexpression of this ABC transporter was both necessary and sufficient for resistance and, notably, circumvented the essentiality of SpsB during
in vitro
culture. Mutation of its predicted ATPase gene abolished resistance, suggesting a possible role for active transport; in these bacteria, resistance to compound 103 occurred with low frequency and through mutations in
spsB
. Bacteria overexpressing the ABC transporter and lacking SpsB were capable of secreting a subset of proteins that are normally cleaved by SpsB and instead were cleaved at a site distinct from the canonical signal peptide. These bacteria secreted reduced levels of virulence-associated proteins and were unable to establish infection in mice. This study reveals the mechanism of resistance to a novel arylomycin derivative and demonstrates that the nominal essentiality of the
S. aureus
signal peptidase can be circumvented by the upregulation of a putative ABC transporter
in vitro
but not
in vivo
.

IMPORTANCE
The type I signal peptidase of
Staphylococcus aureus
(SpsB) enables the secretion of numerous proteins by cleavage of the signal peptide. We synthesized an SpsB inhibitor with potent activity against various clinical
S. aureus
strains. The predominant
S. aureus
strain USA300 develops resistance to this inhibitor by mutations in a novel transcriptional repressor (
cro
/
cI
), causing overexpression of a putative ABC transporter. This mechanism promotes the cleavage and secretion of various proteins independently of SpsB and compensates for the requirement of SpsB for viability
in vitro
. However, bacteria overexpressing the ABC transporter and lacking SpsB secrete reduced levels of virulence-associated proteins and are unable to infect mice. This study describes a bacterial resistance mechanism that provides novel insights into the biology of bacterial secretion.
FtsZ-Dependent Elongation of a Coccoid Bacterium
Authors: Pereira Ana R. , Hsin Jen , Król Ewa , Tavares Andreia C. , Flores Pierre , Hoiczyk Egbert , Ng Natalie , Dajkovic Alex , Brun Yves V. , VanNieuwenhze Michael S. , Roemer Terry , Carballido-Lopez Rut , Scheffers Dirk-Jan , Huang Kerwyn Casey , Pinho Mariana G.
Published: September 2016

A mechanistic understanding of the determination and maintenance of the simplest bacterial cell shape, a sphere, remains elusive compared with that of more complex shapes. Cocci seem to lack a dedicated elongation machinery, and a spherical shape has been considered an evolutionary dead-end morphology, as a transition from a spherical to a rod-like shape has never been observed in bacteria. Here we show that a
Staphylococcus aureus
mutant (M5) expressing the
ftsZ
G193D
allele exhibits elongated cells. Molecular dynamics simulations and
in vitro
studies indicate that FtsZ
G193D
filaments are more twisted and shorter than wild-type filaments.
In vivo
, M5 cell wall deposition is initiated asymmetrically, only on one side of the cell, and progresses into a helical pattern rather than into a constricting ring as in wild-type cells. This helical pattern of wall insertion leads to elongation, as in rod-shaped cells. Thus, structural flexibility of FtsZ filaments can result in an FtsZ-dependent mechanism for generating elongated cells from cocci.

IMPORTANCE
The mechanisms by which bacteria generate and maintain even the simplest cell shape remain an elusive but fundamental question in microbiology. In the absence of examples of coccus-to-rod transitions, the spherical shape has been suggested to be an evolutionary dead end in morphogenesis. We describe the first observation of the generation of elongated cells from truly spherical cocci, occurring in a
Staphylococcus aureus
mutant containing a single point mutation in its genome, in the gene encoding the bacterial tubulin homologue FtsZ. We demonstrate that FtsZ-dependent cell elongation is possible, even in the absence of dedicated elongation machinery.
Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing
Authors: Kalan Lindsay , Loesche Michael , Hodkinson Brendan P. , Heilmann Kristopher , Ruthel Gordon , Gardner Sue E. , Grice Elizabeth A.
Published: September 2016

Chronic nonhealing wounds have been heralded as a silent epidemic, causing significant morbidity and mortality especially in elderly, diabetic, and obese populations. Polymicrobial biofilms in the wound bed are hypothesized to disrupt the highly coordinated and sequential events of cutaneous healing. Both culture-dependent and -independent studies of the chronic-wound microbiome have almost exclusively focused on bacteria, omitting what we hypothesize are important fungal contributions to impaired healing and the development of complications. Here we show for the first time that fungal communities (the mycobiome) in chronic wounds are predictive of healing time, associated with poor outcomes, and form mixed fungal-bacterial biofilms. We longitudinally profiled 100, nonhealing diabetic-foot ulcers with high-throughput sequencing of the pan-fungal internal transcribed spacer 1 (ITS1) locus, estimating that up to 80% of wounds contain fungi, whereas cultures performed in parallel captured only 5% of colonized wounds. The “mycobiome” was highly heterogeneous over time and between subjects. Fungal diversity increased with antibiotic administration and onset of a clinical complication. The proportions of the phylumAscomycotawere significantly greater (P= 0.015) at the beginning of the study in wounds that took >8 weeks to heal. Wound necrosis was distinctly associated with pathogenic fungal species, while taxa identified as allergenic filamentous fungi were associated with low levels of systemic inflammation. Directed culturing of wounds stably colonized by pathogens revealed that interkingdom biofilms formed between yeasts and coisolated bacteria. Combined, our analyses provide enhanced resolution of the mycobiome during impaired wound healing, its role in chronic disease, and impact on clinical outcomes.

IMPORTANCEWounds are an underappreciated but serious complication for a diverse spectrum of diseases. High-risk groups, such as persons with diabetes, have a 25% lifetime risk of developing a wound that can become chronic. The majority of microbiome research related to chronic wounds is focused on bacteria, but the association of fungi with clinical outcomes remains to be elucidated. Here we describe the dynamic fungal communities in 100 diabetic patients with foot ulcers. We found that communities are unstable over time, but at the first clinical presentation, the relative proportions of different phyla predict healing times. Pathogenic fungi not identified by culture reside in necrotic wounds and are associated with a poor prognosis. In wounds stably colonized by fungi, we identified yeasts capable of forming biofilms in concert with bacteria. Our findings illuminate the associations of the fungal mycobiome with wound prognosis and healing.
Congenital depression of the skull in a neonate
Authors: Tayeh Christelle , Bali Bassel , Milad Nadine , Najjar Marwan
Published: September 2016

Congenital depression of the fetal skull is a rare condition. We discuss the case of a 14-days-old male infant, born at term by elective non-complicated caesarean section presenting with a left temporoparietal skull depression. A CT scan was performed which showed no associated fracture. A conservative approach was followed since the infant showed no signs of neurological deficit. Similar cases have been managed successfully in other reports using a conservative approach, with the condition being often self-resolving over the course of a few months.
Statin-associated rhabdomyolysis triggered by drug–drug interaction with itraconazole
Authors: Dybro Anne Mette , Damkier Per , Rasmussen Torsten Bloch , Hellfritzsch Maja
Published: September 2016

A 47-year-old woman had been treated with high-dose simvastatin for several years. After systemic treatment with the antifungal agent itraconazole, she developed muscle pain and highly elevated levels of creatine kinase and myoglobin. Muscle biopsy was compatible with statin-associated rhabdomyolysis, probably caused by a drug–drug interaction between simvastatin and itraconazole. The patient made full recovery. Three commonly used statins—simvastatin, atorvastatin and lovastatin—are metabolised by the liver enzyme CYP3A4. Several potent inhibitors of this enzyme are known, for example, azole antifungal agents such as itraconazole and posaconazole. If antifungal treatment is indicated in a patient using a CYP3A4-metabolised statin, we recommend (1) topical administration of the antifungal agent if possible, (2) the use of a non-CYP3A4-inhibiting antifungal drug such as terbinafine or (3) temporary discontinuation of statin treatment.
Primary healthcare policy implementation in South Asia
Authors: van Weel Chris , Kassai Ryuki , Qidwai Waris , Kumar Raman , Bala Kanu , Prasad Gupta Pramendra , Haniffa Ruvaiz , Rajapaksa Hewageegana Neelamani , Ranasinghe Thusara , Kidd Michael , Howe Amanda
Published: September 2016

Primary healthcare is considered an essential feature of health systems to secure population health and contain costs of healthcare while universal health coverage forms a key to secure access to care. This paper is based on a workshop at the 2016 World Organization of Family Doctors (WONCA) South Asia regional conference, where the health systems of Bangladesh, India, Nepal, Pakistan and Sri Lanka were presented in relation to their provision of primary healthcare. The five countries have in recent years improved the health of their populations, but currently face the challenges of non-communicable diseases and ageing populations. Primary healthcare should be a core component in restructuring health systems. However, there is a lack of understanding among policymakers of the unique contribution of primary healthcare to the health of populations. This results in insufficient investment in facilities and low priority of specialty training in the community setting. Regional collaboration could strengthen the advocacy for primary healthcare to policymakers and other stakeholders. Priorities were investment in community-based health facilities, and access to healthcare through professionals specialty-trained in the primary healthcare setting. This development fits the strategy of the WHO South East Asian Region to use community-based healthcare in achieving universal health coverage for the Asian populations.
Does preoperative depression and/or serotonin transporter gene polymorphism predict outcome after laparoscopic cholecystectomy?
Authors: Wright Barry , Alexander David , Aghahoseini Assad
Published: September 2016

Objective

To determine whether preoperative psychological depression and/or serotonin transporter gene polymorphism are associated with poor outcomes after the common procedure of laparoscopic cholecystectomy.

Design

Patients undergoing laparoscopic cholecystectomy were genotyped for the serotonin transporter gene 5-HTTLPR polymorphism and assessed for psychological morbidity before and 6 weeks after surgery. The main outcome was postoperative depression; secondary outcomes included fatigue, perceived pain, quality of life and subjective perception about return to usual.

Results

Full genetic and psychological data were obtained from 273 out of 330 patients consented to the study (82% female). Significantly fewer people with preoperative depression (Beck Depression Inventory (BDI) score >5) had returned to employment (57% vs 86%, p<0.001) or made a full recovery (11% vs 44%, p<0.001) 6 weeks after surgery. Independent predictors for subjective return to usual after surgery included preoperative depression, body mass index and postoperative pain scores. Independent predictors of postoperative depression included preoperative antidepressant use and preoperative depression. SS genotype was associated with use of antidepressants preoperatively and higher anxiety levels after surgery. However, it was not associated with other salient postoperative psychosocial outcomes.

Conclusions

Depressive psychological morbidity preoperatively, pain and body mass index appear to be important factors in predicting recovery after this common surgical procedure. There may be a place to include preoperative brief psychological screening to enable targeted support. Our results suggest that the serotonin transporter gene is unlikely to be a useful clinical predictor of outcome in this group.

Trial registration number

ISRCTN40219584.
Protocol for a multicentre, prospective, observational cohort study of variation in practice in perioperative analgesic strategies in elective laparoscopic colorectal surgery: the LapCoGesic Study
Authors:   Northern Surgical Trainees Research Association (NoSTRA), Burnell Phillippa , Coates Rachael , Dixon Steven , Grant Lucy , Grey Matthew , Griffiths Ben , Jones Mike , Madhavan Anantha , McCallum Iain , McClean Ross , Naru Karen , Newton Lydia , O'Loughlin Paul , Shaban Fadlo , Sukha Anisha , Somnath Sameer , Shumon Syed , Harji Deena
Published: September 2016

Introduction

Laparoscopic surgery combined with enhanced recovery programmes has become the gold standard in the elective management of colorectal disease. However, there is no consensus with regard to the optimal perioperative analgesic regime in this cohort of patients, with a number of options available, including thoracic epidural spinal analgesia, patient-controlled analgesia, subcutaneous and/or intraperitoneal local anaesthetics, local anaesthetic wound infiltration catheters and transversus abdominis plane blocks. This study aims to explore any differences in analgesic strategies employed across the North East of England and to assess whether any variation in practice has an impact on clinical outcomes.

Methods and analysis

All North East Colorectal units will be recruited for participation by the Northern Surgical Trainees Research Association (NoSTRA). Data will be collected over a consecutive 2-month period. Outcome measures will include postoperative pain score, postoperative opioid analgesic use and side effects, length of stay, 30-day complication rates, 30-day reoperative rates and 30-day readmission rates.

Ethics and dissemination

Ethical approval for this study has been granted by the National Research Ethics Service. The protocol will be disseminated through NoSTRA. Individual unit data will be presented at local meetings. Overall collective data will be published in peer-reviewed journals and presented at relevant surgical meetings.
Predictors of physical functioning after total hip arthroplasty: a systematic review
Authors: Buirs L D , Van Beers L W A H , Scholtes V A B , Pastoors T , Sprague S , Poolman R W
Published: September 2016

Objective

The objective of this systematic review of the literature was to identify the predictors of functional outcome after total hip arthroplasty (THA).

Method

A systematic literature search in Web of Science, CINAHL, EMBASE and PubMed was conducted on 23 June 2015. The articles were selected based on their quality, relevance and measurement of the predictive factor. The level of evidence of all studies was determined using the GRADE rating scheme.

Results

The initial search resulted in 1092 citations. After application of the inclusion and exclusion criteria, 33 articles met our eligibility criteria and were graded. Included studies were classified as level of evidence low (11), moderate (17) or high (5). Of the included studies, 18 evaluated body mass index (BMI), 17 evaluated preoperative physical functions, 15 evaluated age, 15 evaluated gender and 13 evaluated comorbidity. There was strong evidence suggesting an association between BMI, age, comorbidity, preoperative physical functions and mental health with functional outcome after THA. There was weak evidence suggesting an association between quadriceps strength and education with functional outcome after THA. The evidence was inconsistent for associations with gender and socioeconomic status and functional outcome following THA. We found limited evidence suggesting that alcohol consumption, vitamin D insufficiency and allergies were predictors of functional outcome following THA.

Conclusions

We have identified multiple predictors of functional outcome after THA, which will enable general practitioners and orthopaedic surgeons to better predict the improvement in physical functioning for their patients with THA. They can use this information to provide patient-specific advice regarding the referral for THA and the expected outcomes after THA. Further research with consistent measurement tools, outcomes and duration of follow-up across studies is needed to confirm the influence of these factors.
Effect of religious involvement on cognition from a life-course perspective: protocol for a systematic review and meta-analysis
Authors: Hosseini Shera , Chaurasia Ashok , Cooke Martin , Oremus Mark
Published: September 2016

Introduction

Preserving cognitive health is a crucial aspect of healthy ageing. Both abnormal and normal cognitive decline can adversely affect the health of ageing populations. Evidence suggests religious involvement (RI) can preserve cognition in ageing populations. The primary purpose of this review is to examine the evidence regarding the association between RI and cognition from a life-course perspective.

Methods and analysis

This systematic review and meta-analysis has been registered with PROSPERO (registration number CRD42016032331). We will search MEDLINE, PSYCHINFO and EMBASE, and include primary studies with a comparison group, for example, cohort, cross-sectional and case–control studies. To supplement the database search, we will also search the grey literature and the reference lists of included studies. Two reviewers will independently assess and extract data from the articles. Risk of bias and the strength of evidence will be assessed. For sufficiently homogeneous data in domains such as study methods and measures of RI and cognition, we will pool the results using DerSimonian and Laird meta-analysis.

Ethics and dissemination

Since this is a protocol for a systematic review, ethics approval is not required. The findings of this review will be extensively disseminated through peer-reviewed publications and conference presentations.
Sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the CPRD primary care database
Authors: Fairhurst Caroline , Martin Fabiola , Watt Ian , Doran Tim , Bland Martin , Brackenbury William J
Published: September 2016

Introduction

Voltage-gated sodium channel (VGSC)-inhibiting drugs are commonly used to treat epilepsy and cardiac arrhythmia. VGSCs are also widely expressed in various cancers, including those of the breast, bowel and prostate. A number of VGSC-inhibiting drugs have been shown to inhibit cancer cell proliferation, invasion, tumour growth and metastasis in preclinical models, suggesting that VGSCs may be novel molecular targets for cancer treatment. Surprisingly, we previously found that prior exposure to VGSC-inhibiting drugs may be associated with reduced overall survival in patients with cancer, but we were unable to control for the cause of death or indication for prescription. The purpose of the present study is to interrogate a different database to further investigate the relationship between VGSC-inhibiting drugs and cancer-specific survival.

Methods and analysis

A cohort study using primary care data from the Clinical Practice Research Datalink database will include patients with diagnosis of breast, bowel and prostate cancer (13 000). The primary outcome will be cancer-specific survival from the date of cancer diagnosis. Cox proportional hazards regression will be used to compare survival of patients taking VGSC-inhibiting drugs (including antiepileptic drugs and class I antiarrhythmic agents) with patients with cancer not taking these drugs, adjusting for cancer type, age and sex. Drug exposure will be treated as a time-varying covariate to account for potential immortal time bias. Various sensitivity and secondary analyses will be performed.

Ethics and dissemination

The project has been reviewed and approved by the University of York Ethical Review Process. Results will be presented at an international conference and published in open access peer-reviewed journals according to the STROBE and RECORD guidelines.
Cost-effectiveness of screening for hepatitis C virus: a systematic review of economic evaluations
Authors: Coward Stephanie , Leggett Laura , Kaplan Gilaad G , Clement Fiona
Published: September 2016

Objectives

With the developments of near-cures for hepatitis C virus (HCV), who to screen has become a high-priority policy issue in many western countries. Cost-effectiveness of screening programmes should be one consideration when developing policy. The objective of this work is to synthesise the cost-effectiveness of HCV screening programmes.

Setting

A systematic review was completed. 5 databases were searched until May 2016 (NHSEED, MEDLINE, the HTA Health Technology Assessment Database, EMBASE, EconLit).

Participants

Any study reporting an economic evaluation (any type) of screening compared with opportunistic or no screening for HCV was included. Exclusion criteria were: (1) abstracts or commentaries, (2) economic evaluations of other interventions for HCV, including blood donors screening, diagnosis tests for HCV, screening for concurrent disease or medications for treatment.

Primary and secondary outcome measures

Data extraction included type of model, target population, perspective, comparators, time horizon, discount rate, clinical inputs, cost inputs and outcome. Quality was evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist. Data are summarised using narrative synthesis by population.

Results

2305 abstracts were identified with 52 undergoing full-text review. 30 papers met inclusion criteria addressing 7 populations: drug users (n=6), high risk (n=5), pregnant (n=4), prison (n=3), birth cohort (n=8), general population (n=5) and other (n=6). The majority (77%) of the studies were high quality. Drug users, birth cohort and high-risk populations were associated with cost-effectiveness ratios of under £30 000 per quality-adjusted-life-year (QALY). The remaining populations were associated with cost-effectiveness ratios that exceeded £30 000 per QALY.

Conclusions

Economic evidence for screening populations is robust. If a cost per QALY of £30 000 is considered reasonable value for money, then screening birth cohorts, drug users and high-risk populations are policy options that should be considered.
Environmental factors and cardiovascular diseases: the association of income inequality and green spaces in elderly residents of São Paulo, Brazil
Authors: Massa Kaio Henrique Correa , Pabayo Roman , Lebrão Maria Lúcia , Chiavegatto Filho Alexandre Dias Porto
Published: September 2016

Objective

We aimed to analyse the individual and contextual determinants associated with cardiovascular diseases (CVDs) morbidity among the elderly.

Methods

The sample consisted of 1333 individuals aged 60 or older residing in the city of São Paulo, from the Health, Welfare and Aging (SABE) study survey performed in 2010. The association between CVD with both income inequality and green spaces was analysed using Bayesian multilevel models, controlling for individual and contextual factors.

Results

We found a significant association between income inequality and green spaces, and risk of CVD. In comparison to elderly residents in areas with low-income inequality, there was an increased risk for CVD among those residing in the medium–low (OR=1.35, 95% CI 1.15 to 1.59), medium–high (OR=2.71, 95% CI 2.18 to 3.36) and high (OR=1.43, 95% CI 1.14 to 1.79) quartiles of income inequality. Those living in medium–low (OR=0.44, 95% CI 0.39 to 0.49), medium–high (OR=0.56, 95% CI 0.48 to 0.65) and high (OR=0.48, 95% CI 0.43 to 0.55) green spaces levels had lower risk of CVD.

Conclusions

These findings highlight the importance of area-level characteristics on CVD risk and the need to develop healthcare policies focused on the effect of individual and contextual characteristics.
Bed utilisation and increased risk ofClostridium difficileinfections in acute hospitals in England in 2013/2014
Authors: Vella Venanzio , Aylin Paul P , Moore Luke , King Alice , Naylor Nichola R , Birgand Gabriel J C , Lishman Hannah , Holmes Alison
Published: September 2016

Background

The study aimed to identify thresholds for hospital bed utilisation which are independently associated with significantly higher risks forClostridium difficileinfections (CDI) in acute hospitals in England.

Method

A retrospective analysis was carried out on reported data from the English National Health Service (NHS) for the financial year 2013/2014. Reported rates of CDI were used as a proxy for hospital infection rates in acute NHS hospital trusts. Multivariate linear regression was used to assess the relationship between bed utilisation values and CDI controlling for confounding factors. Hospitals were finally plotted in a Pabon Lasso graph according to their average bed occupancy rate (BOR) and bed turnover rate (BTR) per year to visualise the relationship between bed utilisation and CDI.

Results

Among English hospital NHS trusts, increasing BTR and decreasing BOR were associated with a decrease in CDI. However, this effect was not large, and patient mix had a larger impact on CDI rates than bed utilisation.

Conclusions

While policymakers and managers wishing to target healthcare providers with high CDI rates should look at bed utilisation measures, focusing on these alone is unlikely to have the desired impact. Instead, strategies to combat CDI must take a wider perspective on contributory factors at the institutional level.
P2Y12 hyporesponse (PRU>200) is not associated with increased thromboembolic complications in anterior circulation Pipeline
Authors: Bender Matthew T , Lin Li-Mei , Colby Geoffrey P , Lubelski Daniel , Huang Judy , Tamargo Rafael J , Coon Alexander L
Published: September 2016

Introduction

Recent reports suggest that thromboembolic complications are associated with Pipeline embolization device (PED) placement cluster in P2Y12 hyporesponders.

Objective

To evaluate the role of P2Y12 hyporesponse in PED placement by retrospectively reviewing a single-center series of patients.

Methods

We retrospectively reviewed an institutional review board-approved database of patients with an aneurysm at a single institution and identified all patients with a measured P2Y12 reaction unit (PRU)>200 who had undergone anterior circulation PED placement. Events such as transient ischemic attack, stroke, and hemorrhage were identified as well as demographic and procedural details.

Results

Fifty-two patients with a PRU >200 had undergone anterior circulation PED placement. Four patients had prior subarachnoid hemorrhage (SAH) (8%) and 11 aneurysms (21%) had been previously treated. The average aneurysm size was 7.6 mm (±6.2). PED thrombosis occurred intraprocedurally in three patients, none of whom developed neurological deficits after abciximab administration. Treatment of all patients was successful and 48 procedures (92%) had no complications. One patient had a major stroke (2%) with permanent hemiparesis. There were three minor complications (6%): one minor stroke with a visual field cut, one 10 cc intracranial hemorrhage with transient left lower extremity weakness, and one transient neurological deficit not verified by imaging. No deaths or cases of SAH occurred.

Conclusions

P2Y12 hyporesponse (PRU>200) is not associated with increased periprocedural complications in a contemporary series of patients undergoing anterior circulation PED placement. Titration of antiplatelet medications to P2Y12 >200 remains unindicated and may increase the risk of hemorrhagic complications.
Total mastectomy in a cow with gangrenous mastitis
Authors: Ortega‐Pacheco Antonio , Aguilar‐Caballero Armando J , Jimenez‐Coello Matilde , Tzab Rene , Gutierrez‐Blanco Eduardo
Published: September 2016

A three‐year‐old recently calved, dual‐purpose cow (Brown Swiss/zebu) presenting with signs of inappetence was examined. The udder was hot and painful. The left hide teat appeared black in colour and was cold to the touch with a bloody discharge evident on stripping the teat. The other teats had a normal appearance and a few drops of watery milk were coming. A gangrenous mastitis was diagnosed. The histopathology showed the presence of coagulative necrosis and fibrosis. Given the cow's commercial value and udder condition, a total mastectomy was performed. Induction and maintenance of anaesthesia was provided by a constant rate infusion of ketamine‐xylazine and a regional block was performed. Laboratory cultures were positive for Pseudomonas. Ciprofloxacin was provided for 10 days, and topical treatment with a commercial bee honey product was applied covering all the open wounds. After 45 days, the wound granulated; the cow successfully bred and a healthy calf resulted.
Revision of Icacinaceae from the Early Eocene London Clay flora based on X-ray micro-CT
Authors: Stull Gregory W. , Adams Neil F. , Manchester Steven R. , Sykes Dan , Collinson Margaret E.
Published: September 2016

The Early Eocene (Ypresian) London Clay Formation contains one of the most important fruit and seed assemblages from the Paleogene, including a large diversity of taxa (>350 spp.) preserved as pyrite permineralizations retaining 3D structure as well as anatomical detail. Despite the importance of the flora for understanding angiosperm biogeographic and evolutionary history, the majority of the fossil material has not been revisited since the original taxonomic treatments by E.M. Reid and M.E.J. Chandler. Given subsequent advances in our understanding of angiosperm phylogeny and fruit morphology, coupled with technological advances in imaging/visualizing fossil material, many of the taxa represented in the flora deserve further study. Here we present a revision of the pantropical family Icacinaceae using X-ray micro-computed tomography (micro-CT) images of 21 species from the flora. Based on the results, four new combinations are made, a new fossil-genus is established for a distinctive species with affinities to the Phytocreneae, and emended diagnoses are provided for eight taxa. Of the seven genera recognized from the flora, only one, Iodes Blume, is extant. This study offers important insights on the biogeographic and evolutionary history of Icacinaceae, which is one of the most abundant and diverse components of the flora from the London Clay Formation.
Preconcentration of codeine in pharmaceutical and human urine samples by multi-walled carbon nanotubes and its spectrophotometric determination
Authors: Lotfi Ali , Karimi Sepideh , Hassanzadeh Javad
Published: September 2016

A rapid and efficient solid phase extraction method was established for the preconcentration of codeine prior to its simple determination by spectrophotometry. The extraction process is based on the multi-walled carbon nanotubes (CNTs) containing –COOH functional groups. These CNTs showed a great affinity for the low quantities of codeine in certain condition. Various extraction factors including buffer type, concentration and its pH, ionic buffer, incubation time, and eluent were optimized to achieve high sensitivity. The calibration graph was linear in the codeine concentration range of 0.001–4 mg·L−1, with a detection limit (3s) of 0.4 μg·L−1. The relative standard deviation (RSD %) for the repetitive determination of 0.01, 0.5, and 2 mg·L−1codeine (n = 5) were 1.56%, 2.01%, and 1.63%, respectively. Furthermore, comparison with other reported methods showed that the presented method has suitable characteristics. Finally the method was successfully used to accurately determine codeine in pharmaceutical and human urine samples.
Extreme rainfall impacts on soil CO2efflux in an urban forest ecosystem in Beijing, China
Authors: Chen Wenjing , Jia Xin , Li Chunyi , Yu Haiqun , Xie Jing , Wang Ben , Wu Yajuan , Wang Shan
Published: September 2016

Extreme rainfall events are infrequent disturbances that affect urban environments and soil respiration (Rs). Using data measured in an urban forest ecosystem in Beijing, China, we examined the link between gross primary production (GPP) and soil respiration on a diurnal scale during an extreme rainfall event (i.e., the “21 July 2012 event”), and we examined diel and seasonal environmental controls on Rs. Over the seasonal cycle, Rs increased exponentially with soil temperature (Ts). In addition, Rs was hyperbolically related to soil volumetric water content (VWC), increasing with VWC below a threshold of 0.17 m3m−3, and then decreasing with further increases in VWC. Following the extreme rainfall event (177 mm), Rs showed an abrupt decrease and then maintained a low value of ∼0.3 μmol m−2s−1for about 8 h as soil VWC reached the field capacity (0.34 m3m−3). Rs became decoupled from Ts and increased very slowly, while GPP showed a greater increase. A bivariate Q10-hyperbolical model, which incorporates both Ts and VWC effects, better fits Rs than the Q10model in summer but not for whole year.
Mukherjee–Choudhury–Chowdhury spectral problem and the semi-discrete integrable system
Authors: Xu Xi-Xiang , Sun Ye-Peng
Published: September 2016

Starting from the Mukherjee–Choudhury–Chowdhury spectral problem, we derive a semi-discrete integrable system by a proper time spectral problem. A Bäcklund transformation of Darboux type of this system is established with the help of gauge transformation of the Lax pairs. By means of the obtained Bäcklund transformation, an exact solution is given. Moreover, Hamiltonian form of this system is constructed. Further, through a constraint of potentials and eigenfunctions, the Lax pair and the adjoint Lax pair of the obtained semi-discrete integrable system are nonlinearized as an integrable symplectic map and a completely integrable finite-dimensional Hamiltonian system in the Liouville sense. Finally, the involutive representation of solution of the obtained semi-discrete integrable system is presented.
Cluster algebras based on vertex operator algebras
Authors: Zuevsky Alexander
Published: September 2016

Starting from Zhu recursion formulas for correlation functions for vertex operator algebras with formal parameters associated to local coordinates around marked points on a Riemann surfaces, we introduce a cluster algebra structure over a noncommutative set of variables. Cluster elements and mutation rules are explicitly defined. In particular, we propose an elliptic version of vertex operator cluster algebras arising from correlation functions and Zhu reduction procedure for vertex operators on the torus.