bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid‐based proteomics targeted on pathophysiological processes and pathologies in neurodegenerative diseases
Authors: Brinkmalm Ann , Portelius Erik , Brinkmalm Gunnar , Pannee Josef , Dahlén Rahil , Gobom Johan , Blennow Kaj , Zetterberg Henrik
Published: September 2018

Neurodegenerative dementias constitute a broad group of diseases in which abnormally folded proteins accumulate in specific brain regions and result in tissue reactions that eventually cause neuronal dysfunction and degeneration. Depending on where in the brain this happens, symptoms appear which may be used to classify the disorders on clinical grounds. However, brain changes in neurodegenerative dementias start to accumulate many years prior to symptom onset and there is a poor correlation between the clinical picture and what pathology that is the most likely to cause it. Thus, novel drug candidates having disease‐modifying effects that is targeting the underlying pathology and changes the course of the disease needs to be defined using objective biomarker‐based measures since the clinical symptoms are often non‐specific and overlap between different disorders. Furthermore, the treatment should ideally be initiated as soon as symptoms are evident or when biomarkers confirm an underlying pathology (pre‐clinical phase of the disease) to reduce irreversible damage to, for example, neurons, synapses and axons. Clinical trials in the pre‐clinical phase bring a greater importance to biomarkers since by definition the clinical effects are difficult or slow to discern in a population that is not yet clinically affected. Here, we discuss neuropathological changes that may underlie neurodegenerative dementias, including how they can be detected and quantified using currently available biofluid‐based biomarkers and how more of them could be identified using targeted proteomics approaches.

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This article is part of the special issue "Proteomics".
Serum irisin: A prognostic marker for severe acne vulgaris
Authors: Mustafa Amany I. , El‐Shimi Ola S.
Published: September 2018

Background

Acne vulgaris is a common chronic inflammatory skin disease involving pilosebaceous units. Adipokines are secreted by adipose tissue and function as signaling networks communicating it with different organs. They may have role in pathogenesis of acne vulgaris and the associated insulin resistance. Irisin, a hormone like myokine, is one of adipokines with anti‐inflammatory, anti‐oxidant, and anti‐diabetic effects.

Aims

We aimed at evaluation of serum irisin level in patients with acne vulgaris to assess its correlation with disease pathogenesis.

Patients and Methods

Serum irisin level was measured by an ELISA technique in 60 acne vulgaris patients and 60 apparently healthy controls. Insulin resistance was calculated by Homeostasis Model Assessment of Insulin Resistance index.

Results

Serum irisin level was significantly lower in acne vulgaris patients than control group (P < 0.001). It showed a significant negative correlation with insulin resistance among patients (P 0.012). Moreover, it was decreasing significantly with the increase in disease severity (P 0.004).

Conclusions

Our results revealed that lower serum irisin not only to be a biomarker of disease pathogenesis but also to be a potential prognostic predictor for severity in acne vulgaris.
Seasonal aggravation of acne in summers and the effect of temperature and humidity in a study in a tropical setting
Authors: Narang Isha , Sardana Kabir , Bajpai Ram , Garg Vijay K.
Published: September 2018

Background

Effect of seasonality on acne and acne flare has varied interpretations depending on the geographical area of study. In tropical areas, factors like high temperature and humidity may cause acne flares.

Aims

To assess the seasonal variation of acne in patients and to correlate it with the monthly temperature and humidity over a period of 1 year.

Methods

A cross‐sectional study of acne patients was conducted for one year. The patient's acne was graded. Patients were specifically questioned about aggravation, improvement, or no change in their acne with respect to the seasons. The mean temperature and humidity of each month in Delhi were compared with grade of acne. This variation in acne was correlated with the temperature and humidity. A P‐value < 0.05 was considered as statistically significant.

Results

Out of 171 patients, 82 (47.95%) patients reported seasonal variation in their acne. Among them, 69 patients (40.4%) reported aggravation in summer. Eleven (6.42%) and 2 (1.16%) patients reported aggravation in winter and rainy season, respectively. The aggravation in summer as compared to rainy and winter season was statistically significant. The mean temperature and mean humidity significantly varied with seasonal aggravation of acne.

Conclusions

Both temperature and humidity have a contributing role in pathogenesis of acne and are causes of acne flare. In our study, aggravation of acne was more in summer and rainy season.
Effect of beta‐glucan supplementation on feed intake, digestibility of nutrients and ruminal fermentation in Thai native beef cattle
Authors: Cherdthong Anusorn , Seankamsorn Anuthida , Suriyapha Chaichana , Chanjula Pin , Wanapat Metha
Published: September 2018

This study was conducted to evaluate the effect of ß‐glucan on feed intake, digestibility of nutrients and ruminal fermentation in Thai native beef cattle that were fed low‐quality roughage. Four, Thai native beef cattle with initial body weight (BW) of 100 ± 20.0 kg were randomly assigned according to a 4 × 4 Latin square design to receive four treatment by ß‐glucan at 0, 1.6, 3.1 and 4.7 g/day respectively. Supplementation of ß‐glucan at 0–4.7 g in cattle did not affect the intake of DM, OM, CP, NDF or ADF. However, supplementation with ß‐glucan significantly improved rice straw intake (g/kg BW0.75), compared to the nonsupplemented group (p < 0.05), so rice straw intake was higher than in the group without ß‐glucan supplementation. In addition, total feed intake increased with the higher level of ß‐glucan supplementation. The estimated energy intake was not altered by ß‐glucan supplementation (p > 0.05). The experimental diet had no effect (p > 0.05) on the apparent digestibility of DM, OM, NDF or ADF. However, the digestibility of CP was significantly different among treatment and supplementation at 4.7 g/day ß‐glucan which was the highest level (63.2%) among all diets. ß‐glucan supplementation did not affect rumen pH, temperature or ruminal NH3‐N concentration. In addition, blood urea‐N levels were similar among experimental groups. The population of protozoa at 4 hr post‐feeding increased along with ß‐glucan supplementation and was highest at 4.7 g of ß‐glucan. Based on this experiment, it could be concluded that supplementation of ß‐glucan at 4.7 g improved rice straw intake, as well as total intake and digestibility of CP in Thai native beef cattle.
Effects of continuous positive airway pressure on neurocognitive and neuropsychiatric function in obstructive sleep apnea
Authors: Dostálová Veronika , Kolečkárová Sandra , Kuška Martin , Pretl Martin , Bezdicek Ondrej
Published: September 2018

The aim of this study was to determine the neurocognitive and neuropsychiatric effects of continuous positive airway pressure treatment on patients with obstructive sleep apnea. This cross‐sectional, prospective, observational study included 126 patients with sleep apnea. The following tests were performed: the Montreal Cognitive Assessment for the evaluation of cognitive impairment, the Beck Depression Inventory, and the State‐Trait Anxiety Inventory, together with the Epworth Sleepiness Scale for the evaluation of neuropsychiatric symptoms and a person's general level of daytime sleepiness. The first measurement did not show neurocognitive impairment or a higher level of depressive and anxiety symptoms in 126 patients with obstructive sleep apnea in comparison to normative standards. After the 3‐month treatment indicated for 43 patients with obstructive sleep apnea, we did not find any significant improvement in cognitive performance (p = .213). However, patients with sleep apnea with continuous positive airway pressure treatment did show significantly less daytime sleepiness, anxiety and depressive symptoms (all p < .001). In conclusion, short‐term (3 months) treatment of patients with obstructive sleep apnea can substantially alleviate their daytime sleepiness, as well as depressive and anxiety symptoms.
What Is a Social Group in the Eyes of the Law? Knowledge Work in Refugee-Status Determination
Authors: Owens B. Robert
Published: September 2018

This article explores the settling and unsettling of legal concepts in relation to refugee-status determination. To gain admission to the United States, asylum seekers are required to demonstrate a well-founded fear of persecution on the basis of one of five protected grounds: race, religion, nationality, political opinion, or membership in a particular social group. Accordingly, many political asylum claims turn on the interpretation of “particular social group.” This article examines case law disputes in the federal courts of appeals over the meaning of that phrase and describes how statutory interpretation by judges has contributed to the persistence of such disputes over several decades since the passage of the 1980 Refugee Act. My analysis reveals the tensions between different forms of rationality at play in judicial statutory interpretation and applies the concept of legal settling to a new empirical domain.
Renal genetics in Australia: Kidney medicine in the genomic age
Authors: Jayasinghe Kushani , Quinlan Catherine , Stark Zornitza , Patel Chirag , Mallawaarachchi Amali , Wardrop Louise , Kerr Peter G , Trnka Peter , Mallett Andrew J ,   on behalf of the KidGen Collaborative
Published: September 2018

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end‐stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next‐generation sequencing have enabled rapid and cost‐effective sequencing of large amounts of DNA. Next‐generation sequencing‐based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early‐onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at‐risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health‐care systems.
One more left‐wing heave?
Authors: Curtice John
Published: September 2018

The Labour party cannot ignore its newly acquired liberal voters if it is to win the next election
Swedish men and smoking: Views on screening‐detected abdominal aortic aneurysm
Authors: Holmström Inger K. , Bohlin Sofia , Wanhainen Anders , Björck Martin , Fröjd Camilla
Published: September 2018

Abdominal aortic aneurysms (AAA), most common among elderly male smokers, often show no symptoms before rupture. To facilitate better care and counselling targeted to smoking cessation for these patients, more knowledge is required about their views. Therefore, the aim of the present study was to describe the views on AAA and smoking among male smokers with screening‐detected AAA. A qualitative approach with individual interviews with 16 men with screening‐detected AAA was applied. Three had quit smoking by the time of the interviews. Thematic analysis was performed, and four themes emerged: (i) accepting the course of life; (ii) the elusive AAA: a disturbing experiencing or merely a minor inconvenience?; (iii) being in safe hands; and (iv) smoking as an unexpected topic of discussion. Most of the participants felt they were in “safe hands”, although thoughts about death were also evoked. However, the information about smoking cessation was unexpected, and the relationship between AAA and smoking unclear. Presenting the connection between AAA and smoking in a clear manner and motivating smoking cessation in an individually‐targeted way are important.
Adapt your shuttling proteins for virulence: a lesson from the corn smut fungus Ustilago maydis
Authors: Redkar Amey , Di Pietro Antonio
Published: September 2018

This article is a Commentary on Krombach et al., 220: 553–566.
Social Structures and the Ontology of Social Groups
Authors: Ritchie Katherine
Published: September 2018

Social groups—like teams, committees, gender groups, and racial groups—play a central role in our lives and in philosophical inquiry. Here I develop and motivate a structuralist ontology of social groups centered on social structures (i.e., networks of relations that are constitutively dependent on social factors). The view delivers a picture that encompasses a diverse range of social groups, while maintaining important metaphysical and normative distinctions between groups of different kinds. It also meets the constraint that not every arbitrary collection of people is a social group. In addition, the framework provides resources for developing a broader structuralist view in social ontology.
Antibody responses to Schistosoma mansoni schistosomula antigens
Authors: Egesa Moses , Lubyayi Lawrence , Jones Frances M. , van Diepen Angela , Chalmers Iain W. , Tukahebwa Edridah M. , Bagaya Bernard S. , Hokke Cornelis H. , Hoffmann Karl F. , Dunne David W. , Elliott Alison M. , Yazdanbakhsh Maria , Wilson Shona , Cose Stephen
Published: September 2018

While antigens from Schistosoma schistosomula have been suggested as potential vaccine candidates, the association between antibody responses with schistosomula antigens and infection intensity at reinfection is not well known. Schistosoma mansoni‐infected individuals were recruited from a schistosomiasis endemic area in Uganda (n = 372), treated with 40 mg/kg praziquantel (PZQ) and followed up at five weeks and at one year post‐treatment. Pre‐treatment and five weeks post‐treatment immunoglobulin (Ig) E, IgG1 and IgG4 levels against recombinant schistosomula antigens rSmKK7, rSmLy6A, rSmLy6B and rSmTSP7 were measured using ELISA. Factors associated with detectable pre‐treatment or post‐treatment antibody response against the schistosomula antigens and the association between five‐week antibody responses and one year post‐treatment reinfection intensity among antibody responders were examined. Being male was associated with higher pre‐treatment IgG1 to rSmKK7, rSmLy6a and AWA. Five weeks post‐treatment antibody responses against schistosomula antigens were not associated with one year post‐treatment reinfection intensity among antibody responders’ antibody levels against rSmKK7, rSmLy6B and rSmTSP7 dropped, but increased against rSmLy6A, AWA and SEA at five weeks post‐treatment among antibody responders. S. mansoni‐infected individuals exhibit detectable antibody responses to schistosomula antigens that are affected by treatment. These findings indicate that schistosomula antigens induce highly varied antibody responses and could have implications for vaccine development.
Roles of plasma membrane proton ATPases AHA2 and AHA7 in normal growth of roots and root hairs in Arabidopsis thaliana
Authors: Hoffmann Robert D. , Olsen Lene I. , Ezike Chukwuebuka V. , Pedersen Jesper T. , Manstretta Raffaele , López-Marqués Rosa L. , Palmgren Michael
Published: September 2018

Plasma membrane H+‐ATPase pumps build up the electrochemical H+ gradients that energize most other transport processes into and out of plant cells through channel proteins and secondary active carriers. In Arabidopsis thaliana, the AUTOINHIBITED PLASMA MEMBRANE H+‐ATPases AHA1, AHA2 and AHA7 are predominant in root epidermal cells. In contrast to other H+‐ATPases, we find that AHA7 is autoinhibited by a sequence present in the extracellular loop between transmembrane segments 7 and 8. Autoinhibition of pump activity was regulated by extracellular pH, suggesting negative feedback regulation of AHA7 during establishment of an H+ gradient. Due to genetic redundancy, it has proven difficult to test the role of AHA2 and AHA7, and mutant phenotypes have previously only been observed under nutrient stress conditions. Here, we investigated root and root hair growth under normal conditions in single and double mutants of AHA2 and AHA7. We find that AHA2 drives root cell expansion during growth but that, unexpectedly, restriction of root hair elongation is dependent on AHA2 and AHA7, with each having different roles in this process.
Understanding social protection systems in Latin America and the Caribbean: Typologies and efforts of classification
Authors: Steffen Mariana Willmersdorf , Côrtes Soraya Vargas
Published: September 2018

The aim of this article is to present the current debate on Latin American social protection systems. Several studies have addressed this issue from different perspectives, discussing the existence or not of a welfare state in Latin America. In this paper, we focus on authors that have proposed a comparative approach to the analysis of these systems, building either typologies or indexes used to classify the existing social protection systems into groups, according to different criteria. By analyzing these criteria, we seek to understand the main trends and specificities of social protection systems in the region, suggesting which typologies would be the best to fit the subject of future researches. We argue that the studies better prepared to this proposal are those considering the peculiarities of the region, specifically the weight of informal welfare providers and its institutional weaknesses.
Obtaining social justice for victims of domestic minor sex trafficking
Authors: Micetic Sue Frantz
Published: September 2018

In 2000, the U.S. Congress passed the Victims of Trafficking and Violence Protection Act (TVPA) which focused on social justice for victims of human trafficking in foreign countries. The TVPA was soon revised to include domestic minor sex trafficking (DMST) victims. Two major problems continue to complicate the lives of DMST victims: (1) the transitioning social construction of this population and (2) conflicting federal, state, and local laws that yield inconsistent policies for these youth. The numerous institutions involved with these minors which hold different values and perspectives further complicate the issue. This article examines the effect of transitioning social constructions on this population and the problems, policies, and politics that result in social injustice toward the youth who fall victim to this crime.
The contribution of the individual blood elements to the variability of thromboelastographic measures
Authors: Noorman Femke , Hess John R.
Published: September 2018

BACKGROUND

Thromboelastography (TEG) is widely advocated as a rapid method for obtaining critical blood coagulation data to guide resuscitation, but the method suffers well‐known limits in sensitivity, repeatability, and interpretability.

STUDY DESIGN AND METHODS

Mixtures of fresh human blood components were prepared that represent the range of blood element concentrations seen in health and disease and after injury. These mixtures were tested in a TEG device after kaolin, tissue factor and phospholipid, or tissue factor and phospholipid with abciximab activation. The results were measured as reproducibility and nonlinear effects in regression analysis and evaluated for interpretability.

RESULTS

Clot strength was associated with increased platelet (PLT) content and plasma fibrinogen concentration and content. Increasing hematocrit (Hct) reduced while increasing PLT or plasma concentration increased TEG clot strength. The abciximab dose used to block PLT activity did not fully inhibit the PLT contribution to clot strength. Clot strength is logarithmically correlated in the absence and linearly correlated to PLT concentration in the presence of abciximab. TEG clot strength with or without abciximab is dependent on Hct, PLT, and plasma (fibrinogen) concentrations in complex patterns.

CONCLUSION

Interpretation of TEG variables is limited without knowledge of the concentration of the blood components present. When “normal” TEG values are known for a certain PLT‐plasma‐red blood cell concentration, the assay can be used to assess PLT and plasma function in coagulation. The TEG “functional fibrinogen” assay should be used only as a gross estimate of the fibrinogen concentration in whole blood.
Knowledge and practices regarding Middle East Respiratory Syndrome Coronavirus among camel handlers in a Slaughterhouse, Kenya, 2015
Authors: Kamau Esther , Ongus Juliette , Gitau George , Galgalo Tura , Lowther Sara A. , Bitek Austine , Munyua Peninah
Published: September 2018

Dromedary camels are implicated as reservoirs for the zoonotic transmission of Middle East Respiratory Syndrome coronavirus (MERS‐CoV) with the respiratory route thought to be the main mode of transmission. Knowledge and practices regarding MERS among herders, traders and slaughterhouse workers were assessed at Athi‐River slaughterhouse, Kenya. Questionnaires were administered, and a check list was used to collect information on hygiene practices among slaughterhouse workers. Of 22 persons, all washed hands after handling camels, 82% wore gumboots, and 65% wore overalls/dustcoats. None of the workers wore gloves or facemasks during slaughter processes. Fourteen percent reported drinking raw camel milk; 90% were aware of zoonotic diseases with most reporting common ways of transmission as: eating improperly cooked meat (90%), drinking raw milk (68%) and slaughter processes (50%). Sixteen (73%) were unaware of MERS‐CoV. Use of personal protective clothing to prevent direct contact with discharges and aerosols was lacking. Although few people working with camels were interviewed, those met at this centralized slaughterhouse lacked knowledge about MERS‐CoV but were aware of zoonotic diseases and their transmission. These findings highlight need to disseminate information about MERS‐CoV and enhance hygiene and biosafety practices among camel slaughterhouse workers to reduce opportunities for potential virus transmission.
UBC‐Nepal expedition: peripheral fatigue recovers faster in Sherpa than lowlanders at high altitude
Authors: Ruggiero Luca , Hoiland Ryan L. , Hansen Alexander B. , Ainslie Philip N. , McNeil Chris J.
Published: September 2018

Key points

The reduced oxygen tension of high altitude compromises performance in lowlanders. In this environment, Sherpa display superior performance, but little is known on this issue.

Sherpa present unique genotypic and phenotypic characteristics at the muscular level, which may enhance resistance to peripheral fatigue at high altitude compared to lowlanders.

We studied the impact of gradual ascent and exposure to high altitude (5050 m) on peripheral fatigue in age‐matched lowlanders and Sherpa, using intermittent electrically‐evoked contractions of the knee extensors.

Peripheral fatigue (force loss) was lower in Sherpa during the first part of the protocol. Post‐protocol, the rate of force development and contractile impulse recovered faster in Sherpa than in lowlanders. At any time, indices of muscle oxygenation were not different between groups.

Muscle contractile properties in Sherpa, independent of muscle oxygenation, were less perturbed by non‐volitional fatigue. Hence, elements within the contractile machinery contribute to the superior physical performance of Sherpa at high altitude.

Altitude‐related acclimatisation is characterised by marked muscular adaptations. Lowlanders and Sherpa differ in their muscular genotypic and phenotypic characteristics, which may influence peripheral fatigability at altitude. After gradual ascent to 5050 m, 12 lowlanders and 10 age‐matched Sherpa (32 ± 10 vs. 31 ± 11 years, respectively) underwent three bouts (separated by 15 s rest) of 75 intermittent electrically‐evoked contractions (12 pulses at 15 Hz, 1.6 s between train onsets) of the dominant leg quadriceps, at the intensity which initially evoked 30% of maximal voluntary force. Trains were also delivered at minutes 1, 2 and 3 after the protocol to measure recovery. Tissue oxygenation index (TOI) and total haemoglobin (tHb) were quantified by a near‐infrared spectroscopy probe secured over rectus femoris. Superficial femoral artery blood flow was recorded using ultrasonography, and delivery of oxygen was estimated (eDO2). At the end of bout 1, peak force was greater in Sherpa than in lowlanders (91.5% vs. 84.5% baseline, respectively; P < 0.05). Peak rate of force development (pRFD), the first 200 ms of the contractile impulse (CI200), and half‐relaxation time (HRT) recovered faster in Sherpa than in lowlanders (percentage of baseline at 1 min: pRFD: 89% vs. 74%; CI200: 91% vs. 80%; HRT: 113% vs. 123%, respectively; P < 0.05). Vascular measures were pooled for lowlanders and Sherpa as they did not differ during fatigue or recovery (P < 0.05). Mid bout 3, TOI was decreased (90% baseline) whereas tHb was increased (109% baseline). After bout 3, eDO2 was markedly increased (1266% baseline). The skeletal muscle of Sherpa seemingly favours repeated force production at altitude for similar oxygen delivery compared to lowlanders.
Microbiological Analysis from a Phase 2 Randomized Study in Adults Evaluating Single Oral Doses of Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria gonorrhoeae
Authors: Scangarella-Oman Nicole E. , Hossain Mohammad , Dixon Paula B. , Ingraham Karen , Min Sharon , Tiffany Courtney A. , Perry Caroline R. , Raychaudhuri Aparna , Dumont Etienne F. , Huang Jianzhong , Hook Edward W. , Miller Linda A.
Published: September 2018

We evaluated microbiological correlates for the successful treatment of
Neisseria gonorrhoeae
isolates from a phase 2 study of gepotidacin, a novel triazaacenaphthylene antibacterial, for therapy of uncomplicated urogenital gonorrhea. Culture, susceptibility testing, genotypic characterization, and frequency of resistance (FoR) were performed for selected isolates.
Rifampin Resistance in Staphylococci after Rifaximin Intake for Surgical Prophylaxis in Elective Colorectal Surgery
Authors: Padilla Emma , Oms Lluis , Espejo Elena , Gómez Laura , Pagespetit Lurdes , Boada Núria , Bella Feliu , Pérez Josefa
Published: September 2018

The aim of our study was to determine whether rifampin resistance emerges in human skin staphylococci after oral intake of rifaximin for surgical prophylaxis. Rifampin-resistant staphylococci appeared on the skin of 32 out of 74 patients (43.2%) two weeks after prophylactic treatment with rifaximin.
In Vivo
Efficacy of Ellagic Acid against Candida albicans in a Drosophila melanogaster Infection Model
Authors: Sampaio Aline da Graça , Gontijo Aline Vidal Lacerda , Araujo Helena Marcolla , Koga-Ito Cristiane Yumi
Published: September 2018

The aim of this study was to evaluate the antifungal activity and the toxicity of ellagic acid (EA) using a
Drosophila melanogaster
model.
Candida albicans
bacteria were inoculated into Toll heterozygous flies.
A Cotransformation Method To Identify a Restriction-Modification Enzyme That Reduces Conjugation Efficiency in Campylobacter jejuni
Authors: Zeng Ximin , Wu Zuowei , Zhang Qijing , Lin Jun
Published: September 2018

Conjugation is an important horizontal gene transfer mechanism contributing to the evolution of bacterial pathogenesis and antimicrobial resistance.
Campylobacter jejuni
, the leading foodborne bacterial organism, displays significant strain diversity due to horizontal gene transfer; however, the molecular components influencing conjugation efficiency in
C. jejuni
are still largely unknown. In this study, we developed a cotransformation strategy for comparative genomics analysis and successfully identified a restriction-modification enzyme that significantly influences conjugation efficiency in
C. jejuni
. The new cotransformation strategy developed in this study is also expected to be broadly applied in other naturally competent bacteria for functional comparative genomics research.
T5 Exonuclease Hydrolysis of Hepatitis B Virus Replicative Intermediates Allows Reliable Quantification and Fast Drug Efficacy Testing of Covalently Closed Circular DNA by PCR
Authors: Qu Bingqian , Ni Yi , Lempp Florian A. , Vondran Florian W. R. , Urban Stephan
Published: September 2018

cccDNA elimination is a major goal in future curative regimens for chronic HBV patients. However, PCR-based assays for cccDNA quantification show a principally constrained specificity when high levels of input virus or replicative intermediates are present. Here, we characterized T5 exonuclease as a suitable enzyme for medium-throughput
in vitro
assays that preserves cccDNA but efficiently removes rcDNA prior to PCR-based quantification. We compared T5 exonuclease with the previously described exonuclease III and showed that both nucleases are suitable for reliable quantification of cccDNA by PCR. We substantiated the applicability of our method through examination of early cccDNA formation and stable accumulation in several
in vitro
infection models and analyzed cccDNA stability after administration of anti-HBV drugs. Our results support the use of T5 exonuclease for fast and convenient rcDNA removal, especially for early cccDNA quantification and rapid drug testing in
in vitro
studies.
NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN) Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3
Authors: Wuerth Jennifer Deborah , Habjan Matthias , Wulle Julia , Superti-Furga Giulio , Pichlmair Andreas , Weber Friedemann
Published: September 2018

Phleboviruses are receiving increased attention due to the constant discovery of new species and the ongoing spread of long-known members of the genus. Outbreaks of sandfly fever were reported in the 19th century, during World War I, and during World War II. Currently, SFSV is recognized as one of the most widespread phleboviruses, exhibiting high seroprevalence rates in humans and domestic animals and causing a self-limiting but incapacitating disease predominantly in immunologically naive troops and travelers. We show how the nonstructural NSs protein of SFSV counteracts the upregulation of the antiviral interferon (IFN) system. SFSV NSs specifically inhibits promoter binding by IFN transcription factor 3 (IRF3), a molecular strategy which is unique among phleboviruses and, to our knowledge, among human pathogenic RNA viruses in general. This IRF3-specific and stoichiometric mechanism, greatly distinct from the ones exhibited by the highly virulent phleboviruses, correlates with the intermediate level of pathogenicity of SFSV.
The team that plays together stays together: the effect of departmental Christmas party attendance on team cohesion within a healthcare setting
Authors: Cromb Daniel , Thomas Helen , Garcia-Nicoletti Martin , Cheung Ronny
Published: September 2018

Objectives

To understand the effect of attendance at departmental Christmas parties on cohesion and teamwork within the healthcare setting.

Method (design/setting/participants/interventions/outcome measures)

We used the ‘Team Development Measure’ questionnaire to assess team cohesiveness among healthcare professionals before and after departmental Christmas parties took place. A pooled mean score (PMS) of responses was used to compare between groups.

Results

There were no significant differences in perceived measures of team cohesion when comparing responses before (PMSbefore=1.86±0.20) and after (PMSafter=1.91±0.22) the departmental Christmas party (p=0.37), nor was there a significant difference when comparing responses from attendees (PMSbefore=1.83±0.23, PMSafter=1.89±0.24, p=0.52) or non-attendees (PMSbefore=1.84±1.47, PMSafter=1.83±0.15, p=0.91). No difference was observed between professional groups (PMSdoctors=1.85±0.23, PMSnurses=1.95±0.18, p=0.064).

Conclusion

Attendance at departmental Christmas parties does not seem to result in improved team cohesion.
Risk factors for patellofemoral pain: a systematic review and meta-analysis
Authors: Neal Bradley S , Lack Simon D , Lankhorst Nienke E , Raye Andrew , Morrissey Dylan , van Middelkoop Marienke
Published: September 2018

Background

Patellofemoral pain (PFP) is a prevalent condition commencing at various points throughout life. We aimed to provide an evidence synthesis concerning predictive variables for PFP, to aid development of preventative interventions.

Methods

We searched Medline, Web of Science and SCOPUS until February 2017 for prospective studies investigating at least one potential risk factor for future PFP. Two independent reviewers appraised methodological quality using the Newcastle–Ottawa Scale. We conducted meta-analysis where appropriate, with standardised mean differences (SMD) and risk ratios calculated for continuous and nominal scaled data.

Results

This review included 18 studies involving 4818 participants, of whom 483 developed PFP (heterogeneous incidence 10%). Three distinct subgroups (military recruits, adolescents and recreational runners) were identified. Strong to moderate evidence indicated that age, height, weight, body mass index (BMI), body fat and Q angle were not risk factors for future PFP. Moderate evidence indicated that quadriceps weakness was a risk factor for future PFP in the military, especially when normalised by BMI (SMD −0.69, CI −1.02, –0.35). Moderate evidence indicated that hip weakness was not a risk factor for future PFP (multiple pooled SMDs, range −0.09 to −0.20), but in adolescents, moderate evidence indicated that increased hip abduction strength was a risk factor for future PFP (SMD 0.71, CI 0.39, 1.04).

Conclusions

This review identified multiple variables that did not predict future PFP, but quadriceps weakness in military recruits and higher hip strength in adolescents were risk factors for PFP. Identifying modifiable risk factors is an urgent priority to improve prevention and treatment outcomes.
Percutaneous coronary intervention for stable coronary artery disease
Authors: Al-Lamee Rasha K , Nowbar Alexandra N , Francis Darrel P
Published: September 2018

The adverse consequences of stable coronary artery disease (CAD) are death, myocardial infarction (MI) and angina. Trials in stable CAD show that percutaneous coronary intervention (PCI) does not reduce mortality. PCI does appear to reduce spontaneous MI rates but at the expense of causing some periprocedural MI. Therefore, the main purpose of PCI is to relieve angina. Indeed, patients and physicians often choose PCI rather than first attempting to control symptoms with anti-anginal medications as recommended by guidelines. Nevertheless, it is unclear how effective PCI is at relieving angina. This is because, whereas anti-anginal medications are universally required to be tested against placebo, there is no such requirement for procedural interventions such as PCI. The first placebo-controlled trial of PCI showed a surprisingly small effect size. This may be because it is overly simplistic to assume that the presence of a stenosis and inducible ischaemia in a patient means that the clinical chest pain they report is caused by ischaemia. In this article, we review the evidence base and argue that if we as a medical specialty wish to lead the science of procedures for symptom control, we should recognise the special merit of placebo-controlled experiments.
Using perinatal morbidity scoring tools as a primary study outcome
Authors: Hutcheon Jennifer A , Bodnar Lisa M , Platt Robert W
Published: September 2018

Perinatal morbidity scores are tools that score or weight different adverse events according to their relative severity. Perinatal morbidity scores are appealing for maternal–infant health researchers because they provide a way to capture a broad range of adverse events to mother and newborn while recognising that some events are considered more serious than others. However, they have proved difficult to implement as a primary outcome in applied research studies because of challenges in testing if the scores are significantly different between two or more study groups. We outline these challenges and describe a solution, based on Poisson regression, that allows differences in perinatal morbidity scores to be formally evaluated. The approach is illustrated using an existing maternal-neonatal scoring tool, the Adverse Outcome Index, to evaluate the safety of labour and delivery before and after the closure of obstetrical services in small rural communities. Applying the proposed Poisson regression to the case study showed a protective risk ratio for adverse outcome following closures as compared with the original analysis, where no difference was found. This approach opens the door for considerably broader use of perinatal morbidity scoring tools as a primary outcome in applied population and clinical maternal-infant health research studies.
How well can poor child health and development be predicted by data collected in early childhood?
Authors: Straatmann Viviane S , Pearce Anna , Hope Steven , Barr Benjamin , Whitehead Margaret , Law Catherine , Taylor-Robinson David
Published: September 2018

Background

Identifying children at risk of poor developmental outcomes remains a challenge, but is important for better targeting children who may benefit from additional support. We explored whether data routinely collected in early life predict which children will have language disability, overweight/obesity or behavioural problems in later childhood.

Methods

We used data on 10 262 children from the UK Millennium Cohort Study (MCS) collected at 9 months, 3, and 11 years old. Outcomes assessed at age 11 years were language disability, overweight/obesity and socioemotional behavioural problems. We compared the discriminatory capacity of three models: (1) using data currently routinely collected around the time of birth; (2) Model 1 with additional data routinely collected at 3 years; (3) a statistically selected model developed using a larger set of early year’s risk factors for later child health outcomes, available in the MCS—but not all routinely collected.

Results

At age 11, 6.7% of children had language disability, 26.9% overweight/obesity and 8.2% socioemotional behavioural problems. Model discrimination for language disability was moderate in all three models (area under the curve receiver-operator characteristic 0.71, 0.74 and 0.76, respectively). For overweight/obesity, it was poor in model 1 (0.66) and moderate for model 2 (0.73) and model 3 (0.73). Socioemotional behavioural problems were also identified with moderate discrimination in all models (0.71; 0.77; 0.79, respectively).

Conclusion

Language disability, socioemotional behavioural problems and overweight/obesity in UK children aged 11 years are common and can be predicted with moderate discrimination using data routinely collected in the first 3 years of life.
Clinical features and prognosis of amyotrophic lateral sclerosis in Africa: the TROPALS study
Authors: Luna Jaime , Diagana Mouhamadou , Ait Aissa Leila , Tazir Meriem , Ali Pacha Lamia , Kacem Imen , Gouider Riadh , Henning Franclo , Basse Anna , Cisse Ousmane , Balogou Agnon Ayélola Koffi , Kombate Damelan , Agbetou Mendinatou , Houinato Dismand , Millogo Athanase , Agba Thierry , Belo Mouftao , Penoty Marie , Raymondeau-Moustafa Marie , Hamidou Bello , Couratier Philippe , Preux Pierre Marie , Marin Benoit
Published: September 2018

Objective

We describe and compare the sociodemographic and clinical features, treatments, and prognoses and survival times of patients with amyotrophic lateral sclerosis (ALS) in Africa.

Methodology

We conducted a multicentre, hospital-based cohort study in Africa. Patients with ALS diagnosed in the neurology departments of participating hospitals from 2005 to 2017 were included. Subgroup analysis was performed by subcontinent. Survival analyses were conducted using the Cox proportional hazards model.

Results

Nine centres from eight African countries participated. A total of 185 patients with ALS were included: 114 from Northern Africa, 41 from Western Africa and 30 from Southern Africa. A male predominance (male to female ratio 2.9) was evident. The median age at onset was 53.0 years (IQR 44.5–64.0 years). The onset was bulbar in 22.7%. Only 47 patients (26.3%) received riluzole, mainly in Northern and Western Africa. The median survival from the time of diagnosis was 14.0 months (95% CI 10.7 to 17.2 months). The median survival was longer in Northern Africa (19.0 months, 95% CI 10.8 to 27.2 months) than in Western (4.0 months, 95% CI 0.8 to 7.1 months) and Southern (11.0 months, 95% CI 5.6 to 16.4 months) Africa (Breslow test, p<0.0001). Both subcontinental location and riluzole treatment independently affected survival.

Conclusion

More African patients with ALS were male and younger and exhibited a lower proportion of bulbar onset compared with patients with ALS from Western nations. Survival was consistent with that in Western registers but far shorter than what would be expected for young patients with ALS. The research improves our understanding of the disease in Africa.
Unravelling of the paroxysmal dyskinesias
Authors: Erro Roberto , Bhatia Kailash P
Published: September 2018

Paroxysmal dyskinesias (PxD) refer to a rare group of clinically and genetically heterogeneous disorders presenting with recurrent attacks of abnormal movements, typically dystonia, chorea or a combination thereof, without loss of consciousness. Classically, PxD have been categorised according to their triggers and duration of the attacks, but increasing evidence suggests that there is a certain degree of clinical and genetic overlap and challenges the concept that one phenotype is attributable to one single aetiology. Here we review the increasing spectrum of genetic conditions, as well as of other non-genetic disorders, that might present with PxD, provide criteria for case definition and propose a diagnostic workup to reach a definitive diagnosis, on which treatment is heavily dependent.
Disseminated nocardiosis with cerebral and subcutaneous lesions on low-dose prednisone
Authors: Mahajan Kedar R
Published: September 2018

This case report is of a septuagenarian man on chronic low-dose prednisone who presented with disseminated nocardiosis (Nocardia cyriacigeorgica) that was initially mistaken for metastatic brain cancer. Neurologists should be aware of the potential for opportunistic infections with steroid use and to consider a definite tissue diagnosis with culture and histopathology prior to treatment.
Prevalence and correlates of and a risk score to identify asymptomatic anorectal gonorrhoea and chlamydia infection among men who have sex with men in Kisumu, Kenya
Authors: Quilter Laura A S , Obondi Eve , Kunzweiler Colin , Okall Duncan , Bailey Robert C , Djomand Gaston , Otieno-Nyunya Boaz , Otieno Fredrick , Graham Susan M
Published: September 2018

Objectives

In settings where laboratory capacity is limited, the WHO recommends presumptive treatment forNeisseria gonorrhoeae(NG) andChlamydia trachomatis(CT) in asymptomatic men who have sex with men (MSM) at high risk for these infections. However, little is known about how best to target this intervention. We aimed to identify correlates of anorectal NG/CT infection in Kenyan MSM with and without anorectal symptoms and evaluate the performance of an empirical, model-based risk score to identify cases in asymptomatic men.

Methods

Anorectal NG/CT infections were diagnosed by the Abbott RealTime NG/CT nucleic acid amplification testamong 698 MSM at enrolment into the Anza Mapema study. Multivariable logistic regression was used to identify correlates of anorectal NG/CT infection in men with and without anorectal symptoms. Using coefficients from the final multivariable model for asymptomatic men, we calculated a risk score for each participant. Risk score performance was determined by calculating the sensitivity, specificity and number needed to treat (NNT) to identify one NG/CT infection.

Results

Overall anorectal NG/CT infection prevalence was 5.2% (n=36), of which 58.3% (n=21) were asymptomatic. Factors associated with anorectal NG/CT infection in asymptomatic men were aged 18–24 years (aOR=7.6; 95% CI: 1.7 to 33.2), HIV positive serostatus (aOR=6.9; 95% CI: 2.2 to 21.6) and unprotected anal sex in the past 3 months (aOR=3.8; 95% CI: 1.2 to 11.9). Sensitivity and specificity were optimal (81.0% and 66.1%, respectively) at a model-derived risk score cut-point ≥3, and the NNT was 12.

Conclusions

A model-derived risk score based on correlates of anorectal NG/CT infection in asymptomatic participants would be sensitive and efficient (i.e, low NNT) for targeting presumptive treatment. If validated in other settings, this risk score could improve on the WHO algorithm and help reduce the burden of asymptomatic anorectal NG/CT infections among MSM in settings where diagnostic testing is not available.
Fungi decaying the wood of fallen beech (Nothofagus) trees in the South Island of New Zealand
Authors: Hood Ian A. , McDougal Rebecca L. , Somchit Chanatda , Kimberley Mark O. , Lewis Aymee S.R. , Hood Joy O.L.
Published: September 2018

To extend present knowledge of communities of wood decay fungi in native forests, basidiomycetes and ascomycetes were isolated from within 15 fallen stems in beech (Nothofagus, Nothofagaceae) forests in the South Island of New Zealand. Fungal species were identified as precisely as possible using traditional culturing and molecular approaches. The internal distribution of species within stems was determined. Common fungi that occupied significant portions of stems were Ganoderma applanatum sensu Wakefield, Australoporus tasmanicus, Inonotus nothofagi, Pleurotus purpureo-olivaceus, and an unidentified hymenochaetaceous species. Richness and diversity of basidiomycete species were greater in stems of red beech (Nothofagus fusca (Hook. f.) Oerst.) and silver beech (Nothofagus menziesii (Hook. f.) Oerst.) than in those of matai (Prumnopitys taxifolia (Banks & Sol. ex D. Don) de Laub.; Podocarpaceae) and tawa (Beilschmiedia tawa (A. Cunn.) Kirk; Lauraceae), as determined from earlier studies in podocarp hardwood and beech indigenous forests. There was greater similarity in the species composition of basidiomycete fungi colonising the three beech species compared with those colonising rimu (Dacrydium cupressinum Sol. ex Lamb.; Podocarpaceae), tawa, and matai. Based on observations in this study and on international research on the effects of selective logging on basidiomycete biodiversity, the decision to restrict to 50% the extraction of wood following storm damage in beech forests on the West Coast of the South Island appears to have been appropriate.