bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to Comment on “Worldwide evidence of a unimodal relationship between productivity and plant species richness”
Authors: Pither Jason , Fraser Lauchlan H. , Jentsch Anke , Sternberg Marcelo , Zobel Martin , Cahill James , Beierkuhnlein Carl , Bartha Sándor , Bennett Jonathan A. , Boldgiv Bazartseren , Brown Leslie R. , Cabido Marcelo , Campetella Giandiego , Carlyle Cameron N. , Chelli Stefano , Csergő Anna Mária , Diaz Sandra , Enrico Lucas , Ensing David , Fidelis Alessandra , Garris Heath W. , Henry Hugh A. L. , Höhn Maria , Klironomos John , Koorem Kadri , Lawrence-Lodge Rachael , Manning Peter , Mitchell Randall J. , Moora Mari , Pillar Valério D. , Stotz Gisela C. , Sugiyama Shu-ichi , Szentes Szilárd , Tungalag Radnaakhand , Undrakhbold Sainbileg , Wellstein Camilla , Zupo Talita
Published: January 2016

Tredennick
et al
. criticize one of our statistical analyses and emphasize the low explanatory power of models relating productivity to diversity. These criticisms do not detract from our key findings, including evidence consistent with the unimodal constraint relationship predicted by the humped-back model and evidence of scale sensitivities in the form and strength of the relationship.
Decolonization in Prevention of Health Care-Associated Infections
Authors: Septimus Edward J. , Schweizer Marin L.
Published: January 2016

Colonization with health care-associated pathogens such as
Staphylococcus aureus
, enterococci, Gram-negative organisms, and
Clostridium difficile
is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on
S. aureus
decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for
S. aureus
nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin-containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as
Candida
. Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram-negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections.
Progress toward a Respiratory Syncytial Virus Vaccine
Authors: Neuzil Kathleen M.
Published: January 2016

In accompanying papers (P. L. Acosta, M. T. Caballero, and F. P. Polack, Clin Vaccine Immunol 23:189–195, 2016,
http://dx.doi.org/10.1128/CVI.00609-15
; M. Vissers, I. M. L. Ahout, M. I. de Jonge, and G. Ferwerda, Clin Vaccine Immunol 23:243–245, 2016,
http://dx.doi.org/10.1128/CVI.00590-15
) in this issue of
Clinical and Vaccine Immunology
, the history of and immune mechanisms underlying vaccine-enhanced respiratory syncytial virus (RSV) disease and of investigations of mucosal antibodies and their association with viral load in RSV-infected children, respectively, are described. This commentary discusses RSV vaccine candidates, target populations, and the challenges associated with achieving a safe and effective vaccine.
Direct Identification of Urinary Tract Pathogens from Urine Samples, Combining Urine Screening Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Íñigo Melania , Coello Andreu , Fernández-Rivas Gema , Rivaya Belén , Hidalgo Jessica , Quesada María Dolores , Ausina Vicente
Published: January 2016

Early diagnosis of urinary tract infections (UTIs) is essential to avoid inadequate or unnecessary empirical antibiotic therapy. Microbiological confirmation takes 24 to 48 h. The use of screening methods, such as cytometry and automated microscopic analysis of urine sediment, allows the rapid prediction of negative samples. In addition, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a widely established technique in clinical microbiology laboratories used to identify microorganisms. We evaluated the ability of MALDI-TOF MS to identify microorganisms from direct urine samples and the predictive value of automated analyzers for the identification of microorganisms in urine by MALDI-TOF MS. A total of 451 urine samples from patients with suspected UTIs were first analyzed using the Sysmex UF-1000
i
flow cytometer, an automatic sediment analyzer with microscopy (SediMax), culture, and then processed by MALDI-TOF MS with a simple triple-centrifuged procedure to obtain a pellet that was washed and centrifuged and finally applied directly to the MALDI-TOF MS plate. The organisms in 336 samples were correctly identified, mainly those with Gram-negative bacteria (86.10%). No microorganisms were misidentified, and no
Candida
spp. were correctly identified. Regarding the data from autoanalyzers, the best bacteriuria cutoffs were 1,000 and 200 U/μl for UF-1000
i
and SediMax, respectively. It was concluded that the combination of a urine screening method and MALDI-TOF MS provided a reliable identification from urine samples, especially in those containing Gram-negative bacteria.
Development and Validation of a Highly Accurate Quantitative Real-Time PCR Assay for Diagnosis of Bacterial Vaginosis
Authors: Hilbert David W. , Smith William L. , Chadwick Sean G. , Toner Geoffrey , Mordechai Eli , Adelson Martin E. , Aguin Tina J. , Sobel Jack D. , Gygax Scott E.
Published: January 2016

Bacterial vaginosis (BV) is the most common gynecological infection in the United States. Diagnosis based on Amsel's criteria can be challenging and can be aided by laboratory-based testing. A standard method for diagnosis in research studies is enumeration of bacterial morphotypes of a Gram-stained vaginal smear (i.e., Nugent scoring). However, this technique is subjective, requires specialized training, and is not widely available. Therefore, a highly accurate molecular assay for the diagnosis of BV would be of great utility. We analyzed 385 vaginal specimens collected prospectively from subjects who were evaluated for BV by clinical signs and Nugent scoring. We analyzed quantitative real-time PCR (qPCR) assays on DNA extracted from these specimens to quantify nine organisms associated with vaginal health or disease:
Gardnerella vaginalis
,
Atopobium vaginae
, BV-associated bacteria 2 (BVAB2, an uncultured member of the order
Clostridiales
),
Megasphaera
phylotype 1 or 2,
Lactobacillus iners
,
Lactobacillus crispatus
,
Lactobacillus gasseri
, and
Lactobacillus jensenii
. We generated a logistic regression model that identified
G. vaginalis
,
A. vaginae
, and
Megasphaera
phylotypes 1 and 2 as the organisms for which quantification provided the most accurate diagnosis of symptomatic BV, as defined by Amsel's criteria and Nugent scoring, with 92% sensitivity, 95% specificity, 94% positive predictive value, and 94% negative predictive value. The inclusion of
Lactobacillus
spp. did not contribute sufficiently to the quantitative model for symptomatic BV detection. This molecular assay is a highly accurate laboratory tool to assist in the diagnosis of symptomatic BV.
Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation
Authors: Yuen Chun-Kit , Chan Ching-Ping , Fung Sin-Yee , Wang Pei-Hui , Wong Wan-Man , Tang Hei-Man Vincent , Yuen Kit-San , Chan Chi-Ping , Jin Dong-Yan , Kok Kin-Hang
Published: January 2016

Infection with human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis. Type I interferons (IFNs) are key effectors of the innate antiviral response, and IFN-α combined with the nucleoside reverse transcriptase inhibitor zidovudine is considered the standard first-line therapy for ATL. HTLV-1 oncoprotein Tax is known to suppress innate IFN production and response but the underlying mechanisms remain to be fully established. In this study, we report on the suppression of type I IFN production by HTLV-1 Tax through interaction with and inhibition of TBK1 kinase that phosphorylates IRF3. Induced transcription of IFN-β was severely impaired in HTLV-1-transformed ATL cells and freshly infected T lymphocytes. The ability to suppress IRF3 activation was ascribed to Tax. The expression of Tax alone sufficiently repressed the induction of IFN production by RIG-I plus PACT, cGAMP synthase plus STING, TBK1, IKKε, IRF3, and IRF7, but not by IRF3-5D, a dominant-active phosphomimetic mutant. This suggests that Tax perturbs IFN production at the step of IRF3 phosphorylation. Tax mutants deficient for CREB or NF-κB activation were fully competent in the suppression of IFN production. Coimmunoprecipitation experiments confirmed the association of Tax with TBK1, IKKε, STING, and IRF3.
In vitro
kinase assay indicated an inhibitory effect of Tax on TBK1-mediated phosphorylation of IRF3. Taken together, our findings suggested a new mechanism by which HTLV-1 oncoprotein Tax circumvents the production of type I IFNs in infected cells. Our findings have implications in therapeutic intervention of ATL.

IMPORTANCE
Human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL), an aggressive and fatal blood cancer, as well as another chronic disabling disease of the spinal cord. Treatments are unsatisfactory, and options are limited. A combination of antiviral cellular protein alpha interferon and zidovudine, which is an inhibitor of a viral enzyme called reverse transcriptase, has been recommended as the standard first-line therapy for ATL. Exactly how HTLV-1 interacts with the cellular machinery for interferon production and action is not well understood. Our work sheds light on the mechanism of action for the inhibition of interferon production by an HTLV-1 oncogenic protein called Tax. Our findings might help to improve interferon-based anti-HTLV-1 and anti-ATL therapy.
Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor
Authors: Murata Takayuki , Noda Chieko , Narita Yohei , Watanabe Takahiro , Yoshida Masahiro , Ashio Keiji , Sato Yoshitaka , Goshima Fumi , Kanda Teru , Yoshiyama Hironori , Tsurumi Tatsuya , Kimura Hiroshi
Published: January 2016

Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter.

IMPORTANCE
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1.
Biological Nanomotors with a Revolution, Linear, or Rotation Motion Mechanism
Authors: Guo Peixuan , Noji Hiroyuki , Yengo Christopher M. , Zhao Zhengyi , Grainge Ian
Published: January 2016

The ubiquitous biological nanomotors were classified into two categories in the past: linear and rotation motors. In 2013, a third type of biomotor, revolution without rotation (
http://rnanano.osu.edu/movie.html
), was discovered and found to be widespread among bacteria, eukaryotic viruses, and double-stranded DNA (dsDNA) bacteriophages. This review focuses on recent findings about various aspects of motors, including chirality, stoichiometry, channel size, entropy, conformational change, and energy usage rate, in a variety of well-studied motors, including F
o
F
1
ATPase, helicases, viral dsDNA-packaging motors, bacterial chromosome translocases, myosin, kinesin, and dynein. In particular, dsDNA translocases are used to illustrate how these features relate to the motion mechanism and how nature elegantly evolved a revolution mechanism to avoid coiling and tangling during lengthy dsDNA genome transportation in cell division. Motor chirality and channel size are two factors that distinguish rotation motors from revolution motors. Rotation motors use right-handed channels to drive the right-handed dsDNA, similar to the way a nut drives the bolt with threads in same orientation; revolution motors use left-handed motor channels to revolve the right-handed dsDNA. Rotation motors use small channels (<2 nm in diameter) for the close contact of the channel wall with single-stranded DNA (ssDNA) or the 2-nm dsDNA bolt; revolution motors use larger channels (>3 nm) with room for the bolt to revolve. Binding and hydrolysis of ATP are linked to different conformational entropy changes in the motor that lead to altered affinity for the substrate and allow work to be done, for example, helicase unwinding of DNA or translocase directional movement of DNA.
Black bone disease in a healing fracture
Authors: Thiam Desmond , Teo Tse Yean , Malhotra Rishi , Tan Kong Bing , Chee Yu Han
Published: January 2016

Black bone disease refers to the hyperpigmentation of bone secondary to prolonged usage of minocycline. We present a report of a 34-year-old man who underwent femoral shaft fracture fixation complicated by deep infection requiring debridement. The implants were removed 10 months later after long-term treatment with minocycline and fracture union. A refracture of the femoral shaft occurred 2 days after implant removal and repeat fixation was required. Intraoperatively, abundant heavily pigmented and dark brown bone callus was noted over the old fracture site. There was no evidence of other bony pathology and the appearance was consistent with minocycline-associated pigmentation. As far as we are aware, this is the first case of black bone disease affecting callus within the interval period of bone healing. We also discuss the relevant literature on black bone disease to bring light on this rare entity that is an unwelcomed surprise to operating orthopaedic surgeons.
Severe vitamin C deficiency in a child newly diagnosed with T-cell ALL due to nutrient gap
Authors: Harris-Janz Sydney , Johnston Donna , Halton Jacqueline
Published: January 2016

A 10-year-old boy developed a perifollicular rash during interim maintenance of T-Cell acute lymphoblastic leukaemia. Differential diagnoses included drug reaction and inflammatory process. Before diagnosis, the patient had a limited diet—low in vegetables and fruits—due to selective eating, with later anorexia and taste aversions due to chemotherapy treatment. Despite nutritional counselling and starting a multivitamin, the patient incurred severe weight loss (18.5% of his usual body weight). Serum levels of ascorbic acid were non-detectable, at <5 μmol/L, indicative of vitamin C deficiency. The patient began vitamin C supplementation containing 125 mg ascorbic acid three times a day for 7 days, then 125 mg once daily for 3 months to normalise serum vitamin C. After ascorbic acid treatment was completed, the patient started a complete multivitamin and made efforts to eat fruits and vegetables rich in vitamin C. His serum ascorbic acid concentrations normalised to 52 μmol/L 3 months after receiving supplementation.
Hepatic abscess-associatedClostridialbacteraemia presenting with intravascular haemolysis and severe hypertension
Authors: Lim Andrew George , Rudd Kristina Elizabeth , Halliday Melissa , Hess John Rider
Published: January 2016

Clostridium perfringensbacteraemia is a potentially fatal condition, and its early identification is paramount to maximise chances of survival. Prompt recognition of intravascular haemolysis, a known complication ofC. perfringensbacteraemia, can help guide clinical decision-making before microbiology data becomes available. We present a novel finding of severe hypertension in a fatal case ofClostridialbacteraemia with massive haemolysis. A 58-year-old man with no known medical history presented to the emergency department with malaise, fever and hypertension. He developed abdominal pain and a hepatic abscess was identified on CT imaging. Within 4 h of presentation, he developed massive intravascular haemolysis, extreme hypertension, pulmonary oedema and respiratory failure. He died less than 8 h after presentation. His blood cultures subsequently grewC. perfringens. This case underscores the importance of early recognition of intravascular haemolysis complicatingC. perfringensbacteraemia, and discusses the rare complication of hypertensive emergency in this setting.
Rare encounter of unilateral facial nerve palsy in an adolescent with Guillain-Barré syndrome
Authors: Iqbal Mehtab , Sharma Parnika , Charadva Creana , Prasad Manish
Published: January 2016

Unilateral facial nerve palsy is rarely encountered in Guillain-Barré syndrome (GBS). We report a case of an adolescent girl who presented with peripheral ascending weakness, preceded byCampylobacter jejuniinfection. After treatment with intravenous immunoglobulin, the peripheral weakness improved. Electro-diagnostic testing confirmed axonal dysfunction and the patient was positive for antiganglioside antibodies. However, the patient developed unilateral left-sided facial weakness. She was managed with further intravenous immunoglobulin and intensive physiotherapy. The outcome for facial palsy was very good, with almost complete resolution after 2 weeks.
Sodium valproate-induced Fanconi type proximal renal tubular acidosis
Authors: Knights Mark , Thekkekkara Tina , Morris Alistair , Finlay Eric
Published: January 2016

We present a case series of three patients with sodium valproate-induced Fanconi's syndrome, with ages ranging from 5 years to 12 years. The most important diagnostic features of this syndrome include hypophosphataemia, glycosuria and proteinuria, which are also noted in our series. Furthermore, also added is that clinical fractures representing an underlying osteopaenia may provide an opportunity for early intervention as it raises the suspicion of Fanconi's syndrome. Previous case reports suggest there is a subpopulation of individuals who are at risk of developing this condition. These individuals share similar characteristics, including being non-ambulatory, developmentally delayed and/or tube fed. Withdrawing sodium valproate therapy is the ultimate treatment for valproate-induced Fanconi's syndrome and from previous case series, normalised renal function occurs in approximately 6 months. Often, supplement support is also required for deranged electrolyte balance.
Pilonidal sinus of the chin: mistreated as a dental fistula
Authors: Kucukkurt Sercan , Ozle Murat , Rzayev Sharif
Published: January 2016

Pilonidal sinus is a chronic inflammatory condition associated with penetration of hair particles into the skin. It is rare in the chin area and, to our knowledge, there is only one such reported case. A 56-year-old man was previously admitted to a private clinic, with a hard mass on his anterior buccal sulcus. Three of the patient's teeth were extracted as the swelling was thought to be associated with a dental infection. Because the fistula did not resolve, the patient was referred to our department. Following radiological and clinical examinations, the hard mass was reached intraorally and hair shafts were seen inside it. The area was closed primarily after cleaning the inflammatory tissues and the hairs. The recovery period was uneventful. In this case report, we present a pilonidal sinus encountered in the chin area, the wrong treatment initially given to the patient and the subsequent treatment carried out by us.
‘Epinephrine-resistant’ angioedema
Authors: Ange Nikhita , Rabbolini David J , Pidcock Michael , Randall Katrina L
Published: January 2016

A man in his 60s was brought to the emergency department, with airway compromise and dysarthria due to a grossly enlarged tongue. As he was on a current course of antibiotics, he was treated for a likely antibiotic-associated allergic reaction. However, as he failed to improve with intramuscular and nebulised epinephrine, another cause of his symptoms was sought. Further discussion revealed a history of chronic lymphocytic leukaemia (CLL), which had recently relapsed. Investigations were ordered to confirm that the symptoms were due to acquired angioedema, and the patient was managed for this diagnosis based on the presence of an undetectable C4 level. This diagnosis was later confirmed when the results of specialist tests became available. The patient was treated for his relapsed CLL with good effect, and has had no further episodes of angioedema and an improvement in the level of his C1 esterase protein level and function.
Can HIV reverse transcriptase activity assay be a low-cost alternative for viral load monitoring in resource-limited settings?
Authors: Gupta Soham , Palchaudhuri Riya , Neogi Ujjwal , Srinivasa Hiresave , Ashorn Per , De Costa Ayesha , Källander Clas , Shet Anita
Published: January 2016

Objective

To evaluate the performance and cost of an HIV reverse transcriptase-enzyme activity (HIV-RT) assay in comparison to an HIV-1 RNA assay for routine viral load monitoring in resource limited settings.

Design

A cohort-based longitudinal study.

Setting

Two antiretroviral therapy (ART) centres in Karnataka state, South India, providing treatment under the Indian AIDS control programme.

Participants

A cohort of 327 HIV-1-infected Indian adult patients initiating first-line ART.

Outcome measures

Performance and cost of an HIV-RT assay (ExaVir Load V3) in comparison to a gold standard HIV-1 RNA assay (Abbott m2000rt) in a cohort of 327 Indian patients before (WK00) and 4 weeks (WK04) after initiation of first-line therapy.

Results

Plasma viral load was determined by an HIV-1 RNA assay and an HIV-RT assay in 629 samples (302 paired samples and 25 single time point samples at WK00) obtained from 327 patients. Overall, a strong correlation of r=0.96 was observed, with good correlation at WK00 (r=0.84) and at WK04 (r=0.77). Bland-Altman analysis of all samples showed a good level of agreement with a mean difference (bias) of 0.22 log10copies/mL. The performance of ExaVir Load V3 was not negatively affected by a nevirapine/efavirenz based antiretroviral regimen. The per test cost of measuring plasma viral load by the Abbott m2000rt and ExaVir Load V3 assays in a basic lab setting was $36.4 and $16.8, respectively.

Conclusions

The strong correlation between the HIV-RT and HIV-1 RNA assays suggests that the HIV-RT assay can be an affordable alternative option for monitoring patients on antiretroviral therapy in resource-limited settings.

Trial registration number

ISRCTN79261738.
Independent predictors of major adverse cardiovascular events in emergency department patients who are hospitalised with a suspected infection: a retrospective cohort study
Authors: de Groot Bas , van den Berg Stefanie , Kessler Joanne , Ansems Annemieke , Rijpsma Douwe
Published: January 2016

Objective

Emergency department (ED) patients hospitalised with a suspected infection have an increased risk for major adverse cardiovascular events (MACE). This study aims to identify independent predictors of MACE after hospital admission which could be used for identification of high-risk patients who may benefit from preventive strategies.

Setting

Dutch tertiary care centre and urban hospital.

Participants

Consecutive, hospitalised, ED patients with a suspected infection.

Design

This was a secondary analysis using an existing database in which consecutive, hospitalised, ED patients with a suspected infection were prospectively enrolled. Potential independent predictors, including illness severity, as assessed by the Predisposition, Infection, Response, Organ failure (PIRO) score, and classic cardiac risk factors were analysed by multivariable binary logistic regression. Prognostic and discriminative performance of the model was quantified by the Hosmer-Lemeshow test and receiver operator characteristics with area under the curve (AUC) analyses, respectively. Maximum sensitivity and specificity for identification of MACE were calculated.

Primary outcome

MACE within 90 days after hospital admission.

Results

36 (2.1%) of the 1728 included patients developed MACE <90 days after ED presentation. Independent predictors of MACE were the RO components of the PIRO score, reflecting acute organ failure, with a corrected OR (OR (95% CI) 1.1 (1.0 to 1.3) per point increase), presence of atrial fibrillation/flutter; OR 3.9 (2.0 to 7.7) and >2 classic cardiovascular risk factors; 2.2 (1.1 to 4.3). The AUC was 0.773, and the goodness-of-fit test had a p value of 0.714. These predictors identified MACE with 75% sensitivity and 70% specificity.

Conclusions

Besides the classical cardiovascular risk factors, atrial fibrillation and signs of acute organ failure were independent risk factors of MACE in ED patients hospitalised with a suspected infection. Future studies should investigate whether preventive measures like antiplatelet therapy should be initialised in hospitalised ED patients with suspected infection and high risk for MACE.
Psychological interventions to improve psychological well-being in people with dementia or mild cognitive impairment: systematic review and meta-analysis protocol
Authors: Farrand Paul , Matthews Justin , Dickens Chris , Anderson Martin , Woodford Joanne
Published: January 2016

Introduction

Dementia and mild cognitive impairment are associated with an increased risk of depression, anxiety, psychological distress and poor mental health-related quality of life. However, there is a lack of research examining the evidence base for psychological interventions targeting general psychological well-being within this population. Furthermore, there is little research relating to the design of randomised controlled trials examining psychological interventions for dementia and mild cognitive impairment, such as effective recruitment techniques, trial eligibility and appropriate comparators.

Methods and analysis

Systematic review of electronic databases (CINAHL; EMBASE; PsychInfo; MEDLINE; ASSIA and CENTRAL), supplemented by expert contact, reference and citation checking, and grey literature searches. Published and unpublished studies will be eligible for inclusion with no limitations placed on year of publication. Primary outcomes of interest will be standardised measurements of depression, anxiety, psychological distress or mental health-related quality of life. Eligibility and randomisation proportions will be calculated as secondary outcomes. If data permits, meta-analytical techniques will examine: (1) overall effectiveness of psychological interventions for people with dementia or mild cognitive impairment in relation to outcomes of depression, anxiety, psychological distress or mental health-related quality of life; (2) clinical and methodological moderators associated with effectiveness; (3) proportions eligible, recruited and randomised.

Ethics and dissemination

Ethical approval is not required for the present systematic review. Results will inform the design of a feasibility study examining a new psychological intervention for people with dementia and depression, with dissemination through publication in peer-reviewed journals and presentations at relevant conferences.

Trial registration number

CRD42015025177.
School-based intervention for the prevention of HPV among adolescents: a cluster randomised controlled study
Authors: Grandahl Maria , Rosenblad Andreas , Stenhammar Christina , Tydén Tanja , Westerling Ragnar , Larsson Margareta , Oscarsson Marie , Andrae Bengt , Dalianis Tina , Nevéus Tryggve
Published: January 2016

Objective

To improve primary prevention of human papillomavirus (HPV) infection by promoting vaccination and increased condom use among upper secondary school students.

Design

Cluster randomised controlled trial.

Setting

18 upper secondary schools in Sweden.

Participants

Schools were first randomised to the intervention or the control group, after which individual classes were randomised so as to be included or not. Of the 832 students aged 16 years invited to participate during the regular individual health interview with the school nurse, 751 (90.2%) agreed to participate and 741 (89.1%) students completed the study.

Interventions

The intervention was based on the Health Belief Model (HBM). According to HBM, a person's health behaviour can be explained by individual beliefs regarding health actions. School nurses delivered 30 min face-to-face structured information about HPV, including cancer risks and HPV prevention, by propagating condom use and HPV vaccination. Students in the intervention and the control groups completed questionnaires at baseline and after 3 months.

Main outcome measures

Intention to use condom with a new partner and beliefs about primary prevention of HPV, and also specifically vaccination status and increased condom use.

Results

All statistical analyses were performed at the individual level. The intervention had a significant effect on the intention to use condom (p=0.004). There was also a significant effect on HBM total score (p=0.003), with a 2.559 points higher score for the intervention group compared to the controls. The influence on the HBM parameterssusceptibilityandseveritywas also significant (p<0.001 for both variables). The intervention also influenced behaviour: girls in the intervention group chose to have themselves vaccinated to a significantly higher degree than the controls (p=0.02). No harms were reported.

Conclusions

The school-based intervention had favourable effects on the beliefs about primary prevention of HPV, and increased the HPV vaccination rates in a diverse population of adolescents.

Trial registration number

NCT02280967; Results.
Decisions about the use of psychotropic medication during pregnancy: a qualitative study
Authors: Stevenson Fiona , Hamilton Sarah , Pinfold Vanessa , Walker Charlotte , Dare Ceri R J , Kaur Harminder , Lambley Ruth , Szymczynska Paulina , Nicolls Vicky , Petersen Irene
Published: January 2016

Objective

To understand the perspectives of women with severe mental illness concerning the use of psychotropic medicines while pregnant.

Design

Interviews conducted by female peer researchers with personal experience of making or considering decisions about using psychotropic medicines in pregnancy, supported by professional researchers.

Participants

12 women who had had a baby in the past 5 years and had taken antipsychotics or mood-stabilisers for severe mental illness within the 12-month period immediately prior to that pregnancy. Recruitment to the study was via peer networks and the women interviewed came from different regions of England.

Setting

Interviews were arranged in places where women felt comfortable and that accommodated their childcare needs including their home, local library and the research office.

Results

The views expressed demonstrated complex attempts to engage with decision-making about the use of psychotropic medicines in pregnancy. In nearly all cases, the women expressed the view that healthcare professionals had access to limited information leaving women to rely on experiential and common sense evidence when making decisions about medicine taking during pregnancy.

Conclusions

The findings complement existing work using electronic health records by providing explanations for the discontinuation of psychotropic medicines in pregnancy. Further work is necessary to understand health professionals’ perspectives on the provision of services and care to women with severe mental illness during pregnancy.
Paramedical risk framing during field referral of acute stroke and S–T elevation myocardial infarction patients
Authors: Campeau Anthony Gerard
Published: January 2016

Field referral of emergency ambulance patients by paramedics on a widespread basis is a relatively new aspect of paramedicine. Its implementation involves a significant revision to paramedics’ clinical responsibilities and level of interaction with medical specialists. Using grounded theory methodology, this qualitative study uses interviews with paramedics from Ontario, Canada, to explore the framing of risk associated with these referrals in the context of caring for patients with two high-stakes medical conditions: acute stroke and S–T elevation myocardial infarction. The results outline how paramedics have incorporated risk framing into their practice.
Intravascular optical coherence tomography for the evaluation of arterial bifurcations covered by flow diverters
Authors: Iosif Christina , Saleme Suzana , Ponsonnard Sebastien , Carles Pierre , Silveira Eduardo Pedrolo , Waihrich Eduardo , Trolliard Gilles , Yardin Catherine , Mounayer Charbel
Published: January 2016

Background and objective

Due to its high spatial resolution, intravascular optical coherence tomography (OCT) has been used as a valid method for in vivo evaluation of several types of coronary stents at straight lumen and bifurcation sites. We sought to evaluate its effectiveness for flow diverting stents deployed in arterial bifurcation sites involving jailing of a side branch.

Methods

Four large white swine were stented with flow diverting stents covering the right common carotid artery–ascending pharyngeal artery bifurcation. After 12 weeks of follow-up the animals were evaluated by digital subtraction angiography and intravascular OCT and subsequently sacrificed. Neointimal thickness on the parent arteries and the free segments of the stent were measured. The stented arteries were harvested and underwent scanning electron microscopy (SEM) imaging. Ostia surface values were measured with OCT three-dimensional (3D) reconstructions and SEM images.

Results

All endovascular procedures and OCT pullback runs were feasible. Stent apposition was satisfactory on the immediate post-stent OCT reconstructions. At 12-week controls, all stents and jailed branches were patent. Mean neointimal thickness was 0.11±0.04 mm on the free segments of the stent. The mean ostia surface at 12 weeks was 319 750±345 533 μm2with 3D-OCT reconstructions and 351 198±396 355 μm2with SEM image-derived calculations. Good correlation was found for ostia surface values between the two techniques; the values did not differ significantly in this preliminary study.

Conclusions

Intravascular OCT appears to be a promising technique for immediate and follow-up assessment of the orifice of arterial branches covered by flow diverting stents.
Role of microRNAs in gastrointestinal smooth muscle fibrosis and dysfunction: novel molecular perspectives on the pathophysiology and therapeutic targeting
Authors: Krishna Chadalavada Vijay , Singh Jagmohan , Thangavel Chellappagounder , Rattan Satish
Published: January 2016

MicroRNAs (miRNAs) belong to a group of short noncoding RNA molecules with important roles in cellular biology. miRNAs regulate gene expression by repressing translation or degrading the target mRNA. Recently, a growing body of evidence suggests that miRNAs are implicated in many diseases and could be potential biomarkers. Fibrosis and/smooth muscle (SM) dysfunction contributes to the morbidity and mortality associated with several diseases of the gastrointestinal tract (GIT). Currently available therapeutic modalities are unsuccessful in efficiently blocking or reversing fibrosis and/or SM dysfunction. Recent understanding of the role of miRNAs in signaling pathway of fibrogenesis and SM phenotype switch has provided a new insight into translational research. However, much is still unknown about the molecular targets and therapeutic potential of miRNAs in the GIT. This review discusses miRNA biology, pathophysiology of fibrosis, and aging- associated SM dysfunction in relation to the deregulation of miRNAs in the GIT. We also highlight the role of selected miRNAs associated with fibrosis and SM dysfunction-related diseases of the GIT.
Positive airway pressure improves nocturnal beat-to-beat blood pressure surges in obesity hypoventilation syndrome with obstructive sleep apnea
Authors: Carter Jason R. , Fonkoue Ida T. , Grimaldi Daniela , Emami Leila , Gozal David , Sullivan Colin E. , Mokhlesi Babak
Published: January 2016

Positive airway pressure (PAP) treatment has been shown to have a modest effect on ambulatory blood pressure (BP) in patients with obstructive sleep apnea (OSA). However, there is a paucity of data on the effect of PAP therapy on rapid, yet significant, BP swings during sleep, particularly in obesity hypoventilation syndrome (OHS). The present study hypothesizes that PAP therapy will improve nocturnal BP on the first treatment night (titration PAP) in OHS patients with underlying OSA, and that these improvements will become more significant with 6 wk of PAP therapy. Seventeen adults (7 men, 10 women; age 50.4 ± 10.7 years, BMI 49.3 ± 2.4 kg/m2) with OHS and clinically diagnosed OSA participated in three overnight laboratory visits that included polysomnography and beat-to-beat BP monitoring via finger plethysmography. Six weeks of PAP therapy, but not titration PAP, lowered mean nocturnal BP. In contrast, when nocturnal beat-to-beat BPs were aggregated into bins consisting of at least three consecutive cardiac cycles with a >10 mmHg BP surge (i.e., Δ10–20, Δ20–30, Δ30–40, and Δ>40 mmHg), titration, and 6-wk PAP reduced the number of BP surges per hour (time × bin, P < 0.05). PAP adherence over the 6-wk period was significantly correlated to reductions in nocturnal systolic ( r = 0.713, P = 0.001) and diastolic ( r = 0.497, P = 0.043) BP surges. Despite these PAP-induced improvements in nocturnal beat-to-beat BP surges, 6 wk of PAP therapy did not alter daytime BP. In conclusion, PAP treatment reduces nocturnal beat-to-beat BP surges in OHS patients with underlying OSA, and this improvement in nocturnal BP regulation was greater in patients with higher PAP adherence.
Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats
Authors: Kim Yang Gyun , Lee Sang Ho , Kim Se-Yun , Lee Arah , Moon Ju Young , Jeong Kyung-Hwan , Lee Tae Won , Lim Sung Jig , Sohn Il Suk , Ihm Chun-Gyoo
Published: January 2016

The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension.
Modulation of the myogenic mechanism: concordant effects of NO synthesis inhibition and O2− dismutation on renal autoregulation in the time and frequency domains
Authors: Moss Nicholas G. , Gentle Tayler K. , Arendshorst William J.
Published: January 2016

Renal blood flow autoregulation was investigated in anesthetized C57Bl6 mice using time- and frequency-domain analyses. Autoregulation was reestablished by 15 s in two stages after a 25-mmHg step increase in renal perfusion pressure (RPP). The renal vascular resistance (RVR) response did not include a contribution from the macula densa tubuloglomerular feedback mechanism. Inhibition of nitric oxide (NO) synthase [ NG-nitro-l-arginine methyl ester (l-NAME)] reduced the time for complete autoregulation to 2 s and induced 0.25-Hz oscillations in RVR. Quenching of superoxide (SOD mimetic tempol) during l-NAME normalized the speed and strength of stage 1 of the RVR increase and abolished oscillations. The slope of stage 2 was unaffected by l-NAME or tempol. These effects of l-NAME and tempol were evaluated in the frequency domain during random fluctuations in RPP. NO synthase inhibition amplified the resonance peak in admittance gain at 0.25 Hz and markedly increased the gain slope at the upper myogenic frequency range (0.06–0.25 Hz, identified as stage 1), with reversal by tempol. The slope of admittance gain in the lower half of the myogenic frequency range (equated with stage 2) was not affected by l-NAME or tempol. Our data show that the myogenic mechanism alone can achieve complete renal blood flow autoregulation in the mouse kidney following a step increase in RPP. They suggest also that the principal inhibitory action of NO is quenching of superoxide, which otherwise potentiates dynamic components of the myogenic constriction in vivo. This primarily involves the first stage of a two-stage myogenic response.
Greater loss in muscle mass and function but smaller metabolic alterations in older compared with younger men following 2 wk of bed rest and recovery
Authors: Pišot Rado , Marusic Uros , Biolo Gianni , Mazzucco Sara , Lazzer Stefano , Grassi Bruno , Reggiani Carlo , Toniolo Luana , di Prampero Pietro Enrico , Passaro Angelina , Narici Marco , Mohammed Shahid , Rittweger Joern , Gasparini Mladen , Gabrijelčič Blenkuš Mojca , Šimunič Boštjan
Published: January 2016

This investigation aimed to compare the response of young and older adult men to bed rest (BR) and subsequent rehabilitation (R). Sixteen older (OM, age 55-65 yr) and seven young (YM, age 18–30 yr) men were exposed to a 14-day period of BR followed by 14 days of R. Quadriceps muscle volume (QVOL), force (QF), and explosive power (QP) of leg extensors; single-fiber isometric force (Fo); peak aerobic power (V̇o2peak); gait stride length; and three metabolic parameters, Matsuda index of insulin sensitivity, postprandial lipid curve, and homocysteine plasma level, were measured before and after BR and after R. Following BR, QVOL was smaller in OM (−8.3%) than in YM (−5.7%, P = 0.031); QF (−13.2%, P = 0.001), QP (−12.3%, P = 0.001), and gait stride length (−9.9%, P = 0.002) were smaller only in OM. Fo was significantly smaller in both YM (−32.0%) and OM (−16.4%) without significant differences between groups. V̇o2peak decreased more in OM (−15.3%) than in YM (−7.6%, P < 0.001). Instead, the Matsuda index fell to a greater extent in YM than in OM (−46.0% vs. −19.8%, respectively, P = 0.003), whereas increases in postprandial lipid curve (+47.2%, P = 0.013) and homocysteine concentration (+26.3%, P = 0.027) were observed only in YM. Importantly, after R, the recovery of several parameters, among them QVOL, QP, and V̇o2peak, was not complete in OM, whereas Fo did not recover in either age group. The results show that the effect of inactivity on muscle mass and function is greater in OM, whereas metabolic alterations are greater in YM. Furthermore, these findings show that the recovery of preinactivity conditions is slower in OM.
Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings
Authors: Brown M. Christian
Published: January 2016

Medial olivocochlear (MOC) neurons provide an efferent innervation to outer hair cells (OHCs) of the cochlea, but their tonotopic mapping is incompletely known. In the present study of anesthetized guinea pigs, the MOC mapping was investigated using in vivo, extracellular recording, and labeling at a site along the cochlear course of the axons. The MOC axons enter the cochlea at its base and spiral apically, successively turning out to innervate OHCs according to their characteristic frequencies (CFs). Recordings made at a site in the cochlear basal turn yielded a distribution of MOC CFs with an upper limit, or “edge,” due to usually absent higher-CF axons that presumably innervate more basal locations. The CFs at the edge, normalized across preparations, were equal to the CFs of the auditory nerve fibers (ANFs) at the recording sites (near 16 kHz). Corresponding anatomical data from extracellular injections showed spiraling MOC axons giving rise to an edge of labeling at the position of a narrow band of labeled ANFs. Overall, the edges of the MOC CFs and labeling, with their correspondences to ANFs, suggest similar tonotopic mappings of these efferent and afferent fibers, at least in the cochlear basal turn. They also suggest that MOC axons miss much of the position of the more basally located cochlear amplifier appropriate for their CF; instead, the MOC innervation may be optimized for protection from damage by acoustic overstimulation.