bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient involvement in own rehabilitation after early discharge
Authors: Hørdam Britta , Boolsen Merete Watt 
Published: December 2016

BackgroundA European Union Commission report in 2015 concluded that the concept of patient involvement refers specially to the right of patients to have a central position in the healthcare process (EU Commission 2012, http://ec.europa.eu/public_opinion/archives/quali/ql_5937_patient_en.pdf). Recent research suggests that patient involvement after hip replacement is a very effective strategy in older adults with regard to improving walking ability and reducing pain and thereby lessening loss of physical, mental and social aspects of the quality of life. The growing number of older adults all over the world will increase the need for hip surgery.HypothesisOlder adults’ involvement in own rehabilitation improves their health and quality of life after hip replacement.AimTo involve and coach older adults with a hip replacement to self‐care after early discharge in transition between hospital and home.PopulationEmpirical data were collected by carrying out three randomised clinical trials (RCT) focusing on self‐rated health and involvement of patients undergoing total hip replacement in three Danish orthopaedic clinics. Based on power calculation, 260 patients (mean age 67.5 years) were invited to participate. In this third study in 2010–2013, patients were randomised to either an intervention group or a control group.MethodologyRandomised clinical trials (RCT). Questionnaire SF‐36 a generic tool measuring patients’ self‐rated health status and quality of life. All patients filled out SF‐36 before surgery and again 3, 6, 9 and 12 months after surgery. Patients in the intervention group had an additional follow‐up 1, 3 and 7 weeks after discharge by nurses from orthopaedic clinic in hospital. The nurses used a semi‐structured interview guide as intervention model to coach, counsel and involve patients to improve their self‐care and planned rehabilitation after hip replacement.ResultsOlder adults benefit through involvement based on an intervention model of expectations, measurement of self‐rated health and quality of life. The results of the randomised trials one and two documented that patients’ self‐rated health status in the intervention group reached their habitual level 3 months after hip replacement vs. 9 months in the control group. Since our working hypothesis ‘patient involvement in own rehabilitation improves health and quality of life after hip replacement’ was found valid, our ambition is now based on results from this third study to contribute to further research and development within patient involvement.Relevance to clinical practiceTo follow new evidence‐based research, results concluded that walking ability is very necessary in order to increase physical activity to benefit the health of older adults and prevent disease.
An open trial of mindfulness‐based stress reduction for young adults with social anxiety disorder
Authors: Hjeltnes Aslak , Molde Helge , Schanche Elisabeth , Vøllestad Jon , Lillebostad Svendsen Julie , Moltu Christian , Binder Per‐Einar 
Published: December 2016

The present study investigated mindfulness‐based stress reduction (MBSR) for young adults with a social anxiety disorder (SAD) in an open trial. Fifty‐three young adults in a higher education setting underwent a standard eight‐week MBSR program. Eight participants (15%) did not complete the program. Participants reported significant reductions in SAD symptoms and global psychological distress, as well as increases in mindfulness, self‐compassion, and self‐esteem. Using intention‐to‐treat (ITT) analyses, effect sizes ranged from large to moderate for SAD symptoms (Cohen's d = 0.80) and global psychological distress (d = 0.61). Completer analyses yielded large effect sizes for SAD symptoms (d = 0.96) and global psychological distress (d = 0.81). The largest effect sizes were found for self‐compassion (d = 1.49) and mindfulness (d = 1.35). Two thirds of the participants who were in the clinical range at pretreatment reported either clinically significant change (37%) or reliable improvement (31%) on SAD symptoms after completing the MBSR program, and almost two thirds reported either clinically significant change (37%) or reliable improvement (26%) on global psychological distress. MBSR may be a beneficial intervention for young adults in higher education with SAD, and there is a need for more research on mindfulness and acceptance‐based interventions for SAD.
A molecular approach to arthrotardigrade phylogeny (Heterotardigrada, Tardigrada)
Authors: Fujimoto Shinta , Jørgensen Aslak , Hansen Jesper G. 
Published: December 2016

The marine order Arthrotardigrada (class Heterotardigrada, phylum Tardigrada) is known for its conspicuously high morphological diversity and has been traditionally recognized as the most ancestral group within the phylum. Despite its potential importance in understanding the evolution of the phylum, the phylogenetic relationships of Arthrotardigrada have not been clarified. This study conducted molecular phylogenetic analyses of the order encompassing all families except Neoarctidae using nuclear 18S and 28S rRNA fragments. Data from two rare families, Coronarctidae and Renaudarctidae, were included for the first time. The analyses confirmed the monophyly of Heterotardigrada and inferred Coronarctidae as the sister group to all other heterotardigrade taxa. Furthermore, the results support a monophyletic Renaudarctidae + Stygarctidae clade, which has been previously suggested on morphology. Our data indicated that two subfamilies currently placed in Halechiniscidae are only distantly related to this family. We propose that these taxa are each elevated to family level (Styraconyxidae (new rank) and Tanarctidae (new rank)). The morphology of tardigrades is discussed in the context of the inferred phylogeny.
The broadening reach of frustrated Lewis pair chemistry
Authors: Stephan Douglas W. 
Published: December 2016

Cooperation between frustrated partners
What might you do with a hat that had so many decorations dangling from the brim that you couldn't put it on? Lewis acids and bases are the molecular versions of hats and heads. Stephan reviews the surprising chemistry of so-called frustrated Lewis pairs (FLPs), which cannot form their natural complex together. Over the past decade, such systems (most often comprising a borane with a nitrogen or phosphorus partner) have been used to catalyze hydrogenation reactions, activate a number of other small molecules, and generally promote a wide range of cooperative chemical reactivity.

Science
, this issue p.
10.1126/science.aaf7229
Functional and Antigen-Specific Serum Antibody Levels as Correlates of Protection against Shigellosis in a Controlled Human Challenge Study
Authors: Shimanovich Avital A. , Buskirk Amanda D. , Heine Shannon J. , Blackwelder William C. , Wahid Rezwanul , Kotloff Karen L. , Pasetti Marcela F. 
Published: December 2016

ABSTRACTShigellais an important cause of diarrheal disease in young children living in developing countries. No approved vaccines are available, and the development of vaccine candidates has been hindered by the lack of firm immunological correlates of protection, among other reasons. To address this gap in knowledge, we established quantitative assays to measureShigella-specific serum bactericidal antibody (SBA) and opsonophagocytic killing antibody (OPKA) activities and investigated their potential association with protection against disease in humans. SBA, OPKA, and Ipa-, VirG (IscA)-, andShigella flexneri2a lipopolysaccharide-specific serum IgG titers were determined in adult volunteers who receivedShigellavaccine candidate EcSf2a-2 and in unvaccinated controls, all of whom were challenged with virulentShigella flexneri2a. Prechallenge antibody titers were compared with disease severity after challenge. SBA and OPKA, as well as IpaB- and VirG-specific IgG, significantly correlated with reduced illness. SBA and OPKA assays were also used to evaluate the immunogenicity of leading live attenuated vaccine candidatesShigellaCVD 1204 and CVD 1208S in humans. A single oral immunization with CVD 1204 or CVD 1208S resulted in SBA seroconversion rates of 71% and 47% and OPKA seroconversion rates of 57% and 35%, respectively. Higher functional antibody responses were induced by CVD 1204, which is consistent with its lower attenuation. This is the first demonstration of SBA, OPKA, and IpaB- and VirG-specific IgG levels as potential serological correlates of protection against shigellosis in humans. These results warrant further studies to establish their capacity to predict protective immunity and vaccine efficacy.
Field Validation of SYBR Green- and TaqMan-Based Real-Time PCR Using Biopsy and Swab Samples To Diagnose American Tegumentary Leishmaniasis in an Area Where Leishmania (Viannia) braziliensis Is Endemic
Authors: Gomes Ciro Martins , Cesetti Mariana Vicente , de Paula Natália Aparecida , Vernal Sebastián , Gupta Gaurav , Sampaio Raimunda Nonata Ribeiro , Roselino Ana Maria 
Published: December 2016

ABSTRACTThe precise diagnosis of American tegumentary leishmaniasis (ATL) is an essential task due to the disease's associated morbidity. A noninvasive, extremely sensitive, and highly specific exam is critical, particularly for mucosal leishmaniasis (ML), in which a low parasite quantity is expected. We aimed to compare the diagnostic accuracy of swab and biopsy sample analysis using SYBR Green- and TaqMan-based real-time PCR (qPCR) assays with that of a composite reference standard consisting of the Montenegro skin test, serology, histopathology, smears, culture, and conventional PCR. In total, 55 patients with ATL (ML, 18 patients; cutaneous leishmaniasis [CL], 37 patients) and 36 patients without ATL were studied. qPCR analysis of swabs was more accurate when using SYBR Green (87.88%; 95% confidence interval [CI], 77.86 to 93.73 patients) than when using TaqMan (78.79%; 95% CI, 67.49 to 86.92%) (P= 0.031). SYBR Green (84.72%; 95% CI, 74.68 to 91.25%) was also more accurate than TaqMan (73.61%; 95% CI, 62.42 to 82.41%) for biopsy samples (P= 0.008). All qPCR methods were 100% specific. Swabs and biopsy specimens had similar sensitivity when using the same chemistry (P= 0.125 for SYBR Green andP= 0.625 for TaqMan). Moreover, qPCR achieved better performance than most existing techniques used for the diagnosis of ATL and also detected theLeishmaniaparasite in a greater proportion of patients than the associated histopathology, smear, culture, and conventional PCR techniques did. Swabs therefore represent a useful diagnostic tool because they not only are noninvasive but also can achieve an accuracy similar to that of biopsy samples. The high accuracy of SYBR Green-based qPCR may also reduce the requirement for associated parasitological tests for ATL diagnosis.
Stability Study of Cervical Specimens Collected by Swab and Stored Dry Followed by Human Papillomavirus DNA Detection Using the cobas 4800 Test
Authors: Lin Chun-Qing , Zeng Xi , Cui Jian-Feng , Liao Guang-Dong , Wu Ze-Ni , Gao Qian-Qian , Zhang Xun , Yu Xiu-Zhang , Chen Wen , Xi Ming-Rong , Qiao You-Lin 
Published: December 2016

ABSTRACT
Safer, more convenient methods for cervical sample collection and storage are necessary to facilitate human papillomavirus (HPV) DNA testing in low-resource settings. Our study aimed to evaluate the stability of cervical specimens collected with dry swabs and stored dry, compared to liquid-based cytology (LBC) samples, as detected by HPV DNA testing. Women with abnormal cytological findings or HPV-positive results at colposcopy were recruited from the West China Second University Hospital, Sichuan University, between October 2013 and March 2014. From each woman, physicians collected cervical specimens with a swab placed into a Sarstedt tube and a CytoBrush placed into LBC medium. Samples were randomly assigned to be stored at uncontrolled ambient temperature for 2, 7, 14, or 28 days and then were tested for 14 high-risk HPV (HR-HPV) types using the cobas HPV test. The rates of agreement between dry swab and LBC samples for any HR-HPV type, HPV16, HPV18, and the 12 pooled HR-HPV types were 93.8%, 97.8%, 99.4%, and 93.2%, respectively, with kappa values of 0.87 (95% confidence interval [CI], 0.83 to 0.91), 0.94 (95% CI, 0.91 to 0.97), 0.94 (95% CI, 0.87 to 1.00), and 0.86 (95% CI, 0.82 to 0.90). The performance of swab samples for detection of cervical precancerous lesions by means of cobas HPV testing was equal to that of LBC samples, even with stratification by storage time. Dry storage of swab-collected cervical samples can last for 1 month without loss of test performance by cobas HPV testing, compared to LBC samples, which may offer a simple inexpensive approach for cervical cancer screening in low-resource settings.
Validation of Autoclave Protocols for Successful Decontamination of Category A Medical Waste Generated from Care of Patients with Serious Communicable Diseases
Authors: Garibaldi Brian T. , Reimers Mallory , Ernst Neysa , Bova Gregory , Nowakowski Elaine , Bukowski James , Ellis Brandon C. , Smith Chris , Sauer Lauren , Dionne Kim , Carroll Karen C. , Maragakis Lisa L. , Parrish Nicole M. 
Published: December 2016

ABSTRACT
In response to the Ebola outbreak in 2014, many hospitals designated specific areas to care for patients with Ebola and other highly infectious diseases. The safe handling of category A infectious substances is a unique challenge in this environment. One solution is on-site waste treatment with a steam sterilizer or autoclave. The Johns Hopkins Hospital (JHH) installed two pass-through autoclaves in its biocontainment unit (BCU). The JHH BCU and The Johns Hopkins biosafety level 3 (BSL-3) clinical microbiology laboratory designed and validated waste-handling protocols with simulated patient trash to ensure adequate sterilization. The results of the validation process revealed that autoclave factory default settings are potentially ineffective for certain types of medical waste and highlighted the critical role of waste packaging in successful sterilization. The lessons learned from the JHH validation process can inform the design of waste management protocols to ensure effective treatment of highly infectious medical waste.
Emergence of a Viral RNA Polymerase Variant during Gene Copy Number Amplification Promotes Rapid Evolution of Vaccinia Virus
Authors: Cone Kelsey R. , Kronenberg Zev N. , Yandell Mark , Elde Nels C. 
Published: December 2016

ABSTRACT
Viruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial vaccinia virus infections in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high-frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication. Specifically, a Leu18Phe substitution encoded within A24R conferred fitness trade-offs, including increased activation of the antiviral factor protein kinase R (PKR). Intriguingly, this A24R variant underwent a drastic selective sweep during passaging, despite enhanced PKR activity. We showed that the sweep of this variant could be accelerated by the presence of copy number variation (CNV) at the K3L locus, which in multiple copies strongly reduced PKR activation. Therefore, adaptive cases of CNV can facilitate the accumulation of point mutations separate from the expanded locus. This study reveals how rapid bouts of gene copy number amplification during accrual of distant point mutations can potently facilitate poxvirus adaptation to host defenses.

IMPORTANCE
Viruses can evolve quickly to defeat host immune functions. For poxviruses, little is known about how multiple adaptive mutations emerge in populations at the same time. In this study, we uncovered a means of vaccinia virus adaptation involving the accumulation of distinct genetic variants within a single population. We identified adaptive point mutations in the viral RNA polymerase gene A24R and, surprisingly, found that one of these mutations activates the nucleic acid sensing factor PKR. We also found that gene copy number variation (CNV) can provide dual benefits to evolving virus populations, including evidence that CNV facilitates the accumulation of a point mutation distant from the expanded locus. Our data suggest that transient CNV can accelerate the fixation of mutations conferring modest benefits, or even fitness trade-offs, and highlight how structural variation might aid poxvirus adaptation through both direct and indirect actions.
Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4
hi
Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia
Authors: Shaw Julia M. , Miller-Novak Leia K. , Mohanram Venkatramanan , McKinnon Katherine , Demberg Thorsten , Vargas-Inchaustegui Diego A. , Venzon David , Robert-Guroff Marjorie 
Published: December 2016

ABSTRACT

In a recent study, we found that protection following simian immunodeficiency virus (SIV) exposure correlated with rectal plasma cell frequency in vaccinated female rhesus macaques. We sought to determine if the same macaques maintained high mucosal plasma cell frequencies postinfection and if this translated to reduced viremia. Although delayed SIV acquisition did not predict subsequent viral control, alterations existed in the distribution of plasma cells and plasmablasts between macaques that exhibited high or low viremia. Flow cytometric analysis of cells from rectal biopsy specimens, bone marrow, and mesenteric lymph nodes of vaccinated infected, unvaccinated infected, and uninfected macaques identified two main IRF4
hi
subsets of interest: CD138
+
plasma cells, and CD138
−
plasmablasts. In rectal tissue, plasma cell frequency positively correlated with plasma viremia and unvaccinated macaques had increased plasma cells and plasmablasts compared to vaccinated animals. Likewise, plasmablast frequency in the mesenteric lymph node correlated with viremia. However, in bone marrow, plasmablast frequency negatively correlated with viremia. Accordingly, low-viremic macaques had a higher frequency of both bone marrow IRF4
hi
subsets than did animals with high viremia. Significant reciprocal relationships between rectal and bone marrow plasmablasts suggested that efficient trafficking to the bone marrow as opposed to the rectal mucosa was linked to viral control. mRNA expression analysis of proteins involved in establishment of plasma cell niches in sorted bone marrow and rectal cell populations further supported this model and revealed differential mRNA expression patterns in these tissues.

IMPORTANCE
As key antibody producers, plasma cells and plasmablasts are critical components of vaccine-induced immunity to human immunodeficiency virus type 1 (HIV-1) in humans and SIV in the macaque model; however, few have attempted to examine the role of these cells in viral suppression postinfection. Our results suggest that plasmablast trafficking to and retention in the bone marrow play a previously unappreciated role in viral control and contrast the potential contribution of mucosal plasma cells to mediate protection at sites of infection with that of bone marrow plasmablasts and plasma cells to control viremia during chronic infection. Manipulation of niche factors influencing the distribution and maintenance of these critical antibody-secreting cells may serve as potential therapeutic targets to enhance antiviral responses postvaccination and postinfection.
Herpes Simplex Virus 1 UL41 Protein Suppresses the IRE1/XBP1 Signal Pathway of the Unfolded Protein Response via Its RNase Activity
Authors: Zhang Pengchao , Su Chenhe , Jiang Zhangtao , Zheng Chunfu 
Published: December 2016

ABSTRACT
During viral infection, accumulation of viral proteins can cause stress in the endoplasmic reticulum (ER) and trigger the unfolded protein response (UPR) to restore ER homeostasis. The inositol-requiring enzyme 1 (IRE1)-dependent pathway is the most conserved of the three UPR signal pathways. Upon activation, IRE1 splices out an intron from the unspliced inactive form of X box binding protein 1 [XBP1(u)] mRNA and produces a transcriptionally potent spliced form [XBP1(s)]. Previous studies have reported that the IRE1/XBP1 pathway is inhibited upon herpes simplex virus 1 (HSV-1) infection; however, the underlying molecular mechanism is still elusive. Here, we uncovered a role of the HSV-1 UL41 protein in inhibiting the IRE1/XBP1 signal pathway. Ectopic expression of UL41 decreased the expression of XBP1 and blocked XBP1 splicing activation induced by the ER stress inducer thapsigargin. Wild-type (WT) HSV-1, but not the UL41-null mutant HSV-1 (R2621), decreased XBP1 mRNA induced by thapsigargin. Nevertheless, infection with both WT HSV-1 and R2621 without drug pretreatment could reduce the mRNA and protein levels of XBP1(s), and additional mechanisms might contribute to this inhibition of XBP1(s) during R2621 infection. Taking these findings together, our results reveal XBP1 as a novel target of UL41 and provide insights into the mechanism by which HSV-1 modulates the IRE1/XBP1 pathway.

IMPORTANCE
During viral infection, viruses hijack the host translation apparatus to produce large amounts of viral proteins, which leads to ER stress. To restore ER homeostasis, cells initiate the UPR to alleviate the effects of ER stress. The IRE1/XBP1 pathway is the most conserved UPR branch, and it activates ER-associated protein degradation (ERAD) to reduce the ER load. The IRE1/XBP1 branch is repressed during HSV-1 infection, but little is known about the underlying molecular mechanism. Our results show for the first time that UL41 suppresses the IRE1/XBP1 signal pathway by reducing the accumulation of XBP1 mRNA, and characterization of the underlying molecular mechanism provides new insight into the modulation of UPR by HSV-1.
Temporal ocular coherence tomography-measured changes in anterior chamber angle and diurnal intraocular pressure after laser iridoplasty: IMPACT study
Authors: Bourne Rupert R A , Zhekov Ivailo , Pardhan Shahina 
Published: December 2016

AimsTo evaluate temporal change in anterior chamber angle anatomy following argon laser peripheral iridoplasty (ALPI) in eyes with occludable angles postlaser peripheral iridotomy (LPI) compared with control eyes. Additionally, the effect on diurnal intraocular pressure (DIOP) fluctuation (maximum-minimum IOP) was investigated.MethodsTwenty-two patients with bilateral primary angle closure/suspects with gonioscopically occludable anterior chamber angles following LPI were randomised to receive ALPI (n=11) or no further treatment (n=11). Angle opening distance (AOD), trabecular-iris angle, angle recess area and trabecular-iris space area were measured over eight sections with swept-source anterior segment optical coherence tomography and DIOP was measured pre-LPI and repeated at 3 months after ALPI (hourly measures).ResultsAll angle parameters increased following ALPI. This change was maintained for 3 months in seven of the eight sections (eg, inferotemporal AOD500 increased by 0.063 mm, p=0.004 at 1 day; 0.051 mm, p=0.029 at 1 week; 0.059 mm, p=0.006 at 6 weeks and 0.056 mm, p=0.011 at 3 months). The only exception was in the inferior sector (eg, AOD500 increased by 0.041 mm, p=0.025 at 1 day and by 0.029 mm, p=0.054 at 3 months). DIOP at 3 months was significantly reduced (5.04 mm Hg; ±1.61 mm Hg) compared with controls (6.61 mm Hg; ±1.63 mm Hg). Maximum IOP was significantly greater in the non-ALPI group (1.87 mm Hg, p=0.026).ConclusionsALPI widened all angle sections in eyes that remained occludable post-LPI. Changes were maintained for 3 months. ALPI decreased DIOP fluctuation in the treated eyes by lowering the maximum IOP value.