bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal Disorders in Acute Human Immunodeficiency Virus Infection: A Case Series
Authors: Panichsillapakit Theppharit , Patel Derek , Santangelo Joanne , Richman Douglas D. , Little Susan J. , Smith Davey M.
Published: January 2016

Background.  The gastrointestinal (GI) tract is important in the pathogenesis of human immunodeficiency virus (HIV) infection. We report a case series of lower GI endoscopic and histopathologic findings of HIV-infected individuals after presentation with acute infection.

Methods.  We performed a retrospective case review of individuals infected with HIV who enrolled between August 2010 and April 2013 in a primary infection treatment trial. All participants started the trial during acute infection and underwent colonoscopy with biopsies at baseline and after the start of antiretroviral treatment.

Results.  Twenty acutely infected individuals were included in the study (mean age, 33 years; range, 20–54 years). All participants were male who reported having receptive anal sex as an HIV risk factor. Nine individuals (45%) had at least 1 finding by colorectal pathology; 1 person had 2 diagnoses (diverticulosis and focal active proctitis). The histopathological findings revealed anal dysplasia in 3 cases: 2 had high-grade anal intraepithelial neoplasia (AIN) and 1 had low-grade AIN. Two persons had a colorectal polyp, 1 hyperplastic and 1 adenomatous. Three persons were diagnosed with diverticulosis, and 2 persons were diagnosed with proctitis, including 1 with focal active proctitis and 1 with cytomegalovirus proctitis.

Conclusions.  To our knowledge, this is the first case series report of lower GI disorders in acute HIV-infected individuals. Although the causal relationship remains uncertain, we describe the endoscopic findings that were observed during acute HIV infection among men who have sex with men. Understanding the prevalence of these pathologies may likely shed light on how acute HIV infection damages the lower GI tract.
Phase 1 Safety and Immunogenicity Study of a Quadrivalent Seasonal Flu Vaccine Comprising Recombinant Hemagglutinin-Flagellin Fusion Proteins
Authors: Tussey Lynda , Strout Cynthia , Davis Matthew , Johnson Casey , Lucksinger Gregg , Umlauf Scott , Song Langzhou , Liu Ge , Abraham Katalin , White C. Jo
Published: January 2016

Background.  We evaluated the safety and immunogenicity of VAX2012Q, a quadrivalent influenza vaccine comprising 4 hemagglutinin subunits fused to flagellin.

Methods.  In this dose-ranging, open-label study, healthy adults (18–40 years) were divided into 7 cohorts for evaluation of 5 dose levels and 3 component ratios. Dose levels were as follows: (1) 1 mcg per component of VAX128C (H1N1), VAX181 (H3N2), VAX173 (B-YAM), and VAX172 (B-VIC), respectively; (2) 2 mcg per component, respectively; (3) 2, 4, 4, and 4 mcg of each component, respectively; (4) 2, 4, 6, and 6 mcg of each component, respectively; and (5) 3 mcg per component, respectively. Tolerability and immunogenicity data were analyzed.

Results.  Three hundred sixteen subjects received VAX2012Q (309 per protocol). At all dose levels, 54% to 65% of subjects reported mild injection site pain, the most common local reaction. Moderate injection site pain increased at dose levels 2 through 5 (22%–42%, compared with 20% at dose level 1). Systemic symptoms were mostly mild to moderate with moderate symptoms increasing in dose levels 3 and 4. Three dose level 3 subjects (6%) reported severe, transient chills and or fever. Mean fold rises in hemagglutination inhibition titers ranged from 2.5 to 6.9 despite high baseline titers. Mean seroprotection rates were ≥90% and mean seroconversion rates were ≥40% for all strains in all groups postvaccination.

Conclusions.  VAX2012Q elicited immune responses at all dose levels with no significant safety concerns. Doses of 2 or 3 mcg per component provided a favorable balance of tolerability and immunogenicity.
The Effect of Switching to Second-Line Antiretroviral Therapy on the Risk of Opportunistic Infections Among Patients Infected With Human Immunodeficiency Virus in Northern Tanzania
Authors: Ramadhani Habib O. , Bartlett John A. , Thielman Nathan M. , Pence Brian W. , Kimani Stephen M. , Maro Venance P. , Mwako Mtumwa S. , Masaki Lazaro J. , Mmbando Calvin E. , Minja Mary G. , Lirhunde Eileen S. , Miller William C.
Published: January 2016

Background.  Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure, and healthcare providers’ confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching are associated with the risk of opportunistic infections (OI) among patients with unrecognized treatment failure is critical to improve patient outcomes.

Methods.  A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happened at <3 and ≥3 months, respectively, after failure diagnosis was made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing OI.

Results.  Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of OI (adjusted hazards ratio [AHR], 0.4; 95% CI, .2–.6). Compared with patients who received timely switch after failure diagnosis was made, those who delayed switching were more likely to develop OI (AHR, 2.2; 95% CI, 1.1–4.3).

Conclusion.  Delayed switching to second-line ART after failure diagnosis may increase the risk of OI. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes.
Swift/BAT and MAXI/GSC broadband transient monitor
Authors: Sakamoto Takanori , Oda Ryoma , Mihara Tatehiro , Yoshida Atsumasa , Arimoto Makoto , Barthelmy Scott D. , Kawai Nobuyuki , Krimm Hans A. , Nakahira Satoshi , Serino Motoko
Published: January 2016

We present a newly developed broadband transient monitor using the Swift Burst Alert Telescope (BAT) and the MAXI Gas Slit Camera (GSC) data. Our broadband transient monitor keeps vigil for high-energy transient sources from 2 keV to 200 keV in seven energy bands by combining the BAT (15–200 keV) and the GSC (2–20 keV) data. Currently, daily and 90-minute (one orbit) averaged light curves are available for 106 high-energy transient sources. This transient monitor is available to the public through our web server, http://yoshidalab.mydns.jp/bat_gsc_trans_mon/, for wider use by the community. We discuss a daily sensitivity of our monitor and possible future improvements on our pipeline.
Does Ondansetron Modify Sympathectomy Due to Subarachnoid Anesthesia?
Authors: Terkawi Abdullah S. , Mavridis Dimitris , Flood Pamela , Wetterslev Jørn , Terkawi Rayan S. , Bin Abdulhak Aref A. , Nunemaker Megan S. , Tiouririne Mohamed
Published: January 2016

AbstractAbstract

This study assessed the efficacy of ondansetron using standard meta-analysis and more recently developed statistical techniques including small trial bias assessments, selection models, and trial sequential analyses. This study fails to confirm evidence that ondansetron reduces the incidence of hypotension and bradycardia after subarachnoid anesthesia.

Supplemental Digital Content is available in the text.

Background

Disagreement among many underpowered studies has led to an equivocal understanding of the efficacy of the 5-HT3 antagonist ondansetron in preventing the consequences of sympathectomy after subarachnoid anesthesia. The authors assessed the efficacy of ondansetron with respect to the overall quality and statistical power of the meta-analyses.

Methods

The authors used a standard and a newer method of meta-analysis, trial sequential analysis (TSA), to estimate adjusted CIs based on how much information has been accrued. They also used random-effects meta-analyses techniques, small trial bias assessment, selection models, sensitivity analyses, and the Grading of Recommendations on Assessment, Development, and Evaluation system. These results from the aforementioned techniques were compared, and importance of consideration of these factors was discussed.

Results

Fourteen randomized placebo-controlled trials (1,045 subjects) were identified and analyzed. By using conventional meta-analyses, the authors determined that ondansetron was associated with reduction in the incidence of hypotension (relative risk = 0.62 [95% CI, 0.46 to 0.83], P = 0.001; TSA-adjusted CI, 0.34 to 1.12; I
2 = 60%, P = 0.002) and bradycardia (relative risk = 0.44 [95% CI, 0.26 to 0.73], P = 0.001; TSA-adjusted CI, 0.05 to 3.85; I
2 = 0%, P = 0.84). However, the authors found indications of bias among these trials. TSAs demonstrated that the meta-analysis lacked adequate information size and did not achieve statistical significance when adjusted for sparse data and repetitive testing. The Grading of Recommendations on Assessment, Development, and Evaluation system showed that the results had low to very low quality of evidence.

Conclusions

The analyses fail to confirm evidence that ondansetron reduces the incidence of hypotension and bradycardia after subarachnoid anesthesia due to the risk of bias and information sizes less than the required. As results from meta-analysis are given significant weight, it is important to carefully evaluate the quality of the evidence that is input.
A Novel Neonatal Feeding Intolerance and Necrotizing Enterocolitis Risk–Scoring Tool Is Easy to Use and Valued by Nursing Staff
Authors: Naberhuis Jane , Wetzel Christine , Tappenden Kelly A.
Published: January 2016

Background:

Preterm infants are at increased risk of developing feeding intolerance and necrotizing enterocolitis. Comprehensive, targeted nursing assessments can evaluate the risk for and identify early signs of these conditions in an effort to prevent their destructive sequela.

Purpose:

While the long-term goal is to develop a validated risk-scoring tool for the prediction of feeding intolerance and necrotizing enterocolitis, the objective of the preliminary phase presented here is to assess the ease of use and nurses' attitudes toward a novel feeding intolerance and necrotizing enterocolitis risk–scoring tool.

Methods:

A novel risk-scoring nursing tool was implemented in a University of Illinois–affiliated 48-bed level III neonatal intensive care unit. Data were collected from the electronic medical record of all preterm infants with parental consent during the initial 6-month study period. Scoring accuracy (accuracy of selection of risk factors based on electronic medical record data), ease of use, and nurses' attitudes toward the tool were assessed at the study site and by evaluators at a national neonatal nursing conference.

Results:

Fourteen nurses scored 166 tools on the 63 enrolled infants. Sixteen tools (9.6%) contained errors. Mean study site tool ease of use was 8.1 (SD: 2.2) on a 10-point scale. Ninety percent of conference evaluators agreed/strongly agreed that the tool addressed important knowledge gaps.

Implications for Practice:

The tool is easy to use and valued by nurses. Following validation, widespread implementation is expected to be a clinically feasible means to improve infant clinical outcomes for minimal time and financial cost.

Implications for Research:

Tool validation and refinement based on nursing feedback will improve its broad applicability and predictive utility.
Prospective Assessment of the Oncogenic Risk to Patients From Fluoroscopy During Trauma Surgery
Authors: Beebe Michael J. , Jenkins Peter , Rothberg David L. , Kubiak Erik N. , Higgins Thomas F.
Published: January 2016

Objective:

Concern about radiation exposure during surgery has focused on surgeon exposure. However, the patient receives exposure that is more direct and, in surgery about the pelvis and hip, internal pelvic nonskeletal organs often cannot be shielded without obscuring the region of surgical interest. The purpose of this study was to prospectively evaluate patients' radiation exposure during fracture surgery of the acetabulum, pelvic ring, and femur to calculate future cancer incidence (CI).

Design:

Prospective descriptive cohort.

Setting:

Level-1 trauma center.

Patients/Participants:

One hundred eight patients with acetabulum, pelvic, or femur fractures requiring operative repair were prospectively enrolled.

Intervention:

Dosimeters were placed in locations determined for each surgery type by a medical physicist.

Main Outcome Measurements:

Demographics, operative records, and average x-ray emission energy were recorded. Effective dose, specific organ doses, and lifetime CI for a 30-year-old patient were calculated.

Results:

Diagnoses included 27 acetabular fractures, 30 intertrochanteric femur fractures, 26 femoral shafts, and 25 pelvic ring injuries. Patients with pelvic ring injuries received the highest effective dose at 0.91 ± 0.74 mSv. The average lifetime increase in CI, for any cancer type, after pelvic ring fixation is 0.0097% for females and 0.0062% for males. The greatest mean single-organ dose to the ovaries (3.82 ± 3.34 mGy) occurred during pelvic ring surgery, correlating to an increased ovarian cancer risk of 0.0013%. The greatest mean single-organ dose to the prostate (6.81 ± 5.91 mSv) also occurred during pelvic surgery, correlating to increased prostate cancer risk of 0.0024%.

Conclusions:

Fracture surgery to the pelvis and femur is exceptionally fluoroscopy-dependent; however, the radiation exposure incurred represents a relatively small increased risk of future cancer development in patients.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Intramedullary Nailing of Tibial Shaft Fractures: Size Matters
Authors: Donegan Derek J. , Akinleye Sheriff , Taylor Ryan M. , Baldwin Keith , Mehta Samir
Published: January 2016

Objectives:

To determine optimal ratio of intramedullary nail diameter to tibial canal diameter that leads to reliable and timely healing in tibial shaft fractures.

Design:

Retrospective case series.

Setting:

Level I trauma center.

Patients:

One hundred thirty-three fractures in 132 patients with tibial shaft fractures that underwent intramedullary nailing as definitive fixation were identified between June 2004 and July 2012 at our level I trauma center. Of these, 78 had serial radiographs out to 12 months that could be analyzed for radiographic healing with an average age of 37 years old (range 16–86 years). There were 52 males and 26 females.

Intervention:

All patients underwent intramedullary nailing of the tibia with documentation of both the diameter of the nail and radiographic canal width at the isthmus to determine the nail to canal ratio.

Main Outcome Measures:

Patients were followed with serial radiographs for at least 12 months to determine time to healing as a function of nail to canal ratio. The senior author assessed healing at 3, 6, 9, and 12 months using RUST criteria.

Results:

Patients with an intramedullary nail to canal diameter ratio of less than 0.8 or greater than 0.99 were 4.4 times more likely not to heal than patients with a ratio of between 0.8 and 0.99.

Conclusion:

The ideal intramedullary nail to tibial canal diameter ratio to optimize tibial shaft fracture healing is between 0.8 and 0.99.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Focused Critical Care Echocardiography: Development and Evaluation of an Image Acquisition Assessment Tool*
Authors: Gaudet Jonathan , Waechter Jason , McLaughlin Kevin , Ferland André , Godinez Tomás , Bands Colin , Boucher Paul , Lockyer Jocelyn
Published: January 2016

Objectives:

Little attention has been placed on assessment tools to evaluate image acquisition quality for focused critical care echocardiography. We designed a novel assessment tool to objectively evaluate the image acquisition skills of critical care trainees learning focused critical care echocardiography and examined the tool for evidence of validity.

Design:

Prospective observational study.

Setting:

Medical-surgical ICUs at a tertiary care teaching hospital.

Subjects:

Trainees in our critical care medicine fellowship program.

Interventions:

Six trainees completed a focused critical care echocardiography training curriculum followed by performing 20 transthoracic echocardiograms on patients receiving invasive mechanical ventilation. At three assessment intervals (the 1st and 2nd examinations, 10th and 11th examinations, and 19th and 20th examinations), echocardiograms performed by trainees were compared with those of critical care physicians certified in echocardiography and scored according to the focused critical care echocardiography assessment tool. The primary outcome was an efficiency score (overall assessment tool score divided by examination time). Differences in mean efficiency scores between echocardiographers of differing skill levels and changes in trainees’ mean efficiency scores with increasing focused critical care echocardiography experience were compared by using t tests.

Measurements and Main Results:

On the initial assessment, mean efficiency scores (sd) for trainees and experienced physicians were 1.55 (0.95) versus 2.78 (1.38), respectively (p = 0.02), and for the second and third assessments, the corresponding efficiency ratings for trainees and experienced physicians were 2.48 (0.97) versus 4.55 (1.32) (p < 0.01) and 2.61 (1.37) versus 4.17 (2.12) (p = 0.04), respectively.

Conclusions:

Trainees’ efficiency in focused critical care echocardiography image acquisition improved quickly in the first 10 studies, yet, it could not match with the performance of experienced physicians after 20 focused critical care echocardiography studies. The focused critical care echocardiography assessment tool demonstrated evidence of validity and could discern changes in trainees’ image acquisition performance with increasing experience.
SUCCESSFUL REPAIR OF RECURRENT OPTIC DISK PIT MACULOPATHY WITH AUTOLOGOUS PLATELET RICH PLASMA: REPORT OF A SURGICAL TECHNIQUE
Authors: Todorich Bozho , Sharma Sumit , Vajzovic Lejla
Published: January 2016

Purpose:

To describe vitreoretinal surgical technique of using autologous platelet-rich plasma to aid in surgical repair of optic pit maculopathy refractive to previous vitrectomy.

Methods:

A case of an 18-year-old woman presenting with serous macular detachment secondary to optic pit is reported. Patient had previously undergone vitrectomy and peripapillary laser, but had recurrence of subretinal fluid and worsening visual acuity. Autologous platelet-rich plasma was harvested from the patient's blood and purified using Arthrex ACP kit (Arthrex, Inc, Naples, FL). Repeat pars plana vitrectomy was performed with internal limiting membrane peeling extending to the optic nerve. Platelet-rich plasma was layered over the pit and long-acting gas tamponade performed with face-down positioning.

Results:

At 8 months of follow-up, subretinal fluid was resolved, the connection between optic pit and subretinal space collapsed and the ellipsoid zone near completely reconstituted on optical coherence tomography. The patient's vision improved significantly from 20/100 to 20/50, which is largely limited by posterior subcapsular cataract.

Conclusion:

Platelet-rich plasma can augment anatomical and visual outcomes in surgical repair of optic pit maculopathy.
Assessing Intraoperative Bleeding Risk in Patients Undergoing Coronary Artery Bypass Grafting with Prior Exposure to Clopidogrel: Single Center Retrospective Analysis
Authors: Chen Kevin , Garg Jalaj , Malekan Ramin , Spielvogel David , Ahmad Hasan
Published: January 2016

In patients undergoing coronary artery bypass grafting (CABG), intraoperative and postoperative major bleeding requiring blood transfusions and surgical reexploration is associated with increased mortality and morbidity. Our study hypothesized that exposure to clopidogrel is not significantly associated with increased risk for intraoperative bleeding, even when administered less than 5 days before CABG. We also aimed to determine variables associated with intraoperative packed red blood cell (iPRBC) transfusion. Patients of both sexes aged 18 years or older who underwent CABG from July 1, 2011 to December 31, 2012 were included in the analysis. Study population consisted of 2 groups—clopidogrel arm and nonclopidogrel arm. Patients were included in clopidogrel arm if they were exposed to clopidogrel in the past (as one of their home medications or received the medication for first time during the index hospitalization), whereas patients who never received clopidogrel were included in nonclopidogrel arm. We identified a total of 303 adult patients who underwent CABG with a mean age was 64.5 years. Mortality rate in our study was 0.99% (n = 3) with increased mortality in women as compared with men (3.27% vs. 0.41%, P = 04). The mean iPRBC transfused were 1.68 units, with higher units being transfused in women as compared with men (2.23 vs. 1.49 units, respectively, P = 0.03) and no significant difference between clopidogrel and nonclopidogrel arms (1.92 vs. 1.50, respectively, P = 0.18). After multivariate analysis, age [odds ratio (OR) = 1.03, P = 0.01], female sex (OR = 2.61, P = 0.006) and hypertension (OR = 7.10, P = 0.02) predicted increased iPRBC transfusion. Clopidogrel or nonclopidogrel status was not associated with increased iPRBC transfusion (OR = 1.06, P = 0.81). iPRBC transfusion rates were similar in both arms with age, female sex, and hypertension being an independent predictor of iPRBC transfusion.
SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments
Authors: Page Andrew J. , Taylor Ben , Delaney Aidan J. , Soares Jorge , Seemann Torsten , Keane Jacqueline A. , Harris Simon R.
Published: January 2016

Rapidly decreasing genome sequencing costs have led to a proportionate increase in the number of samples used in prokaryotic population studies. Extracting single nucleotide polymorphisms (SNPs) from a large whole genome alignment is now a routine task, but existing tools have failed to scale efficiently with the increased size of studies. These tools are slow, memory inefficient and are installed through non-standard procedures. We presentSNP-siteswhich can rapidly extract SNPs from a multi-FASTA alignment using modest resources and can output results in multiple formats for downstream analysis. SNPs can be extracted from a 8.3 GB alignment file (1,842 taxa, 22,618 sites) in 267 seconds using 59 MB of RAM and 1 CPU core, making it feasible to run on modest computers. It is easy to install through the Debian and Homebrew package managers, and has been successfully tested on more than 20 operating systems.SNP-sitesis implemented in C and is available under the open source license GNU GPL version 3.
ELF3 polyQ variation inArabidopsis thalianareveals PIF4-independent role in thermoresponsive flowering
Authors: Press Maximilian O. , Lanctot Amy , Queitsch Christine
Published: January 2016

Plants have evolved elaborate mechanisms controlling developmental responses to environmental stimuli. A particularly important stimulus is temperature. Previous work has identified the interplay of PIF4 and ELF3 as a central circuit underlying thermal responses inArabidopsis thaliana. However, thermal responses vary widely among strains, possibly offering mechanistic insights into the wiring of this circuit. ELF3 contains a polyglutamine (polyQ) tract that is crucial for ELF3 function and varies in length across strains. Here, we use transgenic analysis to test the hypothesis that natural polyQ variation in ELF3 is associated with the observed natural variation in thermomorphogenesis. We found little evidence that the polyQ tract plays a specific role in thermal responses beyond modulating general ELF3 function. Instead, we made the serendipitous discovery that ELF3 plays a crucial, PIF4-independent role in thermoresponsive flowering under conditions more likely to reflect field conditions. We present evidence that ELF3 acts through the photoperiodic pathway, pointing to a previously unknown symmetry between low and high ambient temperature responses. Moreover, in analyzing two strain backgrounds with vastly different thermal responses, we demonstrate that responses may be shifted rather than fundamentally rewired across strains. Our findings tie together disparate observations into a coherent framework in which multiple pathways converge in accelerating flowering in response to temperature, with some such pathways modulated by photoperiod.
Dynamic Distribution and Interaction of the Arabidopsis SRSF1 Subfamily Splicing Factors
Authors: Stankovic Nancy , Schloesser Marie , Joris Marine , Sauvage Eric , Hanikenne Marc , Motte Patrick
Published: January 2016

Ser/Arg-rich (SR) proteins are essential nucleus-localized splicing factors. Our prior studies showed that Arabidopsis (Arabidopsis thaliana) RSZ22, a homolog of the human SRSF7 SR factor, exits the nucleus through two pathways, either dependent or independent on the XPO1 receptor. Here, we examined the expression profiles and shuttling dynamics of the Arabidopsis SRSF1 subfamily (SR30, SR34, SR34a, and SR34b) under control of their endogenous promoter in Arabidopsis and in transient expression assay. Due to its rapid nucleocytoplasmic shuttling and high expression level in transient assay, we analyzed the multiple determinants that regulate the localization and shuttling dynamics of SR34. By site-directed mutagenesis of SR34 RNA-binding sequences and Arg/Ser-rich (RS) domain, we further show that functional RRM1 or RRM2 are dispensable for the exclusive protein nuclear localization and speckle-like distribution. However, mutations of both RRMs induced aggregation of the protein whereas mutation in the RS domain decreased the stability of the protein and suppressed its nuclear accumulation. Furthermore, the RNA-binding motif mutants are defective for their export through the XPO1 (CRM1/Exportin-1) receptor pathway, but retain nucleocytoplasmic mobility. We performed a yeast two hybrid screen with SR34 as bait and discovered SR45 as a new interactor. SR45 is an unusual SR splicing factor bearing two RS domains. These interactions were confirmed in planta by FLIM-FRET and BiFC and the roles of SR34 domains in protein-protein interactions were further studied. Altogether, our report extends our understanding of shuttling dynamics of Arabidopsis SR splicing factors.
The Physiology of Adventitious Roots
Authors: Steffens Bianka , Rasmussen Amanda
Published: January 2016

Adventitious roots are plant roots that form from any nonroot tissue and are produced both during normal development (crown roots on cereals and nodal roots on strawberry [Fragaria spp.]) and in response to stress conditions, such as flooding, nutrient deprivation, and wounding. They are important economically (for cuttings and food production), ecologically (environmental stress response), and for human existence (food production). To improve sustainable food production under environmentally extreme conditions, it is important to understand the adventitious root development of crops both in normal and stressed conditions. Therefore, understanding the regulation and physiology of adventitious root formation is critical for breeding programs. Recent work shows that different adventitious root types are regulated differently, and here, we propose clear definitions of these classes. We use three case studies to summarize the physiology of adventitious root development in response to flooding (case study 1), nutrient deficiency (case study 2), and wounding (case study 3).
Engineering Triterpene and Methylated Triterpene Production in Plants Provides Biochemical and Physiological Insights into Terpene Metabolism
Authors: Jiang Zuodong , Kempinski Chase , Bush Caroline J. , Nybo S. Eric , Chappell Joe
Published: January 2016

Linear, branch-chained triterpenes, including squalene (C30), botryococcene (C30), and their methylated derivatives (C31–C37), generated by the green alga Botryococcus braunii race B have received significant attention because of their utility as chemical and biofuel feedstocks. However, the slow growth habit of B. braunii makes it impractical as a production system. In this study, we evaluated the potential of generating high levels of botryococcene in tobacco (Nicotiana tabacum) plants by diverting carbon flux from the cytosolic mevalonate pathway or the plastidic methylerythritol phosphate pathway by the targeted overexpression of an avian farnesyl diphosphate synthase along with two versions of botryococcene synthases. Up to 544 µg g−1 fresh weight of botryococcene was achieved when this metabolism was directed to the chloroplasts, which is approximately 90 times greater than that accumulating in plants engineered for cytosolic production. To test if methylated triterpenes could be produced in tobacco, we also engineered triterpene methyltransferases (TMTs) from B. braunii into wild-type plants and transgenic lines selected for high-level triterpene accumulation. Up to 91% of the total triterpene contents could be converted to methylated forms (C31 and C32) by cotargeting the TMTs and triterpene biosynthesis to the chloroplasts, whereas only 4% to 14% of total triterpenes were methylated when this metabolism was directed to the cytoplasm. When the TMTs were overexpressed in the cytoplasm of wild-type plants, up to 72% of the total squalene was methylated, and total triterpene (C30+C31+C32) content was elevated 7-fold. Altogether, these results point to innate mechanisms controlling metabolite fluxes, including a homeostatic role for squalene.
THI1, a Thiamine Thiazole Synthase, Interacts with Ca2+-Dependent Protein Kinase CPK33 and Modulates the S-Type Anion Channels and Stomatal Closure in Arabidopsis
Authors: Li Chun-Long , Wang Mei , Wu Xiao-Meng , Chen Dong-Hua , Lv Hong-Jun , Shen Jian-Lin , Qiao Zhu , Zhang Wei
Published: January 2016

Thiamine is required for both plant growth and development. Here, the involvement of a thiamine thiazole synthase, THI1, has been demonstrated in both guard cell abscisic acid (ABA) signaling and the drought response in Arabidopsis (Arabidopsis thaliana). THI1 overexpressors proved to be more sensitive to ABA than the wild type with respect to both the activation of guard cell slow type anion channels and stomatal closure; this effectively reduced the rate of water loss from the plant and thereby enhanced its level of drought tolerance. A yeast two-hybrid strategy was used to screen a cDNA library from epidermal strips of leaves for THI1 regulatory factors, and identified CPK33, a Ca2+-dependent protein kinase, as interactor with THI1 in a plasma membrane-delimited manner. Loss-of-function cpk33 mutants were hypersensitive to ABA activation of slow type anion channels and ABA-induced stomatal closure, while the CPK33 overexpression lines showed opposite phenotypes. CPK33 kinase activity was essential for ABA-induced stomatal closure. Consistent with their contrasting regulatory role over stomatal closure, THI1 suppressed CPK33 kinase activity in vitro. Together, our data reveal a novel regulatory role of thiamine thiazole synthase to kinase activity in guard cell signaling.
A higher frequency of IL‐10‐producing B cells in Hepatitis B virus‐associated membranous nephropathy
Authors: Liu Yong , Wang Haifeng , Hu Xintong , Qu Zhihui , Zhang Huimao , Crew Rebecca , Ayana Desalegn Admassu , Li Man , Qiu Jinpeng , Jiang Yanfang
Published: January 2016

The purpose of this study is to elucidate the potential role of interleukin (IL)‐10+ regulatory B cells and other B cell subsets in the development of hepatitis B virus‐associated membranous nephropathy (HBV‐MN). A total of 14 patients with new onset HBV‐MN, 12 individuals with immune‐tolerant HBV infection (HBV‐IT), and 12 healthy controls (HC) were examined for the percentages of CD38+, CD86+, CD27+, CD95+ and IL‐10+ B cells by flow cytometry. Serum IL‐10 concentration was examined by enzyme‐linked immunosorbent assay (ELISA). The percentages of CD38+CD19+, CD86+CD19+, CD38+CD86+CD19+, and CD95+CD19+ B cells were significantly higher in HBV‐MN patients than the HBV‐IT and HC. The percentages of CD5+CD19+, IL‐10+CD19+ B cells and serum IL‐10 level in HBV‐MN patients were significantly higher than the HC, and lower than the HBV‐IT. Percentages of CD38+CD19+, and CD86+CD19+ B cells were reduced after treatment, while the percentages of CD5+CD1d+CD19+, CD5+CD1d+IL‐10+CD19+, and IL‐10+CD19+ B cells were increased. The 24 h urinary protein concentration was positively correlated with the percentage of CD38+CD19+, and negatively correlated with the percentage of IL‐10+CD19+ B cells and serum IL‐10 level. Similarly, the value of eGFR was negatively correlated with the percentage of CD38+CD19+, and positively correlated with the percentage of IL‐10+CD19+ B cells and serum IL‐10 level. Serum IL‐10 level and the percentage of IL‐10+CD19+ were negatively correlated with the percentages of CD38+CD19+, and CD86+CD19+ B cells. These results suggest that CD86+CD19+, CD38+CD86+CD19+, CD95+CD19+, and especially CD38+CD19+ and IL‐10+CD19+ cells may participate in the pathogenesis of HBV‐MN.
Identifying the challenges and opportunities to meet the needs of children with speech, language and communication difficulties
Authors: Dockrell Julie E. , Howell Peter
Published: January 2016

The views of experienced educational practitioners were examined with respect to the terminology used to describe children with speech, language and communication needs (SLCN), associated problems and the impact of speech and language difficulties in the classroom. Results showed that education staff continue to experience challenges with the range of terminology used to refer to the children's needs. Terms used to refer to difficulties with speech were least familiar to the respondents. Difficulties were noted in distinguishing between children with SLCN and children where English was an additional language. Respondents indicated a variety of additional difficulties experienced by the children. Literacy difficulties were reported to be more prevalent in children with language difficulties, while levels of bullying and anxiety were reported to be higher in children with speech problems. Respondents reported that tools for identifying speech and language difficulties and procedures for accessing effective resources are required.
Multi‐sensory storytelling: a tool for teaching or an intervention technique?
Authors: Preece David , Zhao Yu
Published: January 2016

This article reports on research undertaken to investigate how multi‐sensory storytelling (MSST) was being used within schools for students with profound and multiple learning difficulties and other special educational needs. Semi‐structured interviews (n = 27) and observations (n = 18) were undertaken in five schools in the East Midlands and south‐east of England. The study identified that MSST was considered to contribute to the curriculum access, assessment, learning and socialisation of students across a wide range of special educational needs. Key opportunities, applications and barriers to use were identified. Findings from this study indicated that the way these teachers used MSST differed from extant research in this area with regard to both design and delivery. It is suggested that the desire to develop a quantitative evidence base may present unnecessary restrictions which inhibit the recognition of pedagogic issues; and that a more fluid conceptualisation of MSST would be reflective of real‐world practice.
Effects of sample design and landscape features on a measure of environmental heterogeneity
Authors: Christianson Danielle S. , Kaufman Cari G.
Published: January 2016

Environmental heterogeneity, an important influence on organisms and ecological processes, can be quantified by the variance of an environmental characteristic over all locations within a study extent. However on landscapes with autocorrelation and gradient patterns, estimating this variance from a sample of locations may lead to errors that cannot be corrected with statistical techniques.

We analytically derived the relative expected sampling error of sample designs on landscapes with particular gradient pattern and autocorrelation features. We applied this closed‐form approach to temperature observations from an existing study. The expected heterogeneity differed, both in magnitude and direction, amongst sample designs over the study site's likely range of autocorrelation and gradient features.

We conducted a simulation study to understand the effects of (i) landscape variability and (ii) design variability on an average sampling error. On 10 000 simulated landscapes with varying gradient and autocorrelation features, we compared estimates of variance from a variety of structured and random sample designs. While gradient patterns and autocorrelation cause large errors for some designs, others yield near‐zero average sampling error. Sample location spacing is a key factor in sample design performance. Random designs have larger range of possible sampling errors than structured designs due to the potential for sample arrangements that over‐ and under‐sample certain areas of the landscape.

When implementing a new sample design to quantify environmental heterogeneity via variance, we recommend using a simple structured design with appropriate sample spacing. For existing designs, we recommend calculating the relative expected sampling error via our analytical derivation.
Childhood trauma, family history, and their association with mood disorders in early adulthood
Authors: Jansen K. , Cardoso T. A. , Fries G. R. , Branco J. C. , Silva R. A. , Kauer‐Sant'Anna M. , Kapczinski F. , Magalhaes P. V. S.
Published: January 2016

Objective

To assess the prevalence of childhood trauma and types of trauma on mood disorders among young adults in a population‐based sample. We further gathered data on family history of mood disorders to test the hypothesis that childhood trauma is a mediating factor for the association between family history of mood disorder and mood disorder in adulthood.

Method

This is a cross‐sectional study, including young adults with bipolar disorder, major depressive disorder, and matched controls without any mood disorder. Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). The Hicks and Tingley implementation was employed to assess whether trauma is a mediator of the effect of family history on diagnosis of any mood disorder.

Results

All types of trauma were associated with both major depression and bipolar disorder, with the exception of sexual abuse, which was only associated with bipolar disorder. Moreover, family history of psychiatric illness was also associated with mood disorder in adulthood and with childhood trauma. Using the presence of any mood disorder as the outcome, a third of the effect of having any family history of mood disorder was mediated via childhood trauma.

Conclusion

This investigation provides further support, in a population‐based sample of young adults, of the association between childhood trauma and mood disorders, with sexual abuse being specifically linked with bipolar disorder. The hypothesis that childhood trauma would function as a partial mediator of the association between family history of mood disorder and mood disorder in adulthood was also confirmed.
Topiramate for cocaine dependence: a systematic review and meta‐analysis of randomized controlled trials
Authors: Singh Mohit , Keer Dipinder , Klimas Jan , Wood Evan , Werb Dan
Published: January 2016

Aims

To assess the efficacy of topiramate in treating cocaine use disorder (i.e. retention, efficacy, safety and craving reduction) through a systematic review and meta‐analysis.

Methods

We searched six scientific databases from inception to 23 December 2014 with no date limits. Data were reviewed, extracted and analysed systematically. Studies were included if they were peer‐reviewed randomized control trials with participants meeting diagnostic criteria for cocaine dependence or cocaine use disorder, with the treatment arm involving topiramate with or without psychosocial intervention, and the control arm involving no intervention or psychosocial intervention with or without placebo. A random‐effects meta‐analytical model was computed.

Results

Five studies met inclusion criteria (n = 518). Topiramate was compared with placebo (four studies) and no medication (one study). In a meta‐analysis, we observed no significant differences between topiramate and placebo in improving treatment retention risk ratio (RR) = 0.85; 95% confidence interval (CI) = 0.60–1.22, P = 0.38. However, compared with a placebo, use of topiramate was associated with increased continuous abstinence in two of five studies (RR = 2.43; 95% CI = 1.31–4.53, P = 0.005). No differences were observed in frequency of adverse effects reported between topiramate and placebo (RR = 1.06; 95% CI = 0.91–1.23, P = 0.48). Topiramate was associated significantly (P < 0.05) with a reduction in craving in only one of five studies.

Conclusions

Evidence does not currently support the use of topiramate to improve treatment retention for cocaine use disorder, although it may extend cocaine abstinence with a similar risk of adverse events compared with placebo.
Impact of men's dairy intake on assisted reproductive technology outcomes among couples attending a fertility clinic
Authors: Xia Wei , Chiu Yu‐Han , Afeiche Myriam C. , Williams Paige L. , Ford Jennifer B. , Tanrikut Cigdem , Souter Irene , Hauser Russ , Chavarro Jorge E. ,   the EARTH study team
Published: January 2016

Intake of full‐fat dairy has been linked to lower semen quality but whether this leads to decreased fertility is unknown. To address this question, we prospectively evaluated the association of men's dairy intake with treatment outcomes of subfertile couples undergoing assisted reproductive technology (ART). We followed 142 men from couples undergoing infertility treatment withARTat an academic fertility centre between 2007 and 2014. Couples completed dietary assessments prior to treatment, and the female partners underwent a total of 248ARTcycles. Multivariable generalized linear mixed models were used to examine the association of dairy intake with fertilization, implantation, clinical pregnancy and live birth rates adjusting for age, body mass index, smoking status, total exercise time, dietary patterns, alcohol, caffeine, total energy intake, and female dairy intake. Intake of dairy foods, regardless of their fat content, was not associated with fertilization, implantation, clinical pregnancy or live birth rates. The adjusted live birth rates (95% confidence interval) for couples in increasing quartiles of men's dairy intake were 0.42 (0.25, 0.60), 0.25 (0.13, 0.42), 0.26 (0.15, 0.41), and 0.44 (0.27, 0.63) (plinear trend = 0.73). Results remained similar after adjustment for female partner intake of dairy foods. Overall, men's dairy intake was not associated with treatment outcomes of couples undergoingART.
Involvement of homocysteine, homocysteine thiolactone, and paraoxonase type 1 (PON‐1) in the etiology of defective human sperm function
Authors: Aitken R. J. , Flanagan H. M. , Connaughton H. , Whiting S. , Hedges A. , Baker M. A.
Published: January 2016

This study reports, for the first time, the significant (p ≤ 0.01) accumulation of homocysteine residues in low density, defective sperm suspensions isolated from patients attending an infertility clinic. This overabundance of homocysteine was not related to a deficiency in folate availability but may have been a reflection of the oxidative stress that characterizes such defective sperm populations. Direct addition of the homocysteine cyclic congener, homocysteine thiolactone, to human spermatozoa resulted in the rapid induction of mitochondrial reactive oxygen species (ROS) generation (p < 0.001), the stimulation of lipid peroxidation (p < 0.01), the promotion of tyrosine phosphorylation (p < 0.001), and the suppression of sperm motility (p < 0.001) in the absence of any significant impact on DNA integrity. The parent homocysteine molecule was less active and took 24 h to stimulate mitochondrial ROS production possibly because of the need to convert this compound to the corresponding thiolactone before it could exert a measureable biological effect. Thiolactone was also effective in suppressing the carboxymethylation of key proteins in the sperm tail, which are thought to be involved in the regulation of sperm movement. The major enzyme responsible for removing thiolactone from proteins, paraoxonase (PON‐1), was shown to be a major target for alkylation by lipid aldehydes, such as 4‐hydroxynonenal, generated as a consequence of oxidative stress. Exposure of human spermatozoa to such aldehydes resulted in a dose‐dependent accumulation of homocysteine in spermatozoa (p < 0.03). These results suggest that one of the consequences of oxidative stress in mammalian spermatozoa is the inhibition of PON‐1, which then enhances the availability of homocysteine thiolactone to interact with the epsilon‐amino group of lysine residues on sperm proteins, triggering a raft of significant biological changes in these cells that ultimately compromise sperm function.
Posterior corneal astigmatism in refractive lens exchange surgery
Authors: Rydström Elin , Westin Oscar , Koskela Timo , Behndig Anders
Published: January 2016

Purpose

To assess the anterior, posterior and total corneal spherical and astigmatic powers in patients undergoing refractive lens exchange (RLE) surgery.

Methods

In 402 consecutive patients planned for RLE at Koskelas Eye Clinic, Luleå, Sweden, right eye data from pre‐ and postoperative subjective refraction, preoperative IOLMaster® biometry and Pentacam HR® measurements were collected. Postoperative Pentacam HR® data were collected for 54 of the patients. The spherical and astigmatic powers of the anterior and posterior corneal surfaces and for the total cornea were assessed and compared, and surgically, induced astigmatism was calculated using vector analysis.

Results

The spherical power of the anterior corneal surface was 48.18 ± 1.69D with an astigmatic power of 0.83 ± 0.54D. The corresponding values for the posterior surface were −6.05 ± 2,52D and 0.26 ± 0.15D, respectively. The total corneal spherical power calculated with ray tracing was 42.47 ± 2.89D with a 0.72 ± 0.48D astigmatic power, and the corresponding figures obtained by estimating the posterior corneal surface were 43.25 ± 1.51D (p < 0.001) with a 0.75 ± 0.49D astigmatic power (p = 0.003). In eyes with anterior astigmatism with‐the‐rule, the total corneal astigmatism is overestimated if the posterior corneal surface is estimated; in eyes, with against‐the‐rule astigmatism it is underestimated. Had the posterior corneal surface been measured in this material, 14.7% of the patients would have received a spheric instead of a toric IOL, or vice versa.

Conclusion

Estimating the posterior corneal surface in RLE patients leads to systematic measurement errors that can be reduced by measuring the posterior surface. Such an approach can potentially increase the refractive outcome accuracy in RLE surgery.