bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Kidney Injury Biomarkers Predict an Increase in Serum Milrinone Concentration Earlier Than Serum Creatinine–Defined Acute Kidney Injury in Infants After Cardiac Surgery
Authors: Gist Katja M. , Cooper David S. , Wrona Julia , Faubel Sarah , Altmann Christopher , Gao Zhiqian , Marino Bradley S. , Alten Jeffrey , Hock Kristal M. , Mizuno Tomoyuki , Vinks Alexander A. , Joy Melanie S. , Wempe Michael F. , Bennett Michael R. , Goldstein Stuart L.
Published: March 2018

Background:

Milrinone, an inotropic agent used ubiquitously in children after cardiac surgery, accumulates in acute kidney injury (AKI). We assessed if urinary AKI biomarkers are predictive of an increase in milrinone concentrations in infants after cardiac surgery.

Methods:

Multicenter prospective pilot study of infants undergoing cardiac surgery. Urinary AKI biomarkers were measured in the urine at specific time intervals after cardiopulmonary bypass initiation. AKI was defined using the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Serum milrinone concentrations were measured at specific intervals after drug initiation, dose changes, and termination. Excessive milrinone activity was defined as a 20% increase in serum concentration between 6 and 36 hours after initiation. The temporal relationship between urinary AKI biomarker concentrations and a 20% increase in milrinone concentration was assessed.

Results:

AKI occurred in 31 (33%) of infants. Milrinone clearance was lower in patients with AKI (4.2 versus 5.6 L/h/70 kg; P = 0.02). Excessive milrinone activity was associated with development of serum creatinine–defined AKI [odds ratio (OR) 3.0; 95% confidence interval (CI), 1.21–7.39; P = 0.02]. Both tissue inhibitor metalloproteinase type 2 and insulin-like growth factor–binding protein type 7 (TIMP-2*IGFBP-7) ≥0.78 at 12 hours (OR 2.72; 95% CI, 1.01–7.38; P = 0.04) and kidney injury molecule 1 (KIM-1) ≥529.57 at 24 hours (OR 2.76; 95% CI, 1.06–7.17; P = 0.04) predicted excessive milrinone activity before a diagnosis of AKI.

Conclusions:

In this pilot study, urine TIMP-2*IGFBP-7 and KIM-1 were predictive of AKI and excessive milrinone activity. Future studies that include a pharmacodynamics assessment of patient hemodynamics, excessive milrinone activity, and AKI biomarker concentrations may be warranted to integrate this concept into clinical practice.
Pyoderma Gangrenosum Secondary to Severe Congenital Neutropenia
Authors: Wakabayashi Nao , Tosa Mamiko , Anzai Shinichi , Ogawa Rei
Published: March 2018

We encountered a case of a man who was diagnosed with severe congenital neutropenia as a child and presented at the age of 45 years with pyoderma gangrenosum (PG) of the lower leg. PG associates with an underlying systemic disease, most commonly inflammatory bowel, rheumatic, or hematological disease or malignancy. However, in many cases, the underlying disease was not known. Surgery can trigger PG. The histopathological features of PG were nonspecific, and diagnosis requires excluding other conditions that have a similar appearance. Our analyses showed that the PG in our case was secondary to severe congenital neutropenia, which had promoted an infection of keratinous cysts. The patient bore a mutation in the ELANE gene encoding neutrophil elastase. Only 1 other case of neutropenia-associated PG has been reported previously: the association was only suspected. The present complex case was effectively treated by systemic treatment of the neutropenia with granulocyte colony–stimulating factor and regional surgical treatment. Histology of the excised tissue revealed keratinous cysts that were diffusely distributed with inflammatory granulation tissue. We believe that the rupture of the walls of the keratinous cysts may have caused the PG. At the time of writing (3 years since the initial presentation), the PG has not recurred. This case shows the importance of performing detailed examinations, including blood tests, to determine the disease underlying PG. This was because if the underlying disease was identified, its treatment was likely to promote healing of the wound after local surgery and prevent recurrence.
A New Approach for the Calculation of Total Corneal Astigmatism Considering the Magnitude and Orientation of Posterior Corneal Astigmatism and Thickness
Authors: Piñero David P. , Caballero María T. , Nicolás-Albujer Juan M. , de Fez Dolores , Camps Vicent J.
Published: March 2018

Purpose:

To evaluate a new method of calculation of total corneal astigmatism based on Gaussian optics and the power design of a spherocylindrical lens (C) in the healthy eye and to compare it with keratometric (K) and power vector (PV) methods.

Methods:

A total of 92 healthy eyes of 92 patients (age, 17–65 years) were enrolled. Corneal astigmatism was calculated in all cases using K, PV, and our new approach C that considers the contribution of corneal thickness. An evaluation of the interchangeability of our new approach with the other 2 methods was performed using Bland–Altman analysis.

Results:

Statistically significant differences between methods were found in the magnitude of astigmatism (P < 0.001), with the highest values provided by K. These differences in the magnitude of astigmatism were clinically relevant when K and C were compared [limits of agreement (LoA), −0.40 to 0.62 D), but not for the comparison between PV and C (LoA, −0.03 to 0.01 D). Differences in the axis of astigmatism between methods did not reach statistical significance (P = 0.408). However, they were clinically relevant when comparing K and C (LoA, −5.48 to 15.68 degrees) but not for the comparison between PV and C (LoA, −1.68 to 1.42 degrees).

Conclusions:

The use of our new approach for the calculation of total corneal astigmatism provides astigmatic results comparable to the PV method, which suggests that the effect of pachymetry on total corneal astigmatism is minimal in healthy eyes.
A Randomized, Double-blind, Active-controlled Clinical Trial of a Cell Culture-derived Inactivated Trivalent Influenza Vaccine (NBP607) in Healthy Children 6 Months Through 18 Years of Age
Authors: Oh Chi Eun , Choi Ui-Yoon , Eun Byung Wook , Lee Taek Jin , Kim Ki Hwan , Kim Dong Ho , Kim Nam Hee , Jo Dae Sun , Shin Sun Hee , Kim Kyung-Ho , Kim Hun , Kim Yun-Kyung
Published: March 2018

Background:

Although a number of cell culture–derived influenza vaccines have been approved for use in adults, there have been few clinical trials of cell culture–derived seasonal influenza vaccines for young children.

Methods:

We conducted a randomized, double-blind phase III clinical trial to evaluate the safety and immunogenicity of a cell culture–derived subunit trivalent inactivated influenza vaccine (NBP607, SK Chemicals Co., Ltd., Seongnam, Korea) in healthy children 6 months of age through 18 years. Subjects were randomized to receive either a study vaccine or an egg-based control vaccine. Antibody levels were measured by the hemagglutination inhibition assay, using cell-derived antigens. Solicited adverse events were assessed for 7 days after each injection. Serious adverse events were collected for 6 months after vaccination.

Results:

A total of 374 participants completed the study. No deaths, vaccine-related serious adverse events or withdrawals resulting from adverse events were reported. Rates of solicited and unsolicited adverse events were similar in 2 groups. Overall, NBP607 met the immunogenicity criteria of the Committee for Proprietary Medicinal Products for the 3 influenza strains. Between the NBP607 group and the control group, immunogenicity endpoints were comparable. Participants younger than 3 years of age had lower immunologic responses against the influenza B virus in both the NBP607 group and the control group.

Conclusions:

The immunogenicity and safety were comparable between the NBP607 group and the control group. NBP607 is well tolerated and immunogenic in children 6 months of age through 18 years.
Congenital Cytomegalovirus and HIV Perinatal Transmission
Authors: Adachi Kristina , Xu Jiahong , Ank Bonnie , Watts D. Heather , Camarca Margaret , Mofenson Lynne M. , Pilotto Jose Henrique , Joao Esau , Gray Glenda , Theron Gerhard , Santos Breno , Fonseca Rosana , Kreitchmann Regis , Pinto Jorge , Mussi-Pinhata Marisa M. , Machado Daisy Maria , Ceriotto Mariana , Morgado Mariza G. , Bryson Yvonne J. , Veloso Valdilea G. , Grinsztejn Beatriz , Mirochnick Mark , Moye Jack , Nielsen-Saines Karin
Published: March 2018

Background:

Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy.

Methods:

cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy. Neonatal urines obtained at birth were tested for CMV DNA by qualitative and reflex quantitative real-time polymerase chain reaction.

Results:

Urine specimens were available for 992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was 470,276 copies/ml (range: < 200–2,000,000 copies/ml). Among 89 HIV-infected infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected infants (P < 0.0001). cCMV was present in 23.2% of infants with in utero and 9.1% infants with intrapartum HIV infection (P < 0.0001). Rates of cCMV among HIV-infected infants were 4-fold greater (adjusted OR, 4.4; 95% CI: 2.3–8.2) and 6-fold greater among HIV in utero–infected infants (adjusted OR, 6; 95% CI: 3–12.1) compared with HIV-exposed, uninfected infants. cCMV was not associated with mode of delivery, gestational age, Apgar scores, 6-month infant mortality, maternal age, race/ethnicity, HIV viral load or CD4 count. Primary cCMV risk factors included infant HIV-infection, particularly in utero infection.

Conclusion:

High rates of cCMV with high urinary CMV VL were observed in HIV-exposed infants. In utero HIV infection appears to be a major risk factor for cCMV in infants whose mothers have not received combination antiretroviral therapy in pregnancy.
Community-acquired Pneumonia With Pleural Effusion in Children and Municipal Human Development Index in Rio de Janeiro, Brazil
Authors: Land Marcelo , Maia Paula , de Fátima March Maria , Ferreira Alvaro , Sant´Anna Clemax
Published: March 2018

Background:

This study evaluated admissions with severe community-acquired pneumonia (CAP) with pleural effusion (PE) in a pediatric university hospital and the impact of the increased average municipal human development index (M-HDI) in the local incidence of the disease in the last decade.

Methods:

This is a retrospective longitudinal study of patients (0–13 years old) with CAP. The municipal human development index (M-DHI) of the place of residence of patients was obtained. We calculate the crude odds ratios (ORs) of variables related to risk of developing PE. The variables that reached a significance level of 80% (P < 0.20) were selected for multivariate analysis. The logistic regression model was used for the selection of the parsimonious model, according to the likelihood ratio.

Results:

The 465 patients’ ages ranged from 1 to 174 months. The median of age (months) in children with PE was 36.00; in children without the PE was 29.00 (P < 0.011); media of variation in M-HDI in the period in patients with PE was 0.767 ± 0.002 and in patients without PE was 0.778 ± 0.002 (P < 0.001). In the logistic regression model, the absence of comorbidity (OR = 2.909) and the HDI < 0.770 (OR = 3.015) were predictive factors associated with PE.

Conclusion:

The progressive increase of the M-DHI during the study period, although to a slightly higher level, was correlated with the reduction in the number of admissions with CAP with PE.
Cost-effectiveness of CI in developing countries
Authors: Magro Isabelle , Emmett Susan D. , Saunders James
Published: March 2018

Purpose of review

Cost-effectiveness of cochlear implants is a major concern for expanding these services to low-income and middle-income developing countries.

Recent findings

Recent studies have applied appropriate methodology to make determination of cost-effectiveness for cochlear implants in developing countries. In addition, important parameters that effect cost-effectiveness have been reviewed in a systematic way. The combination of these new studies along with existing reports of cochlear implant programmes in developing countries allows for a discussion of cost and outcomes determinants that drive cost-effectiveness in these environments.

Cochlear implants are a very cost-effective treatment for profound hearing loss in all high-resource countries and in many low-income and middle-income developing countries. A number of cost considerations affect cost-effectiveness of cochlear implants in developing countries including device cost and device-related expenses such as power consumption and reliability, but also including rehabilitation and access-related expenses. Large-scale programmes confer an advantage for cost-effectiveness, primarily through device-related savings.
The “Double Whammy”: Women's Experiences of Weight Gain After Diagnosis and Treatment for Schizophrenia Spectrum Disorders
Authors: Haracz Kirsti , Hazelton Michael , James Carole
Published: March 2018

High levels of lifestyle risk factors compound medication side effects, resulting in high rates of obesity among people with schizophrenia spectrum disorders (SSDs). Obesity and related comorbidities increase the levels of disability and disadvantage in this population. Little research has explored the lived experiences in relation to this issue, and less has considered the experiences of women. Our aim in this study was to understand the experiences of women who gained weight after their diagnosis and treatment for SSDs. We carried out up to three in-depth qualitative interviews with 11 women over 2 years. Data were analyzed using constructivist grounded theory procedures. The women described a “double whammy”–like experience whereby weight gain and obesity came with their diagnosis and treatment of an SSD and brought with it additional challenges. The double whammy parallels the co-occurrence of mental illness and substance misuse. Implications of these parallels for service provision are discussed.
Biomedical Research Priorities for Modern Syphilis Clinical Management, Diagnosis, and Vaccines: Overview and Commentary for Unit 1
Authors: Kersh Ellen N. , Lukehart Sheila A.
Published: March 2018

The first session at the 2016 Syphilis Summit provided an opportunity for laboratory researchers and clinicians to comment on gaps in biomedical knowledge and technologies. Predominant themes in the presentations and discussion included the need for optimization of existing diagnostic tests, commercial availability, and Food and Drug Administration approval of nucleic acid amplification tests for primary and secondary syphilis, development of sensitive and specific new blood tests for diagnosis of active (vs treated) syphilis infection, clarification of the best measures for adequacy of response to treatment, continued study of complications of syphilis, including neurosyphilis and ocular syphilis, and development of a safe and effective vaccine that will protect against transmission and complications of disseminated infection (including congenital and neurosyphilis). Renewed and sustained support of biomedical syphilis research and an influx of talent could move the needle in the fight against this reemerging ancient disease.
Syphilis Vaccine Development: Requirements, Challenges, and Opportunities
Authors: Cameron Caroline E.
Published: March 2018

Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a prevalent disease in low- and middle-income countries, and has reemerged in key populations, including men who have sex with men, in high-income nations. The rising number of cases shows that syphilis elimination will require augmentation of public health screening and treatment campaigns with syphilis vaccine development and implementation initiatives. Optimal vaccine candidates, deciphered from careful consideration of the pathogenic mechanisms used by T. pallidum, will need to be paired with appropriate human-track adjuvants designed to elicit the correlates of protection needed to prevent infection/disease. This article provides an overview of the development pipeline customized for a syphilis vaccine, including the preferred product characteristics, the investment case, and a proposed vaccinogen selection strategy outlining the essential qualities that need to be targeted by a syphilis vaccine.
Acceptability and Feasibility of Rapid Chlamydial, Gonococcal, and Trichomonal Screening and Treatment in Pregnant Women in 6 Low- to Middle-Income Countries
Authors: Shannon Chelsea Lee , Bristow Claire , Hoff Nicole , Wynn Adriane , Nguyen Minh , Medina-Marino Andrew , Cabeza Jeanne , Rimoin Anne , Klausner Jeffrey D.
Published: March 2018

Background

Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) infections during pregnancy are linked with adverse birth outcomes. However, few countries have prenatal CT, NG, or TV screening programs. In this study, we aimed to evaluate the acceptability and feasibility of CT, NG, and TV screening and treatment among pregnant women across 6 low- to middle-income countries.

Methods

A total of 1817 pregnant women were screened for CT, NG, and TV in Botswana, the Democratic Republic of Congo, Haiti, South Africa, and Vietnam. An additional 640 pregnant women were screened for CT in Peru. Screening occurred between December 2012 and October 2017. Acceptability of screening was evaluated at each site as the proportion of eligible women who agreed to participate in screening. Feasibility of treatment was calculated as the proportion of women who tested positive that received treatment.

Results

Acceptability of screening and feasibility of treatment was high across all 6 sites. Acceptability of screening ranged from 85% to 99%, and feasibility of treatment ranged from 91% to 100%.

Discussion

The high acceptability and feasibility of screening and treatment of CT, NG, and TV among pregnant women supports further research to evaluate the cost-effectiveness of prenatal CT, NG, and TV screening programs.
Reactor Grids for Prioritizing Syphilis Investigations: Are Primary Syphilis Cases Being Missed?
Authors: Cha Susan , Matthias James M. , Rahman Mohammad , Schillinger Julia A. , Furness Bruce W. , Pugsley River A. , Kidd Sarah , Bernstein Kyle T. , Peterman Thomas A.
Published: March 2018

Background

Health departments prioritize investigations of reported reactive serologic tests based on age, gender, and titer using reactor grids. We wondered how reactor grids are used in different programs, and if administratively closing investigations of low-titer tests could lead to missed primary syphilis cases.

Methods

We obtained a convenience sample of reactor grids from 13 health departments. Interviews with staff from several jurisdictions described the role of grids in surveillance and intervention. From 5 jurisdictions, trends in reactive nontreponemal tests and syphilis cases over time (2006–2015) were assessed by gender, age, and titer. In addition, nationally-reported primary syphilis cases (2013–2015) were analyzed to determine what proportion had low titers (≤1:4) that might be administratively closed by grids without further investigation.

Results

Grids and follow-up approaches varied widely. Health departments in the study received a total of 48,573 to 496,503 reactive serologies over a 10-year period (3044–57,242 per year). In 2006 to 2015, the number of reactive serologies increased 37% to 169%. Increases were largely driven by tests for men although the ratios of tests per reported case remained stable over time. Almost one quarter of reported primary syphilis had low titers that would be excluded by most grids. The number of potentially missed primary syphilis cases varied by gender and age with 41- to 54-year-old men accounting for most.

Conclusions

Reactor grids that close tests with low titers or from older individuals may miss some primary syphilis cases. Automatic, computerized record searches of all reactive serologic tests could help improve prioritization.
Reduction in Mortality Following Pediatric Rapid Response Team Implementation*
Authors: Kolovos Nikoleta S. , Gill Jeff , Michelson Peter H. , Doctor Allan , Hartman Mary E.
Published: March 2018

Objective:

To evaluate the effectiveness of a physician-led rapid response team program on morbidity and mortality following unplanned admission to the PICU.

Design:

Before-after study.

Setting:

Single-center quaternary-referral PICU.

Patients:

All unplanned PICU admissions from the ward from 2005 to 2011.

Interventions:

The dataset was divided into pre- and post-rapid response team groups for comparison.

Measurements and Main Results:

A Cox proportional hazards model was used to identify the patient characteristics associated with mortality following unplanned PICU admission. Following rapid response team implementation, Pediatric Risk of Mortality, version 3, illness severity was reduced (28.7%), PICU length of stay was less (19.0%), and mortality declined (22%). Relative risk of death following unplanned admission to the PICU after rapid response team implementation was 0.685.

Conclusions:

For children requiring unplanned admission to the PICU, rapid response team implementation is associated with reduced mortality, admission severity of illness, and length of stay. Rapid response team implementation led to more proximal capture and aggressive intervention in the trajectory of a decompensating pediatric ward patient.
Survival and Long-Term Functional Outcomes for Children With Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation
Authors: Torres-Andres Francesc , Fink Ericka L. , Bell Michael J. , Sharma Mahesh S. , Yablonsky Eric J. , Sanchez-de-Toledo Joan
Published: March 2018

Objectives:

To identify patient- and disease-related factors related to survival and favorable outcomes for children who underwent extracorporeal cardiopulmonary resuscitation after a refractory cardiac arrest.

Design:

Retrospective observational study with prospective assessment of long-term functional outcome.

Patients:

Fifty-six consecutive children undergoing extracorporeal cardiopulmonary resuscitation at our institution from 2007 to 2015. Median age at arrest was 3.5 months (interquartile range, 1–53).

Setting:

Tertiary pediatric university hospital with a referral heart center.

Interventions:

Health-related quality of life and family functioning assessment with the Pediatric Quality of Life Inventory and the McMaster Family Assessment Device.

Measurements and Main Results:

Fifty-eight consecutive extracorporeal cardiopulmonary resuscitation episodes were included, with 46 (79.3%) related to primary cardiac conditions. Initial cannulation site was central in 19 (32.8%) and peripheral in 39 (67.2%). Survival to decannulation was 77.6% with survival at hospital discharge and at the end of the follow-up period being 65.5% and 62.1%, respectively. Time to follow-up was 38 months (interquartile range, 19–52). Patients who survived tended to be younger (3.5 mo [1 mo to 2 yr] vs 7 mo [1.25 mo to 17 yr]; p = 0.3) with decreased extracorporeal cardiopulmonary resuscitation times (28 min [15–47 min] vs 37.5 min [28.5–55 min]; p = 0.04). Those who received therapeutic hypothermia tended to have higher hospital survival (21/28 [75%] vs 16/29 [55%]; p = 0.08). Follow-up assessments of survivors demonstrated good quality of life and family functioning (Pediatric Quality of Life Inventory, 84 [76–89.5]; McMaster Family Assessment Device, 1.62 [1.33–1.83]).

Conclusions:

In this series, extracorporeal cardiopulmonary resuscitation was associated with relatively high survival rates and a good health-related quality of life and family functioning. Larger series are needed to assess whether this technique should be more broadly available in the pediatric critical care community.
Hospital Variation in Intensive Care Resource Utilization and Mortality in Newly Diagnosed Pediatric Leukemia*
Authors: Fitzgerald Julie C. , Li Yimei , Fisher Brian T. , Huang Yuan-Shung , Miller Tamara P. , Bagatell Rochelle , Seif Alix E. , Aplenc Richard , Thomas Neal J.
Published: March 2018

Objectives:

To evaluate hospital-level variability in resource utilization and mortality in children with new leukemia who require ICU support, and identify factors associated with variation.

Design:

Retrospective cohort study.

Setting:

Children’s hospitals contributing to the Pediatric Health Information Systems administrative database from 1999 to 2011.

Patients:

Inpatients less than 25 years old with newly diagnosed acute lymphocytic leukemia or acute myeloid leukemia requiring ICU support (n = 1,754).

Interventions, Measurements, and Main Results:

Evaluated exposures included leukemia type, year of diagnosis, and hospital-wide proportion of patients with public insurance. The main outcome was hospital mortality. Wide variability existed in the ICU resources used across hospitals. Combined acute lymphocytic leukemia and acute myeloid leukemia mortality varied by hospital from 0% (95% CI, 0–14.8%) to 42.9% (95% CI, 17.7–71.1%). A mixed-effects model with a hospital-level random effect suggests significant variation across hospitals in mortality (p = 0.007). When including patient and hospital factors as fixed effects into the model, younger age, acute myeloid leukemia versus acute lymphocytic leukemia diagnosis, leukemia diagnosis prior to 2005, hospital-wide proportion of public insurance patients, and hospital-level proportion of leukemia patients receiving ICU care are significantly associated with mortality. The variation across hospitals remains significant with all patient factors included (p = 0.021) but is no longer significant after adjusting for the hospital-level factors proportion of public insurance and proportion receiving ICU care (p = 0.48).

Conclusions:

Wide hospital-level variability in ICU resource utilization and mortality exists in the care of children with leukemia requiring ICU support. Hospital payer mix is associated with some mortality variability. Additional study into how ICU support could be standardized through clinical practice guidelines, impact of payer mix on hospital resources allocation to the ICU, and subsequent impact on patient outcomes is warranted.
Cognitive Impairment in Fibromyalgia: A Meta-Analysis of Case–Control Studies
Authors: Wu Yu-Lin , Huang Chun-Jen , Fang Su-Chen , Ko Ling-Hsin , Tsai Pei-Shan
Published: March 2018

Objective

Cognitive dysfunction has been reported in individuals with fibromyalgia. However, findings regarding cognitive function examined using neuropsychological tests have been inconsistent. The aim of the study was to determine domain-specific cognitive impairment in patients with fibromyalgia compared with healthy controls.

Methods

We conducted a meta-analysis that systematically searched six databases (PubMed, Ovid MEDLINE, Embase, CINAHL, PsycINFO, and Web of Science) for articles published before September 2017.

Results

Twenty-three case–control studies with a total of 2096 participants were included in the meta-analysis. Cognitive function was significantly lower (g = 0.87, 95% confidence interval [CI] = 0.60–1.15) in individuals with fibromyalgia than in healthy controls. Large effect sizes were found in learning/memory and attention/psychomotor speed (g = 0.94, p = .013; g = 1.22, p < .001, respectively); medium effect sizes were reported in executive function and working memory (g = 0.72, p < .001; g = 0.75, p < .001, respectively). Depression and anxiety scores were associated with the effect size of group differences in cognitive function (B = 0.11, p < .001, 95% CI = 0.09–0.13; B = 0.02, p < .001, 95% CI = 0.01–0.02, respectively).

Conclusions

Cognitive impairment across different cognitive domains was found in individuals with fibromyalgia compared with healthy controls. Mood states (depression and anxiety) may explain the heterogeneity across studies.
A Preliminary Study of Computed Tomography Coronary Angiography Within a Single Cardiac Cycle in Patients With Atrial Fibrillation Using 256-Row Detector Computed Tomography
Authors: Wen Bo , Xu Lei , Liang Junfu , Fan Zhanming , Sun Zhonghua
Published: March 2018

Objective

The purpose of this study was to evaluate the image quality and radiation dose of computed tomography (CT) coronary angiography using a 256-row detector CT scanner in a single cardiac cycle in patients with atrial fibrillation (AF).

Methods

Seventy consecutive patients (41 men and 29 women; age range was from 37 to 84 years, mean age was 61.7 ± 10.2 years; body mass index range was from 15.08 to 36.45 kg/m2, mean body mass index was 25.9 ± 3.5 kg/m2) with persistent or paroxysmal AF during acquisition, who were not receiving any medications for heart rate (HR) regulation, were imaged with a 256-row detector CT scanner (Revolution CT, GE healthcare). According to the HR or HR variability (HRV) the patients were divided into 4 groups: group A (HR, ≥75 bpm; n = 36), group B (HR, <75 bpm; n = 34), group C (HRV, ≥50 bpm; n = 26), and group D (HRV, <50 bpm; n = 44). The snapshot freeze algorithm reconstruction was used to reduce motion artifacts whenever necessary. Two experienced radiologists, who were blinded to the electrocardiograph and reconstruction information, independently graded the CT images in terms of visibility and artifacts with a 4-grade rating scale (1, excellent; 2, good; 3, poor; 4, insufficient) using the 18-segment model. Subjective image quality scores and effective dose (ED) were calculated and compared between these groups.

Results

The HR during acquisition ranged from 47 to 222 bpm (88.24 ± 36.80 bpm). A total of 917 in 936 coronary artery segments were rated as diagnostically evaluable (98.2 ± 0.04%). There was no significant linear correlation between mean image quality and HR or HRV (P > 0.05). Snapshot freeze reconstruction technique was applied in 28 patients to reduce motion artifacts and thus showed image quality was improved from 93.2% to 98.4%. The ED was 3.05 ± 2.23 mSv (0.49–11.86 mSv) for all patients, and 3.76 ± 2.22 mSv (0.92–11.17 mSv), 2.30 ± 2.02 mSv (0.49–11.86 mSv), 3.89 ± 2.35 mSv (1.18–11.86 mSv), and 2.56 ± 2.03 mSv (0.49–11.17 mSv) for groups A, B, C, and D, respectively. There were significant differences in mean ED between groups A and B, as well as C and D (P <0.05).

Conclusions

This study shows that CT coronary angiography with use of a new 256-row detector CT in single cardiac cycle achieves diagnostic image quality but with lower radiation dose in patients with AF. Heart rate or HRV has no significant effect on image quality.
Associations Between Risk Factors and Overactive Bladder: A Meta-analysis
Authors: Zhu Jingzhen , Hu Xiaoyan , Dong Xingyou , Li Longkun
Published: March 2018

Objective

The purpose of this study was to investigate the risk factors of overactive bladder (OAB).

Methods

The PubMed, Embase, and Cochrane Library databases were retrieved through May 2016. Odds ratios (OR) or standard mean differences (SMDs) with 95% confidence intervals (CIs) were used to evaluate the associations between risk factors and OAB. Heterogeneity among studies was examined using χ2 test based on the Q and I
2 tests.

Results

A total of 28 articles were analyzed in our study. The results suggested that age and body mass index were significantly higher in OAB patients than in non-OAB controls (SMDs [95% CIs], 0.30 [0.19–0.41] and 0.39 [0.24–0.53]). A significant negative association was found between employment status and OAB (OR [95% CIs], 0.64 [0.46–0.90]). However, sex, educational level, parity, vaginal delivery, race, menopause, marital status, smoking, and alcohol consumption were not significantly different in OAB and non-OAB control patients (ORs [95% CIs], 0.95 [0.59–1.55], 1.04 [0.82, 1.33], 0.98 [0.56–1.70], 1.66 [0.90–3.07], 0.98 [0.75–1.28], 1.84 [0.23–14.70], 0.97 [0.78–1.19], 0.91 [0.77–1.08], and 0.88 [0.71–1.09], respectively). In addition, the number of parities and vaginal deliveries in OAB patients also showed no significant differences compared with non-OAB control patients (SMDs [95% CI], 0.05 [−0.27 to 0.38] and −0.16 [0.40 to 0.09]).

Conclusions

This meta-analysis suggests that age and body mass index are associated with increased risks of OAB, whereas employment status is associated with a decreased risk of OAB. Further prospective studies with large sample sizes are needed to confirm this conclusion.
Dementia Prevalence in Greece
Authors: Kosmidis Mary H. , Vlachos George S. , Anastasiou Costas A. , Yannakoulia Mary , Dardiotis Efthimios , Hadjigeorgiou Georgios , Sakka Paraskevi , Ntanasi Eva , Scarmeas Nikolaos
Published: March 2018

Introduction:

Study of the epidemiology of dementia to gain insight into putative predisposing and prophylactic factors is the first step toward establishing effective preventive and therapeutic strategies for this ever-growing public health problem. Relevant data in Greece are scattered and outdated.

Methods:

We investigated dementia prevalence as part of a population-representative epidemiological study [Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)] in 2 Greek regions.

Results:

Our sample comprised 1792 adults 65 years of age or older, who received a full neurological and neuropsychological evaluation that led to a consensus diagnosis. The overall prevalence of dementia was 5.0%, with 75.3% of the cases attributed to Alzheimer disease. Dementia odds were 15.8% higher for every year of advancing age and 9.4% lower for every additional year of education. Carrying at least 1 APOE-ε4 allele doubled the risk of dementia, whereas sex did not exert a statistically significant effect.

Conclusions:

Our results are consistent with previous research in Southern European countries; dementia prevalence in Greece is in the lower range of what has been reported globally.
Proteome-level assessment of origin, prevalence and function of Leucine-Aspartic Acid (LD) motifs
Authors: Alam Tanvir , Alazmi Meshari , Naser Rayan , Huser Franceline , Momin Afaque A. , Walkiewicz Katarzyna W. , Canlas Christian G. , Huser Raphaël G. , Ali Amal J. , Merzaban Jasmeen , Bajic Vladimir B. , Gao Xin , Arold Stefan T.
Published: March 2018

Short Linear Motifs (SLiMs) contribute to almost every cellular function by connecting appropriate protein partners. Accurate prediction of SLiMs is difficult due to their shortness and sequence degeneracy. Leucine-aspartic acid (LD) motifs are SLiMs that link paxillin family proteins to factors controlling (cancer) cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin family is poorly understood. To enable a proteome-wide assessment of these motifs, we developed an active-learning based framework that iteratively integrates computational predictions with experimental validation. Our analysis of the human proteome identified a dozen proteins that contain LD motifs, all being involved in cell adhesion and migration, and revealed a new type of inverse LD motif consensus. Our evolutionary analysis suggested that LD motif signalling originated in the common unicellular ancestor of opisthokonts and amoebozoa by co-opting nuclear export sequences. Inter-species comparison revealed a conserved LD signalling core, and reveals the emergence of species-specific adaptive connections, while maintaining a strong functional focus of the LD motif interactome. Collectively, our data elucidate the mechanisms underlying the origin and adaptation of an ancestral SLiM.
Boosting diabetes and pre-diabetes screening in rural Ghana
Authors: Nyarko Bernard Effah , Amoah Rosemary Serwah , Crimi Alessandro
Published: March 2018

Background

Diabetes is a growing worldwide disease with serious consequences to health and with a high financial burden. Ghana is one of the developing African countries where the prevalence of diabetes is increasing. Moreover, many cases remain undiagnosed, when along with pre-diabetic cases they can be easily detected. Pre-diabetes condition occurs when blood sugar levels are higher than normal but are not high enough to be classified as diabetes, and it is still reversible.

The main objective of this study is to propose a novel method to increase diabetes and pre-diabetes early detection in rural areas. A secondary aim is to look for new related behavioral determinants specific to rural Ghana, by comparing subjects at risk with those already diagnosed as diabetic.

Methods

The screening approach was based on tests performed pro-actively by community nurses using glucometers and mobile phone apps. As a pilot for future policies, glycemic tests were carried out on 101 subjects from rural communities in Ghana deemed at risk and unaware of their diabetic/pre-diabetic status. A comparison of dietary and lifestyle habits of the screened people was conducted in regards to a cohort of 103 diabetic patients from the same rural communities.

Results

The pilot screening detected 2 diabetic subjects (2% of the cohort) showing WHO diabetic glycemic values, and 20 pre-diabetic subjects (19.8% of the cohort) which showed the effectiveness of the user-friendly approach. The need for further campaigns about alcohol consumption and physical activities has emerged even in rural areas.

Conclusions

Policies based on prevention screening as reported in the manuscript have the potential to reduce diabetes incidence, if actions are taken while patients are pre-diabetic, reduce complication related to late diagnosis and indirectly related health-care costs in the country.
Chromatin accessibility is dynamically regulated across C. elegans development and ageing
Authors: Jänes Jürgen , Dong Yan , Schoof Michael , Serizay Jacques , Appert Alex , Cerrato Chiara , Woodbury Carson , Chen Ron , Gemma Carolina , Huang Ni , Kissiov Djem , Stempor Przemysław , Steward Annette , Zeiser Eva , Sauer Sasha , Ahringer Julie
Published: March 2018

An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,714 protein-coding promoters and 19,231 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing.
Expanding an expanded genome: long-read sequencing ofTrypanosoma cruzi
Authors: Berná Luisa , Rodríguez Matías , Chiribao María Laura , Parodi-Talice Adriana , Pita Sebastián , Rijo Gastón , Alvarez-Valin Fernando , Robello Carlos
Published: March 2018

Although the genome ofTrypanosoma cruzi, the causative agent of Chagas disease, was first made available in 2005, with additional strains reported later, the intrinsic genome complexity of this parasite (abundance of repetitive sequences and genes organized in tandem) has traditionally hindered high-quality genome assembly and annotation. This also limits diverse types of analyses that require high degree of precision. Long reads generated by third-generation sequencing technologies are particularly suitable to address the challenges associated withT. cruzi´sgenome since they permit directly determining the full sequence of large clusters of repetitive sequences without collapsing them. This, in turn, allows not only accurate estimation of gene copy numbers but also circumvents assembly fragmentation. Here, we present the analysis of the genome sequences of twoT. cruziclones: the hybrid TCC (DTU TcVI) and the non-hybrid Dm28c (DTU TcI), determined by PacBio SMRT technology. The improved assemblies herein obtained permitted us to accurately estimate gene copy numbers, abundance and distribution of repetitive sequences (including satellites and retroelements). We found that the genome ofT. cruziis composed of a "core compartment" and a "disruptive compartment" which exhibit opposite gene and GC content composition. New tandem and disperse repetitive sequences were identified, including some located inside coding sequences. Additionally, homologous chromosomes were separately assembled, allowing us to retrieve haplotypes as separate contigs instead of a unique mosaic sequence. Finally, manual annotation of surface multigene families MUC and trans-sialidases allows now a better overview of these complex groups of genes.
Single-step Enzymatic Glycoengineering for the Construction of Antibody-cell Conjugates
Authors: Li Jie , Chen Mingkuan , Liu Zilei , Zhang Linda , Felding Brunie H. , Lauvau Gregoire , Abadier Michael , Ley Klaus , Wu Peng
Published: March 2018

Employing live cells as therapeutics is a direction of future drug discovery. An easy and robust method to modify the surfaces of cells directly to incorporate novel functionalities is highly desirable. However, many current methods for cell-surface engineering interfere with cells’ endogenous properties. Here we report an enzymatic approach that enables the transfer of biomacromolecules, such as a full length IgG antibody, to the glycocalyx on the surfaces of live cells when the antibody is conjugated to the enzyme’s natural donor substrate GDP-fucose. This method is fast and biocompatible with little interference to cells’ endogenous functions. We applied this method to construct two antibody-cell conjugates (ACCs) using different immune cells, and the modified cells exhibited specific tumor targeting and resistance to inhibitory signals produced by tumor cells, respectively. Remarkably, Herceptin-NK-92MI conjugates exhibits enhanced activities to induce the lysis of HER2+ cancer cells both ex vivo and in a murine tumor model, indicating its potential for further development as a clinical candidate.
Thioredoxins induce oocyte maturation in holothuroids (Echinodermata)
Authors: Leonet Aline , Delroisse Jérôme , Schuddinck Christopher , Wattiez Ruddy , Jangoux Michel , Eeckhaut Igor
Published: March 2018

Chromatographic fractions of a rough extract of echinoid spawn (REES) has been demonstrated to efficiently induce oocyte maturation in aspidochirote holothuroids. The method is so efficient that it is now used in holothuriculture to get fertilised eggs even outside the reproductive period of the aquacultured species. We here isolate and identify from echinoid spawns the molecule responsible for the induction of the oocyte maturation in the Mediterranean holothuroidHolothuria tubulosaand the Indo-PacificHolothuria scabra. The use of proteinase K and dialysing membranes indicates that the active molecule is a protein with a molecular weight superior to 12,000 kDa. The active molecule has been isolated on G-100 Sephadex chromatography column. Active chromatographic fractions include seven proteins identified with nanoLC-MS/MS technique. One of them, identify as a thioredoxin-2 and to which the nameTrx-REEShas been given, leads up to levels of maturation similar to those obtained with the REES and with a commercial thioredoxin extracted fromEscherichia coli. Occurrence of thioredoxin in REES was confirmed by immunoblot analysis, and the maturation-inducing properties of thioredoxin were positively checked in using anti-thioredoxin antibodies. A peptide of 6 AAs corresponding to the active site ofTrx-REES, composed of WCNPCK, was synthesised and its efficiency in holothuroid oocyte maturation tested. At some concentrations, the peptide was 1.2 times more active than the REES.
Identification of cyclic hexapeptides natural products with inhibitory potency against Mycobacterium tuberculosis
Authors: Singh Sheo B. , Odingo Joshua , Bailey Mai A. , Sunde Bjorn , Korkegian Aaron , O’Malley Theresa , Ovechkina Yulia , Ioerger Thomas R. , Sacchettini James C. , Young Katherine , Olsen David B. , Parish Tanya
Published: March 2018

A set of ∼500 purified natural product compounds was screened for inhibition against the human pathogen Mycobacterium tuberculosis. A series of cyclic hexapeptides with anti-tubercular activity was identified. Five analogs from a set of sixteen closely related compounds were active, with minimum inhibitory concentrations ranging from 2.3-8.9 μM. Eleven structural analogs had no significant activity (MIC > 20 μM) demonstrating structure activity relationship. Sequencing of resistant mutant isolates failed to identify changes accounting for the resistance phenotype.
A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs
Authors: Zhang Shasha , Guo Longhua , Guerrero-Hernández Carlos , Ross Eric J , Gotting Kirsten , McKinney Sean A. , Wang Wei , Xiang Youbin , Hawley R. Scott , Sánchez Alvarado Alejandro
Published: March 2018

Understanding how stem cells and their progeny maintain and regenerate reproductive organs is of fundamental importance. The freshwater planarianSchmidtea mediterraneaprovides an attractive system to study these processes because its hermaphroditic reproductive system (RS) arises post-embryonically and when lost can be fully and functionally regenerated from the proliferation and regulation of experimentally accessible stem and progenitor cells. By controlling the function of a nuclear hormone receptor gene (nhr-1), we established conditions in which to study the formation, maintenance and regeneration of both germline and somatic tissues of the planarian RS. We found thatnhr-1(RNAi) not only resulted in the gradual degeneration and complete loss of the adult hermaphroditic RS, but also in the significant downregulation of a large cohort of genes associated with lipid metabolism. One of these,Smed-acs-1, a homologue of Acyl-CoA synthetase, was indispensable for the development, maintenance and regeneration of the RS, but not for the homeostasis or regeneration of other somatic tissues. Remarkably, supplementingnhr-1(RNAi) animals with either bacterial Acyl-CoA synthetase or the lipid metabolite Acetyl-CoA rescued the phenotype restoring the maintenance and function of the hermaphroditic RS. Our findings uncovered a likely evolutionarily conserved role for nuclear hormone receptors and lipid metabolism in the regulation of stem and progenitor cells required for the long-term maintenance and regeneration of animal reproductive organs, tissues and cells.
Longitudinal single cell fate of hematopoiesis in vivo using cellular barcoding and DiSNE movie visualization
Authors: Gao Jerry , Lin Dawn S. , Crampin Edmund , Naik Shalin H.
Published: March 2018

Identifying the progeny of many single progenitor cells simultaneously can be achieved by tagging progenitors with unique heritable DNA barcodes, and allows inferences of lineage relationships, including longitudinally. While this approach has shed new light on single cell fate heterogeneity, data interpretation remains a major challenge. In this study, we applied our developmental interpolated t-Distributed Stochastic Neighbor Embedding (DiSNE) movie approach to visualize the clonal dynamics of hematopoietic reconstitution in primates and identify novel developmental patterns, namely a potential cluster of hematopoietic progenitors with early T cell and later granulocyte production.

Key points

Complex single cell haematopoietic fate heterogeneity can be visualized and assessed with tSNE pie maps

DiSNE movie visualization of in vivo haematopoiesis allows “play back” of the waves of haematopoiesis

Identification of novel hematopoietic progenitors with early T cell and later granulocyte production