bluuebunny/crossref_metadata_2025 huggingface dataset:
Nr5a1b promotes and Nr5a2 inhibits transcription of lhb in the orange-spotted grouper, Epinephelus coioides†
Authors: Shi Boyang , Lu Huijie , Zhang Lihong , Zhang Weimin
Published: July 2019

Nr5a1 (Sf-1) up-regulates lhb expression across vertebrates; however, its regulatory roles on fshb remain to be defined. Moreover, the involvement of Nr5a2 in the regulation of gonadotropin expression is not clear either. In the present study, the involvement of Nr5a1b (a homologue of Nr5a1) and Nr5a2 in the regulation of lhb and fshb expression in the orange-spotted grouper was examined. Dual fluorescent immunohistochemistry using homologous antisera showed that in the pituitary of orange-spotted groupers, Lh cells contain both immunoreactive Nr5a1b and Nr5a2 signals, whereas Fsh cells contain neither of them. In LβT2 cells, Nr5a1b up-regulated basal activities of lhb and fshb promoters possibly via Nr5a sites, and synergistically (on lhb promoter) or additively (on fshb promoter) with forskolin. Surprisingly, Nr5a2 inhibited basal activities of lhb promoter possibly via Nr5a sites and attenuated the stimulatory effects of both forskolin and Nr5a1b. In contrast, Nr5a2 had no effects on fshb promoter. Chromatin immunoprecipitation analysis showed that both Nr5a1b and Nr5a2 bound to lhb promoter, but not fshb promoter in the pituitary of the orange-spotted grouper. The abundance of Nr5a1b bound to lhb promoter was significantly higher at the vitellogenic stage than the pre-vitellogenic stage, whereas that of Nr5a2 exhibited an opposite trend. Taken together, data of the present study demonstrated antagonistic effects of Nr5a1b and Nr5a2 on lhb transcription in the orange-spotted grouper and revealed novel regulatory mechanisms of differential expression of lhb and fshb genes through Nr5a homologues in vertebrates.
Endogenous retrovirus-encoded Syncytin-2 contributes to exosome-mediated immunosuppression of T cells†
Authors: Lokossou Adjimon G , Toudic Caroline , Nguyen Phuong Trang , Elisseeff Xavier , Vargas Amandine , Rassart Éric , Lafond Julie , Leduc Line , Bourgault Steve , Gilbert Caroline , Scorza Tatiana , Tolosa Jorge , Barbeau Benoit
Published: July 2019

Modulation of the activation status of immune cell populations during pregnancy depends on placental villous cytotrophoblast (VCT) cells and the syncytiotrophoblast (STB). Failure in the establishment of this immunoregulatory function leads to pregnancy complications. Our laboratory has been studying Syncytin-2 (Syn-2), an endogenous retroviral protein expressed in placenta and on the surface of placental exosomes. This protein plays an important role not only in STB formation through its fusogenic properties, but also through its immunosuppressive domain (ISD). Considering that Syn-2 expression is importantly reduced in preeclamptic placentas, we were interested in addressing its possible immunoregulatory effects on T cells. Activated Jurkat T cells and peripheral blood mononuclear cells (PBMCs) were treated with monomeric or dimerized version of a control or a Syn-2 ISD peptide. Change in phosphorylation levels of ERK1/2 MAP kinases was selectively noted in Jurkat cells treated with the dimerized ISD peptide. Upon incubation with the dimerized Syn-2 ISD peptide, significant reduction in Th1 cytokine production was further demonstrated by ELISA and Human Th1/Th2 Panel Multi-Analyte Flow Assay. To determine if exosome-associated Syn-2 could also be immunosuppressive placental exosomes were incubated with activated Jurkat and PBMCs. Quantification of Th1 cytokines in the supernatants revealed severe reduction in T cell activation. Interestingly, exosomes from Syn-2-silenced VCT incubated with PBMCs were less suppressive when compared with exosome derived from VCT transfected with control small interfering RNA (siRNA). Our results suggest that Syn-2 is an important immune regulator both locally and systemically, via its association with placental exosomes.
Effect of maternal betamethasone administration on feto-placental vascular resistance in the mouse†
Authors: Cahill Lindsay S , Whitehead Clare L , Hobson Sebastian R , Stortz Greg , Kingdom John C , Baschat Ahmet , Murphy Kellie E , Serghides Lena , Macgowan Christopher K , Sled John G
Published: July 2019

Antenatal corticosteroids are often administered to women at risk of preterm birth to accelerate fetal lung development; however, there is evidence that this treatment may adversely affect placental function in some fetuses. Our group has recently demonstrated that wave reflections in the umbilical artery (UA), measured using high-frequency ultrasound, are sensitive to placental vascular abnormalities. In the present study, we used this approach to investigate the effect of maternal administration of betamethasone, a clinically relevant corticosteroid, on the feto-placental vasculature of the mouse. Fetuses were assessed at embryonic day (E)15.5 and E17.5 in C57BL6/J mice. At both gestational ages, the UA diameter, UA blood flow, and the wave reflection coefficient were significantly elevated in the betamethasone-treated mice compared to vehicle-treated controls. These observations support the interpretation that placental vascular resistance dropped with betamethasone treatment to an extent that could not be explained by vasodilation of the UA alone. Consistent with clinical studies, the effect of betamethasone on UA end-diastolic velocity was heterogeneous. Our results suggest that UA wave reflections are more sensitive to acute changes in placental vascular resistance compared with the UA pulsatility index, and this technique may have clinical application to identify a favorable placental vascular response to fetal therapies such as antenatal corticosteroids, where the fetal heart rate is likely to vary.
Polymethacryloyl-L-Phenylalanine [PMAPA]-Based Monolithic Column for Capillary Electrochromatography
Authors: Derazshamshir Ali , Aşır Süleyman , Göktürk Ilgım , Ektirici Sisem , Yılmaz Fatma , Denizli Adil
Published: July 2019

The ability to detect catecholamines (CAs) and their metabolites is vital to understand the mechanism behind the neuronal diseases. Neurochemistry aims to provide an improved pharmacological, molecular and physiological understanding of complex brain chemistries by analytical techniques. Capillary electrophoresis (CE) is one such analytical technique that enables the study of various chemical species ranging from amino acids and peptides to natural products and drugs. CE can easily adapt the changes in research focus and in recent years remains an applicable technique for investigating neuroscience and single cell neurobiology. The prepared phenylalanine-based hydrophobic monolithic column, Polymethacryloyl-L-phenylalanine [PMAPA], was used as a stationary phase in capillary electrochromatography to separate CAs that are similar in size and shape to each other including dopamine (DA) and norepinephrine (NE) via hydrophobic interactions. Separation carried out in a short period of 17 min was performed with the electrophoretic mobility of 5.54 × 10−6 m2 V−1 s−1 and 7.60 × 10−6 m2 V−1 s−1 for DA and NE, respectively, at pH 7.0, 65% acetonitrile ratio with 100 mbar applied pressure by the developed hydrophobic monolithic column without needing any extra process such as imprinting or spacer arms to immobilize ligands used in separation.
Potential of Minimally Invasive Tissue Sampling for Attributing Specific Causes of Childhood Deaths in South Africa: A Pilot, Epidemiological Study
Authors: Chawana Richard , Baillie Vicky , Izu Alane , Solomon Fatima , Bassat Quique , Blau Dianna M , Breiman Robert F , Hale Martin , Houpt Eric R , Lala Sanjay G , Martines Roosecelis B , Mathunjwa Azwifarwi , Nzenze Susan , Pathirana Jayani , Petersen Karen L , Raghunathan Pratima L , Ritter Jana M , Wadula Jeannette , Zaki Sherif R , Madhi Shabir A
Published: July 2019

Background

Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age.

Methods

MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases, Tenth Revision (ICD-10).

Results

An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished.

Conclusions

MITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality.
Using Participatory Workshops to Assess Alignment or Tension in the Community for Minimally Invasive Tissue Sampling Prior to Start of Child Mortality Surveillance: Lessons From 5 Sites Across the CHAMPS Network
Authors: Blevins John , O’Mara Sage Elizabeth , Kone Ahoua , Maixenchs Maria , Raghunathan Pratima L , Guilaze Rui A , Cossa Saquina , Girma Zerihun , Zegeye Yosef , Ackley Caroline , Hussain Faruqe , Islam Saiful , Myburgh Nellie , Ngwenya Noni , Madhi Shabir A , Otieno Peter , Ochola Kennedy , Munguambe Khátia , Breiman Robert F
Published: July 2019

The Child Health and Mortality Prevention Surveillance (CHAMPS) program is a 7-country network (as of December 2018) established by the Bill & Melinda Gates Foundation to identify the causes of death in children in communities with high rates of under-5 mortality. The program carries out both mortality and pregnancy surveillance, and mortality surveillance employs minimally invasive tissue sampling (MITS) to gather small samples of body fluids and tissue from the bodies of children who have died. While this method will lead to greater knowledge of the specific causes of childhood mortality, the procedure is in tension with cultural and religious norms in many of the countries where CHAMPS works—Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa. Participatory Inquiry Into Community Knowledge of Child Health and Mortality Prevention (PICK-CHAMP) is a community entry activity designed to introduce CHAMPS to communities and gather initial perspectives on alignments and tensions between CHAMPS activities and community perceptions and priorities. Participants’ responses revealed medium levels of overall alignment in all sites (with the exception of South Africa, where alignment was high) and medium levels of tension (with the exception of Ethiopia, where tension was high). Alignment was high and tension was low for pregnancy surveillance across all sites, whereas Ethiopia reflected low alignment and high tension for MITS. Participants across all sites indicated that support for MITS was possible only if the procedure did not interfere with burial practices and rituals.
Standardization of Minimally Invasive Tissue Sampling Specimen Collection and Pathology Training for the Child Health and Mortality Prevention Surveillance Network
Authors: Rakislova Natalia , Fernandes Fabiola , Lovane Lucilia , Jamisse Luisa , Castillo Paola , Sanz Ariadna , Marimon Lorena , Jesri Susan , Ferrando Melania , Delgado Vima , Novela Obdeningo , Muiuane Venceslau , Ismail Mamudo R , Lorenzoni Cesaltina , Blau Dianna M , Bassat Quique , Menéndez Clara , Zaki Sherif R , Carrilho Carla , Ordi Jaume
Published: July 2019

Background

Minimally invasive tissue sampling (MITS) is a simplified postmortem examination technique that has shown to be an adequate approach for cause of death investigation in low-resource settings. It requires relatively low level of infrastructures and can be performed by health professionals with no background in pathology. A training program has been developed for the Child Health and Mortality Prevention Surveillance (CHAMPS) network to guarantee standardization of specimen collection techniques, procedures, and laboratory methods.

Methods

The training program has included assessment of the site capacities and training on a standardized protocol of MITS sampling and histological processing. The project has also introduced a program of training for trainers for the personnel from Mozambique. To guarantee the adequacy of the procedure in each site, a trainer accompanied the local teams when the activities started. Training outcomes were assessed by evaluating the quality of the samples obtained and the quality of the slides produced locally.

Results

Between June 2016 and October 2018, the laboratories of 7 sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) have been evaluated and upgraded. Training has been delivered to 63 staff members from all sites. More than 600 MITS procedures have been performed. The quantity of tissue obtained in the MITS by the local teams was sufficient or abundant in 73%, and 87% of the slides were considered as technically acceptable or excellent.

Conclusions

Satisfactory standardization of MITS and histology procedures has been achieved across all CHAMPS sites through organized capacity-building plans.
Mortality Surveillance Methods to Identify and Characterize Deaths in Child Health and Mortality Prevention Surveillance Network Sites
Authors: Salzberg Navit T , Sivalogan Kasthuri , Bassat Quique , Taylor Allan W , Adedini Sunday , El Arifeen Shams , Assefa Nega , Blau Dianna M , Chawana Richard , Cain Carrie Jo , Cain Kevin P , Caneer J Patrick , Garel Mischka , Gurley Emily S , Kaiser Reinhard , Kotloff Karen L , Mandomando Inacio , Morris Timothy , Nyamthimba Onyango Peter , Sazzad Hossain M S , Scott J Anthony G , Seale Anna C , Sitoe Antonio , Sow Samba O , Tapia Milagritos D , Whitney Ellen A , Worrell Mary Claire , Zielinski-Gutierrez Emily , Madhi Shabir A , Raghunathan Pratima L , Koplan Jeffrey P , Breiman Robert F ,   Child Health and Mortality Prevention Surveillance (CHAMPS) Methods Consortium, Agaya Janet , Akelo Victor , Tippett Barr Beth A , Bari Sanwarul , Islam Farzana , Rahman Afruna , Dessie Yadeta , Gedefa Letta , Kaluma Erick , Keita Adama Mamby , Onwuchekwa Uma U , Sidibe Diakaridia , Jambai Amara , Madrid Lola , Wittmann Stefanie , Mehta Ashka , Munguambe Khátia , Nhacolo Ariel , Vitorino Pio , Sacoor Charfudin , Preslar Jessica , Onyango Dickens , Ordi Jaume , Menéndez Santos Clara , Samura Solomon , Turk Megan , Varo Rosauro
Published: July 2019

Despite reductions over the past 2 decades, childhood mortality remains high in low- and middle-income countries in sub-Saharan Africa and South Asia. In these settings, children often die at home, without contact with the health system, and are neither accounted for, nor attributed with a cause of death. In addition, when cause of death determinations occur, they often use nonspecific methods. Consequently, findings from models currently utilized to build national and global estimates of causes of death are associated with substantial uncertainty. Higher-quality data would enable stakeholders to effectively target interventions for the leading causes of childhood mortality, a critical component to achieving the Sustainable Development Goals by eliminating preventable perinatal and childhood deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network tracks the causes of under-5 mortality and stillbirths at sites in sub-Saharan Africa and South Asia through comprehensive mortality surveillance, utilizing minimally invasive tissue sampling (MITS), postmortem laboratory and pathology testing, verbal autopsy, and clinical and demographic data. CHAMPS sites have established facility- and community-based mortality notification systems, which aim to report potentially eligible deaths, defined as under-5 deaths and stillbirths within a defined catchment area, within 24–36 hours so that MITS can be conducted quickly after death. Where MITS has been conducted, a final cause of death is determined by an expert review panel. Data on cause of death will be provided to local, national, and global stakeholders to inform strategies to reduce perinatal and childhood mortality in sub-Saharan Africa and South Asia.
VariED: the first integrated database of gene annotation and expression profiles for variants related to human diseases
Authors: Lee Chien-Yueh , Chattopadhyay Amrita , Chiang Li-Mei , Juang Jyh-Ming Jimmy , Lai Liang-Chuan , Tsai Mong-Hsun , Lu Tzu-Pin , Chuang Eric Y
Published: July 2019

Integrated analysis of DNA variants and gene expression profiles may facilitate precise identification of gene regulatory networks involved in disease mechanisms. Despite the widespread availability of public resources, we lack databases that are capable of simultaneously providing gene expression profiles, variant annotations, functional prediction scores and pathogenic analyses. VariED is the first web-based querying system that integrates an annotation database and expression profiles for genetic variants. The database offers a user-friendly platform and locates gene/variant names in the literature by connecting to established online querying tools, biological annotation tools and records from free-text literature. VariED acts as a central hub for organized genome information consisting of gene annotation, variant allele frequency, functional prediction, clinical interpretation and gene expression profiles in three species: human, mouse and zebrafish. VariED also provides a novel scoring scheme to predict the functional impact of a DNA variant. With one single entry, all results regarding queried DNA variants can be downloaded. VariED can potentially serve as an efficient way to obtain comprehensive variant knowledge for clinicians and scientists around the world working on important drug discoveries and precision treatments.
Evaluating reach, adoption, implementation and maintenance of Internet-based interventions to prevent eating disorders in adolescents: a systematic review
Authors: Zeiler Michael , Kuso Stefanie , Nacke Barbara , Klesges Lisa M , Waldherr Karin
Published: July 2019

Background

Past research has yielded promising results on the effectiveness of Internet-based interventions to prevent eating disorders (EDs) in adolescents, but further information is needed to evaluate the public health impact of their large-scale dissemination. This article used an established framework to systematically review the extent to which indicators of the reach, effectiveness, adoption, implementation and maintenance [cf. Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM)-framework] of universal and targeted online ED prevention programmes are reported in the literature, in order to estimate their future dissemination potential.

Methods

The literature search was conducted on PubMed, Web of Science and PsycINFO, and complemented by searching existing reviews and the reference lists of the studies included. Twenty-two studies published between 2000 and April 2019 met the inclusion criteria. We extracted data on a total of 43 indicators, within RE-AIM dimensions for each article, including qualitative coding of fostering and hindering factors.

Results

Reach (55.0%) and implementation (54.0%) were the dimensions reported on most frequently, followed by effectiveness (46.8%), adoption (34.7%) and maintenance (18.2%). While internal validity indicators were frequently reported (e.g. sample size, effects and intervention intensity), most studies failed to report on elements of external validity, such as representativeness of participants and settings, adoption rates, implementation costs and programme sustainability.

Conclusions

Evidence indicates that Internet-based ED prevention programmes can reach a large number of adolescents and can be feasibly implemented in school settings. However, given the paucity of large-scale dissemination studies available for review, the degree to which schools are willing to adopt preventive interventions, as well as the transferability of programmes to different settings and geographical regions remains unclear.
Economic Contributions of North Carolina, United States, Forest-Sector Foreign Exports: An Export-Chain Perspective
Authors: Mcconnell T Eric , Altizer Clayton B
Published: July 2019

North Carolina forest-sector foreign exports were quantified by applying an origin-of-production methodology that awarded the state a portion of national export value corresponding to its share of a US forest industry. A US$1.945 billion North Carolina forest export chain (FEC) was identified, producing forest industries, wholesalers, transporters, and port authorities. Contributions of the FEC were determined from a social accounting matrix in terms of output, value added, and employment. Port value multipliers were then calculated to provide context to the FEC’s contributions. Direct contributions were US$602.989 million of value added and 6,870 jobs based upon FEC activities of US$1.945 billion. Total FEC contributions were US$1.439 billion of value added and 16,640 jobs on sales across North Carolina of US$3.494 billion. The output and value-added port value multipliers indicated each US$1.000 million of FEC output and value added generated an additional US$800,000 and US$1.386 million in other industries, respectively, before leaving the state to purchase imported inputs. Each 1,000 FEC-dependent jobs supported an average of 1,420 jobs elsewhere in North Carolina’s economy. Information such as this provides policymakers an improved scope of the contributions driven by exporting to foreign markets.
The Diplomatic Presentation of the State in International Crises: Diplomatic Collaboration during the US-Iran Hostage Crisis
Authors: Banks David E
Published: July 2019

Theories of crisis (de-)escalation often focus on conflict, stress, and information problems. However, crisis (de-)escalation may sometimes hinge on how de-escalation is interpreted by domestic audiences. In this article, I combine Putnam's two-level games model of diplomacy with Erving Goffman's concepts of interaction order and face to create a mechanism I call “diplomatic presentation.” I show how diplomatic presentation can be instrumental for the crafting of diplomatic outcomes that states believe are in their mutual interest but that run the risk of being rejected by their domestic publics. Successful diplomatic presentation requires that states collude together to manage their performance, engage in teamwork, and control the impact of unsympathetic audiences. In evaluating this mechanism, I analyze the diplomacy surrounding the Iran Hostage Crisis. During this crisis, regime officials from the United States and Iran colluded in a theatrical “scenario,” in which both sides adopted specific roles in order to satisfy the sentiments of US and Iranian publics. I show that complications regarding the presentation of this scenario explain escalation of the crisis better than prominent alternatives. This argument contributes to the growing literature on symbolic diplomacy in international relations, while also challenging common assumptions about the adversarial nature of crises.
Effect of Ephestia kuehniella (Lepidoptera: Pyralidae) Larval Diet on Egg Quality and Parasitism by Trichogramma brassicae (Hymenoptera: Trichogrammatidae)
Authors: Moghaddassi Yasaman , Ashouri Ahmad , Bandani Ali Reza , Leppla Norman C , Shirk Paul D
Published: July 2019

Trichogramma spp., among the most common parasitoids used for augmentation biological control, often are mass-reared on eggs of the Mediterranean flour moth, Ephestia kuehniella (Zeller). To evaluate removal of nutritional components from the E. kuehniella larval diet and reduce production costs, colonies were maintained using one of three diets: a standard diet consisting of eight ingredients, a reduced diet containing whole wheat flour, glycerol, and Brewer’s yeast, or a third minimal diet of only whole wheat flour. The standard diet sustained the fastest larval development, female pupae with the greatest mass, the highest level of adult emergence, and production of the most eggs per female. Eggs from moths reared as larvae on the standard or reduced diet had equivalent mass, length, and percent hatch. Females from larvae fed the minimal diet produced eggs with the least mass that were shorter and had the lowest percent hatch. Eggs from the three E. kuehniella colonies were exposed separately to Trichogramma brassicae Bezdenko females to determine their acceptance for oviposition. More of the eggs from the standard diet were parasitized by the females, eggs from the reduced and minimal diets being less acceptable. The percent emergence of the parasitoids was the same regardless of diet; however, the largest wasps emerged from the standard diet eggs and a greater proportion of them were females. Consequently, the standard E. kuehniella larval diet resulted in the highest rate of reproduction and robust eggs that produced superior T. brassicae wasps.
Crossover Dynamics of Culex (Diptera: Culicidae) Vector Populations Determine WNV Transmission Intensity
Authors: Tokarz Ryan E , Smith Ryan C
Published: July 2019

First introduced into the United States in 1999, West Nile virus (WNV) has become endemic and has established itself as the predominant mosquito-borne arbovirus in North America. Transmitted by mosquitoes of the genus Culex, regional landscapes influence local vector species abundance, creating different mosquito ecologies that drive local transmission dynamics. In central Iowa, two mosquito species, Culex restuans Theobald and Culex pipiens Linnaeus, serve as the predominant mosquito vectors. Importantly, these mosquito populations are influenced by seasonal patterns in their abundance, with Cx. restuans preferring cool, early spring temperatures, while Cx. pipiens prefer the warmer, mid- to late-summer months. The point of the season at which Cx. pipiens becomes the dominant species is generally referred to as a ‘crossover’ period. To better understand the influence of crossover dynamics on WNV transmission, we examined environmental and mosquito abundance data, as well as mosquito infection rates and human disease cases from 2016 to 2018. We demonstrate that temperature influences the timing and duration of the crossover period, influencing mosquito abundance and human disease transmission. Together, these results suggest that Culex species crossover is an important variable of WNV transmission dynamics, which may provide an early warning indicators of increased WNV transmission.
Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus: A Report from the Childhood Cancer Survivor Study
Authors: Friedman Danielle Novetsky , Moskowitz Chaya S , Hilden Patrick , Howell Rebecca M , Weathers Rita E , Smith Susan A , Wolden Suzanne L , Tonorezos Emily S , Mostoufi-Moab Sogol , Chow Eric J , Meacham Lillian R , Chou Joanne F , Whitton John A , Leisenring Wendy M , Robison Leslie L , Armstrong Gregory T , Oeffinger Kevin C , Sklar Charles A
Published: July 2019

Background

Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus, but the association between risk and radiation dose and volume is unclear.

Methods

Participants included 20 762 5-year survivors of childhood cancer (4568 exposed to abdRT) and 4853 siblings. For abdRT, we estimated maximum dose to abdomen; mean doses for whole pancreas, pancreatic head, body, tail; and percent pancreas volume receiving no less than 10, 20, and 30 Gy. Relative risks (RRs) were estimated with a Poisson model using generalized estimating equations, adjusted for attained age. All statistical tests were two-sided.

Results

Survivors exposed to abdRT (median age = 31.6 years, range = 10.2–58.3 years) were 2.92-fold more likely than siblings (95% confidence interval [CI] = 2.02 to 4.23) and 1.60-times more likely than survivors not exposed to abdRT (95%CI = 1.24 to 2.05) to develop diabetes. Among survivors treated with abdRT, greater attained age (RRper 10 years = 2.11, 95% CI = 1.70 to 2.62), higher body mass index (RRBMI 30+ = 5.00, 95% CI = 3.19 to 7.83 with referenceBMI 18.5–24.9), and increasing pancreatic tail dose were associated with increased diabetes risk in a multivariable model; an interaction was identified between younger age at cancer diagnosis and pancreatic tail dose with much higher diabetes risk associated with increasing pancreatic tail dose among those diagnosed at the youngest ages (P < .001). Radiation dose and volume to other regions of the pancreas were not statistically significantly associated with risk.

Conclusions

Among survivors treated with abdRT, diabetes risk was associated with higher pancreatic tail dose, especially at younger ages. Targeted interventions are needed to improve cardiometabolic health among those at highest risk.
Giant bladder stone in association with severe kidney injury
Authors: Agrawal Rohit , Taha Khaled , Poudyal Abhushan , Vidal Patricia , Bhattacharjee Poushali
Published: July 2019

Minimal data exist on the causes, incidence and management of giant bladder stones considering their rare occurrence. Only a handful of case reports have reported stones larger than 10 cm, and most of these cases are managed surgically. We present a case of a 56-year-old female who presented with vague, lower urinary tract symptoms who was later found to have severe post-renal acute kidney injury due to a giant bladder stone measuring 11 × 11 × 10.4 cm.
Longitudinal assessment of interstitial lung disease in single lung transplant recipients with scleroderma
Authors: Hinze Alicia M , Lin Cheng T , Hussien Amira F , Perin Jamie , Venado Aida , Golden Jeffrey A , Boin Francesco , Brown Robert H , Wise Robert A , Wigley Fredrick M
Published: July 2019

Objective

To investigate the natural history of fibrotic lung disease in recipients of a single lung transplant for scleroderma-associated interstitial lung disease (ILD).

Methods

Global ILD (including ground glass, nodular opacities and fibrosis) was categorized into severity quintiles on first and last post-transplant CT scans, and percent fibrosis by manual contouring was also determined, in nine single lung transplant recipients. Quantitative mean lung densities and volumes for the native and allograft lungs were also acquired.

Results

In the native lung, global ILD severity quintile worsened in two cases and percent fibrosis worsened in four cases (range 5–28%). In the lung allograft, one case each developed mild, moderate and severe ILD; of these, new fibrotic ILD (involving <10% of lung) occurred in two cases and acute cellular rejection occurred in one. The average change in native lung density over time was +2.2 Hounsfield Units per year and lung volume +1.4 ml per year, whereas the allograft lung density changed by –5.5 Hounsfield Units per year and total volume +27 ml per year (P = 0.011 and P = 0.039 for native vs allograft density and volume comparisons, respectively).

Conclusions

While the course of ILD in the native and transplanted lungs varied in this series, these cases illustrate that disease progression is common in the native lung, suggesting that either the immune process continues to target autoantigens or ongoing fibrotic pathways are active in the native lung. Mild lung disease may occur in the allograft after several years due to either allograft rejection or recurrent mild ILD.
Efficacy and Safety of Low-dose Codeine-containing Combination Analgesics for Pain
Authors: Abdel Shaheed Christina , Maher Christopher G. , McLachlan Andrew J.
Published: July 2019

Objective:

To investigate the efficacy and safety of combination analgesic products containing low-dose codeine (up to 30 mg/dose) for pain.

Methods:

Electronic databases were used to identify eligible placebo-controlled, randomized controlled trials (RCTs). Two authors extracted data and assessed the risk of bias. Data were pooled using a random-effects model with the strength of evidence assessed using Grading of Recommendations Assessment, Development and Evaluation. The primary outcome was immediate pain relief (3 hours post administration) on a 0 to 100 pain scale.

Results:

Ten RCTs were eligible. There is low-quality evidence (4 RCTs, n=211 participants) that a single dose of a combination analgesic product (with an nonsteroidal anti-inflammatory) containing low-dose codeine (15 to 30 mg) provides small pain relief for acute dental pain (mean difference [MD], −12.7; 95% confidence interval [CI], −18.5 to −6.9) and moderate-quality evidence (1 RCT, n=93) of small pain relief for post-episiotomy pain and orthopedic surgery pain (MD,, −10.0; 95% CI, −19.0 to −1.0 and MD, −11.0; 95% CI, −20.7 to −1.3), respectively. There is low-quality evidence (1 RCT, n=80) that a multiple-dose regimen provides small pain relief for acute pain following photorefractive keratectomy (MD, −16.0; 95% CI, −24.5 to −7.5) and moderate-quality evidence of moderate pain relief for certain chronic pain conditions: for hip osteoarthritis (MD, −19.0; 95% CI, −31.2 to −6.8) and for temporomandibular joint pain (MD, −26.0; 95% CI, −44.5 to −7.5). Two studies reported a higher incidence of drowsiness in the treatment group compared with the placebo group (relative risk, 8.50; 95% CI, 1.96, 36.8 and 19.3; 95% CI, 1.2-306.5, respectively).

Discussion:

There is low to moderate level evidence that combination analgesic products containing low-dose codeine provide small to moderate pain relief for acute and chronic pain conditions in the immediate short term with limited trial data on use beyond 24 hours. Further research examining regular use of these medicines is needed with more emphasis on measuring potential harmful effects.
Validation of Pediatric Self-Report Patient-Reported Outcomes Measurement Information System (PROMIS) Measures in Different Stages of Legg-Calvé-Perthes Disease
Authors: Matsumoto Hiroko , Hyman Joshua E. , Shah Hitesh H. , Sankar Wudbhav N. , Laine Jennifer C. , Mehlman Charles T. , Schrader Tim , Kelly Derek M. , Rosenfeld Scott B. , Janicki Joseph A. , Thacker Mihir M. , Trupia Evan , Mcguire Molly F. , Kim Harry K.W.
Published: July 2019

Objectives:

Patient-reported outcomes (PRO) assessing health-related quality of life (HRQoL) are important outcome measures, especially in Legg-Calvé-Perthes disease (LCPD) where symptoms (pain and limping), activity restrictions, and treatments vary depending on the stage of the disease. The purpose of this study was to investigate the validity of the Patient-reported Outcomes Measurement Information System (PROMIS) for measuring HRQoL of patients with LCPD in various stages of the disease.

Methods:

This is a multicenter validity study. Patients with LCPD between 4 and 18 years old were included and classified into modified Waldenström stages of disease: Early (1 or 2A), Late (2B or 3), or Healed (4). Seven PROMIS domains were collected, including Pain Interference, Fatigue, Mobility, Depression, Anger, Anxiety, and Peer Relationships. Convergent, discriminant, and known group validity was determined.

Results:

A total of 190 patients were included (mean age: 10.4±3.1 y). All 7 domains showed the worst scores in patients in the Early stage (known group validity). Within each domain, all domains positively correlated to each other (convergent validity). Patients who reported more anxiety, depression, and anger were associated with decreased mobility and increased fatigue and pain. Peer relationships had no to weak associations with other domains (discriminant validity).

Conclusions:

PROMIS has construct validity in measuring the HRQoL of patients in different stages of LCPD, suggesting that PROMIS has potential to serve as a patient-reported outcome tool for this population.

Level of Evidence:

Diagnostic level III study.
Children with Tourette Syndrome in the United States: Parent-Reported Diagnosis, Co-Occurring Disorders, Severity, and Influence of Activities on Tics
Authors: Wolicki Sara Beth , Bitsko Rebecca H. , Danielson Melissa L. , Holbrook Joseph R. , Zablotsky Benjamin , Walkup John T. , Woods Douglas W. , Mink Jonathan W.
Published: July 2019

Objective:

Describe the diagnostic process for Tourette syndrome (TS) based on parent report, as well as TS severity and associated impairment; the influence of common daily activities on tics; and the presence of co-occurring mental, behavioral, and developmental disorders among children in the United States.

Methods:

Parent-report data from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome on 115 children ever diagnosed with TS were analyzed. Descriptive, unweighted analyses included frequencies and percentages, and means and standard deviations. Fisher's exact test and t-tests were calculated to determine statistically significant differences.

Results:

The mean age that tics were first noticed was 6.3 years, and, on average, TS was diagnosed at 7.7 years. The time from initially noticing tics to TS diagnosis averaged 1.7 years. The mean age when TS symptoms were most severe was 9.3 years. Tic severity was associated with impaired child functioning but not tic noticeability. Almost 70% of parents reported that fatigue and major transitions made their child's tics worse. Children with ever-diagnosed TS had a mean of 3.2 ever-diagnosed co-occurring mental, behavioral, or developmental disorders; a quarter (26.9%) had 5 or more co-occurring disorders.

Discussion:

In this sample of children with TS, the time to diagnosis averaged less than 2 years from when tics were initially noticed. More severe TS was associated with greater functional impairment, and co-occurring disorders were common among children with TS. This study provides insight into the current experiences of children with TS in the United States and their families.
Screening for Both Child Behavior and Social Determinants of Health in Pediatric Primary Care
Authors: Berger-Jenkins Evelyn , Monk Catherine , D'Onfro Katherine , Sultana Majeda , Brandt Lisa , Ankam Jyoti , Vazquez Nadiuska , Lane Mariellen , Meyer Dodi
Published: July 2019

Objective:

To implement comprehensive screening for child behavior and social determinants of health in an urban pediatric practice and explore rates of referrals and follow-up for positive screens.

Method:

Quality improvement methodology was used to implement routine screening using an adapted version of the Survey of Well Being of Young Children, a child behavior and social screen, for all children aged 6 months to 10 years. Rates of screen administration and documentation were assessed for 18 months. Medical records of a convenience sample (N = 349) were reviewed to track referrals and follow-up for positive screens. A secondary analysis explored associations between reported parental concern for their child's behavior and both child behavior symptoms and social stressors.

Results:

Over 18 months, 2028 screens were administered. Screening rates reached 90% after introducing a tablet for screening. Provider documentation of screens averaged 62%. In the convenience sample, 28% scored positive for a behavioral problem, and 25% reported at least 1 social stressor. Of those with positive child behavior or social stressor screens, approximately 80% followed up with their primary medical doctor, and approximately 50% completed referrals to the clinic social worker. Further analysis indicated that referral and follow-up rates varied depending on whether the family identified child behavior or social issues. Logistic regression revealed that parental concern was independently associated with child behavior symptoms (p = 0.001) and social stressors (p = 0.002).

Conclusion:

Implementing a comprehensive psychosocial screen is feasible in pediatric primary care and may help target referrals to address psychosocial health needs.
Racial and Ethnic Disparities in Autism-Related Health and Educational Services
Authors: Bilaver Lucy A. , Havlicek Judy
Published: July 2019

Objective:

The objective of this study is to measure racial and ethnic disparities in autism-related services among U.S. children with parent-reported autism spectrum disorder (ASD).

Methods:

Using the 2011 Survey of Pathways to Diagnosis and Services, we analyzed parent-reported data on 1420 children with current ASD in the nationally representative sample. An estimation method consistent with the Institute of Medicine's definition of health care disparities is used to measure racial and ethnic disparities.

Results:

The findings revealed Latino-white disparities in the percentage of children currently using school-based occupational and physical therapy and Latino-white and “other race”-white disparities in the percentage of children using physical therapy outside of school. There were no statistically significant black-white disparities. Instead, the study found that the percentage of black children with ASD receiving school-based services was 8 points higher than that of white children (p < 0.04). Factors unrelated to the need for autism services were largely unassociated with the receipt of services.

Conclusion:

The findings provide a partial baseline and identify a need for further examination of the source of existing disparities and the lack of disparities found for specific services and minority groups.
Household Chaos, Maternal Emotional Responsiveness, and Child Eating Behavior: A Moderation Analysis
Authors: Saltzman Jaclyn A. , Bost Kelly K. , McBride Brent A. , Fiese Barbara H.
Published: July 2019

Objective:

To address calls for a resilience-informed approach to understand the cause and prevention of childhood obesity, the current study aims to investigate the independent and interactive associations between household chaos, maternal emotional responsiveness, and eating behavior in early childhood.

Method:

A sample of (n = 108) families of 18- to 24-month-olds completed self-report surveys and consented to home visits as part of the larger STRONG Kids 2 (N = 468) study. Videotapes of family mealtimes were collected during home visits and coded for observed maternal emotional responsiveness. Mothers completed questionnaires assessing maternal emotional responsiveness, household chaos, and child eating behaviors. Moderation analyses assessed independent and interactive effects of chaos and emotional responsiveness on child appetite self-regulation.

Results:

In moderation analyses controlling for demographic covariates, higher levels of chaos were associated with more emotional overeating and with more food responsiveness, but only among children of mothers observed engaging in low levels of responsiveness at mealtimes. There was no association between chaos and eating behavior among children of mothers observed engaging in high levels of emotional responsiveness at mealtimes. There was also no independent or interactive association between chaos and child eating behaviors characterized by food avoidance.

Conclusion:

Preliminary evidence suggests that maternal emotional responsiveness at mealtimes may attenuate the deleterious effects of chaos on child overeating and food responsiveness. Future research should prioritize using longitudinal designs, developing observational assessments of early childhood eating behaviors, and understanding these processes among families exposed to greater socioeconomic adversity.
Meropenem, Cefepime, and Piperacillin Protein Binding in Patient Samples
Authors: Al-Shaer Mohammad H. , Alghamdi Wael A. , Graham Emily , Peloquin Charles A.
Published: July 2019

Background:

The mortality rate of patients with a drug-resistant bacterial infection is high, as are the associated treatment costs. To overcome these issues, optimization of the available therapeutic options is required. Beta-lactams are time-dependent antibiotics and their efficacy is determined by the amount of time the free concentration remains above the minimum inhibitory concentration. Therefore, the aim of this study was to assess the extent and variability of protein binding for meropenem, cefepime, and piperacillin.

Methods:

Plasma samples for the analysis of meropenem, cefepime, and piperacillin were collected from patients admitted to a tertiary care hospital as part of the standard care. The bound and unbound drug fractions in the samples were separated by ultrafiltration. Validated liquid chromatography-tandem mass spectrometry assays were used to quantify the total and free plasma concentrations, and the protein binding was determined.

Results:

Samples from 95 patients were analyzed. The median (range) age of patients was 56 years (17–87) and the median (range) body mass index was 25.7 kg/m2 (14.7–74.2). Approximately 59% of the patients were men. The median (range) unbound fraction (fu) was 62.5% (41.6–99.1) for meropenem, 61.4% (51.6–99.2) for cefepime, and 48.3% (39.4–71.3) for piperacillin. In the bivariate analysis, as the total meropenem concentration increased, the fu increased (r = 0.37, P = 0.045). A decrease in piperacillin fu was observed as the albumin concentration increased (r = −0.56, P = 0.005).

Conclusions:

The average fu values were lower than those reported in the literature. There was also a large variability in fu; hence, it should be considered when managing patients administered with these drugs through direct measurements of free drug concentrations.