bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular cloning and epigenetic change detection of Kiss1 during seasonal reproduction in Chinese indigenous sheep
Authors: He Xiaoyun , Liu Qiuyue , Li Xiaoyu , Guo Xiaofei , Wang Xiangyu , Hu Wenping , Di Ran , Chu Mingxing
Published: November 2017

Like most seasonal domesticated species, sheep are short-day breeders, which means that the reproduction axis is activated by short days. The annual photoperiodic cycle affects the amount of daylength information that is transmitted to the hypothalamic–pituitary–gonadal (HPG) axis by regulating pulsatile secretion of gonadotrophin-releasing hormone from the hypothalamus. Kisspeptin, which is encoded by Kiss1, plays a major role in reproductive seasonality. Based on results from our previous Solexa sequencing data obtained from Tan (T) and Small Tail Han (STH) sheep during anoestrus and the breeding season, full-length mRNA information for ovine Kiss1 was obtained; 894 bp in T sheep and 1145 bp in STH sheep. Both encode 135 amino acids. Additionally, T and STH sheep have different transcription start sites of Kiss1. Kiss1 expression during oestrus was significantly higher than that during dioestrus, both in T and STH sheep (P < 0.01). We also found a strong relationship between Kiss1 mRNA levels and histone H3 acetylation status in the 5′ promoter region of ovine Kiss1. These data indicated that epigenetic modification occurs during reproduction in sheep, and this is the first report that histone H3 deacetylation occurs in the hypothalamus of seasonal sheep breeders during the transition from dioestrus to oestrus.
Low education levels are associated with early age of sexual debut, drug use and risky sexual behaviours among young Indigenous Australians
Authors: Wand Handan , Bryant Joanne , Worth Heather , Pitts Marian , Kaldor John M. , Delaney-Thiele Dea , Ward James
Published: November 2017

Background
Earlier age at sexual debut is associated with drug and alcohol use, risky sexual behaviours and sexually transmissible infections (STI). Methods: In the present study, 2320 young Indigenous Australians were surveyed. Results: Most study participants had sex for the first time when they were 14 years or younger (79% and 67% for males and females respectively). More than 80% of participants were categorised as being in the high-risk category for the combined sexual risk factors (i.e. not using condoms, drunk or high at last sexual act, or three or more sexual partners in the past year). There was a linear decreasing trend between the proportion of males and females who had less than high school education and age at first sex (Ptrend < 0.001). Compared with the highest quintile of age at first sexual debut (≥18 years), those in the bottom quintile (<15 years) were less likely to have completed high school (63% vs 32% respectively for males; 68% vs 26% respectively for females; Ptrend < 0.001 for both). Conclusions: The findings of the present study suggest that sex education and STI prevention should start early when targeting Indigenous young people, with age-appropriate messages. Sex education should be comprehensive and address individual risk behaviours, sexual agency and societal vulnerability to not only delay sexual debut, but also to emphasise the importance of STI prevention through condom use, which clearly already works to a certain extent with this group.
Sparsity enables estimation of both subcortical and cortical activity from MEG and EEG
Authors: Krishnaswamy Pavitra , Obregon-Henao Gabriel , Ahveninen Jyrki , Khan Sheraz , Babadi Behtash , Iglesias Juan Eugenio , Hämäläinen Matti S. , Purdon Patrick L.
Published: November 2017

Significance

Subcortical structures play a critical role in brain functions such as sensory perception, memory, emotion, and consciousness. There are limited options for assessing neuronal dynamics within subcortical structures in humans. Magnetoencephalography and electroencephalography can measure electromagnetic fields generated by subcortical activity. But localizing the sources of these fields is very difficult, because the fields generated by subcortical structures are small and cannot be distinguished from distributed cortical activity. We show that cortical and subcortical fields can be distinguished if the cortical sources are sparse. We then describe an algorithm that uses sparsity in a hierarchical fashion to jointly localize cortical and subcortical sources. Our work offers alternative perspectives and tools for assessing subcortical brain dynamics in humans.
Reviewer bias in single- versus double-blind peer review
Authors: Tomkins Andrew , Zhang Min , Heavlin William D.
Published: November 2017

Significance

Scientific peer review has been a cornerstone of the scientific method since the 1600s. Debate continues regarding the merits of single-blind review, in which anonymous reviewers know the authors of a paper and their affiliations, compared with double-blind review, in which this information is hidden. We present an experimental study of this question. In computer science, research often appears first or exclusively in peer-reviewed conferences rather than journals. Our study considers full-length submissions to the highly selective 2017 Web Search and Data Mining conference (15.6% acceptance rate). Each submission is simultaneously scored by two single-blind and two double-blind reviewers. Our analysis shows that single-blind reviewing confers a significant advantage to papers with famous authors and authors from high-prestige institutions.
The association between physical activity and chronic diseases in European adults
Authors: Marques Adilson , Santos Teresa , Martins João , Matos Margarida Gaspar De , Valeiro Miguel González
Published: November 2017

Chronic diseases are the leading cause of morbidity and mortality and are considered to be at epidemic levels worldwide. This is a cross‐sectional multi‐country study based on data from the European Social Survey round 7, 2014, comprising 30,826 participants (14,813 men) with mean age 50.4 ± 18.0. Physical activity and chronic diseases were self‐reported. Men and women who practiced physical activity more often had lower odds of having heart problems, breathing problems, type 2 diabetes, and obesity. Engaged in physical activity 2–4 times/week and ≥5 times/week decrease the odds of having heart problems, high blood pressure, breathing problems, type 2 diabetes, and obesity, compared with men and women who engaged in physical activity 1 or less times per week. For the women, the practice of physical activity ≥5 times/week was significantly and negatively associated with having cancer, when compared with women who engaged in physical activity 1 or less times per week. Physical activity is associated with a lower risk of chronic diseases, in particular: heart problems, high blood pressure, breathing problems, allergies, type 2 diabetes, and obesity. Furthermore, even small amounts of weekly physical activity seem to decrease the risk of chronic diseases.
An atypical CaV1.1 mutation reveals a common mechanism for hypokalemic periodic paralysis
Authors: Cannon Stephen C.
Published: November 2017

Cannon reviews new evidence supporting a key role for anomalous inward currents in the etiology of hypokalemic periodic paralysis.
Significant Influence of EC50 Estimation by Model Choice and EC50 Type
Authors: Noel Zachary A. , Wang Jie , Chilvers Martin I.
Published: November 2017

The effective control to 50% growth inhibition (EC50) is a standard statistic for evaluating dose-response relationships. Many statistical software packages are available to estimate dose-response relationships but, recently, an open source package (“drc”) in R has been utilized. This package is highly adaptable, having many models to describe dose-response relationships and flexibility to describe both hormetic relationships and absolute and relative EC50. These models and definitions are generally left out of phytopathology literature. Here, we demonstrate that model choice and type of EC50 (relative versus absolute) can matter for EC50 estimation using data from Pythium oopapillum and Fusarium virguliforme. For some P. oopapillum isolates, the difference between absolute and relative EC50 was significant. Hormetic effects changed F. virguliforme EC50 distributions, leading to higher estimates than when using four- or three-parameter log-logistic models. Future studies should pay careful attention to model selection and interpretation in EC50 estimation and clearly indicate which model and EC50 measure (relative versus absolute) was used. We provide guidelines for model choice and interpretation for those wishing to set up experiments for accurate EC50 estimation.
Holocrine Poroma: A Distinctive Adnexal Tumor
Authors: Horenstein Marcelo G. , Sandoval Marina P. , Lo Yungtai , Jacob Jack
Published: November 2017

There are 36 cases of complex poroid tumors with folliculosebaceous and apocrine differentiation reported in the literature. The authors evaluated 111 poroid tumors including 63 typical eccrine poromas and 48 poroid tumors with folliculosebaceous elements. Folliculosebaceous poroid tumors (FSPT) had basaloid and squamous cells (100%), ducts with steatocystoma-like cuticles and holocrine secretions (89.6%), infundibular follicular structures (66.7%), and entrapped sebocytes (56.3%). No definite apocrine decapitation secretions in FSPT were found. Immunohistochemistry was strongly positive for CK903 and focally positive for CAM5.2, epithelial membrane antigen, and carcinoembryonic antigen. No loss of MLH-1, MSH-2, or MSH-6 mismatch repair proteins was found. FSPT had distinctive features that differentiate them from eccrine poromas including the frequent head and neck locations (62.5% vs. 20.6%, P < 0.01), squamous cytology (100% vs. 1.6%, P < 0.01), more prominent cytoplasmic vacuolization (score 1.4/4.0 vs. 0.3/4.0, P < 0.01), presence of infundibular follicular structures (score 1.2/4.0 vs. 0.03/4.0, P < 0.01), presence of ducts with steatocystoma-like cuticles (89.6% vs. 0.0%, P < 0.01), and less stromal hyalinization (score 1.0/4.0 vs. 2.5/4.0, P < 0.01). The authors propose that FSPT are distinctive benign tumors originating from the sebaceous gland duct and are therefore best categorized as holocrine poroma.
New Histologic Finding of Amyloid Insulin Bodies at an Insulin Injection Site in a Patient With Diabetes
Authors: Katzman Benjamin D. , Traum Peter , Medline Paul B.
Published: November 2017

Amyloidosis is a heterogeneous group of protein deposition diseases with more than 40 known clinical presentations. Localized amyloidosis occurs when the protein deposits exist in a singular location. Patients with diabetes mellitus who inject insulin at the same site can develop localized insulin-derived amyloidosis (AIns) at the injection site, which can be confused clinically with lipoma, lipohyperplasia, lipoatrophy, and fat necrosis. Histologic examination is performed to confirm localized AIns. We report a case of a patient with a long history of type 2 diabetes who presented with a subcutaneous mass in the abdomen at a preferred insulin injection site. Examination by light microscopy revealed diffuse deposition of eosinophilic material. Two of the tissue fragments contained numerous 30–40 μm spherical bodies within the eosinophilic material. The bodies had dark centers with peripheral eosinophilic material. Polarized sections stained with Congo red showed apple green birefringence, a characteristic of amyloid. Immunohistochemistry was positive for insulin antibodies in the dark spherules and the surrounding matrix. Proteomic analysis by mass spectrometry showed that the Congo red–positive material was insulin. Electron microscopy showed a background matrix consisting of nonbranching protein fibrils measuring 8.8–16.1 nm, consistent with amyloid; the spherules contained dark globular proteins in the center surrounded by nonbranching fibrillary proteins. Because these spherules were positive for insulin by immunohistochemistry and showed amyloid ultrastructurally, we refer to them as amyloid insulin bodies. The identification of AIns, specifically with amyloid insulin bodies, is important for diagnosis and treatment and may further our understanding of amyloidogenesis.
Influence of Syringe Volume on Foam Stability in Sclerotherapy for Varicose Vein Treatment
Authors: Bai Taoping , Jiang Wentao , Fan Yubo
Published: November 2017

BACKGROUND

Despite the popularity of sclerotherapy for treating varicose veins, it still exhibits various problems, such as pulmonary embolism, deep-vein thrombosis, phlebitis, and visual disorders.

OBJECTIVE

To investigate syringe volume influence on foam stability, obtain the foam decay rule, and provide a reference for clinics.

MATERIALS AND METHODS

Five types of syringes are used to prepare foam at room temperature with various liquid–gas ratios. Foam decay process experiments were performed 5 times and recorded by video. The stability indices used include drainage time, half-life, bubble diameter, bubble surface density, and drainage rate.

RESULTS

The 30 and 2-mL syringes, respectively, recorded the highest and lowest drainage speeds. Foam drainage time and half-life, differences varied between 15 and 70 seconds, and 20 and 100 seconds, respectively. Foam bubble diameters were distributed over 0.1 to 2.0 mm with roughly 200 to 700 bubbles per square centimeter.

CONCLUSION

Increased syringe volume causes the bubble diameter to increase. Thus, foam dispersion increases and foam half-life decreases; hence, foam becomes unstable. It is, thus, better to use a small syringe several times to prepare foam in clinics using segmented injections.
Sexual activity and vaginal symptoms in the postintervention phase of the Women's Health Initiative Hormone Therapy Trials
Authors: Gass Margery , Larson Joseph , Cochrane Barbara , Manson JoAnn E. , Lane Dorothy , Barnabei Vanessa , Ockene Judith , Stefanick Marcia L. , Mouton Charles
Published: November 2017

Objective:

To assess the impact of discontinuing oral hormone therapy (HT) on sexual activity, vaginal symptoms, and sexual activity components among participants in the estrogen-progestin therapy (EPT) and estrogen therapy (ET) trial of the Women's Health Initiative.

Methods:

Surveys were sent postintervention to those who were still taking study pills and agreed to continue in the study when the trials were stopped. Comparisons between former HT and placebo users were accomplished with chi-square tests for categorical variables and t tests for continuous variables.

Results:

In all, 13,902 women with mean age at survey 69.9 years (EPT trial, women with intact uterus) and 71.7 years (ET trial, women with history of hysterectomy) responded. Prevalence of sexual activity postintervention was not significantly different between former EPT and placebo users (36.0% vs 34.2%; P = 0.37). Sexual activity of former ET users was 5.6% higher than placebo users (27.6% vs 22.0%; P = 0.001). The majority of sexually active women overall maintained orgasmic capacity and sexual satisfaction. Former EPT users were 10% to 12% more likely than former placebo users to report decreased desire, arousal, intercourse, climax, and satisfaction with sexual activity, and also increased dryness and dyspareunia upon discontinuing study drugs (P < 0.001). Former ET users were more likely than placebo users to report rare to no desire or arousal postintervention (P < 0.001).

Conclusions:

Postintervention ET trial participants formerly assigned to ET were significantly more likely to report sexual activity than those formerly assigned to placebo. Women who discontinued EPT were significantly more likely to report negative vaginal and sex-related effects.
The effects of supplemental vitamin E on hematological parameters in a rat model of ovarian hormone deficiency
Authors: Pourafshar Shirin , Johnson Sarah A. , Keshavarz Behnam , Feresin Rafaela G. , Khalil Dania A. , Chai Sheau C. , Arjmandi Bahram H.
Published: November 2017

Objective:

Menopause is associated with adverse changes in hematological parameters. Although the antioxidative and anti-inflammatory properties of vitamin E have been previously demonstrated, the effects of vitamin E on hematopoietic parameters are not well-documented. This study investigated the effects of supplemental vitamin E on hematological parameters in a rat model of ovarian hormone deficiency.

Methods:

Twelve-month-old female Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx). Animals were randomly divided among five treatment groups (n = 12/group) as follows: Sham; Ovx; Ovx + 300, Ovx + 525, or Ovx + 750 mg/kg diet of vitamin E for 100 days.

Results:

Compared with Sham, ovariectomy increased leukocyte subpopulation counts including lymphocytes (2.01 × 103/mm3; 95% confidence interval [CI] 0.11, 4.03; P = 0.03), monocytes (0.35 × 103/mm3; 95% CI 0.60, 0.11; P = 0.01), neutrophils (0.72 × 103/mm3; 95% CI 0.26, 1.19; P = 0.01), eosinophils (0.07 × 103/mm3; 95% CI 0.12, 0.30; P = 0.00), and basophils (0.13 × 103/mm3; 95% CI 0.04, 0.21; P = 0.02). Medium dose (MD) (−0.26 × 103/mm3; 95% CI −0.47, −0.05; P = 0.007) and high dose (HD) (−0.22 × 103/mm3; 95% CI −0.43, −0.01; P = 0.037) supplemental vitamin E attenuated Ovx-induced increases in monocyte counts. Low dose (LD) (−0.55 × 103/mm3; 95% CI −0.95, −0.15; P = 0.003), MD (−0.61 × 103/mm3; P = 0.001), and HD (−0.54 × 103/mm3; 95% CI −0.95, −0.14; P = 0.004) supplemental vitamin E attenuated Ovx-induced increases in neutrophil counts. LD (−0.05 × 103/mm3; 95% CI −0.08, −0.11; P = 0.006), MD (−0.05 × 103/mm3; 95% CI −0.08, −0.11; P = 0.005), and HD (−0.05 × 103/mm3; 95% CI −0.09, −0.01; P = 0.004) supplemental vitamin E also attenuated the Ovx-induced increase in eosinophil counts. Only LD (−0.09 × 103/mm3; 95% CI −0.17, −0.02; P = 0.009) supplemental vitamin E attenuated the Ovx-induced increase in basophil counts. The remaining hematological parameters assessed were not significantly affected by ovariectomy or supplemental vitamin E.

Conclusion:

These findings suggest that vitamin E in the form of α-tocopherol acetate may provide protection against ovarian hormone deficiency-associated adverse changes in hematological parameters.
Genetic variants associated with earlier age at menopause increase the risk of cardiovascular events in women
Authors: Sarnowski Chloé , Kavousi Maryam , Isaacs Steve , Demerath Ellen W. , Broer Linda , Muka Taulant , Franco Oscar H. , Ikram Mohammad Arfan , Uitterlinden André , Franceschini Nora , Lunetta Kathryn L. , Murabito Joanne M.
Published: November 2017

Objective:

To better understand the relationship between cardiovascular disease risk and age-at-natural menopause using genetic data.

Methods:

Early menopause is associated with cardiovascular disease risk. We constructed a genetic risk score comprising 56 age-at-natural menopause decreasing alleles in men and women from the Framingham Heart Study, the Atherosclerosis Risk in Communities Study, and the Rotterdam Study. If the genetic predisposition to earlier age-at-natural menopause is associated with increased cardiovascular disease risk, it is reasonable to ask whether the risk is shared by men carrying the alleles, despite not experiencing menopause. We estimated the hazard ratio for the score for time to first cardiovascular event. To investigate the possible genetic pleiotropy between age-at-natural menopause and cardiovascular disease, we performed cross-trait linkage disequilibrium score regressions between age-at-natural menopause and cardiovascular disease and risk factors using genome-wide association studies.

Results:

Twenty-two thousand five hundred and sixty-eight cardiovascular disease-free participants at baseline were analyzed (9,808 men, 12,760 women). Each additional unit of the genetic propensity to earlier age-at-natural menopause increased the hazard of both cardiovascular disease and cardiac death in women (cardiovascular disease: hazard ratio 1.10 [1.04-1.16], P = 9.7 × 10−4; cardiac death: 1.12 [1.02-1.24], P = 0.03), whereas no effect was observed for either outcome in men (hazard ratio 0.99 [0.95-1.04], P = 0.71; 1.05 [0.94-1.16], P = 0.34). We found significant negative genetic correlations in women, but not men, between age-at-natural menopause and cardiovascular disease and risk factors.

Conclusion:

Genetic variants associated with earlier age-at-natural menopause are associated with increased cardiovascular disease risk in women, but not men, suggesting sex-specific genetic effects on cardiovascular disease risk.
Strategy for Nasal Reconstruction in Atypical Facial Clefts
Authors: Ghareeb Fouad M. , Elsakka Dalia M. , Elsheikh Yaser M. , Nassar Ahmed T. , Abdelreheim Hosam H.
Published: November 2017

It is difficult to put forward a strategy for the treatment of nasal clefts due to the rarity and diversity of anatomical aberrations of these cases contrary to the common nasal affection in cleft lip and palate patients, which differ in severity rather than differing in the morbid anatomy. This simple strategy for correction of these nasal clefts will hopefully help surgeons to achieve better results. In the mean time I intended to describe the morbid anatomy of these cases by choosing examples of each morbid anatomy.
Central Mound Mastopexy for the Correction of Tuberous/Tubular Breast Deformity
Authors: Abbate Olivia A. , Fan Kenneth L. , Nahabedian Maurice Y.
Published: November 2017

Tuberous and tubular breast deformity are well-recognized abnormalities in the plastic surgery community that incur severe physical and psychological consequences in affected patients. Current reconstructive options for the tuberous and tubular breasts favor the use of prosthetic implants and soft-tissue manipulation. We present a case of tuberous and tubular breast deformity treated with a central mound reduction technique and mastopexy with imbricating sutures without the use of prosthetic implants. The patient remained extremely pleased with her results at long-term follow-up. This represents a unique case of successful reconstruction in a patient with a tuberous and tubular breast deformity using a central mound reduction technique with mastopexy and without a prosthetic device.
Improved Diagnostic Performance of an Immunofluorescence-based Rapid Antigen Detection Test for Group A Streptococci in Children With Pharyngitis
Authors: Lacroix Laurence , Cherkaoui Abdessalam , Schaller Diane , Manzano Sergio , Galetto-Lacour Annick , Pfeifer Ulrich , Tabin René , Gervaix Alain
Published: November 2017

Background:

Accurate diagnosis and appropriate treatment of group A streptococcal (GAS) pharyngitis are important to prevent complications. Most available rapid antigen detection tests (RADTs) have shown excellent specificity but often lack sensitivity. Our objective was to compare the diagnostic performances of a new fluorescence-based immunoassay and a classic immunochromatographic RADT using standard throat culture or polymerase chain reaction as references.

Methods:

Prospective observational study in 2 pediatric emergency departments in children 3–15 years of age presenting with pharyngitis and a McIsaac score ≥2. Three throat swabs were obtained simultaneously: one for culture and one for each of both RADTs. Polymerase chain reaction assay of the DNaseB sequence was performed in case of discordant results (culture negative and either RADTs positive).

Results:

A total of 1002 patients were analyzed, with an overall 37.1% prevalence of GAS pharyngitis. Sensitivity, specificity, positive and negative predictive values were, respectively, 84.9%*, 96.8%, 94.0% and 91.6% for the new fluorescence-based immunoassay, and 75.3%*, 98.1%, 95.9% and 87.0% for the immunochromatographic test (*P < 0.05).

Conclusions:

The immunofluorescence-based assay demonstrated improved diagnostic performances over the standard immunochromatographic RADT. Similarly specific for GAS detection, it demonstrates significantly higher sensitivity in children with McIsaac scores 2 or more. A negative result rules out a risk of GAS pharyngitis in 91.6% of children, making it an appropriate tool in pediatric emergency settings. Combined to the low incidence of rheumatic strains, critical appraisal of current practice to routinely perform a backup throat culture from children with pharyngitis and with negative GAS RADT could be reconsidered.
Mobilization of CD4+ T lymphocytes in inflamed mucosa reduces pain in colitis mice: toward a vaccinal strategy to alleviate inflammatory visceral pain
Authors: Basso Lilian , Boué Jérôme , Augé Céline , Deraison Céline , Blanpied Catherine , Cenac Nicolas , Lluel Philippe , Vergnolle Nathalie , Dietrich Gilles
Published: November 2017

T lymphocytes play a pivotal role in endogenous regulation of inflammatory visceral pain. The analgesic activity of T lymphocytes is dependent on their production of opioids, a property acquired on antigen activation. Accordingly, we investigated whether an active recruitment of T lymphocytes within inflamed colon mucosa via a local vaccinal strategy may counteract inflammation-induced visceral pain in mice. Mice were immunized against ovalbumin (OVA). One month after immunization, colitis was induced by adding 3% (wt/vol) dextran sulfate sodium into drinking water containing either cognate antigen OVA or control antigen bovine serum albumin for 5 days. Noncolitis OVA-primed mice were used as controls. Visceral sensitivity was then determined by colorectal distension. Oral administration of OVA but not bovine serum albumin significantly reduced dextran sulfate sodium–induced abdominal pain without increasing colitis severity in OVA-primed mice. Analgesia was dependent on local release of enkephalins by effector anti-OVA T lymphocytes infiltrating the inflamed mucosa. The experiments were reproduced with the bacillus Calmette–Guerin vaccine as antigen. Similarly, inflammatory visceral pain was dramatically alleviated in mice vaccinated against bacillus Calmette–Guerin and then locally administered with live Mycobacterium bovis. Together, these results show that the induction of a secondary adaptive immune response against vaccine antigens in inflamed mucosa may constitute a safe noninvasive strategy to relieve from visceral inflammatory pain.
Clinical trial designs and models for analgesic medications for acute pain in neonates, infants, toddlers, children, and adolescents: ACTTION recommendations
Authors: Walco Gary A. , Kopecky Ernest A. , Weisman Steven J. , Stinson Jennifer , Stevens Bonnie , Desjardins Paul J. , Berde Charles B. , Krane Elliot J. , Anand Kanwaljeet J.S. , Yaster Myron , Dampier Carlton D. , Dworkin Robert H. , Gilron Ian , Lynn Anne M. , Maxwell Lynne G. , Raja Srinivasa , Schachtel Bernard , Turk Dennis C.
Published: November 2017

Clinical trials to test the safety and efficacy of analgesics across all pediatric age cohorts are needed to avoid inappropriate extrapolation of adult data to children. However, the selection of acute pain models and trial design attributes to maximize assay sensitivity, by pediatric age cohort, remains problematic. Acute pain models used for drug treatment trials in adults are not directly applicable to the pediatric age cohorts–neonates, infants, toddlers, children, and adolescents. Developmental maturation of metabolic enzymes in infants and children must be taken into consideration when designing trials to test analgesic treatments for acute pain. Assessment tools based on the levels of cognitive maturation and behavioral repertoire must be selected as outcome measures. Models and designs of clinical trials of analgesic medications used in the treatment of acute pain in neonates, infants, toddlers, children, and adolescents were reviewed and discussed at an Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) Pediatric Pain Research Consortium consensus meeting. Based on extensive reviews and continuing discussions, the authors recommend a number of acute pain clinical trial models and design attributes that have the potential to improve the study of analgesic medications in pediatric populations. Recommendations are also provided regarding additional research needed to support the use of other acute pain models across pediatric age cohorts.
Lower-Extremity Pruritic Ulcerations
Authors: McKnight Mandy , Gust Peter J. , Jacob Sharon E.
Published: November 2017

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. This is a teledermatology case of lower-extremity pruritic ulcerations.
Thin-Layer Rapid Use Epicutaneous Patch Test (T.R.U.E. Test) for Confirmation of Contact Sensitization
Authors: No Daniel J. , Wahjudi Ingrid , Macknet K. Dale , Jacob Sharon E.
Published: November 2017

The patch test is considered the gold standard for the diagnosis of allergic contact dermatitis. The Thin-Layer Rapid Use Epicutaneous Patch Test (T.R.U.E. Test) is a patch test approved by the U.S. Food and Drug Administration containing 35 preloaded, ready-to-apply allergens and allergen mixes. Our objective is to provide a comprehensive review of the commercially available patch test kit.
A Prospective Observational Cross-Sectional Study Examining the Effect of Using Human Simulation and Moulages to Assist in Skin Cancer Education of Nursing Students
Authors: Siegel Victoria , Eckardt Patricia
Published: November 2017

Background

There has been a dramatic increase in the incidence of skin cancer; over 1 million new cases are diagnosed annually. Approximately one person dies from skin cancer per hour in this country. Nurses are in an excellent position to perform screenings for cancer, and skin cancer screenings should be taught in the nursing curriculum. The use of simulation increases knowledge and efficacy.

Methods

A cross-sectional study examining the use of moulages and simulation as an educational intervention on the knowledge of skin cancer, sun protective behaviors, and role of the nurse in skin cancer prevention in second-year nursing students enrolled in a baccalaureate nursing program.

Results

Students did not differ on baseline knowledge. However, the intervention group showed significant increased knowledge in all outcomes.

Conclusions

Increasing understanding of skin cancer with the use of moulages and simulation enhanced education and expertise in recognizing skin cancers.
When the momentum has gone: what will be the role of extracorporeal lung support in the future?
Authors: Abrams Darryl , Bacchetta Matthew , Brodie Daniel
Published: November 2017

Purpose of review

There has been expanding interest in and use of extracorporeal support in respiratory failure concurrent with technological advances and predominantly observational data demonstrating improved outcomes. However, until there is more available data from rigorous, high-quality randomized studies, the future of extracorporeal support remains uncertain.

Recent findings

Outcomes for patients supported with extracorporeal devices continue to show favorable trends. There are several large randomized controlled trials that are in various stages of planning or completion for extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R) in the acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD), which may help clarify the role of this technology for these disease processes, and which stand to have a significant impact on a large proportion of patients with acute respiratory failure. Novel applications of extracorporeal lung support include optimization of donor organ quality through ex-vivo perfusion and extracorporeal cross-circulation, allowing for multimodal therapeutic interventions.

Despite the ongoing rise in ECMO use for acute respiratory failure, its true value will not be known until more information is gleaned from prospective randomized controlled trials. Additionally, there are modalities beyond the current considerations for extracorporeal support that have the potential to revolutionize respiratory failure, particularly in the realm of chronic lung disease and lung transplantation.
Recent insights into biological functions of mammalian bombesin-like peptides and their receptors
Authors: Qu Xiangping , Wang Hui , Liu Rujiao
Published: November 2017

Purpose of review

The current review highlights recent advances in physiological and pharmacological researches in biology of mammalian bombesin-like peptides (BLPs).

Recent findings

BLPs and their receptors were found to have regulatory roles in many biological processes in central nervous system. Two BLPs, neuromedin B and gastrin-releasing peptide (GRP), and their receptors are required for regulation of basal and induced sighing activity in rodents. This is the first study demonstrating central pathways involved in regulation of sighing activity. GRP receptor (GRPR) expressing neurons are excitatory glutamatergic interneurons located in the dorsal lamina without projections outside the spinal cord and mediate itch signals via vesicular glutamate transporter 2. Those neurons receive itch signals and make synapses with the parabrachial nucleus projecting spinal neurons to transmit itch signals to parabrachial nucleus. GRP expressing interneurons function in a proposed ‘leaky gate model’ to interpret the mechanism of both pain and itch transmission. In addition to recent advances of biology in nervous system, BLPs and their receptors were found to play potential regulatory roles in innate and adaptive immune responses and tissue development.

Several important biological roles of BLPs and their receptors in nervous system were identified. Together with researches regarding central roles of BLPs, studies revealing the regulatory roles of BLPs and their receptors in immunology and tissue development provide us with novel insights into understanding of the biology of BLPs and their receptors.
Endocrine disrupters and pubertal timing
Authors: Greenspan Louise C. , Lee Mary M.
Published: November 2017

Purpose of review

The current review summarizes recent epidemiologic data demonstrating the effects of endocrine disrupting compounds (EDCs) on the timing of puberty and highlights the complexity of understanding the interplay of environmental and genetic factors on pubertal timing.

Recent findings

In girls, there have been mixed results, with some exposures being associated with earlier timing of puberty, and some with later puberty. In boys, prepubertal exposures to nondioxin-like polychlorinated biphenyls accelerate puberty, whereas levels of insecticides, dioxin-like compounds, organochlorine pesticides, and lead delay puberty.

The effects of EDCs on pubertal timing are sexually dimorphic, compound specific, and varies according to the window of exposure. These studies confirm that low-level exposures to a mix of environmental compounds may mask the effects of individual compounds and complicate our ability to translate data from animal studies to human health and to fully understand the clinical implications of environmental epidemiology studies.
Severe Warm Autoimmune Hemolytic Anemia in a 7-Month-Old Infant Associated With a Mycoplasma Pneumoniae Infection
Authors: Wandro Cierra , Dolatshahi Leili , Blackall Douglas
Published: November 2017

A 7-month-old female infant had clinical and laboratory evidence of severe warm autoimmune hemolytic anemia. She also had clinical evidence of an upper respiratory tract infection with molecular detection of Mycoplasma pneumoniae. Although reticulocytopenic initially, she responded to red blood cell transfusion, steroids, and intravenous immunoglobulin and remains well today. With the increasing use of multiplex respiratory viral and bacterial pathogen detection systems, the rare association described in this report may prove to be more common than previously thought and may provide insight into the pathogenesis and clinical consequences of red blood cell autoantibodies.
The Multiple Faces of Programmed Cell Death Ligand 1 Expression in Malignant and Nonmalignant Cells
Authors: Parra Edwin R. , Villalobos Pamela , Rodriguez-Canales Jaime
Published: November 2017

Preliminary data suggest that tumor expression of programmed cell death ligand 1 (PD-L1) protein in human cancers, as determined by immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples, may predict clinical response to anti-PD-1/PD-L1 therapy. PD-L1 is not a specific tumor marker and its expression is also observed in various nonmalignant cells, such as macrophages and lymphocytes, causing confusion in immunohistochemistry analysis when these inflammatory cells are overlapping with tumors cells. The aim of the current study was to examine PD-L1 expression in formalin-fixed, paraffin-embedded malignant and nonmalignant cells from human tumors to establish potential characteristic patterns of PD-L1 expression in tumor tissues. We used a commercial PD-L1 clone (E1L3N) previously validated in our laboratory to characterize PD-L1 expression in surgically resected lung adenocarcinomas, lung squamous cell carcinomas, malignant melanomas, renal cell carcinomas, hepatocellular carcinomas, and ductal breast carcinomas. We observed different patterns of PD-L1 expression by malignant cells and nonmalignant cells as membrane, cytoplasmic, and nuclear expression. The distribution of expression was variable including the entire malignant cells population, heterogonous with random distribution, peripheral distribution, minimal expression by few cells and negative expression. Similar, nonmalignant cells showed randomly and peripherally distribution through the tumors. We concluded that the PD-L1 cell protein expression patterns and distributions are variable and differ between resected tumor specimens. The expression and distribution pattern described here provide a useful knowledgment of PD-L1 expression in tumor samples.
Clinical Impact of External Laryngeal Manipulation During Laryngoscopy on Tracheal Intubation Success in Critically Ill Children*
Authors: Kojima Taiki , Laverriere Elizabeth K. , Owen Erin B. , Harwayne-Gidansky Ilana , Shenoi Asha N. , Napolitano Natalie , Rehder Kyle J. , Adu-Darko Michelle A. , Nett Sholeen T. , Spear Debbie , Meyer Keith , Giuliano John S. , Tarquinio Keiko M. , Sanders Ronald C. , Lee Jan Hau , Simon Dennis W. , Vanderford Paula A. , Lee Anthony Y. , Brown Calvin A. , Skippen Peter W. , Breuer Ryan K. , Toedt-Pingel Iris , Parsons Simon J. , Gradidge Eleanor A. , Glater Lily B. , Culver Kathleen , Li Simon , Polikoff Lee A. , Howell Joy D. , Nuthall Gabrielle , Bysani Gokul K. , Graciano Ana L. , Emeriaud Guillaume , Saito Osamu , Orioles Alberto , Walson Karen , Jung Philipp , Al-Subu Awni M. , Ikeyama Takanari , Shetty Rakshay , Yoder Kathleen M. , Nadkarni Vinay M. , Nishisaki Akira
Published: November 2017

Objectives:

External laryngeal manipulation is a commonly used maneuver to improve visualization of the glottis during tracheal intubation in children. However, the effectiveness to improve tracheal intubation attempt success rate in the nonanesthesia setting is not clear. The study objective was to evaluate the association between external laryngeal manipulation use and initial tracheal intubation attempt success in PICUs.

Design:

A retrospective observational study using a multicenter emergency airway quality improvement registry.

Setting:

Thirty-five PICUs within general and children’s hospitals (29 in the United States, three in Canada, one in Japan, one in Singapore, and one in New Zealand).

Patients:

Critically ill children (< 18 years) undergoing initial tracheal intubation with direct laryngoscopy in PICUs between July 1, 2010, and December 31, 2015.

Measurements and Main Results:

Propensity score–matched analysis was performed to evaluate the association between external laryngeal manipulation and initial attempt success while adjusting for underlying differences in patient and clinical care factors: age, obesity, tracheal intubation indications, difficult airway features, provider training level, and neuromuscular blockade use. External laryngeal manipulation was defined as any external force to the neck during laryngoscopy. Of the 7,825 tracheal intubations, the initial tracheal intubation attempt was successful in 1,935/3,274 intubations (59%) with external laryngeal manipulation and 3,086/4,551 (68%) without external laryngeal manipulation (unadjusted odds ratio, 0.69; 95% CI, 0.62–0.75; p < 0.001). In propensity score–matched analysis, external laryngeal manipulation remained associated with lower initial tracheal intubation attempt success (adjusted odds ratio, 0.93; 95% CI, 0.90–0.95; p < 0.001).

Conclusions:

External laryngeal manipulation during direct laryngoscopy was associated with lower initial tracheal intubation attempt success in critically ill children, even after adjusting for underlying differences in patient factors and provider levels. The indiscriminate use of external laryngeal manipulation cannot be recommended.
Ondansetron Prescription for Home Use in a Pediatric Emergency Department
Authors: Gray James M. , Maewal Jaya D. , Lunos Scott A. , Furnival Ronald A. , Hendrickson Marissa A.
Published: November 2017

Objectives

Ondansetron has been shown to decrease admission rate and the need for intravenous fluids among pediatric emergency department (ED) patients with acute gastroenteritis, but there is limited evidence regarding its use after ED discharge. This study describes prescribing patterns for ondansetron and assesses the effects of ondansetron home prescription on rate of return.

Methods

Data were gathered from the electronic health record on 2 separate but overlapping groups of patients seen in a pediatric ED from 2012 to 2014. The Gastroenteritis Group included all patients with a discharge diagnosis of gastroenteritis by International Classification of Diseases, Ninth Revision, code. The All Ondansetron Group included any child prescribed ondansetron at discharge. Patterns of ondansetron use and 3- and 7-day ED return rate were assessed for both groups. Discharge diagnosis was evaluated for the All Ondansetron Group.

Results

A total of 996 patients with acute gastroenteritis were identified during the study period. Of these, 76% received ondansetron in the ED, and 71% were discharged with prescriptions for ondansetron. Seven-day ED return rates were similar between groups (6% with prescription, 5% without, P = 0.66). A total of 2287 patients received home prescriptions for ondansetron. Fifty-four percent of these patients' discharge diagnoses were classed as gastrointestinal complaints, 14% other infectious conditions, 9% respiratory, and 4% injuries. Their return rate was 6%. There was wide variation in the number of doses prescribed.

Conclusions

Home-use ondansetron is widely prescribed in this urban academic pediatric ED for a variety of indications, without effect on 3- or 7-day ED return. Further prospective studies are necessary to determine the efficacy of this practice.
Should the Absence of Urinary Nitrite Influence Empiric Antibiotics for Urinary Tract Infection in Young Children?
Authors: Chaudhari Pradip P. , Monuteaux Michael C. , Bachur Richard G.
Published: November 2017

Objectives

Screening for urinary tract infection (UTI) includes urinary nitrite testing by dipstick urinalysis. Gram-negative enteric organisms produce urinary nitrite and represent the most common uropathogens. Enterococcus, a less common uropathogen, does not produce nitrite and has a unique antibiotic resistance pattern. Whether to adjust empiric antibiotics in the absence of urinary nitrite has not been established. Our primary objective was to determine prevalence of enterococcal UTI among young children with a nitrite negative urinalysis.

Methods

A retrospective study of children aged less than 2 years evaluated in the emergency department for possible UTI and had a paired urinalysis and urine culture was performed. Urinary tract infection was defined by catheterized culture yielding greater than or equal to 50,000 colony-forming units per milliliter of a single uropathogen. Prevalence of uropathogens among nitrite negative samples was studied.

Results

A total of 7599 children were studied. Median (interquartile range) age was 5.6 (2.3–11.2) months, and 57% were female. Prevalence of UTI was 8.1%. Enterococcus was the uropathogen in 2.1% of UTIs, and all cases had negative dipstick nitrite. Among nitrite negative UTIs, 95.6% of uropathogens were gram-negative and only 3.2% (confidence interval, 1.8%–5.3%) were enterococcus. None of the 200 UTIs with positive nitrite yielded enterococcus (upper confidence interval, 1.4%). Among children with positive leukocyte esterase and negative nitrite, only 0.7% of cases had enterococcal UTI.

Conclusions

Only 3% of nitrite negative UTIs were caused by enterococcus. Given the low prevalence of enterococcal UTI, the absence of dipstick nitrite should not affect routine empiric antibiotic choice for presumptive UTI in young children.
Experienced HIV-Related Stigma in Health Care and Community Settings: Mediated Associations With Psychosocial and Health Outcomes
Authors: Kay Emma S. , Rice Whitney S. , Crockett Kaylee B. , Atkins Ghislaine C. , Batey David. Scott , Turan Bulent
Published: November 2017

Introduction:

There are multiple dimensions of HIV-related stigma that can compromise the mental and physical health of people living with HIV. We focused on the dimension of experienced stigma, defined as exposure to acts of discrimination, devaluation, and prejudice, and investigated its relationship with HIV health and psychosocial outcomes.

Methods:

We examined associations between experienced stigma in the community and health care settings and psychosocial and health outcomes for people living with HIV (N = 203) receiving care at an urban HIV clinic in the Southeastern United States. We also investigated whether those effects are unique to experienced stigma or are mediated by other dimensions of HIV-related stigma.

Results:

Experienced stigma was associated with suboptimal clinical outcomes such as viral nonsuppression, as well as poor affective, cognitive, and mental health outcomes (self-esteem, depressive symptoms, avoidance coping, and blame coping) and interpersonal outcomes such as social support and physician trust. Furthermore, serial mediation models suggested significant indirect effects of experienced stigma through internalized stigma and anticipated stigma from various theoretically expected sources of stigma (eg, community members, friends and family, and health care workers), with varying effects depending on the source.

Conclusions:

These findings suggest nuanced mechanisms for the effects of experienced HIV-related stigma, especially in health care settings, and may be used to inform stigma-reduction interventions. Interventions designed to address experienced stigma in health care settings might be more tailored to specific outcomes, such as depression and physician trust, than interventions designed to address experienced stigma in the community.