bluuebunny/crossref_metadata_2025 huggingface dataset:
The micro-to-macro realities of antidepressant taking: Users’ experiences in the context of contested science and industry promotion
Authors: Hughes Shannon , Lacasse Jeffrey R , Spaulding-Givens Jennifer
Published: August 2019

The macro landscape shaping antidepressant use is marked by uncertain and contested research and vigorous pharmaceutical promotion to doctors and (in the U.S.) patients. While prior studies have investigated antidepressant users’ firsthand experiences of the impacts of medication use on their lives and identities, these studies do not explicitly situate users’ experiences within the macro realities that shape the larger system of care. The aim of this Internet-based qualitative study was to advance a uniquely social work perspective on psychotropic medications by thematically examining the everyday experiences of antidepressant users and framing emergent themes within the broader macro context. The largest sample to date (n = 3243) of user reviews of four antidepressants (escitalopram, duloxetine, vilazodone, and vortioxetine) were downloaded from popular patient-reporting websites and analyzed line-by-line by two independent coders in a general inductive coding process. Antidepressant experiences were characterized by trial-and-error experimentation, limited relief, drug cocktails, uncertainty about causes of change, and unforeseen drug withdrawal challenges. Individual-level experiences are contextualized within the larger landscape of publication bias in clinical drug trials and persistent drug industry promotion of newer, costlier, and add-on drugs. Based on the profession’s systems perspective and social justice commitment, social workers should recognize how macro factors contextualize individual experience and strive to support users in cultivating more informed, empowering relationships with psychiatric drugs. Exploring the meaning of medications, validating users’ firsthand experiences, and monitoring changes throughout treatment and discontinuation are appropriate, critical roles that social workers should consider adopting.
Enablers and Barriers to Registered Nurses Expanding Their Scope of Practice in Australia: A Cross-Sectional Study
Authors: Birks Melanie , Davis Jenny , Smithson John , Lindsay Daniel
Published: August 2019

A number of resources exist to assist registered nurses in Australia to determine their scope of practice; however, the ability of a professional nurse to expand his or her practice is highly context dependent. This article reports on barriers and enablers to expanding scope of practice, as identified by registered nurses across Australia. A cross-sectional survey administered online in 2016 returned 1,205 useable submissions. Results indicated that nurses wishing to expand their practice felt supported to do so by nursing colleagues and were aware of professional and regulatory documents relating to expanding scope of practice. Less support for this process was evident from other health professionals or employers. Respondents also indicated that they were motivated to expand their scope by professional satisfaction, potential for career advancement, and the desire to meet health service user's needs. The majority of respondents identified barriers to expanding scope of practice, including lack of remuneration and the absence of supportive guidelines. Respondents in the early stage of their careers were more likely to perceive organizational support for expanding their scope of practice. When required to expand their role, the majority of respondents indicated that they had undertaken additional training or accessed various resources to guide them in this process. Barriers to expanding nursing scope of practice can result in underutilization of the one of the greatest resources in the health care system. This article identifies a number of strategies that can facilitate role expansion to ensure that nursing continues to make a significant contribution to positive health service outcomes in Australia.
Factors Associated With Reoperation After Silicone Proximal Interphalangeal Joint Arthroplasty
Authors: Lans Jonathan , Notermans Bo J.W. , Germawi Lazin , Lee Hang , Jupiter Jesse B. , Chen Neal C.
Published: August 2019

Background: Silicone proximal interphalangeal (PIP) joint arthroplasty has a high revision rate. It has been suggested that persistent ulnar deviation and joint instability influence the durability of PIP silicone arthroplasties. The goal of this study was to evaluate what factors are associated with reoperation after silicone PIP arthroplasty. Methods: We retrospectively evaluated all adult patients who underwent PIP silicone arthroplasty between 2002 and 2016 at one institutional system for inflammatory-, posttraumatic-, and primary degenerative arthritis. After manual chart review, we included 91 patients who underwent 114 arthroplasties. Fingers operated included 14 index, 41 middle, 38 ring, and 21 small fingers. Results: The overall reoperation rate was 14% (n = 16). Non-Caucasian race ( P = .040), smoking ( P = .022) and PIP silicone arthroplasty for post-traumatic osteoarthritis ( P = .021) were associated with reoperation. The 1-, 5- and 10-year implant survival rates were 87%, 85%, and 85%, respectively. Conclusion: Caution should be exercised when considering PIP silicone arthroplasty of the index finger or in patients with post-traumatic osteoarthritis. It may be worthwhile addressing smoking behavior before pursuing silicone PIP arthroplasty.
Dietary compounds as potential modulators of microRNA expression in psoriasis
Authors: Kocic Hristina , Damiani Giovanni , Stamenkovic Bojana , Tirant Michael , Jovic Andrija , Tiodorovic Danica , Peris Ketty
Published: August 2019

Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between ‘good and bad’ miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other ‘omics’, may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.
Therapies for the management of genitourinary syndrome of menopause
Authors: Palacios Santiago , Combalia Josep , Emsellem Carine , Gaslain Yann , Khorsandi Danial
Published: August 2019

Introduction

The genitourinary syndrome of menopause is a new term that describes various menopausal symptoms and signs including not only genital symptoms (dryness, burning, and irritation) and sexual symptoms (lack of lubrication, discomfort or pain, and impaired function), but also urinary symptoms (urgency, dysuria, and recurrent urinary tract infections).

Methods

We conducted a systematic scoping review of data in women therapies with genitourinary syndrome of menopause or vulvovaginal atrophy in peer-reviewed, English-language publications in the last 20 years.

Results

The terms vulvovaginal atrophy and atrophic vaginitis, which were generally used up until recently, had a limitation because they did not cover the full spectrum of symptoms and did not imply that the symptoms are related to a decreased sex steroid level in menopause. The concept of genitourinary syndrome of menopause was recently introduced and has been gaining widespread use. Since genitourinary syndrome of menopause may have a profound negative impact on the quality of life of postmenopausal women, patients should be made aware of these problems and treated with an appropriate effective therapy. Therefore, in this review we introduce therapies for this syndrome, both local and systemic, and discuss the importance of genitourinary syndrome of menopause comprehension and the need to have an active treatment of this syndrome in postmenopausal women.

Conclusion

The increasing number of therapies for menopausal symptoms opens up new options. In addition, new products have been designed and developed by pharmaceutical companies as new possibilities for patients who did not have any treatment available and also to improve compliance.
Tourist’s Satisfaction in Terms of Accommodation: A Case Study in Vlore, Albania
Authors: Pjero (Beqiraj) Elenica , Gjermëni Orgeta
Published: August 2019

This study aims to explore tourist’s satisfaction on the accommodation provided during their stay in Vlore (Albania) touristic structures, and if there are possible associations between different characteristics related to this service and tourists. Lack of studies on analyzing customer satisfaction in the industry of accommodation, especially for Vlore, have prompted us to undertake this study. The study results are important for local government, the accommodation industry, and is a source of information for whom is interested to improve their accommodation services, or to invest in accommodation industry located in Vlore, Albania. “Netnography” is used to collect data for our research purpose from the reviews in TripAdvisor website. Using descriptive and inferential statistics, this study concludes that 64.9 percent of the ratings are “very good” or “excellent,” regardless of the accommodation structure chosen. Accommodation structures should have a clear defined idea of what kind of tourist they want to attract in a certain period of the year, in order to offer the quality tourists expect. Furthermore, understanding of tourist satisfaction evaluation is important in implementing successful marketing campaigns.
Lateral Medullary Syndrome Due to Left Vertebral Artery Occlusion in a Boy Postflexion Neck Injury
Authors: Alawadhi Abdulla , Saint-Martin Christine , Sabapathy Christine , Sebire Guillaume , Shevell Michael
Published: August 2019

Lateral medullary syndrome is rare in pediatrics. It is characterized by neurological deficits due to an ischemic lesion in the lateral medulla. The authors describe a 17-year-old boy who developed lateral medullary syndrome in the context of a hyperflexion neck injury while diving in shallow water with traumatic vascular injury. He had “crossed” neurological deficits above and below the neck. His magnetic resonance angiography showed intra- and extracranial left vertebral artery occlusion and his magnetic resonance imaging showed signal abnormality involving the left lateral medulla and inferomedial cerebellum in keeping with an infarct secondary to left vertebral artery and left posterior inferior cerebellar artery occlusion. Good neurological recovery was observed on heparin therapy started after surgical treatment of traumatic injury. To our knowledge, this is the first reported case of lateral medullary syndrome in a pediatric population related to a flexion neck injury. The authors emphasize the importance of a high level of suspicion for accurate diagnosis.
Insulin resistance and dysglycemia are associated with left ventricular remodeling after myocardial infarction in non-diabetic patients
Authors: Yang Chen Die , Shen Ying , Lu Lin , Ding Feng Hua , Yang Zhen Kun , Zhang Rui Yan , Shen Wei Feng , Jin Wei , Wang Xiao Qun
Published: August 2019

Background

Adverse cardiac remodeling after ST-segment elevation myocardial infarction (STEMI) is a major cause for poor cardiovascular outcomes such as heart failure. The predisposing factors and underlying mechanisms remain not fully understood. This study investigates the association of insulin resistance and dysglycemia with left ventricular (LV) remodeling after STEMI in non-diabetic patients.

Methods

A total of 485 non-diabetic subjects with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for 12 months. Relation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and glucose levels to changes in echocardiography parameters was studied.

Results

Left ventricular dilation was detected in 49.1% of subjects at 12-month follow-up after STEMI, and was more severe in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and high HOMA-IR levels. HOMA-IR remained correlated to changes in LV dimensions after adjusting for confounding risk factors. Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI. A significant interaction term was present between HOMA-IR and IGT in the model (P = 0.001).

Conclusions

Our study reveals that insulin resistance and dysglycemia are prevalent in non-diabetic patients with STEMI and are predictors of the post-infarction LV dilation.

Trial registration Trials number, NCT02089360; registered on March 17, 2014
RETRACTED ARTICLE: BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway
Authors: Feng Peng-Cheng , Ke Xing-Fei , Kuang Hui-Lan , Pan Li-Li , Ye Qiang , Wu Jian-Bing
Published: August 2019

Background

Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. Bone morphogenetic protein (BMP) exhibits a broad spectrum of biological activities in various tissues including angiogenesis. Here, this study aimed to investigate the mechanism of BMP2 in HCC by mediating the mitogen-activated protein kinase (MAPK)/p38 signaling pathway.

Methods

BMP2 expression was quantified in HCC and adjacent tissues. BMP2 gain- and loss-of-function experiments were conducted by infection with lentivirus over-expressing BMP2 or expressing shRNA against BMP2. The angiogenesis was evaluated with HepG2 cells co-cultured with ECV304 cells. SB-239063 was applied to inhibit the activation of the MAPK/p38 signaling pathway so as to identify the significance of this pathway in HCC progression. Finally, in vivo experiments were conducted to identify the role of BMP2 and the MAPK/p38 signaling pathway in tumor growth and angiogenesis.

Results

BMP2 was highly expressed in HCC. Over-expression of BMP2 was found to accelerate cell proliferation, migration, invasion, microvascular density, and angiogenesis and decrease cell apoptosis in vitro and in vivo. BMP2 silencing exhibited inhibitory effects on HCC cell invasion and angiogenesis. The co-culture system illustrated that HepG2 cells secreted BMP2 in ECV304, and silenced BMP2 in HepG2 cells resulted in the inactivation of the MAPK/p38 signaling pathway, thus suppressing cancer progression, tumor growth, and angiogenesis in HCC.

Conclusion

Taken together, the key findings of this study propose that silencing of BMP2 inhibits angiogenesis and tumor growth in HCC, highlighting BMP2 silencing as a potential strategy for the treatment of HCC.
Throughput maximization-based optimal power allocation for energy-harvesting cognitive radio networks with multiusers
Authors: Wang Yuanyi , Zhao Xiaohui , Liang Hui
Published: August 2019

An optimal power allocation (OPA) policy for orthogonal frequency division multiplexing (OFDM)-based cognitive radio networks (CRNs) using underlay spectrum access model is presented under multiple secondary users (SUs) with energy harvesting (EH). The proposed algorithm can allocate transmission power to each SU on each subcarrier with the objective of maximizing the average throughput of secondary network over a finite time interval. We consider both the interference power constraint limited by primary user (PU) and the minimum throughput constraint of each SU to improve the throughput of SUs while guaranteeing the communication quality of PU. To balance current throughput and expected future throughput, a dynamic programming (DP) problem is defined and solved by the backward induction method. Moreover, for each time slot, a convex immediate optimization is presented to obtain an optimal solution, which can be solved by the Lagrange dual method. Simulation results show that our policy can achieve better performance than some traditional policies and ensure good quality of service (QoS) of PU when SUs access the spectrum.
Ferredoxin 1b Deficiency Leads to Testis Disorganization, Impaired Spermatogenesis, and Feminization in Zebrafish
Authors: Oakes James A , Li Nan , Wistow Belinda R C , Griffin Aliesha , Barnard Lise , Storbeck Karl-Heinz , Cunliffe Vincent T , Krone Nils P
Published: August 2019

The roles of steroids in zebrafish sex differentiation, gonadal development, and function of the adult gonad are poorly understood. Herein, we used ferredoxin 1b (fdx1b) mutant zebrafish to explore such processes. Fdx1b is an essential electron-providing cofactor to mitochondrial steroidogenic enzymes, which are crucial for glucocorticoid and androgen production in vertebrates. Fdx1b−/− zebrafish mutants develop into viable adults in which concentrations of androgens and cortisol are significantly reduced. Adult fdx1b−/− mutant zebrafish display predominantly female secondary sex characteristics but may possess either ovaries or testes, confirming that androgen signaling is dispensable for testicular differentiation in this species, as previously demonstrated in androgen receptor mutant zebrafish. Adult male fdx1b−/− mutant zebrafish exhibit reduced characteristic breeding behaviors and impaired sperm production, resulting in infertility in standard breeding scenarios. However, eggs collected from wild-type females can be fertilized by the sperm of fdx1b−/− mutant males by in vitro fertilization. The testes of fdx1b−/− mutant males are disorganized and lack defined seminiferous tubule structure. Expression of several promale and spermatogenic genes is decreased in the testes of fdx1b−/− mutant males, including promale transcription factor sox9a and spermatogenic genes igf3 and insl3. This study establishes an androgen- and cortisol-deficient fdx1b zebrafish mutant as a model for understanding the effects of steroid deficiency on sex development and reproductive function. This model will be particularly useful for further investigation of the roles of steroids in spermatogenesis, gonadal development, and regulation of reproductive behavior, thus enabling further elucidation of the physiological consequences of endocrine disruption in vertebrates.
Widespread Cell-Specific Prolactin Receptor Expression in Multiple Murine Organs
Authors: Aoki Mari , Wartenberg Philipp , Grünewald Ramona , Phillipps Hollian R , Wyatt Amanda , Grattan David R , Boehm Ulrich
Published: August 2019

The prolactin receptor (Prlr) mediates not only the multiple effects of prolactin, but also those of the placental lactogens and, in humans, some actions of growth hormone. Although Prlr expression has been reported to be widespread in the body, specific cellular expression patterns within tissues are undefined for many organs. One persisting problem in investigating Prlr function is that the protein is difficult to detect using conventional methods. To allow investigation of Prlr expression with a single cell resolution, we have recently developed a knock-in mouse strain in which Cre recombinase is expressed together with the long isoform of the Prlr using an internal ribosome entry site. When crossed to a Cre-dependent reporter mouse strain, Cre-mediated recombination will genetically label cells that acutely express the Prlr as well as cells that have transiently expressed the Prlr during development. We report here the anatomical distribution of cells which express the fluorescent reporter τ green fluorescent protein in a total of 38 organs prepared from young adult male and female Prlr reporter mice. Our results establish a resource for dissecting the functional role of Prlr in multiple murine tissues.
Lipokines and Thermogenesis
Authors: Lynes Matthew D , Kodani Sean D , Tseng Yu-Hua
Published: August 2019

Adaptive thermogenesis is a catabolic process that consumes energy-storing molecules and expends that energy as heat in response to environmental changes. This process occurs primarily in brown and beige adipose tissue. Thermogenesis is regulated by many factors, including lipid derived paracrine and endocrine hormones called lipokines. Recently, technologic advances for identifying new lipid biomarkers of thermogenic activity have shed light on a diverse set of lipokines that act through different pathways to regulate energy expenditure. In this review, we highlight a few examples of lipokines that regulate thermogenesis. The biosynthesis, regulation, and effects of the thermogenic lipokines in several families are reviewed, including oloeylethanolamine, endocannabinoids, prostaglandin E2, and 12,13-diHOME. These thermogenic lipokines present potential therapeutic targets to combat states of excess energy storage, such as obesity and related metabolic disorders.
Sex Differences in Adrenal Bmal1 Deletion–Induced Augmentation of Glucocorticoid Responses to Stress and ACTH in Mice
Authors: Engeland William C , Massman Logan , Miller Lauren , Leng Sining , Pignatti Emanuele , Pantano Lorena , Carlone Diana L , Kofuji Paulo , Breault David T
Published: August 2019

The circadian glucocorticoid (GC) rhythm is dependent on a molecular clock in the suprachiasmatic nucleus (SCN) and an adrenal clock that is synchronized by the SCN. To determine whether the adrenal clock modulates GC responses to stress, experiments used female and male Cyp11A1Cre/+::Bmal1Fl/Fl knockout [side-chain cleavage (SCC)–KO] mice, in which the core clock gene, Bmal1, is deleted in all steroidogenic tissues, including the adrenal cortex. Following restraint stress, female and male SCC-KO mice demonstrate augmented plasma corticosterone but not plasma ACTH. In contrast, following submaximal scruff stress, plasma corticosterone was elevated only in female SCC-KO mice. Adrenal sensitivity to ACTH was measured in vitro using acutely dispersed adrenocortical cells. Maximal corticosterone responses to ACTH were elevated in cells from female KO mice without affecting the EC50 response. Neither the maximum nor the EC50 response to ACTH was affected in male cells, indicating that female SCC-KO mice show a stronger adrenal phenotype. Parallel experiments were conducted using female Cyp11B2 (Aldosterone Synthase)Cre/+::Bmal1Fl/Fl mice and adrenal cortex–specific Bmal1-null (Ad-KO) mice. Plasma corticosterone was increased in Ad-KO mice following restraint or scruff stress, and in vitro responses to ACTH were elevated in adrenal cells from Ad-KO mice, replicating data from female SCC-KO mice. Gene analysis showed increased expression of adrenal genes in female SCC-KO mice involved in cell cycle control, cell adhesion–extracellular matrix interaction, and ligand receptor activity that could promote steroid production. These observations underscore a role for adrenal Bmal1 as an attenuator of steroid secretion that is most prominent in female mice.
Developmental Programming: Contribution of Epigenetic Enzymes to Antral Follicular Defects in the Sheep Model of PCOS
Authors: Guo Xingzi , Puttabyatappa Muraly , Thompson Robert C , Padmanabhan Vasantha
Published: August 2019

Prenatal testosterone (T)-treated sheep, similar to women with polycystic ovary syndrome (PCOS), manifest oligo-/anovulation, hyperandrogenism, and polyfollicular ovary. The polyfollicular ovarian morphology, a result of persistence of antral follicles, arises, in part, by transcriptional changes in key mediators of follicular development that, in turn, are driven by epigenetic mechanisms. We hypothesized that prenatal T excess induces, in a cell-specific manner, transcriptional changes in key mediators of follicular development associated with relevant changes in epigenetic machinery. Expression levels of key mediators of follicular development, DNA methyltransferases (DNMTs), and histone de-/methylases and de-/acetylases were determined in laser-capture microdissection-isolated antral follicular granulosa and theca and ovarian stromal cells from 21 months of age control and prenatal T-treated sheep (100 mg IM twice weekly from gestational day 30 to 90; term: 147 days). Changes in histone methylation were determined by immunofluorescence. Prenatal T treatment induced the following: (i) cell-specific changes in gene expression of key mediators of follicular development and steroidogenesis; (ii) granulosa, theca, and stromal cell-specific changes in DNMTs and histone de-/methylases and deacetylases, and (iii) increases in histone 3 trimethylation at lysine 9 in granulosa and histone 3 dimethylation at lysine 4 in theca cells. The pattern of histone methylation was consistent with the expression profile of histone de-/methylases in the respective cells. These findings suggest that changes in expression of key genes involved in the development of the polyfollicular phenotype in prenatal T-treated sheep are mediated, at least in part, by cell-specific changes in epigenetic-modifying enzymes.
Exosome-Transmitted lncRNA H19 Inhibits the Growth of Pituitary Adenoma
Authors: Zhang Yong , Liu Yan Ting , Tang Hao , Xie Wan Qun , Yao Hong , Gu Wei Ting , Zheng Yong Zhi , Shang Han Bing , Wang Yu , Wei Yong Xu , Wu Ze Rui , Wu Zhe Bao
Published: August 2019

Context

Our previous study demonstrated that the expression of long noncoding RNA (lncRNA) H19 was frequently downregulated in human primary pituitary adenomas and negatively correlated with tumor progression. However, the role of exosomal lncRNA H19 in the inhibition of pituitary tumor growth remains unclear.

Objective

To investigate whether exosomal H19 could be transported across the cell membrane to exert its inhibitory effect on pituitary tumor growth.

Design

Empty lentivirus GH3 cells with or without H19 overexpression were used to establish a xenograft model. Isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking, and Western blotting. The expression levels of serum exosomal H19 from 200 healthy subjects and 206 patients with various subtypes of pituitary tumors were detected by ultracentrifugation and quantitative real-time PCR.

Results

The growth of distal tumor cells was inhibited by transferring exosomal H19, which could be transported through cell membrane and exert its inhibitory effect. Cabergoline increased H19 expression and played a synergic therapeutic effect with exosomal H19. Exosomal H19 inhibited phosphorylation of the mTORC1 substrate 4E-BP1. Of note, the expression level of exosomal H19 in the patients with all subtypes of pituitary tumors was significantly lower than that in the healthy subjects. The change of plasma exosomal H19 level may be correlated with the prognosis or drug response of the patients.

Conclusion

Exosomal H19 inhibits the growth of distal pituitary tumors through inhibiting 4E-BP1 phosphorylation. Plasma exosomal H19 may serve as an important biomarker for predicting medical responses of patients with prolactinomas.
Contribution of Asian Haplotype of KCNJ18 to Susceptibility to and Ethnic Differences in Thyrotoxic Periodic Paralysis
Authors: Noso Shinsuke , Babaya Naru , Hiromine Yoshihisa , Ito Hiroyuki , Taketomo Yasunori , Yoshida Sawa , Niwano Fumimaru , Monobe Keisuke , Minohara Tatsuro , Okada Takuya , Tsugawa Mamiko , Kawabata Yumiko , Ikegami Hiroshi
Published: August 2019

Context and Objectives

Thyrotoxic periodic paralysis (TPP) is an acute complication of thyrotoxicosis that can be lethal. TPP is rare in Caucasians but often affects young men in East Asian populations. This study aimed to clarify the contribution of KCNJ18 to susceptibility to TPP in East Asian populations.

Participants and Methods

The study comprised 635 participants including 13 Japanese patients with TPP, 208 Japanese patients with Graves disease without TPP, and 414 healthy control subjects from the Japanese (n = 208), Korean (n = 111), and Caucasian populations (n = 95). DNA samples from 29 participants (13 with TPP, 8 with Graves disease, and 8 controls) were sequenced for KCNJ18, and all participants (n = 635) were genotyped for six variants of KCNJ18 and a polymorphism of KCNJ2 (rs312691).

Results

Six single-nucleotide variants (SNVs) with amino acid substitutions were identified by direct sequencing of KCNJ18. Among these, four SNVs comprised three haplotypes under strong linkage disequilibrium. Haplotype 1 (AAAG) of KCNJ18 was significantly associated with susceptibility to TPP in the Japanese population (OR = 19.6; 95% CI, 1.5 to 256.9; P = 0.013). Haplotype frequencies in the general East Asian (Japanese and Korean) and Caucasian populations differed significantly (haplotype 1: 80.8% vs 48.4%, P = 1.1×10−27).

Conclusion

A major haplotype of KCNJ18 in East Asian populations is significantly associated with susceptibility to TPP. The haplotype is much more common in East Asian than Caucasian populations, suggesting its contribution to the high prevalence of TPP in East Asian populations.
Diabetes-Related Fracture Risk Is Different in African Americans Compared With Hispanics and Caucasians
Authors: Jain Rajesh K , Weiner Mark G , Zhao Huaqing , Williams Kevin Jon , Vokes Tamara
Published: August 2019

Context

Diabetes mellitus (DM) has been associated with a 60% to 90% increased risk of fracture but few studies have been performed in African American and Hispanic subjects.

Objective

The aim of the present study was to quantify the risk of incident major osteoporotic fractures (MOFs) of the hip, wrist, and humerus in African Americans, Hispanics, and Caucasians with DM compared with those with hypertension (HTN).

Methods

We performed a retrospective cohort study of 19,153 subjects with DM (7618 Caucasians, 7456 African Americans, and 4079 Hispanics) and 26,217 with HTN (15,138 Caucasians, 8301 African Americans, and 2778 Hispanics) aged ≥40 years, treated at a large health care system in Philadelphia, Pennsylvania. All information about the subjects was obtained from electronic health records.

Results

The unadjusted MOF rates for each race/ethnicity were similar among those with DM and those with HTN (Caucasians, 1.85% vs 1.84%; African Americans, 1.07% vs 1.29%; and Hispanics, 1.69% vs 1.33%; P = NS for all). However, the MOF rates were higher for Caucasians and Hispanics with DM than for African Americans with DM (P < 0.01). In a multivariable model controlled for age, body mass index, sex, and previous MOF, DM was a statistically significant predictor of MOFs only for Caucasians and Hispanics [hazard ratio (HR), 1.23; 95% CI, 1.02 to 1.48; P = 0.026] but not for African Americans (HR, 0.92; 95% CI, 0.68 to 1.23; P = 0.56).

Conclusions

Hispanics had a DM-related fracture risk similar to that of Caucasians, but AAs did not have an additional fracture risk conferred by DM.
The Effects of Amiodarone on Thyroid Function in Pediatric and Young Adult Patients
Authors: Barrett Brett , Hawkes Colin P , Isaza Amber , Bauer Andrew J
Published: August 2019

Context

Amiodarone is used in patients with arrhythmias, but thyroid dysfunction [amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH)] is a common adverse effect. As the onset of AIT and AIH has not been studied in children, the timing of dysfunction and long-term monitoring are not known in this population.

Objective

To describe the incidence and timing of amiodarone-induced thyroid dysfunction in children and adolescents, with a secondary aim to identify risk factors for amiodarone-induced thyroid dysfunction, and to identify variance in thyroid hormone surveillance and treatment.

Design

Retrospective review of thyroid dysfunction in children and young adults treated with amiodarone between 2007 and 2018.

Setting

Children’s Hospital of Philadelphia.

Patients

Children and young adults treated with amiodarone.

Main Outcome Measures

Prevalence of amiodarone-induced thyroid dysfunction.

Results

Of 484 patients, 190 had thyroid-function testing; 17.3% were found to have subclinical hypothyroidism, and 13.7% testing developed hypothyroidism. Hyperthyroidism occurred in 2.1%. In patients with subclinical hypothyroidism, 63% returned to normal thyroid function without thyroid hormone replacement. Only 26% of patients with hypothyroidism had spontaneous normalization of thyroid function. Twenty-five percent of AIT patients had spontaneous normalization of thyroid function.

Conclusions

This study looks at a pediatric and young-adult population in an effort to describe the natural history of amiodarone-induced thyroid dysfunction. Based on our data, we recommend that a complete thyroid-function panel be obtained within the first week and then at weekly intervals for the first 5 weeks after initiation. The majority of thyroid dysfunction was noted within the first 35 days of treatment.
Antidiuretic Hormone and Serum Osmolarity Physiology and Related Outcomes: What Is Old, What Is New, and What Is Unknown?
Authors: Kanbay Mehmet , Yilmaz Sezen , Dincer Neris , Ortiz Alberto , Sag Alan A , Covic Adrian , Sánchez-Lozada Laura G , Lanaspa Miguel A , Cherney David Z I , Johnson Richard J , Afsar Baris
Published: August 2019

Context

Although the physiology of sodium, water, and arginine vasopressin (AVP), also known as antidiuretic hormone, has long been known, accumulating data suggest that this system operates as a more complex network than previously thought.

Evidence Acquisition

English-language basic science and clinical studies of AVP and osmolarity on the development of kidney and cardiovascular disease and overall outcomes.

Evidence Synthesis

Apart from osmoreceptors and hypovolemia, AVP secretion is modified by novel factors such as tongue acid-sensing taste receptor cells and brain median preoptic nucleus neurons. Moreover, pharyngeal, esophageal, and/or gastric sensors and gut microbiota modulate AVP secretion. Evidence is accumulating that increased osmolarity, AVP, copeptin, and dehydration are all associated with worse outcomes in chronic disease states such as chronic kidney disease (CKD), diabetes, and heart failure. On the basis of these pathophysiological relationships, an AVP receptor 2 blocker is now licensed for CKD related to polycystic kidney disease.

Conclusion

From a therapeutic perspective, fluid intake may be associated with increased AVP secretion if it is driven by loss of urine concentration capacity or with suppressed AVP if it is driven by voluntary fluid intake. In the current review, we summarize the literature on the relationship between elevated osmolarity, AVP, copeptin, and dehydration with renal and cardiovascular outcomes and underlying classical and novel pathophysiologic pathways. We also review recent unexpected and contrasting findings regarding AVP physiology in an attempt to explain and understand some of these relationships.
The Role of Serum Procalcitonin in Predicting Bacterial Sepsis in Patients With Hypothyroidism
Authors: Shirali Aditya S , Wu James X , Zhu Catherine Y , Ocampo Alfonso , Tseng Chi-Hong , Du Lin , Livhits Masha J , Leung Angela M , Yeh Michael W
Published: August 2019

Context

Serum levels of procalcitonin (PCT), a protein produced by the thyroid C cells under physiologic conditions, are high during sepsis.

Objective

To assess the test performance of serum PCT in predicting bacterial sepsis and septic shock in patients with hypothyroidism compared with those who have euthyroidism.

Design and Methods

This retrospective study evaluated patients with no history of thyroid dysfunction (euthyroid), primary hypothyroidism [medical hypothyroidism (MH)], and postsurgical hypothyroidism from total thyroidectomy (TT) identified from a prospectively maintained database who had PCT testing from 2005 to 2018. Quick Sequential Organ Failure Assessment score ≥ 2 or positive bacterial cultures identified bacterial sepsis, and a mean arterial pressure less than 65 mm Hg or a vasopressor requirement defined septic shock. Sensitivity and specificity of PCT for evaluation of bacterial sepsis and septic shock were measured.

Results

We identified 217 euthyroid patients, 197 patients with MH, and 84 patients with TT. Bacterial sepsis was found in 98 (45.2%), 92 (46.7%), and 36 (42.9%) of these patients, respectively (P > 0.05). Septic shock was identified in 13 (6.0%), 13 (6.6%), and 5 (6.0%) patients (P > 0.05), respectively. With use of a PCT cutoff of 0.5 µg/L for bacterial sepsis, the sensitivity was 59%, 61%, and 53% (P > 0.05) and specificity was 81%, 77%, and 81% (P > 0.05) for the diagnosis of bacterial sepsis in euthyroid, MH, and TT patients, respectively. With use of a PCT cutoff of 2.0 µg/L for septic shock, the sensitivity was 46%, 62%, and 63% (P > 0.05) and specificity was 86%, 82%, and 91% (P > 0.05) for the diagnosis of septic shock in these patients, respectively.

Conclusions

Despite the thyroidal origin of PCT, hypothyroidism did not affect the diagnostic performance of serum PCT levels in predicting bacterial sepsis or septic shock.
Surgical Management, Preoperative Tumor Localization, and Histopathology of 80 Patients Operated on for Insulinoma
Authors: Andreassen Mikkel , Ilett Emma , Wiese Dominik , Slater Emily P , Klose Marianne , Hansen Carsten Palnæs , Gercke Norman , Langer Seppo W , Kjaer Andreas , Maurer Elisabeth , Federspiel Birgitte , Kann Peter H , Bartsch Detlef K , Knigge Ulrich
Published: August 2019

Introduction

Diagnosis and pathological classification of insulinomas are challenging.

Aim

To characterize localization of tumors, surgery outcomes, and histopathology in patients with insulinoma.

Methods

Patients with surgically resected sporadic insulinoma were included.

Results

Eighty patients were included. Seven had a malignant tumor. A total of 312 diagnostic examinations were performed: endoscopic ultrasonography (EUS; n = 59; sensitivity, 70%), MRI (n = 33; sensitivity, 58%), CT (n = 55; sensitivity, 47%), transabdominal ultrasonography (US; n = 45; sensitivity, 40%), somatostatin receptor imaging (n = 17; sensitivity, 29%), 18F-fluorodeoxyglucose positron emission tomography/CT (n = 1; negative), percutaneous transhepatic venous sampling (n = 10; sensitivity, 90%), arterial stimulation venous sampling (n = 20; sensitivity, 65%), and intraoperative US (n = 72; sensitivity, 89%). Fourteen tumors could not be visualized. Invasive methods were used in 7 of these 14 patients and localized the tumor in all cases. Median tumor size was 15 mm (range, 7 to 80 mm). Tumors with malignant vs benign behavior showed less staining for insulin (3 of 7 vs 66 of 73; P = 0.015) and for proinsulin (3 of 6 vs 58 of 59; P < 0.001). Staining for glucagon was seen in 2 of 6 malignant tumors and in no benign tumors (P < 0.001). Forty-three insulinomas stained negative for somatostatin receptor subtype 2a.

Conclusion

Localization of insulinomas requires many different diagnostic procedures. Most tumors can be localized by conventional imaging, including EUS. For nonvisible tumors, invasive methods may be a useful diagnostic tool. Malignant tumors showed reduced staining for insulin and proinsulin and increased staining for glucagon.
Clinical Course of Nonfunctional Pituitary Microadenoma in Children: A Single-Center Experience
Authors: Thaker Vidhu V , Lage Adrianne E , Kumari Garima , Silvera V Michelle , Cohen Laurie E
Published: August 2019

Context

Pituitary lesions consistent with microadenomas are increasingly discovered by MRI. Sparse data are available on the long-term clinical and imaging course of such lesions in children.

Objective

The aim of this study was to define the clinical and imaging course of pituitary lesions representing or possibly representing nonfunctioning microadenomas in children to guide clinical management.

Design

Retrospective observational study.

Methods

The clinical data warehouse at a tertiary care academic children’s hospital was queried with the terms “pituitary” AND “microadenoma” and “pituitary” AND “incidentaloma.” The electronic health records of the identified subjects were reviewed to extract data on the clinical and imaging course.

Results

A total of 78 children had nonfunctioning pituitary lesions incidentally discovered during clinical care, of which 44 (56%) were reported as presumed or possible microadenomas. In the children with microadenoma (median age 15 years, interquartile range 2), a majority (70%) underwent imaging for nonendocrine symptoms, the most common being headache (n = 16, 36%). No significant increase in the size of the microadenoma or cysts or worsening of pituitary function was seen over the average clinical follow-up of 4.5 ± 2.6 years. Four cases of drug-induced hyperprolactinemia resolved with discontinuation of the offending medication.

Conclusions

Asymptomatic pituitary lesions representing cysts, microadenomas, or possible microadenomas follow a benign course in children. In the absence of new endocrine or visual symptoms, repeat MRI may not be needed, and if performed, should be done in no less than a year. When possible, it is prudent to discontinue hyperprolactinemia-inducing medications before imaging.
Unique trophoblast chromatin environment mediated by the PcG protein SFMBT2
Authors: Tang Priscilla , Miri Kamelia , Varmuza Susannah
Published: August 2019

Stem/progenitor cells are maintained by a chromatin environment, mediated in part by Polycomb group (PcG) proteins, that depresses differentiation. The trophoblast-specific PcG protein SFMBT2 is known to be required for maintenance of trophoblast progenitors. Rather than binding to trophoblast specific genes repressed in TSC, SFMBT2 is concentrated at chromocenters and regions rich in repetitive elements, specifically LINE sequences and major satellites, suggesting that it is involved in higher order organization of the trophoblast genome. It is also found enriched at a subset of ncRNAs. Comparison of ChIP-seq data sets for other chromatin proteins reveals several stereotypical distribution patterns, suggesting that SFMBT2 interacts with several different types of chromatin complexes specific to the trophoblast lineage.
DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy
Authors: Nowak Marcel , Suenkel Benjamin , Porras Pablo , Migotti Rebekka , Schmidt Franziska , Kny Melanie , Zhu Xiaoxi , Wanker Erich E. , Dittmar Gunnar , Fielitz Jens , Sommer Thomas
Published: August 2019

The muscle-specific RING-finger protein MuRF1 (also known as TRIM63) constitutes a bona fide ubiquitin ligase that routes proteins like several different myosin heavy chain proteins (MyHC) to proteasomal degradation during muscle atrophy. In two unbiased screens, we identified DCAF8 as a new MuRF1-binding partner. MuRF1 physically interacts with DCAF8 and both proteins localize to overlapping structures in muscle cells. Importantly, similar to what is seen for MuRF1, DCAF8 levels increase during atrophy, and the downregulation of either protein substantially impedes muscle wasting and MyHC degradation in C2C12 myotubes, a model system for muscle differentiation and atrophy. DCAF proteins typically serve as substrate receptors for cullin 4-type (Cul4) ubiquitin ligases (CRL), and we demonstrate that DCAF8 and MuRF1 associate with the subunits of such a protein complex. Because genetic downregulation of DCAF8 and inhibition of cullin activity also impair myotube atrophy in C2C12 cells, our data imply that the DCAF8 promotes muscle wasting by targeting proteins like MyHC as an integral substrate receptor of a Cul4A-containing ring ubiquitin ligase complex (CRL4A).

This article has an associated First Person interview with the first author of the paper.
Theoretical Molecular Dynamics Simulation of the DIF-1 Receptor Activation
Authors: Jiang Tianlong , Saito Tamao , Nanbu Shinkoh
Published: August 2019

The structure prediction of Dictyostelium Histidine Kinase M (DhkM), a candidate for the receptor of differentiation inducing factor-1 (DIF-1), was carried out and the structural determination and refinement were performed with one hundred nanoseconds molecular dynamics (MD) simulations. Three simulations with different initial velocities generated by pseudo-random number seeds were performed to ensure the accuracy of our simulations and almost the same results were obtained. Docking simulations were executed employing the receptor-structures from the very early stage of the MD simulations. The obtained result exhibited that there is a very high possibility that DhkM could be the receptor of DIF-1. The residues in the core part which are adjacent to Leu111, Asp115, Arg150, Val151, Tyr351 and Val354 play a significant role in ligand binding mechanism. Furthermore, the binding energy was also estimated from free energy analysis for verification. The docking simulations for DIF-2 and DIF-3, which have molecular structures similar to DIF-1 have been explored as well. DIF-3 was especially found to have very low capacity of binding/no docking-simulation which was consistent with experimental data, and two chloro groups of DIF-1 could lead to a transition to a multicellular slug.