bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone methyltransferase ATX1 dynamically regulates fiber secondary cell wall biosynthesis inArabidopsisinflorescence stem
Authors: Wang Xianqiang , Wang Denghui , Xu Wenjian , Kong Lingfei , Ye Xiao , Zhuang Qianye , Fan Di , Luo Keming
Published: November 2020

Secondary wall thickening in the sclerenchyma cells is strictly controlled by a complex network of transcription factors in vascular plants. However, little is known about the epigenetic mechanism regulating secondary wall biosynthesis. In this study, we identified that ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1), a H3K4-histone methyltransferase, mediates the regulation of fiber cell wall development in inflorescence stems of Arabidopsis thaliana. Genome-wide analysis revealed that the up-regulation of genes involved in secondary wall formation during stem development is largely coordinated by increasing level of H3K4 tri-methylation. Among all histone methyltransferases for H3K4me3 in Arabidopsis, ATX1 is markedly increased during the inflorescence stem development and loss-of-function mutant atx1 was impaired in secondary wall thickening in interfascicular fibers. Genetic analysis showed that ATX1 positively regulates secondary wall deposition through activating the expression of secondary wall NAC master switch genes, SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1) and NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1). We further identified that ATX1 directly binds the loci of SND1 and NST1, and activates their expression by increasing H3K4me3 levels at these loci. Taken together, our results reveal that ATX1 plays a key role in the regulation of secondary wall biosynthesis in interfascicular fibers during inflorescence stem development of Arabidopsis.
Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6
Authors: Selmi Tommaso , Hussain Shobbir , Dietmann Sabine , Heiß Matthias , Borland Kayla , Flad Sophia , Carter Jean-Michel , Dennison Rebecca , Huang Ya-Lin , Kellner Stefanie , Bornelöv Susanne , Frye Michaela
Published: November 2020

The highly abundant N6-methyladenosine (m6A) RNA modification affects most aspects of mRNA function, yet the precise function of the rarer 5-methylcytidine (m5C) remains largely unknown. Here, we map m5C in the human transcriptome using methylation-dependent individual-nucleotide resolution cross-linking and immunoprecipitation (miCLIP) combined with RNA bisulfite sequencing. We identify NSUN6 as a methyltransferase with strong substrate specificity towards mRNA. NSUN6 primarily targeted three prime untranslated regions (3′UTR) at the consensus sequence motif CTCCA, located in loops of hairpin structures. Knockout and rescue experiments revealed enhanced mRNA and translation levels when NSUN6-targeted mRNAs were methylated. Ribosome profiling further demonstrated that NSUN6-specific methylation correlated with translation termination. While NSUN6 was dispensable for mouse embryonic development, it was down-regulated in human tumours and high expression of NSUN6 indicated better patient outcome of certain cancer types. In summary, our study identifies NSUN6 as a methyltransferase targeting mRNA, potentially as part of a quality control mechanism involved in translation termination fidelity.
Structural basis for guide RNA trimming by RNase D ribonuclease in Trypanosoma brucei
Authors: Gao Yanqing , Liu Hehua , Zhang Chong , Su Shichen , Chen Yiqing , Chen Xi , Li Yangyang , Shao Zhiwei , Zhang Yixi , Shao Qiyuan , Li Jixi , Huang Zhen , Ma Jinbiao , Gan Jianhua
Published: November 2020

Infection with kinetoplastid parasites, including Trypanosoma brucei (T. brucei), Trypanosoma cruzi (T. cruzi) and Leishmania can cause serious disease in humans. Like other kinetoplastid species, mRNAs of these disease-causing parasites must undergo posttranscriptional editing in order to be functional. mRNA editing is directed by gRNAs, a large group of small RNAs. Similar to mRNAs, gRNAs are also precisely regulated. In T. brucei, overexpression of RNase D ribonuclease (TbRND) leads to substantial reduction in the total gRNA population and subsequent inhibition of mRNA editing. However, the mechanisms regulating gRNA binding and cleavage by TbRND are not well defined. Here, we report a thorough structural study of TbRND. Besides Apo- and NMP-bound structures, we also solved one TbRND structure in complexed with single-stranded RNA. In combination with mutagenesis and in vitro cleavage assays, our structures indicated that TbRND follows the conserved two-cation-assisted mechanism in catalysis. TbRND is a unique RND member, as it contains a ZFD domain at its C-terminus. In addition to T. brucei, our studies also advanced our understanding on the potential gRNA degradation pathway in T. cruzi, Leishmania, as well for as other disease-associated parasites expressing ZFD-containing RNDs.
Differences in JUUL Appeal Among Past and Current Youth JUUL Users
Authors: Davis Danielle R , Krishnan-Sarin Suchitra , Bold Krysten W , Morean Meghan E , Jackson Asti , Camenga Deepa , Kong Grace
Published: November 2020

Introduction

JUUL, a closed system e-cigarette with disposable pods, is popular among youth, with positive attributes of this product linked to current use by youth. However, many youth try JUUL and do not continue using; understanding differences in the appeal of this device between current users and those who chose not to continue use can inform regulation and prevention efforts. The aim of the current study is to compare JUUL appeal in youth among past users (ie, used, but not in past month) and current users (ie, used in past month).

Methods

A cross-sectional survey was conducted in four Connecticut high schools in Spring 2018. This survey assessed JUUL use and reasons for liking/disliking JUUL, including its' pharmacological effects (eg, nicotine “buzz”), product characteristics (eg, flavors), peer influence, appeal compared to other e-cigarettes, and concealability. Logistic regressions were conducted to examine differences in liking/disliking JUUL by use status (past vs. current).

Results

Among JUUL users (N = 1374; 43% of total sample), 30.4% were past users and 69.6% were current users. Compared to current users, past users were less likely to like JUUL for positive pharmacological effects (eg, nicotine “buzz”), product characteristics (eg, flavors), and peer use and more likely to dislike JUUL for the adverse pharmacological effects (eg, headache), product characteristics (eg, flavors), and for “other” reasons (open-ended response; eg, perceived harm).

Conclusions

Findings suggest that altering JUUL appeal through regulating nicotine content and flavors may be key in policy aimed at shifting youth to become past JUUL users.

Implications

This study investigates how current and past youth JUUL users differ in their report of the appeal of JUUL. Past users are less likely to report experiencing positive pharmacological effects and product characteristics of JUUL and are less likely to report appeal due to peer use. Understanding how appeal of JUUL may differ among past and current users can aid in our understanding of how to regulate these products so that they are less appealing to current youth users.
Social Work Luminaries: Luminaries Who Contributed to Social Work Theory and Scholarship in the Late 20th and Early 21st Centuries
Authors: Garvin Charles D. , Gutiérrez Lorraine M. , Davis Larry E.
Published: November 2020

Oxford Bibliographies in Social Work includes three articles describing the scholarly writings of a select group of deceased social workers who have been especially prominent and influential in the profession within the United States. We refer to these individuals as social work luminaries. These three bibliographies can be used to identify the publications of prominent individuals who have been most influential in the development of social work. We identified these individuals by first reviewing the biographies of significant social workers in the Franklin’s article on Encyclopedia of Social Work and obituaries collected by the Council on Social Work Education since the publication of the Encyclopedia of Social Work. From this list we reviewed the biographical material and publications, selecting the most prominent luminaries for each of the three articles. For each luminary we provide a brief biographical overview and one to five annotated citations of their most important publications. Respectively, the three articles describe the publications of luminaries (1) who were involved in the founding and creation of the social work profession in the United States during the late 19th and early 20th centuries, (2) who subsequently contributed to the clarification and elaboration of social work practice and theory, and (3) who contributed to social work theory and scholarship in the late 20th and early 21st centuries. This article presents social work luminaries who made major contributions to research and practice in the late 20th and early 21st centuries. Luminaries in this era often made more use of scientific findings than those luminaries in the previous two articles. They related practice and theory to the social conditions of this more current period, and they often were concerned about a research-based (i.e., empirical) practice and incorporated contemporary ideas of social justice into their thinking. In this period, as in the previous one, most luminaries fell into one of several categories in terms of their contributions to social work scholarship, although several luminaries contributed to more than one category. We have organized this article around these different categories, which include contributions to social work methods; specific fields of service; the overall field of social work; diversity, multiculturalism, and empowerment; and social work research.
Young Children and Inclusion
Authors: Cant Annabella
Published: November 2020

Inclusive education is the focus of many thinkers, researchers, teachers, early-childhood educators, and policymakers. It is a current concern of most Western societies. The concept of inclusive education was introduced only in the 1990s, when it replaced the previous concepts of integration and mainstreaming; however, the expressed need and advocacy for inclusion go further back in history. The enormous shift is still felt by many educational institutions. The shift means that it is not the job of the child to adapt to the typical environment, but it is the complex educational ecosystem that needs to be ready for caring, educating, and ensuring success to all children, with or without diversabilities. The necessary progression is one from considering diverse groups of children in an equalizing way, to considering them in an equitable way. Inclusive early-childhood education proposes an environment catered around the unique needs of each child within the classroom. As in many other areas of education, change needs to start early, and, yet, research about the inclusion of young and very young children is not overwhelmingly prevalent. In the 2020s, inclusive practice refers to all differences, not only the ones affecting children’s physical and mental health, including race, gender, culture, ethnicity, language, socioeconomic status, age, etc. If young children grow up in homes and educational environments infused with inclusion, they may become more comfortable engaging in discourses of inequality and exclusion. If their learning environment models positive and genuine relationship building with anyone around them, regardless of their difference, children will grow up being advocates for and allies of the people whom society keeps on silencing. Early inclusion is paramount. So, what hinders the universal adoption of inclusive practices in early-childhood education? Among factors that constitute barriers of inclusion, we find politics, resources, support, teacher education, parents’ and teachers’ perceptions and needs, different philosophical interpretations of the concept of early inclusion, and many others. The current studies in the field of early-childhood inclusion show that there is an acute need for knowledge, collaboration, and support. Parents, policymakers, teachers, and other decision-making adults should start giving children agency and invite them to contribute to decisions that concern their well-being. Being inclusive in early-childhood education means to have trust in the competency of all young children, to cherish difference, to cultivate a respectful learning environment, to work with heart, to welcome and build strong relationships with families of all children, to be in touch with current research in the field of inclusive education, and to see inclusion as a feeling of belonging, being valued, and being respected. Inclusion is fluid as a river, but these are the stones that should always guide its course and flow.
A Novel Role of Salt- and Drought-Induced RING 1 Protein in Modulating Plant Defense Against Hemibiotrophic and Necrotrophic Pathogens
Authors: Ramu Vemanna S. , Oh Sunhee , Lee Hee-Kyung , Nandety Raja Sekhar , Oh Youngjae , Lee Seonghee , Nakashima Jin , Tang Yuhong , Senthil-Kumar Muthappa , Mysore Kirankumar S.
Published: November 2020

Many plant-encoded E3 ligases are known to be involved in plant defense. Here, we report a novel role of E3 ligase SALT- AND DROUGHT-INDUCED RING FINGER1 (SDIR1) in plant immunity. Even though SDIR1 is reasonably well-characterized, its role in biotic stress response is not known. The silencing of SDIR1 in Nicotiana benthamiana reduced the multiplication of the virulent bacterial pathogen Pseudomonas syringae pv. tabaci. The Arabidopsis sdir1 mutant is resistant to virulent pathogens, whereas SDIR1 overexpression lines are susceptible to both host and nonhost hemibiotrophic bacterial pathogens. However, sdir1 mutant and SDIR1 overexpression lines showed hypersusceptibility and resistance, respectively, against the necrotrophic pathogen Erwinia carotovora. The mutant of SDIR1 target protein, i.e., SDIR-interacting protein 1 (SDIR1P1), also showed resistance to host and nonhost pathogens. In SDIR1 overexpression plants, transcripts of NAC transcription factors were less accumulated and the levels of jasmonic acid (JA) and abscisic acid were increased. In the sdir1 mutant, JA signaling genes JAZ7 and JAZ8 were downregulated. These data suggest that SDIR1 is a susceptibility factor and its activation or overexpression enhances disease caused by P. syringae pv. tomato DC3000 in Arabidopsis. Our results show a novel role of SDIR1 in modulating plant defense gene expression and plant immunity.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Botrytis spp.: A Contemporary Perspective and Synthesis of Recent Scientific Developments of a Widespread Genus that Threatens Global Food Security
Authors: Richards Jonathan K. , Xiao Chang-Lin , Jurick Wayne M.
Published: November 2020

This perspective presents a synopsis of the topics contained in the Phytopathology Pathogen Spotlight on Botrytis spp. causing gray mold, including pathogen biology and systematics, genomic characterization of new species, perspectives on genome editing, and fungicide resistance. A timely breakthrough to engineer host plant resistance against the gray mold fungus has been demonstrated in planta and may augment chemical controls in the near future. While B. cinerea has garnered much of the research attention, other economically important Botrytis spp. have been identified and characterized via morphological and genome-based approaches. Gray mold control is achieved primarily through fungicide applications but resistance to various chemical classes is a major concern that threatens global plant health and food security. In this issue, new information on molecular mechanism(s) of fungicide resistance and ways to manage control failures are presented. Finally, a significant leap in fundamental pathogen biology has been achieved via development of CRISPR/Cas9 to assess gene function in the fungus which likely will spawn new control mechanisms and facilitate gene discovery studies.
Establishing an internal abstract review committee
Authors: Welden Lois M. Stallings , Cason Linda , Wathen Ellen
Published: November 2020

Mentoring nurses in writing for nursing excellence
Marital Satisfaction of Infertile Couples Using Natural Procreative Technology (NaProTECHNOLOGY)
Authors: Camacho Anna , Konicki Annette Jakubisin , McGrath Jacqueline M. , Carpentier Paul
Published: November 2020

Infertility affects one in 16 married women in the United States where 12.7% of these seek treatment. The stress of infertility and treatment is known to impact marital satisfaction, which can be further complicated by personal and religious beliefs regarding the ethics of some assistive reproductive technologies. A morally acceptable approach to infertility diagnosis and treatment is natural procreative technology or NaProTECHNOLOGY (NPT) using the Creighton Model FertilityCare™ System. A quantitative, descriptive study utilizing demographic surveys and the Index of Marital Satisfaction found that couples using NPT reported marital satisfaction.
Cirrhotic Cardiomyopathy—A Veiled Threat
Authors: Scarlatescu Ecaterina , Marchenko Sergey P. , Tomescu Dana R
Published: November 2020

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction in patients with liver cirrhosis without preexisting cardiac disease. According to the definition established by the World Congress of Gasteroenterology in 2005, the diagnosis of CCM includes criteria reflecting systolic dysfunction, impaired diastolic relaxation, and electrophysiological disturbances. Because of minimal or even absent clinical symptoms and echocardiographic signs at rest according to the 2005 criteria, CCM diagnosis is often missed or delayed in most clinically stable cirrhotic patients. However, cardiac dysfunction progresses in time and contributes to the pathogenesis of hepatorenal syndrome and increased morbidity and mortality after liver transplantation, surgery, or other invasive procedures in cirrhotic patients. Therefore, a comprehensive cardiovascular assessment using newer techniques for echocardiographic evaluation of systolic and diastolic function, allowing the diagnosis of CCM in the early stage of subclinical cardiovascular dysfunction, should be included in the screening process of liver transplant candidates and patients with cirrhosis in general. The present review aims to summarize the most important pathophysiological aspects of CCM, the usefulness of contemporary cardiovascular imaging techniques and parameters in the diagnosis of CCM, the current therapeutic options, and the importance of early diagnosis of cardiovascular impairment in cirrhotic patients.
Congenital Opticmeningoceles
Authors: Cruz Antonio A. V. , Akaishi Patricia M. S. , Bernardini Francesco , Chahud Fernando
Published: November 2020

Congenital optic nerve cystic-like malformations associated with normally developed globes are extremely rare. We describe 3 children who presented since birth with proptosis, and eye motility limitation. MRI showed in all cases that the intraorbital segment of the optic nerves was malformed with large cystic-like lesions in the intraconal segment of the orbit. In all cases, biopsies of the wall of the lesions were positive for glial fibrillary acidic protein. Since this protein is a neurobiomarker that exists only in astrocytes in the central nervous system, nonmyelinating Schwann cells of peripheral nerves, and enteric glial cells, we believe that these lesions represent true opticmeningoceles.
Clinical manifestation and disease progression in COVID-19 infection
Authors: Tsai Ping-Hsing , Lai Wei-Yi , Lin Yi-Ying , Luo Yung-Hung , Lin Yi-Tsung , Chen Hsiao-Kang , Chen Yuh-Min , Lai Yi-Chun , Kuo Li-Chiao , Chen Shew-Dan , Chang Kao-Jung , Liu Cheng-Hsuan , Chang Shih-Chieh , Wang Fu-Der , Yang Yi-Ping
Published: November 2020

Coronavirus disease 2019 (COVID-19) is mainly an infectious disease of the respiratory system transmitted through air droplets, and pulmonary symptoms constitute main presentations of this disease. However, COVID-19 demonstrates a clinically diverse manifestation ranging from asymptomatic presentation to critically illness with severe pneumonia, acute respiratory distress syndrome, respiratory failure, or multiple organ failure. Accumulating evidences demonstrated that COVID-19 has extrapulmonary involvement, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, dermatologic system, and others. Over a third of COVID-19 patients manifest a wide range of neurological symptoms involving the central/peripheral nervous system. Underlying cardiovascular comorbidities were associated with detrimental outcomes, meanwhile the occurrence of cardiovascular complications correlate to poor survival. Gastrointestinal symptoms frequently occur and have been associated with a longer period of illness. Impaired hepatic functions were associated with the severity of the disease. Higher rate of acute kidney injury was reported in critically ill patients with COVID-19. Endocrinologic presentations of COVID-19 include exacerbating hyperglycemia, euglycemic ketosis, and diabetic ketoacidosis. The most common cutaneous manifestation was acro-cutaneous (pernio or chilblain-like) lesions, and other skin lesions consist of maculopapular rash, vesicular lesions, livedoid/necrotic lesions, exanthematous rashes, and petechiae. This review article summarized the general clinical signs and symptoms, radiologic features, and disease manifestation with progression in patients with COVID-19.
Perioperative Issues With Gender-Diverse Youth
Authors: Aquino Nelson J. , Ganor Oren , Chrisos Haley A. , Oles Norah , Boskey Elizabeth R.
Published: November 2020

A growing number of young people identify as gender diverse, both as transgender and nonbinary. In addition to gender-affirming care such as puberty blockers, hormones, and gender-affirming surgeries, these youth also need to access the full range of other medical and surgical care. As such, it is critical for pediatric healthcare providers to develop competence in working with gender-diverse youth, regardless of whether the facilities they work offer gender-affirming medical or surgical care. This article addresses perioperative care concerns for gender-diverse youth as well as psychosocial assessment for gender-affirming surgeries.
Evolution in Management Trends of Sporadic Vestibular Schwannoma in the United States Over the Last Half-century
Authors: Chan Stephen A. , Marinelli John P. , Hahs-Vaughn Debbie L. , Nye Chad , Link Michael J. , Carlson Matthew L.
Published: November 2020

Objective:

Limited data currently characterize management trends of sporadic vestibular schwannoma (VS) in the United States over recent decades. Serving as the primary patient support organization in the United States, the Acoustic Neuroma Association (ANA) facilitates amalgamation of data from patients treated from 1970 through January 2019. The primary objective of the current study was to characterize the evolution in the management of sporadic VS among ANA survey respondents treated over the last half-century.

Study Design/Intervention:

Cross-sectional survey.

Setting/Patients:

ANA survey respondents diagnosed with sporadic VS.

Main Outcome Measures:

Trends in rates of microsurgery, radiosurgery, and observation from 1970 to 2019.

Results:

Among 953 patients with VS responding during the study period, 876 (92%) were included. Subjects reported the following management strategies: 220 observation (25%), 454 microsurgery (52%), and 193 radiosurgery (22%). The rate of microsurgery decreased from 86–88% from 1970 to 2000 to 44% in the last decade. The proportion of VS observed increased from 7% of all tumors in the 1990s, to 14% in the 2000s, to 33% in the 2010s. The rate of radiosurgery has increased to 28% in the last decades compared with 7% in the 1990s. The rate of subtotal resection in tumors > 2 cm increased from 34% in the 2000s to 60% in the 2010s (p = 0.0011).

Conclusions:

Overall, these data support a progression toward fewer patients treated with microsurgery in recent decades. Radiosurgery and observation became increasingly more common after the turn of the century, possibly due to better detection of small and asymptomatic tumors and a greater understanding of the natural history of disease.
Transient Subacute Facial Nerve Dysfunction After Dual Modality Treatment of Large Vestibular Schwannomas
Authors: Manzoor Nauman F. , Khattab Mohamed H. , Sherry Alexander D. , Perkins Elizabeth L. , Attia Albert , Cmelak Anthony J. , Haynes David S. , Rivas Alejandro
Published: November 2020

Objectives:

1: Describe subacute facial nerve paralysis after salvage stereotactic radiosurgery (SRS). 2: To analyze predictors of facial nerve weakness after dual modality treatment.

Patients:

Adult patients with Vestibular Schwannoma who underwent sub-total resection (STR) followed by salvage radiation.

Intervention(s):

Microsurgical resection of VS, stereotactic radiosurgery, intensity-modulated radiotherapy, proton radiotherapy.

Main Outcome Measure(s):

Serial facial nerve function (House-Brackmann scale).

Results:

Thirteen patients who underwent dual modality treatment for large VS were included (mean age = 43.6 years, 77% females). The mean pre-operative tumor volume was 11.7 cm3 (SD = 6.5) and the immediate mean post-operative remnant volume was 1.5 cm3 (SD = 1.4) with a mean extent of resection of 86.7% (SD = 9.5). The mean salvage-free interval was 20.8 months (SD = 13.3). All patients had excellent one-year FN outcome (HB grade 1, 2) after resection. Three patients developed subacute facial nerve weakness after salvage SRS (4.2–9.4 months after SRS). This paralysis responded to high dose systemic steroids and no surgical interventions for facial rehabilitation were required. At last follow up (mean 61.6 months, SD = 28.5), facial nerve function was favorable (HB grade 1–2 in 12 patients and HB grade 3 in 1 patient). There were no significant associations between various predictors and subacute deterioration of facial nerve function after SRS.

Conclusions:

Sub-acute transient facial nerve dysfunction can develop infrequently over a variable time frame after post-operative salvage SRS and usually responds to steroids. Patients should be adequately counseled about potential of transient deterioration of facial nerve function after salvage SRS.
Validation of the blood pressure measurement technology used in the Novacor Diasys 3 (DIS-0001-00) upper arm device for ambulatory blood pressure measurement, according to the requirements of the AAMI/ANSI/ISO 81060-2:2013 standard (for both a general study and a cardiac-stress study in adults) and of the European Society of Hypertension International Protocol revision 2010
Authors: Atkins Neil , Fania Claudio , Palatini Paolo
Published: November 2020

Objective

The objective of this study was to determine the accuracy of the oscillometric blood pressure measurement technology of the Novacor Diasys 3 (model number DIS-0001-00) blood pressure monitor, intended for ambulatory blood pressure measurement, when used with the recommended Standard (ACC-0213-00), Large (ACC-0214-00) and Paediatric (ACC-0215-00) cuffs.

Methods

The Novacor Diasys 3 (model number DIS-0001-00) was evaluated according to the requirements of the AAMI/ANSI/ISO 81060-2:2013 standard, including an additional cardiac-stress study, a requirement for ambulatory blood pressure measurement devices. It was also validated according to the requirements of the European Society of Hypertension International Protocol revision 2010. The protocol requirements for all thee studies were followed precisely.

Results

The Novacor Diasys 3 (model number DIS-0001-00) fulfilled all of the requirements for a pass in each of the three studies. In the primary AAMI/ANSI/ISO 81060-2:2013 study, the Criterion 1 errors were +3.9 mmHg ± 2.9 mmHg for SBP and +3.4 ± 2.5 mmHg for DBP.

Conclusion

The Novacor Diasys 3 (model number DIS-0001-00), when used with the recommended cuffs, can be recommended for ambulatory blood pressure measurement in the adult population.
Novel c.1505_1509dupCTGCC pathogenic variation in a male case with Christianson syndrome
Authors: Yalcintepe Sinem , Gurkan Hakan
Published: November 2020

Pathogenic variations in the SLC9A6 gene are associated with an X-linked disorder Christianson syndrome characterized by developmental delay, microcephaly, intellectual disability, autistic-like behavior and epilepsy. We identified a novel pathogenic variation in the SLC9A6 gene in a boy with developmental delay and microcephaly. Herein we report the clinical findings of the case diagnosed as Christianson syndrome; his mother was found to carry the same variant.
Differences in amino acid and lipid metabolism distinguish Crohn’s from idiopathic/cryptoglandular perianal fistulas by tissue metabonomic profiling and may offer clues to underlying pathogenesis
Authors: Adegbola Samuel O. , Sarafian Magali , Sahnan Kapil , Ding Nik S. , Faiz Omar D. , Warusavitarne Janindra , Phillips Robin K.S. , Tozer Phil J. , Holmes Elaine , Hart Ailsa L.
Published: November 2020

Introduction

Few studies have investigated perianal fistula etiopathogenesis, and although the cryptoglandular theory is widely accepted in idiopathic cases, in Crohn’s disease, it is thought to involve the interplay between microbiological, immunological and genetic factors. A pilot study was conducted to assess for metabolic variations in Crohn’s perianal fistula tissue that might differ from that of idiopathic (cryptoglandular) perianal fistula tissue as a comparator. The goal was to identify any potential biomarkers of disease, which may improve the understanding of pathogenesis.

Aims and methods

Fistula tract biopsies were obtained from 30 patients with idiopathic perianal fistula and 20 patients with Crohn’s anal fistula. Two different assays were used in an ultra-high-performance liquid chromatography system coupled with a mass spectrometric detector to achieve broad metabolome coverage. Univariate and multivariate statistical data analyses were used to identify differentiating metabolic features corresponding to the perianal fistula phenotype (i.e. Crohn’s disease vs. idiopathic).

Results

Significant orthogonal partial least squares discriminant analysis predictive models (validated with cross-validated-analysis of variance P value <0.05) differentiated metabolites from tissue samples from Crohn’s vs. idiopathic anal fistula patients using both metabolic profiling platforms. A total of 41 metabolites were identified, suggesting alterations in pathways, including amino acid, carnitine and lipid metabolism.

Conclusion

Metabonomics may reveal biomarkers of Crohn’s perianal fistula. Further work in larger numbers is required to validate the findings of these studies as well as cross-correlation with microbiome work to better understand the impact of host-gut/environment interactions in the pathophysiology of Crohn’s and idiopathic perianal fistulas and identify novel therapeutic targets.
The periscreen strip is an accurate and rapid method to diagnose spontaneous bacterial peritonitis among patients with acute-on-chronic liver failure
Authors: Li Chen , Su Hai-Bin , Hu Jin-Hua
Published: November 2020

Background

Leukocyte esterase reagent strips may help diagnose spontaneous bacterial peritonitis (SBP), but their effective application among patients with acute-on-chronic liver failure (ACLF) remains unknown.

Aim

This study aimed to assess the performance of periscreen strips in the rapid diagnosis of SBP among patients with ACLF.

Methods

Periscreen strips were used to test 261 ascites samples taken from 251 inpatients with ACLF between January 2014 and June 2019. The colors of the reagent strip were divided into four colorimetric graduations (‘negative’, ‘trace’, ‘small’, and ‘large’), among which ‘trace’ is used as the SBP detection threshold. The polymorphonuclear neutrophils (PMN) of ascites ≥250/mm3 was used as the gold standard for SBP diagnosis.

Results

SBP was detected in 92 (35.2%) ascite samples. The ascites PMN count of ‘negative’ (32.5/mm3) was lower than those of ‘trace’ (248.2/mm3), ‘small’ (379.0/mm3), and ‘large’ (7426.0/mm3) (P < 0.001). The colorimetric graduations of the strips were positively correlated with ascites PMN count (r = 0.867, P < 0.001). Periscreen strips had 100% sensitivity, 91.1% specificity, 86.0% positive predictive value, 100% negative predictive value, 11.3 positive likelihood ratios, and 0 negative likelihood ratios. For patients with negative results judged by the gold standard, ascites white blood cells count [odds ratio (OR) = 1.007) and ascites PMN count (OR = 1.028) were independent predictors of false-positive cases.

Conclusion

Liver failure did not affect the diagnostic performance of periscreen strips. Therefore, these strips can efficiently and rapidly diagnose SBP among patients with ACLF.
How haematopoiesis research became a fertile ground for regulatory network biology as pioneered by Eric Davidson
Authors: Rothenberg Ellen V. , Göttgens Berthold
Published: November 2020

Purpose of review

This historical perspective reviews how work of Eric H. Davidson was a catalyst and exemplar for explaining haematopoietic cell fate determination through gene regulation.

Recent findings

Researchers studying blood and immune cells pioneered many of the early mechanistic investigations of mammalian gene regulatory processes. These efforts included the characterization of complex gene regulatory sequences exemplified by the globin and T-cell/B-cell receptor gene loci, as well as the identification of many key regulatory transcription factors through the fine mapping of chromosome translocation breakpoints in leukaemia patients. As the repertoire of known regulators expanded, assembly into gene regulatory network models became increasingly important, not only to account for the truism that regulatory genes do not function in isolation but also to devise new ways of extracting biologically meaningful insights from even more complex information. Here we explore how Eric H. Davidson's pioneering studies of gene regulatory network control in nonvertebrate model organisms have had an important and lasting impact on research into blood and immune cell development.

The intellectual framework developed by Davidson continues to contribute to haematopoietic research, and his insistence on demonstrating logic and causality still challenges the frontier of research today.
New robotic surgical systems in urology: an update
Authors: Cisu Theodore , Crocerossa Fabio , Carbonara Umberto , Porpiglia Francesco , Autorino Riccardo
Published: November 2020

Purpose of review

The landscape of robotic surgical systems in urology is changing. Several new instruments have been introduced internationally into clinical practice, and others are in development. In this review, we provide an update and summary of recent surgical systems and their clinical applications in urology.

Recent findings

Robotic-assisted laparoscopic surgery is increasingly becoming a standard skillset in the urologist's technical armamentarium. The current state of the robotic surgery market is monopolized because of a number of regulatory and technical factors but there are several robotic surgical systems approved for clinical use across the world and numerous others in development. Next-generation surgical systems commonly include a modular design, open access consoles, haptic feedback, smaller instruments, and machine learning.

Numerous robotic surgical systems are in development, and several have recently been introduced into clinical practice. These new technologies are changing the landscape of robotic surgery in urology and will likely transform the marketplace of robotic surgery across surgical subspecialties within the next 10--20 years.
Effects of a Complex Case Study and High-Fidelity Simulation on Mechanical Ventilation on Knowledge and Clinical Judgment of Undergraduate Nursing Students
Authors: Salameh Basma , Ayed Ahmad , Kassabry Maysa' , Lasater Kathie
Published: November 2020

Background

Improving nursing students' knowledge and clinical judgment related to mechanical ventilation (MV) is paramount, considering the heightened need for MV due to the current COVID-19 (coronavirus disease 2019) pandemic. High-fidelity simulation (HFS) provides students with real-life clinical experiences that they would rarely confront in clinical training, especially complex case scenarios (such as a patient needing MV).

Purpose

This study assessed students' clinical knowledge and judgment after including HFS involving MV in an undergraduate nursing program.

Methods

This was a quasi-experimental design with a convenience sample of 151 nursing students using the Lasater Clinical Judgment Rubric.

Results

There were significant differences between the intervention and control groups in knowledge (t = 20.42; P = .001) and total clinical judgment scores (t = 19.55; P < .001) post-HFS.

Conclusions

Including a complex case study using MV and HFS significantly improved students' clinical decision-making, clinical knowledge, and self-confidence and enhanced their critical thinking, noticing, interpreting, reflecting, and responding capabilities.
A Narrative Review of Clinical Treatment Outcomes of Neisseria gonorrhoeae Infection With Ciprofloxacin by Minimum Inhibitory Concentration and Anatomic Site
Authors: Chaudry Ameen E. , Klausner Jeffrey D.
Published: November 2020

Background

Neisseria gonorrhoeae infections are becoming increasingly resistant to recommended treatments. Resistance-guided therapy may mitigate the continued emergence of resistance by enabling the use of previously recommended treatments like ciprofloxacin. To describe the effectiveness of ciprofloxacin to treat “susceptible” infections, we estimated the clinical efficacy of ciprofloxacin at various minimum inhibitory concentrations (MICs) and anatomic sites.

Methods

We reviewed publicly available reports using the PubMed.gov database and search terms “gonorrhea/drug therapy”[Mesh] AND “ciprofloxacin”. We included clinical treatment studies in which ciprofloxacin was administered alone to treat N. gonorrhoeae, specimens were collected for N. gonorrhoeae culture from each infection, the MIC was determined for ≥90% of infective strains, and individual treatment outcomes were clearly defined. We recorded those data, ciprofloxacin dose and infection site. We calculated the frequency of treatment success and 95% confidence intervals (CIs).

Results

Twenty studies from 1985 to 2020 met our inclusion criteria. Ciprofloxacin at commonly used doses eliminated 99.2% (95% CI, 98.5%–99.6%; n = 1439) of gonococcal infections with MICs <0.125 μg/mL, 76.3% (95% CI, 59.8%–88.6%; n = 38) of infections with MICs from 0.125 to 0.5 μg/mL, and 30.1% (95% CI, 20.5%–41.2%; n = 83) of infections with MICs ≥1 μg/mL across anatomic sites.

Conclusions

Ciprofloxacin reliably eliminated gonococcal infections with MICs <0.125 μg/mL across anatomic sites. Molecular assays predicting MICs of ciprofloxacin <0.125 μg/mL of gonococcal strains can allow for reintroduction of ciprofloxacin in gonorrhea treatment. Clinicians can confidently use ciprofloxacin to treat susceptible gonococcal infections.
A Comprehensive Outcome Review of Subfascial Breast Augmentation over a 10-Year Period
Authors: Brown Tim
Published: November 2020

Background:

Subfascial placement of breast implants has the advantages of subglandular and submuscular placement without the adverse outcomes. There are few large series with longitudinal follow-up and outcome measures.

Methods:

Seven hundred eighty-three patients underwent subfascial breast augmentation and were followed up for 10 years. Adverse outcomes, changes in breast morphometry, and patient satisfaction were outcome measures.

Results:

All morphometry increased except soft-tissue thickness at the lateral sternal margin. The distance from the nipple-areola complex to the inframammary crease increased by 40 percent, with a concomitant 6.2 percent increase in the distance from the suprasternal notch to the nipple-areola complex. The capsular contracture rate was 6.48 percent, and correlates with a lateral sternal margin of less than 20 mm (r = 0.57, p < 0.001). Ripples occurred in patients with less than 10 mm of soft tissue at the lateral sternal margin; 11.6 percent of patients would choose a larger implant and 2.7 percent would choose a smaller implant.

Conclusions:

Subfascial placement of breast implants provides a reliable technique. It can be used in patients with at least 20 mm of soft tissue at the lateral sternal margin. Those with 10 to 20 mm should be counseled that ripples may occur if they lose body fat. The technique is unsuitable for individuals with less than 10 mm measurable at the lateral sternal margin.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Factors associated with worse cerebrovascular function in aging women with and at risk for HIV
Authors: Chow Felicia C. , Ma Yifei , Manion Maura , Rupert Adam , Lambert-Messerlian Geralyn , Bushnell Cheryl D. , Cedars Marcelle I. , Sereti Irini , Sorond Farzaneh A. , Hsue Priscilla Y. , Tien Phyllis C.
Published: November 2020

Objective:

Women may be disproportionately impacted by the negative effect of HIV on cerebrovascular risk. We examined the association of HIV, sex, menopause, and immune activation with cerebrovascular function among women with HIV (WWH) and at risk for HIV from the Women's Interagency HIV Study and men with HIV.

Design:

Cross-sectional.

Methods:

Participants were aged at least 40 years with coronary heart disease or at least one cardiometabolic risk factor. All persons with HIV were on antiretroviral therapy with undetectable viral load. Cerebral vasoreactivity was assessed by the transcranial Doppler breath-holding test, with lower vasoreactivity corresponding to worse cerebrovascular function. Menopausal status was determined by anti-Müllerian hormone level. We used mixed effects linear regression to identify factors associated with cerebral vasoreactivity.

Results:

Mean cerebral vasoreactivity was similar in WWH (n = 33) and women at risk for HIV (n = 16). A trend toward higher cerebral vasoreactivity in WWH compared with men with HIV (n = 37) was no longer present after excluding women on estrogen replacement therapy (n = 3). In women, menopausal status was not significantly associated with cerebral vasoreactivity. WWH with higher cardiovascular risk (−0.14 for each additional cardiometabolic risk factor, P = 0.038), sCD163 (−0.20 per doubling, P = 0.033), and proportion of CD4+CX3CR1+ T cells (−0.14 per doubling, P = 0.028) had lower cerebral vasoreactivity.

Conclusion:

Among older women at high cardiovascular risk, women with virologically suppressed HIV and women at risk for HIV had similar cerebrovascular function. Our findings, which must be interpreted in the context of the small sample, highlight the contribution of traditional cardiometabolic risk factors and immune activation to cerebrovascular risk in WWH.
Factors Associated With Condom Failure in a Longitudinal Cohort of Men Who Have Sex With Men and Transgender Women in Abuja and Lagos, Nigeria
Authors: Hamill Matthew M. , Hu Fengming , Kokogho Afoke , Shoyemi Elizabeth , Ekeh Charles , Charurat Manhattan E. , Robb Merlin L. , Adebajo Sylvia , Baral Stefan D. , Nowak Rebecca G. , Crowell Trevor A. ,   for the TRUST/RV368 Study Group
Published: November 2020

Background:

Effective condom use is a critical intervention to limit the spread of HIV and other sexually transmitted infections, particularly among individuals in high-risk networks who practice anal sex. We characterized condom failures in cisgender men who have sex with men and transgender women in Nigeria.

Setting:

The TRUST/RV368 cohort provided condoms, compatible lubricants, and safer sex education to men who have sex with men and transgender women at community-engaged health centers in Abuja and Lagos, Nigeria.

Methods:

Participants completed structured interview questions about condom usage and failure every 3–6 months. Robust Poisson regression models with generalized estimating equations were used to estimate relative risks and 95% confidence intervals for prespecified factors potentially associated with condom failure in the previous month.

Results:

From September 2013 to September 2019, 2221 of 2737 participants (81.1%) reported condom use for anal sex with a male partner in the last month, and 305 (13.7%) reported condom failure during this time. Multivariate analyses demonstrated an increased risk of condom failure at postenrollment visits, as well as in participants who reported frequent Internet use, 2 or more casual sexual partners, and 2–4 main sexual partners. Those who cohabited with a woman had reduced risk.

Conclusions:

Condom failure was common in this population despite freely available condoms, compatible lubrication, and education. Increased risk of condom failure over time could reflect message fatigue a ceiling for effective condom use, or new uptake of condoms by inexperienced users.
Access to Subsidized Health Care Affects HIV Pre-Exposure Prophylaxis (PrEP) Uptake Among Gay and Bisexual Men in Australia: Results of National Surveys 2013–2019
Authors: MacGibbon James , Lea Toby , Ellard Jeanne , Murphy Dean , Kolstee Johann , Power Cherie , Crawford David , Bear Brandon , De Wit John , Holt Martin
Published: November 2020

Background:

We assessed willingness to use HIV pre-exposure prophylaxis (PrEP) and current PrEP use among gay and bisexual men (GBM) in Australia.

Methods:

National, online cross-sectional surveys of GBM were conducted in 2013, 2015, 2017, and 2019. Willingness to use PrEP was measured on a previously validated scale. Trends and associations with key measures were analyzed using multivariate logistic regression.

Results:

During 2013–2019, 4908 surveys were completed. Among HIV-negative and untested men not currently using PrEP, willingness to use PrEP increased from 23.0% in 2013 to 36.5% in 2017 (P < 0.001) but then plateaued at 32% in 2019 (P = 0.13). The proportion of current PrEP users increased significantly from 2.5% in 2015 to 38.5% in 2019 (P < 0.001). In 2019, factors independently associated with being a current PrEP user (compared with non-PrEP users who were willing to use PrEP) included having subsidized health care (Medicare), knowing HIV-positive people, being recently diagnosed with an STI other than HIV, having higher numbers of recent male sexual partners, recent condomless sex with casual and regular partners, and frequent PrEP sorting.

Conclusion:

Willingness to use PrEP has plateaued as its use has rapidly increased among GBM in Australia. PrEP use is concentrated among more sexually active men with access to subsidized health care. Free or low cost access schemes may facilitate broader access among GBM who want or need PrEP but lack access to subsidized health care.
Bilateral Silicone Granulomas Mimicking Breast Cancer Recurrence on 18F-FDG PET/CT
Authors: Fernandes Vieira Victor , Dubruc Estelle , Raffoul Wassim , Prior John O. , Meyer Marie
Published: November 2020

We report the case of a 45-year-old woman with a history of right breast reconstruction with silicone implant for breast cancer. An 18F-FDG PET/CT performed several years later revealed the presence of 18F-FDG–avid nodules at the periphery of the silicone implant, in the right internal mammary chain, and in the contralateral breast. Needle core biopsies were positive for bilateral silicone granulomas, without any sign of malignancy. This case displays intense 18F-FDG uptake in silicone granulomas affecting the contralateral breast after implant reconstruction.