bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Intensive Care Unit Admission and In-hospital Mortality Among Hospitalized Adults Identified through the US Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET)
Authors: Kim Lindsay , Garg Shikha , O’Halloran Alissa , Whitaker Michael , Pham Huong , Anderson Evan J , Armistead Isaac , Bennett Nancy M , Billing Laurie , Como-Sabetti Kathryn , Hill Mary , Kim Sue , Monroe Maya L , Muse Alison , Reingold Arthur L , Schaffner William , Sutton Melissa , Talbot H Keipp , Torres Salina M , Yousey-Hindes Kimberly , Holstein Rachel , Cummings Charisse , Brammer Lynnette , Hall Aron J , Fry Alicia M , Langley Gayle E
Published: July 2020

Background

Currently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk factors for severe outcomes among adults hospitalized with COVID-19.

Methods

We analyzed data from 2491 adults hospitalized with laboratory-confirmed COVID-19 between 1 March–2 May 2020, as identified through the Coronavirus Disease 2019–Associated Hospitalization Surveillance Network, which comprises 154 acute-care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality.

Results

The data show that 92% of patients had ≥1 underlying condition; 32% required ICU admission; 19% required invasive mechanical ventilation; and 17% died. Independent factors associated with ICU admission included ages 50–64, 65–74, 75–84, and ≥85 years versus 18–39 years (adjusted risk ratios [aRRs], 1.53, 1.65, 1.84, and 1.43, respectively); male sex (aRR, 1.34); obesity (aRR, 1.31); immunosuppression (aRR, 1.29); and diabetes (aRR, 1.13). Independent factors associated with in-hospital mortality included ages 50–64, 65–74, 75–84, and ≥ 85 years versus 18–39 years (aRRs, 3.11, 5.77, 7.67, and 10.98, respectively); male sex (aRR, 1.30); immunosuppression (aRR, 1.39); renal disease (aRR, 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR, 1.28); neurologic disorders (aRR, 1.25); and diabetes (aRR, 1.19).

Conclusions

In-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19–related complications.
Efficacy and Safety of a Naphthoquine-Azithromycin Coformulation for Malaria Prophylaxis in Southeast Asia: A Phase 3, Double-blind, Randomized, Placebo-controlled Trial
Authors: Yang Henglin , Wang Jingyan , Liu Hui , Zhao Yan , Lakshmi Seetha , Li Xingliang , Nie Renhua , Li Chunfu , Wang Hengye , Cao Yaming , Menezes Lynette , Cui Liwang
Published: July 2020

Background

A prophylactic antimalarial drug that is both effective for protection and improves compliance is in high demand.

Methods

We conducted a randomized, placebo-controlled, double-blinded phase 3 trial to evaluate the 1:1 fixed-dose combination of naphthoquine-azithromycin (NQAZ) for safety and protection against Plasmodium infections in villages along the China-Myanmar border. A total of 631 residents, 5–65 years of age, were randomized into the drug group (n = 319) and the placebo group (n = 312) to receive NZAQ and placebo, respectively, as a single-dose monthly treatment. Follow-ups were conducted weekly to monitor for adverse events and malaria infections.

Results

Of the 531 subjects completing the trial, there were 46 and 3 blood smear–positive Plasmodium infections in the placebo and treatment groups, respectively. For the intent-to-treat analysis, the single-dose monthly NQAZ treatment had 93.62% protective efficacy (95% confidence interval [CI]: 91.72%–95.52%). For the per-protocol analysis, NQAZ treatment provided a 93.04% protective efficacy (95% CI: 90.98%–95.1%). Three smear-positive cases in the NQAZ group were all due to acute falciparum malaria. In comparison, NQAZ treatment provided 100% protection against the relapsing malaria Plasmodium vivax and Plasmodium ovale. The treatment group had 5.6% of participants experiencing transient elevation of liver aminotransferases compared with 2.2% in the placebo group (P > .05).

Conclusions

Monthly prophylaxis with NQAZ tablets was well tolerated and highly effective for preventing Plasmodium infections. It may prove useful for eliminating P. vivax in areas with a high prevalence of glucose-6-phosphate dehydrogenase deficiency in the population.

Clinical Trials Registration

ChiCTR1800020140.
Recommendations for advance care planning in adults with congenital heart disease: a position paper from the ESC Working Group of Adult Congenital Heart Disease, the Association of Cardiovascular Nursing and Allied Professions (ACNAP), the European Association for Palliative Care (EAPC), and the International Society for Adult Congenital Heart Disease (ISACHD)
Authors: Schwerzmann Markus , Goossens Eva , Gallego Pastora , Kovacs Adrienne H , Moons Philip , Swan Lorna , Tobler Daniel , de Stoutz Noémi , Gabriel Harald , Greutmann Matthias , Roos-Hesselink Jolien W , Sobanski Piotr Z , Thomet Corina
Published: July 2020

Survival prospects in adults with congenital heart disease (CHD), although improved in recent decades, still remain below expectations for the general population. Patients and their loved ones benefit from preparation for both unexpected and predictable deaths, sometimes preceded by a prolonged period of declining health. Hence, advance care planning (ACP) is an integral part of comprehensive care for adults with CHD. This position paper summarizes evidence regarding benefits of and patients’ preferences for ACP and provides practical advice regarding the implementation of ACP processes within clinical adult CHD practice. We suggest that ACP be delivered as a structured process across different stages, with content dependent upon the anticipated disease progression. We acknowledge potential barriers to initiate ACP discussions and emphasize the importance of a sensitive and situation-specific communication style. Conclusions presented in this article reflect agreed expert opinions and include both patient and provider perspectives.
Ubiquilin-2 differentially regulates polyglutamine disease proteins
Authors: Gerson Julia E , Safren Nathaniel , Fischer Svetlana , Patel Ronak , Crowley Emily V , Welday Jacqueline P , Windle Alexandra K , Barmada Sami , Paulson Henry L , Sharkey Lisa M
Published: July 2020

Divergent protein context helps explain why polyglutamine expansion diseases differ clinically and pathologically. This heterogeneity may also extend to how polyglutamine disease proteins are handled by cellular pathways of proteostasis. Studies suggest, for example, that the ubiquitin-proteasome shuttle protein Ubiquilin-2 (UBQLN2) selectively interacts with specific polyglutamine disease proteins. Here we employ cellular models, primary neurons and mouse models to investigate the potential differential regulation by UBQLN2 of two polyglutamine disease proteins, huntingtin (HTT) and ataxin-3 (ATXN3). In cells, overexpressed UBQLN2 selectively lowered levels of full-length pathogenic HTT but not of HTT exon 1 fragment or full-length ATXN3. Consistent with these results, UBQLN2 specifically reduced accumulation of aggregated mutant HTT but not mutant ATXN3 in mouse models of Huntington’s disease (HD) and spinocerebellar ataxia type 3 (SCA3), respectively. Normally a cytoplasmic protein, UBQLN2 translocated to the nuclei of neurons in HD mice but not in SCA3 mice. Remarkably, instead of reducing the accumulation of nuclear mutant ATXN3, UBQLN2 induced an accumulation of cytoplasmic ATXN3 aggregates in neurons of SCA3 mice. Together these results reveal a selective action of UBQLN2 toward polyglutamine disease proteins, indicating that polyglutamine expansion alone is insufficient to promote UBQLN2-mediated clearance of this class of disease proteins. Additional factors, including nuclear translocation of UBQLN2, may facilitate its action to clear intranuclear, aggregated disease proteins like HTT.
A systematic literature review of automatic Alzheimer’s disease detection from speech and language
Authors: Petti Ulla , Baker Simon , Korhonen Anna
Published: July 2020

Objective

In recent years numerous studies have achieved promising results in Alzheimer’s Disease (AD) detection using automatic language processing. We systematically review these articles to understand the effectiveness of this approach, identify any issues and report the main findings that can guide further research.

Materials and Methods

We searched PubMed, Ovid, and Web of Science for articles published in English between 2013 and 2019. We performed a systematic literature review to answer 5 key questions: (1) What were the characteristics of participant groups? (2) What language data were collected? (3) What features of speech and language were the most informative? (4) What methods were used to classify between groups? (5) What classification performance was achieved?

Results and Discussion

We identified 33 eligible studies and 5 main findings: participants’ demographic variables (especially age ) were often unbalanced between AD and control group; spontaneous speech data were collected most often; informative language features were related to word retrieval and semantic, syntactic, and acoustic impairment; neural nets, support vector machines, and decision trees performed well in AD detection, and support vector machines and decision trees performed well in decline detection; and average classification accuracy was 89% in AD and 82% in mild cognitive impairment detection versus healthy control groups.

Conclusion

The systematic literature review supported the argument that language and speech could successfully be used to detect dementia automatically. Future studies should aim for larger and more balanced datasets, combine data collection methods and the type of information analyzed, focus on the early stages of the disease, and report performance using standardized metrics.
Single-Laboratory Validation of a Multi-residue Method for Simultaneous Analysis of Multi-class Pesticides in Turmeric by Liquid Chromatography Tandem Mass Spectrometry
Authors: Ghosh Bappa , Bhattacharyya Arijita , Hingmire Sandip , Aher Pushpa , Zende Pradnya , Banerjee Kaushik
Published: July 2020

Background

For years, turmeric has been used in several cuisines worldwide because of its proven health benefits. However, as its cultivation often involves applications of polar and semi-polar pesticides, their residues might cause health hazards to consumers. The dearth of a validated LC-MS/MS method for the residue analysis of these pesticides in turmeric has warranted the present study.

Objective

The aim was to develop and validate a multi-residue method for simultaneous determination of multi-class pesticides in turmeric (both rhizome and powder) by LC-MS/MS.

Method

Both the rhizome and powder samples (1 kg) were soaked in water for 30 min, followed by homogenization. Each homogenate (2 g) was mixed with 10 mL water, and extracted with acetonitrile (10 mL) in the presence of acetic acid and NaCl. The extract was cleaned by using dispersive solid phase extraction (dSPE) with graphitized carbon (5 mg/mL) sorbent. The cleaned extract was measured by LC-MS/MS with a runtime of 20 min. The method was validated on 211 multi-class pesticides.

Results

The method performance was satisfactory at 10 ng/g and higher levels, in compliance with the SANTE/12682/2019 guidelines. The dSPE cleanup was effective in minimizing the matrix effects. The use of matrix-matched calibrations specific for turmeric powder and rhizome corrected all recoveries within the satisfactory range of 70–120%. The precision -RSDs were <20% for all test pesticides. The Horwitz ratio and measurement uncertainty results were satisfactory as well.

Conclusions

As the method was convenient, selective, accurate, and repeatable, it is recommended for regulatory and commercial testing purposes.

Highlights

For the first time, this study reports a validated LC-MS/MS method for the multi-residue analysis of pesticides in turmeric. The method provided a high throughput analysis of multi-class pesticides in turmeric rhizome and powder matrices with satisfactory selectivity, sensitivity, accuracy, and precision. The method performance satisfied the requirements of the SANTE/12682/2019 guidelines, and the method sensitivity complied with the EU-MRL requirements.
Nuclear accumulation of ZFP36L1 is cell cycle-dependent and determined by a C-terminal serine-rich cluster
Authors: Matsuura Yuki , Noguchi Aya , Sakai Shunsuke , Yokota Naoto , Kawahara Hiroyuki
Published: July 2020

ZFP36L1 is an RNA-binding protein responsible for mRNA decay in the cytoplasm. ZFP36L1 has also been suggested as a nuclear-cytoplasmic shuttling protein because it contains a potential nuclear localization signal and a nuclear export signal. However, it remains unclear how the nuclear localization of ZFP36L1 is controlled. In this study, we provide evidence that the nuclear accumulation of ZFP36L1 protein is modulated in a cell cycle-dependent manner. ZFP36L1 protein accumulation in fractionated nuclei was particularly prominent in cells arrested at G1-/S-phase boundary, while it was downregulated in S-phase cells, and eventually disappeared in G2-phase nuclei. Moreover, forced nuclear targeting of ZFP36L1 revealed marked downregulation of this protein in S- and G2-phase cells, suggesting that ZFP36L1 can be eliminated in the nucleus. The C-terminal serine-rich cluster of ZFP36L1 is critical for the regulation of its nuclear accumulation because truncation of this probable disordered region enhanced the nuclear localization of ZFP36L1, increased its stability and abolished its cell cycle-dependent fluctuations. These findings provide the first hints to the question of how ZFP36L1 nuclear accumulation is controlled during the course of the cell cycle.
Filtering of a Ricker wavelet induced by anelastic seismic wave propagation and reflection
Authors: Ker Stephan , Le Gonidec Yves
Published: July 2020

A varying Q factor with depth induces modifications of seismic wave features due to anelastic propagation but also reflections at the discontinuities. Standard signal analysis methods often neglect the reflection contribution when assessing Q values from seismic data. We have developed an analytical quantification of the cumulative effects of both the propagation and reflection contributions by considering Kjartansson's model and a seismic plane wave at normal incidence on a step-like discontinuity. We show that the cumulative effects are equivalent to a frequency filter characterised by a bandform and phase that both depend on the ratio between the elastic and anelastic contrasts. When considering this filter applied to a Ricker wavelet, we establish an analytical expression of the peak-frequency attribute as a function of propagation and reflection properties. We demonstrate that this seismic attribute depends on the anelastic contrast, which cannot be neglected when assessing Q factors: the error in Q estimate is not linearly dependent on the anelastic contrast and we establish an analytical expression for the case where this contrast is weak. An unexpected phenomenon for a step-like interface is an increase in the peak frequency that is observed when the anelastic and elastic contrasts have opposite signs, with a constraint on the anelastic propagation properties. This behaviour allows for assessment of the elastic and anelastic parameters.
The value of asymmetry: how polarity proteins determine plant growth and morphology
Authors: Wallner Eva-Sophie
Published: July 2020

Cell polarity is indispensable for forming complex multicellular organisms. Proteins that polarize at specific plasma membrane domains can either serve as scaffolds for effectors or coordinate intercellular communication and transport. Here, I give an overview of polarity protein complexes and their fundamental importance for plant development, and summarize novel mechanistic insights into their molecular networks. Examples are presented for proteins that polarize at specific plasma membrane domains to orient cell division planes, alter cell fate progression, control transport, direct cell growth, read global polarity axes, or integrate external stimuli into plant growth. The recent advances in characterizing protein polarity during plant development enable a better understanding of coordinated plant growth and open up intriguing paths that could provide a means to modulate plant morphology and adaptability in the future.
Maize YSL2 is required for iron distribution and development in kernels
Authors: Zang Jie , Huo Yanqing , Liu Jie , Zhang Huairen , Liu Juan , Chen Huabang
Published: July 2020

Iron (Fe) is an essential micronutrient and plays an irreplaceable role in plant growth and development. Although its uptake and translocation are important biological processes, little is known about the molecular mechanism of Fe translocation within seed. Here, we characterized a novel small kernel mutant yellow stripe like 2 (ysl2) in maize (Zea mays). ZmYSL2 was predominantly expressed in developing endosperm and was found to encode a plasma membrane-localized metal–nicotianamine (NA) transporter ZmYSL2. Analysis of transporter activity revealed ZmYSL2-mediated Fe transport from endosperm to embryo during kernel development. Dysfunction of ZmYSL2 resulted in the imbalance of Fe homeostasis and abnormality of protein accumulation and starch deposition in the kernel. Significant changes of nitric oxide accumulation, mitochondrial Fe–S cluster content, and mitochondrial morphology indicated that the proper function of mitochondria was also affected in ysl2. Collectively, our study demonstrated that ZmYSL2 had a pivotal role in mediating Fe distribution within the kernel and kernel development in maize.
SINGLE FLOWER TRUSS and SELF-PRUNING signal developmental and metabolic networks to guide cotton architectures
Authors: McGarry Roisin C , Rao Xiaolan , Li Qiang , van der Knaap Esther , Ayre Brian G
Published: July 2020

Patterns of indeterminate and determinate growth specify plant architecture and influence crop productivity. In cotton (Gossypium hirsutum), SINGLE FLOWER TRUSS (SFT) stimulates the transition to flowering and determinate growth, while its closely related antagonist SELF-PRUNING (SP) maintains meristems in indeterminate states to favor vegetative growth. Overexpressing GhSFT while simultaneously silencing GhSP produces highly determinate cotton with reduced foliage and synchronous fruiting. These findings suggest that GhSFT, GhSP, and genes in these signaling networks hold promise for enhancing ‘annualized’ growth patterns and improving cotton productivity and management. To identify the molecular programs underlying cotton growth habits, we used comparative co-expression networks, differential gene expression, and phenotypic analyses in cotton varieties expressing altered levels of GhSFT or GhSP. Using multiple cotton and tomato datasets, we identified diverse genetic modules highly correlated with SFT or SP orthologs which shared related Gene Ontologies in different crop species. Notably, altering GhSFT or GhSP levels in cotton affected the expression of genes regulating meristem fate and metabolic pathways. Further phenotypic analyses of gene products involved in photosynthesis, secondary metabolism, and cell wall biosynthesis showed that early changes in GhSFT and GhSP levels profoundly impacted later development in distal tissues. Identifying the molecular underpinnings of GhSFT and GhSP activities emphasizes their broad actions in regulating cotton architecture.
Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation
Authors: Zhang Jingfeng , Fan Jing-Song , Li Shuangli , Yang Yunhuang , Sun Peng , Zhu Qinjun , Wang Jiannan , Jiang Bin , Yang Daiwen , Liu Maili
Published: July 2020

Human Y-box binding protein 1 (YB-1) is a multifunctional protein and overexpressed in many types of cancer. It specifically recognizes DNA/RNA through a cold shock domain (CSD) and regulates nucleic acid metabolism. The C-terminal extension of CSD and the phosphorylation of S102 are indispensable for YB-1 function. Until now, the roles of the C-terminal extension and phosphorylation in gene transcription and translation are still largely unknown. Here, we solved the structure of human YB-1 CSD with a C-terminal extension sequence (CSDex). The structure reveals that the extension interacts with several residues in the conventional CSD and adopts a rigid structure instead of being disordered. Either deletion of this extension or phosphorylation of S102 destabilizes the protein and results in partial unfolding. Structural characterization of CSDex in complex with a ssDNA heptamer shows that all the seven nucleotides are involved in DNA–protein interactions and the C-terminal extension provides a unique DNA binding site. Our DNA-binding study indicates that CSDex can recognize more DNA sequences than previously thought and the phosphorylation reduces its binding to ssDNA dramatically. Our results suggest that gene transcription and translation can be regulated by changing the affinity of CSDex binding to DNA and RNA through phosphorylation, respectively.
Path Dependence and the Roots of Interorganizational Relationship Challenges
Authors: Sedgwick Donna , Jensen Laura S
Published: July 2020

Governance today often requires concerted action by multiple organizations operating within and across sectors. Although scholars fruitfully have assayed many factors that facilitate or constrain interorganizational collaboration, the extant literature largely ignores the ways in which historical patterns of policy and organizational development may figure in present-day obstacles to collaboration. This is unfortunate, for such obstacles may result from path dependence and, thus, be particularly ingrained and resistant to change. In this article, we detail recent advances in path dependency theory, then illustrate our argument with a case study of path-dependent barriers to collaboration between two public programs pressed to work together after decades of deliberately separate operation. The case confirms the utility of new theoretical developments, yet also suggests necessary clarifications and refinements. Though aspects of path dependence theory should be reexamined, we argue that it is ripe for use by scholars of public management concerned with barriers to collaboration and other contemporary governance challenges.
Gender Matters: Infusing a Gender Analysis into the “Healthy Development of All Youth” Grand Challenge
Authors: Graham Laurie M , Casey Erin A , Carlson Juliana
Published: July 2020

The social work grand challenge to ensure healthy youth development necessarily involves a focus on violence prevention, including the prevention of sexual and dating violence during adolescence. The experience of sexual and dating violence is associated with numerous and often long-lasting detrimental mental, physical, and social outcomes, many of which this grand challenge seeks to prevent. Although evidence shows that gender is a critical axis of identity to consider in violence prevention research and practice efforts, gender is not a central lens applied in the field’s approach to such issues within this grand challenge. First, this article articulates a rationale for infusing a gender analysis into understanding sexual and dating violence and conceptualizing effective violence prevention strategies. Second, authors describe gender-transformative (GT) approaches to sexual and dating violence prevention, a promising practice for both ensuring the healthy development of youths and reducing violence perpetration by focusing on engaging boys and young men. Third, authors discuss the potential for GT strategies to be used in prevention efforts targeting adolescent social issues more broadly. Last, authors call for practitioners and researchers focused on healthy youth development to apply a gender analysis in their efforts and articulate concrete ways to do so.
Mainstreaming Gender: An Examination of Feminist Methodology in Social Work Research
Authors: Lauve-Moon Katie R , Enman Shelby , Hentz Vanessa
Published: July 2020

Despite gender being central to any given social issue and the profession of social work’s commitment to social justice, gender and gender inequality remain tangential to mainstream social work goals as partially indicated by the Grand Challenges for Social Work initiative led by the American Academy of Social Work and Social Welfare. Feminist methodologists prioritize the investigation of gender inequality by elevating the voices of oppressed groups, particularly women, using qualitative and mixed-methods studies, focusing on structural social change, and emphasizing the need for intersectional inquiry. Feminist and other critical methodologies frame structural inequality as central to the examination of all social issues and research questions. This study investigates the extent to which gender and gender inequality are investigated in mainstream social work research. Specifically, drawing on 404 research articles from three mainstream social work journals, this research relies on content analysis to demonstrate the dearth of studies examining gender and gender inequality in mainstream social work research. This work also presents opportunities for social workers to position gender as central to understanding persisting structural inequalities of the 21st century and work toward a more equitable social order.
Variation in outcome reporting and measurement tools in clinical trials of treatments for genitourinary symptoms in peri- and postmenopausal women: a systematic review
Authors: Christmas Monica Michelle , Song Bonnie , Bell Robin J. , Iliodromiti Stamatina , Mitchell Caroline , Hickey Martha
Published: July 2020

Importance:

Genitourinary symptoms affect 40% to 60% of postmenopausal women. Evidence-based approaches to diagnosing and managing these symptoms are limited by inconsistencies in outcomes and measures used in clinical trials.

Objective:

The aim of the study was to systematically review all outcomes and measurement tools reported in randomized clinical trials of interventions for genitourinary symptoms associated with menopause.

Evidence Review:

We searched PubMed, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to December 2018. Randomized controlled trials with a primary or secondary outcome of genitourinary symptoms associated with menopause, English language, and sample size of 20 or more women per study arm were included. Study characteristics, outcomes, and measurement methods were collected.

Findings:

The search yielded 3,478 articles of which 109 met inclusion criteria. Forty-eight different outcomes were reported with “atrophy” as the most common (56/109, 51%) followed by measures of sexual function (19/109, 17%). Almost all (108/109, 99%) trials included patient-reported measures, with 21 different measures and 39 symptom combinations. Clinician-reported scales of vulvovaginal appearance were used in 36 of 109 (33%) trials, with extensive variation in what was measured and reported. Cytological measures from the vaginal epithelium were the most commonly used objective tools (76/109, 70%).

Conclusions and Relevance:

There is heterogeneity in reported outcomes and measures used in clinical trials of treatments for genitourinary symptoms at menopause and uncertainty as to which outcomes best reflect patient priorities and symptoms. The findings from this systematic review have informed an international survey of stakeholders to determine priorities for outcome selection and reporting. This survey will then inform the development of a Core Outcome Set for use in future clinical trials by the COMMA (CoreOutcoMes inMenopAuse) consortium.

Video Summary:http://links.lww.com/MENO/A599.
Retinol-binding protein 4 is associated with arterial stiffness in early postmenopausal women
Authors: Chondrou Asimina , Nigdelis Meletios P. , Armeni Eleni , Augoulea Areti , Rizos Dimitrios , Kaparos George , Alexandrou Andreas , Goulis Dimitrios G. , Patras Raphael , Aivalioti Evmorfia , Stamatelopoulos Kimon , Lambrinoudaki Irene V.
Published: July 2020

Objective:

Recent evidence in postmenopausal women suggested lack of association between serum levels of retinol-binding protein 4 (RBP4) and subclinical atherosclerosis; however, associations with arterial stiffness in this population remain unexplored. We evaluated the association among RBP4 and cardiovascular risk factors, including homocysteine, a marker involved in retinoic acid synthesis, and indices of arterial stiffness, in a sample of apparently healthy postmenopausal women.

Methods:

This cross-sectional study included 123 healthy postmenopausal women, not on hormone therapy, antihypertensive, or hypolipidemic treatment and with a menopausal age 10 years or less. We performed biochemical/hormonal assessment and sonographic evaluation, including carotid-femoral pulse wave velocity (PWV) and carotid artery stiffness index (SI).

Results:

Univariate analysis showed that RBP4 values correlated with age, low-density lipoprotein-cholesterol and estradiol levels. There was a trend of association of SI and PWV with homocysteine and triglycerides. RBP4 differed according to PWV, using the median PWV value as cut-off (RBP4, PWV ≤8.1 vs >8.1 m/s: 10.09 ± 2.05 vs 10.85 ± 1.91 ng/mL, analysis of covariance P value 0.014 adjusted for age, menopausal age, estradiol, pulse pressure). Linear regression analysis showed that PWV was independently associated with RBP4, age, and pulse pressure, whereas SI was independently associated with RBP4. An increase of one standard deviation in RBP4 levels (2.54 ng/mL) was associated with an increase of 0.577 m/s in PWV.

Conclusions:

RBP4 serum levels are associated with arterial stiffness, in a sample of healthy postmenopausal women. If this association is causative, serum RBP4 levels could serve as a marker of arterial stiffness. Prospective studies are required to investigate the significance of our findings.

Video Summary:

http://links.lww.com/MENO/A621.
TX-001HR is associated with a clinically meaningful effect on severity of moderate to severe vasomotor symptoms in the REPLENISH trial
Authors: Constantine Ginger D. , Simon James A. , Kaunitz Andrew M. , Pickar James H. , Revicki Dennis A. , Graham Shelli , Bernick Brian , Mirkin Sebastian
Published: July 2020

Objective:

The aim of the study was to evaluate the clinically meaningful effect of oral TX-001HR (17β-estradiol [E2]/progesterone [P4]) capsules on hot flushes severity (vasomotor symptoms [VMS] severity scale) using the patient-reported Clinical Global Impression (CGI).

Methods:

REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR in postmenopausal women (40-65 y) with a uterus. Those with frequent moderate to severe hot flushes (≥7/d or ≥50/wk) were randomized in a VMS substudy to daily E2/P4 (1/100, 0.5/100, 0.5/50, or 0.25/50 mg/mg), or placebo. Patients rated VMS severity from 1 (mild) to 3 (severe) and symptom improvements with the CGI. CGI results were an anchor in a nonparametric discriminant analysis to define clinically important differences (CIDs) and minimal CID in VMS severity at weeks 4 and 12.

Results:

In the VMS substudy (n = 726), determined CID and minimal CID severity thresholds were reductions of 0.525 and 0.350 points at week 4, respectively, and 0.775 and 0.225 points at week 12. Significantly more women taking the two highest E2/P4 doses (1/100 and 0.5/100) versus placebo met CID severity thresholds at weeks 4 (40% and 44% vs 17%; P < 0.05) and 12 (56% and 48% vs 29%; P < 0.05).

Conclusion:

REPLENISH trial data demonstrated that E2/P4 1/100 and 0.5/100 provided clinically meaningful improvements in hot flushes severity in postmenopausal women. In conjunction with previously demonstrated clinically meaningful VMS frequency improvements, these data support oral E2/P4 1/100 and 0.5/100 for postmenopausal women with a uterus seeking treatment for moderate to severe VMS.
Respiratory Virus-related Emergency Department Visits and Hospitalizations Among Infants in New Zealand
Authors: Prasad Namrata , Trenholme Adrian A. , Huang Q. Sue , Duque Jazmin , Grant Cameron C. , Newbern E. Claire
Published: July 2020

Background:

Estimates of the contribution of respiratory viruses to emergency department (ED) utilization remain limited.

Methods:

We conducted surveillance of infants with acute respiratory infection (ARI) associated ED visits, which then resulted in either hospital admission or discharge home. Seasonal rates of specific viruses stratified by age, ethnicity, and socioeconomic status were estimated for both visits discharged directly from ED and hospitalizations using rates of positivity for each virus.

Results:

During the 2014–2016 winter seasons, 3585 (66%) of the 5412 ARI ED visits were discharged home directly and 1827 (34%) were admitted to hospital. Among visits tested for all respiratory viruses, 601/1111 (54.1%) of ED-only and 639/870 (73.4%) of the hospital-admission groups were positive for at least one respiratory virus. Overall, respiratory virus-associated ED visit rates were almost twice as high as hospitalizations. Respiratory syncytial virus was associated with the highest ED (34.4 per 1000) and hospitalization rates (24.6 per 1000) among infants. ED visit and hospitalization rates varied significantly by age and virus. Māori and Pacific children had significantly higher ED visit and hospitalization rates for all viruses compared with children of other ethnicities.

Conclusions:

Many infants with acute respiratory virus infections are managed in the ED rather than admitted to the hospital. Higher rates of ED-only versus admitted acute respiratory virus infections occur among infants living in lower socioeconomic households, older infants and infants of Māori or Pacific versus European ethnicity. Respiratory virus infections resulting in ED visits should be included in measurements of ARI disease burden.
A Linear Rash
Authors: Davis Kyleen E. , Oehlke Sandra
Published: July 2020

This is a case study of 59-year-old female patient presenting with a linearly distributed rash on the volar aspect of her right wrist. A multiple-choice clinical question is given, followed by a detailed description of the correct diagnosis. Multiple differential diagnoses are also considered in this detailed patient case.
Intranasal Ketamine for Treatment of Acute Pain in Pediatrics
Authors: Ferguson Chelsea L. , Beckett Robert D.
Published: July 2020

Objectives

Intranasal ketamine has not been well studied in acute pain treatment and does not have a recognized place in therapy in current practice guidelines for pediatric patients. Ketamine has a unique mechanism of action with a favorable side effect profile that may provide benefit to the pediatric population for acute pain. The purpose of this review is to summarize the evidence evaluating intranasal ketamine versus any other comparator for children who require acute pain treatment.

Methods

A systematic review was performed to include clinical studies of intranasal ketamine for acute pain that reported any pain-related outcome and adverse events in children 0 to 17 years old. Trials were identified through PubMed, Google Scholar, clinical trial registries, research registries, and key journals through April 2018. The Jadad scoring system was used to assess the methodological quality of the included randomized controlled trials.

Results

Six studies consisting of 261 patients were reviewed. Intranasal ketamine demonstrated pain relief in all included clinical studies; however, there was inconsistency in dosing, comparators, scales, and indications. Two of the randomized controlled trials were rated as high quality, and 1 randomized controlled trial was rated as poor quality on the Jadad scale.

Conclusions

Intranasal ketamine was safe and effective in the 6 clinical studies included in this systematic review.
Sedoanalgesia Versus Infraclavicular Block for Closed Reduction of Pediatric Forearm Fracture in Emergency Department
Authors: Karagoz Selahattin , Tekin Erdal , Aydin Muhammed Enes , Turgut Mehmet Cenk , Yayik Ahmet Murat
Published: July 2020

Objective

Procedural sedoanalgesia is commonly used in pediatric patients in the emergency department (ED) for interventional procedures, diagnosis, and treatment. However, this method causes serious systemic complications, such as respiratory and cardiac depression. To minimize these complications, ultrasound-guided regional anesthesia methods have been used in recent years. We aimed to compare the use of procedural sedoanalgesia (PSA) and infraclavicular block (ICB) in the pain management of pediatric patients who underwent closed reductions of forearm fractures.

Materials and Methods

This prospective, randomized, clinical study included patients aged 3 to 15 years who presented to the ED with forearm fractures. The patients were divided into 2 groups: the procedural sedoanalgesia group (group PSA, n = 30) and ultrasound-guided ICB group (group ICB, n = 30). Pain scores of the patients were evaluated using the Wong-Baker FACES Scale before and during the procedure. Pain scores and parental and operator satisfaction were compared between the groups.

Results

There was no statistical significance in terms of demographic data. The pain scores observed during the procedures were significantly higher in the group PSA than in the group ICB (3.07 ± 1.55 vs 0.47 ± 0.86, respectively; P < 0.001). The parental and operator satisfaction of the ICB group was significantly higher than that of the PSA group (P < 0.001).

Conclusions

Ultrasound-guided ICB is a safe and effective method in the management of pain during closed reduction of forearm fracture in pediatric patients in EDs. It can be used safely in emergency rooms and has a high level of both parental and operator satisfaction.
Pediatric Lamp Oil Injuries Treated in US Emergency Departments
Authors: Forrester Mathias B.
Published: July 2020

Objective

Ingestion and aspiration of lamp oil may result in serious adverse effects and even death. The objective of this study was to describe pediatric lamp oil–related injuries treated at US emergency departments (EDs).

Methods

Cases were lamp oil–related injuries among patients aged 0 to 5 years reported to the National Electronic Injury Surveillance System during 2001–2018. The distribution of the number of cases and national estimate were determined for selected variables.

Results

A total of 317 pediatric lamp oil–related injuries treated at US EDs during 2001–2018 were identified, resulting in a national estimate of 9501 injuries (95% confidence interval, 6937–12,065). The national estimate declined from 1599 in 2001 to 59 in 2014 before increasing once more to 596 in 2017. The patients were 5.4% aged less than 1 year; 62.2%, 1 year; 23.0%, 2 years; 6.6%, 3 years; 2.2%, 4 years; and 0.6%, 5 years; 68.6% of the patients were boys and 31.4% were girls. Ingestions accounted for 91.9% of the injuries, and 82.1% occurred at home. The disposition of the patient was treated or examined and released (68.2%), treated and transferred to another hospital (13.2%), treated and admitted for hospitalization (14.4%), held for observation (4.2%), and not recorded (0.1%).

Conclusions

Although the estimated number of lamp oil–related injuries declined during 2000–2014, it increased during 2015–2017. Most of the patients were aged 1 to 2 years and boys. The majority of the injuries occurred by ingestion and at home. Most of the patients were treated or evaluated and released from the ED.
Immature/transitional B-cell expansion is associated with bone loss in HIV-infected individuals with severe CD4+ T-cell lymphopenia
Authors: Titanji Kehmia , Ofotokun Ighovwerha , Weitzmann M. Neale
Published: July 2020

Background:

Antiretroviral therapy (ART) has led to a significant decline in HIV-related morbidity and mortality in people living with HIV (PLWH). PLWH however experience non-AIDS ageing-associated comorbidities, including decreased bone mass and osteoporosis, earlier and more severely, than uninfected people. We previously reported that total B-cell production of the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL) was elevated in PLWH, concurrent with a decrease in total B-cell production of RANKL's physiological moderator Osteoprotegerin (OPG). The resulting increased total B-cell RANKL/OPG ratio was significantly associated with bone loss in the appendicular (long bones), but not axial (spine) skeletons of PLWH. A role for immature/transitional B cells (BImm) in HIV-induced bone loss has not been reported.

Methods:

BImm frequency was determined by flow cytometry; plasma IL-7 was quantified by ELISA and bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) in a cross-sectional study of 62 ART-naive HIV-infected and 58 HIV-negative individuals.

Results:

BImm expansion correlated with the total B-cell RANKL/OPG ratio in HIV-infected individuals and inversely with BMD at the total hip, femoral neck and the lumbar spine, and with IL-7.

Conclusion:

These data suggest that BImm contribute to the increased B-cell RANKL/OPG ratio in PLWH, and reveal a previously unrecognized link between BImm expansion and HIV-induced bone loss in the axial and appendicular skeletons of severely immunocompromised HIV-infected individuals. BImm expansion may be a novel biomarker for screening patients at risk of osteoporosis.
Influence of hepatitis C virus co-infection and hepatitis C virus treatment on risk of chronic kidney disease in HIV-positive persons
Authors: Mocroft Amanda , Ryom Lene , Oprea Cristiana , Li Qiuju , Rauch Andri , Boesecke Christoph , Uzdaviniene Vilma , Sedlacek Dalibor , Llibre Josep M. , Lacombe Karine , Nielsen Lars N. , Florence Eric , Aho Inka , Chkhartishvili Nikoloz , Szlavik János , Dragovic Gordana , Leen Clifford , Sambatakou Helen , Staub Therese , Laguno Montse , Elinav Hila , Tomažič Janez , Peters Lars
Published: July 2020

Background:

Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.

Methods:

HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m2] between HCV strata.

Results:

Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2–10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46–0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47–0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65–1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49–1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.

Conclusion:

This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.
Ulcerative Colitis as an Independent Risk Factor for Hepatic Steatosis
Authors: Mancina Rosellina Margherita , De Bonis Daniele , Pagnotta Raffele , Cosco Cristina , Cosco Vincenzo , Montalcini Tiziana , Pujia Arturo , Doldo Patrizia , Spagnuolo Rocco
Published: July 2020

Inflammatory bowel disease (IBD) is an inflammatory condition of the gastrointestinal tract encompassing Crohn disease and ulcerative colitis, often associated with extraintestinal manifestations. Nonalcoholic fatty liver disease represents one of the described inflammatory bowel disease–related liver diseases. To understand the IBD contribution to nonalcoholic fatty liver disease onset, we compared liver fat content and fibrosis between IBD patients and healthy controls integrating medical and nursing expertise (integrated nursing approach). A total of 95 patients and 53 healthy volunteers were recruited. Only nondiabetic and nonobese individuals were included in the study. Liver evaluation was performed by an experienced nurse using transient elastography. We found that IBD patients had higher liver fat content than the control group (p = .003). Bonferroni post hoc analyses revealed that patients with Crohn disease or ulcerative colitis had higher liver fat than the control group. We also found that ulcerative colitis was associated with more than a 4-fold increased risk for mild steatosis and 7-fold increased risk for moderate/severe steatosis independently from other risk factors such as glucose and body mass index. In conclusion, we showed for the first time that ulcerative colitis is an independent risk factor for hepatic steatosis measured by transient elastography.
Smaller brained cliff swallows are more likely to die during harsh weather
Authors: Wagnon Gigi S. , Brown Charles R.
Published: July 2020

The cognitive-buffer hypothesis proposes that more harsh and unpredictable environments favour animals with larger brains and resulting greater cognitive skills. Comparisons across taxa have supported the hypothesis, but it has rarely been tested within a species. We measured brain size, as inferred from head dimensions, for 1141 cliff swallow specimens collected in western Nebraska, 1982–2018. Cliff swallows starving to death during unusual late-spring cold snaps had significantly smaller brains than those dying from other causes, suggesting that brain size in this species can affect foraging success and that greater cognitive ability may confer advantages when conditions exceed normal environmental extremes. Brain size declined significantly with the size of the breeding colony from which a specimen came. Larger brains may be favoured in smaller colonies that represent more unpredictable and more challenging social environments where there is less public information on food sources and less collective vigilance against predators, even in relatively normal conditions. Our results provide intraspecific support for the cognitive-buffer hypothesis and emphasize the potential evolutionary impact of rare climatic events.