bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated nicotine exposure increases the intracellular interaction between ERK‐mGluR5 in the nucleus accumbens more in adult than adolescent rats
Authors: Yang Ju Hwan , Sohn Sumin , Kim Sunghyun , Kim Jieun , Oh Jeong Hwan , Ryu In Soo , Go Bok Soon , Choe Eun Sang
Published: April 2020

Intracellular interactions between protein kinases and metabotropic receptors in the striatum regulate behavioral changes in response to drug exposure. We investigated the difference in the degree of interaction between extracellular signal‐regulated kinase (ERK) and metabotropic glutamate receptor subtype 5 (mGluR5) in the nucleus accumbens (NAc) after repeated exposure to nicotine in adult and adolescent rats. The results showed that repeated exposure to nicotine (0.5 mg/kg/day, s.c.) for seven consecutive days increased ERK phosphorylation more in adults than in adolescents. Furthermore, membrane expression of mGluR5 in gamma‐aminobutyric acid (GABA) medium spiny neurons was higher in adults than adolescents as a result of repeated exposure to nicotine. Blockade of mGluR5 with MPEP (0.5 nmol/side) decreased the repeated nicotine‐induced increase in ERK phosphorylation. Either blockade of mGluR5 or inhibition of ERK with SL327 (150 nmol/side) decreased the repeated nicotine‐induced increase in the level of inositol‐1,4,5‐triphosphate (IP3), a key transducer associated with mGluR5‐coupled signaling cascades. Similarly, interference of binding between activated ERK and mGluR5 by the blocking peptide, Tat‐mGluR5‐i (2 nmol/side), decreased the repeated nicotine‐induced increases in IP3 and locomotor activity in adults. These findings suggest that the intracellular interaction between ERK and mGluR5 in the NAc is stronger in adult than in adolescent rats, which enhances the understanding of age‐associated behavioral changes that occur after repeated exposure to nicotine.
Potential resuscitative endovascular balloon occlusion of aorta candidates: defining the potential need using the National Trauma Registry
Authors: Daskal Yaakov , Hershkovitz Yehuda , Peleg Kobi , Dubose Joseph J. , Kessel Boris , Jeroukhimov Igor , Givon Adi , Dudkiewicz Mickey ,   Israel Trauma Group
Published: April 2020

Background

Most of the trauma patients who die in the first 24 h from arrival to the hospital do so as a result of haemorrhagic shock. Resuscitative endovascular balloon occlusion of the aorta (REBOA) facilitates expedient proximal aortic control, potentially bridging a needed gap for partial or non‐responders to traditional resuscitation en route to emergent definitive haemostasis. This resuscitation tool continues to evolve and has recently achieved some consensus defined indications for its use. The aim of this study is designed to examine the potential utility of REBOA among trauma victims who die within 24 h of arrival.

Methods

Data of all trauma patients who died in the first 24 h, from 2012 to 2017 were extracted from the National Trauma Registry in the Gertner Institute for Epidemiology and Health Policy Research. Patients who died in the first half an hour, and those with neck and thorax injuries were excluded. Demographics, clinical and injury data were collected.

Results

Overall, 129 patients were included; 74% male and 26% female with the mean age of 46.4 years. A total of 76% suffered blunt trauma and 24% penetrating trauma. Mean survival time was 5.87 h. The cause of death was major abdominal organ injury in 47.2%, injury to major abdominal vessel in 23.3% and pelvic fractures in 21.7%. A total of 69 patients (53.5%) ultimately required delayed resuscitative thoracotomy in the operation room.

Conclusion

Registry data suggest that there is a subset of patients presenting to modern trauma centres who might benefit from REBOA in order to avoid death.
Total laparoscopic sigmoid vaginoplasty: a novel therapeutic approach
Authors: Wang Junjiang , Wei Gengzhou , Yi Zhiyong , Liu Mubiao , Wu Wulin , Hu Weixian , Zheng Jiabin , Yao Xueqing , Li Yong
Published: April 2020

Background

This study aimed to evaluate the technical feasibility and outcomes of total laparoscopic sigmoid vaginoplasty (TLSV) in women with congenital absence of the vagina.

Methods

We investigated 10 women with congenital absence of the vagina, who underwent TLSV at Guangdong Provincial People's Hospital between April 2013 and July 2016.

Results

All 10 women were unmarried, the mean age was 22.8 (range 17–33) years, mean estimated blood loss was 149.2 ± 54.8 (60–170) mL, mean operative time was 108.4 ± 52.6 (130–210) min, mean post‐operative hospital stay was 8.0 ± 2.8 (6–12) days and the mean neovaginal length was 13.4 ± 3.0 (12–16) cm. Eight of the 10 women were heterosexually active. Trocar port site infection and neovaginal stenosis occurred 3 months after TLSV in one patient; a vaginal mould was used to relieve the stenosis.

Conclusion

TLSV is an optimal minimally invasive procedure to treat women with congenital absence of the vagina and is associated with rapid recovery and acceptable cosmetic effects.
Evaluation of communication to general practitioners when opioid‐naïve post‐surgical patients are discharged from hospital on opioids
Authors: Tran Tim , Taylor Simone E. , George Johnson , Pisasale Daisy , Batrouney Adele , Ngo Janet , Stanley Beata , Elliott Rohan A.
Published: April 2020

Background

To address the opioid crisis, much work has focused on minimizing opioid supply to surgical patients upon hospital discharge. Research is limited regarding handover to primary care providers. The aim of this study was to evaluate the communication of post‐operative opioid prescribing information provided by hospitals to general practitioners (GPs).

Methods

This study comprised two components. First, a retrospective audit of discharge summaries for opioid‐naïve surgical patients supplied with an opioid on discharge was conducted to evaluate accuracy of opioid documentation and presence of an opioid management plan. Second, a survey was distributed to GPs to seek their opinions regarding adequacy of communication about hospital‐initiated opioids in discharge summaries, challenges experienced in opioid management and suggestions for improvement.

Results

Discharge summaries for 285 patients were audited. Twenty‐seven (9.5%) patients had no discharge summary completed. Of the remaining 258, 63 (24.4%) summaries had at least one discrepancy between the opioid(s) listed and the opioid(s) dispensed. Only 33 (12.8%) summaries contained an opioid management plan. From 57 GP‐completed surveys, 41 (71.9%) GPs rarely or never received an opioid management plan from hospital surgical units and 34 (59.7%) were dissatisfied/very dissatisfied with information provided about opioid supply and management. Qualitative responses highlighted difficulties GPs experience managing opioid treatment for post‐surgical patients after discharge, differing patient expectations and the need to improve communication at times of transition.

Conclusion

When opioid‐naive patients are discharged from hospital on opioids, communication from hospitals to GPs is poor. Future interventions should focus on strategies to improve this.
A penalized structural equation modeling method accounting for secondary phenotypes for variable selection on genetically regulated expression from PrediXcan for Alzheimer's disease
Authors: Chen Ting‐Huei , Boughal Hanaa
Published: April 2020

As the global burden of mental illness is estimated to become a severe issue in the near future, it demands the development of more effective treatments. Most psychiatric diseases are moderately to highly heritable and believed to involve many genes. Development of new treatment options demands more knowledge on the molecular basis of psychiatric diseases. Toward this end, we propose to develop new statistical methods with improved sensitivity and accuracy to identify disease‐related genes specialized for psychiatric diseases. The qualitative psychiatric diagnoses such as case control often suffer from high rates of misdiagnosis and oversimplify the disease phenotypes. Our proposed method utilizes endophenotypes, the quantitative traits hypothesized to underlie disease syndromes, to better characterize the heterogeneous phenotypes of psychiatric diseases. We employ the structural equation modeling using the liability‐index model to link multiple genetically regulated expressions from PrediXcan and the manifest variables including endophenotypes and case‐control status. The proposed method can be considered as a general method for multivariate regression, which is particularly helpful for psychiatric diseases. We derive penalized retrospective likelihood estimators to deal with the typical small sample size issue. Simulation results demonstrate the advantages of the proposed method and the real data analysis of Alzheimer's disease illustrates the practical utility of the techniques. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative database.
Generalized reliability based on distances
Authors: Xu Meng , Reiss Philip T. , Cribben Ivor
Published: April 2020

The intraclass correlation coefficient (ICC) is a classical index of measurement reliability. With the advent of new and complex types of data for which the ICC is not defined, there is a need for new ways to assess reliability. To meet this need, we propose a new distance‐based ICC (dbICC), defined in terms of arbitrary distances among observations. We introduce a bias correction to improve the coverage of bootstrap confidence intervals for the dbICC, and demonstrate its efficacy via simulation. We illustrate the proposed method by analyzing the test‐retest reliability of brain connectivity matrices derived from a set of repeated functional magnetic resonance imaging scans. The Spearman‐Brown formula, which shows how more intensive measurement increases reliability, is extended to encompass the dbICC.
A longitudinal study of the impact of change in socioeconomic status on dental caries in the permanent dentition of Swedish children and adolescents
Authors: Östberg Anna‐Lena , Petzold Max
Published: April 2020

Objectives

The overall aim was to analyse longitudinally the development of dental caries in the permanent dentition of children and adolescents in a Swedish region, in relation to possible change in socioeconomic status (SES).

Methods

A total of 259 448 individuals in western Sweden were followed over a 3‐year period, through dental journal records at baseline (3‐19‐year‐olds) and 1‐3 dental check‐ups during the follow‐up period. Official socioeconomic register information (ethnicity, wealth, parental education and employment) was available at both baseline and follow‐up. Data were used both as independent single variables and combined in an index. Gender, age and caries status at baseline and the examination years were included as covariates in the regression models.

Results

Associations over time were found between SES and dental caries in young people. A persistently low SES was associated with the greatest risk of both new and accumulated (decayed plus filled teeth/approximal surfaces) caries; however, any change in SES, whether improved or worsened, led to a greater risk. An increased risk of new caries events was identified for those who were older at baseline and by examination year. On average, the increase per year in decayed and/or filled teeth and in approximal surfaces was 0.23 and 0.12, respectively.

Conclusion

SES was shown to be an important risk factor for dental caries over time in young Swedish people. Prevention programmes should pay particular attention to the needs of socioeconomically vulnerable individuals and groups.
Bidirectional analysis of the association between Ménière’s disease and depression: Two longitudinal follow‐up studies using a national sample cohort
Authors: Kim So Young , Lee Chang Ho , Min Chanyang , Park Il‐Seok , Choi Hyo Geun
Published: April 2020

Objective

This study aimed to delineate the causal relationship between Ménière's disease and depression.

Design

Two longitudinal follow‐up studies.

Main Outcome Measures

The 2002‐2013 Korean National Health Insurance Service‐Health Screening Cohort was used. In study I, Ménière's disease patients were 1:4 matched with the control I group for age group, sex, income group and region of residence, and the occurrence of depression was observed. In study II, the depression patients were 1:4 matched with the control II group for the same variables, and the occurrence of Ménière's disease was observed. The stratified Cox proportional hazard model was used. Subgroup analyses were performed according to age and sex.

Results

In study I, 6.9% (420/6044) of the Ménière's disease patients and 3.7% (885/24 176) of the control I participants experienced depression. The adjusted hazard ratio (HR) of Ménière's disease for depression was 1.94 (95% confidence intervals [CI] = 1.73‐2.18, P < .001). In study II, 1.6% (490/31 649) of the depression patients and 1.0% (1240/126 596) of the control II participants were diagnosed with Ménière's disease. The adjusted HR of depression for Ménière's disease was 1.58 (95% CI = 1.43‐1.76, P < .001). All age and sex subgroups demonstrated higher HRs of Ménière's disease for depression (study I) and depression for Ménière's disease (study II).

Conclusion

Ménière's disease patients showed an increased likelihood of depression. Conversely, depression patients showed an elevated likelihood of Ménière's disease.
Evaluating the ability of the Sodergren score to guide the management of internal haemorrhoidal disease
Authors: Sha H. L. , Roslani A. C. , Poh K. S.
Published: April 2020

Aim

The Sodergren score was developed to objectively measure the severity of haemorrhoidal symptoms. This study aimed to determine if there was a difference in the Sodergren score between patients who were offered surgery and patients who underwent successful rubber band ligation of internal haemorrhoidal disease and to assess its performance in guiding management.

Method

This is a prospective, observational study. The preintervention Sodergren scores of subjects with internal haemorrhoidal disease were recorded and blinded to the surgeon in charge. Sodergren scores of subjects in the two arms were unblinded and compared at the end of the study.

Results

The results for 290 patients were available for final analysis. The median scores of those offered surgery and those who underwent successful rubber band ligation differed significantly [4 (interquartile range 3–10) vs 0 (interquartile range 0–4), P = 0.001]. In predicting treatment, the Sodergren score had an area under the receiver operating characteristic curve of 0.735 (95% CI 0.675–0.795).

Conclusion

There is a significant difference in scores between patients who were offered surgery and patients with successful rubber band ligation. Our study suggests that the Sodergren score has an acceptable discrimination in predicting the need for surgery in internal haemorrhoidal disease. We propose that patients with a Sodergren score of 6 or more be considered for upfront surgery. This score could potentially be used to standardize outcomes of future haemorrhoid trials.
Echocardiography–fluoroscopy fusion imaging: The essential features used in congenital and structural heart disease interventional guidance
Authors: Jone Pei‐Ni , Sandoval Juan Pablo , Haak Alexander , Hammers Jacob , Rodriguez‐Zanella Hugo , Quaife Robert A. , Salcedo Ernesto E. , Carroll John D. , Gill Edward
Published: April 2020

Increased catheter‐based interventions in congenital and structural heart disease require imaging modalities to be oriented in the same visual perspective. The use of echocardiography–fluoroscopy fusion (EFF) imaging has been developed for better characterization of complex anatomy and to facilitate key steps in interventional procedures. This review will detail the technology behind EFF, the differences between the two ultrasound fusion systems, and essential features of EFF imaging in congenital and structural heart disease interventions.
Structure of positive psychotic symptoms in individuals at clinical high risk for psychosis
Authors: Azis Matilda , Rouhakhtar Pamela Rakhshan , Schiffman Jason E. , Ellman Lauren M. , Strauss Gregory P. , Mittal Vijay A.
Published: April 2020

Aim

Positive symptoms are a critical dimension of psychopathology in psychotic disorders and are used as a criterion for diagnosis across the psychosis continuum. Although initially considered as one dimension, there is evidence for multidimensionality within positive symptoms. The positive symptom structure has not been examined in individuals at clinical high risk (CHR) for psychosis. Knowledge of the dimensional structure of positive symptoms within CHR may contribute to our understanding of the aetiology and trajectory of this key facet of psychosis.

Method

Exploratory factor analysis (EFA) was conducted on the Prodromal Questionnaire‐Brief for 183 individuals meeting CHR criteria. Internal consistency was examined to determine the hierarchical structure of the data and alternative models were compared.

Results

EFA revealed a three factor model, grouping in to: perceptual abnormalities, grandiose/unusual delusions and persecutory/thought delusions, with a general factor accounting for 56% of the variance. Confirmatory factor analysis showed that a hierarchical model was the best fit. One item referring to nihilistic thoughts did not load on any factor.

Conclusion

There is a clear three‐dimensional model, distinguishing perceptual abnormalities, and two subgroups of delusions in CHR individuals. The factors are similar to those found in psychotic disorders. The identification and comparison of symptomatic models is useful given the prominent role positive symptoms play in diagnosis, and is crucial to our understanding of the clinical progression of psychosis. This work may provide a useful tool for future studies examining correlations with varying symptom factors and disease progression in CHR.
The normative bond between Kantian autonomy and Sartrean authenticity: A critical existentialist perspective
Authors: Russo Maria
Published: April 2020

Sartre and Kant are not often compared, especially because the former is frequently considered a theorist of a totally arbitrary free will. Nevertheless, this is not a fair interpretation of Sartre. Starting already from Being and Nothingness, he conceived an ethical difference between bad faith and authenticity. More unequivocally, in Notebooks for an Ethics he developed an existentialist ethics, which is more Kantian than expected. In that text, the ethical ideal of authenticity is not so different from the ethical ideal of autonomy in Kant. The aim of this article is to characterize Sartrean authenticity as a radicalization of Kantian autonomy. In both cases, there is a normative criterion, which implies a correct exercise of freedom towards oneself and others. This correct exercise of freedom implies for Kant the exclusion of the will determined by material conditions. For Sartre, this correct exercise means the rejection of bad faith. There is also a similar connection between autonomy and respect in Kant, and between authenticity and generosity in Sartre. Highlighting this little‐known affinity between the two most radical philosophers of freedom could also reveal a non‐ideological Sartre, ready to dialogue with contemporary ethical debate.
Portfolio optimization in the catastrophe space
Authors: Chang Carolyn W. , Chang Jack S. K. , Yu Min‐Teh , Zhao Yang
Published: April 2020

In today's global catastrophe space, the role of insurance‐linked securities has evolved from that of a threatened reinsurance substitute to now being a viable complementary reinsurance product, underpinning the convergence of the two markets. This study constructs a two‐agent sequential optimization framework to mimic the economics of the reinsurance/insurance markets and shows how NPV‐maximizing reinsurers and hedging cost‐minimizing insurers can optimally allocate default‐risky catastrophe reinsurance and default‐free catastrophe bonds at the interface of these two markets. We analyze parametric impacts considering interest rate risk, financial leverage, basis risk, differential markup, catastrophe arrival intensity, and severity, as well as other relevant characteristics.
Synthetic post‐translational modifications of elongation factor P using the ligase EpmA
Authors: Pfab Miriam , Kielkowski Pavel , Krafczyk Ralph , Volkwein Wolfram , Sieber Stephan A. , Lassak Jürgen , Jung Kirsten
Published: April 2020

Canonically, tRNA synthetases charge tRNA. However, the lysyl‐tRNA synthetase paralog EpmA catalyzes the attachment of (R)‐β‐lysine to the ε‐amino group of lysine 34 of the translation elongation factor P (EF‐P) in Escherichia coli. This modification is essential for EF‐P‐mediated translational rescue of ribosomes stalled at consecutive prolines. In this study, we determined the kinetics of EpmA and its variant EpmA_A298G to catalyze the post‐translational modification of K34 in EF‐P with eight noncanonical substrates. In addition, acetylated EF‐P was generated using an amber suppression system. The impact of these synthetically modified EF‐P variants on in vitro translation of a polyproline‐containing NanoLuc luciferase reporter was analyzed. Our results show that natural (R)‐β‐lysylation was more effective in rescuing stalled ribosomes than any other synthetic modification tested. Thus, our work not only provides new biochemical insights into the function of EF‐P, but also opens a new route to post‐translationally modify proteins using EpmA.
Influence of laser shock peening on fatigue performance of LZ50 axle steel for railway wheel set
Authors: Tang Kai , Wang Wenjian , Ding Haohao , Zhou Liucheng , Guo Jun , He Weifeng , Cai Zhenbing , Liu Qiyue , Zhou Zhongrong
Published: April 2020

Laser shock peening (LSP) is a surface treatment technique that forms a strengthened layer on the metal surfaces. In this study, the LSP was applied on the locomotive LZ50 axle steel surface which was interference fitted with the wheel. The microstructures, fracture morphologies and fatigue performances of LSP‐treated and untreated axle steels were explored. The results indicated that after the LSP treatment, a strengthened layer was generated on the axle steel surface. The surface hardness was increased by 25%, that is, from around 204 to around 255 HV0.3. The residual compressive stresses were improved from 260 to 345 MPa along the axial direction and from 165 to 225 MPa along the radial direction. The fatigue limit was increased by 30%, that is, from around 130 to around 170 MPa. The fracture surfaces could be divided into three regions: crack initiation, crack propagation, and short‐break regions. In the crack initiation region, the fatigue striation of the LSP‐treated steel was denser than the untreated steel. In the crack propagation and short‐break regions, the fracture morphologies of the LSP‐treated and the untreated axle steels were similar.
Differential risk premiums and the UIP puzzle
Authors: Biswas Rita , Piccotti Louis R. , Schreiber Ben Z.
Published: April 2020

We respecify the uncovered interest rate parity (UIP) conditions by inverting the market price of the risk (Sharpe ratio) formula. Our empirical model provides new insight indicating that violations to the UIP stem from the existence of a risk premium in the exchange rates and from observed market return differentials being a noisy statistic of the markets’ expected return differentials in our respecified model. Using an integrated macro‐micro structure framework for expected market return differentials improves our model fit and the validity of UIP.
On geopolitics and education: Interventions, possibilities, and future directions
Authors: Nguyen Nicole
Published: April 2020

In this article, I survey the rapidly developing literature on the symbiotic relationship between the education sector and geopolitics. Scholars across disciplines increasingly have studied how schools are implicated in and affected by broader geopolitical goals, particularly related to territorial security and national defense. Given the range of disciplinary interventions from international relations to education studies, discussions on the school‐geopolitics nexus often have been isolated and placed in relationship to other disciplinary conversations, forestalling rich cross‐disciplinary engagements to advance theorizations on the relationship between education and geopolitics. This review article, therefore, places studies on schools and geopolitics in conversation with each other and plots future directions for this emerging subfield. In doing so, I call on geographers to further engage the multi‐scalar analytics of feminist geopolitics, which can generate a more nuanced understanding of the school‐geopolitics nexus by more fully accounting for how geopolitical processes are differentially experienced, negotiated, and contested and for how the education sector itself maintains its own internal logics and contradictions irreducible to the external forces exerted on it.
Genetic testing for hereditary cancer syndromes: patient recommendations for improved risk communication
Authors: Pollard Samantha , Kalloger Steve , Weymann Deirdre , Sun Sophie , Nuk Jennifer , Schrader Kasmintan A. , Regier Dean A.
Published: April 2020

Background

Multi‐gene panel testing is replacing single‐gene testing for patients with suspected hereditary cancer syndromes. The detection of a hereditary cancer syndrome allows tested individuals to initiate enhanced primary and secondary prevention efforts—where available—with a view to reduce disease burden. Current policy prevents testing programmes from communicating genetic test results with potentially affected family members, yet it is well documented that tested individuals face multiple challenges in initiating such discussions with relatives.

Objective

In response to this challenge, we sought patient recommendations about how to improve genetic risk communication to enhance interfamilial discussions about primary and secondary disease prevention.

Design

We conducted 25 semi‐structured interviews with individuals who received genetic testing through British Columbia’s Hereditary Cancer Program between 2017 and 2018. Interviews were professionally transcribed and analysed using a constant comparative approach.

Results

Participants described difficulty engaging in conversations with relatives who were resistant to receiving genetic risk information, when communicating with younger relatives and where participants reported strained familial relationships. Participants recommended that testing facilities provide a summary of results and implications and that resources be made available to prepare patients for challenging discussions with family members.

Discussion

Our study demonstrates that individuals undergoing genetic testing for suspected hereditary cancer syndromes would benefit from additional supportive resources alongside genetic counselling. Providing this on‐going support will enhance the accurate and transparent communication of risk to facilitate the uptake of cascade testing and enhanced prevention strategies.
Identification and characterization of troponin genes in Locusta migratoria
Authors: Liang H.‐F. , Li J. , Li X.‐D.
Published: April 2020

Troponin complex comprises three subunits, namely troponin C (TpnC), troponin I (TpnI) and troponin T (TpnT), and regulates the contraction of striated muscle. We found that the locust Locusta migratoria genome has one TpnT gene (LmTpnT), one TpnI gene (LmTpnI) and three TpnC genes (LmTpnC1, LmTpnC2 and LmTpnC3). Through alternative splicing, LmTpnT and LmTpnI potentially encode two and eight isoforms, respectively. The flight muscle and the jump muscle of L. migratoria express an identical LmTpnT isoform, but different LmTpnC isoforms and LmTpnI isoforms. LmTpnC2 and LmTpnC3 both contain highly conserved residues essential for calcium binding in the EF‐hand II and IV, thus belonging two‐site isoform. LmTpnC1 contains non‐conserved substitutions in the EF‐hand II and all highly conserved residues for calcium binding in the EF‐hand IV. Mutagenesis and tyrosine fluorescence spectroscopic analysis show that both the EF‐hand II and IV of LmTpnC1 can serve as calcium‐binding site. Therefore, all three LmTpnC isoforms belong to two‐site isoform. This is in contrast to the situation in the insect with asynchronous flight muscle, which expresses both one‐site isoform and two‐site isoform of TpnC. Those results suggest that the origination of insect asynchronous flight muscle is associated with the emergence of one‐site isoform of TpnC.
The prognostic role of serum uric acid levels in preeclampsia: A meta‐analysis
Authors: Bellos Ioannis , Pergialiotis Vasilios , Loutradis Dimitrios , Daskalakis Georgios
Published: April 2020

This meta‐analysis aims to compare serum uric acid levels among preeclamptic and healthy pregnant women across the various trimesters and provide a summary of the effect size of this biomarker in predicting adverse pregnancy outcomes. MEDLINE, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception. Observational studies were held eligible if they reported serum uric acid among preeclamptic and healthy pregnant women. Meta‐analysis was conducted regarding uric acid concentration, diagnostic accuracy, and association with perinatal outcomes. The credibility of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The analysis included 196 studies, comprising 39 540 women. Preeclampsia was associated with significantly elevated uric acid levels during the 1st (mean difference [MD]: 0.21 mg/dL, 95% confidence intervals [CI]: 0.06‐0.35) trimester, 2nd (MD: 1.41 mg/dL, 95% CI: 0.78‐2.05) trimester, and 3rd (MD: 2.26 mg/dL, 95% CI: 2.12‐2.40) trimester. Higher uric acid was estimated for severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet syndrome. The sensitivity for adverse perinatal outcome prediction ranged from 67.3% to 82.7% and the specificity from 47.7% to 70.7%. In conclusion, it is suggested that serum uric acid levels are increased in preeclampsia and can be used to predict disease severity and pregnancy complications. Future prospective studies should verify these outcomes, assess the optimal cutoffs, and incorporate uric acid to combined predicting models.
Seizure‐induced impairment in neuronal ketogenesis: Role of zinc‐α2‐glycoprotein in mitochondria
Authors: Tan Changhong , Liu Xi , Peng Wuxue , Wang Hui , Zhou Wen , Jiang Jin , Wei Xin , Mo Lijuan , Chen Yangmei , Chen Lifen
Published: April 2020

Ketone bodies (KBs) were known to suppress seizure. Untraditionally, neurons were recently reported to utilize fatty acids and produce KBs, but the effect of seizure on neuronal ketogenesis has not been researched. Zinc‐α2‐glycoprotein (ZAG) was reported to suppress seizure via unclear mechanism. Interestingly, ZAG was involved in fatty acid β‐oxidation and thus may exert anti‐epileptic effect by promoting ketogenesis. However, this promotive effect of ZAG on neuronal ketogenesis has not been clarified. In this study, we performed immunoprecipitation and mass spectrometry to identify potential interaction partners with ZAG. The mechanisms of how ZAG translocated into mitochondria were determined by quantitative coimmunoprecipitation after treatment with apoptozole, a heat shock cognate protein 70 (HSC70) inhibitor. ZAG level was modulated by lentivirus in neurons or adeno‐associated virus in rat brains. Seizure models were induced by magnesium (Mg2+)‐free artificial cerebrospinal fluid in neurons or intraperitoneal injection of pentylenetetrazole kindling in rats. Ketogenesis was determined by cyclic thio‐NADH method in supernatant of neurons or brain homogenate. The effect of peroxisome proliferator–activated receptor γ (PPARγ) on ZAG expression was examined by Western blot, quantitative real‐time polymerase chain reaction (qRT‐PCR) and chromatin immunoprecipitation qRT‐PCR. We found that seizure induced ketogenesis deficiency via a ZAG‐dependent mechanism. ZAG entered mitochondria through a HSC70‐dependent mechanism, promoted ketogenesis by binding to four β‐subunits of long‐chain L‐3‐hydroxyacyl‐CoA dehydrogenase (HADHB) and alleviated ketogenesis impairment in a neuronal seizure model and pentylenetetrazole‐kindled epileptic rats. Additionally, PPARγ activation up‐regulated ZAG expression by binding to promoter region of AZGP1 gene and promoted ketogenesis through a ZAG‐dependent mechanism.
Essential Long‐Term Care Workers Commonly Hold Second Jobs and Double‐ or Triple‐Duty Caregiving Roles
Authors: Van Houtven Courtney Harold , DePasquale Nicole , Coe Norma B.
Published: April 2020

OBJECTIVES

Long‐term care (LTC) facilities are particularly dangerous places for the spread of COVID‐19 given that they house vulnerable high‐risk populations. Transmission‐based precautions to protect residents, employees, and families alike must account for potential risks posed by LTC workersʼ second jobs and unpaid care work. This observational study describes the prevalence of their (1) second jobs, and (2) unpaid care work for dependent children and/or adult relatives (double‐ and triple‐duty caregiving) overall and by occupational group (registered nurses [RNs], licensed practical nurses [LPNs], or certified nursing assistants [CNAs]).

DESIGN

A descriptive secondary analysis of data collected as part of the final wave of the Work, Family and Health Study.

SETTING

Thirty nursing home facilities located throughout the northeastern United States.

PARTICIPANTS

A subset of 958 essential facility‐based LTC workers involved in direct patient care.

MEASUREMENTS

We present information on LTC workersʼ demographic characteristics, health, features of their LTC occupation, additional paid work, wages, and double‐ or triple‐duty caregiving roles.

RESULTS

Most LTC workers were CNAs, followed by LPNs and RNs. Overall, more than 70% of these workers agreed or strongly agreed with this statement: “When you are sick, you still feel obligated to come into work.” One‐sixth had a second job, where they worked an average of 20 hours per week, and more than 60% held double‐ or triple‐duty caregiving roles. Additional paid work and unpaid care work characteristics did not significantly differ by occupational group, although the prevalence of second jobs was highest and accompanying work hours were longest among CNAs.

CONCLUSION

LTC workers commonly hold second jobs along with double‐ and triple‐duty caregiving roles. To slow the spread of COVID‐19, both the paid and unpaid activities of these employees warrant consideration in the identification of appropriate clinical, policy, and informal supports. J Am Geriatr Soc 68:1657‐1660, 2020.
Parenting experiences of fathers of children with autism spectrum disorder with or without intellectual disability
Authors: Rafferty D. , Tidman L. , Ekas N. V.
Published: April 2020

Background

Fathers of children with autism spectrum disorder (ASD) report more challenges than fathers of typically developing children, which also negatively impacts their psychological well‐being. Although not studied to the same extent in fathers of children with ASD, the challenges experienced by fathers of typically developing children have been shown to impact parenting behaviours. Many children with ASD also have intellectual disability (ID), which adds additional parenting stress. The purpose of this qualitative study was to examine perceptions of parenting roles and father–child relationship quality in fathers of children with ASD and ASD/ID.

Methods

Twenty‐eight fathers of children with ASD (n = 12) and ASD/ID (n = 16) completed a telephone interview. A phenomenological approach was used by two investigators to analyse the interviews. Both investigators coded the interviews and then discussed the final themes.

Results

Five major themes emerged. One theme that emerged was pre‐birth expectations, and the remaining themes related to the post‐diagnosis period: adjustments, experiences, co‐parenting and quality of father–child relationship. Both fathers of a child with ASD and ASD/ID reported on all themes.

Conclusions

Overall, fathers of children with ASD and ASD/ID reported similarly on the themes that emerged. Future research with more diverse samples is needed to continue to understand the fatherhood experience. The findings of this study have implications for the development of parent‐focused programmes that are tailored to fathers' unique experiences.
Gut microbiome-mediated modulation of hepatic cytochrome P450 and P-glycoprotein: impact of butyrate and fructo-oligosaccharide-inulin
Authors: Walsh Jacinta , Gheorghe Cassandra E , Lyte Joshua M , van de Wouw Marcel , Boehme Marcus , Dinan Timothy G , Cryan John F , Griffin Brendan T , Clarke Gerard , Hyland Niall P
Published: April 2020

Objectives

Our objective was to demonstrate microbial regulation of hepatic genes implicated in drug metabolism and transport using germ-free (GF) mice and to explore the impact of a microbial metabolite, butyrate, and a prebiotic dietary intervention on hepatic gene expression in mice.

Methods

Using reverse-transcriptase PCR, we investigated cytochrome P450 (CYP) and multidrug-resistance protein 1 (MDR1) expression in conventional, GF and colonised GF mice. To investigate the effects of butyrate, sodium butyrate (3 g/l) was administered for 21 days to conventional or GF mice. In the prebiotic study, young adult and middle-aged mice received diet enriched with 10% fructo-oligosaccharide (FOS)-inulin for 14 weeks.

Key findings

Colonisation of GF animals normalised expression of Cyp3a11 and Mdr1b to conventional levels. Butyrate upregulated Cyp2b10 in conventional mice (P < 0.05) but overall did not induce widespread changes in hepatic genes. FOS-inulin increased Cyp3a13 expression and had the opposite effect on Mdr1a expression in young adult mice (P < 0.05). Age, on the other hand, influenced the prebiotic effect on Cyp2a4 expression (P < 0.01).

Conclusion

The expression of hepatic genes implicated in drug metabolism and transport displays sensitivity to the microbiome, microbiome-derived metabolites and a microbial-targeted intervention. Our study may provide the impetus to explore microbiota-targeted interventions in normalising host metabolic activity and reducing inter-individual variability in drug pharmacokinetics.
Pharmacokinetic study of oral amitriptyline in horses
Authors: Recchi Lucciana , Alvariza Silvana , Benech Alejandro , Ruiz Natalie , José Estradé María , Suarez Gonzalo , Crosignani Nadia
Published: April 2020

The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1 mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24 hr after administration. Plasma concentrations were determined by high‐performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean maximum plasma concentration (Cmax) of amitriptyline was 30.7 ng/ml, time to maximum plasma concentration (Tmax) 1–2 hr, elimination half‐life (t1/2) 17.2 hr, area under plasma concentration–time curve (AUC) 487.4 ng ml−1 hr−1, apparent clearance (Cl/F) 2.6 L hr−1 kg−1, and apparent volume of distribution (Vd/F) 60.1 L/kg. Jugular vein sampling overestimated the amount of amitriptyline absorbed and should not be used to study uptake following oral administration. Heart rate and intestinal motility showed significant variation (p < .05). Electrocardiography did not provide conclusive results. Further studies are required to discern if multiple dose treatment would take the drug to steady state as expected, consequently increasing plasma concentrations.
Disruption of Plin5 degradation by CMA causes lipid homeostasis imbalance in NAFLD
Authors: Ma Shuo Y. , Sun Ke S. , Zhang Miao , Zhou Xia , Zheng Xiao H. , Tian Si Y. , Liu Yan S. , Chen Ling , Gao Xing , Ye Jing , Zhou Xin M. , Wang Jing B. , Han Ying
Published: April 2020

Background & Aims

The pathological hallmark of nonalcoholic fatty liver disease (NAFLD) is an imbalance in hepatic lipid homeostasis, in which lipophagy has been found to play a vital role. However, the underlying molecular mechanisms remain unclear. We investigated the role of chaperone‐mediated autophagy (CMA) in the pathogenesis of NAFLD.

Methods

CMA activity was evaluated in liver tissues from NAFLD patients and high‐fat diet (HFD)‐fed mice. Liver‐specific LAMP2A‐knockout mice and HepG2 cells lacking LAMP2A [L2A(–) cells] were used to investigate the influence of CMA on lipolysis in hepatocytes. The expression of Plin5, a lipid droplet (LD)‐related protein, was also evaluated in human and mouse liver tissues and in [L2A(–)] cells.

Results

Here, we found disrupted CMA function in the livers of NAFLD patients and animal models, displaying obvious reduction of LAMP2A and concurrent with decreased levels of CMA‐positive regulators. More LDs and higher serum triglycerides accumulated in liver‐specific LAMP2A‐knockout mice and L2A(–) cells under high‐fat challenge. Meanwhile, deleting LAMP2A hindered LD breakdown but not increased LD formation. In addition, the LD‐associated protein Plin5 is a CMA substrate, and its degradation through CMA is required for LD breakdown.

Conclusions

We propose that the disruption of CMA‐induced Plin5 degradation obstacles LD breakdown, explaining the lipid homeostasis imbalance in NAFLD.
Taxonomic novelties within a non‐monophyletic lineage: a new Mexican species of Desmopsis (Annonaceae)
Authors: Espinosa‐Jiménez Josefa Anahí , Ortiz‐Rodriguez Andres Ernesto
Published: April 2020

A new species of Annonaceae endemic to Mexico is described and illustrated. Desmopsis dubia sp. nov. is placed within the Desmopsis–Stenanona clade and is clearly different from all other species of Neotropical Miliuseae by the combination of lower surface of leaves pubescent; tertiary venation strongly percurrent; leafy bracts absent at the base of the pedicels; sepals connate at the base and persistent in fruit; petals fleshy and stiff, elliptic to ovate with food bodies at the base of the inner ones; and cylindrical monocarps with ligneous exocarp. We discuss its phylogenetic relationships and placement within the genus Desmopsis and a key to the Mexican species of Desmopsis and Stenanona with yellow or greenish petals is provided.
Three new synonyms of Rungia stolonifera (Acanthaceae) from China and Vietnam
Authors: Lin Zhe‐Li , Hai Do Van , Deng Yun‐Fei
Published: April 2020

Examination of relevant type materials and living plants has revealed that Rungia axilliflora, R. densiflora and R. evrardii are conspecific with R. stolonifera. A lectotype is designated for the name R. stolonifera. Rungia sect. Stoloniferae is thus recognised as including two species, viz. R. stolonifera and R. mina.
Viola umphangensis (Violaceae), a new species from Thailand
Authors: Nansai Sulisa , Srisanga Prachaya , Hodkinson Trevor R. , Suwanphakdee Chalermpol
Published: April 2020

Viola umphangensis S. Nansai, Srisanga & Suwanph., a new species from Thailand, is described and illustrated. Morphological, anatomical and palynological characters of V. umphangensis are compared with a similar species, V. betonicifolia Sm. An amended key to the Viola species in the Flora of Thailand account is provided.
Cypripedium subtropicum (Orchidaceae) employs aphid colony mimicry to attract hoverfly (Syrphidae) pollinators
Authors: Jiang Hong , Kong Ji‐Jun , Chen Hsin‐Chun , Xiang Zhen‐Yong , Zhang Wei‐Ping , Han Zhou‐Dong , Liao Pei‐Chun , Lee Yung‐I
Published: April 2020

In Orchidaceae, pollination is mostly animal‐mediated, and one‐third of species have evolved a deceptive pollination mechanism without rewards. Cypripedium is a representative lineage of nonrewarding orchids restricted to temperate regions. Cypripedium subtropicum flowers are pollinated by hoverflies and have hairy tufts that visually resemble an aphid colony covered with honey dew.

We recorded the behavior of hoverflies on the flowers, determined the breeding system of the species and the structure of hairy tufts, and investigated the roles of hairy tufts and floral volatiles in this specialized pollination by using pollination experiments, scanning electron microscopy, bioassays and chemical analyses.

The white hairy tufts covering the sidelobes of the labellum provide edible rewards and serve as crucial visual lures for hoverflies. The flowers emit primarily (E)‐β‐farnesene and a smaller amount of β‐pinene that were found to attract hoverflies.

Our results suggest that C. subtropicum uses both visual mimicry of an aphid‐colonized labellum with a reward and chemical mimicry of aphid alarm pheromones to attract hoverflies for pollination. This is the first described example of a rewarding mimicry system in plants, where the models are animals with their secretions and the reward is similar in nutrients to that of the model mimicked.
Modelling the consequence of glacier retreat on mixotrophic nanoflagellate bacterivory: a Bayesian approach
Authors: Schenone Luca , Balseiro Esteban G. , Bastidas Navarro Marcela , Modenutti Beatriz E.
Published: April 2020

Mixotrophic nanoflagellate bacterivory is affected by light; however, in glacially influenced lakes, glacial clay may also interfere with prey uptake. Mechanistic models based on prior quantitative hypotheses and tested with field data are useful for predicting these predator–prey interactions under a changing climate. We modelled the effect of glacial particles on the bacterivory of mixotrophic nanoflagellates, the dominant phytoplankton in mountain lakes in the North Patagonian Andes. Our model equation is based on the classical Michaelis–Menten formulation and Platt's photosynthesis–irradiance curve to account for the interference by glacial particles and the effect of light intensity, respectively. Bayesian inference was applied to estimate model parameters using data from field bacterivory experiments. Light experiments (LE) were performed in lakes with different levels of light penetration without clay particles, while clay experiments (CE) were performed with an experimental gradient of glacial clay concentration at constant light intensity. The LE showed a non‐monotonic effect of light intensity and the CE revealed an exponential negative effect of clay concentration. The obtained model was tested with two independent experiments carried out in a turbid proglacial lake. Our proposed mechanistic model successfully predicted the combined effect of light availability and particle interference on the mixotrophic nanoflagellate–bacteria relationship. The model demonstrated that the effect of light is dampened as clay concentration increases.