bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos
Authors: El Rouby Nihal , Rodrigues Marcatto Leiliane , Claudio Karla , Camargo Tavares Letícia , Steiner Heidi , Botton Marianna R. , Lubitz Steve A. , Fallon Echo N. , Yee Kevin , Kaye Justin , Scott Stuart A. , Karnes Jason , Caleb Junior de Lima Santos Paulo , Duconge Jorge , Cavallari Larisa H.
Published: August 2020

We conducted a multi‐site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from four institutions in the United States (n = 411) and Brazil (n = 663) were genotyped for VKORC1 c.‐1639G> A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test the association between warfarin dose and genotype, adjusting for clinical factors, with further testing in an independent cohort of Brazilians. In the U.S. cohort, VKORC1 and CYP2C9 variants were associated with lower warfarin dose (β = −0.29, P < 2.0 × 10−16; β = −0.21, P = 4.7 × 10−7, respectively) whereas CYP4F2 and NQO1 variants were associated with higher dose (β = 0.10, P = 2 × 10−4; β = 0.10, P = 0.01, respectively). Associations with VKORC1 (β = −0.14, P = 2.0 × 10−16), CYP2C9 (β = −0.07, P = 5.6 × 10−10), and CYP4F2 (β = 0.03, P = 3 × 10−3), but not NQO1*2 (β = 0.01, P = 0.30), were replicated in the Brazilians, explaining 43–46% of warfarin dose variability among the cohorts from the U.S. and Brazil, respectively. We identified genetic associations with warfarin dose requirements in the largest cohort of ancestrally diverse, warfarin‐treated Latinos from the United States and Brazil to date. We confirmed the association of variants in VKORC1, CYP2C9, and CYP4F2 with warfarin dose in Latinos from the United States and Brazil.
Endoscopic retrieval of a misplaced lumen‐apposing metal stent alongside a nasocystic drainage tube during endoscopic ultrasound‐guided cystogastrostomy
Authors: Yang Min Jae , Yoo Byung Moo , Kim Jin Hong
Published: August 2020

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Endoscopic retrieval device for proximally migrated pancreatic and biliary stent: Wire‐guided spiral basket catheter
Authors: Sano Takanori , Miura Shin , Masamune Atsushi
Published: August 2020

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Pseudoaneurysm of the mitral‐aortic intervalvular fibrosa following endocarditis and aortic valve surgery in an infant—Case report and exhaustive systematic review of pediatric cases
Authors: Ahmed Aziez , Shivaram Pushpa , Zakaria Dala
Published: August 2020

Pseudoaneurysm of the mitral‐aortic intervalvular fibrosa (P‐MAIVF) continues to be a rare diagnosis in children. Etiology, presentation, and management strategies are considerably different from adults. We report a fatal case of P‐MAIVF with classical transthoracic and transesophageal echocardiographic findings complemented by CT imaging. The natural course of uncomplicated/asymptomatic P‐MAIVF is largely unknown since most patients are offered surgery. We present an extensive literature review of pediatric P‐MAIVF and highlight important differences from the adult form of this disease.
Safety and feasibility of transesophageal echocardiography in patients with prior esophageal surgery
Authors: Smith Bradford B. , Rehfeldt Kent H. , Meinhardt James R. , Smith Mark M.
Published: August 2020

Background

Transesophageal echocardiography (TEE) is a specialized form of cardiac ultrasound and has been associated with rare but serious complications. In patients with prior esophageal surgery, the risk of esophageal damage or the inability to perform a comprehensive and successful TEE warrants further evaluation.

Methods

Retrospective study of patients with prior esophageal surgery who underwent TEE between June 21, 2002 and October 15, 2019. Medical and echocardiographic records were reviewed for image quality and procedural complications. Post‐procedure complications and 30‐day all‐cause mortality were collected. Evaluation by gastroenterology (GI), otolaryngology/ear, nose, throat (ENT), or thoracic surgery (TS) within 30 days of TEE was reviewed in detail.

Results

Ninety‐five patients with prior esophageal surgery underwent 145 TEEs. The most commonly performed esophageal procedures were anti‐reflux operations (89%). TEE image quality was degraded in 16% while transgastric imaging was not completed in 37% of cases. A comprehensive TEE was completed in 57% of patients with diagnostic study goals achieved in 96% of cases. Comments describing procedural difficulty were reported in 6% while comments on procedural complications occurred in 1% of cases. Post‐procedure complications occurred in 1% of patients including hypotension and unplanned hospital/ICU admission.

Conclusions

Concern for esophageal damage and the inability to perform a comprehensive and diagnostic TEE may limit the usefulness of TEE in patients with prior esophageal surgery. While TEE‐associated complications were rare in this series, a conservative approach with a thorough pre‐procedure assessment, including multi‐disciplinary evaluation when appropriate, is prudent in this complex cohort of patients.
Self‐esteem in individuals at ultra‐high risk for psychosis: A systematic review and meta‐analysis
Authors: Bemrose Holly V. , Akande Isaac O. , Cullen Alexis E.
Published: August 2020

Aim

Low self‐esteem (LSE) has been reported among individuals with psychosis and is hypothesized to act as a risk and maintenance factor for the disorder. However, the extent to which LSE also characterizes individuals deemed at ultra‐high risk (UHR) for psychosis (who present features consistent with the prodromal phase of illness), has yet to be quantified using meta‐analysis. This is important given that LSE is a potentially modifiable target for early intervention services aiming to reduce the risk of psychosis transition in this population.

Methods

We searched Medline, Embase, PsycINFO and Web of Science Core Collection for studies examining self‐esteem in UHR and healthy individuals. Random‐effects models were used to examine group differences in self‐esteem (Hedges'g) with exploratory meta‐regression analyses employed to investigate the effect of study characteristics (mean age of UHR group, the proportion of male participants in the UHR group and study quality) on standardized mean differences.

Results

Six studies were eligible for inclusion. Significant differences in self‐esteem were observed, with individuals at UHR showing reduced self‐esteem relative to healthy controls (g = −1.33 [−1.73 to −0.94] P < .001).However, there was evidence of substantial heterogeneity (I2 = 75%). Exploratory meta‐regression analyses indicated a significant effect of the mean age of the UHR group on effect sizes (B = −0.26, P = .02).

Conclusions

UHR youth present with lower levels of self‐esteem than healthy individuals, a difference that appears to be more pronounced with advancing age. We discuss clinical implications and provide recommendations for future studies.
Integrating quality improvement into the ECHO model to improve care for children and youth with epilepsy
Authors: Joshi Sucheta , Gali Kari , Radecki Linda , Shah Amy , Hueneke Sarah , Calabrese Trisha , Katzenbach Alexis , Sachdeva Ramesh , Brown Lawrence , Kimball Eve , White Patience , McManus Peggy , Wood David , Nelson Eve‐Lynn , Archuleta Pattie
Published: August 2020

Objective

Project ECHO (Extension for Community Healthcare Outcomes), a telementoring program, utilizes lectures, case‐based learning, and an “all teach–all learn” approach to increase primary care provider (PCP) knowledge/confidence in managing chronic health conditions. The American Academy of Pediatrics (AAP) Epilepsy and Comorbidities ECHO incorporated quality improvement (QI) methodology to create meaningful practice change, while increasing PCP knowledge/self‐efficacy in epilepsy management using the ECHO model.

Methods

Monthly ECHO sessions (May 2018 to December 2018) included lectures, case presentations/discussion, and QI review. Pediatric practices were recruited through the AAP. Practices engaged in ECHO sessions and improvement activities including monthly Plan‐Do‐Study‐Act cycles, team huddles, chart reviews, and QI coaching calls to facilitate practice change. They were provided resource toolkits with documentation templates, safety handouts, and medication side effects sheets. QI measures were selected from the American Academy of Neurology Measurement Set for Epilepsy. The AAP Quality Improvement Data Aggregator was used for data entry, run chart development, and tracking outcomes. Participants completed retrospective surveys to assess changes in knowledge and self‐efficacy.

Results

Seven practices participated across five states. Average session attendance was 14 health professionals (range = 13‐17). A total of 479 chart reviews demonstrated improvement in six of seven measures: health care transition (45.3%, P = .005), safety education (41.6%, P = .036), mental/behavioral health screening (32.2% P = .027), tertiary center referral (26.7%, not significant [n.s.]), antiseizure therapy side effects (23%, n.s.), and documenting seizure frequency (7.1%, n.s.); counseling for women of childbearing age decreased by 7.8%.

Significance

This project demonstrated that integrating QI into an ECHO model results in practice change and increases PCP knowledge/confidence/self‐efficacy in managing epilepsy.
De novo hepatocellular carcinoma in living donor liver grafts: A Japanese multicenter experience
Authors: Goto Ryoichi , Kosai‐Fujimoto Yukiko , Yagi Shintaro , Kobayashi Tsuyoshi , Akamatsu Nobuhisa , Shimamura Tsuyoshi , Imura Satoru , Ogiso Satoshi , Mizuno Shugo , Takatsuki Mitsuhisa , Fukuhara Takasuke , Kanto Tatsuya , Eguchi Susumu , Yanaga Katsuhiko , Ogura Yasuhiro , Fukumoto Takumi , Shimada Mitsuo , Hasegawa Kiyoshi , Ohdan Hideki , Uemoto Shinji , Soejima Yuji , Ikegami Toru , Yoshizumi Tomoharu , Taketomi Akinobu , Maehara Yoshihiko
Published: August 2020

Aim

Direct‐acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post‐living donor liver transplantation (LDLT).

Methods

We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post‐LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan.

Results

Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4–15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus‐related cirrhosis, of which two were treated with direct‐acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody‐positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19–463] days).

Conclusion

Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody‐positive grafts, should be carefully followed by surveillance of the liver graft.
The subduction of thePaleo‐PacificPlate to the Jiamusi Block: Evidence from the Early Mesozoic sedimentary rocks of the eastern Jiamusi Block
Authors: Xu Zhongjie , Kong Jintao , Cheng Rihui , Zhou Jianbo
Published: August 2020

In order to provide references of the subduction process of the Paleo‐Pacific Plate beneath the Jiamusi Block, this paper studied the clastic rocks of the Nanshuangyashan Formation using modal analysis of sandstones, mudstone elements geochemistry, and detrital zircon U–Pb dating. These results suggest the maximum depositional age of the Nanshuangyashan Formation was between the Norian and Rhaetian (206.8 ±4.6 Ma, mean standard weighted deviation (MSWD) = 0.17). Whole‐rock geochemistry of mudstone indicates that source rocks of the Nanshuangyashan Formation were primarily felsic igneous rocks and quartzose sedimentary rocks, which were mainly derived from the stable continental block and a magmatic arc. Detrital zircon analysis showed the Nanshuangyashan Formation samples recorded four main age groups: 229–204 Ma, 284–254 Ma, 524–489 Ma and 930–885 Ma, and the provenances were attributed to the Jiamusi Block and a Late Triassic magmatic arc near the study area. Furthermore, the eastern Jiamusi Block was a backarc basin, affected by the subduction of the Paleo‐Pacific Plate in the Late Triassic, but the magmatic arc related to the subduction near the study area finally died out due to tectonic changes and stratigraphic erosion.
A green composite material of calcium phosphate cement matrix with additions of car tire waste particles
Authors: Revelo Carlos F. , Colorado Henry A.
Published: August 2020

The car tire waste have a tremendous adverse environmental impact in nature due to the large volumes generated worldwide, which requires multiple solutions that decrease as much as possible the tires disposed in landfills. Therefore, this research proposes to use part of the unused tire waste in a construction material, phosphate cement with ground rubber waste particles. For that, up to 12wt% of tire waste has been incorporated to cement. The samples characterization was conducted with scanning electron microscope; X‐ray diffraction; compressive strength; thermal stability at 50 and 100°C; density; and Weibull statistics. Results show that this composite can be used as a building material therefore as an environmental solution for the rubber tire waste, mainly in applications requiring similar compressive strengths than concrete with ordinary Portland cement. Weibull statistics showed compression strength changing from 2.85 to 38.29 MPa, which is typical in construction materials and also it enables it to be used as building material. Density of samples was between 1.0 and 1.6 g/cm3, which open up applications for precast panels or other lightweight solutions.
Isotretinoin in the management of acne vulgaris: practical prescribing
Authors: Fallah Haady , Rademaker Marius
Published: August 2020

Since it was first approved for use in 1982, isotretinoin has revolutionized the management of acne vulgaris. Despite almost four decades of widespread use, uncertainty still exists regarding the manner in which it is best prescribed. In this review, we provide an update on the pharmacokinetics, mechanism of action, contraindications, interactions, and appropriate dosing schedule of isotretinoin in the treatment of acne. We also discuss the safety of performing concurrent dermatological procedures in patients taking isotretinoin.
Why Buy Local?
Authors: Ferguson Benjamin , Thompson Christopher
Published: August 2020

This article critically assesses the moral arguments that speak in favour of three consumer options: buying local food, buying global (non‐local) food, and buying global food while also purchasing carbon offsets to mitigate the environmental impact of food transportation. We argue that because the offsetting option allows one to provide economic benefits to the poorest food workers while also mitigating the environmental impact of food transportation it is morally superior to the alternatives.
IKKε and TBK1 in diffuse large B‐cell lymphoma: A possible mechanism of action of an IKKε/TBK1 inhibitor to repress NF‐κB and IL‐10 signalling
Authors: Carr Matthew , Mamand Sami , Chapman Kathryn L. , Perrior Trevor , Wagner Simon D.
Published: August 2020

The IKK‐related kinases, IKKε and TBK1, have essential roles in innate immunity in part through modifying MYD88 signalling from the Toll‐like receptors to regulate NF‐κB signalling. We investigated the expression and function of IKKε and TBK1, in diffuse large B‐cell lymphoma (DLBCL). DLBCL cell lines and patient‐derived xenografts were used to determine their sensitivity to IKKε and TBK1 inhibitors. To understand the function of IKKε and TBK1 secreted factors were determined following administration of inhibitors. Gene expression microarrays were used to determine the transcriptional effects of inhibitors. Higher TBK1 mRNA levels associated with poorer clinical outcome but IKKε and TBK1 were expressed in both germinal centre and non‐germinal centre types of DLBCL. Survival of cell lines Ly10, Ly03 and Pfeiffer, and of some primary human lymphoma cells, was suppressed by a small molecule IKKε/TBK1 inhibitor, DMX3433. DMX3433 reduced IL‐10 production from Ly10 and repressed NF‐κB mediated transcription. Inhibition of IKKε and TBK1 warrants further investigation as a potential therapeutic route to suppress NF‐κB signalling in lymphoma.
Mesenchymal stem cells‐derived exosomes ameliorate intervertebral disc degeneration through inhibiting pyroptosis
Authors: Zhang Jingwei , Zhang Jieyuan , Zhang Yunlong , Liu Wenjun , Ni Weifeng , Huang Xiaoyan , Yuan Junjie , Zhao Bizeng , Xiao Haijun , Xue Feng
Published: August 2020

Mesenchymal stem cell (MSCs)‐based therapies have shown a promised result for intervertebral disc degeneration (IVDD) treatment. However, its molecular mechanisms remain unclear. Exosomes involve cell‐cell communication via transference of its contents among different cells, and the present potential effect on cell death regulation. This study aimed to investigate the role of MSCs‐derived exosomes on IVDD formation. Here, we first found the NLRP3‐mediated nucleus pulposus cell (NP cell) pyroptosis was activated in the IVDD mice model and lipopolysaccharide (LPS)‐induced model. However, MSCs treatment could inhibit NP cell pyroptosis in vitro. We then isolated MSCs‐derived exosomes by differential centrifugation and identified the characteristics. Secondly, we investigated the function of MSCs‐derived exosomes on LPS‐induced NP cell pyroptosis. Finally, we presented evidence that MSCs‐derived exosomal miR‐410 was a crucial regulator of pyroptosis. Results showed that MSCs‐derived exosomes play an anti‐pyroptosis role by suppressing the NLRP3 pathway. Moreover, it suggested that this effect was attributed to miR‐410, which was derived from MSCs‐exosomes and could directly bind to NLRP3mRNA. In conclusion, for the first time, we demonstrated that MSCs‐exosome treatment may inhibit pyroptosis and could be a promising therapeutic strategy for IVDD.
Classifying childhood war trauma exposure: latent profile analyses of Sierra Leone’s former child soldiers
Authors: Su Shaobing , Frounfelker Rochelle L. , Desrosiers Alethea , Brennan Robert T. , Farrar Jordan , Betancourt Theresa S.
Published: August 2020

Background

Former child soldiers are at elevated risk for mental health problems (e.g., traumatic stress, emotion dysregulation, and internalizing and externalizing problems). To examine which groups of former child soldiers are more likely to have difficulties with emotion regulation, interpersonal relationships, and mental health postconflict, we explored patterns of war trauma exposure and their effects on subsequent mental health problems among former child soldiers in Sierra Leone.

Methods

Participants were 415 (23.86% female) Sierra Leonean former child soldiers participating in a 15‐year, four‐wave longitudinal study. At T1 (2002), 282 former child soldiers (aged 10–17) were recruited. T2 (2004) included 186 participants from T1 and an additional cohort of self‐reintegrated former child soldiers (NT2 = 132). T3 (2008) and T4 (2016/2017) participants were youth enrolled in previous waves (NT3 = 315; NT4 = 364). Latent profile analysis (LPA) was used to classify participants based on the first‐time reports of eight forms of war exposure (separation and loss of assets, parental loss, loss of loved ones, witnessing violence, victimization, perpetrating violence, noncombat activities, and deprivation). ANOVA examined whether patterns of war exposure were associated with sociodemographic characteristics and mental health outcomes between T1 and T4.

Results

LPA identified two profiles: higher exposure versus lower exposure, using cumulative scores of eight forms of war‐related trauma exposure. The ‘higher war exposure’ group comprised 226 (54.5%) former child soldiers and the ‘lower war exposure’ group included 189 (45.5%). Significantly higher levels of violence‐related and combat experiences characterized the group exposed to more traumatic events. The ‘higher war exposure’ group reported more PTSD symptoms at T2, more hyperarousal symptoms across all waves, and more difficulties in emotion regulation at T4.

Conclusions

Former child soldiers exposed to higher levels of war‐related traumatic events and loss should be prioritized for mental health services immediately postconflict and as they transition into adulthood.
Does timing of implant placement affect esthetic results in single‐tooth implants? A cohort evaluation based on mPES
Authors: Ghahroudi Amir A. R. , Rokn Amir R. , Shamshiri Ahmad R. , Samiei Nazanin
Published: August 2020

Objective

This study sought to use the mPES to assess various maxillary implant surgical results and placement timing in the esthetic zone.

Materials and methods

This cohort study was conducted on 146 patients undergoing immediate, early, and late implantation. They received maxillary single‐tooth implants in the anterior region during the past 5 years. Patients were clinically examined to determine their mPES and patient−/implant‐related parameters. Simple and multiple nominal regression analyses were applied to show how such parameters correlated with mPES.

Results

The results were found to be in three categories namely the most clinically excellent, acceptable, and unacceptable. Although the most frequent clinically excellent results were noted in the late implantation (late 49.0%, early 25.6%, immediate 24.1%); early implantation was the group with the least frequent clinically unacceptable results (late 16.3%, early 4.7%, immediate 14.8%). The mean width of keratinized tissue was significantly more in patients with clinically excellent results (P‐value = 0.01).

Conclusion

Within the limitations of this study, the author(s) drew the following conclusions: (a) the late implant placement was more likely to be reliable and esthetically acceptable, (b) early implant placement remained the safest method to prevent unaesthetic appearance, and (c) Width of keratinized gingiva (≥3 mm) was a significant factor to achieve implant esthetic results.

Clinical significance

Maxillary single‐tooth implants in the anterior region often have optimal osseointegration and functional performance, but esthetic plays a significant role in the success of these implants. So the aim of the present study was to employ mPES to assess the effect of placement timing and other patient and implant‐related variables on esthetic outcomes.
Serious Falls in Middle‐Aged Veterans: Development and Validation of a Predictive Risk Model
Authors: Womack Julie A. , Murphy Terrence E. , Bathulapalli Harini , Smith Alexandria , Bates Jonathan , Jarad Samah , Redeker Nancy S. , Luther Stephen L. , Gill Thomas M. , Brandt Cynthia A. , Justice Amy C.
Published: August 2020

BACKGROUND/OBJECTIVES

Due to high rates of multimorbidity, polypharmacy, and hazardous alcohol and opioid use, middle‐aged Veterans are at risk for serious falls (those prompting a visit with a healthcare provider), posing significant risk to their forthcoming geriatric health and quality of life. We developed and validated a predictive model of the 6‐month risk of serious falls among middle‐aged Veterans.

DESIGN

Cohort study.

SETTING

Veterans Health Administration (VA).

PARTICIPANTS

Veterans, aged 45 to 65 years, who presented for care within the VA between 2012 and 2015 (N = 275,940).

EXPOSURES

The exposures of primary interest were substance use (including alcohol and prescription opioid use), multimorbidity, and polypharmacy. Hazardous alcohol use was defined as an Alcohol Use Disorders Identification Test ‐ Consumption (AUDIT‐C) score of 3 or greater for women and 4 or greater for men. We used International Classification of Diseases, Ninth Revision (ICD‐9), codes to identify alcohol and illicit substance use disorders and identified prescription opioid use from pharmacy fill‐refill data. We included counts of chronic medications and of physical and mental health comorbidities.

MEASUREMENTS

We identified serious falls using external cause of injury codes and a machine‐learning algorithm that identified serious falls in radiology reports. We used multivariable logistic regression with general estimating equations to calculate risk. We used an integrated predictiveness curve to identify intervention thresholds.

RESULTS

Most of our sample (54%) was aged 60 years or younger. Duration of follow‐up was up to 4 years. Veterans who fell were more likely to be female (11% vs 7%) and White (72% vs 68%). They experienced 43,641 serious falls during follow‐up. We identified 16 key predictors of serious falls and five interaction terms. Model performance was enhanced by addition of opioid use, as evidenced by overall category‐free net reclassification improvement of 0.32 (P < .001). Discrimination (C‐statistic = 0.76) and calibration were excellent for both development and validation data sets.

CONCLUSION

We developed and internally validated a model to predict 6‐month risk of serious falls among middle‐aged Veterans with excellent discrimination and calibration.
Syntaxin 1B regulates synaptic GABA release and extracellular GABA concentration, and is associated with temperature‐dependent seizures
Authors: Mishima Tatsuya , Fujiwara Tomonori , Kofuji Takefumi , Saito Ayako , Terao Yasuo , Akagawa Kimio
Published: August 2020

De novo heterozygous mutations in the STX1B gene, encoding syntaxin 1B, cause a familial, fever‐associated epilepsy syndrome. Syntaxin 1B is an essential component of the pre‐synaptic neurotransmitter release machinery as a soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor protein that regulates the exocytosis of synaptic vesicles. It is also involved in regulating the functions of the SLC6 family of neurotransmitter transporters that reuptake neurotransmitters, including inhibitory neurotransmitters, such as γ‐aminobutyric acid (GABA) and glycine. The purpose of the present study was to elucidate the molecular mechanisms underlying the development of febrile seizures by examining the effects of syntaxin 1B haploinsufficiency on inhibitory synaptic transmission during hyperthermia in a mouse model. Stx1b gene heterozygous knockout (Stx1b+/−) mice showed increased susceptibility to febrile seizures and drug‐induced seizures. In cultured hippocampal neurons, we examined the temperature‐dependent properties of neurotransmitter release and reuptake by GABA transporter‐1 (GAT‐1) at GABAergic neurons using whole‐cell patch‐clamp recordings. The rate of spontaneous quantal GABA release was reduced in Stx1b+/− mice. The hyperthermic temperature increased the tonic GABAA current in wild‐type (WT) synapses, but not in Stx1b+/− synapses. In WT neurons, recurrent bursting activities were reduced in a GABA‐dependent manner at hyperthermic temperature; however, this was abolished in Stx1b+/− neurons. The blockade of GAT‐1 increased the tonic GABAA current and suppressed recurrent bursting activities in Stx1b+/− neurons at the hyperthermic temperature. These data suggest that functional abnormalities associated with GABA release and reuptake in the pre‐synaptic terminals of GABAergic neurons may increase the excitability of the neural circuit with hyperthermia.

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Acute effects of fatty acids on autophagy in NPY neurones
Authors: Reginato Andressa , Siqueira Beatriz Piatezzi , Miyamoto Josiane Érica , Portovedo Mariana , Costa Suleyma de Oliveira , de Fante Thaís , Rodrigues Hosana Gomes , Ignácio‐Souza Letícia Martins , Torsoni Márcio Alberto , Torsoni Adriana Souza , Le Stunff Hervé , Belsham Denise D. , Milanski Marciane
Published: August 2020

High‐fat diet (HFD) feeding is deleterious to hypothalamic tissue, leading to inflammation and lipotoxicity, as well as contributing to central insulin resistance. Autophagy is a process that restores cellular homeostasis by degrading malfunctioning organelles and proteins. Chronic HFD‐feeding down‐regulates hypothalamic autophagy. However, the effects of short‐term HFD‐feeding and the saturated fatty acid palmitate (PA) on hypothalamic autophagy and in neurones that express neuropeptide Y (NPY) and agouti‐related peptide remains unknown. Therefore, we assessed hypothalamic autophagy after 1 and 3 days of HFD‐feeding. We also injected PA i.c.v and analysed the modulation of autophagy in hypothalamic tissue. Both interventions resulted in changes in autophagy‐related gene profiles without significant differences in protein content of p62 and LC3B‐II, markers of the autophagy pathway. When we assessed native NPY neurones in brain slices from PA‐treated animals, we observed increased levels of Atg7 and LC3B protein in response to PA treatment, indicating the induction of autophagy. We then tested the direct effects of fatty acids using the immortalised hypothalamic NPY‐expressing neuronal cell model mHypoE‐46. We found that PA, but not palmitoleate (PO) (a monounsaturated fatty acid), was able to induce autophagy. Co‐treatment with PA and PO was able to block the PA‐mediated induction of autophagy, as assessed by flow cytometry. When the de novo ceramide synthesis pathway was blocked with myriocin pre‐treatment, we observed a decrease in PA‐mediated induction of autophagy, although there was no change with the toll‐like receptor 4 inhibitor, TAK‐242. Taken together, these findings provide evidence that saturated and unsaturated fatty acids can differentially regulate hypothalamic autophagy and that ceramide synthesis may be an important mediator of those effects. Understanding the mechanisms by which dietary fats affect autophagy in neurones involved in the control of energy homeostasis will provide potential new pathways for targeting and containing the obesity epidemic.
A short review of alternative ingredients and technologies of inorganic UV filters
Authors: Nery Érika Minuci , Martinez Renata Miliani , Velasco Maria Valéria Robles , Baby André Rolim
Published: August 2020

Background

The growing need to use sunscreens is a concrete reality, and it is associated with the increase in the population's awareness of the ultraviolet (UV) radiation damage. Inorganic UV filters promote the formation of particles/pigments film over the skin surface, reflecting, dispersing, and absorbing the radiation. Investigations of this class of filters demonstrate the emergence of alternative ingredients and new technologies.

Aims and Methods

In this review, we presented potential candidates for alternative UV inorganic filters, such as hydroxyapatite, cerium dioxide, and hydrotalcite.

Results

Specialized literature identified hydroxyapatite and cerium dioxide as actives with good performances, with a broad spectrum of absorption against UV radiation. Both of them were considered safe against degradation and skin erythema formation. Inorganic compounds as an alternative to circumvent degradation problems of organic UV filters containing PABA were also analyzed, with hydrotalcite having a good performance in improving the performance of classic ingredients, bypassing photoinstability, and improving safety, in addition to preventing skin irritability.

Conclusion

Further investigations of these ingredients and interactions with sunscreen formulations are necessary to overall explore their safety and efficacy, encouraging future researches for more inorganic UV filters.
Describing objectively measured intensive care nurses’ physical work activity behavioural patterns during a 12‐hr shift
Authors: Yu Fiona , Narayanan Anantha , Mackay Lisa , Ward Kim , King Anna , Smith Melody
Published: August 2020

Aim and objectives

To describe intensive care unit (ICU) nurses’ physical work activity behavioural patterns over 12 hr using dual accelerometry, following a job demands–recovery framework.

Background

Limited studies utilised accelerometry to objectively analyse nurses’ physical workloads. Little is known about intensive care nurses’ physical activity patterns during a 12‐hr shift.

Design

A cross‐sectional study was conducted with intensive care nurses from four units in Auckland, New Zealand.

Methods

Each participant wore two Axivity AX3 accelerometers to measure physical activity during a 12‐hr day or night shift. An online survey captured participants’ demographic information. R software (version 3.6.1) and SPSS version 26 were utilised for data analysis. The STROBE was followed.

Results

A total of 102 nurses were included in this study. A high level of light intensity activity behaviours (standing, dynamic standing, walking) was observed throughout the day shifts, with no higher intensity behaviours identified. Activity levels were highest at the beginning of shifts and followed a consistent pattern, with an additional peak around midday for day shifts and at the end of the shift for night shifts. Observable differences were seen between day and night shifts with a greater prevalence of sitting and lying during night shifts. Standing, dynamic standing, sitting, lying and walking were significant factors in the differences of the physical work behaviours between the day shift nurses and the night shift nurses. Significant differences in dynamic standing and lying were found between ICUs.

Conclusions

Intensive care nurses’ physical work activity involved a large amount of standing and dynamic standing during a 12‐hr shift. The overall physical workload during a 12‐hr day shift was significantly higher than that during a 12‐hr night shift.

Relevance to clinical practice

Results may help managers attain a better understanding of nurses’ physical workloads during a 12‐hr shift.
The Clinical Contribution of Neurovascular Ultrasonography in Acute Ischemic Stroke
Authors: Gomez Jonathan R. , Hobbs Kyle S. , Johnson Leilani L. , Vu Quang D. , Bennett John , Tegeler Charles , Wolfe Stacey Q. , Sarwal Aarti
Published: August 2020

BACKGROUND AND PURPOSE

Patients with acute ischemic stroke receive computed tomography angiogram (CTA) and digital subtraction angiogram (DSA) for clinical evaluation. Current guidelines lack in defining indications for transcranial Doppler (TCD) and/or carotid duplex ultrasonography (CUS) in acute stroke evaluation or follow‐up cerebrovascular imaging after reperfusion. We investigated the clinical utility of performing additional TCD/CUS after reperfusion in guiding postacute care stroke management.

METHODS

Retrospective review of acute ischemic stroke patients admitted to a comprehensive stroke center with CTA head and neck and/or DSA followed by TCD/CUS. Cases were reviewed by two authors to determine if TCD/CUS provided additional diagnostic information to aid management. A nominal group process, using a third author, achieved consensus in cases of disagreements.

RESULTS

Only 25 of 198 patients had CTA or DSA followed by TCD/CUS. Ten (40%) cases showed new clinical information from CUS aiding management. Of those with TCD, 5 patients (22.7%) had findings that impacted management. These clinical scenarios included detection of mobile thrombus requiring anticoagulation; distinguishing carotid near‐occlusion from occlusion; confirming hemodynamic significance of intra/extracranial stenosis helping emergent stenting/endarterectomy; detecting hyperperfusion on TCDs causing symptoms; and establishing chronicity of carotid stenosis based on collateral flow patterns, which deferred further intervention.

DISCUSSION

Our experience shows that TCD/CUS may offer additional diagnostic information assisting postacute care management in small subset of patients with acute ischemic stroke. Larger studies are needed to research the clinical impact and cost‐effectiveness of additional imaging and inform clinical guidelines for selecting patients who will benefit from these additional studies.
Early lactate measurements for predictingin‐hospitalmortality in paediatric sepsis
Authors: Jaiswal Priyanka , Dewan Pooja , Gomber Sunil , Banerjee Basu Dev , Kotru Mrinalini , Malhotra Rajeev Kumar , Tyagi Vipin
Published: August 2020

Aim

We compared the performance of plasma lactate with high‐sensitivity C‐reactive protein (hs‐CRP), and paediatric sepsis‐related organ failure assessment (pSOFA) score for predicting mortality in septic children.

Methods

Serial plasma lactate and hs‐CRP levels and pSOFA score was assessed during early hospital stay in septic children.

Results

Out of 149 participants, 45 died. Plasma lactate at 0 h and 6 h was significantly higher, and lactate clearance was significantly lower in non‐survivors. The optimal cut‐off of plasma lactate at 6h for identifying mortality was 2.5 mmol/L (sensitivity 85% and specificity 74%). pSOFA score had the best predictive ability for mortality (AUC 0.89) followed by hs‐CRP at 0 h (AUC 0.86), hs‐CRP at 48 h (AUC 0.83), plasma lactate levels at 6 h (AUC 0.83), and plasma lactate at 0 h (AUC 0.67).

Conclusion

pSOFA score, hs‐CRP and hyperlactemia at 6 h can identify septic children at risk of dying.
Psychologically informed physiotherapy as part of a multidisciplinary rehabilitation program for children and adolescents with functional neurological disorder: Physical and mental health outcomes
Authors: Kasia Kozlowska , Nicola Gray , Stephen Scher , Blanche Savage
Published: August 2020

Aim

Children and adolescents with functional neurological disorder (FND) present with physical impairment and mental health comorbidities. Specialist physiotherapy programs for treating FND have been developed over the last two decades. This article reports outcome data from three cohorts of children treated with a multidisciplinary rehabilitation intervention – the Mind–Body Program – in which a psychologically informed physiotherapy intervention, known as the wellness approach to physiotherapy, was a key component.

Methods

For three cohorts of children (n = 57, n = 60 and n = 25, respectively) treated in the Mind–Body Program, data about functional impairment and mental health concerns were collected at presentation and at follow‐up (4 years, 12 months and 18 months, respectively).

Results

Outcome data show that FND symptoms resolved in 54/57 (95%), 51/60 (85%) and 22/25 (88%) of children in the three cohorts, and that 31/57 (61%), 32/60 (53%) and 13/25 (52%) of children returned to full health and to full‐time school attendance. Changes in Global Assessment of Function (GAF) were significant (t(54) = 21.60, P < 0.001; t(55) = 9.92, P < 0.001; t(24) = 6.51, P < 0.001). Outcomes were less favourable for children with chronic FND symptoms at presentation; those whose comorbid mental health disorders or other (comorbid) functional somatic symptoms did not resolve; and those who subsequently developed chronic mental health problems.

Conclusions

Implementation of a multidisciplinary rehabilitation intervention – with psychologically informed physiotherapy as one of the key treatment components – resulted in resolution of FND symptoms and return to health and well‐being in the large majority of patients.
Organisation, Emergence and Cambridge Social Ontology
Authors: Slade‐Caffarel Yannick
Published: August 2020

John Searle has mistakenly claimed that emergence is the central concept in the account of social ontology defended by Tony Lawson, the central figure in the project now regularly referred to as Cambridge Social Ontology. This is not the case. Rather, if any concept can be considered central for Lawson, it is organisation. In this paper, I explain how Searle could misunderstand Lawson and, in doing so, I bring out the importance of organisation for understanding how phenomena, both social and non‐social, are constituted.
Improved quality of life following direct‐acting antiviral treatment for chronic hepatitis C infection in Rwanda: Results from a clinical trial in sub‐Saharan Africa (the SHARED study)
Authors: Van Nuil Jennifer Ilo , Umutesi Grace , Shumbusho Fabienne , Kateera Frederick , Dushimimana Jean de Dieu , Muvunyi Claude Mambo , Musabeyezu Emmanuel , Mukabatsinda Constance , Ntirenganya Cyprien , Kabahizi Jules , Serumondo Janvier , Makuza Jean Damascene , Nsanzimana Sabin , Grant Philip , Gupta Neil
Published: August 2020

Around 71 million people are living with chronic hepatitis C virus (HCV) infection, with approximately 14% residing in sub‐Saharan Africa. Direct‐acting antiviral (DAA) therapies offer clear benefits for liver‐related morbidity and mortality, and data from high‐income settings suggest that DAA treatments also provide significant benefits in terms of health‐related quality of life (HRQL). In this study, we assessed the effect of DAA treatment on HRQL for individuals treated for HCV in a clinical trial in Rwanda. We assessed the HRQL of participants using an 83‐question composite survey at Day 0 (‘baseline’) and Week 24 (‘endpoint’). Data were analysed in R. A total of 296 participants were included in this analysis. Their ages ranged from 19 to 90, and 184 (62.2%) were female. There were significant improvements from baseline to endpoint median scores for all physical and mental quality of life sub‐scales. Additionally, a reduction—before and after treatment—in the proportion of those classified as depressed and needing social support was statistically significant (both P < .001). Economic productivity increased after treatment (P < .001), and households classified as food secure increased from baseline to endpoint (P < .001). These results demonstrate that Rwandans with chronic HCV infection experience both clinical and HRQL benefits, including household‐level benefits like substantial gains in workforce stability, economic productivity, and poverty alleviation, from DAA treatment. A stronger demonstration of accurate and broader household‐level benefits achieved through treatment of HCV with DAAs will help financing and investment for HCV in resource‐constrained settings become an urgent priority.
The association of sex steroid hormone concentrations with non‐alcoholic fatty liver disease and liver enzymes in US men
Authors: Phan Hong , Richard Aline , Lazo Mariana , Nelson William G. , Denmeade Samuel R. , Groopman John , Kanarek Norma , Platz Elizabeth A. , Rohrmann Sabine
Published: August 2020

Background & Aims

This study aimed to analyse the association of sex hormone levels with liver enzyme levels and non‐alcoholic fatty liver disease (NAFLD) in a nationally representative sample of men.

Methods

A total of 919 men from the US National Health and Nutrition Examination Study (NHANES) III were included in this cross‐sectional analysis of data from 1988 to 1991. We used existing data on serum total and free testosterone, total and free estradiol, androstanediol glucuronide (AAG) and sex steroid‐binding globulin (SHBG), and estimated their associations with aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and NAFLD, as determined using ultrasound, after adjusting for possible confounders including age, race, smoking, alcohol, physical activity, waist circumference and steroid hormones.

Results

Lower total testosterone (TT) and higher free estradiol were associated with higher odds of NAFLD after adjusting for confounders including the other sex hormones. Lower TT was associated with higher odds of elevated AST, but not ALT. Free testosterone, total estradiol, SHBG and AAG were not associated with NAFLD or liver enzymes.

Conclusions

This study supports an inverse association between TT concentration and NAFLD in men independent of other sex hormones (SHBG, AAG and estradiol) and known risk factors, such as obesity, age and lifestyle. Exploration of whether TT might be a non‐invasive marker for NAFLD diagnosis is warranted.
Global gene expression patterns in Porites white patch syndrome: Disentangling symbiont loss from the thermal stress response in reef‐building coral
Authors: Kenkel Carly D. , Mocellin Veronique J. L. , Bay Line K.
Published: August 2020

The mechanisms resulting in the breakdown of the coral symbiosis once the process of bleaching has been initiated remain unclear. Distinguishing the process of symbiont loss from the thermal stress response may shed light on the cellular and molecular pathways involved in each process. This study examined physiological changes and global gene expression patterns associated with white patch syndrome (WPS) in Porites lobata, which manifests in localized bleaching independent of thermal stress. In addition, a meta‐analysis of global gene expression studies in other corals and anemones was used to contrast differential regulation as a result of disease and thermal stress from patterns correlated with symbiotic state. Symbiont density, chlorophyll a content, holobiont productivity, instant calcification rate, and total host protein content were uniformly reduced in WPS relative to healthy tissue. While expression patterns associated with WPS were secondary to fixed effects of source colony, specific functional enrichments combined with a lack of immune regulation suggest that the viral infection putatively giving rise to this condition affects symbiont rather than host cells. Expression in response to WPS also clustered independently of patterns in white syndrome impacted A. hyacinthus, further supporting a distinct aetiology of this syndrome. Expression patterns in WPS‐affected tissues were significantly correlated with prior studies that examined short‐term thermal stress responses independent of symbiotic state, suggesting that the majority of expression changes reflect a nonspecific stress response. Across studies, the magnitude and direction of expression change among particular functional enrichments suggests unique responses to stressor duration and highlights distinct responses to bleaching in an anemone model.
Genomic architecture of gapeworm resistance in a natural bird population
Authors: Ruiz‐López María José
Published: August 2020

Parasites are recognized to be some of the strongest agents of natural selection, sometimes causing major changes in the phenotypes of their hosts. Understanding the genomic determinants leading to these adaptive processes is key to understand host–parasite interactions. However, dissecting the genetic architecture of host resistance in natural systems is difficult because of the multiple factors affecting these complex traits in the wild. In this issue of Molecular Ecology, Lundregan et al. (2020) use an impressive long‐term data set to analyse the genomic architecture of host resistance to gapeworm in a metapopulation of house sparrows. The authors elegantly combine different approaches (variance component analyses, genome partitioning and genome‐wide associations) to reveal that resistance to gapeworm is under polygenic control and can have both a significant additive genetic and dominance variance. This study is one of the first to simultaneously determine genomic architecture and assess additive genetic and dominance genetic variance in parasite resistance in natural populations.