bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for acute kidney injury at presentation among children with CNS malaria: a case control study
Authors: Tembo Derby , Mwanza Suzanna , Mwaba Chisambo , Dallah Ifunanya , wa Somwe Somwe , Seydel Karl B. , Birbeck Gretchen L.
Published: November 2022

Background

Recent research has established that acute kidney injury (AKI) is a common problem in severe paediatric malaria. Limited access to kidney diagnostic studies in the low resources settings where malaria is common has constrained research on this important problem.

Methods

Enrolment data from an ongoing clinical trial of antipyretics in children with central nervous system (CNS) malaria, CNS malaria being malaria with seizures or coma, was used to identify risk factors for AKI at presentation. Children 2–11 years old with CNS malaria underwent screening and enrollment assessments which included demographic and anthropomorphic data, clinical details regarding the acute illness, and laboratory studies including creatinine (Cr), quantitative parasite count (qPC), quantitative histidine rich protein 2 (HRP2), lactate, and bilirubin levels. Children with a screening Cr > 106 µmol/l were excluded from the study due to the potential nephrotoxic effects of the study drug. To identify risk factors for AKI at the time of admission, children who were enrolled in the study were categorized as having AKI using estimates of their baseline (i.e. before this acute illness) kidney function and creatinine at enrollment applying the Kidney Disease: Improving Global Outcome (KDIGO) 2012 guidelines. Logistic regressions and a multivariate model were used to identify clinical and demographic risk factors for AKI at presentation among those children enrolled in the study.

Results

465 children were screened, 377 were age-appropriate with CNS malaria, 22 (5.8%) were excluded due to Cr > 106 µmol/l, and 209 were enrolled. Among the 209, AKI using KDIGO criteria was observed in 134 (64.1%). One child required dialysis during recovery. Risk factors for AKI in both the logistic regression and multivariate models included: hyperpyrexia (OR 3.36; 95% CI 1.39–8.12) and age with older children being less likely to have AKI (OR 0.72; 95% CI 0.62–0.84).

Conclusion

AKI is extremely common among children presenting with CNS malaria. Hyperpyrexia with associated dehydration may contribute to the AKI or may simply be a marker for a more inflammatory systemic response that is also affecting the kidney. Appropriate fluid management in children with CNS malaria and AKI may be challenging since generous hydration to support kidney recovery could worsen malaria-induced cerebral oedema in this critically ill population.

Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03399318
Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer
Authors: Han Qing-Fang , Li Wen-Jia , Hu Kai-Shun , Gao Jie , Zhai Wen-Long , Yang Jing-Hua , Zhang Shui-Jun
Published: November 2022

Exosomes are well-known key mediators of intercellular communication and contribute to various physiological and pathological processes. Their biogenesis involves four key steps, including cargo sorting, MVB formation and maturation, transport of MVBs, and MVB fusion with the plasma membrane. Each process is modulated through the competition or coordination of multiple mechanisms, whereby diverse repertoires of molecular cargos are sorted into distinct subpopulations of exosomes, resulting in the high heterogeneity of exosomes. Intriguingly, cancer cells exploit various strategies, such as aberrant gene expression, posttranslational modifications, and altered signaling pathways, to regulate the biogenesis, composition, and eventually functions of exosomes to promote cancer progression. Therefore, exosome biogenesis-targeted therapy is being actively explored. In this review, we systematically summarize recent progress in understanding the machinery of exosome biogenesis and how it is regulated in the context of cancer. In particular, we highlight pharmacological targeting of exosome biogenesis as a promising cancer therapeutic strategy.
Gender-specific relationship between frequency of food-away-from-home with serum lipid levels and dyslipidemia in chinese rural adults
Authors: Wang Yuyang , Liu Xiaotian , Dong Xiaokang , Liu Beibei , Kang Ning , Huo Wenqian , Mao Zhenxing , Hou Jian , Wang Chongjian
Published: November 2022

Objective

Food-away-from-home (FAFH) is one of the leading dietary patterns in Chinese families. However, the relationship between FAFH and dyslipidemia remains unclear, especially in the rural adult population. This study explored the relationship of FAFH frequency with serum lipid levels and dyslipidemia in rural Chinese adults.

Methods

A total of 12,002 men and 17,477 women aged 18–79 were included from the Henan rural cohort. Serum lipid levels were measured by enzyme colorimetry. Information on FAFH frequency was collected using a validated questionnaire. The associations of FAFH frequency and serum lipid levels were assessed through multiple linear regression modeling. Logistic regression was performed to explore the linkages of the FAFH frequency to dyslipidemia and its four parameter types. Mediation analysis examined whether body mass index (BMI) acted as a mediator between the FAFH frequency and dyslipidemia.

Results

After adjusting for potential confounders, the adjusted odds ratio (OR) and 95% confidence interval (CI) of the groups with 8–11 FAFH times/week for dyslipidemia were 1.991 (1.569, 2.526) in men compared with 0-frequency subgroup. Participants who consumed 8–11 FAFH times/week had a higher risk of high total cholesterol (TC), high triglycerides (TG), high LDL-cholesterol (LDL-C), and low HDL-cholesterol (HDL-C) with the OR and 95% CI of 1.928 (1.247, 2.980), 1.723 (1.321, 2.247), 1.875 (1.215, 2.893), and 1.513 (1.168, 1.959), respectively. In addition, the interaction effect between FAFH and gender was significantly associated with dyslipidemia and lipid levels (P < 0.001). BMI played a fully mediating effect between FAFH frequency and dyslipidemia in men, and the Sobel test showed the significance of the mediating effect (z = 4.2158, P < 0.001).

Conclusion

In rural Chinese adults, FAFH was significantly associated with a higher risk of dyslipidemia, which indicated the importance of FAFH reduction and dietary intervention in patients with dyslipidemia and cardiovascular disease, especially in clinical practice.

Trial Registration

The Henan Rural Cohort Study has been registered on the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15,006,699).
Forthcoming complications in recovered COVID-19 patients with COPD and asthma; possible therapeutic opportunities
Authors: Rajabi Hadi , Mortazavi Deniz , Konyalilar Nur , Aksoy Gizem Tuse , Erkan Sinem , Korkunc Seval Kubra , Kayalar Ozgecan , Bayram Hasan , Rahbarghazi Reza
Published: November 2022

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been growing swiftly worldwide. Patients with background chronic pulmonary inflammations such as asthma or chronic obstructive pulmonary diseases (COPD) are likely to be infected with this virus. Of note, there is an argument that COVID-19 can remain with serious complications like fibrosis or other pathological changes in the pulmonary tissue of patients with chronic diseases. Along with conventional medications, regenerative medicine, and cell-based therapy could be alternative approaches to compensate for organ loss or restore injured sites using different stem cell types. Owing to unique differentiation capacity and paracrine activity, these cells can accelerate the healing procedure. In this review article, we have tried to scrutinize different reports related to the harmful effects of SARS-CoV-2 on patients with asthma and COPD, as well as the possible therapeutic effects of stem cells in the alleviation of post-COVID-19 complications.
GATA3 expression in clear cell adenocarcinoma of the lower urinary tract: a potential diagnostic pitfall
Authors: Akgul Mahmut , Humble Robert , Osme Abdullah , Yuce Servet , Kocak Elif N. , Najafzadeh Parisa , Sangoi Ankur , Pattnaik Niharika , Mishra Sourav , Sharma Shivani , Shaker Nada , Kaushal Seema , Baisakh Manas , Lightle Andrea R. , Balzer Bonnie L. , Xiao Guang-Qian , MacLennan Gregory T. , Osunkoya Adeboye O. , Parwani Anil , Cheng Liang , Bellizzi Andrew , Mohanty Sambit K.
Published: November 2022

Background

Clear cell adenocarcinoma of the lower urinary tract (CCACLUT) is a rare primary malignant neoplasm with heterogenous morphology. There is a paucity of data in the literature regarding its immunohistochemical profile.

Methods

The immunohistochemical features (extent and intensity) of a multinational cohort of CCACLUT were evaluated with comparison between clear cell adenocarcinoma of the female genital tract (CCACFGT, tissue microarray) and nephrogenic adenoma (NA).

Results

33 CCACLUT (24 female, 9 male; mean age 59 years) were collected. CCACLUT most commonly arose from the urinary bladder (26/33, 78%), particularly from the trigone (10/33, 30.3%) followed by the urethra (8/33, 22%). All 12 NA cases were located at the urinary bladder, whereas the most common CCACFGT location was the ovary (29/56, 52%). None of the CCACLUT patients had, intestinal metaplasia, NA, or urothelial carcinoma. One patient had concurrent endometriosis of the sigmoid colon. Most frequently observed morphology in CCACLUT was papillary/tubulocystic (9/3; 27.3%), followed by papillary/tubular (6/33; 18.2%) and papillary/solid (5/33; 15.2%). GATA3 expression was significantly higher in CCACLUT (18/33, 54.5%) and NA (6/12, 50%), when compared to CCACFGT cases 6/56, 11.7%)(p = 0.001 and p = 0.022, respectively). The extent of GATA3 was significantly higher in CCACLUT group (19.2 ± 16.6%) than the other groups (9.6 ± 22.5% in NA and 2.6 ± 9% in CCACFGT group) (p = 0.001). 4/33 patients (12.1) had weak, 10/33 patients (30.3%) had moderate, and 4/33 patients (12.1%) had strong GATA3 intensity in CCACLUT group. In NA group, one patient (8.3%, 1/12) had weak, one patient (8.3%, 1/12) had moderate and 4 patients (33.3%, 4/12) had strong GATA3 intensity. Most cases (CCACLUT 29/33, 88%; NA 11/12, 92%; CCACFGT 46/56, 82.1%) had positive Napsin A expression, by which CCACLUT had significantly more cases with Napsin A expression (p = 0.034). p63 was consistently negative in all cases (30/33 (91.9%) CCACLUT; 12/12 (100%) NA; 42/56 (75%) CCACFGT. Ki67 (MIB) proliferation index was significantly higher in CCACLUT group (54.6 ± 21%) when compared to NA group (4.5 ± 2.7%) and CCACFGT group (35.5 ± 25.8%) (p = 0.001).

Conclusion

CCACLUT has consistent GATA3 expression, which may cause challenge in the diagnosis of urothelial carcinoma but can be used to distinguish CCACLUT from CCACFGT.
Implementation fidelity of a Brazilian drug use prevention program and its effect among adolescents: a mixed-methods study
Authors: Gusmoes Julia D , Garcia-Cerde Rodrigo , Valente Juliana Y , Pinsky Ilana , Sanchez Zila M
Published: November 2022

Background

Based on the US DARE-kiR, a version of the Keepin’ it REAL program, the Drug and Violence Resistance Educational Program (PROERD) is the most widely implemented Brazilian prevention program. It originates from the translation of the DARE-kiR, a version of the Keepin’ it REAL program. Previous results suggest its inefficiency in preventing drug use among Brazilian adolescents. Since kiR fidelity can impact program outcomes, this mixed-methods study evaluates the PROERD implementation fidelity and its effects on preventing drug use among adolescents.

Methods

Data from two cluster randomized controlled trials (cRCTs) with 4,030 students from 30 public schools in São Paulo (1,727 fifth graders and 2,303 seventh graders), assessed at two-time points, were analyzed quantitatively. After implementing each lesson during the cRCT, 19 PROERD instructors answered fidelity forms. The effect of PROERD fidelity on alcohol, cigarettes, marijuana, inhalant, and cocaine use (the last two only among seventh graders) in the six months prior to follow-up assessment was analyzed by logistic regressions for fifth grade and mixed effect models for seventh graders. For qualitative analysis, semi-structured interviews were conducted with PROERD instructors and investigated by thematic analysis.

Results

Quantitative analysis showed that PROERD implementation fidelity had no impact on drug use among fifth and seventh graders. Conversely, the qualitative analysis revealed important aspects that may influence implementation fidelity and consequently program effectiveness, such as adaptations made by instructors, school infrastructure, among others, besides program application.

Conclusion

PROERD requires cultural adaptation to improve its implementation in Brazilian public schools.
Continuous field flooding versus final one-shot CO2 insufflation in minimally invasive mitral valve repair
Authors: Nasso Giuseppe , Condello Ignazio , Santarpino Giuseppe , Di Bari Nicola , Moscarelli Marco , Agrò Felice Eugenio , Lorusso Roberto , Speziale Giuseppe
Published: November 2022

Background

Insufflation of carbon dioxide (CO2) into the operative field to prevent cerebral or myocardial damage by air embolism is a well known strategy in open-heart surgery. However, here is no general consensus on the best delivery approach.

Methods

From January 2018 to November 2021, we retrospectively collected data of one hundred consecutive patients undergoing minimally invasive mitral valve repair (MIMVR). Of these, fifty patients were insufflated with continuous CO21 min before opening the left atrium and ended after its closure, and fifty patients were insufflated with one shot CO210 min before the start of left atrium closure. The primary outcome of the study was the incidence of transient post-operative cognitive disorder, in particular agitation and delirium at discontinuation of anesthesia, mechanical ventilation (MV) duration and intensive care unit (ICU) length of stay.

Results

In all patients that received continuous field flooding CO2, correction of ventilation for hypercapnia during cardiopulmonary bypass (CPB) was applied with an increase of mean sweep gas air (2.5 L) and monitoring of VCO2changes. One patient vs. 9 patients of control group reported agitation at discontinuation of anesthesia (p = 0.022). MV duration was 14 ± 3 h vs. 27 ± 4 h (p = 0.016) and ICU length of stay was 33 ± 4 h vs. 42 ± 5 h (p = 0.029). A significant difference was found in the median number of total micro-emboli recorded from release of cross-clamp until 20 min after end of CPB (154 in the continuous CO2group vs. 261 in the one-shot CO2control group; p < 0.001). Total micro-emboli from the first 15 min after the release of cross-clamp was 113 in the continuous CO2group vs. 310 in the control group (p < 0.001). In the continuous CO2group, the median number of detectable micro-emboli after CPB fell to zero 9 ± 5 min after CPB vs. 19 ± 3 min in the control group (p = 0.85).

Conclusion

Continuous field flooding insufflation of CO2in MIMVR is associated with a lower incidence of micro-emboli and of agitation at discontinuation of anesthesia, along with improved MV duration and ICU length of stay.
Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort
Authors: Lengyel Anna , Pinti Éva , Pikó Henriett , Kristóf Árvai , Abonyi Tünde , Némethi Zaránd , Fekete György , Haltrich Irén
Published: November 2022

Background

Neurodevelopmental disorders are genetically heterogeneous pediatric conditions. The first tier diagnostic method for uncovering copy number variations (CNVs), one of the most common genetic etiologies in affected individuals, is chromosomal microarray (CMA). However, this methodology is not yet a routine molecular cytogenetic test in many parts of the world, including Hungary. Here we report clinical and genetic data of the first, relatively large Hungarian cohort of patients whose genetic testing included CMA.

Methods

Clinical data were retrospectively collected for 78 children who were analyzed using various CMA platforms. Phenotypes of patients with disease-causing variants were compared to patients with negative results using the chi squared/Fisher exact tests.

Results

A total of 30 pathogenic CNVs were identified in 29 patients (37.2%). Postnatal growth delay (p = 0.05564), pectus excavatum (p = 0.07484), brain imaging abnormalities (p = 0.07848), global developmental delay (p = 0.08070) and macrocephaly (p = 0.08919) were more likely to be associated with disease-causing CNVs.

Conclusion

Our results allow phenotypic expansion of 14q11.2 microdeletions encompassing SUPT16H and CHD8 genes. Variants of unknown significance (n = 24) were found in 17 patients. We provide detailed phenotypic and genetic data of these individuals to facilitate future classification efforts, and spotlight two patients with potentially pathogenic alterations. Our results contribute to unraveling the diagnostic value of rare CNVs.
Long term outcome after toxic nodular goitre
Authors: Sjölin Gabriel , Watt Torquil , Byström Kristina , Calissendorff Jan , Cramon Per Karkov , Nyström Helena Filipsson , Hallengren Bengt , Holmberg Mats , Khamisi Selwan , Lantz Mikael , Planck Tereza , Törring Ove , Wallin Göran
Published: November 2022

Background

The purpose of treating toxic nodular goitre (TNG) is to reverse hyperthyroidism, prevent recurrent disease, relieve symptoms and preserve thyroid function. Treatment efficacies and long-term outcomes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery vary in the literature. Symptoms often persist for a long time following euthyroidism, and previous studies have demonstrated long-term cognitive and quality of life (QoL) impairments. We report the outcome of treatment, rate of cure (euthyroidism and hypothyroidism), and QoL in an unselected TNG cohort.

Methods

TNG patients (n = 638) de novo diagnosed between 2003–2005 were invited to engage in a 6–10-year follow-up study. 237 patients responded to questionnaires about therapies, demographics, comorbidities, and quality of life (ThyPRO). Patients received ATD, RAI, or surgery according clinical guidelines.

Results

The fraction of patients cured with one RAI treatment was 89%, and 93% in patients treated with surgery. The rate of levothyroxine supplementation for RAI and surgery, at the end of the study period, was 58% respectively 64%. Approximately 5% of the patients needed three or more RAI treatments to be cured. The patients had worse thyroid-related QoL scores, in a broad spectrum, than the general population.

Conclusion

One advantage of treating TNG with RAI over surgery might be lost due to the seemingly similar incidence of hypothyroidism. The need for up to five treatments is rarely described and indicates that the treatment of TNG can be more complex than expected. This circumstance and the long-term QoL impairments are reminders of the chronic nature of hyperthyroidism from TNG.
Effect of comorbid ADHD on mortality in women with borderline personality disorder
Authors: Kouppis Efthymios , Gerdin Bengt , Björkenstam Charlotte , Björkenstam Emma , Ekselius Lisa
Published: November 2022

Background

Many similarities exist between borderline personality disorder (BPD) and attention-deficit/hyperactivity disorder (ADHD), more so in women than in men. People with comorbid ADHD and BPD represent a subgroup of BPD patients with distinct symptom expression and, consequently, a different prognosis. We used Swedish national high quality registers to assess whether such comorbidity is related to increased mortality risk. The study focused on women with BPD because they are more likely than men to be clinically diagnosed with BPD and present a higher mortality risk, especially for unnatural causes of death, including suicide.

Findings

In a cohort of 15 847 women diagnosed with BPD a subsequent clinical diagnosis of ADHD did not influence the overall risk of mortality, including suicide.

Conclusions

Women with comorbid ADHD and BPD have a similar mortality risk as those only diagnosed with BPD.
Multifocal intraocular lens exchange to monofocal for the management of neuroadaptation failure
Authors: Al-Shymali Olena , Alió del Barrio Jorge L. , McAlinden Colm , Canto Mario , Primavera Laura , Alio Jorge L.
Published: November 2022

Background

The aim of this study was to evaluate visual, refractive, quality of vision, visual function and satisfaction of multifocal intraocular lens (MF-IOL) exchange with a monofocal IOL (MNF-IOL) in dissatisfied patients following MF-IOL implantation.

Methods

This was a retrospective case series. Bilateral IOL exchange (MF-IOL to MNF-IOL) was performed in 13 patients (26 eyes) with neuroadaptation failure. Questionnaires including the Quality of Vision (QoV), Visual Function Index (VF-14 and Rasch-revised VF-8R version), and a satisfaction questionnaire were used.

Results

The mean time for IOL exchange was 15 months. The corrected distance visual acuity (CDVA) improved from 20/26 to 20/23 (P = 0.028). The uncorrected near visual acuity (UNVA) worsened after exchange from 20/47 to 20/62 (P = 0.024). QoV scores improved significantly across all three subscales after exchange. Visual function for far distance improved with a change in VF-14 score from 74.2 ± 24.8 to 90.9 ± 9.1 (P = 0.03). The VF-8R score showed worsening although not statistically significant. Near vision spectacle independence was totally or partially lost in all cases. Ten patients (77%) reported they would not repeat the lens exchange. Safety and efficacy indices changed from 1.23 to 0.85, respectively, at three months to 1.24 (P = 0.871) and 0.89 (P = 0.568), respectively, at one year.

Conclusion

IOL exchange (multifocal to monofocal) to solve neuroadaptation failure in this case series resulted in significant improvements in dysphotopsia and improved distance visual function. However, UNVA worsened and patient satisfaction after exchange remained suboptimal with 77% claiming they would not repeat the lens exchange, suggesting the value of near vision spectacle independence for these patients.
Results from in vitro and in vivo studies evaluating the bioavailability, effects of food, and administration as crushed tablet suspension on vericiguat pharmacokinetics
Authors: Becker Corina , Boettcher Michael , Muenster Uwe , Loewen Stephanie , Lobmeyer Maximilian , Mueck Wolfgang
Published: November 2022

Objective

This article describes in vitro and in vivo studies that aimed to further characterize the biopharmaceutical properties and pharmacokinetic (PK) profile of vericiguat and to guide dosing recommendations.

Methods

Five open-label, phase I studies characterized the biopharmaceutical aspects of vericiguat, including absolute bioavailability, bioavailabilities of different formulations, dose proportionality, and food effect. Area under the curve (AUC) and maximum plasma concentrations (Cmax), determined by a noncompartmental analysis, were compared by analysis of variance, and a mixed-effects power model was used to assess dose proportionality. The effect of food on the dissolution of vericiguat was evaluated in vitro using media simulating the gastrointestinal tract under fed and fasted conditions. In vitro dissolution of intact vs crushed vericiguat tablet was assessed in quality control medium (HCl at pH 2), acetate buffer at pH 4.5, and phosphate buffer at pH 6.8.

Results

Dissolution of vericiguat increased under fed conditions. In healthy subjects, exposure (AUC and Cmax) increased ~ 40% with food vs fasted state (10 mg intact tablet) confirming a food effect on vericiguat bioavailability. Interindividual variability in exposure decreased ~ 20%, irrespective of meal type. Absolute bioavailability of vericiguat 10 mg (intact tablets, fed) was 93%. Vericiguat 2.5–10 mg demonstrated dose proportionality (intact tablets, fed) in healthy subjects. Dissolution studies showed no differences between the formulations, and this was confirmed with in vivo studies.

Conclusion

Vericiguat tablets should be administered with food and may be crushed for patients who have difficulty swallowing.

Graphical Abstract
Long-term geoelectrical monitoring of landslides in natural and engineered slopes
Authors: Chambers Jonathan , Holmes Jessica , Whiteley Jim , Boyd James , Meldrum Philip , Wilkinson Paul , Kuras Oliver , Swift Russell , Harrison Harry , Glendinning Stephanie , Stirling Ross , Huntley David , Slater Nick , Donohue Shane
Published: November 2022

Developments in time-lapse electrical resistivity tomography (ERT) technology are transforming our ability to monitor the subsurface due to purpose-built monitoring instruments, advances in automation and modeling, and the resulting improvements in spatial and temporal resolution. We describe the development of a novel ERT-based remote monitoring system called PRIME that integrates new low-power measurement instrumentation with data delivery, automated data processing and image generation, and web-based information delivery. Due to the sensitivity of ERT to hydrologic processes in the near surface, we focus on the application of PRIME for moisture-driven landslide monitoring. Case examples are considered of landslides in engineered and natural slopes, including those impacting geotechnical assets in rail and highways, where slope hydrology is seen to be controlled by lithology, vegetation, fissuring, and drainage structures. We conclude by taking a forward look at emerging developments in ERT monitoring relating to hardware, software and modeling, and applications.
Near-Surface Views & News: Building bridges between geophysical and engineering communities
Authors: Fantello Nadia , Rupert Sarah L. Morton
Published: November 2022

Over the last few years, the use of geophysics for engineering purposes has been increasing considerably. Geophysical applications within the engineering industry are quite diverse and can range from geotechnical to transportation purposes and to environmental and geohazards studies. Typical applications include detection of bedrock, landfill delineation, water table detection, karst exploration, dam/levee and seepage evaluation, foundation design, pipeline installation, landslide mitigation, earthquake and seismic design parameters, and pavement analysis, among others.
Reviews
Authors: Green William
Published: November 2022

Essentials of Geophysical Data Processing, by Clark R. Wilson, 2022, ISBN 978-1-108-93100-7, Cambridge University Press, 350 p. How the Mountains Grew: A New Geological History of North America, by John Dvorak, 2022, ISBN 978-1-639-36215-8, Pegasus Books, 464 p.
Multiple shapes from a single nematic elastomer sheet activated via patterned illumination
Authors: Giudici A. , Clement A. , Duffy D. L. , Shankar M. Ravi , Biggins J. S.
Published: November 2022

Liquid crystal elastomers (LCEs) undergo a large uniaxial contraction upon thermal or optical stimulation. LCE sheets are often fabricated with a spatially patterned direction of contraction, which can sculpt the sheet into a Gauss-curved surface. Here, we instead consider LCE sheets subject to patterned stimulation intensity, leading to a control of contraction strength. We show such patterns may also sculpt a complex surface, but with the advantage that arbitrarily many surfaces may be achieved sequentially in the same sample, thus breaking the link between microstructure and shape. We first consider a monodomain LCE in which some regions are actuated and others are not. We discuss how to join actuated and unactuated regions compatibly, and use this design rule to generate patterns for cones, anti-cones, arrays of cones and a rolling bi-strip. We validate the patterns numerically via elastic shell simulations and demonstrate them experimentally via patterned photo-chemical actuation. Secondly, we consider an LCE disk with an azimuthal director profile actuated by a radially varying stimulus. We show, theoretically and numerically, how to design a stimulation profile to sculpt any surface of revolution. Such re-configurable actuation offers enticing possibilities for haptics, robotics and locomotion.
A road toward zero-spacing photonic waveguides and circuits
Authors: Song Tongtong , Luo Jie , Lai Yun
Published: November 2022

Like their electronic counterparts, photonic integrated circuits face the challenge of further integration and miniaturization. One of the fundamental limitations comes from waveguide spacing, which leads to serious crosstalk between the neighboring waveguides when it is less than half a wavelength. Here we demonstrate a potential approach to remove this limitation and realize zero-spacing photonic waveguides with extreme compactness. This is achieved by designing pure-dielectric photonic crystal waveguides with shifted spatial dispersion and arranging them with normal dielectric waveguides alternately. Amazingly, the coupling and crosstalk between the two types of waveguides are negligible despite the zero spacing between them. Through proper designs, zero-spacing photonic bending waveguides and circuits can also be realized in practice. Such a finding opens a new avenue for ultra-compact photonic waveguides and circuits with 100% space utilization efficiency.
ODP010 Relaxin Receptor RXFP1 Knockout in Adipose Tissue Progenitor Cells Results in Resistance to High Fat Diet-Induced Weigh Gain
Authors: Bennett Robert , Simpson Ronda , Agoulnik Alexander , Hamel Frederick
Published: November 2022

Relaxin is a polypeptide hormone that signals through its cognate receptor RXFP1. Previous work demonstrated that global RXFP1-knockout mice developed age-related adipose tissue fibrosis and dysfunction. Our preliminary data suggested that adipose tissue progenitor cells (APC) express RXFP1 in the white adipose tissue in mice. To determine the role of APC in relaxin signaling, we crossed floxed RXFP1 mice (RXFP1-fl/fl) with mice expressing tamoxifen-inducible CRE recombinase under control of the platelet-derived growth factor receptor-β (PDGFRβ) promoter to produce conditional RXFP1 knockout in adipose tissue progenitor cells and fibroblasts (RXFP1-PKO). After tamoxifen treatment, both RXFP1-fl/fl and RXFP1-PKO mice were placed on a high fat diet (58% calories from fat) supplemented with sucrose and fructose in the drinking water, or chow diet for 16 weeks. At the end of the study, body mass composition was measured using an Echo-MRI instrument. Adipose tissue fibrosis was assessed histologically by Sirius red staining. In response to the HFD, the control (fl/fl) mice reached an average weight of 48.3 ± 0.6g, while the RXFP1-PKO mice were resistant to weight gain, reaching only 40.3 ±3g (p<. 05). The body mass composition changed in the RXFP1-fl/fl mice on HFD (34. 0% fat/55.2% lean) compared to chow (14.7% fat/68.9% lean). The RXFP1-PKO mice had a significantly lower gain in fat mass on HFD (29.7% fat/59.1% lean on HFD; 12.6% fat/71. 0% lean on chow) compared to the RXFP-fl/fl mice. Histological analysis of the inguinal white adipose tissue (iWAT) revealed that while RXFP1-fl/fl mice developed adipocyte hypertrophy in response to the HFD, the RXFP1-PKO mice had smaller adipocyte size. This was accompanied by increased pericellular and perivascular fibrosis in the iWAT as determined by Sirius red staining. To determine if differentiation of APC was altered by loss of RXFP1, the stromal-vascular fraction of iWAT was extracted by collagenase treatment, and the APC isolated using antibody-coated magnetic beads (Miltenyi Biotec). The purified cells were cultured to confluence, treated with or without tamoxifen to induce CRE expression, then treated with differentiation cocktail. The APC from the RXFP1-PKO mice had a marked impairment in the ability differentiate to mature adipocytes after treatment with tamoxifen compared to untreated cells. In summary, the loss of RXFP1 in PDGFRβ-expressing cells resulted in resistance to HFD-induced weight and adipose tissue mass gain. This was accompanied by increased fibrosis in the iWAT and decreased adipocyte size. The APC had decreased adipogenic potential after loss of RXFP1. Taken together, the findings support a role for RXFP1 in the differentiation of adipose tissue progenitor cells, and in adipose tissue expansion after exposure to an obesogenic diet.

Presentation: No date and time listed
OR23-4 Intestinal FFA2 and FFA3 Mediate Obesogenic Effects in Mice on a Western Diet
Authors: Gough Sophie , Layden Brian , Nnyamah Chioma , Priyadarshini Medha , Wicksteed Barton , Lednovich Kristen
Published: November 2022

Free fatty acid receptor 2 and free fatty acid receptor 3 (FFA2/3) are two highly similar G protein-coupled receptors belonging to the free fatty acid receptor family. Their ligands are short-chain fatty acids (SCFAs), which are key nutrients that play a diverse role in physiological function, including the regulation of metabolic homeostasis and glycemic control. FFA2/3 are broadly expressed in a multitude of tissues including the intestine, pancreas, adipose and central nervous system, where they contribute to metabolic homeostasis via a summation of tissue-specific effects. Consequently, FFA2/3 have been identified as a potential drug target for metabolic diseases including obesity and type-2 diabetes.

Both FFA2 and FFA3 are highly expressed within the intestinal epithelium – the major site of SCFA generation – and have been identified in hormone-secreting enteroendocrine cells as well as intestinal epithelial cells. However, due conflicting data, the respective roles of FFA2/3 within the intestine and their effects on physiology and metabolism are still largely unclear. Previous in vivo studies involving this receptor have largely relied on global knockout mouse models, making it difficult to isolate their effects in the intestine. To overcome this challenge, we generated a novel intestine-specific knockout mouse model for FFA2 and FFA3 individually, utilizing Cre-mediated recombination under the expression of the villin promoter. Here, we report the first in vivo characterization of FFA2/3 in the intestine and reveal novel insights into receptor function.

Following model validation, we conducted a general metabolic assessment of male Villin-Cre-FFA2 (Vil-FFA2) and Villin-Cre-FFA3 (Vil-FFA3) mice on standard chow and observed no major congenital or time-dependent defects. Because dietary changes are known to alter gut microbial composition, and thereby SCFA production, a pilot study was performed on male Vil-FFA2 and Vil-FFA3 mice and their littermate controls to probe for a phenotype on a high-fat, high-sugar "western diet." Mice were placed on either a low-fat control diet (CD) or western diet (WD) at 10 weeks of age and metabolically profiled for 25 weeks. We found that both Vil-FFA2 and Vil-FFA3 mouse strains were largely protected from diet-induced obesity and had significantly lower fat mass as well as adipose hypertrophy. Additionally, both mouse strains had reduced intestinal inflammation and improved glucose homeostasis. These differences were driven by lower food intake in the Vil-FFA2 strain only. Our findings suggest a novel role of FFA2/3 in mediating the metabolic consequences of a western diet – a state of high inflammation, dysbiosis and metabolic stress. Moreover, these data support an intestine-specific role of FFA2/3 in whole-body metabolic homeostasis and in the development of adiposity and hyperglycemia.

Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.
LBODP006 Clinical Usefulness Of The Growth Hormone-releasing Peptide-2 Test For Hypothalamic-pituitary Disorder
Authors: Suzuki Sawako , Ruike Yutarou , Ishiwata Kazuki , Naito Kumiko , Igarashi Katsushi , Ishida Akiko , Fujimoto Masanori , Horiguchi Kentaro , Koide Hisashi , Horiguchi Kentaro , Tatsuno Ichiro , Yokote Koutaro
Published: November 2022

Purpose

Growth hormone deficiency (GHD) develops early in patients with hypothalamic-pituitary disorder and is frequently accompanied by other anterior pituitary hormone deficiencies including secondary adrenal insufficiency (AI). A growth hormone-releasing peptide-2 (GHRP2), which is wildly used for the diagnosis of patients with GHD, has been considered to induce not only growth hormone (GH) release but also ACTH release. However, its clinical usefulness in hypothalamic-pituitary disorder is unclear.

Methods

The GHRP2 test, a cosyntropin stimulation test, corticotropin-releasing hormone (CRH) tests and/or insulin tolerance tests (ITTs) were performed on 36 patients having hypothalamic-pituitary disorder.

Results

Twenty-two (61%) had severe GHD, and 3 (8%) had moderate GHD by GHRP2. There was no difference in baseline ACTH and cortisol between non-GHD, moderate GHD and severe GHD participants. However, a cosyntropin stimulation test and subsequent CRH tests and/or ITTs revealed that 17 (47%) had secondary AI and 16/17 (94%) cases of secondary AI were concomitant with severe GHD. ROC curve analysis demonstrated that the ACTH response in the GHRP2 test was useful for screening pituitary-AI, with a cut-off value of 1.55-fold (83% sensitivity and 88% specificity). Notably, the combination of ACTH response and the peak cortisol level in the GHRP2 test using each cut-off value (1.55-fold and 10 µg/dl, respectively) showed high specificity (100%) with high accuracy (0.94) for diagnosis of pituitary-AI.

Conclusion

We recommend measuring ACTH as well as GH during the GHRP2 test to avoid overlooking and delays in diagnosis of secondary AI that frequently accompanies GHD.

Presentation: No date and time listed
PSAT031 Dietary Influence (smoothies) on Measurements of Plasma and Urinary Metanephrines in a Patient with Hypertension.
Authors: Nath Priti , Shin Terry , Hoang Thanh , Shakir Mohamed
Published: November 2022

Introduction

Pheochromocytoma can be diagnosed by fractionated plasma and urinary metanephrines. However, these tests have several diagnostic issues. Drugs, such as tricyclic antidepressants, and diets both can affect biochemical testing. We report a patient who was consuming a catecholamine rich diet in the form of smoothies which resulted in falsely elevated metanephrines.

Case history

A 37-year-old female was seen in 2021 for evaluation of secondary hypertension. Patient had a history of intermittent palpitations but denied headaches or excessive sweating. She was taking amlodipine 5mg daily and potassium chloride 20mg daily. Significant past medical history included a partial nephrectomy for renal cell cancer at the age of 35 years. She denies family history of pheochromocytoma or MEN 2. Vital signs showed HR 70/min, BP 138/80 mm Hg. Examination of the heart, lungs and abdomen was normal. Skin exam revealed no bruises or abdominal striae. Labs revealed normal CBC, serum K 3.4, aldosterone 20.1 ng/dL (ref 0.0 - 30.0), renin 1.165 ng/mL/hr (0.167-5.360). Following 1-mg dexamethasone suppression test, serum cortisol was 1.0 mcg/dL. Plasma normetanephrine 113.8 pg/mL (0.0 - 110.1), metanephrine 26.1 pg/mL (0.0 - 88), 24-hour urine metanephrines 465 mg/24hr (74 - 297), normetanephrine 963 mg/24hr (105 - 354). Due to the discordant values between the plasma and urinary metanephrines, a detailed history was taken which revealed that her diets included smoothies, consisting of pineapple juice, bananas, papaya, mango, and sea moss. She drank 15 ounces 3 times per week. Additionally, she was also consuming 1 cup of pistachios and 1 cup of elderberries daily. Patient was counseled to stop drinking the smoothies, and eating pistachios and elderberry. Six weeks later her 24-hour urine metanephrines and normetanephrines returned at 80 mcg/24 hrs and 243 mcg/24 hrs, respectively. Additionally, CT of the adrenal glands confirmed normal adrenal glands.

Conclusion

Previous studies have shown that catecholamines from dietary sources can dramatically affect plasma as well urinary concentrations of the 3-O methylated metabolites of catecholamines. In our patient, consumption of catecholamine rich foods such as bananas, oranges, pineapples, and possibly elderberry may have contributed to the false positive results. Additionally, the discrepancy between the baseline plasma and urine metanephrines, the normal adrenal glands on CT and normalization of the metanephrines after discontinuing the smoothie diets confirmed that the false positive laboratory values indeed resulted from dietary influence. It is recommended that a detailed dietary history be taken prior to ordering laboratory testing for catecholamine-secreting tumors. Possible interfering medications and catecholamine rich foods should be discontinued, if possible, before biochemical testing to avoid false positive results.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT034 A Case of Adrenal Crisis in Association With a Febrile Response to the bnt162b2 mRNA COVID-19 (Pfizer) Vaccine Heralding a Diagnosis of Primary Adrenal Insufficiency.
Authors: Kamimoto Jorge J , Kharlip Julia , Kobaly Kristen
Published: November 2022

Background

In the face of the COVID-19 pandemic, messenger RNA (mRNA) vaccines were approved for the first time for use in the general population. Vaccination can trigger a febrile flu-like response that is self-limited in healthy individuals. Febrile illness is a classic trigger of acute adrenal insufficiency in patients who are cortisol deficient, but recognizing this clinical scenario is challenging in patients with undiagnosed adrenal insufficiency.

Case Presentation

A 24-year-old male presented to an acute care community hospital with fatigue, fever, and vomiting 12 hours after receiving the second dose of the BNT162b2 mRNA Covid-19 (Pfizer) vaccine. He was 6 feet tall, and his weight was 175 pounds. He had a temperature of 103 F, a blood pressure of 88/42 mmHg, and a heart rate of 100 bmp on admission. Hypotension persisted despite aggressive fluid resuscitation and broad-spectrum antibiotics. CT of the chest and CT angiogram of the abdomen and Pelvis did not identify an etiology for his presentation. Over a period of hours, he became obtunded, disoriented, and required vasopressor support. He received 100 mg of IV hydrocortisone followed by 50 mg every 6 hours for treatment of presumed sepsis and was transferred to an intensive care unit. Within 24 hours of starting glucocorticoid therapy, he was awake and oriented, defervesced, and became normotensive. This rapid improvement led to suspicion of adrenal insufficiency as an underlying diagnosis. Further questioning revealed a 4-month history of recurrent nausea, vomiting, severe fatigue, to the point where he had trouble climbing a flight of stairs, and a 40-pound unintentional weight loss. He visited an emergency department 3 times over this period and had outpatient evaluations by gastroenterology and cardiology without identifying a cause. Inpatient evaluation revealed a morning Cortisol of 1.4 ug/dL (n 4.8-19.5 ug/dL), aldosterone <3 ng/dL (n <16 ng/dL), and ACTH 1071 pg/mL (n 7.2-63.3 pg/mL) leading to the diagnosis of primary adrenal insufficiency. He was started on physiologic doses of adrenal replacement hormones and discharged home in stable condition 4 days after his admission date.

Conclusions

A severe post-vaccination reaction should elicit physicians to look for an alternative diagnosis. Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency and is uniquely associated with a long lag to diagnosis. The diagnosis is often made in the setting of an intervening illness or physiologic stressor when a patient's condition acutely deteriorates. Patients with known adrenal insufficiency should be reminded to address post-vaccination febrile reactions with an increase in glucocorticoid doses.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT074 Patient-Centered Research in Adrenal Insufficiency for Adults and Children Using a Registry and Longitudinal Cohort
Authors: Regan Elizabeth , Watts Shandi
Published: November 2022

Adrenal insufficiency (AI) leads to loss of critical adrenocortical hormones and untreated can result in death from adrenal crisis. It is the final common manifestation of multiple etiologies including infection, autoimmune disease, trauma, tumor, central nervous system dysfunction and genetic factors. Basal secretion of multiple steroid hormones is reduced or absent and a stress response in cortisol secretion is inadequate or absent. There may be variation in the severity of disease related to etiology and for causes such as autoimmune AI the disease may progress over time. There is limited published data from the US on prevalence, health disparities, outcomes of care and quality of life. A patient registry and longitudinal cohort to study AI in adults was initiated in 2019. This has been expanded to include children with AI. Goals of the Registry are to characterize the natural history of AI, including an at-risk population (family history of AI or active autoimmune disease). Additional goals are to monitor outcomes of care including adrenal crises and provide insight into the impact of AI on children.

Methods

The registry has been reviewed and approved by National Jewish Health and BRANY IRB. Participants provide written informed consent. Contact with the registry is electronic using RedCap for data entry and communication. Information about the registry is disseminated through social media, patient support groups and physician practices with an effort to enroll across a broad geographic and demographic base. Initial enrollment includes characterization of medical history, events, underlying cause of AI, demographics, socioeconomic factors and quality of life inventories (SF-36, AddiQoL and EQ-5D5L). Participants provide copies of medical records and test results to allow classification of AI and these are reviewed and adjudicated. Age-appropriate data collection instruments have been developed using the PROMIS database for children to assess the impact of illness in the domains of anxiety, physical function, fatigue, cognition, and social function. Interval surveys provide longitudinal data.

Results

More than 500 participants have enrolled with completed data entry. More than 150 medical records have been received for adjudication. The majority of participants to date are categorized as primary AI (89%) with 3% CAH and 5% "at-risk".

Sex distribution 82% female and Race, 93% white, 1.5% Black, 4% mixed. Age distribution 18-85 years, mean(SD) = 50(15). Pediatric enrollment to start Feb 2022.

Conclusions

A patient registry for adrenal insufficiency that is accessible electronically is feasible and has the potential to track a geographically diverse population. Initial enrollment has been strong but developing a balanced population that reflects the US will require extensive outreach to institutions and physician practices.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.