bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Pseudomonas aeruginosa pathogenesis and therapeutics in military‐relevant animal infection models
Authors: Bobrov Alexander G. , Getnet Derese , Swierczewski Brett , Jacobs Anna , Medina‐Rojas Maria , Tyner Stuart , Watters Chase , Antonic Vlado
Published: June 2021

Modern combat‐related injuries are often associated with acute polytrauma. As a consequence of severe combat‐related injuries, a dysregulated immune response results in serious infectious complications. The gram‐negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that often causes life‐threatening bloodstream, lung, bone, urinary tract, and wound infections following combat‐related injuries. The rise in the number of multidrug‐resistant P. aeruginosa strains has elevated its importance to civilian clinicians and military medicine. Development of novel therapeutics and treatment options for P. aeruginosa infections is urgently needed. During the process of drug discovery and therapeutic testing, in vivo testing in animal models is a critical step in the bench‐to‐bedside approach, and required for Food and Drug Administration approval. Here, we review current and past literature with a focus on combat injury‐relevant animal models often used to understand infection development, the interplay between P. aeruginosa and the host, and evaluation of novel treatments. Specifically, this review focuses on the following animal infection models: wound, burn, bone, lung, urinary tract, foreign body, and sepsis.
Taking a BiTE out of the CAR T space race
Authors: Patel Ameet , Oluwole Olalekan , Savani Bipin , Dholaria Bhagirathbhai
Published: June 2021

Chimaeric antigen receptor T‐cell (CAR T) therapy has evolved at an exponential pace and seeks to revolutionize the CAR T space with next‐generation CARs and expanding indications in plasma cell dyscrasias. Recent developments in Bispecific T‐cell engager therapy (BiTEs) may level the playing field with CAR T therapy, offering key advantages with off‐the‐shelf or on‐demand treatment and a manageable toxicity profile to encompass a wider pool of eligible patients in the outpatient setting. The coexistence of both modalities will remain important in overall management and accelerate the next iteration of both cellular and BiTEs. This article summarises the current progress, potential future of both therapies for haematologic malignancies, and their economic implications on the healthcare system.
An observational study of volume–outcome effects for robot‐assisted radical prostatectomy in England
Authors: Gray William K. , Day Jamie , Briggs Tim W.R. , Harrison Simon
Published: June 2021

Objectives

To investigate volume–outcome relationships in robot‐assisted radical prostatectomy (RARP) for cancer using data from the Hospital Episodes Statistics (HES) database for England.

Materials and Methods

Data for all adult, elective RPs for cancer during the period January 2013–December 2018 (inclusive) were extracted from the HES database. The HES database records data on all National Health Service (NHS) hospital admissions in England. Data were extracted for the NHS trust and surgeon undertaking the procedure, the surgical technique used (laparoscopic, open or robot‐assisted), hospital length of stay (LOS), emergency readmissions, and deaths. Multilevel modelling was used to adjust for hierarchy and covariates.

Results

Data were available for 35 629 RPs (27 945 RARPs). The proportion of procedures conducted as RARPs increased from 53.2% in 2013 to 92.6% in 2018. For RARP, there was a significant relationship between 90‐day emergency hospital readmission (primary outcome) and trust volume (odds ratio [OR] for volume decrease of 10 procedures: 0.99, 95% confidence interval [CI] 0.99–1.00; P = 0.037) and surgeon volume (OR for volume decrease of 10 procedures: 0.99, 95% CI 0.99–1.00; P = 0.013) in the previous year. From lowest to highest volume category there was a decline in the adjusted proportion of patients readmitted as an emergency at 90 days from 10.6% (0–49 procedures) to 7.0% (≥300 procedures) for trusts and from 9.4% (0–9 procedures) to 8.3% (≥100 procedures) for surgeons. LOS was also significantly associated with surgeon and trust volume, although 1‐year mortality was associated with neither.

Conclusions

There is evidence of a volume–outcome relationship for RARP in England and minimising low‐volume RARP will improve patient outcomes. Nevertheless, the observed effect size was relatively modest, and stakeholders should be realistic when evaluating the likely impact of further centralisation at a population level.
Animal models of diabetes‐associated vascular diseases: an update on available models and experimental analysis
Authors: Choi Judy S. Y. , de Haan Judy B. , Sharma Arpeeta
Published: June 2021

Diabetes is a chronic metabolic disorder associated with the accelerated development of macrovascular (atherosclerosis and coronary artery disease) and microvascular complications (nephropathy, retinopathy and neuropathy), which remain the principal cause of mortality and morbidity in this population. Current understanding of cellular and molecular pathways of diabetes‐driven vascular complications, as well as therapeutic interventions has arisen from studying disease pathogenesis in animal models. Diabetes‐associated vascular complications are multi‐faceted, involving the interaction between various cellular and molecular pathways. Thus, the choice of an appropriate animal model to study vascular pathogenesis is important in our quest to identify innovative and mechanism‐based targeted therapies to reduce the burden of diabetic complications. Herein, we provide up‐to‐date information on available mouse models of both Type 1 and Type 2 diabetic vascular complications as well as experimental analysis and research outputs.

LINKED ARTICLES

This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc
Multidrug resistance proteins preferentially regulate natriuretic peptide‐driven cGMP signalling in the heart and vasculature
Authors: Grange Robert M. H. , Preedy Michael E. J. , Renukanthan Aniruthan , Dignam Joshua P. , Lowe Vanessa J. , Moyes Amie J. , Pérez‐Ternero Cristina , Aubdool Aisah A. , Baliga Reshma S. , Hobbs Adrian J.
Published: June 2021

Background and Purpose

cGMP underpins the bioactivity of NO and natriuretic peptides and is key to cardiovascular homeostasis. cGMP‐driven responses are terminated primarily by PDEs, but cellular efflux via multidrug resistance proteins (MRPs) might contribute. Herein, the effect of pharmacological blockade of MRPs on cGMP signalling in the heart and vasculature was investigated in vitro and in vivo.

Experimental Approach

Proliferation of human coronary artery smooth muscle cells (hCASMCs), vasorelaxation of murine aorta and reductions in mean arterial BP (MABP) in response to NO donors or natriuretic peptides were determined in the absence and presence of the MRP inhibitor MK571. The ability of MRP inhibition to reverse morphological and contractile deficits in a murine model of pressure overload‐induced heart failure was also explored.

Key Results

MK571 attenuated hCASMC growth and enhanced the anti‐proliferative effects of NO and atrial natriuretic peptide (ANP). MRP blockade caused concentration‐dependent relaxations of murine aorta and augmented responses to ANP (and to a lesser extent NO). MK571 did not decrease MABP per se but enhanced the hypotensive actions of ANP and improved structural and functional indices of disease severity in experimental heart failure. These beneficial actions of MRP inhibition were associated with a greater intracellular:extracellular cGMP ratio in vitro and in vivo.

Conclusions and Implications

MRP blockade promotes the cardiovascular functions of natriuretic peptides in vitro and in vivo, with more modest effects on NO. MRP inhibition may have therapeutic utility in cardiovascular diseases triggered by dysfunctional cGMP signalling, particularly those associated with altered natriuretic peptide bioactivity.

LINKED ARTICLES

This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
A Complex Systems Network Approach to Quantifying Peer Effects: Evidence From Ghanaian Preprimary Classrooms
Authors: Wolf Sharon , Gonzalez Canche Manuel S. , Coe Kristen
Published: June 2021

Research on classroom peer effects has focused nearly exclusively on high‐income countries and on academic skills. Little is known about peer effects in low‐income countries and whether effects differ under different educational environments (e.g., teacher‐directed versus child‐centered, conditions of concentrated advantage or disadvantage). Based on a data set of Ghanaian preprimary classrooms in the Greater Accra Region collected in the 2015–2016 school year, we use complex system networks with multilevel modeling to study the presence and magnitude of peer effects. Results corroborated small statistically significant effects on academic and nonacademic skills (d = .06–.10). Peer effects on literacy were larger for children in public schools, who are relatively more disadvantaged than their private school counterparts. Teacher‐directivity intensity did not moderate peer effects.
Continuing care following residential alcohol and other drug treatment: Continuing care worker perceptions
Authors: Ingram Isabella , Kelly Peter J. , Carradus Lenna J. , Deane Frank P. , Baker Amanda L. , Byrne Gerard , McKay James R. , Osborne Briony , Meyer Johanna M. , Nunes Jason L. , Robinson Laura D. , Lunn Joanne
Published: June 2021

Introduction

Little is known about the experiences of continuing care workers (CCW) in the implementation of continuing care programs. The current study sought to understand CCWs and supervisor perceptions of the successes and challenges of implementing a telephone‐based continuing care intervention following residential alcohol and other drug treatment services. It also aimed to provide recommendations for treatment providers wishing to integrate continuing care into their treatment model, including the resources, training and supervision needs of CCWs.

Methods

The participants were eight CCWs and two independent supervisors who completed semi‐structured interviews. Interview coding and analysis was guided by Iterative Categorisation procedures and an implementation framework. The Consolidated Framework for Implementation Research was used.

Results

Telephone delivery was advantageous, but even more enhanced, when there was a face‐to‐face session first to build rapport. Other key successes included CCWs who were confident and competent, as well as a match between the organisation's values and the philosophy of the continuing care program. Key challenges faced by CCWs related to a perceived lack of support from managers, difficulties accessing quiet office spaces and participant disengagement.

Discussion and Conclusions

Interviews revealed several factors that may influence successful delivery of continuing care as part of alcohol and other drug treatment. These included features of the intervention (e.g. telephone delivery, evidence‐based content), characteristics of the individual CCWs (e.g. flexibility in delivery of the intervention while maintaining fidelity), organisational culture (e.g. alignment of organisational values with continuing care) and resources (e.g. office space, flexible work schedules).
Photoperiod‐independent testicular development in the model newt Pleurodeles waltl
Authors: Kyakuno Mitsuki , Nakamori Rei , Tazawa Ichiro , Uemasu Hitoshi , Namba Noriyuki , Tsunekawa Naoki , Noce Toshiaki , Satoh Yukio , Takeuchi Takashi , Hayashi Toshinori
Published: June 2021

Urodele amphibian newts have unique biological properties in male gametogenesis, in addition to their extreme regenerative capacity. Male newts are able to regenerate new testes even after reaching sexual maturity and can possess multiple testes. Notably, these animals maintain primordial germ cell‐like cells in a tissue adjacent to the testis. Spermatogenesis proceeds while synchronizing in a region‐specific manner in the testis. However, the newt species that have been used most commonly require 2–3 years to achieve sexual maturity, and spermatogenesis in these species shows seasonality. These traits have restricted the use of newts for studies on testicular development and spermatogenesis, and testis development in newts remains poorly characterized. Recently, the Iberian ribbed newt Pleurodeles waltl has been established as an emerging model organism. P. waltl reaches sexual maturity more quick after birth than do other newts and is capable of breeding year‐round. Thus, P. waltl is expected to serve as an appealing experimental model for studying the mechanisms of male gametogenesis in the urodeles. In the present study, we use P. waltl to describe the entire developmental process of the newt testis from primordial gonad to maturity. Notably, the mature testes show synchronized progression of spermatogenesis along the anteroposterior axis. Additionally, we demonstrate that the process of spermatogenesis in P. waltl proceeds irrespective of day length. Our results show that P. waltl newts are a suitable model for investigating the process of testicular development. We also expect that these results will be useful for the maintenance of P. waltl bioresources.
Efficacy of liraglutide added to sodium‐glucose cotransporter‐2 inhibitors in type 2 diabetes, stratified by baseline characteristics: Post‐hoc analysis of LIRA‐ADD2SGLT2i
Authors: Blonde Lawrence , Fainberg Udi , Kaltoft Margit S. , Mosenzon Ofri , Ramesh Chethana , Rea Rosangela
Published: June 2021

Aims

The LIRA‐ADD2SGLT2i trial demonstrated that liraglutide + sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) ± metformin significantly improved glycaemic control (not body weight) versus placebo in adults with type 2 diabetes (T2D). This post‐hoc analysis assessed whether baseline characteristics influenced these findings.

Materials and methods

LIRA‐ADD2SGLT2i (NCT02964247) was a placebo‐controlled, double‐blind, multinational trial, wherein participants received liraglutide (≤1.8 mg/day) or placebo (randomized 2:1). Changes from baseline to week 26 in haemoglobin A1c (HbA1c), body weight and waist circumference stratified by HbA1c, body mass index (BMI), diabetes duration, duration of pre‐trial SGLT2i use and Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR) were analysed. These five baseline characteristics were divided into tertiles, and the treatment effect was evaluated using the trial product estimand.

Results

Data from all 303 participants were analysed. There was a significant interaction between baseline HbA1c tertiles (7.0%‐<7.6%; 7.6%‐8.1%; ≥8.2%‐9.5%) and glycaemic control at week 26 (p[interaction] = .011), with the lowest HbA1c estimated treatment difference (95% confidence interval) observed in patients with lowest baseline HbA1c [−0.20% (−0.59, 0.19); −0.68% (−1.03, −0.33); −0.98% (−1.33, −0.64), respectively]. There were no significant interactions in glycaemic control across baseline BMI, diabetes duration, insulin resistance determined by HOMA‐IR or SGLT2i use duration (p[interaction] > .05, all). Across the five characteristics assessed, no significant interactions were found for body weight or waist circumference changes from baseline (p[interaction] > .05, all).

Conclusion

For individuals with T2D and inadequate glycaemic control despite therapy with SGLT2is ± metformin, liraglutide 1.8 mg would provide an effective treatment intensification option, irrespective of HbA1c, BMI, diabetes duration, insulin resistance determined by HOMA‐IR and SGLT2i use duration.
Thioredoxin‐1 regulates calcium homeostasis in MPP+/MPTP‐induced Parkinson's disease models
Authors: Zhang Xianwen , Deng Ruhua , Zhang Se , Deng Juan , Jia Jing Jing , Sun Bo , Zhou Xiaoshuang , Bai Jie
Published: June 2021

Disturbance in calcium (Ca2+) homeostasis has been involved in a variety of neuropathological conditions including Parkinson's disease (PD). The Ca2+ channel, transient receptor potential channel 1 (TRPC1), plays a protective role in regulating entry of Ca2+ activated by store depletion of Ca2+ in endoplasmic reticulum (ER). We have showed that thioredoxin‐1 (Trx‐1) plays a role in suppressing ER stress in PD. However, whether Trx‐1 regulates TRPC1 expression in PD is still unknown. In the present study, we demonstrated that treatment of 1‐methyl‐4‐phenylpyridinum ion (MPP+) significantly reduced the expression of TRPC1 in PC12 cells, which was restored by Trx‐1 overexpression, and further decreased significantly by Trx‐1 siRNA. Moreover, we found that Ca2+ entered into the cells was decreased by MPP+ in PC 12 cells, which was restored by Trx‐1 overexpression, and further decreased by Trx‐1 siRNA. MPP+ significantly increased calcium‐dependent cysteine protease calpain1 expression in PC12 cells, which was suppressed by Trx‐1 overexpression. Calpain1 expression was increased by Trx‐1 siRNA or SKF96365, an inhibitor of TRPC1. Moreover, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) decreased TRPC1 expression in the substantia nigra pars compacta region (SNpc), which was restored in mice overexpressing Trx‐1, and further decreased in mice of knockdown Trx‐1. Inversely, the expression of calpain1 was increased by MPTP, which was suppressed in mice overexpressing Trx‐1, and further increased in mice of knockdown Trx‐1.

In conclusion, Trx‐1 regulates the Ca2+ entry through regulating TRPC1 expression after treatment of MPP+/MPTP.
Immunity and Gilles de la Tourette syndrome: A systematic review and meta‐analysis of evidence for immune implications in Tourette syndrome
Authors: Lamothe Hugues , Tamouza Ryad , Hartmann Andreas , Mallet Luc
Published: June 2021

Background and purpose

The neurobiology of Gilles de la Tourette syndrome (GTS) is known to involve corticostriatal loops possibly under genetic control. Less is known about possible environmental triggers of GTS. Specifically, immune‐related events following possible environmental inducers have been evoked, but important controversies still exist. In this systematic review and meta‐analysis, we looked for evidence in favor of such possibilities.

Methods

We performed a systematic review and meta‐analysis of all immunological data in PubMed.

Results

We found large discrepancies concerning immune dysfunctions in GTS, and meta‐analyzing cytokines data did not allow us to conclude there is an involvement of specific cytokines in GTS neurobiology. When looking specifically at pediatric autoimmune neuropsychiatric disorder associated with streptococcus/pediatric acute onset neuropsychiatric syndrome, we found some important evidence of a possible infectious involvement but in a limited number of studies. Our meta‐analysis found an increased level of anti‐streptolysin O antibodies in GTS patients, but the level of anti‐DNase B antibodies was not increased.

Conclusions

Too many questions still exist to allow us to definitively reach the conclusion that there is an infectious and immunological etiology in GTS. Much work is still needed to elucidate the possible role of immunology in GTS neurobiology and to favor immunological treatment rather than classical treatment.
Efficacy and morbidity of biodegradable versus titanium osteosyntheses in orthognathic surgery: A systematic review with meta‐analysis and trial sequential analysis
Authors: Gareb Barzi , van Bakelen Nico B. , Dijkstra Pieter U. , Vissink Arjan , Bos Ruud R. M. , van Minnen Baucke
Published: June 2021

Titanium osteosynthesis is currently the gold standard in orthognathic surgery. Use of biodegradable osteosyntheses avoids removal of plates/screws in a second operation. This systematic review aimed to assess the efficacy and morbidity of biodegradable vs. titanium osteosyntheses in orthognathic surgery (PROSPERO CRD42018086477). Patients with syndromic disorder(s) and/or cleft lip/palate were excluded. Randomised, prospective and retrospective controlled studies were searched for in nine databases (February 2021). The time periods perioperative, short‐term, intermediate, long‐term, and overall follow‐up were studied. Meta‐analyses were performed using random‐effects models. A total of 9073 records was assessed, of which 33 were included, comprising 2551 patients. Seven RCTs had ‘some concerns’ while another seven RCTs had ‘high’ risk of bias (Cochrane‐RoB2). No differences in malunion (qualitative analyses), mobility of bone segments [RR 1.37 (0.47; 3.99)], and malocclusion [RR 0.93 (0.39; 2.26)] were found. The operative time was longer in the biodegradable group [SMD 0.50 (0.09; 0.91)]. Symptomatic plate/screw removal was comparable among both groups [RR 1.29 (0.68; 2.44)]. Skeletal stability was similar in most types of surgery. Biodegradable osteosyntheses is a valid alternative to titanium osteosyntheses for orthognathic surgery, but with longer operation times. Since the quality of evidence varied from very low to moderate, high‐quality research is necessary to elucidate the potential of biodegradable osteosyntheses.
Epidemiology of nursing home dialysis patients—A hidden population
Authors: Bellin Eran Y. , Hellebrand Alice M. , Kaplan Steven M. , Ledvina Jordan G. , Markis William T. , Levin Nathan W. , Kaufman Allen M.
Published: June 2021

Introduction

Dialysis patients are often discharged from hospitals to skilled nursing facilities (SNFs), but little has been published about their natural history.

Methods

Using electronic medical record data, we conducted a retrospective cohort study of nursing home patients treated with in‐SNF hemodialysis from January 1, 2018 through June 20, 2020 within a dialysis organization across eight states. A dialytic episode began with the first in‐SNF dialysis and was ended by hospitalization, death, transfer, or cessation of treatment. The clinical characteristics and natural history of these patients and their dialytic episodes are described.

Findings

Four thousand five hundred and ten patients experienced 9274 dialytic episodes. Dialytic episodes had a median duration of 18 days (IQR: 8–38) and were terminated by a hospitalization n = 5747 (62%), transfer n = 2638 (28%), death n = 568 (6%), dialysis withdrawal n = 129 (1.4%), recovered function n = 2 (0.02%), or other cause n = 6 (0.06%). Increased patient mortality was associated with advancing age, low serum creatinine, albumin, or sodium, and low pre‐dialytic systolic blood pressure (sBP). U‐shaped relationships to mortality were observed for intradialytic hypotension frequency and for post‐ > pre‐hemodialysis sBP frequency. Prescription of dialysis five times weekly in the first 2 weeks was associated with better survival in the first 90 days (HR 0.77, CI 0.62–0.96; p < 0.02).

Discussion

Provision of in‐SNF dialysis by an external dialysis organization enables discharge from the acute care setting for appropriate treatment with increased nursing contact time in an otherwise under‐resourced environment. SNF ESRD patient clinical characteristics and outcomes are extensively characterized for the first time.
Is home hemodialysis a practical option for older people?
Authors: Wu Henry H. L. , Nixon Andrew C. , Dhaygude Ajay P. , Jayanti Anu , Mitra Sandip
Published: June 2021

An increasing demand for in‐center dialysis services has been largely driven by a rapid growth of the older population progressing to end‐stage kidney disease. Since the onset of the COVID‐19 pandemic, efforts to encourage home‐based dialysis options have increased due to risks of infective transmission for patients receiving hemodialysis in center‐based units. There are various practical and clinical advantages for patients receiving hemodialysis at home. However, the lack of caregiver support, cognitive and physical impairment, challenges of vascular access, and preparation and training for home hemodialysis (HHD) initiation may present as barriers to successful implementation of HHD in the older dialysis population. Assessment of an older patient's frailty status may help clinicians guide patients when making decisions about HHD. The development of an assisted HHD care delivery model and advancement of telehealth and technology in provision of HHD care may increase accessibility of HHD services for older patients. This review examines these factors and explores current unmet needs and barriers to increasing access, inclusion, and opportunities of HHD for the older dialysis population.
Sodium and ultrafiltration profiling in hemodialysis: A long‐forgotten issue revisited
Authors: Ertuglu Lale A. , Demiray Atalay , Basile Carlo , Afsar Baris , Covic Adrian , Kanbay Mehmet
Published: June 2021

Sodium and ultrafiltration profiling are method of dialysis in which dialysate sodium concentration and ultrafiltration rate are altered during the course of the dialysis session. Sodium and ultrafiltration profiling have been used, commonly simultaneously, to improve hemodynamic stability during hemodialysis. Sodium profiling is particularly effective in decreasing the incidence of intradialytic hypotension, while ultrafiltration profiling is suggested to decrease subclinical repeated end organ ischemia during dialysis. However, complications such as increased interdialytic weight gain and thirst due to sodium excess have prevented widespread use of sodium profiling. Evidence suggest that different sodium profiling techniques may lead to different clinical results, and preferring sodium balance neutral sodium profiling may mitigate adverse effects related to sodium overload. However, evidence is lacking on the long‐term clinical outcomes of different sodium profiling methods. Optimal method of sodium profiling as well as the utility of sodium/ultrafiltration profiling in routine practice await further clinical investigation.
Densification of glass powder studied by master sintering curve and master kinetic curve methods
Authors: Talimian Ali , Wondraczek Lothar , Galusek Dušan
Published: June 2021

The master sintering curve method was applied to analyze the sintering and crystallization behavior of 15Na2O.10CaO.75SiO2 (SLS) and 17Na2O.33CaO.50SiO2 (NC2S3) glasses, in mol %. The densification of samples was successfully analyzed using the master sintering curve (MSC) method; it gives activation energy Q = 310–340 kJ.mol−1, which is in good agreement with the expected activation energy of the viscous flow. While the obtained activation energy enables predicting the sintering behavior of SLS glass, the actual results are different from the estimated data for NC2S3. The activation energy of crystallization of NC2S3, determined by constructing Master Kinetic Curves (MKC) was lower than the sintering activation energy: this impairs the prediction ability of MSC for NC2S3 glass.
Effect of immersive virtual reality on pain in different dental procedures in children: A pilot study
Authors: Alshatrat Sabha Mahmoud , Sabarini Jumana M. , Hammouri Hanan M. , Al‐Bakri Isra Abdulkarim , Al‐Omari Wael Mousa
Published: June 2021

Background

Implementing effective pain management is important to increase patient compliance during paediatric dental procedures.

Aim

This pilot study was conducted to evaluate the effectiveness of virtual reality (VR) on pain perception in dental procedures in children.

Material and Methods

Fifty‐four children aged between 5 and 12 years were included. Patients scheduled to receive dental procedures not requiring local anesthesia (eg, fluoride therapy) were assigned to Group A, and patients scheduled to receive painful dental procedures requiring local anesthesia (eg, pulp therapy, teeth extraction) were assigned to Group B. Patients in each group were randomly assigned and were equally likely to either receive VR during their dental procedure, or treatment as usual (without VR). Visual analog scale (VAS), Wong‐Baker FACES rating scale, and the ‘Face, Legs, Activity, Cry, Consolability’ scale (FLACC scale) were used to assess the pain levels during dental procedures.

Results

Patients receiving painful dental procedures requiring local anesthesia reported significant reductions in pain intensity/worst pain during the dental procedure on all subjective and behavioral pain measures of pain intensity with the use of VR distraction technique (P < .05 on each). Patients receiving non‐painful dental procedures showed the predicted pattern but no significant reduction in worst pain during VR.

Conclusion

The use of VR was found to be an effective distraction tool to ease pain and anxiety in the tested dental procedures, for children receiving painful dental procedures.
Estimating sexual knowledge of people with mild intellectual disability through a valid and reliable assessment scale: The ISK‐ID
Authors: Gil‐Llario Mª Dolores , Castro‐Calvo Jesus , Fernández‐García Olga , Elipe‐Miravet Marcel , Ballester‐Arnal Rafael
Published: June 2021

Background

Despite the relevance of assessing sexual knowledge in people with Intellectual Disability, there is a lack of appropriate assessment tools to measure this domain. The current study tests the psychometric properties of the new ‘Inventory of Sexual Knowledge of people with Intellectual Disability’ (ISK‐ID).

Method

345 individuals with mild intellectual disability completed the ISK‐ID before and after the implementation of a sexual education program. Psychometric properties of the ISK‐ID were analysed according to Multidimensional Item Response Theory (MIRT).

Results

Its underlying factorial structure, along with parameters derived from the MIRT (item discrimination, difficulty, and participant's ability), support the use of the ISK‐ID as a measure of sexual knowledge. Moreover, the ISK‐ID was able to detect changes in the level of sexual knowledge resulting from educational interventions (i.e., responsiveness).

Conclusions

The ISK‐ID is an appropriate assessment tool to measure sexual knowledge in men and women with mild intellectual disability.
MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm
Authors: Tao Wuyuan , Hong Yimei , He Haiwei , Han Qian , Mao Mengmeng , Hu Bei , Zhang Hao , Huang Xiaoran , You Wei , Liang Xiaoting , Zhang Yuelin , Li Xin
Published: June 2021

Vascular smooth muscle cells (VSMCs) senescence contributes to abdominal aortic aneurysm (AAA) formation although the underlying mechanisms remain unclear. This study aimed to investigate the role of miR‐199a‐5p in regulating VSMC senescence in AAA. VSMC senescence was determined by a senescence‐associated β‐galactosidase (SA‐β‐gal) assay. RT‐PCR and Western blotting were performed to measure miRNA and protein level, respectively. The generation of reactive oxygen species (ROS) was evaluated by H2DCFDA staining. Dual‐luciferase reporter assay was used to validate the target gene of miR‐199a‐5p. VSMCs exhibited increased senescence in AAA tissue relative to healthy aortic tissue from control donors. Compared with VSMCs isolated from control donors (control‐VSMCs), those derived from patients with AAA (AAA‐VSMCs) exhibited increased cellular senescence and ROS production. Angiotensin II (Ang II) induced VSMC senescence by promoting ROS generation. The level of miR‐199a‐5p expression was upregulated in the plasma from AAA patients and Ang II–treated VSMCs. Mechanistically, Ang II treatment significantly elevated miR‐199a‐5p level, thereby stimulating ROS generation by repressing Sirt1 and consequent VSMC senescence. Nevertheless, Ang II–induced VSMC senescence was partially attenuated by a miR‐199a‐5p inhibitor or Sirt1 activator. Our study revealed that miR‐199a‐5p aggravates Ang II–induced VSMC senescence by targeting Sirt1 and that miR‐199a‐5p is a potential therapeutic target for AAA.
Corneal confocal microscopy: A useful tool for diagnosis of small fiber neuropathy in type 2 diabetes
Authors: Jin Yu , Wang Weimin , Chen Wei , Guo Simin , Li Chenxi , Zhu Dalong , Bi Yan
Published: June 2021

Aim

To investigate the diagnostic utility of corneal confocal microscopy (CCM) for small fiber neuropathy in type 2 diabetes.

Materials and Methods

There were 186 participants with type 2 diabetes enrolled in this cross‐sectional research. Pure small fiber neuropathy and mixed fiber neuropathy were defined using clinical examination, electromyography, and quantitative sensory testing. Demographics and clinical data, corneal confocal microscopy parameters, and other neuropathy measures were compared among the groups. The diagnostic utility of corneal confocal microscopy for small fiber neuropathy was assessed by the receiver operating curve.

Results

Of the 186 patients, 24.7% had a pure small fiber neuropathy and 17.2% of patients were diagnosed with mixed fiber neuropathy. The corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), and corneal nerve fiber length (CNFL) were significantly lower in subjects with pure small fiber neuropathy compared with those without diabetic peripheral neuropathy (all P < 0.05). The receiver operating curve analysis for corneal confocal microscopy diagnosing small fiber neuropathy demonstrated the area under the curve for CNFD of 0.791, CNFL of 0.778, CNBD of 0.710.

Conclusions

Patients with type 2 diabetes with pure small fiber neuropathy showed more corneal nerve loss compared with those without diabetic peripheral neuropathy. It was revealed that corneal confocal microscopy can be a reasonable marker in the diagnosis of small fiber neuropathy in type 2 diabetes.
Pigment epithelium‐derived factor (PEDF) and derived peptides promote survival and differentiation of photoreceptors and induce neurite‐outgrowth in amacrine neurons
Authors: Michelis Germán , German Olga Lorena , Villasmil Rafael , Soto Tamara , Rotstein Nora P. , Politi Luis , Becerra S. Patricia
Published: June 2021

Pigment epithelium‐derived factor (PEDF) is a cytoprotective protein for the retina. We hypothesize that this protein acts on neuronal survival and differentiation of photoreceptor cells in culture. The purpose of the present study was to evaluate the neurotrophic effects of PEDF and its fragments in an in vitro model of cultured primary retinal neurons that die spontaneously in the absence of trophic factors. We used Wistar albino rats. Cell death was assayed by immunofluorescence and flow cytometry through TUNEL assay, propidium iodide, mitotracker, and annexin V. Immunofluorescence of cells for visualizing rhodopsin, CRX, and antisyntaxin under confocal microscopy was performed. Neurite outgrowth was also quantified. Results show that PEDF protected photoreceptor precursors from apoptosis, preserved mitochondrial function and promoted polarization of opsin enhancing their developmental process, as well as induced neurite outgrowth in amacrine neurons. These effects were abolished by an inhibitor of the PEDF receptor or receptor‐derived peptides that block ligand/receptor interactions. While all the activities were specifically conferred by short peptide fragments (17 amino acid residues) derived from the PEDF neurotrophic domain, no effects were triggered by peptides from the PEDF antiangiogenic region. The observed effects on retinal neurons imply a specific activation of the PEDF receptor by a small neurotrophic region of PEDF. Our findings support the neurotrophic PEDF peptides as neuronal guardians for the retina, highlighting their potential as promoters of retinal differentiation, and inhibitors of retinal cell death and its blinding consequences.

image

Cover Image for this issue: https://doi.org/10.1111/jnc.15089
Comparative analysis of effects induced by hyaluronic acid and its combined formula on skin functional parameters in second‐degree photoaging
Authors: Azaryan Helen G. , Khachikyan Khachik M. , Taha Ahmed , Badawy Ezzat
Published: June 2021

Background and Aims

The study aimed to compare the effectiveness of intradermal injections of modified hyaluronic acid (mHA) and combined injections of platelet‐rich plasma (PRP) and mHA (HA‐PRP) on clinical and functional parameters in women with second‐degree photoaging.

Methods

Seventy‐six healthy female participants diagnosed with second degree of skin photoaging were involved in two interventional study groups. The first group was treated with “bio‐reparative” method (mHA) and the second group with “combined HA‐PRP therapy”. Additionally, 20 practically healthy women, with the first degree of photoaging according to Glogau classification, constituted the control group. Parameters of facial skin were evaluated in all groups before and after the injections. The patients in both interventional groups were compared based on skin therapy outcomes, using corneometry, sebumetry, cutometry, transepidermal water loss (TEWL), and skin pH assessments. A post‐interventional analysis was conducted to evaluate the level of satisfaction in physicians and study participants in accordance with GAIS. Intragroup and between‐group analysis for the selected parameters was performed.

Results

Compared with the control group, the combined therapy group did not show significant difference in parameters (p > 0.05) and the scores were significantly improved compared to mHA group (p < 0.001). Control and HA‐PRP–treated groups were different only in sebumetry scores (SigDev = 2.1%). Significant difference was observed in the GAIS scores for patients between the interventional groups (p = 4.03297E−11 and 3.4093E−09, respectively).

Conclusion

Implementation of combined therapy is significantly effective compared to the mHA therapy alone. The higher efficacy is derived from significant recovery of functional parameters and GAIS survey results.
Venoarterial extracorporeal membrane oxygenation as an early treatment for amniotic fluid embolism with cardiac arrest: A case report
Authors: Adachi Mariko , Adachi Takeshi , Fujita Tomoe , Hyuga Shunsuke , Onishi Yoko , Okutomi Toshiyuki
Published: June 2021

Amniotic fluid embolism (AFE) is a rare but fatal obstetric complication, characterized by sudden cardiovascular collapse, respiratory failure, and disseminated intravascular coagulation. Maternal mortality associated with AFE is high, making early recognition and prompt treatment important. In AFE with cardiac arrest, survival following acute cardiopulmonary dysfunction is crucial. In recent years, venoarterial extracorporeal membrane oxygenation (VA‐ECMO) has attracted attention as an aggressive treatment for AFE with cardiac arrest. A 40‐year‐old woman experienced sudden cardiac arrest due to AFE during cesarean section. Cardiopulmonary resuscitation and VA‐ECMO (also called percutaneous cardiopulmonary support) were initiated early. Finally, she recovered without any complications. VA‐ECMO can provide temporary respiratory and hemodynamic support until cardiopulmonary function improves after a few days in intensive care. VA‐ECMO should be considered as an early treatment for AFE with cardiac arrest.
Babu and Magon uterine closure technique during cesarean section: A randomized double‐blind trial
Authors: Tahermanesh Kobra , Mirgalobayat Shahla , Aziz‐Ahari Alireza , Maleki Maryam , Hashemi Neda , Samimi Mansooreh , Fazel Anvari‐Yazdi Abbas , Shahriyaripour Roya , Pecks Ulrich , Allahqoli Leila , Alkatout Ibrahim
Published: June 2021

Aim

We compared the effectiveness of the Babu and Magon uterine closure technique and unlocked double‐layer uterine closure on the integrity and thickness of the uterine scar.

Methods

A randomized double‐blind trial was performed at Hazrat‐e Rasoul ‐e‐Akram Hospital, Tehran, Iran, from March 2018 to December 2019, in 72 pregnant women who were candidates for cesarean section for the first time. Women were randomly assigned to the Babu and Magon uterine closure technique (intervention group, n = 34) or double‐layer closure of the uterine incision (control group, n = 38). The primary outcome of the study was the frequency of myometrial defects at the site of the scar (niche), and a large niche. Secondary outcomes, including the time taken for uterine closure and postpartum hemorrhage (early and late), were compared between groups.

Results

Adjacent myometrium thickness (AMT) between the two groups was not statistically significant. A niche was reported in 23.5% (8/34) and 50% (19/38) of women in the intervention and controls, respectively (p = 0.02). A large niche was reported in 2.9% (1/34) and 23.7% (9/38) of women in the intervention and controls, respectively (p < 0.01). The duration of uterine closure was not statistically significant between the two groups. Hemoglobin levels did not differ significantly between groups during the first 24 h post‐surgery.

Conclusion

The results of the study showed that the technique of uterine closure is one of the main potential determinants of myometrial healing. The Babu and Magon uterine closure technique seems to lead to tissue alignment during suturing and consequently cause better myometrial healing, although this issue calls for well‐founded longer studies of appropriate design.
Dissonance in views between parents and clinicians of children with serious illness: How can we bridge the gap?
Authors: Katz Naomi T , Hynson Jenny L , Gillam Lynn
Published: June 2021

Parents of children with serious illness must find a tolerable way of living each day, while caring for their child and making decisions about their treatments. Sometimes clinicians worry that parents do not understand the seriousness of their child's illness, including possible death. This can lead to tension, disagreement and even conflict. Such situations continue to occur despite expanding literature to help clinicians understand drivers of parental behaviour and decision‐making. Some of this literature relates to the role of hope and how parents characterise being a ‘good parent’. This article will summarise some of the applications and limitations of the hope and ‘good parent’ literature, as well as frameworks to understand grief and loss. We propose, however, that there is at least one missing link in understanding potential dissonance in views between parents and clinicians. We will make a case for the importance of a richer understanding about if, and how, parents ‘visit’ the ‘reality’ that clinicians wish to convey about their child's diagnosis and prognosis. We propose that clinician understanding about the benefits and burdens of ‘visiting’ this ‘reality’ for an individual family may help guide conversations and rapport, which in turn may influence decision‐making with benefits for the child, family and clinicians.
Sentence comprehension in ageing and Alzheimer's disease
Authors: van Boxtel Willem , Lawyer Laurel
Published: June 2021

The ability to correctly interpret complex syntax and long sentences is gradually impaired as people age. Typical ageing is characterised by working memory deficits, which are thought to play an important role in determining whether syntax can be comprehended correctly, and neurodegenerative conditions such as Alzheimer's disease (AD) are thought to exacerbate these limitations. Furthermore, declines in processing speed appear to cause increasing difficulty in the proper allocation of cognitive resources necessary for sentence processing. Typically ageing adults may compensate for these deficits successfully when interpreting sentences using semantics or intact cognitive functions, but AD patients may exhibit deficits too severe for this to occur. The causes of syntax comprehension deficits in Alzheimer's are still contested, and may consist of language‐specific impairments or deficits in general cognition impacting linguistic behaviour. In this review, we aim to give an overview of the main markers of cognitive ageing and AD in the domain of sentence comprehension, as well as discuss potential underlying factors that may affect sentence comprehension in older speakers and Alzheimer's patients.
Maternal depression is associated with less dietary diversity among rural Nepali children
Authors: Miller Laurie C. , Neupane Sumanta , Sparling Thalia M. , Shrestha Merina , Joshi Neena , Lohani Mahendra , Thorne‐Lyman Andrew
Published: June 2021

Maternal depression has been associated with adverse child growth and development; less is known about its relation to children's diet. In a cross‐sectional study embedded at endline of a longitudinal community development intervention, mothers of 629 children (age 23–66 months) in rural Nepal responded to household and children's diet questionnaires and were screened for depression. Child anthropometry and development (Ages and Stages Questionnaire) were assessed. Regression models examined children's diet, growth and development, adjusting for household, child and maternal characteristics. The prevalence of maternal depression was 21%. Maternal depression was associated with 11% lower likelihood that the child consumed one additional food group [Poisson regression, adjusted relative risk (aRR) 0.89, 95% confidence intervals (95% CI 0.81, 0.99), p = 0.024] and 13% lower likelihood that the child consumed one additional animal source food (ASF) [aRR 0.87, (95% CI 0.76, 1.01), p = 0.061] compared with children of nondepressed mothers. However, maternal depression was not associated with either child anthropometry or development: these outcomes were strongly associated with better home child‐rearing quality. Stunting also related to child age and intervention group; child development related to mother's education and household wealth. This study suggests a correlation between maternal depression and child dietary diversity. This association could be due to unmeasured confounders, and therefore, further research is warranted. Understanding the relationship of depression to child outcomes—and the role of other potentially compensatory household factors—could help address some of the earliest, modifiable influences in a child's life and contribute to innovative approaches to improve child well‐being.
Complex frequency identification using real modal shapes for a structure with proportional damping
Authors: Qu Chun‐Xu , Yi Ting‐Hua , Yao Xiao‐Jun , Li Hong‐Nan
Published: June 2021

Modal identification is based on modal superposition theory. For structures with proportional damping, the structural responses are recognized as real modal shapes multiplied by real modal coordinates. However, it is not true because the actual modal shapes should be complex even though they can be normalized to real ones. If the modal shapes are recognized as real ones, the modal superposition theory cannot reflect the actual modal parameters. This paper proposes an innovative method to identify complex frequencies for a structure with proportional damping using the identified real modal shapes, where the complex modal shapes are considered. The proportional damping is ideal but always assumed in practical engineering. The characteristic of the proposed method is that the complex property of frequencies is considered along with modal identification process. First, the reason why the complex modal shapes are hidden is revealed. When the real modal shapes are obtained, the Hilbert transform of analytical responses is used to estimate complex coordinates. Then, formulas to identify the complex frequencies are derived. The k‐means clustering method is employed. Finally, the proposed method is used in a numerical example and a practical bridge example. The results show that the proposed method can estimate the complex frequencies effectively, and can be used in practical engineering.