bluuebunny/crossref_metadata_2025 huggingface dataset:
TargetingPlasmodiumwith constrained peptides and peptidomimetics
Authors: Helton Leah G. , Kennedy Eileen J.
Published: February 2020

Malaria remains a worldwide health concern with an estimated quarter of a billion people infected and nearly half a million deaths annually. Malaria is caused by a parasite infection fromPlasmodiumstrains which are transmitted from mosquitoes into the human host. Although several small molecule inhibitors have been found to target the early stages of transmission and prevent parasite proliferation, multiple drug resistant parasite strains have emerged and drug resistance remains a major hurdle. As an alternative to small molecule inhibition, several peptide‐based therapeutics have been explored for their potential as antimalarial compounds. Chemically constrained peptides or peptidomimetics were developed to target large binding interfaces of parasite‐based proteins that have historically been difficult to selectively inhibit using small molecules. Here, we review ongoing research aimed at developing constrained peptides targeting protein–protein interactions pertinent to malaria pathogenesis. These targets include Falcipain‐2, the J domain of CDPK1, myosin A tail domain interacting protein, the PKA signaling pathway, and an unclear signaling pathway involving angiotensin‐derived peptides. Diverse synthetic methods were also used for each target. Merging parasite biology with synthetic strategies may provide new opportunities to develop alternative methods for uncovering novel antimalarials and may offer an alternate source for targeting drug‐resistant parasite strains.
Onset of asthma‐like symptoms in children with lower respiratory tract infections
Authors: Mao Song , Fang Li , Wu Liangxia , Shi Wenjing , Xu Min
Published: February 2020

Background

Asthma‐like symptoms (ALS) often occur among children with lower respiratory tract infections (LRTIs). We aimed to determine the potential risk factors for ALS onset in LRTIs children.

Methods

A total of 102 LRTIs with ALS and 474 without ALS were enrolled. The relative risk (RR) was used to test the influence of the clinical factors on the ALS risk. We compared the differences of birth data, wheezing history, disease severity, inflammatory markers, infectious pathogens, allergic markers, cardiac, liver, and kidney injury markers between LRTIs with and without ALS onset. Receiver operating curve (ROC) analysis was applied to determine the predictive value of various markers in the ALS risk in LRTIs. Multivariate logistic regression analysis was performed to evaluate the association between various clinical and laboratory parameters and ALS onset in LRTIs.

Results

The RRs of boys/girls ratio and wheezing history for ALS compared with non‐ALS was 1.263 and 2.850, respectively (P = .026, <10−4). There were significant differences of age, WBC, PLT, EOS, and CK between LRTIs with and without ALS onset (P = .004, .041, .006, .049, and .035). ROC analysis showed that significant associations between the parameters of age, WBC, and PLT and ALS risk among LRTIs were observed. Multivariate logistic regression analysis showed that the clinical and laboratory parameters were not independently associated with the risk of ALS onset among LRTIs.

Conclusions

Lower age, male, inflammation, and allergic state were risk factors for ALS onset in LRTIs. Comprehensive monitoring and evaluation of these factors may be helpful for ALS prevention.
Fibroblasts‐dependent invasion of podoplanin‐positive cancer stem cells in squamous cell carcinoma
Authors: Miyashita Tomoyuki , Neri Shinya , Hashimoto Hiroko , Akutsu Asami , Sugano Masato , Fujii Satoshi , Ochiai Atsushi , Ishii Genichiro
Published: February 2020

To clear whether podoplanin‐positive cancer stem cells in squamous cell carcinoma have higher invasion activity during a fibroblasts‐dependent invasion. A collagen gel invasion assay was performed using fluorescent ubiquitination‐based cell cycle indicator‐labeled A431 cells. The total number and number of invading cells in S/G2/M phase were counted using time‐lapse imaging cocultured with fibroblasts. There was no significant difference between the number of invading podoplanin‐positive and negative A431 cells when fibroblasts did not exist. On the contrary, the number of invading podoplanin‐positive cells was significantly higher when fibroblasts existed. The frequency of cells in S/G2/M phase among invasion was no difference. Knockdown of podoplanin decreased the number of invaded A431 cells significantly when fibroblasts existed. Podoplanin‐positive A431 cells display higher invasion activity when fibroblasts exist, suggesting that some biological functions of cancer stem cells might become evident only within the fibrous tumor microenvironment.
Primary cilia mediate parathyroid hormone receptor type 1 osteogenic actions in osteocytes and osteoblasts via Gli activation
Authors: Martín‐Guerrero Eduardo , Tirado‐Cabrera Irene , Buendía Irene , Alonso Verónica , Gortázar Arancha R. , Ardura Juan A.
Published: February 2020

Mechanical stimulation of primary cilia in osteocytes and osteoblasts has been proposed as a mechanism that participates in bone cell survival and skeletal remodeling. Among different signaling pathways stimulated by primary cilia, the hedgehog signaling pathway has been associated with the regulation of bone development. Parathyroid hormone (PTH)‐related protein (PTHrP) signaling through PTH 1 receptor (PTH1R) also regulates bone cell survival and remodeling and has been associated with the hedgehog pathway during skeletal development. We hypothesize that primary cilia and PTH1R concomitantly regulate bone remodeling and cell survival and aim to describe the mechanisms that mediate these effects in osteocytes and osteoblasts. Colocalization of PTH1R with primary cilia was observed in control and PTHrP‐stimulated MLO‐Y4 osteocytic and MC3T3‐E1 osteoblastic cells. Activation of PTH1R by PTHrP increased cell survival, osteoblast gene expression (osteocalcin, runt‐related transcription factor 2, and bone alkaline phosphatase) and the expression of the hedgehog transcription factor Gli‐1 in osteocytes and osteoblasts. These effects were abrogated by small interfering RNAs for the primary cilia protein IFT88 or by a primary cilia specific inhibitor (chloral hydrate). Preincubation of MLO‐Y4 osteocytic and MC3T3‐E1 osteoblastic cells with the Gli‐1 antagonist GANT61 inhibited PTHrP prosurvival actions but did not affect PTHrP‐induced overexpression of osteogenic genes. Mechanical stimulation by fluid flow increased the number of primary cilia‐presenting cells in osteocytes and osteoblasts. We propose that PTH1R activation induces prosurvival actions via primary cilia‐ and Gli‐1‐dependent mechanism and modulates osteogenic responses via a primary cilia‐dependent and Gli‐1‐independent pathway in osteocytes and osteoblasts.
Synthesis and biological evaluation of novel indoleamide derivatives as antioxidative and antitumor agents
Authors: Zhang Zhen , Gu Ying‐Lin , Wang Zheng‐Yang , Wang Huan‐Nan , Zhao Yan , Chu Xue‐Mei , Zhang Chun‐Yan , Yan Mao‐Cai
Published: February 2020

Novel indole amide derivatives C1‐C10 were successfully synthesized and characterized by 1H NMR, 13C NMR, IR, MS, and elemental analysis, and their molecular formulas were C14H10N6O, C13H10N4O, C16H13N3O2, C19H14N2O2, C16H11N3OS, C15H13N3O, C12H9N5O, C16H10ClN3OS, C15H17N3O2, and C13H14N2O3, respectively. The primary biological activities of these compounds were evaluated in vitro by the DPPH assay, H2O2‐induced oxidative stress injury assay, and cytotoxicity assay. The results indicated that compounds C1, C2, C4, C7, and C9 exhibited DPPH·scavenging ability, while C3, C4, C5, and C8 showed potent growth‐inhibitory activities against various human tumor cells, including MDA‐MB‐231, Hela, A549, and HT29. Interestingly, compound C4 showed potent scavenging effects on the DPPH radical and possessed protective effect on H2O2‐induced oxidative stress injury in human neuroblastoma SH‐SY5Y cells at low concentrations; however, C4 exhibited significant toxicity against four human tumor cells at a higher concentration in all treatments, and the range of IC50 value was 7.91 to 13.35 μM.
Is there any link between vitamin D deficiency and vasovagal syncope?
Authors: Usalp Songül , Kemal Hatice , Yüksek Ümit , Yaman Belma , Günsel Aziz , Edebal Oğuzhan , Akpınar Onur , Cerit Levent , Duygu Hamza
Published: February 2020

Background

This study aimed to investigate serum 25[OH]D levels between patients with vasovagal syncope (VVS) diagnosed with head‐up tilt table test (HUTT) and age‐matched healthy people.

Methods

The study included 75 consecutive patients (32.3 ± 10.7 years), who presented with syncope and underwent HUTT and 52 healthy controls (32.9 ± 14.1 years). HUTT patients were divided into two groups according to whether there was syncope response to the test. Patients underwent cardiac, psychiatric, and neurological investigation. Serum 25[OH]D levels were measured by chemiluminescent microparticle immunoassay method.

Results

There was no difference between the two groups in terms of age, gender, body mass index (BMI), echocardiographic findings (P > .05). Mean serum 25[OH]D (24.5 ± 6.3 vs 20.1 ± 8.8 ng/mL, P = .003) and vitamin B12 levels (436.4 ± 199.2 vs 363.1 ± 107.6 pg/mL, P = .009) was lower in syncope patients when compared to the control group. In correlation analyses, syncope was shown as correlated with the vitamin D (r = −264, P = .003) and vitamin B12 levels (r = −233, P = .009). But, multivariate regression analyses showed that only vitamin D increased risk of syncope [OR: 0.946, 95% CI (0.901‐0.994)]. There was no difference in terms of age, gender, BMI, echocardiographic findings between the in HUTT positive (n = 45) and negative groups (n = 29). Only vitamin D level was significantly lower in HUTT positive group (17.5 ± 7.7 vs 24.4 ± 9.1 ng/mL, P = .002). There was no difference among in the vasovagal subgroups in terms of vitamin D level and other features.

Conclusion

Vitamin D and B12 levels were reasonably low in syncope patients, but especially low Vitamin D levels were associated with VVS diagnosed in HUTT.
Cationic Bottlebrush Polymers from Quaternary Ammonium Macromonomers by Grafting‐Through Ring‐Opening Metathesis Polymerization
Authors: Senkum Hathaithep , Gramlich William M.
Published: February 2020

Cationic bottlebrush homopolymers are polymerized using a grafting‐through approach by ring‐opening metathesis polymerization (ROMP) to afford well‐defined polymers. Quaternary ammonium macromonomers (MMs) are prepared by quaternizing tertiary amine MMs synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization. The quaternary ammonium MMs undergo ROMP to target molecular weights (Mn = 30 000–100 000 g mol−1) and a low dispersity (Đ = 1.10–1.30). Halide‐ligand exchange between the third generation Grubbs catalyst (G3) and halide counter ions (bromide and iodide ions) of MMs changes the catalyst activity throughout ROMP, causing it to deviate from pseudo‐first order kinetic behavior; however, the polymerization still follows controlled behavior without significant catalyst termination. Increasing steric bulk of the MMs decreases the polymerization rate as well. Amphiphilic block copolymers are synthesized by sequential polymerization of quaternary ammonium MMs and polystyrene (PS) MMs. Using a PS macroinitiator affords block copolymers with lower Đ values as compared to the less active cationic macroinitiator.
Carboxylic Acid Enriched Porous Organic Polymer as a Platform for Highly Efficient Removal of Methylene Blue from Aqueous Solution
Authors: Yan Kun‐Yun , Chen Jia‐Yi , Li Xin‐Yu , Wang Qiang , Kuang Gui‐Chao
Published: February 2020

To develop highly efficient organic dyes adsorbents are of great importance for environmental issues. In this work, a negatively charged porous organic polymer (POP) is synthesized by simple aromatic nucleophilic substitution (SNAr) and hydrolysis reaction. This polymer POP‐TFP‐COOH structure is confirmed by IR and 13C cross‐polarization/magic‐angle‐spinning nuclear magnetic resonance. Due to the existence of phenyl rings and carboxylic acid groups, POP‐TFP‐COOH displays excellent adsorption ability for the positive dye methylene blue (MB), with a maximum value of 2740 mg g−1. This porous polymer can be reused at least four times without obvious loss of its adsorption capacity.
Adenosine A2A receptor activation reduces brain metastasis via SDF‐1/CXCR4 axis and protecting blood‐brain barrier
Authors: Chen Lei , Li Liangdong , Zhou Changshuai , Chen Xin , Cao Yiqun
Published: February 2020

Brain metastasis is a leading cause of death worldwide, but the mechanism involved remains unclear. Stromal cell‐derived factor‐1 (SDF‐1)/C‐X‐C motif chemokine receptor 4 (CXCR4) signaling has been reported to induce the directed metastasis of cancers, and adenosine A2A receptor activation suppresses the SDF‐1/CXCR4 interaction. However, whether A2A receptor activation implicates the SDF‐1/CXCR4 signaling pathway and thus modulates brain metastasis remains unclear. In this study, Western blot was performed to evaluate the protein levels. Cell invasion and migration assays were used to estimate the metastasis ability of PC‐9 cells. The viability of cells was demonstrated by lactate dehydrogenase and cell proliferation assays. And the findings in vitro were further identified in nude mice. Notably, adenosine A2A receptor activation inhibited the proliferation and viability of PC‐9 cells and thus suppressed the brain metastasis. A2A receptor stimulation protected the function of blood‐brain barrier (BBB). The suppression of brain metastasis and the protection of BBB by A2A receptor relied on SDF‐1/CXCR4 signaling, and treatment using A2A receptor agonist and CXCR4 antagonist protected the nude mice from malignancy metastasis in vivo. Adenosine A2A receptor activation suppressed the brain metastasis by implicating the SDF‐1/CXCR4 axis and protecting the BBB.
Replication‐Based Rearrangements Are a Common Mechanism for SNCA Duplication in Parkinson's Disease
Authors: Seo Soo Hyun , Bacolla Albino , Yoo Dallah , Koo Yoon Jung , Cho Sung Im , Kim Man Jin , Seong Moon‐Woo , Kim Han‐Joon , Kim Jong‐Min , Tainer John A. , Park Sung Sup , Kim Ji Yeon , Jeon Beomseok
Published: February 2020

Background

SNCA multiplication is a genomic cause of familial PD, showing dosage‐dependent toxicity. Until now, nonallelic homologous recombination was suggested as the mechanism of SNCA duplication, based on various types of repetitive elements found in the spanning region of the breakpoints. However, the sequence at the breakpoint was analyzed only for 1 case.

Objectives

We have analyzed the breakpoint sequences of 6 patients with PD who had duplicated SNCA using whole‐genome sequencing data to elucidate the mechanism of SNCA duplication.

Methods

Six patient samples with SNCA duplication underwent whole‐genome sequencing. The duplicated regions were defined with nucleotide‐resolution breakpoints, which were confirmed by junction polymerase chain reaction and Sanger sequencing. The search for potential non‐B DNA‐forming sequences and stem‐loop structure predictions was conducted.

Results

Duplicated regions ranged from the smallest region of 718.3 kb to the largest one of 4,162 kb. Repetitive elements were found at 8 of the 12 breakpoint sequences on each side of the junction, but none of the pairs shared overt homologies. Five of these six junctions had microhomologies (2–4 bp) at the breakpoint, and a short stretch of sequences was inserted in 3 cases. All except one junction were located within or next to stem‐loop structures.

Conclusion

Our study has determined that homologous recombination mechanisms involving repetitive elements are not the main cause of the duplication of SNCA. The presence of microhomology at the junctions and their position within stem‐loop structures suggest that replication‐based rearrangements may be a common mechanism for SNCA amplification. © 2020 International Parkinson and Movement Disorder Society
Comprehensive analysis of prognosis‐related methylated sites in breast carcinoma
Authors: Li Jia , Li Xinzheng
Published: February 2020

Background

Breast carcinoma has become a nonnegligible public health problem in China with its increasing incidence and mortality in woman. As a early event regulating tumorigenesis and development, DNA methylation became one of the focuses of current carcinoma researches on potential diagnostic and therapeutic targets.

Methods

In this study, we comprehensively analyzed the gene expression data and DNA methylation data of breast carcinoma and adjacent normal tissues samples in the Gene Expression Omnibus database. Influences of tumor stage, adjuvant therapy, hormone therapy, and chemotherapy on CpG methylation level were explored by linear regression analysis. Correlations between methylation and gene expression levels were determined by spearman rank correlation analysis. Log‐rank test was applied for determining significance of associations between CpG sites methylation level and breast cancer patients' Kaplan–Meier survival.

Results

A total of 229 CpG sites were found to be significantly associated with tumor stage or treatment, and eight of which were potential markers that affect the survival of breast carcinoma and negatively correlated with their genes' expression levels.

Conclusions

We reported eight CpG sites as potential breast cancer prognosis signatures through comprehensively analyzed gene expression and DNA methylation datasets, and excluding influences of tumor stage and treatment. This should be helpful for breast cancer early diagnosis and treatment.
Kansas treatment center thrives in helping youth with MI
Authors: Canady Valerie A.
Published: February 2020

The overwhelming need to provide more psychiatric services for children and teens in Kansas, and an outpouring of financial and community support, are the driving factors behind a new treatment center that opened six months ago in Wichita. Since then, more than 500 Wichita‐area youth have received life‐saving psychiatric treatment, officials said.
Cough stress tests to diagnose stress urinary incontinence in women with pelvic organ prolapse with indication for surgical treatment
Authors: Espuña‐Pons Montserrat , Diez‐Itza Irene , Anglès‐Acedo Sònia , Covernton Patrick J. O. ,   on behalf of GISPEM group
Published: February 2020

Aims

To evaluate the diagnostic ability of different cough stress tests (CSTs) in women with pelvic organ prolapse (POP), performed during outpatient urogynaecological exams.

Methods

Prospective, multicentre observational study involving women on waiting lists for POP surgery. With a subjectively full bladder, patients were asked to perform five different CSTs: without prolapse reduction ([a] standing, followed by [b] semilithotomy position); keeping semilithotomy position with prolapse reduced (by [c] posterior speculum, followed by [d] pessary); [e] standing again with the pessary in place. Primary outcome was positive CST in at least one of the five CSTs. Bladder volume was measured and symptoms of stress urinary incontinence (SUI) were detected by two validated questionnaires.

Results

A total of 297 women completed all CSTs and were included in the analyses. Mean (SD) age, parity, and body mass index were 64.8 (9.9) years, 2.7 (1.3) deliveries, and 26.6 (3.4) kg/m2, respectively. In total, 99 women (33.3%) reported SUI symptoms. At least one positive CST was recorded in 152 patients (51.1%), and in 90 (59.2%) of these 152, a positive CST was observed only when POP was reduced (occult SUI). The CST was positive in 92 (92.9%) of the 99 patients with coexisting SUI symptoms and in 60 (30.3%) of the 205 asymptomatic patients. The percentage of patients with a positive CST was significantly lower when bladder volume was <200 mL vs ≥200 mL (P = .046).

Conclusions

The identification of urinary leakage cases with CSTs is best achieved using multiple different patient positions, different prolapse reduction methods, and bladder volumes ≥200 mL.
Urethral dysfunction and therapeutic effects of a PDE 5 inhibitor (tadalafil) in a rat model of detrusor underactivity induced by pelvic nerve crush injury
Authors: Takaoka Ei‐Ichiro , Kurobe Masahiro , Suzuki Takahisa , Shimizu Nobutaka , Kwon Joonbeom , Okada Hiroki , Yoshimura Naoki , Chermansky Christopher J.
Published: February 2020

Aims

The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor.

Methods

Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC‐UPP) measurements were performed. Also, in control rats, IC‐UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC‐UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real‐time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats.

Results

PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats.

Conclusions

PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU.
A proactive defense method for the stealthy EDoS attacks in a cloud environment
Authors: Agrawal Neha , Tapaswi Shashikala
Published: February 2020

Cloud computing technology provides flexibility to Cloud Service Provider (CSP) for providing the cloud resources based on the users' requirements. In on‐demand pricing model, the attackers exploit this feature and cause unwanted scaling‐up of the cloud resources without any intent to pay for them. The associated cost for the unpaid malicious usage burdens the CSP, and over a long period, economic losses occur at the CSP end. Thus, the resources and services offered by the CSP become unsustainable, and the attack is termed as Economic Denial‐of‐Sustainability (EDoS) attack. The existing defense approaches for EDoS attacks are reactive. Thus, the associated attack detection/mitigation cost is high; consequently, the approaches are not suitable for the Small and Medium Enterprises (SMEs). The aim of this paper is to detect and mitigate, internal and external, stealthy EDoS attacks proactively. The attack is detected using average CPU utilization threshold and utility function (in terms of cost for the utilized cloud computing resources) and mitigated using virtual firewalls. Amazon Elastic Compute Cloud (Amazon EC2) is used to evaluate the performance of the proposed approach. The proposed approach accurately detects the EDoS attack and mitigates its effect as well with reduced cost. It is observed that the approach provides competitive response time, victim service downtime, and attack reporting time. Thus, the overall performance is improved.
The evolution of interorganizational trust in cross‐sector collaborations: Two comparative cases from China
Authors: Tu Wen , Xu Yuanyuan
Published: February 2020

This study views interorganizational trust as a dynamic process and examines it in two cross‐sector collaborations in community development. Based on in‐depth case study, we conceptualize the evolution of interorganizational trust into four distinct stages: initial propensity, boundary spanning, diffusion and normalization. The findings show that sustainable cross‐sector collaboration requires the full evolution of interorganizational trust. The findings also highlight the importance of internal motivation and the participation of third parties. In addition, while formal rules contribute to rational trust, informal rules arising from interactive experiences can complement formal rules and promote emotional trust.
Examination of the influence of cedar fragrance on cognitive function and behavioral and psychological symptoms of dementia in Alzheimer type dementia
Authors: Takahashi Yuya , Shindo Sho , Kanbayashi Takashi , Takeshima Masahiro , Imanishi Aya , Mishima Kazuo
Published: February 2020

We examined whether symptoms of dementia are improved by olfactory nerve stimulation in Alzheimer type dementia patients. First, a stick‐type olfactory identification ability test was performed in patients with Alzheimer type dementia, to select patients without olfactory dysfunctions. Then, these patients were randomly assigned into the intervention (n = 19) and the control groups (n = 17). To evaluate the effects of olfactory nerve stimulation, we exposed the intervention group to a disinfecting ethanol with added aroma extracts from ceder and the control group to the ethanol without the added aroma extracts. Each group underwent the intervention for 8 weeks, cognitive and behavioral functions were evaluated before and after treatments using the Neuropsychiatric Inventory (NPI), the Japanese version of Zarit Caregiver Burden interview (J‐ZBI), and the Alzheimer's Disease Assessment Scale‐cognitive subscale (ADAS‐cog). A significant improvement was observed in the NPI score and J‐ZBI in the intervention group compared to the control group at 4 and 8 weeks. On the other hand, there was no significant difference in the score of ADAS‐cog. Exposure to cedar fragrance improved behavioral and psychological symptoms of dementia (BPSD) in Alzheimer type dementia and may reduce the burden of nursing care. In addition to its effectiveness, the procedure is simple and minimally invasive and would be a valuable non‐pharmaceutical treatment.
Evolution of a prenatal genetic clinic—A 10‐year cohort study
Authors: Mone Fionnuala , O'Connor Clare , Hamilton Susan , Quinlan‐Jones Elizabeth , Allen Stephanie , Marton Tamas , Williams Denise , Kilby Mark D.
Published: February 2020

OBJECTIVE

To (a) evaluate the proportion of women where a unifying genetic diagnosis was obtained following assessment of an observed pattern of fetal anomalies and (b) assess trends in genetic testing in a joint fetal‐medicine genetic clinic.

METHOD

Retrospective cohort study of all women attending the clinic. Outcomes included (a) indication for referral, (b) genetic test performed and (c) diagnoses obtained.

RESULTS

From 2008 to 2019, 256 patients were referred and reviewed, of which 23% (n = 59) were consanguineous. The main indication for referral was the observed pattern of fetal anomalies. Over 10 years, the number of patients reviewed increased from 11 to 35 per annum. A unifying genetic diagnosis was obtained in 43.2% (n = 79/183), the majority of which were diagnosed prenatally (50.6% [n = 40/79]). The main investigation(s) that was the ultimate diagnostic test was targeted gene panel sequencing 34.2% (n = 27/79), with this and exome sequencing becoming the dominant genetic test by 2019. Pregnancies reviewed due to an abnormal karyotype or microarray decreased as an indication for referral during the study period (21.6% [n = 16/74] 2008‐2012 vs 16.5% [n = 30/182] in 2012‐2019).

CONCLUSION

A prenatal genetic clinic with a structured multi‐disciplinary team approach may be successful in obtaining a unifying prenatal genetic diagnosis.
Agenesis of the septum pellucidum: Prenatal diagnosis and outcome
Authors: Borkowski‐Tillman Tamar , Garcia‐Rodriguez Raquel , Viñals Fernando , Branco Miguel , Kradjen‐Haratz Karina , Ben‐Sira Liat , Lerman‐Sagie Tally , Malinger Gustavo
Published: February 2020

Objective

The purpose of this study is to describe the imaging findings in a group of fetuses with suspected agenesis of the septum pellucidum (ASP) and to evaluate their clinical outcome.

Methods

This is a retrospective multicenter study on a cohort of fetuses diagnosed with suspected ASP, between 2008 and 2017. The records of each patient, including ultrasound (US) and magnetic resonance studies, were reviewed and compared with the postnatal findings.

Results

Forty‐seven patients were included in the study at a mean gestational age of 26.6 weeks. In 17 patients, the ASP was considered isolated. Fourteen patients delivered live‐born, and all 14 are developing normally. Three were lost to follow‐up. Twenty‐four patients had associated malformations involving the central nervous system (CNS); 13 were delivered (normal development [5], abnormal [6] and no follow‐up [2]). Nine patients opted for termination, and two pregnancies were lost to follow‐up.

Six patients had non‐CNS associated findings, two were delivered with normal neurological development and four had a termination.

Conclusions

Isolated ASP is usually associated with a favorable outcome; but in the presence of associated malformations, there is at least a 50% risk of abnormal development. Current imaging techniques can provide an accurate prognosis in cases when ASP appears isolated.
Controversies in antenatal corticosteroid treatment
Authors: Thevathasan Iniyaval , Said Joanne M.
Published: February 2020

Antenatal corticosteroids are now established as one of the cornerstones of therapy in the prevention of neonatal morbidity and mortality prior to preterm birth. Although this practice is widely accepted, a significant number of controversies exist. This review explores the knowledge gaps regarding the use of antenatal corticosteroids in the preterm, late preterm and term populations. Furthermore, the role of antenatal corticosteroids in special populations, such as diabetes, multiple pregnancies and periviable gestations, where high‐quality data from randomized controlled trials are lacking, is also considered.
First‐trimester sonographic diagnosis of sirenomelia: A multicenter series of 12 cases and review of the literature
Authors: Sepulveda Waldo , Bornstein Eran , Andreeva Elena , Montano Ignacio , Gutierrez Jorge , Martinez‐Ten Pilar , Meagher Simon
Published: February 2020

Objective

To determine the key sonographic features for the diagnosis of sirenomelia in the first trimester of pregnancy.

Methods

Cases of sirenomelia from several prenatal diagnosis centers were retrospectively identified and reviewed. The diagnosis was established through the detection of fused lower limbs. Additional sonographic findings were also noted.

Results

A total of 12 cases were collected. The most striking sonographic finding was the detection of malformed lower limbs, which appeared to be fused and in an atypical position. Nuchal translucency thickness was mildly increased in three cases (25%). An abdominal cyst, representing the dilated blind‐ending bowel, was noted in seven cases (58%). Color flow imaging detected a single umbilical artery in six cases (50%) and the associated intra‐abdominal vascular anomalies in three cases (25%). No cases of aneuploidy were detected. The pregnancy was terminated in nine cases (75%) and intrauterine demise occurred in the remaining three cases (25%).

Conclusions

The sonographic detection of abnormal lower limbs or an intra‐abdominal cyst located laterally during the first‐trimester scan may be warning signs of sirenomelia. This should prompt a detailed examination of the fetal lower body and intra‐abdominal anatomy, including the main abdominal vessels, in order to look for additional confirmatory findings.
Exploring mechanisms of rapid automatized naming to arithmetic skills in Chinese primary schoolers
Authors: Wang Yiji , Ye Xiaolin , Deng Ciping
Published: February 2020

Rapid automatized naming (RAN) is associated with children's arithmetic performance, which is multifactorial by nature and consists of arithmetic fluency, arithmetic procedure, and word problems. Yet, it is unclear whether RAN can predict all key aspects of arithmetic skills independently and what cognitive mechanisms may explain this relation. Using a sample of Chinese primary school students (N = 170), results showed that while RAN was associated with all key aspects of arithmetic skills, the relations of RAN–arithmetic procedure and RAN–word problems may be dependent on that of RAN–arithmetic fluency. Supporting the processing speed hypothesis, results further suggested that processing speed may underlie the relation between RAN and arithmetic performance. Findings made unique contribution to understanding the effect of RAN on arithmetic performance and cognitive mechanisms that may underpin this association in the context of Chinese culture.
A chewable pediatric preparation of ibuprofen is palatable and acceptable to children
Authors: Barnett Steven , Bhatt Aomesh
Published: February 2020

The development of palatable and acceptable analgesics for children is a major challenge. Given the majority of medications are administered orally, and children are more sensitive to and less tolerant of bitterness, novel “child‐friendly” preparations need to be developed and tested specifically in this patient population. This study investigated the palatability and acceptability of a therapeutic dose of ibuprofen in the form of soft chewable capsules in 100 healthy children aged 7‐12 years of age and the acceptability of this novel preparation to their caregivers. About 97% of children adhered to a full therapeutic age‐related dose, with 72% of these participants rating the preparation as acceptable on a hedonic facial scale. Despite 22% of children noting a “hot, spicy, or burning” sensation, consistent with known chemesthetic effects of ibuprofen, 83% of children confirmed they would take the medication in future, which rose to 87% in the context of future illness. In addition, after observing their children ingesting the medication, 92% of parents/guardians confirmed that they would be happy to administer this preparation of ibuprofen to their child if they were unwell. In conclusion, ibuprofen administered in the form of soft chewable capsules was palatable and acceptable to the majority of children and their parents/guardians and may provide a convenient and easy to dose preparation to reduce fever and relieve pain in children.
Amphiphilic water soluble cationic ring opening metathesis copolymer as an antibacterial agent
Authors: Islam Muhammad Nazrul , Aksu Burak , Güncü Mehmet , Gallei Markus , Tulu Metin , Eren Tarik
Published: February 2020

Bacterial infection is a global problem, especially resistance acquired by bacteria against to antibiotics; there is urgent need for the development of antibiotics. Here, we proposed dendron‐grafted polymers via ring opening metathesis polymerization (ROMP) featuring different with tailored hydrophobicity/hydrophilicity and cationic charges. Dendritic oxanorbornene derivatives were synthesized having two and six carbon linkers and their corresponding random and block copolymers were prepared having pendant pyridinium salt moieties via ROMP. In total, 12 different water‐soluble dendronized cationic polymers featuring hexyl pyridinium moieties were prepared and investigated. Six carbon linker possessing triple charge density and hexyl pyridinium functionality each repeating unit copolymers exhibited high antibacterial activity against Gram‐positive bacteria (S. aureus). However, all the polymers were inactive against Gram‐negative bacteria (E. coli). Most of the copolymers are non‐hemolytic (>HC
50 = 1,000 μg/ml). It was also observed that, there is no significant effect between block copolymers and random copolymers keeping hydrophobicity and cationic charge density constant. Zeta potential was measured to investigate the mechanism in solution via the interaction of polymers with S. aureus, while scanning electron microscope (SEM) measurements image confirms damage of the bacterial cell wall after implementation of biocidal polymer.
Composition‐dependent crystallization behavior of copolyperoxides from methyl methacrylate and 4‐vinylbenzyl stearate
Authors: Mete Sourav , Goswami Krishna Gopal , De Priyadarsi
Published: February 2020

To study the composition‐dependent crystallization behavior of copolyperoxides, herein a series of copolymers were prepared by varying the ratios of methyl methacrylate (MMA) and 4‐vinylbenzyl stearate (VBS) under 100 psi oxygen pressure using AIBN as an initiator at 50°C in toluene. Both 13C NMR and electron impact mass spectroscopy (EI‐MS) approved an alternative placement of either of the monomer and peroxy (–O–O–) links throughout the polymer chain. Thermal stability of the resulting copolyperoxides was investigated by thermogravimetric analysis (TGA) and the degradation fragments have been recognized from EI‐MS study. In addition, differential scanning calorimetry (DSC) displayed an endothermic peak as well as an exotherm associated with the melting of the side chain crystalline domains and degradation of –O–O– links in the polymer main chain, respectively. Furthermore, DSC thermograms unveiled a systematic decrease of the crystalline melting temperature (Tm) with the enhancement of MMA content in the copolymers. Small angle X‐ray scattering (SAXS) revealed the existence of lamellar morphology (depends on VBS content in the copolyperoxide) in the synthesized polyperoxide materials, further supported by atomic force microscopy (AFM) analysis showing a layered fibrillar assembly with multiple heights of the lamella. The significant crystalline nature of the polyperoxides was further evidenced from the appearance of lattice fringes in the transmission electron microscope (TEM) micrographs. The crystalline morphology with birefringent texture was further evidenced from the polarized optical microscopy (POM) study. Thus, the present study reported the effective variation of crystalline behavior in copolyperoxide materials with the incorporation of MMA units in the copolyperoxide chains.
Assessing and responding to stress related to pulmonary function testing in cystic fibrosis through quality improvement
Authors: Nusbaum Kelsey , Filigno Stephanie S. , Feldstein Julie , Hente Elizabeth , Koch Elizabeth , Mullen Lisa , Weiland Jeanne , Boat Thomas , Siracusa Christopher
Published: February 2020

Background

Pulmonary function tests (PFTs) are performed routinely to evaluate lung function in patients with cystic fibrosis (CF). Staff at the Cincinnati Children's Hospital Medical Center CF Center observed stress in patients before PFTs. An interdisciplinary quality improvement (QI) team was assembled to address this clinical issue.

Methods

The Plan‐Do‐Study‐Act method of QI was used to investigate feasibility of assessing stress and offering brief interventions to reduce stress before PFTs. Interventions included listening to music, covering the PFT screen, or doing breathing meditation before PFTs. Patients rated stress levels on a 1 to 5 Likert scale before and after testing.

Results

Of 75 patient encounters, interventions were trialed in 20. Fifteen patients who tried an intervention reported wanting to use the intervention again (five encounters had missing data); patients reported that the intervention benefited performance on PFTs in eight encounters (40%). The average pre‐PFT stress rating for encounters that trialed an intervention was 2.1 and post‐PFT rating was 2.0. Average stress pre‐PFT and post‐PFT ratings were 1.7 and 1.6 respectively, for encounters that did not trial an intervention. Median length of PFT encounter was 15  minutes regardless of whether intervention was trialed.

Conclusion

Some patients with CF utilized interventions, while many opted out. This QI effort identified feasible outpatient clinic interventions that did not negatively impact clinic flow. Finding ways to reduce stress associated with PFTs could have a meaningful impact on patient performance and emotional well‐being for a subset of patients.
Low fitness and increased sedentary time are associated with worse asthma—The National Youth Fitness Survey
Authors: Lu Kim D. , Forno Erick , Radom‐Aizik Shlomit , Cooper Dan M.
Published: February 2020

Background

Asthma is the most common chronic illness in children and is independently impacted by obesity and by fitness. The National Youth Fitness Survey collected data on aerobic fitness, body composition, and health outcomes in children 6 to 11 years old. The goal of this study is to test hypotheses regarding relationships between asthma, aerobic fitness, and sedentary time in this uniquely studied cohort of young children.

Methods

A total of 665 children (6‐11 years old; 49% male) were included in analyses. We explored relationships between asthma outcomes and aerobic fitness (measured by endurance time), self‐reported sedentary time, and body mass index categories. Fitness was categorized as unfit (lowest 25% of endurance times) or fit. Multivariate logistic regression models were created for asthma outcomes and adjusted for race, age, sex, poverty status, and overweight/obesity.

Results

Among the participants, 17.9% had a previous history of asthma and 11.4% had current asthma. Additionally, 37.3% of participants were overweight or obese. Low fitness was significantly associated with increased odds of past asthma, current asthma, asthma attacks, wheeze with exercise, and wheeze with activity limitations in multivariate models. Increased sedentary time was significantly associated with increased odds of previous asthma, current asthma, asthma attacks, and wheeze with activity limitations.

Conclusion

Decreased aerobic fitness and increased sedentary time were associated with worse asthma outcomes in this group of children (6‐11 years old). This data suggest that fitness and sedentary time, both modifiable factors, each have an independent effect on asthma and should be included in assessments and management of asthma health.
Oxygen insecurity and mortality in resource‐constrained healthcare facilities in rural Kenya
Authors: Otiangala Dickson , Agai Nicholas O. , Olayo Bernard , Adudans Steve , Ng Chin Hei , Calderon Ryan , Forgie Ella , Bachman Christine , Lieberman Daniel , Bell David , Hawkes Michael , Somoskovi Akos
Published: February 2020

Introduction

Pneumonia is the leading cause of death globally in children. Supplemental oxygen reduces mortality but is not available in many low‐resource settings. Inadequate power supply to drive oxygen concentrators is a major contributor to this failure. The objectives of our study were to (a) assess the availability of therapeutic oxygen; (b) evaluate the reliability of the electrical supply; and (c) investigate the effects of suboptimal oxygen delivery on patient outcomes in selected healthcare facilities in rural Kenya.

Materials and Methods

A cross‐sectional descriptive study on oxygen availability and descriptive case series of Kenyan children and youth hospitalized with hypoxemia.

Results

Two of 11 facilities had no oxygen equipment and nine facilities had at least one concentrator or cylinder. Facilities had a median of seven power interruptions per week (range: 2‐147). The median duration of the power outage was 17 minutes and the longest was more than 6 days. The median proportion of time without power was out 7% (range: 1%‐58%). Fifty‐seven patients hospitalized with hypoxemia (median oxygen saturation 85% [interquartile range {IQR}: 82‐87]) were included in our case series. Patients received supplemental oxygen for a median duration of 4.6 hours (IQR: 3.0‐7.8). Eighteen patients (32%) faced an oxygen interruption of the median duration of 11 minutes (IQR: 9‐20). A back‐up cylinder was used in 5/18 (28%) cases. The case fatality rate was 11/57 (19%).

Conclusion

Mortality due to hypoxemia remains unacceptably high in low‐resource healthcare facilities and may be associated with oxygen insecurity, related to lack of equipment and/or reliable power.
Lung biopsy in children's interstitial and diffuse lung disease: Does it alter management?
Authors: Hafezi Niloufar , Heimberger Mark A. , Lewellen Kyle A. , Maatman Thomas , Montgomery Gregory S. , Markel Troy A.
Published: February 2020

Introduction

Pediatric patients with acute life‐threatening consequences of interstitial and diffuse lung disease are often treated with empiric systemic corticosteroids, immune modulators, and/or broad antibiotic therapy. Histological evaluation of lung tissue represents the final necessary step in diagnosis—however, a definitive diagnosis may still remain elusive and medical therapies may not be changed following biopsy. We hypothesized that lung biopsy from pediatric patients with children's interstitial and diffuse lung disease (chILD) without a defined lesion on computed tomography (CT) imaging would guide diagnosis, but not substantially alter clinical management.

Methods

After IRB approval, patients who underwent a lung biopsy at a single large children's hospital between 2013 and 2018 were retrospectively reviewed. Patients without a defined lesion were included. Demographics, length of stay, oxygen‐requirements, steroid, unique number of immune modulators, and antibiotics prebiopsy and postbiopsy were reviewed. Nonparametric data were compared by the Mann Whitney U and Kruskal Wallace tests and expressed as median with interquartile range. Decision tree alterations were analyzed by t test. P < .05 was significant.

Results

Sixty‐four patients underwent lung biopsy during the period. Nineteen (30%) did not have a defined lesion on CT scan, and were included. A significant difference was seen between prebiopsy, 2 weeks, and 2 months postbiopsy prednisone dosing (P = .03), while the number of unique immune modulators, antibiotics, type of oxygen support and FiO2 were not significantly different before or after obtaining biopsy results. Pathology results provided additional information in 12 of 19 (63%) patients which resulted in management changes.

Conclusions

Lung biopsy in chILD may guide clinical management, especially influencing the management of steroid dosing. Although on aggregate the number of antibiotics, immune modulators, mode of oxygen support and FiO2 did not differ significantly before and after biopsy, the pathologic evaluation provided diagnostic information that led to a variety of changes in therapeutic management in greater than half of the population.
Development and validation of a simple‐to‐use nomogram for predicting refractoryMycoplasma pneumoniaepneumonia in children
Authors: Cheng Siying , Lin Jilei , Zheng Xuexiang , Yan Li , Zhang Yin , Zeng Qing , Tian Daiyin , Fu Zhou , Dai Jihong
Published: February 2020

Objective

This study aimed to develop and validate a simple‐to‐use nomogram for predicting refractoryMycoplasma pneumoniaepneumonia (RMPP) in children.

Methods

A total of 73 children with RMPP and 146 children with generalMycoplasma pneumoniaepneumonia were included. Clinical, laboratory, and radiological data were obtained. A least absolute shrinkage and selection operator (LASSO) regression model was used to determine optimal predictors. The nomogram was plotted by multivariable logistic regression. The performance of the nomogram was assessed by calibration, discrimination, and clinical utility.

Results

The LASSO regression analysis identified lactate dehydrogenase, albumin, neutrophil ratio, and high fever as significant predictors of RMPP. This nomogram‐illustrated model showed good discrimination, calibration, and clinical value. The area under the receiver operating characteristic curve of the nomogram was 0.884 (95% CI, 0.823‐0.945) in the training set and 0.881 (95% CI, 0.807‐0.955) in the validating set. Calibration curve and Hosmer‐Lemeshow test showed good consistency between the predictions of the nomogram and the actual observations, and decision curve analysis showed that the nomogram was clinically useful.

Conclusion

A simple‐to‐use nomogram for predicting RMPP in early stage was developed and validated. This may help physicians recognize RMPP earlier.