bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of FadRACB system in formaldehyde detoxification, oxidative stress alleviation and antibiotic susceptibility in Stenotrophomonas maltophilia
Authors: Li Li-Hua , Wu Cheng-Mu , Lin Yi-Tsung , Pan Sz-Yun , Yang Tsuey-Ching
Published: April 2020

Background

Formaldehyde toxicity is invariably stressful for microbes. Stenotrophomonas maltophilia, a human opportunistic pathogen, is widely distributed in different environments and has evolved an array of systems to alleviate various stresses.

Objectives

To characterize the role of the formaldehyde detoxification system FadRACB of S. maltophilia in formaldehyde detoxification, oxidative stress alleviation and antibiotic susceptibility.

Methods

Presence of the fadRACB operon was verified by RT–PCR. Single or combined deletion mutants of the fadRACB operon were constructed for functional assays. Formaldehyde, menadione and quinolone susceptibilities were assessed by observing cell viability in formaldehyde-, menadione- and quinolone-containing media, respectively. Susceptibility to hydrogen peroxide was evaluated by disc diffusion assay. The agar dilution method was used to assess bacterial antibiotic susceptibilities. Expression of fadRACB was assessed by quantitative RT–PCR.

Results

The fadR, fadA, fadC and fadB genes were arranged in an operon. Mutants of fadA and/or fadB were more susceptible to formaldehyde and oxidative stress than the WT KJ strain of S. maltophilia. No significant difference was observed in the ability of a fadC single mutant to ameliorate formaldehyde and oxidative stress; however, simultaneous inactivation of fadA, fadB and fadC further enhanced susceptibility to formaldehyde and oxidative stress. In addition, compared with WT KJ, the triple mutant KJΔFadACB was more susceptible to quinolones and more resistant to aminoglycosides. FadR functions as a repressor for the fadRACB operon. The FadRACB operon has moderate expression in aerobically grown WT KJ and is further derepressed by formaldehyde challenge or oxidative stress, but not by antibiotics.

Conclusions

The FadACB system contributes to mitigation of formaldehyde toxicity and oxidative stress and cross-protects S. maltophilia from quinolones.
Bernese periacetabular osteotomy: functional outcomes in patients with untreated intra-articular lesions
Authors: Lara Joaquín , Garín Alan , Herrera Cristhián , Abara Selim , Besomi Javier , Villegas Diego , Neumann Hassan , Tobar Carlos
Published: April 2020

Developmental dysplasia of the hip (DDH) has been recognized to be a condition leading to osteoarthritis. Periacetabular osteotomy (PAO) has showed good results on hip preservation treatment for these cases. Nevertheless, intra-articular damage may be responsible for persistent post-operative symptoms, so treat the articular damage before or during the PAO has emerged as an alternative to address it. The objective is to identify the prevalence of intra-articular damage, functional outcomes of patients undergoing PAO with untreated intra-articular lesions and the survivorship free total hip arthroplasty (THA) at long-term follow-up. A retrospective review of 103 hips in 92 patients, mean age 26 years old (19–31), 96% females. Mean follow-up 7 years (range: 3–16). Intra-articular damage was evaluated with high-resolution magnetic resonance imaging (MRI) previous to perform the PAO, the chondral damage was evaluated using International Cartilage Repair Society classification. Harris Hip Score (HHS) was obtained in all patients. One hundred per cent of the cases had labral tears on MRI, hypertrophic labrum in 80.8% and paralabral cysts in 20.8%. Acetabular chondral damage was Grade 2 in 88.5% of the hips. HHS was good and excellent in 94%. Survivorship free of THA at 15 years was 87%. Chondrolabral damage is a common finding in patients with DDH. Despite that, excellent results are obtained with PAO without labral repair. We think the focus should be in the biomechanical and anatomical correction of the hip in patients with DDH.
Seasonal Changes of Host Use by Culiseta melanura (Diptera: Culicidae) in Central Florida
Authors: West Richard G , Mathias Derrick K , Day Jonathan F , Acevedo Carolina , Unnasch Thomas R , Burkett-Cadena Nathan D
Published: April 2020

The mosquito Culiseta melanura (Coquillett) is the primary enzootic vector of eastern equine encephalitis virus (EEEV), a zoonotic Alphavirus endemic to eastern North America. In its northern range, Cs. melanura is considered a strict avian biter, transmitting EEEV among susceptible birds in a cycle of enzootic amplification. In its southern range, however, Cs. melanura is more general in host use, feeding heavily upon birds but also reptiles and mammals. The goal of this study was to better understand how host use of Cs. melanura changes throughout the year in Florida, where year-round EEEV transmission is observed. Mosquitoes were sampled in 2018 from nine sites across three central Florida counties. In total, 213 Cs. melanura bloodmeals were identified by PCR consisting of 39 species of birds, reptiles, and mammals. Avian bloodmeals were prominent throughout the year (range = 30–85%), and songbirds were a large portion of identified bloodmeals (37.1%). Reptiles surpassed birds only in spring (April–June), and brown anole (Anolis sagrei Duméril and Bibron, 1837 [Reptilia: Dactyloidae]) was the most commonly detected single host species (22.1% overall). Mammalian bloodmeals were mainly observed in summer, with humans being the most fed on mammal (12.7% overall). This study reveals that in southern foci of EEEV transmission, Cs. melanura host use varies throughout the year with reptiles providing the majority of blood meals in spring (51.3%), and birds are fed on more than other host groups during all other seasons (50.6–70.1%). In addition, feeding on mammals increases during summer months, which may implicate Cs. melanura in epizootic transmission in Florida.
An unusual presentation of acute onset Charcot arthropathy
Authors: Al-Najjar Ammar , Al Shakarchi Julien , Pereira Melwyn , Downing Richard
Published: April 2020

Charcot arthropathy is a progressive condition primarily affecting the lower limbs in patients with diabetes mellitus. It is a rare complication of diabetic neuropathy and if left untreated can lead to severe limb destruction necessitating major amputation. Here, we report the case of a 41-year-old female who presented with rapidly progressive Charcot foot over a 10-day period, necessitating open reduction and internal fixation of Lisfranc-type fracture dislocations. Her presentation with a rapidly progressing red, swollen foot with a blister on the plantar aspect prompted initial treatment on the basis of a diabetic foot infection. The report will therefore serve as a useful reminder to maintain a high index of suspicion for Charcot foot, which may present in an atypical manner.
The size of our causal Universe
Authors: Gaztañaga Enrique
Published: April 2020

A Universe with finite age also has a finite causal scale. Larger scales cannot affect our local measurements or modelling, but far away locations could have different cosmological parameters. The size of our causal Universe depends on the details of inflation and is usually assumed to be larger than our observable Universe today. To account for causality, we propose a new boundary condition, that can be fulfill by fixing the cosmological constant (a free geometric parameter of gravity). This forces a cancellation of vacuum energy with the cosmological constant. As a consequence, the measured cosmic acceleration cannot be explained by a simple cosmological constant or constant vacuum energy. We need some additional odd properties such as the existence of evolving dark energy (DE) with energy-density fine tuned to be twice that of dark matter today. We show here that we can instead explain the current cosmic acceleration without DE (or modified gravity) as a the result of a primordial inflation with a causal scale smaller than the observable Universe today. Such scale corresponds to half the sky at z = 1 and 60 deg at z= 1100, which is consistent with the anomalous lack of correlations observed in the CMB.
In vitro modeling of glioblastoma initiation using PDGF-AA and p53-null neural progenitors
Authors: Bohm Alexandra K , DePetro Jessica , Binding Carmen E , Gerber Amanda , Chahley Nicholas , Berger N Dan , Ware Mathaeus , Thomas Kaitlin , Senapathi U , Bukhari Shazreh , Chen Cindy , Chahley Erin , Grisdale Cameron , Lawn Sam , Yu Yaping , Wong Raymond , Shen Yaoqing , Omairi Hiba , Mirzaei Reza , Alshatti Nourah , Pedersen Haley , Yong Wee , Weiss Samuel , Chan Jennifer , Cimino P J , Kelly John , Jones Steve , Holland Eric , Blough Michael , Cairncross Gregory
Published: April 2020

Background

Imagining ways to prevent or treat glioblastoma (GBM) has been hindered by a lack of understanding of its pathogenesis. Although overexpression of platelet derived growth factor with two A-chains (PDGF-AA) may be an early event, critical details of the core biology of GBM are lacking. For example, existing PDGF-driven models replicate its microscopic appearance, but not its genomic architecture. Here we report a model that overcomes this barrier to authenticity.

Methods

Using a method developed to establish neural stem cell cultures, we investigated the effects of PDGF-AA on subventricular zone (SVZ) cells, one of the putative cells of origin of GBM. We microdissected SVZ tissue from p53-null and wild-type adult mice, cultured cells in media supplemented with PDGF-AA, and assessed cell viability, proliferation, genome stability, and tumorigenicity.

Results

Counterintuitive to its canonical role as a growth factor, we observed abrupt and massive cell death in PDGF-AA: wild-type cells did not survive, whereas a small fraction of null cells evaded apoptosis. Surviving null cells displayed attenuated proliferation accompanied by whole chromosome gains and losses. After approximately 100 days in PDGF-AA, cells suddenly proliferated rapidly, acquired growth factor independence, and became tumorigenic in immune-competent mice. Transformed cells had an oligodendrocyte precursor-like lineage marker profile, were resistant to platelet derived growth factor receptor alpha inhibition, and harbored highly abnormal karyotypes similar to human GBM.

Conclusion

This model associates genome instability in neural progenitor cells with chronic exposure to PDGF-AA and is the first to approximate the genomic landscape of human GBM and the first in which the earliest phases of the disease can be studied directly.
1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine treatment after brain irradiation preserves cognitive function in mice
Authors: Bhat Kruttika , Medina Paul , He Ling , Zhang Le , Saki Mohammad , Ioannidis Angeliki , Nguyen Nhan T , Sodhi Sirajbir S , Sung David , Magyar Clara E , Liau Linda M , Kornblum Harley I , Pajonk Frank
Published: April 2020

Background

Normal tissue toxicity is an inevitable consequence of primary or secondary brain tumor radiotherapy. Cranial irradiation commonly leads to neurocognitive deficits that manifest months or years after treatment. Mechanistically, radiation-induced loss of neural stem/progenitor cells, neuroinflammation, and demyelination are contributing factors that lead to progressive cognitive decline.

Methods

The effects of 1-[(4-nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) on irradiated murine neurospheres, microglia cells, and patient-derived gliomaspheres were assessed by sphere-formation assays, flow cytometry, and interleukin (IL)-6 enzyme-linked immunosorbent assay. Activation of the hedgehog pathway was studied by quantitative reverse transcription PCR. The in vivo effects of NSPP were analyzed using flow cytometry, sphere-formation assays, immunohistochemistry, behavioral testing, and an intracranial mouse model of glioblastoma.

Results

We report that NSPP mitigates radiation-induced normal tissue toxicity in the brains of mice. NSPP treatment significantly increased the number of neural stem/progenitor cells after brain irradiation in female animals, and inhibited radiation-induced microglia activation and expression of the pro-inflammatory cytokine IL-6. Behavioral testing revealed that treatment with NSPP after radiotherapy was able to successfully mitigate radiation-induced decline in memory function of the brain. In mouse models of glioblastoma, NSPP showed no toxicity and did not interfere with the growth-delaying effects of radiation.

Conclusions

We conclude that NSPP has the potential to mitigate cognitive decline in patients undergoing partial or whole brain irradiation without promoting tumor growth and that the use of this compound as a radiation mitigator of radiation late effects on the central nervous system warrants further investigation.
Clinical utility of circulating miR-371a-3p for the management of patients with intracranial malignant germ cell tumors
Authors: Murray Matthew J , Ajithkumar Thankamma , Harris Fiona , Williams Rachel M , Jalloh Ibrahim , Cross Justin , Ronghe Milind , Ward Dawn , Scarpini Cinzia G , Nicholson James C , Coleman Nicholas
Published: April 2020

Background

The current biomarkers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) have limited sensitivity/specificity for diagnosing malignant germ cell tumors (GCTs) and “marker-negative” patients require histological confirmation for diagnosis. However, GCTs at intracranial sites are surgically relatively inaccessible and biopsy carries risks. MicroRNAs from the miR-371~373 and miR-302/367 clusters are over-expressed in all malignant GCTs and, in particular, miR-371a-3p shows elevated serum levels at diagnosis for testicular disease.

Methods

Using our robust preamplified qRT-PCR methodology, we quantified miR-371a-3p levels in serum and cerebrospinal fluid (CSF) in a series of 4 representative clinical cases, 3 with intracranial malignant GCT and 1 with Langerhans cell histiocytosis (LCH), compared with appropriate control cases.

Results

Serum and/or CSF miR-371a-3p levels distinguished those with intracranial malignant GCTs from LCH and, if known in real time, could have helped clinical management. The benefits would have included (1) the only confirmatory evidence of an intracranial malignant GCT in 1 case, supporting clinical decision making; (2) early detection of intracranial malignant GCT in another, where an elevated CSF miR-371a-3p level preceded the histologically confirmed diagnosis by 2 years; and (3) confirmation of an intracranial malignant GCT relapse with an elevated serum miR-371a-3p level, where serum and CSF AFP and HCG levels were below thresholds for such a diagnosis.

Conclusions

This series highlights the potential for microRNA quantification to assist the noninvasive diagnosis, prognostication, and management for patients with intracranial malignant GCTs. Serum and CSF should be collected routinely as part of future studies to facilitate the extension of these findings to larger patient cohorts.
The Impact of a Less Restrictive Poststernotomy Activity Protocol Compared With Standard Sternal Precautions in Patients Following Cardiac Surgery
Authors: Holloway Caitlyn , Pathare Neeti , Huta Jean , Grady Dana , Landry Andrea , Christie Claire , Pierce Patricia , Bopp Charity
Published: April 2020

Objective

Guidelines following median sternotomy typically include strict sternal precautions (SP). Recently, alternative approaches propose less functional restrictions while avoiding excessive stress to the sternum. The study aimed to determine the effect of a less restrictive (LR) approach versus a standard SP protocol after median sternotomy.

Methods

The study was a cross-sectional design (n = 364; SP: n = 172, 66.3 [SD = 11.2] years; LR: n = 196, 65.2 [SD = 11.2] years). This study ran in 2 consecutive phases and compared 2 groups after median sternotomy at a community-based hospital. The LR group received instructions on the Keep Your Move in the Tube approach. At 2 to 3 weeks after discharge, sternal instability was assessed using the Sternal Instability Scale, and patients completed a self-reported survey (perceived pain rating/frequency, sternal instability, and functional mobility). The 2 groups were compared using the Mann-Whitney U test and chi-square test (P < .05).

Results

There were no significant differences between the 2 groups for all the outcomes, Sternal Instability Scale, pain rating, pain frequency, perceived sternal instability, difficulty with functional mobility, length of stay, and discharge disposition.

Conclusions

In our study, the implementation of the LR approach, Keep Your Move in the Tube, had no adverse effect on outcomes 2 to 3 weeks following median sternotomy. Although no statistically significant differences were noted for all outcomes, patients with the LR approach reported less difficulty with functional mobility.

Impact Statement

These data are useful in clinical decision-making regarding alternative approaches for mobility following sternotomy.
DEFORMATION THEORY OF THE CHOW GROUP OF ZERO CYCLES
Authors: Lüders Morten
Published: April 2020

We study the deformations of the Chow group of zerocycles of the special fibre of a smooth scheme over a Henselian discrete valuation ring. Our main tools are Bloch’s formula and differential forms. As a corollary we get an algebraization theorem for thickened zero cycles previously obtained using idelic techniques. In the course of the proof we develop moving lemmata and Lefschetz theorems for cohomology groups with coefficients in differential forms.
Translating research into clinical practice: quality improvement to halve non-adherence to methotrexate
Authors: Barton Anne , Jani Meghna , Bundy Christine , Bluett James , McDonald Stephen , Keevil Brian , Dastagir Faraz , Aris Melissa , Bruce Ian , Ho Pauline , McCarthy Eoghan , Bruce Ellen , Parker Ben , Hyrich Kimme , Gorodkin Rachel
Published: April 2020

Objective

MTX remains the cornerstone for therapy for RA, yet research shows that non-adherence is significant and correlates with response to therapy. This study aimed to halve self-reported non-adherence to MTX at the Kellgren Centre for Rheumatology.

Methods

An anonymous self-report adherence questionnaire was developed and data collected for 3 months prior to the introduction of interventions, and then regularly for the subsequent 2.5 years. A series of interventions were implemented, including motivational interviewing training, consistent information about MTX and development of a summary bookmark. Information on clinic times was collected for consultations with and without motivational interviewing. Surveys were conducted to ascertain consistency of messages about MTX. A biochemical assay was used to test MTX serum levels in patients at two time points: before and 2.8 years following introduction of the changes. Remission rates at 6 and 12 months post-MTX initiation were retrieved from patient notes and cost savings estimated by comparing actual numbers of new biologic starters compared with expected numbers based on the numbers of consultants employed at the two time points.

Results

Between June and August 2016, self-reported non-adherence to MTX was 24.7%. Following introduction of the interventions, self-reported non-adherence rates reduced to an average of 7.4% between April 2018 and August 2019. Clinic times were not significantly increased when motivational interviewing was employed. Consistency of messages by staff across three key areas (benefits of MTX, alcohol guidance and importance of adherence) improved from 64% in September 2016 to 94% in January 2018. Biochemical non-adherence reduced from 56% (September 2016) to 17% (June 2019), whilst remission rates 6 months post-initiation of MTX improved from 13% in 2014/15 to 37% in 2017/18, resulting is estimated cost savings of £30 000 per year.

Conclusion

Non-adherence to MTX can be improved using simple measures including focussing on the adherence and the benefits of treatment, and providing consistent information across departments.
Effect of sleep on upper airway dynamics in obese adolescents with obstructive sleep apnea syndrome
Authors: Bitners Anna C , Sin Sanghun , Agrawal Sabhyata , Lee Seonjoo , Udupa Jayaram K , Tong Yubing , Wootton David M , Choy Kok Ren , Wagshul Mark E , Arens Raanan
Published: April 2020

Study Objectives

The biomechanical basis of obstructive sleep apnea syndrome (OSAS) may influence upper airway dynamics. In this study, we investigate dynamic changes during respiration in wakefulness and sleep in obese adolescents with and without OSAS.

Methods

Respiratory-gated dynamic magnetic resonance imaging (MRI) at the retropalatal and retroglossal regions was performed with simultaneous measurement of SpO2 and nasal-oral mask airflow and pressure. Airway cross-sectional area (CSA) was determined using AMIRA. Percent change in CSA was calculated from five continuous tidal breaths in states of wakefulness and sleep. Mixed effects models were used to evaluate interactions between group (OSAS/control), site (retropalatal/retroglossal), and stage (wake/sleep).

Results

We studied 24 children with OSAS (mean age 15.49 ± 2.00 years, mean apnea–hypopnea index [AHI] 16.53 ± 8.72 events/h) and 19 controls (mean age 14.86 ± 1.75 years, mean AHI 2.12 ± 1.69 events/h). Groups were similar in age, sex, height, weight, and BMI Z-score. Participants with OSAS had a 48.17% greater increase in percent change of airway CSA during sleep than controls (p < 0.0001), while there was no difference between groups during wakefulness (p = 0.6589). Additionally, participants with OSAS had a 48.80% increase in percent change of airway CSA during sleep as compared with wakefulness (p < 0.0001), whereas no such relationship was observed in controls (p = 0.5513).

Conclusions

This study demonstrates significant effects of sleep on upper airway dynamics in obese children with OSAS. Dynamic MRI with physiological data can potentially provide further insight into the biomechanical basis of OSAS and assist in more effective management.
The prevalence of common sleep disorders in young adults: a descriptive population-based study
Authors: McArdle Nigel , Ward Sarah V , Bucks Romola S , Maddison Kathleen , Smith Anne , Huang Rae-Chi , Pennell Craig E , Hillman David R , Eastwood Peter R
Published: April 2020

Sleep disorders in adults are associated with adverse health effects including reduced quality of life and increased mortality. However, there is little information on sleep disorders in young adults. A cross-sectional observational study was undertaken in 1,227 young adults participating in the Western Australian Pregnancy (Raine) Study (2012–2014) to describe the prevalence of common sleep disorders. In-laboratory polysomnography (PSG) and validated survey methods were used, including the Epworth Sleepiness Scale, Pittsburgh Sleep Symptom Questionnaire-Insomnia, and International Restless Legs Syndrome Study Group criteria. A total of 1,146 participants completed a core questionnaire, 1,051 completed a sleep-focused questionnaire and 935 had analyzable PSG data. Participants had a mean age of 22.2 years and female to male ratio of 1.1 to 1. The respective sleep disorder prevalences in females and males were: obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI]: ≥5 events/hour) 14.9% (95% CI: 11.8–18.5) and 26.9% (95% CI: 22.9–31.2); chronic insomnia, 19.3% (95% CI: 16.7–23.9) and 10.6% (95% CI: 8.3–13.9); restless legs syndrome, 3.8% (95% CI: 2.4–5.6) and 1.9% (95% CI: 0.9–3.4); and abnormal periodic leg movements during sleep (>5 movements/hour), 8.6% (95% CI: 6.3–11.5) and 9.6% (95% CI: 7.1–12.7). There were statistically significant differences in prevalence between sexes for OSA and insomnia, which persisted after adjustment for body mass index and education. In those with complete data on all sleep-related assessments (n = 836), at least one sleep disorder was present in 41.0% of females and 42.3% of males. Sleep disorders are very common in young adults. Health practitioners should be aware of these high prevalences, as early identification and treatment can improve quality of life and may reduce later morbidity and mortality.
Visual Body Part Representation in the Lateral Occipitotemporal Cortex in Children/Adolescents and Adults
Authors: Okamoto Yuko , Kitada Ryo , Kochiyama Takanori , Naruse Hiroaki , Makita Kai , Miyahara Motohide , Okazawa Hidehiko , Kosaka Hirotaka
Published: April 2020

The lateral occipitotemporal cortex (LOTC) that responds to human bodies and body parts has been implicated in social development and neurodevelopmental disorders like autism spectrum disorder (ASD). Neuroimaging studies using a representational similarity analysis (RSA) revealed that body representation in the LOTC of typically developing (TD) adults is categorized into 3 clusters: action effector body parts, noneffector body parts, and face parts. However, its organization of younger people (i.e., children and adolescents) and its association with individual traits remain unclear. In this functional MRI study, TD adults and children/adolescents observed photographs of hands, feet, arms, legs, chests, waists, upper/lower faces, the whole body, and chairs. The univariate analysis showed that fewer child/adolescent participants showed left LOTC activation in response to whole-body images (relative to those of chairs) than adult participants. Contrastingly, the RSA on both age groups revealed a comparable body representation with 3 clusters of body parts in the bilateral LOTC. Hence, this result indicates that, although response to whole-body images can differ, LOTC body part representations for children/ adolescents and adults are highly similar. Furthermore, sensory atypicality is associated with spatial LOTC organization, suggesting the importance of this region for understanding individual difference, which is frequently observed in ASD.
Survey of Incidence and Nested PCR Detection of Sugarcane White Leaf in Different Varieties
Authors: Zhang Rong-Yue , Shan Hong-Li , Huang Ying-Kun , Wang Xiao-Yan , Li Jie , Li Wen-Feng , Cang Xiao-Yan , Yin Jiong , Luo Zhi-Ming
Published: April 2020

Sugarcane white leaf (SCWL) is a devastating sugarcane (Saccharum officinarum) disease caused by a 16SrXI group phytoplasma, which is extremely harmful to sugarcane production. To determine the occurrence of SCWL in different varieties in 2018, we conducted a field survey and performed nested PCR detection of SCWL phytoplasma in cane-planting areas of Mangweng and Hepai in Gengma, Yunnan province, which are the areas most severely affected by SCWL in China. The results of the field survey showed that the symptomatic incidence of SCWL differed among varieties. The mean symptomatic incidence of SCWL on variety Yuetang60 was the highest (73.50%), and it was the lowest on Liucheng05-136 (13.67%). Using nested PCR, the SCWL phytoplasma was detected in symptomatic plants of all varieties more than 90% of the time; the SCWL phytoplasma was detected in 91 and 97% of symptomatic plants of Yingyu91-59 and Liucheng05-136 varieties, respectively. The SCWL phytoplasma was detected by PCR in 82% of the asymptomatic plant samples. The results of this study showed that field survey based on white leaf symptoms did not accurately reflect the actual occurrence of the SCWL phytoplasma.
Spinal Deformity in Sotos Syndrome: First Results of Growth-friendly Spine Surgery
Authors: Verhofste Bram P. , Glotzbecker Michael P. , Marks David S. , Birch Craig M. , McClung Anna M. , Emans John B.
Published: April 2020

Background:

Sotos syndrome (SS), or cerebral gigantism, describes children with macrocephaly, craniofacial abnormalities, general overgrowth, ligamentous laxity, developmental delay, and neurological disabilities. Fewer than 500 cases have been reported since Sotos and colleagues described the condition in 1964 and no literature exists on the management of spinal deformity in children under 10 years old.

The aims of this study were: (1) to characterize the presentation of spinal deformities in patients with SS; and (2) to provide preliminary results of growth-friendly instrumentation (GFI) in these children.

Methods:

Thirteen children (9 boys) with SS and minimum of 2-year follow-up were identified from 2 multicenter early-onset scoliosis (EOS) databases (1997-2017). Mean age at index surgery and follow-up duration were 5.0 years (range, 1.8 to 10 y) and 7.2 years (range, 2.1 to 14.9 y), respectively. Patients underwent GFI for a mean of 5.7 years (range, 2 to 10.2 y), with an average of 9 lengthenings (range, 2 to 18). Definitive spinal fusion was performed in 4 patients (31%). Major curve magnitude, T1-T12 and T1-S1 lengths, thoracic kyphosis, and lumbar lordosis were evaluated preindex, postindex, latest GFI, and postfusion, when possible.

Results:

Five thoracolumbar (38%), 4 double major (31%), 2 main thoracic (15%), and 2 double thoracic curves (15%) were seen that spanned a mean of 6.8 levels (5 to 9). Major curves improved 36% (range, 5% to 71%), from a mean of 71 degrees (range, 48 to 90 degrees) to 46 degrees (range, 20 to 73 degrees) postindex surgery (P<0.001). Major curves remained stable at a mean of 52 degrees (range, 20 to 87 degrees) at latest GFI (P=0.36). True T1-T12 and T1-S1 growth velocities during GFI were 0.5 mm/mo (range, 0.4 to 0.8 mm/mo) and 0.8 mm/mo (range, 0.1 to 2.1 mm/mo), respectively. Twenty-six complications occurred in 9 patients (69%) averaging 2 complications per patient (range, 0 to 7).

Conclusions:

This is the first study to evaluate the outcomes of GFI in children with SS and EOS. Compared with published data for outcomes of GFI in EOS, children with SS may have less major curve correction. Growth-friendly surgery remains an effective treatment method for EOS in patients with SS.

Levels of Evidence:

Level IV—retrospective case-series.
Risk Factors for Adverse Radiographic Outcomes After Elastic Stable Intramedullary Nailing of Unstable Diaphyseal Tibia Fractures in Children
Authors: Pennock Andrew T. , Huang Sharon G. , Pedowitz Jason M. , Pandya Nirav K. , McLaughlin Dell C. , Bastrom Tracey P. , Ellis Henry B.
Published: April 2020

Objectives:

Elastic stable intramedullary nails (ESIN) are commonly utilized to treat unstable pediatric tibia fractures but have been associated with complications. The purpose of this study was to identify risk factors for adverse radiographic outcomes after ESIN of pediatric tibia fractures.

Methods:

A retrospective review of all patients who underwent diaphyseal tibia fracture stabilization with ESIN between 2010 and 2018 at 3 pediatric level 1 trauma centers was performed. Inclusion criteria were open growth plates, no intra-articular or physeal fracture involvement, and radiographic follow-up until union. Patient demographics, injury mechanism, fracture characteristics, and implant fill relative to the medullary canal were recorded. Radiographic outcome measures included achievement of and time to union, residual angular deformity, and additional procedures.

Results:

One hundred seventy-two patients met inclusion criteria and were followed for a mean of 1.2 years. Nonunions were observed in 3% of the patient cohort. Another 10% required >6 months to heal, but did not require further surgical intervention. Angular deformities were common with 57% having a residual deformity ≥5 degrees and 14% having a residual deformity ≥10 degrees. Of the patients with a residual deformity between 5 and 10 degrees, 3% were symptomatic, where as 26% of the patients with a residual deformity ≥10 degrees were symptomatic. Greater angular deformities were associated with open fractures, compartment syndrome, and longer time to union. Patient age, weight, tibial comminution, and canal fill were not associated with nonunions or malunions.

Conclusions:

ESIN of pediatric tibia fractures results in reliable healing for a majority of patients, but poses risks for residual angular deformities and delayed healing. Open fractures and compartment syndrome were associated with adverse radiographic outcomes.
Evaluation of Sedation Outcomes Following Increased Dexmedetomidine Use in the ICU
Authors: Schuler Brian R. , Kovacevic Mary P. , Dube Kevin M. , Szumita Paul M. , DeGrado Jeremy R.
Published: April 2020

Objective:

To evaluate sedation practices following a dexmedetomidine guideline update in the ICU.

Design:

Single-center, retrospective chart review.

Setting:

Tertiary academic medical center.

Patients:

Patients were included in this analysis if they were admitted to the ICU and were ordered for continuous infusion sedatives or opioids from September to November 2016 (PRE) and from September to November 2017 (POST). Patients were excluded from this analysis if they met any of the following criteria: mechanical ventilation less than 12 hours, admitted with acute neurologic injury, burn of greater than 20% total body surface area, chronic tracheostomy, admitted to the neuroscience or cardiac surgery ICU, on extracorporeal membrane oxygenation support, or received an infusion of neuromuscular blockers.

Interventions:

Patients admitted during a restricted dexmedetomidine prescribing guideline were compared with patients admitted during an expanded prescribing guideline.

Measurements and Main Results:

Of the 1,426 patients evaluated for inclusion, 427 patients met the criteria in this analysis. Of these, 217 patients were in the PRE and 210 patients in the POST. A majority of patients were excluded for admission to neuroscience or cardiac surgery ICU. Dexmedetomidine was used in 13.8% of encounters in the PRE and 51.9% of encounters in the POST (p < 0.001). The median duration of mechanical ventilation was 49 hours (24–110 hr) in the PRE and 47.5 hours (26–98 hr) in the POST (p = 0.8). ICU length of stay was a median of 136 and 121 hours in the PRE and POST, respectively (p = 0.2). The median hospital length of stay was 296 and 326 hours in the PRE and POST, respectively (p = 0.35). After controlling for possible confounders, ventilation time remained unchanged between the PRE and POST (p = 0.98).

Conclusions:

The expansion of a hospital dexmedetomidine prescribing guideline resulted in an increased use of dexmedetomidine but was not associated with a difference in length of mechanical ventilation.
Nonpharmacologic Treatment for Heart Failure
Authors: Malangu Boniface , Lanier Gregg M. , Frishman William H.
Published: April 2020

There has been significant interest in research for the development of device-based therapy as a treatment option of heart failure (HF), whether it is with reduced or preserved ejection fraction. This is due to the high morbidity and mortality rate in patients with HF despite recent advances in pharmacologic treatment. Following the success of cardiac resynchronization therapy, baroreceptor activation therapy has emerged as another novel device-based treatment for HF. The Barostim neo was developed by CVRx Minneapolis, MN for the treatment of mild to severe HF. The device works by electrically activating the baroreceptor reflex with the goal to restore the maladaptive autonomic imbalance that is seen in patients with HF. Preliminary clinical investigations have given promising results with an encouraging safety profile. Baroreceptor activation therapy as a treatment option is still investigational at this time; however, several trials in different patient populations have already shown benefit with a very good safety profile. In this review, we will summarize the current state of technology and the available literature of the use of baroreceptor activation therapy in patients with different comorbidities, with a focus on this device-based therapy in patients with HF.
Diuretic Resistance in Heart Failure
Authors: Rahman Rubayat , Paz Pablo , Elmassry Mohamed , Mantilla Barbara , Dobbe Logan , Shurmur Scott , Nugent Kenneth
Published: April 2020

Decompensated heart failure accounts for approximately 1 million hospitalizations in the United States annually, and this number is expected to increase significantly in the near future. Diuretics provide the initial management in most patients with fluid overload. However, the development of diuretic resistance remains a significant challenge in the treatment of heart failure. Due to the lack of a standard definition, the prevalence of this phenomenon remains difficult to determine, with some estimates suggesting that 25–30% of patients with heart failure have diuretic resistance. Certain characteristics, including low systolic blood pressures, renal impairment, and atherosclerotic disease, help predict the development of diuretic resistance. The underlying pathophysiology is likely multifactorial, with pharmacokinetic alterations, hormonal dysregulation, and the cardiorenal syndrome having significant roles. The therapeutic approach to this common problem typically involves increases in the diuretic dose and/or frequency, sequential nephron blockade, and mechanical fluid movement removal with ultrafiltration or peritoneal dialysis. Paracentesis is potentially useful in patients with intra-abdominal hypertension.
A Cautionary Note on Extended Kaplan–Meier Curves for Time-varying Covariates
Authors: Sjölander Arvid
Published: April 2020

The Kaplan–Meier curve is a standard statistical tool that is used in cohort studies to illustrate how survival during follow-up depends on time-fixed covariates that are measured at baseline. For time-varying covariates, an extended Kaplan–Meier curve has been proposed that is constructed by letting subjects move across risk sets as their covariate levels change during follow-up. It has been claimed, but not proven, that, under a particular independence assumption, this extended Kaplan–Meier curve has a causal interpretation as representing a hypothetical cohort whose covariate values remain constant during follow-up. In this note, we show that, in the absence of confounding, this claim is indeed correct. However, we argue that the causal implications of this independence assumptions are highly unrealistic, and that a causal interpretation of the extended Kaplan–Meier curve is therefore typically unwarranted.
Using Transportability to Understand Differences in Mediation Mechanisms Across Trial Sites of a Housing Voucher Experiment
Authors: Rudolph Kara E. , Levy Jonathan , Schmidt Nicole M. , Stuart Elizabeth A. , Ahern Jennifer
Published: April 2020

Background:

Randomized trials may have different effects in different settings. Moving to Opportunity (MTO), a housing experiment, is one such example. Previously, we examined the extent to which MTO’s overall effects on adolescent substance use and mental health outcomes were transportable across the sites to disentangle the contributions of differences in population composition versus differences in contextual factors to site differences. However, to further understand reasons for different site effects, it may be beneficial to examine mediation mechanisms and the degree to which they too are transportable across sites.

Methods:

We used longitudinal data from MTO youth. We examined mediators summarizing aspects of the school environment over the 10–15 year follow-up. Outcomes of past-year substance use, mental health, and risk behavior were assessed at the final timepoint when participants were 10–20 years old. We used doubly robust and efficient substitution estimators to estimate (1) indirect effects by MTO site and (2) transported indirect effects from one site to another.

Results:

Differences in indirect effect estimates were most pronounced between Chicago and Los Angeles. Using transport estimators to account for differences in baseline covariates, likelihood of using the voucher to move, and mediator distributions partially to fully accounted for site differences in indirect effect estimates in 10 of the 12 pathways examined.

Conclusions:

Using transport estimators can provide an evidence-based approach for understanding the extent to which differences in compositional factors contribute to differences in indirect effect estimates across sites, and ultimately, to understanding why interventions may have different effects when applied to new populations.
Reducing Bias Due to Outcome Misclassification for Epidemiologic Studies Using EHR-derived Probabilistic Phenotypes
Authors: Hubbard Rebecca A. , Tong Jiayi , Duan Rui , Chen Yong
Published: April 2020

Epidemiologic studies using electronic health record (EHR)-derived phenotypes as outcomes are subject to bias due to phenotyping error. In the case of dichotomous phenotypes, existing methods for misclassified outcomes can be used to reduce bias. In this article, we present a bias correction approach for EHR-derived probabilistic phenotypes: continuous predicted probabilities of the outcome of interest. This approach makes use of correction factors that can be computed by hand and do not require specialized software. We used simulation studies to investigate the performance of the proposed approach under a variety of scenarios for accuracy of the probabilistic phenotype, strength of the outcome/exposure association, and prevalence of the outcome of interest. Across all scenarios investigated, the proposed approach substantially reduced bias in association parameter estimates relative to a naive approach. We demonstrate the application of this approach to a study of pediatric type 2 diabetes using data from the PEDSnet network of children’s hospitals. This straightforward correction factor can substantially reduce bias and improve the validity of EHR-based epidemiology.
Cardiac Surgery During Pregnancy
Authors: SHOOK LYDIA L. , BARTH WILLIAM H.
Published: April 2020

The need for cardiac surgery during pregnancy is rare. Only 1% to 4% of pregnancies are complicated by maternal cardiac disease and most of these can be managed with medical therapy and lifestyle changes. On occasion, whether due to natural progression of the underlying cardiac disease or precipitated by the cardiovascular changes of pregnancy, cardiac surgical therapy must be considered. Cardiac surgery is inherently dangerous for both, the mother and fetus with mortality rates near 10% and 30%, respectively. For some conditions, percutaneous cardiac intervention offers effective therapy with far less risk to the mother and her fetus. For others, cardiac surgery, including procedures that mandate the use of cardiopulmonary bypass, must be entertained to save the life of the mother. Given the extreme risks to the fetus, if the patient is in the third trimester, strong consideration should be given to delivery before surgery involving cardiopulmonary bypass. At earlier gestational ages when this is not feasible, modifications to the perfusion protocol including higher flow rates, normothermic perfusion, pulsatile flow, and the use of intraoperative external fetal heart rate monitoring should be considered.
Effects of Self-acupunctural Hand Massage Using Aromatic Oil on Alleviating the Stress, Fatigue, and Vital Signs of Korean Middle-Aged Women
Authors: Park Yi Kyun , Kim Jung Hee , Gu Min Kyung , Hwang Myoung Hee , Park Hyon Shin , Yim Eunji , Sok Sohyune R.
Published: April 2020

The study aimed to examine the effects of self-acupunctural hand massage using aromatic oil on the stress, fatigue, and vital signs of Korean middle-aged women. A quasi-experimental study using a pretest/posttest control group, nonsynchronized design was employed. The study participants consisted of 55 middle-aged women (27 in the experiment group and 28 in the control group), who visited a community center in Seoul, South Korea. Self-acupunctural hand massage using aromatic oil as an experimental intervention was performed once per day, 6 minutes per session for the left and right hands each, for 3 weeks. A questionnaire was designed to measure the general characteristics, stress, fatigue, and vital signs (blood pressure and pulse rate). There were significant differences in the degrees of stress, fatigue, and vital signs (blood pressure) between the 2 groups. Self-acupunctural hand massage using aromatic oil decreased the stress, fatigue, and vital signs (blood pressure) of Korean middle-aged women. Self-acupunctural hand massage using aromatic oil can be utilized as an effective nursing intervention for decreasing stress, fatigue, and vital signs (blood pressure) for middle-aged women in clinical practice.
Determination of Use of Alternative Medicine Methods in Patients With Ankylosing Spondylitis
Authors: Özel Filiz , Çökmez Yetim Burcu , Yatarkalkmaz Sevgi , Karabulut Gonca
Published: April 2020

This study aimed to examine complementary and alternative medicine (CAM) use among patients with ankylosing spondylitis (AS) who had or who had not received treatment with biological agents; the study also aimed to determine the types of CAM methods used by these patients. This is a comparative and cross-sectional study. This research was conducted at a rheumatology outpatient clinic of a university hospital in Turkey. A total of 120 patients who had (n = 60) and had not (n = 60) received therapy with biological agents participated in this study. A patient identification form and a questionnaire prepared by the researchers were used to collate the study data. This study found that the most commonly used method among patients who did not receive biological therapy was thermal facilities, at a rate of 28.3%; and that the most commonly used method among patients who did receive biological therapy was the use of thermal facilities, at a rate of 25%. No significant difference was found between patients who had received and patients who had not received biological therapy in terms of age and disease duration. Information was provided by health professionals to the patients concerning frequently used CAM modalities.
Perceived Learning Needs of Patients With Heart Failure in Jordan: Perspectives of Patients, Caregivers, and Nurses
Authors: Ashour Ala , Al-Rawashdeh Sami , Alwidyan Mahmoud , Al-Smadi Ahmed , Alshraifeen Ali
Published: April 2020

Background

Identifying learning needs is an important component of care among patients with heart failure (HF). There is a discrepancy in the level of importance of information as perceived by patients, caregivers, and nurses. No studies have been conducted to identify learning needs among patients with HF in Jordan.

Objective

The aim of this study was to identify the learning needs of patients with HF in Jordan from the perspective of patients, family caregivers, and their nurses.

Methods

A descriptive comparative design using a convenience sample of 67 patients with HF, 67 family caregivers, and 67 nurses was used. The Heart Failure Learning Needs Inventory was used to identify the learning needs. The mean scores were compared among the 3 groups and ranked by importance for each item to determine the most important areas of perceived needs for each group.

Results

All groups had high total Heart Failure Learning Needs mean scores: patients, 4.12 ± 0.92; caregivers, 4.14 ± 0.65; and nurses, 4.08 ± 0.54. The top priority learning need for both patients and caregivers was “the recommended daily salt intake,” whereas for nurses, it was “why I am taking each medication and its side effects”; nurses significantly perceived it as more important to learn than patients and caregivers did. Younger and employed patients requested more information than other patients.

Conclusions

Although some similarities exist, there are important differences among the 3 groups on perceived importance of information. Understanding these differences may be critical in developing a tailored educational program for patients and caregivers and improving nursing practice.