bluuebunny/crossref_metadata_2025 huggingface dataset:
Deconstructing and reconstructing joint hypermobility on an evo-devo perspective
Authors: Castori Marco
Published: February 2021

Joint hypermobility is a common characteristic in humans. Its non-casual association with various musculoskeletal complaints is known and currently defined “the spectrum”. It includes hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). hEDS is recognized by a set of descriptive criteria, while HSD is the background diagnosis for individuals not fulfilling these criteria. Little is known about the aetiopathogenesis of the spectrum. It may be interpreted as a complex trait according to the integration model. Particularly, the spectrum is common in the general population, affects morphology, presents extreme clinical variability and is characterized by marked sex bias without a clear Mendelian or hormonal explanation. Joint hypermobility and the other hEDS systemic criteria are intended as qualitative derivatives of continuous traits of normal morphological variability. The need for a minimum set of criteria for hEDS diagnosis implies a tendency to co-vary of these underlying continuous traits. In evolutionary biology, such a co-variation (i.e. integration) is driven by multiple forces, including genetic, developmental, functional and environmental/acquired interactors. The aetiopathogenesis of the spectrum may be resolved by a deeper understanding of phenotypic variability, which superimposes on normal morphological variability.
Association between socioeconomic status and longitudinal sleep quality patterns mediated by depressive symptoms
Authors: Lee Ga Bin , Kim Hyeon Chang , Jeon Ye Jin , Jung Sun Jae
Published: February 2021

Study Objectives

We aimed to examine whether associations between socioeconomic status (SES) and longitudinal sleep quality patterns are mediated by depressive symptoms.

Methods

We utilized data on 3347 participants in the Korean Genome and Epidemiology Study aged 40–69 years at baseline from 2001 to 2002 who were followed up for 16 years. A group-based modeling approach was used to identify sleep quality trajectories using the Pittsburgh Sleep Quality Index (years 2, 6, 8, 10, and 12). Educational attainment (college graduated or less), monthly household income (≥$2500 or less), and occupation (unemployed, manual labor, and professional labor) at baseline (year 0) were used for analyses. Depressive symptoms were assessed using Beck’s Depression Inventory at year 4. Associations between SES and sleep quality patterns were examined using a multinomial logistic regression model. The mediation effect of depressive symptoms was further examined using PROC CAUSALMED.

Results

We identified five distinct sleep quality trajectories: “normal-stable” (n = 1697), “moderate-stable” (n = 1157), “poor-stable” (n = 320), “developing to poor” (n = 84), and “severely poor-stable” (n = 89). Overall, associations between SES levels and longitudinal sleep patterns were not apparent after full adjustment for sociodemographic and lifestyle factors measured at baseline. Depressive symptoms, however, tended to fully mediate associations between SES levels and sleep quality patterns (odds ratio range for indirect effects of depressive symptoms: for education, 1.05-1.17; for income, 1.05-1.15).

Conclusion

A significant mediating role for depressive symptoms between SES levels and longitudinal sleep quality warrants consideration among mental healthcare professionals.
Restless sleep disorder in children with NREM parasomnias
Authors: Senel Gulcin Benbir , Kochan Kizilkilic Esra , Karadeniz Derya
Published: February 2021

Study objectives

Restless sleep disorder (RSD) is a newly defined sleep disorder in the pediatric age group. Here, we investigated the frequency of RSD and the sleep characteristics in children with NREM (non-rapid eye movements) parasomnias associated with RSD.

Methods

We analyzed all patients with NREM parasomnias for the last 1 year, and investigated the clinical and polysomnographic characteristics.

Results

Twenty-eight children with NREM parasomnias and age- and gender-matched 20 healthy children were analyzed. The diagnosis of RSD was made in eight children with NREM parasomnias (28.6%), and none of the children had RSD in controls (p = 0.008). The most common diagnosis among children with RSD was somnambulism (six children), but not significantly (p = 0.308). Sleep efficiency was lower in children with RSD than those without RSD (p = 0.033). In cyclic alternating pattern analysis (CAP), CAP rate, durations and the indices of phases A1, A2, and A3 were significantly higher in children with NREM parasomnias in compared to controls. CAP parameters between children with or without RSD; however, were similar, except for higher index of phase A3 in children with RSD, suggesting arousal reactions accompanying RSD.

Conclusions

We demonstrated that RSD was present in almost one third of the children with NREM parasomnias. Sleep quality was worse in children with NREM parasomnias and RSD. An increase in sleep instability compatible with NREM parasomnia was present, while an increased phase A3 in RSD was remarkable. RSD is associated with a worse sleep quality and increased arousals, and should be questioned in children with NREM parasomnias.
Effects of six weeks of chronic sleep restriction with weekend recovery on cognitive performance and wellbeing in high-performing adults
Authors: Smith Michael G , Wusk Grace C , Nasrini Jad , Baskin Pamela , Dinges David F , Roma Peter G , Basner Mathias
Published: February 2021

Chronic sleep loss is associated with escalating declines in vigilant attention across days of sleep restriction. However, studies exceeding 2 weeks of chronic sleep loss are scarce, and the cognitive performance outcomes assessed are limited. We assessed the effects of 6 weeks of chronic sleep restriction on a range of cognitive domains in 15 high-performing individuals (38.5 ± 8.2 years, 6 women) confined to small space in groups of 4. Sleep opportunities were limited to 5 h on weekdays and 8 h on weekends. Individual sleep–wake patterns were recorded with actigraphy. Neurobehavioral performance was assessed in evenings with Cognition, a computerized battery of ten tests assessing a range of cognitive domains. There were some small to moderate effects of increasing sleep debt relative to pre-mission baseline, with decreases in accuracy across cognitive domains (standardized β = –0.121, p = 0.001), specifically on tests of spatial orientation (β = –0.289, p = 0.011) and vigilant attention (β = –0.688, p < 0.001), which were not restored by two nights of weekend recovery sleep. Cognitive and subjective decrements occurred despite occasional daytime napping in breach of study protocol, evening testing around the circadian peak, and access to caffeine before 14:00. Sensorimotor speed, spatial learning and memory, working memory, abstraction and mental flexibility, emotion identification, abstract reasoning, cognitive throughput, and risk decision making were not significantly affected by sleep debt. Taken together with modest lower subjective ratings of happiness and healthiness, these findings underline the importance of sufficient sleep, on both an acute and chronic basis, for performance in selected cognitive domains and subjective wellbeing in operationally relevant environments.
The Role of Hepatic Vagal Tone in Ozone-Induced Metabolic Dysfunction in the Liver
Authors: Colonna Catherine H , Henriquez Andres R , House John S , Motsinger-Reif Alison A , Alewel Devin I , Fisher Anna , Ren Hongzu , Snow Samantha J , Schladweiler Mette C , Miller Desinia B , Miller Colette N , Kodavanti Prasada Rao S , Kodavanti Urmila P
Published: February 2021

Air pollution has been associated with metabolic diseases and hepatic steatosis-like changes. We have shown that ozone alters liver gene expression for metabolic processes through neuroendocrine activation. This study aimed to further characterize ozone-induced changes and to determine the impact of hepatic vagotomy (HV) which reduces parasympathetic influence. Twelve-week-old male Wistar-Kyoto rats underwent HV or sham surgery 5–6 days before air or ozone exposure (0 or 1 ppm; 4 h/day for 1 or 2 days). Ozone-induced lung injury, hyperglycemia, glucose intolerance, and increases in circulating cholesterol, triglycerides, and leptin were similar in rats with HV and sham surgery. However, decreases in circulating insulin and increased HDL and LDL were observed only in ozone-exposed HV rats. Ozone exposure resulted in changed liver gene expression in both sham and HV rats (sham > HV), however, HV did not change expression in air-exposed rats. Upstream target analysis revealed that ozone-induced transcriptomic changes were similar to responses induced by glucocorticoid-mediated processes in both sham and HV rats. The directionality of ozone-induced changes reflecting cellular response to stress, metabolic pathways, and immune surveillance was similar in sham and HV rats. However, pathways regulating cell-cycle, regeneration, proliferation, cell growth, and survival were enriched by ozone in a directionally opposing manner between sham and HV rats. In conclusion, parasympathetic innervation modulated ozone-induced liver transcriptional responses for cell growth and regeneration without affecting stress-mediated metabolic changes. Thus, impaired neuroendocrine axes and parasympathetic innervation could collectively contribute to adverse effects of air pollutants on the liver.
Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation
Authors: Varshavsky Julia R , Robinson Joshua F , Zhou Yan , Puckett Kenisha A , Kwan Elaine , Buarpung Sirirak , Aburajab Rayyan , Gaw Stephanie L , Sen Saunak , Gao Songmei , Smith Sabrina Crispo , Park June-Soo , Zakharevich Igor , Gerona Roy R , Fisher Susan J , Woodruff Tracey J
Published: February 2021

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%–100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3–2.8 (95% confidence limits from 1.2–3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5–3.4) and 3.6 (95% CI: 2.2–3.1) ng/ml, respectively, compared to <1 ng/ml for bis(2-chloroethyl) phosphate (BCEP) and bis(1-chloro-2-propyl) phosphate (BCIPP). We found inverse associations of PFASs or OPFRs with ITGA1 or CDH5 immunoreactivity and positive associations with indicators of placental stress in multiple basal plate regions, indicating these chemicals may contribute to abnormal placentation and future health risks. Associations with blood pressure and lipid concentrations warrant further examination. This is the first study of these chemicals with placental biomarkers measured directly in human tissues and suggests specific biomarkers are sensitive indicators of exposure during a vulnerable developmental period.
Genome Sequence Resource of Phomopsis longicolla YC2-1, a Fungal Pathogen Causing Phomopsis Stem Blight in Soybean
Authors: Zhao Xiaolin , Zhang Zhichao , Zheng Sujiao , Ye Wenwu , Zheng Xiaobo , Wang Yuanchao
Published: February 2021

Diaporthe-Phomopsis disease complex causes considerable yield losses in soybean production worldwide. As one of the major pathogens, Phomopsis longicolla T. W. Hobbs (syn. Diaporthe longicolla) is not only the primary agent of Phomopsis seed decay but is also one of the agents of Phomopsis pod and stem blight and Phomopsis stem canker. We performed both PacBio long-read sequencing and Illumina short-read sequencing and obtained a genome assembly for the strain P. longicolla YC2-1, which was isolated from soybean stem with Phomopsis stem blight disease. The 63.1 Mb genome assembly contains 87 scaffolds, with a minimum, maximum, and N50 scaffold length of 20 kb, 4.6 Mb, and 1.5 Mb respectively, and a total of 17,407 protein-coding genes. The high-quality data expand the genomic resource of P. longicolla species and will provide a solid foundation for a better understanding of their genetic diversity and pathogenic mechanisms.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
TRAPPC13 Is a Novel Target of Mesorhizobium amorphae Type III Secretion System Effector NopP
Authors: Liu Dongying , Luo Yantao , Zheng Xiaofeng , Wang Xinye , Chou Minxia , Wei Gehong
Published: February 2021

Similar to pathogenic bacteria, rhizobia can inject effector proteins into host cells directly to promote infection via the type III secretion system (T3SS). Nodulation outer protein P (NopP), a specific T3SS effector of rhizobia, plays different roles in the establishment of multiple rhizobia-legume symbiotic systems. Mesorhizobium amorphae CCNWGS0123 (GS0123), which infects Robinia pseudoacacia specifically, secretes several T3SS effectors, including NopP. Here, we demonstrate that NopP is secreted through T3SS-I of GS0123 during the early stages of infection, and its deficiency decreases nodule nitrogenase activity of R. pseudoacacia nodules. A trafficking protein particle complex subunit 13–like protein (TRAPPC13) has been identified as a NopP target protein in R. pseudoacacia roots by screening a yeast two-hybrid library. The physical interaction between NopP and TRAPPC13 is verified by bimolecular fluorescence complementation and coimmunoprecipitation assays. In addition, subcellular localization analysis reveals that both NopP and its target, TRAPPC13, are colocalized on the plasma membrane. Compared with GS0123-inoculated R. pseudoacacia roots, some genes associated with cell wall remodeling and plant innate immunity down-regulated in ΔnopP-inoculated roots at 36 h postinoculation. The results suggest that NopP in M. amorphae CCNWGS0123 acts in multiple processes in R. pseudoacacia during the early stages of infection, and TRAPPC13 could participate in the process as a NopP target.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Jasmine (Jasminum officinale L. var. grandiflorum) Flower Extracts Inhibit the Formation of Methylglyoxal Induced Advanced Glycation Endproducts
Authors: Tang Xiaodan , Cai Ang , Li Dongli , Dain Joel A. , Seeram Navindra P. , Ma Hang
Published: February 2021

Our laboratory initiated a program to investigate the chemical constituents and biological activities of medicinal plants and functional foods grown in the Lingnan region (“South of the Nanling Mountains”; region of Guangdong, Guangxi, and Hainan provinces in China). Jasmine (Jasminum officinale L. var. grandiflorum) is one of these medicinal plants that has traditionally been used as a functional food and dried jasmine flowers are often consumed as a tea for numerous health beneficial effects. However, the inhibitory effects of jasmine on the formation of advanced glycation endproducts (AGEs) are unknown. Herein, we evaluated the anti‐glycation effects of jasmine flower extracts using an assay model of methylglyoxal‐induced glycation of human serum albumin at 37 °C for 14 days. Jasmine flowers were extracted with 90% aqueous ethanol to afford a crude ethanol extract (JFE). JFE then was subjected to partitioning sequentially with organic solvents including petroleum ether (PE), ethyl acetate (EA), and n‐butanol (BuOH) to obtain extracts including JFPE, JFEA, and JFBuOH, respectively. These extracts were evaluated for their anti‐glycation effects. JFEE, JFPE, JFEA, and JFBuOH (at concentrations at 250 and 500 μg/mL) inhibited the formation of AGEs by 33.3% and 54.7%, 24.1% and 41.6%, 18.0% and 47.7%, and 10.5 and 38.0%, respectively. The mechanisms of the inhibitory effects of jasmine flower extracts on the formation of AGEs are currently being investigated by our group.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Delivery of Lethal dsRNAs in Insect Diets by Branched Amphiphilic Peptide Capsules
Authors: Barros Sheila M. , Chandrasekar Raman , Wilkinson‐Nutsch Kayla E. , Yoonseong Park , Reeck Gerald , Tomich John M. , Avila L. Adriana
Published: February 2021

Branched Amphiphilic Peptides Capsules (BAPCs™) are a novel class of nano‐carriers constituted from the spontaneous co‐assembly of two unique, engineered peptide sequences. We recently reported on a thermally induced variant of BAPC™ that demonstrates promise as a vehicle for nucleic acid delivery and transcript knockdown. These BAPCs™ display a uniform size of 20–30 nm; they are easy to synthesize, stable and produce minimal immunogenic and inflammatory responses, in contrast to those commonly observed with viral and cationic lipid based approaches for gene delivery. BAPCs™ act as cationic nucleation centers allowing nucleic to wrap around them in a nucleosome like fashion, generating peptide‐nucleic complexes with sizes ranging from 80 to 200 nm. In this study, development of new and specific insect pest management methods capable of overcoming pesticide resistance and collateral off‐target killings are described. Gene silencing by feeding dsRNA to insects shows promise in this area. Here Branched Amphiphilic Peptide Capsules (BAPCs), facilitate cellular uptake of dsRNA by insects through feeding. The insect diets included dsRNA (300–400 bps) with and without complexation with BAPCs. The selected insect species come from two different Orders with different feeding mechanisms: Tribolium castaneum and Acyrthosiphon pisum. The gene transcripts tested (BiP and Armet) are part of the unfolded protein response (UPR) and suppressing their translation resulted in lethality. For Acyrthosiphon pisum, ingestion of BiP‐dsRNA associated with BAPCs led to the premature death of the aphids (t1/2 = 4–5 days) compared to ingestion of the same amounts of free BiP‐dsRNA (t1/2 = 11–12 days). Tribolium castaneum was effectively killed using a combination of BiP‐dsRNA and Armet‐dsRNA complexed with BAPCs; most dying as larvae or during eclosion (~75%). Feeding dsRNA alone resulted in fewer deaths (~30%). The results show that complexation of dsRNA with BAPCs enhanced the oral delivery of dsRNA over dsRNA alone.

Support or Funding Information

Partial support for this project was provided by the Terry Johnson Cancer Center at Kansas State University and by the USDA's National Institute of Food and Agriculture through the Specialty Crops Research Initiative/Citrus Disease Research & Extension, USDA NIFA Award No. 2015‐70016‐23028 and an Institutional Development Award (IDeA) from NIGMS grant P20 GM103418.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intensive Care Admission and Management of Patients With Acute Ischemic Stroke: A Cross-sectional Survey of the European Society of Intensive Care Medicine
Authors: Robba Chiara , Giovannini Martina , Meyfroidt Geert , van der Jagt Mathieu , Citerio Giuseppe , Smith Martin ,   Collaborators
Published: February 2021

Background:

No specific recommendations are available regarding the intensive care management of critically ill acute ischemic stroke (AIS) patients, and questions remain regarding optimal ventilatory, hemodynamic, and general intensive care unit (ICU) therapeutic targets in this population. We performed an international survey to investigate ICU admission criteria and management of AIS patients.

Methods:

An electronic questionnaire including 25 items divided into 3 sections was available on the European Society of Intensive Care Medicine Web site between November 1, 2019 and March 30, 2020 and advertised through the neurointensive care (NIC) section newsletter. This survey was emailed directly to the NIC members and was endorsed by the European Society of Intensive Care Medicine.

Results:

There were 214 respondents from 198 centers, with response rate of 16.5% of total membership (214/1296). In most centers (67%), the number of AIS patients admitted to respondents’ hospitals in 2019 was between 100 and 300, and, among them, fewer than 50 required ICU admission per hospital. The most widely accepted indication for ICU admission criteria was a requirement for intubation and mechanical ventilation. A standard protocol for arterial blood pressure (ABP) management was utilized by 88 (58%) of the respondents. For patients eligible for intravenous thrombolysis, the most common ABP target was <185/110 mm Hg (n=77 [51%]), whereas for patients undergoing mechanical thrombectomy it was ≤160/90 mm Hg (n=79 [54%]). The preferred drug for reducing ABP was labetalol (n=84 [55.6%]). Other frequently used therapeutic targets included: blood glucose 140 to 180 mg/dL (n=65 [43%]) maintained with intravenous insulin infusion in most institutions (n=110 [72.4%]); enteral feeding initiated within 2 to 3 days from stroke onset (n=142 [93.4%]); oxygen saturation (SpO2) >95% (n=80 [53%]), and tidal volume 6 to 8 mL/kg of predicted body weight (n=135 [89%]).

Conclusions:

The ICU management of AIS, including therapeutic targets and clinical practice strategies, importantly varies between centers. Our findings may be helpful to define future studies and create a research agenda regarding the ICU therapeutic targets for AIS patients.
Crystalglobulinemia: A Rare Presenting Manifestation of Multiple Myeloma
Authors: El Enany Galal , Nagui Noha , Nada Hanan , Abdelkader Heba A. , Sany Iman , Nada Ahmed , Mostafa Mona , El-Ghanam Omar , Abdel-Halim Mona R. E.
Published: February 2021

Crystalglobulinemia (CG) is a rare disorder characterized by crystallization of monoclonal immunoglobulins in the microcirculation leading to multiorgan vascular thrombosis and ischemic injury. The main cause of CG is multiple myeloma. We report a case of a 52-year-old man who presented with widespread necrotizing plaques and ulcerations. A skin biopsy revealed eosinophilic rectangular-shaped crystals occluding the lumina of blood vessels with no associated features of vasculitis. The crystals were Periodic acid-Schiff stain positive. The findings were diagnostic of CG. Extensive work up lead to the discovery of multiple myeloma. Awareness of CG is important because it may be the first presenting manifestation of an underlying serious hematological malignancy.
High-Dose Fluvoxamine Augmentation to Clozapine in Treatment-Resistant Psychosis
Authors: Leising Julie , Barr Alasdair M. , Procyshyn Ric M. , Ainsworth Nicholas J. , White Randall F. , Honer William , Vila-Rodriguez Fidel
Published: February 2021

Background

Although clozapine is the gold standard for treatment-resistant schizophrenia, more than 30% of patients remain unresponsive to clozapine monotherapy and may benefit from augmentation strategies. Fluvoxamine augmentation of clozapine may be beneficial in treatment resistance because of pharmacokinetic interactions, allowing for lower clozapine dosages with higher clozapine serum levels and an increased clozapine-to-norclozapine ratio, which can modify adverse effects. An augmentation strategy using higher fluvoxamine doses may also improve persistent negative, anxiety, and obsessive-compulsive symptoms through fluvoxamine's serotonergic activity.

Methods

Through chart review, we identified 4 cases of patients with treatment-resistant psychosis who underwent high-dose fluvoxamine augmentation of clozapine to target residual negative symptoms, refractory psychosis, anxiety, and obsessive-compulsive symptoms.

Findings

This augmentation strategy continued in 2 patients after discharge who showed clinical improvement without significant adverse effects. Two patients experienced adverse effects that led to the fluvoxamine discontinuation. Despite the fact that fluvoxamine augmentation led to symptom improvement in only 2 patients, all patients achieved high serum clozapine levels. Hematologic parameters were monitored in all patients, and no abnormalities were observed. No severe adverse effects of clozapine were experienced.

Conclusions

Although high variability of responses and adverse effects were observed during fluvoxamine augmentation to clozapine, this strategy was successful in increasing clozapine serum levels. Through fluvoxamine's serotonergic effects, this strategy may confer benefit to residual negative, obsessive, and anxiety symptoms. Limitations of this case series include the retrospective nature, absence of controls, diversity of diagnoses, multiple interventions in each patient, and lack of masked raters.
Pharmacotherapy Prescriptions for Relapse Prevention of Psychotic Depression After Electroconvulsive Therapy
Authors: Patel Dina A. , Flint Alastair J. , Rothschild Anthony J. , Whyte Ellen M. , Meyers Barnett S. , Mulsant Benoit H. , Voineskos Aristotle N. , Marino Patricia , Alexopoulos George S. ,   on behalf of the STOP-PD II Study Group
Published: February 2021

Purpose/Background

Electroconvulsive therapy (ECT) is effective in the treatment of acute episodes of psychotic depression. However, no adequately powered studies have directly investigated the efficacy of antipsychotic pharmacotherapy in relapse prevention of psychotic depression after ECT. In the absence of such literature, we reviewed the clinical practice of 4 academic medical centers that have made research contributions in the treatment of psychotic depression over the past 20 years.

Methods/Procedures

We reviewed medical records of patients with a diagnosis of psychotic depression who received 1 or more acute courses of ECT over the span of 3 years. Chi-square tests were used to compare pharmacotherapy prescribed at the time of completion of ECT.

Findings/Results

A total of 163 patients received 176 courses of ECT for separate episodes of psychotic depression. The combination of an antidepressant plus an antipsychotic was the most common regimen, ranging from 61.9% to 85.5% of all prescriptions. One center added lithium in 45.5% of cases treated with the combination of an antidepressant plus an antipsychotic. An antipsychotic alone was prescribed in less than 10% of cases. An antidepressant alone or other drug combinations were rare.

Implications/Conclusions

The combination of an antidepressant plus an antipsychotic was the most commonly prescribed regimen at the completion of ECT for relapse prevention in patients with psychotic depression acutely treated with ECT. Although this report offers a view of the clinical practice of 4 academic medical centers, it also points to the need of randomized controlled trials on continuation pharmacotherapy after treatment of psychotic depression with ECT.
Clozapine-Associated Myocarditis
Authors: Griffin Jan M. , Woznica Edgar , Gilotra Nisha A. , Nucifora Frederick C.
Published: February 2021

Background

Clozapine is the only medication with Food and Drug Administration approval for treatment-resistant schizophrenia. However, it is underutilized in the United States because of several life-threatening adverse effects, including clozapine-associated myocarditis (CAM), and a limited understanding of how to manage these complications. To date, recommendations for rechallenging patients with CAM that incorporate the cardiac literature or cardioprotective medications have not been developed.

Findings

In this article, we outline a protocol developed with cardiologists and guided by the cardiac literature that provides direction on how to monitor for the initial development of CAM and how to rechallenge patients with CAM. Furthermore, we present 2 successful cases of clozapine rechallenge that were managed using this protocol.

Conclusions

In both cases, the patients showed marked improvement in their psychiatric symptoms and functioning, demonstrating the importance of considering rechallenge in patients after CAM.
Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Lisdexamfetamine in Healthy Adults
Authors: Faison Shamia L. , Fry Nicholas , Adewole Toyin , Odebo Oyinkansola , Wang Zhao , Maletic Vladimir , Nasser Azmi
Published: February 2021

Background

Viloxazine extended-release is a novel nonstimulant under investigation as a potential treatment for attention-deficit/hyperactivity disorder (ADHD). Given the potential for viloxazine extended-release to be co-administered with stimulant ADHD pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine extended-release + lisdexamfetamine dimesylate (lisdexamfetamine) versus viloxazine extended-release and lisdexamfetamine alone.

Methods

In this single-center, cross-over, open-label trial, healthy, non-ADHD adults received single oral doses of 700 mg viloxazine extended-release alone, 50 mg lisdexamfetamine alone, and a combination of viloxazine extended-release (700 mg) + lisdexamfetamine (50 mg), with blood samples collected over 4 days postadministration. The active drug in viloxazine extended-release (viloxazine) and primary metabolite of lisdexamfetamine (d
-amphetamine) were measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events, vital signs, echocardiograms, and clinical laboratory evaluations.

Results

Thirty-six adults were enrolled, and 34 completed the trial. The least squares geometric mean ratios are reported as [combination / single drug (90% confidence intervals)]. Viloxazine extended-release: Cmax = 95.96% (91.33–100.82), area under the concentration–time curve from 0 to the last measurable time (AUC0-t) = 99.19% (96.53–101.91), and area under the concentration–time curve from 0 to infinity (AUCinf) = 99.23% (96.61–101.93). Lisdexamfetamine: Cmax = 112.78% (109.93–115.71), AUC0-t = 109.64% (105.25–114.22), and AUCinf = 109.52% (105.19–114.03). All reported adverse events, except 1 (moderate vomiting), were mild in severity.

Conclusions

Co-administration of viloxazine extended-release and lisdexamfetamine did not impact the pharmacokinetics of viloxazine or d
-amphetamine relative to administration of either drug alone. After single dose administration, the combination appeared to be safe and well tolerated.
Workers’ Stress During the First Lockdown
Authors: Parent-Lamarche Annick , Boulet Maude
Published: February 2021

Objective:

This study sheds light on the pathways leading to an increase in workers stress levels and the resulting effects on job performance during a pandemic.

Methods:

Path analyses were conducted on a sample of 459 Canadian workers using MPlus software. These analyses allowed us to determine whether the association between potential stressors during lockdown and job performance was mediated by workers’ stress.

Results:

The results revealed four significant indirect associations. Work–life balance dissatisfaction, gender (women), and marital tensions were indirectly associated with lower job performance because of their positive associations with stress. Teleworking was associated with higher job performance because of its negative association with stress.

Conclusions:

The results suggest that specific stressors are worth targeting with interventions to ensure job performance.
Incidence and Etiology of System Exchanges in Patients Receiving Extracorporeal Membrane Oxygenation
Authors: Nagler Bernhard , Hermann Alexander , Robak Oliver , Schellongowski Peter , Buchtele Nina , Bojic Andja , Schmid Monika , Zauner Christian , Winter Max Paul , Heinz Gottfried , Ullrich Roman , Kraft Felix , Wiedemann Dominik , Bernardi Martin H. , Staudinger Thomas , Lamm Wolfgang
Published: February 2021

Extracorporeal membrane oxygenation (ECMO) has established as a cornerstone therapy in severe acute respiratory distress syndrome and refractory hemodynamic failure. As circuit integrity is crucial for adequate organ support, component failure may necessitate a system exchange. In this retrospective study, incidence and etiology of system exchanges during applications of venovenous, venoarterial ECMO, and extracorporeal CO2 removal were examined. Sixty-three (44.4%) of 142 patients were affected by one or more exchanges, totaling 105 replaced circuits. The predominant exchange reason was clotting (n = 20), followed by hemolysis (n = 19), systemic coagulation disorders (n = 13), reconfiguration (n = 13), impaired gas exchange (n = 10), mechanical complications (n = 8), bleeding (n = 6), failed weaning (n = 5), prophylactic exchange (n = 3), and undocumented/other (n = 8). Nineteen (18.1%) events were classified as acute and 70 (66.7%) events as elective exchanges. Patients with circuit exchanges more frequently underwent renal replacement therapy at ECMO initiation (49.2% vs. 29.1%; p = 0.023), had a longer ECMO treatment duration (18 vs. 7.5 days, p < 0.001), and lower hospital survival (29.5% vs. 57.1%; p = 0.002). Considering the high occurrence of coagulation complications, further optimization of coagulation management is deemed necessary.
Systematic Review and Meta-Analysis of Antibiotic and Antimicrobial Lock Solutions for Prevention of Hemodialysis Catheter-Related Infections
Authors: Abdul Salim Sohail , Masoud Ahmed Taher , Thongprayoon Charat , Cheungpasitporn Wisit , Soliman Karim M. , Garla Vishnu , Sofy Ahmed Adel , Ahmed Ahmed Saeed , Abdelsattar Ahmed Taha , Zsom Lajos , Tapolyai Mihaly , Fülöp Tibor
Published: February 2021

Catheter-related bloodstream infection (CRBSI) with hemodialysis catheters are associated with increased mortality, morbidity and pose significant financial burden on healthcare. Antibiotic and antimicrobial locking solutions are effective in reducing risk of CRBSI. From inception to April 2020, we looked for relevant clinical controlled trials throughout the following databases: EBSCO, PubMed, Cochrane CENTRAL, MEDLINE, EMBASE, clinicaltrial.gov, and Google Scholar performing a metanalysis comparing antibiotic and antimicrobial lock solutions to heparin. Twenty-six studies with 4,967 patients reported the incidence of catheter-related bacteremia (CRB). The overall pooled risk ratio (RR) showed that the intervention group was associated with a significantly lower incidence of CRB by 30% compared with heparin (RR = 0.30, 95% confidence interval [CI] [0.25, 0.36], p < 0.001). Subgroup analysis showed that administration of antibiotic regimens led to a decreased risk of CRB episodes by 28% compared with the heparin group (RR = 0.28, 95% CI [0.21, 0.37], p < 0.0001). Antimicrobial solutions was associated with reduced risk of CRB by 32% compared with patients of the control group (RR = 0.32, 95% CI [0.25, 0.41], p < 0.0001). A test of subgroup differences was revealed no significant favoring of any of the two interventions. Both antibiotic and antimicrobial solutions are effective in reducing CRBSI.
The Impact of Vitamin D on Response to Anti-tumor Necrosis Factor-α Therapy in Children With Inflammatory Bowel Disease
Authors: Hizarcioglu-Gulsen Hayriye , Kaplan Jess L. , Moran Christopher J. , Israel Esther J. , Lee Hang , Winter Harland
Published: February 2021

Objectives:

Experimental studies have shown that vitamin D has an immunomodulatory effect on the innate and adaptive immune systems. Associations between vitamin D deficiency and development or progression of inflammatory bowel diseases (IBDs) are reported, but a cause-and-effect relationship between pretreatment 25 hydroxyvitamin D [25(OH)D] levels and response to anti-tumor necrosis factor-α (anti-TNF) therapy is not established.

Methods:

This retrospective study evaluated pediatric IBD patients who had 25(OH)D levels drawn within 3 months of initiating infliximab and/or adalimumab treatment. Demographic features, Paris classification, baseline 25(OH)D levels, disease activity, and laboratory results before and after 3 months of anti-TNF therapy were collected. The interaction between vitamin D insufficiency at induction and lack of response to anti-TNF therapy at 3 months was determined.

Results:

Of the 383 patients, 76 met inclusion criteria. Sixty-five patients (85.5%) had Crohn disease (CD) and 11 (14.5%) had ulcerative colitis. Seven patients had 25(OH)D levels obtained during both infliximab and adalimumab induction; hence 83 subjects were evaluated (infliximab: 70 patients, adalimumab: 13 patients). 25(OH)D <30 ng/mL was found in 55 of 83 (66.3%) subjects. There were no differences in gender, IBD type, disease activity scores between vitamin D-sufficient and vitamin D-insufficient groups. In CD, proximal gastrointestinal tract inflammation was associated with vitamin D insufficiency (P = 0.019), but other Paris classification parameters and laboratory results were similar in 2 groups. Early termination of anti-TNF therapy was significantly higher in patients who had vitamin D insufficiency (14.5% vs 0%, P = 0.034).

Conclusions:

Vitamin D insufficiency before anti-TNF treatment may result in poor response to induction therapy.
Enteral Feeding and Necrotizing Enterocolitis: Does Time of First Feeds and Rate of Advancement Matter?
Authors: Masoli Daniela , Dominguez Angelica , Tapia José L. , Uauy Ricardo , Fabres Jorge
Published: February 2021

Objective:

The aim of the study was to determine if time to initial enteral feeding (EF) and rate of advancement are associated with necrotizing enterocolitis (NEC) or death.

Methods:

Secondary analysis of prospectively collected data of very-low-birth-weight infants (VLBWI: 400--1500 g) born in 26 NEOCOSUR centers between 2000 and 2014.

Results:

Among 12,387 VLBWI, 83.7% survived without NEC, 6.6% developed NEC and survived, and 9.6% had NEC and died or died without NEC (NEC/death). After risk adjustment, time to initial EF (median = 2 days) was not associated with NEC; however, delaying it was protective for NEC/death (odds ratio [OR] = 0.96; 95% confidence interval [CI] 0.93--0.99). A slower feeding advancement rate (FAR) was protective for NEC (OR = 0.97; 95% CI = 0.94–0.98) and for NEC/death (OR = 0.98; 95% CI = 0.96–0.99).

Conclusions:

In VLBWI, there was no association between an early initial EF and NEC, although delaying it was associated with less NEC/death. A slower FAR was associated with lower risk of both outcomes.
Neurotrophic Factors in Human Milk in Early Lactation and the Effect of Holder and Microwave Pasteurization on Their Concentrations
Authors: Martysiak‐Żurowska Dorota , Puta Małgorzata , Kiełbratowska Bogumiła , Wesołowska Aleksandra
Published: February 2021

Objectives:

The objective of this study was to determine the level of brain‐derived neurotrophic factor (BDNF) and glial cell line‐derived neurotrophic factor (GDNF) in human milk in the first 2 weeks of breast‐feeding and compare the effects of Holder pasteurization (HoP, 62.5 °C, 30 minutes) and microwave pasteurization (MP) at constant temperature (62.5 °C) on the concentraion of both neurotrophic factors (NFs).

Methods:

Concentration of NFs in human milk was determined using a commercially available ELISA assay.

Results:

The average concentration of BDNF and GDNF in milk was 11 ± 6 ng/mL and 336 ± 238 pg/mL, respectively. There was a positive correlation between the concentrations of BDNF and GDNF in human milk and day of lactation (r = 0.441, P < 0.05 and r = 0.482, P < 0.05, respectively). In addition, there was a significant correlation between the levels of BDNF and GDNF (r = 0.366, P < 0.05). HoP and MP for 10 minutes affected both NF levels similarly, causing degradation of BDNF by about 24% and 17%, and GDNF by 47% and 45%, respectively. Use of MP for 5 minutes resulted in preservation of nearly 91% BDNF and 79% GDNF in human milk.

Conclusions:

In the pasteurization processes carried out, results showed that GDNF is more susceptible to degradation under the influence of high temperature. To the authors’ best knowledge, this is the first study evaluating the effects of HoP and MP at constant temperature on the concentration of NFs in human milk. It was found that the MP for 5 minutes is the optimal method.
A 30-Year Retrospective
Authors: Zander Karen
Published: February 2021

Purpose:

In an attempt to avoid future revisionist history, the author offers a 30-year retrospective (1986–2016) on the evolution of strategies to reduce length of stay (LOS). She and her colleagues have been involved from the onset by developing tools such as critical paths, roles such as clinical case management, and operational systems for managing measureable outcome-driven care from the bedside to the boardroom.

Primary Practice Setting:

Acute care hospitals.

Findings/Conclusions:

The LOS for all inpatients has changed dramatically from 1970 (average LOS = 7.8 days) through solidly between 2005 and 2012 (average LOS = 4.5 days in 2012) despite a significant increase in the average age of hospital inpatients (C. J. DeFrances & M. J. Hall, 2007
;
A. Weiss & A. Elixhauser, 2014). For patients 65 years and older, who comprised 38% of all inpatients, the decrease has been more drastic: from 12.6 days in 1970 to 5.5 days in 2005–2010 (CDC/National Center for Health Statistics, 2010).

With the exception of hospitalists and case management staff, acute care hospitals have essentially doubled productivity without adding additional direct care full-time equivalents! Described in terms of “low-hanging” to “high-hanging” fruit, this article outlines the classic methods used to reduce LOS and concludes with some implications of LOS for health care reform. The U.S. health system could not have accomplished this feat without case managers and social workers.

Implications for Case Management:

Acute care services should be very proud of their achievements and use their reputation to empower their work for the next frontier, which will be reducing cost per case, especially in risk contracts. Everything old seems new again.
Attitudes and Perceived Barriers to Sexually Transmitted Infection Screening Among Graduate Medical Trainees
Authors: Zucker Jason , Carnevale Caroline , Theodore Deborah A. , Castor Delivette , Meyers Kathrine , Gold Jeremy A. W. , Winetsky Daniel , Scherer Matt , Cohall Alwyn , Gordon Peter , Sobieszczyk Magdalena E. , Olender Susan
Published: February 2021

Graduate medical training is an opportune time to improve provider delivery of sexually transmitted infection (STI) screening. A survey of trainees found that the majority feel STI screening is their job but identified barriers to successful screening. Training that intentionally address service-specific barriers will be valuable in ending the STI epidemic.
The P2Network—Advancing Pediatric Emergency Care With Point-of-Care Ultrasound
Authors: Lam Samuel H. F. , Berant Ron , Chang Todd P. , Friedman Lucas , Gold Delia L. , Kornblith Aaron E. , Lin-Martore Margaret , Pade Kathryn H. , Skaugset L. Melissa , Toney Amanda G. , Wang-Flores Helena
Published: February 2021

Over the last 2 decades, the use of point-of-care ultrasound (POCUS) in pediatric emergency medicine (PEM) has grown exponentially. In 2014, a group of PEM POCUS leaders met and formed the P2Network. The P2Network provides a platform to build collaborative relationships and share expertise among members from various countries and practice settings. It works with educators and researchers within and outside of the field to advance POCUS practice in PEM. As an organization, the P2Network promotes the evidence-based application of POCUS to facilitate and improve care in the PEM setting and addresses issues related to integration of the PEM POCUS practitioner in this nascent field. The P2Network is building and augmenting its infrastructure for PEM POCUS research and education and has already made some progress in the areas, with published manuscripts and ongoing clinical research studies under its sponsorship. Future goals include developing a PEM POCUS research agenda, formalizing teaching and assessment of PEM POCUS skills, and implementing multicenter research studies on potentially high impact applications.
Transfers From a Pediatric Urgent Care to an Academic Pediatric Emergency Department
Authors: Eason Margaret , Clingenpeel Joel , Vazifedan Turaj , Guins Theresa , Amond Gwen
Published: February 2021

Objectives

Patient transfers from outpatient urgent care centers are common occurrences in a pediatric emergency department (ED). A previous study done at our institution evaluated the clinical appropriateness of transfers from general urgent care centers into our pediatric ED, showing that a significant proportion (27%) of such transfers were discharged home with minimal ED resource utilization. This study investigated the hypothesis that transfers to a pediatric ED from a pediatric urgent care have higher rates of ED resource utilization when compared with patients transferred from general urgent care centers.

Methods

A retrospective chart review was completed during an 11-month period on all patients transferred from a pediatric urgent care center to the pediatric ED. Demographic, diagnoses, reason for transfer, ED resource utilization, ED disposition, and 72-hour ED return data were collected from the electronic medical record. Each encounter was classified as acute or nonacute based on previously established resource utilization criteria. This data were then compared with findings from a prior study of transfers from all urgent care centers to our institution's pediatric ED.

Results

A total of 240 patients met the inclusion criteria. Of these, 160 (66.7%) were discharged from the ED. Twenty-six (10.8%) of the transferred patients met the nonacute transfer criteria. The odds of nonacute transfer from pediatric urgent care were 0.66 times lower than from general urgent care (odds ratio, 0.34; 95% confidence interval, 0.18–0.93).

Conclusions

A significantly lower proportion of transfers from the pediatric urgent care center were classified as nonacute, as compared with transfers from general urgent care centers. This suggests that the pediatric urgent care model may help to reduce the number of nonacute ED visits, thus producing cost savings and better patient care.