bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 InformationPartial 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

Abstract:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.
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

ABSTRACT

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

ABSTRACT

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

ABSTRACTObjectives: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

Abstract
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.