bluuebunny/crossref_metadata_2025 huggingface dataset:
DEPRESCRIBING AND PROGNOSIS IN OLDER PATIENTS WITH ARTERIAL HYPERTENSION AND CHRONIC HEART FAILURE
Authors: Efremova Elena , Shutov Alexander , Antonova Elena , Bykova Alina , Samsonova Natal’ja , Hramova Anna , Cheremnyh Anastasija
Published: April 2021

Objective:

Treatment of older patients with arterial hypertension is complicated by comorbidity and frailty syndrome. Deprescribing is a possible option for comorbid patients. The aim of this study was to investigate deprescribing and prognosis in older hypertensive patients with chronic heart failure (CHF).

Design and method:

119 older hypertensive patients with CHF (89 males, mean age was 68.9 ± 6.7 years) were studied. Arterial hypertension was defined according to ESC Guidelines for the diagnosis and treatment of arterial hypertension, 2018. Charlson comorbidity index (CCI) was estimated. Comorbidity was regarded as high at index more or equal 6 scores. Quality of life, frailty syndrome, personal characteristics were evaluated. GerontoNet ADR Risk Score was used for predicting ADRs. Follow-up period was 1 year, primary endpoint - all-cause mortality.

Results:

The CCI was 5.9 ± 1.9 scores. 67 (56.3%) older hypertensive patients with CHF had high comorbidity, 19 (10%) - frailty syndrome. The total number of drugs was 5 [4;7]. According to GerontoNet ADR Risk Score patients had 3 [2;4] scores. Most of patients (92;77.3%) had more than 5 scores (high risk of ADRs). Only 30 (25%) patients had high adherence to drug therapy. Patients with high comorbidity had more scores according to GerontoNet ADR Risk Score, than patients with low comorbidity (4 [3;6]. and 2 [1;4] resp., p = 0.0003). During the follow-up 13 patients died. The deceased patients compared to the surviving patients had a higher level of comorbidity (7.5 ± 1.9 and 5.8 ± 1.9 resp., p = 0.001)) and higher scores according to GerontoNet ADR Risk Score (4 [3;7]. and 3 [2;4] resp., p = 0.0006)). Relative risk of death within 12 months in older hypertension patients with CHF and high risk of adverse drug reactions (more or equal 6 scores according to GerontoNet ADR Risk Score) was 3.85 times (95% CI 1.42 - 10.48) higher risk of death in patients with low risk of ADRs.

Conclusions:

Older patients with arterial hypertension and CHF are characterized by high comorbidity, polypharmacy and low adherence to treatment. GerontoNet ADR Risk Score may be recommended for assessing prognosis in older hypertensive patients with CHF.
IN MIXED MARTIAL ARTS (MMA) WEIGHT LOSS BY DEHYDRATION RESULTS IN ACUTE EFFECTS ON KIDNEY FUNCTION
Authors: Pereira Antonio André Jarsen , Casarini Dulce Elena
Published: April 2021

Objective:

Currently there is a significant growth in the world in the number of professional fighters and practitioners of Mixed Martial Arts (MMA). To promote greater preservation of athletes physical integrity, weight categories were created, however some fighters in the attempt of insertion into inferior categories, use the dehydration for their drastic weight reduction. The method used may trigger some damage to the body, such as a decrease in the volume of renal blood flow. We aimed to identify the acute effects of weight loss by dehydration on kidney function in a MMA fighter.

Design and method:

The volunteer is MLC, 34 years old, male, black, single, resident in Maceió-AL-Brazil, without metabolic diseases, with a family history of arterial hypertension. It does not use drugs or dietary supplementation. The athlete has participated in the fights in the last 3 years, losing 7 kg per dehydration for a month before the fight. The signature of the Free and Informed Consent Term was collected. Three collections were carried out: one month before the fight, in the official weighing day and the day of the event.

Results:

In this study in response to reduction of body weight by dehydration of around 7 kg, it was observed that the athlete presented some abnormalities during the body weight loss/gain cycle as glycosuria, non-reversible positive leukocyturia and proteinuria within 24 hours, elevated serum creatinine (1.3 mg/dL) and urea (42 mg/dL) during the peak of dehydration (day of weighing and fighting). Blood ureic nitrogen/creatinine ratio (15.8) and creatinine clearance (126.1 mL/min) were elevated during the three moments of observation, namely 30 days pre-fight, day of weighing and fighting.

Conclusions:

Elevated creatinine clearance suggests renal damage with increased filtration rate with possible renal damage from dehydration. We are completing the analysis of 10 athletes. Our data suggest that athletes need to be instructed so that the training method is less detrimental to their physical integrity.

Supported by CAPES
PRECIOUS TRIAL CONFIRMS SAFETY AND EFFICACY OF GUIDELINE'S SINGLE-PILL COMBINATION STRATEGY
Authors: Brguljan Jana , Chazova Irina E. , Gaciong Zbignew , Simic Dragan , Vajer Peter , Zelveian Parounak , Jelakovic Bojan
Published: April 2021

Objective:

To assess the efficacy and safety of guideline's SPC strategy with perindopril/amlodipine (dual SPC arm) and perindopril/amlodipine/indapamide (triple SPC arm) with the goal of reaching blood pressure (BP) control in newly diagnosed and uncontrolled hypertensive patients.

Design and method:

450 adults with essential hypertension were assessed in the interventional, open-label, prospective, international, multicentre PRECIOUS trial. Treatment duration was 16 weeks, divided into four treatment periods. Office BP was measured with a validated automated BP-measuring device by a qualified health professional following guidelines protocol. At the inclusion naïve or patients uncontrolled on previous mono or dual therapy (other than perindopril/amlodipine (P/A)) were assigned to dual SPC arm with initial dose of 4/5 mg P/A. Those uncontrolled on previous dual or triple therapy were assigned to triple SPC arm with initial dose of 4/5/1.25 mg perindopril/amlodipine/indapamide (P/A/I). If BP control was not reached, the initial dose was up-titrated in 4-week intervals to 8/5 mg, 8/10 mg P/A or 8/10/2.5 mg P/A/I in dual SPC arm and to 8/5/2.5 mg, or 8/10/2.5 mg P/A/I in triple SPC arm.

Results:

After 4 months of treatment mean office BP lowered from 159.5 ± 11.6/ 99.6 ± 8.6 mmHg to 128.6 ± 9.4/81.7 ± 7.2 mmHg and from 162.4 ± 14.3/ 99.5 ± 9,6 mmHg to 127.8 ± 11.3/80.2 ± 7.5 mmHg in dual and triple SPC arm (all p < 0.001), respectively. Significant decrease by -17.1/-10.9 mmHg in dual and -14.4/-9.0 mmHg in triple SPC arm was achieved after one month of treatment (both p < 0.001). Target BP of <140/90 mmHg was achieved in 77.7% of patients in dual and in 83.0% of patients in triple SPC arm. The majority of the effect was observed within 3 months. Approximately 1/3 of patients remained on initial dose, and 1/3 needed one up-titration of the therapy. 85% of patients experienced no adverse events, recorded ones were clinically irrelevant.

Conclusions:

Guideline's SPC strategy with perindopril/amlodipine and perindopril/amlodipine/indapamide resulted in fast achievement of guideline's recommended target BP with no or just 1 up-titration therapy step in approximately 2/3 of patients, accompanied by good tolerability.
NOCTURNAL NON-DIPPING STATUS AND LEFT VENTRICULAR HYPERTROPHY IN HYPERTENSIVE PATIENTS
Authors: Amaral Teresa , Castro Daniel Pereira de , Rua Inês , Ruivo Pedro
Published: April 2021

Objective:

Ambulatory Blood Pressure Monitoring (ABPM) is used to assess the dipping status in hypertensive patients according to the nocturnal blood pressure (NBP) decline: extreme dippers, dippers, non-dippers and inverted dippers.

Increased NBP is currently regarded as a risk factor for cardiovascular (CV) events and hypertension-mediated organ damage (HMOD).

One of the most common HMOD include left ventricular (LV) remodelling as chronic BP elevation may progressively increase LV thickness.

The aim of this study is to determine if there is a higher prevalence of LVH in echocardiographic (ECHO) parameters in patients with increased NBP.

Design and method:

Prospective observational study.

Inclusion criteria: subjects with treated hypertension undergoing ABPM performed in our Primary Health Care Unit and with ECHO in the last 3 years.

Fisher's exact test was used whenever appropriate to assess independence and statistical significance of reported factors. Logistic regression analysis was performed to assess the effects and its statistical significance between established parameters. Statistical differences were indicated as p < 0.05 and p < 0.01. Statistical analysis was performed using R version 4.0.3.

Results:

For this study, 67 patients were screened, from which 44 were male and 23 females, average age of 55 years old.

We obtained a distinct distribution of dipper and non-dipper profiles in a LVH dependent manner. The non-dipper presented higher significant effect with LVH (p < 0.01) and the results obtained from the fisher test showcase a statistically significant relation between non-dippers and LVH (annex 1)

Conclusions:

The limitations of this study included the small sample size and the usage of a questionable diagnose of dipping status in a 24 h period since it is often highly variable. Based on the results, there seems to be an impact of NBP on LV structure since there is a statistically significant relation between non-dipper status and LVH.

Hypertensive patients should be submitted to ECHO and other forms of HMOD screening, especially non-dippers, considering their increased CV risk, in order to improve CV risk stratification therapeutic strategies.
ActiGraph and Short-term Heart Rate Variability Study Protocol
Authors: Luong Anna , Goodyke Madison , Dunn Susan L. , Baynard Tracy , Bronas Ulf
Published: April 2021

Background

ActiGraph accelerometry is widely used in nursing research to estimate daily physical activity. Heart rate variability (HRV), a measure of autonomic modulation, can be assessed in conjunction with the ActiGraph using a Polar H7 Bluetooth heart rate monitor. There is a paucity of nursing literature to guide nurse researchers' protocol development when using the ActiGraph to assess both physical activity and short-term HRV via its Bluetooth capabilities.

Objectives

The aim of this study was to describe a standardized research ActiGraph and HRV (ActiGraph HRV) protocol for an ongoing randomized controlled trial to measure physical activity and short-term HRV in patients with ischemic heart disease who report hopelessness.

Methods

We outline the study protocol for the standardization of reliable and rigorous physical activity and HRV data collection using the ActiGraph wGT3X-BT and Polar H7 Bluetooth heart rate monitor, and data analysis using ActiLife and Kubios software programs.

Results

Sixty-four participants enrolled in the randomized controlled trial to date, and 45 (70.3%) have completed or are actively participating in the study. Heart rate variability data have been collected on 43 of the 45 participants (96%) to date. During the first data collection time point, 42 of 44 participants (95.5%) wore the ActiGraph for a minimum of 5 valid days, followed by 28 of 31 participants (90.3%) and 25 of 26 participants (96.2%) at subsequent data collection time points. The intraclass correlation for physical activity in this study is 0.95 and 0.98 for HRV.

Discussion

Revisions to the protocol were successfully implemented at the onset of the COVID-19 pandemic for data collection using social distancing. The protocol was additionally amended in response to an unanticipated problem with ActiGraph battery life using Bluetooth technology. Use of the ActiGraph HRV protocol has led to a reliable and rigorous measurement of physical activity and HRV for patients with ischemic heart disease who report hopelessness in this randomized controlled trial.

Conclusion

We provide an ActiGraph HRV protocol that can be adapted as a model in the development of ActiGraph HRV protocols for future nursing research in community and home-based settings while maximizing social distancing in the current and future pandemics.
A Quality Improvement Initiative Is Associated With Reduced Time to Administer Biologics and Small Molecules and Emergency Room Visits in Inflammatory Bowel Disease
Authors: Battat Robert , Galati Jonathan S. , Lukin Dana , Chabouni Fatiha , Sockolow Robbyn , Carter Jeff , Fajardo Kristina , Yang Stevie , Reich Jenna , Jacobs Vinita , Abramowitz Meira , Kumar Anand , Christos Paul , Longman Randy S. , Burakoff Robert , Simone Laura , Sapir Tamar , Crawford Carl V. , Scherl Ellen J.
Published: April 2021

Background:

Delays in biologic or small molecule medication administration are associated with increased adverse events, hospitalization, and surgery in inflammatory bowel disease (IBD). We evaluated the impact of a quality improvement (QI) intervention on the time to administration of biologics or small molecules (TABS) in IBD.

Methods:

Data were retrospectively extracted for IBD patients prescribed biologics or small molecules from a convenience sample of providers participating in an accredited QI educational intervention (baseline cohort). Subsequent to the intervention, data were prospectively collected from patients prescribed these medications (postintervention cohort). Dates related to steps between a treatment decision to medication administration were collected. The primary outcome compared TABS in baseline and postintervention cohorts.

Results:

Eighteen physicians provided survey and patient data for 200 patients in each cohort (n=400). The median time to medication administration (TABS) decreased from baseline to postintervention cohorts (30 vs. 26 d, P=0.04). Emergency room visits before medication administration also decreased (25.5% vs. 12.5%, P=0.001). Similar numerical TABS reductions were observed in subgroups limited to physicians providing patients to both cohorts and for individual medications prescribed. Primary contributors to delays included filling prescriptions subsequent to insurance approval and dispensation subsequent to this.

Conclusions:

A QI intervention successfully reduced medication administration times (TABS) by accelerating provider-dependent steps. This intervention was associated with reduced emergency room visits. We propose TABS as a quality metric to assess the effective delivery of therapies in IBD. Further evaluation of QI interventions, patient education on prescription drug insurance, and quality metrics are warranted.
Association of sex with the clinical course and outcome of internal emergency department patients: a secondary data analysis
Authors: Thomas Clara , Möckel Martin , Searle Julia , Vollert Jörn Ole , Somasundaram Rajan , Slagman Anna
Published: April 2021

Background and importance

Differences between men and women visiting the emergency department (ED) with nonsurgical complaints have mostly been investigated in small, diagnosis-based subpopulations.

Objective

This study investigated sex-differences in an unselected cohort of nonsurgical ED patients.

Design

Secondary data of all patients attending two EDs of the Charité, Universitätsmedizin Berlin collected in the framework of their medical evaluation was reviewed.

Settings and participants

Within a 1-year-period all 34 333 adult internal patients presenting to one of the two EDs were included and analysed.

Outcomes measure and analyses

Sex-stratified descriptive analysis of the in-hospital course and outcome of the ED patients was performed as primary endpoint. Admission data, ED processes and diagnoses were analyzed as secondary endpoints.

Main results

A total of 51.2% of all patients were women. Women were slightly younger (median 56 years vs. men 58 years; P < 0.001) and presented more frequently with abdominal pain and headache. Men rather showed chest pain and dyspnea. Accordingly, women had more gastroenterological diseases; men were more often diagnosed with cardiological and pneumological diseases. Women were less frequently admitted for inpatient treatment [35.3 vs. men 43.7%; difference 8.4 percentage points (95% confidence interval (CI), 7.3–9.4)] and intensive care treatment [5.8 vs. men 9.0%; difference 3.2 percentage points (95% CI, 2.7–3.8)]. Inpatient-mortality did not show significant sex differences [4.6 women vs. 4.8% men; difference 0.2 percentage points (95% CI, −0.6 to 0.8)].

Conclusions

There are significant differences in characteristics, symptoms, diagnoses and clinical course between men and women. Further investigations could identify causes and measures like sex-specific algorithms for ED-work processes.
The Work of Oskar Herzberg—Did Psychosis or the Residence in a Psychiatric Institution Serve as a Catalyst for Creativity?
Authors: Strube Sebastian , Steinberg Holger
Published: April 2021

In the 1920s, the Heidelberg psychiatrist and art historian Hans Prinzhorn collected pictorial works by “mentally ill people”—today’s Prinzhorn Collection.

His colleague Paul Schilder sent him works by Oskar Herzberg thereto, which Prinzhorn included as “Case 355” in his famous work Bildnerei der Geisteskranken.

Using Herzberg as an example, we approached the general issue of the relationship between mental illness, creativity, and art from a historical psychiatric perspective.

It was not before his admission to the Leipzig clinic due to his schizophrenic illness that Herzberg began to paint. Prinzhorn and his doctor Ernst Jolowicz considered this late start of artistic activities to be the expression of an immanent creative urge caused by exceptional psychotic experiences. Our study intends to view such artworks outside a rather pathological context. Therefore, we discuss being secluded in psychiatry, supplied painting utensils, and released from his daily constrains as other possible triggering factors for Herzberg’s artistic development.
Classifying Microscopic Acute and Old Myocardial Infarction Using Convolutional Neural Networks
Authors: Garland Jack , Hu Mindy , Duffy Michael , Kesha Kilak , Glenn Charley , Morrow Paul , Stables Simon , Ondruschka Benjamin , Da Broi Ugo , Tse Rexson Datquen
Published: April 2021

Convolutional neural network (CNN) has advanced in recent years and translated from research into medical practice, most notably in clinical radiology and histopathology. Research on CNNs in forensic/postmortem pathology is almost exclusive to postmortem computed tomography despite the wealth of research into CNNs in surgical/anatomical histopathology. This study was carried out to investigate whether CNNs are able to identify and age myocardial infarction (a common example of forensic/postmortem histopathology) from histology slides. As a proof of concept, this study compared 4 CNNs commonly used in surgical/anatomical histopathology to identify normal myocardium from myocardial infarction. A total of 150 images of the myocardium (50 images each for normal myocardium, acute myocardial infarction, and old myocardial infarction) were used to train and test each CNN. One of the CNNs used (InceptionResNet v2) was able to show a greater than 95% accuracy in classifying normal myocardium from acute and old myocardial infarction. The result of this study is promising and demonstrates that CNN technology has potential applications as a screening and computer-assisted diagnostics tool in forensic/postmortem histopathology.
Fatal Coronary Artery Vasculitis With Mixed Features
Authors: Birsic George W. , Hentschel Brynn E. , Overton-Hennessy Zo C. , Ward Michael E. , Fiester Steven E. , Fulcher James W.
Published: April 2021

Atherosclerotic cardiovascular disease (ASCVD) is often investigated by medical examiners as a cause of sudden death. Because of the variation in presentation of atherosclerotic cardiovascular disease, the examiner must be cautious when assigning a final diagnosis. The presented case depended upon histologic examination of coronary artery lesions to reach an appropriate final diagnosis of vasculitis with mixed features. Autopsy findings showed hepatosplenic vasculitis with noncaseating granulomas, and multifocal diffuse coronary fibrosis with histologic findings consistent with late-stage polyarteritis nodosa (PAN). However, the patient lacked the hallmark renal involvement observed in PAN. Furthermore, the vasculitis within the liver showed a highly granulomatous appearance, more consistent with IgG4 disease. In these mixed-appearance cases with limited history, exact categorization of the disease may prove difficult to impossible. Herein, we review a differential diagnosis of classic vasculitides with a focus on those that commonly affect the coronary arteries in adults, namely, PAN.
Death Due to Adrenal Crisis
Authors: Gitto Lorenzo , Stoppacher Robert , Serinelli Serenella
Published: April 2021

Adrenal crisis is a life-threatening manifestation of acute adrenal insufficiency. One of the most important underlying causes is Addison disease (primary adrenal insufficiency).

A 42-year-old White woman with a medical history of Addison disease on chronic steroid therapy was admitted to the emergency department due to sustained episodes of cardiopulmonary arrest. Upon admission, she was hypotensive and hypoglycemic. Despite resuscitation attempts, she developed multiorgan failure and eventually died. At autopsy, no definitive adrenal gland tissue was grossly identified, but histology detected atrophy of adrenal glands with patchy chronic inflammation. Evidence of acute pneumonia was seen. The cause of death was determined to be complications of adrenal/Addisonian crisis.

A review of the literature showed only a few autopsy studies regarding deaths due to adrenal crisis. Forensic pathologists should include adrenal crisis in their differential diagnosis. Adequate medical history and pertinent autopsy findings can corroborate deaths due to adrenal crisis, but exhaustive biochemical analyses are mandatory to support the diagnosis further.
The Intra.Ox Near-Infrared Spectrometer Measures Variations in Flap Oxygenation That Correlate to Flap Necrosis in a Preclinical Rodent Model
Authors: Khavanin Nima , Darrach Halley , Kraenzlin Franca , Yesantharao Pooja S. , Sacks Justin M.
Published: April 2021

Background:

Mastectomy flap necrosis affects 7 to 40 percent of patients undergoing immediate breast reconstruction, with many cases resulting in infection and/or explantation. The Intra.Ox near-infrared spectrometer is a novel device that assesses tissue perfusion by measuring the interactions of light with oxygenated and deoxygenated hemoglobin. This handheld device facilitates serial flap perfusion assessment and may objectively identify at-risk tissues and guide evidence-based treatment algorithms. In this preliminary study, we hypothesized that the Intra.Ox spectrometer detects differences in tissue oxygenation that correlate to tissue necrosis.

Methods:

Dorsal, random-pattern flaps measuring 10 × 3 cm were raised in eight male Sprague-Dawley rats. Intraoperative tissue oxygen saturation was measured using Intra.Ox in 10 standardized locations. On postoperative day 7, the skin flaps were evaluated for full-thickness necrosis. Data were analyzed using the chi-square test and one-way analysis of variance. A receiver operating characteristic curve assessed the accuracy of intraoperative tissue oxygenation in predicting the risk of flap necrosis.

Results:

Tissue oxygen saturation exhibited a strong negative correlation to distance from the flap pedicle (r = −0.798). Oxygen saturation in tissue that developed necrosis averaged 32 percent, compared to 59 percent in tissues that did not (p < 0.001). The area under the receiver operating characteristic curve was 0.969. Post hoc oxygen saturation cutoffs with 100 percent specificity and sensitivity in predicting necrosis were identified at 46 percent and 54 percent, respectively.

Conclusions:

Intra.Ox detects significant differences in tissue oxygenation saturation that are associated with the risk for flap necrosis. This technology can be used to identify at-risk tissues and represents an avenue for research aimed at preventing flap necrosis.
Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc
Authors: Bastard Jean-Philippe , Pelloux Véronique , Alili Rohia , Fellahi Soraya , Aron-Wisnewsky Judith , Capel Emilie , Fève Bruno , Assoumou Lambert , Prifti Edi , Katlama Christine , Clément Karine , Capeau Jacqueline
Published: April 2021

Objective:

To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a protease inhibitor regimen to raltegravir/maraviroc.

Design:

Sub-study of the ANRS157 ROCnRAL study with the investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end.

Methods:

We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used the Wilcoxon-paired test.

Results:

The patients (n = 8) were mainly male (7/8), aged (mean ± standard error of the mean) 54.9 ± 1.2 years, BMI 26.1 ± 1.2 kg/m2, CD4+ 699 ± 56 cells/mm3, all viral load (VL) <50 copies/ml. After a follow-up of 6 ± 0.5 months, all PLWH remained with VL <50 copies/ml. BMI, trunk and limb fat amounts were unchanged yet systemic insulin resistance increased. Adipose tissue histology was unchanged except for borderline increased adipocyte diameter (P = 0.1). Among the 16 094 RNA transcripts, 458 genes were up-regulated and 244 were down-regulated. Analyses of the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases, evaluating modifications in the main functional pathways, revealed that genes related to immune recognition/function were less expressed as were genes encoding T-cell receptor and receptor signaling pathways. The gene expression profiles indicated decreased inflammation but genes involved in adipogenesis and insulin resistance were overexpressed.

Conclusion:

After 6 months of raltegravir/maraviroc, adipogenesis-related gene profile was enhanced in SCAT, in agreement with a tendency for increased adipocyte size. Enhanced SCAT insulin resistance-related profile was concordant with higher systemic insulin resistance. However, the immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.
Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age
Authors: MacBrayne Christine E. , Rutstein Richard M. , Wiznia Andrew A. , Graham Bobbie , Alvero Carmelita G. , Fairlie Lee , Lypen Kathryn , George Kathleen H. , Townley Ellen , Moye Jack , Costello Diane G. , Reding Christina A. , Barroso Hofer Cristina , Crauwels Herta M. , Woot de Trixhe Xavier , Tambuyzer Lotke , Vanveggel Simon , Opsomer Magda , Kiser Jennifer J.
Published: April 2021

Objective:

To describe the pharmacokinetics, safety, and efficacy of etravirine (ETR) in HIV-infected children 1 to less than 6 years of age.

Design:

Phase I/II, open-label, multicenter, dose-finding study.

Methods:

Antiretroviral therapy (ART)-experienced children in two age cohorts (I: 2 to <6 years; II: 1 to less than 2 years) received weight-based ETR, swallowed whole or dispersed in liquid, with optimized ART including a ritonavir-boosted protease inhibitor. Intensive pharmacokinetics occurred 7–18 days after starting ETR. Participants with ETR AUC12h less than 2350 ng h/ml had a dose increase and repeat pharmacokinetics.

Results:

Twenty-six children enrolled and 21 (15 in cohort I and 6 in cohort II) had evaluable intensive pharmacokinetics sampling at the final weight-based dose. On the final dose, the geometric mean ETR AUC12h was 3823 ng h/ml for cohort I and 3328 ng h/ml for cohort II. Seven children (33.3%) on the final dose, all taking ETR dispersed, had an AUC12 
h less than 2350 ng h/ml and underwent a dose increase. ETR AUC12 
h was 3.8-fold higher when ETR was swallowed whole vs. dispersed, P less than 0.0001. On the final dose, 75 and 33.3% in cohorts I and II, respectively, had HIV-1 RNA 400 copies/ml or less or at least 2 log reductions from baseline at week 48. Three children (11.5%) experienced a grade at least 3 adverse event related to ETR but only 1 discontinued.

Conclusion:

ETR was well tolerated. Predefined pharmacokinetics targets were met but overall exposures were low vs. historical data in adults, particularly in young children taking dispersed tablets. A high rate of viral efficacy was observed among those aged 2 to more than 6 years but not in those less than 2 years.
Pseudomonas carbonaria sp. nov., isolated from charcoal
Authors: Kämpfer Peter , Glaeser S. P. , McInroy John A. , Clermont Dominique , Criscuolo Alexis , Busse Hans-Jürgen
Published: April 2021

A beige-pigmented, oxidase-positive bacterial isolate, Wesi-4T, isolated from charcoal in 2012, was examined in detail by applying a polyphasic taxonomic approach. Cells of the isolates were rod shaped and Gram-stain negative. Examination of the 16S rRNA gene sequence of the isolate revealed highest sequence similarities to the type strains of

Pseudomonas matsuisoli

and

Pseudomonas nosocomialis

(both 97.3 %). Phylogenetic analyses on the basis of the 16S rRNA gene sequences indicated a separate position of Wesi-4T, which was confirmed by multilocus sequence analyses (MLSA) based on the three loci gyrB, rpoB and rpoD and a core genome-based phylogenetic tree. Genome sequence based comparison of Wesi-4T and the type strains of

P. matsuisoli

and

P. nosocomialis

yielded average nucleotide identity values <95 % and in silico DNA-DNA hybridization values <70 %, respectively. The polyamine pattern contains the major amines putrescine, cadaverine and spermidine. The quinone system contains predominantly ubiquinone Q-9 and in the polar lipid profile diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine are the major lipids. The fatty acid contains predominantly C16 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and summed feature 8 (C18 : 1ω7c and/or C18 : 1 ω6c). In addition, physiological and biochemical tests revealed a clear phenotypic difference from

P. matsuisoli

. These cumulative data indicate that the isolate represents a novel species of the genus

Pseudomonas

for which the name Pseudomonas carbonaria sp. nov. is proposed with Wesi-4T (=DSM 110367T=CIP 111764T=CCM 9017T) as the type strain.
Performance of Repeat BinaxNOW SARS-CoV-2 Antigen Testing in a Community Setting, Wisconsin, November-December 2020
Authors: Shah Melisa M. , Salvatore Phillip P. , Ford Laura , Kamitani Emiko , Whaley Melissa J. , Mitchell Kaitlin , Currie Dustin W. , Morgan Clint N. , Segaloff Hannah E. , Lecher Shirley , Somers Tarah , Van Dyke Miriam E. , Bigouette John Paul , Delaney Augustina , DaSilva Juliana , O’Hegarty Michelle , Boyle-Estheimer Lauren , Abdirizak Fatima , Karpathy Sandor E. , Meece Jennifer , Ivanic Lynn , Goffard Kimberly , Gieryn Doug , Sterkel Alana , Bateman Allen , Kahrs Juliana , Langolf Kimberly , Zochert Tara , Knight Nancy W. , Hsu Christopher H. , Kirking Hannah L. , Tate Jacqueline E.
Published: April 2021

Repeating the BinaxNOW antigen test for SARS-CoV-2 by two groups of readers within 30 minutes resulted in high concordance (98.9%) in 2,110 encounters. BinaxNOW test sensitivity was 77.2% (258/334) compared to real-time reverse transcription-polymerase chain reaction. Repeating antigen testing on the same day did not significantly improve test sensitivity while specificity remained high.
Infant RSV immunoprophylaxis changes nasal epithelial DNA methylation at six years of age
Authors: Xu Cheng-Jian , Scheltema Nienke M. , Qi Cancan , Vedder Rolf , Klein Laura B.C. , Nibbelke Elisabeth E. , van der Ent Cornelis K , Bont Louis J. , Koppelman Gerard H.
Published: April 2021

Background

Respiratory syncytial virus (RSV) infection has been associated with childhood wheeze and asthma, and potential mechanisms include persistent epigenetic effects.

Methods

In the randomized, placebo-controlled MAKI trial, 429 preterm infants randomly received RSV immunoprophylaxis with palivizumab or placebo during their first RSV season. Children were followed until age 6 for asthma evaluation. DNA methylation in cells obtained by nasal brushes at age 6 was measured by Illumina MethylationEPIC array.

Results

RSV immunoprophylaxis in infancy had significant impact on global methylation patterns in nasal cells at age 6. The first principal component related to the immunoprophylaxis intervention was enriched for the pathway “positive regulation of defense response to virus by host” and “antigen processing and presentation” and driven by methylation changes in NOD2, DGKG, MSH3, and ITPR2. Three CpGsites, cg18040241, cg08243963, cg19555973 were differentially methylated at genome-wide significance, but were not associated with asthma. Differential methylation region analysis identified regions near genes that were previously implicated in the development of asthma and allergy such as HLA-DPA1, HLA-DPB1, FASLG, and CHI3L1.

Conclusions

The study provides the first proof of concept that RSV immunoprophylaxis during infancy has long-term effects on nasal epigenetic signatures at age 6, relating to host antiviral defense pathways.
Metabolome-wide association study on ABCA7 demonstrates a role for ceramide metabolism in impaired cognitive performance and Alzheimer’s disease
Authors: Dehghan Abbas , Pinto Rui , Karaman Ibrahim , Huang Jian , Durainayagam Brenan R , Liggi Sonia , Whiley Luke , Mustafa Rima , Kivipelto Miia , Solomon Alina , Ngandu Tiia , Kanekiyo Takahisa , Aikawa Tomonori , Chekmeneva Elena , Camuzeaux Stephane , Lewis Matthew R. , Kaluarachchi Manuja R , Ghanbari Mohsen , Ikram M Arfan , Holmes Elaine , Tzoulaki Ioanna , Matthews Paul M. , Griffin Julian L. , Elliott Paul
Published: April 2021

Genome-wide association studies (GWAS) have identified genetic loci associated with risk of Alzheimer’s disease (AD), but underlying mechanisms are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWAS using untargeted metabolic profiling (metabolomics) by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0x 10−5 to 1.3 x 10−44). We show that plasma LacCer concentrations are associated with cognitive performance in humans and concentrations of sphingomyelins, ceramides, and hexose-ceramides were altered in brain tissue from ABCA7 knock out mice, compared to wild type (WT) (P =0.049 to 1.4 x10−5). We then used Mendelian randomisation to show that the association of LacCer with AD risk is potentially causal. Our work suggests that risk for AD arising from functional variations in ABCA7 are mediated at least in part through ceramides. Modulation of their metabolism or downstream signalling may offer new therapeutic opportunities for AD.
Performance Comparison of a Flow Cytometry-based and Two Commercial Chemiluminescent Immunoassays for Detection and Quantification of Antibodies Binding to SARS-CoV-2 Spike Protein
Authors: Valdivia Arantxa , Tarín Fabián , Alcaraz María Jesús , Piñero Paula , Torres Ignacio , Marco Francisco , Albert Eliseo , Navarro David
Published: April 2021

The performance of a laboratory-developed quantitative IgG/IgA flow cytometry-based immunoassay (FCI) using Jurkat T cells stably expressing full-length native S protein was compared against Elecsys® electrochemiluminiscent (ECLIA) Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), and LIAISON®SARS-CoV-2 TrimericS IgG chemiluminiscent assay (CLIA) (Diasorin S.p.a, Saluggia, IT) for detection and quantitation of SARS-CoV-2-specific antibodies. A total of 225 serum/plasma specimens from 120 acute or convalescent COVID-19 individuals were included. Overall, IgG/IgA-FCI yielded the highest number of positives (n=179), followed by IgA-FCI (n=177), Roche ECLIA (n=175), IgG-FCI (n=172) and Diasorin CLIA (n=154). Positive percent agreement between FCI and compared immunoassays was highest for Roche ECLIA, ranging from 96.1% (IgG/IgA-FCI) to 97.7% (IgG-FCI), whereas negative percent agreement was higher between FCI and Diasosin CLIA, regardless of antibody isotype. A strong correlation (Rho:0.6-0.8) was found between IgG-FCI or IgA-FCI levels and antibodies quantified by Roche ECLIA and Diasorin CLIA. The trajectory of antibody levels delineated by the different immunoassays in 22 of patients with sequential specimens (≥3) was frequently discordant, with the exception of IgG and IgA determined by FCI assay and to a lesser extent antibodies quantified by Roche ECLIA and Diasorin CLIA. The data suggest that FCI may outperform Roche ECLIA and Diasorin CLIA in terms of clinical sensitivity for serological diagnosis of SARS-CoV-2 infection.
Decoding Neural Activity in Sulcal and White Matter Areas of the Brain to Accurately Predict Individual Finger Movement and Tactile Stimuli of the Human Hand
Authors: Bouton Chad , Bhagat Nikunj , Chandrasekaran Santosh , Herrero Jose , Markowitz Noah , Espinal Elizabeth , Kim Joo-won , Ramdeo Richard , Xu Junqian , Glasser Matthew F. , Bickel Stephan , Mehta Ashesh
Published: April 2021

Millions of people worldwide suffer motor or sensory impairment due to stroke, spinal cord injury, multiple sclerosis, traumatic brain injury, diabetes, and motor neuron diseases such as ALS (amyotrophic lateral sclerosis). A brain-computer interface (BCI), which links the brain directly to a computer, offers a new way to study the brain and potentially restore these losses in patients living with debilitating conditions. One of the challenges currently facing BCI technology, however, is how to minimize surgical risk. Minimally invasive techniques, such as stereoelectroencephalography (SEEG) have become more widely used in clinical applications since they can lead to fewer complications. SEEG electrodes also give access to sulcal and white matter areas of the brain but have not been widely studied in brain-computer interfaces. We therefore investigated the viability of using SEEG electrodes in a BCI for recording and decoding neural signals related to movement and the sense of touch and compared its performance to electrocorticography electrodes (ECoG) placed on gyri. Initial poor decoding performance and the observation that most neural modulation patterns were highly variable trial-to-trial and transient (significantly shorter than the sustained finger movements studied), led to the development of a feature selection method based on a repeatability metric using temporal correlation. An algorithm based on temporal correlation was developed to isolate features that consistently repeated (required for accurate decoding) and possessed information content related to movement or touch-related stimuli. We subsequently used these features, along with deep learning methods, to automatically classify various motor and sensory events for individual fingers with high accuracy. Repeating features were found in sulcal, gyral, and white matter areas and were predominantly phasic or phasic-tonic across a wide frequency range for both HD (high density) ECoG and SEEG recordings. These findings motivated the use of long short-term memory (LSTM) recurrent neural networks (RNNs) which are well-suited to handling both transient and sustained input features. Combining temporal correlation-based feature selection with LSTM yielded decoding accuracies of up to 92.04 +/-1.51% for hand movements, up to 91.69 +/-0.49% for individual finger movements, and up to 80.64 +/-1.64% for focal tactile stimuli to the finger pads and palm while using a relatively small number of SEEG electrodes. These findings may lead to a new class of minimally invasive brain-computer interface systems in the future, increasing its applicability to a wider variety of conditions.
Short-range exposure to airborne virus transmission and current guidelines
Authors: Wang Jietuo , Alipour Mobin , Soligo Giovanni , Roccon Alessio , Paoli Marco De , Picano Francesco , Soldati Alfredo
Published: April 2021

After the Spanish flu pandemic, it was apparent that airborne transmission was crucial to spreading virus contagion, and research responded by producing several fundamental works like the experiments of Duguid [J. Hyg. 44:6, 1946] and the model of Wells [Am. J. Hyg., 20:611–18,1934]. These seminal works have been pillars to past and current guidelines published by health organizations. However, in about one century, understanding of turbulent aerosol transport by jets and plumes has enormously progressed and it is now time to use this body of developed knowledge. In this work, we use detailed experiments and accurate computationally-intensive numerical simulations of droplet-laden turbulent puffs emitted during sneezes in a wide range of environmental conditions. We consider the same emission – number of drops, drop size distribution and initial velocity – and we change environmental parameters as temperature and humidity, and we observe strong variation in droplets evaporation or condensation in accordance with their local temperature and humidity microenvironment. We assume that 3% of the initial droplet volume is made of non-volatile matter. Our systematic analysis confirms that droplets lifetime is always about one order of magnitude larger compared to previous predictions, in some cases up to 200 times. Finally, we have been able to produce original virus exposure maps, which can be a useful instrument for health scientists and practitioners to calibrate new guidelines to prevent short-range airborne disease transmission.

Significance Statement

Violent expiratory events represent an important route for the spread of respiratory viruses, as the SARS-CoV-2 virus. We use finely-resolved experiments and simulations to quantify how the turbulent cloud of moist air exhaled during a sneeze largely increases the airborne time and the lifespan of virus-loaded droplets. By providing visualizations of the spatial distribution of the virus copies, we highlight the high infection risk associated with droplets that remain airborne in the near proximity of an infected individual. The present study aims at raising awareness among public health authorities about this infection risk, which is grossly underestimated by current guidelines.
Differences in sustained attention but not distraction in preschoolers from lower socioeconomic status backgrounds
Authors: Hoyer Roxane S. , Pakulak Eric , Bidet-Caulet Aurélie , Karns Christina M.
Published: April 2021

In children, the ability to listen to relevant auditory information and suppress distracting information is a foundational skill for learning and educational achievement. Distractibility is supported by multiple cognitive components (voluntary attention orienting, sustained attention, distraction, phasic arousal, as well as impulsivity and motor control) that may mature at different ages. Here we used the Competitive Attention Test (CAT) to measure these components in 71 4- and 5-year-old children. The goal of this study was to characterize the changes in efficiency of attention during the preschool period, and to explore differences in distractibility in preschool children that could be related to the socioeconomic status (SES) background of the child’s family. We found that sustained attention improves from age 4 to 5, while voluntary attention orienting is still immature during the preschool period. In addition, independent of age, task-irrelevant sounds induced distraction, phasic arousal, and impulsivity. Children from lower SES backgrounds showed reduced sustained attention abilities and increased impulsivity. However, 3-year-old children and a minority of 4- and 5-year-olds did not manage to perform the task according to the instructions; the CAT thus seems suitable to assess distractibility only in preschoolers with sufficiently developed sustained attention skills to efficiently complete the task. Taken together, the present findings suggest that distractibility is still developing during the preschool period and is likely to vary depending on the SES background of a child’s family.
Elevated CO2reduces a common soybean leaf endophyte
Authors: Christian Natalie , Basurto Baldemar Espino , Toussaint Amber , Xu Xinyan , Ainsworth Elizabeth A. , Busby Posy E. , Heath Katy D.
Published: April 2021

Free-air CO2enrichment (FACE) experiments have elucidated how climate change affects plant physiology and production. However, we lack a predictive understanding of how climate change alters interactions between plants and endophytes, critical microbial mediators of plant physiology and ecology. We leveraged the SoyFACE facility to examine how elevated [CO2] affected soybean (Glycine max)leaf endophyte communities in the field. Endophyte community composition changed under elevated [CO2], including a decrease in the abundance of a common endophyte,Methylobacteriumsp. Moreover,Methylobacteriumabundance was negatively correlated with co-occurring fungal endophytes. We then assessed howMethylobacteriumaffected the growth of co-occurring endophytic fungiin vitro.Methylobacteriumantagonized most co-occurring fungal endophytesin vitro, particularly when it was more established in culture before fungal introduction. Variation in fungal response toMethylobacteriumwithin a single fungal operational taxonomic unit (OTU) was comparable to inter-OTU variation. Finally, fungi isolated from elevated vs. ambient [CO2] plots differed in colony growth and response toMethylobacterium, suggesting that increasing [CO2] may affect fungal traits and interactions within the microbiome. By combiningin situandin vitrostudies, we show that elevated [CO2] decreases the abundance of a common bacterial endophyte that interacts strongly with co-occurring fungal endophytes. We suggest that endophyte responses to global climate change will have important but largely unexplored implications for both agricultural and natural systems.
Relationship between shear wave velocity and muscle activation is inconsistent across different muscle types
Authors: Bernabei Michel , Ludvig Daniel , Sandercock Thomas G. , Perreault Eric J. , Lee Sabrina S. M.
Published: April 2021

There is an increasing use of shear wave ultrasound elastography to quantify mechanical properties of muscles under various conditions such as changes muscle length and levels of activation in healthy and pathological muscle. However, little is known about the variability in shear wave velocity among muscles as most studies investigate one specific muscle. The purpose of this study was to determine if the relationship between SWV and muscle activation is consistent across muscles with different architectures: biceps brachii, tibialis anterior, and medial gastrocnemius, All measures were made at matching levels of activation and approximately at the optimal length for each muscle to control for length-dependent changes in the relationship between activation and force or stiffness. We also conducted a control experiment to determine how the passive force within a muscle alters the relationship between muscle activation and shear wave velocity. The relationship between shear wave velocity-squared and activation above 10% MVC differed across muscles, with biceps brachii and medial gastrocnemius showing a lower slope than tibialis anterior. Shear wave velocity-squared also differed between muscles at the shortest length (p<0.001) and the increase in shear wave velocity-squared with muscle lengthening also differed between muscle types (p = 0.005) Muscle-specific differences could not be explained by the architectural features such as pennation angle, fiber length, and physiological cross-sectional area. Our results demonstrate that there is not a unique relationship between muscle activation and shear wave velocity, highlighting the importance of understanding the many factors contributing to shear wave propagation in muscle before elastography can be used to make quantitative comparisons across muscle types.