bluuebunny/crossref_metadata_2025 huggingface dataset:
Weak binding to the A2RE RNA rigidifies hnRNPA2 RRMs and reduces liquid–liquid phase separation and aggregation
Authors: Ryan Veronica H , Watters Scott , Amaya Joshua , Khatiwada Balabhadra , Venditti Vincenzo , Naik Mandar T , Fawzi Nicolas L
Published: August 2020

hnRNPA2 is a major component of mRNA transport granules in oligodendrocytes and neurons. However, the structural details of how hnRNPA2 binds the A2 recognition element (A2RE) and if this sequence stimulates granule formation by enhancing phase separation of hnRNPA2 has not yet been studied. Using solution NMR and biophysical studies, we find that each of the two individual RRMs retain the domain structure observed in complex with RNA but are not rigidly confined (i.e. they move independently) in solution in the absence of RNA. hnRNPA2 RRMs bind the minimal rA2RE11 weakly but at least, and most likely, two hnRNPA2 molecules are able to simultaneously bind the longer 21mer myelin basic protein A2RE. Upon binding of the RNA, NMR chemical shift deviations are observed in both RRMs, suggesting both play a role in binding the A2RE11. Interestingly, addition of short A2RE RNAs or longer RNAs containing this sequence completely prevents in vitro phase separation of full-length hnRNPA2 and aggregation of the disease-associated mutants. These findings suggest that RRM interactions with specific recognition sequences alone do not account for nucleating granule formation, consistent with models where multivalent protein:RNA and protein:protein contacts form across many sites in granule proteins and long RNA transcripts.
Flavors Enhance Nicotine Vapor Self-administration in Male Mice
Authors: Cooper Skylar Y , Akers Austin T , Henderson Brandon J
Published: August 2020

Introduction

Although the use of combustible cigarettes has decreased in many urban regions of America, the use of electronic nicotine delivery systems (ENDS) has dramatically increased. ENDS, or electronic cigarettes (e-cigarettes), differ from combustible cigarettes given that there are no restrictions on flavorant additives in e-liquids. With 95% of ENDS users vaping flavored e-liquids, it is critical to understand how flavors alter vaping-related behaviors. We have previously shown that menthol and green apple flavors enhance nicotine reward-related behavior in a mouse model and in the present study have investigated how menthol and green apple flavors alter e-Vape self-administration behavior in male mice.

Methods

Adult C57/BL6J male mice were used in vapor-inhalation self-administration assays. Mice were assigned vaping e-liquids (6 mg/mL nicotine with or without menthol or green apple flavor) to escalate on a fixed-ratio 1 (FR1) schedule in daily 3-hour sessions to examine initiation-related behaviors. Following escalation, mice were transitioned to a FR3 and progressive ratio schedules in 3-hour sessions to examine reinforcement-related behaviors.

Results

Here we observed that male mice exhibited increased rates of self-administration escalation on a FR1 schedule when assigned to flavored e-liquids. Upon transition to FR3, mice continued to exhibit enhanced levels of reinforcement with flavored e-liquids. We also observed that mice self-administer zero-nicotine green apple flavored e-liquids.

Conclusions

These data provide additional evidence that ENDS flavors enhance vaping-related initiation and reinforcement-related behavior and promote the need to continue investigating the role ENDS flavors play in vaping-related behaviors.

Implications

There has been much discussion recently regarding the impact of flavors on vaping-related behavior. Our study here shows that flavors significantly enhance the acquisition and reinforcement of vaping-related behavior. This suggests that flavors in electronic nicotine delivery systems significantly increase the risk of addiction-related behaviors among users of vaping products.
Covid-19: statutory means of scrutinizing workers’ deaths and disease
Authors: Agius R M
Published: August 2020

Background

By law, covid-19 disease and deaths in workers may lead to coroners’ inquests and/or Health and Safety Executive (HSE) investigations.

Aims

This study assesses the adequacy of these statutory means to yield recommendations for prevention of acquiring covid-19 infection from work.

Methods

Covid-19 guidance from the chief coroner and the HSE was appraised, including using Office for National Statistics (ONS) data. Practitioners were asked to estimate the likelihood that covid-19 disease may have arisen from ‘near-miss’ scenarios. Data from the judiciary and the HSE were analysed.

Results

The coroners’ guidance allowed a wider range of reports of death than did the HSE and conformed better with ONS data on covid-19 mortality by occupation. In the practitioner survey, 62 respondents considered a higher likelihood that reported covid-19 cases would have arisen from the scenario deemed unreportable as a ‘dangerous occurrence’ by HSE than the reportable scenario (P < 0.001). On average there was only one coroner’s report to prevent future death from occupational disease every year in England and Wales. The HSE dealt with a yearly average of 1611 reports of work-related disease including 104 on biological agents, but has received about 9000 covid-19 reports.

Conclusions

Current HSE guidance for reporting work-related covid-19 may miss many thousands of cases and needs further iteration. Coroners have very limited experience of inquiry into occupational disease caused by biological agents compared with the HSE. Concerns regarding national policy such as on protective equipment warrant a full public inquiry.
Infective Endocarditis Guidelines: The Challenges of Adherence—A Survey of Infectious Diseases Clinicians
Authors: Huang Glen , Gupta Siddhi , Davis Kyle A , Barnes Erin W , Beekmann Susan E , Polgreen Philip M , Peacock James E
Published: August 2020

Background

Guidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown.

Methods

An electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America’s Emerging Infections Network.

Results

Five hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The duration of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double β-lactam therapy was “usually” or “almost always” employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians.

Conclusions

The finding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double β-lactam regimens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed.
Rural–urban differences in body mass index and obesity-related behaviors among low-income preschoolers
Authors: Contreras Dawn A , Martoccio Tiffany L , Brophy-Herb Holly E , Horodynski Mildred , Peterson Karen E , Miller Alison L , Senehi Neda , Sturza Julie , Kaciroti Niko , Lumeng Julie C
Published: August 2020

Background

With one in eight preschoolers classified as obese in the USA, childhood obesity remains a significant public health issue. This study examined rural–urban differences in low-income preschoolers’ body mass index z-scores (BMIz), eating behaviors, dietary quality, physical activity (PA) and screen time.

Methods

Pre-intervention data from 572 preschooler-parent dyads participating in a randomized, controlled obesity prevention trial in the Midwest USA were analyzed. We examined the associations among living in rural versus urban areas, child BMIz and child obesity-related behaviors, including eating behaviors, dietary quality, PA and screen time.

Results

Rural children had higher BMIz, more emotional overeating behaviors and more time spent playing outdoors compared with urban children. We found no associations between children living in rural versus urban areas and dietary quality and screen time.

Conclusions

The study found that rural–urban differences in BMIz may start as early as 3–4 years of age, if not earlier. To reverse the weight-related health disparities between rural and urban low-income preschoolers, structural changes in rural locations and family supports around coping skills may be needed.
Sustained-release diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate) for knee osteoarthritis: a randomized phase 2 study
Authors: Nishida Yoshihiro , Kano Kazuyuki , Nobuoka Yuji , Seo Takayuki
Published: August 2020

Objective

To evaluate the efficacy and safety of diclofenac etalhyaluronate (DF-HA) (ONO-5704/SI-613), a novel DF-conjugated hyaluronate, in patients with knee OA in Japan.

Methods

In this randomized, double-blind, placebo-controlled phase 2 study, patients were randomly assigned (1:1) to receive either 30 mg of DF-HA or placebo intra-articularly at weeks 0, 4 and 8 and were followed up for 24 weeks. The primary outcomes were changes from baseline in the WOMAC pain subscores, 50-foot walk test pain score and daily pain score. The secondary outcomes were the WOMAC physical function subscores, patient global assessment, responder rate and safety outcome.

Results

Overall, 176 patients received the investigational drugs (87 received DF-HA and 89 received placebo). The mean changes in the WOMAC pain subscores and daily pain score from baseline over 12 weeks after the first injection were significantly higher in the DF-HA than placebo group; the mean difference was −7.0 mm [95% CI, −12.7, −1.2; P =0.018] and −0.61 (95% CI, −1.06, −0.16; P =0.008), respectively. The difference in the 50-foot walk test pain score was −5.0 mm (95% CI, −10.3, 0.3; P =0.065). Improvement of pain by DF-HA was observed at week 1 and maintained from week 12 to week 24. Significantly greater improvements in the secondary outcomes were also observed with DF-HA than with placebo. No clinically significant adverse events occurred.

Conclusion

DF-HA reduced pain in patients with knee OA without major safety concerns.

Trial registration

UMIN Clinical Trials Registry, https://www.umin.ac.jp/ctr/index.htm, UMIN000015858
The burden of obstructive sleep apnea in pediatric sickle cell disease: a Kids’ inpatient database study
Authors: Tsou Po-Yang , Cielo Christopher M , Xanthopoulos Melissa S , Wang Yu-Hsun , Kuo Pei-Lun , Tapia Ignacio E
Published: August 2020

Study Objectives

Obstructive sleep apnea (OSA) is associated with cardiovascular and cerebrovascular morbidity. Patients with sickle cell disease (SCD) are at increased risk for both neurologic complications (NC) and OSA. However, the relationship between OSA and SCD complications is unclear. We hypothesized that there would be an association between OSA diagnosis and SCD complications.

Methods

Hospital discharge records of patients with SCD aged < 19 years were obtained for the years 1997, 2000, 2003, 2006, 2009, and 2012 from the Kid’s Inpatient Database. The primary outcome, NC, a composite of stroke, transient ischemic attack, and seizures. Secondary outcomes included acute chest syndrome (ACS), vaso-occlusive crisis, length of hospital stay, and inflation-adjusted cost of hospitalization. Multivariable regression was conducted to ascertain the association of OSA with primary and secondary outcomes. Analyses were adjusted for the use of noninvasive mechanical ventilation (NIMV) to determine its role as NC risk modifier.

Results

There were 203,705 SCD discharges included in the analysis, of which 2,820 (1.4%) and 4,447 (2.2%) also included OSA and NC diagnoses. Multivariable logistic regression indicated that OSA was associated with NC (adjusted odds ratio [OR], 1.50 [95% CI 1.02–2.21], p = 0.039) and ACS (OR, 1.34 [95% CI 1.08–1.67], p = 0.009) in children with SCD. In the multivariable analysis adjusted for NIMV, the significant association between OSA and NC was no longer observed (OR, 1.39 [95% CI 0.94–2.05], p = 0.100).

Conclusions

OSA is associated with a 50% increase of odds of NC in children with SCD in this nationwide dataset. The use of NIMV to treat OSA may modify the risk of OSA-associated NC.
Another stripe on the tiger makes no difference? Unexpected diversity in the widespread tiger tarantula Davus pentaloris (Araneae: Theraphosidae: Theraphosinae)
Authors: Candia-Ramírez Daniela T , Francke Oscar F
Published: August 2020

Integrative taxonomy is relevant for the discovery and delimitation of cryptic species by incorporating different sources of evidence to construct rigorous species hypotheses. The genus Davus was recently revised and it was found that Davus pentaloris presents high morphological variation across its widespread distribution. However, tarantulas usually present low dispersal capabilities that occasionally result in local endemism. In order to evaluate species boundaries within this taxon, we examine the morphological variation and, additionally, employ four strategies based on mtDNA data (COI): two distance-based [automatic barcode gap discovery (ABGD) and Neighbor-Joining (NJ)] and two tree-based methods [general mixed Yule coalescent (GMYC) and Bayesian Poisson tree process (bPTP)]. Available morphological evidence recovers 13 putative morphospecies, but the different methods based on molecular data recover a variable number of candidate species (16–18). Based on the congruence across all analyses and the available morphological data, we recognize 13 clearly diagnosable species, 12 of them new to science. We conclude that the underestimation of the diversity in D. pentaloris was mainly caused by deficient practices in taxonomy, rather than by the presence of cryptic diversity. Although COI is a functional barcoding marker and it gives reliable results in our study, we recommend combining multiple sources of evidence and strategies to construct better species delimitation hypotheses.
Seedling Disease of Corn Caused by Pythium Increases With Proximity of Rye
Authors: Kurtz Sarah M. , Acharya Jyotsna , Kaspar Thomas C. , Robertson Alison E.
Published: August 2020

Yield loss of corn following a winter rye cover crop (CC) has been associated with increases in seedling disease caused by Pythium spp. We hypothesized that physical separation between the CC and corn could reduce the risk of seedling disease, and benefit corn growth and development. In a growth chamber experiment, corn seedlings were planted at 0 cm and 8 to 10 cm from terminated winter rye plants. Root rot severity was assessed at crop development stage V2, and quantitative PCR was used to estimate the abundance of Pythium clade B and clade F members present in corn roots. Radicle and seminal root rot severity was numerically greater when seedlings were planted 0 cm from terminated rye plants compared with seedlings planted 8 to 10 cm away. Moreover, a greater abundance of Pythium clade B was detected in corn grown within the terminated winter rye compared with corn planted further away (P = 0.0003). No effect of distance between corn and winter rye was detected for Pythium clade F. These data contribute to our understanding of the effect of a winter rye cover crop on corn and will inform field trial management practices for farmers to reduce occasional yield loss of corn following a winter rye cover crop.
Genome-Wide Association Study on Resistance to Rice Black-Streaked Dwarf Disease Caused by Rice black-streaked dwarf virus
Authors: Liu Qing , Lan Guofang , Zhu Yajun , Chen Kai , Shen Congcong , Zhao Xiuqin , Zhang Fan , Xu Jianlong , Li Zhikang
Published: August 2020

Rice black-streaked dwarf disease caused by Rice black-streaked dwarf virus (RBSDV) is one of the most destructive viral diseases of rice. Thus, it is imperative that resistant rice germplasms are screened for novel RBSDV-resistant genes. RBSDV resistance of a diverse global collection comprising 1,953 rice accessions was evaluated under natural conditions across 3 years. The average disease incidences of the Xian/indica (XI) subgroup were significantly lower than those of the Geng/japonica (GJ) subgroup. Interestingly, most XI-1A accessions in the Xian subgroup were significantly more susceptible than XI-1B accessions, even though XI-1A and XI-1B have a close phylogenetic relationship. Four Xian accessions stably and highly resistant to RBSDV were consistently identified in 2 years. Ten genomic regions (GRs) with 147 single nucleotide polymorphisms associated with RBSDV resistance were detected by a single-locus genome-wide association study (GWAS), of which five were repeatedly identified in a multilocus GWAS. Two previously reported GRs, grRBSDV-6.1 and grRBSDV-6.3, which were repeatedly detected as stably and highly associated with RBSDV resistance, contained 17 and seven genes, respectively, with significant differences of resistance among haplotypes. Haplotype analyses of the candidate genes LOC_Os06g03150 in grRBSDV-6.1 and LOC_Os06g31190 in grRBSDV-6.3 suggested that the former gene is mainly associated with the differentiation of resistance within the Xian subgroup and the latter gene mainly explains the difference in the resistance between Xian and Geng. Another three novel resistance GRs (grRBSDV-1.1, grRBSDV-7.1, and grRBSDV-9.1) were identified. Our findings may enhance the application of disease-resistant rice germplasms for breeding RBSDV-resistant varieties.
Effects of exercise training on renal interstitial fibrosis and renin–angiotensin system in rats with chronic renal failure
Authors: Yamakoshi Seiko , Nakamura Takahiro , Mori Nobuyoshi , Suda Chihiro , Kohzuki Masahiro , Ito Osamu
Published: August 2020

Objective:

To clarify the mechanisms of the renal protective effects of exercise training, we examined the effects of exercise training on the renal interstitial fibrosis and renin–angiotensin system (RAS) in rats with chronic renal failure.

Methods:

Six-week-old male Sprague-Dawley rats were divided into three groups: sham operation; 5/6 nephrectomy + sedentary; 5/6 nephrectomy + exercise training. The 5/6 nephrectomy + exercise training group underwent treadmill running (20 m/min, 60 min/day, 5 days/week). After 12 weeks, renal function, histology and protein expression of collagen type I, transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP), tissue inhibitors of metalloproteinase (TIMP) and RAS components in the renal cortex were examined.

Results:

Exercise training ameliorated the 5/6 nephrectomy-induced hypertension, proteinuria, renal dysfunction, glomerular sclerosis and renal interstitial fibrosis. 5/6 Nephrectomy increased the expression of collagen type I, TGF-β1, MMP-2, MMP-9, TIMP-1, angiotensinogen, angiotensin-converting enzyme (ACE), (pro)renin receptor and angiotensin II type 1 receptor, and exercise training inhibited the 5/6 nephrectomy-increased expression of collagen type I, TGF-β1, TIMP-1, angiotensinogen and ACE expressions. 5/6 Nephrectomy decreased the expression of renin, ACE2, angiotensin II type 2 receptor and Mas receptor, and exercise training inhibited the 5/6 nephrectomy-decreased expressions.

Conclusion:

These results indicated that exercise training attenuates the progression of glomerular sclerosis and renal interstitial fibrosis in chronic renal failure rats. The renal protective effects of exercise training may be mediated by ameliorating the renal collagen turnover and the exacerbation of renal RAS.
A Review of Siblings' Needs and Interventions Supporting Their Adaptation in the Neonatal Intensive Care Unit
Authors: Savanh Phoukim , Aita Marilyn , Héon Marjolaine
Published: August 2020

Many aspects may interfere with siblings' adaptation when an infant is born prematurely and hospitalized in the neonatal intensive care unit (NICU). During this critical period, siblings may have sudden change of behaviors if their needs are not adequately met. Parents and neonatal nurses are often unaware of the importance of supporting siblings in the NICU. In this narrative review, siblings' needs and interventions to support them in the NICU will be synthesized and discussed. A total of 14 articles were reviewed to better understand siblings' needs and discuss findings related to interventions supporting siblings' adaptation in the NICU. Further studies should be conducted with validated and reliable evaluation tools to validate these findings. Overall, interventions for siblings in the NICU appear to be beneficial for siblings and their parents.
Attentional bias to somatosensory stimuli in chronic pain patients: a systematic review and meta-analysis
Authors: Broadbent Philippa , Liossi Christina , Schoth Daniel E.
Published: August 2020

This systematic review and meta-analysis aimed to evaluate the evidence pertaining to attentional bias for painful and nonpainful somatosensory stimuli in individuals with chronic pain. Eligible studies were identified through searches of Medline, PsycINFO, CINAHL, Web of Science, Scopus, and Cochrane Library databases. Search terms were words and phrases organised into 3 concept blocks: pain condition, cognitive process, and stimuli/paradigm. The search identified 29 eligible studies (reporting 32 eligible experiments), of which quantitative meta-analysis was possible for 16 studies (19 experiments). The meta-analysis found that chronic pain patients, excluding somatoform pain patients, showed significantly greater attentional bias to stimuli in the somatosensory modality than healthy controls (k = 9, g = 0.34). In addition, meta-analysis of studies that used a temporal order judgement task found that patients with unilateral chronic pain showed a spatial attentional bias away from somatosensory stimuli (k = 7, effect estimate = 22.43 ms) and visual stimuli (k = 2, effect estimate = 13.75 ms) on or near the painful body side. Most studies of attentional bias to the somatosensory modality recruited samples of patients with fibromyalgia, whereas most studies of spatial attentional bias assessed patients with complex regional pain syndrome. The extent to which these results generalise to other pain conditions is therefore unclear. We recommend future research test spatial and modality attentional biases across chronic pain conditions and examine the psychometric properties of attentional bias measurement paradigms for use with chronic pain populations. PROSPERO registration number CRD42019124510.
Increased peptidergic fibers as a potential cutaneous marker of pain in diabetic small fiber neuropathy
Authors: Karlsson Pall , Provitera Vincenzo , Caporaso Giuseppe , Stancanelli Annamaria , Saltalamacchia Anna Maria , Borreca Ilaria , Manganelli Fiore , Santoro Lucio , Jensen Troels Staehelin , Nolano Maria
Published: August 2020

Diabetic polyneuropathy (DPN) is a common complication of diabetes and is often associated with neuropathic pain. The mechanisms underlying development and maintenance of painful DPN are largely unknown, and quantification of intraepidermal nerve fiber density from skin biopsy, one of the neuropathological gold standard when diagnosing DPN, does not differentiate between patients with and without pain. Identification of possible pain pathophysiological biomarkers in patients with painful DPN may increase our knowledge of mechanisms behind neuropathic pain. Animal models of painful DPN have been shown to have an increased density of peptidergic nerve fibers (substance P and calcitonin gene-related peptide). In this study, we performed a detailed skin biopsy analysis in a well-characterized group of DPN patients with primarily small fiber involvement, with and without pain, and in healthy controls and test for correlation between skin biopsy findings and pain intensity and quantitative sensory testing. We found that although there was no difference in intraepidermal nerve fiber density using protein gene product 9.5 between patients with and without pain, patients with pain had increased density of dermal peptidergic fibers containing substance P and calcitonin gene-related peptide compared with patients with painless DPN and healthy controls. Peptidergic nerve fiber density correlated with pain ratings in patients with pain (R = 0.33; P = 0.019), but not with quantitative sensory testing results. In this article, we show, for the first time in humans, an increased density of dermal peptidergic fibers in painful DPN. These findings provide new insight in the pathophysiological mechanisms of pain in diabetes and open the research towards new therapeutic targets.
Tall Pines Healthcare COVID-19 Outbreak Experience in Rural Waldo County, Maine, April 2020
Authors: Kuhn Carol , Rose Alana
Published: August 2020

As a family physician and a family nurse practitioner in a Federally Qualified Health Center in rural Maine, we experienced a COVID-19 outbreak at our local long-term care facility, which involved 32 patient cases, 11 staff cases, 19 recovered cases, and 13 deaths over 34 days in April 2020. There were many lessons to be learned that may inform and guide others or help prevent facilities from facing some predictable challenges.
Pandemic Notes From a Maine Direct Primary Care Practice
Authors: Pierce Brian R. , Pierce Claire
Published: August 2020

The effects of coronavirus disease-2019 (COVID-19) pandemic fear and its economic impact in rural primary care are still being felt, as they have affected demand for office visits and how we deliver care. Our finances and our ability to sustainably deliver this care, however, have not yet changed significantly due to the nature of our business model as a direct primary care practice.
Fighting the COVID-19 Merciless Monster
Authors: Rosenthal E. Lee , Menking Paige , Begay Mae-Gilene
Published: August 2020

Over 100 Community Health Representatives (CHRs) as part of the oldest and largest Community Health Worker (CHW) program in the United States serve the Dine People on the Navajo Nation. The CHRs work under a tribally determined scope of practice that embraces the importance of self-determination of tribal nations, a philosophy central to the CHW field nationally. Navajo CHRs are the epitome of frontline workers, as they extend their traditional role to encompass long-term emergency response during coronavirus disease-2019 (COVID-19). This article describes the Navajo CHR role in the pandemic through the lens of an interview with the program's director, Mae-Gilene Begay.
The value of brain natriuretic peptide in the prosthetic valve thrombosis
Authors: Bayram Zübeyde , Gündüz Sabahattin , Güner Ahmet , Kalçik Macit , Doğan Cem , Gürsoy Mustafa Ozan , Karakoyun Süleyman , Özkan Mehmet
Published: August 2020

We aimed to investigate how prosthetic valve thrombosis (PVT) affects brain natriuretic peptide (BNP) levels and how BNP changes following thrombolytic therapy. The study included 70 consecutive patients with left-sided mechanical PVT who received thrombolytic therapy. The patients were divided into two groups, namely obstructive thrombus (n = 42) and nonobstructive thrombus (NOT, n = 28). BNP levels of patients were assessed before and after thrombolytic therapy. BNP levels were higher in obstructive thrombus group than NOT group in whole study population, in patients with mitral PVT and in patients with aortic PVT [325.0 (189.5–496.0) vs. 84.0 (44.5–140.0), P < 0.001, 323.0 (193–449.0) vs. 59.0 (37.0–131.0), P < 0.001 and 321.0 (132.0–525.0) vs. 99.0 (60.5–173.0), P < 0.001]. BNP levels were positively correlated with transmitral and transaortic mean gradients, and negatively correlated with mitral valve area (r: 0.374, P = 0.013; r: 0.432, P = 0.035 and; r: −0.642, P < 0.001, respectively). BNP values above 165 pg/ml may predict the presence of obstructive thrombus with a sensitivity of 88.0%, and a specificity of 79.0% (AUC = 0.928, 95% confidence interval: 0.871–0.986, P < 0.001). Following thrombolytic therapy, BNP levels (pg/ml) significantly decreased from 325.0 (189.5–496.0) to 137.0 (101.7–224.5), P < 0.001, in all patients with obstructive thrombus, from 323.0 (193.0–449.0) to 129.0 (98.0–223.0), P < 0.001, in patients with only mitral obstructive thrombus and from 321.0 (132.0–525.0) to 181.0 (99.0–217.5), P < 0.001, in patients with only aortic obstructive thrombus. BNP levels are significantly higher in prosthetic valve patients with obstructive thrombus than in those with NOT and decrease in patients with obstructive thrombus after thrombolytic therapy. A cut off value of BNP of at least 165.0 pg/ml was found to discriminate obstructive thrombus from NOT.
The case for cochlear implantation in unilateral and asymmetric sensorineural hearing loss
Authors: Bojrab Dennis , Hong Robert S.
Published: August 2020

Purpose of review

Cochlear implants have been used to treat bilateral deafness for over 40 years. A more recent development has been the application of this technology toward single-sided deafness (SSD) and asymmetric hearing loss (AHL), culminating in the Food and Drug Administration (FDA) approval in the United States for this indication in July of 2019. This review examines the recent literature on cochlear implants for SSD and AHL, focusing on speech perception, sound localization, tinnitus, and quality of life.

Recent findings

There is an expanding body of literature supporting the use of cochlear implant in SSD/AHL patients. The cochlear implant offers a unique rehabilitation option for this subset of patients as it potentially restores binaural hearing (direct stimulation of both ears). A review of the literature reveals significant improvements with the cochlear implant in speech perception in quiet and noise, sound localization, tinnitus, and quality of life. In addition, these improvements appear to be greater than what conventional options such as a contralateral routing of signal (CROS) hearing aid and bone conduction device (BCD) are able to achieve.

Cochlear implants offer additional benefits over previously available options of CROS and BCDs and have recently been approved by the FDA for use in patient with SSD/AHL. Given the growing body of literature demonstrating the benefit of cochlear implant over other devices, it is important to offer cochlear implant as an option to these patients.
The Role of Anxiety in Patients With Persistent Atrial Fibrillation Undergoing Elective Cardioversion: An Observational Study
Authors: García-Izquierdo Eusebio , Fajardo-Simón Lourdes , Cruz-Utrilla Alejandro , Aguilera-Agudo Cristina , Jiménez-Sánchez Diego , Sánchez-García Manuel , Lobo Ana Blasco , Escudier-Villa Juan M. , Ortega-Marcos Javier , Silva-Melchor Lorenzo , Castro-Urda Victor , Toquero-Ramos Jorge , de Arce-Cordón Rosario , Fernández-Lozano Ignacio
Published: August 2020

Objective

Anxiety is often present among patients with atrial fibrillation (AF). This condition has been associated with greater symptom severity and worse quality of life in these patients. However, the influence of anxiety on the risk of AF recurrence is not well known. We aimed to define the level of anxiety in patients with persistent AF undergoing elective cardioversion (EC) and determine whether there is an association between anxiety and the risk of early AF recurrence after EC.

Methods

Anxiety was measured before EC using the State-Trait Anxiety Inventory. Early AF recurrence was assessed with a control electrocardiogram at 30-day follow-up.

Results

We included 107 patients undergoing effective EC. Early AF recurrence was diagnosed in 40 patients (37.4%). Compared with those who remained in sinus rhythm, individuals with early AF recurrence had significantly higher levels of trait anxiety (23.1 [10.4] versus 17.9 [9.5]; p = .013) and larger left atrial volume index (45.8 [12.3] versus 37.9 [13.3] ml/m2; p = .004). Both variables remained independently associated with early AF recurrence after multivariate analysis. A predictive model including trait anxiety score >20 and left atrial volume index >41 ml/m2 showed acceptable accuracy for the diagnosis of early AF recurrence (area under the curve = 0.733; 95% confidence interval = 0.634–0.832; p < .001).

Conclusions

Our study shows that trait anxiety is an independent risk factor for early AF recurrence after EC. Further studies are warranted to assess the beneficial role of anxiety-reducing strategies on the outcomes of patients with AF.
Decompressing Stoma a s Bridge to Elective Surgery is an Effective Strategy for Left-sided Obstructive Colon Cancer
Authors: Veld Joyce V. , Amelung Femke J. , Borstlap Wernard A. A. , van Halsema Emo E. , Consten Esther C. J. , Dekker Jan Willem T. , Siersema Peter D. , ter Borg Frank , van der Zaag Edwin S. , Fockens Paul , Bemelman Willem A. , de Wilt Johannes H. W. , van Hooft Jeanin E. , Tanis Pieter J.
Published: August 2020

Objective:

The purpose of this population-based study was to compare decompressing stoma (DS) as bridge to surgery (BTS) with emergency resection (ER) for left-sided obstructive colon cancer (LSOCC) using propensity-score matching.

Summary Background Data:

Recently, an increased use of DS as BTS for LSOCC has been observed in the Netherlands. Unfortunately, good quality comparative analyses with ER are scarce.

Methods:

Patients diagnosed with nonlocally advanced LSOCC between 2009 and 2016 in 75 Dutch hospitals, who underwent DS or ER in the curative setting, were propensity-score matched in a 1:2 ratio. The primary outcome measure was 90-day mortality, and main secondary outcomes were 3-year overall survival and permanent stoma rate.

Results:

Of 2048 eligible patients, 236 patients who underwent DS were matched with 472 patients undergoing ER. After DS, more laparoscopic resections were performed (56.8% vs 9.2%, P < 0.001) and more primary anastomoses were constructed (88.5% vs 40.7%, P < 0.001). DS resulted in significantly lower 90-day mortality compared to ER (1.7% vs 7.2%, P = 0.006), and this effect could be mainly attributed to the subgroup of patients over 70 years (3.5% vs 13.7%, P = 0.027). Patients treated with DS as BTS had better 3-year overall survival (79.4% vs 73.3%, hazard ratio 0.36, 95% confidence interval 0.20-0.65) and fewer permanent stomas (23.4% vs 42.4%, P < 0.001).

Conclusions:

In this nationwide propensity-score matched study, DS as a BTS for LSOCC was associated with lower 90-day mortality and better 3-year overall survival compared to ER, especially in patients over 70 years of age.
The ILLS Laparoscopic Liver Surgery Fellow Skills Curriculum
Authors: Krenzien Felix , Schöning Wenzel , Brunnbauer Philipp , Benzing Christian , Öllinger Robert , Biebl Matthias , Bahra Marcus , Raschzok Nathanael , Cherqui Daniel , Geller David , Han Ho-Seong , Wakabayashi Go , Schmelzle Moritz , Pratschke Johann
Published: August 2020

Introduction:

Laparoscopy is becoming the standard approach in liver surgery. As the degree of difficulty varies greatly from core skills to advanced procedures, strategies for teaching young surgeons need to be reconsidered. We here aimed to design a skills curriculum for LLR.

Methods:

Using the nominal group technique, 22 substeps of LLR were identified by 61 hepatobiliary surgeons. The raters were asked to rate (1) the difficulty of substeps and (2) the minimum number of times that the substep must be performed for mastery of the technique. According to the frequency of defined substeps, being estimated on the basis of high volume center experiences (n = 222 LLR; 1/2017–12/2018), the center's training capacity and defined goals for a 2-year fellowship were calculated.

Results:

Ten surgical substeps (45%) are routinely performed and can thus be taught sufficiently at centers carrying out ≥50 LLR in 2 years. As the mobilization of the right liver lobe and the dissection of the hepatic artery or portal vein is performed in only 27% and 28% of all LLR, respectively, sufficient training can only be provided at centers with ≥100 LLRs in 2 years. Mastery of complex parenchymal dissection (19%) and hilar lymphadenectomy (8%) can only be achieved in center performing ≥200 LLR in 2 years.

Conclusion:

We here suggest a stepwise approach for training of hepatobiliary fellows in LLR. Based on the estimated complexity of the substeps and the size of the center, not every substep can be learned within 2 years.
Pancreatic Inflammation and Proenzyme Activation Are Associated With Clinically Relevant Postoperative Pancreatic Fistulas After Pancreas Resection
Authors: Wüster Carina , Shi Haoyun , Kühlbrey Christian M. , Biesel Esther A. , Hopt Ulrich T. , Fichtner-Feigl Stefan , Wittel Uwe A.
Published: August 2020

Objective:

We investigated the activation of pancreatic proenzymes and signs of peripancreatic inflammation in patients with clinically relevant postoperative pancreatic fistulas (POPFs).

Summary Background Data:

An increase of systemic amylase concentration was associated with POPFs. This suggested parallels in the pathomechanisms between the development of POPFs and pancreatitis.

Methods:

Trypsinogen, procathepsin B, and IL-6 concentrations as well as cathepsin B, myeloperoxidase and trypsin activities were determined throughout the first 7 postoperative days in drain fluids of 128 consecutive patients after pancreas resection. Histology and immunohistochemistry were performed in pancreatic specimens after total pancreatectomy due to complications and after placing experimental pancreatic sutures in the pancreatic tail of C57/Bl6 mice.

Results:

Trypsin activity, cathepsin B activity and myeloperoxidase activity on the first postoperative day were elevated and predictive for clinically relevant pancreatic fistulas. Drain fluid stabilized trypsin activity and prevented the activation of the cascade of digestive enzymes. Leukocytes were the source of cathepsin B in drain fluid. Findings differed between fistulas after distal pancreatectomy and pancreatoduodenectomy. Immunohistochemistry of the pancreatic remnant revealed an inflammatory infiltrate expressing cathepsin B, independent of the presence of pancreatic fistulas. The infiltrate could be reproduced experimentally by sutures placed in the pancreatic tail of C57/Bl6 mice.

Conclusions:

Trypsinogen activation, increased cathepsin B activity and inflammation around the pancreato-enteric anastomosis on post operative day 1 are associated with subsequent clinically relevant POPFs after pancreatoduodenectomy. The parenchymal damage seems to be induced by placing sutures in the pancreatic parenchyma during pancreatic surgery.
Prognostic Impact of Frozen Section Investigation and Extent of Proximal Safety Margin in Gastric Cancer Resection
Authors: Berlth Felix , Kim Woo-Ho , Choi Jong-Ho , Park Shin-Hoo , Kong Seong-Ho , Lee Hyuk-Joon , Yang Han-Kwang
Published: August 2020

Background and Aims:

Guidelines propose different extents of macroscopic proximal margin for gastric cancer and frozen margin investigation in selected cases, but data is lacking. This study was to evaluate the necessary extent of macroscopic proximal margin, accuracy of frozen margin investigation, and prognostic impact of tumor-free proximal margin length in pT2-pT4 gastric cancer.

Study Design:

Proximal and distal frozen margins were routinely investigated intraoperatively in all pT2-pT4 gastric cancers resected between 2011 and 2017. Macroscopic and microscopic proximal margin lengths were correlated. For R0-resections, survival analysis was performed for distal gastrectomy (DG) with microscopic proximal margin length ≤3 cm versus >3 cm.

Results:

Overall, 1484 patients were included. Microscopic proximal margin lengths were macroscopically more often misestimated in diffuse histology (P = 0.0004), but extent of underestimation in centimeter was similar to intestinal and mixed/undetermined type (P = 0.134). Fifteen cases (1.0%) resulted in R1-resection, 10 at distal, and 5 at proximal margin but none with macroscopic proximal margin ≥3 cm and negative frozen section. Overall agreement of frozen margin and final pathology was 2951/2968 (99.4%). Proximal margin length in DG did not correlate with survival or recurrence in R0-resected patients.

Discussion:

Diffuse histology is at higher risk for underestimation of proximal margin length, but extent of underestimation is similar in other Laurén subtypes. If ≥3 cm macroscopic proximal margin length is applied with intraoperative frozen margin confirmation, R1-resection can be avoided.

Conclusion:

In pT2-T4a gastric cancer, proximal margin of ≥3 cm plus frozen margin confirmation provides high oncological safety. In DG patients with R0-resection, proximal margin length does not correlate with survival or recurrence.
Hypothermic Oxygenated Perfusion Versus Normothermic Regional Perfusion in Liver Transplantation From Controlled Donation After Circulatory Death
Authors: Muller Xavier , Mohkam Kayvan , Mueller Matteo , Schlegel Andrea , Dondero Federica , Sepulveda Ailton , Savier Eric , Scatton Olivier , Bucur Petru , Salame Ephrem , Jeddou Heithem , Sulpice Laurent , Pittau Gabriella , Allard Marc-Antoine , Mabrut Jean-Yves , Dutkowski Philipp , Clavien Pierre-Alain , Lesurtel Mickael
Published: August 2020

Objective:

To compare HOPE and NRP in liver transplantation from cDCD.

Summary of Background Data:

Liver transplantation after cDCD is associated with higher rates of graft loss. Dynamic preservation strategies such as NRP and HOPE may offer safer use of cDCD grafts.

Methods:

Retrospective comparative cohort study assessing outcomes after cDCD liver transplantation in 1 Swiss (HOPE) and 6 French (NRP) centers. The primary endpoint was 1-year tumor-death censored graft and patient survival.

Results:

A total of 132 and 93 liver grafts were transplanted after NRP and HOPE, respectively. NRP grafts were procured from younger donors (50 vs 61 years, P < 0.001), with shorter functional donor warm ischemia (22 vs 31 minutes, P < 0.001) and a lower overall predicted risk for graft loss (UK-DCD-risk score 6 vs 9 points, P < 0.001). One-year tumor-death censored graft and patient survival was 93% versus 86% (P = 0.125) and 95% versus 93% (P = 0.482) after NRP and HOPE, respectively. No differences in non-anastomotic biliary strictures, primary nonfunction and hepatic artery thrombosis were observed in the total cohort and in 32 vs. 32 propensity score-matched recipients

Conclusion:

NRP and HOPE in cDCD achieved similar post-transplant recipient and graft survival rates exceeding 85% and comparable to the benchmark values observed in standard DBD liver transplantation. Grafts in the HOPE cohort were procured from older donors and had longer warm ischemia times, and consequently achieved higher utilization rates. Therefore, randomized controlled trials with intention-to-treat analysis are needed to further compare both preservation strategies, especially for high-risk donor-recipient combinations.
Centralization and Oncologic Training Reduce Postoperative Morbidity and Failure-to-rescue Rates After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies
Authors: Noiret Barbara , Clement Guillaume , Lenne Xavier , Bruandet Amelie , Glehen Olivier , Voron Thibault , Piessen Guillaume , Eveno Clarisse
Published: August 2020

Objective:

Evaluate at a national level the postoperative mortality (POM), major morbidity (MM) and failure-to-rescue (FTR) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) across time and according to hospital-volume.

Background:

CRS/HIPEC is an effective therapeutic strategy commonly used to treat peritoneal surface malignancies. However, this aggressive approach has the reputation to be associated with a high POM and MM.

Methods:

All patients treated with CRS/HIPEC between 2009 and 2018 in France were identified through a national medical database. Patients and perioperative outcomes were analyzed. A cut-off value of the annual CRS/HIPEC caseload affecting the 90-day POM was calculated using the Chi-squared Automatic Interaction Detector method. A multivariable logistic model was used to identify factors mediating 90-day POM.

Results:

A total of 7476 CRS/HIPEC were analyzed. Median age was 59 years with a mean Elixhauser comorbidity index of 3.1, both increasing over time (P < 0.001). Ninety-day POM was 2.6%. MM occurred in 44.2% with a FTR rate of 5.1%. The threshold of CRS/HIPEC number per center per year above which the 90-day POM was significantly reduced was 45 (3.2% vs 1.9%, P = 0.01). High-volume centers had more extended surgery (P < 0.001) with increased MM (55.8% vs 40.4%, P < 0.001) but lower FTR (3.1% vs 6.3%, P = 0.001). After multivariate analysis, independent factors associated with 90-day POM were: age >70 years (P = 0.002), Elixhauser comorbidity index ≥8 (P = 0.006), lower gastro-intestinal origin, (P < 0.010), MM (P < 0.001), and <45 procedures/yr (P = 0.002).

Conclusion:

In France, CRS/HIPEC is a safe procedure with an acceptable 90-day POM that could even be improved through centralization in high-volume centers.
Neuronal immunoglobulin superfamily cell adhesion molecules in epithelial morphogenesis: insights fromDrosophila
Authors: Finegan Tara M. , Bergstralh Dan T.
Published: August 2020

In this review, we address the function of immunoglobulin superfamily cell adhesion molecules (IgCAMs) in epithelia. Work in theDrosophilamodel system in particular has revealed novel roles for calcium-independent adhesion molecules in the morphogenesis of epithelial tissues. We review the molecular composition of lateral junctions with a focus on their IgCAM components and reconsider the functional roles of epithelial lateral junctions. The epithelial IgCAMs discussed in this review have well-defined roles in the nervous system, particularly in the process of axon guidance, suggesting functional overlap and conservation in mechanism between that process and epithelial remodelling. We expand on the hypothesis that epithelial occluding junctions and synaptic junctions are compositionally equivalent and present a novel hypothesis that the mechanism of epithelial cell (re)integration and synaptic junction formation are shared. We highlight the importance of considering non-cadherin-based adhesion in our understanding of the mechanics of epithelial tissues and raise questions to direct future work.

This article is part of the discussion meeting issue ‘Contemporary morphogenesis’.
TheDrosophilamicropyle as a system to study how epithelia build complex extracellular structures
Authors: Horne-Badovinac Sally
Published: August 2020

Dynamic rearrangements of epithelial cells play central roles in shaping tissues and organs during development. There are also scenarios, however, in which epithelial cell movements synergize with the secretion of extracellular matrix to build rigid, acellular structures that persist long after the cells are gone. The formation of theDrosophilamicropyle provides an elegant example of this epithelial craftsmanship. The micropyle is a cone-shaped projection of the eggshell through which the sperm will enter to fertilize the oocyte. Though simple on the surface, both the inner structure and construction of the micropyle are remarkably complex. In this review, I first provide an overview of egg development, focusing on the key events required to understand micropyle formation. I then describe the structure of the micropyle, the cellular contributions to its morphogenesis and some interesting open questions about this process. There is a brief discussion of micropyle formation in other insects and fish to highlight the potential for comparative studies. Finally, I discuss how new studies of micropyle formation could reveal general mechanisms that epithelia use to build complex extracellular structures.

This article is part of a discussion meeting issue ‘Contemporary morphogenesis'.