bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylodynamic Inference of Bacterial Outbreak Parameters Using Nanopore Sequencing
Authors: Steinig Eike , Duchêne Sebastián , Aglua Izzard , Greenhill Andrew , Ford Rebecca , Yoannes Mition , Jaworski Jan , Drekore Jimmy , Urakoko Bohu , Poka Harry , Wurr Clive , Ebos Eri , Nangen David , Manning Laurens , Laman Moses , Firth Cadhla , Smith Simon , Pomat William , Tong Steven Y C , Coin Lachlan , McBryde Emma , Horwood Paul
Published: February 2022

Nanopore sequencing and phylodynamic modeling have been used to reconstruct the transmission dynamics of viral epidemics, but their application to bacterial pathogens has remained challenging. Cost-effective bacterial genome sequencing and variant calling on nanopore platforms would greatly enhance surveillance and outbreak response in communities without access to sequencing infrastructure. Here, we adapt random forest models for single nucleotide polymorphism (SNP) polishing developed by Sanderson and colleagues (2020. High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic nanopore sequencing. Genome Res. 30(9):1354–1363) to estimate divergence and effective reproduction numbers (Re) of two methicillin-resistant Staphylococcus aureus (MRSA) outbreaks from remote communities in Far North Queensland and Papua New Guinea (PNG; n = 159). Successive barcoded panels of S. aureus isolates (2 × 12 per MinION) sequenced at low coverage (>5× to 10×) provided sufficient data to accurately infer genotypes with high recall when compared with Illumina references. Random forest models achieved high resolution on ST93 outbreak sequence types (>90% accuracy and precision) and enabled phylodynamic inference of epidemiological parameters using birth–death skyline models. Our method reproduced phylogenetic topology, origin of the outbreaks, and indications of epidemic growth (Re > 1). Nextflow pipelines implement SNP polisher training, evaluation, and outbreak alignments, enabling reconstruction of within-lineage transmission dynamics for infection control of bacterial disease outbreaks on portable nanopore platforms. Our study shows that nanopore technology can be used for bacterial outbreak reconstruction at competitive costs, providing opportunities for infection control in hospitals and communities without access to sequencing infrastructure, such as in remote northern Australia and PNG.
GREEN-DB: a framework for the annotation and prioritization of non-coding regulatory variants from whole-genome sequencing data
Authors: Giacopuzzi Edoardo , Popitsch Niko , Taylor Jenny C
Published: February 2022

Non-coding variants have long been recognized as important contributors to common disease risks, but with the expansion of clinical whole genome sequencing, examples of rare, high-impact non-coding variants are also accumulating. Despite recent advances in the study of regulatory elements and the availability of specialized data collections, the systematic annotation of non-coding variants from genome sequencing remains challenging. Here, we propose a new framework for the prioritization of non-coding regulatory variants that integrates information about regulatory regions with prediction scores and HPO-based prioritization. Firstly, we created a comprehensive collection of annotations for regulatory regions including a database of 2.4 million regulatory elements (GREEN-DB) annotated with controlled gene(s), tissue(s) and associated phenotype(s) where available. Secondly, we calculated a variation constraint metric and showed that constrained regulatory regions associate with disease-associated genes and essential genes from mouse knock-outs. Thirdly, we compared 19 non-coding impact prediction scores providing suggestions for variant prioritization. Finally, we developed a VCF annotation tool (GREEN-VARAN) that can integrate all these elements to annotate variants for their potential regulatory impact. In our evaluation, we show that GREEN-DB can capture previously published disease-associated non-coding variants as well as identify additional candidate disease genes in trio analyses.
Small molecule targeting CELF1 RNA-binding activity to control HSC activation and liver fibrosis
Authors: Tan Yang , Sun Xueqing , Xu Yizhu , Tang Bingjie , Xu Shuaiqi , Lu Dong , Ye Yan , Luo Xiaomin , Diao Xu , Li Fulong , Wang Tianyi , Chen Jiayu , Xu Qiang , Wu Xingxin
Published: February 2022

CUGBP Elav-like family member 1 (CELF1), an RNA-binding protein (RBP), plays important roles in the pathogenesis of diseases such as myotonic dystrophy, liver fibrosis and cancers. However, targeting CELF1 is still a challenge, as RBPs are considered largely undruggable. Here, we discovered that compound 27 disrupted CELF1-RNA binding via structure-based virtual screening and biochemical assays. Compound 27 binds directly to CELF1 and competes with RNA for binding to CELF1. Compound 27 promotes IFN-γ secretion and suppresses TGF-β1-induced hepatic stellate cell (HSC) activation by inhibiting CELF1-mediated IFN-γ mRNA decay. In vivo, compound 27 attenuates CCl4-induced murine liver fibrosis. Furthermore, the structure-activity relationship analysis was performed and compound 841, a derivative of compound 27, was identified as a selective CELF1 inhibitor. In conclusion, targeting CELF1 RNA-binding activity with small molecules was achieved, which provides a novel strategy for treating liver fibrosis and other CELF1-mediated diseases.
The Promise of Polygenic Risk Prediction in Smoking Cessation: Evidence From Two Treatment Trials
Authors: Bray Michael , Chang Yoonhoo , Baker Timothy B , Jorenby Douglas , Carney Robert M , Fox Louis , Pham Giang , Stoneking Faith , Smock Nina , Amos Christopher I , Bierut Laura , Chen Li-Shiun
Published: February 2022

Introduction

Tobacco use disorder is a complex behavior with a strong genetic component. Genome-wide association studies (GWAS) on smoking behaviors allow for the creation of polygenic risk scores (PRSs) to approximate genetic vulnerability. However, the utility of smoking-related PRSs in predicting smoking cessation in clinical trials remains unknown.

Aims and Methods

We evaluated the association between polygenic risk scores and bioverified smoking abstinence in a meta-analysis of two randomized, placebo-controlled smoking cessation trials. PRSs of smoking behaviors were created using the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN) consortium summary statistics. We evaluated the utility of using individual PRS of specific smoking behavior versus a combined genetic risk that combines PRS of all four smoking behaviors. Study participants came from the Transdisciplinary Tobacco Use Research Centers (TTURCs) Study (1091 smokers of European descent), and the Genetically Informed Smoking Cessation Trial (GISC) Study (501 smokers of European descent).

Results

PRS of later age of smoking initiation (OR [95% CI]: 1.20, [1.04–1.37], p = .0097) was significantly associated with bioverified smoking abstinence at end of treatment. In addition, the combined PRS of smoking behaviors also significantly predicted bioverified smoking abstinence (OR [95% CI] 0.71 [0.51–0.99], p = .045).

Conclusions

PRS of later age at smoking initiation may be useful in predicting smoking cessation at the end of treatment. A combined PRS may be a useful predictor for smoking abstinence by capturing the genetic propensity for multiple smoking behaviors.

Implications

There is a potential for polygenic risk scores to inform future clinical medicine, and a great need for evidence on whether these scores predict clinically meaningful outcomes. Our meta-analysis provides early evidence for potential utility of using polygenic risk scores to predict smoking cessation amongst smokers undergoing quit attempts, informing further work to optimize the use of polygenic risk scores in clinical care.
Prospective Assessment of Symptoms to Evaluate Asymptomatic SARS-CoV-2 Infections in a Cohort of Health Care Workers
Authors: Goguet Emilie , Powers John H , Olsen Cara H , Tribble David R , Davies Julian , Illinik Luca , Jackson-Thompson Belinda M , Hollis-Perry Monique , Maiolatesi Santina E , Pollett Simon , Duplessis Christopher A , Wang Gregory , Ramsey Kathleen F , Reyes Anatalio E , Alcorta Yolanda , Wong Mimi A , Ortega Orlando , Parmelee Edward , Lindrose Alyssa R , Moser Matthew , Samuels Emily C , Coggins Si’Ana A , Graydon Elizabeth , Robinson Sara , Campbell Wesley , Malloy Allison M W , Voegtly Logan J , Arnold Catherine E , Cer Regina Z , Malagon Francisco , Bishop-Lilly Kimberly A , Burgess Timothy H , Broder Christopher C , Laing Eric D , Mitre Edward
Published: February 2022

Background

The frequency of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unclear and may be influenced by how symptoms are evaluated. In this study, we sought to determine the frequency of asymptomatic SARS-CoV-2 infections in a prospective cohort of health care workers (HCWs).

Methods

A prospective cohort of HCWs, confirmed negative for SARS-CoV-2 exposure upon enrollment, were evaluated for SARS-CoV-2 infection by monthly analysis of SARS-CoV-2 antibodies as well as referral for polymerase chain reaction testing whenever they exhibited symptoms of coronavirus disease 2019 (COVID-19). Participants completed the standardized and validated FLU-PRO Plus symptom questionnaire scoring viral respiratory disease symptom intensity and frequency at least twice monthly during baseline periods of health and each day they had any symptoms that were different from their baseline.

Results

Two hundred sixty-three participants were enrolled between August 25 and December 31, 2020. Through February 28, 2021, 12 participants were diagnosed with SARS-CoV-2 infection. Symptom analysis demonstrated that all 12 had at least mild symptoms of COVID-19, compared with baseline health, near or at time of infection.

Conclusions

These results suggest that asymptomatic SARS-CoV-2 infection in unvaccinated, immunocompetent adults is less common than previously reported. While infectious inoculum doses and patient factors may have played a role in the clinical manifestations of SARS-CoV-2 infections in this cohort, we suspect that the high rate of symptomatic disease was due primarily to participant attentiveness to symptoms and collection of symptoms in a standardized, prospective fashion. These results have implications for studies that estimate SARS-CoV-2 infection prevalence and for public health measures to control the spread of this virus.
Warm Temperature Promotes Shoot Regeneration inArabidopsis thaliana
Authors: Lambolez Alice , Kawamura Ayako , Takahashi Tatsuya , Rymen Bart , Iwase Akira , Favero David S , Ikeuchi Momoko , Suzuki Takamasa , Cortijo Sandra , Jaeger Katja E , Wigge Philip A , Sugimoto Keiko
Published: February 2022

Many plants are able to regenerate upon cutting, and this process can be enhanced in vitro by incubating explants on hormone-supplemented media. While such protocols have been used for decades, little is known about the molecular details of how incubation conditions influence their efficiency. In this study, we find that warm temperature promotes both callus formation and shoot regeneration in Arabidopsis thaliana. We show that such an increase in shoot regenerative capacity at higher temperatures correlates with the enhanced expression of several regeneration-associated genes, such as CUP-SHAPED COTYLEDON 1 (CUC1) encoding a transcription factor involved in shoot meristem formation and YUCCAs (YUCs) encoding auxin biosynthesis enzymes. ChIP-sequencing analyses further reveal that histone variant H2A.Z is enriched on these loci at 17°C, while its occupancy is reduced by an increase in ambient temperature to 27°C. Moreover, we provide genetic evidence to demonstrate that H2A.Z acts as a repressor of de novo shoot organogenesis since H2A.Z-depleted mutants display enhanced shoot regeneration. This study thus uncovers a new chromatin-based mechanism that influences hormone-induced regeneration and additionally highlights incubation temperature as a key parameter for optimizing in vitro tissue culture.
Pre-Eruptive Conditions and Dynamics Recorded in Banded Pumices from the El Abrigo Caldera-Forming Eruption (Tenerife, Canary Islands)
Authors: González-García Diego , Petrelli Maurizio , Perugini Diego , Giordano Daniele , Vasseur Jérémie , Paredes-Mariño Joali , Marti Joan , Dingwell Donald B
Published: February 2022

The El Abrigo member of the Diego Hernández Formation (Tenerife, Canary Islands) represents the final (170 ka) and most voluminous eruption (>20-km3 DRE) of the last cycle of explosive activity of the Las Cañadas volcano. It is a dominantly phonolitic ignimbrite containing both mafic and banded pumices, suggesting that magma mixing played an important role in triggering the eruption and modulating eruptive dynamics. Here we use petrology, together with glass and mineral geochemistry of enclave-rich mafic scoriae, banded and phonolitic pumices from El Abrigo ignimbrite, to shed light on the pre-eruptive storage conditions and processes governing magma ascent and interaction dynamics and to provide a first-order assessment of the contribution of magma mixing and crystal mush melting to the dynamics of this eruptive event. The distribution of major elements in glasses is consistent with diffusive exchange between the interacting melts whereby Na transfers from the phonolite to the tephriphonolitic melt. However, V, Zr, Ba, and Eu suggest a complex scenario in which an intruding tephritic to phonotephritic magma interacted with two distinct zones of a phonolitic magma chamber, one occupied by a crystal-rich, low-Zr, and high-Ba phonolite, and the other by an evolved, crystal-poor, high-Zr phonolite. These results, coupled with mineral–melt thermobarometry, allow us to reconstruct the Las Cañadas plumbing system at the end of the Diego Hernández cycle and to evaluate the contribution of cumulate mush melting and magma mixing in as follows: (1) the parental tephritic magma was stored at or near the Moho (410–450 MPa) at 1050°C where it was periodically replenished by more primitive basanitic magma; (2) upon ascent, the tephrite intruded into a shallow and zoned phonolitic storage system, triggering the disruption of a crystal mush in its base; and (3) subsequently interacted with a crystal-poor zone within the reservoir. Energy balance evaluations suggest that relative mafic magma volume ratios ranged from 20 to 43 vol%, and the conservation of small-scale magma mingling structures and their geochemical distribution suggest that the mixing event took place very shortly before the eruption, on a timescale of hours.
High mobility group A3 enhances transcription of the DNA demethylase gene SlDML2 to promote tomato fruit ripening
Authors: Li Zhifei , Pi Ying , Fan Junmiao , Yang Xinxin , Zhai Changsheng , Chen Hong , Wang Feng , Ding Jing , Gu Tingting , Li Yi , Wu Han
Published: February 2022

DNA methylation plays an important role in regulating tomato (Solanum lycopersicum) fruit ripening. Although SlDML2, a DNA demethylase (DML) gene, is critically involved in tomato fruit ripening, little is known about genes that regulate its expression. Using yeast one-hybrid screening, we identified a High Mobility Group A protein, named SlHMGA3, and demonstrated its binding activity to the AT-rich region of the SlDML2 promoter. We produced slhmga3 tomato mutants using CRISPR/Cas9 and observed that slhmga3 fruit reached the breaker stage much later than fruit from the wild-type. We further demonstrated that at the initiation stage of fruit ripening, the increased expression of SlDML2 and ethylene biosynthetic and signaling genes was significantly delayed in slhmga3 fruit, along with delays in ethylene production and demethylation and activation of ripening-associated transcription factor genes. Our results demonstrate that SlHMGA3 plays a role in enhancing SlDML2 expression, and its effects on tomato fruit ripening are largely through DNA demethylation of ripening-associated transcription factor genes.
I Hear You Feel Confident
Authors: Bricker Adam Michael
Published: February 2022

Here I explore a new line of evidence for belief–credence dualism, the thesis that beliefs and credences are distinct and equally fundamental types of mental states. Despite considerable recent disagreement over this thesis, little attention has been paid in philosophy to differences in how our mindreading systems represent the beliefs and credences of others. Fascinatingly, the systems we rely on to accurately and efficiently track others’ mental states appear to function like belief–credence dualists: Credence is tracked like an emotional state, composed of both representational and affective content, whereas belief is tracked like a bare representational state with no affective component. I argue on a preliminary basis that, in this particular case, the mechanics of mentalizing likely pick out a genuine affective dimension to credence that is absent for belief, further strengthening the converging case for belief–credence dualism.
The Slope of the Phillips Curve: Evidence from U.S. States
Authors: Hazell Jonathon , Herreño Juan , Nakamura Emi , Steinsson Jón
Published: February 2022

We estimate the slope of the Phillips curve in the cross section of U.S. states using newly constructed state-level price indices for nontradeable goods back to 1978. Our estimates indicate that the slope of the Phillips curve is small and was small even during the early 1980s. We estimate only a modest decline in the slope of the Phillips curve since the 1980s. We use a multiregion model to infer the slope of the aggregate Phillips curve from our regional estimates. Applying our estimates to recent unemployment dynamics yields essentially no missing disinflation or missing reinflation over the past few business cycles. Our results imply that the sharp drop in core inflation in the early 1980s was mostly due to shifting expectations about long-run monetary policy as opposed to a steep Phillips curve, and the greater stability of inflation between 1990 and 2020 is mostly due to long-run inflation expectations becoming more firmly anchored.
Factors associated with depressive symptoms in Japanese women with rheumatoid arthritis
Authors: Hamasaki Miwa , Origuchi Tomoki , Matsuura Emi
Published: February 2022

Objectives

It has been suggested that patients with RA are more likely to suffer from depression. Therefore, this study identified the factors associated with depressive states in female RA patients to inform future patient care.

Methods

A self-assessment questionnaire was administered to 150 female RA patients aged ≥20 years regarding their satisfaction with disease activity, pain (measured using a visual analogue scale), self-rated depression scale (SDS), stress content (illness, work, family, difficulty in daily life, appearance, treatment and other), confidence in stress management and satisfaction (treatment effect, health status and relationships with health-care professionals). The factors related to depression and the presence of depressive tendencies were investigated.

Results

Data from 145 patients were analysed. Eighteen patients (12.4%) showed depressive tendencies according to their SDS scores. Among these patients, SDS scores were positively correlated with disease activity and with scores on the modified HAQ, visual analogue scale for pain, and stress content. The SDS score was also negatively correlated with patients’ confidence in stress management and health status satisfaction.

Conclusion

Female RA patients had family problems and various stressors in their daily lives. Nurses need to conduct regular mental health assessments to monitor their self-management status and support them to improve their confidence and satisfaction in coping. To achieve this, it is important for health-care teams involving various health-care professionals to collaborate and cooperate.
Loosening of Associations in Chronic Schizophrenia: Intersectionality of Verbal Learning, Negative Symptoms, and Brain Structure
Authors: Nestor Paul G , Levitt James J , Ohtani Toshiyuki , Newell Dominick T , Shenton Martha E , Niznikiewicz Margaret
Published: February 2022

In 1908, Bleuler proposed a unitary theory of schizophrenia, hypothesizing a “loosening of associations” as the central mechanism underlying disturbances in thinking, motivation, and affective expression. Here, we test Bleuler’s model in an archival sample of 79 healthy controls and 76 patients with chronic schizophrenia who had completed neuropsychological tests, including a measure of learning of novel word pairs, which was specifically selected to probe the structure and formation of new verbal associations. The patients also had positive and negative symptoms ratings, including measures of flat affect, anhedonia, and thought disorder. A subset of patients and controls (n = 39) had available prior archival 3-T magnetic resonance imaging (MRI) measures of prefrontal cortex (PFC) gray matter volumes. In relation to controls, patients showed evidence of a selective impairment in associative learning, independent of their overall reduced neuropsychological functioning. This neuropsychological impairment, in turn, correlated significantly with overall levels of negative but not positive symptoms, with the data showing an especially strong contribution of flattened emotional expression to verbal associate learning deficits in this patient sample. Moreover, the archival MRI data were consistent with prior research pointing to an important role of the PFC in supporting verbal associate learning and memory in patients and controls. Taken together, the current results provided evidence of a selective impairment in schizophrenia on a PFC-supported verbal associate learning and memory task, which was accompanied by negative symptoms in general, and flattened emotional expression, in particular.
Diversity of anesthesia workforce – why does it matter?
Authors: Chiem Jennifer , Libaw Justin , Ehie Odinakachukwu
Published: February 2022

Purpose of review

Although recent census demonstrates that women comprise 50.8% and ethnic minority groups collectively consist of 42.1% of the US population, the field of anesthesiology still demonstrates disparity in representation and health outcomes across race, ethnicity, and gender. In addition, the growing percentage of people that identify as lesbian, gay, bisexual, transgender, and queer (LGBTQ) compounded with limited representation among providers of their care can augment existing disparate outcomes within this community.

Recent findings

Compared to male colleagues, women physicians across all specialties have a decreased likelihood of professorship as well as equitable pay and leadership roles. Additionally, a 2019 study of anesthesia residents across race and ethnicity within the Accreditation Council for Graduate Medical Education established that whites were 58.9%, Asians were 24.7%, Hispanics were 7.8%, Blacks were 5.9%, multiracial groups were 3.8%, and Native Americans were 0.3% of the total 6272 residents. In a survey of members of the American Society of Anesthesiologists, self-identification as part of the sexual and gender minoritycommunity was independently associated with an increased risk of burnout. Furthermore, teams with higher diversity in cognitive styles solve problems more efficiently.

To achieve an optimized quality of healthcare, anesthesiologists and other providers should be a reflection of the communities they serve, including women, people of color, and LGBTQ. In this way, there is an increased likelihood of empathy, effective communication, and insightful perspectives on how to bridge the gap in health equity. A diverse lens is essential to ensure grassroots efforts lead to lasting transformational change.
Rapid Overlap Initiation Protocol Using Low Dose Buprenorphine for Opioid Use Disorder Treatment in an Outpatient Setting: A Case Series
Authors: Suen Leslie W. , Lee Trevor G. , Silva Michael , Walton Paulette , Coffin Phillip O. , Geier Michelle , Soran Christine S.
Published: February 2022

Objectives

Fear and risk of precipitated withdrawal are barriers for initiating buprenorphine in individuals with opioid use disorder, particularly among those using fentanyl. A buprenorphine rapid overlap initiation (ROI) protocol (also knownas “rapidmicro-dosing”) utilizing small, escalating doses of buprenorphine can overcome this barrier, reaching therapeutic doses in 3 to 4 days. We sought to demonstrate the feasibility of implementing a buprenorphine ROI protocol for buprenorphine initiation in the outpatient setting.

Methods

We conducted a retrospective chart review of patients prescribed an outpatient ROI protocol at the Office-based Buprenorphine Induction Clinic from October to December 2020. The ROI protocol utilizes divided doses of sublingual buprenorphine tablets and blister packaging for easier dosing. Patients were not required to stop other opioid use and were advised to follow up on day 4 of initiation.

Results

Twelve patients were included, of whom eleven (92%) were using fentanyl at intake. Eleven patients picked up their prescription. Seven patients returned for follow-up (58%), and all 7 completed the ROI protocol. One patient reported any withdrawal symptoms, which were mild. At 30 days, 7 patients (58%) were retained in care, and 5 (42%) were still receiving buprenorphine treatment, 4 (33%) of whom had been abstinent from nonprescribed opioid use for ≥2 weeks.

Conclusions

The ROI protocol was successful in initiating buprenorphine treatment for patients in our outpatient clinic, many of whom were using fentanyl. The ROI protocol may offer a safe alternative to traditional buprenorphine initiation and warrants further study.
Postoperative Cesarean Pain Management and Opioid Use Disorder: Anticipate the Need for Higher Opioid Doses and Communicate Expectations With Patients and the Obstetric Team
Authors: Cleary Erin M. , Rood Kara M.
Published: February 2022

Peripartum care coordination for the obstetric patient on medications for opioid use disorder (OUD) can be challenging and is best accomplished by a multidisciplinary team. The benefits of buprenorphine, methadone, or naltrexone initiation or continuation in pregnancy are well established and beyond the scope of this commentary; instead, we narrow the focus on planning for sufficient pain management in labor and during recovery from cesarean delivery. Conversations about postoperative pain management should begin in the antepartum period, and likely do for the 15%–20% of individuals with a history of cesarean delivery who schedule a repeat cesarean. Nevertheless, 18%–20% of pregnant individuals deliver via primary cesarean delivery, underscoring the need for universal antepartum counseling on the possibility of undergoing and recovering from an unanticipated major abdominal surgery. The optimal intrapartum and postpartum pain regimen for individuals with OUD remains incompletely characterized as research on this topic is limited. Enhanced understanding of the unique needs of postpartum individuals with OUD will aid in closing knowledge gaps and elevate the standard of care in this population.
Quality of Labor Analgesia with Dural Puncture Epidural versus Standard Epidural Technique in Obese Parturients: A Double-blind Randomized Controlled Study
Authors: Tan Hon Sen , Reed Sydney E. , Mehdiratta Jennifer E. , Diomede Olga I. , Landreth Riley , Gatta Luke A. , Weikel Daniel , Habib Ashraf S.
Published: February 2022

Background

The dural puncture epidural technique may improve analgesia quality by confirming midline placement and increasing intrathecal translocation of epidural medications. This would be advantageous in obese parturients with increased risk of block failure. This study hypothesizes that quality of labor analgesia will be improved with dural puncture epidural compared to standard epidural technique in obese parturients.

Methods

Term parturients with body mass index greater than or equal to 35 kg · m–2, cervical dilation of 2 to 7 cm, and pain score of greater than 4 (where 0 indicates no pain and 10 indicates the worst pain imaginable) were randomized to dural puncture epidural (using 25-gauge Whitacre needle) or standard epidural techniques. Analgesia was initiated with 15 ml of 0.1% ropivacaine with 2 µg · ml–1 fentanyl, followed by programed intermittent boluses (6 ml every 45 min), with patient-controlled epidural analgesia. Parturients were blinded to group allocation. The data were collected by blinded investigators every 3 min for 30 min and then every 2 h until delivery. The primary outcome was a composite of (1) asymmetrical block, (2) epidural top-ups, (3) catheter adjustments, (4) catheter replacement, and (5) failed conversion to regional anesthesia for cesarean delivery. Secondary outcomes included time to a pain score of 1 or less, sensory levels at 30 min, motor block, maximum pain score, patient-controlled epidural analgesia use, epidural medication consumption, duration of second stage of labor, delivery mode, fetal heart tones changes, Apgar scores, maternal adverse events, and satisfaction with analgesia.

Results

Of 141 parturients randomized, 66 per group were included in the analysis. There were no statistically or clinically significant differences between the dural puncture epidural and standard epidural groups in the primary composite outcome (34 of 66, 52% vs. 32 of 66, 49%; odds ratio, 1.1 [0.5 to 2.4]; P = 0.766), its individual components, or any of the secondary outcomes.

Conclusions

A lack of differences in quality of labor analgesia between the two techniques in this study does not support routine use of the dural puncture epidural technique in obese parturients.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Outcomes of Pediatric Scaphoid Nonunions Treated With Distal Radius Cancellous Autograft
Authors: Lin James S. , Grenier Gregory , Balch Samora Julie
Published: February 2022

Background:

The optimal management of pediatric scaphoid fracture nonunions is controversial. We hypothesize that pediatric patients with scaphoid fracture nonunions will have favorable functional outcomes with the utilization of nonvascularized distal radius cancellous autograft with open reduction and internal fixation (ORIF).

Methods:

A review was performed from 2012 to 2017 identifying skeletally immature patients with scaphoid fracture nonunions treated with ORIF and nonvascularized distal radius cancellous autograft, including demographic data, mechanism of injury, length of time from injury to treatment, operative procedure, length of immobilization, time to union, and complications.

Results:

Ten patients (9 males, 1 female) met inclusion criteria. Mean age was 14.3 SD 1.5 years. The majority of fractures were sustained during sports or secondary to a fall. Mean time between injury and orthopaedic evaluation was 33 weeks (SD 20 wk). Eight fractures occurred at the waist, and 2 occurred at the proximal pole. Four patients had a humpback deformity, and three presented with a dorsal intercalated segmental instability deformity. Nine patients were treated with a single cannulated compression screw with distal radius autograft. One patient also received a single Kirschner wire fixation in addition to a single cannulated screw and graft. Patients underwent a mean postoperative immobilization period of 14 SD 5 weeks. Two patients received a bone stimulator postoperatively. Radiographic union was documented after initial surgery in nine patients, with mean time to union of 17 SD 5 weeks. The 1 patient with persistent radiographic nonunion underwent revision fixation and repeat nonvascularized distal radius autograft, achieving union and resolution of symptoms. All patients ultimately reported full return to activity.

Conclusions:

Pediatric scaphoid fracture nonunions that undergo ORIF using nonvascularized distal radius cancellous autograft have favorable rates of consolidation and functional outcomes. Surgeons should consider this source of grafting in operative management of scaphoid nonunions in children and adolescents.

Level of Evidence:

Level IV, therapeutic.
Gaisbock Syndrome: A Review of Contemporary Studies, Pathogenesis, Complications, and Possible Treatment
Authors: Manal Nabeela , Rizvi Mariam , Nugent Kenneth
Published: February 2022

Gaisbock syndrome is the term ascribed to several conditions initially observed by Felix Gaisbock, MD, (from Innsbruck, Tyrol, Austria) in 1905 when he described a group of hypertensive male patients who had high hematocrit levels, normal leukocyte counts, and no splenomegaly. These patients had an overweight, stocky habitus, a plethoric appearance with suffusion of the eyes, tense and anxious personalities, a cigarette smoking habit, vascular disease, headaches, and facial rubor. Later studies identified alcoholism, diuretic therapy, and physical or emotional stress as additional risk factors that might contribute to the onset of this syndrome. This review revisits Gaisbock syndrome based on recent literature, and will highlight contemporary studies that have established an association between erythrocytosis and hypertension and associated risk factors. Several mechanisms help explain the pathophysiology underlying Gaisbock’s observations, and these include psychiatric disorders resulting in chronic stress, volume contraction secondary to diuretics and hypertension, and obstructive sleep apnea with nocturnal hypoxemia and erythropoietin production. Complications associated with this syndrome include the formation of microthrombi with cerebral infarction; treatment should focus on the management of hypertension and a reduction in risk factors, such as obesity, cigarette smoking, and alcohol use. Gaisbock syndrome involves several clinical disorders, has a complex pathogenesis, and leads to a better understanding of the causes of erythrocytosis during patient evaluation.
Acute Intoxications and Fatalities Associated With Benzimidazole Opioid (Nitazene Analog) Use: A Systematic Review
Authors: Montanari Eva , Madeo Graziella , Pichini Simona , Busardò Francesco Paolo , Carlier Jeremy
Published: February 2022

Background:

Synthetic benzimidazole opioids (BOs) are highly potent µ-opioid receptor agonists with heroin-like effects. Isotonitazene was first available in 2019 in the drug market, although new analogs have multiplied recently. The authors aimed to identify BO use trends and gather toxicological data from BO-related cases to assist in clinical and forensic investigations.

Methods:

A systematic literature search was conducted according to the PRISMA guidelines. PubMed and Scopus databases were accessed in October 2021 to identify scientific reports of BO-related intoxication and fatalities. Publication dates, case descriptions, symptoms, autopsy findings, and concentrations of BOs and metabolites in biological matrices were compiled.

Results:

Data from 8 case reports with 93 fatalities involving isotonitazene (n = 65), metonitazene (n = 20), etonitazepyne (N-pyrrolidino etonitazene) (n = 8), flunitazene (n = 4), and/or butonitazene (n = 1), and 1 acute intoxication involving etonitazepyne were collected. Autopsy findings included pulmonary congestion/high lung weight (66%), cardiomegaly/high cardiac weight (39%), cerebral edema (22%), gastric contents in the airways (22%), and organ congestion (22%). Median peripheral blood concentrations were 1.7 ng/mL for isotonitazene (0.4–9.5 ng/mL, n = 13), 5.4 ng/mL for metonitazene (0.52–33 ng/mL, n = 17), 5.4 ng/mL for etonitazepyne (2.4–8.3 ng/mL, n = 2), 1.3 ng/mL for flunitazene (0.58–2.1 ng/mL, n = 2), and 3.2 ng/mL for butonitazene (n = 1). Central nervous system depressants were almost always coadministered.

Conclusions:

Isotonitazene was predominant in cases from 2019 to mid-2020 and was replaced by metonitazene after scheduling in the United States. Typical findings on opioid overdoses have been reported. Peripheral blood concentrations were consistent with a potency similar to that of fentanyl. These results must be interpreted carefully, considering the scarcity of reports on BO-related cases and drug co-exposures.
Pediatric Forensic Analysis
Authors: Hornor Gail , Benzinger Elizabeth , Doughty Katherine , Hollar Jessica , Wolf Kathryn
Published: February 2022

Background

Although the presence of forensic evidence aids in successful prosecution of sexual abuse, controversy remains regarding the timing and indications for collection of forensic evidence in child sexual abuse/assault.

Objective

The purpose of this study was to describe forensic evidence findings in acute child sexual abuse after implementing more inclusive indications for collection of evidence in a pediatric emergency department and to identify factors associated with yield of DNA.

Results

Of the 306 evidence kits collected and analyzed, 110 (35.9%) kits were positive for an interpretable DNA profile foreign to the patient, which may or may not have contributed to the investigation of the sexual abuse concern. Several factors were associated with increased forensic yield of identifiable foreign DNA: increased age of child victim, 48 hours or less between the latest incident of sexual abuse and the collection of forensic evidence, child disclosure of high-severity sexual abuse acts (anal–genital or genital–genital contact) in the pediatric emergency department forensic interview, and sexual abuse by a nonrelative perpetrator.

Conclusions

Finally, although certain factors were associated with increased yield of identifiable foreign DNA within each factor, there were multiple outliers where failure to collect forensic evidence would have resulted in a loss of recoverable foreign DNA.
The Effects of Relaxation Techniques on Pain, Fatigue, and Kinesiophobia in Multiple Sclerosis Patients: A 3-Arm Randomized Trial
Authors: Kesik Gülşah , Ozdemir Leyla , Mungan Ozturk Semra
Published: February 2022

BACKGROUND: In addition to the available medical treatment options, multiple sclerosis (MS) patients may tend toward complementary and integrative therapies. Relaxation techniques are a nonpharmacological and side-effect–free therapy option currently available to alleviate the symptoms of many different chronic diseases. The aim of this study was to examine and compare the effects of relaxation techniques on the pain, fatigue, and kinesiophobia in MS patients. METHODS: This 3-arm randomized controlled trial consisted of 80 MS patients. Relaxation techniques, progressive muscle relaxation and Benson relaxation technique were applied to 2 intervention groups, the third was the control group. The study lasted 12 weeks, and the patient information form, visual analog scale, Fatigue Severity Scale, and Tampa Scale for Kinesiophobia were used for data collection. RESULTS: There was a statistically significant decrease in pain, fatigue, and kinesiophobia levels in the intervention groups compared with the control group (P < .05). Progressive muscle relaxation was more effective than Benson relaxation technique (P < .05). CONCLUSION: Relaxation techniques are recommended for the management of symptoms of pain, fatigue, and kinesiophobia, which can often cause disability in MS patients, because they have no side effects and are practical administrations. These exercises are also promising in the rehabilitation process of MS patients.
Neonatal Vascular Access Practice and Complications
Authors: McIntyre Colette , August Deanne , Cobbald Linda , Lack Gill , Takashima Mari , Foxcroft Katie , Marsh Nicole , Smith Patricia , New Karen , Koorts Pieter , Irwin Adam , Ullman Amanda
Published: February 2022

Vascular access devices play vital roles within neonatal care. We aimed to identify neonatal vascular access device insertion and management practices, and describe the incidence and risk factors for complication development. This is a prospective cohort study of neonates requiring vascular access devices over 3 months in an Australian quaternary-referral neonatal intensive care unit. In addition to describing current practices, primary outcomes were device failure, complications, and skin complications. Results are reported using descriptive statistics and with risk factors calculated via Cox proportional hazards regression. A total of 104 neonates required 302 vascular access devices, over 1375 catheter days. Peripheral intravenous catheters (PIVCs) were most used (n = 186; 62%), followed by umbilical venous catheters (n = 52; 17%). Insertion attempts were often undocumented; but for those recorded, 5% of devices (n = 15) required 4 attempts or more. Device failure occurred in 28% (n = 82), at an incidence rate of 62.5 per 1000 catheter days (95% confidence interval [CI] 49.7-75.9). Failure was most frequent in PIVCs (37%; n = 68), peripheral arterial catheters (33%; n = 2), and peripherally inserted central catheters (20%; n = 6). Infiltration and extravasation were the most frequent cause of PIVC failure (12%; n = 35). A birth weight less than 1500 g was associated with a significant decrease in PIVC failure (hazard ratio 0.58; 95% CI 0.34-0.99).
Parent Readiness for Their Preterm Infant's Neonatal Intensive Care Unit Discharge
Authors: Franck Linda S. , Kriz Rebecca M. , Bisgaard Robin , Gay Caryl L. , Sossaman Sharon , Sossaman Jeramy , Cormier Diana M. , Joe Priscilla , Sasinski Juliet K. , Kim Jae H. , Lin Carol , Sun Yao
Published: February 2022

This study aims to examine the influence of hospital experience factors on parental discharge readiness, accounting for key background characteristics. Parents/guardians of infants 33 weeks of gestation or less at birth receiving neonatal intensive care at 6 sites were enrolled from April 2017 to August 2018. Participants completed surveys at enrollment, 3 weeks later, and at discharge. Multiple regression analysis assessed relationships between parental experience, well-being, and perceived readiness for infant discharge, adjusting for socioenvironmental, infant clinical, and parent demographic characteristics. Most (77%) of the 139 parents reported high levels of readiness for their infant's discharge and 92% reported high self-efficacy at discharge. The multiple regression model accounted for 40% of the variance in discharge readiness. Perceptions of family-centered care accounted for 12% of the variance; measures of parent well-being, anxiety, and parenting self-efficacy accounted for an additional 16% of the variance; parent characteristics accounted for an additional 9%; and infant characteristics accounted for less than 3% of the variance. Parental perceptions of the family-centeredness of the hospital experience, anxiety, and parenting self-efficacy accounted for a substantial proportion of the variance in readiness for discharge scores among parents of preterm infant. These influential perceptions are potentially modifiable by nursing-led interventions.
A Mixed-Methods Study of Experiences During Pregnancy Among Black Women During the COVID-19 Pandemic
Authors: Dove-Medows Emily , Davis Jean , McCracken Lindsey , Lebo Lauren , Misra Dawn P. , Giurgescu Carmen , Kavanaugh Karen
Published: February 2022

Pregnant women experienced disruptions in their prenatal care during the coronavirus disease-2019 (COVID-19) pandemic. While there is emerging research about the impact of COVID-19 on experiences of pregnancy, the majority of studies that have reported on prenatal care and birth during COVID-19 have not incorporated the first-person accounts of Black women. The purpose of this mixed-methods study was to explore the perspectives of Black women on prenatal care, labor, and birth during the pandemic. A total of 33 participants completed questionnaires. Fourteen of these 33 women and an additional 2 participated in qualitative interviews. Descriptive statistics and a mixed-methods analysis were employed. Participants expressed disappointment about disruptions in their experiences of pregnancy including the way their prenatal care was experienced, cancellation of planned “rites of passage,” and visitor policy restrictions during and after the birth. Forty-five percent of participants reported being worried about getting COVID-19 and (61%) about their infant getting COVID-19. Many participants experienced a sense of loss that may permeate through other aspects of their lives. Providing extra support and points of contact can help lessen feelings of isolation during the pandemic and can also offer more explanation for rapidly changing policies and procedures.
The Relationship Between Colorectal Polyps and Serum Lipid Levels
Authors: Zhang Ruxuan , Yin Jianli , Huo Chuanyi , Li Xu , Ye Jiaming , Zhao Weisen , Zhou Liting , Ye Lin
Published: February 2022

Colorectal polyp has been considered as the precancerous lesion of colorectal cancer, to which serum lipid levels are closely related. At present, there is no consensus on the relationship between colorectal polyps and serum lipid levels. We performed a meta-analysis to explore the effects of lipid levels on colorectal polyps. Relevant articles published from 2000 to 2020 were searched in PubMed, Web of Science, EMBASE, and Cochrane Library databases. The mean value and SD of serum lipid indexes and body mass index in colorectal polyps groups and control groups were extracted from the included articles. Combined weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated to assess the effect size of serum lipid levels on colorectal polyps. The publication bias of the included studies were assessed based on the Egger test. Thirty-seven articles containing 19,464 cases and 63,979 controls were included. There were no significant publication bias. The levels of high-density lipoprotein cholesterol in the cases were lower than those in the controls (WMD: −2.589 mg/dL, 95% CI: −3.273, −1.906). While the levels of triglyceride (WMD: 16.933 mg/dL, 95% CI: 13.131, 20.736), total cholesterol (WMD: 5.561 mg/dL, 95% CI: 3.477, 7.645), low-density lipoprotein cholesterol (WMD: 3.109 mg/dL, 95% CI: 0.859, 5.359) and body mass index (WMD: 0.747 mg/dL, 95% CI: 0.588, 0.906) were higher in the cases. Colorectal polyps were associated with serum lipid levels and obesity. Hyperlipidemia and obesity may be the risk factors for colorectal polyps.
Disease-specific gaps within fungal respiratory tract infections: clinical features, diagnosis, and management in critically ill patients
Authors: Martin-Loeches Ignacio , Nseir Saad , Rodriguez Alejandro , Azoulay Elie
Published: February 2022

Purpose of review

We aim to examine the most recent findings in the area of invasive pulmonary fungal infections to determine the appropriate/and or lack of prevention measures and treatment of upper fungal respiratory tract infections in the critically ill.

Recent findings

This will be addressed by focusing on the pathogens and prognosis over different bedridden periods in ICU patients, the occurrence of invasive fungal respiratory superinfections in patients with severe coronavirus disease 2019 which has been recently noted following the SARS-CoV-2 pandemic. Relevant reports referenced within include randomized controlled trials, meta-analyses, observational studies, systematic reviews, and international guidelines, where applicable. Of note, it is clear there is a significant gap in our knowledge regarding whether bacterial and fungal infections in coronavirus disease 2019 are directly attributable to SARS-CoV-2 or a consequence of factors such as managing high numbers of critically unwell patients, and the prolonged duration of mechanical ventilation/ICU admission duration of stay.

An optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, invasive aspergillosis, candidemia, and endemic mycoses continues to be limited clinically. There is a lack of standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues and suboptimal diagnostic approaches for mould blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures (i.e., the routine use of bronchoscopic examination in ICU patients with influenza-associated pulmonary aspergillosis) for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens.