bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary metabolite quantitative trait loci in children and their interaction with dietary factors
Authors: Calvo-Serra Beatriz , Maitre Léa , Lau Chung-Ho E , Siskos Alexandros P , Gützkow Kristine B , Andrušaitytė Sandra , Casas Maribel , Cadiou Solène , Chatzi Leda , González Juan R , Grazuleviciene Regina , McEachan Rosemary , Slama Rémy , Vafeiadi Marina , Wright John , Coen Murieann , Vrijheid Martine , Keun Hector C , Escaramís Geòrgia , Bustamante Mariona
Published: December 2020

Human metabolism is influenced by genetic and environmental factors. Previous studies have identified over 23 loci associated with more than 26 urine metabolites levels in adults, which are known as urinary metabolite quantitative trait loci (metabQTLs). The aim of the present study is the identification for the first time of urinary metabQTLs in children and their interaction with dietary patterns. Association between genome-wide genotyping data and 44 urine metabolite levels measured by proton nuclear magnetic resonance spectroscopy was tested in 996 children from the Human Early Life Exposome project. Twelve statistically significant urine metabQTLs were identified, involving 11 unique loci and 10 different metabolites. Comparison with previous findings in adults revealed that six metabQTLs were already known, and one had been described in serum and three were involved the same locus as other reported metabQTLs but had different urinary metabolites. The remaining two metabQTLs represent novel urine metabolite-locus associations, which are reported for the first time in this study [single nucleotide polymorphism (SNP) rs12575496 for taurine, and the missense SNP rs2274870 for 3-hydroxyisobutyrate]. Moreover, it was found that urinary taurine levels were affected by the combined action of genetic variation and dietary patterns of meat intake as well as by the interaction of this SNP with beverage intake dietary patterns. Overall, we identified 12 urinary metabQTLs in children, including two novel associations. While a substantial part of the identified loci affected urinary metabolite levels both in children and in adults, the metabQTL for taurine seemed to be specific to children and interacted with dietary patterns.
Heterozygous loss of WBP11 function causes multiple congenital defects in humans and mice
Authors: Martin Ella M M A , Enriquez Annabelle , Sparrow Duncan B , Humphreys David T , McInerney-Leo Aideen M , Leo Paul J , Duncan Emma L , Iyer Kavitha R , Greasby Joelene A , Ip Eddie , Giannoulatou Eleni , Sheng Delicia , Wohler Elizabeth , Dimartino Clémantine , Amiel Jeanne , Capri Yline , Lehalle Daphné , Mory Adi , Wilnai Yael , Lebenthal Yael , Gharavi Ali G , Krzemień Grażyna G , Miklaszewska Monika , Steiner Robert D , Raggio Cathy , Blank Robert , Baris Feldman Hagit , Milo Rasouly Hila , Sobreira Nara L M , Jobling Rebekah , Gordon Christopher T , Giampietro Philip F , Dunwoodie Sally L , Chapman Gavin
Published: December 2020

The genetic causes of multiple congenital anomalies are incompletely understood. Here, we report novel heterozygous predicted loss-of-function (LoF) and predicted damaging missense variants in the WW domain binding protein 11 (WBP11) gene in seven unrelated families with a variety of overlapping congenital malformations, including cardiac, vertebral, tracheo-esophageal, renal and limb defects. WBP11 encodes a component of the spliceosome with the ability to activate pre-messenger RNA splicing. We generated a Wbp11 null allele in mouse using CRISPR-Cas9 targeting. Wbp11 homozygous null embryos die prior to E8.5, indicating that Wbp11 is essential for development. Fewer Wbp11 heterozygous null mice are found than expected due to embryonic and postnatal death. Importantly, Wbp11 heterozygous null mice are small and exhibit defects in axial skeleton, kidneys and esophagus, similar to the affected individuals, supporting the role of WBP11 haploinsufficiency in the development of congenital malformations in humans. LoF WBP11 variants should be considered as a possible cause of VACTERL association as well as isolated Klippel-Feil syndrome, renal agenesis or esophageal atresia.
Extracorporeal life support in therapy-refractory cardiocirculatory failure: looking beyond 30 days
Authors: Guenther Sabina P W , Hornung Roman , Joskowiak Dominik , Vlachea Polyxeni , Feil Katharina , Orban Martin , Peterss Sven , Born Frank , Hausleiter Jörg , Massberg Steffen , Hagl Christian
Published: December 2020

OBJECTIVES

Venoarterial extracorporeal life support (ECLS) has emerged as a potentially life-saving treatment option in therapy-refractory cardiocirculatory failure, but longer-term outcome is poorly defined. Here, we present a comprehensive follow-up analysis covering all major organ systems.

METHODS

From February 2012 to December 2016, 180 patients were treated with ECLS for therapy-refractory cardiogenic shock or cardiac arrest. The 30-day survival was 43.9%, and 30-day survivors (n = 79) underwent follow-up analysis with the assessment of medium-term survival, quality of life, neuropsychological, cardiopulmonary and end-organ status.

RESULTS

After a median of 1.9 (1.1–3.6) years (182.4 patient years), 45 of the 79 patients (57.0%) were alive, 35.4% had died and 7.6% were lost to follow-up. Follow-up survival estimates were 78.0% at 1, 61.2% at 3 and 55.1% at 5 years. NYHA class at follow-up was ≤II for 83.3%. The median creatinine was 1.1 (1.0–1.4) mg/dl, and the median bilirubin was 0.8 (0.5–1.0) mg/dl. No patient required dialysis. Overall, 94.4% were free from moderate or severe disability, although 11.1% needed care. Full re-integration into social life was reported by 58.3%, and 39.4% were working. Quality of life was favourable for mental components, but a subset showed deficits in physical aspects. While age was the only peri-implantation parameter significantly predicting medium-term survival, adverse events and functional status at discharge or 30 days were strong predictors.

CONCLUSIONS

This study demonstrates positive medium-term outcome with high rates of independence in daily life and self-care but a subset of 10–20% suffered from sustained impairments. Our results indicate that peri-implantation parameters lack predictive power but downstream morbidity and functional status at discharge or 30 days can help identify patients at risk for poor recovery.
Determination of Aflatoxin M1 in Liquid Milk, Cheese, and Selected Milk Proteins by Automated Online Immunoaffinity Cleanup with Liquid Chromatography‒Fluorescence Detection
Authors: Wood Jackie E , Gill Brendon D , Indyk Harvey E , Rhemrev Ria , Pazdanska Monika , Mackay Naomi , Marley Elaine
Published: December 2020

Background

Aflatoxins are secondary metabolites produced by a number of species of Aspergillus fungi. Aflatoxin M1 (AFM1) is a hydroxylated metabolite of aflatoxin B1 and is found in the milk of cows fed with feed spoilt by Aspergillus species. AFM1 is carcinogenic, especially in the liver and kidneys, and mutagenic, and is also an immunosuppressant in humans.

Objective

A high-throughput method for the quantitative analysis of AFM1 that is applicable to liquid milk, cheese, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), and whey powder (WP) was developed and validated.

Method

AFM1 in cheese, milk, and protein products is extracted using 1% acetic acid in acetonitrile with citrate salts. The AFM1 in the resulting extract is concentrated using RIDA®CREST/IMMUNOPREP® ONLINE cartridges followed by quantification by HPLC‒fluorescence.

Results

The method was shown to be accurate for WP, WPC, WPI, MPC, liquid milk, and cheese, with acceptable recovery (81–112%) from spiked samples. Acceptable precision for WP, WPC, WPI, MPC, liquid milk, and cheese was confirmed, with repeatabilities of 4–12% RSD and intermediate precisions of 5–13% RSD. Method detection limit and ruggedness experiments further demonstrated the suitability of this method for routine compliance testing. An international proficiency scheme (FAPAS) cheese sample showed that this method gave results that were comparable with those from other methods.

Conclusions

A method for high-throughput, routine testing of AFM1 is described. The method was subjected to single-laboratory validation and was found to be accurate, precise, and fit-for-purpose.

Highlights

An automated online immunoaffinity cleanup HPLC‒fluorescence method for milk proteins, cheese, and milk was developed and single-laboratory validated. It allows for high-throughput analysis of AFM1 and can be used for the analysis of AFM1 in whey protein products.
Combined Effects of Methoprene and Metformin on Reproduction, Longevity, and Stress Resistance inAnastrepha ludens(Diptera: Tephritidae): Implications for the Sterile Insect Technique
Authors: Aceves-Aparicio Eva , Pérez-Staples Diana , Arredondo José , Corona-Morales Aleph , Morales-Mávil Jorge , Díaz-Fleischer Francisco
Published: December 2020

Survival and mating success are traits of quality in mass-reared sterile males. Thus, studying the trade-offs between these traits may help to improve process in the sterile insect technique (SIT). Here, we tested the hypothesis that modifying individual metabolism, especially of energetic reserves, may reduce the negative impact of an early reproduction on the survival of Anastrepha ludens flies. Appling metformin (a drug used to treat type II diabetes) that improves insects’ survival, through dietary restriction mimicry, and methoprene (a juvenile hormone analogue) that accelerates the age to reproduction in insects, we explore the dynamic of this trade-off. We fed A. ludens flies with metformin, methoprene, or a mixture of metformin–methoprene for five consecutive days. We determined the effect of these treatments on the fecundity and fertility (number of eggs and percentage of hatching) of females, on sexual maturation and mating success of males, and on the survival of both sexes. The results showed that the acceleration in sexual maturation by the action of methoprene significantly reduced survival in both sexes of two different fly strains. However, adding metformin to the diet buffered this negative effect, without reducing the mating propensity compared with the males treated only with methoprene. The response to metformin was sex-specific since females responded to high doses of the substance, whereas males responded better to low doses. These results suggest that trade-offs between survival and reproduction do not necessarily depend on energy reserves but they are intrinsically related to metabolic regulation and hormonal control.
Can Insectary Plants Enhance the Presence of Natural Enemies of the Green Peach Aphid (Hemiptera: Aphididae) in Mediterranean Peach Orchards?
Authors: Aparicio Yahana , Riudavets Jordi , Gabarra Rosa , Agustí Nuria , Rodríguez-Gasol Neus , Alins Georgina , Blasco-Moreno Anabel , Arnó Judit
Published: December 2020

Conservation biological control could be an alternative to insecticides for the management of the aphid Myzus persicae (Sulzer). To develop sustainable strategies for M. persicae control in peach orchards in the Mediterranean, a 2-yr field experiment was conducted to identify the key predators of the aphid; to determine whether the proximity of insectary plants boost natural enemies of M. persicae in comparison to the resident vegetation; and whether selected insectary plants enhance natural enemy populations in the margins of peach orchards. Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae) and Episyrphus balteatus De Geer (Diptera: Syrphidae) were the most abundant predators found among sentinel aphid colonies, accounting for 57% and 26%, respectively. Samplings during 2015 yielded twice as many hoverflies in M. persicae sentinel plants close to the insectary plants as those close to the resident vegetation. The abundance of other natural enemies in sentinel plants, depending on their proximity to the insectary plants, was not significantly different in either of the 2 yr. Hoverflies hovered more often over the insectary plants than over the resident vegetation and landed significantly more often on Lobularia maritima (L.) Desv., Moricandia arvensis (L.) DC., and Sinapis alba L. (Brassicales: Brassicaceae) than on Achillea millefollium L. (Asterales: Compositae). Parasitoids were significantly more abundant in L. maritima and A. millefollium. The vicinity of selected insectary plants to peach orchards could improve the presence of hoverflies, which might benefit the biological control of M. persicae.
A biomechanical analysis of ischiofemoral impingement in a cadaver model
Authors: Murata Yoichi , Fukase Naomasa , Utsunomiya Hajime , Brady Alex W , Rosenberg Samuel I , Quinn Patrick , Uchida Soshi , Martin Hal David , Philippon Marc J
Published: December 2020

Ischiofemoral impingement (IFI) occurs due to the diminishing of space between the ischium and lesser trochanter. During a robotic hip study, one hip presented with indications of IFI, an opportunity to explore the pathophysiology and treatment strategies for this unusual condition. This specimen underwent kinematic tests in two states: (i) native lesser trochanter and (ii) resected lesser trochanter. The ‘Resected lesser trochanter’ state was found to increase the hip range of motion and decrease femoral head translation by eliminating contact between the femur and pelvis. These results suggest that lesser trochanteric resection would provide physical benefit for IFI patients.
An enhanced personality detection system through user’s digital footprints
Authors: Mobasher Mohammad , Farzi Saeed
Published: December 2020

One of the most important aspects of any person's life is personality, which affects one's speech, decision, well-being, feeling and mental health. Personality detection is usually based on data collected by a questionnaire that comprises some critical problems such as the lack of direct access to the individuals and explicit personal information. However nowadays, one of the valuable resources for such studies is social networks. The footprint and tracking of users on social networks have provided valuable information for personality recognition. Specifically, this research introduces an intelligence personality recognition system based on modeling user behavior using sophisticated features, i.e., Statistical, Emotional, and Linguistic. Furthermore, a dataset called KNTU_Personality based on the MBTI personality model with the profile information and tweets has been collected. The experimental study follows two scenarios with complementing objectives. First the sensitivity analysis is performed respecting to setting parameters, introduced features and different learning algorithms. Next the proposed system has been compared with well-known personality detection systems. The results demonstrate the superiorities of the proposed system regarding its counterparts in terms of F-Score, Precision, Recall and Accuracy.
Corticosteroids alter alveolar macrophage control of Lichtheimia corymbifera spores in an ex vivo mouse model
Authors: Brunet Kévin , Arrivé François , Martellosio Jean-Philippe , Lamarche Isabelle , Marchand Sandrine , Rammaert Blandine
Published: December 2020

Alveolar macrophages (AM) are the first-line lung defense against Mucorales in pulmonary mucormycosis. Since corticosteroid use is a known risk factor for mucormycosis, the aim of this study was to describe the role of corticosteroids on AM capacities to control Lichtheimia corymbifera spore growth using a new ex vivo model. An in vivo mouse model was developed to determine the acetate cortisone dose able to trigger pulmonary invasive infection. Then, in the ex vivo model, male BALB/c mice were pretreated with the corticosteroid regimen triggering invasive infection, before AM collection through bronchoalveolar lavage. AMs from corticosteroid-treated mice and untreated control AMs were then exposed to L. corymbifera spores in vitro (ratio 1:5). AM control of fungal growth, adherence/phagocytosis, and oxidative burst were assessed using optical densities by spectrophotometer, flow cytometry, and 2', 7'-dichlorofluoresceine diacetate fluorescence, respectively. Cortisone acetate at 500 mg/kg, at D-3 and at D0, led to pulmonary invasive infection at D3. Co-incubated spores and AMs from corticosteroid-treated mice had significantly higher absorbance (fungal growth) than co-incubated spores and control AMs, at 24 h (P = .025), 36 h (P = .004), and 48 h (P = .001). Colocalization of spores with AMs from corticosteroid-treated mice was significantly lower than for control AMs (7.6 ± 1.9% vs 22.3 ± 5.8%; P = .003), reflecting spore adherence and phagocytosis inhibition. Finally, oxidative burst was significantly increased when control AMs were incubated with spores (P = 0.029), while corticosteroids hampered oxidative burst from treated AMs (P = 0.321). Corticosteroids enhanced fungal growth of L. corymbifera through AM phagocytosis inhibition and burst oxidative decrease in our ex vivo model.

Lay Summary

The aim of this study was to describe the impact of corticosteroids on alveolar macrophage (AM) capacities to control Mucorales growth in a new murine ex vivo model. Corticosteroids enhanced fungal growth of L. corymbifera through AM phagocytosis inhibition and burst oxidative decrease.
DEVELOPMENT OF A NEUTRON DOSIMETRY SYSTEM BASED ON DOUBLE SELF-ACTIVATED CSI DETECTORS FOR MEDICAL LINAC ENVIRONMENTS
Authors: Hanada Yumika , Nohtomi Akihiro , Fukunaga Junichi , Shioyama Yoshiyuki
Published: December 2020

In the present study, by using double self-activated CsI detectors, the development of a neutron dosemeter system whose response indicates better agreement with the International Commission on Radiological Protection-74 rem-response was carried out to simply evaluate the neutron dose with high accuracy. The present double neutron dosemeter system, using a slow-neutron dosemeter (thermal to 10 keV) and a fast-neutron dosemeter (above 10 keV), consists of CsI scintillators wrapped with two types of neutron energy filtering materials: polyethylene and B4C silicon rubber. After optimization of each filter thickness, to confirm the validity of our method, the neutron ambient dose equivalents under several operating conditions of medical linear accelerators (Linacs) were evaluated using a Monte Carlo simulation and an experiment with the present dosemeter. From these results, the present dosimetry system has enabled a more accurate neutron dose evaluation than our conventional dosemeter, and the present dosemeter was suitable for the neutron dosimetry for 10 MV Linac environments.
An asymmetry in past and future mental time travel following vmPFC damage
Authors: Ciaramelli Elisa , Anelli Filomena , Frassinetti Francesca
Published: December 2020

The role of ventromedial prefrontal cortex (vmPFC) in mental time travel toward the past and the future is debated. Here, patients with focal lesions to the vmPFC and brain-damaged and healthy controls mentally projected themselves to a past, present or future moment of subjective time (self-projection) and classified a series of events as past or future relative to the adopted temporal self-location (self-reference). We found that vmPFC patients were selectively impaired in projecting themselves to the future and in recognizing relative-future events. These findings indicate that vmPFC damage hinders the mental processing of and movement toward future events, pointing to a prominent, multifaceted role of vmPFC in future-oriented mental time travel.
Stereotypes bias face perception via orbitofrontal–fusiform cortical interaction
Authors: Barnett Benjamin O , Brooks Jeffrey A , Freeman Jonathan B
Published: December 2020

Previous research has shown that social-conceptual associations, such as stereotypes, can influence the visual representation of faces and neural pattern responses in ventral temporal cortex (VTC) regions, such as the fusiform gyrus (FG). Current models suggest that this social-conceptual impact requires medial orbitofrontal cortex (mOFC) feedback signals during perception. Backward masking can disrupt such signals, as it is a technique known to reduce functional connectivity between VTC regions and regions outside VTC. During functional magnetic resonance imaging (fMRI), subjects passively viewed masked and unmasked faces, and following the scan, perceptual biases and stereotypical associations were assessed. Multi-voxel representations of faces across the VTC, and in the FG and mOFC, reflected stereotypically biased perceptions when faces were unmasked, but this effect was abolished when faces were masked. However, the VTC still retained the ability to process masked faces and was sensitive to their categorical distinctions. Functional connectivity analyses confirmed that masking disrupted mOFC–FG connectivity, which predicted a reduced impact of stereotypical associations in the FG. Taken together, our findings suggest that the biasing of face representations in line with stereotypical associations does not arise from intrinsic processing within the VTC and FG alone, but instead it depends in part on top-down feedback from the mOFC during perception.
Become your own SLEEPexpert: design, implementation, and preliminary evaluation of a pragmatic behavioral treatment program for insomnia in inpatient psychiatric care
Authors: Schneider Carlotta Louisa , Hertenstein Elisabeth , Fehér Kristoffer , Maier Jonathan Gabriel , Cantisani Andrea , Moggi Franz , Berger Thomas , Nissen Christoph
Published: December 2020

Study Objectives

The majority of patients with mental disorders suffer from insomnia, associated with adverse health outcomes. Cognitive behavioral therapy for insomnia (CBT-I) represents the first-line treatment, but is too complex for severely ill patients and not systematically implemented in inpatient psychiatric care. This project aimed to develop a pragmatic behavioral treatment program that empowers inpatients with severe mental disorders to take care of their own sleep health.

Methods

CBT-I was adapted based on implementation research involving 24 inpatients with psychiatric disorders across diagnostic entities and comorbid insomnia and 30 health care providers at the University Hospital of Psychiatry and Psychotherapy, Bern. The program was implemented and evaluated by 15 patients and 22 health care providers based on interviews and questionnaires before participation and prior to discharge.

Results

Implementation research resulted in the SLEEPexpert intervention, centering on bedtime restriction and circadian adaptation in three phases; therapist-guided treatment initiation, self-management with nursing support, and self-management. Evaluative pre-post assessments in 15 patients demonstrated feasibility. Time in bed decreased by 60 minutes (520 ± 105.3 vs. 460 ± 78.1, p = 0.031, d = 0.6) and total sleep time increased by around 45 minutes (331 ± 110.6 vs. 375 ± 74.6, p = 0.09, d = 0.5), resulting in increased sleep efficiency (65.3 ± 21.8 vs. 81.9 ± 11.2%, p = 0.011, d = 0.8). Patients improved on the Insomnia Severity Index (18.3 ± 4.6 vs. 11.4 ± 4.4, p < 0.001, d = 1.2) and Pittsburgh Sleep Quality Index (12.9 ± 3.8 vs. 10.3 ± 3.3, p = 0.031, d = 0.6).

Conclusions

We propose a new pragmatic behavioral treatment program (SLEEPexpert) customized to the needs of patients and health care providers in inpatient psychiatric care. Data demonstrate feasibility. An improvement of insomnia severity was observed, but a control comparison is needed to further test for efficacy.
Effects of an Environmentally Relevant Mixture of Organophosphate Esters Derived From House Dust on Endochondral Ossification in Murine Limb Bud Cultures
Authors: Yan Han , Hales Barbara F
Published: December 2020

Organophosphate esters (OPEs) are used widely as flame retardants and plasticizers but much remains unknown about their potential toxicity. Previously, we reported that 4 individual OPEs suppress endochondral ossification in murine limb bud cultures. However, real-life exposure is to complex OPE mixtures. In the present study, we tested the hypothesis that a Canadian household dust-based OPE mixture will affect endochondral ossification in gestation day 13 CD1 mouse embryo limb buds expressing fluorescent markers for the major cell populations involved in the process: collagen type II alpha 1-enhanced cyan fluorescent protein (proliferative chondrocytes), collagen type X alpha 1-mCherry (hypertrophic chondrocytes), and collagen type I alpha 1-yellow fluorescent protein (osteoblasts). Limbs were cultured for 6 days in the presence of vehicle or dilutions of the OPE mixture (1/1 000 000, 1/600 000, and 1/300 000). All 3 OPE mixture dilutions affected cartilage template development and the progression of endochondral ossification, as indicated by the fluorescent markers. The expression of Sox9, the master regulator of chondrogenesis, was unchanged, but the expression of Runx2 and Sp7, which drive chondrocyte hypertrophy and osteoblastogenesis, was dilution-dependently suppressed. RNA-seq revealed that exposure to the 1/300 000 dilution of the OPE mixture for 24 h downregulated 153 transcripts and upregulated 48 others by at least 1.5-fold. Downregulated transcripts were enriched for those related to the immune system and bone formation. In contrast, upregulated transcripts were enriched for those with stress response functions known to be regulated by ATF4 activation. Thus, exposure to the mixture of OPEs commonly found in house dust may have adverse effects on bone formation.
From Isolation to Interaction: A Social Network Perspective on Older Teachers’ Position in School Organizations and Age-Related HR Practices
Authors: Brouhier Quentin , März Virginie , Van Waes Sara , Raemdonck Isabel
Published: December 2020

Since workforce is greying, increasing pressure has been put on many sectors, including the public sector, to raise legal retirement age. Nevertheless, older workers, and specifically teachers, usually retire much earlier. In the organizational and educational literature, most studies regarding later career have been applying a deficit perspective: reporting on senior teachers’ challenges and difficulties. Only a limited amount of studies considers senior teachers’ potentials, learning, and further career development. In this present article, we approach late-career teachers from a non-deficit perspective. This article aims to contribute to a better understanding of senior teachers at work, by analyzing HR practices that target them. Inspired by a strengths use perspective, we focus on end-of-career teachers’ knowledge and expertise exchange and their position within the school’s network. In particular, we conducted a comparative mixed-methods case study (interviews, social network analysis) in 2 secondary schools with a sample of 10 end-of-career teachers, 4 younger teachers, and 2 principals. The results illustrate that older teachers hold central positions in their workplace and have, in accordance with the socio-emotional selectivity theory, limited but strong bounds with colleagues. Moreover, school principals in both schools seem to benefit from older teachers’ organizational knowledge by involving them in decision-making processes. Nevertheless, results show that the principals in the 2 schools mainly apply remedial measures to deal with changes due to aging. This paper ends with some implications for school principals: Applying a non-deficit developmental approach is key for sustainable HR management in schools across the lifespan.
An Electroencephalogram Metric of Temporal Complexity Tracks Psychometric Impairment Caused by Low-dose Nitrous Oxide
Authors: Vrijdag Xavier C. E. , van Waart Hanna , Mitchell Simon J. , Sleigh Jamie W.
Published: December 2020

Background

Nitrous oxide produces non–γ-aminobutyric acid sedation and psychometric impairment and can be used as scientific model for understanding mechanisms of progressive cognitive disturbances. Temporal complexity of the electroencephalogram may be a sensitive indicator of these effects. This study measured psychometric performance and the temporal complexity of the electroencephalogram in participants breathing low-dose nitrous oxide.

Methods

In random order, 20, 30, and 40% end-tidal nitrous oxide was administered to 12 participants while recording 32-channel electroencephalogram and psychometric function. A novel metric quantifying the spatial distribution of temporal electroencephalogram complexity, comprised of (1) absolute cross-correlation calculated between consecutive 0.25-s time samples; 2) binarizing these cross-correlation matrices using the median of all channels as threshold; (3) using quantitative recurrence analysis, the complexity in temporal changes calculated by the Shannon entropy of the probability distribution of the diagonal line lengths; and (4) overall spatial extent and intensity of brain complexity, was quantified by calculating median temporal complexity of channels whose complexities were above 1 at baseline. This region approximately overlay the brain’s default mode network, so this summary statistic was termed “default-mode-network complexity.”

Results

Nitrous oxide concentration correlated with psychometric impairment (r = 0.50, P < 0.001). Baseline regional electroencephalogram complexity at midline was greater than in lateral temporal channels (1.33 ± 0.14 bits vs. 0.81 ± 0.12 bits, P < 0.001). A dose of 40% N2O decreased midline (mean difference [95% CI], 0.20 bits [0.09 to 0.31], P = 0.002) and prefrontal electroencephalogram complexity (mean difference [95% CI], 0.17 bits [0.08 to 0.27], P = 0.002). The lateral temporal region did not change significantly (mean difference [95% CI], 0.14 bits [−0.03 to 0.30], P = 0.100). Default-mode-network complexity correlated with N2O concentration (r = −0.55, P < 0.001). A default-mode-network complexity mixed-effects model correlated with psychometric impairment (r
2 = 0.67; receiver operating characteristic area [95% CI], 0.72 [0.59 to 0.85], P < 0.001).

Conclusions

Temporal complexity decreased most markedly in medial cortical regions during low-dose nitrous oxide exposures, and this change tracked psychometric impairment.

Editor’s Perspective

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Internal Consistency and Convergent Validity of the Inventory of Hyperacusis Symptoms
Authors: Aazh Hashir , Danesh Ali A. , Moore Brian C. J.
Published: December 2020

Objectives:

The aim was to assess the internal consistency and convergent and discriminant validity of a new questionnaire for hyperacusis, the Inventory of Hyperacusis Symptoms (IHS; Greenberg & Carlos 2018), using a clinical population.

Design:

This was a retrospective study. Data were gathered from the records of 100 consecutive patients who sought help for tinnitus and/or hyperacusis from an audiology clinic in the United Kingdom. The average age of the patients was 55 years (SD = 13 years). Audiological measures were the pure-tone average threshold (PTA) and uncomfortable loudness levels (ULL). Questionnaires administered were: IHS, Tinnitus Handicap Inventory (THI), Hyperacusis Questionnaire (HQ), Insomnia Severity Index, Generalized Anxiety Disorder, and Patient Health Questionnaire-9.

Results:

Cronbach’s alpha for the 25-item IHS questionnaire was 0.96. Neither the total IHS score nor scores for any of its five subscales were correlated with the PTA of the better or worse ear. This supports the discriminant validity of the IHS, as hyperacusis is thought to be independent of the PTA. There were moderately strong correlations between IHS total scores and scores for the HQ, Tinnitus Handicap Inventory, Generalized Anxiety Disorder, and Patient Health Questionnaire-9, with r = 0.58, 0.58, 0.61, 0.54, respectively. Thus, although IHS scores may reflect hyperacusis itself, they may also reflect the coexistence of tinnitus, anxiety, and depression. The total score on the IHS was significantly different between patients with and without hyperacusis (as diagnosed based on ULLs or HQ scores). Using the HQ score as a reference, the area under the receiver operating characteristic for the IHS was 0.80 (95% confidence interval = 0.71 to 0.89) and the cutoff point of the IHS with highest overall accuracy was 56/100. The corresponding sensitivity and specificity were 74% and 82%.

Conclusions:

The IHS has good internal consistency and reasonably high convergent validity, as indicated by the relationship of IHS scores to HQ scores and ULLs, but IHS scores may also partly reflect the co-occurrence of tinnitus, anxiety, and depression. We propose an IHS cutoff score of 56 instead of 69 for diagnosing hyperacusis.
Jones fractures outcome measurement: a case series
Authors: Al-Ashhab Mohamed E.
Published: December 2020

Background:

Jones fracture of the base fifth metatarsal is one of the most common foot injuries. Delayed union, nonunion and, refracture are all known complications that can occur, and operative intervention then must be considered.

Methodology:

Seventy-five patients who had recent Jones fractures were treated surgically by intramedullary cannulated screws. Age of the patients ranged from 18 to 40 yr with an average age of 26.4 yr. There were 51 male patients and 24 female patients.

Results:

All fractures were united within 6 to 12 wk, with an average of 7.2 wk. According to American Orthopaedic Foot and Ankle Society (AOFAS) score, final scores ranged from 95 to 98 points with an average of 97.5 points. An irritant screw that needed to be removed after fracture union was encountered in two patients.

Conclusions:

The use of primary intramedullary screws is a safe and effective option for patients who have Jones fractures, especially those who need early ambulation and excellent osseous union rates.

Level of Evidence:

Level IV.
The Dorsal Periosteal Curtain for Distal Radius Osteotomy Via the Volar Approach
Authors: Potter J. Alexa , Ross Mark
Published: December 2020

Volar wedge osteotomy and angle stable volar plating is now considered a standard approach for correction of distal radius malunion. In previous descriptions of the technique, soft tissue release has been performed with periosteal incision in line with the bony osteotomy. We present a technique whereby the dorsal periosteum is incised more proximally creating a dorsal vascularized periosteal “curtain.” Our technique has several advantages including systematic release of restraining soft tissues to allow better distraction and reduction of the malunion; a dorsal periosteal curtain of vascular tissue with which to contain bone graft, protect extensor tendons and expedite healing; and better access to locally available bone graft. The previously described rotation-advancement of pronator quadratus is also used for plate coverage. We have found this technique straightforward to execute and teach, and useful in mitigating against some of the potential risks of the standard technique.
Hidden in plain sight: sex and gender in global pandemics
Authors: Scully Eileen P.
Published: December 2020

Purpose of review

The global pandemic caused by the severe acute respiratory virus coronavirus 2 (SARS-CoV-2) has a male bias in mortality likely driven by both gender and sex-based differences between male and female individuals. This is consistent with sex and gender-based features of HIV infection and overlap between the two diseases will highlight potential mechanistic pathways of disease and guide research questions and policy interventions. In this review, the emerging findings from SARS-CoV-2 infection will be placed in the context of sex and gender research in the more mature HIV epidemic.

Recent findings

This review will focus on the new field of literature on prevention, immunopathogenesis and treatment of SARS-CoV-2 referencing relevant articles in HIV for context from a broader time period, consistent with the evolving understanding of sex and gender in HIV infection. Sex-specific features of epidemiology and immunopathogenesis reported in COVID-19 disease will be discussed and potential sex and gender-specific factors of relevance to prevention and treatment will be emphasized.

Multilayered impacts of sex and gender on HIV infection have illuminated pathways of disease and identified important goals for public health interventions. SARS-CoV-2 has strong evidence for a male bias in disease severity and exploring that difference will yield important insights.
Radiologically-proven New Development of Superior Semicircular Canal Dehiscence Associated With Development of Superior Semicircular Canal Dehiscence Syndrome
Authors: Chari Divya A. , Juliano Amy F. , Jung David H.
Published: December 2020

Objective:

This report describes a case of development of radiologic superior semicircular canal dehiscence and reviews the literature for pertinent clinical and radiologic findings in patients with superior semicircular canal dehiscence syndrome (SCDS).

Patient:

A 28-year-old man presented with auditory and vestibular symptoms of SCDS and underwent a high-resolution temporal bone computed tomography scan that showed frank dehiscence of the right superior semicircular canal. Diagnosis of SCDS was further verified with audiometric and cervical vestibular-evoked myogenic potential (cVEMP) thresholds. The patient had previously undergone a computed tomography scan 12 years prior for work-up of sudden sensorineural hearing loss that showed no evidence of superior semicircular canal dehiscence bilaterally.

Interventions:

A combination of diagnostic and therapeutic interventions was conducted consisting of preoperative audiometric and cVEMP thresholds, followed by middle fossa craniotomy for surgical repair of the dehiscence.

Main Outcome Measure:

Postoperative audiometric and cVEMP thresholds and symptomatic improvement of SCDS after surgical repair of the dehiscence.

Results:

The patient reported resolution of his clinical symptoms after surgical repair of the dehiscence. Postoperative cVEMP thresholds improved to the normal range and the mild low-frequency conductive hearing loss resolved.

Conclusions:

To our knowledge, this case report is the first description of radiologically proven new development of superior canal dehiscence. Further prospective studies that include serial imaging examinations may help with visualizing and understanding the temporal evolution of superior canal dehiscence, and better elucidate the relationship between development/ progression of superior canal dehiscence and onset of clinical symptoms.
Chlamydia Testing in New Zealand: Analysis of the 2014/2015 National Health Survey
Authors: Righarts Antoinette , Gray Andrew R. , Morgan Jane , Saxton Peter J. , Green Jane Alison , Connor Jennie L. , Dickson Nigel P.
Published: December 2020

Background

Diagnosis rates of Chlamydia trachomatis are high in New Zealand; 1.3% of men and 3.7% of women aged 15 to 29 years were diagnosed in 2016. Because testing rates are also higher in women, we sought to understand chlamydia testing by demographic and behavioral characteristics.

Methods

Chlamydia testing in the past year, sexual behavior, and demographic characteristics were reported in the population-based 2014/2015 New Zealand Health Survey. Those aged 16 to 44 years who had a sexual partner in the past year were included. Testing prevalence was calculated, and associations were modeled.

Results

A total of 1677 men and 2323 women participated (89% response rate). Of these, 5.6% (95% confidence interval, 4.3%–7.2%) of men and 16.6% (14.7%–18.7%) of women were tested in the past year. Likelihood of testing in men was associated with having multiple partners and any condomless sex (adjusted relative risk, 11.93; 95% confidence interval, 5.70–24.98) and multiple partners with consistent condom use (3.77, 1.40–10.15) compared with one sexual partner and consistent condom use, and with Māori ethnicity (1.87, 1.05–3.31) compared with European/other. Among women, testing was associated with multiple partners with and without condomless sex (3.61 [2.69–4.85] and 2.81 [1.95–4.05], respectively), pregnancy (1.61, 1.18–2.18), and Asian ethnicity (0.52, 0.30–0.89).

Conclusions

The study confirms that New Zealand men are much less likely to be tested than women, a potential reason for ongoing high chlamydia incidence among both sexes. The high testing rate in women includes many at low risk, and this divergence from recommendations is another issue to address.
INSM1 Is Less Sensitive But More Specific Than Synaptophysin in Gynecologic High-grade Neuroendocrine Carcinomas
Authors: Zou Qiong , Zhang Lily , Cheng Zhiqiang , Guo Xiaojing , Cao Dengfeng
Published: December 2020

Insulinoma-associated protein 1 (INSM1) has emerged as a promising diagnostic marker for high-grade neuroendocrine carcinomas (HGNECs); however, it is controversial whether INSM1 is more sensitive than conventional markers chromogranin, synaptophysin, and CD56. Here, we investigated immunohistochemical expression of INSM1 in 75 gynecologic HGNECs using full tissue sections (30 small-cell carcinomas [SmCCs], 34 large-cell neuroendocrine carcinomas [LCNECs], and 11 mixed SmCC and LCNEC), with specificity analysis in 422 gynecologic non-neuroendocrine tumors (410 in tissue microarrays and 12 full sections) and comparison with conventional neuroendocrine markers for their sensitivity and specificity. Positive INSM1 staining was seen in 69 (92%) HGNECs, whereas chromogranin, synaptophysin, and CD56 staining was seen in 61 (81%), 72 (96%), and 44 (69%) tumors, respectively (INSM1 vs. chromogranin, P=0.09; INSM1 vs. synaptophysin, P=0.4942; and INSM1 vs. CD56, P<0.001). The mean percentage of INSM1-positive tumor cells was 54% (median: 60%, range: 0% to 100%), similar to chromogranin (58%, P=0.2903) and higher than CD56 (30%, P=0.00001) but significantly lower than synaptophysin (89%, P<0.00001). INSM1 showed no staining difference among SmCCs, LCNECs, and mixed SmCC-LCNECs. Among the 422 non-neuroendocrine tumors, positive staining was seen in 5% tumors for INSM1, 18% for chromogranin, 19% for synaptophysin, and 25% for CD56. Our study indicates that INSM1 is a highly specific marker (95% specificity) for gynecologic HGNECs with high sensitivity (92%), but it is less sensitive than synaptophysin (96% sensitivity). INSM1 is more specific than chromogranin, synaptophysin, and CD56 for gynecologic HGNECs. Our literature review reveals that INSM1 has consistently (the same antibody clone A8 used for all reported studies) shown higher or similar sensitivity to chromogranin (for all 3 chromogranin antibody clones LK2H10, DAK-A3, DAKO polyclonal); however, whether INSM1 is more or less sensitive than synaptophysin or CD56 for HGNECs is highly dependent on the antibody clones used for synaptophysin (clones MRQ-40 and SNP88 showing higher sensitivity than clones 27G12 and DAK-SYNAP) or CD56 (clones CD564, MRQ-42, and MRQ-54 showing higher sensitivity than clones 123C3D5, 1B6, and Leu243).
Dyskinetopsic Palinopsia: Palinopsia Accompanied by Moving Afterimages
Authors: Lahiri Durjoy , Ardila Alfredo , Chatterjee Subham , Dubey Souvik , Ray Biman Kanti
Published: December 2020

Palinopsia refers to the abnormal persistence, or recurrence, of visual images after a visual stimulus has subsided. We describe here a case of palinopsia accompanied by a visual motion perception disorder as manifested by moving afterimages. A 71-year-old man presented to us after having experienced acute-onset, vivid, visual hallucinations for 1 week. A detailed history revealed that he was hallucinating multiple living and nonliving objects. He also complained of a persistence of afterimages, particularly in the left visual field. He reported that, on a few occasions, while sitting by the window in his room, he had seen a moving car on the road; immediately after the car had disappeared from his sight, he had then seen the same car moving backward at almost the same speed—as if the driver had applied the reverse gear. A neuropsychological assessment did not reveal any deficits in attention, language, or episodic memory. Visual field testing by confrontational perimetry suggested left hemianopia. An MRI of the brain revealed an arteriovenous malformation in the medial part of the right occipital lobe, affecting both the lingual gyrus and the inferior occipital gyrus. Palinopsia has generally been described in reference to static afterimages. In our case, not only was the afterimage that was perceived by the patient in motion, but the direction of the movement was also opposite to that of the actual object. We propose the term dyskinetopsic palinopsia, or simply motion-related palinopsia, for this particular condition.
Reversible Splenial Lesion Syndrome (RESLES) After Chemotherapy of Oral Tegafur-uracil in a Female With Locally Rectal Adenocarcinoma
Authors: Ge Yu-Xing , Lin Ying-Ying , Bi Qian-Qian , Chen Yu-Juan
Published: December 2020

A 42-year-old woman with reversible splenial lesion syndrome (RESLES) and rectal adenocarcinoma presented with sudden-onset delirium after the sixth cycle of her chemotherapy drug, oral tegafur-uracil (300 mg/m2/day, days 1–14, with treatment cycle repeated every 21 days). Accompanied by the anti-CV2 antibody, paraphasia, and a loss of bimanual coordination, the patient’s etiology and clinical manifestations of RESLES are unlike those of other reported cases of RESLES. Tegafur-uracil is an oral fluoropyrimidine that has a similar effect to 5-fluorouracil as an adjuvant treatment for colorectal cancer. The possibility that the toxicity of chemotherapeutic drugs may play a role in the pathogenesis of cytotoxic edema in the splenium of the corpus callosum and extracallosal white matter should be investigated further.
Socially cued anticipatory adjustment of female signalling effort in a moth
Authors: Pham Hieu T. , McNamara Kathryn B. , Elgar Mark A.
Published: December 2020

Juvenile population density has profound effects on subsequent adult development, morphology and reproductive investment. Yet, little is known about how the juvenile social environment affects adult investment into chemical sexual signalling. Male gumleaf skeletonizer moths,
Uraba lugens,
facultatively increase investment into antennae (pheromone receiving structures) when reared at low juvenile population densities, but whether there is comparable adjustment by females into pheromone investment is not known. We investigate how juvenile population density influences the ‘calling' (pheromone-releasing) behaviour of females and the attractiveness of their pheromones. Female
U. lugens
adjust their calling behaviour in response to socio-sexual cues: adult females reared in high juvenile population densities called earlier and for longer than those from low juvenile densities. Juvenile density also affected female pheromonal attractiveness: Y-maze olfactometer assays revealed that males prefer pheromones produced by females reared at high juvenile densities. This strategic investment in calling behaviour by females, based on juvenile cues that anticipate the future socio-sexual environment, likely reflects a response to avoid mating failure through competition with neighbouring signallers.