bluuebunny/crossref_metadata_2025 huggingface dataset:
Biofilm Formation on Breast Implant Surfaces by Major Gram-Positive Bacterial Pathogens
Authors: Rezende-Pereira Gabriel , Albuquerque Julia P , Souza Monica C , Nogueira Barbara A , Silva Marlei G , Hirata Raphael , Mattos-Guaraldi Ana L , Duarte Rafael S , Neves Felipe P G
Published: December 2020

Background

Bacterial biofilm on surfaces of mammary implants is a predisposing factor for several outcomes. Because Gram-positive bacteria are potential agents of biomaterial-associated infections (BAIs), their abilities to form biofilm on breast implants should be elucidated.

Objectives

The aim of this study was to evaluate biofilm formation on different mammary prosthesis surfaces by major Gram-positive bacterial pathogens involved in BAIs.

Methods

We initially evaluated biofilm formation on polystyrene plates with and without fibrinogen or collagen for 1 reference strain and 1 clinical isolate of Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. We also tested the ability of clinical isolates to form biofilm on 4 different implant surfaces: polyurethane foam and smooth, microtextured, and standard textured silicone. Biofilm structure and cell viability were observed by scanning electron microscopy and confocal laser scanning microscopy.

Results

All strains showed strong biofilm formation on polystyrene. After fibrinogen or collagen treatment, biofilm formation varied. With fibrinogen, reference strains of S. aureus and S. pyogenes increased biofilm formation (P < 0.05). Reference strains of all species and the clinical isolate of S. pyogenes increased biofilm formation after collagen treatment (P < 0.05). In general, S. aureus showed higher capacity to produce biofilm. Scanning electron microscopy showed that biofilm attached to all surfaces tested, with the presence of extracellular polymeric substances and voids. Viable cells were more frequent for E. faecalis and S. pyogenes.

Conclusions

All species produced biofilm on all prosthesis surfaces and under different conditions. Micrographies indicated thicker bacterial biofilm formation on microtextured and/or standard textured silicone by all species, except E. faecalis.
The PTP1B mutant PTP1B∆2–4 is a positive regulator of the JAK/STAT signalling pathway in Hodgkin lymphoma
Authors: Zahn Malena , Kaluszniak Bianca , Möller Peter , Marienfeld Ralf
Published: December 2020

The neoplastic Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) depend on chronic activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathways to maintain survival and proliferation. Accumulating reports highlight the importance of the inactivation or reduced expression of negative JAK/STAT regulators such as the protein-tyrosine phosphatase 1B (PTP1B/PTPN1) in this process. Various PTPN1 mRNA variants as well as truncated PTP1B proteins were identified in cHL cell lines and primary cHL tumour samples. These PTPN1 mRNA variants lack either one or several exon sequences and therefore render these PTP1B variants catalytically inactive. Here, we show that one of these mutants, PTP1B∆2–4, is not only a catalytically inactive variant, but also augmented the IL-4-induced JAK/STAT activity similar to the recently reported PTP1B∆6 splice variant. Moreover, while PTP1B∆6 diminished the activity and protein levels of PTP1BWT, PTP1BWT remained unaffected by PTP1B∆2–4, arguing for different molecular mechanisms of JAK/STAT modulation by PTP1B∆6 and PTP1B∆2–4. Collectively, these data indicate that PTPN1 variants missing one or more exon sequences originated either from alternative splicing or from gene mutation, create PTP1B gain-of-function variants with oncogenic potential by augmenting JAK/STAT signalling in cHL.
Odor Canopy: A Method for Comfortable Odorant Delivery in MRI
Authors: Gorodisky Lior , Livne Ethan , Weiss Tali , Weissbrod Aharon , Weissgross Reut , Mishor Eva , Furman-Haran Edna , Sobel Noam
Published: December 2020

Functional magnetic resonance imaging (fMRI) has become the leading method for measuring the human brain response to sensory stimuli. However, olfaction fMRI lags behind vision and audition fMRI for 2 primary reasons: First, the olfactory brain areas are particularly susceptible to imaging artifacts, and second, the olfactory stimulus is particularly difficult to control in the fMRI environment. A component of the latter is related to the odorant delivery human–machine interface, namely the point where odorants exit the dispensing apparatus to reach at the nose. Previous approaches relied on either nasal cannulas or nasal masks, each associated with particular drawbacks and discomforts. Here, we provide detailed descriptions and instructions for transforming the MRI head-coil into an olfactory microenvironment, or odor canopy, where odorants can be switched on and off in less than 150 ms without cannula or mask. In a proof-of-concept experiment, we demonstrate that odor canopy provides for clearly dissociable odorant presence and absence, with no nonolfactory cues. Moreover, we find that odor canopy is rated more comfortable than nasal mask, and we demonstrate that using odor canopy in the fMRI generates a typical olfactory brain response. We conclude in recommending this approach for minimized discomfort in fMRI of olfaction.
Simultaneous HPLC Assay of Gliclazide and Ciprofloxacin in Plasma and its Implementation for Pharmacokinetic Study in Rats
Authors: Sasongko Lucy , Pratiwi Gladdis K , Leo Margaretha , Adiwidjaja Jeffry
Published: December 2020

A simple and reliable high-performance liquid chromatography method for simultaneous quantitation of gliclazide and ciprofloxacin in plasma sample has been developed and validated. This method implements protein precipitation, a simple and practical pretreatment method by the addition of acetonitrile that gives a clean supernatant. The separation was carried out in a system consisted of a C18 column with acetonitrile and KH2PO4 (0.01 M, 0.1% v/v of triethylamine, pH 2.7) as the mobile phase in a gradient elution at a total flow-rate of 1 mL/min. Gliclazide and ciprofloxacin were quantitated using an ultraviolet detector set at wavelengths of 229 and 277 nm, respectively, which ensures optimal sensitivity for both compounds. This method possesses an excellent linearity at concentration ranges of 0.5–50 mg/L for gliclazide and 0.1–10 mg/L for ciprofloxacin. High within- and between-run accuracy for both gliclazide (% error of −8.00 to 0.45%) and ciprofloxacin (% error of −10.00 to 7.63%) were demonstrated. The intra- and inter-day precision (expressed as %CV) was <8 and 12% for gliclazide and ciprofloxacin, respectively. Both analytes were stable during storage and sample processing. The method reported in this study can be implemented for pharmacokinetic interaction study in rats.
Novel Criteria for Diagnosing Acute and Early Human Immunodeficiency Virus Infection in a Multinational Study of Early Antiretroviral Therapy Initiation
Authors: Crowell Trevor A , Ritz Justin , Coombs Robert W , Zheng Lu , Eron Joseph J , Mellors John W , Dragavon Joan , van Zyl Gert U , Lama Javier R , Ruxrungtham Kiat , Grinsztejn Beatriz , Arduino Roberto C , Fox Lawrence , Ananworanich Jintanat , Daar Eric S ,   AIDS Clinical Trials Group A5354/EARLIER (Early ART to Limit Infection and Establishment of Reservoir) Study Team, Alli Oladapo , Anisman-Posner Deborah , Borowski LuAnn , Chi Benjamin , Cohn Susan E , Collier Ann , Gapara Morgan , Heath Sonya , Higgins Tydie , Hoagland Brenda , Kaytes Andrew , Kliemann Dimas , Kroon Eugène , Nair Gonasagrie , Persaud Deborah , Riddler Sharon , Rooney James , Sieg Scott , Sobieszczyk Magdalena , Tiu Jennifer , Whitson Kyle
Published: December 2020

Background

Antiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation.

Methods

AIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA. HIV status and Fiebig stage were confirmed by centralized testing.

Results

From 2017 through 2019, 195 participants were enrolled with median age of 27 years (interquartile range, 23–39). Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, 4 (2.0%) participants were found to have chronic infection, and 3 (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II–IV AEHI cases with no false-positive results.

Conclusions

Novel AEHI criteria that incorporate ARCHITECT S/CO facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice.

Clinical Trials Registration

NCT02859558.
Fulminant myocarditis in a COVID-19 positive patient treated with mechanical circulatory support – a case report
Authors: Papageorgiou Joanna-Maria , Almroth Henrik , Törnudd Mattias , van der Wal Henriëtte , Varelogianni Georgia , Lawesson Sofia Sederholm
Published: December 2020

Background

Coronavirus disease 2019 (COVID-19) spreading from Wuhan, Hubei province in China, is an expanding global pandemic with significant morbidity and mortality. Even though respiratory failure is the cardinal form of severe COVID-19, concomitant cardiac involvement is common. Myocarditis is a challenging diagnosis due to heterogeneity of clinical presentation, ranging from mild symptoms to fatal arrhythmia and cardiogenic shock (CS). The aetiology is often viral and endomyocardial biopsy (EMB) is the gold standard for definite myocarditis. However, the diagnosis is often made on medical history, clinical presentation, magnetic resonance imaging, and blood tests.

Case summary

We present a 43-year-old man with mixed connective tissue disease treated with hydroxychloroquine who rapidly developed CS 4 days from symptom onset with fever and cough, showing positive polymerase chain reaction nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. While computed tomography of the thorax was normal, high-sensitivity troponin T was elevated and electrocardiogram showed diffuse ST elevation and low voltage as signs of myocardial oedema. Echocardiography showed severe depression of left ventricular function. The myocardium recovered completely after a week with mechanical circulatory support (MCS). EMB was performed but could neither identify the virus in the cardiomyocytes, nor signs of inflammation. Still the most probable aetiology of CS in this case is myocarditis as a sole symptom of COVID-19.

Discussion

COVID-19 patients in need of hospitalization present commonly with respiratory manifestations. We present the first case of fulminant myocarditis rapidly progressing to CS in a COVID-19 patient without respiratory failure, successfully treated with inotropes and MCS.
Gerbode defect following surgical mitral valve replacement and tricuspid valve repair: a case report
Authors: Haraf Rebecca H , Karnib Mohamad , El Amm Chantal , Plummer Sarah , Bocks Martin , Sabik Ellen M
Published: December 2020

Background

Gerbode defect is a congenital or acquired communication between the left ventricle and right atrium. While the defect is becoming a more well-recognized complication of cardiac surgery, it presents a diagnostic and therapeutic challenge for providers. This case highlights the predisposing factors and imaging features that may assist in the diagnosis of Gerbode defect, as well as potential approaches to treatment.

Case summary

We report a patient with severe mitral stenosis as a result of remote mediastinal radiation who underwent extensive decalcification during surgical mitral valve replacement and tricuspid valve repair. Following the procedure, he developed progressive heart failure refractory to medical management. Extensive workup ultimately led to the diagnosis of iatrogenic acquired Gerbode defect. Close collaboration between adult cardiology, cardiothoracic surgery, and the congenital cardiology services led to an optimal treatment plan involving percutaneous closure of the defect.

Discussion

Gerbode defect is a rare complication of invasive procedures involving the interventricular septum or its nearby structures. An understanding of the key echocardiographic features will aid providers in timely diagnosis. Percutaneous repair should be strongly considered for patients who may be poor surgical candidates.
Parental Involvement and the Intergenerational Transmission of Economic Preferences, Attitudes and Personality Traits
Authors: Zumbuehl Maria , Dohmen Thomas , Pfann Gerard
Published: December 2020

We empirically investigate the link between parental involvement and shaping of the economic preferences, attitudes and personality traits of their children. We exploit information on the risk and trust attitudes, the Big Five personality traits and locus of control of parents and their children, as well as rich information about parental efforts in the upbringing of their children from the German Socio-Economic Panel Study (SOEP). Our results show that parents who are more involved in the upbringing of their children have children with more favourable attitudes and traits. These children rank higher in traits that further their success in life, and they are more similar to their parents in those attitudes, where the optimum level is more ambiguous.
Antithrombotic therapy for stroke prevention in patients with atrial fibrillation who survive an intracerebral haemorrhage: results of an EHRA survey
Authors: Ivany Elena , Lane Deirdre A , Dan Gheorghe-Andrei , Doehner Wolfram , Farkowski Michal M , Iliodromitis Konstantinos , Lenarczyk Radoslaw , Potpara Tatjana S
Published: December 2020

The aim of this survey is to provide a snapshot of current practice regarding antithrombotic therapy (ATT) in patients with atrial fibrillation (AF) comorbid with intracerebral haemorrhage (ICH). An online survey was distributed to members of the European Heart Rhythm Association. A total of 163 clinicians responded, mostly cardiologists or electrophysiologists (87.7%), predominantly working in University hospitals (61.3%). Most respondents (47.2%) had seen one to five patients with AF comorbid with ICH in the last 12 months. Among patients sustaining an ICH on oral anticoagulation (OAC), 84.3% respondents would consider some form of ATT post-ICH, with 73.2% preferring to switch from a vitamin-K antagonist (VKA) to a non-VKA oral anticoagulant (NOAC) and 37.2% preferring to switch from one NOAC to another. Most (36.6%) would restart OAC >30 days post-ICH. Among patients considered unable to take OAC, left atrial appendage occlusion procedure was the therapy of choice in 73.3% respondents. When deciding on ATT, respondents considered patient’s CHA2DS2-VASc score, ICH type, demographics, risk factors, and patient adherence. The main reason for not restarting or commencing ATT was concern about recurrent ICH (80.8%). National or international clinical guidelines would be advantageous to support decision-making (84.3%). Other helpful resources reported were multidisciplinary team involvement (46.9%) and patient education (82%). In summary, most survey respondents would prescribe OAC therapy for patients with AF who have sustained an ICH on OAC and would restart OAC >30 days post-ICH. The risk of recurrent ICH was the main reason for not prescribing any ATT post-ICH.
On the aftershock productivity in mining-induced seismicity—insight into seismicity of Rudna copper ore mine, Poland
Authors: Kozłowska Maria , Jamroz Mateusz , Olszewska Dorota
Published: December 2020

Mining-induced seismic events can be followed by aftershocks that increase the risk associated with the exploitation. The understanding of the aftershock generation process in induced seismicity may improve post-earthquake safety procedures applied in mines. Rudna copper ore mine in southwestern Poland commonly experiences intense and strong seismic activity accompanying the room-and-pillar exploitation of copper ore. Some strong (magnitude >2) mining events are followed by numerous aftershocks and some are not followed by any. In this study, we seek to find whether there is any geological, technological or seismological cause of this diversity. We study 46 strong mining events and focus on their aftershock productivity. We analyse the geological and mining setting of the studied events, their signal similarity, stress drops and the ground motion effect using data from three different seismic networks. Our results show that seismic events producing large aftershock sequences may share similar focal mechanisms and have larger ground effects than events with no aftershocks. The results also indicate the potential differences in stress drops. This interesting observation may help to better evaluate the aftershock hazard in mines. It also indicates the need for a more detailed analysis of the focal mechanisms of strong events and their relationship to the exploitation technique.
Interactions between nitrogen nutrition, canopy architecture and photosynthesis in rice, assessed using high-resolution 3D reconstruction
Authors: Burgess Alexandra J , Herman Tiara , Ali Asgar , Murchie Erik H
Published: December 2020

Increasing nitrogen use efficiency is a key target for yield improvement programs. Here we identify features of rice canopy architecture during altered N availability and link them to photosynthetic productivity. Empirical mathematical modelling, high-resolution 3-dimensional (3D) reconstruction and gas exchange measurements were employed to investigate the effect of a mild N deficiency vs. surplus N application on canopy architecture, light and photosynthesis distribution throughout development. Three contrasting rice lines: two Malaysian rice varieties (MR219 and MR253) and a high-yielding indica cultivar (IR64) were cultivated. 3D reconstruction indicated key N-dependent differences in plant architecture and canopy light distribution including changes to leaf area index (LAI), tiller number, leaf angle and modelled light extinction coefficients. Measured leaf photosynthetic capacity did not differ substantially between the high and reduced N treatments; however, modelled canopy photosynthesis rate indicated a higher carbon gain per unit leaf area for the reduced N treatment but a higher carbon gain per unit ground area for the high N treatment. This is a result of altered canopy structure leading to increased light distribution under reduced N which partially offsets the reduced LAI. Within rice, altered N availability results in the development of full photosynthetically functional leaves, but leads to altered canopy architecture, light distribution and overall productivity suggested that N availability can be fine-tuned to optimize biomass production. We propose wider use of 3D reconstruction to assess canopy architecture and productivity under differing N availabilities for a range of species.
Partial stellar explosions – ejected mass and minimal energy
Authors: Linial Itai , Fuller Jim , Sari Re’em
Published: December 2020

Many massive stars appear to undergo enhanced mass-loss during late stages of their evolution. In some cases, the ejected mass likely originates from non-terminal explosive outbursts, rather than continuous winds. Here we study the dependence of the ejecta mass, mej, on the energy budget E of an explosion deep within the star, using both analytical arguments and numerical hydrodynamics simulations. Focusing on polytropic stellar models, we find that for explosion energies smaller than the stellar binding energy, the ejected mass scales as $m_{\rm ej} \propto E^{\varepsilon _{\rm m}}$, where εm = 2.4–3.0 depending on the polytropic index. The loss of energy due to shock breakout emission near the stellar edge leads to the existence of a minimal mass-shedding explosion energy, corresponding to a minimal ejecta mass. For a wide range of progenitors, from Wolf–Rayet stars to red supergiants (RSGs), we find a similar limiting energy of $E_{\rm min} \approx 10^{46}\!-\!10^{47} \rm \, erg$, almost independent of the stellar radius. The corresponding minimal ejecta mass varies considerably across different progenitors, ranging from ${\sim } 10^{-8} \, \rm M_\odot$ in compact stars, up to ${\sim } 10^{-2} \, \rm M_\odot$ in RSGs. We discuss implications of our results for pre-supernova outbursts driven by wave heating, and complications caused by the non-constant opacity and adiabatic index of realistic stars.
Interstellar comet 2I/Borisov: dust composition from multiband photometry and modelling
Authors: Busarev Vladimir V , Petrova Elena V , Shcherbina Marina P , Ikonnikova Natalia P , Burlak Marina A , Belinski Alexander A
Published: December 2020

We present results from multiband photometry of the interstellar comet 2I/Borisov (C/2019 Q4). The observations were carried out in the two months before its perihelion passage. The UBVri photometric data obtained for comet 2I were converted to its reflectance by means of observations of neighbouring solar analogues, which allowed the reflectance of the comet with wavelength to be calculated. The registered prominent changes in the reflectance spectra of 2I while it was approaching the Sun from 2.40 to 2.01 au, and numerical simulations of the light scattering by aggregate particles provide insight into the chemical-mineralogical and structural properties of the cometary dust particles. The close agreement between the trends observed in the spectral characteristics of 2I and some models suggests that, during the observations, conglomerates of magnesium-ferrous (and, probably, organic) submicron particles prevailed in the scattering by its matter, H2O ice particles induced no noticeable spectral signals, and the gas contribution to the scattering by the coma was relatively small.
Searching for energy-resolved quasi-periodic oscillations in AGN
Authors: Ashton Dominic I , Middleton Matthew J
Published: December 2020

X-ray quasi-periodic oscillations (QPOs) in active galactic nucleus (AGN) allow us to probe and understand the nature of accretion in highly curved space–time, yet the most robust form of detection (i.e. repeat detections over multiple observations) has been limited to a single source to-date, with only tentative claims of single observation detections in several others. The association of those established AGN QPOs with a specific spectral component has motivated us to search the XMM–Newton archive and analyse the energy-resolved light curves of 38 bright AGNs. We apply a conservative false alarm testing routine folding in the uncertainty and covariance of the underlying broad-band noise. We also explore the impact of red-noise leak and the assumption of various different forms (power-law, broken power-law, and Lorentzians) for the underlying broad-band noise. In this initial study, we report QPO candidates in six AGNs (seven including one tentative detection in MRK 766) from our sample of 38, which tend to be found at characteristic energies and, in four cases, at the same frequency across at least two observations, indicating they are highly unlikely to be spurious in nature.
MOCCA Survey Database: extra Galactic globular clusters. I. Method and first results
Authors: Leveque A , Giersz M , Paolillo M
Published: December 2020

Over the last few decades, exhaustive surveys of extra Galactic globular clusters (EGGCs) have become feasible. Only recently, limited kinematical information of globular clusters (GCs) were available through Gaia Data Release 2 spectroscopy and also proper motions. On the other hand, simulations of GCs can provide detailed information about the dynamical evolution of the system. We present a preliminary study of EGGCs’ properties for different dynamical evolutionary stages. We apply this study to 12-Gyr-old GCs simulated as part of the MOCCA Survey Database. Mimicking observational limits, we consider only a subsample of the models in the data base, showing that it is possible to represent observed Milky Way GCs. In order to distinguish between different dynamical states of EGGCs, at least three structural parameters are necessary. The best distinction is achieved by considering the central parameters, those being observational core radius, central surface brightness, ratio between central and half-mass velocity dispersion, or similarly considering the central colour, the central V magnitude, and the ratio between central and half-mass radius velocity dispersion, although such properties could be prohibitive with current technologies. A similar but less solid result is obtained considering the average properties at the half-light radius, perhaps accessible presently in the Local Group. Additionally, we mention that the colour spread in EGGCs due to internal dynamical models, at fixed metallicity, could be just as important due to the spread in metallicity.
Continuous flow synthesis and antimicrobial evaluation of NHC* silver carboxylate derivatives of SBC3 in vitro and in vivo
Authors: O'Beirne Cillian , Piatek Magdalena E , Fossen Jen , Müller-Bunz Helge , Andes David R , Kavanagh Kevin , Patil Siddappa A , Baumann Marcus , Tacke Matthias
Published: December 2020

N-heterocyclic silver carbene compounds have been extensively studied and shown to be active agents against a host of pathogenic bacteria and fungi. By incorporating hypothesized virulence targeting substituents into NHC–silver systems via salt metathesis, an atom-efficient complexation process can be used to develop new complexes to target the passive and active systems of a microbial cell. The incorporation of fatty acids and an FtsZ inhibitor have been achieved, and creation of both the intermediate salt and subsequent silver complex has been streamlined into a continuous flow process. Biological evaluation was conducted with in vitro toxicology assays showing these novel complexes had excellent inhibition against Gram-negative strains E. coli, P. aeruginosa, and K. pneumoniae; further studies also confirmed the ability to inhibit biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA) and C. Parapsilosis. In vivo testing using a murine thigh infection model showed promising inhibition of MRSA for the lead compound SBC3, which is derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*).
Interoceptive active inference and self-representation in social anxiety disorder (SAD): exploring the neurocognitive traits of the SAD self
Authors: Gerrans Philip , Murray Ryan J
Published: December 2020

This article provides an interoceptive active inference (IAI) account of social anxiety disorder (SAD). Through a neurocognitive framework, we argue that the cognitive and behavioural profile of SAD is best conceived of as a form of maladaptive IAI produced by a negatively biased self-model that cannot reconcile inconsistent tendencies to approach and avoid social interaction. Anticipated future social interactions produce interoceptive prediction error (bodily states of arousal). These interoceptive states are transcribed and experienced as states of distress due to the influence of inconsistent and unstable self-models across a hierarchy of interrelated systems involved in emotional, interoceptive and affective processing. We highlight the role of the insula cortex, in concert with the striatum, amygdala and dorsal anterior cingulate in the generation and reduction of interoceptive prediction errors as well as the resolution of social approach-avoidance conflict. The novelty of our account is a shift in explanatory priority from the representation of the social world in SAD to the representation of the SAD self. In particular, we show how a high-level conceptual self-model of social vulnerability and inadequacy fails to minimize prediction errors produced by a basic drive for social affiliation combined with strong avoidant tendencies. The result is a cascade of interoceptive prediction errors whose attempted minimization through action (i.e. active inference) yields the symptom profile of SAD. We conclude this article by proposing testable hypotheses to further investigate the neurocognitive traits of the SAD self with respect to IAI.
Posterior Midline Approach for a C2 Schwannoma: 2-Dimensional Operative Video
Authors: Aldea Sorin , Alkhairy Abdu , Joitescu Irina , Guerinel Caroline Le
Published: December 2020

C2 schwannomas are rare lesions that may develop in the spinal canal, in the area of the C2 ganglion situated posterior to the C1C2 articulation, in the extraspinal area or in a combination of these 3 sectors.
1,2
The surgical removal of these lesions is delicate because of the intimate relationships the schwannomas develop with the V3 segment of the vertebral artery.

 A variety of lateral, far-lateral, or extreme lateral approaches have been described in order to tackle these lesions. We use a posterior midline approach that takes advantage of the predominantly extradural development of C2 schwannomas. In this technique, the main step is the debulking of the posterior articular sector of the tumor, which is easily accessible through a midline posterior approach and necessitates minimal bone removal. In most cases, removal of the homolateral posterior arch of C1 is sufficient in order to create an adequate access. These maneuvers create the necessary space for dissecting both the intradural and extraspinal sectors of the schwannoma.

 We present this technique through a case with a minimal intradural component exerting mainly a lateral compression of the spinal cord. The tumor was operated through the midline mini-invasive posterior approach with a favorable result. We demonstrate the surgical technique in video and discuss the nuances.
Multilevel Pedicle Subtraction Osteotomy for Correction of Severe Rigid Adult Spinal Deformities: A Case Series, Indications, Considerations, and Literature Review
Authors: Lau Darryl , Haddad Alexander F , Fury Marissa T , Deviren Vedat , Ames Christopher P
Published: December 2020

BACKGROUND

Rigid and ankylosed thoracolumbar spinal deformities require three-column osteotomy (3CO) to achieve adequate correction. For severe and multiregional deformities, multilevel 3CO is required but its use and outcomes are rarely reported.

OBJECTIVE

To describe the use of multilevel pedicle subtraction osteotomy (PSO) in adult spinal deformity (ASD) patients with severe, rigid, and ankylosed multiregional deformity.

METHODS

Retrospective review of 5 ASD patients who underwent multilevel PSO for the correction of severe fixed deformity and review the literature regarding the use of multilevel PSO.

RESULTS

Five patients presented with spinal imbalance secondary to regional and multiregional spinal deformities involving the thoracolumbar spine. All patients underwent a single-stage two-level noncontiguous PSO, and 2 of the patients underwent a staged third PSO to treat deformity involving a separate spinal region. Significant radiographic correction was achieved with normalization of spinal alignment and parameters. Two-level PSO was able to provide greater than 80 degrees of sagittal plane correction in both the lumbar and thoracic spine. Two patients experienced new postoperative weakness which recovered to preoperative baseline at 3 to 6 mo follow-up. At most recent follow-up, 4 of the 5 patients gained significant pain relief and had improved functionality.

CONCLUSION

Noncontiguous multilevel PSO is a formidable surgical technique. Additional risk (compared to single-level 3CO) comes in the form of greater blood loss and higher risk for postoperative weakness. Nonetheless, multilevel PSO is feasible and effective for correcting severe multiplanar and multiregional ASD, and patients gain significant benefits in increased functionality and pain relief.
Allylic Hydroxylation Activity Is a Source of Saponin Chemodiversity in the Genus Glycyrrhiza
Authors: Fanani Much Z , Sawai Satoru , Seki Hikaru , Ishimori Masato , Ohyama Kiyoshi , Fukushima Ery O , Sudo Hiroshi , Saito Kazuki , Muranaka Toshiya
Published: December 2020

Licorice (Glycyrrhiza) produces glycyrrhizin, a valuable triterpenoid saponin, which exhibits persistent sweetness and broad pharmacological activities. In the genus Glycyrrhiza, three species, Glycyrrhiza uralensis, Glycyrrhiza glabra and Glycyrrhiza inflata, produce glycyrrhizin as their main triterpenoid saponin, which has a ketone group at C-11. Other Glycyrrhiza species produce mainly oleanane-type saponins, which harbor homoannular or heteroannular diene structures that lack the C-11 ketone. Although the glycyrrhizin biosynthetic pathway has been fully elucidated, the pathway involving saponins with diene structures remains unclear. CYP88D6 from G. uralensis is a key enzyme in glycyrrhizin biosynthesis, catalyzing the sequential two-step oxidation of β-amyrin at position C-11 to produce 11-oxo-β-amyrin. In this study, we evaluated the functions of CYP88D6 homologs from the glycyrrhizin-producing species G. glabra and G. inflata and from the non-glycyrrhizin-producing species Glycyrrhiza pallidiflora and Glycyrrhiza macedonica, using yeast engineered to supply β-amyrin as a substrate. Yeast expressing CYP88D6 homologs from glycyrrhizin-producing species produced 11-oxo-β-amyrin. However, yeast expressing CYP88D6 homologs (such as CYP88D15) from the non-glycyrrhizin-producing Glycyrrhiza species accumulated oleana-9(11),12-dien-3β-ol and oleana-11,13(18)-dien-3β-ol; these diene compounds are non-enzymatic or yeast endogenous enzymatic dehydration derivatives of 11α-hydroxy-β-amyrin, a direct reaction product of CYP88D15. These results suggest that the activities of CYP88D6 homologs, particularly their ability to catalyze the second oxidation, could influence glycyrrhizin productivity and diversify the chemical structures of saponins in Glycyrrhiza plants. A synthetic biological approach to engineer CYP88D15 could enable the production of pharmacologically active saponins with diene structures, such as saikosaponins, whose biosynthetic pathways have yet to be fully characterized.
COVID-19 and force majeure clauses: an examination of arbitral tribunal’s awards
Authors: Kiraz Ş Esra , Üstün Esra Yıldız
Published: December 2020

The coronavirus (COVID-19) pandemic has taken a toll on people all across the world in various aspects. The severe consequences of this pandemic can be seen in international trade and commercial contracts. The underlying principle of contract law is that the parties are bound by the promises given under an agreement; however, events such as COVID-19 affect the parties’ performance of contractual duties. The harsh measures, such as prohibition on importation and exportation of goods or travel bans, have seriously affected the parties’ performances. In such situations, force majeure clauses, which serve as an exemption from non-performance, come into play. This article aims to reveal how COVID-19 will be assessed in terms of force majeure and the possible attitudes of arbitral tribunals towards these cases. This assessment is undertaken in light of force majeure clauses laid under the Convention on Contracts for the International Sales of Goods, the Unidroit Principles of International Commercial Contracts, and the International Chamber of Commerce’s 2020 Force Majeure Clause.
Endophthalmitis in Eyes With the Boston Type I Keratoprosthesis: Incidence, Recurrence, Risk Factors, and Outcomes
Authors: Bostan Cristina , Nayman Taylor , Szigiato Andrei-Alexandru , Morfeq Hussein , Harissi-Dagher Mona
Published: December 2020

Purpose:

To determine the incidence and recurrence of Boston type I keratoprosthesis (KPro)-associated endophthalmitis, and its microbiological profile, risk factors, and outcomes.

Methods:

This is a retrospective study of 158 consecutive KPro procedures with a median follow-up of 78.4 months. Medical charts were reviewed for ocular history, contact lens and topical antibiotic use, visual acuity, and complications. For eyes with endophthalmitis, time to infection, culture results, and recurrences were collected. Cox regression analyses identified risk factors for endophthalmitis and compared the risk for visual failure, KPro retention, and globe loss between eyes with and without endophthalmitis.

Results:

The incidence and recurrence rates of endophthalmitis were of 1.7% and 6.0% per procedure-year, respectively. First episodes occurred at a median of 18.6 months. Eight of 18 episodes (44%) were culture positive, isolating mainly Gram-positive bacteria (7 [88%]). Previous ocular burn (hazard ratio: 7.34, 95% confidence interval: 1.91–28.15), infectious keratitis (5.09, 1.70–15.22), corneal melt (4.55, 1.50–13.83), and postoperative contact lens wear (4.19, 1.17–15.04) were risk factors. Eyes with endophthalmitis did not have a higher risk for visual failure (1.74, 0.78–3.91) but were more likely to not retain the KPro (2.81, 1.15–6.88) and undergo evisceration (2.81, 1.15–6.88). All eyes lost ≥ 2 lines of vision during the endophthalmitis episode.

Conclusions:

Endophthalmitis is rare but vision and globe threatening in eyes with KPro. Given the increased associated risk, corneal melts and infectious keratitis must be promptly treated, postoperative contact lenses should be considered on a case-by-case basis, and patients with ocular burns might require more aggressive antimicrobial prophylaxis.
Risk of Airborne COVID-19 Transmission While Performing Humphrey Visual Field Testing
Authors: Jain Nikhil , Kaur Simerdip , Kopsachilis Nikolaos , Zia Rashid
Published: December 2020

Precis:

Designing and demonstrating an experiment that shows the risk of airborne transmission of COVID-19 between patients having visual fields analyzed is low.

Purpose:

The aim was to investigate the possibility of airborne transmission of COVID-19 during Humphrey visual field testing in a real-world scenario.

Methods:

A particle counter was placed within the bowl of Humphrey visual field analyzer (HFA) before and after turning on the machine to ascertain the effect of the air current produced by the ventilation system on aerosols. A second experiment was run where the particle counter was placed in the bowl and recorded particulates, in the air, as a 24-2 SITA standard was performed by a mock patient and then again immediately after the patient had moved away. We measured aerosol particle counts sized ≤0.3 μm, >0.3≤0.5 μm, >0.5≤1 μm, >1≤2.5 μm, >2.5≤5 μm, and >5≤10 μm.

Results:

Particulates of all sizes were shown to be significantly reduced within the bowl after turning the machine on, demonstrating that the air current produced by the HFA pushes air out of the bowl and it cannot stagnate. There was no significant difference in measurement of aerosol while there was a patient performing the test and immediately after they had moved away, suggesting that aerosols breathed out by the patient are not able to remain in suspension in the bowl because of the ventilation current.

Conclusion:

There is no significant difference between aerosol count in the bowl of a HFA before, during and after testing. This suggests the risk of airborne transmission of COVID-19 is low between subsequent patients. This is in keeping with manufacturer’s guidance on Humphrey visual field testing.
Recommendations for the diagnosis and management of transthyretin amyloidosis with gastrointestinal manifestations
Authors: Nakov Radislav , Suhr Ole B. , Ianiro Gianluca , Kupcinskas Juozas , Segal Jonathon P. , Dumitrascu Dan L. , Heinrich Henriette , Mikolasevic Ivana , Stojkovic-Lalosevic Milica , Barbov Ivan , Sarafov Stayko , Tournev Ivailo , Nakov Ventsislav , Wixner Jonas
Published: December 2020

Transthyretin amyloid (ATTR) amyloidosis is an adult-onset, rare systemic disorder characterized by the accumulation of misfolded fibrils in the body, including the peripheral nerves, the heart and the gastrointestinal tract. Gastrointestinal manifestations are common in hereditary (ATTRv) amyloidosis and are present even before the onset of the polyneuropathy in some cases.

Delays in diagnosis of ATTRv amyloidosis with gastrointestinal manifestations commonly occur because of fragmented knowledge among gastroenterologists and general practitioners, as well as a shortage of centers of excellence and specialists dedicated to disease management. Although the disease is becoming well-recognized in the societies of Neurology and Cardiology, it is still unknown for most gastroenterologists.

This review presents the recommendations for ATTRv amyloidosis with gastrointestinal manifestations elaborated by a working group of European gastroenterologists and neurologists, and aims to provide digestive health specialists with an overview of crucial aspects of ATTRv amyloidosis diagnosis to help facilitate rapid and accurate identification of the disease by focusing on disease presentation, misdiagnosis and management of gastrointestinal symptoms.
Sticking It Straight
Authors: Price Amanda , Greene H. Michelle , Stem Christopher T. , Titus M. Olivia
Published: December 2020

Objectives

Literature demonstrates that pediatric residents are not graduating with procedural confidence and competency. This was confirmed with our own institution's Accreditation Council for Graduate Medical Education and internal surveys. Our primary objective was to improve procedural confidence among pediatric residents with the introduction of a mandatory longitudinal pediatric procedural curriculum, including simulation in combination with online modules.

Methods

We performed a quality improvement intervention to increase resident comfort level performing Accreditation Council for Graduate Medical Education-required procedures. This study involved pediatric residents, postgraduation year (PGY) 1–3, at an academic, tertiary care hospital. Between April 2015 and June 2017, the combination of online self-directed learning modules and hands-on simulation curriculum was implemented for pediatric residents. Surveys were administered at 1-year intervals to assess self-reported comfort level on 12 procedures using a Likert scale (1 for “strongly disagree” to 5 for “strongly agree, maximum score of 60 for all procedures).

Results

Forty (63%) of 63 participant presurveys and 45 (71%) of 63 postsurveys were available for analysis. The mean comfort level for all procedures demonstrated a statistically significant increase from 32.4 to 37.1, or 12.7% (P = 0.005). By PGY level, the score increased from 24.4 to 30.9 (21%) for PGY1, 34.4 to 37.5 (8.3%) for PGY2, and 38.6 to 42.8 (9.8%) for PGY3 (P < 0.005). Overall, pediatric residents rated the simulation experience very favorably.

Conclusions

A mandatory longitudinal procedure curriculum improved procedural comfort level among pediatric residents. Iterative curriculum designs found the most productive combination to be deliberate practice within mastery learning simulation sessions with required precourse online modules.
The Effect of Health Care Professional Disruptive Behavior on Patient Care: A Systematic Review
Authors: Hicks Sophia , Stavropoulou Charitini
Published: December 2020

Background

Disruptive behavior among health care professionals can adversely affect patient care. These behaviors undermine cultures of safety, exposing patients to preventable risk. Existing evidence associates disruptive behaviors with a negative effect at the organizational level and on the health care professional, but the effect on patient care has been less well documented.

Objectives

This study aimed to identify and synthesize the empirical evidence of health care professional disruptive behaviors on the following outcome measures of patient care: clinical outcomes, patient safety, patient satisfaction, or quality of care.

Methods

A systematic literature review was conducted. Between June 6 and July 23, 2019, 6 databases were searched for published empirical studies that examined disruptive behaviors and patient outcomes. Excluded from this pool were studies that did not make associations with patient care. Studies were analyzed using thematic analysis.

Results

Twenty-five studies met the inclusion criteria and were included in the review. The prevalence and type of disruptive behavior varied, but it consistently contributed to a reduction in the quality and safety of patient care. The effects on patient care was manifested through adverse incidents, neglect of care needs, never events, and complaints. Disruptive behaviors significantly impaired the safety culture leading to reduced patient safety, evidenced by worse clinical outcomes.

Conclusions

Disruptive behaviors among health care professionals are a significant threat to patient safety and quality of care. Organizations must harness the benefits of awareness programs, policy, and interventions to generate a culture change where these behaviors are not accepted, thereby protecting patients from preventable harm.
Lack of RH2 gene expression may have influenced the HIV pandemic in sub-Saharan Africa
Authors: Nthobatsang Kadimo , Ncenga Tshimologo Lone , Mwangi-Woto Chipo , Wedu Tuelo J. , Gabatlhaolwe Tebogo , Moyo Sikhulile , Marlink Richard , Kasvosve Ishmael , Gabaitiri Lesego , Motswaledi Modisa S.
Published: December 2020

Objective:

To evaluate the association between the Rhesus system RH2-blood group expression and susceptibility to HIV infection, viral load, CD4+ cell count and rate of CD4+ decline. We also aimed to determine if a country's HIV prevalence may be predicted from its RH2 relative frequency.

Design:

Our previous studies did not find any HIV-infected RH2 homozygotes. Therefore, the current cross-sectional study analysed a larger sample to determine whether HIV-infection also occurs in homozygotes. We also conducted a cross-sectional analysis of RH2 expression in an HIV natural history cohort in Botswana. Lastly, we analysed published data from 60 countries around the world to interrogate the link between RH2 frequency and HIV prevalence.

Methods:

One thousand and six hundred anticoagulated blood samples (800 HIV-positive and 800 HIV-negative) were phenotyped for RH2 using serological methods. The proportion of RH2-positive samples was compared across categories of HIV status and odds ratios calculated. Mean viral load and CD4+ cell counts from a natural history cohort study were also compared across categories of RH2. Kaplan--Meier plots were generated for 4-year CD4+-decline to 350 cells/μl.

Results:

No RH2 homozygotes were found among HIV-positives. Moreover, RH2-negatives were 1.37 times more likely to be HIV-positive than heterozygotes (P = 0.02) and 33 times more likely than RH2 homozygotes (P = 0.01). RH2-positive patients showed significantly higher mean CD4+ cell counts (P < 0.0001), lower viral load (P = 0.024) and slower CD4+ decline (P = 0.038).

Conclusion:

RH2 is potentially a critical host genetic factor determining susceptibility of any population to HIV infection, and probably transcends most other factors in importance for HIV risk of infection.