Steric Repulsion Forces Contributed by PEGylation of Interleukin-1 Receptor Antagonist Reduce Gelation and Aggregation at the Silicone Oil-Water Interface

Silicone oil, used as a lubricating coating in pharmaceutical containers, has been implicated as a cause of therapeutic protein aggregation. After adsorbing to silicone oil-water interfaces, proteins may form interfacial gels, which can be transported into solution as insoluble aggregates if the interfaces are perturbed. Mechanical interfacial perturbation of both monomeric recombinant human interleukin-1 receptor antagonist (rhIL-1ra) and PEGylated rhIL-1ra (PEG rhIL-1ra) in siliconized syringes resulted in losses of soluble monomeric protein. However, the loss of rhIL-1ra was twice that for PEG rhIL-1ra; even though in solution, PEG rhIL-1ra had a lower ΔG_unf and exhibited a more perturbed tertiary structure at the interface. Net protein-protein interactions in solution for rhIL-1ra were attractive but increased steric repulsion because of PEGylation led to net repulsive interactions for PEG rhIL-1ra. Attractive interactions for rhIL-1ra were associated with increases in intermolecular β-sheet content at the interface, whereas no intermolecular β-sheet structures were observed for adsorbed PEG rhIL-1ra. rhIL-1ra formed interfacial gels that were 5 times stronger than those formed by PEG rhIL-1ra. Thus, the steric repulsion contributed by the PEGylation resulted in decreased interfacial gelation and in the reduction of aggregation, in spite of the destabilizing effects of PEGylation on the protein’s conformational stability.     

Transmission of Grapevine Red Blotch Virus by Spissistilus festinus [Say, 1830] (Hemiptera: Membracidae) between Free-Living Vines and Vitis vinifera ‘Cabernet Franc’

Grapevine red blotch disease emerged within the past decade, disrupting North American vine stock production and vineyard profitability. Our understanding of how grapevine red blotch virus (GRBV), the causal agent of the disease, interacts with its Vitis hosts and insect vector, Spissistilus festinus, is limited. Here, we studied the capabilities of S. festinus to transmit GRBV from and to free-living vines, identified as first-generation hybrids of V. californica and V. vinifera ‘Sauvignon blanc’ (Vcal hybrids), and to and from V. vinifera ‘Cabernet franc’ (Vvin Cf) vines. The transmission rate of GRBV was high from infected Vcal hybrid vines to healthy Vcal hybrid vines (77%, 10 of 13) and from infected Vvin Cf vines to healthy Vcal hybrid vines (100%, 3 of 3). In contrast, the transmission rate of GRBV was low from infected Vcal hybrid vines to healthy Vvin Cf vines (15%, 2 of 13), and from infected Vvin Cf vines to healthy Vvin Cf vines (19%, 5 of 27). No association was found between transmission rates and GRBV titer in donor vines used in transmission assays, but the virus titer was higher in the recipient leaves of Vcal hybrid vines compared with recipient leaves of Vvin Cf vines. The transmission of GRBV from infected Vcal hybrid vines was also determined to be trans-stadial. Altogether, our findings revealed that free-living vines can be a source for the GRBV inoculum that is transmissible by S. festinus to other free-living vines and a wine grape cultivar, illustrating the interconnected roles of the two virus hosts in riparian areas and commercial vineyards, respectively, for virus spread. These new insights into red blotch disease epidemiology will inform the implementation of disease management strategies.     

Perceptions of familiar and unfamiliar ear- and eyewitnesses

A witness’s relationship with a defendant is frequently discussed in criminal trials, yet investigations into perceptions of this relationship have been scarce. Further, an exploration of witnesses other than eyewitnesses has been missing from the literature. The present studies explored how witness type and familiarity with a defendant impact the perceived credibility of a witness. In Study 1, a familiar earwitness was perceived as more credible and honest than a stranger earwitness but the same was not found for eyewitnesses. Results from Study 2 suggest an eyewitness was seen as more credible and believable than an earwitness, and that a familiar witness was seen as more reliable than a stranger, but not than an acquaintance. There was no impact of familiarity or witness type on legal decisions. The present studies indicate that the prior definitions of familiarity might only capture a restricted range of potentially familiar relations.Key words: Earwitness, eyewitness, familiarity, perceived credibility, witness type

Particularly when there is little or no physical evidence, witness evidence can become a central element in building a criminal case. As a result, the perceived credibility and reliability of witnesses become crucial in both investigative and prosecutorial decisions, as well as potentially in determining the outcome of a trial. Witnesses are assessed not only at trial by triers of fact, but also at various stages through the legal process. Witnesses might be assessed by police officers and lawyers, such as when they decide whether enough evidence is available to prosecute or when they determine which witness will be put on the stand. As such, understanding witnesses’ perceived credibility is essential in understanding how a range of legal decisions are made. There are several factors that may impact perceptions of witness credibility; the present focus is on the familiarity between a witness and a defendant. Many crimes are committed by perpetrators that are unknown to a witness, but many perpetrators are also familiar (Bruer et al., 2017). In either case, identifying who committed the crime is critical to establish guilt. Accurately recalling the details of the crime may be of little use if the perpetrator is not identified. Witness recognition of a perpetrator can be based on visual exposure during the commission of a crime (i.e. eyewitness), as is most commonly studied in the witness literature (e.g. Fitzgerald & Price, 2015). However, witnesses without visual exposure during the crime might be able to identify another aspect of the perpetrator, such as their voice (i.e. earwitness). It is important to note that there may be different types of voice identification such as layperson earwitnesses, police earwitnesses and experts using the methods such as voice spectrography (see Morrison et al., 2016). Here, we focus on layperson earwitnesses.Although explored substantially less frequently in the literature, earwitnesses can, and do, play an important part in the identification of perpetrators and can contribute to similar miscarriages of justice to those for eyewitnesses. For example, in the United States, at least 17 cases of wrongful convictions were due, in part, to earwitness evidence (Sherrin, 2015). As the (mis)use of voice identification can have dire consequences, it is important to explore the nature of these identifications and the impact they might have on the perceived credibility of a witness and subsequent legal decisions.Identification accuracyIt is generally accepted that identifying a familiar face is easier than identifying a face of a stranger; a familiar face is processed in a fundamentally different way than an unfamiliar face (see Johnston & Edmonds, 2009, for review). Although the identification of familiar faces may be more resistant to factors that can negatively impact identification (e.g. different angles; Bruce, 1982), identification of a familiar face is not necessarily accurate. For example, a change in lighting between initial viewing of a face and identification can have a similar negative impact on familiar and unfamiliar faces, dropping accurate identification rates significantly (Hill & Bruce, 1996). Such results demonstrate that prior exposure is not the only factor that drives the influence of familiarity on identification.Like eyewitnesses who have previously seen the perpetrator, the familiarity of a voice to an earwitness may increase their identification accuracy (Abberton & Fourcin, 1978). Yarmey et al. (2001) asked participants to listen to potentially familiar voices and make a decision about whether or not they knew who the voice belonged to. Voices that were moderately to highly familiar were identified more accurately than voices that were low-familiar or unfamiliar voices. Additionally, unfamiliar voices were mistakenly identified more than any other level of familiarity, where a mistaken identification was defined as identifying the voice as familiar but attributing it to the wrong individual. Of course, in identifications of familiar voices, false identifications still happen, even for those who have known each other for a long period of time. Yarmey et al. (2001) found that, although fewer incorrect identifications were made with familiar voices, false identification rates still ranged from 5% (high familiar) to 23% (low familiar). Similarly, Foulkes and Barron (2000) asked participants to identify a single voice of a close friend with whom they were currently living and found that 10% of identifications were mistaken. False identification rates for less familiar individuals are even more substantial (Yarmey et al., 2001). Thus, although witness–perpetrator familiarity is a contributor to witness credibility, current research suggests that it should not be the sole indicator in assessing identification accuracy.Perceptions of witnessesAlthough there has been some research examining the effect of witness–perpetrator familiarity on the perceived credibility of eyewitnesses, a gap in knowledge exists regarding perceptions of familiar and unfamiliar earwitnesses. When looking to the eyewitness credibility literature, most explorations of familiarity have used criteria related to number or duration of previous visual exposures. Lindsay et al. (1986) found no impact of familiarity (defined as 5-s exposure, 30-min exposure or 30-min exposure with conversation) on mock juror verdict decisions. Similarly, Pozzulo et al. (2014) manipulated number of prior exposures to a defendant (never seen before, 3 prior exposures, 6 prior exposures) and found no effect on verdict decisions, guilt ratings or perceptions of the eyewitness. When a witness had either zero or eight prior exposures, however, Sheahan et al. (2018) found a significant effect of familiarity on verdict decisions and guilt ratings. These findings suggest that a larger number of exposures may be required to classify a defendant as familiar enough to a witness to make a difference in identification accuracy.Vallano et al. (2018) also examined the accused–witness relationship on the perceived credibility of a witness, defining familiarity in terms of both number of recent exposures and the recency of a previous exposure (i.e. saw a few hours ago, a few months ago). Vallano et al. (2019) found that both the number and recency of prior exposures had a small impact on participants’ ratings of the defendant’s likelihood of guilt, with a familiar witness resulting in higher guilty ratings than a stranger. However, an increase from somewhat familiar (i.e. seen once before, months before) to highly familiar (i.e. seen many times before, hours before) did not influence guilt ratings, demonstrating no benefit of a more familiar witness. Pica et al. (2018) further explored familiarity of a defendant, defining familiarity in terms of the relationship between the witness and defendant. Participants were presented with a witness who had a familiar relationship (i.e. a former teacher), an acquaintance relationship (i.e. a former lunch monitor) or a stranger relationship with the defendant. When a defendant was familiar to the witness, participants assigned the defendant a significantly higher guilt rating than when the witness was a stranger. These inconsistent findings in the familiarity required to increase perceptions of witness credibility, and contribute to higher judgments of guilt, demonstrate a need to investigate further conceptualizations of familiarity.Given that the prior research exploring witness–perpetrator familiarity has focused on eyewitness identifications, it is also important to examine whether and how the observed patterns will extend to other forms of identification, like earwitnesses. In one of very few studies examining the perceived credibility of different witness types, McAllister et al. (1993) presented participants with three types of line-up (audio, visual and audio-visual), along with a control condition. No differences in verdict decisions were found across line-up conditions, suggesting that participants viewed these varied forms of identification similarly.Present studiesAlthough eye- and earwitnesses may be more accurate when identifying a familiar perpetrator than an unfamiliar perpetrator, familiarity does necessarily result in accurate identifications, and what comprises a familiar relationship is unclear. The extant literature indicates that potential triers of fact may perceive witnesses who are familiar with the perpetrator as more credible, which results in an increased perception of guilt, at least for eyewitness identifications. However, these findings have been somewhat inconsistent. Additional research is required to more clearly define what makes a witness familiar enough with the suspect to benefit from the enhanced credibility evaluations associated with identifying a familiar person. Additionally, the understanding of familiarity must be extended to other types of witnesses, like earwitnesses, who may also be tasked with identifying a familiar perpetrator, and who may fall victim to the same biases as those observed in eyewitness identifications. The present studies aim to increase the body of knowledge on familiar ear- and eyewitnesses, with a particular focus on perceived credibility.Limitations and future directionsIf triers of fact have only a witness’s testimony to rely upon in making their decision, any helpful or hindering factor in perceived credibility can be critical in informing verdict decisions. As witnesses and defendants may often know each other (Bruer et al., 2017), it is important to understand how this relationship can impact how a witness is evaluated. Our findings suggest that potential triers of fact may have a high threshold for the level of familiarity that they believe will increase the accuracy of an eyewitness identification, although this threshold may be lower for earwitnesses.Additionally, we observed impacts of the independent variables on the perceived credibility of the witness, but not on legal decisions. As noted above, the lack of legal decision effects may be due to the nature of the case presented; participants may not have found the prosecution’s case strong enough to convict, no matter the strength of the witness’s testimony, as evidenced by the high number of acquittals in Study 1. The argument presented in the mock trial for Study 2 was designed to help strengthen the case against the defendant to help counteract this possible limitation, but a similar pattern emerged. Future research should explore the effect of additional evidence or alternative motivations on verdict decisions in a similar context.Further, all participants were asked to make credibility decisions, followed by legal decisions. This order was intended to mirror a real-world scenario in which triers of fact make implicit credibility judgements during a trial before rendering a verdict. Also, by asking for credibility ratings first, it allowed us to explore the influence of familiarity on credibility independent of verdict decisions – which may better reflect how other legal decision-makers perceive witnesses (i.e. law enforcement). Of course, to disentangle differential influences on perceptions of credibility and legal processes, one must counterbalance order of these questions. Given the patterns observed in the present studies, we believe such a disentangling would be worthy of investigation in future research. Further, investigating the potential for perceived credibility to act as a moderator or mediator for legal decisions may be an exciting next step to take.The lack of significant differences in credibility between familiar and unfamiliar witnesses, except when interacting with witness type, indicates that the relationship presented here was not strong enough to increase eyewitness credibility. After observing the lack of familiarity effect on eyewitnesses in Study 1, the familiarity of the case and materials were strengthened in Study 2. Yet, similar results were found. Further research exploring different levels of earwitness familiarity, manipulating factors described earlier that could refine understanding of familiarity, is required to understand the impact on perceived credibility. The present research is an important early step in this important investigation.     

Neutrophil extracellular traps and thrombosis in COVID-19

Journal of Thrombosis and Thrombolysis - Studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events....     

Rapid review of virus risk communication interventions: Directions for COVID-19

ObjectiveIn response to COVID-19, we conducted a rapid review of risk communication interventions to mitigate risk from viruses to determine if such interventions are efficacious.MethodsWe searched for risk communication interventions in four databases: Medline, PsycInfo, the ProQuest Coronavirus Research Database, and CENTRAL. The search produced 1572 articles. Thirty-one articles were included in the final review.ResultsResults showed risk communication interventions can produce cognitive and behavior changes around viruses. Results were more consistently positive for interventions focused on HIV/AIDS as compared to influenza. There was no consistent best intervention approach when comparing peer health, audio/visual, and intensive multi-media interventions. Tailoring risk communication toward a target population, in comparison to not tailoring, was related to better outcomes.ConclusionThe results suggest that risk communication interventions can be efficacious at reducing risk from viruses. They also highlight the complexity of risk communication interventions. Additional research is needed to understand the mechanisms that lead risk communication to reduce risk from viruses.Practical valueResults support risk communication interventions to reduce risk from viruses.     

Comparison of the whole slide imaging and conventional light microscopy in the grading of oral epithelial dysplasia: a multi-institutional study

Background Whole Slide Imaging (WSI) is an alternative method to light microscopy (LM). However, few studies have compared the diagnostic agreement between WSI and LM, especially to grade oral epithelial dysplasia (OED). The purpose of this study was to evaluate the variability in grading OED by the World Health Organization grading system, using WSI and conventional LM, and to investigate whether the access to clinical information, and psychologic or physical states of the pathologists could interfere with the diagnosis. Material and Methods eleven experienced pathologists from seven Brazilian universities independently evaluated twenty-five OED cases. The analyses were performed in duplicate for each method, with an interval of at least 30 days, and the time consumed in each analysis was measured. Physical and psychologic states were evaluated by blood pressure levels, heart rate and two questionnaires: State-Trait Anxiety Inventory and Perceived Stress Scale. Clinical information was provided after the second evaluation using WSI and the pathologist could change their diagnostic decision or not. Results LM showed a higher inter-examiner agreement (k=0.53) than WSI (k=0.45) and a smaller time consumed by the pathologists (mean of 65.53 seconds compared to 91.02 seconds in WSI). In the first analysis using conventional microscopy, there was a positive correlation between kappa values and anxiety (r=0.47, p=0.02), and stress (r=0.64, p<0.01), and an inverse correlation with heart rate (r=-0.48, p=0.02). In the digital analysis, there was also a positive correlation between kappa values and anxiety (r=0.75, p<0.001). After clinical information was given, there was a slight change in 11.3% of the cases, and a great discrepancy in 1.1% of the cases, mainly increasing the OED grade. Conclusions both microscopy systems had similar results, although LM had slightly higher kappa values, and WSI was more time consuming. Key words:Pathology, microscopy, diagnosis, leukoplakia oral, anxiety.     

Oral pigmented lesions: Clinicopathologic features and review of the literature

Diagnosis of pigmented lesions of the oral cavity and perioral tissues is challenging. Even though epidemiology may be of some help in orientating the clinician and even though some lesions may confidently be diagnosed on clinical grounds alone, the definitive diagnosis usually requires histopathologic evaluation. Oral pigmentation can be physiological or pathological, and exogenous or endogenous. Color, location, distribution, and duration as well as drugs use, family history, and change in pattern are important for the differential diagnosis. Dark or black pigmented lesions can be focal, multifocal or diffuse macules, including entities such as racial pigmentation, melanotic macule, melanocytic nevus, blue nevus, smoker’s melanosis, oral melanoacanthoma, pigmentation by foreign bodies or induced by drugs, Peutz-Jeghers syndrome, Addison´s disease and oral melanoma. The aim of this review is to present the main oral black lesions contributing to better approach of the patients. Key words:Pigmentation, melanin, oral, diagnosis, management.