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Malaria, Zika virus, West Nile virus, Dengue fever, and Lyme disease are common causes of morbidity and mortality around the world. While arthropod bites may cause local inflammation and discomfort, a greater concern is the potential to develop deadly systemic infection. The use of insect repellents (IR) to prevent systemic infections constitutes a fundamental public health effort. Cost-effectiveness, availability, and high-efficacy against arthropod vectors are key characteristics of an ideal IR. Currently, numerous IRs are available on the market, with DEET (N,N-diethyl-3-methylbenzamide) being the most widely used. DEET has an excellent safety profile and remarkable protection against mosquitoes and various other arthropods. Other EPA-registered IR ingredients (permethrin, picaridin, IR3535, oil of lemon eucalyptus, oil of citronella, catnip oil, and 2-undecanone) are alternative IRs of great interest due to some having efficacies comparable to that of DEET. These alternative IRs possess low toxicity and favorable customer experiences in utilization (e.g., cosmetically pleasant, naturally occurring). This review summarizes currently available EPA-registered IRs: the origins, mechanisms of action, side effect profiles, and available formulations will be discussed. This review will enable the clinician to select the best IR option to meet patients' needs and provide the greatest protection from arthropod bites and sequelae.

This article presents current relevant data on the serogroups and antimicrobial susceptibility of Salmonella strains isolated in the southern provinces of the Socialist Republic of Vietnam. There were examined 189 Salmonella strains isolated from: human feces in acute diarrhea (86 strains); and pork samples (103 strains). Serological O-group identification was performed by slide agglutination with O- and H-antisera and multiplex PCR to detect H phase-1 and phase-2. Antimicrobial susceptibility testing was performed by using the disk-diffusion method according to the EUCAST (version 2019) recommendations. Strains isolated from humans predominantly belonged to O4 group (69.8%). The percentage of other serogroups varied from 1.2% (rare group O16) to 11.6% (O9). About a half of strains (44.7%) isolated from pork samples turned out to belong to the О3,10 serogroup (vs 7.0% of strains from humans). Serogroups О7, О4 and О8 were less frequent (22.3%, 14.6% and 13.6%, respectively). Single strains belonged to serogroups О9, О13, and О18. Regardless of the isolation source, about 80% of Salmonella strains were resistant to antibiotics from different antimicrobial groups (besides carbapenems): 67.0% were resistant to tetracycline; about half were resistant to pefloxacin, ampicillin and chloramphenicol (54.0%, 47.1%, 46.6%); and up to 40% were resistant to trimethoprim/sulfamethoxazole and nalidixic acid. The proportion of strains resistant to ceftriaxone and gentamycin was markedly higher in those of human vs pork origin: 12.8% vs 1.0% and 30.2 vs 1.9%, respectively. Moreover, 62.8% and 43.7% strains of human and pork origin, respectively, showed multidrug resistance (to 3 and more antimicrobial groups). In addition, simultaneous resistance to 6 antimicrobial groups was detected much more frequently in Salmonella strains isolated from humans vs pork samples (15.1% vs 1.0%, respectively). Multidrug resistance (MDR) was observed in strains of different serovars, predominantly S. Typhimurium (36.4%). The predominant MDR (30.3%) phenotype (AMP, TE, QN, C, SXT) was revealed in serovars of S. Typhimurium, S. Bredeney, S. Corvallis, S. Give, S. London, S. Rissen, and S. Meleagridis. Thus, Salmonella strains isolated in the southern Vietnamese provinces featured resistance to fluoroquinolones and cephalosporins. Taking into account simultaneous loss of susceptibility to old antimicrobials (ampicillin, chloramphenicol, trimethoprim/sulfamethoxazole), it crucially restricts the list of effective medicines to treat complicated salmonellosis cases.

IntroductionClinical tools are neither standardized nor ubiquitous to monitor volumetric or morphological changes in the periorbital region and ocular adnexa due to pathology such as oculofacial trauma, thyroid eye disease, and the natural aging process. We have developed a low-cost, three dimensionally printedPHotogrammetry forAutomatedCarE(PHACE) system to evaluate three-dimensional (3D) measurements of periocular and adnexal tissue.MethodsThe PHACE system uses two Google Pixel 3 smartphones attached to automatic rotating platforms to image a subject’s face through a cutout board patterned with registration marks. Photographs of faces were taken from many perspectives by the cameras placed on the rotating platform. Faces were imaged with and without 3D printed hemispheric phantom lesions (black domes) affixed on the forehead above the brow. Images were rendered into 3D models in Metashape (Agisoft, St. Petersburg, Russia) and then processed and analyzed in CloudCompare (CC) and Autodesk’s Meshmixer. The 3D printed hemispheres affixed to the face were then quantified within Meshmixer and compared to their known volumes. Finally, we compared digital exophthalmometry measurements with results from a standard Hertel exophthalmometer in a subject with and without an orbital prosthesis.ResultsQuantification of 3D printed phantom volumes using optimized stereophotogrammetry demonstrated a 2.5% error for a 244μL phantom, and 7.6% error for a 27.5μL phantom. Digital exophthalmometry measurements differed by 0.72mm from a standard exophthalmometer.ConclusionWe demonstrated an optimized workflow using our custom apparatus to analyze and quantify oculofacial volumetric and dimensions changes with a resolution of 244μL. This apparatus is a low-cost tool that can be used in clinical settings to objectively monitor volumetric and morphological changes in periorbital anatomy.

SARS-CoV-2 Omicron variants emerged in 2022 with >30 novel amino acid mutations in the spike protein alone. While most studies focus on the impact of receptor binding domain changes, mutations in the C-terminal of S1 (CTS1), adjacent to the furin cleavage site, have largely been ignored. In this study, we examined three Omicron mutations in CTS1: H655Y, N679K, and P681H. Generating a SARS-CoV-2 triple mutant (YKH), we found that the mutant increased spike processing, consistent with prior reports for H655Y and P681H individually. Next, we generated a single N679K mutant, finding reduced viral replicationin vitroand less diseasein vivo. Mechanistically, the N679K mutant had reduced spike protein in purified virions compared to wild-type; spike protein decreases were further exacerbated in infected cell lysates. Importantly, exogenous spike expression also revealed that N679K reduced overall spike protein yield independent of infection. Together, the data show that N679K is a loss-of-function mutation reducing overall spike levels during omicron infection, which may have important implications for disease severity, immunity, and vaccine efficacy.One Sentence SummarySpike substitution N679K attenuates SARS-CoV-2 Omicron variants by decreasing spike protein and has potential implications for immunity and vaccine efficacy.

PurposeTo compare a custom Photogrammetry for Anatomical CarE (PHACE) system with other cost-effective 3-dimensional (3D) facial scanning systems to objectively characterize morphology and volume of periorbital and adnexal anatomy.MethodsThe imaging systems evaluated include the low-cost custom PHACE system and commercial software product for the iPhone called Scandy Pro (iScandy) application (Scandy, USA), and the mid-priced Einscan Pro 2X (Shining3D Technologies, China) device and Array of Reconstructed Cameras 7 (ARC7) facial scanner (Bellus3D, USA). Imaging was performed on a manikin facemask and humans with various Fitzpatrick scores. Scanner attributes were assessed using mesh density, reproducibility, surface deviation, and emulation of 3D printed phantom lesions affixed above the superciliary arch (brow line).ResultsThe Einscan served as a reference for lower cost imaging systems because it qualitatively and quantitatively renders facial morphology with the highest mesh density, reproducibility (0.13 ± 0.10 mm), and volume recapitulation (approximately 2% of 33.5 μL). Compared to the Einscan, the PHACE system (0.35 ± 0.03 mm, 0.33 ± 0.16 mm) demonstrated non-inferior mean accuracy and reproducibility root mean square (RMS) compared to the iScandy (0.42 ± 0.13 mm, 0.58 ± 0.09 mm), and significantly more expensive ARC7 (0.42 ± 0.03 mm, 0.26 ± 0.09 mm). Similarly, the PHACE system showed non-inferior volumetric modeling when rendering a 124 μL phantom lesion compared to the iScandy and more costly ARC7 (mean percent difference from the Einscan: 4.68 ± 3.73%, 9.09 ± 0.94%, and 21.99 ± 17.91% respectively).ConclusionsThe affordable PHACE system accurately measures periorbital soft tissue as well as other established mid-cost facial scanning systems. Additionally, the portability, affordability, and adaptability of PHACE can facilitate widespread adoption of 3D facial anthropometric technology as an objective measurement tool in ophthalmology.PrecisWe demonstrate a custom system for facial photogrammetry (Photogrammetry for Anatomical CarE -PHACE) to produce 3D renderings of facial volume and morphology which compares with more expensive alternative 3D scanning technologies.

Background Small vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries. Case presentation We report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group. Conclusion We present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.

Understanding the molecular basis of innate immune evasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important consideration for designing the next wave of therapeutics. Here, we investigate the role of the nonstructural protein 16 (NSP16) of SARS-CoV-2 in infection and pathogenesis. NSP16, a ribonucleoside 2’-O methyltransferase (MTase), catalyzes the transfer of a methyl group to mRNA as part of the capping process. Based on observations with other CoVs, we hypothesized that NSP16 2’-O MTase function protects SARS-CoV-2 from cap-sensing host restriction. Therefore, we engineered SARS-CoV-2 with a mutation that disrupts a conserved residue in the active site of NSP16. We subsequently show that this mutant is attenuated both in vitro and in vivo, using a hamster model of SARS-CoV-2 infection. Mechanistically, we confirm that the NSP16 mutant is more sensitive to type I interferon (IFN-I) in vitro. Furthermore, silencing IFIT1 or IFIT3, IFN-stimulated genes that sense a lack of 2’-O methylation, partially restores fitness to the NSP16 mutant. Finally, we demonstrate that sinefungin, a methyltransferase inhibitor that binds the catalytic site of NSP16, sensitizes wild-type SARS-CoV-2 to IFN-I treatment. Overall, our findings highlight the importance of SARS-CoV-2 NSP16 in evading host innate immunity and suggest a possible target for future antiviral therapies.ImportanceSimilar to other coronaviruses, disruption of SARS-CoV-2 NSP16 function attenuates viral replication in a type I interferon-dependent manner. In vivo, our results show reduced disease and viral replication at late times in the hamster lung, but an earlier titer deficit for the NSP16 mutant (dNSP16) in the upper airway. In addition, our results confirm a role for IFIT1, but also demonstrate the necessity of IFIT3 in mediating dNSP16 attenuation. Finally, we show that targeting NSP16 activity with a 2’-O methyltransferase inhibitor in combination with type I interferon offers a novel avenue for antiviral development.

The standard neurology clinical experience in medical school focuses primarily on bedside patient encounters; however, the limitations of the clinical environment due to the current COVID-19 pandemic have accelerated the need for virtual curriculum development. To provide guidance to Neurology clerkship directors during this unprecedented time, the American Academy of Neurology (AAN) Undergraduate Education Subcommittee (UES) formed a workgroup to develop an outline for a virtual curriculum, provide recommendations, and describe models of integrating virtual curricula into the neurology clerkship. In this overview, we discuss different methods of virtual instruction, hybrid models of clerkship training and the challenges to its implementation, professionalism issues, and modification of feedback and assessment techniques specific to the virtual learning environment. We also offer suggestions for implementation of a hybrid virtual curriculum into the neurology clerkship. The virtual curriculum is intended to supplement the core neurology in-person clinical experience and should not be used for shortening or replacing the required neurology clinical clerkship.

The motion of domain walls is a crucial factor in piezoelectric properties and is usually related to the irreversible and hysteretic behaviors. Herein, we report on the investigation of inverse and transverse piezoelectric coefficients of capacitor-based and microcantilever-based Pb(Zr0.52Ti0.48)O3 films with a change in the DC bias and the AC applied voltage. A large inverse piezoelectric strain coefficient of about 350 p.m./V, and a low strain hysteresis of about 7.1%, are achieved in the film capacitors under a low applied voltage of 2 V (20 kV/cm) which can benefit the actuators for motion control in high-precision systems. The field-dependences of the transverse piezoelectric coefficients, obtained from four-point bending and microcantilever displacement, are in good agreement with each other. The results also reveal that the irreversible domain-wall motion is attributed to the nonlinearity in the field-dependent piezoelectric strain and cantilever displacement.

Group B enteroviruses, including coxsackievirus B3 (CVB3), can persistently infect cardiac tissue and cause dilated cardiomyopathy. Persistence is linked to 5’ terminal deletions of viral genomic RNAs that have been detected together with minor populations of full-length genomes in human infections. In this study, we explored the functions and interactions of the different viral RNA forms found in persistently-infected patients and their putative role(s) in pathogenesis. Since enterovirus cardiac pathogenesis is linked to the viral proteinase 2A, we investigated the effect of different terminal genomic RNA deletions on 2A activity. We discovered that 5’ terminal deletions in CVB3 genomic RNAs decreased the proteinase activity of 2A but could not abrogate it. Using newly-generated viral reporters encoding nano-luciferase, we found that 5’ terminal deletions resulted in decreased levels of viral protein and RNA synthesis in singly-transfected cardiomyocyte cultures. Unexpectedly, when full-length and terminally deleted forms were co-transfected into cardiomyocytes, a cooperative interaction was observed, leading to increased viral RNA and protein production. However, when viral infections were carried out in cells harboring 5’ terminally deleted CVB3 RNAs, a decrease in infectious particle production was observed. Our results provide a possible explanation for the necessity of full-length viral genomes during persistent infection, as they would stimulate efficient viral replication compared to that of the deleted genomes alone. To avoid high levels of viral particle production that would trigger cellular immune activation and host cell death, the terminally deleted RNA forms act to limit the production of viral particles, possibly as trans-dominant inhibitors.ImportanceEnteroviruses like coxsackievirus B3 are able to initiate acute infections of cardiac tissue and, in some cases, to establish a long-term persistent infection that can lead to serious disease sequelae, including dilated cardiomyopathy. Previous studies have demonstrated the presence of 5’ terminally-deleted forms of enterovirus RNAs in heart tissues derived from patients with dilated cardiomyopathy. These deleted RNAs are found in association with very low levels of full-length enterovirus genomic RNAs, an interaction that may facilitate continued persistence while limiting virus particle production. Even in the absence of detectable infectious virus particle production, these deleted viral RNA forms express viral proteinases at levels capable of causing viral pathology. Our studies provide mechanistic insights into how full length and deleted forms of enterovirus RNA cooperate to stimulate viral protein and RNA synthesis without stimulating infectious viral particle production. They also highlight the importance of targeting enteroviral proteinases to inhibit viral replication while at the same time limiting the long-term pathologies they trigger.

Background Penicillin allergy is the most commonly reported drug allergy in the pediatric population. However, most reports do not represent true IgE-mediated or late-onset severe hypersensitivity reactions. False allergy labels can lead to unnecessarily broad and/or non-first line antibiotic utilization, the development of antibiotic resistance, adverse drug side effects, and have implications for the use of antimicrobials in adulthood. In an effort to decrease inappropriate allergy labeling, we have implemented a multipronged approach for the evaluation of documented beta-lactam allergies in pediatric patients and potential “de-labeling” of inaccurate or outdated allergies. Methods We performed retrospective chart review of pediatric patients (0-18 years) with a documented beta-lactam allergy who were seen in clinic at a single tertiary medical center between 2014-2019. Prospective telephone screening then began to further characterize reaction symptoms and timing to determine patient candidacy for allergy testing (Fig. 1). Inpatient screening began in April 2022. If amenable to referral, eligible patients are then referred for outpatient Allergy and Immunology (A/I) assessment. Figure 1Process map for pediatric beta-lactam allergy risk-stratifying algorithm. Results A total of 1160 eligible pediatric patients were identified, and initial results are summarized (Fig. 2). Of those screened, 48 (57%) patients were referred. 5 (6%) patients were de-labeled via screening, of which 3 had received and tolerated repeat dosing. 11 (33%) patients have attended allergy appointments; 4 (36%) were tested and all were de-labeled (ages 6-11 years) from mostly non-IgE-mediated reactions. Additionally, 16 patients have upcoming appointments, and recruitment efforts are ongoing to include increased inpatient recruitment. Conclusion Use of an inpatient and outpatient algorithm can help identify pediatric patients less likely to have a true or persistent beta-lactam allergy (delayed-onset mild symptoms, or IgE-mediated reaction >5 years ago) and who could benefit from formal allergy testing to potentially remove their allergy label. In the future, algorithm implementation within the electronic medical record may assist clinicians in thorough documentation of beta-lactam allergies and expeditious referral for allergy testing when appropriate. Disclosures All Authors: No reported disclosures.

BACKGROUND The health effects of fine particulate matter (PM2.5) may be worse at higher temperatures. OBJECTIVE To investigate temperature's effect on PM2.5-mortality/morbidity associations in Lima, Peru. METHODS Time-series regressions relating PM2.5 and temperature to mortality and emergency room (ER) visits during 2010-2016. Daily PM2.5 levels (assigned to 40 Lima districts) and daily maximum temperature (Lima-wide) were estimated based on ground monitors, remote sensing, and modeling. We analyzed all-cause, cardiovascular (ICD codes I00-I99), and respiratory (ICD codes J00-J99) mortality, and cardiovascular and respiratory causes for ER visits. RESULTS The average PM2.5 concentration was 20.9 µg/m3 (IQR 17.5-23.5). The mean daily maximum temperature was 23.8 °C (IQR 20.8-26.9). PM2.5's effect on all-cause, respiratory, and circulatory disease mortality was significantly (p