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1.
Vet Surg ; 2024 May 29.
Article En | MEDLINE | ID: mdl-38808526

OBJECTIVE: To determine the outcome of tenoscopically guided palmar/plantar annular ligament (PAL) desmotomy to treat PAL constriction without concurrent intrathecal soft-tissue injury, notably of the digital flexor tendons and manica flexoria. STUDY DESIGN: Retrospective multicenter cohort study. ANIMALS: Sixty-five horses. METHODS: Horses from four UK equine hospitals, with digital flexor tendon sheath (DFTS) tenosynovitis, which underwent tenoscopically guided PAL desmotomy for treatment of PAL constriction between 2017 and 2022 were included. All horses had lameness isolated to the DFTS/PAL, and PAL constriction was diagnosed tenoscopically when there was difficulty maneuvering the endoscope into or through the fetlock canal. Horses with tearing of the digital flexor tendons and/or manica flexoria, or any other intrathecal pathology, were excluded. Follow up was via structured telephone questionnaire. RESULTS: Follow up (median 25 months) was available for 61 horses with cobs and ponies predominating. Forty-two returned to their previous level of work, or a higher level, postoperatively and 50 owners were satisfied with the outcome of surgery. Eleven horses returned to lower level exercise, and six were retired/euthanized as they did not regain soundness. Fifty-two horses achieved soundness (median 3 months postoperatively). CONCLUSION: Tenoscopically guided PAL desmotomy for the treatment of PAL constriction in the absence of intrathecal soft tissue injury had a good prognosis for return to previous levels of exercise in a UK horse population. CLINICAL SIGNIFICANCE: The prognosis for horses undergoing tenoscopically guided PAL desmotomy to treat PAL constriction in the absence of intrathecal injury is better than previously described. Cobs and ponies seem to be predisposed to PAL constriction in agreement with the previous literature.

2.
Curr Issues Personal Psychol ; 12(1): 11-19, 2024.
Article En | MEDLINE | ID: mdl-38756194

BACKGROUND: Personality traits are known factors that may influence levels of physical activity and other healthy lifestyle measures and behaviors that ultimately lead to health problems later in life. Participants And Procedure: The aim of this study was to examine the association between personality traits (HEXACO) and levels of physical activity and resting heart rate (RHR) - measured using Fitbits, BMI, and a self-reported whole-person healthy lifestyle score for N = 2580 college students. Data were collected and analyzed for students enrolled in a University Success type course from August 2017 to May 2021. The relationships between HEXACO personality traits and various physical activity and healthy lifestyle behaviors were analyzed by building several multiple regression models using R version 4.0.2. Results: In general, students who are extraverted were more physically active and students who are more open to experience had a higher RHR, even when controlling for gender. Females and males however had different profiles as to how personality influenced physical activity and other health-related measures. Male extraverts with high negative emotionality scores tend to be more physically active, whereas females tend to be more physically active when they were high in extroversion and conscientiousness, and low in openness to experience. BMI values were higher for female participants with high honesty-humility and low agreeableness and conscientiousness scores. Females also had a lower RHR for high honesty-humility and emotionality and low conscientiousness scores. CONCLUSIONS: Personality can influence levels of physical activity, RHR, and BMI. This is especially true of women. Being aware of one's personality and the relationship of personality traits to levels of physical activity and other measures of leading a healthy lifestyle can be beneficial in determining strategies to improve long-term health outcomes.

3.
Circ Cardiovasc Qual Outcomes ; 17(5): e010477, 2024 May.
Article En | MEDLINE | ID: mdl-38567507

BACKGROUND: Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system. METHODS: Prospective, type III hybrid effectiveness-implementation cohort study measuring performance at 21 EDs in Utah and Idaho (stroke centers [4]/nonstroke centers [17]) from January 2018 to February 2020 using a nonrandomized stepped-wedge design, monthly repeated site measures and multilevel hierarchical modeling. Each site received the implementation strategies in 1 of 6 steps providing control and intervention data. Co-primary outcomes were percentage of DTN times ≤60 minutes and median DTN time. Secondary outcomes included percentage of door-to-activation of neurological consult times ≤10 minutes and clinical effectiveness outcomes. Results were stratified between stroke and nonstroke centers. RESULTS: A total of 855 474 ED patient encounters occurred with 5325 code stroke activations (median age, 69 [IQR, 56-79] years; 51.8% female patients]. Percentage of door-to-activation times ≤10 minutes increased from 47.5% to 59.9% (adjusted odds ratio, 1.93 [95% CI, 1.40-2.67]). A total of 615 patients received tPA of ≤3 hours from symptom onset (median age, 71 [IQR, 58-80] years; 49.6% female patients). The percentage of DTN times ≤60 minutes increased from 72.5% to 86.1% (adjusted odds ratio, 3.38, [95% CI, 1.47-7.78]; stroke centers (77.4%-90.0%); nonstroke centers [59.3%-72.1%]). Median DTN time declined from 46 to 38 minutes (adjusted median difference, -9.68 [95% CI, -17.17 to -2.20]; stroke centers [41-35 minutes]; nonstroke centers [55-52 minutes]). No differences were observed in clinical effectiveness outcomes. CONCLUSIONS: A centrally led implementation strategy with local site tailoring led to faster delivery of tPA across disparate EDs in a multihospital system with no change in clinical effectiveness outcomes including rates of complication. Disparities in performance persisted between stroke and nonstroke centers.


Emergency Service, Hospital , Fibrinolytic Agents , Stroke , Thrombolytic Therapy , Time-to-Treatment , Tissue Plasminogen Activator , Humans , Female , Male , Prospective Studies , Aged , Time Factors , Fibrinolytic Agents/administration & dosage , Tissue Plasminogen Activator/administration & dosage , Middle Aged , Stroke/diagnosis , Stroke/therapy , Treatment Outcome , Quality Improvement , Utah , Guideline Adherence , Aged, 80 and over , Quality Indicators, Health Care , Healthcare Disparities , Outcome and Process Assessment, Health Care
4.
Ann Plast Surg ; 91(3): 326-330, 2023 09 01.
Article En | MEDLINE | ID: mdl-37405878

BACKGROUND: Increased representation from both women and non-White ethnicities remains a topic of discussion in plastic surgery. Speakers at academic conferences are a form of visual representation of diversity within the field. This study determined the current demographic landscape of aesthetic plastic surgery and evaluated whether underrepresented populations receive equal opportunities to be invited speakers at The Aesthetic Society meetings. METHODS: Invited speaker's names, roles, and allotted time for presentation were extracted from the 2017 to 2021 meeting programs. Perceived gender and ethnicity were determined by visual analysis of photographs, whereas parameters of academic productivity and professorship were collected from Doximity, LinkedIn, Scopus, and institutional profiles. Differences in opportunities to present and academic credentials were compared between groups. RESULTS: Of the 1447 invited speakers between 2017 and 2021, 20% (n = 294) were women and 23% (n = 316) belonged to a non-White ethnicity. Representation from women significantly increased between 2017 and 2021 (14% vs 30%, P < 0.001), whereas the proportion of non-White speakers did not (25% vs 25%, P > 0.050) despite comparable h-indexes (15.3 vs 17.2) and publications (54.9 vs 75.9) to White speakers. Non-White speakers oftentimes had more academic titles, significant in 2019 ( P < 0.020). CONCLUSIONS: The proportion of female invited speakers has increased, with room for further improvement. Representation from non-White speakers has not changed. However, significantly more non-White speakers holding assistant professor titles may indicate increased ethnicity diversity in years to come. Future efforts should focus on improving diversity in positions of leadership while promoting functions that target young minority career individuals.


Physicians, Women , Surgery, Plastic , Humans , Female , Male , Societies, Medical , Bibliometrics , Efficiency
5.
Front Mol Biosci ; 9: 1017392, 2022.
Article En | MEDLINE | ID: mdl-36406267

Over the past few decades, regulatory RNAs, such as small RNAs (sRNAs), have received increasing attention in the context of host-microbe interactions due to their diverse roles in controlling various biological processes in eukaryotes. In addition, studies have identified an increasing number of sRNAs with novel functions across a wide range of bacteria. What is not well understood is why cells regulate gene expression through post-transcriptional mechanisms rather than at the initiation of transcription. The finding of a multitude of sRNAs and their identified associated targets has allowed further investigation into the role of sRNAs in mediating gene regulation. These foundational data allow for further development of hypotheses concerning how a precise control of gene activity is accomplished through the combination of transcriptional and post-transcriptional regulation. Recently, sRNAs have been reported to participate in interkingdom communication and signalling where sRNAs originating from one kingdom are able to target or control gene expression in another kingdom. For example, small RNAs of fungal pathogens that silence plant genes and vice-versa plant sRNAs that mediate bacterial gene expression. However, there is currently a lack of evidence regarding sRNA-based inter-kingdom signalling across more than two interacting organisms. A habitat that provides an excellent opportunity to investigate interconnectivity is the plant rhizosphere, a multifaceted ecosystem where plants and associated soil microbes are known to interact. In this paper, we discuss how the interconnectivity of bacteria, fungi, and plants within the rhizosphere may be mediated by bacterial sRNAs with a particular focus on disease suppressive and non-suppressive soils. We discuss the potential roles sRNAs may play in the below-ground world and identify potential areas of future research, particularly in reference to the regulation of plant immunity genes by bacterial and fungal communities in disease-suppressive and non-disease-suppressive soils.

6.
J Soc Cardiovasc Angiogr Interv ; 1(4): 100349, 2022.
Article En | MEDLINE | ID: mdl-35992189

Background: Transcatheter aortic valve replacement (TAVR) is the treatment of choice for patients with severe aortic stenosis who are at a moderate or higher surgical risk. Stroke is a recognised and serious complication of TAVR, and it is important to identify patients at higher stroke risk. This study aims to discover if aortic valve calcium score calculated from pre-TAVR computed tomography is associated with acute stroke in TAVR patients. Methods: We conducted a retrospective, observational cohort study of 433 consecutive patients undergoing TAVR between January 2017 and December 2019 at the Hammersmith Hospital. Results: This cohort had a median age of 83 years (interquartile range, 78-87), and 52.7% were male. Fifty-two patients (12.0%) had a history of previous stroke or transient ischemic attack. Median aortic valve calcium score was 2145 (interquartile range, 1427-3247) Agatston units. Twenty-two patients had a stroke up to the time of discharge (5.1%). In a logistic regression model, aortic valve calcium score was significantly associated with acute stroke (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.01-1.53; P = .02). Acute stroke was also significantly associated with peripheral arterial disease (OR, 4.32; 95% CI, 1.65-10.65; P = .0018) and a longer procedure time (OR, 1.01; 95% CI, 1.00-1.02; P = .0006). Conclusions: Aortic valve calcium score from pre-TAVR computed tomography is an independent risk factor for acute stroke in the TAVR population. This is an additional clinical value of the pre-TAVR aortic valve calcium score and should be considered when discussing periprocedural stroke risk.

7.
BMJ Case Rep ; 15(4)2022 Apr 29.
Article En | MEDLINE | ID: mdl-35487639

Cardiac myxomas are scarce and their clinical manifestations can often be misdiagnosed or confused with other medical conditions. However, early diagnosis and surgical resection can prevent devastating complications of myxomas.We herein describe a case of a huge left atrial myxoma of a female patient in her late 30s. What makes our case unique, apart from the massive size of the myxoma, is the unusual clinical presentation with incessant cough and haemoptysis for more than 6 months. The diagnosis was made by echocardiography and cardiac MR and successful surgical resection was performed with good long-term outcome.


Heart Neoplasms , Myxoma , Echocardiography , Female , Heart Atria/diagnostic imaging , Heart Atria/surgery , Heart Neoplasms/complications , Heart Neoplasms/diagnostic imaging , Heart Neoplasms/surgery , Hemoptysis/etiology , Humans , Myxoma/complications , Myxoma/diagnostic imaging , Myxoma/surgery
8.
Ecol Lett ; 25(5): 1215-1224, 2022 May.
Article En | MEDLINE | ID: mdl-35229976

Plant biodiversity and consumers are important mediators of energy and carbon fluxes in grasslands, but their effects on within-season variation of plant biomass production are poorly understood. Here we measure variation in control of plant biomass by consumers and plant diversity throughout the growing season and their impact on plant biomass phenology. To do this, we analysed 5 years of biweekly biomass measures (NDVI) in an experiment manipulating plant species richness and three consumer groups (foliar fungi, soil fungi and arthropods). Positive plant diversity effects on biomass were greatest early in the growing season, whereas the foliar fungicide and insecticide treatments increased biomass most late in the season. Additionally, diverse plots and plots containing foliar fungi reached maximum biomass almost a month earlier than monocultures and plots treated with foliar fungicide, demonstrating the dynamic and interactive roles that biodiversity and consumers play in regulating biomass production through the growing season.


Fungicides, Industrial , Grassland , Biodiversity , Biomass , Ecosystem , Fungi/physiology , Plants , Seasons
9.
Motiv Emot ; 46(2): 226-253, 2022.
Article En | MEDLINE | ID: mdl-35034996

Social emotional abilities (i.e., specific skills), defined as the set of cognitive abilities, emotion-based knowledge, and behavioral competencies (i.e., skill levels) that facilitate adaptively employing prosocial processes and behaviors (i.e., "actions"), such as emotional regulation and sympathetic and empathetic response behaviors, is contemporarily modeled and measured as emotional intelligence. This conceptualization can be problematic, however, as the two concepts are not the same and traditional methods of measuring emotional intelligence can have limited practical utility. The social emotional ability development (SEAD) theoretical model introduced in this treatise represents a pragmatic and simplified approach to the development of social emotional ability and competency as abstracted from constructs of emotional intelligence, social intelligence, and sociocultural learning theory. Further, the SEAD model reaches beyond the individual as the unit of analysis to explore, conceptualize, differentiate, investigate, and define the hierarchal, bi-directional, and contextual nature of the dimensions of social emotional ability within close relationships. Implications for how the SEAD model can be used by researchers, practitioners, educators, individuals, families, and couples across a broad spectrum of domains and interventions are discussed.

10.
Cureus ; 13(9): e18116, 2021 Sep.
Article En | MEDLINE | ID: mdl-34692327

INTRODUCTION: Angioedema is a rare but potentially life-threatening adverse effect associated with the use of angiotensin-converting enzyme (ACE) inhibitors. Various therapies, including ecallantide, icatibant, complement-1 esterase inhibitors, and fresh frozen plasma, have been used for treatment with inconsistent results and significant adverse effects. Tranexamic acid (TXA) is used as an alternative for the treatment of hereditary angioedema and it may be an attractive option for the treatment of ACE inhibitor-induced angioedema (ACEi-AE) in the emergency department (ED). The purpose of this study was to evaluate the impact of TXA administration on rates of intubation in patients presenting to the ED with suspected ACEi-AE. METHODS: This was an institutional review board-approved, retrospective cohort study conducted at a single-site ED. All patients who received TXA for ACEi-AE in the ED between January 1, 2019 and March 31, 2021 were eligible for inclusion. The primary outcome was the proportion of patients who required intubation for suspected ACEi-AE. RESULTS: A total of 16 patients received TXA in the ED for suspected ACEi-AE during the study timeframe. Of these, two patients were intubated prior to administration of TXA. The remaining 14 patients did not require intubation following TXA administration. CONCLUSION: Administration of TXA was associated with a low rate of adverse effects and did not contribute to further morbidity when added to standard care in patients presenting to the ED with suspected ACEi-AE.

12.
Am J Emerg Med ; 50: 437-441, 2021 Dec.
Article En | MEDLINE | ID: mdl-34487951

BACKGROUND: Recombinant monoclonal antibody therapies have been utilized under emergency use authorization (EUA) for the prevention of clinical decompensation in high-risk COVID-19 positive patients for up to 10 days from symptom onset. The purpose of this study was to determine the impact of the timing of the monoclonal antibody, bamlanivimab, on clinical outcomes in high-risk COVID-19 positive patients. METHODS: This was an IRB-approved, retrospective evaluation of adult patients who received bamlanivimab per EUA criteria in the emergency department (ED). Patients were dichotomized into two groups- 3 days of symptoms or less (early) versus 4 to 10 days (late). The primary outcome was hospitalization for COVID-related illness at 28 days (or treatment failure). Secondary outcomes were COVID-related ED visits at 28 days, hospital and intensive care unit (ICU) length of stay (LOS), and in-hospital mortality at 28 days. RESULTS: A total of 839 patients were included in the analysis. There was no difference observed in COVID-related hospitalization rates within 28 days between the early and late bamlanivimab administration groups (7.5% vs. 8.2%, p = 0.71). There was no difference in COVID-related ED visits within 28 days with 13% of patients returning to the ED. CONCLUSIONS: In conclusion, there were no differences in the rates of hospitalization at 28 days when bamlanivimab was administered in the first 3 days of illness versus days 4 to 10. Future prospective studies are warranted to expand upon the characteristics of patients that may or may not benefit from monoclonal antibody therapy.


Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Neutralizing/administration & dosage , Antiviral Agents/administration & dosage , COVID-19 Drug Treatment , Patient Readmission , Adolescent , Adult , Age Factors , Aged , Body Mass Index , COVID-19/diagnosis , COVID-19/mortality , Drug Administration Schedule , Emergency Service, Hospital , Female , Hospital Mortality , Humans , Length of Stay , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome , Young Adult
13.
ACS Appl Mater Interfaces ; 13(15): 18264-18273, 2021 Apr 21.
Article En | MEDLINE | ID: mdl-33823581

In situ metal-organic chemical vapor deposition growth of SiNx passivation layers is reported on AlGaN/GaN high-electron-mobility transistors (HEMTs) without surface damage. A higher SiNx growth rate, when produced by higher SiH4 reactant gas flow, enables faster lateral coverage and coalescence of the initial SiNx islands, thereby suppressing SiH4-induced III-nitride etching. The effect of in situ SiNx passivation on the structural properties of AlGaN/GaN HEMTs has been evaluated using high-resolution X-ray diffraction. Electrical properties of the passivated HEMTs were evaluated by clover-leaf van der Pauw Hall measurements. The key findings include (a) a correlation of constituent gas chemistry with SiNx stoichiometry, (b) the degree of suppression of strain relaxation in the barrier layer that can be optimized through the SiNx stoichiometry, and (c) optimum strain relaxation by tailoring the SiNx passivation layer stoichiometry that can result in near-ideal AlGaN/AlN/GaN interfaces. The latter is expected to reduce the carrier scatterings and improve electron mobility. Under optimized conditions, low sheet resistance and high electron mobility are obtained. At 10 K, a sheet resistance of 33 Ω/sq and a mobility of 16,500 cm2/V-s are achieved. At 300 K, the sheet resistance is 336 Ω/sq and mobility is 2020 cm2/V-s with a sheet charge density of 0.78 × 1013 cm-2.

14.
Sci Rep ; 11(1): 2546, 2021 01 28.
Article En | MEDLINE | ID: mdl-33510286

Rhizoctonia solani causes damaging yield losses on most major food crops. R. solani isolates belonging to anastomosis group 8 (AG8) are soil-borne, root-infecting pathogens with a broad host range. AG8 isolates can cause disease on wheat, canola and legumes, however Arabidopsis thaliana is heretofore thought to possess non-host resistance as A. thaliana ecotypes, including the reference strain Col-0, are resistant to AG8 infection. Using a mitochondria-targeted redox sensor (mt-roGFP2) and cell death staining, we demonstrate that both AG8 and a host isolate (AG2-1) of R. solani are able to infect A. thaliana roots. Above ground tissue of A. thaliana was found to be resistant to AG8 but not AG2. Genetic analysis revealed that ethylene, jasmonate and PENETRATION2-mediated defense pathways work together to provide resistance to AG8 in the leaves which subsequently enable tolerance of root infections. Overall, we demonstrate a significant difference in defense capabilities of above and below ground tissue in providing resistance to R. solani AG8 in Arabidopsis.


Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Arabidopsis/microbiology , Cyclopentanes/metabolism , Ethylenes/metabolism , N-Glycosyl Hydrolases/metabolism , Oxylipins/metabolism , Plant Diseases/microbiology , Signal Transduction , Disease Resistance , Host-Pathogen Interactions , Immunohistochemistry , Plant Roots/metabolism , Plant Roots/microbiology , Rhizoctonia , Stress, Physiological
15.
Cureus ; 13(12): e20200, 2021 Dec.
Article En | MEDLINE | ID: mdl-35004021

An 11-year-old male presented to the pediatric emergency department with a one-day history of peri-umbilical pain with nausea, anorexia, and scant vomiting. On examination, he had moderate tenderness in the right upper quadrant with moderate guarding and rebound tenderness. Imaging showed concern for early acute appendicitis. The patient was admitted and underwent laparoscopic appendectomy. Despite the appendectomy, the patient continued to have fevers and abdominal pain. Four days after the initial presentation, the patient decompensated and was diagnosed with multisystem inflammatory syndrome. This case is interesting because the patient never met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C) prior to his decompensation. If a patient's symptoms continue or worsen despite seemingly appropriate management, the patient must be reassessed for other causes of pathology. Surgeons must have a high index of suspicion for MIS-C in patients with recent COVID-19 diagnoses, and this case demonstrates that MIS-C can present in phases and not all at once.

16.
Rev Urol ; 22(3): 93-101, 2020.
Article En | MEDLINE | ID: mdl-33239968

We evaluated the impact of safety protocols, including rapid testing and contact tracing, on coronavirus disease 2019 (COVID-19) risk exposure and transmission rates amongst healthcare workers in the outpatient care setting. Over an 11-week period, a total of 254 employees representing 38% of our total workforce had potential COVID-19 exposure and underwent voluntary COVID-19 testing. Data was stratified based on severity of risk exposure and job description. During this period, the probability of a COVID exposure being high risk decreased in Administrative (-93.0%; P < 0.01) and Clinical (-77.0%; P < 0.01) staff; simultaneously, viral transmission rates declined in Administrative (-73.4%; P = 0.03) and Clinical (-69.9%; P = 0.04) staff as well. Systematic safety protocols effectively reduce exposure risk and transmission rates in outpatient healthcare workers and should be ubiquitously adopted.

17.
Clin Pract Cases Emerg Med ; 4(3): 295-298, 2020 Aug.
Article En | MEDLINE | ID: mdl-32926670

INTRODUCTION: Frequent thrombotic complications have been reported in patients with severe coronavirus disease 2019 (COVID-19) infection. The risk in patients with mild disease is unknown. CASE REPORT: We report a case series of three individuals recently diagnosed with COVID-19, who presented to the emergency department with chest pain and were found to have pulmonary emboli. The patients had mild symptoms, no vital sign abnormalities, and were negative according to the pulmonary embolism rule-out criteria. CONCLUSION: This suggests that patients with active or suspected COVID-19 should be considered at elevated risk for pulmonary embolism when presenting with chest pain, even without common risk factors for pulmonary embolism.

18.
ACS Appl Mater Interfaces ; 12(35): 39397-39404, 2020 Sep 02.
Article En | MEDLINE | ID: mdl-32805930

Growth of single-crystalline GaN on polycrystalline diamond is reported for the first time. The structure was achieved using a combined process including selective diamond growth on GaN/Si wafers using hot filament chemical vapor deposition (CVD) and epitaxial lateral overgrowth of GaN on the window region between then above the diamond stripes via metal organic CVD. Optimization of the growth was performed by varying the ammonia to trimethylgallium mole ratio (V/III), chamber pressure, and temperature in the range of 8000-1330, 40-200 Torr, and 975-1030 °C, respectively. A lower pressure, higher V/III ratio, higher temperature, and GaN window mask openings along [11̅00] resulted in enhanced lateral growth of GaN. Complete lateral coverage and coalescence of GaN were achieved over a [11̅00]-oriented 5 µm-wide GaN window between 5 µm diamond stripes when using V/III = 7880, P = 100 Torr, and T = 1030 °C. The crystalline quality of overgrown GaN was confirmed using cross-sectional scanning electron microscopy, high-resolution X-ray diffraction, micro-Raman spectroscopy, transmission electron microscopy, and selective-area electron diffraction.

19.
ACS Omega ; 5(31): 19827-19833, 2020 Aug 11.
Article En | MEDLINE | ID: mdl-32803078

Covalent cross-linking of biomolecules can be useful in pursuit of tissue targeting or dual targeting of two receptors on cell surfaces for avidity effects. Long linkers (>10 kDa) can be advantageous for such purposes, and poly(ethylene glycol) (PEG) linkers are most commonly used due to the high aqueous solubility of PEG and its relative inertness toward biological targets. However, PEG is non-biodegradable, and available PEG linkers longer than 5 kDa are heterogeneous (polydisperse), which means that conjugates based on such materials will be mixtures. We describe here recombinant linkers of distinct lengths, which can be expressed in yeast, which are polar, and which carry orthogonal reactivity at each end of the linker, thus allowing chemoselective cross-linking of proteins. A conjugate between insulin and either of the two trypsin inhibitor peptides/proteins exemplifies the technology, using a GQAP-based linker of molecular weight of 17 848, having one amine at the N-terminal, and one Cys, at the C-terminal. Notably, yeast-based expression systems typically give products with mixed disulfides when expressing proteins that are equipped with one unpaired Cys, namely, mixed disulfides with glutathione, free Cys amino acid, and/or a protein homodimer. To obtain a homogeneous linker, we worked out conditions for transforming the linker with mixed disulfides into a linker with a homogeneous disulfide, using excess 4-mercaptophenylacetic acid. Subsequently, the N-terminal amine of the linker was transformed into an azide, and the C-terminal Cys disulfide was reduced to a free thiol and reacted with halo-acetyl insulin. The N-terminal azide was finally conjugated to either of the two types of alkyne-containing trypsin inhibitor peptides/proteins. This reaction sequence allowed the cross-linked proteins to carry internal disulfides, as no reduction step was needed after protein conjugations. The insulin-trypsin inhibitor conjugates were shown to be stabilized toward enzymatic digestions and to have partially retained binding to the insulin receptor.

20.
Hum Vaccin Immunother ; 16(9): 2219-2221, 2020 09 01.
Article En | MEDLINE | ID: mdl-32735161

In the Northern Hemisphere, the persistence or reemergence of coronavirus circulation into the 2020-2021 influenza season threatens to overwhelm health-care resources and systems and increase mortality and morbidity. Data from Australia show that stay-at-home policies have reduced both influenza and coronavirus cases early in the season, thus "flattening the curve." However, influenza vaccination is critical to ensure the reduction in co-infection. Several policies, such as vaccination strategies to accommodate physical distancing measures, change population recommendations, and timing and location of vaccination have been implemented to increase influenza vaccine uptake during the pandemic. This commentary explores those policies.


Coronavirus Infections/epidemiology , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Mass Vaccination , Pneumonia, Viral/epidemiology , Australia/epidemiology , Betacoronavirus , COVID-19 , Communication , Health Planning , Humans , Influenza Vaccines/supply & distribution , Influenza, Human/epidemiology , Mass Vaccination/methods , Mass Vaccination/organization & administration , Pandemics , SARS-CoV-2 , Seasons
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