Racial/ethnic disparities in exposure to e-cigarette advertising among U.S. youth.

OBJECTIVES: This study aims to assess exposure to e-cigarette advertising across multiple marketing channels among U.S. youth and to examine whether racial/ethnic disparities exist in exposure to e-cigarette advertisements. STUDY DESIGN: This is a cross-sectional study. METHODS: Cross-sectional data were drawn from a longitudinal survey of participants recruited from two nationally representative panels (NORC's AmeriSpeak® and GfK's KnowledgePanel). A total of 2043 youth aged 13-17 completed the initial 2018 survey, and 2013 youth completed the follow-up survey in 2019 (including a replenishment sample of 690 youth). Outcome variables were self-reported e-cigarette advertisement exposure in the past three months through various sources, such as television, point of sale, and online/social media. Generalized estimating equation models were used to estimate the adjusted odds ratios (AOR) of the association between racial/ethnic identity and e-cigarette advertisement exposure. RESULTS: The prevalence of reported exposure to e-cigarette advertisements through any channel was 79.8% (95% CI: 77.1-82.2) in 2018 and 74.9% (95% CI: 72.5-77.1) in 2019, respectively. Point of sale was the most common source of e-cigarette advertisement exposure in both years. Non-Hispanic Black and non-Hispanic Asian youth were more likely to report exposure to e-cigarette advertisements through television (AOR = 2.07, 95% CI: 1.44-2.99 and AOR = 2.11, 95% CI: 1.17-3.82, respectively) and online/social media (AOR = 1.61; 95% CI: 1.11-2.33 and AOR = 1.99, 95% CI: 1.10-3.59, respectively) channels compared with non-Hispanic White youth. CONCLUSIONS: A substantial proportion of U.S. youth reported exposure to e-cigarette advertising through a variety of marketing channels. Significant racial/ethnic disparities existed, with non-Hispanic Black and Asian youth reporting more marketing exposure than their non-Hispanic White counterparts.

Health Economic Impact of a Multicenter Quality-of-Care Initiative for Reducing Unplanned Healthcare Utilization Among Patients With Inflammatory Bowel Disease.

INTRODUCTION: A multicenter adult inflammatory bowel disease learning health system (IBD Qorus) implemented clinical care process changes for reducing unplanned emergency department visits and hospitalizations using a Breakthrough Series Collaborative approach. METHODS: Using Markov decision models, we determined the health economic impact of participating in the Collaborative from the third-party payer perspective. RESULTS: Across all 23 sites, participation in the Collaborative was associated with lower annual costs by an average of $2,528 ± $233 per patient when compared with the baseline period. DISCUSSION: Implementing clinical care process changes using a Collaborative approach was associated with overall cost savings. Future work should examine which specific interventions are most effective and whether such cost savings are sustainable.

A qualitative inquiry into patients' perspectives on individualized priorities for treatment outcomes in inflammatory bowel diseases.

PURPOSE: Patients with inflammatory bowel diseases (IBD) experience a variety of symptoms and limitations due to their condition. While many outcome measures are available to assess IBD symptom level and disease activity, individual patients' preferences are usually not accounted for. Individualized outcome measures allow individual patients to select and weigh outcomes based on their relative importance, and have been developed in other medical disciplines. In this study, we explored IBD patients' perspectives on different strategies to prioritize IBD-specific health outcomes. METHODS: Existing individualized measures were modified for relevance to IBD patients. We performed six focus groups, in which patients were asked to rate and weigh these measures in a series of exercises and to discuss the pros and cons of five different prioritization methods (Likert scale, ranking, selecting outcomes, distribute points, and using a rotating disk) using a semi-structured approach. A thematic analysis revealed key themes in the data. RESULTS: Patients' thoughts could be grouped into four key themes with 2-4 subthemes each: (1) prioritizing outcomes; (2) differences between methods; (3) outcomes to include; and (4) practical use. Overall, it was challenging for many patients to prioritize outcomes. Among the different prioritization methods, the rotating disk was perceived as the most intuitive. Patients anticipated that this visualization would also help them communicate with their physician. CONCLUSION: In a series of focus groups, a visual rotating disk was found to be an intuitive and holistic way to elicit the relative importance of different outcomes for individual IBD patients.

Chikungunya virus infection prevalence in Africa: a contemporaneous systematic review and meta-analysis.

OBJECTIVES: The (re)emergence of chikungunya virus (CHIKV) in Africa requires better knowledge on the epidemiology of CHIKV infection in the continent for efficient public health strategies. We aimed to describe the epidemiology of CHIKV infection in Africa, a neglected tropical disease (NTD). STUDY DESIGN: This was a systematic review with meta-analysis of studies reporting CHIKV infection prevalence. We searched Embase, PubMed, Africa Journal Online and Global Index Medicus to identify observational studies published from January 2000 to September 2017. METHODS: We used a random-effect model to pool the prevalence of CHIKV infections reported with their 95% confidence interval (CI). Heterogeneity was assessed via the Chi-squared test on Cochran's Q statistic. Review registration is in PROSPERO CRD42017080395. RESULTS: A total of 39 studies (37,881 participants; 18 countries) were included. No study was reported from Southern Africa. Thirty-two (82.0%), seven (18.0%) and no studies had low, moderate and high risk of bias, respectively. Outside outbreak periods, the pooled immunoglobulin M (IgM) and immunoglobulin G (IgG) seroprevalence was 9.7% (95% CI 3.0-19.6; 16 studies) and 16.4% (95% CI 9.1-25.2; 23 studies), respectively. The IgM seroprevalence was lower in Northern Africa, and there was no difference for IgG prevalence across regions in Africa. The IgM and IgG seroprevalences were not different between acute and non-acute febrile participants. The seroprevalence was not associated with GPS coordinates (latitude, longitude and altitude). CONCLUSIONS: Although considered a NTD, we find high prevalence of CHIKV infection in Africa. As such, chikungunya fever should deserve more attention from healthcare providers, researchers, policymakers and stakeholders from many sectors.

Interaction of 5-hydroxy-l-tryptophan and negative dietary cation-anion difference on calcium homeostasis in multiparous peripartum dairy cows.

Hypocalcemia affects almost 50% of all dairy cows. Our laboratory has previously demonstrated that infusions of the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP) increase circulating calcium concentrations in the Holstein transition cow. It is unknown whether feeding a negative dietary cation-anion difference (DCAD) diet alters the relationship between 5-HTP and hypocalcemia. The main objective of this study was to determine whether feeding a negative DCAD (-DCAD) diet before calving in conjunction with 5-HTP treatment could further diminish the magnitude of hypocalcemia at the time of calving. We used a randomized complete block design with a 2 × 2 factorial arrangement. Thirty-one multiparous Holstein cows were fed either a positive (+13 mEq/100 g) or negative (-13 mEq/100 g) DCAD diet 21 d before parturition and were intravenously infused daily with saline or 5-HTP (1 mg/kg) starting 7 d before the estimated date of parturition. Cows were blocked by parity and were randomly assigned to 1 of 4 treatment groups: positive DCAD plus saline, positive DCAD plus 5-HTP, negative DCAD plus saline, and negative DCAD plus 5-HTP, resulting in n = 8 per group. Total calcium (tCa), ionized calcium (iCa), and feed intake were recorded. The iCa was elevated prepartum in the -DCAD/5-HTP group compared with the other treatment groups as well as on d 0 and 1 postpartum. Although differences in tCa were not significant across the pre- or postpartum periods, tCa was numerically higher on d 0 and significantly higher on d 1 in -DCAD/5-HTP cows compared with all other groups. Prepartum the -DCAD/5-HTP treatment group ate less than the other treatment groups; however, postpartum dry matter intake differences were not significant. These findings demonstrate that feeding a -DCAD diet in conjunction with 5-HTP prepartum can increase postpartum circulating iCa concentrations and therefore diminish the magnitude of hypocalcemia at the time of parturition.

Temporarily decreasing progesterone after timed artificial insemination decreased expression of interferon-tau stimulated gene 15 (ISG15) in blood leukocytes, serum pregnancy-specific protein B concentrations, and embryo size in lactating Holstein cows.

Our objective was to evaluate the effects of temporarily decreasing progesterone (P4) after timed artificial insemination (TAI) on embryonic growth in dairy cows. Lactating Holstein cows (n = 80) were submitted to a Double-Ovsynch protocol for first TAI and were assigned randomly to receive 12.5 mg of PGF2α 5 d after the last GnRH treatment (LowP4) or remain untreated (control). Blood samples were collected thrice weekly from 5 to 29 d after TAI for all cows and from 32 to 67 d for pregnant cows, and were analyzed for P4 and pregnancy-specific protein B concentrations. Expression of interferon-tau stimulated gene 15 (ISG15) was assessed in blood leukocyte mRNA 18 and 20 d after TAI. Pregnancy diagnosis was performed weekly using ultrasound from 32 to 67 d after TAI, and embryonic crown-rump length was measured 32, 39, and 46 d after TAI. Data were analyzed by ANOVA and logistic regression using the MIXED and GLIMMIX procedures of SAS. The LowP4 cows had less P4 than control cows from 6 to 11 d after TAI; however, pregnancy outcomes 32 d after TAI and pregnancy loss from 32 to 67 d after TAI did not differ between treatments. Control cows diagnosed pregnant 32 d after TAI had greater expression of ISG15 20 d after TAI than LowP4 cows diagnosed pregnant 32 d after TAI, and pregnant control cows had greater pregnancy-specific protein B concentrations from 25 to 67 d after TAI than pregnant LowP4 cows. Embryo size did not differ between treatments 32 and 39 d after TAI, but control cows had larger embryos 46 d after TAI. In conclusion, temporarily decreasing P4 after TAI decreased embryonic growth during early pregnancy in lactating Holstein cows but did not affect pregnancies per artificial insemination or pregnancy loss.

Autocrine-paracrine regulation of the mammary gland.

The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the autocrine-paracrine regulation of the mammary gland, with an examination of both foundational work and the progress made within the last 10 to 20 yr of research.

Evaluation of eluents for the recovery of an enveloped virus from hands by whole-hand sampling.

AIMS: The objective of this research is to evaluate eluents for recovery of an enveloped bacteriophage, Φ6, using whole-hand sampling. METHODS AND RESULTS: Virus was applied to the hands of volunteers and sampled by the glove juice method with 1.5% beef extract (BE), phosphate buffered saline (PBS), 0.01 and 0.1% Tween 80, tryptic soy broth (TSB) and 9% NaCl. Each volunteer underwent multiple rounds application and hand sampling. Mean log10 virus loss across trials was 2.6 for BE, 2.8 for PBS, 2.4 for TSB, 3.8 for NaCl, 3.0 for 0.1% Tween 80, and 2.9 for 0.01% Tween 80. Within each volunteer, there was a decline in viral loss from the first to last trial. CONCLUSIONS: These eluents can recover Φ6 from hands with approx. 2-3 log10 loss, comparable to recoveries previously reported for influenza. Protein and detergent-based eluents may have similar recoveries, but recovery may still vary across repeated sampling. SIGNIFICANCE AND IMPACT OF THE STUDY: Based on current work, protein-based eluents such as beef extract can maximize recovery of enveloped viruses during hand sampling, providing methods for evaluating survival and transmission of enveloped viruses on hands. Further exploration is needed of the effect of repeated sampling on recovery from whole-hand sampling.

Genome-scale phylogeny of the alphavirus genus suggests a marine origin.

The genus Alphavirus comprises a diverse group of viruses, including some that cause severe disease. Using full-length sequences of all known alphaviruses, we produced a robust and comprehensive phylogeny of the Alphavirus genus, presenting a more complete evolutionary history of these viruses compared to previous studies based on partial sequences. Our phylogeny suggests the origin of the alphaviruses occurred in the southern oceans and spread equally through the Old and New World. Since lice appear to be involved in aquatic alphavirus transmission, it is possible that we are missing a louse-borne branch of the alphaviruses. Complete genome sequencing of all members of the genus also revealed conserved residues forming the structural basis of the E1 and E2 protein dimers.

Concordance and Discordance Between Patient-reported Remission, Patient-reported Outcomes, and Physician Global Assessment.

BACKGROUND: Although validated patient-reported outcome (PRO) measurements can categorize patients with inflammatory bowel disease (IBD) into clinical remission or active disease, patients may have different definitions of remission. The purpose of this study was to compare patient-defined remission to remission based on PRO measures and physician global assessment (PGA) and to understand the clinical and demographic factors associated with disagreements. METHODS: We retrospectively analyzed 3257 de-identified surveys from 2004 IBD patients who consented to participate in the Crohn's and Colitis Foundation's IBD Qorus Learning Health System between September 2019 and February 2021. We used logistic regression models with generalized estimating equations to analyze the clinical and demographic factors (eg, age, disease duration, health confidence) associated with discordance between patient-defined remission (yes/no) and PRO-defined remission for ulcerative colitis (UC; PRO2: stool frequency, rectal bleeding) and Crohn's disease (CD; PRO-3: average number of liquid stools, abdominal pain, well-being). RESULTS: Among patients with UC, overall concordance was 79% between patient self-report and PRO2-defined remission and 49% between patient self-report and PGA-defined remission. Among patients with CD, overall concordance was 69% between patient self-report and PRO3-defined remission and 54% between patient self-report and PGA-defined remission. Patients in PRO-defined remission were more likely to report active disease if they had IBD <5 years and low health confidence. Patients with PRO-defined active disease were more likely to report remission if they were not using prednisone and had high health confidence. CONCLUSION: Discordance exists between how remission is defined by patients, PRO measures, and PGA.

Discordance between patients' self-reported remission and remission defined based on patient-reported outcomes was observed in 31% of Crohn's disease visits and 21% of ulcerative colitis visits. Disease duration and health confidence were associated with discordance.

One Health epidemic preparedness: Biosafety quality improvement training in Nigeria.

Background and Aim: One of the key components of the One Health approach to epidemic preparedness is raising awareness and increasing the knowledge of emerging infectious diseases, prevention, and risk reduction. However, related research can involve significant risks to biosafety and biosecurity. For this purpose, we organized a multidisciplinary biosafety hands-on workshop to inform and increase the knowledge of infectious diseases and risk mitigation. This study aimed to describe the process and outcome of a hands-on biosafety training program using a One Health approach across a multidisciplinary and multi-specialty group in Nigeria. Materials and Methods: A face-to-face hands-on training for 48 participants was organized by the West African Center for Emerging Infectious Diseases (WAC-EID) at the Jos University Teaching Hospital, serving as a lead institution for the Nigeria project site. Topics covered included (1) an overview of the WAC-EID research; (2) overview of infection prevention and control; (3) safety in animal handling and restraint, sample collection, and processing; (4) safety in field studies including rodent, bird and bat handling; (5) safety practices in the collection of mosquito and other arthropod vectors; (6) personal protective equipment training (disinfection, donning and doffing); and (7) safety in sample collection, labeling, and transportation. The program was executed using a mixed method of slide presentations, practical hands-on sessions, and video demonstrations. Pre- and post-course evaluation assessments and evaluation measures were used to assess training. Results: A total of 48 trainees participated in this training, with 12 (25%), 16 (33.3%), 14 (29.2%), 6 (12.5%) categorized as ornithology, entomology, mammalogy, and clinical interest groups, respectively. The pass rate for the pre-test was 29.4%, while for the post-test, it was 57.1%, or a 28% improvement. 88.6% of the trainees rated the training as relevant to them. Conclusion: Didactic and hands-on biosafety training is relevant in this era of zoonotic epidemics and pandemic preparedness. During this training program, there was a clear demonstration of knowledge transfer that can change the current practices of participants and improve the safety of infectious diseases research.

Analysis of intrahost variation in Venezuelan equine encephalitis virus reveals repeated deletions in the 6-kilodalton protein gene.

RNA viruses exist as a spectrum of mutants that is generated and maintained during replication within the host. Consensus sequencing overlooks minority genotypes present in the viral sample that may impact the population's phenotype. In-depth sequencing of an original field isolate of subtype IE Venezuelan equine encephalitis virus (VEEV) demonstrated the presence of multiple deletions within the 6,000-molecular-weight (6K) protein gene. Using in vitro and in vivo experiments, similar deletions were generated in an additional VEEV strain originating from an infectious cDNA clone. Time course experiments demonstrated that the deletions are produced during acute infection although not until 24 h postinfection. Molecular clones containing some of these deletions were generated, and although the larger deletions appear to be noninfectious, viruses with the smaller deletions were viable and formed small plaques. Serial passages provided no evidence that these deletion mutants function as defective interfering particles. Furthermore, since wild-type infections generally occur at a low multiplicity of infection, it is unlikely that these deletions are propagated in natural transmission cycles. However, they could affect pathogenesis at later stages of infection. Because they are ubiquitously generated both in vivo and in vitro, further investigation is warranted to understand the generation of these deletions and their significance for disease.

Health Confidence Is Associated With Disease Outcomes and Health Care Utilization in Inflammatory Bowel Disease: A Nationwide Cross-sectional Study.

BACKGROUND: We aimed to examine the associations between health confidence (one's belief on the degree of control on their health and disease), inflammatory bowel disease (IBD) outcomes, and health care utilization among adults with IBD. METHODS: In total, 17,205 surveys were analyzed from a cross-sectional sample of IBD patients at 23 gastroenterology (GI) practices participating in the Crohn's and Colitis Foundations' IBD Qorus Learning Health System. We used bivariate analyses and multivariable logistic regression to examine associations between health confidence and disease activity, opioid use, glucocorticoid use, well-being, and health care utilization. We used receiver operating curve analysis to determine a clinically relevant cutoff for health confidence (0-10 Likert scale). RESULTS: Health confidence was highly correlated with patients' well-being, symptomatic disease activity, opioid use, and glucocorticoid use (all P < .0001). Health confidence scores <8 had 69% sensitivity for emergency department (ED) visits and 66% for hospitalizations. In patients with inactive disease, patients with low health confidence (<8) were 10 times more likely to call/message the GI office >4 times/month (adjusted odds ratio [aOR], 10.3; 95% CI, 6.1-17.3; P < .0001), 3-4 times more likely to have an IBD-related ED visit (aOR, 4.0; 95% CI, 2.9, 5.4. P < .0001), or hospitalization (aOR, 3.0, 95% CI, 2.1, 4.1, P < .0001) compared with patients with high health confidence (≥8). CONCLUSIONS: In a large, national sample of adults with IBD, there were strong associations between patients' health confidence and multiple disease outcome measures. Health confidence scores <8 on a 0-10 Likert scale may be clinically useful to screen for patients who are at risk for ED visits and hospitalizations.

BiTE secretion from in situ-programmed myeloid cells results in tumor-retained pharmacology.

Bispecific T-Cell Engagers (BiTEs) are effective at inducing remission in hematologic cancers, but their use in solid tumors has been challenging due to their extreme potency and on-target, off-tumor toxicities in healthy tissue. Their deployment against solid tumors is further complicated by insufficient drug penetration, a hostile tumor microenvironment, and immune escape. To address these challenges, we developed targeted nanocarriers that can deliver in vitro-transcribed mRNA encoding BiTEs to host myeloid cells - a cell type that is actively recruited into the tumor microenvironment. We demonstrate in an immunocompetent mouse model of ovarian cancer, that infusion of these nanoparticles directs BiTE expression to tumor sites, which reshapes the microenvironment from suppressive to permissive and triggers disease regression without systemic toxicity. In contrast, conventional injections of recombinant BiTE protein at doses required to achieve anti-tumor activity, induced systemic inflammatory responses and severe tissue damage in all treated animals. Implemented in the clinic, this in situ gene therapy could enable physicians - with a single therapeutic - to safely target tumor antigen that would otherwise not be druggable due to the risks of on-target toxicity and, at the same time, reset the tumor milieu to boost key mediators of antitumor immune responses.

Development of Balanced Whole System Value Measures for Inflammatory Bowel Disease Care in the IBD Qorus Collaborative Using a Modified Delphi Process.

BACKGROUND: The IBD Qorus Collaborative aims to reduce variation and increase the value of care for the adult inflammatory bowel disease (IBD) community. To evaluate the success of the collaborative, we aimed to develop a balanced set of outcome measures that reflect a multistakeholder view of value in IBD care. To achieve this, we used the Clinical Value Compass framework and engaged a mixed-stakeholder group to conduct a modified Delphi process. The end result was a 10-measure set to assess the value of IBD care. METHOD: The modified Delphi process included 3 iterative rounds of blinded voting and interactive webinar-style discussion. We recruited 18 participants for the Delphi panel, including clinicians, researchers, patients, Crohn's & Colitis Foundation staff, and payers. Participants first identified constructs to measure, then identified the tools to measure those constructs. A literature review and environmental scan of current measures in 4 domains were performed, and relevant measures were proposed for discussion and voting in each domain. Throughout the process, participants were invited to contribute additional measures. CONCLUSION: The modified Delphi process led to selection of 10 value measures across 4 domains: (1) patient experience; (2) functional status; (3) clinical status; and (4) health care costs and utilization. We have successfully completed a 3-stage modified Delphi process to develop a balanced set of value measures for adult IBD care. The value measure set expands upon prior efforts that have established quality measures for IBD care by adding cost and experience of care elements. This work positions IBD Qorus to better assess, study, improve, and demonstrate value at individual, system, and population levels and will inform and empower related research, improvement, and implementation efforts.

Life after lower extremity amputation in diabetics.

UNLABELLED: Lower limb amputees typically have reduced mobility which affects their ability to perform daily tasks and to successfully reintegrate into community life. A major goal of rehabilitation for amputees is to improve quality of life (QOL). This study therefore focussed on QOL and functional independence for persons with lower limb amputations secondary to diabetes. OBJECTIVE: To determine the QOL and functional independence of lower limb diabetic amputees one to three years post amputation, using variables such as age, gender and amputation level. METHOD: A total of 87 participants were selected from the 2006-2009 physiotherapy records at the St Ann's Bay Hospital. These participants completed the World Health Organization Quality of Life Scale (WHO QOL-BREF) and the Functional Independence Measure (FIM). Data were analysed using SPSS (version 12) and the mean values for QOL and functional independence were calculated. Relationships between the variables: age, gender and level of amputation with QOL and functional independence were analysed using descriptive and inferential statistical techniques. RESULTS: Among the 35 males and 52 females participating in the study, below knee amputees recorded higher scores for QOL (p < 0.05) and functional independence (p < 0.0001) compared to the above knee amputees. The result also showed that females had a significantly higher average score than males among the four domains for QOL. Similar results were obtained from the FIM where women again had significantly higher scores than males (p < 0.0001). The majority of females across the age groups reported average to high QOL (p < 0.0001) compared to the males. A positive correlation (r = 0.5999, p < 0.0001) was found between functional independence and quality of life of all participants. CONCLUSION: The results showed that below knee amputees functioned better than those with above knee amputations and that females were more likely to cope and function with the disability than males.

SARS-CoV-2 decontamination of skin with disinfectants active during and after application.

BACKGROUND: The coronavirus disease 2019 pandemic has resulted in high levels of exposure of medical workers to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Hand decontamination is one of the actions recommended to reduce the risk of infection. AIM: Two disinfectants - BIAKOS antimicrobial skin and wound cleanser (AWC) and AWC2 (Sanara MedTech, Fort Worth, TX, USA) - were tested to determine whether they can inactivate SARS-CoV-2 upon contact or as a coating applied before contact with the virus. METHODS: The ability of AWC and AWC2 to inactivate SARS-CoV-2 was tested in liquid and dried form on plastic surfaces and porcine skin. FINDINGS: AWC and AWC2 were effective in reducing the infectious titre of SARS-CoV-2 in liquid form during application and in dried form 4 h after application. Virus on skin was reduced up to 2 log10-fold and 3.5 log10-fold after treatment with AWC and AWC2, respectively. CONCLUSION: Application of AWC and AWC2 to skin reduces the level of SARS-CoV-2 and the risk of infection.

Chronic elevation of plasma cortisol causes differential expression of predominating glucocorticoid in plasma, saliva, fecal, and wool matrices in sheep.

There is increasing interest in using nonblood measures of glucocorticoids to assess the physiological response to chronic stress conditions. In sheep, cortisol has been measured in various matrices including saliva, feces, and wool, but comprehensive studies of the relationship between plasma concentrations of cortisol and concentrations in these nonblood matrices are lacking. Therefore, we tested the hypothesis that administration of cortisol to sheep would result in elevated concentrations of cortisol in blood, saliva, feces, and wool. Merino ewes were administered with saline or 2 mg/kg BW/d hydrocortisone acetate (HCA) by intramuscular (i.m.) injection for 28 d. This treatment was imposed to mimic circulating cortisol concentrations experienced during periods of chronic stress. Cortisol and cortisone were directly measured in plasma, saliva, and wool before, during, and after treatment with saline or HCA. A 14-d pre-treatment and a 14-d post-treatment period were used to measure time taken for glucocorticoid concentrations in each of the matrices to return to baseline levels. Cortisol was also measured in feces before, during, and after treatment. Wool growth was also measured. Before treatment, there was no difference in the concentration of cortisol or cortisone in plasma, saliva, feces, or wool in animals treated with saline or HCA. In contrast, treatment with HCA increased (P < 0.05) concentrations of both cortisol and cortisone in plasma, saliva, and wool and of cortisol in feces. In plasma, cortisol concentrations were higher than cortisone (P < 0.05), whereas saliva cortisol and cortisone concentrations did not differ significantly. In wool, the concentration of cortisone was about 19-fold higher than that of cortisol during treatment and post-treatment periods. Treatment with HCA inhibited wool growth. These results demonstrate that an increase in glucocorticoids in the blood of sheep is reflected in increases in saliva (after 7 d of treatment), feces (21 d), and wool (14 d). Therefore, measures of glucocorticoids in these matrices may provide a measure of activation of the adrenal glands over time in sheep, thereby providing a retrospective indicator of chronic stress. With respect to wool, it appears that cortisol is predominantly metabolized to cortisone in the skin or wool follicle and is stored as cortisone. Therefore wool cortisone may also provide an important measure in quantifiying chronic stress in sheep.

Chondrocytic and pharmacokinetic properties of Phlpp inhibitors.

Objective: The pleckstrin homology domain leucine-rich repeat protein phosphatases (Phlpp1/2) were recently identified as potential therapeutic targets for cartilage regeneration in osteoarthritic joints. Phlpp inhibitors NSC 117079 and NSC 45586 increase chondrocyte proliferation and matrix production, but the pharmacodynamics and pharmacokinetics of these compounds are not known. Design: Chondrocytic effects of Phlpp inhibitors, NSC 117079 and NSC 45586, were measured by western blotting of Phlpp substrates, glycosaminoglycan (GAG) assays, and transcriptomic assays. Liquid chromatography/mass spectroscopy assays were established to measure NSC 117079 and NSC 45586 in vitro and in vivo. The effects of NSC 117079 and NSC 45586 on articular cartilage structure in vivo after intra-articular injection were determined by histology. Results: The Phlpp inhibitors NSC 117079 and NSC 45586 were highly stable in vitro and stimulated GAG, Sox9, proteoglycan 4 and collagen 2 production in maturing but not more differentiated chondrocytes in vitro. Both molecules reduced Phlpp1/2 levels and suppressed matrix degradation to functionally extend their inhibitory effect on these phosphatases. In vivo, NSC 117079 was eliminated from the bloodstream within 4 â€‹h after intravenous injection, while NSC 45586 was eliminated in 8 â€‹h and had a higher volume distribution. Both molecules increased articular cartilage area on lateral and medial tibial plateaus and femoral condyles by 15% in C57Bl/6 mice between four and five weeks of age. Conclusion: These data advance our understanding of how Phlpp inhibitors promote and preserve cartilage formation and provide a basis for understanding their safety and activity in vivo.