Cooperation of immune regulators Tollip and surfactant protein A inhibits influenza A virus infection in mice.

BACKGROUND: Influenza A virus (IAV) infection is a significant risk factor for respiratory diseases, but the host defense mechanisms against IAV remain to be defined. Immune regulators such as surfactant protein A (SP-A) and Toll-interacting protein (Tollip) have been shown to be involved in IAV infection, but whether SP-A and Tollip cooperate in more effective host defense against IAV infection has not been investigated. METHODS: Wild-type (WT), Tollip knockout (KO), SP-A KO, and Tollip/SP-A double KO (dKO) mice were infected with IAV for four days. Lung macrophages were isolated for bulk RNA sequencing. Precision-cut lung slices (PCLS) from WT and dKO mice were pre-treated with SP-A and then infected with IAV for 48 h. RESULTS: Viral load was significantly increased in bronchoalveolar lavage (BAL) fluid of dKO mice compared to all other strains of mice. dKO mice had significantly less recruitment of neutrophils into the lung compared to Tollip KO mice. SP-A treatment of PCLS enhanced expression of TNF and reduced viral load in dKO mouse lung tissue. Pathway analysis of bulk RNA sequencing data suggests that macrophages from IAV-infected dKO mice reduced expression of genes involved in neutrophil recruitment, IL-17 signaling, and Toll-like receptor signaling. CONCLUSIONS: Our data suggests that both Tollip and SP-A are essential for the lung to exert more effective innate defense against IAV infection.

Alcalase-Based Chickpea (Cicer arietinum L.) Protein Hydrolysates Efficiently Reduce Systolic Blood Pressure in Spontaneously Hypertensive Rats.

Studies on antihypertensive chickpea protein hydrolysates have rarely performed in vivo evaluations, limiting the entry of such hydrolysates into functional food development and clinical trials. Thus, our aim was to optimize the hydrolysis conditions to produce an alcalase-based chickpea hydrolysate with a hypotensive effect in vivo at convenient oral doses. The hydrolysis reaction time, temperature, and alcalase/substrate concentration were optimized using a response surface analysis (RSA). ACE-I inhibition was the response variable. The optimized hydrolysis conditions were time = 0.5 h, temperature = 40 °C, and E/S concentration = 0.254 (U/g). The IC50 of the optimized hydrolysate (OCPH) was 0.358 mg/mL. Five hydrolysates from the RSA worksheet (one of them obtained after 5 min of hydrolysis (CPH15)) had an ACE-I inhibitory potential similar to that of OCPH (p > 0.05). At 50 mg/kg doses, OCPH and CPH15 promoted a clinically relevant hypotensive effect in spontaneously hypertensive rats, up to -47.35 mmHg and -28.95 mmHg, respectively (p < 0.05 vs. negative control). Furthermore, the hypotensive effect was sustained for at least 7 h post-supplementation. Overall, OCPH and CPH15 are promising ingredients for functional food development and as test materials for clinical trials.

Infection preventionists in public health, consultant and academic roles: Results from the 2020 APIC MegaSurvey.

BACKGROUND: Infection preventionists (IPs) work and practice in a variety of roles across many practice settings. While the health care-based IP role has been well studied, less is known about IPs who work in public health, consultant, and academic roles. METHODS: Data were collected as a subset of the Association for Professionals in Infection Prevention and Control and Epidemiology 2020 MegaSurvey. Descriptive and bivariate analyses were performed to compare the responses of 147 IPs working in public health, consulting, or academic roles. RESULTS: Respondents identified their primary IP role as public health (40%), consulting (39%), or academic (21%). Most were White and non-Hispanic females working in long-term care, acute care, and outpatient settings. Most had over 11 years of experience in health care before IP, with nursing being the most common. More consultants were certified in infection control (74%). While half of the respondents in public health reported being certified in infection control, and a third had 6 or more years of experience in infection prevention and control, they reported the lowest annual salary and satisfaction with total compensation. DISCUSSION: These findings highlight the characteristics and contributions of infection prevention and control in nontraditional roles and settings. Certification and fair compensation are crucial factors for professional development and job satisfaction. CONCLUSIONS: These insights can guide future education, recruitment, and retention strategies for IPs in public health, consulting, and academic roles.

Effects of post-spawning ration restriction on reproductive development and the growth hormone/insulin-like growth factor-1 axis in female rainbow trout (Oncorhynchus mykiss).

In iteroparous female salmonids, the growth and reproductive endocrine axes interact during the period after spawning. Energy depletion due to pre-spawn fasting, migration, and ovarian development must be restored, and the next reproductive cycle is initiated in consecutively maturing fish. In the natural environment, food availability is often limited during the post-spawn period. To investigate the growth and reproductive endocrinology of the post-spawn period, we sampled female rainbow trout over the 30 weeks following their first spawning. Fish were fasted for 2 months prior to spawning, then fed a standard or a restricted ration. Analysis was confined to reproductive fish. Plasma estradiol-17ß decreased during the 8 weeks following spawning and then began increasing in both ration groups and was lower in feed-restricted versus standard ration fish from 8 weeks onward. Plasma insulin-like growth factor-1 increased over the same period and then remained constant in both ration groups and was lower in feed-restricted versus standard ration fish from week 8 to week 30. Plasma growth hormone decreased following spawning in standard ration fish and became elevated in feed-restricted versus standard ration fish at 20- and 30-weeks post-spawn. Growth rates, condition factor, and muscle lipid levels were higher in standard ration versus feed-restricted fish within 2-4 weeks after spawning. These results suggest that two phases occurred during the post-spawn period: recovery from spawning and restoration of energy reserves over weeks 0 to 8, followed by adjustment of the growth and reproductive endocrine axes to ration level over weeks 8 to 30.

What's theory got to do with it: measuring effects of theory on lifestyle behaviors and weight in the Better Me Within Randomized Trial.

Background: Knowing which theoretical constructs work best to design effective interventions is essential for populations with increased disease burden. African American women (AAW) experience greater prevalence of chronic diseases and fewer benefits from weight loss interventions compared to White women. Purpose: To examine how theoretical constructs were associated with lifestyle behaviors and weight outcomes in the Better Me Within (BMW) Randomized Trial. Methods: BMW used a tailored diabetes prevention program implemented in churches among AAW with BMI ≥ 25. Regression models assessed relationships between constructs (self-efficacy, social support and motivation), and outcomes (physical activity (PA), calories, and weight). Results: Among 221 AAW (mean (SD) age 48.8 years (11.2); mean weight 215.1 pounds (50.5), several significant relationships were found including an association between change in motivation for activity and change in PA (p=.003), and change in motivation for diet and weight at follow-up (p=<.001). Discussion: The clearest relationships emerged for PA with motivation for activity and weight management social support demonstrating significance in all models. Translation to Practice: Self-efficacy, motivation and social support show promise to promote changes in PA and weight among church-going AAW. Opportunities to keep engaging AAW in research are essential for eliminating health inequities in this population.

Desert particulate matter from Afghanistan increases airway obstruction in human distal lungs exposed to type 2 cytokine IL-13.

Introduction: Deployment related asthma-like symptoms including distal airway obstruction have been described in U.S. military personnel who served in Iraq and Afghanistan. The mechanisms responsible for the development of distal airway obstruction in deployers exposed to desert particulate matter (PM) is not well understood. We sought to determine if respiratory exposure to PM from Afghanistan (PMa) increases human distal airway hyperresponsiveness (AHR) with or without exposures to IL-13, a type 2 cytokine. We further tested whether mitochondrial dysfunction, such as ATP signaling and oxidative stress, may contribute to PMa- mediated AHR. Methods: Precision-cut lung slices from donors without a history of lung disease, tobacco smoking, or vaping were pre-treated with IL-13 for 24 h. This was followed by exposure to PMa or PM from California (PMc, control for PMa) for up to 72 h. The role of hydrogen peroxide and ATP in AHR was assessed using the antioxidant enzyme catalase or an ATP receptor P2Y13 antagonist MRS2211. AHR in response to methacholine challenges as well as cytokine IL-8 production were measured. Results: PMa alone, but not PMc alone, trended to increase AHR. Importantly, the combination of PMa and IL-13 significantly amplified AHR compared to control or PMc+IL-13. PMa alone and in combination with IL-13 increased IL-8 as compared to the control. PMa increased H2O2 and ATP. MRS211 and catalase reduced AHR in PCLS exposed to both PMa and IL-13. Discussion: Our data suggests that PMa in a type 2 inflammation-high lung increased AHR in part through oxidative stress and ATP signaling.

Single cell RNA-sequencing of human precision-cut lung slices: A novel approach to study the effect of vaping and viral infection on lung health.

Vaping is an increasing health threat in the US and worldwide. The damaging impact of vaping on the human distal lung has been highlighted by the recent epidemic of electronic cigarette or vaping use-associated lung injury (EVALI). The pathogenesis of EVALI remains incompletely understood, due to a paucity of models that recapitulate the structural and functional complexity of the human distal lung and the still poorly defined culprit exposures to vaping products and respiratory viral infections. Our aim was to establish the feasibility of using single cell RNA-sequencing (scRNA-seq) technology in human precision-cut lung slices (PCLS) as a more physiologically relevant model to better understand how vaping regulates the antiviral and pro-inflammatory response to influenza A virus infection. Normal healthy donor PCLS were treated with vaping extract and influenza A viruses for scRNA-seq analysis. Vaping extract augmented host antiviral and pro-inflammatory responses in structural cells such as lung epithelial cells and fibroblasts, as well as in immune cells such as macrophages and monocytes. Our findings suggest that human distal lung slice model is useful to study the heterogeneous responses of immune and structural cells under EVALI conditions, such as vaping and respiratory viral infection.

Feeding after spawning and energy balance at spawning are associated with repeat spawning interval in steelhead trout.

Consecutive and skip repeat spawning (1- or ≥2-year spawning interval) life histories commonly occur in seasonally breeding iteroparous fishes. Spawning interval variation is driven by energetic status and impacts fisheries management. In salmonids, energetic status (either absolute level of energy reserves or the rate of change of energy reserves, i.e., energy balance) is thought to determine reproductive trajectory during a critical period ∼1 year prior to initial spawning. However, information on repeat spawners is lacking. To examine the timing and the aspects of energetic status that regulate repeat spawning interval, female steelhead trout (Oncorhynchus mykiss) were fasted for 10 weeks after spawning and then fed ad libitum and compared to ad libitum fed controls. Plasma growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels were measured to assess long-term energy balance. Plasma estradiol levels showed that some fish in both groups initiated a consecutive spawning cycle. In fasted fish, GH was lower at spawning in consecutive versus skip spawners. In consecutive spawners, GH was higher at spawning in fed versus fasted fish. These results suggest that fish with a less negative energy balance at spawning initiated reproductive development in the absence of feeding, but that feeding during the post-spawning period enabled initiation of reproduction in some fish with a more negative energy balance at spawning. Thus, both energy balance at spawning and feeding after spawning regulated reproductive schedules. These results show that the critical period model of salmonid maturation applies to regulation of repeat spawning, and that the reproductive decision window extends into the first 10 weeks after spawning.

Airway epithelial immunoproteasome subunit LMP7 protects against rhinovirus infection.

Immunoproteasomes (IP) serve as an important modulator of immune responses to pathogens and other pathological factors. LMP7/ß5i, one of the IP subunits, plays a critical role in autoimmune diseases by downregulating inflammation. Rhinovirus (RV) infection is a major risk factor in the exacerbations of respiratory inflammatory diseases, but whether LMP7 regulates RV-mediated inflammation in the lung particularly in the airway epithelium, the first line of defense against RV infection, remains unclear. In this study, we determined whether airway epithelial LMP7 promotes the resolution of RV-mediated lung inflammation. Inducible airway epithelial-specific LMP7-deficient (conditional knockout, CKO) mice were generated to reveal the in vivo anti-inflammatory and antiviral functions of LMP7. By using LMP7-deficient primary human airway epithelial cells generated by CRISPR-Cas9, we confirmed that airway epithelial LMP7 decreased pro-inflammatory cytokines and viral load during RV infection. Additionally, airway epithelial LMP7 enhanced the expression of a negative immune regulator A20/TNFAIP3 during viral infection that may contribute to the anti-inflammatory function of LMP7. We also discovered that induction of LMP7 by a low dose of polyinosinic:polycytidylic acid (PI:C) reduced RV-mediated inflammation in our CKO mice infected with RV. Our findings suggest that airway epithelial LMP7 has anti-inflammatory and antiviral functions that is critical to the resolution of RV-mediated lung inflammation. Induction of airway epithelial LMP7 may open a novel avenue for therapeutic intervention against RV infection.

State of infection prevention and control in nonacute care US settings: 2020 APIC MegaSurvey.

BACKGROUND: Strengthening infection prevention and control programs in nonacute care settings is a national priority. Efforts require thorough and ongoing appraisal of organizational structures, human resources including personnel training and competencies, system challenges and adaptive strategies implemented. Assessment of those in infection preventionist (IP) roles outside of the acute care setting is necessary to capture ongoing changes and challenges in the IP profession. METHODS: This cross-sectional study utilized data derived from the 2020 APIC MegaSurvey and applied descriptive and bivariate analyses to describe the state of infection prevention and control programs and personnel across nonacute clinical settings in the United States. RESULTS: Of 1,991 respondents, 57% of frontline IPs or administration/director IPs (1,051) indicated working in 1 or more nonacute care clinical settings. Of these, 33% (343) worked exclusively in only 1 type of nonacute care setting. Consistent with findings from the 2015 APIC MegaSurvey, IPs employed in nonacute care settings are a homogenous group with 88% of respondents indicating they are white, non-Hispanic (88%), female (94%), with nursing as their primary discipline (95%). A notable change in the proportion of time spent on health care-associated infection (HAI) activities in general was found, with a 31% decrease in reported time spent compared to respondents from the 2015 survey. Nearly half (47%) of respondents reported an annual salary of $50,000-$80,000; only 35% of respondents reported they were satisfied with their overall compensation. More than half (57%) of respondents reported having 5 or less years' experience in IPC and the majority, 82% reported they expected to be working in the IP profession in the next 5 years. CONCLUSIONS: The majority of IPs in nonacute care settings also worked in acute care. Of those who exclusively worked in nonacute care settings, they were predominately female, white, and had an educational background in nursing. A decrease in time spent on HAI activities was noted compared to respondents in 2015. Although the 2020 APIC MegaSurvey captured information previously not assessed in 2015, further studies are necessary to more robustly characterize the IP profession in nonacute care settings. Enhancements to current resources and services provided by APIC may serve to fill gaps in nonacute care settings related to gaining experience in research, general expertise, advocacy, and diversity.

Electronic cigarette vapor exposure exaggerates the pro-inflammatory response during influenza A viral infection in human distal airway epithelium.

Electronic cigarettes or vaping products have been marketed as a safer alternative to smoking, but very little is known about the health effects in the human lung, particularly in the distal airways, a key site of airway obstruction and destruction in chronic obstructive pulmonary disease that is often exacerbated by viral infections. The aim of this study was to investigate the effects of electronic cigarette vapor (e-vapor) on human distal airway epithelial responses to influenza A virus (IAV) infection. We isolated primary small airway epithelial cells (SAECs) from donor lungs free of lung disease, and cultured them at air-liquid interface (ALI). To measure markers of epithelial injury such as integrity of epithelial barrier structure and function, we selected a regimen of non-toxic, barrier preserving e-vapor exposure of cultured cells to 15 puffs of e-vapor from a commercially available e-cigarette once per day for 3 days, prior to IAV infection. After 72 h of infection, media and cell lysates were collected to measure cytokines involved in inflammatory and antiviral responses. Pre-exposure to e-vapor with IAV infection, compared to IAV infection alone, significantly increased inflammatory and antiviral mediators including IL-8, CXCL10, IFN-beta, and MX1. Our results suggest that e-vapor exposure amplifies human distal airway pro-inflammatory response to IAV infection, independently of the severity of cell injury during viral infection.

Human Bronchial Epithelial Cell Culture Models for Cigarette Smoke and Vaping Studies.

Despite the continuing public health efforts to stop or reduce smoking, cigarette smoke use remains popular in the youth and adult population. A recent surge in the use of electronic cigarette and vaping products has created another major health challenge in public health. There is an urgent need to use physiologically relevant models to study the health effect of smoking or vaping in human subjects. Airway diseases such as bronchitis (Landman et al., CMAJ 191:E1321-E1331, 2019; Goniewicz, et al. Harm Reduct J 17:91, 2020; Xie et al., JAMA Netw Open 3:e2020816, 2020) have been described in people who smoke, vape, or both. Here, we will describe methods to collect, expand, and culture human airway epithelial cells from endobronchial brushings and expose these cells cultured at the air-liquid interface to cigarette smoke or electronic cigarette vapor.

Tollip Inhibits IL-33 Release and Inflammation in Influenza A Virus-Infected Mouse Airways.

Respiratory influenza A virus (IAV) infection continues to pose significant challenges in healthcare of human diseases including asthma. IAV infection in mice was shown to increase IL-33, a key cytokine in driving airway inflammation in asthma, but how IL-33 is regulated during viral infection remains unclear. We previously found that a genetic mutation in Toll-interacting protein (Tollip) was linked to less airway epithelial Tollip expression, increased neutrophil chemokines, and lower lung function in asthma patients. As Tollip is involved in maintaining mitochondrial function, and mitochondrial stress may contribute to extracellular ATP release and IL-33 secretion, we hypothesized that Tollip downregulates IL-33 secretion via inhibiting ATP release during IAV infection. Wild-type and Tollip knockout (KO) mice were infected with IAV and treated with either an ATP converter apyrase or an IL-33 decoy receptor soluble ST2 (sST2). KO mice significantly lost more body weight and had increased extracellular ATP, IL-33 release, and neutrophilic inflammation. Apyrase treatment reduced extracellular ATP levels, IL-33 release, and neutrophilic inflammation in Tollip KO mice. Excessive lung neutrophilic inflammation in IAV-infected Tollip KO mice was reduced by sST2, which was coupled with less IL-33 release. Our data suggest that Tollip inhibits IAV infection, potentially by inhibiting extracellular ATP release and reducing IL-33 activation and lung inflammation. In addition, sST2 may serve as a potential therapeutic approach to mitigate respiratory viral infection in human subjects with Tollip deficiency.

Association between magnesium intake and cognition in US older adults: National Health and Nutrition Examination Survey (NHANES) 2011 to 2014.

INTRODUCTION: Identifying nutrition- and modifiable lifestyle-based risk factors for cognitive decline and dementia may contribute future primary prevention strategies. This study aimed to evaluate the associations between magnesium intake and cognition in older adults in the United States. METHODS: Based on the National Health and Nutrition Survey (NHANES) between 2011 and 2014, the study included 2508 participants aged 60 years and older. Linear regression models were used to examine the association of total magnesium intake with cognition. RESULTS: After adjusted demographic and other confounding factors, intakes of energy and total calcium, and serum vitamin D level, higher intake of total magnesium was independently associated with 0.15 higher global cognitive z-score (95% confidence interval, 0.02 to 0.28 for highest vs. lowest quartile, P trend = .037). The positive association of total magnesium intake with global cognition was primarily presented among women, non-Hispanic Whites, and those with sufficient serum vitamin D levels (≥50 nmol/L), although interactions were not significant. There were no clear linear associations for global cognition with serum vitamin D level. DISCUSSIONS: Our findings suggest that high magnesium intake alone may improve cognition in older adults, particularly among non-Hispanic Whites and subjects with sufficient levels of serum vitamin D. Further studies are needed to confirm the findings.

Factors related to the accurate application of NHSN surveillance definitions for CAUTI and CLABSI in Texas hospitals: A cross-sectional survey.

Previous studies indicate variability in the accurate application of National Healthcare Safety Network surveillance criteria with limited data on possible contributing factors. In this cross-sectional, convenience sampled web-based survey sent to members of Texas infection prevention and control organizations, training, experience, and time spent on surveillance was collected and assessed including 2 case studies. Our results indicate correct identification of catheter-associated urinary tract infection (CAUTI) and central line-associated bloodstream infection (CLABSI) criteria may be associated with 2019 National Healthcare Safety Network training (CAUTI: aOR = 0.17, 95% CI: 0.04, 0.80; CLABSI: aOR = 0.45, 95% CI: 0.045, 4.56) and increased years of infection prevention experience (CAUTI: aOR = 1.35, 95% CI: 0.42, 4.33; CLABSI: aOR = 1.23, 95% CI: 0.24, 6.38). Routinely performing more hours of surveillance may increase accuracy of CLABSI identification, but not CAUTI.

Journal club: "Racial disparities in catheter related urinary tract infections among elderly trauma patients in the US".

In this article for Journal Club commentary entitled "Racial Disparities in Catheter Related Urinary Tract Infections Among Elderly Trauma Patients in the US", Keneally et al, conducted a study with the goal of assessing the role of social disparities in catheter associated urinary tract infections (CAUTIs). This cross-sectional study utilized secondary data to determine the possible CAUTI risk in ventilated, older (≥ 65 years of age) trauma patients exploring possible racial structural bias in healthcare. The analysis addressed the following questions in this specific population:While this study does consider race and discusses structural biases, which are important and sparsely researched in healthcare-associated infection (HAI) outcomes, the practice implementations are somewhat limited due to study design and analysis. Therefore, the focus of this Journal Club commentary will be reviewing basic steps Infection Preventionists (IPs) can take to critically appraise the literature for application in their facility's patient population.

Community college competencies for student educational leadership development and degree pathways.

This article highlights the gap in formal credit-based community college student leadership development opportunities. The authors offer eight leadership competencies to guide the development of a stackable community college leadership development certificate. This certificate serves to enhance equitable workplace development skills for the large demographic of racially minoritized students who access postsecondary education through the community college system.

Clinical Symptoms of Arboviruses in Mexico.

Arboviruses such as Chikungunya (CHIKV), Dengue (DENV), and Zika virus (ZIKV) have emerged as a significant public health concern in Mexico. The existing literature lacks evidence regarding the dispersion of arboviruses, thereby limiting public health policy's ability to integrate the diagnosis, management, and prevention. This study seeks to reveal the clinical symptoms of CHIK, DENV, and ZIKV by age group, region, sex, and time across Mexico. The confirmed cases of CHIKV, DENV, and ZIKV were compiled from January 2012 to March 2020. Demographic characteristics analyzed significant clinical symptoms of confirmed cases. Multinomial logistic regression was used to assess the association between clinical symptoms and geographical regions. Females and individuals aged 15 and older had higher rates of reported significant symptoms across all three arboviruses. DENV showed a temporal variation of symptoms by regions 3 and 5, whereas ZIKV presented temporal variables in regions 2 and 4. This study revealed unique and overlapping symptoms between CHIKV, DENV, and ZIKV. However, the differentiation of CHIKV, DENV, and ZIKV is difficult, and diagnostic facilities are not available in rural areas. There is a need for adequately trained healthcare staff alongside well-equipped lab facilities, including hematological tests and imaging facilities.