During the Coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is universally susceptible to all types of populations. In addition to the elderly and children becoming the groups of great concern, pregnant women carrying new lives need to be even more alert to SARS-CoV-2 infection. Studies have shown that pregnant women infected with SARS-CoV-2 can lead to brain damage and post-birth psychiatric disorders in offspring. It has been widely recognized that SARS-CoV-2 can affect the development of the fetal nervous system directly or indirectly. Pregnant women are recommended to mitigate the effects of COVID-19 on the fetus through vaccination, nutritional supplements, and psychological support. This review summarizes the possible mechanisms of the nervous system effects of SARS-CoV-2 infection on their offspring during the pregnancy and analyzes the available prophylactic and treatment strategies to improve the prognosis of fetal-related neuropsychiatric diseases after birth. Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) declared COVID-19 as a global pandemic in March 2020. It has since been called “the most critical global health disaster of the century and the greatest challenge facing humanity since World War II” . HoweverSince the COVID-19 epidemic, several studies have reported that the clinical symptoms and laboratory findings of patients with combined SARS-CoV-2 infection in pregnancy are consistent with those of the general population, with patients showing increased C-reactive protein (CRP) and decreased lymphocytes in their hemogram . TanacanMaternal trophoblasts, specific natural killer cells, and meconium leukocytes secrete IFN-γ during the pregnancy and are involved in the differentiation of meconium natural killer cells, placenta formation, and meconium maintenance . HoweverThere is a study that reported that pregnant women during the influenza pandemics had a high incidence of psychiatric disorders in their offspring, including schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD) . SimilarPast epidemiological studies have shown that a large number of viral infections during maternal pregnancy can lead to abnormalities in the nervous system in the fetus . AlthougDuring fetal brain development, genetic defects, environmental disturbances or pathogens can lead to defective mitosis or apoptosis of neural stem cells, which can disrupt the stem cell homeostasis and affect the differentiation of stem cells to other neural cells, manifesting as neurodevelopmental disorders, such as microcephaly and multiple sclerosis . And theThe immune system plays an important role in nervous system injury caused by viral infection . PersistAngiotensin-converting enzyme 2 (ACE2), a cardiovascular and cerebrovascular protective factor, is also abundantly expressed in glial cells, and SARS-CoV-2 has a high affinity for ACE2, and its spine protein interacts with ACE2 to disrupt the BBB and attack the nervous system. Children complete myelin development by the age of 2 years, and SARS-CoV-2 infection of oligodendrocytes causes demyelinating lesions, such as multiple sclerosis . Patientβ = 0.82, P < 0.001), suggesting that high maternal stress and negative emotions during the pregnancy can have an unwanted impact on the nervous system of the offspring [The form of COVID-19 remains severe and people are inevitably affected and prone to stress and anxiety, and depression . A meta-ffspring .Deoni et al. found that children born after the COVID-19 pandemic were found to have lower developmental scores and these children had significantly lower language, motor, and overall cognitive skills . Anti-epThere is still no specific medicine for COVID-19, and the most common treatments for infection in pregnant women are antibiotics, antivirals, and oxygen support. However, both the public and the scientific community pay great attention to the safety and impacts of these treatment measures on the fetus. A meta-study analysis showed that the use of antibiotics and antivirals is higher in Asian countries than in other countries, suggesting a possibility of antibiotic abuse . The useVaccination against infectious pathogens is one of the most influential public health interventions to reduce infection-related morbidity and mortality worldwide . TheoretBased on previous experience with disease pandemics and experience with other respiratory viruses and animal models, increasing maternal choline levels and other nutrient levels may reduce the effects of infection on fetal brain development . CholineThe use of antidepressants such as selective serotonin reuptake inhibitor (SSRI) may be associated with a reduced risk of clinical deterioration in patients with SARS-CoV-2 infection. It may benefit depression patients with COVID-19 infection, since SSRIs exert anti-inflammatory effects on the damaged striatal neurons , 66. AltPsychotherapy is a safer strategy with less adverse effects than pharmacological treatments. Cognitive behavior therapy (CBT) is currently the most well-studied and popular treatment modality . In viewCOVID-19 affects fetal neurological development through multiple pathways during the pregnancy, although most newborns born in a COVID-19 pandemic setting are not directly infected with SARS-CoV-2. We need to pay attention not only to the neurological symptoms of neonatal impairment at birth, but also to the neuropsychiatric symptoms during the growth, and therefore improving the prognosis by early intervention. There is still a need for extensive follow-up studies to determine whether the fetal damage will be continued in adulthood, and new-onset psychiatric symptoms will be developed in adulthood. Most importantly, it is essential to create a safer environment and provide great support for pregnant women and their offspring.


The COVID-19 pandemic has been linked to poor mental health outcomes and may be particularly damaging for young adults who may be more affected by governmental pandemic responses such as mandatory school and work closures, online schooling, and social isolation. Exposure to Adverse Childhood Experiences (ACEs) has also been shown to have a significant impact on mental health among young adults. This prospective study examined whether young adults with higher ACE profiles were more vulnerable to COVID-19 stressors. Using pre-COVID-19 data from the Niagara Longitudinal Heart Study and a follow-up online survey during COVID-19, we examined 171 young adults and found that high COVID-19-related stress, especially emotional and relationship stress, led to a greater reduction in mental health among young adults with higher levels of ACEs. Findings indicate that young adults with high ACE profiles may benefit from resources and intervention programs directed at mental health in times of crisis, such as the COVID-19 pandemic. ACEs are generally defined as exposure to traumatic experiences such as abuse and maltreatment, severe household dysfunction, and witnessing intimate partner violence involving parents/caregivers before the age of 18 ,3,4,5,6.Young adults, as a cohort in a transitional life course stage, may be particularly affected by the COVID-19 pandemic and the governmental measures implemented to mitigate its impact ,17,18,19It is unclear whether past exposure to ACEs compounds the negative effect of COVID-19-related stressors, placing some individuals at even greater risk of negative mental health outcomes. A few studies have examined this connection linked to other population-level events and experiences. For example, one study examined the impact of ACEs on 549 Syrian child and adolescent refugees fleeing the civil war. Surprisingly, they found that exposure to ACEs was the most important predictor of PTSD, operating independently of their exposure to the war and refugee experience . AnotherWith respect to COVID-19, we are aware of some studies that have examined the potential link with ACEs. One cross-sectional study found that Chinese adolescents with higher exposure to cumulative ACEs such as neglect and family abuse were most at risk psychologically where COVID-19 lockdowns and social isolation were imposed . A seconPre-COVID-19 data came from the ongoing Niagara Longitudinal Heart Study (NLHS) . From MaThe COVID-19 follow-up questionnaire was sent to all 248 participants having consented to be followed up for future research. They were contacted using email and social media and asked to complete an online survey using Qualtrics XM online survey software . Of the 248 contacted, 171 participants completed the survey, a response rate of 69%. Data collection occurred over an approximately 2-month period between 27 July 2020, and 5 October 2020, when Ontario, and Canada more generally, were in-between COVID-19 waves and were loosening social restrictions. The NLHS and the COVID-19 survey both received Research Ethics Board approval .The NLHS questionnaire covered a broad array of topics including measures of ACEs and mental health  The COVID-19 survey included many of the same questions as the initial NLHS questionnaire to allow for longitudinal analysis. In addition, the online survey included questions about COVID-19-related stressors and the impact of the lockdowns .ACEs were assessed (pre-COVID-19) using the Childhood Trust Events Survey v.2.0 (CTES 2.0)—a 26-item inventory adapted from the Traumatic Stress Survey  that scrCOVID-19 stressors were measured based on work by Lavoie and Bacon (2020) . We examAll outcomes were measured as continuous variables with higher scores indicating greater mental health problems. Depressive symptomatology was assessed using the Centre for Epidemiological Studies-Depression scale (CESD) by Radloff  consistiAll analyses were adjusted for sex , age, and education status, all measured pre-COVID-19. The analysis proceeded in four steps including an attrition analysis, descriptive statistics for pre-COVID-19 and during COVID-19 data, correlational analysis of the during COVID-19 data, and longitudinal, mixed-model regression analyses to adjust for biased standard errors and intraclass correlation within participants. The regression analyses assessed (1) the independent effect of ACEs and each COVID-19 stressor on change over time for each outcome and (2) the interaction between ACEs and each COVID-19 stress over time to assess their conditional effects on change over time for each outcome. All analyses were conducted using SAS 9.4 .The attrition analysis comparing NLHS (pre-COVID-19) data between those who participated in the during COVID-19 survey (171) to those who did not (77) found no differences across any of the mental health outcomes (results not shown). There were also no significant differences across sex or age. Those who participated reported significantly higher education status compared to those who did not complete the online survey. Descriptive statistics of the 171 participants are reported in The correlation analysis found that ACEs were significantly and positively correlated with all mental health outcomes measured during COVID-19. ACEs were also significantly correlated with frustration, drug use, inability to pay rent/mortgage and food, and serious arguments with the people one lives with. All mental health outcomes were significantly correlated with all emotional-based stressors, inability to pay for food, and serious arguments. In addition, alcohol use was correlated with anxiety while recreational drug use was correlated with depression, anxiety, and perceived stress. Decreased income was correlated with depression while inability to pay rent/mortgage was correlated with depression, hostility, and perceived stress .Mixed effects, longitudinal regression assessed how exposure to ACEs and COVID-19-related stress related to changes across mental health outcomes employing a series of two-way and three-way interaction models. These models assessed the independent and conditional effects of ACEs with COVID-19 stressors over time . The firTests of three-way interactions exploring whether the effect of higher COVID-19 stress is conditional on the level of ACEs score on mental health outcomes over time indicated a notable pattern . This paThis study examined how exposure to greater numbers of ACEs may compound the negative effects of COVID-19 stressors on changes in mental health among young adults. To our knowledge, it is one of the few studies that examines pre- to during COVID-19 changes in mental health prospectively based on ACEs exposure. The original NLHS study focused on young adults, providing a unique opportunity to study a cohort which may be especially vulnerable to the governmental responses to mitigating the impact of the COVID-19 pandemic based on their transitional life-course stage . SpecifiPast research has made it clear that both ACEs and COVID-19 stress impact health and well-being. High exposure to ACEs has been independently linked to many mental health problems such as depression, substance use, antisocial behaviors, and personality disorders, as well as the risk of developing chronic physical conditions and diseases later in life ,28,29,47Most stressors associated with COVID-19, especially emotional and relationship stressors, are a direct result of governmental actions such as physical distancing and lockdowns aimed at controlling the spread of the virus to minimize hospital and intensive care unit (ICU) admissions. Interestingly, we found that most of the significant interaction effects between ACEs and COVID-19 on decreases in mental health over time were concentrated in these domains, specifically loneliness and isolation, irritability and frustration, suspiciousness, and distrustfulness of others, and having serious arguments with the people you live with. Financial stressors, while important, may have played a smaller role due to the Canadian government’s income subsidies including the Canadian Emergency Response Benefit (CERB) and extended employment insurance benefits for those who lost their job or had their hours reduced. As the service and hospitality industries which employ a large proportion of young adults were the hardest hit by closures, these employees likely benefited disproportionately from these emergency employment benefits.It is also possible that some of the observed reductions in mental health may already be occurring for reasons other than the pandemic. Since there could be up to a 2-year lag for some participants between data points, we are unable to discount this possibility. However, those that reported higher COVID-19-related stress had significantly greater increases than those with lower stress and those with both high ACEs and high COVID-19-related stress had the greatest increases in mental health problems. While acknowledging the potential for pre-existing factors that may account for some of these increases over time, these results indicate that those with a combination of higher ACEs and higher COVID-19-related stress had the greatest increases in mental health problems.Finally, with a universal, public healthcare system in Canada, job losses or significant reductions in hours would not threaten medical coverage and access to care beyond the limitations that were imposed by COVID-19 or the loss of extended employment benefits, such as coverage for dental care, prescriptions, and ancillary health care . However, there were significant reductions in accessibility to many mental health resources as a result of lockdowns. Most of the mental health care resources that remained available were moved to virtual and phone appointments impeding access for a variety of reasons such as access to appropriate, stable internet services. For example, rural areas, which in countries such as Canada and the US include up to 63% of counties , would bThis analysis examined changes in mental health outcomes prospectively from before to during the COVID-19 pandemic among a sample of young adults. Unlike most studies that are either cross-sectional or longitudinal but started after COVID-19 began, we were able to assess these changes using baseline data collected prior to the COVID-19 pandemic and the governmental responses/lockdowns. The study uses a broad array of validated measures of mental health outcomes including depression, anxiety, hostility, and perceived stress that were measured both prior to and during COVID-19.Notwithstanding these strengths, there were also a number of limitations, First, the COVID-19-related stress measures taken from an international study initiated at the beginning of the pandemic by Lavoie and Bacon  have notYoung adults who were exposed to greater numbers of ACEs appear to be more vulnerable to the stressful effects of COVID-19 with respect to mental health beyond any independent, additive effects of each one ,49,50. AThe findings of this study emphasize the importance of considering exposure to ACEs as an enduring risk factor in the face of more proximal stressors, making these individuals more vulnerable to the negative effects of COVID-19 stress. As such, individuals with high ACE profiles may benefit from intervention programs and resources directed at mental health during times of population-level events. In addition, the findings highlight the serious impact of wide-scale governmental actions and policies meant to control the spread of the pandemic. These imposed, system-wide responses resulted in a unique set of stressors that had a notable effect on the mental health of young adults with higher ACE profiles. Consideration of previous childhood exposures may provide clinicians with further knowledge to both identify and treat those who are at greater risk to adverse mental health outcomes.


The original version of the Nurse Managers’ Empowering Behavioral Scale for Staff Nurses (NMEB-SN) was both unique and comprehensive. However, it was considered lengthy. Hence, the intention of this particular study was to develop a shortened version of the NMEB-SN comprising 15 items across five subscales. Responses from 1268 staff nurses working at 10 Japanese hospitals were included in the analysis to confirm the validity and reliability of the scale. The results ensured internal consistency, construct and criterion-related validity, and test–retest reliability. The NMEB-SN short version is applicable in the context of practical and efficient nursing management to attract more nurses to the workplace. The concept of psychological empowerment was developed as a component of motivation ,2 and deThe Nurse Managers’ Empowering Behavioral Scale for Staff Nurses (NMEB-SN)  was deveThe minimum number of items that would ensure reliability with content validity of each subscale was set at three. To identify the items to be included in the NMEB-SN short version, three nursing management researchers worked together in this study to select three items from each subscale . For eacThis study utilized the data  that wasParticipants provided information regarding their demographic characteristics, the NMEB-SN items, and external criteria that were used in the criterion-related validity of the NMEB-SN. The NMEB-SN items were scored on a 5-point Likert scale, and the other external criteria items were scored on a 7-point Likert scale. A higher score indicated that nurse managers exhibit psychologically empowering and motivating behaviors toward staff nurses.Leader–member exchange was evaluated using the 12-item multidimensional measure of leader–member exchange Japanese version (LMX-MDM-J) . Higher Psychological empowerment was evaluated using the Japanese translation  of SpreiAffective commitment was evaluated using the 3-item Affective Organizational Commitment Scale . Higher Work engagement was evaluated using the 9-item Japanese version of the Utrecht Work Engagement Scale , whereinJob satisfaction and turnover intention were individual items evaluated on the 7-point Likert scale, wherein higher scores denote higher job satisfaction and turnover intention.Following the NMEB-SN development procedure, the reliability and validity of the short version were verified. Internal reliability was verified by Cronbach’s alpha coefficient. To verify the test–retest reliability, an intra-class correlation coefficient (ICC) of the NMEB-SN short version was performed. Construct validity was verified by confirmatory factor analysis (CFA). Whether the model fit was acceptable was assessed by the comparative fit index (CFI) and root mean square error of approximation (RMSEA). Criterion-related validity was tested using Pearson’s correlations.p < 0.001; A total of 1268 participants were included in the study, with a mean age of 31.8 years (standard deviation: SD 8.97) and a mean years of experience of 8.52 (SD 7.95). Of the participants, 1151 (90.8%) were women, 1145 (90.3%) were staff who were not in the position of deputy nurse manager, and 915 (72.2%) were from a vocational school. Construct validity was assessed by the goodness-of-fit indices of CFA. The CFI value was 0.979 and the RMSEA value was 0.070 , which met the criteria for acceptable model fit . The CroAs a result of implementing CFA, the model fit met the following criteria: CFI ≥ 0.90 and RMSEA < 0.08 . TherefoThe shortened version of the scale was created using data from the development of the original version of the NMEB-SN. The NMEB-SN items were developed from the results of interviews conducted with staff nurses working in actual nursing workplaces. These items are characterized by the particular actions of the nurse managers that staff nurses recognize. As the shortened version is used in additional research, its reliability and validity will be characterized further.The NMEB-SN shortened version can be used to examine and understand the relationship between the nurse managers’ empowerment behavior toward staff nurses and other variables, whereas the original long version can be used to investigate nurse managers’ behavior in detail. This should lead to nursing management that will attract more nurses to the workplace. The use of the scale might also encourage inter-organizational and international comparative studies.The validity and reliability of the NMEB-SN short version, comprising 15 items across five subscales, were verified. The scale can be used to measure the empowerment provided by nurse managers’ behavior, which in turn can help psychologically empower and motivate staff nurses, resulting in improved performance and engagement in the workplace.


Aging is a primary risk factor for cardiovascular disease (CVD), which is the leading cause of death in developed countries. Globally, the population of adults over the age of 60 is expected to double by the year 2050. CVD prevalence and mortality rates differ between men and women as they age in part due to sex-specific mechanisms impacting the biological processes of aging. Measures of vascular function offer key insights into cardiovascular health. Changes in vascular function precede changes in CVD prevalence rates in men and women and with aging. A key mechanism underlying these changes in vascular function is the endothelin (ET) system. Studies have demonstrated sex and sex hormone effects on endothelin-1 (ET-1), and its receptors ETA and ETB. However, with aging there is a dysregulation of this system resulting in an imbalance between vasodilation and vasoconstriction. Thus, ET-1 may play a role in the sex differences observed with vascular aging. While most research has been conducted in pre-clinical animal models, we describe more recent translational data in humans showing that the ET system is an important regulator of vascular dysfunction with aging and acts through sex-specific ET receptor mechanisms. In this review, we present translational evidence  that the ET system is a key mechanism regulating sex-specific changes in vascular function with aging, along with therapeutic interventions to reduce ET-mediated vascular dysfunction associated with aging. More knowledge on the factors responsible for the sex differences with vascular aging allow for optimized therapeutic strategies to attenuate CVD risk in the expanding aging population. Aging is a primary risk factor for cardiovascular disease (CVD), which is the leading cause of death in developed countries. Currently, 13% of the world population and 16% of the population in the United States is over the age of 65 . MoreoveThe endothelium is a monolayer of endothelial cells that creates a barrier between the blood and vascular smooth muscle cells (VSMC), forming the lumen of the blood vessel. To maintain homeostasis, the endothelium produces and releases both vasodilating and vasoconstricting factors, the most potent being nitric oxide (NO) and endothelin-1 (ET-1), respectively. Endothelial dysfunction, which precedes the development of cardiovascular pathologies such as atherosclerosis is a non-traditional risk factor for CVD . EndotheAging is associated with declines in endothelial function. Notably, there are sex differences in age-related declines in endothelial function. Young women tend to have greater endothelium-dependent dilation compared to men . In men,The mechanisms underlying sex differences in the age-related decline in endothelial function remain under investigation, but accumulating evidence indicates that the ET system is a key sex-specific regulator of vascular dysfunction associated with aging. The ET system is active in many tissues such as neural, kidney, lung, and vasculature  and playAging also increases the risk for CVD through other adverse effects on the arterial wall, including VSMC growth, apoptosis, vascular hypertrophy and enhanced matrix metalloproteinase activity, which can lead to arterial remodeling and stiffening . In contThe ET peptide is a potent vasoconstrictor primarily released from endothelial cells . There a1-31 is an inactive intermediate which is converted to active ET-1 neprilysin , and act as a clearance receptor to help remove local ET-1  is produced through a chymase enzymatic reaction and is also biologically active although less potent than ET-1 produced through its traditional pathway  and intermediates of ET-1 have also been measured in the plasma, and higher levels are associated with the presence of CVD pathology and severity . The 31- pathway . Plasma patients . ET-11-3ublished . Additioublished . Patientublished . An addiublished . Each peDespite the benefits of measuring plasma ET-1, plasma concentrations of ET-1 may not always be reflective of tissue or cellular ET-1; local concentrations of ET-1 are tissue dependent and can be 100-fold higher than plasma concentrations . In animThere is evidence in both animals and humans of reductions in ET-1 sensitivity with aging, which could suggest age-related increases in ET-1 expression and augmented endothelin-mediated vasoconstrictor tone. In humans, blunted vasoconstrictor responses to exogenous ET-1 have been reported in older compared to younger men , suggest2, and thromboxane. NO is a regulator of ET-1, and increased NO can downregulate ET-1 production  during menopause could be a factor contributing to the changes in the ET system. Estradiol not only directly impacts ET-1, but also enhances NO and PGI2 . To bett2 . Thus, bThe use of animal models, specifically ovariectomy (OVX), a form of surgical menopause that reduces levels of ovarian hormones in females, with E2 add-back, have been a useful tool to study the effects of E2 on the ET system. OVX leads to increased plasma and cellular ET-1 levels as well as increased ET-1 mediated constriction . IncreasET receptor expression is also impacted by E2. In an animal model using OVX and E2 add-back, the loss of ovarian hormones increased ET receptor expression, however this response was attenuated when E2 was restored . ETA recInvestigation of the underlying mechanistic pathways to explain the role of E2 on the ET system are ongoing. In cell culture models, E2 treatment was able to attenuate ET-1 production in cells stimulated with numerous secretagogues including angiotensin-II, thrombin, TNF-α, and cyclic strain . This coMore recently the G-protein estrogen receptor (GPER) has been shown to play a role in modulating the ET system by attenuating the ET-1 vasoconstrictor response in VSMC  as well The ET system also contributes to vascular dysfunction in men. In young men ETB and ETA receptors mediate vasoconstrictor tone . In oldeTo evaluate the impact of androgens on the vasculature, testosterone treatment has been used in animal models. In a study using aortas from male rabbits, testosterone was found to worsen endothelial function . This efAdditional evidence of the impact of testosterone on the ET system is found in cell culture experiments. In human aortic endothelial cells, testosterone increased the number of cells secreting ET-1 and upregulated ET-1 mRNA within 3 h . In porcGiven that the ET system contributes to numerous vascular pathologies, its receptors are a target for pharmacological intervention. ET-receptor antagonists (ERA) have been studied in several pathologies; however, the studies were stopped early due to an increase in adverse effects of ERA treatment including increased fluid retention and liver toxicity, with the outcomes falling short of expectations . AlthougNew study designs have helped to increase efficacy by using an enrichment-responder design that identifies participants who demonstrate a response to the drug at low doses and who will potentially be less likely to have an adverse event. The SONAR trial was the first to use this approach in patients with type 2 diabetes and kidney disease, and demonstrated that in responders, Atrasentan, a selective low dose ERA targeting ETA receptors, reduced the risk of renal events . It was Novel therapeutics targeting different parts of the ET system as well as novel ways to antagonize receptor function have shown promise in early studies. New methods using immunotherapy to create custom antibodies to ET receptors also show promise for the treatment of PAH. A specific antibody against the ETR-002 epitope of the ETA receptor was able to reduce right ventricle systolic pressure in PAH animals . AdditioExercise training also has beneficial effects on health and longevity and can reduce CVD risk. Vascular endothelial function is reduced in middle-aged and older sedentary adults and aerobic exercise training can rescue these impairments. Given the distinct role of ET-1 on age-associated impairments in endothelial function in both men  and womeClear evidence demonstrates aerobic exercise training improves ET system function in previously sedentary older men, and similarly, endothelial function is preserved in habitually active older men . These fIn women, the impact of aerobic exercise on endothelial function is equivocal, with data showing endothelial function is not consistently preserved  in habitE2 is known to modulate the ET system as described above. Recent data indicate that E2 plays an essential role to “transduce” the benefits of exercise on the vasculature in postmenopausal women . TherefoIn summary, sex-specific differences in the ET-1 signaling pathway plays a large role in sex differences observed in endothelial function with aging . In womeGiven the ET system is a critical player in regulating vascular function as well as numerous pathological conditions, the ability to regulate the ET system through lifestyle or pharmacological interventions are valuable therapeutic tools. Finding windows of opportunity for preventative or early treatment is critical to reducing CVD. More research is needed to develop new methods to manipulate production of ET-1 and receptor function as therapeutic targets, since currently approved drugs tend to have numerous side effects. Targeting specific ET receptors based on receptor subtype and tissue location could help to attenuate the ET system and help preserve vascular function without systemic side effects. Lifestyle changes are often first line treatments to prevent, delay, and reverse elevations in CVD risk. ET system activity may be an important mechanism underlying the sex-specific differences in adaptations to aerobic exercise and is an important question that warrants future study. This is critical given that less than 1 in 4 adults report sufficient activity to meet the relevant national physical activity guidelines for both aerobic and muscle strengthening exercise . Finally


The factors affecting preventive health behaviors were fear of infection , perceived benefits of COVID-19 infection control , educational needs concerning COVID-19 infection control , and perceived barriers to COVID-19 infection control . To improve preventive health behaviors of nursing students against COVID-19, effective and practical education is required, and a systematic infection prevention education program should be developed considering the fear of COVID-19 infection and the perceived benefits and barriers in infection control.This study was conducted to identify factors affecting preventive health behaviors and to provide basic data for developing coronavirus disease 2019 (COVID-19) prevention and education programs. The participants were 218 students enrolled in two nursing colleges located near Gyeongsang and Jeolla province, Republic of Korea. Data were collected in December 2020 and analyses were conducted using  Coronavirus disease 2019 (COVID-19) broke out in Wuhan, Hubei Province, China, in December 2019, and spread rapidly across the world. On 30 January 2020, the World Health Organization declared it a Public Health Emergency of International Concern—the highest alert for infectious diseases. On 11 March 2020, the highest level of stages 1–6 according to the risk level of infectious diseases was declared .According to the Korean Central Disaster and Safety Countermeasure Headquarters, 241 people were infected with COVID-19 among healthcare workers as of 5 April 2020, accounting for 2.4% of all confirmed patients  [Nurses tend to have the most direct contact with patients among medical personnel at medical facilities and local healthcare institutions that are at the forefront of treating the COVID-19 pandemic. There is thus a higher risk of nurses being exposed to environments where they are vulnerable to infection and of them spreading infectious diseases to others ,7.However, nursing students who were training to become nurses were often unable to gain practical clinical experience for the first semester of 2020 due to the COVID-19 pandemic. Compared to nurses who graduated pre-COVID-19, newly graduated nurses may be at higher risk of exposure to infectious diseases due to their lack of proficiency and expertise . NursingTo better understand preventive health behaviors, it is necessary to identify the various factors that determine these behaviors. First, knowledge of COVID-19 can affect healthcare workers’ risk perception or prevention strategies ,11. ThisFear of becoming infected can be linked to a person’s anxiety levels, which means that whenever a new infectious disease emerges this can result in the public—and nursing students—experiencing negative emotional effects ,17,18. IWhile a number of studies have been conducted related to vaccination in relation to COVID-19 preventive health behaviors ,26, veryNurses in the COVID-19 era are required to improve future-oriented education and curricula that can promote global citizenship and cooperative teamwork, and high-level professional nursing services should be provided smoothly . TherefoFirst, we wished to identify what knowledge of COVID-19 infection control is needed as well as relevant information concerning educational needs related to COVID-19 infection control, fear of COVID-19 infection, benefits and barriers in COVID-19 infection control, and preventive health behaviors of nursing students. Second, we wished to identify differences in relation to knowledge of COVID-19 infection control, educational needs related to COVID-19 infection control, fear of COVID-19 infection, benefits and barriers to COVID-19 infection control, and preventive health behaviors according to the demographic characteristics of nursing students. Third, we wished to investigate the correlation between knowledge of COVID-19 infection control, educational needs related to COVID-19 infection control, fear of COVID-19 infection, benefits and barriers in COVID-19 infection control, and preventive health behaviors of nursing students. Fourth, we wished to identify the factors influencing COVID-19 preventive health behavior in nursing college students.This study adopted a descriptive, questionnaire-based cross-sectional approach to investigate the factors that affect COVID-19 preventive health behavior among nursing students in the Republic of Korea.The participants in the study were nursing college students enrolled in two universities located in the Gyeongsangbuk-do and Jeolla-do provinces of the Republic of Korea. A total of 220 questionnaires were distributed to nursing students and 220 questionnaires were collected. Among them, 218 questionnaires were used in the final data analysis, two questionnaires having been excluded for containing insufficient survey data.Participants were selected based on their responses. The inclusion criteria comprised participants who: (1) could communicate clearly with other individuals, (2) understood the purpose of the study, and (3) consented to voluntarily and freely take part in the study. The G-Power 3.1.9.7 program  was used to calculate the number of participants required for this study. The sample size was estimated at a significance level of 0.05, a statistical power of 0.95, and an effect size of 0.15 for multiple regression analysis, indicating that the minimum number of participants required was 184 . ConsideBefore it was distributed to the participants, the survey questionnaire was examined by four nursing college students to determine whether there were any problems with the length, difficulty, and appropriateness of the questions and the response time provided. No issues were raised by the reviewing students at this time, and the responses of these four students to the questionnaire were not included in the survey analysis.After obtaining approval from the head of the department, a notice was posted on the boards of the respective departments as well as the departments’ websites. The notice advised that the input of research participants was needed for a particular study. The researcher explained the purpose of the study and the contents of the study directly to all nursing students who expressed their intention to participate in the study and then the participants completed the survey questionnaire.The data for this study were collected during the period December 8 to 31 December 2020, in person and via e-mail. This study was approved by the Public Institutional Review Board designated by the Korean Ministry of Health and Welfare to ethically protect study participants (IRB no. P01-202011-21-025). After explaining the purpose and method of the survey to the study participants, written consent forms for participation in the study were distributed to the participants. The researcher explained to the participants that if they did not wish to participate in the study at any stage they could withdraw from the study at any time. It was explained to the participants that their anonymity was guaranteed and that the data collected would be discarded after the completion of the study and not be used for any purpose other than research. Data were anonymized and safely stored in an envelope so as to ensure confidentiality.This study used a self-reported questionnaire consisting of six sections: (1) demographic characteristics , (2) knowledge of COVID-19 infection control, (3) educational needs concerning COVID-19 infection control, (4) fear of COVID-19 infection, (5) perceived benefits and barriers in COVID-19 infection control, and (6) COVID-19 preventive health behaviors.Knowledge of COVID-19 infection control was reviewed in relation to the ninth edition of the COVID-19 Response Guideline , and twoThe specialized group of reviewing nurses evaluated each question on a four-point Likert scale . To ensure consistency between the experts, the item-level content validity index (I-CVI) was calculated. The I-CVI is calculated as a response ratio for three and four points per item, and if the I-CVI is 0.78 or higher, it is considered appropriate . The I-CEducational needs concerning COVID-19 infection control were reviewed in relation to the ninth edition of the COVID-19 Response Guideline , and twoThe fear of COVID-19 infection variable was revised and supplemented to suit COVID-19 with an instrument that Lee et al.  developeThe perceived benefits and perceived barriers for the COVID-19 infection control variable were revised and supplemented to suit COVID-19 with the instrument that Lee  used to For COVID-19 preventive health behaviors, two nursing professors prepared the initial questions by reviewing Korean official Basic Guidelines for Distancing in Daily Life . The quet-test and analysis of variance (ANOVA) were used to determine the difference in variables related to COVID-19 preventive health behaviors according to demographic characteristics, and the Scheffé test was performed for variables with statistically significant differences. Third, the correlation between variables was analyzed using the Pearson correlation coefficient. Fourth, stepwise multiple regression was used to identify the factors affecting COVID-19 preventive health behaviors.The data collected in this study were processed using the SPSS/WIN 25.0 program , and the data analysis method was as follows. First, descriptive statistics were used for participant demographic characteristics and variables. Second, a The general characteristics of the nursing students are shown in p < 0.01), satisfaction with university life , and satisfaction with major choice . The average score of female students was higher than that of male students. As a result of the Scheffé test, in the case of satisfaction with university life and satisfaction with their major choice, the students who responded with “good” had higher average scores than those who responded with “moderate”.The effects of demographic characteristics on COVID-19 preventive health behaviors are shown in As seen in p < 0.01), educational needs concerning COVID-19 infection control , fear of COVID-19 infection , perceived benefits of COVID-19 infection control , and perceived barriers to COVID-19 infection control  showed a statistically significant correlation.As can be seen in p < 0.001), perceived benefits of COVID-19 infection control , educational needs concerning COVID-19 infection control , and perceived barriers to COVID-19 infection control . The explanatory power of the regression model was 19%, and the regression equation was statistically significant .Through a stepwise multiple regression analysis, the factors affecting COVID-19 preventive health behaviors among the participants were examined and are presented in This study was conducted to provide foundational data to assist in the development of COVID-19 education programs by identifying the factors that affect preventive health behaviors in nursing students.We found statistically significant differences depending on sex, satisfaction with university life, and satisfaction with major choice. In a study by Lee , who repStudents who responded that they were satisfied with their university life had higher than average scores than those who responded that they were only moderately satisfied. In terms of whether or not students were aware of the need for COVID-19 infection control education, students who responded with “yes” had higher than average scores than those who responded with “no”, and the same results were found in a similar study by Lee . In the However, in this study, there was a statistically significant difference found according to satisfaction with the student’s choice of major, but in the study of Lee , there wWe found that the higher the fear of becoming infected with COVID-19, the higher the perceived benefits of COVID-19 infection control, the lower the perceived barriers to COVID-19 infection control, and the higher the educational needs of COVID-19 infection control, the more the level of COVID-19 preventive health behaviors was increased.A study on the predictors of MERS-related preventive behavior performance among clinical practice students in a tertiary hospital  reportedWe found that the higher the perceived benefits and the lower the perceived barriers in relation to COVID-19 infection control, the higher the level of COVID-19 preventive health behaviors. In particular, the influence of perceived benefits was high, and since studies on perceived benefits and barriers among nursing students related to COVID-19 infection are insufficient, we would recommend that further studies on the performance of infection control by nurses be carried out. Perceived benefits appeared to be the most influential factor affecting the performance of infection control in relation to multidrug-resistant organisms among general hospital nurses  and in tThe results of this study showed that the higher the educational needs concerning COVID-19 infection control, the higher the level of COVID-19 preventive health behaviors. Although there has been limited research conducted involving nursing students and college students specifically concerning preventive health behaviors, there are some studies that allow for comparison with our study. In a study conducted by Kim et al.  on colleThis study has several strengths. The participants in this study included nursing students who engaged in clinical practice in areas where COVID-19 first had a major effect in South Korea, and it is noteworthy that they participated in this study on preventive health behaviors affecting COVID-19 infection at a time when COVID-19 was so prevalent. Furthermore, along with investigating the influencing factors of preventive health behaviors against COVID-19 infection, which is a topic that has primarily involved nurses thus far, this study focused on nursing students and considered additional factors such as educational needs and perceived benefits and barriers, which are critical influencing factors.Nevertheless, this study has some limitations. First, this study was conducted within only two provinces of South Korea. The exclusion of nursing students from other provinces may affect the generalizability of the results. Second, a cross-sectional study design cannot establish a causal link between the variables under investigation. Third, regarding the data collection procedure, using two different methods (face-to-face and online) may produce a certain bias in the responses.This study analyzed the factors affecting preventive health behaviors in relation to COVID-19 among nursing college students. The key factors affecting COVID-19 preventive health behaviors among nursing students were identified in descending order of importance as follows: fear of COVID-19 infection, perceived benefits of COVID-19 infection control, educational needs concerning COVID-19 infection control, and perceived barriers to COVID-19 infection control. Therefore, to improve the preventive health behaviors of nursing students against COVID-19, effective and practical education is required. Nursing colleges and clinical practice organizations should be systematically organized, taking into consideration nursing students’ fear of COVID-19 infection and the perceived benefits and barriers of infection control when developing COVID-19 infection prevention education programs.We recommend further research with a larger sample size that could include other variables considered likely to affect COVID-19 preventive health behaviors, as well as further research on the effect of COVID-19 education programs on nursing students with respect to COVID-19 preventive health behaviors.


The revelation of the HOXB13 gene adds novel insights into the genetic determinism of the sheep tail phenotype. This new genetic highlight will lead to further advances in sheep breeding using selection-based strategies and molecular genetics-based tools.Understanding the genetic basis of sheep tails is of great importance to improve sheep production and welfare. In this Comment, we discussed recent findings showing that  homeobox B13 (HOXB13) as a regulator of sheep tail length and their impact on sheep breeding via selection-based strategies and molecular genetics-based tools are discussed.Recent findings implicating  Several factors influence the sheep tail phenotype, including length, fat deposition level, and directionality. The overall tail length is controlled by the number and length of caudal vertebrae. On the other hand, tail fat deposition is controlled by the size and number of adipocytes. Several tail phenotypic patterns have been shown in sheep, including the thin-long tail, thin-short tail, fat-short tail, fat-long tail, and fat-rumped tail . Of these issues, tail docking, as a painful practice, is the most critical6. Revealing the genetic determinism of sheep tails will help to direct the selection towards the desired phenotypes8 and provide access to new biotechnological tools to directly introduce the desired variant(s) into the targeted breed10. Recently, three genes/regions were reported to be significantly associated with the sheep tail phenotype. These include the platelet derived growth factor D (PDGFD) gene12 and the intergenic region between the bone morphogenetic protein 2 (BMP2) and hydroxyacid oxidase 1 (HAO1) genes, referred to as the IBH region15 linked with the fat-tail phenotype, and the T-box transcription factor T (TBXT) gene18 linked with variations in caudal vertebrae. Recent studies highlighted a new gene, HOXB13, which is highly associated with the sheep tail length23  in the form of a short insertion associated with the long-tail phenotype, adding a new critical member to the gene repertoire of the sheep tail configuration.The tail phenotype, an obvious body segment, has been described as a significantly divergent trait in sheep23, the HOXB13 gene was first highlighted to be significantly associated with the sheep tail phenotype in a genomic comparison that included Ethiopian fat-rumped and short fat-tailed sheep breeds vs. Ethiopian long fat-tailed and Sudanese long thin-tailed sheep breeds22. In this genomic analysis, a haplotype specific to Ethiopian long fat-tailed and Sudanese long thin-tailed sheep breeds was highlighted 22. Subsequently, by applying the long-read PacBio sequencing and verifying the frequency spectrum of SVs in an expanded dataset, the most differentiated SV was detected as insertion of 169 bp  close to the 5’ untranslated region (5’UTR) of the HOXB13 gene21. The prevalence of this potential insertion was observed in long-tailed sheep breeds. The long-read sequencing approach could also reveal previously undetected SVs in sheep tail-related genes. These include six highly differentiated SVs in the IBH selective region (the largest event was a 7728-bp insertion) and three SVs in the PDGFD selective region (the largest one was an 867-bp insertion)21. More recently, in the Merinolandschaf breed, the same variant was highlighted as a 167-bp insertion in the promotor region of HOXB13 with a completely linked nonsynonymous mutation in the first exon of HOXB13 located 132 bp downstream of the insertion 23. This 167-bp insertion was flanked by 14-bp direct repeats (CTGCCAGCGATTTA) on both sides, which suggests the potential that this insertion is a short interspersed nuclear element (SINE)23. Differences in the length and position of this variant were indicated as a result of sequencing error due to the presence of a long ‘T’ base homopolymer in the detected SINE repeat element23. Future investigations may particularly identify the exact role of the HOXB13 insertion variant. The synchronized discovery of this critical variant by these two independent studies using different breeds supports its high potential causality in the formation of sheep tail length.In recent studies21. A similar finding was also observed in the Merinolandschaf sheep, where tail lengths of homozygous carriers, heterozygous carriers, and non-carriers of the insertion were 31.5, 25.7, and 24.1 cm, respectively23. The expression of HOXB13 with and without the detected insertion variant was investigated using a luciferase reporter assay21. Compared to the wild-type sequence, the insertion decreased the luciferase activity by 10-fold21, indicating that the reduced HOXB13 transcriptional level was linked with the long-tail phenotype. Interestingly, such results were previously proven using mouse models. By applying genetic manipulation techniques to induce HOXB13 gene loss- and gain-of-function activities in mice, HOXB13 deficiency causes tail overgrowth and an increased number of caudal vertebrae, whereas HOXB13 overexpression results in prematurely truncated tails and transgenic HOXB13-overexpressing mice have shorter tails26. These novel findings in sheep and previous investigations in mice support the involvement of the HOXB13 gene in patterning tail length in mammals.The influence of this insertion on the tail phenotype was also highlighted. In 211 individuals from an F2 population of backcrossing East Friesian sheep (♂) with [Hu sheep (♀) × East Friesian sheep (♂)], the tail length of the homologous carriers of the insertion was significantly longer than that of the heterozygous carriers by 2.77 cmHOXB13, as member of the gene repertoire of the sheep tail configuration, a clearer picture regarding the genetic structure of sheep tails could be drawn. The wild ancestor of sheep, Asiatic mouflon , shows a short thin-tail phenotype27, which suggests that sheep breeds with divergent tail phenotypes, e.g., long thin and long fat phenotypes, emerged later (~5000 years ago)28. The first domesticated sheep were initially used as a source of food29. After several millennia, the production and processing of wool have emerged, leading to the selection and a worldwide spread of wool sheep . These wool-producing breeds are characterized by long tails and there is a common occurrence of fine wool and long tail, rising the hypothesis that these two traits are genetically linked or emerged as a result of the same artificial selector30. Fat-tailed sheep are known for storing fat in their tails as an energy reserve, which is considered an adaptive response to the harsh environment and food scarcity28. Additionally, ancient breeders selected them for their adaptability and as a traditional cooking fat and energy source for human consumption. Therefore, selection for the fat-tailed phenotype could have been initiated and promoted by extreme climatic conditions and/or artificial selectors’ preferences31. Particularly, by combining single nucleotide polymorphisms (SNPs) of the male-specific region of the Y chromosome with mitochondrial DNA (mtDNA) variations and whole-genome sequences of rams from the worldwide sheep population, Deng et al.31 reported that (i) the first domestic (hair-coated) sheep spread ~10,500 years BP  from the Fertile Crescent (the Near Eastern domestication center); (ii) the selection for secondary products  triggered the second expansion of sheep populations ~8000–7000 years BP, most likely from Southwest Asia at first; and (iii) a later (third) spread was likely associated with the expansion event of fat-tail sheep ~3400 years BP (1700–5300) from the Middle East to Northern Africa, Central and Eastern Asia, and the eastern edge of Europe.With the emergence of PDGFD, BMP2, TBXT, and HOXB13) have a relationship with cancer development and progression35. The above-mentioned four genomic signals were detected to influence the sheep tail phenotype at both levels, the caudal vertebrae number (TBXT and HOXB13)23 and the level of tail fat deposition (PDGFD and BMP2)36. Thus, making the genetic framework of the sheep tail phenotype clearer to be inferred. Here, based on the potential function and variant association of these four genes/regions, we hypothesize a potential genetic structure of the five main sheep tail phenotypes 17 that was functionally validated using genome editing18 and it is expected to carry derived alleles in one or both of the genomic signatures linked with tail fat deposition (PDGFD and/or BMP2)15. Long thin-tailed sheep are expected to carry a derived allele in the HOXB13 gene23 with ancestral alleles for the two fat deposition-related genomic signatures. Long fat-tailed sheep are expected to carry derived alleles in the HOXB13 gene and one or both of the fat deposition-related genomic signatures. The same situation was observed in the case of the short fat-tailed sheep, but potentially with an ancestral HOXB13 allele. In long thin-tailed, long fat-tailed, and short fat-tailed sheep, the potential role of the TBXT gene in tail patterning is unknown.The expanded patterns of tails at the caudal vertebrae and fat deposition levels require active growth factors. It is not surprising that all the detected genes for the sheep tail phenotype  and TBXT (refs. 38) have been shown to increase and reduce the tail length, respectively. Although the obvious roles of the currently known genomic signatures, other causal variants explaining a wider range of phenotypic variance are likely still unknown.Collectively, in terms of tail length, both genes, 40. Genetic intervention could solve issues related to production, fertility, environmental adaptation, and animal welfare. In sheep, there are two main ways to eliminate the undesired long and/or fat tail phenotypes, including tail docking and crossbreeding. Tail docking is a painful procedure implicated in animal welfare issues. On the other hand, crossbreeding can generate a proportional reduction in tail length. However, a potential loss of previously achieved breeding progress of economically important traits is highly expected. Thus, the accumulated genomic knowledge regarding the sheep tail phenotype could help improve sheep breeding without compromising other desired traits. The revelation of causative variants, such as HOXB13 variants, could provide solutions through the direct gene-assisted selection of the desired short tail ancestral alleles ‘back to the roots23’. In addition, potential biotechnological intervention using modern genome-editing tools could be used to install desired variants without compromising other previously selected genome content. Potential HOXB13 variant(s) might be solely helpful to shorten the tail length in thin long-tailed sheep breeds. In long fat-tailed breeds, it can play a role in combination with tail fat deposition-related gene(s) to generate a shorter tail with a reduced level of fat deposition.Sequencing and annotating livestock genomes are important for improving breeding based on known genetic background43. In sheep, SVs have been shown to play major roles in phenotypic variations. These include, e.g., SVs in relaxin family peptide receptor 2 (RXFP2) (refs. 45) and interferon regulatory factor 2 binding protein 2 (IRF2BP2) (refs. 47), are linked with horn and wool phenotypes, respectively. Further application of long-read sequencing technologies is needed to interrogate the ovine genome. These genomic advances can ameliorate the sheep industry to face future challenges, including climate change, the increasing human population, and the ever-increasing demand for animal products. This could be possible by applying genetic-based strategies, including direct gene-assisted selection and the application of modern genome-editing tools.Significant SVs have been discovered due to emerging long-read sequencing technologiesnr-reporting-summary


Topological spin structures of light, including the Skyrmion, Meron, and bi-Meron, are intriguing optical phenomena that arise from spin–orbit coupling. They have promising potential applications in nano-metrology, data storage, super-resolved imaging and chiral detection. Aside from the electric part of optical spin, of equal importance is the magnetic part, particularly the H-type electromagnetic modes for which the spin topological properties of the field are dominated by the magnetic field. However, their observation and measurement remains absent and faces difficult challenges. Here, we design a unique type of anapole probe to measure specifically the photonic spin structures dominated by magnetic fields. The probe is composed of an Ag-core and Si-shell nanosphere, which manifests as a pure magnetic dipole with no electric response. The effectiveness of the method was validated by characterizing the magnetic field distributions of various focused vector beams. It was subsequently employed to measure the magnetic topological spin structures, including individual Skyrmions and Meron/Skyrmion lattices for the first time. The proposed method may be a powerful tool to characterize the magnetic properties of optical spin and valuable in advancing spin photonics. For instance, the magnetic Skyrmions formed by a swirling magnetization in magnetic materials have potential applications in high density magnetic information storage and transfer derived from their excellent stability established through topological protection and by low driven currents10. Moreover, photonic analogies of magnetic Skyrmions were proposed and demonstrated recently either in 2D form in evanescent waves including steady photonic spin Skyrmions/merons formed through spin–orbit coupling16 and time-varying field Skyrmion lattice18 in the absence of optical spin, or in 3D form in propagating structured lights19. The deep-subwavelength features of spin structures provide novel tools for optical metrology including high-precision displacement sensing and monitoring of magnetic domains20.Topological nontrivial spin textures are intriguing in various physical systems, ranging from high energy to condensed matter physics, because they are insusceptible to disturbances that may be exploited for exotic technologies21, photoemission electron microscopy23 and near-field scanning optical microscopy (NSOM) with fiber probes or nanoscatters30. The last was further adapted so that optical spin angular momentum (SAM) associated with the electric fields were able to be measured33. In addition to the electric part in optical spin, the magnetic part is important as well35, in particular, for transverse electric (TE) modes (H-type waves), for which magnetic fields mainly determine the optical spin topological properties. Although several near-field mapping techniques have been developed for characterizing the magnetic fields, either using a NSOM probe with specific apex38 or high refractive index nanoparticles40, they succumb to inevitable influences from the electric field42. This would affect the vector properties of the measured magnetic field and hence impair the robustness of the system in characterizing the spin topological properties associated with the magnetic fields. The anapole mode of nanoparticles with pure magnetic field response might be a great solution. It has drawn much attention in researches related to near-field optics, nano-optics, etc. because of its intriguing properties, including non-radiation properties realized in dielectric/plasmonic systems46 and nonlinear responses48.The previous Skyrmion structures of light were observed in surface plasmon polaritons, which are transverse magnetic (TM) modes (E-type waves) sustained at a metal-dielectric interface, with electric fields dominating their wave properties. To map the electric-field distributions at near field, many approaches have been proposed in the past including fluorescence imagingIn this paper, we propose a unique magnetic probe with an anapole mode (hereafter named the anapole probe) that is useful in measuring the topological spin structures of evanescent waves governed by magnetic fields. The probe is composed of an Ag-core and Si-shell nanosphere, for which the excited electric dipole and toroidal dipole modes experience a destructive interference, thereby forming the anapole mode and suppressing scattered radiation caused by electric fields Fig. . This an49  and a linear polarizer were inserted in the collection section of the setup [Fig. λ/4 wave-plate and the linear polarizer plate to alternate between ±45° using a high-speed motorized rotation mount , the intensity of the right-handed (IRCP) and left-handed (ILCP) circular polarized components of the in-plane magnetic fields can be extracted. Figure IRCP and ILCP of the excited waveguide mode under the illumination with the azimuthal polarized vortex beam. The normalized z-component SAM (Sz) distribution can then be obtained from Eq.  can be reconstructed from the measured Sz component using the same methodology demonstrated in refs. 32. The spin vector pattern was then obtained [Fig. We then use the above experimental setup to measure various topological spin structures of TE modes dominated by the magnetic field. In the excitation section of the setup, a spiral phase with topological charge of 1 was coded onto the SLM to convert the azimuthal polarized beam to an azimuthal polarized vortex beam. The excited waveguide mode in this circumstance generates a Bessel vortex beam where the spin–orbit coupling results in the formation of a TE-type photonic Skyrmion. To characterize this new type of spin Skyrmion, a quarter-wave plate . With a 6-fold symmetry, two sets of hexagonal sub-lattices for the Skyrmion were obtained with the spin states gradually changing from an upward state in the center to a downward state at the edge (Skyrmion number n = 1). All the measured patterns were reproduced in theoretical calculations with high reliability and predictability.Finally, to form and analyze the spin-Meron and spin-Skyrmion lattices of the TE mode, fan-like intensity masks with different symmetries were inserted into the azimuthal polarized vortex beam Fig.  were obtWe designed an anapole probe to measure the magnetic part of various photonic spin topological textures. The probe is a mixed nanosphere composed of an Ag-core and outer Si-shell, for which the magnetic dipole resonance dominates completely at the desired wavelength along with the elimination of electric-field scattering by the anapole mode. A designed nano-probe was incorporated into our home-built near-field mapping system to map with high robustness the in-plane magnetic field distributions of various tightly focused waveguide modes. Furthermore, photonic spin topological textures formed by the TE-type evanescent waves, including individual Skyrmion, and Skyrmion/Meron lattices with different symmetries, were measured for the first time. The proposed method will facilitate the study of physical processes related to the magnetic components of electromagnetic fields and be valuable in advancing spin photonics.55. Perfectly matched layers were used to simulate open space, and the core-shell nanosphere was illuminated by a normal-incident plane wave polarized along the x-axis. The center of the nanosphere was set as the origin for the coordinate system. The electric fields E(r) at every discretized point r inside the core-shell nanosphere were recorded using a 3D frequency-domain field monitor. By introducing the polarization current J(r), the electric, toroidal, and magnetic multipole moments  may be calculated from56:εr(r) and εd denote the relative permittivities of the nanosphere and air background, respectively, ε0 denotes the vacuum permittivity, ω the angular frequency, i, j = x, y, z. The total scattering cross-section σsca and the total scattering efficiency Qsca are calculated fromE0 denotes the incident electric field and a the outer radius of the nanosphere.To perform multipole decomposition of the scattering spectra for the Ag-core and Si-shell nanospheres, 3D finite-difference time-domain simulations were conducted using commercial software Lumerical. The optical constants for the Ag-core and Si-shell were taken from published dataThe scattering efficiency curves Fig.  were all4 times of dilution, the diluted nanoparticle suspension was dropped on the metal-dielectric waveguide structure and vapored naturally. Then the nanoparticles immobilized steadily on the surface of the metal-dielectric waveguide were left after a rinse using deionized-water. Once dried using nitrogen gas, the samples are ready to use. The sample was checked by a dark-field microscopy, and the proper concentration was that there exists only one nanoparticle in the region of detection.The metal-dielectric waveguide structure was fabricated through electron-beam evaporation. The Au layer (thickness: 40 nm) and the alumina film (thickness: 145 nm) were deposited on a cover slip. The Ag-core and Si-shell nanoparticle was customized by XFNANO Materials Tech Co., Ltd. The solvent was deionized-water, and ultrasonic oscillation for ~30 min was needed before use. After ~10


Photoinduced carrier dynamics of nanostructures play a crucial role in developing novel functionalities in advanced materials. Optical pump-probe scanning tunneling microscopy (OPP-STM) represents distinctive capabilities of real-space imaging of such carrier dynamics with nanoscale spatial resolution. However, combining the advanced technology of ultrafast pulsed lasers with STM for stable time-resolved measurements has remained challenging. The recent OPP-STM system, whose laser-pulse timing is electrically controlled by external triggers, has significantly simplified this combination but limited its application due to nanosecond temporal resolution. Here we report an externally-triggerable OPP-STM system with a temporal resolution in the tens-picosecond range. We also realize the stable laser illumination of the tip-sample junction by placing a position-movable aspheric lens driven by piezo actuators directly on the STM stage and by employing an optical beam stabilization system. We demonstrate the OPP-STM measurements on GaAs(110) surfaces, observing carrier dynamics with a decay time of  To this end, many time-resolved techniques in combination with methods such as electron microscopy4, photoemission electron microscopy6, and X-ray diffraction7 have been reported. Scanning tunneling microscopy/spectroscopy (STM/STS) is a powerful technique to probe topographic and spectroscopic properties of various material surfaces with high spatial and energy resolutions. However, the temporal resolution of conventional STM is limited to the sub-millisecond range by the preamplifier bandwidth  techniques to STM can circumvent the limitations of the circuit bandwidth, achieving higher temporal resolutions16.The ability to measure carrier dynamics in nanoscale materials and devices is an important capability that requires experimental techniques with both high spatial and high temporal resolutions17. With subsequent noise-level and delay-time improvements19, the OPP-STM is now capable of probing the nonequilibrium dynamics of systems such as the atomic scale carrier dynamics around a single impurity on GaAs(110) surface21, the visualization of the ultrafast carrier dynamics in a GaAs-PIN junction22, and the relaxation dynamics of polarons bound to oxygen vacancies on rutile TiO23. Furthermore, recent studies have realized another time-resolved STM utilizing a sub-cycle electric field as bias voltage between the STM tip and sample, called electric-field-driven STM. By measuring an instantaneous tunneling current induced by the sub-cycle electric field, ultrafast time-resolved measurements can be performed. The electric-field-driven STM enables the temporal resolution faster than 1 ps and 30 fs while maintaining the spatial resolution of STM using terahertz (THz) and mid-infrared pulses31. These efforts have substantially expanded the possibilities of time-resolved STM. However, the use of sub-cycle pulsed electric fields still requires various expertise, including the creation and control of electric fields.An OPP-induced tunneling current is generally weak to detect so that we need to employ a modulation technique using a lock-in amplifier. However, the modulation of optical intensity causes severe problems such as thermal expansions of STM tip and sample. Since changes in the tip-sample distance are exponentially multiplied in the tunneling current, such conventional OPP methods cannot be directly combined with STM. In 2004, an exquisite delay-time modulation technique to suppress the thermal expansion effect has been invented33, but the temporal resolutions have been limited to the nanosecond range. For example, recent time-resolved observation of exciton dynamics in transition metal dichalcogenides has revealed the lifetime of exciton in several tens picosecond ranges34. It is thus indispensable to improve the temporal resolution higher than the nanosecond range.The recent OPP-STM systems, whose laser-pulse timing is electrically controlled by external triggers, have significantly improved both the ease of use and the stability of the optical systemIn addition, in most previous OPP-STM systems, the focus lens is placed at a viewport on the ultrahigh vacuum (UHV) chamber while hanging the STM stage by springs for vibration isolation. This configuration causes unstable laser illumination of the tip-sample junction because relative positions of the sample and the lens are affected by vibration noises. The change in the light intensity due to the unstable laser illumination causes unexpected problems such as the thermal expansion effect, making it difficult to observe physical phenomena of interest correctly. Therefore, to utilize this experimental technique in a wider range of research fields, further improvements in the stability of the laser spot with a high temporal resolution are strongly required.In this study, we report the design and performance of a newly developed externally-triggerable OPP-STM system that enables us to conduct tens-picosecond time-resolved measurements with long-term stability. To simplify the optical system, we employ externally-triggerable picosecond laser systems  that controls one pair of active mirrors to stabilize each of the pump laser and of the probe laser spot position on the position sensitive detector (PSD) Fig. . In addientclass1pt{minimaTo demonstrate the stability of laser spot on the sample surface, we monitor a tip and its mirror image on GaAs(110) cleaved surface together with a laser spot focused at the tip-sample junction. Figure In the OPP-STM measurement, the sample surface under the tip is first excited by a pump pulse, and subsequently by a probe pulse with a delay time mentclass2pt{minimIn contrast, when }td Fig. b.When 17 , a high-speed switch  and a frequency dividing circuit   surface, where we measure I-V curves both under dark conditions (without laser illumination), and with laser illumination at a repetition rate of 1 MHz. The atomically flat and clean surface is obtained by cleaving a commercially available n-type (100)-oriented GaAs wafer  via recombination, drift and diffusion  is chosen so that most of curves are well fitted with a single exponential function. The decay time map in Fig. Additionally, we fit OPP tunneling current curves taken inside the bump structure with two exponential functions, separating the fast and the slow components. Figures 33.Finally, we conduct an OPP-STM measurement on low-temperature-grown GaAs (LT-GaAs) to directly demonstrate the tens-picosecond range temporal resolution Fig. . The fas34 can be investigated using this system. Second, the optical system has significantly improved the stability of the laser illumination of the tunnel junction. The long-term stability of the laser illumination allows us to perform OPP tunneling current mapping, thereby visualizing carrier dynamics in the form of, for example, decay time maps as shown in Figs. 42. Photo catalysis23 and photo induced phase transition43 are also interesting phenomena to be investigated. Since a wide delay time range is available from ps to We discuss the future possibilities of the OPP-STM technique presented in this study. First, the temporal resolution in the tens-picosecond range will greatly expand the range of applications. For example, the picosecond range exciton dynamics in transition metal dichalcogenides44. Cutting-edge laser technology, which has been rapidly developing, may realize a higher-performance optical system enabling a wavelength-variable, externally-triggerable laser system with a shorter pulse width in the future.Because in this work, the laser wavelength is fixed at 532 nm (2.33 eV), the selection of a laser system according to the band energy gap of the sample of interest is still necessary. The externally-triggerable picosecond laser systems with a wide range of wavelengths (532–1550 nm) are currently available23. We note that a time-resolved STM system  consisting of almost the same configuration as Fig. 30, indicating the potential capability of the atomic resolution with optical excitation in the OPP-STM system developed in this study.The spatial resolution can be further improved down to the atomic level, as already demonstrated by several groups45. Although we still need to either tune the laser excitation energy to a spin splitting energy, or find a suitable material possessing the spin splitting energy matching with the laser excitation energy, it is possible to conduct such spin dynamics measurements based on the circular polarization modulation technique45 by both adding a Pockels cell and a quarter-wave plate after each pump and probe laser, and by modifying the electronic circuit in the delay-time control system in Fig. 46. The mapping technique presented in this study may resolve the spatial distribution of the spin lifetime of Mn atoms.By using circular polarized illumination, ultrafast spin dynamics can be probed with a spatial resolution of mentclass2pt{minim47, monolayer and bilayer WSe48, and exciton dynamics in an in-plane WS34. The placement of a position-movable aspheric lens directly on the multiprobe stage will similarly improve the stability of laser spot on the sample surface, allowing us to conduct time-resolved mapping experiments.Furthermore, applying the OPP-STM technique to multiprobe systems offers us great opportunities to study carrier dynamics of various nanoscale structures. For example, small island structures on an insulating substrate, which are inaccessible to a single probe STM, can be observed by using one tip as an electrode, while conducting STM measurements using the other tip. Such OPP-multiprobe techniques have already been developed and applied for investigating a monolayer island of a WSe49, in which the thermal expansion effect needs to be similarly suppressed. Since the long-term stability of the laser spot on the sample surface is commonly indispensable for other time-resolved techniques, the optical system reported in this study can be applied for various time-resolved measurements to improve data quality.The optical system developed in this study is also applicable for time-resolved atomic force microscopyThis work reports the development of an externally-triggerable OPP-STM system capable of conducting tens-picosecond range, long-term time-resolved measurements. We achieve this both by controlling the laser pulse sequence electrically, and by placing the aspheric lens on the same stage with the STM head together with the use of the beam stabilization system. The optical system enables us to conduct OPP-STM measurements with a temporal resolution of Supplementary Information.


Critical bone defects were created on six New-Zealand-breed rabbit skulls and covered with the membranes. A sham defect without a membrane was used as the control. After six weeks, a histological analysis (toluidine blue technique) was employed to determine the area percentages of newly formed bone, osteoid bone, and soft tissue. The measurements were performed by dividing the total defect area into top (close to the membrane) and bottom (close to the dura mater) regions, or peripheral (adjacent to the old bone) and central (the sum of the remaining zones) regions. The peripheral regions of the defects showed higher osteogenic capacity than the central areas when the membranes were present. The proportion of new bone adjacent to the dura was similar to that adjacent to the membrane only when the HOOC-Si-Membranes and Zn-HOOC-Si-Membranes were used, indicating a direct osteoinductive effect of the membranes.Our objective is to evaluate the regional regenerative potential of calvarial bone in critical-sized defects in a rabbit model using novel nanostructured silica-loaded membranes doped with zinc or doxycycline. Nanostructured membranes of (MMA) Guided bone regeneration (GBR) is a consolidated treatment modality to accomplish bone regeneration, particularly in the maxillofacial region to gain bone volume  facing tGBR treatment is based on the application of bone substitute materials frequently used in conjunction with barrier membranes to cover an osseous defect . TraditiMembranes based on nonresorbable materials such as expanded polytetrafluoroethylene (e-PTFE) constitute the first generation of barrier membranes. These membranes are characterized by maintaining structural integrity during healing, as well as good biocompatibility. Nonresorbable membranes have mostly shown positive results, both in research with experimental studies and in some clinical application procedures ,10. Howe1-co-(HEMA)1 and (MA)3-co-(HEA)2 were synthesized in order to enhance hydrophilicity, mechanical properties, cell–membrane interactions, and osteogenic properties, as well as to confer antibacterial properties [2-NPs), as well as adding zinc and doxycycline to the membrane’s formulation, improved the bone formation potential of these novel membranes [Novel nonresorbable composite membranes based on electrospun fibers of a mixture of (MMA)operties . Previouoperties . The incembranes . They alembranes  responseembranes . Future Bone regeneration takes place predictably following GBR application in critical-sized calvarial defects. The bone formation process is achieved via a standard basic pattern that closely resembles bone development and growth during intramembranous ossification. A defect can be assumed as critical when it cannot close spontaneously and depends on specific bone and subject . Histori®  using an innovative polymeric blend: (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 50/50 wt doped with 5 wt% of SiO2-NPs. For 2 h, the membranes were incubated in a sodium carbonate buffer solution  in order to activate them with carboxyl groups (HOOC-Si-Membrane). The carboxyl group disposition on the surface of the artificial tissue and the partial hydrolysis of ester bonds made functionalization possible [−1 of ZnCl2 and 800 mg L−1 of Dox [2-NP-doped membrane (HOOC-Si-Membrane), (2) a SiO2-NP-doped membrane functionalized with Zn (Zn-HOOC-Si-Membrane), and (3) a SiO2-NP-doped membrane functionalized with Dox (Dox-HOOC-Si-Membrane). The membranes were then placed at the bottom of a 24-well plate  and sterilized using an ultraviolet radiation sterilization desk .Nanostructured membranes were manufactured by NanomyPpossible . Then, tpossible . Immedia1 of Dox . Three dad libitum food and water were provided by Rabbit Maintenance Harlan Teklad Lab Animal Diets (2030). The experiment was developed according to the US National Institute of Health  and European Directive 86/609/EEC guidelines concerning animals care and use for experimentation. This study also accomplished the European Directive 2010/63/EU concerning animal protection for scientific purposes and all the local laws and regulations. Approval from the Ethics Committee of the institution (CCMI-Ref026/18) was obtained. For ethical reasons, as required by the legislative framework, the minimum number of animals was used. Concerning animal experimentation and histological methods, comparable models have been published [For this research, six New-Zealand-breed experimental white rabbits with identical characteristics (weighing 3.5–4 kg and aged 6 months) were selected. The rabbits were adequately sheltered; daily ublished .Before starting the surgery, the animals’ vital signs were obtained, and then they were immobilized. The rabbits were anesthetized using both Propofol (5 mg/kg) and Midazolam (0.25 mg/kg) infiltrated intravenously for induction with 2.8% inspired sevoflurane gas inhalation. Ketorolac (1.5 mg/kg) and tramadol (3 mg/kg) provided the analgesia. Once the animals were sedated and prepared, incisions between their eyes and their ear bases with a number 15 scalpel blade were made. A triangular field was formed when connecting the two incisions with another one in the skull midline. The bone surface was exposed after the connective, muscular, and epithelial tissues were detached from the operation field using a Prichard periosteotome. Then, the skull surface was washed with sterile saline solution. Four critical bone defects were made on the parietal bone: two on each side of the skull midline separated 3 mm from each other. The defect dimensions were 8 mm in diameter and 3 mm in depth, and they were prepared using a trephine  coupled with an implant micromotor operating at 2000 rpm under saline irrigation. The trephine presented an external diameter of 8 mm, a length of 30 mm, and teeth of 2.35 mm. Piezo surgery was handled to remove the inner table and the medullary bone in every defect. In order to control the depth, a periodontal probe was used. Three bone defects were covered by randomly allocated membranes. The fourth bone defect was not covered (sham group) . To genedura mater. Furthermore, the total area of the zones close to the old bone was considered as the peripheral region of the defect, whereas the central region was the combination of the remaining zones [The samples were prepared from each rabbit skull by cutting them on the anatomical sagittal plane. To fix the undecalcified bone, a 5% buffered formaldehyde solution (pH 7.4) was employed. The blocks with regenerated bone defects were retrieved using an oscillating autopsy saw . Subsequently, the dissected specimens were immersed in a 4% formaldehyde and 1% calcium solution, included in acrylic resin, and prepared for ground sectioning. All the sections were coded, and a light microscope  was used to blindly evaluate the histology and histomorphometry. For rapid-contrast tissue analysis, metachromatic dye and histological staining  were employed with a 1% toluidine blue (TB) solution pH of 3.6) adjusted with HCl. The samples were exposed to the dye with distilled water and air-dried for 10 min at room temperature (23.0 ± 1.0 °C). An Eclipse LV100 microscope  with 20× and 5× lenses was employed to visualize bone from the toluidine morphometric studies. A DSPDS-Fi1 camera  with NIS Elements BR 4.0 software  was used to obtain pictures. In each defect, the area percentages of new bone area (NBA), osteoid area (OA), and soft tissue area (STA) were calculated ,17. The  adjustedp ≤ 0.05. The assessments were undertaken by means of IBM SPSS Statistics v.24 software .The means and standard deviations (SDs) were obtained. A nonparametric Friedman test was used for variance analysis, and a nonparametric pairwise comparison of the Friedman rank sums method for post-hoc analysis was employed. The level of significance was set at The sites healed uneventfully during retrieval surgery under macroscopic observations. During the experimental period, no visual manifestations or inflammations of surgical complications were determined.The histological examinations showed a substantial amount of bone formed in all the defects, specifically in the membrane groups. There was an increasing presence of trabecular woven bone that emerged from the lateral walls toward the center of the defect . The bonThe relative proportion of the woven bone was determined in the total defect area, as well as in different regions of the defects. The new bone was preferentially localized at the periphery rather than in the center of the defects A. The nedura mater or at the bottom attained the same proportion as that adjacent to the membrane or at the top region of the defect in all the groups, including the sham group ; in the other regions, the NBA and STA were similar, in general . The higdura mater (bottom) and the polymeric membrane (top), except when doxycycline was used for membrane doping, which showed higher new bone area values in the contiguous zone to the dura mater.Based on histomorphometric criteria for GBR in calvarial bone defects, a higher proportion of new bone was formed at the periphery compared with the bone found centrally at the defects. The bone regeneration was similar in zones adjacent to both the New bone formed centrally vs. peripherally should be quantified separately because the mechanism of bone formation for each area appears to be different . Advancedura [dura mater, the latter being the most influential. The different patterns of bone distribution could be explained by the release of Si, doxycycline, or Zn, which were assumed to spread out in the defects in concentration gradients with optimal levels at the periphery and detrimental levels at the center [In contrast, the formation of the central bone was mainly attributed to the contact of the defects with the dura . Centraldura  and is ldura . Differedura , who repe center ,6. ThereThe highest percentage of new bone that was formed in either the central and lateral or peripheral areas of the defects treated with HOOC-Si-Membranes and Zn-HOOC-Si-Membranes in comparison to Dox-HOOC-Si-Membranes  could beThough bone formation and osteoid induction in alveolar bone after doxycycline administration have been reported , in the dura lines the inner [dura mater have been determined [Interstitial connective tissue and areas of trabecular bone formation were observed in all samples A. Bone rhe inner . Incomplhe inner  and the he inner . In animtermined . Doxycyctermined . In the termined ,30. Moretermined . Newly ftermined  . When the top and bottom regions of the defect were compared, histological observations revealed a greater degree of bone formation at the top for those membranes that were considered bioactive because of an osteoinductive effect . Increased bone formation, especially in the R2 region, demonstrated the active participation of the aforementioned membranes in the regenerative process instead of being a passive barrier [dura mater rather than on the periosteal sides. The healing period following GBR application is a crucial factor influencing the amount of experimental neogenic bone formation [Multiple factors influence the bone-healing process, making the GBR of critical defects complex and poorly understood. Among these factors are the osteogenic properties of the adjacent  defects . As alre barrier . Though  barrier  at the t barrier . Compari barrier , and tim barrier  observedormation . We specormation  stated tStudies should quantify bone regeneration histometrically instead of subjectively evaluating healed vs. unhealed defects. The present report indicated that the results for optimizing bone regeneration within calvarial defects varied on the basis of the type of membrane barrier used. In the present study, it was found that bone regeneration within critical defects (8 mm in diamenter) in rabbit calvarial over 6 weeks was optimized after the placement of HOOC-Si-Membranes and Zn-HOOC-Si-Membranes. To the best of our knowledge, this was the first study to elucidate the potential of HOOC-Si-Membranes and Zn-HOOC-Si-Membranes to enhance osteogenesis compartmentalized by region in the bone defect for GBR. This research was promising but preliminary, and some limitations need to be addressed before clinical application. For example, the use of different time points further than 6 weeks, an increase in the sample size used (six rabbits), and the use of a positive control should be considered for future action. Related to the period of healing (6 weeks), we preferred to concentrate the full power of the study on the intermediate stages of healing where the effects of modifications in improving healing should have become apparent, compared to normal healing in the body. At a later date, the complete healing of the bone in a standard way may possibly hide, for the most part, the improvement produced by our modifications. Concerning the number of animals, it should be stressed that this limited number of specimens was adequate to identify significant differences, as long as there was a significant change in bone healing. This is in line with the sample sizes used in other publications from other teams. Two more items should be taken into account for the future of the research employing large animal models including the application of experimental membranes for guided tissue regeneration. Aiming to verify bone regeneration engineering efficiency for clinical applications, in vitro studies should required focus on molecular mechanisms and biomarker analyses. In a rabbit model, several limitations that jeopardize the methodology were encountered with the lack of fixation devices to immobilize the clot and potential bone damage due to high animal mobility . FinallyNew bone formation under a guided bone regeneration membrane should also be analyzed separately in specific regions of a defect, as the results encountered in the entire defect may mask possible differences between membranes.The peripheral regions of the bone defects showed higher osteogenic potential than the central areas when a nanostructured membrane was present, except in the sham group, which showed no differences. Zones adjacent to both the dura mater and the membrane within the calvarial defects showed similar osteogenic potentials, except when HOOC-Si-Membranes and Zn-HOOC-Si-Membranes were present, which promoted higher new bone area values in the center of the defects and under the membranes. HOOC-Si-Membranes promoted the highest proportion of osteoid area in the peripheral-top regions of the defect, and R3 attained the highest proportion among the regions. Among the calvarial defects treated with Dox-HOOC-Si-Membranes, adipose-like tissue concentrated more in the top-central areas, revealing the regions with the least osteogenic potential. Meanwhile, the rest of the groups performed similarly in any location.


Background: As the world grapples with the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is important to consider the full impact of coronavirus disease 2019 (COVID-19) on healthcare delivery. Evidence from outbreaks of novel H1N1 and Ebola indicates that response to these types of outbreaks requires extraordinary resources, which are diverted from routine infection prevention and control activities. However, little is known about the impact of COVID-19 on adherence to patient safety protocols in hospitals, including infection prevention and control activities. We have described the reports of acute-care registered nurses (RNs) in adhering to patient safety protocols while delivering care to COVID-19 patients. Methods: In October 2020, we conducted a cross-sectional electronic survey of all active RNs in the state of New Jersey who provided direct patient care in a New Jersey hospital in an emergency or adult inpatient unit during the onset of the COVID-19 pandemic. Results: More than 3,027 RNs participated in the survey, for a 15% response rate based on number of eligible RNs. Moreover, 15% of respondents reported that they tested positive for COVID-19 during the initial peak of COVID-19 in New Jersey (March–June 2020). Most RNs reported that the number of patients they were assigned during the first peak of the pandemic affected their ability to adhere to patient safety protocols . In open-ended responses, they shared that being understaffed, the extra time it took for downing and doffing of PPE, the lack of access to ancillary staff , and the need to cluster care affected the quality of care. A nurse working in the intensive care unit (ICU) lamented, “We were sometimes given 4–5 ICU patients who were very sick and required a lot of care. Shortcuts had to be taken to prioritize the most important needs. Sometimes IVs remained longer than desired. Foleys remained in longer. To avoid PPE shortages, we didn’t go into the rooms nearly as much as we normally would, [and] things got missed.” Feelings of being overwhelmed and helpless permeated the nurses’ comments. Conclusions: When caring for COVID-19 patients, frontline nurses struggled with adherence to necessary patient safety protocols, which ultimately disrupted care delivery. Future research should quantify the extent to which the COVID-19 pandemic affected care delivery, including adherence to patient safety protocols among frontline providers.Funding: NoDisclosures: None