Population Attributable Fraction of Nonvaccination of COVID-19 Due to Vaccine Hesitancy, United States, 2021.

Understanding the extent of coronavirus disease 2019 (COVID-19) nonvaccination attributable to vaccine hesitancy versus other barriers can help prioritize approaches for increasing vaccination uptake. Using data from the Centers for Disease Control and Prevention's Research and Development Survey, a nationally representative survey fielded from May 1 to June 30, 2021 (n = 5,458), we examined the adjusted population attribution fraction (PAF) of COVID-19 vaccine hesitancy attributed to nonvaccination according to sociodemographic characteristics and health-related variables. Overall, the adjusted PAF of nonvaccination attributed to vaccine hesitancy was 76.1%. The PAF was highest among adults who were ≥50 years of age (87.9%), were non-Hispanic White (83.7%), had a bachelor's degree or higher (82.7%), had an annual household income of at least $75,000 (85.5%), were insured (82.4%), and had a usual place for health care (80.7%). The PAF was lower for those who were current smokers (65.3%) compared with never smokers (77.9%), those who had anxiety or depression (65.2%) compared with those who did not (80.1%), and those who had a disability (64.5%) compared with those who did not (79.2%). Disparities in PAF suggest areas for prioritization of efforts for intervention and development of messaging campaigns that address all barriers to uptake, including hesitancy and access, to advance health equity and protect individuals from COVID-19.

A Prospective Study of Bladder Function Following Endometriosis Surgery With Up to Eight years Follow-up.

STUDY OBJECTIVE: To assess long-term urinary function for women having laparoscopic surgery for endometriosis. DESIGN: Institutional Review Board-approved nested cohort study within a larger randomized controlled trial assessing urinary function following any benign laparoscopy for gynecological presentations. SETTING: Two tertiary-level university-affiliated hospitals. PATIENTS: Women with histologically confirmed endometriosis within the randomized controlled trial between April 2012 and November 2019, where baseline urinary function was determined. INTERVENTIONS: Women with histologically confirmed endometriosis were contacted between February and October 2020, and urinary function was re-assessed. MEASUREMENTS AND MAIN RESULTS: Urinary function was assessed using validated questionnaires across the domains of filling, voiding, incontinence, and quality of life determined distant from surgery. Higher scores correlated with a greater severity of symptoms. From 518/711 (72.9%) women with histologically confirmed endometriosis, 289/518 (55.8%) consented to the nested study. At a mean of 50 months (range 12-103 months) post-operatively, 35 participants (12.1%) had sought treatment for bladder symptoms, and 81 participants (28.0%) reported at least one urinary tract infection since their index surgery. There was a significant worsening of symptoms for filling, voiding, incontinence, and quality of life pre-operative to post-operatively (2.27 vs 3.32, 0.93 vs 2.02, 1.06 vs 2.32, 0.83 vs 2.13 respectively, p <.001). There was no statistically significant difference in urinary questionnaire scores in participants with and without uterovesical endometriosis. There was no statistically significant difference in any parameter when comparing any revised American Society of Reproductive Medicine (rASM) stage of endometriosis. Participants who had post-operative urinary retention reported a higher mean voiding score than those who did not (3.24 vs 1.94, p = .017), while participants with post-operative urinary tract infection reported a higher mean frequency score than those who did not (5.17 vs 3.24, p = .016). CONCLUSION: This study suggests a decline in urinary function over time following laparoscopic surgery for endometriosis that is not dependent on the severity or location of the disease.

Long Interspersed Nuclear Element-1 Analytes in Extracellular Vesicles as Tools for Molecular Diagnostics of Non-Small Cell Lung Cancer.

Aberrant expression of the oncogenic retrotransposon LINE-1 is a hallmark of various cancer types, including non-small cell lung cancers (NSCLCs). Here, we present proof-of-principle evidence that LINE-1 analytes in extracellular vesicles (EVs) serve as tools for molecular diagnostics of NSCLC, with LINE-1 status in tumor cells and tissues mirroring the LINE-1 mRNA and ORF1p cargos of EVs from lung cancer cell culture conditioned media or human plasma. The levels of LINE-1 analytes in plasma EVs from ostensibly healthy individuals were higher in females than males. While the profiles of LINE-1 mRNA and ORF1p in African Americans compared to Hispanics were not significantly different, African Americans showed slightly higher ORF1p content, and 2-3 times greater ranges of LINE-1 values compared to Hispanics. Whole plasma ORF1p levels correlated with EV ORF1p levels, indicating that most of the circulating LINE-1 protein is contained within EVs. EV LINE-1 mRNA levels were elevated in patients with advanced cancer stages and in select patients with squamous cell carcinoma and metastatic tumors compared to adenocarcinomas. The observed EV LINE-1 mRNA profiles paralleled the patterns of ORF1p expression in NSCLC tissue sections suggesting that LINE-1 analytes in plasma EVs may serve to monitor the activity of LINE-1 retroelements in lung cancer.

Promising Practices Observed in High-Throughput COVID-19 Vaccination Sites in the United States, February-May 2021.

Objectives. To identify promising practices for implementing COVID-19 vaccination sites. Methods. The Centers for Disease Control and Prevention (CDC) and Federal Emergency Management Agency (FEMA) assessed high-throughput COVID-19 vaccination sites across the United States, including Puerto Rico, after COVID-19 vaccinations began. Site assessors conducted site observations and interviews with site staff. Qualitative data were compiled and thematically analyzed. Results. CDC and FEMA conducted 134 assessments of high-throughput vaccination sites in 25 states and Puerto Rico from February 12 to May 28, 2021. Promising practices were identified across facility, clinical, and cross-cutting operational areas and related to 6 main themes: addressing health equity, leveraging partnerships, optimizing site design and flow, communicating through visual cues, using quick response codes, and prioritizing risk management and quality control. Conclusions. These practices might help planning and implementation of future vaccination operations for COVID-19, influenza, and other vaccine-preventable diseases. Public Health Implications. These practices can be considered by vaccination planners and providers to strengthen their vaccination site plans and implementation of future high-throughput vaccination sites. (Am J Public Health. 2023;113(8):909-918. https://doi.org/10.2105/AJPH.2023.307331).

Immediate versus delayed urinary catheter removal following non-hysterectomy benign gynaecological laparoscopy: a randomised trial.

OBJECTIVE: To compare rates of urinary retention and postoperative urinary tract infection between women with immediate versus women with delayed removal of indwelling catheter following benign non-hysterectomy gynaecological laparoscopic surgery. DESIGN: This randomised clinical trial was conducted between February 2012 and December 2019, with follow-up to 6 weeks. SETTING: Two university-affiliated teaching hospitals in Sydney, Australia. POPULATION: Study participants were 693 women aged 18 years or over, undergoing non-hysterectomy laparoscopy for benign gynaecological conditions, excluding pelvic floor or concomitant bowel surgery. METHODS: Three hundred and fifty-five participants were randomised to immediate removal of urinary catheter and 338 participants were randomised to delayed removal of urinary catheter. MAIN OUTCOME MEASURES: The co-primary outcomes were urinary retention and urinary tract infection. Secondary outcomes included hospital readmission, analgesia requirements, duration of hospitalisation and validated bladder function questionnaires. RESULTS: Urinary retention was higher after immediate compared with delayed removal of the urinary catheter (8.2% vs 4.2%, RR 1.8, 95% CI 1.0-3.0, p = 0.04). Although urinary tract infection was 7.2% following delayed removal of the urinary catheter and 4.7% following immediate removal of the urinary catheter, the difference was not statistically significant (RR 0.7, 95% CI 0.3-1.2, p = 0.2). CONCLUSIONS: There is an increased risk of urinary retention with the immediate compared with the delayed removal of the urinary catheter following benign non-hysterectomy gynaecological laparoscopic surgery. The difference in urinary tract infection was not significant. There is 1/12 risk of re-catheterisation after immediate urinary catheter removal. It is important to ensure that patients report normal voiding and emptying prior to discharge, to reduce the need for readmission for the management of urinary retention.

Parents' Willingness to Vaccinate Children for COVID-19: Conspiracy Theories, Information Sources, and Perceived Responsibility.

Understanding parental decision-making about vaccinating their children for COVID-19 is essential to promoting uptake. We conducted an online survey between April 23-May 3, 2021, among a national sample of U.S. adults to assess parental willingness to vaccinate their child(ren). We also examined associations between parental intentions to VACCINATE their children for COVID-19 and conspiracy theory beliefs, trusted information sources, trust in public authorities, and perceptions regarding the responsibility to be vaccinated. Of 257 parents of children under 18 years that responded, 48.2% reported that they would vaccinate their children, 25.7% were unsure, and 26.1% said they would not vaccinate. After adjusting for covariates, each one-point increase in the Vaccine Conspiracy Beliefs Scale was associated with 25% lower odds of parents intending to vaccinate their children compared to those who did not intend to (adjusted odds ratio (AOR) = 0.75, 95% confidence interval (CI): 0.64-0.88). Parents that perceived an individual and societal responsibility to be vaccinated were more likely to report that they intended to vaccinate their children compared to those that did not intend to vaccinate their children (AOR = 5.65, 95% CI: 2.37-13.44). Findings suggest that interventions should focus on combatting conspiracy beliefs, promoting accurate and trusted information sources, and creating social norms emphasizing shared responsibility for vaccination.

COVID-19 Vaccination Coverage, Behaviors, and Intentions among Adults with Previous Diagnosis, United States.

To determine the extent of gaps in coronavirus disease (COVID-19) vaccine coverage among those in the United States with and without previous COVID-19 diagnoses, we used data from a large, nationally representative survey conducted during July 21-August 2, 2021. We analyzed vaccine receipt (≥1 dose and full vaccination) and intention to be vaccinated for 63,266 persons. Vaccination receipt was lower among those who had a prior diagnosis of COVID-19 compared to those without: >1 dose: 73% and 85%, respectively, p<0.001; full vaccination: 69% and 82%, respectively, p<0.001). Reluctance to be vaccinated was higher among those with a previous COVID-19 diagnosis (14%) than among those without (9%). These findings suggest the need to focus educational and confidence-building interventions on adults who receive a COVID-19 diagnosis during clinic visits, or at the time of discharge if hospitalized, and to better educate the public about the value of being vaccinated, regardless of previous COVID-19 infection.

Population Attributable Fraction of Nonvaccination of Child and Adolescent Vaccines Attributed to Parental Vaccine Hesitancy, 2018-2019.

Understanding the role of vaccine hesitancy in undervaccination or nonvaccination of childhood vaccines is important for increasing vaccine confidence and uptake. We used data from April to June interviews in the 2018 and 2019 National Immunization Survey-Flu (n = 78,725, United States), a nationally representative cross-sectional household cellular telephone survey. We determined the adjusted population attributable fraction (PAF) for each recommended childhood vaccine to assess the contribution of vaccine hesitancy to the observed nonvaccination level. Hesitancy is defined as being somewhat or very hesitant toward childhood vaccines. Furthermore, we assessed the PAF of nonvaccination for influenza according to sociodemographic characteristics, Department of Health and Human Services region, and state. The proportion of nonvaccination attributed to parental vaccine hesitancy was lowest for hepatitis B birth dose vaccine (6.5%) and highest for ≥3-dose diphtheria and tetanus toxoids and acellular pertussis vaccine (31.3%). The PAF of influenza nonvaccination was highest for non-Hispanic Black populations (15.4%), households with high educational (17.7%) and income (16.5%) levels, and urban areas (16.1%). Among states, PAF ranged from 25.4% (New Hampshire) to 7.5% (Louisiana). Implementing strategies to increase vaccination confidence and uptake are important, particularly during the coronavirus disease 2019 pandemic.

Prevalence and Clonal Diversity of over 1,200 Listeria monocytogenes Isolates Collected from Public Access Waters near Produce Production Areas on the Central California Coast during 2011 to 2016.

A 5-year survey of public access surface waters in an agricultural region of the Central California Coast was done to assess the prevalence of the foodborne pathogen Listeria monocytogenes. In nature, L. monocytogenes lives as a saprophyte in soil and water, which are reservoirs for contamination of preharvest produce. Moore swabs were deployed biweekly in lakes, ponds, streams, and rivers during 2011 to 2016. L. monocytogenes was recovered in 1,224 of 2,922 samples, resulting in 41.9% prevalence. Multiple subtypes were isolated from 97 samples, resulting in 1,323 L. monocytogenes isolates. Prevalence was higher in winter and spring and after rain events in some waterways. Over 84% of the isolates were serotype 4b. Whole-genome sequencing was done on 1,248 isolates, and in silico multilocus sequence typing revealed 74 different sequence types (STs) and 39 clonal complexes (CCs). The clones most isolated, CC639, CC183, and CC1, made up 27%, 19%, and 13%, respectively, of the sequenced isolates. Other types were CC663, CC6, CC842, CC4, CC2, CC5, and CC217. All sequenced isolates contained intact copies of core L. monocytogenes virulence genes, and pathogenicity islands LIPI-3 and LIPI-4 were identified in 73% and 63%, respectively, of the sequenced isolates. The virulence factor internalin A was predicted to be intact in all but four isolates, while genes important for sanitizer and heavy metal resistance were found in <5% of the isolates. These waters are not used for crop irrigation directly, but they are available to wildlife and can flood fields during heavy rains. IMPORTANCE Listeria monocytogenes serotype 4b and 1/2a strains are implicated in most listeriosis, and hypervirulent listeriosis stems from strains containing pathogenicity islands LIPI-3 and LIPI-4. The waters and sediments in the Central California Coast agricultural region contain widespread and diverse L. monocytogenes populations, and all the isolates contain intact virulence genes. Emerging clones CC183 and CC639 were the most abundant clones, and major clones CC1, CC4, and CC6 were well represented. CC183 was responsible for three produce-related outbreaks in the last 7 years. Most of the isolates in the survey differ from those of lesser virulence that are often isolated from foods and food processing plants because they contain genes encoding an intact virulence factor, internalin A, and most did not contain genes for sanitizer and heavy metal resistance. This isolate collection is important for understanding L. monocytogenes populations in agricultural and natural regions.

Mental health symptoms and association with COVID-19 vaccination receipt and intention to vaccinate among adults, United States.

Early studies suggest that adults with mental health conditions are at greater risk for COVID-19 infection, severe complications, and higher mortality, yet face barriers in accessing timely health services. Data from the Census Bureau's Household Pulse Survey, a large, nationally representative survey fielded from March 17-29, 2021 (n = 77,104) were analyzed to examine COVID-19 vaccination and intention among adults with mental health symptoms. Separate multivariable regression models were conducted to examine associations between symptoms of anxiety, depression, and anxiety or depression on vaccine receipt (≥ 1 dose) and intention to be vaccinated. Reasons for not being vaccinated were also assessed. Approximately 35% of adults had symptoms of anxiety or depression. This population was less likely to receive COVID-19 vaccination (adjusted prevalence ratio (aPR) = 0.94, 95%CI: 0.91-0.98) but more likely to intend to get a vaccine (aPR = 1.13, 95%CI: 1.08-1.19) than those without these conditions. Females with mental health symptoms were less likely to receive a COVID-19 vaccination but more likely to intend to get vaccinated, while there were fewer significant associations between mental health symptoms and vaccination coverage and intentions to vaccinate among males. Reasons for not getting vaccinated, including concerns about possible vaccine side effects, efficacy, cost, dislike of vaccines, as well as lack of trust in the government and vaccines, were all greater among those with any symptoms of anxiety or depressive disorders than those without symptoms. Efforts are needed to increase vaccination uptake and confidence among this vulnerable population by increasing vaccine confidence and addressing concerns about the vaccine.

Epilepsy and neurobehavioral abnormalities in mice with a dominant-negative KCNB1 pathogenic variant.

Developmental and epileptic encephalopathies (DEE) are a group of severe epilepsies that usually present with intractable seizures, developmental delay, and often have elevated risk for premature mortality. Numerous genes have been identified as a monogenic cause of DEE, including KCNB1. The voltage-gated potassium channel KV2.1, encoded by KCNB1, is primarily responsible for delayed rectifier potassium currents that are important regulators of excitability in electrically excitable cells, including neurons. In addition to its canonical role as a voltage-gated potassium conductance, KV2.1 also serves a highly conserved structural function organizing endoplasmic reticulum-plasma membrane junctions clustered in the soma and proximal dendrites of neurons. The de novo pathogenic variant KCNB1-p.G379R was identified in an infant with epileptic spasms, and atonic, focal and tonic-clonic seizures that were refractory to treatment with standard antiepileptic drugs. Previous work demonstrated deficits in potassium conductance, but did not assess non-conducting functions. To determine if the G379R variant affected KV2.1 clustering at endoplasmic reticulum-plasma membrane junctions, KV2.1-G379R was expressed in HEK293T cells. KV2.1-G379R expression did not induce formation of endoplasmic reticulum-plasma membrane junctions, and co-expression of KV2.1-G379R with KV2.1-wild-type lowered induction of these structures relative to KV2.1-WT alone, consistent with a dominant negative effect. To model this variant in vivo, we introduced Kcnb1G379R into mice using CRISPR/Cas9 genome editing. We characterized neuronal expression, neurological and neurobehavioral phenotypes of Kcnb1G379R/+ (Kcnb1R/+) and Kcnb1G379R/G379R (Kcnb1R/R) mice. Immunohistochemistry studies on brains from Kcnb1+/+, Kcnb1R/+ and Kcnb1R/R mice revealed genotype-dependent differences in the expression levels of KV2.1 protein, as well as associated KV2.2 and AMIGO-1 proteins. Kcnb1R/+ and Kcnb1R/R mice displayed profound hyperactivity, repetitive behaviors, impulsivity and reduced anxiety. Spontaneous seizures were observed in Kcnb1R/R mice, as well as seizures induced by exposure to novel environments and/or handling. Both Kcnb1R/+ and Kcnb1R/R mutants were more susceptible to proconvulsant-induced seizures. In addition, both Kcnb1R/+ and Kcnb1R/R mice exhibited abnormal interictal EEG activity, including isolated spike and slow waves. Overall, the Kcnb1G379R mice recapitulate many features observed in individuals with DEE due to pathogenic variants in KCNB1. This new mouse model of KCNB1-associated DEE will be valuable for improving the understanding of the underlying pathophysiology and will provide a valuable tool for the development of therapies to treat this pharmacoresistant DEE.

COVID-19 Vaccination Coverage, Intent, Knowledge, Attitudes, and Beliefs among Essential Workers, United States.

We assessed coronavirus disease vaccination and intent and knowledge, attitudes, and beliefs among essential workers during March-June 2021. Coverage was 67%; 18% reported no intent to get vaccinated. Primary concerns were potential side effects, safety, and lack of trust in vaccines, highlighting the importance of increasing vaccine confidence in this population.

COVID-19 Vaccination Intent, Perceptions, and Reasons for Not Vaccinating Among Groups Prioritized for Early Vaccination - United States, September and December 2020.

As of February 8, 2021, 59.3 million doses of vaccines to prevent coronavirus disease 2019 (COVID-19) had been distributed in the United States, and 31.6 million persons had received at least 1 dose of the COVID-19 vaccine (1). However, national polls conducted before vaccine distribution began suggested that many persons were hesitant to receive COVID-19 vaccination (2). To examine perceptions toward COVID-19 vaccine and intentions to be vaccinated, in September and December 2020, CDC conducted household panel surveys among a representative sample of U.S. adults. From September to December, vaccination intent (defined as being absolutely certain or very likely to be vaccinated) increased overall (from 39.4% to 49.1%); the largest increase occurred among adults aged ≥65 years. If defined as being absolutely certain, very likely, or somewhat likely to be vaccinated, vaccination intent increased overall from September (61.9%) to December (68.0%). Vaccination nonintent (defined as not intending to receive a COVID-19 vaccination) decreased among all adults (from 38.1% to 32.1%) and among most sociodemographic groups. Younger adults, women, non-Hispanic Black (Black) persons, adults living in nonmetropolitan areas, and adults with lower educational attainment, with lower income, and without health insurance were most likely to report lack of intent to receive COVID-19 vaccine. Intent to receive COVID-19 vaccine increased among adults aged ≥65 years by 17.1 percentage points (from 49.1% to 66.2%), among essential workers by 8.8 points (from 37.1% to 45.9%), and among adults aged 18-64 years with underlying medical conditions by 5.3 points (from 36.5% to 41.8%). Although confidence in COVID-19 vaccines increased during September-December 2020 in the United States, additional efforts to tailor messages and implement strategies to further increase the public's confidence, overall and within specific subpopulations, are needed. Ensuring high and equitable vaccination coverage across all populations is important to prevent the spread of COVID-19 and mitigate the impact of the pandemic.

COVID-19 Vaccination Coverage and Intent Among Adults Aged 18-39 Years - United States, March-May 2021.

Since April 19, 2021, all persons aged ≥16 years in the United States have been eligible to receive a COVID-19 vaccine. As of May 30, 2021, approximately one half of U.S. adults were fully vaccinated, with the lowest coverage and lowest reported intent to get vaccinated among young adults aged 18-39 years (1-4). To examine attitudes toward COVID-19 vaccination and vaccination intent among adults in this age group, CDC conducted nationally representative household panel surveys during March-May 2021. Among respondents aged 18-39 years, 34.0% reported having received a COVID-19 vaccine. A total of 51.8% were already vaccinated or definitely planned to get vaccinated, 23.2% reported that they probably were going to get vaccinated or were unsure about getting vaccinated, and 24.9% reported that they probably or definitely would not get vaccinated. Adults aged 18-24 years were least likely to report having received a COVID-19 vaccine and were most likely to report being unsure about getting vaccinated or that they were probably going to get vaccinated. Adults aged 18-39 years with lower incomes, with lower educational attainment, without health insurance, who were non-Hispanic Black, and who lived outside of metropolitan areas had the lowest reported vaccination coverage and intent to get vaccinated. Concerns about vaccine safety and effectiveness were the primary reported reasons for not getting vaccinated. Vaccination intent and acceptance among adults aged 18-39 years might be increased by improving confidence in vaccine safety and efficacy while emphasizing that vaccines are critical to prevent the spread of COVID-19 to friends and family and for resuming social activities (5).

Report of Health Care Provider Recommendation for COVID-19 Vaccination Among Adults, by Recipient COVID-19 Vaccination Status and Attitudes - United States, April-September 2021.

Vaccination is critical to controlling the COVID-19 pandemic, and health care providers play an important role in achieving high vaccination coverage (1). To examine the prevalence of report of a provider recommendation for COVID-19 vaccination and its association with COVID-19 vaccination coverage and attitudes, CDC analyzed data among adults aged ≥18 years from the National Immunization Survey-Adult COVID Module (NIS-ACM), a nationally representative cellular telephone survey. Prevalence of report of a provider recommendation for COVID-19 vaccination among adults increased from 34.6%, during April 22-May 29, to 40.5%, during August 29-September 25, 2021. Adults who reported a provider recommendation for COVID-19 vaccination were more likely to have received ≥1 dose of a COVID-19 vaccine (77.6%) than were those who did not receive a recommendation (61.9%) (adjusted prevalence ratio [aPR] = 1.12). Report of a provider recommendation was associated with concern about COVID-19 (aPR = 1.31), belief that COVID-19 vaccines are important to protect oneself (aPR = 1.15), belief that COVID-19 vaccination was very or completely safe (aPR = 1.17), and perception that many or all of their family and friends had received COVID-19 vaccination (aPR = 1.19). Empowering health care providers to recommend vaccination to their patients could help reinforce confidence in, and increase coverage with, COVID-19 vaccines, particularly among groups known to have lower COVID-19 vaccination coverage, including younger adults, racial/ethnic minorities, and rural residents.

Prior COVID-19 Infection, Mental Health, Food and Financial Insecurity, and Association With COVID-19 Vaccination Coverage and Intent Among College-Aged Young Adults, US, 2021.

INTRODUCTION: More than 700,000 COVID-19 cases have been linked to American colleges and universities since the beginning of the pandemic. However, studies are limited on the effects of the pandemic on college-aged young adults and its association with their COVID-19 vaccination status and intent. METHODS: Using the Census Bureau's Household Pulse Survey (HPS), a large, nationally representative survey fielded from April 14 through May 24, 2021, we assessed the effects of the pandemic (COVID-19 infection, mental health, food and financial security) on COVID-19 vaccination coverage (≥1 dose) and intentions toward vaccination among college-aged young adults in the United States (N = 6,758). We examined factors associated with vaccination coverage and intent, and reasons for not getting vaccinated. RESULTS: Approximately one-fifth (19.6%) of college-aged young adults had a previous diagnosis of COVID-19, 43.5% and 39.1% reported having anxiety or depression, respectively, 10.9% reported that they sometimes or often did not have enough food to eat, and 22.6% and 12.3% found it somewhat or very difficult, respectively, to pay for household expenses. Of college-aged young adults, 63.1% had received at least 1 dose of the COVID-19 vaccine, 15.4% probably would be vaccinated or were unsure about getting the vaccine, and 14.0% probably will not or definitely will not get vaccinated. Adults who were non-Hispanic Black (vs non-Hispanic White) or had food or financial insecurities (vs did not) were less likely to be vaccinated or intend to be vaccinated. Among adults who probably will not or definitely will not be vaccinated, more than one-third said that they did not believe a vaccine was needed. CONCLUSION: Ensuring high and equitable vaccination coverage among college-aged young adults is critical for safely reopening in-person learning and resuming prepandemic activities.

Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms: A Randomized Clinical Trial.

Importance: Postmenopausal vaginal symptoms are common and frequently detrimental to a woman's quality of life. Fractional carbon dioxide vaginal laser is increasingly offered as a treatment, but the efficacy remains unproven. Objective: To determine the efficacy of fractional carbon dioxide laser for treatment of vaginal symptoms associated with menopause. Design, Setting, and Participants: A double-blind, randomized, sham-controlled trial with 12-month follow-up was undertaken at a single tertiary referral hospital in Sydney, Australia. Enrollment commenced on September 19, 2016, with final follow-up on June 30, 2020. Participants were postmenopausal women with vaginal symptoms substantive enough to seek medical treatment. Of 232 participants approached, 85 were randomized. Interventions: Three treatments using a fractional microablative carbon dioxide laser system performed 4 to 8 weeks apart, with 43 women randomized to the laser group and 42 to the sham group. Main Outcomes and Measures: The co-primary outcomes were symptom severity assessed using a visual analog scale (VAS; range, 0-100; 0 indicates no symptoms and 100 indicates the most severe symptoms) and the Vulvovaginal Symptom Questionnaire (VSQ; range, 0-20; 0 indicates no symptoms and 20 indicates the most severe symptoms) at 12 months. The minimal clinically important difference was specified as a 50% decrease in both VAS and VSQ severity scores. There were 5 prespecified secondary outcomes, including quality of life (range, 0-100; higher scores indicate better quality of life), the Vaginal Health Index Score (range, 5-25; higher scores indicate better health), and vaginal histology (premenopausal or postmenopausal status). Results: Of 85 randomized participants (mean [SD] age, 57 [8] years), 78 (91.7%) completed the 12-month follow-up. From baseline to 12 months, there was no significant difference between the carbon dioxide laser group and the sham group in change in symptom severity (VAS score for overall vaginal symptoms: -17.2 vs -26.6; difference, 9.4 [95% CI, -28.6 to 47.5]; VAS score for the most severe symptom: -24.5 vs -20.4; difference -4.1 [95% CI, -32.5 to 24.3]; VSQ score: -3.1 vs -1.6; difference, -1.5 [95% CI, -5.9 to 3.0]). There were no significant differences between the laser and sham group in the mean quality of life score (6.3 vs 1.4; difference, 4.8 [95% CI, -3.9 to 13.5]) and Vaginal Health Index Score (0.9 vs 1.3; difference, -0.4 [95% CI, -4.3 to 3.6]) or in histological comparisons between laser and sham treatment groups. There were 16 adverse events in the laser group and 17 in the sham group, including vaginal pain/discomfort (44% vs 68%), spotting, discharge, and lower urinary tract symptoms. No severe adverse events were reported in either group. Conclusions and Relevance: Among women with postmenopausal vaginal symptoms, treatment with fractional carbon dioxide laser vs sham treatment did not significantly improve vaginal symptoms after 12 months. Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001403426.

Using electrodermal activity to validate multilevel pain stimulation in healthy volunteers evoked by thermal grills.

We have tested the feasibility of thermal grills, a harmless method to induce pain. The thermal grills consist of interlaced tubes that are set at cool or warm temperatures, creating a painful "illusion" (no tissue injury is caused) in the brain when the cool and warm stimuli are presented collectively. Advancement in objective pain assessment research is limited because the gold standard, the self-reporting pain scale, is highly subjective and only works for alert and cooperative patients. However, the main difficulty for pain studies is the potential harm caused to participants. We have recruited 23 subjects in whom we induced electric pulses and thermal grill (TG) stimulation. The TG effectively induced three different levels of pain, as evidenced by the visual analog scale (VAS) provided by the subjects after each stimulus. Furthermore, objective physiological measurements based on electrodermal activity showed a significant increase in levels as stimulation level increased. We found that VAS was highly correlated with the TG stimulation level. The TG stimulation safely elicited pain levels up to 9 out of 10. The TG stimulation allows for extending studies of pain to ranges of pain in which other stimuli are harmful.

Reversible Vision Loss Due to Transependymal Oedema of the Optic Apparatus Secondary to Ventriculoperitoneal Shunt Malfunction.

A 29-year-old male with a history of pilocytic astrocytoma status post-multiple ventriculoperitoneal shunt (VPS) revisions presented with vision loss, ocular motor deficits, and headaches. His shunt was revised but he experienced persistent vision loss despite resolution of his headaches and diplopia. Magnetic resonance imaging (MRI) of the head revealed hydrocephalus and T2 hyperintensity consistent with transependymal oedema surrounding the midbrain, pons, and optic apparatus. His shunt was again revised, but was complicated by an infection that required removal. He underwent an endoscopic third ventriculostomy and an external ventricular device was temporarily placed. Repeat MRI revealed marked improvement of the transependymal oedema and hydrocephalus. His vision returned to baseline and remained stable at 6-months follow-up.

Griffithsin Retains Anti-HIV-1 Potency with Changes in gp120 Glycosylation and Complements Broadly Neutralizing Antibodies PGT121 and PGT126.

Griffithsin (Grft) is an antiviral lectin that has been shown to potently inhibit HIV-1 by binding high-mannose N-linked glycosylation sites on HIV-1 gp120. A key factor for Grft potency is glycosylation at N295 of gp120, which is directly adjacent to N332, a target glycan for an entire class of broadly neutralizing antibodies (bNAbs). Here, we unify previous work on the importance of other glycans to Grft potency against HIV-1 and Grft's role in mediating the conformational change of gp120 by mutating nearly every glycosylation site in gp120. In addition to a significant loss of Grft activity by the removal of glycosylation at N295, glycan absence at N332 or N448 was found to have moderate effects on Grft potency. Interestingly, in the absence of N295, Grft effectiveness could be improved by a mutation that results in the glycan at N448 shifting to N446, indicating that the importance of individual glycans may be related to their effect on glycosylation density. Grft's ability to alter the structure of gp120, exposing the CD4 binding site, correlated with the presence of glycosylation at N295 only in clade B strains, not clade C strains. We further demonstrate that Grft can rescue the activity of the bNAbs PGT121 and PGT126 in the event of a loss or a shift of glycosylation at N332, where the bNAbs suffer a drastic loss of potency. Despite targeting the same region, Grft in combination with PGT121 and PGT126 produced additive effects. This indicates that Grft could be an important combinational therapeutic.